Scripta Scientifica Medica Med i cal Uni ver sity
Transcription
Scripta Scientifica Medica Med i cal Uni ver sity
Medical University Prof. Dr. Paraskev Stoyanov VARNA, Bulgaria Scripta Scientifica Medica Vol. 40 (2), 2008 pp. 105-196 SCRIPTA SCIENTIFICA MEDICA An official publication of Medical University "Prof. Dr. Paraskev Stoyanov", Varna Editor-in-Chief: Prof. Anelia Klissarova, MD, PhD, DSc Rector of Medical University of Varna e-mail: klisarova@mu-varna.bg Co-Editor-in-Chief: Assoc. Prof. Rossen Madjov, MD, PhD Vice Rector of Medical University of Varna e-mail: madjov@mu-varna.bg Editorial Board: Assoc Prof. Peter Genev, MD, PhD Department of Pathoanatomy E-mail: peterghenev@yahoo.com Assoc. Prof. Boriana Varbanova, MD, PhD Department of Pediatrics and Medical Genetics E-mail: dr_boriana_varbanova@abv.bg Assoc. Prof. Minko Minkov, MD, PhD Head, Department of Anatomy, Histology and Embryology E-mail: anatomia@mu-varna.bg Assoc. Prof. Zhaneta Georgieva, MD, PhD Vice Rector University Hospital Coordination and Postgraduate Education E-mail: zhana_georgieva@abv.bg Assoc. Prof. Krasimir Ivanov, MD, PhD Head, Department of Surgery E-mail: kivanov@gisurgery.com Assoc. Prof. Svetoslav Georgiev, MD, PhD Department of Internal Medicine E-mail: georgievs@pro-lan.net Assoc. Prof. Iskren Kotsev, MD, PhD Department of Hepato - Gastroenterology E-mail: uni@mu-varna.bg Assoc. Prof. Negrin Negrev, MD, PhD Vice Rector for Students Affair E-mail: zam_rector_ud@mu-varna.bg Assoc. Prof. Marinka Peneva, MD, PhD Dean, Faculty of Medicine E-mail: marinka_peneva@mail.bg Assoc. Prof. Stoyanka Popova, MD, PhD Dean, Faculty of Public Health E-mail: popova@mu-varna.bg Assoc. Prof. Vasil Svechtarov, DMD, PhD Dean, Faculty of Dental Medicine E-mail: svechtarov@yahoo.co.uk Assoc. Prof. Violeta Tacheva, PhD Head, Department of Language Teaching, Communications and Sports E-mail: tachevai@mu-varna.bg Assoc. Prof. Diana Ivanova, MD, PhD Head, Department of biochemistry molecular medicine and nutragenomics E-mail: divanova@mu-varna.bg Assoc. Prof. Valentina Madjova, MD, PhD Department of Family Medicine E-mail: v_madjov@abv.bg Assoc. Prof. Emanuela Mutafova, PhD Head, Department of Economics and Healthcare Management E-mail: emoutafova@yahoo.com Assoc. Prof. Radoslav Radev, MD, PhD Head, Department of Surgery E-mail: radev@hotmail.com Secretary: Nikola Kolev, MD Department of Surgery University Hospital "St. Marina" Rumyana Kuyumdzhieva Library of the Medical University E-mail: rumika_99@yahoo.com CONTENTS Kerekovska A., N. Feschieva, K. Dokova, N. Usheva - HEALTH STATUS OF THE BULGARIAN POPULATION: SOCIAL DETERMINANTS, RECENT DYNAMICS AND POLICY IMPLICATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 Radev R. Zl., G. Bekyarova, M. Marinov, K. Mirchev, M. Hristova IMPROVING THE EDUCATION IN PATHOPHYSIOLOGY BY BRINGING IN CLINIACAL CASES DURING SEMINAR LESSONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 Bontcheva S., G. Bontchev - DIFFICULTIES MET BY MEDICAL STUDENTS IN THE COURSE OF BIOPHYSICS: A COMPARATIVE ANALYSIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 Stoyanov Zl., M. Marinov - ANXIETY AND STRESS RESPONSE: EFFECTS OF ANXIETY LEVELS AND SEX. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125 Romanova H. - SOCIOLOGICAL RESEARCH OF STUDENTS FROM MEDICAL UNIVERSITY – VARNA TO DETERMINE THE LEVEL OF KNOWLEDGE AND READINESS FOR PROTECTION IN CASE OF DISASTROUS SITUATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 Ivanova F. - STRUCTURAL AND FUNCTIONAL CHARACTERISTICS OF INSULIN RECEPTORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 Ivanov K., V. Ignatov, N. Kolev, A. Tonev, D. Hristov, S. Konsulova, B. Balev, R. Madjov - DIAGNOSIS AND TREATMENT OF LIVER ABSCESSES . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Deenichin G., R. Dimov, V. Molov, Ch. Stefanov - SYNCHRONOUS MALIGNANT TUMORS OF THE COLON . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 Dyakov Sv., A. Hinev, M. Siderova, H. Bohchelian, K. Hristozov, V. Platikanov ÅMPHYSEMATOUS PYELONEPHRITIS – CLINICORENTGENOLOGIC DIAGNOSIS, REQUIRING URGENT SURGICAL TREATMENT CASE REPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 Marev D. - POST-TONSILLECTOMY HAEMORRHAGE: A RETROSPECTIVE COMPARISON OF ABSCESS- AND ELECTIVE TONSILLECTOMY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 Nedev P. - THE BINDER SYNDROME: REVIEW OF THE LITERATURE AND CASE REPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 Tonchev T. - OUR OWN METHOD FOR REDUCTION AND OBLITERATION OF THE CAVITY IN CASES OF FRONTOETHMOIDAL MUCOCELE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 Tonchev T. - SURGICAL TREATMENT OF TUMORS OF THE LACRIMAL GLAND BY CORONAL APPROACH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 Bachvarova S., P. Drumeva, R. Bachvarova, V. Chakalova - ANXIETY AND DEPRESSION DISTURBANCES IN SOME CHRONIC SKIN DISEASES . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 S. Racheva - ETIOLOGY OF CHRONIC NON-ALLERGIC URTICARIA . . . . . . . . . . . . . . . . . . . . . . . . . 167 Burulianova I., V. Konstantinova, V. Dokov - SUDDEN INFANT DEATH SYNDROME - THE CAUSE OF DEATH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 Burulianova I., V. Konstantinova, D. Radoinova - METHYL ALCOHOL POISONING A MORPHOLOGICAL STUDY FOR 20-YEARS PERIOD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 Dokov W. V. - ANALYSIS OF FATAL ELECTRICAL TRAUMAS IN THE REGION OF VARNA FOR A 41-YEAR-LONG PERIOD. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177 Zlateva S., M. Iovcheva, Marinov P. - LETHALITY FROM ACUTE INTOXICATIONS WITH ORGANOPHOSPHATE PESTICIDES IN VARNA REGION FOR A PERIOD OF 15 YEARS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 Margaritova V. - THE INFLUENCE OF PSYCHOLOGICAL PREPARATION ON FOOTBALL AND KARATE TRAINING IN PRIMARY SCHOOL PUPILS . . . . . . . . . . . . . . . . . . . . . . . . . . 183 Shishkova A., P. Petrova, À. Tînev, G. Iliev, P. Bahlova, Ogn. Softov, E. Kalchev - ANALYSIS OF BODY COMPOSITION USING BIOIMPEDANCE (BIA) DATA . . . . . . . . . 187 AU THOR'S INDEX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193 PERMUTERM SUBJECT INDEX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194 INSTRUCTIONS TO AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 Scripta Scientifica Medica, vol. 40 (2008), pp 111-116 Copyright © Medical University, Varna HEALTH STATUS OF THE BULGARIAN POPULATION: SOCIAL DETERMINANTS, RECENT DYNAMICS AND POLICY IMPLICATIONS Kerekovska A., N. Feschieva, K. Dokova, N. Usheva Department of Social Medicine and Health Care Organisation, Prof. Paraskev Stoyanov Medical University of Varna Reviewed by: Assoc. Prof. S. Popova, MD, PhD ABSTRACT This paper sets out to review the situation with regard to health status of the Bulgarian population and its main determinants. Revealing their recent dynamics, the study also aims to predict the future trends. It tries to interrelate the diseases burden and its determinants with necessary policy responses. Highlighting the main challenges it draws out policy implications. The methods involve analysis of the current demographic and health situation and assessment of its dynamics. Some trends are analyzed comparatively for the different gender and residence population groups. The study is based on an analysis of previously published reports and official statistics. It also draws upon a number of national and local health surveys. Targeted and sustained investment is necessary to reverse the negative trends of population health and its social determinants. Clearly formulated, evidence-based, comprehensive and consistent policy is needed for integrated control of risk factors and chronic diseases, emphasizing on prevention and health promotion. Tangible political commitment, multisectoral collaboration and public participation are required for developing, implementing and sustaining healthy public policies. Keywords: health status, social determinants, policy implications, Bulgaria INTRODUCTION The socio-political transformations that have taken place in Bulgaria since 1989 have had a big impact on the population's health. The dramatic economic and social changes throughout the 1990s caused serious demographic consequences and generally worsened health indicators - associated with low birth rates; increased mortality rates (especially infant and middle-aged male); net emigration and falling populations (particularly those of working age). Demographic change has increased the proportion of elderly people. The prevalence and burden of chronic non-communicable diseases substantially increased. The pattern of increased morbidity and mortality from vascular diseases and cancer is very much associated with unhealthy lifestyles such as high rates of smoking, alcohol consumption and high blood pressure; lack of exercise, unbalanced nutrition, and substance abuse. Social insecurity during the transition period has been an underlying health determinant along with rising unemAddress for correspondence: A. Kerekovska, Dept. of Social Medicine and Healthcare Organisation, Medical University Prof. Dr. Paraskev Stoyanov, 55 Marin Drinov St, BG-9002 Varna, BULGARIA E-mail: kerekovska_a@yahoo.com ployment, poverty and health care system deficiencies. The health impacts of social and economic factors are clearly manifested by the socio-economic differences in population health. Indeed, the transition years in Bulgaria have been characterized by a rapid increase in the socio-economic, residence and gender differences in health. Widening inequalities are also observed from an international perspective, as the gap between Bulgarian health indicators and those of Western and even Central European countries has been increasing for the last decades. These trends of worsening demographic and health indicators, rising prevalence of risk factors and widening inequalities in health are worrying and require more research and an adequate political response. They will continue to pose a major challenge for health policy in Bulgaria especially in the processes of transforming the health care system and acceding the European Union. This paper sets out to review the situation with regard to health status of the Bulgarian population and its main determinants. Revealing their recent dynamics, it also aims to predict the future trends. It tries to interrelate the disease burden and its determinants with necessary policy responses. Highlighting the main challenges it draw out some policy implications. 111 Kerekovska A., N. Feschieva, K. Dokova ... MATERIAL AND METHODS The methods involve an analysis of the current demographic and health situation in Bulgaria and assessment of its dynamics. Some trends are analyzed comparatively for the different gender and residence population groups. Indicators and tendencies assessments are based on both quantitative data as well as qualitative (expert) information coming from different national (Ministry of Health, National Centre on Health Information; National Statistical Institute, national public health centers, etc.) and international (World Health Organisation, World Bank, etc.) sources. The study is based on an analysis of previously published reports and official statistics. It also draws upon a number of national and local health surveys. RESULTS AND DISCUSSION Health Status The period since 1989 is characterized by a rapid population fall from 8,948,649 to 7,801,273 in 2003 [4,11]. Before 1990, the natural growth in Bulgaria has been positive although continuously dropping: from 7.2%o in 1970 to 3.4%o in 1980 and 0.8%o in 1989. Since 1990, Bulgaria has a negative natural growth starting from -0.4%o (in 1990), reaching its maximum of -7%o in 1997, and keeping negative rates of between -5.2 to -5.8 for the 2001-2004 period [4]. The population loss in the last 15 years is also due to large-scale emigration of mainly young and active people. Over 600,000 people have left the country between 1989 and 1995. Since 1995, the average annual number of emigrating individuals has been estimated at 30,000 [8]. Initially, this phenomenon had predominantly political nature, including members of the ethnic Turkish community in the wake of attempts at forcible assimilation by the previous regime. Later, factors of economic origin started to determine the emigration flows. The high unemployment rates and the lack of professional perspective resulted in mass emigration of many young people seeking better opportunities for education and greater job satisfaction. This process negatively influences the overall demographic situation of the country leading to rapid population fall, intensive aging of the Bulgarian population and negatively impacting upon its birth potential. The decrease in the young population groups caused by the emigration along with the persisting low fertility rates speed up the population-aging trend. While in 1990 the proportion of people aged 65 and above was 13.4%, it became 17.1% in 2003 along with a parallel decrease in the youngest population group (under 14 years of age) that reaches the level of 14.6% in 2003. The population ageing leads to an increase in the average age, which in the 1990s changed faster than in the previous decades, and after 2000 exceeds 40 years. Compared to the urban areas, the rural regions of the country are significantly more affected by the aging-population process. Data for 2004 [4] reveals average population age of 45.0 years for the rural and 39.3 years for the urban areas (total country average of 41.0 years). The population decrease and aging processes in Bulgaria will further deepen according to projections of independent studies [13]. The World Bank estimates that the proportion of 'over 65s' will rise from its current level of 17% to around 28% by 2050 [6]. The declining tendency of births, existing for decades has accelerated in the 1990s, and birth rates have been decreasing very steeply to roughly half the rates of the pre-transition years. From 13.3%o in 1988, births in Bulgaria have declined to 7.7%o in 1997 - the lowest in Europe. Despite the slight increase since late 1990s, it is still one of the lowest birth rates in Europe - 9.0%o for 2004. Total fertility declined from 1.81 in 1990 to 1.29 in 2004, reaching its lowest rates of 1.09 in 1997 [4]. For the last 15 years it has not exceeded 1.3, which is substantially lower than the level of 2.2 - necessary for replacement of the population. These negative reproductive tendencies are determined demo- Table 1. Key Health Indicators for Bulgaria, 1990 - 2004 [4] 112 Crude death rate per Population growth 1,000 rate per 1,000 Total fertility rate per woman Infant mortality rate per 1,000 live births -0.4 1.81 14.8 13.6 -5.0 1.23 14.8 7.7 14.7 -7.0 1.09 17.5 2000 9.0 14.1 -5.1 1.27 13.3 2001 8.6 14.1 -5.6 1.20 14.4 2002 8.5 14.3 -5.8 1.21 13.3 2003 8.6 14.3 -5.7 1.23 12.3 2004 9.0 14.2 -5.2 1.29 11.6 Year Birth rate per 1,000 1990 12.1 12.5 1995 8.6 1997 Health status of the bulgarian population: ... graphically by the intensive process of population aging and the respective decrease in the number of women in reproductive age. They are also closely related to the social-economic conditions in the country during the transition period such as impoverishment and uncertainty of the families making the decision for childbirth difficult. Although decreasing, abortions rates are still high in Bulgaria - about three times the EU average. Bulgaria ranks among the countries in Europe with the highest birth rates in young (adolescent) age of maternity, indicating inefficient family planning. A particular problem for Bulgaria is the high proportion of low birth weight births - increasing from 5.7 per 100 live births in 1986 to 7.2 in 1994 [7] and 8.9 per 100 live births in 2002 [4]. The tendency of constantly increasing mortality existing since the 1960s (8.1%o in 1960, 10.3%o in 1975 and 12.0%o in 1985) has deepened during the transition years. During the 1990s, the crude mortality rates steeply increased from 12.9%o in 1993 to 14.7%o in 1997, and keep a stable but high for the European standards level of about 14.2%o for the 2001-2004 period [4]. This process is observed for both sexes, though with greater intensity among male population. The most risky age group is men at the age of 40-59 years whose death rates are much higher than those for women in the same age group. Mortality rates are higher in the rural areas - 19.4%o - compared to the urban ones - 11.9 %o (2004) [4]. The more unfavourable working conditions, poor life style behaviours (unbalanced nutrition and alcohol abuse), increasing differences in access to health services and the quality of health care by place of residence could have contributed to the poor health status of men living in the villages and their high rates of premature mortality. Infant mortality indicators and their dynamics in Bulgaria are very indicative for the substantial influence of the social, economic and health services factors on population's health. While infant mortality rates have been steeply decreasing during the 1960s-1970s from 45.1%o in 1960 to 23.1%o in 1975 and continued its downward trend with slower speed in the next decade to reach 13.6%o in 1988, in the 1990s they began increasing again to reach its highest level since 1983 - 17.5 per 1000 live births in 1997 [4]. This unfavourable dynamics can be related to the worsening economic conditions in the country as well as to the withdrawal of the national policy from childcare as a priority. High teenage birth rates in Bulgaria, heavy smoking, poor nutrition, insufficient knowledge in contraception and sexual behaviour along with the very high rates of prematurely born and low birth weight babies have contributed to the worsening trends of this indicator. Since 1998, however, infant mortality gradually declines to 12.3 per 1000 live births in 2003 and 11.6 per 1000 live births in 2004 [4]. Though it has been decreasing for the last few years, it still remains high by the European standards double the EU average rates of 4.9%o [15]. Infant mortality is much higher in the rural areas (16.5 per 1000 live births for 2004) than in the urban ones (10.7 per 1000 live births) and this differ- ence increases during the transition years [4]. Infant mortality is particularly high in the Roma population. Life expectancy at birth has also decreased during the transition period. During the early 1990s the average life expectancy at birth fell down to the levels of the mid 1960s 70.64 years. The tendency in men has been particularly unfavourable - with a life expectancy of 67.11 years (1993-1995), which is below the average level of the 1960s. Only after 1998 a slow steady increase in life expectancy has started which reaches 72.4 years for 2004 (68.9 for men and 76.0 for women) [3], still among the lowest in Europe not only compared with many developed countries, where it is close to or exceeds 80 years but as well as compared with the other Central and Eastern European countries (CEEC). A growing gap between the male's life expectancy at birth and that of female's is observed in favour of the women. In 1970 it has been 1 year and now it is about 6.5 years difference between the two sexes with the higher mortality of men in their active age contributing to this. For the last decades there has been a continuously increasing trend of reported mortality from non-communicable diseases. Nearly 90 % of all deaths in Bulgaria (2003 data) are caused by the following groups of diseases: circulatory system diseases (67.6%), neoplasms (14.1%), accidents and poisonings (external causes) (3.6%), and diseases of the respiratory system - (3.1%) [3]. While in the 1960s the death rate from circulatory system diseases for men in active age was among the lowest in Europe, it started increasing at a rapid pace and in 1995 moved up to a level twice higher than the EU average (Standardized Death Rates (SDR) for circulatory system diseases for Bulgaria - 724.03 per 100,000 compared with the EU average of 474.76 per 100,000). Unlike the declining tendencies in Western Europe, this indicator continues its upward trend in Bulgaria to 967.3 per 100,000 in 2003 and is higher among men (1009.4 per 100,000) than in women (927.5 per 100,000) [3]. The SDR in 1970 for cardiovascular diseases for males aged 0-64 years in the Central and Eastern European Countries (CEEC), including Bulgaria, were similar to the EU average, but since then in most CEEC they have increased, and the Bulgarian rates have almost doubled. By 2000, Bulgaria had one of the highest mortality rates among the CEEC, and three times the EU rate, which itself has halved since 1970 [12]. Mortality rates from cerebro-vascular diseases have also increased, with stroke deaths being six times the EU average. Official mortality data, derived from death certificates, show Bulgaria to rank near the top for stroke mortality among European countries to the west of the former Soviet Union [10]. Official data reveals higher stroke mortality rates for rural than urban population Mortality rates from neoplasms have also been increasing from 173.6 per 100,000 in 1990 to 201.8 per 100,000 in 2003 [3]. The transition years developed adverse tendencies in the morbidity dynamics of the non-communicable and some communicable diseases in Bulgaria. Many common, non-communicable diseases have remained more prevalent 113 Kerekovska A., N. Feschieva, K. Dokova ... than in the EU such as cardiovascular diseases and stroke. In addition, some communicable diseases that were previously controlled have begun to rise. The biggest share of all morbidity is taken by the diseases of the respiratory system - 37.7% (2002) [4]. The incidence and prevalence rates of circulatory system diseases have been rising consistently since the 1970 becoming the major cause of death. The proportion of people with high blood pressure is steadily high in Bulgaria. It is the most spread chronic disease, which affects 18.3% of male and 24.4% of female population and is increasingly affecting younger age groups. Local studies have estimated that a very large proportion of the people with hypertension, receive inadequate treatment or no treatment at all [1,3]. Along with the high stroke incidence, a great regional variation is observed in Bulgaria, being particularly high in North-Eastern parts of the country. Stroke register-based data from a study (2000-01) conducted in defined urban and rural populations in Varna region (North-East Bulgaria) indicates stroke incidence in the rural areas is amongst the highest yet reported for a European population. There is a marked gradient in stroke incidence from very high rates in males living in the rural areas to less elevated rates in females living in the urban areas [10]. The incidence of neoplasms has been consistently increasing during the transition years - from 252.8 per 100,000 in 1990 to 376.4 per 100,000 in 2003 [4]. A number of dangerous communicable diseases in Bulgaria in the past were eliminated or reduced to sporadic cases by the 1980s. However, the incidences of some of them have increased substantially since then. The morbidity rate of tuberculosis sharply decreased in the period 1980-1990 (from 178,2 per 100,000 in 1980 to 108,1 in 1989), but in the 1990s the trend reversed. In 2000, the morbidity rate is 173.4 per 100,000; in 2002 it is estimated at 188.7; and in 2003 - 168.2 per 100,000. A serious problem since the beginning of the 1990s has been the continuous increase in new cases of tuberculosis. From the level of 25.9 per 100,000 in 1990, the incidence rate rises up to 47.8 in 2002 per 100,000 and stabilizes at this high level (41.7 per 100,000 for 2003) [3]. This tendency is associated with the impoverishment of the population and its poor nutrition. The primary health care reform deteriorated the preventive practices and especially check-ups of the vulnerable groups in settings with limited access to health services like small villages. Mental health disorders have increased in Bulgaria for the last 15 years as alcohol and drug-related psychoses, alcohol addiction syndromes, schizophrenia, maniac depressive psychoses, severe stress and adaptation reactions, and psychosomatic disorders have become more frequent. Determinants of Health The sharp deterioration of the macroeconomic conditions in the beginning of the 1990s and the severe economic crisis in 1996-97 substantially deteriorated the living standards of a large number of households. Since 1990 there has been a significant decline of the income, and in the 114 1997 the reported real income decrease exceeded two-thirds compared to the beginning of the decade. In the late 1990s, the income of 65.5% of the population was under the social minimum, while about half of the population lived at the limit of the subsistence minimum [2]. Along with general income decline a deteriorated cost structure was also observed. Household expenses analysis reveals a rather high portion of the income (over 40%) to be spent on food - indicating impoverishment of the population and deteriorated cost structure. The population categories being most affected by the poverty consequences are Roma ethnic minority groups, long-term unemployed and less educated people. Unemployment rate in Bulgaria has increased dramatically since 1990 reaching its highest level during the 1999-2001 period (17.9% in 2000), however slowly declining for the last years - 16.8% in 2002 and 13.7% for 2003. There is a large (28%) proportion of long-term unemployment (for over 3 years) contributing to increased poverty and social deprivation [5]. Unemployment rates are significantly higher among the less educated population groups - 33.5% among those with lower education (primary and secondary level) compared with 6.8% in those with higher education. Substantial regional differences are also observed in unemployment rates throughout the country - rural regions being more affected (16.2%) than the urban ones (12.9%), and some regions with unemployment rates of over 32% [5]. Rates of tobacco use have risen rapidly in recent decades with the proportion of smokers in the male population among the highest in Europe. Just for 5 years - from 1996 to 2001, smoking prevalence in adult population (over 15 years) has increased by 5% - from 35.6% to 40.5%. This trend has been steeper for the female population - increasing from 16.7% in 1986 to 23.8% in 1996 and reaching 29.8% in 2001. Every second man in Bulgaria is a tobacco smoker, and this has been a stable and long-lasting tendency - 49.0% in 1986; 49.2% in 1996 and 51.7% in 2001. Among the 15-24 age group 41.3 % are smokers and over half (58.5 %) of the Bulgarian population in the age range of 25-44 smokes Teen-age smoking (13-16 years) has rapidly increased as data for 2002 reveals that 42.7% of the girls and 31.3% of the boys in this age group smoke. Smoking is higher among the higher social groups [6]. The proportion of regular alcohol users has increased for the 1986-2001 period from 76.3% to 81.4% in men, and doubled in women - from 33.6% to 67.0%. The increase has been particularly high for the youngest age group (15-24 years), where the increase is from 52% in 1996 to 70.0% in 2001. Liberalization of prices, decreasing subsidies of agricultural and food products production, and decline in real income of the population have led to an increase in the proportion of income spent on food and shifting consumption to cheaper foods. This has increased the risk of nutrient deficiencies and extended the problems of unbalanced and unhealthy diet of the Bulgarian population established during the preceding years, especially in socially deprived groups. Data obtained in nationwide nutrition surveys carried out in Health status of the bulgarian population: ... 1997-98 [9] revealed alarming tendencies in the dietary habits and nutritional status of the Bulgarian population: high energy intake due to great amount of fat consumption; high intake of saturated fatty acids related to the increased red meat consumption and low fish consumption; insufficient intake of dietary fibres because of increased refined foods consumption; seasonal deficit of fresh fruit and raw vegetables intake; high consumption of refined sugar products especially by children and adolescents, and limited variety of foods consumed. Deficient energy and essential nutrients (vitamins, minerals and proteins) intake is observed for some population groups such as: children and adolescents aged 10-14 years; women 18-30 years old and elderly people - corresponding to the substantial prevalence of underweight in these groups (15-16%). At the same time, overweight is highly prevalent (12.6% to 58%) in almost every age/sex group. Along with the traditional determinants (high smoking prevalence, blood pressure distribution, plasma cholesterol distribution, BMI distribution) the high burden of vascular disease in Bulgaria especially in rural male population is also determined by some dietary habits such as the high salt intake and seasonal deficit in fresh fruit and vegetables [10]. According to existing data from several local surveys [1,3], above 80% of the population aged 15 years and older was leading an extremely sedentary lifestyle, with low physical loading at work (91.1% for women and 83.1% for men) and low physical activity off work (88.7%). A frequent combination of physical inactivity with other cardiovascular risk factors, such as high blood pressure, obesity and smoking is also observed by CINDI survey [1]. This survey also identifies overweight as a serious problem for most population groups. Data indicates that two thirds of the Bulgarians aged 25-64 are overweight (BMI 25 or more) and obesity (BMI 30 or more) prevalence varies between 12% and 24% for men and 14% and 39% for women [1,3]. It is argued whether the worsening health status of the population and the increasing inequalities in health are mainly due to the socio-economic factors or are mostly explained by the unhealthy lifestyle behaviours. Their influence on health, however, cannot be separated, as the socio-economic factors impact on lifestyle and determine a certain pattern of health-related behaviours. This interrelationship is demonstrated by the results from local lifestyle surveys carried out in late 1990s [12] revealing significantly pronounced differences between the distinctive education and employment groups. Both lower education level and unemployment impacted negatively on the lifestyle behaviours such fruit and vegetables consumption, physical exercise and alcohol use. CONCLUSION Increasing poverty, sustained unemployment, deteriorated cost structure and consumption pattern, a worsening environment, unhealthy lifestyles, and deficiency of the health care system - all contribute to the worsening health status of the Bulgarian population during the transition period. Men's health is particularly poor especially in rural areas. The inequalities in health are increasing both between the different social groups of the Bulgarian society and on a global level with the other European populations. These worrying trends are progressing. Impacting negatively on the future of the nation they will continue to pose a major challenge for health policy. Therefore, urgent action is needed encompassing adequate political response. The recommendations for policy implications drawn out in this respect refer to the following: · Assessment of the effectiveness of existing health, demographic, and social policies emphasizing on the policy for prevention, early detection and control of the diseases posing the greatest burden to society; · Development of science-based capacity to solve public health problems and establishment of infrastructure for public health research; · Development and implementation of public health approaches addressing more effectively the broader determinants of health in their interrelationships; · Comprehensive and targeted action towards decreasing social inequalities in health; Strengthening the implementation of policies for diminishing poverty, unemployment and social isolation; · Giving priority to prevention, health promotion and evidence-based medicine in policy discussions and agendas for action; · Strengthening public health capacity by training of professionals; · Increasing intersectoral collaboration integrating the efforts of all institutions and involving civic and community public health action; · Strengthening activities of the national public health programmes and decentralizing their implementation through alerting and mobilizing local governments to adjust their programmes and choose priorities for health care; · Development of a system for risk factors surveillance, monitoring and control; · Strengthening the efficiency and stability of the health system through measures improving its financial security and access to health services. Targeted and sustained investment is necessary to reverse the negative trends of population health and its determinants. Clearly formulated, evidence-based, comprehensive and consistent policy is needed for integrated control of risk factors and chronic diseases, emphasizing on prevention and health promotion. Tangible political commitment, multisectoral collaboration and public participation are required for developing, implementing and sustaining healthy public policies. Without a healthy population, Bulgaria, an accession country cannot move forward and runs the risk of being a burden rather than a contributing and vital member of Europe. 115 Kerekovska A., N. Feschieva, K. Dokova ... REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. Âàñèëåâñêè, Í., Âóêîâ, Ì. Ðàçïðåäåëåíèå íà ðèñêîâèòå çà çäðàâåòî ôàêòîðè ñðåä èçâàäêà îò äåìîíñòðàöèîííèòå çîíè íà ïðîãðàìà ÑÈÍÄÈ Áúëãàðèÿ. Ñîöèàëíà ìåäèöèíà, 2003, No 4, 15-18. Ìèíèñòåðñòâî íà çäðàâåîïàçâàíåòî. Íàöèîíàëíà çäðàâíà ñòðàòåãèÿ "Ïî-äîáðî çäðàâå çà ïî-äîáðî áúäåùå íà Áúëãàðèÿ", Ñ., 2001. Ìèíèñòåðñòâî íà çäðàâåîïàçâàíåòî. Äîêëàä çà çäðàâåòî íà íàöèÿòà â íà÷àëîòî íà 21 âåê. Àíàëèç íà ïðîâåæäàíàòà ðåôîðìà â çäðàâåîïàçâàíåòî, 2004. (http://www.mh.government.bg/programmes). Íàöèîíàëåí ñòàòèñòè÷åñêè èíñòèòóò. Íàöèîíàëåí öåíòúð ïî çäðàâíà èíôîðìàöèÿ. "Çäðàâåîïàçâàíå", ÌÇ, Ñ., 1970-2004. Íàöèîíàëåí ñòàòèñòè÷åñêè èíñòèòóò. Ñîöèàëíî-èêîíîìè÷åñêî ðàçâèòèå íà Áúëãàðèÿ, 2003. Ñ., 2004. Georgieva, L., Powels, J., Genchev, G., Salchev, P. Bulgarian population in transitional period. Croatian Medical Journal, 43, 2002, No 2, 240-244. Feschieva, N., Popova, S. Reproductive pattern in a period of socio-economic change, Bulgaria (1986-1994). Archives of Public Health, 1996, 51. Koulaksazov, S. et al. In: Health Care Systems in Transition. Bulgaria. E. Tragakes, ed. Copenhagen, European Observatory on Health Care Systems, 2003. 116 9. 10. 11. 12. 13. 14. 15. Petrova, S. (ed.) Dietary and nutritional status of the population in Bulgaria, March 1998. National Centre of Hygiene, Medical Ecology and Nutrition, Sofia, 1998. Powles, J., Kirov, P., Feschieva, N., Stanoev, M., Atanasova, V. Stroke in urban and rural populations in North-East Bulgaria: incidence and case fatality findings from a 'hot pursuit' study. BMC Public Health, 2002, No 2, 24. Rangelova, R. Aging, health status and determinants of health expenditure. Work package II ENEPRI Project Health and Morbidity in the Accession Countries. Country Report: Bulgaria, 2004 (http://www.enepri.org/Bulgaria.pdf) Uitenbroek, D., Kerekovska, A., Feschieva, N. Health lifestyle behaviour and socio-demographic characteristics. A study of Varna, Glasgow and Edinburgh. Soc. Sci. Med. 43, 1996, No 3, 367-377. World Bank. World development indicators 2003 database, 2003 (accessed: http://www.worldbank.org/data/wdi2003/index.htm). WHO. Highlights on health in Bulgaria. Copenhagen: WHO Regional Office for Europe, 2001 (accessed: http://www.euro.who.int/Document/E73818.pdf). WHO. European Health for All database. Copenhagen: WHO Regional Office for Europe, 2005 (accessed: http://hfadb.who.dk/hfa). Scripta Scientifica Medica, vol. 40 (2008), pp 117-120 Copyright © Medical University, Varna IMPROVING THE EDUCATION IN PATHOPHYSIOLOGY BY BRINGING IN CLINIACAL CASES DURING SEMINAR LESSONS Radev R. Zl., G. Bekyarova, M. Marinov, K. Mirchev, M. Hristova Faculty of Ðathophysiology, Medical University - Varna Reviewed by: Assoc. Prof. N. Negrev, MD, PhD ABSTRACT Nowadays, high quality education is the centre of attention in every medical school. Searching for new ways to introduce the educational units is a natural drift for every discipline. Introducing new educational technique: "Solving of Clinical Case", aims at building a spontaneous bridge between preclinical knowledge and future work in the hospital in immediate and unattended contact with patients. Clinical case solving is a prerequisite for increasing the motivation of students, enhancing logical thinking and stimulating the student for additional investigation at home. The clinical case is based on real patients and the history of their diseases and it is related to the topic of the exercise. It includes the whole data from the moment the patient is seen by doctor for the first time until definitive diagnosis is formulated and medication prescribed. The clinical case is divided in two parts, discussed in two subsequent seminar classes. During the first part the tutor does not give any additional information about the case, he just guides the discussion. The students work by themselves, formulate hypothesis and argument them by building logical connections between causes and results, using the model: causes (and conditions) - altered structure - harmed function - clinical symptom - set of symptoms (syndromes) - disease. At the end of the first part hypothesis are rearranged by their probability. The students may use the time between the to parts to find additional information on the topic and gain some knowledge on the hypothesis that have been discussed, using either traditional forms of education - textbooks, monographies, lectures, original scientific issues and reviews or any kind of source including the www. The second part is used for discussing what kind of laboratory, functional or instrumental tests are still needed to prove or exclude the hypothetical diagnosis. The way it is created, every clinical case emphasizes not only on the biomedical side of the patient's problem, but also the socio-judicial aspects. Keywords: new education technique, clinical case, pathophysiology INTRODUCTION The high quality of education is in the centre of attention of every medical school. An innovative approach towards medical education requires not only changes in traditional learning curricula (5) but also changes in the way material is introduced to the student (15). Searching for new ways to introduce the educational units to the students is a natural drift for every discipline (12). The end goal is helping the formation of professionals of high competency. This very kind of young doctors, having as a foundation a blend of knowledge, skills and practices acquired during the processes of education will be able to meet the requirements of EU member-countries for this kind of professionals (3).The analysis of "Status quo", following the in the course of education, shows that there is à big gap between research and practice. It takes too long until the scientific discovery goes all the way to practical application and teaching (6). Medical students in our university seem to be poorly motivated to use original sources both new issues and reviews. It appears that most of them prefer to use just the textbooks or short versions, most of which are too old and cannot replace the real knowledge come from original materials (13). There are researches suggesting that introduction problem-based education in medical studies is successful and also increases the level of interest in the subject (1,2,8, 14). This kind of education shows good results world-wide. The students are working in small groups - discussing and interpreting the given data thus the processes of education is being brought maximally near to clinical subjects, connecting structure and function (7). Plays a key role in connecting basic preclinical disciplines: biochemistry, biophysics, physiology and anatomy on one hand, and on the other hand clinical disciplines: internal diseases, surgery, neurology, etc (4). In addition, vast knowledge in the field of physiology and pathophysiology is a prerequisite for adequate acquisition of general principals in pathology and pharmacology (11). The considerations stated above in combination with the experience of own colleagues in the Medical University - Pleven encouraged us to include new educational technique as a part of the education on pathophysiology since 2004 - "Solving of Clinical Case" .It 117 Radev R. Zl., G. Bekyarova, M. Marinov ... aims at building a spontaneous bridge between preclinical knowledge and future work in the hospital in immediate and unattended contact with patients. Clinical case solving is a prerequisite to increasing the motivation of the students, enhancing logical thinking and stimulating the student for additional investigation at home. MATERIALS AND METHODS The clinical case is prepared by co-worker in the faculty of Pathophysiology in MU - Varna. It is based on real patients and the history of their diseases and it is related to the topic of the exercise. It includes the whole data from the moment the patient is seen by doctor for the first time till diagnosis is formulated and medication prescribed. The clinical case in divided in two parts which are discussed in two subsequent seminar classes (exercises in pathophysiology). The part consists of: A. FIRST PART 1. Brief presentation of a real patient but under false name and the complaints he presents with during the first meeting with doctor, most often this is a general practitioner (GP). 2. Mnemonic help - a list of medical terms giving hints to the affected anatomical region, the physiological deviations, basic pathophysiological reactions, processes and conditions leading to developing of the disease , and all addition factor - genetic, congenital, legal, ecomonic,social factoors,etc help or hinder the development of the disease. 3. On the basis of the patient's history and using the mnemonic help the students formulate several hypothesis for the possible ethilogical factors and pathogenitic mechanisms, leading to the suspected disease. 4. Patients History - a real history, taken by a physian,as some of the information irrelavant to the disease has been omited 5. Physical examition -systems, organs and functions, including inspetion, percussion, palpation and auscultation 6. Rearranging the hypothesis for the susptected disease by their probabylity, baking their hypthesis up using the only data form the presentation, history and physical examinarion. The students are to pick just the first 5 or 6 most probable diagnosys/diseases. During the first part the tutor does not give any additinal information about the case, he just guides the discussion between the students.The students are woriking alone - formulating hypothesis and argumentating them by explaning the logical connetions between causes and results, namely: causes (and conditions) - altered structure - harmed fuction - clinical symptom - set of symptoms (syndroms) - disease. At the end of the first part the tutor gives oral direction to the students how to prepare for the second part. The studenst may use the time between the to parts to find additional information on the topic and gain some knowledge 118 on the hypothesis that have been discussed, using either traditional form of education - textbooks, monographies,lectures, original scietific issues and review or any kind of infomation source including the world wide web. B. SECOND PART 1. Set of laboratory results that the doctor seaching for the diagnosis may want to be made. Together with the labratory results, there are referent values also. 2. Additional fuctional and instrumental tests.As their is a great variaty the tests are limited to those that are most commonly used in practice and are relevant to the case, and giving maximum information, namely: blood pressure, ECG, EEG, EMG.X-ray, CT.MRI, ect. 3. The final rearrangement of the hypothesis considering all data from both the first and the second part.and giving accurate diagnosis,corresponding to the particular clinical case. The students are encoured to give ideas about ethilogical or pathological treatment. All discussions during the two parts are being recorded on the materials given by the tutor, so they can be used later for referance and self preparation. DISCUSSION AND RESULTS Until now, the faculty of pathophysiology has addapeted several clinical cases , including diseases like : diabetis mellitus, hipertension, cronic pancreatitis, peptic ulcer, chronic kidney failurem and brain vessel disease. During the first part, the students manage to point out which are the major conplaints/syptoms form those the patient presents with during the meeting with the GP. Th analysis ot the data show that about 80% of the students take part in the discussion. During the discussion the general directions, for building hyposthesis about the possible disease, are formed.The mnemoinic help assist in forming of accurate methodological thinking in a real meeting with the patient. A small part of the students neglect the mnemonic help, which inevitably reflects on their work on the clinical case later on. The tutor encouges the students to write down as many diseases that can lead to those sympthoms as possible, without giving them any hints. The students should back up every hypothesis with explanation on what they have based their conclusions. This aims to develop clinical thinking in the situation of a game, where there is a history of an actual patient .The students should explain the pathophysiological patterns pointing causes and circumstances, risk factor and provoking moments for the suspected disease. The building of hypothesis contributes to the in-depth view of the clinical case in question. The experience showed that during discussion on the clinical case the students are motivate to write more than 20-25 possible hypothesis, most of whom are able to argument the possibility of their suggestions relevantly adequate and logically true. It can be marked as a week point that the topic of the seminar directs the thinking of the students towards the disease without, sometimes without any objective facts baking Improving the education in pathophysiology by bringing in cliniacal cases ... this up. The role of the tutor here is to minimize the guessing by provoking a spirit of competitiveness, dividing the students into small teams of 3 or 2. This aids the creating of ideas for analysis and oral and written communication between the students (10). Other authors also report (7,14) that by the history and the description of the physical examination of a real patient makes the situation more close to the real work of a doctor, which increases the students' interest and is relevantly successful. At the same time, the tutor can evaluate the knowledge of the students by the reasoning of the hypothesis which are based on previously studied disciplines. The tutor can draw the students attention to gaps in their preparation and emphasize on the need for filling them up in the time between the two parts . In consonance with his professional competency, the tutor can catch if the student manage to use their knowledge on basic pathophysiology (nosology, types of pathological processes), in building a hypothesis. He can ask them directing questions to help the overcome any possible difficulties. The problems in reasoning the hypothesis are most often due to gaps in the comprehension of the anatomical and physiological substrate of the impairment, poor preparation on the studied unit in pathophysiology, or trying to use knowledge form introduction to internal diseases and surgery, as an end of its self, without paying attention to the pathophysiological mechanism. If time is adequately divided, at the end of the first part the tutor must have enough time to draw the attention and the preparation of the students to the next part so they understand the problems of the patient properly and thoroughly. Using the World Wide Web in preparation is of great value and very attractive (11). The experience with our work with clinical cases shows that with little exceptions (mainly foreign students, due to the language barrier), the students are active and motivated to take part in the discussion in the first part of the clinical case. They are able to identify the facts that they need the definite solving of the clinical case during the second part. The results of the second part indicate some decrease in the activity of the students. Without any doubt, results of laboratory test with the referent values help remembering the values. These tests, in combination to all the additional functional and instrumental tests, that can be done give the future doctor the opportunity to get became acquainted with them, when it is need to be done, and what kind of information they can give. Unfortunately, because of the simultaneous studying of diagnostic imaging, clinical laboratory and pathophysiology and because of the specificity of the more complicated diagnostic investigations, the students encounter them in the pathophysiology seminars for the first time. The help the disciplines in question but it is brings about certain obstacles in leading active discussion in the second part of the clinical cases We give an account of the fact that predominantly more studious students, who have use the time between the two parts not only to work with the textbook and other reference books but also to exchange experience with other colleagues, to discuss with professors from different faculties take part, and of course to search in the internet (13). The role of the tutor-regulator here is of great significance. He is able to involve the maximum number of student in the discussion, to put accent on the risk factors and socially significant diseases and to contribute to increasing the activity of the students. Delaying maximally the moment of reaching the definite diagnosis, helping the students to interpret the lab results and the functional-instrumental tests properly, the tutor draws the attention to rearranging the hypothesis for the corresponding disease, forming, in the course of discussion, the method to differentiate between the significant and in significant complaints of the patient, emphasizes on the problems of the patients which should be looked at in a medico-biological , and socially legal aspect (9). Thus he maintains the interest and motivation for active position of the students till the end of the second part. CONCLUSION Nevertheless our modest experience in this field , bringing in clinical questions during seminar lessons as a part of the course of pathophysiology we have developed I applied for the needs of teaching a convenient , attractive and beneficial to the students form of education. It gives the student a wonderful possibility to build a bridge between preclinical studies and the work of the doctor with immediate contact with the patient. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. Blumberg, Ph., J. Mi chael, H. Zeitz. Role of student generated learning issues in problem - based learning. Teaching and Learning in Medicine, 1990, vol. 2, N 3, pp 149-154. Col li ver, J. Effectiveness of problem-based learning curricula research and theory. Acad. Med., 2000, vol. 75, N 3, pp 259-266. Conncil of Europe Committee of Ministers, Recommendation N R (90) 21 of the Committee to Member States on Training Strategies for Health Information System, adopled by the Committee of Ministers on the 18 October 1990. Dimova, S., M. Marinov, K. Demireva. Pathophysoilogy and the new strategies for medical education. Bulg. Medicine, 2002, vol. 10, N 2, pp 28-30. Good man, L. et al. An experiment in medical education. JAMA, 1991, vol. 265, N 18, pp 2373-2376. Goswami, U Neuroscience and education: from research to practice? Nat Rev. Neurosci., 2006, vol. 7, N 5, pp 406-411. Hud son, J. N., P. Bucvley, I.C. McMillen. Linking cardiovascular theory to practice in an undergraduate medical curriculum. Adv. Physiol. Educ., 2001, vol. 25, N 1-4, pp 193-201. Nor man, G., H. Schmidt. Effectiveness of problem-based learning curricula: theory, practice and paper darts. Med Educ., 2000, vol. 34, N 9, pp 721-728. 119 Radev R. Zl., G. Bekyarova, M. Marinov ... 9. Pulanic, D., H. Vrazic, Cuk, M. Petroveski. Ethiks in medicine: students' opinions on disclosure of true diagnosis. Croat. Med. J., 2002, vol. 43, N 1, pp 75-79. 10. Rivers, D. B. Using a course - long theme for ingucry - based laboratories in a comparative ghysiology course. Adv. Physiol. Educ., 2002, vol. 26, N 1-4, pp 317 - 326. 11. Sarbadhikari, S. N. Basic medical science must include medical informatics. Indian J. Physiol. Pharmacol., 2004, vol. 48, N 4, pp 395-408. 120 12. Suwandwela, Ch. et al. Long. Term ontcome of innovative curricular tracks used in four conntries. Acad. Med., 1993, vol. 68, N 2, pp 128-132. 13. Valdum, C., CH. Zhao, D. Chen. Are current textbooks good enongh for physiology education? For example, the ECL cells are missing. Adv. Physiol. Educ., 2001, vol. 25, N 1-4, pp 123-126. 14. Wolters, M. R. Problem - based learning within entocrine physiology lectures. Adv. Physiol. Educ., 2001, vol. 25, N 1-4, pp 225-227. 15. Zeitz H., H. Paul. The alternative curriculum. Chicago Medicine, 1990, vol. 93, N 12, pp 16-20. Scripta Scientifica Medica, vol. 40 (2008), pp 121-123 Copyright © Medical University, Varna DIFFICULTIES MET BY MEDICAL STUDENTS IN THE COURSE OF BIOPHYSICS: A COMPARATIVE ANALYSIS Bontcheva S., G. Bontchev Medical University Prof. P. Stoyanov - Varna Reviewed by: Assoc. Prof. N. Negrev, MD, PhD ABSTRACT The systematical observation on students studying biophysics draws attention on some difficulties, regularly appearing during laboratory exercises. These difficulties could be easily defined as well as split in groups by their origins, which is clearly proven using an appropriate questionnaire technique. Meeting some requirements arisen in last few years, the educational process in biophysical labs undergoes certain rearrangements. Tracking the distribution of main difficulties met in experimental work and analyzing the students’ response one can judge the capability of academic work. The aim of this pedagogical research is to find out the main difficulties met by the medical students studying biophysics, to retrieve the origins of these difficulties and, if it possible, to suggest some measures concerning their elimination. Furthermore, the presented pedagogical analysis is focused on answering the question: “Which organization of laboratory exercises is most effective?”. Thus, we can achieve a substantial growth in quality of education. Keywords: biophysics, quality of education, pedagogical analysis INTRODUCTION · Group II has half a time for assistance in experimental work, compared to Group I. Biophysics is among the obligatory preclinical courses during the medical education (2nd term of year I). It consists of lectures as well as practical exercises. In order to increase the efficiency of teaching, students are encouraged to be well acquainted with theory concerning every exercise to go; and also, they should prepare an empty laboratory report in which they fill in the corresponding experimental data. During 2003/04 and 2004/05 academic years two groups of students (consisted of 28 and 27 peoples, respectively) are studied in order to determine the main difficulties met by the students in their course of biophysics. These two groups were studied identically, offering the students at the end of every particular exercise the same questionnaire set. The only difference between 2003/04 (Group I) and 2004/05 (Group II) groups was in the set-up of the laboratory work. Whereas students in Group I prepare and do the same exercise at a time, Group II was divided in two subgroups, each working simultaneously on a separate topic. The last one set-up was provoked by increased number of students per group, which could not be met by the hardware equipment available. Due to difference of work organization between Group I and Group II, there are some details that should be mentioned here: · Group II has half a time for checking students’ theoretical preparation, compared to Group I; MATERIALS AND METHODS Pedagogical diagnostics represents “a good empirical analysis which, in some cases, could take experimental forms” [1, p.356]. As a practical activity, the pedagogical diagnostics “is aimed on ... an adequate and expedient use as well as future development in pedagogical practice” of the methods, created by research worker [1, p.357]. One of the most popular methods, widely used in the pedagogical analysis, is the questionnaire [2, p.271]. Reliability of the questionnaire results are usually measured by “agreement rate of the data, collected in number of consequent observations” [2, p.270]. Therefore, in order to avoid the negative influence of some factors on result’s reliability, identical conditions for investigation are provided in any stage of the questionnaire research. The questionnaire sets used were the same by the form (written), content (one and the same questions), type (partially standardized) and time distribution (end of the exercise). Each questionnaire set has the general form as follows: Major difficulties met A) In general: a) In theory b) Connection between theory and practice c) In experimental work d) I had no difficulties 121 Bontcheva S., G. Bontchev e) Other: ..................... B) In particular: a) [Answer 1] b) [Answer 2] c) [Answer 3] d) I had no difficulties e) Other: ..................... Corresponding to the separate type of the topics studied, every questionnaire set includes different positions in section B): Answers 1-3. Each student of Group I and Group II was offered to give his answer to the 13 questionnaire sets in the whole course of biophysics (13 experimental exercises provided). RESULTS AND DISCUSSION In summary, results concerning the general part (section A) of our questionnaire study are represented in Table 1. Table 1. Results of questionnaire study in summary (Section A: in general). Answers are given in percents. Topics MAJOR DIFFICULTIES À) in general 2003/2004 (Group I) 2004/2005 (Group II) a) in theory 26 32 b) connection between theory and practice 3 5 c) in experimental work 6 11 d) I had no difficulties 64 52 e) other 1 0 Analyzing the results shown, one can draw a set of some important conclusions. At first, it is obvious that regardless of exercise’s set-up, approximately half of the students have no difficulties at all. This leads to the conclusion that teaching biophysics is well-organized, well-balanced process, so that suitably prepared students can meet the requirements of experimental exercises. In other hand, it is expected that large number of students (as it is shown – merely 50%) will encounter problems studying physics and biophysics: in their last 2-3 years at secondary school their efforts are usually focused on biology and chemistry (subjects of entrance exam at Medical University) [3]. At second, it is noticeable that the major part of difficulties is connected to the theory of processes. Traditionally, the explanation of that fact assumes problems understanding the mathematical models, vastly used in biophysics. As it is mentioned above, at the secondary school, the mathematics along the physics is neglected by the pupils, which intend to study medicine. Another yet suggestion should be made here: students organize their self-training incorrectly. Before the particular exercise the main student’s target is prep122 aration of empty laboratory report. That is intolerable, because consumes a lot of time and, sadly, shifts the aim of teaching from understanding the matter to some technical work. One possible course to solve this problem is to offer students a ready set of empty laboratory reports, which should be filled in with an appropriate data and observations. Such an approach is already accepted by many preclinical departments. In addition, the results shows that minority of students have difficulties with experiment itself as well as the connection between the experiment and theory. Therefore biophysical exercises are chosen in accordance with students’ skills and satisfactory explained. Absence of answers of type “e) other” proves that the general part of questionnaire is comprehensively constructed. However, the most important conclusion should be drawn toward the set-up of exercises. Results presented in Table 1 undoubtedly prove that switching the exercise organization from Group I type to Group II type leads to the significant decrease of efficiency. Percent of students with no problems falls; percent of students which met difficulties in theory, practice and their connection rises. Such a drawback is somewhat expected: as it has been mentioned already, splitting students in two subgroups (as it was done in Group II) reduces the time for assistance and explanation. Though, Group II type of organization was set in students’ favor. From some years on, number of students per group has been increased. Hardware equipment of biophysical lab cannot meet these changes effectively. In order to involve every particular student directly in experimental work, splitting students into separate teams was a reasonable solution. In such a way, generally speaking, there was given an accent to the practical skills development in return for slight decrease of teaching efficiency. Results concerning the special part (section B) of our questionnaire study are represented in Table 2. Table 2. Results of questionnaire study in summary (Section B: in particular). Answers are given in percents. MAJOR DIFFICULTIES B) in particular Topics, classified by meaning 2003/2004 (Group I) 2004/2005 (Group II) 1. Understanding physical concepts 26 31 2. Working out formulas and solving equations 19 16 3. Constructing and reading graphs 14 16 4. Doing experimental tasks 13 25 5. Working with tables 9 11 6. Other 19 1 Difficulties met by medical students in the course of biophysics: a comparative analysis Examining these results, one can conclude once more that the major problems met by medical students, studying biophysics, are connected with theory, not practice. However, splitting the students in two teams doubles the number of experimental difficulties. That is, reduced assistance time is definitely insufficient for making students familiar with the physical devices as well as theory of the topic. But theory could be understood using textbooks, while developing an experimental experience – can not. This brightly demonstrates the importance of encouraging students to be engaged in real experimental activities. Among other particular problems one can outline the work with graphs, tables and scientific calculators. Frequency of these topics remains statistically equal comparing Group I and Group II. Hence, their origins most likely could be found in some kind of fault in secondary school education. Taking this in account, we propose establishing a separate topic to be included into the course of physics/biophysics course. In Table 2 appears an unexplained and considerable shift concerning frequency of answer 6 (other particular difficulties). The reason could be the different rate of ethnical homogeneity of Group I (39% foreign students) and Group II (26% foreign students). It is well-known phenomenon of “answers spreading” among the students: giving the same answer when not sure which one to choose. shows the persistence of problems observed as well as the adequacy of questionnaire sets used; 2. Major part of difficulties is assigned to the theory of biophysics. Instead of making their own laboratory reports, students should be offered ready (but empty) ones, including questions concerning each separate topic, thus encouraging them to understand the root of the matter being studied. Moreover, it should be kept in mind that involving students in theoretical work is not an easy task due to their negative response; 3. It is firmly demonstrated that on-line assistance is essential not for development of theoretical knowledge, but for gaining practical experience. This should underline the importance of keeping the number of students per group relatively small – corresponding to the hardware equipment available. Unfortunately, it is seldom in capability of the department to organize details of that matter. However, it should be kept in mind that involving students in experimental work is a rewarding task (positive response); 4. Special attention needs the fact that medical student often do have problems with some routine tasks (working with graphs, tables, calculators). Such a simple obstacle could dramatically decelerate work and shifts students’ attention away from the main goal. Introducing an appropriate training into the course of physics/biophysics/chemistry should be in help. CONCLUSION REFERENCES Taking into account gathered results as well as their analysis, one can draw some conclusions concerning main difficulties met by medical students in course of biophysics, their origins and organization of experimental exercises. On this basis, some measures leading to improvement of education could also be proposed. 1. Reproducibility of results obtained during two different years from two different group of students clearly 1. 2. 3. Bijkov G. Pedagogical diagnostics, Sofia,“St. Kl. Ochridski” (1999) – in Bulgarian Bijkov G., Kraevski V. Methodology and methods of pedagogical investigations, Sofia-Noscow, “St. Kl. Ochridski” (1999) – in Bulgarian Bontcheva S., Diagnostics of difficulties met by the medical students in course of biophysics. Pedagogika, 2 (2005), p. 35-44 – in Bulgarian 123 Scripta Scientifica Medica, vol. 40 (2008), pp 125-128 Copyright © Medical University, Varna ANXIETY AND STRESS RESPONSE: EFFECTS OF ANXIETY LEVELS AND SEX Stoyanov Zl., M. Marinov Department of Physiology and Pathophysiology, Medical University - Varna Reviewed by: Assoc. Prof. N. Negrev, MD, PhD ABSTRACT It is an undisputed fact that anxiety may modulate human stress response. However, the existing data on the specificity of the psychophysiological reactivity of high-anxious and low-anxious individuals, and on the presence of sex differences in this context, are controversial. The presented review summarizes recent literary data and analyses some of the neurobiological underpinnings of the sex differences in the association between anxiety and stress response. Keywords: anxiety, stress, sex Anxiety is a complex psychological construct with various dimensions and manifestations. It contains cognitive, emotional and behavioural components and is accompanied by various physiological changes, which reflect the activity of the autonomic nervous system and neuroendocrine axes (4,22,21,36,16). In the literature on anxiety and autonomic control there prevail data on increased sympathetic activity, decreased vagal tonic influence on the heart, and reduced autonomic flexibility. Anxiety is associated with increased heart rate (HR), reduced respiratory sinus arrhythmia, increased arterial blood pressure, and higher levels of skin conductance (4,21,16). Some authors find these autonomic changes to be logical, as the mechanisms underlying anxiety are closely connected with the mechanisms of fear and the responses of the type "fight-or-flight" provoked by them (2). It is no accident that many studies put emphasis on the existing two-way close relationship between anxiety and stress. It is assumed that anxiety may be both a natural reaction to a stressor and a part of the complex of the stress response, as well as a post-stressor phenomenon (as in post-traumatic disorder, for example) (2,24). It is also pointed out that anxiety may modulate the stress response and the abilities for coping with stress (9,33,19). Specificity in the psychophysiological reactivity in low-anxious and high-anxious individuals? One of the interesting questions arising in the context of anxiety and autonomic control is whether a psychophysiological stereotyping of the relationship beAddress for correspondence: Zlatislav Stoyanov, Dept. of Physiology and Pathophysiology, Medical University, 55 Marin Drinov St, BG-9002 Varna, BULGARIA E-mail: zsd@mu-varna.bg tween anxiety and autonomic control is possible, and whether there exists specificity in the autonomic reactivity in low-anxious and high-anxious individuals. In a number of publications on the problem, independent of the methodological differences (different measures of anxiety, different stressors and conditions) data are presented that point out that anxiety may moderate psychophysiological reactivity. Reports exist that individuals with high levels of emotional reactivity and trait anxiety are likely to react with a more marked increase of HR and blood pressure (7). In the conditions of cognitive stress Clements and Graham (10) find out that HR reactivity correlates positively with trait anxiety. In the experiments carried out by Gonzalez-Bono et al. (18) and concentrated on the anticipatory autonomic response, a moderating effect of trait anxiety is again presented: high-anxious individuals demonstrate a greater HR reactivity. According to results by Gramer and Saria (19) trait social anxiety exerts a substantial influence on cardiovascular reactivity in active performance situations: high-anxious individuals overall exhibit greater HR reactivity. In a more recent publication, however, which analyses in more detail the cardiovascular effects of the stressor anticipation period, Gramer and Sprintschnik (20) present slightly different data, namely, that high socially anxious individuals overall exhibit lower blood pressure and HR reactivity. That corresponds with the earlier data by Wilken et al. (44), who also report of poorer reactivity in high-anxious individuals. Similar are the data from the population-based study of Young et al. (47): individuals with high trait anxiety demonstrated reduced cardiovascular reactivity whereas individuals with trait anxiety demonstrated increased reactivity. It is important to draw attention to the fact that in that study the group of high anxiety subjects consisted predominantly of women. In contrast to the above, in their study Mauss et al. (28) find out that the psychophysiological responses of high-anxious individuals 125 Stoyanov Zl., M. Marinov during anticipatory anxiety are similar to those of low-anxious individuals. In accordance with them is the opinion of Barret and Armony (2) that individual differences in trait anxiety do not affect the autonomic responses associated with a mental task. Not so definitive are also some data from the studies analyzing the neuroendocrine activity. Some authors report that in anxiety disorder patients exaggerated acute neuroendocrine responses to psychosocial stressors are observed (8). Other studies point out, however, that individuals with high levels of TA have reduced neuroendocrine reactivity to stressors. Jezova et al. (22) established that subjects with high trait anxiety exhibit lower plasma levels of adrenocorticotropic hormone (ACTH) and cortisol, and lower stress-induced activation of epinephrine and norepinephrine secretion. There also exist mixed results: Gerra et al. (17) report that after a psychological stress the concentrations of norepinephrine, growth hormone and testosterone increase significantly only in anxious individuals, but substantial changes in the concentrations of ACTH, cortisol and epinephrine are absent. Takahashi et al. (36) find out significant positive correlation between trait anxiety, autonomic reactivity and basal cortisol levels at rest, but not in stress conditions. Sex differences in the association between anxiety and psychophysiological responses to stress The reasons for the ambiguous and conflicting results may be different, but it is not impossible for it to be due to the fact that the role of the sex has not been analysed in detail (18): either mixed groups have been studied and the data for both sexes have been interpreted together, or the conclusions have been reached over observation of only men (17,21,36), or only women (18,33,19,20). Concentrating on the role of the sex is well-founded not only because of the different levels of anxiety reported in men and women - many authors share the view that women are more anxious than men (3,31,15,26,11), but also because of the existing data for a different pattern of the association between emotions and physiological parameters in men and women (30). There are reports that anxious men show higher reactivity of the diastolic blood pressure and cortisol secretion while anxious women show more pronounced changes in the HR (13). Under laboratory stress (public speech) Carrillo et al. (9) find out in men significant positive correlation between state anxiety and peripheral pulse volume, but not between state anxiety and HR. In contrast to that, in women the same authors observe positive correlation between anxiety and reactivity of HR. The differentiated by sex analysis of our experimental results suggests the existence of typical cardiovascular responses to mental stress of low-anxious and high-anxious individuals (27), however the parameters of this stereotyping are reciprocal for men and women, which may mask as a whole the effect of the anxiety on the cardiovascular response to stress. So we support the view of Naveteur and Freixa-i-Baque (32) that anxiety may moderate the 126 psychophysiological responses to stressful situations, but unlike them, we believe that in this aspect there exist sex differences. We will also add that our results do not correlate with the data of Takai et al. (37) as well, about the absence of sex differences in the sympathetic-adrenomedullar activity during stress in high-anxious and low-anxious individuals. According to the same authors however, during stress the cortisol levels in high-anxious women are significantly lower that those in high-anxious men. In several of the researches that study the correlations between anxiety and psychophysiological reactivity to stress in women (33,19,20), the established type of reaction in high-anxious and low-anxious individuals is interpreted within the framework of active coping and energization and is connected with the subjective evaluations of the individuals as to the gravity of the task, the efforts invested and the likelihood of success, their perception of stress and the means to cope with it. There do not exist, however, enough comparable data for men. When clarifying the role of the sex in the relationship between anxiety and stress, there should also be taken into account the existence of sex differences in stress reactivity. Most (but not all) of the data present in literature outline a tendency to a more acute stress response of the sympathetic-adrenal mechanisms in men when compared to women (25,23). A different pattern of brain activity in men and women in stress conditions has also been established. Mental stress in men is associated with activation of the right prefrontal cortex and reduced activity in the left orbitofrontal cortex, while in women structures of the limbic system become active, like the ventral striatum, putamen, insula and cyngular cortex (43). At the same time the dominating right-sided prefrontal activity during stress in men correlates significantly and with changes in the physiological parameters like the cortisol response, but the limbic activation in women correlates quite weakly with cortisol. In addition to this, in women correlation is established between anxiety related personality traits and regional brain volume in the left anterior prefrontal cortex smaller brain volume in the left anterior prefrontal cortex underlies the basis for higher anxiety-related traits (46). The question of the sex differences in the association between anxiety and psychophysiological responses to stress becomes even more topical due to the fact that in recent years there are attempts to isolate two different models of stress response: "fight-or-flight" and "tend-and-befriend" (39,40,38). As we pointed above, data from our study showed that high-anxious men are characterized by a more strongly expressed cardiovascular reactivity under stress, while high-anxious women are characterized with less expressed response of HR and vascular tone. The "logic" of the established sex differences in the correlation between trait anxiety and cardiovascular reactivity could be partly explained with the mentioned two different models of stress response: "fight-or-flight", accepted for a "male" type, and "tend-and-befriend", accepted for a "female" type (39,40,38). It is known that non-pathological anxiety could be a useful factor for adequate organization of the behavior Anxiety and stress response: effects of anxiety levels and sex under potential threat for the individual (34,6). According to their evolutionary role (hunters and warriors) men should have optimally secured reactions of the "fight-or-flight" type. In that context it seems logical that in men there exists a marked positive correlation (or maybe potentiation) between anxiety and autonomic stress response. It is possible for androgens to act as mediators in this association. It is known that testosterone levels (in principle higher in men) increase significantly with acute stress (39). There are also data that make us think that the prenatal organizational effects of testosterone on the brain could be reflected in anxiety as well (14,1). The stress response of "tend-and-befriend", accepted as more typical for women, reflects the evolutionary role of women to ensure the survival of the offspring and for that purpose it is expedient for them for preserve themselves through other behavioral strategies (39,40,38). The authors cited suggest that female responses to stress may build on attachment/caregiving processes that downregulate sympathetic and hypothalamic-pituitary-adrenocortical responses to stress. Oxytocin is ascribed a controlling effect in such situations (29,39,38), and there are data that it increases the excitability of vagal neurones (12,35) and decreases sympathetic activity (41). On that background it can be speculated that anxiety "serves" in different ways the stress response in men and women. The positive correlation between trait anxiety and cardiovascular reactivity to stress in men suggests that in male sex the higher anxiety may act as a catalyst of the autonomic parameters of stress response. If we accept that the weaker cardiovascular reactivity observed by us in high-anxious women is a manifestation of downregulation of the autonomic mechanisms, then we should suppose that in women the higher anxiety compensates to some extent the tendency for weaker sympathetic-adrenal reaction and ensures specific adequacy of the stress response on principle. Here, however, a certain discrepancy arises. The mechanisms of downregulation in "tend-and-befriend" are accepted to be oxytocin-mediated and moderated by the estrogens and the endogenous opioids (45,39), but these hormones and peptides are known to have anxiolytic properties (45,39,42). Probably it has to do with a more complex reaction of the brain regions (cortex, subcortical nuclei, diencephalon) whose interaction ensures the brain integration of mental and physiological (somatic) functions. The cohesion of some data from studies of the brain correlates of anxiety and stress gives reason to think that the sex differences in the association between anxiety and psychophysiological reactivity to stress reflect the existence of special sex features of the brain integration of cognitive processes, emotions and autonomic control. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. REFERENCES: 16. 1. Alpers, G., W., A. B. M. Gerdes. Show of hands: first evidence for an influence of prenatal testosterone on anxiety disorders. In: Psychologie und 17. Gehirn. E. Wascher, M. Falkenstein, G. Rinkenauer, M. Grosjean, Eds. 2007, 96. http://www.ifado.de/pg2007/Tagung_Abstracts.pdf Barret, J., J. Armony. The influence of trait anxiety on autonomic response and cognitive performance during an anticipatory anxiety task.-Depress. Anxiety, 23, 2006, 210-219. Ben-Zur, H., M. Zeidner. Sex differences in anxiety, curiosity, and anger: A cross-cultural study.-Sex Roles, 19, 1988, 335-347. Bernston, G. G., J. T. Cacioppo. Heart rate variability: stress and psychiatric conditions. In: Dynamic Electrocardiography. M. Malik, A. J. Camm, Eds., Elmsford, New York, Blackwell Futura Publishing, 2004, 57-64. Bersenev, V., G. Guba, O. Pyatak. Handbook of Clinical Neurovegetology, Kiev, Zdorovya, 1990, 191-194. (in Russian) Brown, L. A., J. B. Doan, N. C. McKenzie, S. A. Coo per. Anxiety-mediated gait adaptations reduce errors of obstacle negotiation among younger and older adults: Implications for fall risk.-Gait Posture, 24, 2006, 418-423. Carels, R. A., J. A. Blumenthal, A. Sherwood. Emotional responsivity during daily life: relationship to psychosocial functioning and ambulatory blood pressure.-Int. J. Psychophysiol., 36, 2000, 25-33. Carrasco, G. A., L. D. Van de Kar. Neuroendocrine pharmacology of stress. Eur. J. Pharmacol., 463, 2003, 235- 272. Carrillo, E., L. Moya-Albiol, E. Gon za lez-Bono, A. Sal va dor, J. Ricarte, J. Gomez-Amor. Gender differences in cardiovascular and electrodermal responses to public speaking task: the role of anxiety and mood states.-Int. J. Psychophysiol., 42, 2001, 253-264. Clements, K., T. Gra ham. Life event exposure, physiological reactivity, and psychological strain.-J. Behav. Med., 23, 2000, 73-94. Dickie, E. W., J. L. Armony. Amygdala response to unattended fearful faces: Interaction between sex and trait anxiety.-Psychiat. Res-Neuroim., 162, 2008, 51-57. Dreifuss, J. J., M. Dubois-Dau phin, H. Widmer, M. Raggenbass. Electrophysiology of oxytocin actions on central neurons.-Ann. NY Acad. Sci., 652, 1992, 46-57. Earle, T. L., W. Lin den, J. Wein berg. Differential effects of harassment on cardiovascular and salivary cortisol stress reactivity and recovery in women and men.-J. Psychosom. Res., 46, 1999, 125-141. Evardone, M., G. M. Al ex an der. Anxiety, sex-linked behaviors, and digit ratios (2D:4D).-Arch. Sex. Behav., 2007, 10.1007/s10508-007-9260-6 (Epub ahead of print). Feingold, A. Gender differences in personality: A meta-analysis.-Psychological Bulletin, 116, 1994, 429-456. Fried man, B. H. An autonomic flexibility-neurovisceral integration model of anxiety and cardiac vagal tone.-Biol. Psychol., 74, 2007, 185-199. Gerra, G., A. Zaimovic., U. Zambelli, M. Tim pano, N. Reali, S. Bernasconi et al. 127 Stoyanov Zl., M. Marinov 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. Neuroendocrine Responses to Psychological Stress in Adolescents with Anxiety Disorder.-Neuropsychobiology, 42, 2000, 82-92. Gon za lez-Bono, E., L. Moya-Albiol, A. Sal va dor, E. Carrillo, J. Ricarte, J. Gomez-Amor. Anticipatory autonomic response to a public speaking task in women. The role of trait anxiety.-Biol. Psychol., 60, 2002, 37-49. Gramer, M., K. Saria. Effects of social anxiety and evaluative threat on cardiovascular responses to active performance situations.-Biol. Psychol., 74, 2007, 67-74. Gramer, M., E. Sprintschnik. Social anxiety and cardiovascular responses to an evaluative speaking task: The role of stressor anticipation.-Pers. Indiv. Differ., 44, 2008, 371-381. H o f ma n n , S. G . , D . A . Mo s co v i tc h , B. T . L i t z , H. J . K im, L . L . D a v i s, D . A . Pizzagalli . The worried mind: autonomic and prefrontal activation during worrying.-Emotion, 5, 2005, 464-475. Jezova, D., A. Makatsori, R. Duncko, F. M o n c e k , M . J a k u b e k . High trait anxiety in healthy subjects is associated with low neuroendocrine activity during psychosocial stress.-Prog. Neuro-psychoph., 28, 2004, 1331-1336. K a j a nt i e , E . , D. I . P h i ll i p s. The effects of sex and hormonal status on the physiological response to acute psychosocial stress.-Psychoneuroendocrino., 31, 2006, 151-178 K e an e , T . M. , K . L . T a y l o r , W . E . P e n k. Differentiating Post-Traumatic Stress Disorder (PTSD) from Major Depression (MDD) and Generalized Anxiety Disorder (GAD).-J. Anxiety Disord., 11, 1997, 317-328. K u d i e l k a , B . M . , C . K i r s c h b a u m. Sex differences in HPA axis responses to stress: a review.-Biol. Psychol., 69, 2005, 113-132. L i n d o v á, J . , M. H r u sk o vá, M . P i v o n k o vá, A. Kubena, J. Fleger . Digit ratio (2D:4D) and Cattell's personality traits.-Eur. J. Personality, 2007, DOI: 10.1002/per.664. Marinov, M., Z. Stoyanov, I. Boncheva, I. V a r t a n y a n , T . C h e r n i g o v s k a y a . Trait anxiety and peripheral vascular response to mental stress - sex differences.-Int. J. Psychophysiol., 2008 (in press). M a us s, I . B . , F . H. W i l h e l m, J . J. G r o ss. Autonomic recovery and habituation in social anxiety.-Psychophysiology, 40, 2003, 648-653. Mc Car thy, M. M. Estrogen modulation of oxytocin and its relation to behavior. In: Oxytocin: Cellular and molecular approaches in medicine and research. R. Ivell, J. Russell, Eds. New York, Plenum Press, 1995, 235-242. Moya-Albiol, L., A. Sal va dor, R. Costa, S. Mar ti nez-Sanchis, E. González-Bono, J. Ricarte et al. Psychophysiological responses to the Stroop task after a maximal cycle ergometry in elite sportsmen and physically active subjects.-Int. J. Psychophysiol., 40, 2001, 47-59. Nakazato, K., Y. Shimonaka. The Japanese State-Trait Anxiety Inventory: age and sex differences.-Percept. Motor Skill., 69, 1989, 611-617. 128 32. Naveteur, J., E. Freixa-i-Baque. Individual differences in electrodermal activity as a function of subjects' anxiety.-Pers. Indiv. Differ., 8, 1987, 615-626. 33. Naveteur, J., S. Buisine, J. H. Gruzelier. The influence of anxiety on electrodermal responses to distractors.-Int. J. Psychophysiol., 56, 2005, 261-269. 34. Nesse, R. M. What Darwinian Medicine Offers Psychiatry. In: Evolutionary Medicine. W. R. Trevathan, J. J. McKenna, E. O. Smith. Eds. New York, Oxford University Press, 1999, 351-373. 35. Raggenbass, M., J. J. Dreifuss. Mechanism of action of oxytocin in rat vagal neurones: induction of a sustained sodium-dependent current.-J. Physiology, 457, 1992, 131-142. 36. Takahashi, T., K. Ikeda, M. Ishikawa, N. Kitamura, T. Tsukasaki, D. Nakama et al. Anxiety, reactivity, and social stress-induced cortisol elevation in humans.-Neuroendocrinol. Lett., 26, 2005, 351-354. 37. Takai, N., M. Yamaguchi, T. Aragaki, K. Eto, K. Uchihashi, Y. Nishikawa. Gender-specific differences in salivary biomarker responses to acute psychological stress.- Ann. NY Acad. Sci., 1098, 2007, 510-515. 38. Tay lor, S. E. Tend and befriend: biobehavioral bases of affiliation under stress.-Curr. Dir. Psychol. Sci., 15, 2006, 273-277. 39. Tay lor, S. E., L. C. Klein, B. P. Lewis, T. L. Gruenewald, R. A. R. Gurung, J. A. Updegraff. Biobehavioral responses to stress in females: tend-and-befriend, not fight-or-flight.-Psychol. Rev., 107, 2000, 411-429. 40. Turton, S., C. Campbell. Tend and befriend versus fight or flight: gender differences in behavioral response to stress among university students.-J. Appl. Biobehav. Res., 10, 2005, 209-232. 41. Uvnas-Moberg, K. Oxytocin linked antistress effects - the relaxation and growth response.-Acta Psychol. Scand., Suppl. 640, 1997, 38-42. 42. Walf, A. A., C. A. Frye. A review and update of mechanisms of estrogen in the hippocampus and amygdala for anxiety and depression behavior.-Neuropsychopharmacol., 31, 2006, 1097-1111. 43. Wang, J., M. Korczykowski, H. Rao, Y. Fan, J. Pluta, R. C. Gur, et al. Gender difference in neural response to psychological stress.-Soc. Cogn. Affect. Neurosci., 2, 2007, 227-239. 44. Wilken, J. A., B. D. Smith, K. Tola, M. Mann. Trait anxiety and prior exposure to non-stressful stimuli: effects on psychophysiological arousal and anxiety.- Int. J. Psychophysiol., 37, 2000, 233-242. 45. Windle, R. J., N. Shanks, S. L. Lightman, C. D. Ingram. Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats.-Endocrinology, 138, 1997, 2829-2834. 46. Yamasue, H., O. Abe, M. Suga, H. Yamada, H. Inoue, M. Tochigi, et al. Gender-common and -specific neuroanatomical basis of human anxiety-related personality traits.-Cereb. Cortex, 18, 2008, 46-52 47. Young, E. A., R. M. Nesse, A. Weder, S. Jul ius. Anxiety and cardiovascular reactivity in the Tecumseh population.-J. Hypertens., 16, 1998, 1727-1733. Scripta Scientifica Medica, vol. 40 (2008), pp 129-131 Copyright © Medical University, Varna SOCIOLOGICAL RESEARCH OF STUDENTS FROM MEDICAL UNIVERSITY – VARNA TO DETERMINE THE LEVEL OF KNOWLEDGE AND READINESS FOR PROTECTION IN CASE OF DISASTROUS SITUATIONS Romanova H. Department of Hygiene and Disastrous situations, Medical University Prof. P. Stoyanov - Varna Reviewed by: Assoc. Prof. S. Popova, MD, PhD ABSTRACT The sociological research is carried out by the method of individual inquiry with questionnaire, included 32 questions, with students of Medical University. In connection with presentation of the discipline Medicine of the disastrous situations (catastrophe), it is followed the raise of knowledge and the readiness for protection in case of disasters. Before the beginning of the teaching about Medicine of the disastrous situations the knowledge of the students about the questions connected with damages with radioactive substances chlorine and ammonia, are totally insufficient, especially at the foreign students. The level of the preliminary knowledge about the origin of the epidemics is higher. Better are the knowledge for the right attitude in case of danger of intestinal infectious diseases than the protection of air dropped infections. The preliminary subjective evaluation of the students for the lack of readiness for protection became positive and the self-confidence increase till 88,33% foreign students and 93,33% Bulgarian students. Keywords: disaster medicine, protection in case of disastrous situations INTRODUCTION The protection against catastrophes (disasters) is leaded in different directions: preliminary measures, prognosis, observation of the elemental process and active intervention on it, rescue operations, medical activities and other /3/. The level of the preliminary preparation and knowledge are of prime importance for survival and rendering help of the sufferers /4, 5/. The training and the practical preparation of medical students about the questions concern the protection and medical help in case of disastrous situations are of extreme importance. When the students in training are convinced of the necessity for precise knowledge, the process of teaching going easier and the gained knowledge are more lasting /1, 2/. The purpose of the research is observation, the level of raise of knowledge and readiness for protection in case of disaster, of students at the beginning and after the training at the discipline Disaster medicine. opinion and 5 questions are under the form of situation task. The principle of anonymity is observed, witch make clear more objectively the thoroughness of knowledge about discussed problems and give more reliable rating for the readiness for protection. The inquired persons are 120 students between 21-29 years from third course, subject medicine. In the statistic processing of the results are used no parametric, alternative and graphical analysis. RESULTS AND DISCUSSION At Table 1 is presented the number of the participants, distributed by sex and nationality. Table 1. Table 1 Participants at the research Number MATERIAL AND METHODS The research is leaded in 09.2005 and in the end of 12.2005 at the Medical University – Varna. The sociological research is made by the method of individual inquiry with questionnaire with 32 questions. Twenty two questions are preliminary formulated and specified all possible answers. 5 questions are open and it is given a possibility for other Men Women Total 120 100% 73 60,84% 47 39,16% Bulgarian students 56 46,67% 21 17,50% 35 29,16% Foreign students 64 53,33% 52 43,34% 12 10,00% The distribution by sex is: 60,84% men and 39,16% women. 129 Romanova H. At the question “What kind of disasters do you know?” at the beginning of the training 66,67% of all give and enumerate several natural disasters and 40% know anthropological disasters too; in the end of the training 100% enumerate natural disasters and 93,33% anthropological. The majority of the inquired put at the beginning like the biggest danger of disasters in Varna region – storms and hurricanes 51,17%; in the end of the training – landslides 66,67%. The evaluation the level of danger from anthropological disasters and in the both cases, the students mark like the biggest, the danger of chemical damages – 35%. In the beginning of the training insufficient are the knowledge of the inquired refer to pollution with radioactive substances after damages in NPP (nuclear power plants), mainly in the group of foreign students. The answers of the question “Which of the following food products could be polluted in case of through out radioactive substances at the environment?” are presented at Table 2. Table 2 Which of the following food products could be polluted in case of through out radioactive substances at the environment? Sort of products Total Bulgarian students Foreigners Milk and milk products 70 58,33% 50 41,66% 20 16,67% Bread and bread products 68 56,67% 49 40,83% 19 15,83% Vegetable products 85 70,83% 55 45,83% 30 25,00% Meat and meat products 65 54,17% 48 40,00% 17 14,17% /P<0,05/ between the answers of the Bulgarian and foreign students in the end of the training. The knowledge of the inquired students about their behavior in case of damage and pollution of the air with chlorine and ammonia in the beginning of the course are insufficient. The results are presented at Fig. 1 and Fig. 2. The knowledge for right behavior in case of pollution with chlorine and ammonia in the end of the course arise in the interval of 92-100%. The level of knowledge in the beginning of the training is higher about the questions refer to arise of epidemics (Bulgarian and foreign students). According to 70,83% the biggest danger of arise of epidemics will be the use of biological weapon, according to 67,50% - the floods too. About the question “Which are the possible ways for infection with biological weapon?” – 77,50% respiratory ways, 62,50% - skin and mucous membrane, 50% - alimentary and only 29,17% - by insects suck blood. The students are good informed in the beginning of the training that cholera – 68,33%, anthrax – 75% and plague – 70% are especially dangerous infections, controlled by World Health Organization (WHO). Detailed analysis determine that the students` behavior in case of epidemic in the region, will be visibly incorrect and that will threaten their health. Completely incorrect 69,17% will leave the region in case of epidemic and that will lead to dissemination and change for the worse of the epidemic situation. 55,83% will act correctly – looking for means for prophylaxis and 37,50% - information and instructions. Better are the preliminary knowledge for the right behavior in danger of intestinal infectious diseases: 87,50% know that they have to wash regularly their hands; 74,17% will execute good thermal treatment of the food; 61,67% will boil the water and 57,50% will regularly clean and disinfect the toilets. Less are informed for protection of air-dropped infections: only 61,67% will put cotton-gauze mask; 39,00% 38,00% 37,00% 36,00% 35,00% 34,00% 33,00% 35% Put cotton-gauze mask with vinegar (wrong answer) 35,83% Put cotton-gauze mask with sodium bicarbonate (right answer) 37,5% Climbing higher floor (right answer) 38,33% Going lower floor (wrong answer) Fig. 1. In result of damage pollution of the air with chlorine at the region where you are appears. What is your behavior? In the end of the course almost all are informed what have to be made in home conditions in doubt for pollution of food products with radioactive substances: 93,33% know that the products have to be washed lavishly with water; 83,33% - have to peel the surface and 70,83% will bone the meat, salt and boil with salt and soak in acetic solution. In the research there are not visible statistic differences 130 52,50% will immunize themselves with lymph; 35% will ventilate and disinfect; 31,67% will look for a medical help and only 10% will stay at their homes. In the end of the training the knowledge of the inquired about the questions according to protection of epidemics are as follows: 90-95% for the foreign students and 95-100% for Bulgarian. Sociological research of students from Medical University – Varna to determine the level of ... 40,00% 35,00% 30,00% 25,00% 20,00% 15,00% 10,00% 5,00% 0,00% 37,17% Put cottongauze mask with vinegar (right answer) 35% Put cotton-gauze mask with sodium bicarbonate (wrong answer) 31,67% Climbing higher floor (wrong answer) 29,17% Going lower floor (right answer) Fig. 2. In case of air pollution with ammonia, what you will do? In the beginning of the course, particularly significant is the subjective evaluation of the students, about a readiness for protection in case of disastrous situations – more than 50% consider, that they are not prepared. Fig. 3 33,34% 55,83% 2. 10,83% 3. 4. 10,83% Yes 33,34% Particularly 55,83% No Fig. 3. Do you have readiness for protection in case of disastrous situations? 5. In the end of the training the self-confidence of the students increases and the subjective evaluation for protection in case of disaster is positive for 88,33% foreign and 93,33% Bulgarian students. Predominant number (87,50%) want to have at their homes, means for protection like: cotton-gauze mask, medical goods, means for cleaning and disinfection in case of rise of epidemic or other disaster. The majority of the inquired (83,33%) consider that it is necessary and obligatory, the knowledge of the population for protection in case of disaster to be raised: 12,50% - at will and only 4,17% do not consider raising of knowledge for necessary. Fig. 4 There are no visible differences at the answers of the inquired students according to their sex and age. CONCLUSION according to damages and pollution with radioactive substances, chlorine and ammonia, especially of the foreign students. The right answers increase till 90-100% in the end of the course, without visible differences according to nationality. Higher is the level of the preliminary knowledge about questions, according to rise of epidemics (all students). Better are the knowledge for right behavior in case of danger of intestinal infections disease than the protection of air-dropped infections. There are not visible differences at the answers of the inquired students according to their sex and age. The subjective evaluation for lack of readiness for protection, transforms into positive and the self-confidence arise till 88,33% foreign students and 93,33% Bulgarian students, after the training to Disaster medicine. The majority of the inquired students (83,33%) consider that it is necessary and obligatory, the knowledge of the population for protection in case of disaster to be raised. LITERATURE 1. 2. 3. 4. 5. Ãðàäåâ, Ä. Ñîöèàëíà ïñèõîëîãèÿíà ìàñîâîòî ïîâåäåíèå, èçä. „Ñâ. Êëèìåíò Îõðèäñêè”, Ñîôèÿ, 1995. Éîëîâ, Ã. Áåäñòâèÿ è ìàñîâà ïñèõèêà, Ñîôèÿ, 1989. Ìàðäèðîñÿí, Ã. Åêîêàòàñòðîôè, ÈÊ”Âàíåñà”, Ñîôèÿ, 1995. Ðîìàíîâà, Õð. Áåäñòâåíè ñèòóàöèè è ìåäèöèíñêî îñèãóðÿâàíå, Êîëîð Ïðèíò, Âàðíà, 2005. Ðîìàíîâà, Õð. Ìåäèöèíà íà áåäñòâåíèòå ñèòóàöèè, ÐÈÀ Ñïåêòðà, Âàðíà, 2007. 1. Before the training to Disaster medicine, the students` knowledge is absolutely insufficient about questions, 131 Scripta Scientifica Medica, vol. 40 (2008), pp 133-135 Copyright © Medical University, Varna STRUCTURAL AND FUNCTIONAL CHARACTERISTICS OF INSULIN RECEPTORS Ivanova F. Laboratory of Clinical Immunology, MU - Varna Reviewed by: Assoc. Prof. Sv. Balev, MD, PhD ABSTRACT The insulin receptor delivers the signal from the hormone insulin to the target cells. Structurally and functionally it belongs to the superfamily of the receptors with tyrosin kinase activity. Insulin receptor is known for more than 30 years and during this time a lot of assays for detecting it have been developed. Analyzing the expression and functional characteristics of this receptor is helpful for better understanding the pathogenesis of different diseases. INTRODUCTION The isulin is long known to the medical science. This hormone was found in 1921 by the Canadian scientists Frederick Banting and Chars Best. The first practical approach of the gene engineering was the synthesizing of human insulin. The presence of a specific insulin receptor was first proposed by Roth and coworkers in 1971(2). The mechanism of the biologic effect of this receptor is due to its tyrosin kinase activity. The ligands and receptors of the family of the Insulin/Insulin-like growth factor (IGF) take an important role in the regulation of different processes in the organism - growth, metabolism, reproduction (5). Besides the two non-allelic insulin genes another nine ones are discovered, which code insulin-like peptides. There are at least three different receptors interacting with these ligands - insulin receptor (IR), receptors for IGF-1 and IGF-2. IR belongs to the family of ligand activated receptor kinases. Other members of this family are Phospho-c-Abl, EGF Receptor, SAPK/JNK, p70 S6 Kinase e.c. Biochemical structure of the IR The IR is a transmembrane glycoprotein and a member of the superfamily of the receptors with tyrosin kinase activity. Unlike the other members it is a heterodimer of two disulphide bond monomers, each consisting of a- and b-chain. Insulin binding place of the molecule is on the a-subunit which has a molecule weight of 135kDa. In contrast the b-subunit (95kDa) has a short extracytoplasmic Address for correspondence: Feodora Ivanova, Laboratory of Clinical Immunology, University hospital "St. Marina", Varna 9010, "Hr. Smirnenski"str. 1, BULGARIA, E-mail: feodora@mail.bg part and a long intracytoplasmic tail with tyrosin kinase activity. The IR is bivalent; the affinity to the first insulin molecule bond is greater than to the second one (4). The two a-chains form a ligand binding tunnel. The amino acid sequence responsible for the insulin binding is from 240 to 250 residues - Thr-Cys-Pro-Pro-Pro-Tyr-Tyr-HisPhe-Gln-Asp (8). The insulin molecule binds to the receptor through electrostatic interactions. When the insulin molecule comes into the ligand binding tunnel, it leads to conformational changes in the receptor and the a-chains get nearer to one another and so do the b-chains. Thus the intracytoplasmic tails become close enough to phosphorilate the appropriate parts. This inner autophosphorilation of the IR activates it and makes possible the initiation of a cascade of intracellular kinases and a signal transdusing (10). IR IRS PI3K PKC Glucose uptake GLUT 4 Grb2 mTOR PKB Protein synthesis Glycogen synthesis MAPK Gene transcription Fig.1. Signal delivery pathways of the IR. IR - insulin receptor; IRS - insulin receptor substrate; PI3K phosphor-inositol-3-kinase; PKC- protein-kinase C; mTOR - mammalian target of rapamycin; PKB protein-kinase Â; Grb-2 - growth factors adaptor protein; MAPK - mitogen activated kinase. The main substrates of the phosphorilation are IRS-1, 2, 3 and 4 (insulin receptor substrate). IRSs are other tyrosin 133 Ivanova F. kinases and their substrates - PI3K, Fyn, HSP-2, take part in the further delivery of the insulin signal into the cell. It is considered that IRS-1 and 2 have major role in the glucose metabolism in the hepatocytes, IRS-1 and 3 - in the adipocytes, and IRS-2 has a crucial role in the signal delivery in the b-cells of the pancreas. PI3K phosphorilates further some serin-treonin kinases, which mediate effects like glucose assimilation, glyconeogenesis, lipogenesis, protein synthesis, cell survival (fig.1) (7). Genetics The sequence of the IR is cloned in 1985 and the structure of exones is described in 1989 by Seino et al. The gene locus is on the short arm of 19. chromosome -19ð13.1. There are two isoforms of the IR, which differ by twelve amino acid residues in the C-terminus of the a-chain, encoded by exon 11. These two forms are marked as 11+ and 11- and do not have any considerable functional differences (3). MA-20, B6), as well as for the b-chain (CT-3, 18-44) of the IR. The flowcytometry is a technique appropriate for evaluating the expression of particular cell surface molecules in the single cell suspension. Through some standardized procedures the number of IRs on each cell could be measured. The flowcytometry is useful also for detecting the tyrosin kinases and their activity, thus for functional characterization of the IR. (Tabl. 1.) Tabl. 1. Number of IRs, detected on different cells. Number of IR per cell References 200 000 Rhodes C.J., M. White. Molecular insights into insulin action and secretion. European Journal of Clinical Investigation, 32 (Suppl. 3), (2002) 3-13 Lymphocytes 2 200 Olefsky J., G.M. Reaven. Decreased insulin binding to lymphocytes from diabetic subjects. The journal of clinical investigation, vol. 54, 1974, 1323-1328 Monocytes 15 000 Olefsky J. et al. Insulin binding in diabetes. Diabetes, 26, 1977 Monocytes 700 - 22 000 Erythrocytes 20 - 350 Granulocytes 100 Platelets 570 Cells Adipocytes and Hepatocytes Physiological regulation of the expression of IR by the intracytoplasmic glucose level The IR delivers the signal from insulin for increased uptake and utilization of glucose in the cell. The high level of intracytoplasmic glucose exerts feed back inhibition on this process leading to decreasing the expression of IR and thus to diminishing the glucose uptake. Such lessening of the IRs is observed in the peripheral tissues and in the b-cell of pancreas. The high level of intracytoplasmic glucose and the low level of IRs increase the production and secretion of insulin (3). Methods for IR analysis The researching of the IR started with the radiological assays in the 70's. These methods use insulin conjugated with 125 I and not conjugated insulin. The radioactive emission of the samples is measured and insulin binding sites are calculated (6). The modern radiological methods apply monoclonal antibodies for detecting IR. There are some assays for visualizing cell surface molecules, which use colloidal gold (cAu) as a marker. These techniques imply absorption of colloidal gold on some proteins (for example insulin) and the binding of the latest to some cells is demonstrated through transmission electron microscopy (9). Polyclonal and monoclonal antibodies against the IR, IRS, and PKB are used by immunoprecipitation and Western Blot techniques for quantitative and qualitative identification of these proteins (7). The antibodies, conjugated with an appropriate dye, make it possible to detect the IRs through immunohistochemistry and immunofluorescence. The monoclonal antibodies are used for allocating the IR in different tissues in the human organism and this receptor is appointed as CD220 in the Cluster of Differentiation (VII Workshop, 2001). There are different clones of monoclonal antibodies specific for a-chain (83-7, 83-14, 47-9, MA-10, MA-5, 134 Áîðèñîâà È. Ðåöåïòîðè çà ïåïòèäíè õîðìîíè, íàó÷åí îáçîð, ÌÀ, ÖÍÈÌÇ, Ñîôèÿ 1985 Crystalographic and spectrographic methods are applied for studying the quaternary structure of the IR. In addition to these data, the three dimensional view and the atomic organization of the complex insulin - IR are characterized through scanning transmissional electronic micrography (STEM). This method determines the order, centre of gravity and the rotation of the separated domains (10). The molecular techniques are widely used for detecting of some mutation in the genes of IR and the second messengers. Implication of the expression of the IR in the pathogenesis of some diseases In the human organism the b-cells of the pancreas organize and start functioning about the 25. gestation week and after that the level of insulin increases. The defects in the development, caused by deficiency of insulin or IR, appear in the same time of age of the fetus. Pathophysiological mechanisms of diabetes mellitus type 2 are connected with defects of insulin secretion as well as peripheral insulin resistance. The insulin resistance has a crucial role and precedes the clinical manifestation with some years. It is conditioned by low levels of expression, lowered affinity and dysfunction of the IR. Massimo Bacterial structure and antimicrobial susceptibility of ... Federichi et al. show that muscle cells from patients with diabetes mellitus type 2 express significantly less IRs and have triple lower capacity for binding insulin compared to healthy people (1). Leprechaunismus represents the heaviest form of insulin resistance, caused by mutation or absence of IR. It is characterized by retardation in the time of birth and no putting on weight. Heavy postprandial hyperglycemia and fasting hypoglycemia in the presence of hyperinsulinemia is observed. It takes years before the b-cells of the pancreas decompensate (5). CONCLUSION Knowing the mechanisms of regulation of expression and function of the IR is crucial for understanding the pathogenesis of diseases like diabetes mellitus type 2, obesities, syndrome X, as well as other processes associated with metabolism and growth. REFERENCES 1. 2. Federici M., L. Zucaro, O. Porzio et al. Increased expression of insulin/insulin-like growth factor-i hybrid receptors in skeletal muscle of Noninsulin-dependent Diabetes Mellitus Subjects. Journal of Clinical Investigation, 98(12), 1996, 2887-2893. Freychet P, J. Roth, D. Neville. Insulin receptors in liver; specific binding of 125I-insulin to the plasma membrane and its relations to insulin bioactivity. Proc Natl Acad Sci USA, 68, 1971, 1833-1837. 3. Hribal M., L.Perego, S. Lovari et al. Chronic hyperglycemia impairs insulin secretion by affecting insulin receptor expression, splicing, and signalingin RIN â-cell line and human islets of Langerhans. The FASEB Journal, 2003 4. Jianping J., Guidotti G. Construction and characterization of a monomeric insulin receptor. The journal of biological chemistry, vol.57, 2002, 27809-27817. 5. Nakae J, Y. Kido, D. Accili. Distinct and overlapping functions of insulin and IGF-I receptors - Endocrine Rewiews 22(6) , 2001, 818-835. 6. Olefsky J., G.M. Reaven. Decreased insulin binding to lymphocytes from diabetic subjects. The journal of clinical investigation, vol. 54, 1974, 1323-1328. 7. Paz K., S. Boura-Halfon, L. Wyatt et al. The juxtamembrane but not the carboxyl-terminal domain of the insulin receptor mediates insulin's metabolicfunctions in primary adipocytes and cultured hepatoma cells. Journal of Molecular Endocrinology 24, 2000,419-432. 8. Rafaeloff R., R. Patel, C. Yip et al. Mutation of the high cysteine region of the human insulin receptor a-subunit increases insulin receptor binding affinity and transmembrane signaling. The journal of biological chemistry. Vol. 264, No. 27,1989, 15900-15904. 9. Warlchol J.B., R. Brelinska, D. Her bert. Analysis of colloidal gold methods for labeling proteins. Histochemistry, 76, 1982, 567-573. 10. Yip C., P. Ottensmeyer. Three-dimentional structural interactions of insulin and its receptor. The journal of biological chemistry, vol. 278(30), 2003, 27329-27332. 135 Scripta Scientifica Medica, vol. 40 (2008), pp 137-139 Copyright © Medical University, Varna DIAGNOSIS AND TREATMENT OF LIVER ABSCESSES Ivanov K., V. Ignatov, N. Kolev, A. Tonev, D. Hristov, S. Konsulova, B. Balev*, R. Madjov**. Department of General and Operative Surgery, *Department of Imaging Diagnostics, **Department of Hepato-Biliary Surgery ,University Hospital "St. Marina" - Varna, Bulgaria Reviewed by: Assoc. Prof. R. Radev, MD, PhD ABSTRACT Pyogenic abscesses are rare and difficult problem for modern surgery because of the high mortality rate. After the 70s of the last century the introduction of new image methods as ultrasound diagnostics, percutaneous and direct cholangiography and biliary drainage, guided aspiration, and percutaneous drainage of the abscess cavity dramatically changed both the diagnosis and treatment of these patients. The routine diagnostic methods are ultrasound and CT scan. Percutaneous aspiration and drainage under ultrasound or CT control is applied as first-line treatment of hepatic abscesses. Keywords: liver, abscess, CT, ultrasound, percutaneous drainage INTRODUCTION Pyogenic abscesses are rare and difficult problem for modern surgery because of the high mortality rate. In the first 3 decades of the last century the most frequent reason fot that kind of disease - the pileflebitis, caused by apendicitis, in 75-80% of cases was the main reason for death. The most frequent cause for hepatic abscesses in the later periods of last century to nowadays were the bingn and malign obstructions of biliary tree, which caused multiple abscesses with total mortality about 45-50%. After the 70's, with introducing of the methods for imaging diagnosis as ultrasonogrphy, percutaneus and endoscopic cholangiography and biliac drainage, directed aspiration and percutaneus drainage of abscesses's cavities. The diagnostics and treatment of such cases have changed dramaticly. At the same time more aggressive operative and non operative approaches for treatment of hepatobiliar and pancreatic neoplasm led to increasing the frequency of pyogenic hepatic abscesses as well as penetration of the infection to the liver on the way of hepatic arteria. AIM The aim of this study is to follow-up the epidemilogy, ethiology, bacteriology, diagnosis and treatment of hepatic abscesses in patients, treated in University Hospital "St. Marina", Varna. MATERIAL AND METHODS In University Hospital "St. Marina" for a period of 5 years /2002 to 2006/ were treated 47 patients with pyogenic hepatic abscesses, distributed in groups of age and sex as follows: Table 1 Distribution of the patients with hepatic abscesses in groups of age and sex. 2002 2003 2004 2005 2006 Total Male 5 4 6 10 2 27 Female 2 1 3 9 6 21 The median age of the males was 44.4 years, and the median age of the females was 64.7 years. RESULTS In the past years the median age of male patients with heaptic abscesses decrese.  ïîñëåäíèòå ãîäèíè ñðåäíàòà âúçðàñò íà ïàöèåíòèòå ñ ÷åðíîäðîáåí àáñöåñ íàìàëÿâà. The proportion male/female without statistical significance is with male prevalence. Ethiology In dependence of the way of infection's spread, the heaptic abscesses have an ethiological calssification in 6 grpups: · Through the biliary ducts · Through the portal vein · Direct penetration of the agent · By trauma · Through the heaptic arteria · Cryptogenic abscesses The cholangiocarcinoma is the most frequent reason for malign obstruction in the past years. [30] The usage of internal 137 Ivanov K., V. Ignatov, N. Kolev ... biliar stents in such patients has reflection. The hepatic metastases are other frequent cause for presence of pyogenic process. The hepatic arteria become a source of infection in the past years, because the inreasing of immunosuppresed patiens and the arterial embolisation. [5,14]. The percent of patients with reducted hepatic function has droped, probably because the increased frequency of the abscceses in patients with biliar stents. [14]. Diagnostics Routine methods for diagnosis are the ultrasonography and CT. The cholangiography remains important diagnostic tool for 30-40% of the patients. [14]. The CT is with highest sensibility - 93%. That method could find abscesses with 0.5-1.0 cm in size and that make this method more sensible then ultrasonography (83%). The cholangiography is indicated 2/3 of hepatic abscesses, originated from biliary ducts. Radionucleoid examinataion of the liver and Ro-graphy of abdomen are less sensitive methods and are led away from the practice for diagnosis of hepatic abscesses. Microbiologic investigation Results for the microbilogical agents could be attained by taking a puncture from the hepatic cavity, blie ducts and hemocultures. The results from the puncture and bile ducts usually are positive, while only 55-60% of the hemocultures have bacterial growth. [14]. Table 2. Distribution of microbilogical agents Puncture Hemoculture Bile Byopsy 88 82 50 Positive 97 56 84 Anaerobs 25 32 15 Resistent agents 25 10 37 Fungi 22 11 37 According to the data in the literature, the most frequent agents are E. coli, Klebsiela, Streptococcus spp., as in the past years we can observe a tendency for decreasing the infections with E. Col, and increasing the infections caused by Klebsiela, Streptococcus spp. and Pseudomonas. A reason for this is the usage of stents. The significant increasing of the fungi infections is connected with usage of wide-spectered antibiotics in patients with biliary drainage in which there are often expression of cholangitis. From the anaerobic microbs the most common isolated are Bacteroides spp., Clostridia, Streptococcus spp. [3,6,34]. The most comon agents causing hepatic abscesses in the University Hospital "St. Marina" - Varna are Ps. aeruginosa, E. coli, E. Faecalis, Seratia spp. All microbiologic agents were resistent to mass-applied beta-lactams. We have observed bacterial sensitvity to fluochinolons, aminoglucosides, and some of the bacterial 138 strains are sensitive to macrolides and the strategical antibacterial drugs - carbapanems and cephalosporines (3 and 4 generation). Treatment In approximately 35% of the patients wourldwide drainage of abscces cavity is needed. The percutaneous drainage is applied as first step in the treatment in 45% of the patients. In a small per cent carefuly selected patients percutaneous aspiration without drainage is applied. [13,14,32,33]. In the surgical clinics in University Hospital "St. Marina" Varna as a method of choice in the treatment of hepatic abscesses is the application of percutaneous aspiration and draiange plcement under ultrasonographic or CT control and eventual lavage of the abscessic cavity after the aspiration. In single cases with selected patients with small sized abscesses aspiration of the cavity content without drainage placement is adequate. After that strict control of the cavity using the US or CT methods must be applied. In all cases with hepatic abscesses we have applied paraenteral and antimicrobic treatment, which started with wide-spectered antibacterial combination and after identification of bacterial agent and his antibacterial sensitivity adequate drug therapy was prescribed. Mortality rate and the risk factors that increase it. The mortality, conneceted to hepatic abscesses decreases because of the multiple abscesses mortality drop. Increasing of mortality is observed only in through-hepatic arteria-penetrated infections. [14]. The risk factors connected with significant increase of mortality rate are [24]: · Multiple abscesses · Concomitant malignant disease · Jaundice · Hypoalbuminemia · Leucocytosis · Bacteriemia · Fungal infection · Septic chock CONCLUSION 1. The freqency of hepatic abscesses is increased mainly because of the aggressive approach in treatment of hepatobiliary and pancreatic neoplasms. 2. The application of biliary stends changes bacterial flora in hepatic abscesses and the application of wide-spectered antibiotics in these patients leads to mixed bacterial infection and fungal infection. 3. The advantage of image diagnostic methods improves the diagnoses. The development of percutaneous drainage under CT control contibutes to significant decrease of the mortality. 4. The biliary tract obstruction and particularly the obstruction of malignant processes is the mos common Diagnosis and treatment of liver abscesses 5. 6. 7. 8. 9. reason of hepatic abscesses. Biliary drainage in patients with malignant biliary tree obstruction inproves the survival rate in patients underwent palliative or radical operation. In these patients, however the hepatic abscess is more rearly appeared with pain and normal hepatic function is observed. There is an increase of the patients with hepatic metastases in which embolisation of hepatic artria is applied, also increased are the patients with heavy immunosuppresion in which hepatic abscesses was developed. [5,7,16]. The development of US and CT diagnosis contributes improvement of diagnostic approaces to many diseases. These examiantions make easier the early diagnosis of pyogenic abscesses and the application of percutaneous drainage and in that way improve the patients' prognosis. CT is diagnostic method of choice. MRI could be used for the adequate diagnosis, too. But using CT can increase the examination duration, also the high price and the lack of possibility for percutaneous drainage limitates the application of this method. [21]. The importance of anaerobic bacteria is noticed for a long time. Our data showed that there is no significant change in the frequency of hepatic abscesses caused by anaerobic bacteria during the past years. However, the apppearance of abscesses from multiresistent and mixed bacteria is comparatively new phenomenon. It is connected with comaratively high number of patients with biliary stents, recidiving cholangitis and multiple antibiotic treatments. The fungal superinfection that is noticed in patients with malignant blood diseases is in significance. [5,7,18]. The application and improvement of percutaneous biliary drainage during the past decade changes significantly the treatment of patients with hepatic abscesses. Antibacterial therapy combined with percutaneous drainage gives excellent results. [5,8,16,36,38]. The application of percutanepus drainage is most appropriate for solitary hepatic lesion. The multiple abscesses caused by biliary tree obstruction could be treated by percutaneous drainage of the biliary ducts. Percutaneous and open drainage are most commonly known as aditional each others methods and the last one is applied in cases that the first one had not given success, as well as in patients that surgical intervention is needed because of other occasion. Indications for operative treatment are the multiple abscesses and the therapy with corticosteroides in patients with ascites. The combination of percutaneous aspiration and antibacterial treatment is appropriate only in small number of cases of small solitary hepatic abscesses and precise image control. [7,11,36]. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. At tar B, Levendoglu H, Cuasay NS. CT-guided percutaneous aspiration and catheter drainage of pyogenic liver abscesses. Am J Gastroenterol. 1986; 81:550 -555. Baek SY, Lee MG, Cho KS, et al. Therapeutic percutaneous aspiration of hepatic abscesses: effectiveness in 25 patients. AJR Am J Roentgenol. 1993;160:799-802. Barakate MS, Ste phen MS, Waugh RC, et al. Pyogenic liver abscess: a review of 10 years' experience in management. Aust N Z J Surg. 1999;69:205-209. Bertel CK, van Heerden JA, Sheedy PF 2nd. Treatment of pyogenic hepatic abscesses: surgical vs percutaneous drainage. Arch Surg. 1986; 121:554 -558. Branum GD, Tyson GS, Branum MA, Meyers WC. Hepatic abscess: changes in etiology, diagnosis and management. Ann Surg 1990; 212:655-662. Chu KM, Fan ST, Lai EC, et al. Pyogenic liver abscess: an audit of experience over the past decade. Arch Surg. 1996;131:148 -152. Civardi G, Filice C, Caremani M, et al. Hepatic abscesses in immunocompromised Don o van AJ, Yellin AE, Ralls PW. Hepatic Abscess. World J Surg 1991; 15:162-169. Farges O, Leese T, Bis muth H. Pyogenic liver abscess: an improvement in prognosis. Br J Surg. 1988;75:862- 865. Gerzof SG, John son WC, Rob bins AH, et al. Intrahepatic pyogenic abscesses: treatment by percutaneous drainage. Am J Surg. 1985;149:487494. Giorgio A, Tarantino L, Mariniello N, et al. Pyogenic liver abscesses: 13 years of experience in percutaneous needle aspiration with US guidance. Radiology 1995; 195:122-124. Her bert DA, Fogel DA, Rothman J, et al. Pyogenic liver abscesses: successful non-surgical therapy. Lancet. 1982;1:134 -136. Herman P, Pugliese V, Montagnini AL, et al. Pyogenic liver abscess: the role of surgical treatment. Int Surg. 1997;82:98 -101. Huang CJ, Pitt HA, Lipsett PA, et al. Pyogenic hepatic abscess: changing trends over 42 years. Ann Surg. 1996;223:600-607. John son RD, Mueller PR, Ferrucci JT Jr, et al. Percutaneous drainage of pyogenic liver abscesses. AJR Am J Roentgenol. 1985;144:463- 467. Lambiase RE, Deyoe L, Cronan JT, et al. Percutaneous drainage of 335 consecutive abscesses: results ofprimary drainage with oneyear follow-up. Radiology 1992; 184:167-173. Lipsett PA, Huang CJ, Lillemoe KD, et al. Fungal liver abscess: etiology and management. J Gastrointest Surg. Marcus SG, Walsh TJ, Pizzo PA, Danforth DN. Hepatic abscess in cancer patients. Arch Surg 1993; 128:1358-1364. Mc Don ald MI, Corey GR, Gallis HA, et al. Single and multiple pyogenic liver abscesses: natural 139 Ivanov K., V. Ignatov, N. Kolev ... 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. history, diagnosis and treatment, with emphasis on percutaneous drainage. Medicine (Baltimore). 1984;63: 291-302. Mc Fadzean AJS, Chang KPS, Wong CC. Solitary pyogenic abscess treated by closed aspiration and antibiotics: fourteen consecutive cases with recovery. Br J Surg. 1953;41:141-152. Mendez RJ, Schiebler ML, Outwater EK, Kressel HY. Hepatic abscesses: MR imaging findings. Radiology 1994; 190:431-436. Miedema BW, Dineen P. The diagnosis and treatment of pyogenic liver abscesses. Ann Surg. 1984;200:328 -335. Miller FJ, Ahola DT, Bretzman PA, et al. Percutaneous management of hepatic abscess: a perspective by interventional radiologists. J VascInterv Radiol. 1997;8:241-247. Mischinger H, Hauser H, Rabl H, et al. Pyogenic liver abscess: studies of therapy and analysis of risk factors. World J Surg 1994; 18:852-858. Neoptolemos JP, Macpherson DS, Holm J, et al. Pyogenic liver abscess: a study of forty-four cases in two centres. Acta Chir Scand. 1982;148: 415-421. Nordbach IH, Pitt HA, Coleman J, et al. Unresectable hilar cholangiocarcinoma: percutaneous versus operative palliation. Surgery 1994; 115:597-603. Northover JM, Jones BJ, Dawson JL, et al. Difficulties in the diagnosis and management of pyogenic liver abscess. Br J Surg. 1982;69:48 -51. Ochsner A, DeBakey M, Murray S. Pyogenic abscess of the liver. Am J Surg 1938; 40:292-353. Pen ning ton L, Kaufman S, Cameron JL. Intrahepatic abscess as a complication of long-term 140 30. 31. 32. 33. 34. 35. 36. 37. 38. percutaneous internal biliary drainage. Surgery 1982; 91:642-648. Pitt HA, Nakeeb A, Abrams RA, et al. Perihilar cholangiocarcinoma: postoperative radiotherapy does not improve survival. Ann Surg 1995; 221:788-798. Pyogenic Hepatic Abscess Over 42 Years 607 Pitt HA. Liver abscess. In: Zuidema GD, ed. Surgery of the Alimentary Tract. 3rd ed. Philadelphia: WB Saunders, 1991: 152-159. Pitt HA. Surgical management of hepatic abscess. World J Surg 1990; 14:498-504. Rob ert JH, Mirescu D, Ambrosetti P, et al. Critical review of the treatment of pyogenic hepatic abscess. Surg Gynecol Obstet 1992; 174:97-102. Seeto RK, Rockey DC. Pyogenic liver abscess: changes in etiology, management, and outcome. Medicine (Baltimore). 1996;75:99 -113. Sil ver S, Weinstein AJ, Cooperman A. Changes in the pathogenesis and detection of intraphepatic abscess. Am J Surg. 1979;137:608-610. Stain SC, Yellin AE, Don o van AJ, Brien HW. Pyogenic liver abscess. Arch Surg 1991; 126:991-996. Wong E, Khardori N, Carrgsco CH, et al. Infectious complications of hepatic artery catheterization procedures in patients with cancer. Rev Infect Dis 1991; 13:583-589. Yinnon AM, Hadas-Halpern I, Shapiro M, Hershko C. The changing clinical spectrum of liver abscess: the Jerusalem experience. Postgrad Med J 1994; 70:436-439. Scripta Scientifica Medica, vol. 40 (2008), pp 141-143 Copyright © Medical University, Varna SYNCHRONOUS MALIGNANT TUMORS OF THE COLON Deenichin G., R. Dimov, V. Molov, Ch. Stefanov Department of Surgery III Medical University, Plovdiv Reviewed by: Assoc. Prof. R. Madjov, MD, PhD ABSTRACT According to literature the synchronous malignant tumors of the colon are 2-11% from all cases of sporadic nonhereditary colorectal cancer. This big difference in the frequency is due to variations in the accuracy of the used diagnostic methods, and also to the intentional search for associated lesions. The synchronous tumors have different biology and prognosis than solitary tumors. Investigations performed with the methods of genetic engineering over p53 gene abnormalities strongly suggest that the great majority of synchronous colonic adenocarcinomas arise as independent neoplasms and their worsened prognosis is not a result of unusually early metastatic spread. The aim of our one-year retrospective study was to find out the frequency of these tumors towards all patients with colorectal cancer, the time for correct diagnosis (intraoperationem or before the operation), and the peculiarities in the surgical tactics. We analyzed retrospectively 106 patients with colorectal cancer treated in the Department of Surgery III Medical University Plovdiv for one year period (01.06.2006-01.06.2007), 61 men (57.5%) with mean age 64+-2.5 years and 45 (42.5%) women with mean age 61+-3.1 year. Keywords: Synchronous malignant tumors, Colon From the whole number of 106 patients with cancer of the colon and rectum, 6 were with synchronous malignant tumors of the colon (5.66%). Four of these six cases were with cancer of the sigmoid colon and descendent colon, and two with sigmoid colon and ascendent colon localization. In three of the patients the diagnosis of multiple pathology was confirmed preoperatively, and in the other three-intraoperationem because of the impossibility to perform full colonoscopy due to the almost total obstruction of the distal tumor. The operation in the group of patients with tumors of the sigmoid and the descendent colon was left hemicolectomy, while in the other group with combined tumors of the sigmoid and ascendent colon –right hemicolectomy and resection of the sigmoid colon. All six patients operated for synchronous tumors of the colon were in stage III (Dukes C colon cancer). The frequency of the synchronous tumors of the colon is high-according to our data is 5.66% from all cancers of the colon, and because of the bettered diagnosis and the bigger absolute numbers of the tumors of the colorectal zone is with a tendency to grow. The genetic engineering proved the multicentricity of the process, and the hystoanalisis show, that the patients with colorectal cancer have an unstable epithelium and an uncommon predisposition to develop several mucosal alterations synchronously or metachronously. We emphasize the need for a full evaluation of the colon in all patients with colorectal carcinoma. In the case of incomplete preoperative evaluation, intraoperative colonoscopy is to be considered; if this is not feasible it should be performed one month after surgery. We consider the total colectomy to be indicated in specific situations, and not as an obligatory element in the process of treatment of the synchronous malignant tumors of the colon. It is necessary to think about the possibility for such kind of pathology and to seek it hard. INTRODUCTION The synchronous malignant tumors of the colon are unusual, but well known phenomenon and according to literature data are 2-11% from all cases of sporadic nonhereditary colorectal cancer (1), 1.5-7.6% (2), 1.7-9.3% (3), 5-10% (4). This big difference in the frequency is due to variations in the accuracy of the used diagnostic methods, and also the intentional search for associated lesions. The unsuccess of the correct diagnostics of the synchronous tumors results in mistakes in the treatment tactics and worsens the prognosis (5). There is an opinion, based on investigation of 160 patients with total amount of 339 synchronous tumors, according to which the patients with solitary tumors of the colon and rectum have similar development of the disease and survival rate as those with synchronous tumors (6). Much more accepted is the opinion, that the synchronous tumors have different biology and prognosis than solitary ones. Investigations performed with the methods of genetic engineering over p53 gene abnormalities using the polymerase chain reaction, followed by analysis confirm the polymorphism and strongly suggest that the great majority of synchronous colonic adenocarcinomas 141 Deenichin G., R. Dimov, V. Molov ... arise as independent neoplasma and their worsened prognosis is not a result of unusually early metastasis spread (1). For clinical purposes in practice for staging of the colorectal cancer in the abdominal surgery is used successfully the three grade scale of Dukes, including A, B and C, later modified by Astler-Coller, they include one more grade D. Nowadays is used the latest modification of the scale from 1978y., proposed from Gunderson and Sosin with subgroups B1 and B2 in stage Duke B, and C1 and C2 in stage Dukes C. Modified Duke’s scale: 1. Modified Duke A colon cancer-the tumor penetrates only the mucosal membrane of the intestinal wall. 2. Modified Duke B colon cancer: B1-the tumor penetrates in, but not through muscularis propria of the intestinal wall. B2-the tumor penetrates in and through the muscularis propria of the intestinal wall. 3. Modified Duke C colon cancer: C1-the tumor penetrates in, but not through the muscularis propria; there is evidence for tumor changes in the lymph nodes. C2-the tumor penetrates in and through the muscularis propria of the intestinal wall; there is evidence for tumor changes in the lymph nodes. 4. Modified Duke D colon cancer-the tumor is widespread far away of the lymph nodes borders to the other organs-liver, lung, bones etc. The tumor can be in any size including or not including changed lymph nodes. For diagnostic purposes there are proposed different approaches –roentgen images with contract material, fibro colonoscopy and thorough exploration during the operation. According to some big studies on the subject the investigation with barium enema give unsatisfactory results, the false negative results from fibro colonoscopy are about 30%, while the intraoperative palpation finds out nearly 60% of the unexpected synchronous tumors (7). It is considered, that the fibro colonoscopy combined with a thorough intraoperative palpation of the whole colon are crucial for the early diagnosis of the synchronous colorectal cancer (8). AIM The aim of our one-year retrospective study was to find out the frequency of these tumors towards all patients with colorectal cancer, the time and the method for confirming the correct diagnosis (intraoperationem or before the operation), and the peculiarities of the surgical tactics. (01.06.2006-01.06.2007), 61 men (57.5%) with mean age 64+-2.5 years and 45 (42.5%) women with mean age 61+-3.1 year. RESULTS AND DISCUSSION From the whole number of 106 patients operated in the Department for one-year period for colorectal cancers, 6 were with synchronous malignant tumors of the colon (5.66%). Four of these six cases were with cancer of the sigmoid colon and descendent colon, and two with sigmoid colon and ascendant colon localization. In three of the patients the diagnosis of multiple pathology was confirmed preoperatively, and in the other three-intraoperationem because of the impossibility to perform full colonoscopy due to the almost total obstruction of the distal tumor. The operation in the group of patients with tumors of the sigmoid and descendent colon was left hemicolectomy, while in the group with combined cancer of the sigmoid colon and ascendant colon–right hemicolectomy and resection of the sigmoid colon. All six patients operated for synchronous tumors of the colon were in stage III (Duke’s C colon cancer). CONCLUSIONS The frequency of the synchronous tumors of the colon is high-according to our data is 5.66% from all cancers of the colon, and because of the bettered diagnosis and the higher absolute number of tumors of the colorectal zone is with a tendency to grow. The genetic engineering proved the multicentricity of the process, and the hystoanalisis show, that the patients with colorectal cancer have an unstable epithelium and an uncommon predisposition to develop several mucosal alterations synchronously or metachronously (9). We emphasize the need for a full evaluation of the colon in all patients with colorectal cancer. In cases of incomplete preoperative evaluation, intraoperative colonoscopy is to be considered; if this not feasible it should be performed one month after surgery. We consider the total colectomy to be indicated in specific situations, and not as an obligatory element in the process of treatment of the synchronous malignant tumors of the colon. It is necessary to think about the possibility for such kind of pathology and to seek it hard. REFERENCES 1. MATERIALS AND METHODS 2. We analyzed retrospectively 106 patients with colorectal cancer treated in the Department of Surgery III Medical University Plovdiv for one year period 142 Koness RJ, King TC, Scheechter S, McLean SF, Lodowsky C and HJ Wanebo. Synchronous colon carcinomas: molecular-genetic evidence for milticentricity. Ann Surg Oncology 1066; 3(2): 136-143. Fegis G, Ramacciato G, Indinnimeo M, De Angelis R and P Barillari. Synchronous large bowel cancer: a series of 47 cases. Ital J Surg Sci 1989; 19(1):23-8. Synchronous malignant tumors of the colon 3. 4. 5. 6. Schaal JC, Mondino JC, Paris F, Piat JM and D Jaeck. Synchronous colorectal cancers. J Chir (Paris) 1991 Nov; 128(11):476-80. Pedroni M, Tamassia MG, Percesepe A, Roncucci L, Benatti P, Lanza G Jr, Gafa R et al. Human cancer. Microsatellite instability in multiple colorectal tumors. Int J Cancer 1999 Nov; 81(1):1-5. Feffer VF, Sprekelsen BJC, Di ana FCA, Perez AJ, Prado VA, Coret GMJ, Puchades GF and PR Trullenque. Multiple colon tumors. Diagnosis and follow-up of 450 patients with colorectal carcinoma. Rev Esp Enferm Dig 1997 Oct; 89(10):759-63. Passman MA, Pom mi er RF and JT Vetto. Synchronous colon primaries have the same prognosis as 7. 8. 9. solitary colon cancers. Dis Colon Rectum 1996 Mar; 39(3):329-334. Chen HS and Sheen-Chen SM. Synchronous and “early” metachronous colorectal adenocarcinoma: analysis of prognosis and current trends. Dis Colon Rectum 2000 Aug;43(8):1093-9. Tuscano D, D’Amore L, Ne gro P, Scaccia M, Talacito C, Gosseti F, Flati D and M Carboni. Double synchronous occluding tumors of the large bowel: A report of three cases. Surgery Today 1996 Nov; 26(11):926-8. Martines GEE, Pena REJP, Villanueva-Saenz E, Alvarez-Tostado FGF and M Are nas-Sanchez. Synchronous neoplasmas in colorectal cancer. Rev Gastroenterol Mex. 2000; 65(2):63-8. 143 Scripta Scientifica Medica, vol. 40 (2008), pp 145-147 Copyright © Medical University, Varna ÅMPHYSEMATOUS PYELONEPHRITIS – CLINICORENTGENOLOGIC DIAGNOSIS, REQUIRING URGENT SURGICAL TREATMENT CASE REPORT Dyakov Sv.1, A. Hinev1, M. Siderova2, H. Bohchelian2, K. Hristozov2, V. Platikanov3 1 UMHAT “St. Marina” Varna, Third Clinic of Surgery, Division of Urology, 2UMHAT “St. Marina” Varna, Clinic of Endocrinology and Metabolic Diseases, 3UMHAT “St. Marina” Varna, Clinic of Anaesthesiology and Intensive Care Reviewed by: Assoc. Prof. K. Nenov, MD, PhD ABSTRACT Emphysematous pyelonephritis is a rare and life-threatening suppurative infection of the renal parenchyma and the perirenal tissues, characterized by spontaneous gas production. Although uncommon, it occurs almost exclusively in diabetic patients (60-80% of the cases). We describe a recent case of a diabetic woman with emphysematous pyelonephritis, managed by unilateral nephrectomy. While the symptoms are usually general and nonspecific, the diagnostic approach is crucial in many cases. Ultrasonography should be the first diagnostic tool, as it is noninvasive, fast, and cost effective. However, CT scan is more specific and sensitive, and it should always be taken into consideration, as it enables the proper treatment decisions. Keywords: emphysematous pyelonephritis, diabetes mellitus, ketoacidosis, ultrasound INTRODUCTION Emphysematous pyelonephritis (EPN) is a rare, rapidly progressive, necrotizing infection, which is mainly characterized by gas production in the renal parenchyma and the perirenal tissues. It occurs almost exclusively in diabetic patients, which constitute 60-80% of the cases [2, 5]. However, 15% of the patients present without a prior history of diabetes [1, 6]. Other risk factors, associated with EPN, include: diabetic ketoacidosis, polycystic kidneys, renal failure, cirrhosis, alcoholism, and malnutrition. Mortality is within the range between 25 to 80%, and it is even higher in case of bilateral kidney involvement. We describe a recent case of a diabetic woman with emphysematous pyelonephritis, managed by unilateral nephrectomy. CASE PRESENTATION A 63-year-old female (PIR, Medical Record No 30554 / 6.11.2007) with 20-year history of diabetes mellitus and hypertonic disease was admitted to our hospital. She comAddress for correspondence: Svetoslav Dyakov. Department of Surgery, Division of Urology, Varna Medical University, 55 Marin Drinov Str., Varna 9002, Bulgaria. E-mail: sve_dyakov@yahoo.com plained of fever, chills, nausea, chest and abdominal pain for the past few days. At admission the patient was conscious but confused, febrile up to 39oC, tachydyspnoic, tachycardic, hypotonic with blood pressure 85/40mmHg. The abdomen was tympanic on percussion, with slow peristalsis, no guarding, rigidity or rebound tenderness, the left side was painful on palpation. The left flank was painful on percussion. There were some depressions of the ST-segment on ECG. Therefore, the patient was first admitted in the ICU ward. A few hours later she was transferred to the Clinic of Endocrinology, because no myocardial infarction was present and high levels of blood glucose were detected in the serum. Her laboratory results were as follows: Hemoglobin 112 g/l, WBC 19.000/mm3, 202 000 platelets/mm3, high cholesterol and triglycerides, BUN 22, Creatinine 231 mcmol/l, serum blood glucose 25 mmol/l. Blood gas analysis showed metabolic acidosis. The urine was positive for glucose and protein, and the sediment was rich in WBC. Urine and blood cultures were negative (however, they both were performed upon triple antibiotic treatment regimen). In the next 36-48 hours the patient became comatose, her general common condition gradually worsened, despite the antibiotic and insulin therapy. Consultations with neurologist and pulmologist were performed. Following the consultation of a nephrologist and the US of the abdomen, a consultation with urologist was done on day 3. Diagnostic imaging Brain CT: It was performed after a consultation with neurologist in order to identify any organic cause for the comatose state of the patient. The brain CT showed no abnormalities. 145 Dyakov Sv, A. Hinev, M. Siderova ... Ultrasound of the abdomen: It showed gas collection in the left kidney area, and in the urinary bladder. CT of the abdomen: On the whole body scan the stomach and the bowels were full of gas, and in the area of the upper pole of the left kidney a gas collection was visible /Fig. 1/. Transversal scans showed gas in the parenchyma and subcapsular gas collection in the upper-dorsal area of the left kidney /Fig. 2/. proach diagnostic procedure led us to the initial diagnosis. The final diagnosis of emphysematous pyelonephritis was made when the abdominal CT was performed. The patient was consulted by an urologist, who took a decision for immediate surgical treatment. Because of the developing septic shock, an urgent nephrectomy was performed. Intraoperative findings The left kidney was approached via transversal laparotomy, cutting the posterior peritoneal layer. The kidney and the perirenal tissues were infiltrated and inflamed. The ureter and the renal vein and artery were ligated and cut. At the time of the extraction of the kidney, the renal capsule at the upper pole (at the site of the gas collection) was torn. A sudden, loud crackle was heard and gas with unpleasant odor spread in the operation theatre. The section of the specimen revealed small amount of pus in the renal pelvis. The boundaries of the gas cavity were evident in the upper-rear subcapsular region, compressing the renal parenchyma /Fig. 3/. Fig. 1. Whole body scan, showing gas collection in the stomach and the bowels, as well as in the area of the upper pole of the left kidney (arrow). Fig. 3. Cross section of the surgical specimen. The boundaries of the gas cavity are shown by arrows. Fig. 2. Transversal CT scan, showing gas collection in the left kidney. Diagnosis The clinical signs were nonspecific, showing evidence of infection as the main cause for the uncontrolled blood glucose levels. US as a noninvasive, cheap and easy to ap146 Hystological findings Histological specimen (¹ 12506-10 / 14.11.2007) showed evidence of chronic inflammatory process with necrosis that invaded the perirenal and pararenal tissues. Postoperative period After surgery, the patient was admitted in the Clinic of Anesthesiology and Intensive Treatment. The operative wound healed primarily. The drainage tubes and the sutures were removed in the usual terms. Despite the lack of surgical problems, the stabilizing of the febrile state and the normalized levels of blood glucose, the patient remained comatose and unable to regain spontaneous breathing. Several attempts to be extubated and left to breathe spontaneously were done. However, after any such attempt, just a few hours later, she had to be intubated again, because of Åmphysematous pyelonephritis – clinicorentgenologic diagnosis ... the low saturation. Tracheotomy had to be performed, due to the long intermittent positive pressure ventilation (IPPV). Despite all these intensive cares, the respiratory distress syndrome (RDS) could not be overcome, and the patient died on the 50th day after surgery. DISCUSSION The first case of emphysematous pyelonephritis was published over 100 years ago [3]. Since then, sporadic cases of EPN were reported in the literature [1-6]. E. coli (69%), Klebsiella pneumonia (29%) and Proteus are the most commonly microorganisms isolated from the blood, or from the urine [6]. The presence of gas is attributed to rapid glucose fermentation by gas producing bacteria. Previous studies have shown that the most common gas is nitrogen, followed by oxygen, hydrogen, and carbon dioxide [1,2,4,6] Diagnosis of EPN can be made by plain X-ray, sonography, although CT scan is more specific and sensitive [4]. As our case illustrates, sonogram gave us the initial diagnosis and was the reason for a CT. Due to the prevalence of diabetic patients among those with EPN, and the high mortality rate of EPN [2,5] we recommend US of the abdomen to be performed immediately after admission. US is noninvasive, relatively cheap and easy-to-approach diagnostic tool. When EPN is suspected on US, a CT should be made to confirm the diagnosis. Unfortunately, the US in our case was made 48 hours after the patient was brought to the hospital. Radiologically, four classes of emphysematous pyelonephritis are described on computed tomography [2]. In EPN Class 1 and 2, the gas is localized in the collecting renal system and in the renal parenchyma, respectively, without extension to the extrarenal space. In EPN Class 3A, as seen in this case, there is extension of gas into the perinephric space, and in Class 3B, to the pararenal space. Bilateral EPN, or EPN of a solitary kidney, represent the most severe forms of the disease (Class 4). Emphysematous pyelonephritis is associated with a high mortality rate (40%) when treated with antibiotics alone [2]. Although milder forms of the disease (Class 1 and 2) have been successfully treated by a combination of percutaneous renal drainage and antibiotics, these modalities alone may be insufficient in more severe presentations of the disease, or in patients presenting with septic shock. In such patients, early nephrectomy is recommended as the method of choice [1,2]. The patient in our case had emphysematous pyelonephritis that clinically resembled ketoacidosis with abdominal pain. The patient was febrile and appeared toxic. Her abdomen was diffusely tender with dilated stomach and colon, tympanic on percussion and decreased bowel sounds. US was suspicious for emphysematous pyelonephritis with gas detected in the kidney and in the bladder. The CT scan proved to be essential in making the definitive diagnosis. CONCLUSION Emphysematous pyelonephritis is an uncommon, life-threatening entity, which should always be suspected in a febrile toxic diabetic patient. The combined use of immediate diagnostic US with CT or MRI, followed by prompt surgical intervention, could be lifesaving. REFERENCES 1. 2. 3. 4. 5. 6. Ab dul-Halim, H., E. Kehinde, S. Abdeen, I. Lashin, A. Al-Hunayaa, K. Al-Awadi. Severe emphysematous pyelonephritis in diabetic patients. Urol Int. 2005, 75(2), 123-128. Huang J., C. Tseng. Emphysematous pyelonephritis: clinicoradiological classification, management, prognosis, and pathogenesis.Arch Inter Med. 2000, 160(6), 797-805. Kelly, H., W. Mac Callum. Pneumaturia. JAMA. 1898, 31, 375. Kuo, Y., M. Chen, G. Liu, C. Huang, C. Huang, C. Huang. Emphysematous pyelonephritis: imaging diagnosis and follow-up. Kaohsiung J Med Sci. 1999, 15(3), 159-170. McHugh, T., S. Albanna, N. Stew art. Bilateral emphysematous pyelonephritis. Am J Emerg Med. 1998, 16(2), 166-169. Muttarak, M., W. Mai. Clinics in diagnostic imaging. Left emphysematous pyelonephritis. Singapore Med J. 2004, 45(7), 340-342. 147 Scripta Scientifica Medica, vol. 40 (2008), pp 149-152 Copyright © Medical University, Varna POST-TONSILLECTOMY HAEMORRHAGE: A RETROSPECTIVE COMPARISON OF ABSCESS - AND ELECTIVE TONSILLECTOMY Marev D. Department of Otorhinoloryngology, "Sv. Marina" University Hospital,"Prof. P. Stoyanov"- Varna University of Medicine, Bulgaria Reviewed by: Assoc. Prof. R. Radev, MD, PhD ABSTRACT Objective: There is still controversy as regards the optimal management of peritonsillar abscess. Opponents of tonsillectomy á chaud cite an increased postoperative bleeding risk. Most authors who compared the risks of postoperative haemorrhage after tonsillectomy á chaud and tonsillectomy á froid did not take into consideration criteria such as the age and gender of the patients or the experience of the surgeon. We aimed to eliminate this bias by performing a retrospective study in which a large series of abscess tonsillectomies were compared with an age- and gender-matched group of elective tonsill. Material and methods: All patients had been operated on at the Department of Otorhinoloryngology,"Sv. Marina" University Hospital, "Prof. P. Stoyanov"- Varna University of Medicine 1994 and August 2000. There were 350 patients in the abscess tonsillectomy group (61% male, 39% female; mean age 31.8 years; range 3-88 years) and 311 in the elective tonsillectomy comparison group (61% male, 39% female; mean age 30.0 years; range 2-83 years). Results: In the abscess tonsillectomy group, 9 patients (2.6%; confidence level 1.1-4.8%) had postoperative haemorrhages which required treatment under general anaesthesia, compared to 17 (5.5%; confidence level 3.2-8.6%) in the age- and gender-matched group of "selected" elective tonsillectomies. The difference between these two rates was not significant (p=0.056). The fairly high rate of haemorrhages in the elective tonsillectomy group was mainly due to the effect of the age-matching procedure, which excluded a considerable number of usually unproblematic tonsillectomies for tonsillar hyperplasia in young children. Moreover, our results show that there is a learning curve for surgeons performing tonsillectomies with regard to postoperative haemorrhages. Conclusion: There is no increased risk of postoperative haemorrhage for abscess tonsillectomies in comparison to elective tonsillectomies. Keywords: abscess,tonsillectomy,postoperative haemorrhage INTRODUCTION Peritonsillar abscess (PTA) is the commonest deep infection of the head and neck. It occurs most often in older children and young adults (1). Insufficiently treated abscesses may penetrate into the parapharyngeal space and either downwards to the mediastinum or upwards to the base of the skull (2) Sepsis, dyspnoea and other life-threatening dangers may follow. There is controversy regarding the optimal management of PTA. The two major therapeutic strategies are immediate tonsillectomy (tonsillectomy á chaud) or incision and drainage of the abscess followed by tonsillectomy á froid 6-12 weeks later (3) Contradictorily, both approaches have been associated with the highest postoperative haemorrhage rate (4) There are only a few prospective studies (5,6) comprising a small number of cases in which postoperative haemorrhage rates have been compared between the two strategies. Retrospective studies of large series of abscess tonsillectomies have used "normal" tonsillectomies (and not tonsillectomies á froid) as controls and have not taken epidemiological factors such as age, gender or smoking habits into consideration. (Young children operated on for simple tonsillary hyperplasia rarely suffer complications in our experience.) We aimed to eliminate this bias by using similar control groups. In addition we investigated surgical experience as a potential risk factor for a postoperative haemorrhage. MATERIAL AND METHODS We retrospectively compared a group of 350 abscess tonsillectomies performed in our department between March 1994 and August 2000 with a group of elective tonsillectomies performed over the same time period, matching patients for age, gender and smoking habit. Owing to the limited number of elective tonsillectomies a 1:1 match for the three variables could not strictly be performed. Despite this 149 Marev D. fact the two groups were statistically comparable concerning age, gender and smoking habits . Further variables which were not used as criteria for the matching procedure are listed below. Tumour tonsillectomies were excluded. The patients in the abscess group (61% male, 39% female) had a mean age of 31.8 years (range 3-88 years) and 55% were smokers. In the comparison group of 311 elective tonsillectomies (61% male, 39% female), the mean age was 30.0 years (range 2-83 years) and 50% were smokers. Data regarding the occurrence of postoperative haemorrhage and the experience of the surgeons (number of years of ENT training) were sought by reviewing the patients' medical records. In both groups tonsillectomy was performed using blunt dissection under general anaesthesia (GA). Haemostasis was achieved with bipolar electrocoagulation close to the tonsillar capsule. Ligature was only performed if bleeding occurred from visible arterial vessels or larger vessels. In patients regarded as having a high risk of haemorrhage, e.g. those with hepatic insufficiency, we stitched the palatopharyngeal to the palatoglossal arch, but never on the abscess side. Beside the total number of bleeding events postoperative haemorrhage like in most publications was defined as bleeding that required a return to theatre and an intervention under GA. Furthermore, we distinguished between primary (<24 h) and secondary (>24 h) bleeds. Haemorrhage rates were statistically analysed using confidence levels (CLs) or the [chi]2 test. RESULTS Incidence of postoperative haemorrhagePerforming abscess tonsillectomy did not result in an increase in postoperative haemorrhage. In fact, our data suggest that the risk of postoperative haemorrhage in this group was reduced (p=0.056) . Of the 661 tonsillectomies, there were no cases of haemorrhage that required ligature of the external carotid artery or embolization. Abscess tonsillectomy Of the 350 patients who underwent abscess tonsillectomy, 28 (8%) had documented postoperative haemorrhage: 6/28 of these patients (21%) had recurrent haemorrhage, 5/28 patients bled twice and 1 patient bled 4 times, making a total of 36 bleeding events. Of the 28 patients who experienced postoperative haemorrhage, 9 needed an intervention under GA (9/350; 2.6%). Three haemorrhages occurred on the abscess side, four on the contralateral side and in one patient haemorrhage occurred on both sides. In one case the bleeding side was not documented. Elective tonsillectomy Of the 311 patients who underwent elective tonsillectomy, 36 (11.6%) had postoperative haemorrhage: 8/36 of these patients (22%) had recurrent haemorrhage, 5 patients bled twice, 2 patients bled 3 times and 1 patient bled 4 times, 150 making a total of 49 events. GA was necessary in 19/49 cases of haemorrhage to arrest bleeding (17/311; 5.5%). Time of occurrence of the postoperative haemorrhageThe incidence of postoperative haemorrhage within the first 24 h (primary haemorrhage) was comparably rare in both groups: abscess tonsillectomy, 3/36 (8.3%; CL 1.8-22.5%); elective tonsillectomy, 5/49 (10.2%; CL 3.4-22.2%). In both groups there were significantly more secondary (>24 h) than primary haemorrhages. Abscess tonsillectomy Postoperative haemorrhages occurred between the day of operation and the 21st postoperative day, with a maximal incidence of 9 cases on the 6th postoperative day ; 18/36 haemorrhages occurred after postoperative Day 6 (50%). Thus 9 cases, or just 25% of bleedings, happened within the first five postoperative days. Elective tonsillectomy All haemorrhages took place between the day of operation and the 19th postoperative day, with a maximum of 6/48 cases on the 5th postoperative day; 23/48 bleeding events (47%) were seen between postoperative Days 5 and 9 and >60% after the 5th postoperative day. Influence of age and gender on postoperative haemorrhageThe median age of patients who developed postoperative haemorrhage was 28 years; for those who required GA it was 25 years. For patients aged <16 years only 1/92 (1.1%; CL 0.03-5.9%) had a haemorrhage that required treatment under GA . For patients aged >16 years, 25/569 (4.4%; CL 2.9-6.4%) had to be treated under GA. The binomic CLs underline a general tendency that patients aged <16 or even <20 years of age have a smaller risk of a postoperative haemorrhage. After abscess tonsillectomy, 6/214 (2.8%; CL 1.0-6.0%) male and 3/136 (2.21%; CL 0.5-6.3%) female patients had a postoperative haemorrhage, compared to 11/190 (5.8%; CL 2.9-10.1%) male and 6/121 (4.4%; CL 1.6-7.9%) female patients after elective tonsillectomy. Among all 661 operations, 17/404 (2.8%; CL 1.0-6.0%) male and 9/257 (3.5%; CL 1.6-6.5%) female patients had a haemorrhage. There were 13 smokers and 13 non-smokers among the 26 patients who experienced severe bleeding and the overall incidence of smoking in the study population was 53%.Experience of the surgeonsElective tonsillectomy was predominantly performed by trainees in their 1st year of ENT specialization (101/311 cases; 32.5%) and abscess tonsillectomy by those in their 2nd year (93/350 cases; 26.6%) .Patients who were operated on by trainees in their first and second years of ENT specialization had significantly more bleedings (4.2%; CL 1.7-8.5%) as a result of abscess tonsillectomies than those operated on by more experienced trainees (1.1%; CL 0.1-3.9%). There was no significant difference between trainees in their first and second years concerning bleedings after abscess (4.2%) and elective tonsillectomies (5.1%). Efficiency of prophylactic techniques As mentioned above, we stitched the palatopharyngeal to the palatoglossal arch if an increased risk of a postoperative Post-tonsillectomy haemorrhage: A retrospective comparison of abscess ... haemorrhage was predicted. This was done in 54/311 patients (17.4%), 9 of whom had postoperative bleeding. A total of 3/54 cases (5.6%) needed treatment for haemorrhage under GA. Predisposing factorsAbscess tonsillectomyA total of 19/350 patients (5.4%) were taking anticoagulant medication when admitted for PTA (aspirin, n=18; coumarin, n=1); 4/19 (21%) of these had postoperative haemorrhage, 2 of whom required GA. Two patients suffered from arterial hypertension , one of whom developed haemorrhage requiring GA. Elective tonsillectomyA total of Elective tonsillectomy:14/311 patients (4.5%) were taking anticoagulants, which were discontinued prior to the operation; 4/14 (29%) of them presented with haemorrhage, 1 of whom required GA. Previous medical conditions for this patient group included malignant haematological diseases (chronic lymphatic leukaemia), n=2; arterial hypertension, n=7; and hepatic insufficiency (pre-liver transplantation), n=4. None had known bleeding tendencies. Only 2 of these 13 high-risk patients bled postoperatively, 1 of whom had to be treated under GA. DISCUSSION The incidence of postoperative haemorrhage after tonsillectomy has been reported to range between 2% and 3.5% (7-12). There is still controversy regarding the rate of postoperative bleeding after abscess tonsillectomy. There have been no randomized prospective studies with large enough samples in which tonsillectomy á chaud was compared with tonsillectomy á froid with regard to the risk of a postoperative haemorrhage. In our department, the abscess tonsillectomy has been standard practice for many years and we are convinced of its benefits. We did not consider it ethical to offer stab incision and tonsillectomy á froid to our patients in order to perform a prospective study and therefore used elective tonsillectomy as a control. In several studies (13) relationships have been shown between the risk of a postoperative haemorrhage after tonsillectomy and both male gender and adulthood. The commonest indication for performing a tonsillectomy in young children is tonsillar hyperplasia, although laser tonsillotomy is becoming an increasingly accepted therapeutic alternative. In teenagers and adults, tonsillectomy is more often undertaken for recurrent or chronic tonsillitis. A history of chronic tonsillitis represents a risk factor for postoperative haemorrhage, as a result of fibrosis, scarring and neovascularization of chronically infected tonsils(14). Additionally, there may also be a relation with dietary trauma. Adults have more autonomy with regard to dietary intake, which may also explain the frequent occurrence of bleeding directly after discharge. Smoking, alcohol intake and sexual behaviour may also play a role. These epidemiological factors were ignored in previous studies in which quinsy tonsillectomy was compared with unselected elective tonsillectomy. Elective tonsillectomy is more often practised in children, whereas PTA rarely occurs in children and hence abscess tonsillectomy is rarely performed. This may explain the age distribution in other studies, such as that of Windfuhr and Chen(15), in which the average age of the abscess group was 33.4 years (median 29 years) and that of the tonsillectomy group was 24.6 years (median 21 years). In our unselected group of 350 abscess tonsillectomies, 55% of the patients were smokers, a rate far higher than that expected from the frequency of smoking in the general population. This supports the suggestion of Dilkes et al. (16)that there may be a link between smoking and quinsy. To avoid these confounding variables we matched our comparison group with our study group with regard to age, gender and smoking habits. In our control group of elective tonsillectomies, the mean age of the patients was 30 years, 61% were males and 50% smokers. Our results showed a strong statistical tendency for young adults to be the predominant postoperative bleeders; children aged <16 years rarely bled. The difference between male (4.2%) and female (3.5%) bleeders in our study group was not significant, and nor was smoking statistically correlated with postoperative haemorrhage. Other variables, e.g. arterial hypertension, also did not influence the haemorrhage rates of the two groups . Haemorrhage after tonsillectomy predominantly occurs within the first 24 h after surgery (primary) or else is delayed (secondary), with a peak occurrence after 5-10 days or even later . Primary haemorrhage is more brisk and profuse than secondary; moreover, it occurs when the patient's protective airway reflexes are blunted by post-anaesthetic or narcotic effects . Therefore, most authors consider it to be more serious than late (secondary) bleeding . In contrast to those studies in which it was concluded that the majority of secondary bleedings happened during the first postoperative days, our data, like those of other studies, show that the majority of secondary bleedings occur at the end of the first week or even later. This is the period after which the patient has usually been discharged and bleeding occurs during the healing phase, in which there is shedding of superficial eschar. The method of haemostasis used during tonsillectomy is supposed to have an influence on the timing of postoperative haemorrhage. Some authors reported ligation to be more associated with primary bleeding and cauterization to be more associated with secondary bleeding. This may explain the rather late haemorrhages observed in our study. However, there is no need for longer postoperative surveillance after an abscess tonsillectomy than after an elective tonsillectomy with regard to bleeding risks. The length of postoperative hospitalization is more likely to be dictated by the general state of the patient, who often feels very ill after abscess formation, which is characterized by odyno-/dysphagia and the need for complicated tonsillectomy. Some authors have described a relationship between postoperative haemorrhage after tonsillectomy and surgical experience. Other authors did not find a statistically significant relationship. Most of those authors did not explain the method of comparison or just compared .trainees with consultants (without subdividing the trainees according to the year of their training) All operations performed by trainees in our institution are 151 Marev D. supervised by one of our ENT specialists. Even so, our results show a learning curve for surgeons doing tonsillectomies. Surgeons in their first and second years of training did not have a higher rate of haemorrhage for abscess tonsillectomies (4.8%) than for elective tonsillectomies (5.1%), but they did have more haemorrhages than more experienced surgeons (1.1%). There are two possible explanations for this. Firstly, the inexperienced surgeon may have difficulty dissecting the tonsil out of the right layer and bleeding of the remaining tonsillar tissue may prompt him/her to perform excessive cauterization. Secondly, the surgeon may aim to reduce the operation time by performing exaggerated field cauterization. The result will be the same: excessive cauterization will increase the risk of secondary bleeding by leaving large fields of bacteria-digested necrosis. Although the majority of haemorrhages in our patients were secondary (occurring after electrocauterization), none of our patients had a severe haemorrhage that needed ligation of the external carotid artery. A special technique, such as suturing together the tonsillar pillars, seems to be indicated for high-risk elective tonsillectomy patients . Our results show that, with this method, the rate of a postoperative haemorrhage for these high-risk patients was not higher than that for all other patients. Our postoperative haemorrhage rate of 2.6% after abscess tonsillectomy is comparable with those reported after ordinary tonsillectomy and abscess tonsillectomy and supports the claim that there is no elevated risk of postoperative haemorrhage after tonsillectomy á chaud for PTA. Furthermore, our results suggest that, if a comparison group is ageand sex-matched with a typical abscess tonsillectomy group, the rate of postoperative haemorrhage after elective tonsillectomy will be even higher (5.5%) than that in other studies. This should be taken into consideration when appraising previous studies. Abscess tonsillectomy has advantages over the alternative of stab incision and elective tonsillectomy. An abscess tonsillectomy relieves the symptoms directly, additionally detects malignancies presenting as tonsillar abscess and prevents complications due to incomplete drainage as a result of incision, obscure abscesses of the contralateral tonsil (3.4% of our patients), multiple abscesses in the ipsilateral tonsil or even parapharyngeal abscess which may not be detected by needle aspiration or incision under local anaesthesia . Without tonsillectomy, abscess recurrence after incision was reported in up to 22% of cases; in particular, younger patients will have continuous symptoms such as abscess, recurrent tonsillitis or episodic pharyngitis in 50-63% of cases . Neither the duration of the operation nor the duration of hospitalization is prolonged with an abscess tonsillectomy. Tonsillectomy á chaud is an economical therapy for quinsy; at the very least it is cheaper than stab incision and a second hospitalization for tonsillectomy á froid. Only in a few types of patient, such as those using anticoagulants, those with bleeding tendencies, those with severe comorbidity limiting the use of GA and those who are pregnant, do we favour abscess incision and intravenously applied antibiotics only. However, many patients may refuse to have a tonsillectomy performed subsequently. 152 CONCLUSION Abscess tonsillectomies are not associated with an increased rate of postoperative haemorrhage in comparison to elective tonsillectomies and therefore represent the medically and economically indicated primary treatment for PTA, especially in younger patients in whom recurrence of quinsy is common. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. Lock hart R, Parker GS, Tami TA. Role of quinsy tonsillectomy in the management of peritonsillar abscess. Ann Otol Rhinol Laryngol 100: 1991; 569-71. Bonding P. Tonsillectomy á chaud. J Laryngol Otol 87: 1973; 1171-82. Herbild O, Bond ing P. Peritonsillar abscess: recurrence rate and treatment. Arch Otolaryngol 107: 1981; 540-2. Kristensen S, Tveteras K. Post-tonsillectomy haemorrhage: a retrospective study of 1150 operations. Clin Otolaryngol 9: 1984; 347-50. Chowdhury CR, Bricknell MCM. The management of quinsy-a prospective study. J Laryngol Otol 106: 1992; 986-8. Fagan JJ, Wormald PJ. Quinsy tonsillectomy or interval tonsillectomy-a prospective randomised trial. S Afr Med J 84: 1994; 689-90. Carmody D, Vamadevan T, Coo per SM. Post-tonsillectomy haemorrhage. J Laryngol Otol 96: 1982; 635-8. Myssiorek D, Alvi A. Post-tonsillectomy hemorrhage: an assessment of risk factors. Int J Pediatr Otorhinolaryngol 37: 1996; 35-43. Tami TA, Parker GS, Tay lor RE. Post-tonsillectomy bleeding: an evaluation of risk factors. Laryngoscope 97: 1987; 1307-11. Windfuhr JP, Chen YS. Immediate abscess tonsillectomy-a safe procedure?. Auris Nasus Larynx 28: 2001; 323-7. Windfuhr JP, Sesterhenn K. Blutung nach Tonsillektomie. HNO 49: 2001; 706-12. Windfuhr JP, Ulbrich T. Post-tonsillectomy hemorrhage: results of a 3-month follow-up. Ear Nose Throat J 80: 2001; 794-8. Rob erts C, Jayaramachandran S, Raine CH. A prospective study of factors which may predispose to post-operative tonsillar fossa haemorrhage. Clin Otolaryngol 17: 1992; 13-7. Moesgaard Niel sen V, Greissen O. Peritonsillar abscess. II. Cases treated with tonsillectomy á chaud. J Laryngol Otol 95: 1981; 801-7. Dilkes MG, Dilkes JE, Ghufoor K. Smoking and quinsy. Lancet 339: 1992; 1552. Klask J, Windfuhr JP, Schmelzer A. Haemostasis as a cost-factor in post-tonsillectomy haemorrhage. Gesundh oekon Qual manag 8: 2003; 238-43. Scripta Scientifica Medica, vol. 40 (2008), pp 153-156 Copyright © Medical University, Varna THE BINDER SYNDROME: REVIEW OF THE LITERATURE AND CASE REPORT Nedev P. Department of Neurosurgery, Othorhinolaryngology and Ophthalmology - Medical University Varna; Clinic of Otorhinolaringology - University Hospital "Saint Marina" -Varna Reviewed by: Assoc. Prof. D. Marev, MD, PhD ABSTRACT Binder syndrome or maxillo-nasal dysplasia (nasomaxillary hypoplasia) is an uncommon developmental anomaly affecting primarily the anterior part of the maxilla and nasal complex. A 4-year-old boy with maxillo-nasal dysplasia (Binder's syndrome), featuring maxillary hypoplasia and relative mandibular prognathism, combined with acute leucosis. We review the literature and describe how 3-dimensional CT scanning was used to evaluate the facial morphology. The principal features, diagnosis and management of the syndrome are discussed. Keywords: Binder syndrome, maxillo-nasal dysplasia, nasomaxillary hypoplasia INTRODUCTION The essential features of maxillo-nasal dysplasia were initially described by Noyes in 1939(1) although it was Binder in 1962 (2), who first defined it as a distinct clinical syndrome. He reported on three cases and recorded six specific characteristics - arhinoid face, abnormal position of nasal bones, inter-maxillary hypoplasia with associated malocclusion, reduced or absent anterior nasal spine, atrophy of nasal mucosa and absence of frontal sinus (not obligatory). Despite the frequent presence of dental malocclusion in patients with maxillo-nasal dysplasia, very little is to be found in the otorhinolaryngologic literature. Traditionally, plastic surgeons have been more closely involved with the syndrome, presenting different methods of surgical correction to solve the aesthetic and/or functional problems. also reduced sagittal development of the nose. Transversally there was no apparent facial asymmetry. The lips were competent at rest. Intra-oral examination of the dentition revealed the presence of all permanent teeth apart from the third molars (fig. 1. fig. 2. and fig. 3.). CASE REPORT A 4-year-old boy, diagnosed with acute leucosis, attended the pediatric department following referral from a ENT specialist. The mid-face profile was hypoplastic, the nose was flattened, the upper lip was convex with a broad philtrum, the nostrils were typically crescent in shape due to the short collumela, and a deep fold between the upper lip and the nose, resulting in an acute nasolabial angle. Mid-face hypoplasia was evident with an absence of fronto-nasal angle reflected in a straight profile. There was Address for correspondence: Plamen Kostov Nedev, 23, 9010 Varna, E. Georgiev str. B-10, BULGARIA e-mail: drnedev@abv.bg Fig. 1. A 4-year-old boy with maxillo-nasal dysplasia. Frontal view of the case Nasal hypoplasia with reduced naso-frontal angle was identified with suspected mild hypertelorism. The flat dorsum and short septum of the nose, enlarged nasal angle, small naso-labial angle, maxillary micrognathism, and augmented upper lip, what makes the concave midface profile are the symptoms of Binder syndrome (maxillonasal displasia). There was a mild form of hypertelorism. Radio153 Nedev P. graphic and CT exams report small anterior nasal spine, thin labial plate over incisor roots, nasomaxillary hypoplasia (absence of nasal bone and processus frontalis maxillae). No other structural abnormalities were seen. Fig. 2. Right profile view of the case Fig. 3 A three-dimensional CT image - a small anterior nasal spine, nasomaxillary hypoplasia (absence of nasal bone and processus frontalis maxillae). DISCUSSION Many researchers suggest that Binder type maxillonasal dysplasia does not represent a distinct disease entity or syndrome, but, rather, is a nonspecific abnormality of the nasomaxillary regions. In most cases, the condition appears to occur randomly for unknown reasons (sporadically); rare familial cases have also been reported. The aetiology of this condition is connected with a disturbance of the prosencephalic induction centre during embryonic growth. (3) However, it has been suggested that there is a common concurrent induction process for both the prosencephalic area and the vertebrae, accounting for the increase of vertebral anomalies associated with the condition. (4) Birth trauma has also been suggested as a possible causative factor, but is not further substantiated in the literature.(5) The possibility of a family history was put forward by Ferguson and Thompson.(6) However, Olow-Nordenram and 154 Valentin were unable to disprove the possibility of a genetic aetiology in a study of 50 patients with the condition, involving 60 families.(7) In a further study of 97 individuals with Binder's syndrome, Olow-Nordenram (8) reported a positive family history was for 36 per cent. Gorlin et al. suggest that maxillo-nasal dysplasia is a non-specific abnormality of the nasomaxillary complex. They believed that familial examples are a result of complex genetic factors, similar to those involved in producing a malocclusion.(9) Nasal bone is formed in the third month of intrauterine life, from the centers of ossification (cells migrated from the neural crest) next to the cartilage of the nasal bone. In this complicated process, exogenous, genetic, and chromosomal factors all play a part. There is evidence that vitamin K-deficiency during human pregnancy can be caused by some chemicals as lithium, ethanol or the therapeutic use of warfarin or phenytoin. The pregnancy histories of three cases of Binder's syndrome are reported (10). One was associated with warfarin exposure, one with phenytoin exposure and one with alcohol abuse. It is proposed that Binder's syndrome can be caused by prenatal exposure to agents that cause vitamin K-deficiency (10). It is generally agreed that the lack of population frequency data has affected the evaluation of aetiological findings (5). Individuals with Binder's syndrome have a characteristic appearance that is easily recognizable.The characteristic findings are a failure of development in the premaxillary area with associated deformities of the nasal skeleton and the overlying soft tissues. Affected individuals typically have an unusually flat, underdeveloped midface (midfacial hypoplasia), with an abnormally short nose and flat nasal bridge, underdeveloped upper jaw, relatively protruding lower jaw. The sense of smell is completely normal. Five per cent of affected individuals have been found to have hearing loss and 5% nonspecific congenital heart defects(22). Maxillo-nasal dysplasia can also be combined with other malformations. For example, Olow-Nordenram and Radberg reported 44.2 per cent of a study sample to have malformation of cervical vertebrae (7,8). The association with pseudo-mandibular prognathism has also been described (1,11). In the most severe cases, the syndrome is associated with true mandibular prognathism, which requires combined orthodontic and surgical treatment (7). As the literature review shows maxillo-nasal dysplasia is often combined with different morbid conditions. Maxillonasal dysplasia is considered as a predisposing factor to frequent diseases of the upper airway tract. In our patient case the Binder syndrome is accompanied with acute leucosis. As a syndrome maxillonasal dysostosis (defective ossification) is characterized by a short nose with a flat bridge, a short columella, an acute nasolabial angle, perialar flatness, a convex upper lip and a tendency to angle class III malocclusion (3). Since then there have been many reported cases of Binder syndrome, but no such diagnosis has been made antenatally. Binder syndrome, as it is seen in newborns, children or adolescents, is characterized by the naso-frontal angle being absent with the nose being hypoplastic with a small tip. The nostrils are usually half moon shaped and the The Binder syndrome: review of the literature and case report upper lip is convex with a high arched palate. Mild hypertelorism is usually present as well as malocclusion and a lower overbite. There are various anomalies of the cervical spine which may be seen, such as separate odontoid process, spina bifida occulta, short posterior arch and block verterbrae (11). Strabismus and mild mental retardation have been occasionally described (12). The frontal sinuses are often hypoplastic or absent in 40-50% of cases (13). When maxillonasal dysplasia is observed at birth it is usually not thought to be important if it presents as a single finding. Individuals may also be seen as children or adolescents by orthodontists or plastic surgeons, and their facial features are then diagnosed as Binder syndrome (14). In 1866, Langdon Down described the phenolype of patients with trisomy 21, indicating that they had "skin...deficient in elasticity, giving the appearance of being too large for the body... The face is flat and broad, and destitute of prominence…and the nose is small". With that description Down laid the foundation for two ultrasonographic markers for this chromosomopathy: the nuchal translucency and the nasal bone. In 1966, Kisling (15) performed a radiological study on 68 adults with Down's syndrome and confirmed the absence of nasal bone in nine of them (12%). Other authors supponed these findings. In 1994, Sandikcioglu (16) studied aborted fetuses with trisomy 21 and found radiological anomalies of nasal bone in 60% of those (26% absent, 34% hypoplastic). For many years, sonographers have known that the subjective impression of a "flat profile" can serve as an indicator of Down's syndrome, but only in 2001, a publication of Cicero et al. (17) revolutionized the world of the prenatal diagnosis: in 701 high-risk fetuses between 11 and 14 weeks of gestation, nasal bone was absent in three out of 603 (0.5%) normal fetuses and 43 out of 59 (73%) fetuses with trisomy 21. A study of 5525 fetuses found absent nasal bone in 70% of trisomy 21 fetuses compared with 0.5% of fetuses with normal genetic characteristics (19). In their latest assessment of the absent fetal nasal bone in a multiethnic population of 3788, Cicero et al. (20) found an absent nasal bone in 161/242 (66.9%) of trisomy 21 fetuses compared to 93/3358 (2.3%) of fetuses with normal chromosomes. The ultrasonographic examination of 7054 fetal profile Gamez 2005 (21) a nasal bone hypoplasia found in 1.8% of cases. Women aged 35 years or more in current prenatal care are considered high risk for Down syndrome pregnancy and are therefore routinely offered invasive tests (amniocentesis) in order to exclude chromosomal abnormalities. Nova days there are introduced noninvasive tests, using useful markers for fetal abnormalities, especially for chromosomal aberrations. (18) Treatment Surgical treatment can be limited only to reconstruction of the nasal dorsum and apex or additionally maxillary advancement. The management consists of nasal and maxillary correction followed by orthodontic rehabilitation. The treatment schedule in Binder syndrome depends on the progress of the symptoms in the face occlusion. Surgical treatment can be limited only to reconstruction of the nasal dorsum and apex or additionally maxillary advancement. Grafting to the osteo-chondral scafold of the nose can be carry out from 14-year-old, and osteotomy of the nose or maxilla should be planned after 18-year-old. It is important to examine prenatal the facial features as they may well give an indication of an underlying severe fetal abnormality. However, the finding of a small flattened nose with no other abnormal features, in a fetus with a normal karyotype, is likely to carry a good prognosis with the possibility of satisfactory surgical correction (23). We could conclude that the survey of the literature did not disprove the possibility of a genetic etiology, although it might not be the full explanation for the syndrome. The feature and degree of the abnormality depend on the time of exposition to harmful teratogenic factors. We recommend ultrasound screening and noninvasive genetic tests to look for congenital anomalies as well as assessment of gestational age. In conclusion, individuals with maxillonasal dysplasia shall be subjected to a treatment planning in collaboration between orthodontists and ENT surgeons. REFERENCES Noyes FB. Case report. Angle Orthod 1939; 9: 160-165 2. Binder KH. Dysostosis maxillo-nasalis, ein archinencephaler Missbildungskomplex. Deutsche Zahnarztuche Zeitschift 1962; 17: 438-44. 3. Holmstrom H. Kahnberg K. Surgical approach in severe cases of maxillonasal dysplasia (Binder's syndrome). Swedish Dental Journal 1988; 12: 3-10. 4. Olow-Norderam M, Radberg CT. Maxillonasal dysplasia (Binder syndrome) and associated malformations of the cervical spine. Acta Radiologica Diagnosis 1984; 25:353-360 5. Dyer F.,Wil lmot D. R., Maxillo-nasal dysplasia, Binder's syndrome: review of the literature and case report. Journal of Orthodontics, 2002Vol. 29, No. 1, 15-21 6. Fer gu son JW, Thomp son RPJ. Maxillonasal dysostosis (Binder syndrome) a review of the literature and case reports. Eur J Orthod 1985; 7: 145-148. 7. Olow-Nordenram M, Thilander B. The craniofacial morphology in persons with maxillonasal dysplasia (Binder syndrome). Am J Orthod Dentofac Orthop 1989; 95: 148-58. 8. Olow-Nordenram M, Valentin J. An etiologic study of maxillonasal dysplasia-Binder's syndrome. Scand J Dent Res 1987; 96: 69-74. 9. Gorlin R, Pindborg JJ, Co hen M Jr. Maxillonasal dysplasia (Binder syndrome). Syndromes of the head and neck. 1976 2nd Edition New York: McGraw-Hill 10. Howe AM; Web ster WS; Lipson AH; Halliday JL; Sheffield LJ Binder's syndrome due to prenatal vitamin K deficiency: a theory of pathogenesis. Australian dental Journal. 1992 Dec; Vol. 37 (6), 453-60. 11. Demas PN, Braun TW. Simultaneous reconstuction of maxillary and nasal deformity in a patient with Binder's syndrome (Maxillonasal dysplasia). J Oral Maxillofac Surg, 1992; 50: 83-86. 1. 155 Nedev P. 12. Win ter RM, Baraitser M. Multiple congenital anomalies. In: A Diagnostic Compendium. London: Chapman & Hall, 1991: 75 - 76 13. Horswell BB, Holmes AD, Barnett JS, Lev ant BA. Maxillonasal dysplasia (Binder's Syndrome): A critical review and case study. J Oral Maxillofac Surg 1987; 45: 114-122. 14. McCollum AG; Wolford LM ; Binder syndrome: literature review and long-term follow-up on two cases. The International Journal of Adult Orthodontics and Orthognathic Surgery. 1998; Vol. 13 (1), 45-58. 15. Kisiing E. Cranial morphology in Down's syndrome. Thesis, Munksgaard, Copenhagen; 1966. 16. Sandikcioglu M, Molsted K, Kjaer I. The prenatal development of the human nasal and vomeral bones. J Craniofac Genet Dev Biol 1994; 14: 124-34. 17. Cicero S, Curcio P, Papageorghiou A, et al. 2001. Absence of nasal bone in fetuses with trisomy 21 at 11-14 weeks of gestation: an observational study. The Lancet 358: 9294. 18. Sieroszewski P., Perenc M., Baoe-Budecka E., Suzin J. Ultrasound diagnostic schema for the 156 19. 20. 21. 22. determination of increased risk for chromosomal fetal aneuploidies in the first half of pregnancy Journal of Applied Genetics 2006, 47(2), 177-185 Zoppi MA, Ibba RM, Axiana C, Floris M, Manca F, Monni G, Absence of fetal nasal bone and aneuploidies at first-trimester nuchal translucency screening in unselected pregnancies, Prenat Diagn 2003; 23(6): 496-500 Cicero S, Longo D, Rembouskus G, Sacchini C, Nicolaides KH. Absent nasal bone at 11-14 weeks of gestation and chromosomal defects. Ultrasound Obstet Gynecol 2003; 22: 31-35. Gamez F., Ferreiro P.: Fetal nasal bone as ultrasonographic marker for trisomy 21 in a low-risk population between 18 and 22 gestational weeks. The Ultrasound Review of Obstetrics and Gynecology, September 2005; 5(3): 171-177 Cook, K., Prefumo F., Presti F., Homfray T., and Camp bell S. The prenatal diagnosis of Binder syndrome before 24 weeks of gestation: case report Ultrasound in Obstetrics and Gynecology Volume 16 Issue 6 Page 578-581. Scripta Scientifica Medica, vol. 40 (2008), pp 157-160 Copyright © Medical University, Varna OUR OWN METHOD FOR REDUCTION AND OBLITERATION OF THE CAVITY IN CASES OF FRONTOETHMOIDAL MUCOCELE Tonchev T. Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Medical University Varna Reviewed by: Assoc. Prof. D. Marev, MD, PhD ABSTRACT The frontoethmoidal mucocele engaging the orbit and neighboring structures is relatively uncommon. The presented case uses operative treatment with coronal approach in which for reduction and obliteration of the cavity and the nasofrontal canal the author uses his' own method of a flap that consists of periost and galea aponeurotica. The article describes the sequence of the treatment and the operation. The case report confirms a very good postoperative result and lack of recurrence thirty six months after surgery. The author is reviewing the contemporary literature and the clinical approach with this disease. Keywords: Orbit, Surgery, Frontoethmoidal mucocele, Coronal approach, Reduction, Obliteration INTRODUCTION When for one reason or another, the normal drainage of the secret that is produced by the mucus epithelium has been disturbed a cystic lesion with a slow expansive growth develops. It is called mucocele (2;3;6;8). The mucocele engages the frontal sinus with its anterior ethmoidal cells in 64% of the cases, the maxillary sinus in 18.6%, the sphenoidal sinus in 8.4% and independently-the ethmoidal cells in 6.7% (11). Etiological factors could be: inflammation of the paranasal cavities and the nasal mucus; allergic rhinosinuitis including nasal polyposis; trauma associated with dislocation of bone fragments and leading to obstruction of the drainage; tumor processes engaging the nasal canal or the foramen of the sinus; prior surgical treatment and of course a certain number of cases with unclear etiology (3;4;6;8). In the presence of some of these preconditions the mucus collects in the sinus cavity exercising hydraulic pressure on the surrounding tissues. As a result in the submucosal layer of the mucosa starts a process of fibroids transformation, as well as deformation and thinning of the surrounding bone structures, most often of the orbital wall (5;9;10). In the cases of prior surgery of the frontal sinus the bone lamella is removed and the formation grows towards the orbit (4). The treatment of the patients is operative. Depending on the localization, different methods are being used. The use of endoscopic methods combined with external access is predominant in the last decades. The incisions Address for correspondence: Tsvetan Tonchev, Medical University Varna, Faculty of Dental Medicine, Department of OMFS, 55 Marin Drinov st., 9002 Varna, BULGARIA E-mail: mfstonchev@mu-varna.bg; mfstonchev@mail.bg are made in visually unavailable areas, most often in the hairy part of the head. For obliteration of the sinus cavity is used fat tissue or, in the last few years, a combination of non organic filler (Medpor) and tissue glue (Tissucol) with haemostatic sheet (Surgicel) (7). For contouring and obliteration a cortical plate taken from the parietal area could be used as well as titanium grid (2; 7). PURPOSE The author presents his own method for reduction and obliteration of the cavity and the nasofrontal canal in a case of frontoethmoidal mucocele, by using a flap that consists of periost and galea aponeurotica. DESCRIPTION A 72 years old woman has been sent for treatment in the Department of Oral and Maxillofacial surgery. The patient's current complaints are swelling of the inner upper part of the left orbit, difficulty in the eye movement and diplopia. These are dating from 8-10 months back when during examination a formation in the upper medial quadrant of the left orbit has been discovered. Some 25-30 years ago the diseased underwent an operation of the frontal sinus from the same side, which was proven by the old operative cicatrices medially in the eyebrow area with a length of 3 cm. There was no available data for the size and the type of the prior operation. The patient has been treated with few courses of corticosteroid therapy in another hospital on the occasion of accepted diagnosis pseudotumor of the orbit. From about 5 years the diseased suffers from badly con- 157 Tonchev T. trolled diabetes. During the clinical examination we determine a presence of formation in the upper medial quadrant of the left orbit, pushing forward the eye bulb in lower lateral position. There are disturbances in the upper and medial eye movement and a presence of diplopia (Fig.1). Fig. 1 Fig.1 Preoperative view of the patient (bird view): Expressed deformation of the left orbit with pseudoptosis of the eyelid and exophtalmos After clinical discussion of the case we agreed to an extirpation of the formation using coronal approach. The advantages of the method are many and undeniable but in the present case the main motives were the prior operation and the spread of the formation towards the middle part of the orbit. After coronal incision we used Raney clips for haemostasis. Through supraperiostal dissection we reached level of about 3 cm. from the supraorbital edge, from where we continued to subperiostal plan (Fig.5). After reaching the supraorbital edge the cystic cavity was uncovered (Fig.6). The cyst was removed after partial evacuation of the content which formatted a cavity neighboring the orbit (Fig.7). In the lower medial part we identified the nasolacrimal canal which was curettaged. From the scalping flap we prepared periostogaleal flap for the obturation of the canal and for partial filling of the cavity formed by the mucocele (Fig.8). Aspiration drainage, type Redon was placed and the tissues were sawed layer by layer. Fig. 4 Fig. 2 Fig. 5 Fig. 3 The CT shows a presence of cystic formation, engaging the left frontal sinus, part of the anterior ethmoidal cells and the orbit in its upper medial quadrant. There is a lack of sharp division between the formation and the eye bulb. There is no bone wall between the frontal sinus and the orbit (Fig.2-3). Fig.2 Parasagittal CT reconstruction: The lesion engages the frontal sinus and the anterior ethmoidal cells; Fig.3 Axial CT: A presence of cystic formation engaging the left frontal sinus and extending to the middle of the left orbit; 158 Fig.4 Coronal approach to the two orbits. Fig.5 Uncovering of the mucocele (the instrument shows the upper edge of the defect) Fig.6 Preparation of the periostogaleal flap (arrow) used for obturation of nasolacrimal canal and partial filling of the cavity. The post operative period was covered by antibiotic treatment and dynamic correction of the data, given the accompanying diseases. The patient was discharged from hospital in good condition after twelve days. The following check through ophthalmological examination in the third month showed a full recovery of the eye movement and lack of diplopia. One year after surgery the patient had no complaints. The author reports a very good aesthetic result with correct and symmetrical position of the two eyes. Only in the medial part of the brow and frontal parasagittal area we Our Own Method for Reduction and Obliteration of the Cavity in Cases of ... find caving, due to the flap used for obturation and obliteration of the nasolacrimal canal and the frontal sinus (Fig.9). The follow-up period is 3 years, for which term no recurrence has been detected. Fig. 6 with feeding base branches from a. and v. supratrochleares and a. and v. supraorbitales. We consider a better decision, than the ones used so far, the use of a flap taken from vital tissues for filling the defect. Essential disadvantage of the method is the disturbed symmetry and deformation of the donor site which especially in young people can be a serious aesthetic issue. The coronal approach we used gives an excellent opportunity for visualization of the whole supra and inter orbital segment, the orbit itself, as well as for adequate reconstruction (7). The realization of the incision in the hairy part of the scalp is a serious aesthetic advantage along with the above mentioned. The case presented is interesting mainly for two reasons: the operative access and the relation towards the sinus cavity. Using endoscopic technique in the presence of prior operative treatment and engagement of the orbit next to the eye bulb holds some serious risks (3;4). CONCLUSION Fig. 7 Fig.7 External view of the diseased an year after surgery. A presence of correct and symmetrical position of the eyes. Vaguely expressed asymmetry in the medial part of the eyebrow and in the frontal parasagittal area, where the donor site is.) DISCUSSION Still there is no consensus about the treatment of the postoperative cavity (1;7;11). Relatively the methods can be divided into two: the ones purposing obliteration and the ones which expand the existing nasolacrimal canal for the purpose of better drainage and prevention of the retention leading to the development of mucocele. The most commonly used method is the one of obliteration with fat tissue, and the use of tissue glue and bone taken during the operation from the external lamella of the parietal bone for obturation of the canal. According to us each of the two methods has its advantages and disadvantages. Expanding the nasolacrimal canal for the purpose of better drainage can be determined as more physiological method as far as the existing anatomical structures are kept untouched. On the other hand, the presence of cavity covered with epithelium which characteristics differ from those of the normal sinus mucosa and has decreased secretory function, is a precondition for inflammation later on in time. The immediate proximity of the brain predefines the dangerous course of such inflammation. The method applied for obturation and obliteration using periostogaleal flap belongs to the first group of methods. The main advantage is the use of a flap The main purpose in the treatment of the frontoethmoidal mucocele is the radical removal of the formation with minimal functional and aesthetic consequences and lack of recurrence. There is a necessity of conducting a wide range of imaging studies preoperatively for the purpose of pr?cising the correlation to the orbit and endocranium. The author's own method is easy for execution and provides a reliable solution in the cases of small sized bone defects. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. Am ble F, et al.: Nasofrontal duct reconstruction with silicone rubber sheeting for inflammatory frontal sinus disease: analysis of 164 cases. Laryngoscope 1996; 106: 809-15. Arrue P, et al.: Mucoceles of the paranasal sinuses: uncommon location. The Journal of Laryngology and Otology; 1998, 112: 840-844. Busaba N, Salman S: Maxillary sinus mucoceles: Clinical presentation and long-term results of endoscopic surgical treatment. Laryngoscope; 1999, 109: 1446-1449. Chandra A, et al.: Frontoethmoidal mucocele associated with bilateral increased intraocular pressure and proptosis. Can J Ophthalmol. 2007; 42(1): 143-4. Chiarini L, et al.: Mucocele gigante dei seni frontali ad estensione intracranica. Graz/Austria: Eur Ass Cranio-Maxillo-Facial Surg 2000:40-4. Marks S, et al.: Mucoceles of the maxillary sinus. Otolaryngology Head and Neck Surgery; 1997, 117:18-21. Molteni G, et al.: Voluminous frontoethmoidal mucocele with epidural involvement. Surgical treatment by coronal approach. Acta Otorhinolaryngol Ital. 2003; 23(3): 185-90. Pino Rivero V, et al.: Frontoethmoidal mucocele. Diagnosis and treatment in 7 cases. An Otorrinolaringol Ibero Am. 2007; 34(4):359-65. 159 Tonchev T. 9. Perugini S, et al.: Mucoceles in the paranasal sinuses involving the orbit. Neuroradiology 1982; 23: 133-9. 10. Rashid M, et al.: Frontoethmoidal mucocele with intraorbital extension: an unusual cause of diplopia. J Coll Physicians Surg Pak. 2006 May; 16(5):371-2. 160 11. Rombaux P, et al.: Endoscopic endonasal surgery for paranasal sinus mucoceles. Acta Otorhinolaryngol Belg 2000; 54: 115-22. Scripta Scientifica Medica, vol. 40 (2008), pp 161-163 Copyright © Medical University, Varna SURGICAL TREATMENT OF TUMORS OF THE LACRIMAL GLAND BY CORONAL APPROACH Tonchev T. Medical University Varna, Faculty of Dental Medicine, Department of Oral and Maxillofacial Surgery Reviewed by: Assoc. Prof. V. Svestarov, MD, PhD ABSTRACT The purpose of this research is examination of the clinical characteristics, the preparation and the course of the operative treatment of the tumors of the lacrimal gland. The following article presents four cases where a lateral orbitotomy with coronal approach is used. A complete excision of the tumor is conducted. The postoperative observation of the diseased varies between 18 and 114 months, and includes an analysis of the results. Keywords: lacrimal gland tumors, orbital tumors, coronal approach, lateral orbitotomy BACKGROUND nosis and preparations, the operative treatment and the following postoperative period when treating these tumors. The tumors of the lacrimal gland are relatively rarely found and are mostly benign. As a whole they represent 9% from all orbital processes (1). The diseases of the lacrimal gland are divided into inflammatory and lymphoid, followed by the metastatic processes and the primary epithelial tumors (2;3). Primary epithelial lacrimal gland tumors are histologically similar to those arising in the salivary glands. The pleomorphic adenoma and adenoid cystic carcinoma are the most common benign and malignant tumors, respectively (4;5). Given the low frequency of these tumors many publications offer a description of single cases and only a few consider larger groups of patients, observed for a longer period of time (6). The purpose of this study is the examination of the clinical features, the preoperative diag- Tab. 1. Anamnestic and paraclinical data in the four cases (R - Right; L - Left; CT - computer tomography; MRI - magnetic resonance imaging) ¹ Gender Age Complaints (months) Side Investigations 1. F 51 12 L CT 2. F 51 5 R CT 3. F 72 10 R CT 4. Ì 62 8 R CT; MRI Tab. 2 Clinical data in the four cases (-/+ - anamnesis/examination; ACa - adenocarcinoma; NHL - non-Hodgkin lymphoma; PA - pleomorphic adenoma) Diplopia Anamnestic Examination Size ìì ¹ Exophtalmy Treatment Diagnosis Observation (months) Reoccurence 1. + - + 26Õ13 Extirpation ACa 114 No 2. + -/+ + 40Õ35 Extirpation NHL 56 No 3. + -/+ + 30Õ25 Extirpation PA 43 No 4. + - + 25Õ20 Extirpation PA 18 No Address for correspondence: Tsvetan Tonchev, Medical University Varna, Faculty of Dental Medicine, Department of OMFS, 55 Marin Drinov st., 9002 Varna, BULGARIA E-mail: mfstonchev@mu-varna.bg; mfstonchev@mail.bg MATERIAL AND METHODS In the period 1998-2006 in the Department of Maxillofacial surgery of Naval Hospital –Varna have been operatively treated 4 diseased with tumor of the lacrimal gland. Based 161 Tonchev T. on the hospital’s documentation the author performs an analysis of the data divided in: gender, age, the beginning of the disease, the side of the gland and the type of imaging study (tab. 1). The clinical symptoms, the size of the tumor, the operative treatment and histological diagnosis, as well as the term of postoperative observation and the discovery of reoccurrence can be found in tab.2. Exophtalmometric study has been made using the Hertel method. The given data is anamnestic. The sign (-) marks the lack of diplopia, the sign (-/+) marks cases in which diplopia occurs only on superior and lateral gaze, (+) marks the presence of diplopia. RESULTS The average age of the patients operated is 59 years, (between 51 and 72) - three women and a man. The period marking the beginning of the disease until hospitalization is between 5 and 12 months (8.75 in average). For first sign of the disease we accept the moment in which the patient realizes the presence of a problem and seeks medical help. In three of the cases the process engages the right lacrimal gland, and in one case – the left. The imaging studies include mainly CT, and in one case MRI. In all four cases we determine well limited tumor formations with benign CT characteristics, with no data for infiltration of the surrounding structures. The preoperative exam shows marked proptosis in all 4 patients. The diplopia was analyzed as anamnestic data and at the same time a clinical exam was conducted for the discovery of hidden diplopia. The anamnesis accented on the occurrence of double vision in everyday duties. The result from the clinical examination showed manifested diplopia in all 4 patients. The operative treatment in all four cases included total extirpation of the tumor. This was conducted trough lateral orbitotomy where the access was secured with a coronal approach. Tab. 2 shows the dimensions of the tumor in each case. The size of the tumor after removal varies between 8 ñm3 and 21 ñm3. The postoperative treatment includes observation by an ophthalmologist and a maxillofacial surgeon and, in the case ¹ 2 – a hematologist to determine the postoperative treatment concerning the leading disease. The surgical treatment was thorough in the other 3 cases. The postoperative observation was between 18 and 114 months (57.75 months average). During the whole period of observation no sign for reoccurrence of the disease was found in all four cases. DISCUSSION The lacrimal gland is divided by the orbital septum into two parts: palpebral which is superficial and orbital which is deeply situated. The tumors of the lacrimal gland most often originate from the deeper part, which is the reason for the late diagnostic, and to be accurate- the period when disturbances of the eyesight appear or there is a facial asym- 162 metry and aesthetics (7). Most of the tumors of the lacrimal gland are benign and from them the pleomorphic adenoma is most frequent. The ratio is the same as with the tumors of the salivary glands (2;4;8). Clinically they appear as well limited, slowly growing, painless swelling, which in the beginning leads to deformation of the upper external quadrant of the orbit and as a result leads to ptosis of the upper eyelid, exophthalmia, decreased mobility of the eyeball and diplopia. Possible impairment of vision is common. Two of the patients are diagnosed with these symptoms. The malignant transformation of the pleomorphic adenoma is possible in long term cases or when the excision of the tumor was not radical enough and there have been conducted more than one operation. Some authors recommend an operative treatment by excising the tumor after diagnosing it, excluding the biopsy (3;9). For preoperative diagnostics fine needle biopsy can be used as minimally invasive and informative method, enough to precise the surgical treatment. In the present cases this method did not give the information required, which can be explained with the lack of experience with the conduction of the technique and interpretation of the result. In cases of malignant tumors of the lacrimal gland the adenocystic carcinoma is most common, followed by the adenocarcinoma. The surgical treatment of malignant tumors with such localization is still very discussible. According to some authors there is no substantial difference in the life expectancy when the capacity of the operation is increased. In confirmation of this fact we give the case in which the tumor was removed together with the orbital part of the gland, and the result was ten years outlive and lack of reoccurrence. Almost 25% of non-Hodjkin lymphomas are with extra nodal localization from which 3% develop in the head and neck region (12). The tumor is in 5-14% with orbital localization and is the most frequent primarily malignant tumor of the orbit (13). The tumor most commonly originates from MALT (mucosa-associated lymphoid tissue) cells or from the germinal centers of the lymph nodules. In principle the orbital localization of non-Hodjkin lymphoma is distinguished by slowly growing formation in the orbital area and the periorbital tissues. Choice of treatment is chemotherapy and radiotherapy. Between 50 and 80% of the patients are in total remission (14). Typical feature of the orbital surgery when treating non-Hodjkin lymphoma is not so much the radicalism of the operative method as the aspiration for providing enough tissue for histological and immunehistochemical test for the purpose of exact typification and a following chemotherapeutic treatment (15). In the present case the tumor was a non Hodjkin lymphoma connected to the gland and with a volume of 21 ñm3. With the average size of the orbit around 30 ñm3 this represents around 2/3 of the capacity of the orbit (5). The patient was in full remission for 56 months after a course of chemotherapy. The recovery of the anatomical and functional integrity of the operated orbit was complete, with no disturbances or deficit. Surgical treatment of tumors of the Lacrimal Gland by Coronal Approach CONCLUSIONS The diagnosis and the operative treatment of the tumors of the lacrimal gland require serious knowledge of the pathology of the orbit and is subject of interdisciplinary partnership. The leading role of the ophthalmologist demands early conduction of imaging study in all cases of asymmetry in the area or deficit in the mobility of the eyeball reported by the patient or determined during examination. The interpretation of the data based on the imaging studies requires participation of specialists in orbital surgery. The decision for operative treatment should be based on a thorough analysis of the clinical and preclinical facts and should be individual. The results from the operative treatment correlate to the biology of the tumor, the level of the preoperative diagnosis, the type of the operation and the possibilities of following treatment if necessary. 6. 7. 8. 9. 10. 11. REFERENCES 12. 1. 2. 3. 4. 5. Shields J, Shields C, Scartozzi R. Survey of 1264 patients with orbital tumors and simulating lesions: Ophthalmology 2004; 111: 997–1008. Font R, Shan non LS, Bryan RG. Malignant epithelial tumors of the lacrimal glands. A clinicopathologic study of 21 cases. Arch Ophthalmol; 1998;116:613– 6. P a u l i n o A , H u v o s A G . Epithelial tumors of the lacrimal glands: a clinicopathologic study. Ann Diagn Pathol ; 1999;3:199 –204. Chuo N, Ping-Kuan K, Dryja TP. Histopathological classification of 272 primary epithelial tumors of the lacrimal gland. Chin Med J;1992;6:481–5. Rootman J, Stew ard B, Goldberg R, et al: Orbital surgery: a conceptual approach. Philadelphia, Lippincott-Raven Publisher, 1995; pp. 75; 79. 13. 14. 15. Esmaeli B, Ahmadi MA, Youssef A, et al. Outcomes in patients with adenoid cystic carcinoma of the lacrimal gland. Ophthal Plast Reconstr Surg, 2004; 20: 22– 6. Perez D, Pires F, Almeida O, Kowalski L. Epithelial lacrimal gland tumors: a clinicopathological study of 18 cases. Otolaryngol Head Neck Surg. 2006 Feb;134(2):321-5. Wright J, Rose G, Gar ner A. Primary malignant neoplasms of the lacrimal gland. Br J Ophthalmol 1992; 76: 401–7. Chandrasekhar J, Farr D, Whear N. Pleomorphic adenoma of the lacrimal gland: case report. Br J Oral Maxillofac Surg 2001; 39: 390 –3. Sturgis C, Silverman J, Kennerdell J, et al. Fine-needle aspiration for the diagnosis of primary epithelial tumors of the lacrimal gland and ocular adnexa. Diagn Cytopathol 2001; 24: 86 –9. Polito E, Leccisotti A. Epithelial malignancies of the lacrimal gland: survival rates after extensive and conservative therapy. Ann Ophthalmol 1993; 25: 422–26. Skarin A, Diagnosis in oncology. Unusual sites of malignancy. J Clin Oncol 2001; 19: 1570–1575. Hohn J, Suh C, Lee S, Yang W: Primary lymphoma of the eye. Yonsei Med J 1998; 39: 196–201. Hitch cock S, Ng AK, Fisher D, Sil ver B, Bernardo M, Dorfman D, Mauch P: Treatment outcome of mucosa-associated lymphoid tissue/marginal zone non-Hodgkin’s lymphoma. Int J Radiat Biol Phys 2002; 52: 1058–1066. Wanyura H, Uliasz M, Kaminski A, Samolczyk-Wanyura D, Smolarz- Wojnowska A. Diagnostic difficulties and treatment of non-Hodgkin lymphoma of the orbit. J Craniomaxillofac Surg. 2007 Jan; 35(1): 39-47. 163 Scripta Scientifica Medica, vol. 40 (2008), pp 165-166 Copyright © Medical University, Varna ANXIETY AND DEPRESSION DISTURBANCES IN SOME CHRONIC SKIN DISEASES Bachvarova S.1, P. Drumeva2, R. Bachvarova3, V. Chakalova3 1 Clinic of Neurology and Psychiatry, Department of Clinical Medical Sciences, Faculty of Dental Medicine, 2Clinic of Dermatovenereology and 3Department of Psychiatry and Medical Psychology, Faculty of Medicine, Medical University of Varna Reviewed by: Assoc. Prof. R. Shiskov, MD, PhD ABSTRACT A Hospital Anxiety and Depression Scale (HADS) was applied to follow-up the degree of anxiety and depression of 61 patients with skin diseases, 32 males and 29 females aged between 21 and 68 years occasionally examined in the outpatient consulting room of the Clinic of Dermatovenereology at the Medical University of Varna. The results vary within the limits of slight to moderate aberrations. They demonstrate, however, a high level of co-morbidity between anxiety and depression. In this respect, anxiety disorders occupy a leading position. Keywords: chronic skin disease, anxiety, depression, Hospital Anxiety and Depression Scale, co-morbidity INTRODUCTION Chronic skin diseases exert a considerable psychotraumatic influence on the affected patients. Numerous authors report a manifested co-morbidity with anxiety and depression. According to some publications, the percentage of affective disturbances reaches up to 25-40% (1-3). Certain skin diseases such as acne vulgaris, psoriasis, and eczema present even with suicidal ideation enhancement (1). The expression of the motional reactions is directly related to the localization and duration of skin lesions. Usually, psychotic troubles are not shared in the consulting room where, most commonly, physician’s meeting with the patient takes place as the patients are seldom admitted to hospital and most often, exacerbations are mastered under outpatient conditions only. All this calls for a more comprehensive study of the psychopathology in the outpatient dermatological practice. The purpose of the present study is to follow-up the degree of anxiety and depression of the patients with chronic skin diseases located on the visible part of the body who are within their normal society and follow their usual life rhythm. MATERIAL AND METHODS We used a cross-sectional study design. It covered a total of 61 patients, 32 males and 29 females aged between 21 and 68 years. They presented with chronic skin diseases affecting the open parts of the body. These patients had occasionally undergone medical examinations in the outpatient consulting room of the Clinic of Dermatovenereology at the Medical University of Varna. The patients with psychotic diseases, organic disorders of the central nervous system, psychoactive-drug abuse (i. e., of narcotics, alcohol, and medicines) as well as with severe somatic diseases were excluded from the study. A self-assessment Hospital Anxiety and Depression Scale (HADS) (6) was applied. It consists of 14 questions to be answered spontaneously by the patients. Every question presents with for answers scored between 0 and 3 scores. The questions with odd numbers relate to anxiety while those with even ones relate to depression. Sums for both depression and anxiety are calculated alone and give us an idea about the degree of the aberrations. The span between 0 and 7 is considered a standard one. The rest results correspond to the following characteristics: 8-10 scores - slight; 11-14 scores - median, and 15-21 scores - severe disorders. The questionnaire is filled-in under anonymous conditions in order to avoid additional psychotraumatic harmful agents and thus to obtain more objective results. Twenty healthy individuals matched according to age and social status who had visited the outpatient examination room on the occasion of issuing their medical certificates concerning jobs, arms and ammunition, and marriage in St. Marina Diagnostic and Consulting Centre of Varna served as controls. RESULTS AND DISCUSSION The mean parameters of patients’ anxiety and depression are significantly higher than those of the control individuals (p < 0,05). Concerning the pathology, there are abnormalities predominantly in the field of anxiety (in 47,54% of the cases). Their structure is the following: a slight disorder in 165 Bachvarova S., P. Drumeva, R. Bachvarova ... 62,06%, a median disorder in 24,13%, and a severe disorder - in 13,79% of the cases. Despite the great number of the affected patients it is evident that the high levels of anxiety are manifested in a small part of these patients only. The slight and median abnormalities prevail. A more detailed analysis of the results indicates, however, that the patients more often feel strained, they can not relax, they experience uneasiness when they need to travel as well as they are attacked by troubling thoughts during the “greatest part of the time” and “from time to time, however, not very often”. Panic attacks and somatic complaints are most rarely observed. Cosmetic defects on the open parts of the body cause depressive experiences in 36,06% of the patients. In the depression scale, there exist mainly slight disorders. Five patients present with median disturbances and only two female patients present with 17 or 19 scores, respectively, thus coming close to the borderline states between the median and severe disturbances. The analysis of the results demonstrates, however, that the symptoms are, usually, combined and, therefore, pure depressive or anxiety disorders seldom occur, indeed. There exists co-morbidity where anxiety disturbances occupy a leading position (in 84,31% of the cases). It is an alarming fact that independently of the presence of emotional experiences even after the filling-in the questionnaire, nobody of the respondents has shared with the treating physician some psychological problem and has asked for a advice for a consultation with a specialist at all. Poot et al. (2007) define the necessary knowledge to practice psychodermatology and suggest that the European Academy of Dermatology and Venereology together with the European Society for Dermatology and Psychiatry are able to provide the specific education for dermatologists and psychotherapists. The diagnostic criteria for psychosomatic research have been found to yield valuable integrative information, in addition to DSM-IV nosology, in a variety of medical dermatological diseases (4). 166 CONCLUSION We could draw the conclusion that the cross-sectional observation performed by us testifies to the high co-morbidity rate of the chronic skin diseases affecting the visible part of the body with affective disorders. Underestimation of psychopathology not only by the dermatologist but also by the patient can, to a certain extent, reduce the effect of the treatment of the skin disease as well as to influence, eventually, on the duration of the remission. The results from our pilot investigation allow us to continue the dynamic investigations in this field by performing more detailed analyses of the emotional disorders accompanying chronic skin diseases according to their diagnosis, patient’s gender and degree of dissemination of the skin affections as well as by looking for concrete mechanisms for the improvement of patient’s status within the outpatient dermatological practice. REFERENCES 1. 2. 3. 4. 5. 6. Gupta, M., A. Gupta. Depression and suicidal ideation in dermatology patients with acne, alopecia areata, atopic dermatitis and psoriasis.- Br. J. Dermatol., 139, 1998, 846-850. Milard, L. Dermatological practice and psychiatry.Br. J. Dermatol., 143, 2000, 920-921. Picardi, A., D. Abeni, C. Melichi, et al. Psychiatric morbidity in dermatological outpatients: an issue to be recognized.- Br. J. Dermatol., 143, 2000, 983-991. Picardi, A., P. Porecelli, P. Pasquini, et al. Integration of multiple criteria for psychosomatic assessment of dermatological patients.- Psychosomatics, 47, 2006, 122-128. Proot, F., F. Sammpogna, L. Onnis. Basic knowledge in psychodermatology.- J. Eur. Acad. Dermatol. Venereol., 21, 2007, 227-234. Zigmond, A. S., R. P. Snait. The hospital anxiety and depression scale.- Acta Psychiatr. Scand., 67, 1983, 361-370. Scripta Scientifica Medica, vol. 40 (2008), pp 167-169 Copyright © Medical University, Varna ETIOLOGY OF CHRONIC NON-ALLERGIC URTICARIA S. Racheva MedicalUniversity - Varna, Clinic of Dermatology and Venerology Reviewed by: Assoc. Prof. Zh. Georgieva, MD, PhD ABSTRACT The chronic non-allergic urticaria /CNU/ is a frequent malady; almost 25% of a given population has suffered incidents of Urticaria. Often the causes provoking it remain undiscovered and Urticaria is defined as idiopathic. Besides this form, CNU includes physical Urticaria and urticarial reactions, the secondary causes of which are other somatic disorders (chronic infections, autoimmune diseases, malign proc-esses etc.) The effective treatment of CNU is set after precise etiological clarification. The research includes 122 patients with CNU, tested and viewed as having a somatic disorder, physical outside stimuli provoking the urticaria; as allergic reactions to the usual sensibilizing factors are excluded. With 113 of the patients the etiology of the CNU was clarified: in 55.7% of them the urticaria was connected with other somatic disorders (in 69.1% - chronic infection, and in 26.4% - with autoimmune disease). In 36.8% of the tested patients various forms of physical urticaria were proved (33.3% - cholinergic urticaria, 24.4% - cold urticaria, 15.5% - delayed pressure urticaria, 11.1% - solar urticaria). In 7.3% of the cases the urticaria was diagnosed as idiopathic. The conclusions drawn predetermine the right choice of the respective therapy and prophylactics. Keywords: Chronic Urticaria, Physical Urticaria, Cholinergic Urticaria, Non-allergic Urticaria, delayed pressure urticaria, cold urticaria, solar urticaria The chronic non-allergic urticaria /CNU/ is a frequent malady; almost 25% of a given population has suffered incidents of urticarial reaction (19). It is a syn-drome of the "nerve mastoid cell". It is associated with infections, autoimmune diseases, metabolic disorders, malign processes and physical stimuli. The chronic urticaria includes various forms of physical urticaria (PU), idiopathic urticaria (IU) and secondary urticarial reactions, caused by other somatic disor-ders. The cases of urticaria with a length of over 6 weeks and with undiagnosed cause are defined as IU. IU covers 25-45% of all urticarial reactions and recent research shows its autoimmune genesis (10). PU includes the subgroups of chronic urticaria, shows frequency between 14% and 17% (23,17 ), and is provoked by physical stimuli, such as trauma, pressure, light, cold, heat, water, vibrations . CNU causes considerable therapy problems due to its various forms and to the mul-tidirectional treatment. This requires maximum efforts towards the etiological clari-fication of each concrete case and the personified and adequate treatment approach. The present research aims to clarify the etiology of the CNU of a group of patients, tested and observed in the Clinic of Skin and Venereal Diseases - Varna. MATERIAL AND METHODS pending on the clinic picture and the medical his-tory, as well as the clinic observation, the patients were tested for somatic disorder. With those with data of PU provocative tests were held with an ice cube (with expo-sure from 1 to 10 minutes) and a single and repeated pressure test. All patients were tested for allergic reactions to atopens, bacterial and food allergies, pollens in order to exclude allergic genesis of the urticaria. RESULTS AND DISCUSSION: In 113 of the tested patients, etiological clarification of CNU was achieved (table 1): in 55.7% of the cases the urticaria was connected with another somatic disorder, in 36.8% PU was proven, and in 7.3% of the patients the urticaria was diagnosed as idiopathic due to the lack of concrete data for its causes. Table 1. Etiology of the Chronic Urticaria (122 patients) Etiologic Diagnosis Number of Patients % Urticaria connected with other disorders 68 55.7 Physical Urticaria 45 36.8 Idiopathic Urticaria 9 7.3 122 100 Total The research covers 122 patients with CNU, tested and observed for a period of five years in an allergology surgery. De167 S. Racheva The data received about the frequency of CNU, associated with other diseases corre-sponds to that in literature. Montureux P. (1988) establishes chronic infections in 81% of the cases, but there are authors pointing to a lower percentage (23). The fre-quency of the PU in the research shows a percentage higher than that in literature ( 23), while that of IU - lower. The patients with CNU connected with another disease showed the following distri-bution (table 2): in 47 patients (69.11%) a connection with chronic infections (with two people - rheumatism, with 10 - intestinal parasites, with 5 toxoplasmosis, with 7 - hepatitis C virus infection, with 7 Heliobacter pylori-infection and with 16 - with other banal infections). In 18 patients (26.7%) CNU was connected with autoimmune diseases (12 - with autoimmune thyroditis, 1 - with Lupus erythema-todes, 1 - with Dermatomyoisits, 4 - with other endocrine diseases). In two patients (2.9%) the urticaria was on the background of a malign process (mediastinal tumors) and in one patient (1.4%) a hereditary angioedema was discovered. Table 2. Etiology of the Chronic Non-allergic Urticaria, connected with other diseases Etiologic Diagnosis Number of Patients % Urticaria connected with chronic infections 47 69.1 Urticaria connected with autoim-mune disorders 18 26.4 Urticaria connected with malign processes 2 2.9 Urticaria connected with genetic factors 1 1.4 Total 68 100 The variety of chronic infections, causing CNU which were established during the research correlate with those in literature: CNU, associated with hepatitis C virus infection (28,18), with rheumatism (19), with intestinal parasites (11). A number of authors point to the direct and indirect role of Helicobacter pylori infection in the development of CNU (27,30). The connection CNU - autoimmune or another endocrine disorder is discussed at length in literature (9) as the autoimmune thyroditis is named as the most frequent urticaria cause (9), as well as the tendency of an increase of these cases (13). The urticaria is assumed to be an autoimmune disorder (12), proven in over 25% of the cases (11). Many authors find in 45-50% of the CNU a skin autoimmune disorder (14). The CNU is rarely connected with a malign process; the risk of such a connec-tion is 3% (26). The physical forms of the CNU in the research showed the following distribution (Table 3): U. cholinergica was found in 15 patients (33.3%), U. a'frigore - in 11 pa-tients (24.4%), U a'pressionem I in 7 patients (15.5 %), symptom- 168 atic dermo-graphism - in 7 patients (15.5%) and U. solar in 5 patients (11.1%). Table 3. Etiology of the Physical Forms of Chronic Non-Allergic Urticaria (45 patients) Etiological Diagnosis Number of Patients % U. cholinergica 15 33.3 U. a'frigore 11 24.4 U a'pressionem 7 15.5 Symptomatic dermographism 7 15.5 U. Solar 5 11.1 Total 45 100 The Cholinergic Urticaria according to literature data varies from 4% (8) to 56% (17) among all forms of chronic urticaria. A number of authors find it more often in the atopens (15) than in the general population. The agents provoking it could be various: stress (15), perspiration (15), physical exertion (31), taste stimuli (29), haemodialysis (2). Urticaria a'pressionem is described as a form of PU, with frequency of 5% (8) among adults and 24% among children, more often met in the atopens, mediated by histamine, appearing quickly after pressure and with wheals duration of 30 minutes. Another form of Urticaria a'pressionem is the urticaria caused by pressure - delayed type when pressure on the skin makes the mastocytes join the process, but with an unknown mediator (7,3) and probably a cellular-based reaction (3). This type of ur-ticaria appears 4 hours after the appliance of the physical stimulus and lasts up to 3 days. The data received from the research of Urticaria a'pressionem (15.5%) in-cludes both types of pressure urticaria reactions. It has to be taken into account that the delayed type pressure urticaria very often combines with other forms of chronic urticaria; with IU (10), with cold 2% and with cholinegic - 11% (1), as well as with delayed dermographism (1,5). The cold urticaria is described as inherited (16) or acquired (24). It can be associated with cryogobulinemia (20), associated with vasculitis (6) or virus infections (4). The solar urticaria is among 4% to 5.3% of the cases of the photodermatoses (25), more often associated with atopy. It is viewed as an IgE mediated reaction, caused by photo allergens with various length of the waves (21) or by nonspecific photo allergens as photo protection or anti-microbic means, fragrances, medicaments as promethazin, chlorpromazine. CONCLUSIONS With the etiology of the CNU considerable importance have the chronic infections, autoimmune diseases and different physical stimuli (cold, pressure, physical exer-cises, sun light). The detail clarification of the causes of the urti- Etiology of Chronic Non-allergic Urticaria caria in every single case determines the suitable and adequate methods and possible therapy. 15. BIBLIOGRAPHY 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Barlow, R J, K. Wat son, A.K. Black,M.W. Greaves, Diagnosis and incidence of delayed pressure urticaria in patients with chronic urticaria, J. Am. Acad .Dermatol, 199, 29 (6), 954- 8. Confino-Co hen, R, A. Goldberg, E. Magen, Y.A. Mekori, Haemodialisis-induced rash: a unique case of chronic urticaria, J Allergy Clin Immunol, 1995, 95(6), 1002 - 4. Czarnetzki, BM, J. Meetken, G. Kolde, E.B. Brocker, Morpholgy of the cellular infiltrate in delayed pressure urticaria, J Am Dermatol,1985,12(2), 253 - 9. Doeglas, HMG., W.J.Rijnten, F.P. Schroder, J. Schirm, Cold urticaria and virus infections: A clinical and serological study in 39 patients, Br J Dermatol,1986,114,3,311-318. Do ver, JS, A.K. Bleck, A.M. Word, M.W. Greaves, Delayed pressure urticaria. Clinical features, laboratory investigations, and response to therapy of 44 patients, J Am Acad Dermatol, 1989,21(3), 588-9. Eady, RAJ, T.M. Keahey, R. Sibbald, A. Kobza Black, Clin Exp Darmatol, 1981, 6, 4, 355-366. Esten ,SA, C.W.Yung, Delayed pressure urticaria: an investigation of some parameters of lesion induction, J Am Acad Dermatol, 1981, 5(1), 25-31. Giam, YC,V.S. Rajan, An approach to urticaria, Ann Acad Med Singapore, 1983, 12(1), 74-80. Giminez-Arnau, A, R.M. Pojol-Vallverde, J.G. Camarasa, 10-th Congress of European Academy of Dermatology & Venerology, Munich, 10-14 October 2001. Grattan, CE, D.M. Fran cis, N.G. Slat er, R.J. Barlow, M.W.Greaves, Plasmapheresis for severe, unremitting, chronic urticaria, Lancet, 1992, 2, 339, 8001, 1078-80. Greaves, M, Chronic urticaria, J Allergy Clin Immunol, 2000, 105(4), 664-72. Ferrer, M,J.P. Kinet,A.P. Kaplan, Comparative studies of functional and binding assays of IgE anti-Fc (epsilon RIalpha(alpha-subunit) in chronic urticaria, J Allergy Clin Immunol,1998, 101(5), 672-6. Heymann,WR, Chronic urticaria and angioedema associated with thyrid autoimmunity: review and therapeutic implications, J Am Acad Dermatol, 199, 40(2pt1), 229-32. Hide ,M, D.M. Fran cis, C.E.Grattan, J. Hakimi, J.P. Kochan, M.W. Greaves, Autoantibodies against the hige-affinity IgE receptor as a cause of histamine release in chronic urticaria, 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. New England Jornal of Medicine, 1993, 328 (22), 1599-604. Hirschmann, JV, F. Lawlor, J.S. Englich, J.B. Louback, R. K. Winkelmann, M. W. Greaves, Cholinergic urticaria. A clinical and histologic study, Arch Dermatol, 1987, 123(4), 462-7. Hoffman , HM, A.A. Wan derer, D.H. Broide, Familial cold autoinflamatory syndrome: phenotype and genotype of an autosomal dominant periodic fever, J Allergy Clin Immunol, 2001, 108 (4), 615-20. Humphreys, F, J.A. Hunter, The characteristics of urticaria in 390 patients, Br J Dermatol, 1998, 138(4), 635-8. Krengel, S, B. Tebbe , S. Goerdt, M. Stoffler-Meilick, C.E. Orfanos, Hepatitis C virus- associated dermatoses: a review, Hautarzt, 1999, 50(9), 629-36. Kulp-Shorten , CL, J.P.Callen, Urticaria, angioedema, and rheumatologic diseases, Rheum Dis Clin North Am, 1996, 22 (1), 95-115. Mittelbach, F, Kalturticaria and Purpura bey Kryoglobulinamie, Z Hautkrankh, 1987, 62,6,48, 496. Miyauchi, H, T. Horio, Detection of action, inhibition and augmentation spectra in solar urticaria, Dermatology, 1995, 191(4), 286-61. Montureux, P, Acute urticaria in infancy and early childhood: a prospective study, Arch Dermatol, 1988, 134(3), 319-23. Nettis, E, A. Pannofino, C. D'Aprile, A. Ferrannini, A. Tursi, Clinical and aetiological aspects in Urticaria and angio-oedema, Br J Dermatol, 2003, 148(3), 501-8. Pazzaque Ahmed, A, R. Moy, Acquirid cold urticaria, Int J Dermatol, 1981, 20, 9, 582-584. Roe lands, R, Diagnosis and treatment of solar urticaria, Dermatol Ther, 2003, 16 (1), 52- 6. Sigurgeirsson, B, Skin disease and malignancy. An epidemiological study, Acta Derm Venereol Suppl, 1992, 178, 1-110. Tebbe, B, C. C. Geilen, J. D. Schulzke, C. Bojarski, Helicobacter Pylori infection and chronic urticaria, J Am Acad Dermatol, 1996, 34(4), 685-6. Toossi , P, M. Rahmati, The relationship between urticaria and hepatits-C, 10-th Congress of European Academy of Dermatology& Venerology, Munich, 10-14 October 2001. Tupker, R.A, H.M. Doeglas, Water vapour loss threshold and induction of cholinergic urticaria, Dermatolgica, 1990, 181(1), 23-5. Valsecchi, R, P. Pigatto, Chronic urticaria and Helicobacter pylori, Acta Derm Venereol, 1998, 78(6), 440-2. Volcheck ,GW, J. T. Li, Axercise- induced urticaria and anaphylaxis, Mayo Clin Proc, 1997, 72 (2), 140-7. 169 Scripta Scientifica Medica, vol. 40 (2008), pp 171-174 Copyright © Medical University, Varna SUDDEN INFANT DEATH SYNDROME - THE CAUSE OF DEATH Burulianova I., V. Konstantinova*, V. Dokov* Department of Forensic Medicine, Department of General and Clinical Pathology, Varna Medical University Reviewed by: Assoc. Prof. D. Radoinova, MD, PhD ABSTRACT Studies on the potential role of agents in SIDS have been published over the years in a variety of journals and involved specific micro-organisms, sleeping position, dysfunction of the central nervous system, damaged arousal reflex cigarette smoking, lower socioeconomic way of life, specific age. Although, there aren't criteria to established specific risk factors. SIDS still remains unexplained in spite of thorough case investigation, including complete autopsy, examination of the death scene and review of the clinical history. Our humble contribution to this problem included 12 sudden death cases in babies from 20 days to 1 year. We may place our cases in the group of unexpected explained death, because the main cause of death in most babies is pneumonia. The histological changes in lungs were microhaemorrhages in alveoles and interstitium, congestion, oedema, pulmonary emphysema, atelectases, haemosiderin-laden macrophages, bronchitis and catharral-desquamating pneumonia or catharralhaemorragic pneumonia, but in two cases there were a purulent pneumonia. In conclusion most authors consider no laboratory or pathological tests to establish a diagnosis of SIDS and no lesions are found at autopsy in most cases. Hovewer, as recent reports pointåd out, the affected infant would not be perfectly well before death. Most authors pointed the histopathological changes in lungs that we established and pointed above. INTRODUCTION Studies on the role of agents in SIDS have been published in a variety of journals. The articles in this issue examine evidence for the involvement of specific micro-organisms, sleeping position, dysfunction of the central nervous system, histopathological changes in lungs, heart, damaged arousal reflex, cigarette smoking, lower socioeconomic way of life, specific age. Although, there aren't criteria to established specific risk factors and morphological characteristics. SIDS still remains unexplained in spite of thorough case investigation, including complete autopsy, examination of the death scene and review of the clinical history. Definition and risk factors Sudden infant death syndrome /SIDS/ is a postmortem medical diagnosis which stands on a "negative autopsy". The relative large concentration of deaths in the perinatal period and infancy and the need to provide explanation for parents might suggest that clinicians frequently turn to pathologists for information of postmortem examination (5). Address for correspondence: Irina Burulianova, Department of Forensic Medicine, Medical University Prof. Dr. Paraskev Stoyanov, 55 Marin Drinov St, BG-9002 Varna, BULGARIA e-mail: burulianova@abv.bg Sudden death in babies was first reported in London - 1913 year, but the term SIDS was defined iin 1969 at the Second International Conference as "the sudden death of any infant or young child, which is unexplained by history, and the thorough post-mortem examination fails to demonstrate an adequate cause of death"(3). After 1992 year SIDS is on the second or third place among leading death causes in babies between one month and one year. The peak is between 2 and 4 months. There is a seasonal distribution (in January). Prof. Zekov's investigation revealed that the most babies died after midnight, particularly in the motning about 4-5 a.m.(1). The upper age limit was defined one year (23). There are more than 120 different theories on the possible causes of SIDS. Bed sharing is a very interesting issue. US study established 64 death cases in babies between a month and 2 years when they sleep with their mother and father. Some researchers think that there is any survival advantage to a baby sleeping with his/her mother. There is an incredible amount of interactions between two - more arousals (waking up during the night) of both mother and baby when they sleep together. Arousal may be an important mechanism to rescue babies from potentially dangerous situations during sleep. Dr Fleming believes that it is usually the baby who wakes the mother not back to front. However, there are not scientific studies to confirm bed sharing. Some investigations revealed damaged arousal reflex and the babies wasn't 171 Burulianova I., V. Konstantinova, V. Dokov able to wake up when arose the problems in breathing, heart rate, blood pressure and tempereture. Matturi L. at al revealed changes of the neuronal population of medullary arcuate nucleus in SIDS victims.(16). Severe hypoplasia were established in 30% of the babies morphometrically in this nucleus. Concerning interleukins, IL-I may cause sudden infant death by depressing brainstem neurons important for the control of ventilation. In a Norwegian study, cerebrospinal fluid levels of IL-6 were higher in infants dying of SIDS than in infants dying violently, but lower than in infants dying of infectious diseases. Disfunction of the central nervous system, cardiorespiratory insufficiency due to infections including atypical immune reactions, and cardiac dysregulation have been discussed during the previous decade. Some authors investigated 387 SIDS cases and established disturbances of the heart after inflammatory diseases of the respiratory tract (70 cases out of 387) (2). Concerning conduction system, Matturri et al. carried out a systematic investigation of this system in 69 SIDS cases and found no significant differences except for the presence of resorptive degeneration (in 97% of SIDS cases compared to 75% of the controls) (17). Dettmayer's study revealed enteroviruses in 22,5%, adenoviruses in 3,2%, Epstein-Barr viruses in 4,8% and parvovirus B19 in 11,2% SIDS cases (all SIDS cases were 62). Control group samples were completely virus negative. Applying a comprehensive combination of molecular and immunohistochemical techniques, their results demonstrate a clearly higher prevalence of viral myocardial affections in SIDS (9). There are many articles which have reported about relationship between SIDS and sleeping position. The recent drastic decrease in the number of SIDS cases has been associated with infant sleeping supine instead of prone (15).The prone position are related with increased risk of SIDS (10,11,13). In public health review from Sweden epidemilogical research has shown that prone sleeping is major risk factor for sudden infant death syndrome (12). Since 1992 the American Academy of Pediatrics has recommended that infant has to be placed on his back in order to reduce the risk of sudden infant death syndrome. Since then , the frequency of prone sleeping has decreased from about 70% to approximately 20% of US infants and SIDS-rate - by more than 40%. The reason of death is unknown, but the mechanism is similar like suffocation in soft materials(cot death). There are several potentially risk factors - maternal smoking, low socioeconomic position, more black babies and male sex, the importance of soft bedding and covered airways. Some researchers from New Zealand also found in their epidemiological studies that bed sharing and cigarette smoking is associated with a marked increased risk for SIDS. Cigarette smoking induces nitric oxide production and retards hypothalamic development by augmented apoptosis. Fetal haemoglobin induces hypoxia wich is a stimulator of the immune response, while vasodilatator gases (CO and NO) reduce hypothalamic function. Hypothalamic failure elevates blood pirogens, induces toxic shock - a feature of SIDS (19). 172 Infection is not a new idea, but in 2002 (Emma Ross in the European congress of Clinical microbiology and infectious diseases in Milan) is the first time that E.coli was found in the blood of all SIDS babies. There were significant correlation between endotoxin levels in blood and the various organs particularly in SIDS cases and child controls and blood endotoxin levels in SIDS cases were higher in those infants where there was histological evidence of mild to moderate inflammation (6). If bacterial toxins are involved in precipitating SIDS, the possibility of passive immunisation or earlier immunisation of infants with low levels of antibodies to the toxins might reduce further the numbers of these deaths (4). There is a considerable evidence suggesting that respiratory viral infection is involved in the genesis of the sudden infant death syndrome with rates of about 20 % of SIDS victims compared to about 13 % of controls. Most of the viruses were obtained from children between 3 weeks and 4 months of age (21). Neonatal immaturity of both the acute febrile response and hypothalamus promote neonatal protection from SIDS. Reid (18) poited out that SIDS are associated with serious pathological changes - elevated hepatic iron, bone marrow hyperplasia, hypomyelinated respiratory control centres, elevated lung immunoglobulins, cerebral hypoperfusion resemling lesions induces by chronic hypoxaemia, ischemia, congenital heart disease and congenital myopathy. Nitric oxide and adenosine are additive as dilators of coronary blood vessels. Blood pressure collapses. NO binds to cytochrome oxidase inhibiting respiration. When NO reaches dangerous levels, the cell turns on production of heme oxygenase. Heme is broken down to iron, carbon monoxide and bile pigments. NO has a huge affinity for hemoglobin which catalyses NO degradation to nitrate. Futhermore, NO is a product of smoke and SIDS incidence is higher in smoking mothers. The mixture of exhaled air and the fresh air during sleep (state with carbon dioxide contamination) can be associated with hypoxia and apnoea and this apnoea can provide an explanation for some cases of SIDS(6). Our results Our humble contribution to this problem included 12 sudden death cases in babies from 20 days to 1 year. We may place our cases in the group of unexpected explained death, because the main cause of death in most babies is pneumonia. Only in one of them we have found compound reason of death - bronchiolitis, pneumonia and meningitis and in one baby- only meningitis purulenta. The histological changes in lungs were microhaemorrhages in alveoles and interstitium, congestion, oedema, pulmonary emphysema, atelectases, haemosiderin-laden macrophages, bronchitis and catharral-desquamating pneumonia or catharralhaemorragic pneumonia, but in two cases there were a purulent pneumonia with the areas of abscedent pneumonia in one of them. We found these changes also in the baby with meningitis. Thymic gland has shown a cystic transformation, diminished number of Hassall's corpuscles and in one case - a lot of Hassall's corpuscles, but with cys- Sudden infant death syndrome - the cause of death tic degeneration and associated phagocytosis by macrophages ("starry-sky" spaces) - these features are the marks for acute or accidental involution. In one baby there was a third type of thymic hyperplasia with prominent cortical zone (this type is a common feature for sudden respiratory death. In one case we established cytomegalovirus infection. We didn't observed seasonal variation. DISCUSSION Most authors consider no laboratory or pathological tests are available to establish a diagnosis of SIDS and no lesions are found at autopsy in most cases. Hovewer, as recent reports pointåd out, the affected infant would not be perfectly well before death(23). Some authors (22) insisted that hemosiderin-containing macrophages in SIDS cases would be a hallmark of repeated "near-miss" episode that produced pleural petechiae. They pointed out that the age of death of the babies with pulmonary hemosiderin-laden macrophages but no evidence of pulmonary inflammation was predominantly between 1 and 3 months. The increase of the alveolar macrophages could be merely a result of small, but frequent episodes of aspiration. More late investigation revealed that higher macrophage counts observed in non-SIDS cases and those with SIDS - average or below average macrophage count (8). Other insisted that the siderophages are not increased in SIDS and unexplained pulmonary siderophages can be a marker for trauma or repeated hypoxia/asphyxia (20). Severity of pneumonia is one of the most worrisome problem to make a diagnosis of sudden death. It would be somewhat subjective and there is no pathological standart to classify whether the lesion is morbid enough to be a cause of death. Some authors revealed that proximal and distal tracheal chronic inflammation was less severe in the SIDS cases than in the control cases and are neither a cause of SIDS, nor a specific marker for lethal respiratory infection in infants (24). Clinical experience indicates that interstitial pneumonitis or bronchiolitis sufficiently severe to cause death is preceded by clinical illness with signs of lethargy, tachypnea, respiratory distress, feeding difficulties and/or apnea (14). Most authors pointed the following histopathological changes in SIDS: pulmonary congestion, oedema, microhaemorrhages, increase of alveolar macrophages, atelectasis, emphysema, bronchitis and pneumonia. These findings are the most often features in almost all our babies. In Shu's work (21) the majority of the cases of SIDS (60%) died in the autumn and winter months. The same in Valdes-Depena's work (23)- in January are the most death cases. Decrease in the number of SIDS cases has been associated with infant sleeping supine instead of prone. 1. Unique death distribution with the majority occuring between 2 and 5 months of age (1week to 1 year). 2. Excessive number of deaths during the winter months. 3. Higher death rates among blacks and male infants. 4. Mother who usually are of a lower socioeconomic status, predominantly young and with limited education, sometimes unmarried. 5. Frequently they used legal - tobacco and alcohol before, during and after pregnancy and illegal drugs. 6. Most authors pointed the following histopathological changes in SIDS: pulmonary congestion, oedema, microhaemorrhages, increase of alveolar macrophages, atelectasis, emphysema, bronchitis and pneumonia. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. CONCLUSION 12. Based on author's experimental, epidemiological, pathological and pathophysiological, we may conclude that SIDS include combination of factors: 13. Zekov, G - Sudden death in infant and early childhood, Sofia, 1980, Centrum for scientific information in medicine with central medical library Bajanowski,T et al - Pathological changes of the heart in sudden infant death - International Journal of Legal medicine (2003),117 :193-203 Beckwith JB /1970/ - Observations on the pathological anatomy of the SIDS. In Bergman AB, Beckwith JB, Ray CG - International conference on causes of sudden death in infants. University of Washington Press, Seattle London, pp 83-139 Blackwell, C. et al. - Infection, inflammation and sleep: more pieces to the puzzle of sudden infant death syndrome(SIDS), Acta Pathol. Microbiol. Immunol.Scand.(1999)107, 455-473 Chis wick, M - Perinatal and infant mostmortem examination - BMJ, 1995| 310 141-142 (21 January). Corbin JA - Mechanisms of sudden infant death and the contamination of inspired air with exhaled air Med Hypotheses, 2000 03, 54: 3, 345-52 Craw ley, B.A.and al - Endotoxin in blood and tissue in the sudden infant death syndrome, FEMS Immunology and Medical Microbiology 25 (1999) 131-135 Delaney, K, R. Hanzlick, W. Mitchel - Pulmonary Macrophage Counts in Deceased Infants: Baseline Data for Further Study of Infant Mortality, Am.J For.Med.Pathol, 21,{4}, 2000, 315-318 Dettmeyer R. et al. - Immunhistochemische Diagnostik viraler Miokarditiden bei plotzlicher Todesfallen in Kindersalter, Rechtsmedizin 11:187, 2001 Funayama, M, Azumi, J. and Murai N - Sudden unexpected death of infants and prone position. Autopsy cases of infants during 1 year in Tokio Medical Examiner Office - JJPS, 97, 1190 - 1198, 1993 Guntheroth, W.G. and Spi ers, P.S Guntheroth, W.G. and Spi ers, P.S - Sleeping prone and the risk of sudden infant death syndrome. JAMA, 267, 2359-2362,1992 Hogberg U., Bergstrom, E - Suffocated prone: the iatrogenic tragedy of SIDS, Am.J Public Health, 2000, 4,90: 4, 527-31. Kravitz, H, R. Scherz - The importance of the position of infants on the sudden infant death syndrome. 173 Burulianova I., V. Konstantinova, V. Dokov 14. 15. 16. 17. 18. 19. A new hypothesis - Clin. Pediatr., 17, 1978, 5,403-408. Krous, F. et al - A comparison of respiratory symptoms and inflammation in SIDS and in accidental or inflicted infant death Mallak C. et al - A deadly anti-SIDS device, Am.J.For.Med. Pathol, 2000, 21:1, 79-82 Matturi, L. et al. - Severe hypoplasia of the medullary arcuate nucleus: quantitative analysis in SIDS, Acta Neuropathol (Berl), 2004, 99:4, 371-5. Matturri, L et al - Sudden infant death syndrome (SIDS): a study of cardiac conduction system. Cardiovasc.Pathol., 2000, 9 : 147-148 Reid, G.- Association of sudden infant death syndrome with grossly deranged iron metabolism and nitric oxide overload, Source Med. Hypotheses, 2000 01, 54: 1, 137-9 Reid, G., Tervit, H. - Sudden infant death syndrome: hypothalamic failure to sense elevated blood pyrogens, Source Med.Hypotheses, 2000 01, 54: 1, 84-90. 174 20. Schluckebier, D et al - Pulmonary siderophages and unexpected infant death, Am J For. Med.Pathol, vol.23, No 4, Dec 2002, 360-363 278 (1993) 21. Shu F. et all - Role of respiratoty viral infection in SIDS: detection of viral nucleic acid by in situ hybridization, Journal of Pathology, vol.171: 271-278 (1993) 22. Stew art, S. Fawcett, J. and Ja cob son, W. - Interstitial haemosiderin in the lungs of SIDS : A histological hallmark of "near-miss "episodes ?, J.Pathol, 145, 53-58, 1985 23. Valdes-Depena, M - A pathologist's perspective on the sudden infant death syndrome -1991. Pathol. Ann, 27:133-164, 1992 24. Yasuhiro Aoki -Histopathological findings of the lung and trachea in Sudden Infant Death Syndrome Review of 105 cases, autopsied at Dade County Medical Examiner Department, Jpn J Legal Med, 48(3), 141-149, 1994 Scripta Scientifica Medica, vol. 40 (2008), pp 175-176 Copyright © Medical University, Varna METHYL ALCOHOL POISONING - A MORPHOLOGICAL STUDY FOR 20-YEARS PERIOD Burulianova I., V. Konstantinova*, D. Radoinova Department of Forensic Medicine, Department of General and Clinical pathology*, Varna Medical University Reviewed by: Assoc. Prof. D. Radoinova, MD, PhD INTRODUCTION The clinical manifestations of methanol poisoning have been the subject of several review articles over the past forty years (2, 11), though detailed postmortem pathologic studies are relatively few. The earliest autopsy studies on methanol poisoning have emphasized the acute changes secondary to hypoxic or ischemic injury to the gray matter, cerebral oedema and acute neuronal injury. Postmortem studies of individuals, who survive intoxication several days or weeks have shown brain injury characterized by bilateral putamen necrosis, particularly affecting the lateral portions of the nuclei (1,10). In some of the cases there has also been a dramatic pattern of white matter hemorrhagic necrosis, involving the centrum semiovale, especially affecting subcortical regions /10/. The precise mechanism of methanol toxicity remains a matter of debate /2/. The observed lesions represent direct toxic effects of methanol and its metabolities and injury, secondary to anoxia and acidosis. Injury to the putamen likely represents a selective toxic effect, possibly potentiated by poor venous drainage. The pathogenesis of the white matter hemorrhagic necrosis remains unexplained /6/. MATERIAL AND METHODS The aim of this study was to examine morphological changes in the internal organs in methyl alcohol poisoning cases. The records of the Forensic Medicine Department in Varna Medical University were reviewed retrospectively for 20-years period - from 01.01.1986 to 01.01.2006. There were 16 methanol poisoning from 8028 autopsies or 0,2%. The victim's sex was mainly male -14 men (87,5%) and only 2 woman (12,5%). The age of men varies from 30 to 66-years, woman are 50 and 52-years old. The content of methanol in blood varies from 0,104 %o to 3,05%o in 52-old woman. We performed microscopical examinations in 7 cases (43,75%), in which there were blocks on disposal. Address for correspondence: Irina Burulianova, Department of Forensic Medicine, Medical University Prof. Dr. Paraskev Stoyanov, 55 Marin Drinov St, BG-9002 Varna, BULGARIA e-mail: burulianova@abv.bg RESULTS There were cerebral perivascular and pericellular oedema, congestion, severe degenerative changes in most cases, particularly around vessels (in one case there were focuses of encephalomalacia), arteriolar hyalinosis in some vessels (in most cases). There was a loss of Purkinje cells in the cerebellum in one case and pseudocystes in other case. The histological changes in lungs were: microhaemorrhages in alveoles, congestion, oedema, pulmonary emphysema, atelectases, haemosiderin-laden macrophages. Microscopical changes in the myocardium include interstitial oedema, congestion, myocardiofibrosis, focal lipomatosis, hyalinosis in the arterioles. The most prominent changes were in liver-different kind of fatty degeneration, hydropic degeneration, hyperemia, intrahepatal cholestasis, hyalinosis of the arterioles. We found severe renal tubular degeneration in kidney, capilary dilatation and congestion. There was congestion in the other organs. DISCUSSION Our results showed that the most frequent changes were: fatty degeneration in liver, intrahepatal cholestasis, cerebral oedema, degeneration around brain vessels, hyalinosis, interstitial oedema, lipomatosis, congestion in the myocardium, renal tubular degeneration, microhaemorrhages in alveoles, haemosiderophages, pulmonary oedema, emphysema, atelectases. Most authors revealed the same changes. Except these histological changes, they investigated putamen, caudate nucleus, pontine tegmentum and optic nerves and found necrosis and haemorrhages (3,4,7,8,9). Retinal damage is believed to be due to the inhibition of retinal hexokinase by formaldehyde an intermediate metabolite of methanol. In one case we observed pseudocysts in brain. The same were Mc Lean's results (5). Autopsies revealed cystic resorbtion of the putamen and the frontocentral subcortical white matter in addition to widespread neuronal damage throughout the cerebrum, cerebellum, brainstem, spinal cord. In one our case there was the loss of Purkinje cells in the cerebellum. We haven't blocks of optic nerves, putamen, caudate nucleus and pontine tegmentum. We also estab175 Burulianova I., V. Konstantinova, D. Radoinova lished degeneration in the parietal area of the brain. Mittal et al. observed degeneration in the parietal cortex in 85,7% of cases, but putamental degeneration and necrosis in 7,14% (7). We didn't meet in literature explaining of the cholostasis. Maybe the mechanism is severe degeneration of the liver cells. According Mittal (7) liver fatty degeneration was seen in 67,8% and microvesicular fat in hepatocytes-in 42,5%. LITERATURE 1. 2. 3. Betta P.G. Forno G (1988) Necrosi emorragica del putamen da intossicazione acuta da alcool metilico. Pathologica 80: 215-218. Bruyn G.W., AL-Deeb S:, Vielvoye G.J.(1994) Methanol intoxication. In: Handbook of Clinical Neurology, Vinken PJ, Bruyen GW, Vol 64, pp 95-106, Eslevier: Amsterdam Gaul, HP, Wallace CJ, Auer RN, Fong TC -MR findings in methanol intoxication, Am J. Neuroradiol., 1995, 16, 1783-1786 176 Kaye, S.-Insidious methyl alcohol poisoning, Virginia Med. Monthly, 1958, 85, 670. 5. Mc Lean DR, Jacobs H, Mielke BW - Methanol poisoning: a clinical and pathological stugy. 6. Menne FR et al- Final diagnosis - methanol poisoning, Ann.Neurol, 8: 161-167 7. Mittal BV, Desai AP, Knade KR - 28 fatal out of the 97 cases of methylalcohol poisoning, J.Postgrad.Med. 1991, 37, 9-13. 8. Ravichandran RR, Dudani RA, Almeida AF, Chawla RP, Acharya VN - Methylalcohol poisoning ( Experience of an outbreak in Bombay), Am.J.Neurol., 1984, 30, 269-274) 9. Sharma HS -Methyl induced optic nerve cupping, Arch.Ophthalmol., 1999, 117:286-287 10. Suit PE, Esstes ML (1990) Methanol intoxication: clinical features and differential diagnosis. Cleve Clin J Med 57:465-471 11. Schneck SA(1979) - Methyl alcohol. In: Handbook of Clinical Neurology, Vinken PJ, Bruyn GW, Vol 36, pp 351-360, Eslevier:Amsterdam 4. Scripta Scientifica Medica, vol. 40 (2008), pp 177-178 Copyright © Medical University, Varna ANALYSIS OF FATAL ELECTRICAL TRAUMAS IN THE REGION OF VARNA FOR A 41-YEAR-LONG PERIOD Dokov W. V. Department of Forensic medicine, Prof. Paraskiev Stoyanov Medical University of Varna Reviewed by: Assoc. Prof. D. Radoinova, MD, PhD ABSTRACT Introduction. Electrotraumatism (ET) is rare to observe, but it presents a significant problem both for public health and forensic medicine. Purpose. The purpose of this study is to identify some features and circumstances typical of ET on the territory of Varna District. Material and methods. Forensic medicine documentation has been examined from 16,780 autopsies for the period 1965-2005 performed at the Chair of Forensic Medicine and Deontology, the Medical University of Varna. The results have been processed by the statistical methods of alternative, variational and graphical analysis. Results. Over the 41-year-long period, a total of 280 ET autopsies have been performed, which accounts for 1.67% (ð±D1,5) of all autopsies. Lethal injuries by electric current typically occur in young age. Young males prevail. More than half of the events have been domestic ET. In the studied group, the number of accidents caused by high voltage is about the same as the number of accidents caused by low voltage. Suicide by electric current is relatively rare. A forensic medicine expert participated in 99 (62.26% ð±D9.55) of the inspections on the scene of accident. Conclusions. ET affects mainly young males in domestic ÅÒ. Keywords: Electro-traumatism, Varna District INTRODUCTION Electrotraumatism (ET) is rare to observe, but it presents a significant problem both for public health and forensic medicine. Its relatively low incidence is not conducive to major studies due to which there are scarce data on this problem in literature. This prompted us to undertake the present study. PURPOSE The purpose of this study is to identify some features and circumstances typical of ET on the territory of Varna District. RESULTS AND DISCUSSION Over the 41-year-long period, a total of 280 ET autopsies have been performed, which accounts for 1.67% ( ð±D1.5) of all autopsies. The average age of the deceased from ET is 35.47±2.91 years, within the scope of 1 to 83 years. Male gender prevails over the female with 242 (86.43% ð±D4.22) to 38 (13.57% ð±D9.39). The difference in the relative share between males (M) and females (F) is statistically reliable (p<0.001). F 31,57% Ì 86,43% MATERIAL AND METHODS Forensic medicine documentation has been examined from 16,780 autopsies for the period 1965-2005 performed at the Chair of Forensic Medicine and Deontology, the Medical University of Varna. The results have been processed by the statistical methods of alternative, variational and graphical analysis. Address for correspondence: W. Dokov, Department of Forensic Medicine, Medical University Prof. Dr. Paraskev Stoyanov, 55 Marin Drinov St, BG-9002 Varna, BULGARIA e-mail: Dokov@seznam.cz M F Fig. 1 Distribution by gender of the deceased from electrotrauma. More than half of the cases are domestic ET (DET): 160 (57.14% ð±D7.67), and about 1/3 are labour-related electrotraumas (LET): 86 (30.71% ð±D9.75). Suicides 177 Dokov W. V. (SC) by electric current are relatively rare to observe: 17 (6.07% ð±D11.35) In 18 cases (6.43% ð±D11.33), there are no data about the type of the accident on inspection or the autopsy (N/A). Not Data 6% SC 6% LÅÒ 31% DÅÒ 57% these, we could not agree more with the recommendations given by Nursal TZ, et al (2003 ) according to whom prevention, public discussion of the problem and strict observance of the rules when distributing electric power would notably reduce this type of traumatism. While the data given by Celik A, et al (2004) point to a prevalence of injuries due to electric current of high voltage: 63%, our results show a relatively even distribution of the cases either of high or low voltage. At the other end of the scale are the data given by Byard RW(2003): a very rare occurrence of accidents caused by high voltage. Our study brings forth a question of pressing interest about the effectiveness of the process of diagnostics and expertise in relation to the data from the inspection of the accident scene. The relatively high percentage of cases (37.74%) where a forensic medicine expert was not present on the inspection point to feasible opportunities to increase the speed and quality of expert activities in this direction. CONCLUSIONS Fig. 2 Structure of ET depending on the type of electrotrauma. Injuries caused by low voltage (<220V), 93 (33.21% ð±D9.57), and by high voltage (>220V), 91 (32.5 ð±D9.62), are approximately the same number without a significant difference (ð> 0.5). In 96 cases (34.28 ð±D9.49) there are no data about the voltage of the electric current at the beginning of the expertise, which impedes the diagnostic process. A large part of information significant for the forensic-medical diagnosis and expertise can be ascertained as soon as the scene of accident is inspected. Forensic-medical expert participated in 99 inspections (62.26% ð±D.55) out of a total 159 cases studied by us, but quite a few, 60 (37.74% ð±D12.27), were performed in his absence. Electrotraumas account for 3.1% (1) respectively 5% (3), 5.1% (5) up to 21% (4) of all cases of burns. Our data have revealed that ET is observed in 1.67% of all autopsies after violent or non-violent death. Our study has discovered a characteristic age-related peculiarity. ET affect mainly young people (õ=35.47±2.91 years) of working age. There is a peculiar distribution of the cases by gender. We have ascertained that males are mainly affected (86.43% ð±D4.22). Similar results are reported by Nursal TZ, et al (2003) and Celik A, et al (2004) according to whom males are affected in 67% or 95% of the cases, respectively. The results of our study show that the prevailing part of ET are domestic or labour-related accident. With results like 178 Fatal injuries due to electric current are typical of young age. There is a prevalence of persons of male gender. More than half of the cases result from domestic electrotraumatism. The injuries due to high or low voltage current are distributed approximately evenly by number in the group under study. REFERENCES 1. 2. 3. 4. 5. Borisov VG, Kashin IuD, Oliunina NA. Deep electrothermal burns Khirurgiia (Mosk). 1995;6 :29-31. Byard RW, Hanson KA, Gilbert JD, James RA, Nadeau J, Blackbourne B, Krous HF. Death due to electrocution in childhood and early adolescence. J Paediatr Child Health. 2003 ;39(1):46-8. Celik A, Ergun O, Ozok G. Pediatric electrical injuries: a review of 38 consecutive patients. J Pediatr Surg. 2004 ;39(8):1233-7. Nursal TZ, Yildirim S, Tarim A, Caliskan K, Ezer A, Noyan T. Burns in southern Turkey: electrical burns remain a major problem. J Burn Care Rehabil. 2003 24(5):309-14. Henckel von Donnersmarck G, Muhlbauer W, Herndl E, Schmidt A. Reconstruction of the cranial vault and soft tissues of the skull after electrotrauma Langenbecks Arch Chir Suppl II Verh Dtsch Ges Chir. 1989;:847-51. Scripta Scientifica Medica, vol. 40 (2008), pp 179-181 Copyright © Medical University, Varna LETHALITY FROM ACUTE INTOXICATIONS WITH ORGANOPHOSPHATE PESTICIDES IN VARNA REGION FOR A PERIOD OF 15 YEARS Zlateva S., M. Iovcheva, Marinov P. Department of Toxicology, Naval Hospital- Varna Reviewed by: Assoc. Prof. V. Ikonomov, MD, PhD ABSTRACT An analysis of the lethality in cases of acute exogenous intoxications /AEI/ with organophosphate pesticides /OP/ in Varna region for a period of 15 years -1991-2005 was done. It was established that from 207 patients with acute OP poisonings there were 40 lethal cases. The frequency of the lethal cases was 19.32%. 28 / 70%/ of them were men and 12 /30%/ were women. The lethality was significantly higher in men. The proportion of lethal cases in men and women was 2.33: 1. The average age of deceased patients was 59 years. It was reported that with growing up of the age the average lethality had grown bigger too. All the lethal poisonings were by an oral ingestion. In 35 cases /87.5%/ suicidal attempts were done and in 5 cases /12.5%/ accidental household poisonings took place. The main reason about the death was a development of syndrome of multiorgan insufficiency /SMOI/. Keywords: acute intoxication, organophosphorus pesticide, lethality INTRODUCTION The widespread use of OP and their significant toxicity determine the high frequency of intoxications in some countries. /8,19, 22, 24/. During recent years in Varna region the relative share of OPAEI has grown smaller. /3/. The hospital lethality from these intoxications varies in different studies and is in the range within 20% and 25%. /1,11,12,18, 23,26/.OP are the cause of 10% to 46% of the lethal cases of all acute intoxications /10,21/. Although the highly toxic substances were replaced by less toxic OP pesticides and more contemporary methods of treatment had been introduced the acute OP poisonings continue to have a high lethal rate and represent one of the most serious problems of the nowadays clinical toxicology. /5,20/. Some omissions in the first medical aid also contribute to this fact. /4/. In this relation we have put ourselves a task to study the lethality from AEI with OP in Varna region during the period 1991-2005 in order to establish the frequency of the lethal outcomes, to analyze the lethality according to sex, age, years, type of the pesticide, relative part of different pesticides in the death rate, and also the concrete reasons for the lethal exit. MATERIAL AND METHODS Address for correspondence: Snezha Zlateva, Clinic of Toxicology, Military Medical Academy, Naval Hospital, Varna, E-mail: snezha zlateva@abv.bg A retrospective study of the hospital case files and the forensic protocols of the autopsies of all 40 patients with lethal outcome previously treated at the Department of Toxicology, Naval Hospital-Varna. RESULTS AND DISCUSSION 207 patients with acute OP intoxications were treated at the Department of Toxicology, Naval Hospital-Varna, during the examined period. Lethal outcome was registered in 40 cases /19.32%/. This frequency corresponds to the frequency shown in the specialized literature in many researches. /1,11,12,18,23,26/. The analysis of the lethality by years showed significant variances. In 2001 there were no lethal cases, but there were only 2 patients with OP poisonings during this year. The highest death rate was registered in 1992- 33.3 %, when 21 patients with OP intoxications were treated at the Department of Toxicology. OP poisonings were the cause of lethality in 25.24% of the total death rate from acute intoxications. In 28 lethal cases /70%/ the patient was a man and in 12 lethal cases /30%/ - a woman. The death rate of male patients was significantly higher than that of female patients- 2.33: 1. These results are due to the fact that OP AEI are more frequent in men than in women /3,5/ as well as to the fact that usually suicidal attempts in men are more grave and lead to more serious poisoning. The distribution of the patients with lethal OP poisonings according to the age showed lowest death rate in the age group of young patients / younger than 24 179 Zlateva S., M. Iovcheva, Marinov P. years/ and highest in the age group of patients over 60 years. /Table 1/ The main cause of death was development of a syndrome of multiorgan insufficiency /SMOI/. Table 1. Distribution of the lethality from OP acute intoxications according to the age group Table 3. Causes of death in OP acute exogenous intoxications. Age group Total number of treated OP Lethal cases intoxications Number of lethal cases Percentage Syndrome of multiorgan insufficiency 33 82.5 % Heart rhythm disorders 4 10.0 % Intermediary syndrome 2 5.0 % Myocardial infarction 1 2.5 % Total 40 100 % Cause of death Percentage Under 24 years 25 1 4% 25- 44 years old 41 3 7.32 % 45- 60 years old 72 15 20.83 % Over 60 years 69 21 30.43 % Total number 207 40 19.32 % The average age of the deceased patients was 59 years. It makes an impression that with the growing of the age the death rate is increasing too. This fact can be explained with more severe clinical course of the intoxication and less adaptive potential of the elder patients, a result of existing serious co morbidity which weakens the resistive and reparative potential in the course of the OP poisoning and which can undoubtedly influence the clinical course and outcome of the poisoning. Lethal outcome from OP poisoning with 5 different OP pesticides was registered. In one case the type of OP pesticide could not be established. /table 2/. The prevailing part of the death cases was caused by Dimethoate /Bi-58/- an OP pesticide with middle toxicity. These results are due to banishment of the highly toxic and dangerous OP pesticides as Parathion, Intrathion, etc. in Bulgaria and to the widespread use of Dimethoate in our country nowadays. Table 2. Relative part of different OP pesticides which had led to lethal acute exogenous OP intoxication. In practice the syndrome of multiorgan insufficiency was the cause of death in 37 cases /92.5 %/. Each of the patients who had died from immediate cause of death rhythm disorder had clinical data about SMOI as well. With the introduction into use of contemporary methods and means of reanimation and intensive treatment permitting elongation of the life or survival of the critically ill the OP poisonings lead to the development of typical symptoms of multiorgan disorders and multiorgan failure which consequently can cause the death of the patients. /2,6,9,27/. The lethality of the patients with SMOI grew from 8.3 % to 100 % with the increasing of the number of the involved organs and systems with insufficiency. /2/. In two cases the death occurred after a peripheral type of paralysis of the respiration - development of intermediary syndrome. In one case the immediate cause of death was an acute myocardial infarction in a patient with coexisting ischemic disease of the heart, on the eighth day of the intoxication, on the background of slow restoring of the cholinesterase activity. CONCLUSION Number of the lethal cases Percentage Dimethoate 33 82.5 % Neocidol 3 7.5 % Nurele D 1 2.5 % Fenitrothion 1 2.5 % Azodrin 1 2.5 % Not identificated 1 2.5 % Total 40 100 % OP pesticide All the described lethal OP poisonings took place after an oral ingestion of pesticides. 35 cases /87.5 %/ were suicidal attempts and 5 cases / - accidental household poisonings. The oral ingestion of a pesticide , especially when done with a suicidal purpose , leads to a massive entry of great quantity pesticide in human organism and consequently- to more severe clinical course of the intoxication and high death rate. 180 We consider that OP acute exogenous intoxications continue to be a serious test for the doctors- toxicologists as they quite often end with lethal outcome. We establish lethality of 19.32 %. This relatively high death rate is due to the severe forms of intoxication - a result mainly of suicidal attempts with oral ingestion of great quantity of OP and high average age of the intoxicated. The death rate was higher in male patients than female. The proportion male to female patients was 2.33: 1. We report that with the growing of the age the lethality is increasing too. The main cause of lethal outcome was the development of a syndrome of multiorgan insufficiency. REFERENCES 1. Ëóæíèêîâ Å. À., Ë. Ã. Êîñòîìàðîâà. Îñòðûå îòðàâëåíèÿ, Ìîñêâà, Ìåäèöèíà, 1989. Lethality from acute intoxications with organophosphate pesticides in Varna region ... 2 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Ìàðèíîâ Ï., Ò. Òàøåâ, Ì. Àñïàðóõîâà. Ñèíäðîì íà ìíîãîîðãàííà íåäîñòàòú÷íîñò ïðè îñòðè åêçîãåííè èíòîêñèêàöèè ñ ôîñôîðîðãàíè÷íè ïåñòèöèäè. Ñïåøíà ìåäèöèíà, ò.6, 4, 1998, 42-44. Ìàðèíîâ Ï., Ò.Òàøåâ, Þ.Ñúáåâà è äð. Åïèäåìèîëîãè÷íè òåíäåíöèè ïðè îñòðèòå åêçîãåííè èíòîêñèêàöèè ñ ôîñôîðîðãàíè÷íè ïåñòèöèäè âúâ Âàðíåíñêè ðåãèîí â ïåðèîäà íà ïðåõîä êúì ïàçàðíî ñòîïàíñòâî. Õèãèåíà è çäðàâåîïàçâàíå, vol. XLII, 1, 1999, 3-5. Ìàðèíîâ Ï., Þ.Ñúáåâà, Ì.Àñïàðóõîâà è äð. Àíàëèç íà åôåêòèâíîñòòà íà ïúðâàòà ìåäèöèíñêà ïîìîù ïðè îñòðè åêçîãåííè èíòîêñèêàöèè ñ ôîñôîðîðãàíè÷íè ïåñòèöèäè â äîáîëíè÷íèÿ ïåðèîä âúâ Âàðíåíñêè ðåãèîí. Õèãèåíà è çäðàâåîïàçâàíå, vol. XLII, 2, 1999, 8-10. Ìàðèíîâ Ï. Íÿêîè àñïåêòè íà åïèäåìèîëîãèÿòà, òîêñèêîêèíåòèêàòà, êëèíè÷íîòî ïðîòè÷àíå, ëå÷åíèåòî è ïðîãíîçàòà ïðè îñòðèòå åêçîãåííè èíòîêñèêàöèè ñ ôîñôîðîðãàíè÷íè ïåñòèöèäè. Äèñåðòàöèÿ, Âàðíà, 2002. Agostini M, Bianchin A. Acute renal failure from organophosphate poisoning: a case of success with haemofiltration. Hum Exp Toxicol 2003; 22 (3): 165-7. Asari Y., Kamijyo Y., Soma K. Changes in the hemodynamic state of patients with acute lethal organophosphate poisoning. Vet Hum Toxicol 2004; 46(1): 5-9. Batra AK., Keoliya AN., Jadhav GU. Poisoning: an unnatural cause of morbidity and mortality in rural India. J Assoc Physicians India. 2003; 51: 955-9. Betrosian A., Balla M., Kafiri G. et al. Multiple systems organ failure from organophosphate poisoning. J Toxicol Clin Toxicol 1995; 33(3): 257-60. Daisley H., Simmons V. Forensic analysis of acute fatal poisoning in the southern districts of Trinidat. Vet Hum Toxicol 1999; 41(1): 23-25. Fabritius K., Balasescu M. Acute non-occupational intoxications with pesticides in Romania: a comparative study from 1988 to 1993. Toxicol Lett 1996; 88:211-4. Gnyp L., Lewandowska-Stanek H. The analysis of organophosphates poisoning cases treated at the Centre for Acute Poisoning in Lublin Provincial Hospital in 1994-1996. Przegl Lek. 1997; 54(10): 734-736. Grmec S., Mally S., Klemen P. Glasgow Coma Scale score and QTc interval in the prognosis of organophosphate poisoning. Acad Emerg Med. 2004; 11(9): 925-30. Guloglu C., Kara IH. Acute poisoning cases admited to a university hospital emergency depart- 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. ment in Diyarbakir, Turkey. Hum Exp Toxicol. 2005; 24(2): 49-54 Iliev Y., Akabaliev V., Doychinov I. Characteristics of adult acute poisoning mortality in a large industrial-agrarian region of Bulgaria during socioeconomic transition and crisis (1990-1998). Vet Hum Toxicol. 2000; 42(6): 366-9. Juarez-Aragon G., Gastanon-Gon za lez JA., Pe ter-Mo rales AJ et al. Clinical and epidemiological characteristics of severe poisoning in an adult population admited to an intensive care unit. Gas Med Mex. 1999; 135(6): 669-75. Lin CL., Yang CT., Pan KY. et al. Most common intoxication in nephrology ward organophosphate poisoning. Ren Fail 2004; 26(4): 349-54. Munidasa UA., Gawarammana IB., Kularatne SA. et al. Survival pattern in patients with acute organophosphate poisoning receiving intensive care. J Toxicol Clin Toxicol. 2004; 42(4): 343-7. Nagami H., Nishigaki Y., Matsushima S. et al. Hospital-based survey of pesticide poisoning in Japan, 1998-2002. Int J Occup Environ Health. 2005; 11(2): 180-4. Seydaoglu G., Satar S., Alparsian N. Frequency and mortality risk factors of acute adult poisoning in Adana, Turkey, 1997-2002. Mt Sinai J Med. 2005; 72(6): 393-401. Singh D., Tyagy S. Changing trends in acute poisoning in Chandigar zone: a 25 year autopsy experience from a tertiary care hospital in northern India. Am J Forensic Med Pathol. 1999; 20(2): 203-210. Srivastava A., Peshin S., Kaleekal T. et al. An epidemiological study of poisoning cases reported to the National Poisons Information Centre, All India Institute of Medical Sciences, New Delhi. Hum Exp Toxicol 2005; 24(6): 279-285. Sungur M., Guven M. Intensive care management of organophosphate insecticide poisoning. Crit Care. 2001; 5(4): 211-5. Tagwireyi D., Ball DE., Nhachi CF. Toxicoepidemiology in Zimbabwe: pesticide poisoning admissions to major hospitals. Clin Toxicol. 2006; 44(1): 59-66. Ulmeanu C., Nitescu Gimita VG. Mortality rate in acute poisoning in a pediatric toxicology department. Przegl Lek. 2005; 62(6): 453-5. Yamashita M. et al. Analysis of 1000 consocutive cases of acute poisoning in the suburb of Tokio leading to hospitalisation. Vet Hum Toxicol. 1996; 38: 34-35. Zivot U., Castorena JL., Garriott JC. A case of fatal ingestion of malathion. Am J Forensic Med Pathol 1993; 14(1): 51-3. 181 Scripta Scientifica Medica, vol. 40 (2008), pp 183-185 Copyright © Medical University, Varna THE INFLUENCE OF PSYCHOLOGICAL PREPARATION ON FOOTBALL AND KARATE TRAINING IN PRIMARY SCHOOL PUPILS Margaritova V. Plovdiv University "Paisii Hilendarski" Reviewed by: Prof. A. Klisarova, MD, PhD, D.Sci ABSTRACT Through psychological preparation physical readiness is formed. Psychological preparedness is a complex phenomena which is a reflection of the level of preparation of an individual for action in different situations. For many coaches training is the process of physical preparation, but the end result is also heavily influenced by psychological factors. In the present work we look at the influence of psychological preparation in the training of football and karate with pupils of primary school age. Keywords: Psychological preparation, psychological readiness, training All human action requires a certain amount of physical and psychological preparation, and in sport this is even more true. Sports preparation is a whole system of inter-dependent and mutually conditional aspects physical, technical, tactical, and psychological. Neglect of one element in the system has a negative effect on results. Psychological preparation is an important part of the many faceted and complex preparation in the educational-training process. Many scholars regard psychological preparation simply as a test of separate psychological qualities or process', but by doing so they fail to fathom the full essence of the phenomena but only aspects of it. Psychological preparation is an important part of the many faceted and complex preparation of athletes and teams. According to T. Yancheva (1977) psychological preparation is a prerequisite and a result of the educational-training process: a prerequisite because the effectiveness and quality of the sporting performance and results depend on the level of physical preparation, because the sporting level reached has a psychological impact. Indeed, psychological preparation may be even regarded as the basis for the development of physical preparation. Vasilev (1987) separates psychological preparation into four categories: general, specialized, collective and specific. In his opinion psychological preparation forms the necessary capacities, will and emotional qualities. Physical preparation is the second sub-structure of psychological preparation. Different views on physical preparation veil its essence. Address for correspondence: Valentina Margaritova, Plovdiv University "Paisii Hilendarski", 24, Tsar Asen Str., 4000 Plovdiv, BULGARIA e-mail: valia_margaritova@abv.bg For many authors physical preparation is a sports-education process for the many aspects of physical development, for controlling the motor functions and for achieving a certain level of physical capability (Kr. Rachev, 1987). In our opinion physical preparation is a condition and a process: on one hand is the manifestation of physical development, physical ability and the functional condition of the individual; on the other hand the process directed towards reaching a certain level. Therefore physical preparation is geared towards creating an adequate level of physical preparation which consists of physical qualities, condition and process'. Practical action is realized through physical preparation. Psychological preparation facilitates physical preparation. In the activity of physical exertion the concept of psycho-physical is used as a unitary combination of physical and psychological. In the rich theory of personality and human activity the term psycho-physical has also emerged. This development has become possible with the emergence of new mathematical methods for measuring and modulating the psychological and motor phenomena and the discovery of the determinants in their indicators. Due to the basis attained by science, conditions have been created for the discovery of new aspects of the concept of psycho-physical. According to D. Kare (1973) sporting accomplishments are the result, not only of theoretical and technical preparation, but also of the psychological preparation of the competitors. In the process of self-realization psychological preparation plays a key role. In the modern hectic and changing times the contents of the human activity area also changing. Mobility in the modern individual is lessening, physical activity giving way to mental. The aim of psychological preparation is formation of psycho-physical preparedness. If we proceed from the 183 Margaritova V. assumption of the unity of internal and external activity in the structure of the activity we define psycho-physical readiness as - an integral condition which determines the unity of physical and psychological preparedness in the structure of the individuals activity during his adaptation to changing conditions in his environment for a certain period of time. Psycho-physical preparedness is a complex phenomena which reflects the readiness of an individual to act in different situations. Through it one may control the actions and behavior of an individual and to diagnose his level of preparation to accomplish given aims and tasks. The structure of psycho-physical preparedness is confined by models, including the correlation dependence between separate psychological structures, factors, elements and components. With the increasing power of inter-relations between constructive factors, elements and components of the structure of psycho-physical preparedness an adequate readiness is formed and in the case of a reduction - an inadequate one. D. Kaikov (1990) investigated the complex system of steps of adequate preparedness: standard, raised, high and highly elevated, and inadequate raised, low, demobilizing. The object of the research is to pinpoint the effects of the models created by us on primary coaching in football and karate on the psychological preparedness of pupils at primary school. The study encompassed 127 pupils of primary school age, who were separated into 5 groups: 3 experimental and 2 control. On I ÅG (experimental group) - football, II ÅG -karate, boys and III ÅG - karate, girls, the model constructed by us was put into effect. I ÊG (control group) girls and II ÊG boys trained by standard methods in different sporting sections. For concrete comparison data on the differences constituted we used t-criteria of the student with suitable guaranteed probability. Analysis of the indicators characterizing the dynamics of the development of psychological qualities was carried out on the basis of quantitative characteristics of the various indicators reflected in the tables. The dynamics of the development of psychological qualities in the three experimental groups will be studied through the following statistical parameters: average mathematical value of variation, standard divergence, co-efficient of variation, reliability. The test, through which the psychological preparation of the children training football and karate is measured, is temporal awareness. The higher the awareness the children have of the passage of time, the higher and more adequate is their level of preparation. The research illustrates that as a result of training certain changes in temporal awareness occur. (Òable 1). In the given time of 17 seconds, research on the first test shows time passes quicker by 3.2 sec. in KG I, 2.8 sec. in KG II and 2.9 sec. in KG III, in comparison with the given control time. In the second test the accuracy in defining the time taken improves: with a difference of 1.9 sec. in CG I, 1.5 sec. in KG II, 0.2 sec. in EG I, 0.9 sec. in EG II, and 0.8 184 sec. in EG III. This difference is due to the special methods used in the training of the two sport types. Òàble 1. Indicators in the test for temporal awareness Research First Test Groups x s Second Test V (%) x s V Difference (%) Reliability (%) ² CG 20,2 5,0 25 18,9 3,8 20 1,3 98 II CG 19,6 5,1 26 18,5 3,7 20 1,1 98 ² EG 19,5 4,0 20,5 16,8 3,5 21 2,7 99 II EG 19,8 4,2 21 17,9 3,1 17 1,9 99 III EG 19,9 4,5 23 17,8 2,9 16 2,1 99 The improvement in temporal awareness is one of the basic factors indicating the level of psychological preparation and the ability of the children to regulate internal stress in the process of football and karate training. From the study of the results of temporal awareness we can surmise that, as a result of the effects of the model, accuracy is improved as an element of psychological preparation and a factor of its improvement and creation of an adequate level of psychological preparation. In order to form adequate psychological preparation, perception also plays a key role. Audience perception is one of the main factors which define the level of preparation for action in various situations. In table 2 clarity level and latent time are presented. Second Research First Research Indicator Group x ² CG s V (%) x s V (%) Reliability Ð (%) 3,40 0,58 17 3,75 0,52 14 99 II CG 3,50 0,54 15 3,75 0,54 14 98 Clarity ² CG 3,50 0,50 14 4,00 0,49 12 level II CG 3,25 0,52 16 4,25 0,48 11 99 99 III CG 3,75 0,48 13 4,25 0,42 10 99 ² CG 4,5 0,69 15 4,0 0,53 13 98 4,9 0,62 13 4,5 0,66 15 99 4,8 0,55 11 3,7 0,52 14 99 4,3 0,53 12 3,5 0,50 14 99 III ÅG 4,4 0,50 11 3,5 0,49 14 99 II CG Latent ² ÅG time II ÅG From table 2 it is obvious that the level of clarity in the control groups has increased slightly: 0.35 for CG I and 0.25 for CG II. The improvement is greater among the experimental groups: 0.5 in EG's I and II and 1.00 in EG II. The latent time has also improved significantly: in CG I lessening by 0.5 sec., 0.4 sec. in CG II, 0.9 sec. in EG I, 0.8 The Influence of Psychological Preparation on Football and ... sec. in EG II, and 0.9 sec. in EG III. These changes are a basic indicator through which one can adjudicate an improvement in the psychological preparation structure. One may conclude that a substantial change in psychological awareness is to be observed in the subjects studied by us who underwent football and karate training. Furthermore, the latent time for forming the image has a significant effect on the clarity of the image (r = - 0,62) (fig. 1). This dependence is significant for the regulation and optimization of psychological preparation, and thus for the individuals actions: for heightening the clarity of perception and imagination it is necessary during training to shorten the time for forming perception. 2. The applied models for psycho-physical preparation have a significant effect on the formation of psychological qualities, improving the value of the indicators and links between them. In karate the model has a greater effect on the accuracy of psychological activity and in football - on speed. RECOMMENDATIONS 1. To research the effectiveness of the model on students in higher classes. 2. Tested models to be applied in the football and karate training systems. BIBLIOGRAPHY 1. Fig. 1. Inter-dependence in the structure of perception KEY: Latent time for forming perception; Level of clarity CONCLUSIONS 1. Football and karate are activities linked to a high level of concentration of physical and psychological effort for quick and accurate action, determined by adequate psychological preparation. 2. 3. 4. 5. 6. Âàñèëåâ, Â. Çà ñúäúðæàíèåòî è ñòðóêòóðàòà íà ïñèõè÷åñêàòà ïîäãîòîâêà. À. Ïðåãëåä. Ñ., 1987 Êàéêîâ, Ä. Ïñèõîôèçè÷åñêà ïîäãîòîâêà çà äåéñòâèå â åêñòðåìàëíè ñèòóàöèè. Ñ., 1983 Êàéêîâ, Ä. Ïñèõîôèçè÷åñêà ïîäãîòîâêà çà çàùèòà íà îòå÷åñòâîòî. Ñ.,1990 Ðà÷åâ, Ê. ÒÌÔÂ. Ñ., 1987 Õàðå, Ä. Ó÷åíèå çà òðåíèðîâêàòà.. Translation from German. Ñ., 1973 ßí÷åâà, Ò. Ïñèõîëîãè÷åñêî îñèãóðÿâàíå íà ñïîðòíàòà ïîäãîòîâêà. Ñ.,1997 185 Scripta Scientifica Medica, vol. 40 (2008), pp 187-191 Copyright © Medical University, Varna ANALYSIS OF BODY COMPOSITION USING BIOIMPEDANCE (BIA) DATA Shishkova A., P. Petrova*, À. Tînev*, G. Iliev*, P. Bahlova, Ogn. Softov, E. Kalchev Medical center “Medica-Albena” EAD, resosrt Albena, Medical university Varna* Reviewed by: Assoc. Prof. N. Negrev, MD, PhD ABSTRACT BACKGROUND: Knowledge of body composition in health and disease has been a continuing interest for clinicians, because components of the body often provide more useful information than the whole-body measurements of weight, height, and the derived parameter, body mass index. Bioelectrical impedance analysis (BIA) is a widely used method to estimate body composition. The technology is relatively simple, quick, and noninvasive. The porpose of this study was to determine the body composition changes of 11-days clinic-based weight management program. SUBJECTS AND METHODS: For a period of two years (2004-2005) we studied 519 overweight and obese women (BMI, X ±SD, 32,94 ±6,51 kg/m2). The diagnostic protocol included antropometric data, body composition analyse with Tanita ® leg-to-leg BIA system (model TBF – 300A), blood analysis, cardiological, dietological and physiotherapeutical specialist consult. All of patients keep to a low-calory diet, intensive everyday exercise and physioterapy procedures. The lectures course included of basis nutrition, healthy eathing, long-term exercise programm. RESULTS: Weight loss for the group was 2.57 kg. The fat-mass loss was 1.25 kg, free-fat mass was also decrease 1.31 kg. Reductions in circumferenses of waist and hip for the group was 3.9 cm and 3.09 cm respectively. Basal metabolic rate was significantly reduced (p < 0.001). Patients had improved some components (total cholesterol, HDL cholesterol, fasting glucose, blood pressure). CONCLUSION: These results support the field use of BIA for estimating changes in fat mass as it is simple to use, requires minimal training and is used across a spectrum of ages, body weights, and disease states. Keywords: bioelectrical impedance analysis, body composition, fat mass Bioelectrical impedance analysis (BIA) was developed in the 1960s and has emerged as one of the most popular methods for estimating relative body fat [1–3]. BIA is relatively simple, quick, portable and noninvasive and is currently used in diverse settings, including private clinicians’ offices, wellness centers and hospitals [4]. Òhe technology actually determines the electrical impedance of body tissues, which provides an estimate of total body water (TBW). Using these values of TBW derived from BIA, fat-free mass (FFM) and body fat may then be estimated. BIA measures the opposition of body tissues to the flow of a small (less than 1 mA) alternating current. Impedance is a function of two components (vectors): the resistance of the tissues themselves, and the additional opposition (reactance) due to the capacitance of membranes, tissue interfaces, and nonionic tissues [5]. The standard error of estimate (SEE) or prediction error for BIA is about 3.5% [3]. There is still debate over whether or not BIA accurately predicts changes in body composition during a weight loss program [6]. Published studies are mixed, with some supporting the accuracy of BIA in detecting FFM and body composition changes [7–9], while others claim there is substantial over- or under-estimation when compared to the underwater weighing method [10 –15]. Standardization of the procedures used to obtain BIA measurements is essential to provide meaningful estimates of TBW or fatness. In principle, BIA would appear to have many advantages in collecting these body composition parameters. Measurement of impedance is precise, consistent, easy to obtain, portable, and relatively inexpensive [5]. Single frequency BIA (SF-BIA), generally at 50 kHz, is passed between surface electrodes placed on foot-to-foot, hand-to-hand or hand-to-foot electrodes [16, 17]. Nuñez et al [18] evaluated a single-frequency 50-kHz leg-to-leg BIA system combined with a digital scale that uses stainless steel pressure-contact foot pad electrodes. This leg-to-leg BIA system is functionally different from other BIA systems, which require the use of arm and leg electrodes and separate measurement of body weight. Data from Nuñez et al [18] indicated that pressure-contact electrodes provided impedance measurements and body-composition stimates that were comparable with those obtained with use of conventional gel electrodes, and offered the advantage of increased speed and ease of measurement. In most studies evaluating the use of BIA in monitoring changes in the body composition of obese subjects, subject numbers were small, very-low-energy diets were used, and changes in fat-free mass were below the SEE of the BIA 187 Shishkova A., P. Petrova*, À. Tînev ... method [10–14, 19-23]. In no studies were subjects randomly assigned to moderate energy restriction, exercise and physiotherapeutical procedures as is typical in multicomponent clinic-based weight-management programs. This study had 2 objectives: to determine the validity of the leg-to-leg BIA system in 1) estimating body composition in obese and overweight man and women and 2) assessing changes in body composition in these patients after 2 wk multicomponent clinic-based weight-management programs. In addition, standardized testing procedures must be followed. Although the relative redictive accuracy of the BIA method is similar to that of the skinfold method, BIA may be preferable for the following reasons: (a) the method does not require a high degree of technical skill, (b) the method is more comfortable and less intrusive for the client, and (c) this method can be used to estimate body composition of obese individuals (31). Recently, less expensive, segmental bioimpedance analyzers have been marketed. The Tanita® analyzer measures lower-body resistance between the right and left legs as the individual stands on the electrode plates of the analyzer MATERIALS AND METHODS Subjects and Research Design Overweight and obese women (n = 519) with no overt disease were take part of weight management program. Subjects were recruited according to these selection criteria obtained from a pre-study medical history questionnaire: 1) in good health and with no known diseases including cancer, diabetes and coronary heart disease, 2) pre-menopausal women, 3) a body mass index (BMI) between 25 and 55 kg/m2, 5) not currently on a weight loss diet and weight stable within 5% of body weight over the past year, 6) less than 30 minutes of moderate-to-vigorous exercise a day and 7) not experiencing any pain that would interfere with full participation. All subjects were prescribed an energy-restriction diet, exercise program and physiotherapeutical procedures for 2 weeks, with body composition and nutrient intake measured pre-study and after week 2. Laboratory Procedures After an overnight fast, subjects came from hotel to the laboratory (~ 200m) at 8,30 AM. For determination of blood parameters, blood was drawn via an antecubital vein into a serum tube or in a tube filled with EDTA. Laboratory parameters: hemoglobin, blood glucose levels, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, were determined in a certified laboratory using standard methods. Anthropometry Height and weight was obtained using a mobile combinat stadiometer-digital balance (model 225; Seca, Hamburg, Germany). Fat distribution was investigated by measuring 188 the waist and hip circumference and calculating the waist to hip ratio (WHR). The waist circumference was measured at the smallest circumference between the rib cage and the iliac crest with the subject standing. The hip circumference was measured at the widest circumference between the waist and the thighs. The WHR was calculated by dividing the waist circumference by the hip circumference. Body composition In the first day of the weight management program, and the last week of the 2-wk study, the body composition of all obese subjects were assessed. In order to ensure the predictive accuracy of these equations, clients must strictly follow each of the BIA Testing Guidelines. Before testing, subjects were required to adhere to these BIA testing guidelines (3): 1) to not eat or drink within 4 h of the test, 2) to maintain normal body hydration, 3) to not consume caffeine or alcohol within 12 h of the test, 4) to not exercise within 12 h of the test, 5) to not take diuretics within 7 d of the test, 6) to urinate within 30 min of the test, and 7) No testing of female clients who perceive they are retaining water during that stage of their menstrual cycle [24]. BIA measurements were taken by using the Tanita ® leg-to-leg BIA system (model TBF – 300A). The Tanita® analyzer measures lower-body resistance between the right and left legs as the individual stands on the electrode plates of the analyzer. Subjects were measured while standing erect, in bare feet, on the analyzer’s footpads and wearing either a swimsuit or undergarments. The system’s 2 electrodes are in the form of stainless steel foot pads. Leg-to-leg impedance and body mass are simultaneously measured as the subject’s bare feet make pressure contact with the electrodes and digital scale. The body fat monitor/analyzer automatically measures weight and then impedance. Computer software (a microprocessor) imbeded in the product uses the measured impedance, the subject’s gender, height, fitness level, and in some cases age, (which have been preprogrammed), and the weight to determine body fat percentage based on equation formulas. Through multiple regression analysis, Tanita has derived standart formulas to determine body fat persentage. Tanita’s equations are generaluzed for standard adults and athletes. Specialist consultation Cardiological consultation. The nurse make the standart cardiogram and after that, patient visit the cardiologist. Cardiologist examine cardiovascular fitness, blood pressure, puls, give an interpretation to cardiogram. Seated blood pressure was measured in duplicate after 10 minutes of rest, 2 to 3 minutes apart. If the readings differed by 4 mm Hg or higher, then a third reading was taken. Extreme blood pressures were confirmed on a subsequent visit. Physiotherapy consultation. Physiotherapist examine the health status, especially condition of the articulations, joints pain and movement, also skin status and other diseases. Specialist determine the contraindication for physiotherapy and prescribe some Analysis of body composition using bioimpedance (BIA) data physical procedures, like anticellulitis massage, termotherapy, electrotherapy, underwater massage, ets. Dietology consultation. All of patients have the conversation with dietologist. Specialist determine the daily feeding, nutrition status, basal metabolic rate and give the recommendation for diet at home. Dietologist have a talk with group above the basis of nutrition and dietetics. behavioral principles to modify eating patterns, to initiate and/or continue moderate exercise and to increase the activities of daily living were introduced. Several daily educational classes (e.g., emotional eating, stress management, mood management, time management, maintaining behavioral changes), and optional support groups and individual therapy were provided. Energy-Restriction Diet Each subject’s basal metabolic rate (BMR) was estimated automaticaly using the Tanita ® leg-to-leg BIA system (model TBF – 300A). Obese subjects were prescribed a 1000–1200 kcal/d diet for 2 wk. The dietary menu was based on National dietary recommendations (Bulgaria). The goal of the intervention was a weight loss of 0.5–1.0 kg/week. Caloric intake was restricted using a balanced diet (~ 50% carbohydrates, ~ 30% protein, 20–60 g fat/day). A minimum volume intake of at least 2 l was suggested using 1,5 l mineral water or 0,5 l herbal tea with soft diuretic and laxative effect as beverage. Intentional weight loss was controlled by weight control and by bioelectric impedance analysis at indicated times. Caloric intake restriction was supported by a behavioural program, which consisted of group sessions. Training program In addition to weight management program, patients underwent a regular training program, which was performed every day per week at a level of 60–80% of their initial heart rate reserve. The patients arranges in 2 training groups according to intensity and difficulty of exercise. The exercise routine consisted of 20 min of morning gymnastics, 30 min complex of curative aerobic gimnastic, 60 – 90 min outdoor walking or jogging (terenkur), aqua-aerobic exercises in swimming pool with mineral water (25 min), individual analytic training (up to 60 min), cycle ergometry (60 W, up to 30 min) and dance teaching (up to 120 min). Patients wore the pedometer (Tanita ®) every day of study and daily distance was recorded in an exercise log. A trained exercise physiologist supervised all exercise sessions, and performed random checks of heart rate. Each exercise session was supervised to ensure correct technique and to monitor the appropriate amount of exercise and rest intervals. No injuries or complications were reported from the exercise testing and training program. Physiotherapy program All of patint’s are prescription for some procedures after the physiotherapy consultation and assessment of health status. Everyday are followed procedures: manual massage of the targeted zones with anticellulitic cream (15 min.), underwater massage (20 min.), electrotherapy procedure (30 to 45 min.), phytotherapy – tea with appetite-depressing and light diuretic effect. Behavior modification The behavioral component of the intervention was based on the principles and processes of the National Recommendation For Healty Lifestyle (Bulgaria). Motivational and RESULTS Subjects complying with all aspects of the study design included 519 overweight and obese women. Baseline characteristics of subjects enrolled in the trial are shown in Table ¹1. Table ¹1 present the mean value, standart deviation and range of values in pre-intervention study. Òable ¹. Subject characteristics (n = 519) Subject Characteristics Mean ±SD Range Age (years) 42.66 ±10.87 22 - 62 Height (m) 162.20 ±5.81 147 - 173 Weight (kg) 86,74 ±17,46 58,00 - 140.8 Body mass index (kg/m2) 32,94 ±6,51 25,10 - 54,90 BMR (kcal) 1565,15 ±187,78 1244 - 2151 BMR (kJ) 6520,72 ±670,55 5249 - 8001 505 ±66 345 - 750 Fat mass (%) 41,25 ±4,86 31,30 - 51,50 Fat mass (kg) 36,47 ±11,33 19,40 - 70.5 Fat-free mass (kg) 50,25 ±6,83 38,6 - 77 Waist circumference (cm) 94,28 ±12,56 77 - 129 Hip circumference (cm) 116,33 ±11,94 98 - 156 0,81 ±0,06 0,64 - 0,95 Impedance (ohms) WHT Table 2. Weight and antropometric changes from baseline to post-intervention in a study group (n = 519). Subject Characteristics Baseline (SD) Post (SD) Difference Weight (kg) 86,74 (17,46) 84,18 (16,73) - 2,57 Body mass index (kg/m2) 32,94 (6,51) 31,93 (6,30) - 1,00 Waist circumference (cm) 94,28 (12,56) 90,38 (12,83) - 3,90 Hip circumference 116,33 (11,94) 113,23 (11,74) (cm) - 3,09 Waist-to-hip ratio - 0,02 0,81 (0,06) 0,79 (0,14) 189 Shishkova A., P. Petrova*, À. Tînev ... Weight and antropometric changes was significantly decrease, weight loss was 2.57 kg (3% of total average group weight for 2 wk). The results of body composition change are presented in Table ¹3. Mean body mass decrease was 2.57 kg with free fat mass accounting for about 51% of this change. This is adequat result after the first 2 wk of intensive weight reduction program, becàuse a main loss is total water in the body 0.96 kg (73% of reduced free fat mass). The content of fat mass is reduced with 1.25 kg on the average (49% of the reduced tissues). In the end of intervention basal metabolic rate was decråàse. Table 3. Body composition changes from baseline to post-intervention in a study group using the Tanita® analyzer (n = 519). Subject Characteristics Baseline Post Difference Fat mass (%) 41,25 (4,86) 41,06 (5,19) - 0,19 Fat mass (kg) 36,47 (6,83) 35,22 (11,48) - 1,25 Fat-free mass (kg) 50,25 (6,83) 48,94 (5,84) - 1,31 Total body water (kg) 36,78 (5,00) 35,82 (4,28) - 0,96 6. 7. 8. 9. 10. BMR (kcal) 1565,15(187,78) 1547,37 (176,57) - 17,79 BMR (kJ) 6520,72 (670,55) 6459,64 (661,73) - 61,09 CONCLUSION These results support the field use of BIA for estimating changes in fat mass as it is simple to use, requires minimal training and is used across a spectrum of ages, body weights, and disease states. 11. 12. 13. 14. REFERENCES 1. 2. 3. 4. 5. National Institutes of Health Technology Assessment Conference Statement: Bioelectrical impedance analysis in body composition measurement. Am J Clin Nutr 64(Suppl):524S–532S, 1996. Heymsfield SB, Wang QM, Visser M, Gallagher D, Pierson RN: Techniques used in the measurement of body composition: An overview with emphasis on bioelectrical impedance analysis. Am J Clin Nutr 64(Suppl):478S–484S, 1996. Heyward VH, Stolarczyk LM: “Applied Body Composition Assessment.” Champaign, IL: Human Kinetics, 1996. Leslie A. Powell, MA, RD, Da vid C. Nieman . Assessment of Body Composition Change in a Community-Based Weight Management Program. Journal of the American College of Nutrition, Vol. 20, No. 1, 26–31 (2001) NIH Consensus statement. Bioelectrical impedance analysis in body composition measurement. National 190 15. 16. 17. 18. Institutes of Health Technology Assessment Conference Statement. December 12-14, 1994. Nutrition 1996 Nov-Dec; 12(11-12):749-62. Heyward VH: Evaluation of body composition: current issues. Sports Med 22:146–156, 1996 Ev ans EM, Saunders MJ, Spano MA, Arngrimmson SA, Lewis RD, Cureton KJ: Body-composition changes with diet and exercise in obese women: a comparison of estimates from clinical methods and a 4-component model. Am J Clin Nutr 70:5–12, 1999. Ross R, Legar L, Marin P, Roy R: Sensitivity of bioelectrical impedance to detect changes in human body composition. J Appl Physiol 67:1643–1648, 1989. Kushner RF, Kunigk A, Alspaugh M, Andronis PT, Leitch CA, Schoeller DA: Validation of bioelectrical impedance analysis as a measurement of change in body composition in obesity. Am J Clin Nutr 52:219–223, 1990. Deurenberg P, Westrate JA, van der Kooy K: Body composition changes assessed by bioelectrical impedance measurements. Am J Clin Nutr 49:401–443, 1989. Van der Kooy K, Leenen R, Deurenberg P, Seidell JC, Westerterp KR, Hautvast JG: Changes in fat-free mass in obese subjects after weight loss: a comparison of body composition measures. Int J Obes 16:675–683, 1992. Vazquez JA, Janosky JE: Validity of bioelectrical-impedance analysis in measuring changes in lean body mass during weight reduction. Am J Clin Nutr 54:970–975, 1991. Carella MJ, Rodgers CD, An der son D, Gossain VV: Serial measurements of body composition in obese subjects during a verylow-energy diet (VLED) comparing bioelectrical impedance with hydrodensitometry. Obes Res 5:250–256, 1997. Hendel HW, Gotfredsen A, Hojgaard L, Andersen T, Hilsted J: Change in fat-free mass assessed by bioelectrical impedance, total body potassium and dual X-ray absorptiometry during prolonged weight loss. Scand J Clin Lab Invest 56:671–679, 1996. Bumgartner RN, Ross R, Heymsfield SB: Does adipose tissue influence bioelectric impedance in obese men and women? J Appl Physiol 84:257–262, 1998. Heyward VH: Evaluation of body composition: current issues. Sports Med 22:146–156, 1996. Jebb SA, Cole TJ, Doman D, Murgatroyd PR, Prentice AM. Evaluation of the novel Tanita body-fat analyser to measure body composition by comparison with a four-compartment model. Brit J Nutr 2000;83:115–22. Ut ter AC, Nieman DC, Ward AN, Butterworth DE. Use of the leg-to-leg bioelectrical impedance method in assessing body-composition change in obese women. Am J Clin Nutr 1999;69:603–7. Nuñez C, Gallagher D, Visser M, Pi-Sunyer FX, Wang Z, Heymsfield SB. Bioimpedance analysis: evaluation of leg-to-leg system based on Analysis of body composition using bioimpedance (BIA) data pressure contact foot-pad electrodes. Med Sci Sports Exerc 1997;29:524–31. 19. Kotler DP, Burastero S, Wang J, Pierson RN. Prediction of body cell mass, fat-free mass, and total body water with bioelectrical impedance analysis: effects of race, sex, and disease. Am J Clin Nutr 1996;64(suppl):489S–97S. 20. Houtkooper LB, Lohman TG, Go ing SB, Howell WH. Why bioelectrical impedance analysis should be used for estimating adiposity. Am J Clin Nutr 1996;64(suppl):436S–48S. 21. Lukaski HC. Methods for the assessment of human body composition: traditional and new. Am J Clin Nutr 1987;46:537–56. 22. Segal KR, Van Loan M, Fitz ger ald PF, Hodgdon JA, Van Itallie TB. Lean body mass estimation by bioelectrical impedance: a four-site cross-validation study. Am J Clin Nutr 1988;47:7–14. 23. Kushner RF, Schoeller DA. Estimation of total body water in bioelectrical impedance analysis. Am J Clin Nutr 1986;44:417–24. 24. Heyward V. Asep methods recommendation: body composition assessment. JEPonline. 2001;4(4):1-12. 25. Brozek J, Grande F, An der son JT, Kemp A. Densitometric analysis of body composition: revision of some quantitative assumptions. Ann N Y Acad Sci 1963;110:113–40. 191 AUTHOR'S INDEX Bachvarova R. .................165 Bachvarova S...................165 Bahlova P. .......................187 Balev B. ...........................137 Bekyarova G....................117 Bohchelian H...................145 Bontchev G......................121 Bontcheva S.....................121 Burulianova I...................171, 175 Chakalova V. ...................165 Deenichin G.....................141 Dimov R. .........................141 Dokov V. .........................171 Dokov W. V.....................177 Dokova K. .......................111 Drumeva P.......................165 Dyakov Sv. ......................145 Feschieva N. ....................111 Hinev A. ..........................145 Hristov D. ........................137 Hristova M.......................117 Hristozov K. ....................145 Ignatov V.........................137 Iliev G..............................187 Ilnev A.............................187 Iovcheva M......................179 Ivanov K..........................137 Ivanova F.........................133 Kalchev E. .......................187 Kerekovska A. .................111 Kolev N. ..........................137 Konstantinova V..............171, 175 Konsulova S. ...................137 Madjov. R........................137 Marev D...........................149 Margaritova V. ................183 Marinov M.......................117, 125 Marinov P........................179 Mirchev K. ......................117 Molov V. .........................141 Nedev P. ..........................153 Petrova P. ........................187 Platikanov V....................145 Racheva S. .......................167 Radev R. Zl......................117 Radoinova D....................175 Romanova H....................129 Shishkova A. ...................187 Siderova M. .....................145 Softov Ogn. .....................187 Stefanov Ch. ....................141 Stoyanov Zl. ....................125 Tonchev T. ......................157, 161 Tonev A...........................137 Usheva N. ........................111 Zlateva S..........................179 PERMUTERM SUBJECT INDEX abscess, liver, CT, ultrasound, percutaneous drainage_________________________________137 abscess, tonsillectomy, postoperative haemorrhage _____________________________149 acute intoxication, organophosphorus pesticide, lethality _________________________179 anxiety, chronic skin disease, depression, Hospital Anxiety and Depression Scale, co-morbidity _____________________________165 anxiety, stress, sex ________________________125 Binder syndrome, maxillo-nasal dysplasia, nasomaxillary hypoplasia ___________________153 bioelectrical impedance analysis, body composition, fat mass ______________________187 biophysics, quality of education, pedagogical analysis _______________________121 body composition, bioelectrical impedance analysis, fat mass _________________________187 chronic skin disease, anxiety, depression, Hospital Anxiety and Depression Scale, co-morbidity _____________________________165 Chronic Urticaria, Physical Urticaria, Cholinergic Urticaria, Non-allergic Urticaria, delayed pressure urticaria, cold urticaria, solar urticaria ________________167 clinical case, new education technique, pathophysiology __________________________117 Colon, Synchronous malignant tumors ________141 diabetes mellitus, emphysematous pyelonephritis, ketoacidosis, ultrasound ________145 disaster medicine, protection in case of disastrous situations _______________________129 Electro-traumatism, Varna District __________177 emphysematous pyelonephritis, diabetes mellitus, ketoacidosis, ultrasound _____________145 health status, social determinants, policy implications, Bulgaria ______________________111 lacrimal gland tumors, orbital tumors, coronal approach, lateral orbitotomy __________161 liver, abscess, CT, ultrasound, percutaneous drainage______________________137 maxillo-nasal dysplasia, Binder syndrome, nasomaxillary hypoplasia ___________________153 new education technique, clinical case, pathophysiology __________________________117 Orbit, Surgery, Frontoethmoidal mucocele, Coronal approach, Reduction, Obliteration _____157 organophosphorus pesticide, acute intoxication, lethality _________________________________179 orbital tumors, lacrimal gland tumors, coronal approach, lateral orbitotomy _________________161 Physical Urticaria, Chronic Urticaria, Cholinergic Urticaria, Non-allergic Urticaria, delayed pressure urticaria, cold urticaria, solar urticaria _________167 protection in case of disastrous situations, disaster medicine__________________________129 Psychological preparation, psychological readiness, training ________________________183 psychological readiness, Psychological preparation, training _______________________183 quality of education, biophysics, pedagogical analysis _______________________121 social determinants, health status, policy implications, Bulgaria ______________________111 stress, anxiety, sex ________________________125 Surgery, Orbit, Frontoethmoidal mucocele, Coronal approach, Reduction, Obliteration _____157 Synchronous malignant tumors, Colon _______141 tonsillectomy, abscess, postoperative haemorrhage _____________________________149 Varna District, Electro-traumatism, __________177 INSTRUCTIONS TO AUTHORS Scripta Scientifica Medica is the official publication of Medical University Prof. Dr. Paraskev Stoyanov, Varna, Bulgaria. It is currently disseminated among medical university libraries from all over the world on exchange basis. This peer-reviewed annual accepts for publication original articles, unpublished papers recently presented at national and international congress proceedings, and book reviews from Bulgarian and foreign authors. The contributions should be devoted to actual topics in contemporary biomedicine, clinical medicine and interdisciplinary fields as well. They should not have been submitted or accepted for publication elsewhere. The journal publication is offered to the national and international readership in English only. The manuscript signed by all the authors has to be submitted in duplicate to the Editor-in-Chief of Scripta Scientifica Medica: Prof. Anelia Klisarova, MD, PhD, DSc Medical University Prof. Dr. Paraskev Stoyanov, Varna 55 Marin Drinov Street BG-9002 Varna Bulgaria Phone: +359-52- 611 899 Fax: +359-52- 650 019 E-mail: scripta@mu-varna.bg The contributors are encouraged to submit the files of the text and figures of their revised manuscripts on a 3,5”-diskette in any recent MS Word format. The authors must strictly follow some main instructions listed below. The manuscript of an original paper should not exceed 7 double-spaced pages with wide margins. The total volume of the text, tables, and references should not exceed 15000 characters. The structure of the article should include the following sections: Introduction, Material and Methods, Results and Discussion, and Conclusion(s). Additionally, there should be: a structured abstract of 200-250 words; key-words (5 to 6 words or non-verbal phrases); a reference list (up to 20 references); a complete address of the author for correspondence (postal and e-mail address, if available), and, eventually, an appropriate number of tables and figures. The tables and legends to the figures should be provided on separate sheets. Data sheets of diagrams should be obligatorily provided. Location of tables and figures should be indicated in the text and on the left margin of the corresponding page. No data reiteration in the text, tables, and figures is permitted. Photographs and microphotographs have to be sufficiently contrasted and up to 12x18 cm in size. Black-and-white pictures, drawings and diagrams are accepted only. Cited authors are ordered alphabetically in the reference list starting with those in the Cyrillic alphabet. Most commonly, these authors should be identified in the text of the article by Arabic numerals in parentheses. Please, do not make use of CapsLock option at all. PREPARATION OF REFERENCES Numbering of all the publications cited in the text should correspond to that in the list of references. Bibliographic citations of articles in journals should contain initials and names of all the authors (or at least the first six ones), article title, abbreviated title of the journal according to the style used in Index Medicus (National Library of Medicine, Bethesda, MD, USA), volume, year of publication, issue number (absolutely obligatory for Bulgarian and Russian journals), and page numbers (from-till). The citations of books should contain initials and names of the authors (up to three), book title, number of edition (if any), editor(s) (if any), location of publishing, publishing house and year of publication. Book chapters should contain initials and names of the authors of the chapter, title of the whole book, editor(s) (if any), location of publishing, publishing house, year of publication and page numbers (from-till). Congress proceedings should contain along with data as for book chapters, location and date of the corresponding meeting, kind of materials (abstracts or full papers), and page numbers. Author’s name of the dissertation, title, location, institution, and year of defence should be indicated. With patents and licences, author’s names (if any), registration number, and year of publication should be shown. Personal communications containing the name of the author cited and the date should be accompanied by his (her) permission in written for the corresponding statement. Let us give some examples. 1. 2. 3. Biderman, I., S. Somien, Z. Shimshoni. In: Tissue Nutrition and Viability. A. R. Hargens, ed. New York, etc., Springer-Verlag, 1986, 121-134. Goute, A. M., A. R. Haynes, M. J. Owen. New aspects of psychotic drug usage.- J. Clin. Psychopharmacol., 8, 1988, No 4, 315-317. Youmans, G. P., A. N. Lewin. Tuberculosis. 3rd ed. Philadelphia, etc., W. W. Saunders, 1979. The authors will receive 25 reprints of their articles along with a sample copy of the issue free of charge. SCRIPTA SCIENTIFICA MEDICA, VOL. XXXX Editor-in-Chief: Prof. Anelia Klisarova, MD, PhD, DSc Co-Editor-in-Chief: Assoc. Prof. Rossen Madjov, MD, PhD Cover art editor: E. Spasov Technical editor: A. Antonov Proof-reader: Assoc. Prof. Rossen Madjov, MD, PhD Publ. Lit. group: III-3 Sent to printers: August, 2007 Print sheets: 23 Format: 8/60x84 Approved for printing: March, 2007 Total print: 300 ISSN 0582-3250 Med i cal Uni ver sity 55 Marin Drinov Street, Varna, BG-9002