acta facultatis medicae naissensis

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ACTA FAC MED NAISS
YU ISSN 0351-6083
Volume 24 / 2007 / No
2
ACTA
FACULTATIS
MEDICAE
NAISSENSIS
MEDICINSKI FAKULTET
UNIVERZITETA U NIŠU
Bul. dr Zorana Đinđića br. 81, Niš
Faculty of Medicine
University of Nis
Nis, 81 Dr Zoran Djindjic Blvd.
Scientific Journal ACTA FACULTATIS MEDICAE NAISSENSIS The Faculty of Medicine, Nis
Naučni časopis Medicinskog fakulteta,
Univerziteta u Nišu
Scientific Journal of the Faculty of Medicine,
University of Nis
ACTA FACULTATIS MEDICAE NAISSENSIS
Dekan Medicinskog fakulteta u Nišu
Prof. dr Milan Višnjić
Niš, Dr Zorana Đinđića 81
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Telefon 018/ 226 712, Fax 018/ 238 770
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Professor Milan Višnjić MD
Serbia, 18000 Nis
Phone +381 18 226 712, Fax +381 18 238 770
IZDAVAČKI SAVET
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Janković Momčilo, Milan
Janković Slobodan, Kragujevac
Jovanović Dušan, Sremska Kamenica
Jovanović Sergije, Berlin
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EDITORIAL COUNCIL
Chairman
Professor Milan Višnjić MD
Lass Piotr, Gdansk
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UREĐIVAČKI ODBOR
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Proofreading
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graduated philologist in Serbian language and literature
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graduated philologist in English language and literature
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Published by the Faculty of Medicine,
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Printed by GIP "PUNTA" - Nis, Serbia
www.medfak.ni.ac.yu / Acta facultatis
ACTA FAC MED NAISS
YU ISSN 0351-6083
Volume 24 / 2007 / No
2
ACTA
FACULTATIS
MEDICAE
NAISSENSIS
MEDICINSKI FAKULTET
UNIVERZITETA U NIŠU
Bul. dr Zorana Đinđića br. 81, Niš
Faculty of Medicine
University of Nis
Scientific Journal ACTA FACULTATIS MEDICAE NAISSENSIS the Faculty of Medicine, Nis
Štampanje časopisa Acta Facultatis Medicae Naissensis tokom 2007. godine pomoglo je Ministarstvo za nauku i zaštitu životne sredine Republike Srbije.
The publication of the Journal Acta Facultatis Medicae Naissensis in 2007 was provided thanks to cofinancing of the Ministry of Science and Environmental Protection of Republic of Serbia.
ACTA FAC MED NAISS
UDC 616.314-089.28
Professional article
ACTA FAC MED NAISS 2007; 24 (2): 53-58
1
Cezary Kłosiński
1
Anna Lasecka
2
Dariusz Świetlik
1
Department of Prosthodontic
Dentistry, Medical University,
Gdańsk, Poland
2
Laboratory of Medical Informatics
and Neural Networks,
Medical University, Gdańsk, Poland
BRIDGES MADE OF COMPOSITES
REINFORCED WITH GLASS FIBRE,
ANCHORED ON ABUTMENT TEETH
WITH CROWN INLAYS – SELECTED
CASES
SUMMARY
The usage of traditional bridges in the treatment of single dental gaps
requires considerable grinding of the abutment teeth that should be protected
with prosthetic crowns. An alternative to traditional bridges in the treatment of
patients with single dental gaps can be fixed restorations, where crown inlays
connect the pontic with abutment teeth.
The aim of this study was to present an alternative method of treatment
of single dental gaps with composite bridges reinforced with glass fibres,
supported by selected clinical cases. The restorations were performed with
composites reinforced with glass fibres: Targis/Vectris, Sinfony/StickTM,
Sculpture/FibreKor. While preparing the abutment teeth, the existing fillings or
cavities adjacent to the toothless gap were used to make crown inlays as
retention elements for the bridges.
Based on the treatment conducted and the literature, it is possible to
affirm that bridges anchored with inlays on a glass fibre foundation are a very
good alternative to conventional restorations in the selected cases.
Key words: bridge, inlay, fibreglass
INTRODUCTION
Single dental gaps allow physicians to use
different kinds of prosthetic restorations. Modern
prosthetics proposes implants as restorations the
least invasive to the teeth surrounding the gap.
However, the numerous contraindications, high cost,
as well as fear of surgery do not always permit their
use. Conventional bridges commonly used in the
treatment of single dental gaps require considerable
grinding of abutment teeth which is not harmless to
the prepared teeth, and the most frequent problems
encountered are: caries (18%) and the need for
endodontic treatment (11%) (1). Moreover, aesthetic
concerns lead to the usage of subgingival crowns as
retention elements of bridges, which is associated
with the possibility of paradontium damage (2).
Corresponding author • E-mail: cezary.klosinski@op.pl
Well-known adhesive metal restorations
with retention elements such as pins and wings have
been used quite cautiously especially as restorations
of side teeth, although clinical investigations have
shown a high degree of success. They assured
economical preparation of dental tissues, but the
aesthetic effect was not fully satisfactory. Moreover,
the connection of bridges stuck on a metal
foundation with tooth tissues caused the appearance
of two boundary layers (metal-composite and
composite-tooth), which increased the risk of these
restorations getting unstuck and of the development
of secondary caries. An alternative to traditional
bridges in the treatment of patients with single dental
gaps are fixed restorations, where crown inlays
connect the pontic with abutment teeth. This type of
prosthetic reconstruction creates the possibility of
economical preparation of abutment teeth as well as
53
Cezary Kłosiński, Anna Lasecka, Dariusz Świetlik
permits to utilize existing fillings or cavities in dental
hard tissues (3).
The possibility of irreversible damage to
abutment teeth pulp is smaller in comparison to
conventional bridges (4). Bridges made of noble
alloys as well as metal-ceramic ones, anchored by
means of crown inlays, have been successfully used
(5-7). The most often observed damages occurred
between the metal and opaque ceramics. The
presence of a metal frame is associated with the
possibility of allergies as well as toxic effects of
metal ions produced as a result of corrosion (8).
Symptoms such as xerostomia, burning sensation in
the mucous membrane, altered taste, pain,
parodontal diseases, osteonecrosis and soft tissues
necrosis have been observed.
The development of materials technology
and technological processes is directed towards
restorations without a metal foundation, thus there
have been attempts at using modern ceramics for the
construction of bridges anchored by means of inlays.
However, the usage of certain ceramics, due to their
insufficient durability, is still limited in the posterior
section of the dental arch (6). Restorations on a
zirconium oxide foundation are recently becoming
more and more popular. In vitro investigations have
proven this type of bridges anchored with crown
inlays to be highly durable, which gives reason for
optimism, yet has to be confirmed in clinical
observations (6).
In the 1990s, composite materials reinforced
with glass fibre were introduced to the market. The
characteristic features of these materials are: high
tensile strength and crushing strength and flexibility
module similar to dentine, which permits to make
prosthetic restorations with a capacity for damping
and absorption of mechanical stresses (6). Moreover,
these materials are available in several colours and
are characterized by light conductivity particularly
beneficial in adhesive cementation with the so-called
dual cements.
The structure of fibres can be one-way (all
fibres arranged parallel to each other) or in the form
of heterogeneous weaves. The glass fibres used in
constructions of bridges anchored on abutment teeth
with inlays are one-way fibres pre-proofed with
resin. In vitro investigations have shown a higher
deflection strength of composites reinforced with
one-way glass fibres in comparison to glass fibres in
the form of weaves and polyethylene fibres that are
used in dentistry, too (9,10). The endurance of a
construction reinforced with glass fibres is greater
for one-way fibres arranged perpendicularly to
emerging forces, particularly when the layer of glass
fibre is located in the lower part of the bridge pontic,
namely in the layer subject to tension.
54
Ceromers used for facing are marked by low
water absorption, abrasion approximate to enamel
and fluorescence, permitting to achieve a successful
aesthetic effect. The usage of adhesive cements for
fastening bridges anchored on abutment teeth by
means of crown inlays has assured a perfect
connection of those bridges with tooth tissues.
However, one should remember that crown inlays
are a weaker kind of retention elements for bridges
than crowns and, therefore, their usage should be
limited to the reproduction of single dental gaps.
Moreover, the usage of bridges anchored on
abutment teeth by means of crown inlays is
contraindicated in cases of high susceptibility to
caries, too extensive damage to dental crown, dead
teeth, short dental crown and too thin walls
surrounding the gap (the possibility of preparation
under the inlay after lowering of approximately 2mm
of bumps). The relative contraindications to using
bridges anchored on dental pillars by means of crown
inlays are: the inability of making a sufficient pit,
presence of all-ceramic or metal-ceramic restorations as antagonists and advanced bruxism.
Hebr. et al. observed 72 % survivability of
these restorations after 3 years of observation. After
4 years, Freilich et al. observed 75 % of success and
an increase of survivability to 86 % after enlarging
the quantity of fibres (11). Other studies have shown
86% of success after 2 years of usage of restorations.
Göhring et al. described the longest observation time
(5 years) and they presented 71 % of success. The
most frequent damage was the separation of layers
from the facing material, connected with overestimated loading strength of the facing material (3). The
author assesses boundary leak tightness as satisfactory. He observed an insignificant deterioration of leak
tightness after a year of usage of the restorations,
while in the next years he did not find any significant
change. There have also been changes rather
associated with the facing material, such as change of
colour and gloss of the composite used. Even though
the restorations presented are not free from defects,
the slight reduction of dental tissues, satisfactory
appearance and easiness of repair are the incentives
to use them.
The aim of this study was to present three
selected cases of prosthetic treatment of patients with
single dental gaps by means of composite bridges on
a glass fibre foundation as an alternative method of
treatment of single gaps in the side section: Targis/Vectris (Ivoclar Vivadent, Sweden), Sinfony (3M
ESPE, USA)/StickTM (Stick Tech Ltd, Finland) and
Sculpture/FibreKor (Jeneric/Pentron, Germany).
The restorations were bonded adhesively with
Variolink II (Ivoclar Vivadent, Sweden) or Calibra
cement (DENTSPLY DeTry Gmbh, Germany).
Bridges Made of Composites Reinforced with Glass Fibre, Anchored on Abutment Teeth with Crown Inlays – Selected Cases
MATERIAL AND METHODS
Abutment teeth were processed in accordance with the principles applicable to inlays to
assure one track of introducing the restoration and to
avoid the location of the edges of the processed
surface in the area of contact with antagonistic teeth
(9) (Figure 1). A one-step two-layer impression was
taken with Zetaplus/Oranwash L mass (Zhermack,
Italy) and KKD Kondisil mass (KKD Gmbh,
Germany).
Figure 3. Preparation of internal walls in parallel or
slightly divergently (angle between bottom and axial
wall 90ş ÷ 100º) – to obtain internal retention.
Preparation of all internal angles in a rounded way to prevent additional tensions (Figure 4).
Figure 1. Avoid the location of edges of the prepared
surface in the area of contact with antagonistic teeth
Making a pit on the occlusive surface with
dimensions dependent on the material used (Figure
2): for Vectris it was necessary to make a pit 3 mm
high, 2 mm wide and 2 mm long, while for
FibreKor/StickTM and Sinfony/StickTM Systems –
a pit of 2x2x 2mm.
Figure 4. Preparation of all internal angles
in a rounded way
Removal of undercuts by filling them with a
primer, e.g. glassionomer (Figure 5).
Figure 2. Making a pit on occlusive surface with sizes
dependent on chosen material: Targis/Vectris:
3 mm heigh, 2mm deep and 2 mm wide, and for
Sinfony/StickTM and Sculpture/FibreKor
a pit of 2 x 2 x 2mm.
Preparation of internal walls parallel to each
other or slightly divergent (the angle between the
bottom and axial wall 90° ÷ 100°) - to obtain internal
retention (Figure 3).
Figure 5. Removal of undercuts by filling them
with primer
RESULTS
Case I. The patient aged 30, arrived to have
missing tooth 25 restored (Figure 6). In tooth 26, a
55
composite MO filling was found. Tooth 24 intact.
Inlay bridge 24 x 26 was planned. Upon preparation
of the teeth according to the above-presented steps, a
one-step two-layer impression was taken with
Zetaplus/Oranwash L mass, an impression of
opposite teeth with alginate mass, check-bite
impression. The colour was chosen according to the
Chromascop key.
Case II. The patient aged 32, arrived to have
missing tooth 25 restored. In the clinical
examination, amalgam MO filling in tooth 26 was
found. Tooth 24 intact (Figure 9). A 24 x 26 inlay
bridge was planned.
Figure 6. Condition before treatment. Missing tooth 25
Figure 9. Condition before treatment. Missing tooth 25
The bridge was made from Targis/Vectris
(Figure 7).
The preparation of abutment teeth was done
(Figure 10), a one-step two-layer impression was
taken with KKD Kondisil mass, an impression of
opposite teeth with alginate mass, check-bite
impression. The colour was chosen according to the
Vita key. The restoration was made from
Sinfony/StickTM material.
Figure 7. Teeth model after preparation. Bridge from
Targis/Vectris
During the second clinical visit, after
checking the restorations, the teeth were cemented
with adhesive cement Variolink II (Figure 8).
Figure 10. Abutment teeth 24, 26 after preparation
Figure 8 Bridge 24 x 26 cemented in oral cavity
A very good aesthetic and functional effect
was obtained. The patient has now been wearing the
restoration for 3 years.
56
After a check-up of the oral cavity, the
bridge was cemented with Variolink II (Figure 11). A
very good aesthetic and functional effect was
obtained. The clinical observation was being carried
out for 2,5 years.
Case III. The patient aged 24, a student of
dentistry, arrived to have missing teeth 35 and 45
restored (Figure 12).
Bridges Made of Composites Reinforced with Glass Fibre, Anchored on Abutment Teeth with Crown Inlays – Selected Cases
After a check-up of the finished restoration
in the oral cavity, the bridges were cemented with
Calibra cement. A very good functional and aesthetic
effect was obtained as a result of the treatment,
confirmed by frequent follow-up visits and the
patient's objective assessment (Figure 14). The
period of observation was going on for 3 years.
Figure 12. Condition before treatment
The patient did not report any stomatognatic
complaints. After an analysis of the conditions in the
oral cavity, execution of bridges on a glass fibre
foundation with 34 x 36 and 44 x 46 pillars was
planned. One-step preparation of abutment teeth was
performed on both sides of the dental arch (Figure
13). A one-step two-layer impression was taken
using KKD Kondisil mass, an impression of opposite
teeth – with alginate mass, check-bite impression.
The colour was chosen according to the Vita key. The
bridges were made from Sculpture/FibreKor material.
Figure 13. Abutment teeth 34, 36, 44, 46
after preparation
Figure 14. Bridges 44 x 46 and 34 x 36 cemented
in oral cavity
DISCUSSION AND CONCLUSION
To recapitulate, it should be noted that
composite bridges on a glass fibre foundation, in
which crown inlays are the retention elements, are
aesthetic restorations of small dental gaps and favor
the prophylaxis of paradontium. Besides composite
bridges on a glass fiber, foundation assures economical grinding of abutment teeth, using existing cavities and fillings and do not require abutment teeth to
be parallel (12). Composite bridges provide the possibility of examining the vitality of abutment teeth,
can be used in patients allergic to metals and make it
possible to repair minor damages in the oral cavity.
They are characterized by a simple laboratory procedure and comparatively low treatment costs, and in
certain cases offer an alternative to conventional
prosthetic restorations.
REFERENCES
1. Goodacre C J, Bernal G, Rungcharassaeng K, Kan J
Y. Clinical complications in fixed prosthodontics. J Prosthe Dent
2003; 90: 31-41.
2. Knoernschild K L, Campbell S D. Periodontal tissue
responses after insertion of artificial crowns and fixed partial
dentures. J Prosthet Dent 2000; 84: 492-498.
3. Gőehring T N, Peters O A, Lutz F. Marginal
adaptation of inlay-retained adhesive fixed partial dentures after
mechanical and thermal stress: An in vitro study. J Prosthet Dent
2001; 86: 81-92.
4. El-Mowafy O, Rubo M H. Resin-bonded fixed
partia dentures-a literature review with presentation of novel
approach. Int J Prosthodont 2000; 13: 460-467.
5. Imbery T A, Eshelman E G. Resin-bonded fixed
partial dentures: a review of three decades of progress. J Am
DentAssoc 1996; 127: 1751-1760.
6. Mehmet A, Kiliçarslan P, Kedici S, Küçükeşmen H
C, Uludağ B C. In vitro fracture resistance of posterior metalceramic and all-ceramic inlay-retained resin-bonded partial
dentures. J Prosthetic Dent 2004; 92: 365-370.
7. Stokholm R, Isidor F. Resin-bonded inlay retainer
prostheses for posterior teeth. A 5-year clinical study. Int J
Prosthodont 1996; 9: 161-166.
8. Johansson B I. Corrosion of copper, nickel and gold
dental casting alloys: an in vitro and in vivo study. J Biomed
Mater Res 1989; 23: 349-361.
9. Serdar C H, Ozturk B. Posterior bridges retained by
resin-bonded cast metal inlay retainers: a raport of 60 cases
followed for 6 years. J Oral Rehabil 1997; 24: 697-704.
10. Dyer S R., Lippo V J, Jokkinen M, Vallitu P K.
Effect of fiber position and orientation on fracture load of fiberreinforced composite. Dental Materials 2004; 10: 947-955.
57
11. Freilich M A, Meiers J C, Duncan J P, Eckrote K A,
Goldberg A J. Clinical evaluation of fiber-reinforced fixed
bridges. JAm DentAssoc 2002; 133: 1524-1534.
12. Monaco C, Ferrari M, Miceli G P, Scotti R. Clinical
evaluation of fiber-reinfoced composite inlay FPDs. Int J
Prosthodont 2003; 16: 319-325.
KOMPOZITNI MOSTOVI OJAČANI STAKLENIM VLAKNIMA,
FIKSIRANI NA ABATMENTIMA SA
RAZLIČITIM INLEJIMA - ODABRANI SLUČAJEVI
1
1
2
Cezary Kłosiński , Anna Lasecka , Dariusz Świetlik
1
Odeljenje za zubnu protetiku, Medicinski fakultet, Gdansk, Poljska
2
Laboratorija za medicinsku informatiku i neuralne mreže,
Medicinski fakultet, Gdansk, Poljska
SAŽETAK
Upotreba tradicionalnih mostova u lečenju pojedinačnog nedostatka zuba zahteva
značajno brušenje nadomeštenih zuba, koje treba zaštititi protetičkim krunicama.
Alternativa za tradicionalne mostove u lečenju pacijenata sa pojedinačnim nedostatkom
zuba su fiksne restauracije gde krunični inleji povezuju pontične i nadomeštene zube.
Cilj studije je bio da se prikaže alternativni metod lečenja pojedinačnog
nedostatka zuba kompozitnim mostovima ojačanim staklastim vlaknima, što je i prikazano
na primeru nekoliko kliničkih slučajeva. Restauracije su urađene kompozitima ojačanim
staklenim vlaknima: Targis/Vectris, Sinfony/StickTM, Sculpture/FibreKor. U toku
pripreme nadomeštenih zuba, postojeće plombe ili šupljine koje su se nalazile pored mesta
gde je trebalo nadoknaditi zub su upotrebljene za izradu kruničnih inleja koji služe kao
retencioni elementi za mostove.
Na osnovu sprovedenog tretmana i dostupne literature, može se reći da su
poluprovodni mostovi ojačani staklenim vlaknima veoma dobra alternativa u
konvencionalnim restauracijama odabranih slučajeva.
Ključne reči: most, inlej, staklasta vlakna
58
ACTA FAC MED NAISS
UDC 616.728.2-089.84
Original article
Dusan Vlatkovic
Marko Vukovic
REVISING HIP
ARTHROPLASTY
Department of General Surgery
and Orthopaedics
General Hospital Trebinje
SUMMARY
A number of requests for revision of previously fitted prosthesis has
become often due to numerous causes and is likely to be more frequent in the
future. By an intervention we want to remove some of the complications related
to prosthetic replacement of the hip joint and its application.
The causes are often interconnected. Those are biological problems
related to prosthesis usage. We think that patient's behaviour leads to a number
of complications as well.
What you need for this intervention is an experienced team, wide range
of fitting appliances and a set of good instruments.
We replaced cement prostheses with cement ones in all but one case, and
non-cement with non-cement or cement prostheses. We conducted antithrombosis prophylaxis and put a patient on antibiotics of high dosage for four
days. Upright position was allowed depending on the general state starting from
the third to seventh day.
Key words: revising hip arthroplasty, complications of primary
arthroplasty
INTRODUCTION
Revising hip arthroplasty is the procedure of
replacements of the previously fitted hip prosthesis
for different reasons. Essentially, it means solving a
problem caused by using prosthesis (1).
Nowadays, artificial joints of the hip are
being increasingly fitted in young patients that shall
result in more and more complications as the time
passes. Even 20 years ago, more than 2,000 total hip
prostheses were fitted daily, which actually means
around 700,000 annually (2). In the USA, there are
about 250,000 fractures of the femur neck with an
estimate that, in 2050, that number would exceed
750,000 likewise in many other developed parts of
the world (3,4). It is normal to expect, having in
mind the number of patients, a considerable number
of different complications which require the revision
operation, in most cases the prosthesis replacement.
That is why the awareness on possible complications
is the first and important preventive measure.
When we are to make decision on the hip
prosthesis fitting, we should always think about
"what to do later" or take into account the opinion of
Wiliam Osler "the solution of today becomes the
problem of tomorrow" or "what is considered to be
wisdom today, it will be nonsense tomorrow". We
treated the patients with complications that require
the prosthesis replacement, i.e. rearthroplastics. That
is why we decided to analyze our modest amount of
material and present it with the basic aim to present
which complications require revision.
The aim of the paper was to present, based
on our modest experience, both the reasons for
Corresponding author. Tel: 00387 59 223 755, lok. 16 • E-mail: tbhospit@spinter.net
59
Dusan Vlatkovic, Marko Vukovic
replacement of the previously implanted hip
prosthesis and technical operation difficulties and
results.
The prosthesis aseptic loosening, as the
reason for revision hip arthroplasty, was the case in
two of our patients (Figure 2a);
We analyzed disease histories i.e. clinical
and radiological results of those patients who had
been fitted the hip prosthesis. They were revised in
three hospitals in the Eastern part of Republic of
Srpska. It total, there were 18 patients (Figure 1).
We could analyze neither indication for
fitting of the primary prosthesis nor the postoperative course, because 16 patients were operated
outside our area. Two patients were primarily
operated in our institutions. The reason for fitting of
the revision prosthesis was pain in the femur
diaphysis, and as far as another patient was
concerned, it was dislocation of the prosthesis
femoral component.
Figure 2a. Postoperative radiography in the same patient
ASEPTIC
LOOSENING
Figure 1. Diagram of the number of patients according to the indications for the revision hip arthroplasty
Indications for the revising arthro-plastics
are the following:
1. Aseptic loosening of one or both
prosthesis components (Figure 2).
2. Progressive loss of the bone mass of the
femur or acetabulum. Protrusion of prosthesis and
osteolysis of spine or/and deeper parts of the femur.
As the reason for revision hip arthroplasty,
femoral component dislocation of the prosthesis was
the case in five patients, and acetabular component
dislocation of the prosthesis was the case in four
patients. Dislocation of both components of the
prosthesis was the case in two patients.
3. Infected prosthesis - stable or unstable
the infection was the case in one patient.
Figure 2. Aseptic loosening of the acetabulum
component in the patients preoperatively
60
Revising hip arthroplasty
4. Fractures of the implants of the trunk or
joint - we have not had such cases.
10. The coming period shall bring new
complications for sure.
5. Irreducible prosthesis-we have not had
such cases.
During the operations, we implanted the
standard prostheses of the Aesculap type, such as 18
cemented prostheses and 2 cementless ones. We
implanted neither hybrid nor revision prostheses.
The primary hip prosthesis was worn in the
period of 3 to 20 years, with mean duration of 11.5
years.
Mean age of the patients was 66.8 years,
(range 57 - 76 years).
Of the operated patients, 10 were women
and 8 were men.
6. Fractures of bones near implants or
implants and bones' fractures - as the reason for
revision hip arthroplasty, femur diaphysis fracture
was the case in three patients (Figure 3a, 3b).
RESULTS
Figure 3a.
Fractures of bones
near implants
Figure 3b.
Postoperative radiography
in the same patient
7. Periprosthetic problems - ectopy ossification and fracture of trochanter.
8. Pain without clear cause usually in the
femur diaphysis.
pain of unclear genesis was the case in one patient
(Figure 4).
In the respective period, from one to five
years, we did not have the cases of death, infections
and thromboemboly. In one case, there was a
recurrence of dislocation, and as for the second case,
there was some pain in the upper leg without clinical
and radiological sings of other complications.
Equalling (equalling of the legs' length) was
achieved in 15 patients while there was reduction of
the operated extremities in 3 patients, on average by
2,8 cm.
The patients' rehabilitation was initiated in
cooperation with the physical therapist immediately
after the operation in the sense of breathing;
mobilization in bed, static exercises in bed, and the
second postoperative day after aspiration drainage
outlet was removed, sitting in bed and vertical
positioning accompanied with previous exercises.
On the third day, the patients started to walk on
crutches or walker. Physical rehabilitation was
continued after the patient was discharged from the
hospital, the clinic of the physical medicine, because
at that time the Health Insurance Fund did not finance
the health resort treatments that those patients
needed. Few patients, i.e. three of them financed
themselves for the health resort treatments after
operation.
All the patients were ready for their
everyday activities, but since all 18 patients were
retired persons, there was no need for their
professional rehabilitation.
The patients used crutches or walker for 3 or
4 months, but a great number of patients, 12 of them,
continued to use the stick for ever.
DISCUSSION
Figure 4. Postoperative radiography of patient with
pain of unclean genesis
9. Prosthesis wearing out.
The number of patients with the artificial hip
joint inserted is increasing. The reason for that is the
wish of patients to keep painless and mobile hip.
Objectively, better knowledge about the hip
61
biomechanics, better prosthesis design and improved
knowledge of the operative technics lead towards
this aim. Apart from that, the age of patients is
growing, so more and more often there are objective
reasons for this intervention. Nowadays, 1.2
prostheses are inserted per 1,000 people annually.
The requests for the revising hip prosthesis are
present in all big medical institutions, while the
number of these interventions will be growing in the
future.
The aim of each intervention is to remove
the problem and make the hip more functional,
considering the expected life time of the patient.
Almost all complications related to prosthetic hip
may lead to prosthesis replacement. We had the
following cases in our material:
• The occurrence of aseptic loosening in
our patients was in 11.1% and the causes of its
occurrence are of still insufficiently explained
pathogenesis (5-9). The cause of this complication
has not been sufficiently explained so far, but it is
stated as follows: cementing technics, prosthesis
positioning, reaction of the organism to a foreign
body (6-9). Generally speaking, it can be said that it
is the result of maladaptation and reaction of the live
tissue to a foreign body (cement and metal).
• The occurrence of aseptic loosening is 35%, analyzing the five-year period of the operated
patients (10). It is clinically manifested with the
sharp pain on burden and its disappearance while at
rest. Radiological visible area of luminous state
around the cement, i.e. prosthesis, is not always the
proof of clinical instability. According to Ritter, it is
unstable sign because it is visible in 39% of cases,
while prosthesis migration in those circumstances is
present only in 4% of patients (11). We accepted this
sign only in those cases followed by pain on burden
which disappeared while lying.
The findings of the nucleotide radiography
are very often unreliable because accumulation of
nucleotids in the surrounding tissue is huge and there
are not any of them at the place of dead bone. In that
way, we can get both false negative and false positive
results.
Aseptic loosening is more frequent in the
femoral than in acetabulum component of the
prosthesis, which used to be the case with our
patients (27.7%:16.6%). Russoti et al. found some
1.2% of loosened femoral and 0.4% acetabulum
components of prosthesis in patients five years after
the operation, compared to the previous study in the
same institution where the percentage was 24% and
12.5%, respectively. They concluded that decrease
in the number of loosening was caused by the
improvement of the operative technics for prosthesis
fitting.
62
It is very difficult to notice the difference in
biological and mechanical processes occurring in
relation to inflammatory destruction of bones and
development of loosening in cement and noncement prosthesis (12).
There was also an aggressive role of
granulocytosis noticed in the bones' destruction (13).
Maloney emphasizes the importance of biomechanical and histological research on the autopsy
material (14).
Prevention of prosthesis aseptic loosening
partly depends on the surgeon, while considerable
part is contributed to biology of patients, which the
surgeon cannot have the influence on (15).
It was also proven that polymetil metacrylat
causes release of factors which support the bone
resorption, i.e. leads to the aseptic loosening (16).
Prosthesis dislocation of one or both parts
was the most typical complication in our patients.
Dislocation of the prosthesis femoral component is,
in most of the cases, the consequence of incorrect
biomechanical relations established by operation i.e.
prosthesis centralizing and non-physiological
transfer of burden (6). The spine osteolysis leads to
modified mechanical behavior of the prosthesis
femoral component, which consequently leads to the
femur diaphysis osteolysis in the upper part of
prosthesis, especially its lateral wall (9).
Prosthesis dislocation is the most frequent in
the back access and it is up to 16%, 6% in the lateral
access and below 4% in the front one (9,15) (Figure
5).
Figure 5. Irreducible prosthesis
We personally believe that dislocations are
sometimes caused by behavior of patients,
particularly in the first months after the operation.
Inappropriate centralizing of any prosthesis
components or axial instability anyway supports this
condition.
Progressive loss of the bone mass can also
be attributed to intolerance of bones towards the
Revising hip arthroplasty
foreign body, but even more to non-physiological
allocation of the burden forces which lead to the
femur diaphysis spine ostheolysis around the
prosthesis top. (9) Progressive loss of the bone mass
will always bring about prosthesis loosening and
theoretically, all patients will have it if they live long
enough (8,17).
Hip joint osteolysis is caused by excessive
reanimation of the joint, excessive number of deep
holes for the cement entrance to the hip and
biological reaction of the bone to the foreign body.
Apart from that, this complication may also be
caused by bad positioning of the acetabulum
components of prosthesis, acetabulum displasia,
patients suffering from rheumatic arthritis and
neuromuscular disease and etc. It is also necessary to
mention the inevitable impact of biological factors
on occurrence of this complication as well as
additional fracture of acetabulum (protrusion), to a
great extent caused by the behavior of patients. It is
particularly related to young population whose
physiological activity exceeds tolerance of the
connection of prosthesis-bone.
Infection: Regardless of the fact that the
number of infections is reduced from 10% to
acceptable 0,5%, applying antibiotics and providing
surgery rooms with filtered air, it is still one of the
most dangerous complications of the operated hip
(18,19). Its diagnosis is difficult unless there is fistula. Nowadays, numerous clinical and laboratory diagnostic procedures are used to establish the diagnosis
of the infected alloplastics of the hip joint (20).
We had a case of deep prosthesis infection
caused by Staphyloccocuss epidermidis established
twice during preoperative puncture or 5.5%. In this
case we removed prosthesis and fitted it, revising six
months later. Fortunately, it passed without infection
two years after revising.
Prosthesis trunk fracture did not occur in
our patients, but it regularly occurs after the spine
osteolysis, while the prosthesis peak is steadily
impacted in the channel, when the force of bending
is transmitted to the trunk which leads to fatigue of
the material and occurrence of this complication.
Femur diphysis fracture was the problem
registered in three patients, or 16,6%, and in our
opinion, it was caused by primary fitting of the too
short trunk, possibly overlooked perforation of the
channel during the first insertion as well as inappropriate behavior of patients. We were regularly removing the existing prosthesis trunk and upon osteofixation of the fracture point AO osteosynthesis, we
fitted revising prosthesis depending on quality of
bones and possible selection of prosthesis.
Periprosthetic problems, such as ectopic
ossification and trochanter fractures are rare
indications for revision. We did not have it in our
patients.
It is necessary to emphasize that all the
aforementioned complications rarely occur alone,
and more often there are two or more complications.
Therefore, aseptic loosening often occurs along with
prosthesis dislocation. Loosening and infection
regularly go together, progressive loss of the bone
mass often accompany the femur diahpysis fracture
and acetabulum protrusion. All of them make more
complicated the delicate operations of the fitting of
revising prosthesis which are complicated by their
nature.
CONCLUSION
We presented 18 patients who had the
revising arthroplasty hip joint made, causes of
revision as we could see and explain them and gave
possible reasons for their occurrence. Unfortunately,
we could not precisely determine the time from the
primary to revising operations. Out of 18 patients
only two were primarily operated in our institution,
and most of others somewhere in the former
Yugoslavia. Following the postoperative period of
our patients for five years, we did not have the cases
of death, infections or tromboembolism. In one case,
we had dislocation relapse, and in other case there
was some pain in the upper leg without clinical and
radiological sings of other complications.
We emphasize that the following most
optimum conditions, for this branch of surgery,
should be met for the revising hip arthroplasty:
experienced team of surgeons, good surgery theaters,
wide range of implants and good instruments.
Publication of papers including a small number of patients broadens the experience in certain
fields, which is the reasons for our presentation.
63
REFERENCES
1. Gregori M., Alberton M., Whitney A. et all.
Dislocationem after revision total hip arthroplasty. JBJS 2002;
84:10.
2. Pšorn V.: Indikacije za ugradnju totalnih proteza
zgloba kuka. U Artroplastika kuka. 64-70, Medicinski fakultet
Zagreb, l988.
3. Commings S. R., Rubin S.M.: The future of hip
fractures in the United States. Numbers, costs and patient efects
of the postmenstrual estrogen. Clin Orthop. 1990; 252:163.
4. Herman S.: ENDOPROTEZA KUKA. U
Artroplastika kuka. Medicinski fakultet Zagreb. 1988; 140-144.
5. Beckenbaugh R., Ilstrup D., Total hip arthroplasty:
A review of the hundred thirthy three cases with long follow up.
J. Bone Joint Surg. 1978; 60A:306.
6. Collvile J., Raunio P.: Charnley low friction
arthroplastys in rheumatoid arthritis: Study of complications and
results of 378 arthroplastys. J. Bone Joint Surg. 1978; 60 B: 498503.
7. Crownisebield R.D., Brand R.A.: A stress
analysisof the acetabular recontruction in protrusio acetabuli. J.
Bone Joint Surg. 1983; 65A:495.
8. Harris W. H., Schiller A. L., Choler J. M. et all.
Extensive localised bone resorption in the femur following total
hip replacement. JBJS. 1976; 58A:612.
9. Woo. R. Moorey B., Dislocation of total hip
prothesis. JBJS. 1992; 64A:1306.
10. Orlić D., Grospić R., Komplikacije u vezi ugradnje
totalne endoproteze zgloba kuka. U Artroplastika kuka. 1986;
93-98. Medicinski fakultet Zagreb.
11. Cotes H. E., Favis M. P., Ritter M. A., Polyethilene
wear with cemental backed acetabular cups. J. Bone Joint Surg.
1993; 75B:249.
12. Hozack W. J., Balderston at all. Cemented versus
cementless total hip arthroplasty. A comparative study of
equivalent patient populations. Clin. Orthop. 1993; 289:161.
13. Santarista S., Hoikka R., Ascola A. et all. Agresive
granulomatosus laesions in cementless total hip arthroplasty. J.
Bone Joint Surg. 1990; 72 B:986-990.
14. Maloney W. J., Justy M., Burke D. W. et all.
Biomechanical and histological investigation of cemented total
hip arthroplasty. Astudy of autopsy retrivied femurs after in
vivo cycling. Clin. Orthop. 1989; 249:129.
15. Rao J. F., Bronstain R.: Dislocations following
arthroplasty of the hip. Incidence, prevention and treatment.
Orthop. Rev. 1991; 20:261.
16. Herman J. H., Sovder W. G., Anderson D. et all.
Polimetil metacrilate induced release of bone resorbing factors.
J. Bone Joint Surg. 1989; 71:A,1530.
17. Bobyn J. D., Moortiraer E. S., Glossman A. H. at
all. Producing and amoiding stress shielding laboratory and
clinical opservations of noncemented total hip arthroplasty. Clin.
Art. 1992; 274:79.
18. Schulcer S. F. Harris W. H.: Deep infection after
total hip replacement under asepticconditions. JBJS. 1988; 70 A:
724 .
19. Nelson J. P.; Deep infection following total hip
arthroplasty. J. Bone Joint Surg. 1977; 59A:1042-1044.
20. Lyons C. W.: Evaluation of radiografic finding in
painfull arthroplastys. Clin Orthrop. 1985; 195, 239-251.
REVIZIONE ARTROPLASTIKE KUKA
Dušan Vlatković, Marko Vuković
Odjeljenje za opštu hirurgiju i ortopediju - Opšta bolnica Trebinje
SAŽETAK
Broj zahtjeva za revizijom ranije ugrađene proteze iz brojnih uzroka postao je čest
i vjerovatno će biti u budućnosti još češći. Zahvatom se želi otkloniti neka od komplikacija
vezanih za protetsku zamjenu zgloba kuka i njenu upotrebu.
Uzroci su često međusobno vezani. To su biološki i problemi vezani za upotrebu
proteze. Mislimo da i ponašanje bolesnika dovodi do određenog broja komplikacija.
Za ovaj zahvat neophodna je iskusna ekipa, veliki izbor ugradbenog materijala i
dobar instrumentarij.
Mi smo cementirane proteze zamjenjivali cementiranim, sem u jednom slučaju, a
necementirane necementiranim ili cementiranim. Provodili smo antitrombotičnu
profilaksu i davali 4 dana visoke doze antibiotika. Uspravljanje pacijenta smo dozvoljavali
zavisno od opšteg stanja pacijenta od 3 do 7 dana.
Ključne riječi: reviziona artroplastika kuka, komplikacije primarne artroplastike
64
ACTA FAC MED NAISS
UDC 616.24-006.6-073.75
Professional article
Ljiljana Vasic
Department of
Radiation Oncology,
University Hospital,
University of Kragujevac,
Kragujevac, Serbia
A ROLE OF CYFRA 21-1 AMONG
TUMOR MARKERS FOR
NON-SMALL-CELL LUNG CANCER
SUMMARY
Lung cancer is the most common cancer worldwide. More than
1,000,000 new cases are registered each year. Therefore, it is not surprising that
it has become a global problem, and a major focus of interest of thoracic
oncologists on both hemispheres.
The aim of this assay is to rewiew the main characteristics of available
tumor markers used in NSCLC.
CYFRA 21-1 shows the best sensitivity in NSCLC and higher sensitivity
for squamous cell carcinoma than other histological subtypes, a good correlation
with disease extent, and a strong specificity in non-malignant lung diseases.
Before any treatment, CYFRA 21 – 1 shows the highest sensitivity for squamous
cell carcinoma when compared to CEA, NSE, CA 19-9, CA 15-3 and CA 125.
Therefore, CYFRA 21-1 is the marker of first choice in NSCLC. However, this
marker is not suitable for early diagnosis of NSCLC.
Combinations of markers, identified either by standard
immunohistochemical techniques or by more novel complementary DNA arrays
may prove quite useful for diagnosis and treatment of lung cancer.
Key words: non-small-cell lung cancer, tumours markers, clinical
practice
INTRODUCTION
Lung cancer is the most common cancer
worldwide. More than 1,000,000 new cases are
registered each year (1). Therefore, it is not
surprising that it has become a global problem, and a
major focus of interest of thoracic oncologists on
both hemispheres. Its incidence makes it a major
problem of public health. It is the most frequent
cause of cancer-related deaths, representing 28.2%
of all cancer deaths (2).
Of patients who initially present with lung
cancer, 55% have distant metastatic disease, 30%
have disease spread to regional lymph nodes, and
only 15% have disease confined to the lung (2).
The achievements we made during the last
several decades enabled incremental, but
continuous, improvements in this field. With the
wide introduction of computerized tomography (CT)
scanning in the diagnostic approach of these tumors,
we become capable of better imaging and,
consequently, better clinical staging. Coupled with
CT is a recent introduction of positron emission tomography (PET) scanning, combining morphological and functional imaging. These two imaging
approaches are increasingly being combined in both
diagnostic and therapeutic approaches. They also
serve as a tool for evaluating treatment response.
While the number of centers using this approach is
still limited, it is not hard to imagine it bursting into
Corresponding author. Tel: 381 (0)64 159 33 29, 381 (0)34 34 77 25 • E-mail: ljiljana76@eunet.yu
65
Ljiljana Vasic
the future with consequential changes in imageoriented treatment decisions focusing more on tumor
physiology.
The main four histological types of lung cancer are squamous cell carcinoma, adenocarcinoma,
large cell carcinoma and small cell carcinomaSCLC. The first three subtypes are generally combined on the heading of non-small-cell carcinoma
(NSCLC) and account for approximatelely 80% of
lung cancer (3).
Surgical resection is the accepted treatment
for patients with stage I and II NSCLC, with full
lobar or greater resections preferable to sublobar
resections. The performance of systematic
mediastinal lymph node dissection improves the
accuracy of staging and may have therapeutic
benefits. There is no proven benefit of adjuvant or
neoadjuvant chemotherapy for early stage NSCLC.
At least 50% of these patients will develop local
relapse or distant metastases (4).
Furthermore, 70% of patients are inoperable
at the time of presentation because of either locally
advanced disease or distant metastases (5). Most
patients with advanced disease ask for a specific
treatment even if the possible benefit expected by
currently available chemotherapy regimens is
modest.
CEA suggest tumor size and their progression is
generally related to disease outcome. It sholud be
noted that this marker can be substantially increased
in smokers (6).
Neuron specific enolase (NSE) was reported
as higly suggestive of neuroendocrine tumors. It is
considered as a marker of choice in small lung cancer
where its sensitivity ranges 50-80% according to
disease extent. Nevertheless, an increase of NSE can
be expected in NSCLC. It has been suggested that it
may be associated with neuroendocrine component
of the tumor. In fact, NSE is frequently elevated in all
subtypes of advanced NSCLC (7).
Carbohydrat-antigen 19-9 (CA 19-9) is
generally used as tumor marker in digestive, mainly
pancreatic malignancies. Nevertheless, it has no
clear specificity and does not seem to have any
prognostic value.
Carbohydrat-antigen 15-3 (CA 15-3) is a
tumor marker mainly used in the therapeutic
management of breast cancer. It can also be elevated
in other malignancies especialy in advanced
NSCLC.
Carbohydrat-antigen 125 (CA -125) is a
tumor marker mainly used in diagnosis and followup of ovarian tumors. It is frequently elevated in case
of pleural effusions in case of lung tumors.
Purpose of tumor markers in lung cancer
CYFRA 21-1: Clinical characteristics of
cytokeratins
Large programs of screening in the
population have failed to demonstrate any benefit for
early detection of lung tumors and the vast majority
of patients are diagnosed either by chance or when
they present symptoms. Currently, there are no
specific tumor markers enabling detection of lung
cancer at an early stage.
On the other hand, the diagnosis of relapse
after curative treatment or the evaluation of the
objective effect of systemic therapies are often
difficult to determine and serum tumor markers can
help in menagement of NSCLC as it is the case with
other malignancies.
The ideal profile of tumor markers should
include sensitivity, specificity, prognostic value and
ability to detect response and early recurrences.
The aim of this assay was to rewiew the main
characteristics of available tumor markers used in
NSCLC.
Characteristics of clinically used tumor markers
in lung cancer treatment
Carcinoembryonic antigen (CEA) is the
most frequently used tumor marker in adult
malignancies. Its sensitivity is about 30% in limited
NSCLC and 55% in advanced NSCLC. Levels of
66
The cytokeratins are a part of intermediate
filament protein group, wich is a major component of
the cell cytoskeleton. There are 20 different
cytokeratins with molecul weights ranging from 40
to 70 Kilodaltons (KD), classified according to their
isoelectric point into two types: acid (type I), basic
(type II). Low molecular weights are found in simple
epithelium and heavy molecular weights are found in
epidermis. Under the influence of intrinsic or
extrinsic factors, each cell will express different
types of cytokeratins in the course of its evolution.
These factors have an important role in epidermal
differentiation. The type of cytokeratin synthesized
by a cell is also affected by the growth and
differentiation rate.
CYFRA 21-1 (cytokeratinfragment 21-1) is
a fragment of cytokeratin 19 wich is a part of
cytoskeleton in epithelial cells, and can be found in
an overexpressed way in tumors of epithelial origin.
CYFRA 21-1 shows the best sensitivity in
NSCLC and higher sensitivity for squamous cell
carcinoma than other histological subtypes, a good
correlation with disease extent, and a strong
specificity in non-malignant lung diseases. Before
any treatment, CYFRA 21 – 1 shows the highest
sensitivity for squamous cell carcinoma when
A role of CYFRA 21-1 between tumor markers for non-small-cell lung cancer
compared to CEA, NSE, CA 19-9, CA 15-3 and CA
125. Therefore, CYFRA 21-1 is the marker of first
choice in NSCLC (8, 9).
For the diagnosis of adenocarcinoma, the
combination of the markers CYFRA 21-1 and CEAis
recommended (10).
However, this marker is not suitable for
early diagnosis of NSCLC (8).
Tumor marker analyses can be of great
importance in the follow-up patients under
treatment. Post-surgical values show that CYFRA
21-1 is closely correlated with radical surgery of the
tumor mass. Nevertheless, a residual tumor mass
without marker production cannot be excluded
completely. Furthermore, CYFRA 21-1 gives, when
initially increased, an accurate estimate of the
efectiveness of chemotherapy and radiotherapy of
NSCLC, but cannot differentiate between complete
and partial remission with ultimate certainty (11-13).
Serial measurement of serum concentration
of tumor markers during follow-up can serve for
early detection of tumor progression. This fact was
proved by NSE in SCLC and by CYFRA 21-1 in
squamous cell carcinoma. There are different
opinions about the clinical value of such an early
recognition of tumor progression.
CONCLUSION
Physicians are still looking for ideal tumor
markers in malignant diseases, useful for patient
screening, early diagnosis, prognosis and therapeutic
monitoring. Most tumor markers tested in NSCLC
are today of poor or moderate sensitivity and
specificity and cannot be proposed for screening.
During the past ten years, considerable insight has been obtained regarding the molecular basis of lung cancer. As a result, numerous studies have
been performed to ascertain if spesific mutational
events have unique prognostic significance. In particular, these transitional efforts have focused on
common aberrations regarding expression of genes
regulating cell/cycle progression, apopotosis,
invasion and metastasis.
Many growth factor/receptor systems are
expressed by either the lung tumor or adjacent
normal cells, thus providing autocrine or paracrine
growth stimulatory loops. These are excellent new
terapeutic targets. Overexpression of epidermal
growth factor receptor (EGFR) is observed in
approximately 70% of NSCLCs and may be a
prognostic factor for poor survival (15).
Coexpression of EGFRs and their ligands, especially
transforming growth factor – α, by lung cancer cells
indicates the presence of an autocrine growth factor
loop (16). Gefitinib (ZD 1839, Iressa) is a specific
inhibitor of EGFR-tyrosine kinase that demonstrates
antitumor activity in patients with NSCLC.
Monoclonal antibodies against the extracellular
domain of EGFR, such as C225, are another way of
therapeutic targeting this key pathway (17).
ERBB2 (HER 2/neu) is higly expressed in
more than a third of NSCLCs, especially adenocarcinomas, although gene amplification as seen in breast
cancer is not usually the underlying mechanisam in
lung cancer. A meta-analysis suggested that overexpression of ERBB2 is a factor of poor prognosis
for survival in NSCLC (18). Trastuzumab (Herceptin
®), a recombinant humanized monoclonal antibody
that recognizes HER2, thus blocking its activity, is
being tested for efficacy in NSCLC as a single agent
or in combination with chemotherapy (19).
Overexpression of epidermal growth factor
receptor (EGFR), particularly ERBB2, correlates
with survival in lung cancer patients after resections.
Increased expression of mitogen-activated protein
kinase as well as K-RAS and p53 mutations correlate
with adverse outcome in lung cancer patients (14-15,
20-22).
Given the molecular heterogeneity of lung
cancer, it is not surprising that no single biomarker
has emerged that uniformly correlates with prognosis in lung cancer patients. On the other hand, combinations of markers, identified either by standard
immunohistochemical techniques or by more novel
complementary DNA arrays may prove quite useful
for diagnosis and treatment of lung cancer.
Nevertheless, together with this prognostic
factors, a tumor marker can be used to monitor the
clinical course, treatment and follow-up of patients.
67
Ljiljana Vasic
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MasudaA, Yatabe Y, et al. The sensitivity of lung cancer cell lines
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HER-2/neu abnormalities in 345 stage I non-small cell
carcinomas (NSCLC) and 207 stage I-III neuroendocrine
tumours (NET) of the lung. Int J Cancer 2005;113(1):101-8.
19. Langer CJ, Stephenson P, Thor A, Vangel M,
Johnson DH Trastuzumab in the Treatment of Advanced NonSmall-Cell Lung Cancer: Is There a Role? Focus on Eastern
Cooperative Oncology Group Study 2598. Clin Oncol 2004;
22(7):1180-7.
20. Traxler P, Allegrini P, Brandt R, Brueggen J,
Cozeus R, Fabbro D, Grosios K. A dual family epidermal growth
factor receptor/ErbB2 and vascular endothelial growth factor
receptor tyrosine kinase inhibitor with antitumor and
antiangiogenic activity, Cancer Res 2004;64:4931-4941.
21. Meert AP, Martin B, Verdebout JM, Paesmans M,
Berghmans T, Ninane V, Sculier JP. Correlation of different
markers (p53, EGF-R, c-erbB-2, Ki-67) expression in the
diagnostic biopsies and the corresponding resected tumors in
non-small cell lung cancer. Lung Cancer 2004; 44(3):295-301.
22. Minami Y. Prognostication of small-sized primary
pulmonary adenocarcinomas by histopatological and
kariometric analysiy Lung Cancer 2005; 48(3): 339-348.
A role of CYFRA 21-1 between tumor markers for non-small-cell lung cancer
ULOGA CYFRA 21-1 MEĐU TUMORSKIM MARKERIMA ZA ODREĐIVANJE
NEMIKROCELULARNOG KARCINOMA PLUĆA
Ljiljana Vasić
Centar za onkologiju, Odeljenje radioterapije
KC Kragujevac, Kragujevac, Srbija
SAŽETAK
Karcinom pluća je širom sveta najčešći malignitet. Preko 1000000 novih
slučajeva otkrije se tokom svake godine. Zbog toga ne čudi što je opšti problem i glavno
interesovanje grudnih onkologa na obe hemisfere.
Cilj ovog rada bio je da prikaže glavne karakteristike dostupnih tumorskih
markera koji se mogu koristiti u kliničkoj praksi NSCLC.
CYFRA 21-1 je senzitivan u NSCLC, posebno u slučaju skvamocelularnog
podtipa, ukazujući na proširenost bolesti i visoko je specifičan među bolestima pluća
nemaligne etiologije. Pre započetog bilo kog lečenja, CYFRA 21-1 pokazuje visoku
specifičnost među skvamocelularnim karcinomima u odnosu na CEA, NSE, CA 19-9,
CA15-3 i CA125. Zbog toga je CYFRA21-1 tumorski marker izbora u slučaju NSCLC.
Za adenokarcinome preporučuje se kombinacija markera CYFRA 21-1 i CEA.
Međutim, ovaj marker nije pogodan za ranu dijagnozu NSCLC.
Jedino kombinacija markera, identifikovanih bilo imunohistohemijski ili
komplementarnim novim DNA istraživanjima, mogu biti vrlo korisni za dijagnozu i
lečenje karcinoma pluća. Bez obzira na sve, sa navedenim prognostičkim faktorima,
tumorski marker se može koristiti za nadgledanje kliničkog toka, lečenja i
preživljavanje bolesnika.
Ključne reči: nemikrocelularni karcinom pluća, tumorski markeri, klinička
praksa
69
ACTA FAC MED NAISS
UDC 619:616.993.1:636.7
Original article
1
Aleksandar Tasic
1,2
Suzana Tasic
1,2
Natasa Miladinović-Tasic
1
Dragan Zdravkovic
3
Jovana Djordjevic
1
Public Health Institute Nis
Faculty of Medicine in Nis
3
Student of Medicine
PREVALENCE OF
DIROFILARIA REPENS CAUSE OF ZOONOSIS IN DOGS
2
SUMMARY
Systematic research of zoonosis caused by species Dirofilaria repens
have not been performed till now in Serbia, so that this is the first such study.
The aim of the paper was to detect and identify the presence of
Dirofilaria repens microfilariae in the canine peripheral blood, covering the
territory of Serbia (territory of the City of Nis and Vojvodina). The examination
comprised a total of 45 dogs from the territory of the City of Nis and 193 dogs
from the territory of Vojvodina. For detection of microfilariae in the canine
peripheral blood, a modified Knott's test was used. Identification of Dirofilaria
repens microfilariae was performed according to their morphological and
morphometric characteristics. All morphometric parameters were obtained
using a modern automatic television system for picture analysis Lucia M
(NIKON, 3.51 ab).
By diagnostic technique application, the species Dirofilaria repens was
identified in 95 dogs (49.22%) at the territory of Vojvodina, which is a significant
district area for canine filarioses and transitional hosts for filariae. At the
territory of the City of Nis, microfilariae of Dirofilaria repens were not found in
any of the examined dogs.
Key words: Dirofilaria repens, zoonosis, canine filariosis
INTRODUCTION
Filariae of the genus Dirofilaria, the cause of
zoonosis in nature, are frequent parasites of various
animal species worlwide. For these filariae's life
cycle development, two hosts are needed, a mosquito
or some other transient host, as well as a man who
gets infected by the infected insect's bite (1,2).
The important filaria, which can cause
infection in humans, is certainly Dirofilaria repens.
Mostly, this filaria resides in the cutaneous and
subcutaneous tissue of animals, usually dogs.
Infection in humans occurs sporadically, but so far,
the cases of superficial and visceral forms of human
dirofilariases have been described (1-4).
The whole larval development of this
parasite up to the infective stage III goes on in the
appropriate transient host without multiplication.
After being ingested with the blood meal taken from
the infected host, microfilariae further migrate into
the inner organs of mosquito, where they terminate
their larval development in the course of 14-21 days.
Infective stage III larvae migrate into the thorax and
labium, from where they are inoculated into the dog
by mosquito or some other transient host ( 5-9).
At the moment when the infected mosquito
or some other transient host bites the dog, the labium
bursts into small larvae, which reside in it, and go
into the wound on the skin, made by biting. In the
subcutaneous and fatty tissue, and musculature of the
dog, the larvae spend 85-120 days, during which they
attain the length of 5 cm, approximately. Then, they
Corresponding author. Tel: 381 18 226 384; fax: 381 18 238 770 • E-mail: atasic@bankerinter.net
71
Aleksandar Tasic, Suzana Tasic, Natasa Miladinović-Tasic, Dragan Zdravkovic, Jovana Djordjevic
penetrate into the blood and lymphatic vessels (5-9).
The adult forms reside in the subcutaneous tissue and
lymphatic vessels, whereas microfilariae can be
detected in the blood and skin.
Some papers stress the importance of
filariasis in medicine by presenting 56 cases of
human ocular filariasis (4,10,11). Only in six cases,
the extirpation from the eye, description and
identification of parasites were successful. In three
cases, the cause was Dipetalonema sp., and in one
case Dirofilaria sp.
Dirofilariasis in dogs is an endemic disease,
spread in the tropics, inclining to spread into the
regions with moderate climate.
With geographical spreading of infection
caused by D.repens in dogs, more frequent infections
in humans caused by these species of parasites
should be expected. Therefore, an appropriate
importance should be attached to continuous control
and follow-up of the occurrence and distribution of
filariasis in dogs as a health problem.
Dirofilaria repens, the cause of zoonosis in
Europe, have been discovered at the territory of
Serbia, too. Until our investigation conducted in
2004, Vojvodina was suspected of being endemic
region with canine filariosis, since it abounds with
great areas of stagnant waters and big plain rivers
with slow water currents. Some identified sporadic
cases of canine and human dirofilarioses in this
region illustrate this (2,3,10,11).
The aim of this paper was to identify the
presence of Dirofilaria repens microfilariae in the
canine peripheral blood, covering the territory of
Vojvodina, some regions that represent mosquito
districts, and the territory of the City of Nis.
literature criteria (8,12). All morphometric
parameters were obtained using a modern automatic
television system for picture analysis Lucia M 1996
(NIKON, 3.51 ab).
RESULTS
Using the aforementioned diagnostic
methods, microfilariae were determined in the
peripheral blood in total of 95 (49.22%) examined
dogs from Vojvodina (Table 1, Figure 1). At the
territory of the City of Nis, microfilariae of
Dirofilaria repens were not found in any of the
examined dogs, as presented in Table 1.
Table 1. Finding of microfilariae in canine blood at the
territory of Vojvodina and Nis
Locations
Examined
dogs
Dirofilaria repens
number/%
Vojvodina
193
95/49.22%
Nis
45
0
The samples of peripheral blood taken from
dogs living at the territory of Vojvodina and the City
of Nis were investigated in this paper.
Examination comprised 193 dogs from
Vojvodina and 45 working dogs from Nis, which
were kept under the regime of controlled life conditions (standardized conditions of accommodation,
nutrition, care, training, work, health protection, and
veterinary-sanitary protection). These dogs had not
left our country until the moment of examination.
Immediately before blood sampling, a general
clinical examination of every single dog was
performed. For detection and identification of
microfilariae in the canine peripheral blood in this
research, the modified Knott's test was used (8).
Identification of microfilariae was
performed based on their morphological and
morphometric characteristics, following the
72
Figure 1. Microfilaria of species Dirofilaria repens in
canine blood
DISCUSSION
Human infections caused by dirofilariae are
rare in Serbia and Montenegro, and so far, some
sporadic cases of visceral and superficial filariosis
caused by species D. repens have been described
(4,11).
Systematic researches of this parasitosis of
dogs in our country have not been performed until
now, so this is the first study of that kind. In recent
years, several epidemiological studies have been
performed in different countries. Parasites are widely
distributed in Africa, Asia, Australia, Latin America
and Mediterranean counties (13-15).
Prevalence of Dirofilaria repens - cause of zoonosis in dogs
In Croatia (former republic of Yugoslavia),
D. repens infection of dog sporadically reported in
the past are now being reported with quite high
prevalence (6%) (16). Increased prevalence and
infection spread was also found for D. repens in other
European countries, such as Spain and Greece
(16,17).
Results of the investigations indicated that
examined dogs from the territory of Vojvodina were
significantly infected by D. repens (95 /49.22%),
which thoroughly coincided with results of numerous authors who investigated filariosis spreading in
Europe (17-21).
Since the territory of Vojvodina abounds
with great stagnant water areas (marshes, swamps,
canals, effluents, stagnant tributaries) and great plain
rivers with slow water currents, it can be regarded as
a district area for a great number of different kinds of
potential transient hosts for different species of
filariae.
This survey also included our region, but
contrary to Vojvodina, not a single infected dog was
registered at the territory of the City of Nis.
CONCLUSION
The prevalence of infection in 95 dogs
(49.22%) with D. repens at the territory of Vojvodina indicates that this zoonosis deserves special
attention in the sense of further investigations and
undertaking appropriate measures, so as to diminish
the possibility of infection. The territory of the City
of Nis is not the region with canine filariosis.
REFERENCES
1. Blitva-Mihajlovic G, Ralic M., Miletić B. Bolest
srcane gliste. Simpozijum Male zivotinje – zivot i zdravlje.
Beograd, 1995.
2. Kulisic Z, Misic Z, Milosavljevic P, Popovic N.
Dirofilarioza pasa u Jugoslaviji. 8. Savetovanje veterinara
Srbije. Zlatibor, 1995.
3. Milosavljevic P,
Kulisic Z. Prvi slucajevi
dirofilarioze pasa u Jugoslaviji. Veterinarski glasnik 1989; 43;
(1): 71-76.
4. Beaver P C. Intraocular filariasis: a brief review. Am
J Trop Med Hyg 1989: 40 (1): 40-45.
5. Flynn J R. Parasites of laboratory animals. The Iowa
State University Press /AMES, Ied 1973..
6. Сонин, М. Д.: Основы нематодологии, том
XXIV, Филяриаты животных и человека и вызываемые ими
заболевания, часть третья, Филярииды, онхоцерцины.
Издательство "Наука", Москва, 1975.
7. Brumpt E. Précis de parasitologie. Sixième édition.
Paris, 1949.
8. Kelly J D. Canine Parasitology. Veterinary Review
1977; 17: 25-33.
9. Simic, C, Petrovic Z. Helminti coveka i domacih
zivotinja. Beograd, 1962.
10. Tasic A, Katic-Radivojevic S, Klun I, Misic Z, Ilic
Prevalencija filarioza pasa u nekim
T, Dimitrijevic S.
područjima Vojvodine. 15. Savetovanje veterinara Srbije.
Zlatibor, 2003.
11. Džamić A, Arsić-Arsenijević V, Radonjić I,
Mitrović S, Marty P, Kranjčić-Zec I. Subcutaneous Dirofilaria
repens infection of the eyelid in Serbia. Parasite 2004; 11: 23940.
12. Eckert J, Kutzer E, Rommel M, Bürger JH, Körting
W. Veterinärmedizinische Parasitologie. 1992, Verlag Paul
Parey, Berlin und Hamburg, 1992, 613-623.
13. Quinn PJ, Donnelly WJC, Carter ME, Markey
BKJ, Torgerson PR, Breathanh RMS. Microbial and Parasitic
Disease of Dog and Cat. London 1997; 267-271.
14. Mehlohrn H. Encyclopedic Reference of
Parasitology, Disease, Treatment, Therapy 2nd ed., Dusseldorf,
Germany, 2001, 100-101.
15. Muro A, Genchi C, Cordero M, Simon F. Human
dirofilariasis in the European Union Parasitol Today 1999; 15:
386-389.
16. Genchi C, Rinaldi L, Cascone C, Mortarino M,
Cringoli G. Is Hearthworm Disease Really Spreading in Europe?
Vet Parasitol 2005; 133: 137-148.
17. Aranda C, Panyella O, Eritja R, Castella J. Canine
filariasis. Importance and transmission in the Baix Llobregat
area, Barcelona (Spain). Vet Parasitol 1998; 77 (4): 267-275.
18. Petrocheilou V, Theodorakis M, Williams J, Prifti
H,. Georgilis K, Apostolopoulou I,
Mavrikakis M.
Microfilaremia from a Dirofilaria-like parasite in Greece. Case
report.APMIS 1998; 106 (2): 315-318.
19. Rossi L, Pollono F, Meneguz PG, Gribaudo L,
Balbo T. An eidemiological study of canine filarioses in NorthWest Italy: What has changed in 25 years? Vet Res Commun
1996; 20: 308-315.
20. Van Heerden J,. Verster A, Gouws DJ.
Neostigmine-responsive weakness and glomerulonephritis
associated with heartworm Dirofilaria immitis infestation in a
dog. J SAfr VetAssoc 1980; 51 (4): 251-253.
21. Zahler M, Glaser B, Gothe R. Imported parasites in
dogs: Dirofilaria repens and Dipetalonema reconditum. Tierarztl
Prax 1997; 25 (4): 388-392.
73
PREVALENCA DIROFILARIA-E REPENS
KAO UZROČNIKA ZOONOZE KOD PASA
Aleksandar Tasić1, Suzana Tasić1,2, Nataša Miladinović-Tasić1,2,
Dragan Zdravković1, Jovana Đorđević3
1
Zavod za zaštitu zdravlja, Niš
2
Medicinski fakultet u Nišu
3
Student medicine
SAŽETAK
Studija predstavlja prvo istraživanje u ovoj oblasti u našoj zemlji jer do danas,
sistemska ispitivanja vezana za zoonoze izazvane vrstom Dirofilaria repens na teritoriji
Srbije nisu urađena.
Cilj rada bio je utvrditi prisustvo i identifikovati mikrofilarije vrste Dirofilaria
repens u perifernoj krvi pasa na teritoriji Srbije (Niš i Vojvodina).
Istraživanjem je obuhvaćeno 45 pasa iz našeg regiona i 193 sa teritorije
Vojvodine. Za detekciju mikrofilarija u perifernoj krvi pasa korišćen je modifikovani
Knott test. Identifikacija vrste Dirofilaria repens izvršena je na osnovu njihovih
morfoloških i morfometrijskih karakteristika. Svi morfometrijski parametri utvrđeni
su korišćenjem modernog automatskog televizijskog sistema za analizu slike Lucia M
(NIKON, 3.51 ab).
Primenom dijagnostičkih tehnika, vrsta Dirofilaria repens, identifikovana je
kod 95 (49,22%) pasa na teritoriji Vojvodine što ukazuje da ovo područje predstavlja
distrikt za filarioze pasa i prelazne domaćine filarija. Na teritoriji grada Niša, ni kod
jednog ispitivanog psa nije utvrđeno prisustvo mikrofilarija vrste Dirofilaria repens.
Ključne reči: Dirofilaria repens, zoonoze, filarioze pasa
74
ACTA FAC MED NAISS
UDC 616.89-008.44:159.97
Original article
1
Maja Simonovic
1,2
Grozdanko Grbesa
1
Clinic for Mental Health Protection,
Neurology and Psychiatry
of the Developmental Age,
Department for Stress
Related Disorders,
Clinical Center Nis
2
Faculty of Medicine
CLINICAL PRESENTATION
OF COMORBID DEPRESSION
AND POST-TRAUMATIC
STRESS DISORDER
SUMMARY
Comorbidity of post-traumatic stress disorder (PTSD) and
depression offers the possibility to explore a broad spectrum of
interactions of mood and anxiety disorders in several domains: in the
domain of clinical presentation as well as in the treatment effectiveness
and in the domain of pathophysiology of the two disorders.
The aim of the paper was to determine characteristics of the
clinical presentation of comorbid PTSD and depression.
The investigation included 60 patients assessed by means of the
following intruments: The Structured Clinical Interview for DSM-IV
AXIS I Disorders, Investigator Version (SCID-I (modified), (SCID for
DSM-IV), Clinician-Administrated PTSD Scale for DSM-IV (CAPSDX), Montgomery-Asberg Depression Rating Scale (MADRS) and 17item Hamilton Rating Scale for Depression (HAMD). The data were
analyzed using the methods of descriptive statistics. Differences between
groups were evaluated using the t- test.
The results obtained indicated that comorbidity of depression
and PTSD is associated with higher intensity of intrusive symptoms'
cluster, especially with flash-backs and intrusive thoughts distinctive to
either PTSD or to depression, with broader spectrum of emotional and
mood experiences and with more patient's suffering.
The analysis of the clinical presentation and complex spectrum
of interactions of depression and PTSD inclusively enabled better
understanding of symptoms presented by the patients, choice of the more
effective treatment strategies and shed some light onto possible
mechanisms of the human reactivity to extreme traumatic experiences.
Key words: comorbidity, depression, PTSD
INTRODUCTION
The category of post-traumatic stress
disorder provided an extraordinary potential to
understand the human reactivity to extreme
traumatic events. The symptoms of this nozological
entity – intrusive, numbing and hyperarousal
symptoms comprise a broad range of mental
phenomena and conceptualize them into a unitary
whole.
The destiny of the sensory input and altered
information processing that lead to the change of the
Corresponding author. Mob.tel: 063 1094323, fax 018 232 421 • E-mail: maja.sim@bankerinter.net
75
Maja Simonovic, Grozdanko Grbesa
process of perception, reactivity and reasoning, and
to the formation of the post-traumatic stress disorder
symptoms have been perfectly conceptualized so far.
There was not sufficient effort invested in order to
investigate the affects encompassing traumatization,
and investigate persistent consequences of the
traumatic events on emotional states or mood.
The epidemiological data in our country
indicate an increasing number of the cases diagnozed
as post-traumatic stress disorder and depressive
reactions (1).
Psychiatrists in clinical practice are faced
with the following problem: precise diagnosis of the
complaints presented by a patient is needed in the
shortest possible time. Only precise diagnosis
completed on time enables the implementation of the
efficacious therapeutic programme which is of the
utmost importance in the treatment of reactive states
(2).
A well-known fact is that diagnostics in the
initial stages of illness is always difficult.
Traumatized persons develop a broad range of
complaints – they present global and broad picture of
disturbance reflecting many different symptoms (35). The group of registered symptoms refers most
often to post-traumatic stress disorder as well as to
depression. The problem in differential diagnosis of
those entities is due to the facts that there are
significant symptoms overlapping between two
disorders, and due to the fact that post-traumatic
stress disorder and depression most often are
developed as comorbid disorders (6).
Our motive was to analyze delineated psychiatric entities and their interaction. Using the standard methodological inventary for characterization
of depression and post-traumatic stress disorder, we
analyzed the elements of the clinical presentation
which indicate that the person suffers from comorbid
post-traumatic stress disorder and depression. The
results of the investigation will enable better diagnosis and therapy of traumatized persons. The interpretation of results in the light of patophysiological
mechanisms underlying the symptoms enables the
insight in the posssible mechanisms of interaction of
two disorders whose occurrence in comorbidity is
common.
The aim of the paper was to determine the
characteristics of clinical presentation of the comorbid complex of symptoms of post-traumatic
stress disorder and of depression and to determine
whether the use of the clinical intruments for measuring the presence and intensity of disorders enables
valid diagnosis of the comorbidity of delineated
disorders.
76
The investigation was performed at the
Department for Post-traumatic Stress Disorder at the
Clinic for Mental Health Protection in Nis, from July
1999 to December 2000, according to recommendation of the expert team recommended for the investigation of post-traumatic stress disorder (7). There
were 60 subjects divided in two groups: the experimental group consisted of the subjects meeting
DSM-IV criteria for post-traumatic stress disorder
and for comorbid depressive episode. The control
group comprised subjects meeting criteria for Posttraumatic Stress Disorder only. The initial diagnosis
was performed using the Structured Clinical
Interview for DSM-IV AXIS I Disorders, Investigator Version (SCID-I) (modified) to establish the
diagnosis of Post-traumatic Stress Disorder (PTSD)
and major depressive episode (MDE) (8). After
initial assessment, we administrated the following
instruments for measuring the presence and intensity
of disorders: Clinician-Administrated PTSD Scale
for DSM-IV (CAPS-DX), Montgomery-Asberg
Depression Rating Scale (MADRS) and 17-item
Hamilton Rating Scale for Depression (HAMD) (911). The data analysis was performed using the t-test.
RESULTS
Comparison of the results in experimental
and in control groups on CAPS instrument (Tables 14) showed that the two groups differed most
significantly (p<0,001) in the following symptoms:
flash-backs and acting or feeling as events were
recurring, diminished interest in activities,
detachment or estrangement, restricted range of
affect, in the level of total score of the avoidance and
restriction of affect symptom cluster and the level of
total CAPS score. Differences of less significant
levels (p<0,01) were found in the following
symptoms: intrusive recollections, the level of total
score of the intrusive cluster symptoms and the level
of total score of the hyperarousal cluster (Table 1 –
4). The symptoms: psychological distress, avoidance
of thoughts, sense of forshortened future, sleep
disurbance, difficulty concentrating, exaggerated
strartle response differed in the least level of
significance (p<0,05) in experimental and in control
group (Tables 1 – 4). The symptoms on the CAPS
instrument: distressing dreams, physiological
reactivity, irrritability or outburst of anger did not
differ significantly.
Clinical Presentation of Comorbid Depression and Post-traumatic Stress Disorder
Presentation of results on CAPS instrument in experimental and control group
Table 1. Values of intrusive symptoms in subjects with PTSD and PTSD-D
Table 2. Values of symptoms of avoidance and constrictions of affect in subjects with PTSD and PTSD-D
Table 3. Values of hyperarousal symptoms in subjects with PTSD and PTSD-D
Table 4. Values of total CAPS score in subjects with PTSD and PTSD-D
Comparison of the results on MADRS instrument showed that all the symptoms differed on MADRS
instrument (Table 5).
Table 5. Values of MADRS score in subjects with PTSd and PTSD-D
77
The most significant difference (p<0,001)
found using MADRS instrument was in the
following symptoms: apparent sadness, reported
sadness, reduced sleep, lassitude, inability to feel,
pessimistic thoughts, suicidal thoughts and in the
total MADRS score. The difference at the lower level
of significance was found in the following symptoms
(p<0,01): inner tension, reduced appetite and
concentration difficulties.
Comparison of the HAMD scores of the
experimental and control group showed that the two
groups differed most significantly (p<0,001) in the
symptoms: depressed mood, guilt, suicide, work and
interests, retardation, agitation, psychic anxiety,
somatic anxiety, gastrointestinal somatic symptoms,
general somatic symptoms, genital symptoms, loss
of weight and in the level of total HAMD score
(Table 6).
diagnosis of disturbances presented by a patient.
Application of the aforementioned instruments
makes possible identification and estimation of the
severity of the comorbid depressive episode despite
the existance of the overlapping symptoms of posttraumatic stress disorder and depression, by which
the danger in everyday clinical work is eliminated,
cited by Blank, and which we experienced ourselves
that depressive episode can be ommitted and
undiagnosed because it is overshadowed by the
flamboyant picture of the reactive state (12).
Our results are in accordance with the results
of the study of Blanshard, which states that posttraumatic stress and depression are not manifestations of the same unitary response to trauma. They
are different disorders and not slightly different manifestations of the same disorders, which confirmed
Table 6. Values of HAMD score in subjects with PTSd and PTSD-D
PTSD (1)
X
SD
H1 Depressed mood
1.53 0.57
H2 Guilt
1.03 0.41
H3 Suicide
0.00 0.00
H4 Insomnia (initial)
1.77 0.57
H5 Insomnia (middle)
1.90 0.31
H6 Insomnia (late)
1.83 0.46
H7 Work and activity
1.50 0.68
H8 Retardation
0.47 0.51
H9 Agitation
1.20 0.55
H10 Anxiety-psychic
1.37 0.49
H11 Anxiety-somatic
1.60 0.50
H12 Somatic symptoms-gastrointestinal 0.20 0.41
H13 Somatic symptoms-general
0.90 0.71
H14 Genital symptoms
0.17 0.38
H15 Hypochondriasis
0.53 0.78
H16 Loss of weight
0.03 0.18
H17 Insight
0.00 0.00
HAMDtot
16.03 2.43
HAMD
The experimental and control group did not
differ in the following symptoms: initial insomnia,
middle insomnia, late insomnia, hypochondriasis
and insight.
DISCUSSION
The results obtained indicate that clinical
presentation of the comorbid complex of symptoms
of post-traumatic stress disorder and depression
differ significantly from the presentation of posttraumatic stress disorders without depression, which
enabled making conclusions important for clinical
work.
In this way, it was confirmed that the use of
delineated clinical instruments permits precise
78
PTSD-D (1)
Cv
X
SD
37.26 3.07 0.45
40.05 2.03 0.41
1.17 0.87
32.17 1.97 0.18
16.06 1.97 0.18
25.15 1.93 0.25
45.49 3.10 0.96
108.73 1.23 0.68
45.91 2.17 0.75
35.86 2.27 0.58
31.14 2.73 0.52
203.42 1.63 0.49
79.11 2.00 0.00
227.43 1.80 0.48
145.51 0.83 0.79
547.72 1.13 0.82
0.17 0.53
15.14 31.20 3.52
t
Cv
14.67 11.55
20.35 9.36
74.94 7.31
9.28 1.84
9.28 1.03
13.12 1.04
30.95 7.44
55.05 4.95
34.46 5.71
25.73 6.47
19.05 8.61
30.01 12.32
0.00 8.46
26.90 14.55
94.98 1.48
72.29 7.18
318.40 1.72
11.27 19.44
p
0.0000
0.0000
0.0000
0.0716
0.3087
0.3023
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.1437
0.0000
0.0907
0.0000
the validity of clinical construct of post-traumatic
stress disorder and confirmed that neither the correlation is the illusion, as Yehuda doubted, nor the
epiphenomenon of the imperfect diagnostic criteria
used for those disorders (13-15).
Further analyses of the results showed that
clinical presentation of the comorbid complex of
symptoms of post-traumatic stress disorders and
depression differs significantly from the presentation
of post-traumatic stress disorder with no depression
in certain symptom clusters. Delineated symptom
clusters can be used as an indicator for the immediate
orientation of a clinician that a patient suffers from
both post-traumatic stress disorder and depression,
so there is no danger that depressive episode can be
overshadowed, undiagnosed and not cured.
The result showed that clinical presentation
of comorbid complex symptoms of post-traumatic
stress disorder and depression is characterized by
more intense intrusive symptom cluster, more
intense affective disturbances, but probably with
growing tendency of the patients to report the
symptomatology of affects and by the greater global
disturbance and subjective suffering.
The first characteristic of comorbidity of
post-traumatic stress disorder and depression is more
intense intrusive symptom cluster.
At first glance, the greatest difference in B3
symptom – flash backs and reexperience of events
between experimental and control group was
surprising. Symptom B3, dissociative by its genesis,
correlated by its significance with the symptoms of
affective cluster that indicated its importance and
that it is strengthened by the comorbid depressive
reactivity. The explanation for this elevation was
found in the literature that the visual cortex stimulation, where flash-backs phenomena are generated, is
an automatic concequence of the stimulation of
amigdala, which is philogenetically originated and is
present disregarding the physical properties of the
stimuli. More intense visual cortex stimulation upon
exposure of disturbing stimuli occurs more often in
depressive subjects than in control ones, which was
also found in this investigation (16).
The intrusive symptomatology regarding B2
symptom – intrusive thoughts and recollections
refers, perhaps, to the increased cognitive activity
which depression brings into post-traumatic stress
disorder. Current understanding does not permit one
to take the standpoint if it were a manifestation of an
interaction mechanism–of an affect-based activation
of the contents of traumatic memory or of intensified
efforts to integrate fragmented elements of traumatic
event. The data in traditional psychiatric literature
point to the fact that formation of traumatic script,
creation of narrative, telling the story of event is a
reliable and well-known process of semantic
memory activation, enabling mastering the traumatic
event and putting the event into the past (17).
The conclusion indicates that depression in
post-traumatic stress disorder brings intensified
cognitive activity – higher frequency and intensity of
intrusive thoughts. The concequences of this
phenominon have not been analyzed so far, but this
area, together with the nature and complexity of
mental intrusions deserves further investigation.
Another characteristic of comorbidity of
post-traumatic stress disorder and depression is
higher intensity of symptoms associated with affecti-
ve symptomatology whithin post-traumatic stress
disorder associated with symptomatology of depression.
Conclusively, the patients with post-traumatic stress disorder and comorbid depressive episode
demonstrate more intense emotional experiences
and broader range of emotional manifestations: diminished interest in activities, detachment or
estrangement, restricted range of effects, sadness,
lassitude, pessimistic thoughts, suicidal thoughts,
depressed mood, guilt, retardation, agitation, anxiety
and genital symptoms, regarding those suffering of
post-traumatic stress disorder only.
The third feature of comorbidity of posttraumatic stress disorder and depression is greater
subjective suffering. The repetition of intrusive
contents, tragic evaluation of outcome, sadness,
anhedonia and guilt, together with non-modulated
emotional manifestations, together with the decrease
in control over impulses and beheviour, loss of selfregulatory capacities and social dissolution produce
more intense subjective suffering and higher suicide
risk. (18-23)
CONCLUSION
The results pointed out that comorbidity of
post-traumatic stress disorder and depression is
characterized by the existance of a particular group
of symptoms. Defining of the aforementioned group
of symptoms is important for clinical work.
Identification of those symptoms lead the clinician,
faced with traumatized patient presenting broad and
undifferentiated picture of global disturbance which
represent many versatile symptoms and is based on
real tragic events, to establish directly the diagnosis
of post-traumatic stress disorder and depression.
The obtained results showed that the
application of the above quoted clinical instruments
enables thorough diagnostics of the trauma-related
psychopathology. The importance of recognition the
comorbidity of post-traumatic stress disorder and
depression lies in the fact that the patient identified in
that way develops more severe form of disorder and
is more subjectively disturbed and more functionally
disabled. Diagnostics of the comorbid depression
leads the clinician to think about the suicidality that
presents a great problem in post-traumatic stress
disorder and has a higher rate in the cases of
comorbidity of post-traumatic stress disorder and
depression, keeping in mind that the patients with
comorbid disorders manifest higher chronicity of
illness and lesser rate of spontaneous remission and
to adapt the applied methods of medicamentous and
individual psychotherapy.
79
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Milosavljevic Lj. Razvoj simptoma posttraumatskog stresnog
poremećaja u uslovima specifičnog traumatskog događaja.
XXXIII dani preventivne medicine. Uvodno predavanje.
Zbornik rezimea 1999: 8-14.
2. Kecmanovic D. Psihijatrija. Medicinska knjiga.
Beograd, 1986.
3. Keane TM, Wolfe J. Comorbidity in post-traumatic
stress disoredr: an analysis of community and clinical studies. J
Appl Soc Psychol 1990; 20: 1776-1788.
4. Hyer L, Boudewyns P, Harrison WR, O'Leary WC,
Bruno RD, Saucer R, & Blount JB. Vietnam veterans:
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Assess, 1988; 52(3):475-486.
5. Hyer L, O'Leary W, Saucer R, Blount J, Harrison W,
& Boudewuns P. Inpatient diagnosis of the post-traumatic stress
disorder. J Consult Clin Psychol 1986; 54(5):698-702.
6. Bleich A, Koslowsky M, Dolev A, & Lerer B. Posttraumatic stress disorder and depression. Br J Psychiatry
1997;170: 479-482.
7. Charney DS, Davidson JRT, Friedman M, Judge R,
Keane T, McFarlane S, Martenyl F, Mellman TA, Petty J, Putnam
F, Romano S, van der Kolk BA, Yehuda R, Zohar J. A consensus
meeting on effective research practise in PTSD. CNS Spectrum
1998; 7(suppl 2):7-11.
8. First MB, Gibbon M, Spitzer RL, Williams JBW.
SCID – I. Structured clinical interview for DSM-IV axis I
disorders, Biometrics Research, New York, 1997.
9. Blake DD, Weathers FW, Nagy L.M, Kaluopek
DG, Charney DS, Keane TM. Clinician-administrated PTSD
scale for DSM-IV, National Center for PTSD. Behavioural
Science Division – Boston VA Medical Center, Neurosciences
Division – West Haven VAMedical Center, 1997.
10. Montgomey SA, Asberg M. A new depression
scale designated to be sensitive to change. Br J Psychiatry
1979;134:382-389.
11. Hamilton M. A rating scale for depression. J
Neurol Neurosurg Psychiatry 1969; 23:56-62.
12. Blank AS. Clinical detection, diagnosis and
differential diagnosis of post-traumatic stress disorders.
Psychiatr Clin NorthAm 1994;17:351-383.
13. Blanchard B E, Buckley C T, Hickling J E, &
Taylor E A. Post-traumatic stress disorder and comorbid major
depression: Is the correlation an Illusion? J Anxiety Disord
1998;12, 21-37.
14. Yehuda R. Is correlation an illusion? Comment at
the NIMH-National Center for PTSD Conference on diagnosis
of PTSD (Boston, MA, Nov. 7 and 8, 1995).
15. Keane TM, & Kaloupek DG. Comorbid
Psychiatric Disorders in PTSD. Implications for Research. Ann
NYAcad Sci 1998;24-34.
16. Davidson РJ, Irwin W, Anderie MJ, Kalin NH. The
neural substrates of affective processing in depressed patients
treated with venflaxine.Am J Psychiatry 2003;160:64-75.
17. van der Kolk. General approach to treatment. In:
van der Kolк, A B, McFarlane C A, & Weisaeth L. (eds):
Traumatic Stress: The Effects of Overwhelming Experience on
Mind, Body and Society, The Guilford Press, New York, 1996.
18. Fontana А, Rosenheck R. Attempted suicide
among Vietnam Veterans: A Model of Etiology in a Community
Sample.Am J Psychiatry 1995; 152: 102-109.
19. Ferrada-Noli M, Asberg M, Ormstad K, Lundin T,
and Sundbom E. Suicidal behavior after severe trauma. Part I:
PTSD diagnoses, psychiatric comorbidity, and assessments of
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Anxiety disorders and major depression, together and apart.
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23. Breslau N, Davis GC, Andreski P, & Peterson E.
Traumatic events and post-traumatic stress disorder in an urban
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KLINIČKA PREZENTACIJA KOMORBIDITETA DEPRESIJE I
POSTTRAUMATSKOG STRESNOG POREMEĆAJA
Maja Simonović1, Grozdanko Grbeša1,2
1
Klinika za zaštitu mentalnog zdravlja, Neurologija i psihijatrija razvojnog doba,
Odsek za posttraumatske stresne poremećaje, Klinički centar Niš,
2
Medicinski fakultet Niš
SAŽETAK
Komorbiditet posttraumatskog stresnog poremećaja (PTSP) i depresije pružio
je mogućnost sagladavanja širokog niza interakcija anksioznih i poremećaja
raspoloženja i to u više domena: u domenu kliničke prezentacije, kao i u domenu
procene efikasnosti tretmana i psihofiziologije ovih poremećaja.
Cilj rada bio je određivanje karakteristika kliničke prezentacije
komorbiditeta PTSPi depresije.
80
Evaluirano je 60 pacijenata uz korišćenje sledećih instrumenata: Strukturisani klinički dijagnostički instrument za Axis I poremećaje (SCID za DSM.IV), Skala
za kliničku procenu PTSP (CAPS.DX), Montgomeri-Osberg skala za depresiju
(MADRS) i Hamiltonova skala za depresiju (HAMD). Podaci su analizirani korišćenjem metoda deskriptivne statistike. Statističke značajnosti razlika između grupa su
utvrđene korišćenjem T testa.
Rezultati su pokazali da je komorbiditet depresije i PTSP povezan sa višim
intenzitetom intruzivnih simptoma, posebno sa fleš bekovima i intruzivnim mislima
koje su ukazivale ili na PTSP ili na depresiju, sa širim spektrom emocionalnih
doživljavanja i raspoloženja i sa većom subjektivnom patnjom pacijenta.
Analiza kliničke prezentacije i kompleksnog spektra interakcija depresije i
PTSP omogućava bolje razumevanje simptoma prezentovanih od strane pacijenta,
izbor efikasnijih terapijskih strategija i baca svetlo na moguće mehanizme ljudske
reaktivnosti na ekstremne traumatske doživljaje.
Ključne reči: komorbiditet, depresija, PTSP
81
ACTA FAC MED NAISS
UDC 616.718.4-001.5-089
Original article
1
1
Sasa Karalejic , Desimir Mladenovic
1
1
Ivan Micic , Zoran Golubovic
1
Predrag Stojiljkovic
2
Danilo Stojiljkovic
1
Clinic of Orthopedics and
Traumatology of the
Clinical Center Nis
2
Surgical Clinic, Clinical Center Nis
TREATMENT OF THE FEMORAL
SHAFT FRACTURE BY
SELF-DYNAMISABLE INTERNAL
FIXATOR MITKOVIC
SUMMARY
The paper presents initial results in the application of a new method for
the osteosynthesis of comminuted and unhealed femoral shaft fractures.
A self-dynamisable internal fixator Mitkovic was applied in 38 patients,
out of which 23 patients with comminuted femur fractures and 15 patients with
unhealed fractures.
The method of placement and results of the work and their estimation
according to the modified system of the Karlstrom-Olerud method are
presented. Good condition was registered in 17 patients, satisfactory in 9,
approximately good in 6 patients, and poor condition in 6 patients. An average
healing time for the femur fractures is 34 weeks, which depends on the type of the
femur fracture and treatment of unhealed fractures.
The method of self-dynamisable internal fixator Mitkovic application
provides complete stability of the fracture and makes spontaneous biological
dynamization of the fracture possible. It does not damage the periosteal and
medullary bone vascularization, which favors osteosynthesis and considerably
contributes to osteogenesis.
Key words: femoral shaft fracture, self-dynamisable internal fixator
Mitkovic
INTRODUCTION
Fast development of traffic, industry, agricultural mechanizations, sports and other activities
consequently brought about the phenomenon of
epidemics of traumatology. The injuries of the
extremities are prevalent, the most frequent of which
are fractures of the shin and thigh. The fracture of the
femoral shaft occurs as a consequence of direct or
indirect force effect.
The intensity of external force inducing a
bone fracture is of crucial importance for the type and
kind of fracture. It affects the degree of soft
structures' damages in the vicinity of bones as well as
degree of fragments' dislocation. The forces of great
kinetic energy break bones into more fragments,
dislocate them and considerably damage the adjacent
soft tissue. Consequently, there are comminuted
fractures with greater number of fragments, damages
to vascular network of bone fragments, especially
loose fragments, as well as disruption of periosteal
circulation (1). This kind of fracture is hard to
stabilize, and even if stability is attained by classic
osteosynthetic devices (intramedullary nails, plates
and screws), there is a great secondary damage to
bone vascularization, so that the fracture usually
does not heal or the process of osteogenesis is slow
and rather long (2). The self-dynamisable internal
fixator Mitkovic for femur is a new osteosynthetic
device. Its basic characteristic and advantage is the
application along the femoral shaft without
deperiostation of fragments, by which the periosteal
Corresponding author. Tel/fax: 018 230184, mob: 063 410103 • E-mail: karalejics@bankerinter.net
83
Sasa Karalejic, Desimir Mladenovic, Ivan Micic, Zoran Golubovic, Predrag Stojiljkovic, Danilo Stojiljkovic
and periosseous vascularizations are not disrupted.
The fixator preserves the biological bone milieu, so
that this method is biological and non-compromising
for soft tissues and vascularization. This procedure
contributes to the process of osteogenesis which
generally depends on numerous factors, the most
important of which are: type of fracture, degree of
primary damage to bone and its vicinity, degree of
the fracture stabilization and vascularization of
bones and adjacent soft tissues (3).
AIMS
The aim of the paper was to point to the
application of the self-dynamisable internal fixator
Mitkovic in the management of comminuted and
unhealed fractures of femur, as well as to present the
biological advantages of this method.
The self-dynamisable internal fixator
Mitkovic consists of the metal oval bar which is 10
mm in width and 15-30 cm in length. In the upper part
of the bar there is an oval slot for the cortical screw by
which the pin is fixed to the femur, and which plays
the role of antirotation of the upper fragment. In the
lower part, there is a groove of 2 cm in length which
serves for the placement of the cortical screw with
antirotational role in regard to the lower bone
fragment. This screw is placed in the lower part of the
groove along which the fixator slides downwards in
the case of spontaneous dynamization and
fragments' compression. An integral part of the selfdynamisable internal fixator is clamps which slide
along the bar and serve for the placement of screws in
different planes as well as for stabilization of
fractures.
This retrospective study included 38
patients. In 23 patients (60%), the internal fixator
was applied as a primary osteosynthetic device for
stabilization of comminuted fracture of femur. In 15
patients (40%), the internal fixator was applied in the
secondary surgical procedure:
• after turning the external fixation into
internal one after the appearance of surface infection
around pins of external fixator,
• after nonhealing of the fracture or after
wound management, that is the management of the
open fracture of femur,
• in the treatment of nonunions of femur,
treated by some other method of osteosynthesis,
• after breaking of osteosynthetic material
(intramedullary nail, plate) applied in the treatment
of the femur fracture.
84
The internal fixator is placed along the
femur, and then introduced upwards through the cut
of 2-3 cm in length. In the proximal part, there is an
upper part of the fixator and through the cut we place
a cortical screw through the fixator hole. Then, we
place internal fixator along the femoral shaft, do the
fragments' reposition and then place the cortical
screw along the groove in the lower part of the
fixator. This screw is deliberately placed in the lower
part of the groove to enable sliding of the pin along
the vertical femur axis. This is how the sliding of the
upper fragment starts, inducing compression of the
lower part. The cortical screws are antirotational –
they do not allow rotation of fragments but only
vertical sliding. Along the bar, two clamps are placed
for proximal and distal fragments. They are the
screws' carriers that we place into two planes
convergently so as to achieve stability of fragments
at the site of fracture. The site of fracture should not
be opened. Instead, we do the reposition of fragments
stabilizing them by screws. Rarely, when the
reposition of fragments is impossible or
unsatisfactory, the fracture site should be opened
with doing the open reduction of the fracture but
without deperiostation of ends. Also, the
interpositum should be taken out of the fracture site –
usually, it is muscles.
RESULTS
The final results of the group examined were
assessed by the modified method Karstrom-Olerud.
We followed the subjective symptoms (pain,
aggravation of walking, difficulty walking up the
stairs, aggravation of condition after training sports,
limitation of working ability) as well as the objective
signs (skin condition, deformity, muscles' atrophy,
leg length discrepancy, loss of movements in the hip
and knee). Based on these parameters, a modified
score system was introduced as well as five groups
with different scores (Figure 1).
Figure 1. The final results of the examined group were
assessed by the modified method Karstrom-Olerud
Treatment of the femoral shaft fracture by self-dynamisable internal fixator Mitkovic
An excellent result at the end of the
treatment was registered in 2 patients (5%). The
examinees were young people with comminuted
fractures of the femoral shaft. These injuries
occurred in a car accident and were treated by
internal fixator (Figures 2-4).
Figure 4. Fracture healing after 20 weeks
Figure 2. Comminuted femoral shaft fracture
Figure 3. Fracture treated by self-dynamisable internal
fixator Mitkovic
The consequences were not serious: mild
atrophy of the thigh reduced the ability of running
and training previous sports, reduced working ability
related to jobs involving long walking, standing or
some effort.
Good results were registered in 17 patients
(45%) and satisfactory one in 9 patients (23%).
Approximately good results were registered
in 6 examinees (16%), while poor results were
noticed in 4 examinees (11%).
There is a great group of examinees with
good and satisfactory results, in total 26 examinees
(68%). The treatment of this group of patients was
terminated without more serious consequences.
The most usual consequences typical of this
group were: aggravation of walking, difficulty
walking up and down the stairs, reduction of working
ability with regard to hard and moderately hard
physical jobs, shortening of the operated leg by 1-2
cm in 8 examinees, and hypertrophy of muscles by 12 cm in 17 examinees. All these consequences are
tolerable, and did not change activities and habits of
the examinees.
Serious consequences were noted in the
group of examinees with approximately good as well
as poor functional results. In this group, there were
10 patients (27%) with the following consequences:
• 2 patients suffered from chronic femoral
osteomyelitis, which resulted from getting injured by
shrapnels and gunshots. Initially, they were treated
by the method of external fixation which was later
replaced by internal fixation.
85
• in 6 patients, there was a reduction in the
knee flexion – possible up to 80°, which was the
result of long period of physical inactivity. As for
these patients, the treatment started with plates and
screws.
• in 4 examinees, there was a shortening of
the extremity by more than 3%, which was the result
of primary comminution and bone defect.
• In all patients, there was a marked
hypertrophy as a consequence of long inactivity of
the extremities.
DISCUSSION
In traumatology, there is a great choice of
methods of treatment of the femoral shaft fractures.
Depending on the fracture type and its comminution,
the following can be applied: plates with screws,
Küncher's nail, intramedullary nail, external fixator
(4,5). At the Clinic of Orthopedics and Traumatology
in Nis, the self-dynamisable internal fixator by
Mitkovic is applied.
Numerous factors determine the process of
osteogenesis and directly influence the course and
outcome of fracture. Among them, the most important are: the type of fracture, stability of fixation and
preserving the fracture site vascularization.
The internal fixator provides stability of
fragments and contributes to the process of osteogenesis. It excludes the fracture from the lever chain
and takes over the role of the fractured bone. It
bridges the fracture focus and with its interponation
into the bone itself makes a whole (6-9). The fixator
rigidity is an important invariable category, which
can be the key factor in early bone union. The internal
fixator does not disrupt the intramedullary circulation, but preserves it providing condition for its recovery, which is an important precondition for the
endosteal callus formation (3, 10).
The pressure between bone fragments plays
an important role in the process of osteogenesis.
Many authors have pointed that an optimal pressure
in the healing process is 80N. Weaker compression
leads to disappearance of bone, while greater
compression brings about resorption of bones and
nonunion (11, 12).
The biochemical role of internal fixator is:
• to keep fragments in proper relation, that is
to provide the contention of fragments,
• to prevent torsion-axial forces which are
quite unfavorable in the process of osteogenesis,
since they constantly bring about damages to
fibrous-cartilage callus structures, disrupting thus
their transformation into bone structures.
86
Dynamization phenomenon induces transmission of axial loading over the bone fragments (4).
The apparatus dynamization occurs spontaneously
several weeks after the operation, when the micromovements appear at the fracture site, which substantially stimulates and speeds up the process of
osteogenesis (1). Dynamization should start early
when the fibrous callus has provided a rest of fragments, which in the case of femoral fractures occurs
after 7-8 weeks (2, 11-13). After this period, doctors
should insist on verticalization and walking with the
use of crutches with gentle leaning on the operated
leg.
The construction of internal fixator allows
spontaneous dynamization. Then, the axial moving
of fragments and decreasing of the fracture gap
occur. With initial weight-bearing on the operated
leg, the sliding of the whole apparatus with the upper
bone fragments starts downwards, along the
antirotational screw placed in the groove at the lower
pole of internal fixator. The screws placed
convergently in the fixator provide stability of
fragments in all planes over the clamps. They are
placed as far from the fracture site as possible so as to
provide stability, to exclude the rotation-axial forces,
and to provide the axial movement of fragments and
compression in the bone focus.
An important factor in the process of
osteogenesis is vascularization of bones (2, 14, 15).
The degree of the bone vascular network damage
affects the speed and kind of callus formation. The
periosteal arterial and intramedullary circulation,
that is the circulation around the adjacent soft tissue
have the greatest role in the early period of
osteogenesis. In comminuted fractures, the fracture
focus loses both periosteal and medullary
circulation.
Osteosynthetic material considerably
disrupts bone vascularization. A plate with screws
can seriously disrupt the periosteal circulation, while
intramedullary fixation disrupts the bone medullary
vascular network, inducing thus avascularity of the
inner part of entire cortex (2, 5, 16, 17).
The internal fixator is ultimately sparing for
the entire bone network. It is applied over the bone
without deperiostation, so that it disrupts neither
periosteal nor medullary circulation. It is placed in
the way that it can skip the fracture site without
opening, so that the primary hematoma does not
enlarge. With the placement like this, there is a
minimal disruption of the periosteal circulation, and
therewith the process of osteogenesis depends only
on primary, initial disruption occurring at the
moment of trauma.
Treatment of the femoral shaft fracture by self-dynamisable internal fixator Mitkovic
CONCLUSION
The self-dynamisable internal fixator
Mitkovic is a new osteosynthetic device and a new
biological method of the femoral shaft fracture
fixation. The results are encouraging since this
fixator provides conditions for a minimal surgical
intervention. It also provides tridimensional stability
of bones, as well as fragments' dynamization. In
regard to the bone circulation network, it is
ultimately sparing, providing thus conditions for the
formation of great periosteal callus equally formed
around the fracture site.
This fixator can be relatively easy and
quickly applied, and the results obtained in this study
justify its broad application in fixation of femoral
shaft fractures and management of femoral
pseudoarthrosis.
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11. Kelly PJ, Montgomery RJ, Brouk JT. Reaction of
the circulatory sistem to injury and regeneration. Clin Orthop
1990; 254: 275-288.
12. Kenwright J, Goodship EA, Kelly JD at al. Effect
of controlled axial micromovement on healing of tibial fractures.
Lancet 1986; 2(8517):1185-7.
13. Mitković M. Spoljna fiksacija u traumatologiji.
Prosveta, Niš, 1992.
14. Mitkovic M, Bumbasirevic M, Golubovic Z,
Mladenovic D, Milenkovic S, Micic I. New biological method of
internal fixation of the femur. Acta Chir Jugosl 2005; 52(2):1136.
15. Claes L, Heitemeyer U, Krischak G, Braun H,
Hierholzer G. Fixation technique influences osteogenesis of
comminuted fractures. Clin Orthop Relat Res 1999; 365(8):2219.
16. Barron SE, Robb RA, Taylor WF, Kelly PJ. The
effest of fixation with intramedularry rods and plates on fracturesite blood flow and bone remodeling in dogs. J Bone Joint Surg
1977; 59A: 376-385.
17. Calhoun JH, Li F, Ledbetter BR, Gill CA.
Biomechanics of the Ilizarov fixator for fracture fixation. Clin
Orthop 1992; 280: 15-22.
LEČENJE PRELOMA DIJAFIZE FEMURA SAMODINAMIZIRAJUĆIM
UNUTRAŠNJIM FIKSATOROM MITKOVIĆ
Saša Karalejić 1, Desimir Mladenović 1, Ivan Micić 1, Zoran Golubović 1,
Predrag Stojiljković 1, Danilo Stojiljković 2
1
Ortopedsko-traumatološka klinika, Klinički centar Niš
2
Hirurška klinika, Klinički centar Niš
SAŽETAK
U radu su prikazani rezultati primene nove metode za osteosintezu
kominutivnih i nezaraslih preloma dijafize femura.
Primenili smo samodinamizirajući unutrašnji fiksator po Mitkoviću kod 38
bolesnika i to kod 23 bolesnika kao primarno osteosintetsko sredstvo za stabilizovanje
kominutivnog preloma femura i kod 15 bolesnika u sekundarnom hirurškom
postupku.
Prikazana metoda plasiranja samodinamizirajućeg unutrašnjeg fikastora je,
kao i rezultati rada i njihova procena, po modifikovanom sistemu metode KarlstromOlerud. Dobro stanje utvrđeno je kod 17 bolesnika, zadovoljavajuće kod 9, približno
87
dobro stanje kod 6 bolesnika i slabo stanje kod 4. Prosečno vreme zarastanja teških
kominutivnih i nezaraslih preloma dijafize femura iznosilo je 34 nedelje.
Metoda primene samodinamizirajućeg unutrašnjeg fiksatora daje potpunu
stabilnost preloma i omogućuje spontanu-biološku dinamizaciju preloma. Ne oštećuje
periostalnu i medularnu vaskularizaciju kostiju, što je velika prednost osteosinteze, a
time znatno doprinosi razvoju osteogeneze.
Ključne reči: prelom dijafize femura, samodinamizirajući unutrašnji fiksator
Mitković
88
ACTA FAC MED NAISS
UDC 616.25-006
Original article
1
Tatjana Radjenovic Petkovic
1
2
Tatjana Pejcic , Vojin Savic
2
Predrag Vlahovic
1
Desa Nastasijević Borovac
3
Danijela Radojkovic
1
Clinic for Lung Diseases Knez Selo
Nephrology Clinic
3
Endocrinology Clinic
2
USE OF C- REACTIVE PROTEIN
IN PLEURAL FLUID FOR
DIFFERENTIAL DIAGNOSIS
OF BENIGN AND
MALIGNANT EFFUSION
SUMMARY
The aim of this study was to determine the validity of pleural fluid Creactive protein (CRP) concentrations and pleural fluid /serum CRP ratio for
differentiating pleural effusion of malignant from non-malignant etiology.
Pleural fluid and serum CRP levels were obtained in 82 patients with
pleural effusion, using an immunoturbidimetric method (Olympus autoanalyser). Patients were subdivided in two groups, group I (n= 41) with malignant,
and group II (n=41) with non-malignant (tuberculous, inflammatory, transudative) pleural effusion.
Statistical analysis was conducted using the MannWhitney Rank sum
test.
There were statistically significant differences in pleural fluid CRP
values between group I (15.6 ±10.55), and group II (25.7 ±12.475), and there
were significant differences between CRPpleural fluid/serum ratio in group I vs.
group II (0.318 ±0.157, vs. 0.430± 0.229). In addition, there were statistically
significant differences between pleural fluid CRP values in patients with
parapneumonic compared to patients with tuberculous and malignant effusions. In differential diagnosis of pleural effusion, pleural fluid CRP may prove
rapid and practical method of differentiating malignant from non-malignant
pleural effusion.
Key words: pleural effusion, C-reactive protein, malignant, nonmalignanat
INTRODUCTION
Pleural effusion is a common problem in clinical practice. It can be caused by several mechanisms including increased permeability of pleural
membrane, increased pulmonary capillary pressure,
decreased negative intrapleural pressure, decreased
oncotic pressure, and obstruction of lymphatic flow
(1).
Pleural effusion points to disease which can
be pulmonary, pleural or extrapulmonary. One of the
most common etiologies of pleural effusion is
Corresponding author. Tel/fax +381 64 2662539
malignancy, among which lung cancer corresponds
to a great number of cases. However, other infectious
and other non- infectious diseases contribute to this
clinical manifestation, too.
Differentiation of malignant from non-malignant pleural effusion is of great importance.
Measurement of C-reactive protein (CRP) levels is
clinicaly valuable screening test for inflammatory
disease as a measure of response to therapy (2-4).
Acute phase response is a general response
to inflammation, trigered by cytokines, released
from the sites from injury or inflammation (5).
89
Tatjana Radjenovic Petkovic, Tatjana Pejcic, Vojin Savic, Predrag Vlahovic, Desa Nastasijević Borovac, Danijela Radojkovic
C-reactive protein is an acute phase protein,
produced in the liver. Increased production of this
protein is triggered by citokones, IL 6, TNFα and IL
1, released by inflamatory cells (6). A major function
of C-reactive protein is the ability to bind
phosphocholine and thus recognize some foreign
pathogenes as well as phospholipid constituents of
damaged cells. It can activate complement system
when bound to one of its ligand, and can also bind to
phagocytic cells. It can also induce synthesis of
inflammatory cytokines and tissue factor. C-reactive
protein has many pathophysiological roles in
inflammatory process (3).
AIMS
The aim of the study was to investigate
wheather C-reactive protein (CRP) could be
clinicaly valuable for differentiating malignant from
non-malignant pleural effusion.
Cytology is a standard method for diagnosis
of malignant effusion, and positive pleural cytology
is diagnostic of malignant pleurisy, while a positive
biochemical marker values are only indicative of
inflammatory process.
We collected serum and pleural fluid
samples from 82 patients, (48 man and 34 women,
mean age 62,9 years) admitted to the Clinic for Lung
Diseases and Clinic for Lung Surgery between
March 2006 and March 2007. Blood samples were
centrifuged at 1500/ 0 for 10 minutes, the pleural
fluid samples were centrifuge at 2000 /o for 10
minutes to remove blood.
The levels of glucose, total protein, lactic
dehydrogenase, albumin and cholesterol were
measured in both sets of samples. Gram-staining and
aerobic culture were performed on the pleural fluid
samples. The test for mycobacterium Ziel Nilsen
staining was performed after homogenisation, and
the samples were cultivated in Lowenstain Jansen
culture media.
CRP analysis was performed on autoanalyzer Olympus, Tokyo, Japan, using immunoturbidimetric method. CRP values are given in mg/L.
The patients were divided in two groups,
group I with malignant, and group II with nonmalignant pleural effusion. Effusions were
considered malignat if malignant cells were found
on the cytologic examination, or in the biopsy
specimen.
Classification of pleural effusion into
transudative or exudative is based upon Light criteria. This criteria discriminate pleural exudate on
the basis of pleural fluid to serum lactate dehydrogenase ratio >0,6 , or pleural fluid to serum protein
ratio >0,5 .
The diagnosis of tuberculous pleurisy was
made by positive smear or culture on mycobacterium tuberculosis.
Criteria for parapneumonic effusion were:
clinical, biochemical and radiological signs suspected on acute inflammation, positive culture for
aerobe, positive Gram staining, presence of purulent
effusion or neutrophil predominance in pleural
effusion (7).
Statistical analysis was made by Mann
Whitney test used to analuze the difference between
groups. The level of significanse was considered as
<0,05.
RESULTS
Of 82 subjects, 41 were diagnosed with
malignant (group I), and 41 were diagnosed with
non-malignant pleural effusion (group II). Of 41
malignant effusion, 21 subjects (51.2%) were male,
and 20 (48.8%) were female. The mean age of this
group was 62,8 years (range 48-80 years). Of 41
benign cases, 29 subjects (70.8%) were male, and 12
(29.2%) were female, with mean age 63.1 years
(range 25-85 years). In group II, 9 (21.9%) patients
had transudative, and 32 (78.1%) patients had exudative effusion. In malignant group, all patients had
exudative pleural effusion. Distribution of pleural
effusion etiologies are presented in Table 1.
Table 1. Cases of malignant and non-malignant pleural effusion
90
CAUSE
malignant
lung cancer
mesotelioma
breast cancer
ovary cancer
endometrium
renal cancer
NUMBER
41
28
2
4
2
1
1
prostate cancer
HML
carcinoma hepatis
1
1
1
CAUSE
non- malignant
parapneumonic
empyema
tuberculosis
morbus cordis
cyrrhosis
status post implantationem
valvulae mitralis
lupus erytematosus
number
41
13
9
9
6
2
1
1
Use of C- reactive protein in pleural fluid for differential diagnosis of benign and malignant effusion
Table 2. Pleural fluid C-reactive protein levels in study group
column
n
Median
Mean±SS
(mg/l)
SE
Max
Min
malignant
nonmalignant
41
39
15.60
25.700
20.27±16,05
44.397±42,39*
2.51
6.788
65.30
1.20
148.900 1.500
p
*
*data are given in mg/l, significance determinated as p<0,05 malignant vs non-malignant effusion
Pleural fluid C-reactive protein values were
significantly higher in non-malignant vs. malignant
pleural effusion ( Table 2.), (p<0,05). CRP values
were significantly higher in parapneumonic than in
malignant (p<0,001),transudative p<0,001, and in
tuberculous effusions (p<0,01) (Table 3).
Differential cell counting can add some
diagnostic information. Pleural lymphocytosis is
common in malignant and tuberculous effusions,
while neutrophilia is the sign of acute infection (9).
It is well-known that C- reactive protein values in
serum is one of the most sensitive and specific
Table 3. Pleural fluid CRP values in non- malignant effusion
Column
n
Median
parapneumonic
tuberculous
transudative
21
9
9
65.40
19.50
8.300
Mean±SD
SE
Max
(mg/l)
68.12±43.82 9.56
148.90
22.28±18.15 6.05
58.50
11.15±11.53 3.84
39.40
Min
p
12.70
4.10
1.50
*
**
***
data are given in mg/l, significance determinated as p<0,05; * p<0,001 compared with malignant,
** p<0,01 compared to parapneumonic, *** p<0,001 compared to parapneumonic effusion
The ratio of pleural fluid to serum CRP
values was also significantly higher in nonmalignant than in malignant group (p<0,05) (Table
4). Also, CRP pleural fluid to serum ratio was
significantly higher in parapneumonic than in
malignant and tuberculous group, while there were
not significant differences beetwen transudative and
other groups.
markers for bacterial pneumonia, and it is diagnostic
as prognostic marker (10,11). There is less
information about C- reacitve protein in pleural
fluid. Turay et al. found that pleural fluid CRP levels
>30mg/L had sensitivity of 93,7% and specifity for
76,5% for inflammatory pleural effusions (12).
Table 4. Serum/pleural fluid CRP ratio, significance determinated as p<0,05
column
malignant
non-malignant
parapneumonic
tuberculous
transudative
n
41
39
21
9
9
Median
0.280
0.410
0.48
0.29
0.340
Mean±SD
0.318±11.53
0.430±0.229
0.51±0.25
0.30±0.12
0.36±0.19
SE
0.0245
0.0366
0.054
0.039
0.063
Max
0.870
1.020
1.02
0.54
0.70
Min
0.1000
0.0900
0.09
0.12
0.13
p
*
**
***
* p<0,05 compared to parapneumonic, ** compared to malignant effusion ,*** compared to tuberculous effusion
DISCUSSION
Pleural effusion is often a clinical problem in
medical practice, as the differential diagnosis
includes a wide variety of local and systemic
diseases.
Although many different diseases may cause
a pleural effusion, the most common causes in the
United States are congestive heart failure,
pneumonia, and cancer (8). In our study, the most
common cases of pleural effusion were cancer and
pneumonia, which can be due to a small number of
patients with congestive heart failure in our hospital.
There is a standard classification of pleural
effusion into transudative an exudative effusions,
based on the Light criteria. However, the etiology
classification of effusions is much complex. Until
now, measurements of cholesterol, bilirubin,
amylase have been used, but with limited success.
Vidriales at al., Turay at al. found that CRP pleural
fluid levels were highly elevated in parapneumonic
effusion, than in other types of effusion (12, 13). Our
study show similar results. Also, the study of Turales
show that pleural fluid/serum CRP ratio are much
higher in parapneumonic than in malignant or
tuberculous effusions. The same was with our
91
Tatjana Radjenovic Petkovic, Tatjana Pejcic, Vojin Savic, Predrag Vlahovic, Desa Nastasijević Borovac, Danijela Radojkovic
results. In our study, pleural fluid CRP was
significantly different in malignant vs. nonmalignant pleural effusion, but there is not
significant difference between malignant and
tuberculous effusions. On the contrary, Chierakul et
al. and Garcia Patchon et al. study of CRP levels in
lymphocyte pleural effusion found that CRP levels
were twice as high in tuberculous than in malignant
effusion, while Turay found higher CRP effusion
value in malignant effusion (14,15). Retrayo et al.
found that pleural fluid CRP may prove to be a rapid,
practical, and accurate method to define bacterial
pneumonia (16). Most of the authors who research
pleural fluid CRP have found that it could be a useful
marker for differentiating parapneumonic effusion
from other types of effusion.
CONCLUSION
In differential diagnosis of pleural effusions
higher CRP levels may prove to be a rapid, practical
and accurate method of differentiating parapneumonic effusions from other exudate types. The pleural
CRP level may also be helpful in discriminating
between malignant from non-malignant pleural
effusions.
REFERENCES
1. NA Maskell RJA. Butland. BTS guidelines for the
investigation of a unilateral pleural effusion in adult. Thorax
2003; 58: 8–17.
2. Castana O, Vidriales JL, Amores Antequera C. Use
of pleural fiuid C-reactive protein in laboratory diagnosis of
pleural effusions. Eur J Med 1992; 1: 201-207.
3. Gubay C, Kushner I. Acute phase proteins and other
systemic responses to inflammation. England Journal of
Medicine 1999; 340: 448-454.
4. Diederichsen HZ, Skamling M, Diederichsen A,
Grinsted P, Antonsen S. Randomised controlled trial of CRP
rapid test as a guide to treatment of respiratory infections in
general practice. Per Scand J Prim Health Care 2000; 141-148.
5. Melbye H. Point of care testing for C-reactive
protein: A new path for Australian GPs? Australian Family
Physician 2006; 35: 513-515.
6. Clyne B, Olshaker JS. The C- reactive protein. J
Emerg Med 1999; 17: 1019–1025.
7. Hamm H, Light RW. Parapneumonic effusion and
empyema. Eur Respir J 1997; 10: 1150–1156.
8. Light RW. Pleural effusion. N Engl J Med 2002;
346: 1971-1977.
9. Medford A, Maskell N. Pleural effusion. Postgrad
Med J 2005;81:702–710.
10. Castro-Guardiola A, Armengou-Arxe A, ViejoRodrıguez AL, Penarroja-Matutano G, Garcia-Bragado F.
Differential diagnosis between community-acquired pneumonia
and nonpneumonia diseases of the chest in the emergency ward.
Eur J Intern Med 2000; 11:334–339.
11. Solh AE, Pineda L, Bouquin P, Mankowski C.
Determinants of short and long term functional recovery after
hospitalization for community-acquired pneumonia in the
elderly: role of inflammatory markers. BMC Geriatrics 2006;
6:12-15.
12. Turay YU, Yildirim Z, Turkoz Y, Biber C, Erdogan
Y, KeyfAI, Ugurman F,AyazA, Ergun P, Harputluoglu M. Use of
pleural fluid C-reactive protein in diagnosis of pleural effusions.
Respir Med. 2000; 94 (5):432-435.
13. Vidriales JL, Antaquera AC. Use of C reactive
protein in laboratory diagnosis of pleural effusions. Eur J Med
1992;1:201-207.
14. Chierakul N, Kanitsap A, Viriataveekul R. Simple
C-reactive protein measurement for the differentiation between
tuberculous and malignant pleural effusion. Respirology 2004;
9: 66–69.
15. Garcia-Patchon E, Soler MJ, Padilla-Navas I,
Romero V, Shum C. C-Reactive Protein in Lymphocytic Pleural
Effusions: A Diagnostic Aid in Tuberculous Pleuritis.
Respiration 2005; 72: 486-489.
16. Requejo HZ, Cocoza AM. C-reactive protein in
the diagnosis of community-acquired pneumonia. Braz J Infect
Dis 2003; 7: 241-244.
DIJAGNOSTIČKI ZNAČAJ C-REAKTIVNOG PROTEINA U RAZLIKOVANJU
MALIGNIH OD NEMALIGNIH IZLIVA
Tatjana Rađenović Petković1, Tatjana Pejčić1, Vojin Savić2, Predrag Vlahović2
Desa Nastasijević Borovac1, Danijela Radojković3
1
Klinika za plučne bolesti i TBC Knez Selo, 2Klinika za nefrologiju,
3
Klinika za endokrinologiju
SAŽETAK
Cilj ovog rada bio je da se ispita dijagnostički značaj određivanja C-reaktivnog
proteina u izlivu, kao i odnosa CRP u izlivu i serumu, u razlikovanju malignih od
nemalignih izliva.
92
Use of C- reactive protein in pleural fluid for differential diagnosis of benign and malignant effusion
Ispitivanjem je obuhvaćeno 82 pacijenta sa kliničkim i radiološkim znacima
pleuralnog izliva, hospitalizovanih u Klinici za plućne bolesti u periodu 2006-2007. godine.
CRP je u pleuralnom izlivu i serumu određivan imunoturbidimetrijskom
metodom, na autoanalajzeru Olimpus, Japan. Pacijenti su podeljeni u dve grupe, grupu I
sa izlivom u sklopu maligne bolesti, i grupu II, sa nemalignom etiologijom izliva. Statistička
obrada rezultata urađena je korišćenjem MannWhitney test Ran sum testa.
Postoji statistički značajna razlika u vrednostima CRPa u izlivu u grupi I i grupi II
(p<0,05). Takođe, postoji značajna razlika u odnosu CRPa u izlivu i serumu u grupi I u
odnosu na grupu II (p<0,05). CRP u izlivu takođe je bio statistički značajno viši kod
zapaljenskih (parapneumoničnih i empijema), u odnosu na maligne (p<0,001),
transudativne (p<0,001) i tuberkulozne (p<0,01) izlive.
Na osnovu urađenih ispitivanja, možemo zaključiti da merenje C-reaktivnog
proteina u serumu predstavlja brz, dostupan test, koji može pomoći u diferenciranju
malignih od nemalignih, kao i zapaljenskih od drugih tipova izliva.
Ključne reči: pleuralni izliv, maligni, nemaligni, C-reaktivni protein
93
ACTA FAC MED NAISS
UDC 616.155.1-053.2
Case report
Vesna Bogicevic, Gordana Kostic
Danijela Jovancic
Gordana Bjelakovic, Mira Ilic
Bojko Bjelakovic, Ljiljana Pejcic
Verica Ilic
CASE REPORT OF A PATIENT
WITH THALASSEMIA AND
HEMOGLOBIN LEPORE
Children's Internal Clinic
Clinical Centre Nis
SUMMARY
Thalassemias are inherited disorders of hemoglobin synthesis,
characterized by reduced output of one or other globin chains of adult
hemoglobin. The red blood cells are vulnerable to mechanical injury and die
easily. To survive, many people with thalassemia need blood transfusions at
regular intervals. Hereby, we present the case of a six-year-old boy, I.U. from
Zitoradja, who was admitted to the Children's Internal Clinic in Nis in July
2005, due to paleness, exhaustion, higher body temperature, vomiting and
diarrhoea. During hospitalization, autoimmune haemolytic anemia was
dismissed and therapy was administered against infection with
supplementation of folic acid and vitamin B12. Although no members of the
nuclear family had similar symptoms, based on the findings of the boy's
abdominal ultrasound examination, as well as enlarged spleen and data on the
previous non-responsive treatment of anemia with iron medicine, there arose a
doubt that it was the case of hereditary haemolytic anemia. Molecular genetic
examination of the boy revealed heterozygosity for beta thalassemia and Hb
Lepore, a rare type of hereditary haemolytic anemia at the territory of Serbia.
During the last two years from the diagnosis, the boy has been in good condition
and has not fallen behind in growth and development in relation to his mates.
The values of haemoglobin have been maintained at satisfactory level, and so far,
no erythrocyte transfusion has been applied. Splenectomy is planned to
eliminate subjective discomfort that the boy has been feeling last months.
Key words: ß-thalassemia, hemoglobin Lepore, splenomegaly
INTRODUCTION
Thalassemias are a group of genetic disorders of hemoglobin (Hb) synthesis, characterized by
decrease in creation of one or more globin chains (1).
In 1925, Thomas Cooley and Pearl Lee described a
form of severeanemia occurring in children of Italian
origin, associated with splenomegaly and characteristic bone changes. Because all early cases were
reported in children of Mediterranean origin, the
disease was later termed thalassemia, from the Greek
Corresponding author. Tel/fax 018/514-014 064/1810-880
word for sea, thalassa (2). It has been estimated that
there are 180 million people who are heterozygotic
carriers of various types of thalassemia throughout
Asia, North Africa, and Europe. This high frequency
of genes results in a significant annual number of
births of homozygotic gene carriers and complex
heterozygotic conditions (double heterozygot) that
remain clinical problems (3,4).
Thalassemias are classified, according to the
particularglobin chain that is ineffectively produced,
as ά, β, δβ and γδβ thalassemias. Thalassemia, which
95
Vesna Bogicevic, Gordana Kostic, Danijela Jovancic, Gordana Bjelakovic, Mira Ilic, Bojko Bjelakovic, Ljiljana Pejcic, Verica Ilic
is caused by a decrease in the production of β-globin
chains, affects multiple organs and is associated with
considerable morbidity and mortality (5). The
symptoms start when the g chain production is
switched off and the b chains fail to form in adequate
numbers (1). Manifestations of anemia include
extreme pallor and enlarged abdomen due to
hepatosplenomegaly (4).
In many populations in which thalassemia is
common, the genes for structural hemoglobin
variants such as hemoglobins S, C, and E are also
common, soit is not unusual for individuals to inherit
a gene for thalassemia from one parent and that for a
hemoglobin variant from the other. A combination of
Hb Lepore with β-thalassemia results in a severe
clinical condition resembling β-thalassemia major.
Most of the important forms of thalassemia are
inherited in a Mendelian recessive fashion (6). When
one parent carries the β-thalassemia trait and the
other parent the Hb Lepore trait, there is a 25%
chance in each pregnancy that the child will be born
with HbLepore/β-thalassemia.
Treatment of patients with β-thalassemia
major has improved dramatically during the past 40
years; however, the current clinical status of these
patients remains poorly characterized (7). Regular
red blood cell transfusions eliminate the
complications of anemia and compensatory bone
marrow expansion, permit normal development
throughout childhood, and extend survival. In
parallel, transfusions result in a "second disease"
while treating the first, that of the inexorable
accumulation of tissue iron that, without treatment
(use of chelating therapy), is fatal in the second
decade of life (5,8).
CASE REPORT
The boy I.U. six years of age, from Zitoradja,
was admitted to the Children's Internal Clinic in Nis
in July, 2005, due to paleness, exhaustion, and higher
body temperature.
Anamnesis: One day prior to admission, the
boy got high body temperature (39,4°C) followed by
headache, stomach pain, diarrhoea, and vomiting.
Parents reported that in the last few months he had
been paler than usual, which was the reason why the
outpatient department doctor sent them for a hospital
examination and treatment.
From personal anamnesis we learn that it
was the second child from the fourth pregnancy (the
two prior terminated willingly). The delivery was in
term, the baby was born vital, 4400/56. Early
psychomotor development was proper. Since the boy
was two years of age, sometimes, his urine has been
dark-coloured and had severe paleness which lasted
96
for a few days. Except for often colds, up to now he
has been treated in the outpatient department with
iron medicines because of anemia, yet without
significant improvement in the blood quality.
In the family anamnesis there was no
evidence of similar symptoms in the members of the
nuclear family.
From the status: On admission, the boy
aged 6 years, conscious, subfebrile, eutrophic, BM
23kg, eupnoic RF 24/min, tachycardia SF 132/min,
distinctly pale-yellow skin colour and visible mucus
tissue, preserved muscle tonus, turgor, and skin
elasticity.
From the systems' findings we registered
the presence of light hyperaemia of palatal arches,
systolic noise over the entire precordium, painful
sensitivity of abdomen to palpation and spleen
enlargement for three transversal fingers bellow the
left rib arch. The other systems findings were clear.
Laboratory and clinical examination:
Blood test results showed low values of erythrocytes
(3,2x1012), haemoglobin (6,8g/dl), and hematocrit
(22%), while the values of leukocytes and
thrombocytes were within the range of referential
values. The number of reticulocytes was 8/1000. On
the preparation - distinctive anisopoikilocytosis –
erythrocytes in the tear shape, fragmentary
elyptocytes and a sporadic acidophilic erythroblasts.
Urine: dark yellow to red colour, albumin in
traces, urobilinogen positive, haemoglobin negative.
In urine sediment - sporadic leukocytes, plenty of
amorphous salts.
Biochemical examinations: glycaemia,
urea, creatinine, hepatogram, overall proteins and
acidobasic status within the range of referential
values. Total bilirubin 37,35 μmol/l (ref.values:020,52), indirect bilirubine 37,35 μmol/l (ref. values:5,13-15,39), direct bilirubin negative. Serum iron
14.2 μmol/l(ref.values:12,5-23,2), TIBC 42,2mol/l
(ref.values:45-63), UIBC 28 μmol/l(ref.values:34,540,2). The LDH values increased (697), and ferritin
normal.
Direct Coombs test negative.
Sodium in erythrocytes 14 .8 μmol/l
(ref.values:18-21), Potassium in erythrocytes 91.6
μmol/l (ref. values: 80-86). Osmotic resistance of
erythrocytes positive.
Electrophoresis of hemoglobin – HbA1
32,7%, HbS 64,3%(0%), HbA2 3% . Normal adult
hemoglobin contains the following components:
HbA(95-98%), HbA2(2-3%), HbA1(3-6%) and
HbF(<1%).
Myelogram – hypercellularity of bone marrow. There are all developmental forms of all three
myeloid threads, without morphological changes.
Distinctively irritated erythroid thread.
Case report of a patient with Thalassemia and hemoglobin lepore
Abdomen ultrasound examination: liver,
gallbladder, pancreas, and kidneys of normal echofinding. Spleen diameter over 15cm, homogenous,
with free hilus. Paraaortal and paracaval spaces free.
RTG pulmo et cor: Radiological finding of
lungs and heart normal.
During hospitalization, in order to deal with
infection and correct the anemia, the parenteral antibiotic and corticosteroid therapy, Folic acid replacement and Vit. B12 with intravenous rehidration were
administered. After ten days, the boy was discharged
in good condition. The advice was to continue with
Folan therapy and decrease cortico therapy
according to the scheme until cessation. Because of
the doubt of hereditary hemolitic anemia and impossibility of molecular-genetic examination in our
institution, the boy and his parents were directed to
the Research Center for Genetic Engineering and
Biotechnology in Skoplje, to professor dr
G.D.Efremov.
The following findings of hemoglobin
analysis were obtained (Figure 1).
DISCUSSION
The patient I.U. is a double heterozygote for
β -thalassemia and Hb Lepore. Molecular
characterization of beta globin genes showed that the
gene inherited from the mother was a hybrid gene
under whose control Hb Lepore was created, while
the gene inherited from the father was mutated in 6th
nucleotide of the first interventive sequence (IVS-I6). The mother of the patient is the carrier (heterozygote) for HbLepore, while the father is the carrier
(heterozygote) for beta-thalassemia (IVS-I-6).
After diagnosis, during the previous two
years, the boy was under constant hematological
control, that included regular blood control,
occasional checks of ferritin level, and ultrasound
examination of the spleen diameter. He was in a good
condition, and did not fall behind in growth and
development in relation to his mates. Fifteen days a
month, he took tabletes Folan. The aim was early
prevention and curing of infections. Until a few
months ago, hemoglobin values were in the range of
8,3 to 10 g/dl, so that there has not been any
erythrocyte substitution so far. However, at the last
check-up, the hemoglobin values were up to 8,5g/l.,
the spleen diameter at the last control was 17cm
(normal diameter for that age being 8,5 – 11cm), and
the boy complained of occasional discomfort in the
sense of swelling and weight in the stomach. As
splenomegaly is obviously aggravating the anemia
and disturbs the boy's acitivity by pressing the abdomen organs, splenectomy is planned after vaccination.
CONCLUSION
We presented a patient with intermediary
type of beta-thalassemia which is rare in our country,
but frequently occurs in the population of the
neighbouring countries - Macedonia, Greece, South
Italy. Due to constant migrations during last ten
years, we may expect higher occurence of these
hereditary types of hemolytic anemias. Diagnostic
procedures should be directed towards discovering
molecular-genetic abnormalities of hemoglobin,
unless there are no usual reasons for its occurrence in
the patient with anemia.
Figure 1. Familial haemoglobin analysis
97
REFERENCES
1. Stefanovic S. Anemije zbog naslednih poremećaja
sinteze hemoglobina. U: Hematologija. Medicinska knjiga,
Beogad-Zagreb,1989;359-405.
2. Olivieri NF. The ß-Thalassemias. NEJM 1999;
341(2):99-109.
3. Patrinos GP , Kollia P , Papadakis MN Molecular
diagnosis of inherited disorders: lessons
from
hemoglobinopathies. Human Mutation 2005;26(5): 399 – 412.
4. Cvetkovic P.Talasemija.U: Savremeno lečenje
bolesti krvi dečjeg doba.Mrlješ,Beograd, 1995;119-136.
5. Rund D, Rachmilewitz E. ß – Thalassemia. NEJM
2005; 353(11): 1135-1146.
6. Weatherall DJ. Fortnightly review: The
thalassemias. BMJ 1997;314:1675 .
7. Cunningham MJ, Macklin EA, Neufeld EJ, Cohen
AR. Complications of ß-thalassemia major in North America.
Blood 2004;104:34-39.
8. Nancy F, Brittenham O, BrittenhaGM .IronChelating Therapy and the Treatment of Thalassemia. Blood
1997; 89 (3) :739-761.
PRIKAZ PACIJENTA SA ß - TALASEMIJOM I HEMOGLOBINOM LEPORE
Vesna Bogićević, Gordana Kostić, Danijela Jovančić, Gordana Bjelaković, Mira Ilić,
Bojko Bjelaković, Ljiljana Pejčić, Verica Ilić
Dečija interna klinika Kliničkog centra Niš
SAŽETAK
Talasemije su nasledne bolesti sinteze hemoglobina koje se karakterišu
smanjenom proizvodnjom jednog ili drugog globinskog lanca adultnog hemoglobina.
Eritrociti su podložni mehaničkim ostećenjima i lako stradaju. Transfuzije krvi u
odredjenim vremenskim periodima su nekim ljudima koji boluju od talasemije potrebne za
preživljavanje. Prikazujemo šestogodišnjeg dečaka I.U. iz Žitoradje, koji je jula 2005.
godine primljen na Dečiju internu kliniku u Nišu zbog bledila, malaksalosti, povišene
telesne temperature i simptoma gastroenterokolitisa. Tokom hospitalizacije isključena je
autoimuna hemolizna anemija i primenjena terapija u cilju sanacije infekcije uz
suplementaciju Folnom kiselinom i Vitaminom B12. Iako niko od članova uže porodice
nije imao slične tegobe, kod dečaka je na osnovu ultrazvučnog nalaza uvećane slezine i
podataka o prethodno bezuspešnom lečenju anemije preparatima gvoždja, postavljena
sumnja da se radi o naslednoj hemoliznoj anemiji. Molekularno genetskim ispitivanjem,
kod dečaka je otkrivena heterozigotnost za beta talasemiju i Hb Lepore, redak oblik
nasledne hemolizne anemije na prostorima Srbije. Tokom protekle dve godine od
dijagnoze, dečak je u dobroj kondiciji i ne zaostaje u rastu i razvoju u odnosu na vršnjake.
Vrednosti hemoglobina se održavaju na zadovoljvajućem nivou, te do sada ni jednom nije
primenjena transfuzija eritrocita. Planira se splenektomija radi otklanjanja subjektivnih
tegoba koje dečak oseća poslednjih meseci.
Ključne reči: talasemija, hemoglobin Lepore, splenomegalija
98
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ACTA FACULTATIS MEDICAE NAISSENSIS
BRIDGES MADE OF COMPOSITES REINFORCED WITH GLASS FIBRE,
ANCHORED ONABUTMENT TEETH WITH CROWN INLAYS – SELECTED CASES .............................................. 53
REVISING HIPARTHROPLASTY .................................................................................................................................. 59
Ljiljana Vasic
AROLE OF CYFRA21-1 BETWEEN TUMOR MARKERS FOR NON-SMALL-CELL LUNG CANCER ................... 65
PREVALENCE OF DIROFILARIAREPENS - CAUSE OF ZOONOSIS IN DOGS ......................................................... 71
CLINICAL PRESENTATION OF COMORBID DEPRESSIONAND POST-TRAUMATIC STRESS DISORDER ....... 75
TREATMENT OF THE FEMORAL SHAFT FRACTURE
BY SELF-DYNAMISABLE INTERNAL FIXATOR MITKOVIC ................................................................................... 83
Tatjana Radjenovic Petkovic, Tatjana Pejcic, Vojin Savic, Predrag Vlahovic, Desa Nastasijevic Borovac, Danijela Radojkovic
USE OF C- REACTIVE PROTEIN IN PLEURAL FLUID FOR DIFFERENTIAL DIAGNOSIS
OF BENIGNAND MALIGNANT EFFUSION ................................................................................................................. 89
CASE REPORT OFAPATIENT WITH THALASSEMIAAND HEMOGLOBIN LEPORE ............................................ 95

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