Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study.

OBJECTIVE: To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy. DESIGN: A review of all published cohort studies to identify key indications and a population based case-control study to test these indications. SETTING: Review of PubMed, Web of Science, and Embase for papers about carbamazepine exposure in the first trimester of pregnancy and specific malformations, and the EUROCAT Antiepileptic Study Database, including data from 19 European population based congenital anomaly registries, 1995-2005. PARTICIPANTS: The literature review covered eight cohort studies of 2680 pregnancies with carbamazepine monotherapy exposure, and the EUROCAT dataset included 98 075 registrations of malformations covering over 3.8 million births. MAIN OUTCOME MEASURES: Overall prevalence for a major congenital malformation after exposure to carbamazepine monotherapy in the first trimester. Odds ratios for malformations with exposure to carbamazepine among cases (five types of malformation identified in the literature review) compared with two groups of controls: other non-chromosomal registrations of malformations and chromosomal syndromes. RESULTS: The literature review yielded an overall prevalence for a major congenital malformation of 3.3% (95% confidence interval 2.7 to 4.2) after exposure to carbamazepine monotherapy in the first trimester. In 131 registrations of malformations, the fetus had been exposed to carbamazepine monotherapy. Spina bifida was the only specific major congenital malformation significantly associated with exposure to carbamazepine monotherapy (odds ratio 2.6 (95% confidence interval 1.2 to 5.3) compared with no antiepileptic drug), but the risk was smaller for carbamazepine than for valproic acid (0.2, 0.1 to 0.6). There was no evidence for an association with total anomalous pulmonary venous return (no cases with carbamazepine exposure), cleft lip (with or without palate) (0.2, 0.0 to 1.3), diaphragmatic hernia (0.9, 0.1 to 6.6), or hypospadias (0.7, 0.3 to 1.6) compared with no exposure to antiepileptic drugs. Further exploratory analysis suggested a higher risk of single ventricle and atrioventricular septal defect. CONCLUSION: Carbamazepine teratogenicity is relatively specific to spina bifida, though the risk is less than with valproic acid. Despite the large dataset, there was not enough power to detect moderate risks for some rare major congenital malformations.

Fas ligand elicits a caspase-independent proinflammatory response in human keratinocytes: implications for dermatitis.

Fas ligand (FasL) causes apoptosis of epidermal keratinocytes and triggers the appearance of spongiosis in eczematous dermatitis. We demonstrate here that FasL also aggravates inflammation by triggering the expression of proinflammatory cytokines, chemokines, and adhesion molecules in keratinocytes. In HaCaT cells and in reconstructed human epidermis (RHE), FasL triggered a NF-kappaB-dependent mRNA accumulation of inflammatory cytokines (tumor necrosis factor-alpha, IL-6, and IL-1beta), chemokines (CCL2/MCP-1, CXCL1/GROalpha, CXCL3/GROgamma, and CXCL8/IL-8), and the adhesion molecule ICAM-1. Oligomerization of Fas was required both for apoptosis and for gene expression. Inhibition of caspase activity abolished FasL-dependent apoptosis; however, it failed to suppress the expression of FasL-induced genes. Additionally, in the presence of caspase inhibitors, but not in their absence, FasL triggered the accumulation of CCL5/RANTES (regulated on activation normal T cell expressed and secreted) mRNA. Our findings identify a novel proinflammatory role of FasL in keratinocytes that is independent of caspase activity and is separable from apoptosis. Thus, in addition to causing spongiosis, FasL may play a direct role in triggering and/or sustaining inflammation in eczemas.

Am I my brain or my genitals? A nature-culture controversy in the hermaphrodite debate from the mid-1960s to the late 1990s.

The groundbreaking and prophetic rhetoric of neuroscience has recently highlighted the fetal brain as the most promising organ for understanding why transsexuals feel "trapped in the wrong body", and for predicting whether children born with "ambiguous" genitalia will grow up to feel like a man or a woman.This article proposes a recent history of the cerebralization of intersexuality and of transsexuality as atypical neurodevelopmental conditions. It examines the ways in which the organizational theory of brain sex differentiation developed in the late 1950s in behavioral neuroendocrinology has gained increased prominence in and through controversies over best practice issues in the case management of intersex newborns, and the etiology of transsexuality.It focuses on the American context and on the leading warrior in this battle: Milton Diamond, now a most prominent figure in professional debates about the clinical management of intersexuality, and the intersex person's best friend. Persons with an intersexed or transsexual condition consider, not their gonads, but their brains, their core sense of self, as the primary determinant of sex. (Diamond and Beh 2005, 6-7, note 1)

PRPF31 alternative splicing and expression in human retina

PURPOSE: To provide a mechanistic link between mutations in PRPF31, and essential and ubiquitously expressed gene, and retinitis pigmentosa, a disorder restricted to the eye. METHODS: We investigated the existence of retina-specific PRPF31 isoforms and the expression of this gene in human retina and other tissues, as well as in cultured human cell lines. PRPF31 transcripts were examined by RT-PCR, quantitative PCR, cloning and sequencing. RESULTS: Database searching revealed the presence of a retina-specific PRPF31 isoform in mouse. However, this isoform could not be experimentally identified in transcripts from human retina or from a human whole eye. Nevertheless, four different PRPF31 isoforms, that were common to all analyzed tissues and cell lines, were isolated. Three of these harbored the full-length PRPF31 coding sequence, whereas the fourth was very short and probably non-coding. The amount of PRPF31 mRNA was previously found to be lower in patients with mutations in this gene than in healthy individuals, making it likely that retinal cells are more sensitive to variation in PRPF31 expression. However, quantitative PCR experiments revealed that PRPF31 mRNA levels in human retina were comparable to those detected in other tissues. CONCLUSIONS: Our results show that the retina-restricted phenotype caused by PRPF31 mutations cannot be explained by the presence of tissue-specific isoforms, or by differential expression of PRPF31 in the retina. As a consequence, the etiology of PRPF31-associated retinitis pigmentosa likely relies on other, probably more subtle molecular mechanisms.

Acute ulcerative jejunal diverticulitis: case report of an uncommon entity.

Jejunal diverticulosis is a rare entity with variable clinical and anatomical presentations. Its reported incidence varies from 0.05% to 6%. Although there is no consensus on the management of asymptomatic jejunal diverticular disease, some complications are potentially life threatening and require early surgical treatment. We report a case of an 88-year-old man investigated for acute abdominal pain with a high biological inflammatory syndrome. Inflammation of multiple giant jejunal diverticulum was discovered at abdominal computed tomography (CT). As a result of the clinical and biological signs of early peritonitis, an emergency surgical exploration was performed. The first jejunal loop showed clear signs of jejunal diverticulitis. Primary segmental jejunum resection with end-to-end anastomosis was performed. Histopathology report confirmed an ulcerative jejunal diverticulitis with imminent perforation and acute local peritonitis. The patient made an excellent rapid postoperative recovery. Jejunal diverticulum is rare but may cause serious complications. It should be considered a possible etiology of acute abdomen, especially in elderly patients with unusual symptomatology. Abdominal CT is the diagnostic tool of choice. The best treatment is emergency surgical management.

Development and evaluation of a shaken baby syndrome prevention program.

OBJECTIVE: To evaluate parents' and nurses' opinions regarding the adequacy of an educational program on shaken baby syndrome: the Perinatal Shaken Baby Syndrome Prevention Program (PSBSPP). DESIGN: Qualitative and quantitative assessments in the form of interviews and questionnaires administered in French. SETTING: Two birthing institutions in Montréal, QC, Canada: a university hospital and a regional center. PARTICIPANTS: Two hundred and sixty-three parents (73.8% mothers, 26.2% fathers) received the intervention after the birth of their child, and 69 nurses administered it. METHODS: Parents' and nurses' assessments of the adequacy and relevance of the program and nurses' assessments of the training they received to administer the program were evaluated. RESULTS: Both parents and nurses supported this initiative. Most parents appreciated the usefulness of the information. Nurses believed the program was adequate, and their training to deliver the program was satisfactory. All participants reported that the program was highly relevant, especially for new parents. CONCLUSION: The Perinatal Shaken Baby Syndrome Prevention Program achieves the goals of (a) increasing parents' knowledge about infant crying, anger, and shaken baby syndrome and (b) helping parents identify coping strategies. The relevance of introducing the PSBSPP in all birthing institutions is supported. Future studies should focus on vulnerable and culturally diverse populations, and longitudinal follow-up could help determine if the PSBSPP reduces the incidence of shaken baby syndrome.

Le choc anaphylactique [Anaphylactic shock]

Anaphylactic shock is an unexpected, sudden and sometimes deadly event that attacks the patient in 75% of the cases without pre-existent history of allergy. In general, drugs, hymenopteric poisons and nutrients (according to the recent concept) are responsible. Beside the classical IgE-mediated anaphylactic shock there exists another anaphylactic shock, identical in its clinical picture and treatment but not in the mechanism of development. Epinephrine is the only effective drug in case of respiratory (bronchial asthma, laryngeal edema) or cardiovascular (hypotension, arrhythmias, hypovolemic shock) manifestation. It has to be administered as rapidly as possible

Effets du travail de nuit sur la santé

Dans les pays industrialisés, 20% des salariés sont concernés par le travail de nuit. Pourtant, les effets du travail de nuit sur la santé sont peu traités par les revues médicales générales, alors que le travail de nuit a des conséquences non négligeables sur les systèmes cardiovasculaires et digestifs entre autres, comme l'ont démontré de nombreuses études ces dernières décennies. Le travail de nuit a encore récemment attiré l'attention quand il a été déclaré cancérigène probable (catégorie 2A) par le Centre international de recherches sur le cancer. Ainsi dans cet article, seront passés en revue les troubles de la santé qui peuvent être générés ou aggravés par le travail de nuit. Deux cas pratiques illustreront la problématique et permettront d'aborder la conduite à tenir. 20% of employees in industrialized countries are concerned by shift work. Nevertheless, there is very little information in general medical journals about the effects of shift work on health. Shift work can have several major effects on health such as cardiovascular and digestive disorders among others, as demonstrated by several studies in recent decades. Shift work has attracted considerable attention recently when it was declared probable carcinogen by the International Agency for research on cancer. We review the health disorders that may be generated or aggravated by shift work and illustrate the problem by two case studies of occupational medicine and discuss the appropriate attitude to take

Etude des liens entre l'alexithymie, l'expérience dépressive et la dépendance interpersonnelle chez des sujets addictifs [Relationships between alexithymia, depression and interpersonal dependency in addictive subjects].

In the scientific literature, the term of addiction is currently used to describe a whole range of phenomena characterized by an irresistible urge to engage in a series of behaviors carried out in a repetitive and persistent manner despite accruing adverse somatic, psychological and social consequences for the individual. It has been suggested that subjects presenting such behaviors would share specific features of personality which support the appearance or are associated with these addictive behaviors. Dimensions such as alexithymia and depression have been particularly well investigated. The aim of this study was to explore the hypothesis of a specific psychopathological model relating alexithymia and depression in different addictive disorders such as alcoholism, drug addiction or eating disorders. Alexithymic and depressive dimensions were explored and analyzed through the statistical tool of path analysis in a large clinical sample of addicted patients and controls. The results of this statistical method, which tests unidirectional causal relationships between a certain number of observed variables, showed a good adjustment between the observed data and the ideal model, and support the hypothesis that a depressive dimension can facilitate the development of dependence in vulnerable alexithymic subjects. These results can have clinical implications in the treatment of addictive disorders.

Endocarditis prophylaxis revisited: experimental evidence of efficacy and new Swiss recommendations. Swiss Working Group for Endocarditis Prophylaxis.

Because of its severity, it is agreed that infectious endocarditis should be prevented whenever possible. Determining adequate prophylactic measures involves establishing (a) the patients at risk, (b) the procedures that might provoke bacteraemia, (c) the most effective prophylactic regimen, and (d) a balance between the risks of side effects from prophylaxis and of developing infectious endocarditis. Patients at risk and procedures inducing bacteraemia have been identified by clinical studies. On the other hand, the efficacy of prophylactic antibiotics has been based on animal studies. Randomised, placebo-controlled studies do not exist in humans because they would require large patient numbers and would raise ethical issues due to the severity of the disease. Case-control studies have indicated that infectious endocarditis prophylaxis is effective, but prevents only a limited number of cases. Animal experiments have revealed several key issues for human application. First, antibiotics do not prevent the early stages of valve colonisation, but rather kill the microorganisms after their attachment to the cardiac lesions. Second, the duration of antibiotic presence in the serum is critical. Under experimental conditions, the drugs must remain above their minimal inhibitory concentration for the organisms for > or = 10 h, to allow time for bacterial clearance from the valves. Third, antibiotic-induced killing is not the only mechanism allowing bacterial clearance. Other factors, such as platelet microbicidal proteins, may act in concert with the drugs to sterilise the lesions. Recommendations for prophylaxis have recently been revised in Europe and the USA. New information has improved the definition of groups at risk. Since most cases of infectious endocarditis are not preceded by medical procedures, primary prevention of infectious endocarditis should target infected foci responsible for spontaneous bacteraemia (e.g. poor dental hygiene). The purpose of this article is to update the existing recommendations in Switzerland, under the perspective of changing epidemiology, the availability of new drugs, and harmonisation with recommendations in other countries.

Trends in smoking and lung cancer mortality in Switzerland.

Patterns of cigarette smoking in Switzerland were analyzed on the basis of sales data (available since 1924) and national health surveys conducted in the last decade. There was a steady and substantial increase in cigarettes sales up to the early 1970s. Thereafter, the curve tended to level off around an average value of 3,000 cigarettes per adult per year. According to the 1981-1983 National Health Survey, 37% of Swiss men were current smokers, 25% were ex-smokers, and 39% were never smokers. Corresponding porportions in women were 22, 11, and 67%. Among men, smoking prevalence was higher in lower social classes, and some moderate decline was apparent from survey data over the period 1975-1981 mostly in later middle-age. Trends in lung cancer death certification rates over the period 1950-1984 were analyzed using standard cross-sectional methods and a log-linear Poisson model to isolate the effects of age, birth cohort, and year of death. Mortality from lung cancer increased substantially among Swiss men between the early 1950s and the late 1970s, and levelled off (around a value of 70/100,000 men) thereafter. Among women, there has been a steady upward trend which started in the mid-1960s, and continues to climb steadily, although lung cancer mortality is still considerably lower in absolute terms (around 8/100,000 women) than in several North European countries or in North America. Cohort analyses indicate that the peak rates in men were reached by the generation born around 1910 and mortality stabilized for subsequent generations up to the 1930 birth cohort. Among females, marked increases were observed in each subsequent birth cohort. This pattern of trends is consistent with available information on smoking prevalence in successive generations, showing a peak among men for the 1910 cohort, but steady upward trends among females. Over the period 1980-1984, about 90% of lung cancer deaths among Swiss men and about 40% of those among women could be attributed to smoking (overall proportion, 85%).

Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren's syndrome.

BAFF (BLyS, TALL-1, THANK, zTNF4) is a member of the TNF superfamily that specifically regulates B lymphocyte proliferation and survival. Mice transgenic (Tg) for BAFF develop an autoimmune condition similar to systemic lupus erythematosus. We now demonstrate that BAFF Tg mice, as they age, develop a secondary pathology reminiscent of Sjögren's syndrome (SS), which is manifested by severe sialadenitis, decreased saliva production, and destruction of submaxillary glands. In humans, SS also correlates with elevated levels of circulating BAFF, as well as a dramatic upregulation of BAFF expression in inflamed salivary glands. A likely explanation for disease in BAFF Tg mice is excessive survival signals to autoreactive B cells, possibly as they pass through a critical tolerance checkpoint while maturing in the spleen. The marginal zone (MZ) B cell compartment, one of the enlarged B cell subsets in the spleen of BAFF Tg mice, is a potential reservoir of autoreactive B cells. Interestingly, B cells with an MZ-like phenotype infiltrate the salivary glands of BAFF Tg mice, suggesting that cells of this compartment potentially participate in tissue damage in SS and possibly other autoimmune diseases. We conclude that altered B cell differentiation and tolerance induced by excess BAFF may be central to SS pathogenesis.