Epidemiological surveillance implemented in southeast France during the 2006 Olympic Winter Games.
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Biomedical subjects
Publications and source records attributed to F Franke.
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At the end of May 2003, the Marseilles Hospital Centre's virology laboratory informed the French public heath institute of 5 cases of confirmed measles among young adults living in Marseilles. An investigation was conducted, consulting different community and hospital health services, to determine the virus circulation in the Provence-Alpes-Côte d'Azur (PACA) region by the southern interregional epidemiological cell. The investigation identified 259 cases: 183 clinical, 74 serologically confirmed and 2 epidemiologically linked cases. The first cases were identified during the first six months of 2003, with a peak in April. This outbreak of measles in the PACA region was favoured by poor vaccination coverage, which created groups of susceptible population. The real number of cases was probably higher than the number identified. This investigation has outlined the limitations of the measles surveillance system in France: the sentinel network had not detected any case for this period. France needs to reach the WHO objective of measles elimination by 2010 and the surveillance tools used must be those already used in the most countries that are furthest advanced in the elimination process. To reach this goal, the Direction Générale de la Santé has nominated a working group to be in charge of proposing a national plan to interrupt indigenous measles transmission in France.
The effector hormone of the renin-angiotensin system, angiotensin II, plays a major role in cardiovascular regulation. In rats, both angiotensin receptor subtypes, AT(1) and AT(2), are up-regulated after myocardial infarction but previous studies failed to identify the cell types which express the AT(2) receptor in the heart. To address this question we established a single-cell reverse transcriptase-polymerase chain reaction for AT(1) and AT(2) receptors to determine whether these receptor subtypes are expressed in adult rat cardiomyocytes before and 1 day after myocardial infarction. By laser-assisted cell picking, section profiles of single cells without genomic DNA contamination were isolated. After dividing samples into two identical aliquots, polymerase chain reaction amplification for AT(1) and AT(2) receptors was carried out and polymerase chain reaction products were subjected to gel electrophoresis. Compared to control (n = 4) and sham-operated animals (n = 4), the number of cardiomyocytes expressing the AT(1) receptor mRNA 1 day after myocardial infarction (n = 4) was not changed (42% and 33% versus 45%, respectively). On the other hand, AT(2) receptor mRNA was expressed in 8% and 13%, respectively, of cardiomyocytes gained from control (n = 4) and sham-operated animals (n = 4) and in 14% isolated after myocardial infarction (n = 4). These results demonstrate for the first time that the AT(2) receptor is expressed in adult cardiomyocytes in vivo. They further suggest that the previously observed up-regulation of cardiac AT(1) and AT(2) receptors after myocardial infarction involves cell types other than cardiomyocytes.
AIM: To localize cardiac angiotensin-converting enzyme (ACE) during left ventricular repair after myocardial infarction (MI). METHODS: Cardiac ACE was examined by immunohistochemical staining using monoclonal and polyclonal antibodies against ACE 24 h, 1 wk, 2 wk, 3 wk, and 6 wk after coronary artery ligation in rats. Immunofluorescent double staining technique was applied to distinguish the cells which express ACE. RESULTS: ACE staining was confined to the endothelial cells and distributed in normal cardiac tissue in a gradient pattern along the vascular tree: present around the whole circle of arterial endothelium, present in about 20% of the capillaries, and absent in the veins. One week after MI, ACE expression was noted in the granulation tissue. Three weeks after MI, necrosis within the infarction was replaced by granulation tissue and fibrous tissue which showed strong over-expression of ACE. Six weeks after MI, the region with positive ACE staining regressed and the area with high collagen content on the endocardial side showed only weak ACE stain. Most of the ACE-positive cells in the ACE-over-expression-area were endothelial cells. A few macrophages seen in these regions were also ACE-positive. CONCLUSION: Cardiac ACE was over expressed during the process of tissue repair following MI, reaching a peak in 3 wk. Endothelial cells took the most part of ACE expression.
CD44 is a transmembrane glycoprotein occurring in several isoforms with different extracellular regions. The various transcripts are encoded by one gene locus containing 20 exons, of which at least 10 can be alternatively spliced in nascent RNA. Isoforms encoded by the variant exons (termed CD44v) are highly restricted in their distribution in nonmalignant tissue as opposed to the standard form of CD44 (CD44s) abundant in many tissues. Specific variant isoforms containing exon 6v have been shown to render nonmetastatic rat tumor cells metastatic. Based on the prominent role in rat metastasis formation, CD44v isoforms were suggested to be involved in human tumor progression. Correlations between prognosis and expression of CD44v have been reported for gastric and colon carcinoma, for non-Hodgkin's lymphoma, and recently for breast carcinoma. We evaluated the expression of CD44 isoforms in node-positive (n = 119) and node-negative (n = 108) cases of breast carcinoma by immunohistochemistry using CD44v exon-specific mAbs. In a subset of 43 cases of high-risk patients, reverse transcription-PCR was used to determine the exon composition of the transcripts. Protein and RNA expression data were probed statistically for their correlation to survival of the patients and clinical risk factors. In contrast to recently published data (M. Kaufmann et al., Lancet, 345: 615-619, 1995), in our cohort disease-free and overall survival data did not indicate significant correlations with the expression of the analyzed isoforms in univariate and multivariate analyses. Comparison of CD44 protein expression with established clinical risk factors for survival such as tumor size (pT1+pT2) and histological grading revealed correlations with the presence of CD44s (P = 0.02 and P = 0.03, respectively) and CD44-9v (P = 0.05 for histological grading). Carcinoma tissues with elevated estrogen and progesterone receptor levels showed positive correlation with CD44-6v (P = 0.001), while a trend for significant coexpression of CD44s and CD44-9v isoforms was observed in estrogen receptor-positive tissues (P = 0.08 and 0.06, respectively). In breast cancer, CD44s, CD44-9v, and CD44-6v are apparently markers for cellular differentiation but not for tumor progression. Our data suggest that steroid hormone receptors may be associated with the in vivo expression of CD44-6v-containing isoforms in human mammary carcinoma.
HISTORY AND CLINICAL FINDINGS: A 47-year-old man without previously known illness was admitted to hospital because of acute haematomas in the legs: the history revealed no cause. The pale-looking patient reported having large and foul-smelling stools once or twice daily. There were large haematomas and swellings on both legs. His general and nutritional state was reduced. "Bleeding of unknown origin" was suspected at this time. INVESTIGATIONS: Haemoglobin concentration was 5.6 g/dl, while iron was normal and ferritin reduced. Quick value was below 5%, activated partial thromboplastin time prolonged to 180 s. Vitamin A and E concentrations were reduced; coumarin derivatives were not demonstrated in blood. Abdominal ultrasonography showed clearly thickened intestinal walls. TREATMENT AND COURSE: Four units of erythrocyte concentrate were immediately administered, together with 2000 IU factors II, VII, X and anti-haemophilic factor B (PPSB), and 10 mg vitamin K intravenously. As intestinal malabsorption was suspected, a vitamin A absorption test was performed: it indicated malabsorption. Upper intestinal endoscopy showed coeliac disease, as did a biopsy. The patient's state quickly improved after he had been given vitamins A, D, E and K and put on a gluten-free diet. CONCLUSION: Coeliac disease can take a clinically unremarkable course for a long time and may finally become manifest through an isolated abnormality, such as bleeding.
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We recently reported that alpha 6 integrin mediates experimental metastasis in mice by functioning in the adhesion of tumor cells to the vascular endothelium. In the current study, we investigated the expression of human alpha 6 integrin in invasive breast carcinomas of 119 women. In 50% of the tumors alpha 6 integrin was expressed in the majority of the cells, and this expression was correlated with reduced survival time. By contrast, the 24% of patients with breast tumors devoid of alpha 6 integrin expression all survived. The tumors were also evaluated for clinical risk factors including histological grading and steroid receptor level. The combination of these factors with alpha 6 integrin expression was superior in predicting overall survival than considering the other factors alone. The correlation with decreased survival time was consistent, regardless of whether the tumors expressed the alpha 6 integrin A or B forms, which differ in their cytoplasmic domain. On the basis of this pilot study we consider alpha 6 integrin expression to be a novel prognostic marker for human breast cancer.
We studied the cellular distribution of angiotensin-converting enzyme (ACE) in the heart related to the cell types involved in left ventricular repair and remodeling before and after myocardial infarction by immunohistochemical techniques using monoclonal and polyclonal antibodies. In noninfarcted myocardium of both human and rat, ACE expression was confined to endothelial cells and subendocardial cell layers of the aortic valve. ACE was prominent in endothelia of small arteries and arterioles, whereas only half the coronary capillaries were immunoreactive and venous vessels were almost completely devoid of the enzyme. In a rat model of myocardial infarction, ACE distribution was determined 1, 3, and 7 days and 2, 3, and 6 weeks after coronary occlusion. Three and 7 days after infarction, endothelial cells of sprouting capillaries and macrophages in the marginal zone of necrosis revealed ACE expression. In both human and rat with the onset of fibrosis, intense staining of the enzyme was found in the marginal zone of the repair tissue. In situ hybridization for collagen type I in the rat revealed that zones with high collagen content had almost no ACE immunoreactivity. Vascular smooth muscle cells and cardiomyocytes revealed no ACE expression throughout the study. We conclude that endothelial cells are the principal source for the expression of ACE after myocardial infarction. The observed induction of ACE with the onset of fibrosis suggests a role of this enzyme that is related to tissue repair and remodeling.
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Children and adolescents, who received an autologous reimplant of the spleen because of traumatic injury between 1979 and 1986 were matched to a cohort of patients, splenectomized because of traumatic injury of the spleen as well and to a control group of healthy age matched individuals. In addition to a physical check-up, markers of humoral and cellular immunity (e.g. lymphocyte subpopulations and phagocytosis of pneumococcy) as well as the coagulatory and fibrinolytic system were examined. All parameters tested, were found to between results from splenectomized and healthy individuals. Our studies stress the fundamental ability of autologous spleen transplants to take over part of the splenic function on the basis of a largerly histomorphologic restitution. Thus autologous reimplantation of the spleen in children and adolescents is an excellent choice as compared to otherwise necessary splenectomy, if preservation of the organ is impossible.
Variant isoforms of CD44 have been strongly implicated in malignant transformation and cancer metastasis. To ascertain the pattern of expression of these isoforms in human normal, fetal and tumor tissues (breast carcinomas, renal cell carcinomas, malignant melanomas, colon carcinomas, non-Hodgkin-lymphomas, neuroblastomas and brain tumors), we generated monoclonal antibodies against CD44 variant regions. Monoclonal antibodies were produced against variant regions encoded by exons 4v, 6v and 9v. CD44 variant isoforms are expressed on normal epithelial cells in a different pattern. Regions of epithelia that expressed the highest levels of the variant isoforms were those with a high rate of cell division. CD44 variant isoforms were not expressed by all investigated tumors (not by malignant melanomas, brain tumors and neuroblastomas). It is interesting that the expression of CD44 isoforms in non-Hodgkins lymphomas and colon carcinomas shows possibly a correlation with malignancy.
A 55-year-old previously healthy woman developed disseminated neurological symptoms together with an organic psychosis over a period of several months. The symptoms progressed continuously despite all therapeutic attempts, and finally the patient died in a state of tetraparesis and coma. Brain biopsy showed necrosis and gliosis of the white matter, but no vasculitic changes. Autopsy revealed numerous necroses of the cerebral cortex and white matter. Signs of inflammation were absent throughout the whole brain. The adventitia of the brain-supplying arteries, especially both carotid arteries, showed a marked cellular infiltrate that consisted mainly of plasma cells and foam cells. The findings represent an unusual type of cerebral vasculitis whose etiology and pathogenesis are unknown.
In 97 patients with radiolucent solitary gallbladder stones, the density of the calculi was evaluated by computed tomography (CT) prior to extracorporeal shock wave lithotripsy (ESWL). Sixty-three percent of the stones were isodense to bile (mean 48 +/- SD 11 HU), and 37% could be identified on CT-sections (maximal density 105 +/- 46 HU, mean density at the largest cross-section 53 +/- 31 HU). There was a slight trend toward better stone fragmentation and higher clearance rate in patients with isodense stones. However, the probability of complete fragment clearance was not significantly different in stones with a high or low CT-density. From these data we conclude that stone selection for ESWL and adjuvant bile acid therapy in patients with radiolucent solitary stones as assessed by oral cholecystography is only marginally improved by computed tomography.
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A 4-year-old boy with a stage III abdominal neuroblastoma was studied. Direct chromosome preparation revealed a t(1;?)(p36;?) in three tumor metaphases (one with a chromosome number of 64). After partial resection of the tumor and further tumor shrinkage by intensive combination chemotherapy, the residual tumor mass was removed by a "second-look" operation, and the patient received postoperative radiotherapy to the tumor area. Chromosome analysis from the peripheral blood taken at that time showed tetraploidy in 14% and hypodiploidy in 66% of 50 available metaphases. Structural abnormalities, mainly involving the distal short arm of chromosome 1, could be identified in seven metaphases. A t(1;?)(p36;?) in a diploid blood cell looked identical to the translocation found in the hyperdiploid tumor metaphase. A del(1)(p36) was also found in a blood cell. It is suggested that an association exists between a chromosome fragility at 1p36, in this case postoperatively induced in vivo by chemoradiotherapy, and the development of neuroblastoma.