[National surveillance of bacterial meningitis in children].
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Biomedical subjects
Publications and source records attributed to R Cohen.
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DESIGN: The hormonal serum marker for the presence and course of patients with medullary thyroid cancer (MTC) is the mature calcitonin (CT) peptide. Other CALC-1 gene products such as the 116-amino acid polypeptide prohormone, procalcitonin, as well as its component calcitonin precursors (CTpr) may also be increased in their sera. We performed a study to evaluate the clinical utility of serum levels CTpr in these patients. METHODS: Twenty-one patients with MTC (9 males, 12 females; 23-76 years of age) were evaluated. The diagnosis was confirmed by histologic examination, except for 2 (a proven RET mutation plus an abnormal pentagastrin-stimulated CT level). Nine patients had postoperative hypercalcitoninemia and 3 of these died. The specific assay for mature CT was a commercial immunoradiometric assay (hCT-IRMA); the immunoluminometric assay for CTpr (B.R.A.H.M.S Diagnostica, Berlin, Germany) detects intact procalcitonin and the free CT:CT carboxypeptide-1. RESULTS: All patients had detectable serum CTpr. These levels considerably exceeded those of mature CT, averaging 7.6-fold greater. CTpr levels correlated positively with mature CT (r = 0.61; p < 0.001). After pentagastrin administration, there was a parallelism of response between the two assays. Whenever there were known metastases, CTpr increased markedly. CONCLUSION: This study demonstrates the universal presence of CTpr in the blood of patients with MTC. The measurement of these peptides may offer a new dimension to the clinical evaluation of this malignancy.
Many complex networks in nature have directed links, a property that affects the network's navigability and large-scale topology. Here we study the percolation properties of such directed scale-free networks with correlated in and out degree distributions. We derive a phase diagram that indicates the existence of three regimes, determined by the values of the degree exponents. In the first regime we regain the known directed percolation mean field exponents. In contrast, the second and third regimes are characterized by anomalous exponents, which we calculate analytically. In the third regime the network is resilient to random dilution, i.e., the percolation threshold is p(c)-->1.
The genus Pleurotus comprises a group of edible ligninolytic mushrooms with medicinal properties and important biotechnological and environmental applications. The cultivation of Pleurotus spp is an economically important food industry worldwide which has expanded in the past few years. P. ostreatus is the third most important cultivated mushroom for food purposes. Nutritionally, it has unique flavor and aromatic properties; and it is considered to be rich in protein, fiber, carbohydrates, vitamins and minerals. Pleurotus spp are promising as medicinal mushrooms, exhibiting hematological, antiviral, antitumor, antibiotic, antibacterial, hypocholesterolic and immunomodulation activities. The bioactive molecules isolated from the different fungi are polysaccharides. One of the most important aspects of Pleurotus spp is related to the use of their ligninolytic system for a variety of applications, such as the bioconversion of agricultural wastes into valuable products for animal feed and other food products and the use of their ligninolytic enzymes for the biodegradation of organopollutants, xenobiotics and industrial contaminants. In this Mini-Review, we describe the properties of Pleurotus spp in relation to their biotechnological applications and potential.
INTRODUCTION: The frequent etiology of panhypopituitarism is a hypopituitary adenoma. An exceptional cause, with less than 40 cases in the literature, is intra-sellar carotid aneurism. OBSERVATION: A 55 year-old woman was treated for panhypopituitarism related to bilateral aneurism of the carotid arteries. Hormone exploration revealed anterior pituitary deficiency involving all the axes except the corticotrophin and prolactin functions. Pituitary MRI showed an atrophic pituitary, compressed by two calcified aneurismal formations located on the terminals of two internal, partially thrombotic, carotid arteries. Surgical treatment was not envisaged 12 years later. Replacement therapy for life was initiated. COMMENTS: The mechanisms explaining the occurrence of panhypopituitarism secondary to intra-cranial aneurism are hypothetical: compressive phenomena, ischemia and apoplexy of a pituitary adenoma related to the aneurism.
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BACKGROUND: Behçet's disease is known to be strongly associated with HLA-B51 in many different ethnic groups. Recently, it was suggested that MIC-A (major histocompatibility complex class I related gene A) is the pathogenic gene after strong association was found between the MIC-A A6 allele of the transmembrane region and the disease in Japanese and Greek patients, although in Greek patients this association was found to be due to linkage disequilibrium with HLA-B51. OBJECTIVES: To investigate microsatellite polymorphism in Arab and non-Ashkenazi Jewish (NAJ) patients in Israel, to determine whether this association occurs in these groups with Behçet's disease, and elucidate the associated HLA allele of the disease. METHODS: Forty four Israeli patients with Behçet's disease, including 20 Arabs and 24 NAJ, and 130 ethnically matched healthy controls were examined for MIC-A microsatellite polymorphism of the transmembrane region using polymerase chain reaction, autoradiography, and sequence analysis. RESULTS: The MIC-A A6 allele was significantly more frequent in the Arab patient group (19/20 (95%)) than in healthy Arab controls (25/42 (60%)) (p(corr)=0.015, OR=12.92), but not in the NAJ patients (16/24 (67%)) compared with NAJ healthy controls (48 /88 (55%)) (p(corr)=1.02, OR=1.667). In stratification analysis of the Arab subgroup, on the confounding effect of MIC-A A6 on HLA-B51 association and vice versa, Behçet's disease was distinctly associated only with HLA-B51. CONCLUSIONS: These results imply strong association between the MIC-A A6 allele and the disease in Israeli Arabs, but not in Israeli NAJ patients. The stratification analysis indicates that this association results secondarily from a strong linkage disequilibrium with HLA-B51, and the real disease susceptibility gene which plays a part in the development of Behçet's disease is most probably the HLA-B51 allele itself.
BACKGROUND: Faecal incontinence occurs in over one third of patients with systemic sclerosis. The aetiology is multifactorial. Conventional treatment is often unsuccessful. Sacral nerve stimulation is a new effective treatment for resistant faecal incontinence. AIMS: To evaluate sacral nerve stimulation in patients with systemic sclerosis. PATIENTS: Five women, median age 61 years (30-71), with scleroderma associated faecal incontinence were evaluated. All had failed maximal conventional treatment. Median number of preoperative weekly episodes of incontinence was 15 (7-25), median duration of incontinence was five years (5-9), and scleroderma 13 years (4-29). METHODS: All patients were screened with temporary stimulation. Those who benefited underwent permanent implantation. At baseline and after stimulation a bowel diary, the SF-36 quality of life assessment, endoanal ultrasound, and anorectal physiology were performed. RESULTS: Four patients were continent at a median follow up of 24 months (6-60). One patient failed temporary stimulation and was not permanently implanted. The weekly episodes of incontinence decreased from 15, 11, 23, and 7 to 0. Urgency resolved (median time to defer <1 minute (0-1) v 12.5 minutes (5-15)). Quality of life, especially social function, improved. Endoanal ultrasound showed an atrophic internal anal sphincter (median width 1.0 mm (0-1.6)). Anorectal physiology showed an increase in median resting pressure (37 pre v 65 cm H(2)O post) and squeeze pressure (89 v 105 cm H(2)O). Stimulation produced enhanced rectal sensitivity to distension. There were no major complications. CONCLUSIONS: Sacral nerve stimulation is a safe and effective treatment for resistant faecal incontinence secondary to scleroderma. The benefit is maintained in the medium term.
Ectopic GH RH is a very uncommon cause of acromegaly (<1% of acromegaly). We report the case of an 41 year-old woman with acromegaly due to a GH-RH-secreting bronchial carcinoid tumor. Elevated serum GH (14 ng/ml) was paradoxically stimulated after glucose loading. Magnetic resonance imaging revealed a normal pituitary gland. The thoracic CT demonstrated a voluminous (8 cm) bronchial tumor visualised with octreotide scintigraphy. Acromegaly due to ectopic GH RH secretion was confirmed by very high plasma immunoreactive GH RH level. After removal of the carcinoid tumor, plasmat GH, IGF1 and GH RH levels were normalised.
We study the tolerance of random networks to intentional attack, whereby a fraction p of the most connected sites is removed. We focus on scale-free networks, having connectivity distribution P(k) approximately k(-alpha), and use percolation theory to study analytically and numerically the critical fraction p(c) needed for the disintegration of the network, as well as the size of the largest connected cluster. We find that even networks with alpha < or = 3, known to be resilient to random removal of sites, are sensitive to intentional attack. We also argue that, near criticality, the average distance between sites in the spanning (largest) cluster scales with its mass, M, as square root of [M], rather than as log (k)M, as expected for random networks away from criticality.
BACKGROUND: A growing body of literature suggests that schizophrenic patients often do not show the normal brain hemispheric asymmetry. We have found this for simple tones presented to the right ear in a previous study. In this study we extended this investigation to left ear stimulation and verbal stimuli. METHODS: With a whole-head neuromagnetometer, contra- and ipsilateral auditory-evoked magnetic fields in response to tones (1000 Hz) and to the syllables ("ba") delivered to the left and right ears in separate runs were compared between schizophrenic patients (n = 17) and healthy control subjects (n = 15). RESULTS: In response to tones, all control subjects showed the expected asymmetry (contralateral predominance) of the auditory-evoked magnetic N100m (dipole moment). In the patient sample asymmetry was reversed following tones presented to the left ear in 47% and following tones to the right ear in 24%. In response to syllables, the asymmetry was similar between groups. In patients compared with control subjects the N100m was located more anterior without asymmetry between hemispheres. CONCLUSIONS: Results suggest that deviation from the normal functional lateralization in schizophrenia appears in a proportion of patients at a basic stage of auditory processing, but may be compensated for at higher levels such as the processing of syllables.
Extensive scientific efforts are directed towards finding new and improved platinum anticancer agents. A promising approach is the encapsulation of cisplatin in sterically stabilized, long circulating, PEGylated 100 nm liposomes. This liposomal cisplatin (STEALTH cisplatin, formerly known as SPI-77) shows excellent stability in plasma and has a longer circulation time, greater efficacy and lower toxicity than much free cisplatin. However, so far, the physicochemical characterization of STEALTH cisplatin has been limited to size distribution, drug-to-lipid ratio and stability. Information on the physical state of the drug in the liposome aqueous phases and the drug's interaction with the liposome membrane has been lacking. This study was aimed at filling this gap. We report a multinuclear NMR study in which several techniques have been used to assess the physical nature of cisplatin in liposomal formulations and if and to what extent the drug affects the liposome phospholipids. Since NMR detects only the soluble cisplatin in the liposomes and not the insoluble drug, combining NMR and atomic absorption data enables one to determine how much of the encapsulated drug is soluble in the intraliposomal aqueous phase. Our results indicate that almost all of the cisplatin remains intact during the loading process, and that the entire liposomal drug is present in a soluble form in the internal aqueous phase of the liposomes.
OBJECTIVE: The objective of this study was to determine the clinical outcomes of patients with fallopian tube carcinoma treated with paclitaxel-based combination chemotherapy following primary cytoreductive surgery. METHODS: Twenty-four patients with the diagnosis of primary tubal adenocarcinoma treated between 1993 and 1998 were identified through the gynecology service database and the Memorial Sloan-Kettering Cancer Center tumor registry. Medical records were reviewed for information on age, stage, chemotherapy regimen, surgical intervention, relapse, and survival. All patients had their histologic material initially read or reviewed at Memorial Sloan-Kettering Cancer Center prior to treatment. The original slides were reviewed again by one of the authors (P.E.S.) to confirm the diagnosis of primary fallopian tube cancer. RESULTS: The mean age of the patients was 63 years (range, 44-76). Distribution by stage was as follows: four patients (17%) were Stage I, three patients (12%) were Stage II, 16 patients (67%) were Stage III, one patient (4%) was Stage IV. Four patients had grade 2 tumors, 20 had grade 3. Sixteen patients (67%) had optimal cytoreduction at the time of initial surgery with residual disease less than 1 cm. Eight patients (33%) had suboptimal cytoreduction. Following initial surgery, all patients were treated with paclitaxel-based chemotherapy for a median of five cycles. Twenty-three patients received paclitaxel at the dose of 135-175 mg/m(2) in combination with carboplatin or cisplatin; the majority, 17 of 23 (74%), received carboplatin. One patient received paclitaxel alone. Median follow-up from time of initial surgery was 24 months (range, 1-73 months). Two patients are dead of disease. Overall survival for the entire group was 96% at 12 months by Kaplan-Meier analysis, and 90% at 3 years. The overall median progression-free survival was 27 months (range, 5-57 months) for the entire group. The median disease progression-free survival at 3 years was 67% (95% CI, 45-100) in the optimally debulked group as compared with 45% in the suboptimally debulked group (95% CI, 27-57). Twelve patients (50%) had evidence of recurrence or persistent disease. There were fewer recurrences in the optimally debulked group: 5 of the 16 patients (31%) versus 7 of the 8 patients (88%) with suboptimal cytoreduction. CONCLUSION: Optimally cytoreduced patients with primary fallopian tube carcinoma treated with a paclitaxel-based chemotherapy regimen have an excellent possibility of survival.
A syntactic and a semantic task were performed by German-speaking healthy subjects and aphasics with lesions in the dominant left hemisphere. In both tasks, pictures of objects were presented that had to be classified by pressing buttons. The classification was into grammatical gender in the syntactic task (masculine or feminine gender?) and into semantic category in the semantic task (man- or nature made?). Behavioral data revealed a significant Group by Task interaction, with aphasics showing most pronounced problems with syntax. Brain event-related potentials 300-600 ms following picture onset showed different task-dependent laterality patterns in the two groups. In controls, the syntax task induced a left-lateralized negative ERP, whereas the semantic task produced more symmetric responses over the hemispheres. The opposite was the case in the patients, where, paradoxically, stronger laterality of physiological brain responses emerged in the semantic task than in the syntactic task. We interpret these data based on neuro-psycholinguistic models of word processing and current theories about the roles of the hemispheres in language recovery.
Event-related potentials (ERPs) were recorded from 19 aphasic patients and 18 controls in four versions of a feature comparison task, in which the verbal or pictorial representation of a first stimulus (S1) had to be compared with the verbal or pictorial representation of a second stimulus (S2) presented 2 s later. These tasks were designed to cover some of the discriminatory variance of the token test (TT) including the analytical isolation, encoding and short-term storage of individual features of objects, independent of auditory verbal comprehension. Aphasics made more errors and had longer response latencies than controls in all four tasks, performance being poorest when verbal stimuli had to be processed. ERP analyses - restricted to subjects performing well above chance and to trials with correct responses - were confined to the slow wave (SW) (250-750 ms post-S1-onset) and the contingent negative variation (CNV) preceding the S2. There was no overall group difference that would have suggested that the patients activated different cortical areas than controls on correct performance. A left-hemispheric predominance of the negative SW was found in all four tasks and in both groups, although it was more pronounced in aphasics, and more pronounced in non-fluent than in fluent aphasics. The CNV was characterized by a left-hemispheric accentuation which was more pronounced in controls than in aphasics, particularly in tasks with a verbal S2. Results indicate that successful feature comparisons in the present tasks activate primarily left-anterior cortical areas. During encoding and short-term storage this activation is more pronounced in aphasics than in controls.
High levels of prostaglandins (PGs) are currently found in tumoral cells, due to expression of the inducible PGs synthesis enzyme, the cyclooxygenase 2 (COX 2). Non Steroidal Anti Inflammatory Drugs (NSAIDs) possess an antitumoral effect related, in a large extend, to the inhibition of this enzyme. It was recently suggested that the decreased activity of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme catabolysing PGs, may be responsible too for experimentally induced colon tumor enhancement. We report here, for the first time, that indomethacin, an NSAID, decreased TT cell proliferation, derived from a human Medullary Thyroid Carcinoma (MTC). This effect is time and concentration-dependent. Moreover, indomethacin enhanced expression and activity of 15-PGDH. The 15-PGDH levels were negatively correlated with TT cell proliferation (r = -0.52, p < 0.001). Indomethacin, known to decrease COX levels and activity, could also act in modifying catabolism of PGs. This suggests that 15-PGDH is involved in tumoral development, and could therefore be considered as a target for NSAIDs.
Streptococcus pneumoniae is the leading cause of community acquired infections. We conducted a 5 years retrospective study to assessed mortality of pneumococcal infections in children in the area of Paris. Regarding the provided answers, the mortality rate is 0.3/100.000/year in the 0-15 years old children. The majority of them are toddlers. Only 30% of cases occurred in high-risk children. Meningitis was the main cause of death. Pneumococcal resistance to antibiotics did not appear as a risk factor of mortality.
Carcinoma of the breast is relatively rare among men, accounting for less than 1% of all malignancies. An increased risk has been associated with benign breast diseases, such as gynecomastia, Klinefelter's syndrome, testicular disorders, exogenous estrogen use, radiation, or a family history of male or female breast cancer. To date, hypogonadotrophic hypogonadism has never been associated with male breast cancer. We report here the first case of breast cancer coexisting with Kallmann's syndrome in a 66-year-old man.