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Biomedical subjects

J Goldfarb

Publications and source records attributed to J Goldfarb.

120 records · Page 7Linked to original sources

Effects of estrogen on tight junctional resistance in cultured human umbilical vein endothelial cells.

OBJECTIVE: To study the effects of estrogen on transendothelial paracellular permeability in women. METHODS: Human umbilical vein endothelial cells (HUVEC) obtained from women were grown on filters. The paracellular permeability characteristics were determined in terms of changes in the permeability to the polar acid pyranine (Ppyr) and as changes in the transendothelial electrical resistance (RTE). Tight junctional resistance characteristics were assayed by lowering luminal NaCl and measuring the dilution potential, and were expressed as the ratio of monoion mobility uCl/uNa (cation selectivity). RESULTS: Low extracellular calcium and hyperosmolarity increased Ppyr and decreased RTE. The former but not the latter condition abolished the endothelium-specific cation selectivity. Treatment with 10 nM of estradiol-17 beta had no effect on RTE, but it increased the cation selectivity. The effect of estradiol required 1-6 hours' incubation with the hormone; it was dose dependent and saturable, with a median effective concentration of estradiol of 1 nM. Diethylstilbestrol, but not estriol, could mimic the effect of estradiol, and the estrogen receptor antagonist ICI-182, 780 blocked it. CONCLUSION: Cultured HUVEC cells form patent tight junctions. Estrogens increase the cation selectivity across HUVEC cultures. The effect of estrogen may be mediated by an estrogen receptor. These effects may be important for vasculoprotection in cases of sudden changes in ions levels across the capillary wall, such as ischemia or reperfusion.

Calcium↗

Beneficial effects of estrogen on cardiac stunning in female rabbits.

OBJECTIVE: To determine the effect of estrogen treatment on the contractile, relaxation, and chronotropic responses of hearts of female rabbits to cessation of perfusion. METHODS: Adult female rabbits were treated either with estradiol or with the vehicle (control). The hearts were then isolated and perfused at constant pressure by the Langendorff technique. A saline-filled balloon connected to a pressure transducer was inserted in the left ventricle in order to assess the mechanical function of the isolated heart. Cardiac stunning was induced by halting the perfusion of the coronary vasculature for four successive periods of 1, 3, 5, and 5 minutes, followed by reperfusion between nonperfusion periods. Changes in cardiac function induced by the cessation of perfusion were assessed by monitoring the changes in heart rate and in left ventricular pressure ([dP/dt]max as an index of ventricular contractility and [dP/dt]min as an index of ventricular relaxation). Changes in coronary flow were determined at baseline and following reperfusion. RESULTS: Halting coronary perfusion decreased (dP/dt)max, and (dP/dt)min and slowed left ventricular contractions both in control and in estrogen-treated hearts. The depressant effects of flow cessation on left ventricular (dP/dt)max and (dP/dt)min were smaller in estrogen-treated hearts than in control hearts. Treatment with estrogen had no effect on the changes on the heart rate in responses to cessation of flow and to reperfusion. Treatment with estrogen increased coronary flow by 40%. Coronary reperfusion increased coronary flow transiently, but the effects did not differ significantly between control and estrogen-treated hearts. CONCLUSION: Short-term treatment of adult female rabbits with doses of estrogen that are physiologic for the rabbit exerts a protective effect on cardiac contractility from repetitive periods without perfusion.

Animals↗

Fatal cryptosporidiosis complicating Kaposi's sarcoma in an immunocompromised man.

Fatal cryptosporidiosis in a bisexual immunosuppressed man with disseminated Kaposi's sarcoma and intractable diarrhea is described. Cryptosporidium sp. was isolated from the stool antemortem by Sheather's floation technique. This parasite should be considered in immunosuppressed hosts with chronic diarrhea when routine methods fail to demonstrate etiologic agent. Since this organism is already infectious when passed, stool precautions should be maintained.

Acquired Immunodeficiency Syndrome↗

The MMPI as a predictor of outcome in low-back surgery.

Between 1965 and 1975, 103 low-back patients were rated preoperatively for general level of functioning, and each completed a Minnesota Multiphasic Personality Inventory (MMPI) test. Following surgery, patients were rated in terms of treatment effectiveness at 6 months and 1 year. The MMPI hypochondriasis and hysteria scales were moderately related to surgical success, as were the severity of initial restriction in the level of functioning and the number of operations performed during the study. However, the MMPI profiles were strikingly similar for all patients. Factors which were not predictive of surgical outcome included age, sex, duration of symptoms, number of back surgeries prior to entering this clinic, and the degree of pathologic condition discovered at operation. The failure to find a potent prediction scheme confirms that MMPI information must be used with considerable caution in treatment planning and only as an adjunct to other clinical and psychological data.

Adult↗

Amitriptyline and chronic low-back pain. A randomized double-blind crossover study.

The effect of antidepressant medication on chronic low-back pain patients was studied in a randomized blind crossover study. Among those patients who completed the study, there was a 46% decrease in the use of analgesics while on amitriptyline when compared to placebo (P less than 0.005). There was also improvement in affect, but no measurable change in activity level. The MMPI profile of those patients who were unable to comply with the study protocol differed from that of patients who completed the study. The noncompliers demonstrated an elevation of the F, Pd, Pt (P less than 0.05) and Mf (P less than 0.01) scales. Although the interpretation of such a profile is left open to speculation, it may serve as an indicator of noncompliant individuals.

Activities of Daily Living↗

Kinetics of response and drug action.

Vascular smooth muscle tone is modulated in vivo by the functional interaction of a variety of vasoconstrictor and vasodilator stimuli. Endogenous substances (e.g., epinephrine) acting on smooth muscle, simultaneously activate alpha-adrenergic receptors (alpha-AR) eliciting contraction and beta-adrenergic receptors (beta-AR) which relax the muscle. This study characterizes the beta-adrenergic response in the isolated rabbit aorta precontracted with phenylephrine (PE) or serotonin (5-hydroxytryptamine [5-HT]). The beta-adrenergic agonist isoproterenol (ISO) produces a biphasic response that is composed of a rapid relaxation followed by a slower regaining of tension identified as desensitization. An exploratory kinetic model that describes both relaxation and desensitization as first order processes provides a good description of the experimental data. The five parameters used to describe the ISO response are: the observed rate constants for relaxation and desensitization (krel and kdes), the fractional magnitudes of the changes in tension for the two processes (R/C) and D/R), and the observed delay in the onset of the desensitization response, td. The krel and R/C were dependent on concentration of ISO in a saturable manner in rings precontracted with either 1 mumol/L PE or 1 mumol/L 5-HT and inversely related to the concentration of the contractile agonist. Yet, although the degree of fractional relaxation in the presence of PE covered the full range, that of 5-HT extended over a range of 20%. This behavior leads to the conclusion that the functional interaction between the contractile and relaxing stimuli is non additive. No dependence on the concentration of ISO was observed for D/R, kdes, and td.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Electrophysiologic studies of serotonin receptor activation. Answered and unanswered questions.

Cellular electrophysiologic responses to serotonin and serotonin agonists in vertebrate neurons and cell cultures derived from neuronal or neuroblastoma x glioma hybrids are reviewed. Emphasis is on local rather than systemic drug administration, and on intracellular and patch clamp recording. Activation of serotonin receptors can open and close potassium channels, reduce voltage-dependent calcium currents and calcium-activated potassium currents, enhance hyperpolarization-activated cation currents, and open ligand-gated cation channels. The pharmacology of these responses is described and the assignment of serotonin receptor subtypes discussed. The review is selective rather than inclusive and was concluded in November 1989.

Animals↗

Meta-analysis in the evaluation of treatment for streptococcal pharyngitis: a review.

Penicillin has been first-line therapy for the treatment of streptococcal pharyngitis for more than 40 years. Since the 1980s, there have been a number of reports suggesting that bacteriologic failure rates with penicillin may be rising. A number of alternative therapies have been proposed, including oral cephalosporins. To evaluate the efficacy of these agents, two meta-analyses have recently been performed. In the meta-analysis performed by Pichichero and Margolis, oral cephalosporins were reported to achieve a significantly greater bacteriologic cure rate than penicillin (92% with cephalosporins vs 84% with penicillin, P < 0.0001) when results from 19 studies were analyzed. A separate meta-analysis performed by Deeter et al reported that the oral cephalosporin cefadroxil monohydrate achieved significantly greater bacteriologic cure rates (94.8% cefadroxil vs 87.5% penicillin, P < 0.05) than oral penicillin when 9 trials in 1406 patients with streptococcal pharyngitis were analyzed. A review of 65 studies of the use of penicillin for the treatment of streptococcal pharyngitis has shown that bacteriologic failure rates in the period 1980 to 1993 were approximately 12% to 13%, slightly but not significantly greater than during the period 1953 through 1979. Oral cephalosporins such as cefadroxil monohydrate provide reasonable alternatives for the treatment of streptococcal pharyngitis.

Administration, Oral↗