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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 253 records · Page 14Linked to original sources

Noninvasive monitoring of fetal heart rate during the last ten days of gestation in sows.

OBJECTIVE: To develop and evaluate a noninvasive technique for monitoring and analyzing porcine fetal heart rate (FHR) during late gestation. ANIMALS: 8 fetuses of 8 pluriparous sows in late gestation. PROCEDURE: With the sow positioned in lateral recumbency, the most caudal fetus was identified, using real time ultrasonography, and its heart rate was recorded for 60 minutes by use of Doppler cardiography. The same fetus was identified and monitored repeatedly during the last 10 days of gestation, excluding the 24 hours before delivery. Visual inspection and computerized analysis of the recordings were performed. RESULTS: 66 one-hour recordings were obtained from 8 fetuses, 1 in each of 8 sows. Mean signal loss was 37.5%. Episodes of low FHR and low FHR variation (FHR pattern A) alternated with episodes of high FHR and high FHR variation (FHR pattern B). This cyclic alternation between 2 distinct. FHR patterns was observed in 46 of 66 (69.7%) recordings, and suggests the presence of different behavioral states in fetal pigs. Basal FHR decreased toward parturition in 7 fetuses, but increased in 1 fetus with abdominal ascites. Basal FHR and long-term FHR variation were negatively correlated (r[S] = -0.73; P < 0.001). CONCLUSION: Noninvasive monitoring of FHR is possible and feasible during late gestation in pigs. This method permits longitudinal studies under pathophysiologic conditions and the evaluation of the effects of endogenous and exogenous influences on porcine FHR.

Animals↗

Differences in the RNA binding sites of iron regulatory proteins and potential target diversity.

Posttranscriptional regulation of genes of mammalian iron metabolism is mediated by the interaction of iron regulatory proteins (IRPs) with RNA stem-loop sequence elements known as iron-responsive elements (IREs). There are two identified IRPs, IRP1 and IRP2, each of which binds consensus IREs present in eukaryotic transcripts with equal affinity. Site-directed mutagenesis of IRP1 and IRP2 reveals that, although the binding affinities for consensus IREs are indistinguishable, the contributions of arginine residues in the active-site cleft to the binding affinity are different in the two RNA binding sites. Furthermore, although each IRP binds the consensus IRE with high affinity, each IRP also binds a unique alternative ligand, which was identified in an in vitro systematic evolution of ligands by exponential enrichment procedure. Differences in the two binding sites may be important in the function of the IRE-IRP regulatory system.

Alternative Splicing↗

Hyalocytes synthesize and secrete inhibitors of retinal pigment epithelial cell proliferation in vitro.

BACKGROUND: Retinal pigment epithelial (RPE) cells that enter the vitreous in pathologic conditions, such as retinal detachment, may proliferate and contribute to the formation of epiretinal membranes. OBJECTIVE: To study whether hyalocytes, endogenous vitreous cells, play a role in modulating the proliferation of RPE cells. METHODS: Cell proliferation was measured by tritiated thymidine incorporation in density-arrested human RPE cells after incubation with media that had been conditioned by cultured bovine hyalocytes. Preliminary characterization of inhibitory activity in hyalocyte-conditioned medium was performed, including blocking experiments with a neutralizing antibody to transforming growth factor-beta 2 (TGF-beta) and proliferation assays that used MV-1-Lu mink lung epithelial cells. Northern blots were done to asses hyalocyte expression of TGF-beta messenger RNA. RESULTS: Hyalocyte-conditioned medium inhibited tritiated thymidine incorporation in RPE cells and MV-1-Lu mink lung epithelial cells in the presence or absence of serum or protease inhibitors. A portion of the inhibitory activity was neutralized by an antibody directed against TGF-beta. Northern blots of hyalocyte RNA demonstrated the presence of messenger RNA for TGF-beta 2. These data suggest that TGF-beta is responsible for a portion of the inhibitory activity secreted by hyalocytes. Additional inhibitory activity is attributable to one or more low-molecular-weight molecules distinct from TGF-beta. CONCLUSIONS: Hyalocyte-conditioned medium inhibits RPE cell proliferation in vitro through TGF-beta and at least one other molecule. Production of these factors by hyalocytes in vivo could provide a deterrent for epiretinal membrane formation that may be perturbed under pathologic conditions.

Animals↗

Vincristine-induced alterations in Schwann cells of mouse peripheral nerve.

The sciatic nerve of C57Bl mice was examined with a transmission electron microscope to study the ultrastructural alterations in Schwann cells following treatment with escalating doses of vincristine. Results indicated that the drug exerts a dose-related effect. Total doses up to 8 micrograms/mouse did not cause any visible damage to Schwann cells. Higher doses induced not only damage to individual cells, but also affected a greater percentage of them. The myelin sheath was the most affected organelle. Schwann cells of myelinated fibers showed greater damage than those of unmyelinated fibers.

Animals↗

Cultured retinal capillary pericytes die by apoptosis after an abrupt fluctuation from high to low glucose levels: a comparative study with retinal capillary endothelial cells.

A number of clinical observations concerning cases of glycemic fluctuation have prompted us to study whether or not a rapid change in blood glucose concentration can aggravate retinal microvascular pathology during the early stage of diabetic retinopathy. We conducted a comparative study of retinal capillary pericytes and endothelial cells in vitro. Both types of cells, either in single culture or in co-culture, were initially incubated in medium with high glucose (20-40 mmol/l), followed by a rapid reduction of glucose to 3.5, 1, or 0.5 mmol/1. This type of reduction of extracellular glucose resulted in depletion of intracellular glucose, occurring much faster in pericytes than in endothelial cells. The abrupt reduction in glucose caused pericyte cell shrinkage and nuclear condensation associated with DNA fragmentation, followed by loss of cell viability. All of these pericyte changes are apoptosis-like characteristics. This apoptotic process was prevented by the addition of cycloheximide, a protein synthesis inhibitor, or by platelet-derived growth factor BB, which is known competent factor for pericyte growth. In analysis of signalling pathways during the abrupt fluctuation of glucose, the occurrence of pericyte apoptosis was an intracellular calcium-dependent, protein kinase C and protein kinase A mediated, and poly (ADP-ribose) synthetase-dependent process. Interestingly, a larger degree of DNA fragmentation was observed with a higher magnitude and a longer duration of pre-existing hyperglycaemia. These results suggest that the magnitude and duration of pre-existing hyperglycaemia prime the apoptotic responsiveness of pericytes. Retinal capillary endothelial cells, after an identical glucose fluctuation treatment did not undergo an apoptotic process.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Results of contemporary surgical treatment of descending thoracic aortic aneurysms: experience in 198 patients.

Between April 1987 and March 1995, 198 patients (133 males [67.17%] and 65 female [32.83%]; mean age 63.85 years) underwent descending thoracic aortic aneurysm repair. Of these, 142 patients (71.71%) had symptoms. In most patients (n = 123 [62%]) the aneurysmal disease was extensive, involving at least two thirds of the descending aorta. In 153 patients (77.27%), the repair was completed with the simple clamp technique (mean clamping time 24.6 minutes). Left atrium-to-femoral bypass was used in 26 patients (13.13%) at high risk (mean clamping time 37.4 minutes). Profound hypothermia and circulatory arrest were necessary in 19 patients (9.6%) with extensive aneurysms that involved the arch and ascending aorta (mean circulatory arrest time 46 minutes). Operative mortality was 5.1% (n = 10). The causes of death were cardiac in three patients (1.5%), pulmonary in four (2.0%), and renal in three (1.5%). Postoperative paraplegia occurred in three patients (1.5%). Important predictors (p < 0.05) of mortality at regression analysis included renal failure, pulmonary complications, and paraplegia. The only independent predictor of paraplegia was clamping time. In conclusion, the simple clamp procedure remains the technique of choice in the majority of patients with descending aortic aneurysms. Atriofemoral bypass is an important adjunct in patients at high risk.

Adolescent↗

Treatment of symptomatic nonachalasia esophageal motor disorders with botulinum toxin injection at the lower esophageal sphincter.

The purpose of this study was to determine if botulinum toxin injection at the lower esophageal sphincter improves symptoms in patients with nonachalasia spastic esophageal motility disorders. Fifteen patients with nonachalasia spastic esophageal motility disorders (diffuse esophageal spasm, nonspecific esophageal motility disorders, and lower esophageal sphincter dysfunction) unresponsive to medical therapy underwent endoscopic injection of botulinum toxin at the level of the gastroesophageal junction. Symptoms were scored (0 = no symptoms, 1 = mild, 2 = moderate, 3 = severe and 4 = very severe) before treatment, at seven days and every 30 days after treatment. There was significant improvement in chest pain, dysphagia, and regurgitation at 7,30,60 and 90 days after treatment. At one month after treatment, 11 of 15 (73%) patients had a good or excellent response to treatment. At the last patient interview (mean follow-up of 10.6 months), five (33%) patients continued to have a good to excellent response, whereas 10 (67%) underwent subsequent treatment with repeat botulinum toxin, pneumatic dilation, or bougienage. We conclude that botulinum toxin injection at the gastroesophageal junction leads to significant symptom improvement in patients with nonachalasia esophageal motility disorders. These results suggest that botulinum toxin may be an effective treatment option in some of these patients not responsive to conventional medical therapy.

Adolescent↗

Epidural analgesia for labour and delivery: fentanyl or sufentanil?

PURPOSE: The highly lipid soluble opioids, fentanyl and sufentanil, are used in combination with local anaesthetics with/without epinephrine to provide epidural analgesia during labour and delivery. Our aim was to determine whether wither opioid was superior when used with low dose local anaesthetic. METHODS: In a double-blind study patients were randomized to two epidural infusion groups: Group I (n = 50) fentanyl 2 micrograms.ml-1 with bupivacaine 0.015% and epinephrine 2 micrograms.ml-1, Group II(n = 50) sufentanil 1 microgram.ml-1 with bupivacaine 0.015% and epinephrine 2 micrograms.ml-1. Following a 20 ml bolus of the study solution an infusion was started at 10 ml.h-1. To achieve analgesia patients could receive two boluses of 5 ml of the study solution and if analgesia was still inadequate, a further 5 ml bupivacaine 0.25% was used. Pain and overall satisfaction were assessed with a 10-point visual scale. Plasma samples obtained from the mother at the time the infusion was discontinued and from the umbilical cord vein at delivery were assayed to determine opioid concentration. RESULTS: Pain scores were greater for Group I than for Group II patients throughout the first and second stages of labour (P = 0.002). More patients in Group I (42%) requested a dose of bupivacaine 0.25% than in Group II (6%) (P < 0.001) and the total dose of bupivacaine given to Group I patients was greater than that of Group II, 26.0 +/- 22.0 mg vs. 13.4 +/- 12.6 mg, P = 0.005. There were no differences with respect to first or second stage duration, incidence of side effects, infusion duration, outcome of labour or neonatal Apgar scores. There was no opioid accumulation in either maternal or foetal blood. CONCLUSION: Epidural opioid infusion with very low dose bupivacaine (0.015%) achieved an overall high level of patient satisfaction in both groups without serious maternal or neonatal side effects. At the fentanyl-to-sufentanil ratio used here patients receiving sufentanil had lower pain scores and substantially fewer patients required bupivacaine rescue.

Analgesia, Epidural↗

The suprachiasmatic nucleus in stationary organotypic culture.

Suprachiasmatic nuclei, derived from neonate rats, were maintained for several weeks in stationary organotypic culture. Hypothalamic slice explants, supported by Millicell filters and incubated in Petri dishes containing serum-based medium, flattened appreciably, yet preserved the organization of the suprachiasmatic nucleus and the surrounding hypothalamic tissue. After two to three weeks, cultures were fixed, and three neuronal sub-populations were identified as vasopressinergic, vasoactive intestinal peptide-containing, or GABA-containing. The GABAergic component of the cultured suprachiasmatic nucleus was particularly profuse, projecting extensively into the hypothalamic slice. Unilateral ablation of the nucleus in the explant dramatically reduced ipsilateral GABA-immunoreactivity in the slice. Explants in which an incision separated the bilateral suprachiasmatic nucleus from the paraventricular nucleus, deprived the latter of its fine-caliber GABA-immunoreactive input. Extra- or intra-cellular electrophysiological recordings from the suprachiasmatic nucleus were obtained in 51 of 58 cultures. The electrical properties of the long-term cultured suprachiasmatic nucleus were similar to those recorded in acute slices from adult rats. In six cultures recordings were extended for up to 10-24 h. Within long-term stationary organotypic cultures of the suprachiasmatic nucleus, sub-populations of neurons, intrinsic to the nucleus in vivo, were identified immunocytochemically. Lesion studies supported the observation that the main source of the GABAergic innervation within the entire hypothalamic slice explant appeared to be the suprachiasmatic nucleus. Electrophysiological studies confirmed the viability of the long-term cultured nucleus and revealed changes in spontaneous electrical activity that may indicate circadian fluctuation.

Animals↗

Wnt signal transduction: more than one wat to skin a (beta-)cat?

Genetic and biochemical studies have suggested that signal transduction by the Wnt pathway is very different to the familiar protein-kinase cascade of the Ras pathway. Among the more intriguing findings is that beta-catenin, a component of intercellular adhesive junctions, is a central component in the Wnt signalling pathway. Recent studies suggest ways in which beta-catenin might serve as a focal point for regulation of adhesion, gene expression and cell proliferation.

Journal Article↗

Use of high-resolution endoscopic ultrasonography to assess esophageal wall damage after pneumatic dilation and botulinum toxin injection to treat achalasia.

OBJECTIVE: The purpose of this study was to utilize high-resolution endoscopic ultrasonography to assess esophageal wall damage in patients with achalasia treated by either pneumatic dilation or botulinum toxin injection and to compare their symptomatic response. METHODS: Twenty-nine patients were treated with pneumatic dilation (11) or botulinum toxin injection (18) in a nonrandomized, controlled manner. An achalasia balloon dilator inflated at the gastroesophageal junction was used for dilation. Botulinum toxin was injected during endoscopy into the gastroesophageal junction. Endoscopic ultrasonography was performed at the level of the diaphragm before, immediately after, and 24 hours after treatment. Symptoms were assessed before and 7, 30, 60, and 90 days after therapy. RESULTS: The mucosal-submucosal thickness increased significantly immediately after pneumatic dilation, but normalized by 24 hours. No significant change in mucosal-submucosal thickness occurred after botulinum toxin injection. No significant alteration in muscularis propria thickness was observed after either procedure. Dysphagia and regurgitation improved significantly at 7, 30, 60, and 90 days after both procedures. CONCLUSIONS: Pneumatic dilation produced transient thickening of the mucosa-submucosa, but no thickening or breaks in the muscularis propria. This transient wall damage suggestive of edema was not seen after botulinum toxin injection. Over a 3-month period, botulinum toxin was equivalent to pneumatic dilation in relieving dysphagia and regurgitation in patients with achalasia.

Adolescent↗

Social support and adjustment to cancer: reconciling descriptive, correlational, and intervention research.

Several research literatures are reviewed that address the associations of emotional, informational, and instrumental social support to psychological adjustment to cancer. Descriptive studies suggest that emotional support is most desired by patients, and correlational studies suggest that emotional support has the strongest associations with better adjustment. However, the evidence for the effectiveness of peer discussion groups aimed at providing emotional support is less than convincing. Moreover, educational groups aimed at providing informational support appear to be as effective as, if not more effective than, peer discussions. Reasons for inconsistencies between the correlational and intervention literatures are discussed, and future directions are outlined.

Adaptation, Psychological↗

Trauma and the developmental process. Excerpts from an analysis of an adopted child.

The adopted child faces a complex developmental task. Having a vital need for a parent, he has to deal with the traumatic loss of one set of parents and at the same time has to allow new, alien adults to become his parents. Some implications of this life situation on the developing representations of self and other and on self-other relations are explored in the three-year course of psychoanalysis of a five-and-a-half-year-old boy.

Adoption↗

AIDS prevention training for pharmacy workers in Mexico City.

Mexican pharmacies play an important adjunct health care role in sexually transmitted disease prevention and treatment. In light of the rapid spread of the AIDS pandemic, research was initiated in 1989 to investigate the feasibility of pharmacies assisting in AIDS and STD prevention and control through community education and condom promotion. This study was implemented in three stages: a needs assessment, development of a training course and complementary materials, and an evaluation of the course and materials. The instruments used in the needs assessment were a KAP questionnaire and 'mystery shopper' visits to pharmacies. The evaluation design utilized pre- and post-tests, condom sales tracking and 'mystery shopper' visits. The needs assessment found that pharmacy employees have some basic knowledge about AIDS and STDs, but lack important information and do not communicate effectively with clients in spite of client interest in these topics. Pharmacy workers expressed great in learning more about AIDS and STDs. The evaluation of the intensive 8-hour course and supporting materials showed that, when given together, the course and materials increased short term knowledge about AIDS and condom use. However, the interventions were less successful in achieving longer term information retention, transfer of knowledge to clients or in influencing condom sales. Adjustments in the training course content and in participant recruitment strategies are recommended.

Acquired Immunodeficiency Syndrome↗

Cytokine function: a study in biologic diversity.

Cytokines are a group of hormone-like polypeptide mediators that play a variety of regulatory roles in both host defense and normal and abnormal homeostatic mechanisms. They may he produced by diverse cell types and exert their function on a variety of cells. Their effects (which may be suppressive or enhancing) are on cellular proliferation, differentiation, activation, and motility. In addition, cytokines can exert cytodestructive effects on infectious agents or tumor cells, either directly or by activating cells with cytodestructive potential. Any given cytokine may have many different biologic effects. However, two different cytokines may have similar or identical activities. Cytokines may be classified on the basis of their cell of origin, their spectrum of activity, the category of activity they influence, the cells that are their targets, or on specific features of their ligand-receptor interaction. The mode of action of many of the cytokines involves typical signal transduction events such as protein phosphorylation, and to date there is only limited understanding of the mechanisms that lead to one activity over another when a specific cytokine is involved in a specific biologic reaction. Nevertheless, elucidation of their role in other pathologic processes has provided insight into autoimmune and allergic diseases, as well as a variety of systemic disorders. Because of their broad spectrum of activity, cytokines have been used in a variety of therapeutic settings involving both infectious diseases and neoplasia. As the number of known cytokines continues to grow, it will be increasingly difficult for the non-"cytokinologist" to follow the exponentially expanding literature. Hopefully, this brief review will provide an overview that can serve as a framework for the understanding of this important area of biology and pathology.

Chemokines↗

The effects of triiodothyronine on hemodynamic status and cardiac function in potential heart donors.

Brain death is associated with altered cardiac function and low concentrations of circulating triiodothryronine (T3). However, the effects of T3 administration on hemodynamic status and cardiac function in potential heart donors remain controversial. Thirty-seven brain-dead patients were randomly and blindly allocated to receive an intravenous bolus of either 0.2 microgram/kg T3 (n = 19) or saline placebo (n = 18). Measurements included conventional hemodynamic and echocardiographic variables of cardiac volume conditions and systolic function of the left ventricle (fractional area change [FAC], velocity of myocardial fiber shortening) using a transesophageal probe, arterial and mixed venous blood gas parameters, and serum thyroid hormone concentrations. The mean concentration of T3 was 1.86 +/- 1.55 pmol/L, and only six patients (16%) had normal values of T3 in control conditions. There was no significant correlation between T3 concentration and FAC (R = 0.17, not significant). All patients receiving T3 had normalized serum T3 concentration (7.55 +/- 2.56 pmol/L) in contrast to patients receiving saline (1.48 +/- 1.26 pmol/L). No significant differences in hemodynamic and echocardiographic parameters were observed between the placebo and T3 groups. Indeed, FAC remained unchanged after T3 (44% +/- 17% vs 46% +/- 22%) or placebo (47% +/- 18% vs 50% +/- 14%) administration. In 20 patients with impaired left ventricular function (FAC < 50%), FAC remained unchanged after T3 (n = 10; 34% +/- 12% vs 30% +/- 10%) or placebo (n = 10; 38% +/- 12% vs 35% +/- 13%) administration. In 17 patients in whom organ harvesting was delayed, transesophageal echocardiography was performed 6 h later and no significant changes in FAC were noted in the T3 group (n = 8; 49% +/- 17% vs 44% +/- 17%) and the placebo group (n = 9; 51% +/- 18% vs 47% +/- 18%). In conclusion, T3 administration did not improve hemodynamic status and myocardial function in brain-dead patients, suggesting that the euthyroid sick syndrome is not the main determinant of myocardial dysfunction in these patients.

Adolescent↗