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Biomedical subjects

H Cohen

Publications and source records attributed to H Cohen.

At least 199 records · Page 11Linked to original sources

The treatment of comorbid premature ejaculation and panic disorder with fluoxetine.

Premature ejaculation is a common sexual disturbance among men. Both open-label and double-blind studies have demonstrated the effectiveness of serotonergic medications for this disorder. These studies support the hypothesis that the serotonergic system has an important role in the modulation of sexual response, especially attainment of orgasm. Serotonergic dysfunction also has been linked to the pathogenesis of panic disorder. Several studies have demonstrated the efficacy of serotonergic drugs in this disorder. The purpose of the present study was to examine the efficacy of fluoxetine, a serotonin selective reuptake inhibitor for the treatment of comorbid premature ejaculation and panic disorder, in 10 men in an open-label design. The patients were given 20 mg of fluoxetine for 8 weeks of the study. Parameters pertaining to sexual function and measures of anxiety were examined. Improvement of premature ejaculation was noted as of week 2 of the study, whereas measures of panic and sexual satisfaction became statistically significant only as of week 4. Further studies with larger samples and longer periods of follow-up are needed in order to determine the usefulness of fluoxetine for the treatment of comorbid premature ejaculation and panic disorder.

Adult↗

The role of motor evoked potentials during surgery for intramedullary spinal cord tumors.

OBJECTIVE: This is a prospective study of the methodology and clinical applications of motor evoked potentials (MEPs) during surgery for intramedullary spinal cord tumors. METHODS: Transcranial electrical stimulation was used to activate corticospinal motoneurons, and the traveling waves of the spinal cord were recorded through catheter-electrodes placed epi- or subdurally. Intraoperative MEP monitoring was performed in 32 consecutive patients (age range, 1-50 yr) undergoing resection of intramedullary spinal cord tumors. In 19 patients, MEPs were present before myelotomy (monitorable group), and in 10 patients, MEPs were absent before myelotomy (unmonitorable group). Placement of an epidural electrode was not possible in two patients, and technical problems prevented recording in one. RESULTS: MEP amplitudes decreased intraoperatively by more than 50% of baseline in three patients, all of whom had postoperative paraplegia. Two of these patients recovered within 1 week after surgery, and one remained paraplegic. None of the patients with preserved MEP amplitude (> 50%) sustained immediate significant postoperative deterioration. Motor function was significantly deteriorated 1 week after surgery in one patient in the monitorable group and in five patients in the unmonitorable group. MEP monitorability was significantly associated with good surgical outcome for adult patients (P < 0.05), although not for pediatric patients (P > 0.6). Preoperative motor status and surgical outcome were not significantly associated for the adult (P = 0.13) or pediatric groups (P > 0.4). CONCLUSION: MEP monitorability was a better predictor of functional outcome than the patient's preoperative motor status for the adult group. Significant predictors of MEP monitorability in the adult group were preoperative motor function (P < 0.01), history of no previous treatment (surgery or irradiation) (P < 0.01), and small tumor size (P < 0.05). Weak associations with monitorable MEPs existed for low-grade tumors (P = 0.09), the presence of baseline somatosensory evoked potentials (P = 0.10), and tumor pathological abnormalities (ependymoma) (P = 0.13). No associations were determined for sex (P > 0.4), associated syrinx (P > 0.3), or tumor location (P > 0.5). In the pediatric group, none of the examined factors were associated with MEP monitorability (P > 0.3). A decline of more than 50% in MEP amplitude during tumor removal should serve as a serious warning sign to the surgeon.

Child↗

Helicobacter pylori.

Helicobacter pylori is a gram-negative bacterium which causes chronic gastritis and plays important roles in peptic ulcer disease, gastric carcinoma, and gastric lymphoma. H. pylori has been found in the stomachs of humans in all parts of the world. In developing countries, 70 to 90% of the population carries H. pylori. In developed countries, the prevalence of infection is lower. There appears to be no substantial reservoir of H. pylori aside from the human stomach. Transmission can occur by iatrogenic, fecal-oral, and oral-oral routes. H. pylori is able to colonize and persist in a unique biological niche within the gastric lumen. All fresh isolates of H. pylori express significant urease activity, which appears essential to the survival and pathogenesis of the bacterium. A variety of tests to diagnose H. pylori infection are now available. Histological examination of gastric tissue, culture, rapid urease testing, DNA probes, and PCR analysis, when used to test gastric tissue, all require endoscopy. In contrast, breath tests, serology, gastric juice PCR, and urinary excretion of [15N]ammonia are noninvasive tests that do not require endoscopy. In this review, we highlight advances in the detection of the presence of the organism and methods of differentiating among types of H. pylori, and we provide a background for appropriate chemotherapy of the infection.

Anti-Bacterial Agents↗

Costs and effectiveness of a nurse specialist anticoagulant service.

AIMS: To determine the costs and effectiveness of an anticoagulant nurse specialist service compared with a conventional consultant service based on two hospital sites in northwest Hertfordshire. METHODS: Sequential design comparing retrospectively the conduct and outcomes of a consultant service with a nurse specialist service over two six month periods. In each of the six month study periods, all new patients consecutively referred for anticoagulation over a three month period (group A) at the start of each study period and a random selection of patients who had already been attending the anticoagulant service for one year or more (group B) were included in the study. Group A patients wre followed for up to three months and group B patients for six months. The main outcome measures were costs of service provision and effectiveness. Costs included those for the use of the anticoagulant service, those related to general practitioner (GP) visits and hospitalisations, and running costs (staff time, laboratory tests, patient transport). Measures of effectiveness were the mean proportion of time patients spend in the therapeutic range, the number of drugs being taken that could interact adversely and/or inhibit haemostatic function, and patient and GP satisfaction with service provision. RESULTS: In the consultant service, for group A there were more patients aged 66-75 years (p = 0.004) and fewer patients aged more than 76 years (p = 0.001); and for group B, there were fewer patients on anticoagulation for cardiac conditions (p = 0.001), but more on anticoagulation for thromboembolic conditions (p = 0.02) than in the nurse specialist service. The clinic running costs of the nurse specialist service were 4.99 Pounds per attendance, compared with 4.75 Pounds in the consultant service. Including all other costs related to treatment, there was no statistically significant difference in cost per patient. There was no significant difference in the proportion of time patients spent in the therapeutic range between the consultant service and the nurse specialist service. In the nurse specialist service, fewer patients in group A were taking drugs that could interact adversely and/or inhibit haemostatic function (p = 0.01) and more patients were satisfied with service provision (p = 0.04) compared with the consultant service. There was no significant variation in GP satisfaction between the two services. CONCLUSION: In the provision of outpatient anticoagulation, the nurse specialist service was no more expensive than the consultant service and, using our primary outcome, at least as effective. The nurse specialist service has some clear advantages compared to the consultant service: provision of domicilliary care for housebound patients, fewer new patients taking drugs that could interact adversely and/or inhibit haemostatic function patients, it is preferred by newly referred patients to the consultant service, and it is as acceptable to their GPs.

Aged↗

Hypothalamic-pituitary-adrenal function following cranial irradiation.

We assessed the effect of cranial irradiation on hypothalamic-pituitary (HP)-adrenal function in 17 patients (12 females, 5 males) treated with cranial/ craniospinal irradiation for acute leukemia (2 patients) or tumors distant from the hypothalamus and pituitary (8 medulloblastoma, 3 astrocytoma, 3 rhabdomyosarcoma, 1 ependymoma). Estimated doses of radiation (RT) to the HP region ranged from 18 to 72 Gy. Thirteen of seventeen patients were also treated with chemotherapy. Patients were a median of 3.75 years of age (1.5-19 years) at diagnosis and were studied at a median of 5 years (0.1-20 years) after RT. Patients received corticotropin-releasing factor (oCRF, 1 microgram/kg i.v.), and sampling for cortisol and ACTH levels was performed at -15, 0, 15, 30, 60, 90 and 120 min. The-5- and 0-min levels were combined for a standardized baseline value (Base). Cortisol levels at 0, Base, 30 and 120 min, as well as the peak cortisol response, were significantly lower in the patients. Twelve of seventeen patients' peak cortisol levels fell below the normal range. The patients' mean integrated values for cortisol (area under the curve) were not, however, different from controls. The ACTH responses to oCRF did not differ between patients and controls. No relationship was observed between ACTH or cortisol responses and the time elapsed from treatment or dose of HP RT. Further, in 10 of 12 patients, 0-min dehydroepiandrosterone sulfate levels were lower than the expected normal mean levels for age, sex and pubertal status, and in 4 of these 10 patients the values were below the normal range. These data suggest that some patients treated with HP RT may be at risk for adrenal insufficiency.

Adolescent↗

Metanephric adenoma of the kidney.

Metanephric adenoma is a morphologically distinct renal tumor that appears histologically benign and whose epithelial component is predominant. We report a case of metanephric adenoma in a 42-year-old woman. The tumor was composed of immature epithelial cells forming tubules with abortive glomeruloid structures. The bland appearance of the cells forming this tumor were in accordance with the apparently benign postnephrectomy clinical course.

Adenoma↗

Sublytic concentrations of the membrane attack complex of complement induce endothelial interleukin-8 and monocyte chemoattractant protein-1 through nuclear factor-kappa B activation.

Activation of the complement cascade and subsequent assembly of the membrane attack complex (MAC) occur in a number of pathophysiological settings. When formed on the surface of endothelial cells in sublytic concentrations, the MAC can induce a number of proinflammatory activities, including the secretion of soluble mediators (eg, interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1) and the up-regulation of cell surface adhesion molecules. Available data indicate that MAC-induced cell activation may occur through several complex signal transduction pathways, but little is known about the intranuclear mechanisms by which complement-derived products promote the up-regulation of inflammatory mediators. Using purified distal complement proteins (C5-9) to assemble functional MAC on early-passage human umbilical vein endothelial cells (HUVECs), we examined mechanisms of MCP-1 and IL-8 induction. Formation of sublytic concentrations of MAC promoted an increase in nuclear factor (NF)-kappa B DNA binding activity within 60 minutes as determined by serial electrophoretic mobility shift assay. Cytosolic to nuclear translocation of NF-kappa B was confirmed by Western immunoblot and immunocytochemical analyses. Formation of the C5b-8 complex also promoted NF-kappa B translocation but to a lesser degree than observed in HUVECs containing complete MAC. No cytosolic to nuclear translocation of the p65 NF-kappa B subunit was observed in unstimulated HUVECs or in cells incubated with the MAC components devoid of C7. Preincubation of HUVECs with pyrrolidine dithiocarbamate prevented MAC-induced increases in IL-8 and MCP-1 mRNA concentrations and protein secretion. A direct cause and effect linkage between MAC assembly and NF-kappa B activation was established through examination of the pharmacological effect of the peptide SN50 on IL-8 and MCP-1 expression. SN50 is a recently engineered 26-amino-acid peptide that contains a lipophilic cell-membrane-permeable motif and a nuclear localization sequence that specifically competes with the nuclear localization sequence of the NF-kappa B p50 subunit. This study provides direct in vitro evidence that the distal complement system (MAC) can promote proinflammatory endothelial cell activation, specifically, increases in IL-8 and MCP-1 mRNA concentrations and protein secretion, and that cytosolic to nuclear translocation of NF-kappa B is necessary for this response.

Blotting, Northern↗

[Analysis of delivery facilities and conditions in 1991 in mothers of infants with birth weights below 1500 grams and/or gestational age under 33 weeks].

AIMS: To identify maternities (in terms of level of activity and linkage with pediatric services) where, in 1991, mothers gave birth to infants of gestational age less than 33 weeks and/or with birth weight under 1500 g. To analyse factors linked to the probability of choosing a particular maternity as place of delivery for this population and measure the impact of maternal transferts on the rates of deliveries. To estimate the number of neonate transferts which could be avoided with simple recommendations. To propose policies that would allow France to come closer to the results of other reference countries in term of management of obstetrical and neonate care. MATERIAL AND METHOD: We extracted from a retrospective sample of 84,279 births (out of a total of 770,148), 717 infants meeting previously defined criteria and related to the population described above, using univariate and multivariate analysis and logistic regression. RESULTS: The Odds-ratio for a delivery to take place in a maternity with a volume of more than 2000 deliveries a year, compared with those doing less than 300 deliveries, is 4, 12. Only 15.8% of those deliveries took place in maternities linked to a level 3 pediatric unit (i.e where an intensive care neonates unit was located in the same building). 39.5% of births took place in level 1 maternities where no required pediatric service existed. Logistic regression techniques showed that the choice of a maternity for mother referral was more linked to the number of deliveries than to its level of pediatric services. In the studied population, 46% of the difference between the observed number of births in high volume maternities (compared to the expected number) could be explained by a maternal referral. The analysis of deliveries showed that for 34% of mothers who gave birth to a baby in a level 1 or 2 maternity, there was a possibility of being referred easily in a level 3 maternity. CONCLUSION: This study shows that the level of care of mothers at high risk of delivering a very premature and/or hypotrophic infant is far from international standards. Simple actions could double the number of births taking place in adapted maternities. We propose to both obstetricians and pediatrists, a common program to enhance the level of care.

Analysis of Variance↗

[Cesarean sections in France: impact of organizational factors on different utilization rates].

In this study, we analysed the potential impact of organizational factors to explain the variation of cesarean sections' rates. We used a retrospective sample of 84,372 deliveries and two subsamples of low risk deliveries for cesarean sections. We determined different organisational factors that included: juridical and financial status of maternities, their architecture, the type of on-call for obstetricians, pediatrists and anesthetists, the annual number of deliveries and the level of pediatric staff and equipments of the maternities. We used multiple regression techniques to study the specific effect of each parameter, while controlling effects of age and parity of the mothers. We have found that even on the low risk samples, variation of rates were important. The type of on-call, the level of pediatric services and the architecture of maternities exerted a strong and significant effect on the rate of cesarean sections compared to the absence of impact of the number of deliveries. We discuss the reasons why, explaining the occurrence of those factors and then, stress the need to take into account the relevant factors for organizational audits. It appears that, in the context of the new regulation of the health system, these results should give obstetricians reasons to enhance their efforts to correct inefficient practices and to respect consensual guidelines and joint accreditation of obstetric and pediatric units.

Adult↗

Identification of differentially expressed genes during hepatocytes development and characterization of their prenatal hormonal induction.

Upon birth, the liver acquires new functions as a result of the initiation of expression of key enzymes. One example is the initiation of gluconeogenesis which depends on the induced appearance of phosphoenolpyruvate carboxykinase (P-pyruvate-CK) at birth. To characterize other genes that undergo such regulation, a differential screening was performed on a cDNA library from well-differentiated hepatoma cells. The pattern of tissue-specific and developmental-specific expression was determined for seven genes. Three clones, out of which two encode for the known genes alcohol dehydrogenase class I (ADH) and phenylalanine 4-monooxygenase (PAH) and a new gene (clone 116-3), exhibited a pattern of expression similar to that of the P-pyruvate-CK gene, i.e. their expression was liver and kidney specific and induced in the liver upon birth. Determination of the sequence of clone 116-3 revealed that it belonged to the UDP-glucuronosyltransferases type 2 (UGT2) family and thus was named UGT2B-rH4. To examine whether expression of the various genes could be prematurely induced by hormones in the fetal liver, either high levels of cAMP or low levels of insulin were induced in utero. The results demonstrated that cAMP induced a marked expression only of the genes for P-pyruvate-CK and ADH but not of those for PAH or UGT2B-rH4, while insulin deficiency induced premature expression of all four genes. We suggest that a set of genes whose expression is specifically induced in the liver upon birth can be prematurely induced by the hormones in utero.

Alcohol Dehydrogenase↗

Coexpression of Drosophila TRP and TRP-like proteins in Xenopus oocytes reconstitutes capacitative Ca2+ entry.

Capacitative Ca2+ entry is a component of the inositol-lipid signaling in which depletion of inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+ stores activates Ca2+ influx by a mechanism that is still unknown. This pathway plays a central role in cellular signaling, which is mediated by many hormones, neurotransmitters, and growth factors. Studies of Drosophila photoreceptors provided the first putative capacitative Ca2+ entry mutant designated transient receptor potential (trp) and a Drosophila gene encoding TRP-like protein (trpl). It is not clear how the Ca2+ store depletion signal is relayed to the plasma membrane and whether both TRP and TRPL participate in this process. We report here that coexpressing Drosophila TRP and TRPL in Xenopus oocytes synergistically enhances the endogenous Ca(2+)-activated Cl- current and produces a divalent inward current. Both of these currents are activated by Ca2+ store depletion. In the absence of Ca2+, Mg2+ is the main charge carrier of the divalent current. This current is characterized by lanthanum sensitivity and a voltage-dependent blocking effect of Mg2+, which is relieved at both hyperpolarizing (inward rectification) and depolarizing (outward rectification) potentials. The store-operated divalent current is neither observed in native oocytes nor in oocytes expressing either TRP or TRPL alone. The production of this current implicates a cooperative action of TRP and TRPL in the depletion-activated current.

Animals↗

Arachidonic acid up-regulates and prostaglandin E2 down-regulates the expression of pancreatic-type phospholipase A2 and prostaglandin-endoperoxide synthase 2 in uterine stromal cells.

It is well known that arachidonic acid, as a substrate of prostaglandin G/H synthase (PGHS), is converted into prostaglandins of the two-series. In this work, we attempted to determine whether arachidonic acid and prostaglandin E2 might regulate the expression of PGHS and the pancreatic-type phospholipase A2 (PLA2I), which may be involved in the liberation of arachidonic acid from membrane phospholipids. For this purpose, we used the uterine stromal cell line UIII, which produces prostaglandin E2 and expresses both the constitutive and inducible PGHS enzymes (PGHS1 and PGHS2) and PLA2 I. The results show that PGHS1, which is expressed at a high level in UIII cells, was not modified by arachidonic acid. The expression of PGHS2 and PLA2 I was up-regulated by increasing arachidonate concentrations (1-10 microM). The maximal response was obtained at 24 h, reaching a 2.3-fold and 2.6-fold increase for PGHS2 and PLA2 I expression, respectively, compared to the control level. To discriminate between the effect of arachidonic acid and that of prostaglandins, which are highly increased in the presence of exogenous arachidonic acid, we treated the cells with two inhibitors of PGHS activity, aspirin and meclofenamic acid. Both inhibitors failed to suppress the arachidonate-induced increase of PLA2 I and PGHS2 expression and even enhanced it either in the presence or absence of arachidonic acid. In contrast, the addition of prostaglandin E2 to the culture medium decreased the expression of both enzymes in a dose-dependent manner, the maximal response being reached at 1 microM. We conclude that arachidonic acid up-regulates the expression of PLA2 I and PGHS2 in the uterine stromal cells, independently of prostanoids, and that prostaglandin E2 is capable of down-regulating enzyme expression.

Animals↗

Prolactin up-regulates prostaglandin E2 production through increased expression of pancreatic-type phospholipase A2 (type I) and prostaglandin G/H synthase 2 in uterine cells.

Uterine stromal cells produce and release PGE2, both processes being regulated by hormonal factors. In this study, we examined the effect of PRL on the PGE2 production and release measured by radioimmunoassay. For this purpose, we used a rat uterine stromal cell line, UIII cells, which produce PGE2 and contain PRL receptors. The expression of sPLA2I and PGHS (PGHS1 and PGHS2), enzymes required for PGE2 production, was also estimated by immunocytochemistry and 'Western blotting' in response to PRL. PRL (10 to 60 ng/ml) significantly increased the PGE2 release (up to 6-fold) and production, in a dose-dependent manner. Results show that PGHS1 and PGHS2 are both expressed constitutively in the uterine UIII cells, although PGHS2 is expressed at a low level. PRL did not increase PGHS1 expression, but stimulated the expression of sPLA2I and PGHS2 by 3.5- and 2.5-fold, respectively. These data show for the first time a regulation of sPLA2I and PGHS2 expression by PRL and may indicate that, in uterine cells, PRL enhances the PGE2 release and production by increasing the expression of both sPLA2I and PGHS2.

Animals↗

The level of pancreatic PLA2 receptor is closely associated with the proliferative state of rat uterine stromal cells.

Rat uterine stromal cells (U(III)) express pancreatic type PLA2 (PLA2-I) receptor and internalize the enzyme bound to receptors. Here, we investigate the proliferating effect and alterations in binding of PLA2-I. There is a dramatic decline in PLA2-I binding in U(III) cells as they progress from a non-confluent proliferating state (40,000 sites/cell) to a confluent state (1300 sites/cell). Intracellular concentration of PLA2-I changed with the alteration in binding, suggesting that regulation in the PLA2 binding capacity may have important implications in growth control mechanisms.

Animals↗