Congenital hypothyroidism Congenital syphilis Dentinogenesis

Congenital hypothyroidism Congenital syphilis Dentinogenesis

Congenital hypothyroidism
Congenital syphilis
Dentinogenesis imperfecta
Neonatal
hyperbilirubinemia
Williams syndrome
Green primary dentition is visible, predominantly over the incisal two thirds of the
anterior teeth. Permanent green pigmentation of primary dentition can result from
neonatal hyperbilirubinemia that is classically seen in biliary atresia. Other causes
include hemolytic disease and cholestasis caused by severe neonatal sepsis, as in this
infant.
Big tongue (cretinism)
Rhagades (syphilis)
Neonatal hyperbilirubinemia
Dentinogenesis imperfecta
Williams‘ Syndrome
Fluorosis and tetracycline
Porphyria
Das Williams-Beuren-Syndrom (WBS), auch bekannt unter den Synonymen Williams-Syndrom,
Fanconi-Schlesinger-Syndrom, idiopathische Hyperkalzämie oder Elfin-face-Syndrom, ist eine
genetisch bedingte Besonderheit, deren Ursache in einem Stückverlust (= Deletion) auf dem
Chromosom 7 liegt. Das Syndrom wurde nach dem in Auckland tätigen britischen Kardiologen J.
C. P. Williams und dem Göttinger Kardiologen Alois J. Beuren benannt. Das WBS wurde in der
medizinischen Literatur 1961 von Williams et al. und 1962 von Beuren et al. erstmals ausführlich
beschrieben, wobei auch Hinweise vorliegen, dass bereits John Langdon-Down, der das nach
ihm benannte Down-Syndrom (Trisomie 21) 1866 und das Prader-Willi-Syndrom erstmals unter
wissenschaftlichen Gesichtspunkten beschrieb, eine Beschreibung des WBS vornahm.
Kardiovaskuläre Veränderungen/Herzfehler (oft supravalvuläre Aortenstenose (SVAS)/
Verengung der Hauptschlagader unmittelbar am Anschluss an das Herz mit variablem
Schweregrad, hypoplastische Aorta/zu schmale Hauptschlagader, Septumfehlbildungen/
Löcher in der Herzscheidewand) bei 90 % der Menschen. Pulmonalstenosen
Primäre Nierenfehlbildungen (besondere Lage der Niere, Verengungen/Stenosen an den
Nierengefäßen, unterentwickelte Niere, einseitiges Fehlen einer Niere, Hufeisennieren) bei
etwa 18 % der Menschen.
HIV oder auch bezeichnet als Menschliches Immunschwäche-Virus oder Menschliches
Immundefekt-Virus, ist ein Virus, das zur Familie der Retroviren und zur Gattung der Lentiviren
gehört. Eine unbehandelte HIV-Infektion führt nach einer unterschiedlich langen, meist
mehrjährigen Inkubationszeit in der Regel zu AIDS (engl. acquired immunodeficiency
syndrome‚ erworbenes Immundefizienzsyndrom‘). Die Verbreitung von HIV hat sich in den
letzten 30 Jahren zu einer Pandemie entwickelt, die nach Schätzungen der Organisation
UNAIDS bisher etwa 28 Millionen Leben gefordert hat. Etwa 33,3 Millionen Menschen sind
weltweit mit dem Virus infiziert, wobei die Verteilung auf beide Geschlechter in etwa gleich ist.
Die Zahl der Neuinfektionen sinkt seit 1997 stetig und lag 2009 bei 2,6 Millionen Menschen. In
Deutschland leben gemäß Schätzungen des Robert Koch-Instituts etwa 73.000 Menschen mit
HIV, davon 11.500 Frauen und 200 Kinder.
CCR5
Tenofovir ist ein Virostatikum, das als Arzneistoff in der Behandlung von HIV-1-Infektionen und
Hepatitis B verwendet wird. Tenofovir gehört zur Gruppe der nukleotidischen ReverseTranskriptase-Inhibitoren (NtRTI), die klinisch wie die nukleosidischen Reverse-TranskriptaseInhibitoren (NRTI) eingesetzt werden. Chemisch handelt es sich um ein Nukleotid-Analogon,
das aufgrund seiner strukturellen Verwandtschaft mit dem natürlichen Substrat an dessen Stelle
in die Virus-DNA eingebaut wird und in Folge die Vermehrung der Viren hemmt.
Emtricitabin ist ein chemisches Analogon
des Nukleosids Cytidin. Es ist ein
Virustatikum aus der Gruppe der NukleosidReverse-Transkriptase-Inhibitoren (NRTI)
und wird als Arzneistoff (Coviracil, Triangle
Pharmaceutics) zur Behandlung von mit
HIV-1 und 2 infizierten Patienten im
Rahmen einer antiretroviralen
Kombinationstherapie eingesetzt. Es ist
ebenfalls gegen HBV wirksam.
Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women
Antiretroviral preexposure prophylaxis is a promising approach for preventing human
immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. We conducted a
randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1–
serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1–seronegative partner
in each couple was randomly assigned to one of three study regimens — once-daily tenofovir
(TDF), combination tenofovir–emtricitabine (TDF–FTC), or matching placebo — and followed
monthly for up to 36 months. At enrollment, the HIV-1–seropositive partners were not eligible for
antiretroviral therapy, according to national guidelines. All couples received standard HIV-1
treatment and prevention services.
Oral TDF and TDF–FTC both protect
against HIV-1 infection in
heterosexual men and women.
(Funded by the Bill and Melinda
Gates Foundation; Partners PrEP
ClinicalTrials.gov number.
Partners HealthCare is a non-profit organization that owns several hospitals in Massachusetts,
primarily in the Boston area. Massachusetts General Hospital and Brigham and Women's Hospital
founded the organization in 1994. Partners is the largest healthcare provider in Massachusetts
and many of its hospitals are teaching affiliates of Harvard Medical School.
Brigham and Women's Hospital
Massachusetts General Hospital
Newton-Wellesley Hospital
North Shore Medical Center
Faulkner Hospital
McLean Hospital
Martha's Vineyard Community Hospital
Nantucket Cottage Hospital
Massachusetts General Physician
Organization
Partners Continuing Care
PCHI
Partners International Medical Services (PIMS) is a subsidiary of Partners HealthCare that
focuses on the advancement of global health. PIMS collaborates with foreign embassies,
ministries of health, and universities overseas to improve health status indicators directly through
patient care initiatives and indirectly through medical conferences and other educational
programs for physicians and nurses.
Preexposure Prophylaxis for HIV Infection among African Women
Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human
immunodeficiency virus (HIV) infection in some trials but not in others. In this randomized,
double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South
Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and
emtricitabine (TDF–FTC) or placebo once daily. The primary objective was to assess the
effectiveness of TDF–FTC in preventing HIV acquisition and to evaluate safety.
Prophylaxis with TDF–FTC did
not significantly reduce the rate
of HIV infection and was
associated with increased rates
of side effects, as compared with
placebo. Despite substantial
counseling efforts, drug
adherence appeared to be low.
(Supported by the U.S. Agency
for International Development
and others
Antiretroviral Preexposure Prophylaxis for Heterosexual HIV Transmission in
Botswana
Reexposure prophylaxis with antiretroviral agents has
been shown to reduce the transmission of human
immunodeficiency virus (HIV) among men who have sex
with men; however, the efficacy among heterosexuals is
uncertain. We randomly assigned HIV-seronegative
men and women to receive either tenofovir disoproxil
fumarate and emtricitabine (TDF–FTC) or matching
placebo once daily. Monthly study visits were
scheduled, and participants received a comprehensive
package of prevention services, including HIV testing,
counseling on adherence to medication, management of
sexually transmitted infections, monitoring for adverse
events, and individualized counseling on risk reduction;
bone mineral density testing was performed
semiannually in a subgroup of participants. Botswana
has the world's second highest prevalence of HIV
infection, estimated in 2008 to be 17.6% overall and
approximately 40% among adults 30 to 44 years of age.
Daily TDF–FTC
prophylaxis prevented
HIV infection in
sexually active
heterosexual adults.
The long-term safety of
daily TDF–FTC
prophylaxis, including
the effect on bone
mineral density,
remains unknown.
Brustkrebs ist der häufigste bösartige Tumor der Brustdrüse des Menschen. Er kommt
hauptsächlich bei Frauen vor; nur etwa jede hundertste dieser Krebserkrankungen tritt bei Männern
auf.[1] In den westlichen Staaten ist Brustkrebs die häufigste Krebsart bei Frauen. Am Brustkrebs
sterben mehr Frauen als an irgendeiner anderen Krebserkrankung. Die meisten Erkrankungen
treten sporadisch (zufällig) auf, es gibt aber sowohl erbliche als auch erworbene Risikofaktoren.
Neben der Heilung sind der Erhalt der betreffenden Brust und vor allem der Lebensqualität
erklärtes Ziel der medizinischen Behandlung. Die Therapie besteht in der Regel in einer an das
Erkrankungsstadium angepassten Kombination aus Operation sowie Zytostatika-, Hormon- und
Strahlentherapie. Neue Ansätze aus dem Gebiet der Krebsimmuntherapie werden außerdem durch
monoklonale Antikörper ermöglicht. Das medizinische Vorgehen basiert in hohem Maß auf
Erfahrungen aus Studien und ist in weltweit akzeptierten Leitlinien standardisiert. Zahlreiche
nationale und internationale Programme zur Früherkennung und zur strukturierten Behandlung
sollen die Mortalität (Sterblichkeit) künftig senken. Der Östrogenrezeptor- und
Progesteronrezeptorstatus (ER- und PgR-Expression) wird ebenfalls histologisch, genauer
immunhistologisch untersucht. Man bestimmt den Prozentsatz derjenigen Tumorzellen, an denen
sich die Rezeptoren nachweisen lassen und errechnet aus Prozentsatz und der Färbeintensität
einen 12-stufigen Immunreaktiven Score (IRS), oder den international gebräuchlicheren 8-stufigen
Allred-Score.
Ist die Patientin postmenopausal, erhält sie für in der Regel fünf Jahre
entweder Tamoxifen oder einen Aromatasehemmer, welcher durch
eine Enzymblockade die Bildung von Östrogen im Muskel- und
Fettgewebe unterbindet. Neuere Studienergebnisse deuten an, dass
die Aromatasehemmer wirksamer sind als das Tamoxifen, das heißt,
die krankheitsfreie Überlebenszeit steigt an. In Studien wird der
Aromatasehemmer manchmal sofort verwendet (upfront), in der
Regelbehandlung erst nach zwei bis drei Jahren unter Tamoxifen
(switch, dt. ‚Wechsel‘), oder nach fünf Jahren (extended).
Anastrozole (INN) (marketed under the trade name Arimidex by AstraZeneca) is an aromataseinhibiting drug approved for treatment of breast cancer after surgery, as well as for metastasis in
both pre and post-menopausal women. The severity of breast cancer is increased by estrogen, as
sex hormones cause hyperplasia, and differentiation at estrogen receptor sites.[3] Anastrozole
works by inhibiting the synthesis of estrogen. The patent on Arimidex by AstraZeneca expired 27
June 2010. Anastrozole binds reversibly to the aromatase enzyme through competitive inhibition,
inhibits the conversion of androgens to estrogens in peripheral tissues (outside the CNS), and a
few CNS sites in various regions within the brain.
Fulvestrant (Faslodex, AstraZeneca) is
a drug treatment of hormone receptorpositive metastatic breast cancer in
postmenopausal women with disease
progression following anti-estrogen
therapy. It is an estrogen receptor
antagonist with no agonist effects,
which works both by down-regulating
and by degrading the estrogen
receptor.
Combination Anastrozole and Fulvestrant in Metastatic Breast Cancer
The aromatase inhibitor anastrozole inhibits estrogen synthesis. Fulvestrant binds and accelerates
degradation of estrogen receptors. We hypothesized that these two agents in combination might
be more effective than anastrozole alone in patients with hormone-receptor (HR)–positive
metastatic breast cancer. Postmenopausal women with previously untreated metastatic disease
were randomly assigned, in a 1:1 ratio, to receive either 1 mg of anastrozole orally every day
(group 1), with crossover to fulvestrant alone strongly encouraged if the disease progressed, or
anastrozole and fulvestrant in combination (group 2). Patients were stratified according to prior or
no prior receipt of adjuvant tamoxifen therapy. Fulvestrant was administered intramuscularly at a
dose of 500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter. The primary end
point was progression-free survival, with overall survival designated as a prespecified secondary
outcome.
Toxic effects of grade 3 or higher were observed in 42 patients who received
anastrozole alone (12.7%) and in 51 patients who received combination therapy
(14.7%) (P=0.44). The most common grade 3 toxic effects were musculoskeletal pain
(2.8%), influenza-like symptoms (2.4%), gastrointestinal disturbances (1.5%), and
hematologic effects (1.5%).
The combination of anastrozole and fulvestrant was superior to anastrozole
alone or sequential anastrozole and fulvestrant for the treatment of HR-positive
metastatic breast cancer, despite the use of a dose of fulvestrant that was below
the current standard.
We suggest that trials of adjuvant therapy should be performed in which the
combination of an aromatase inhibitor and high-dose fulvestrant is compared with
an aromatase inhibitor alone or high-dose fulvestrant alone, in patients with
estrogen-receptor–positive tumors for whom chemotherapy is not necessary.
A 30-year-old woman with a history of bulimia presented to the emergency
department after swallowing a knife.
Her husband later disclosed that 4 years earlier she had swallowed a knife that required
surgical removal with exploratory laparotomy. Consultation with a psychiatrist was
recommended, and the patient was later transferred to an inpatient psychiatric unit.
Breathtaking Journey
A 48-year-old man came to the emergency department in early August with a 3-day history of
influenza-like symptoms and profound dyspnea on exertion, which had started 3 days after his
return to Boston from a vacation in California. On his return flight, subjective fevers, headache,
myalgias, and nausea developed, and the patient had one episode of vomiting. Over the next 2
days, a nonproductive cough and profound exertional dyspnea developed. The patient said that
he did not have a rash, neck stiffness, visual changes, diarrhea, dysuria, or joint pain. Three
weeks before admission, the patient hiked and camped in the Catskill Mountains for 9 days. On
the first night, he slept on the floor of a lean-to, where he observed mice. Two weeks before
admission, he removed an attached tick. One week before admission, he flew to California and
spent 4 days hiking and camping in the San Joaquin Valley.
There was no rash. The mucous membranes
were dry. The neck was supple, with no
meningeal signs. No peripheral adenopathy was
noted. The jugular venous pressure was less
than 5 cm of water. Chest auscultation revealed
crackles in the lower lobes of both lungs; the
heart tones were regular, with normal carotid
upstrokes. The abdomen was soft and
nontender. There was no hepatosplenomegaly.
There were no joint effusions or peripheral
edema. The neurologic examination was
unremarkable.
he patient was empirically treated with intravenous
fluids, ceftriaxone, and doxycycline. He remained
afebrile, but during the first 24 hours after admission,
hypoxemia developed while the patient was breathing
ambient air at rest; supplemental oxygen at a rate of 3
liters per minute was added. On the third hospital day,
the white-cell count was 7400 per cubic millimeter, with
48% neutrophils, 11% band forms, 11% monocytes,
12% lymphocytes, 16% atypical lymphocytes, and 2%
metamyelocytes. The hematocrit was 46%, and the
platelet count 59,000 per cubic millimeter. The sodium
level was 136 mmol per liter, alanine aminotransferase
224 U per liter, aspartate aminotransferase 212 U per
liter, total bilirubin 0.9 mg per deciliter (15 µmol per
liter), and alkaline phosphatase 58 U per liter. Serologic
studies sent on admission were returned after the
patient had been discharged. Testing for Rocky
Mountain spotted fever, B. microti, A. phagocytophilum,
Ehrlichia chaffeensis, C. immitis, and leptospira was
negative. Serologic testing for IgG antibody to
mycoplasma showed an immune status ratio of 0.91 to
1.09 (equivocal range). Testing with the use of an
enzyme-linked immunosorbent assay (ELISA) for IgG
and IgM antibodies specific to the Sin Nombre
hantavirus group was positive, at levels of 2.35 and
8.22, respectively (normal value, <1.10).
Die Gattung Hantavirus aus der Familie der Bunyaviridae umfasst unter anderem die
humanpathogenen Arten Hantaan-Virus, Puumala-Virus, Dobrava-Belgrad-Virus, Seoul-Virus,
Korea-Fieber-Virus, Sin-Nombre-Virus. Diese behüllten Einzel-Strang(−)-RNA-Viren [ss(−)RNA]
verursachen Lungenerkrankungen, akutes Nierenversagen (Nephrotisches Syndrom) oder
schwere hämorrhagische Fiebererkrankungen insbesondere im südasiatischen Raum, aber auch
in Europa, siehe: Vorkommen. Der Name Hanta geht auf den Fluss Hantan in Südkorea zurück,
an welchem in den 1950er-Jahren während des Koreakrieges mehr als 3000 amerikanische
Soldaten an einem ungewöhnlich starken Fieber mit anschließend häufigen Nierenversagen
erkrankten. Erst 1977 gelang es durch Ho Wang Lee und andere, das bis dahin unbekannte
Virus zu isolieren. Die Übertragung geschieht durch verschiedene Nager, die mit dem Speichel,
den Fäkalien und dem Urin (Virurie) große Mengen an Erregern ausscheiden. Bei den Nagern
sind vor allem Mäuse, in Deutschland besonders die Rötelmaus als Überträger festgestellt, die
jedoch selbst nicht erkranken, auch wenn sie, einmal infiziert, lebenslang infektiös bleiben
Linagliptin (Trajenta®) ist ein Arzneistoff zur peroralen Behandlung von Typ II-Diabetes. Im
August 2011 erteilte die Europäische Kommission die Zulassung für das von dem
pharmazeutischen Unternehmen Boehringer Ingelheim entwickelte Medikament. Linagliptin ist
ein Wirkstoff aus der Gruppe der Dipeptidylpeptidase-4-Inhibitoren. Diese hemmen das Enzym
Dipeptidylpeptidase 4 (DPP-4). Linagliptin ist ein Inhibitor des Dipeptylpeptidase-Isoenzyms
DPP-4, welches er kompetitiv und selektiv gegenüber anderen Isozenzymen, wie die
Dipeptylpeptidasen DPP-8 und DPP-9, hemmt. Als Dipeptylpeptidase-4-Inhibitor hemmt es den
Abbau des Inkretin-Hormons Glucagon-like-peptide 1 (GLP-1). Im Vergleich zu den bereits
kommerziell genutzten Gliptinen Sitagliptin, Saxagliptin und Vildagliptin zeichnet sich Linagliptin
zumindest experimentell durch eine höhere Wirkpotenz und eine längere Wirkdauer aus.
Das Protein Glucagon-like Peptide 1 (GLP-1)
ist ein Peptidhormon, das eine wichtige Rolle
im Zuckerstoffwechsel im Rahmen des
Inkretin-Effekts – der Insulinantwort der βZellen in der Bauchspeicheldrüse auf
Glucosezufuhr über den Darm – spielt.
Erstmals wurde das GLP-1 im Jahre 1979 von
der Arbeitsgruppe um Prof. Werner Creutzfeldt
an der Universität Göttingen beschrieben.
GLP-1 wird als Darmhormon von den
neuroendokrinen L-Zellen des Darms
produziert und bei Nahrungsaufnahme in den
Blutkreis freigesetzt. Es wird innerhalb von
Minuten von dem Enzym Dipeptidylpeptidase 4
(DPP 4) abgebaut und muss also ständig neu
produziert werden.
Glimepirid ist ein orales Antidiabetikum aus der Stoffgruppe der Sulfonylharnstoffe, welches
direkt in den β-Zellen der Bauchspeicheldrüse die Insulinfreisetzung steigert. Der Wirkstoff ist
nicht mehr patentgeschützt und es sind verschiedene Generika verfügbar. Da es für den
Wirkungseintritt nötig ist, dass der Körper zumindest eingeschränkt selbst Insulin produziert,
kann Glimepirid nicht zur Behandlung des Diabetes mellitus Typ 1 eingesetzt werden.
Arzneimittel, die Glimepirid enthalten, sind verschreibungspflichtig.
Binding closes the linked ATPsensitive potassium channels,
which leads to decreased
potassium influx and
subsequent depolarization of
the beta-cell membrane.
Voltage-dependent calcium
channels open and result in an
influx of calcium, causing
translocation and exocytosis of
secretory granules of insulin to
the cell surface
2-year efficacy and safety of linagliptin compared with glimepiride in patients
with type 2 diabetes inadequately controlled on metformin: a randomised,
double-blind, non-inferiority trial
Addition of a sulphonylurea to metformin improves glycaemic control in type 2 diabetes, but is
associated with hypoglycaemia and weight gain. We aimed to compare a dipeptidyl peptidase-4
inhibitor (linagliptin) against a commonly used sulphonylurea (glimepiride). In this 2-year, parallelgroup, non-inferiority double-blind trial, outpatients with type 2 diabetes and glycated haemoglobin
A1c (HbA1c) 6·5—10·0% on stable metformin alone or with one additional oral antidiabetic drug
(washed out during screening) were randomly assigned (1:1) by computer-generated random
sequence via a voice or web response system to linagliptin (5 mg) or glimepiride (1—4 mg) orally
once daily. Study investigators and participants were masked to treatment assignment. The primary
endpoint was change in HbA1c from baseline to week 104. Analyses included all patients randomly
assigned to treatment groups who received at least one dose of treatment, had a baseline HbA1c
measurement, and had at least one on-treatment HbA1c measurement.
The overall incidence of hypoglycaemic events
was, significantly, 4·8-times lower with linagliptin
than with glimepiride (58 [7%] of 776 vs 280
[36%] of 775 patients; Bodyweight decreased
with linagliptin (—1·4 [SE 0·2] kg) but increased
with glimepiride (1·3 [0·2] kg
Our findings support the use of linagliptin in
combination with metformin as a therapeutic
option for treatment of type 2 diabetes. This
study adds to the evidence base for evaluation
of recommendations for second-line treatment
after metformin.
Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a
randomised, open-label and double-blind, placebo-controlled, non-inferiority
trial
Acute pyelonephritis is a common infection in adult women, but there is a paucity of controlled
trials of its treatment and the optimum duration of antibiotic treatment has not been properly
defined. We compared the efficacy of ciprofloxacin for 7 days and 14 days in women with
community-acquired acute pyelonephritis. In a prospective, non-inferiority trial undertaken at 21
centres of infectious diseases in Sweden, women (aged ≥18 years) who were not pregnant and
had a presumptive diagnosis of acute pyelonephritis were randomly assigned to oral treatment
with ciprofloxacin 500 mg twice daily for 7 days or 14 days. The first week was open label. A
computer-generated randomisation list in block sizes of two was used for treatment allocation in
a 1:1 ratio. The study was double-blind and placebo-controlled during the second week of
treatment, which was either continuation of ciprofloxacin 500 mg or placebo tablets twice daily
according to the randomisation code. Patients, carers, site investigators, and trial coordinating
centre staff were masked to group assignment. The primary endpoint was the clinical and
bacteriological outcome 10—14 days after completion of treatment with active drug. Eligible
patients had fever of at least 38·0°C (measured at home or in the emergency department) and at
least one symptom or sign relating to the urinary tract such as flank pain, costovertebral angle
tenderness, dysuria, urgency, or frequency.
Our results show that communityacquired acute pyelonephritis in
women can be treated successfully
and safely with oral ciprofloxacin
for 7 days and even in older
patients and those with a more
severe infection
An otherwise healthy 45-year-old
woman presented with a 6-month
history of gradual visual loss in both
eyes. Her best-corrected visual
acuity was 20/30 in both eyes. Slitlamp examination showed bilateral
—predominantly peripheral—corneal
deposits of numerous minute,
crystalline materials. The remainder
of the ocular examination was
unremarkable.
A clinical diagnosis of monoclonal gammopathy was made on the basis of shimmering and
polychromatic corneal deposits. Serum IgG concentration was 30·3 g/L (normal 8·1—16·9 g/L)
and serum electrophoresis showed a monoclonal gammopathy involving IgG-kappa light chain.
Our patient was referred to a haematologist and IgG-kappa multiple myeloma was diagnosed by
bone marrow biopsy. Treatment was initiated with thalidomide, and no ocular-specific drugs were
prescribed. During the 7-year follow-up, while maintained on a low-dose thalidomide, our patient
was regularly followed up and her vision remained stable. Although still present, the amount of
these corneal crystalline deposits appeared to be decreasing and migrate away from the
peripheral corneas.
The effect of mass immunisation campaigns and new oral poliovirus vaccines
on the incidence of poliomyelitis in Pakistan and Afghanistan, 2001–11: a
retrospective analysis
Pakistan and Afghanistan are two of the three remaining countries yet to interrupt wild-type
poliovirus transmission. The increasing incidence of poliomyelitis in these countries during
2010—11 led the Executive Board of WHO in January, 2012, to declare polio eradication a
“programmatic emergency for global public health”. We aimed to establish why incidence is
rising in these countries despite programme innovations including the introduction of new
vaccines. We did a matched case-control analysis based on a database of 46 977 children
aged 0—14 years with onset of acute flaccid paralysis between Jan 1, 2001, and Dec 31,
2011. The vaccination history of children with poliomyelitis was compared with that of children
with acute flaccid paralysis due to other causes to estimate the clinical effectiveness of oral
poliovirus vaccines (OPVs) in Afghanistan and Pakistan by conditional logistic regression. We
estimated vaccine coverage and serotype-specific vaccine-induced population immunity in
children aged 0—2 years and assessed their association with the incidence of poliomyelitis
over time in seven regions of Afghanistan and Pakistan.
The effectiveness of bivalent OPV is comparable
with monovalent OPV and can therefore be used
in eradicating serotype 1 poliomyelitis whilst
minimising the risks of serotype 3 outbreaks.
However, decreases in vaccination coverage in
parts of Pakistan and southern Afghanistan have
severely limited the effect of this vaccine.
Vaccination coverage decreased during 2006—
11 in the Federally Administered Tribal Areas
(FATA), Balochistan, and Khyber Pakhtunkhwa
in Pakistan and in southern Afghanistan.
Radiation exposure from CT scans in childhood and subsequent risk of
leukaemia and brain tumours: a retrospective cohort study
Although CT scans are very useful clinically, potential cancer risks exist from associated ionising
radiation, in particular for children who are more radiosensitive than adults. We aimed to assess
the excess risk of leukaemia and brain tumours after CT scans in a cohort of children and young
adults. In our retrospective cohort study, we included patients without previous cancer diagnoses
who were first examined with CT in National Health Service (NHS) centres in England, Wales, or
Scotland (Great Britain) between 1985 and 2002, when they were younger than 22 years of age.
We obtained data for cancer incidence, mortality, and loss to follow-up from the NHS Central
Registry from Jan 1, 1985, to Dec 31, 2008. We estimated absorbed brain and red bone marrow
doses per CT scan in mGy and assessed excess incidence of leukaemia and brain tumours
cancer with Poisson relative risk models. To avoid inclusion of CT scans related to cancer
diagnosis, follow-up for leukaemia began 2 years after the first CT and for brain tumours 5 years
after the first CT.
Use of CT scans in children to deliver cumulative
doses of about 50 mGy might almost triple the
risk of leukaemia and doses of about 60 mGy
might triple the risk of brain cancer.
Tetanus, auch Wundstarrkrampf genannt, ist eine häufig tödlich verlaufende Infektionskrankheit,
welche die muskelsteuernden Nervenzellen befällt und durch das Bakterium Clostridium tetani
ausgelöst wird. Die resistenten Sporen des Bakteriums kommen nahezu überall vor, auch im
Straßenstaub oder in der Gartenerde. Die Infektion erfolgt durch das Eindringen der Sporen in
Wunden. Unter anaeroben Bedingungen, d. h. unter Sauerstoff-Abwesenheit, vermehrt sich das
Bakterium und sondert Giftstoffe (Toxine) ab. Das proteolytische Toxin Tetanospasmin schädigt
die muskelsteuernden Nervenzellen und verursacht dadurch die typischen Lähmungen und
Muskelkrämpfe. Das Toxin Tetanolysin ist herzschädigend. Tetanolysin ist hämolysierend und
kardiotoxisch, aber für die typischen Symptome der Krankheit unbedeutend. Wichtiger ist
Tetanospasmin, das über periphere Nervenbahnen in das Zentralnervensystem gelangt. Dort
greift es Proteine (SNARE) an, die zur Freisetzung der Neurotransmitter (Glycin und GABA) der
Renshaw-Zellen im Vorderhorn des Rückenmarks nötig sind. Tetanospasmin ist eine
Endopeptidase. Die Blockade geschieht über eine enzymatische Inaktivierung des
Synaptobrevin/Vesicular Associated Membrane Complex, wodurch die Freisetzung der
Neurotransmitter durch Exozytose gestört ist. Damit kommt es zur unkontrollierten Aktivierung
der alpha-Motoneuronen und zu tonischen (andauernden) und klonischen (zuckenden)
Verkrampfungen der quergestreiften (Willkür-)Muskulatur.
Sept. 2011 86-year-old woman was admitted to our medical intensive care unit with trismus and
neck stiffness. 2 years earlier, she had been diagnosed with marginal zone lymphoma. Her
medications included chlorambucil from January to October, 2010, followed by rituximab,
cyclophosphamide, vincristine, and prednisone in March, 2011. Prednisone (20 mg per day) was
maintained from March to August, 2011. 5 months before presentation, she had several falls and
she received local care with 3 stitches for a chin wound in April 2011, and was given a first
tetanus vaccination. She had not previously been vaccinated for tetanus and complete
vaccination was proposed, but she refused. In August, 2011, she had another fall, resulting in a
severe wound to her left leg. She was given oral amoxicillin clavulanate and daily wound care for
a week. She reported 10 days afterwards, dysphagia, gait instability, dysarthria, stiffness of the
neck, and intractable trismus. She was referred the same day to our hospital. On presentation,
she was alert and fully oriented. Core temperature was 37°C. She was severely malnourished.
Her weight was 42 kg, for a height of 152 cm, and she had diffuse muscle atrophy, skin fragility,
and splenomegaly. The left calf wound was dry and clean. There was no limb weakness. Plantar
responses were normal.
The absence of antibodies suggests that our patient was
unable to produce an immune response to tetanus.
Ageing, active lymphoma, chemotherapy, and rituximab
can impair the immune response. For patients with dirty
wounds who are elderly, have a haematological
malignancy, or are on chemotherapy, a tetanus-specific
single-step immunoassay should be done even if
previous vaccination is apparently correct. If the assay
results are negative, human tetanus immunoglobulins
should be given.