Search PubMed⌕ Search

Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 793 records · Page 44Linked to original sources
PubMed1993

Prolactin response to fenfluramine and placebo challenge following maintenance pharmacotherapy withdrawal in remitted depressed patients.

Plasma prolactin (PRL) response to fenfluramine (FF) (60 mg orally) and placebo challenge was examined in eight remitted depressed patients who were withdrawn for 14 days from maintenance pharmacotherapy with clomipramine (CMI) plus lithium carbonate (Li) (n = 6) or Li alone (n = 2), 6 months after recovering from their major depressive episode. The patients had undergone identical FF challenge tests while drug free prior to commencing treatment with electroconvulsive therapy (ECT) (n = 4) or CMI supplemented with Li (n = 4) and after completing the above treatments. PRL response to FF in the remitted, drug-free state was significantly enhanced compared to the response prior to treatment (while depressed and drug-free) and not significantly different from the response following treatment with ECT (n = 4) or CMI plus Li (n = 4) 6 months before. Other work of a similar nature supports the view that enhanced serotonergically mediated hormone release in drug-withdrawn, remitted depressives, represents a long-standing change in central serotonergic responsiveness and not a continued effect of antidepressant treatment or a manifestation of medication withdrawal.

Clomipramine↗
PubMed1993

Treatment of septic shock with antibodies to tumour necrosis factor.

The high mortality associated with septic shock has prompted intensive study of the pathophysiological basis of this syndrome in an effort to better understand the processes that lead to tissue injury. One important outcome of this work has been the recognition that the cytokine tumour necrosis factor (TNF) is an important mediator of endotoxin-induced lethality. Accordingly, studies were done which showed that antibodies to TNF could protect animals from death in a variety of model systems, and based on these findings, clinical studies were initiated. This paper reviews the present status of clinical trials of anti-TNF in sepsis. These antibodies appear to be safe, and preliminary experience suggests that they may be effective in some patients with the sepsis syndrome. A final assessment of efficacy must await the large, placebo-controlled trials that are now in progress.

Adult↗
PubMed1993

Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides.

A systematic evaluation of structure-absorption relationships using a high throughput intraduodenal rat screening model has led to the delineation of a set of structural parameters that appear to govern bioavailability in a series of peptide-based renin inhibitors. Optimum structures, exemplified by 25 and 41, incorporated a single, solubilizing substituent at the C- or N-terminus combined with a lipophilic P2-site residue. Both inhibitors gave unprecedented plasma drug levels upon intraduodenal administration to monkeys, and the calculated bioavailability for 41 (14 +/- 4%) is the highest reported for any peptidic renin inhibitor.

Animals↗
PubMed1993

Studies directed toward the design of orally active renin inhibitors. 2. Development of the efficacious, bioavailable renin inhibitor (2S)-2-benzyl-3- [[(1-methylpiperazin-4-yl)sulfonyl]propionyl]-3-thiazol-4-yl-L-alanine amide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (A-72517).

Employing a set of empirical guidelines for the design of well-absorbed renin inhibitors, we have followed two strategies to improve potency while maintaining bioavailability. One process involved incorporation of an extended N-terminal residue bearing a weakly basic substituent and is exemplified by compound 25. The other approach centered on the inclusion of an N-terminal sulfonamide and culminated in the discovery of inhibitor 32 (A-72517). Both 25 and 32 showed excellent bioavailability in the rat and ferret (> 25%) and, while subject to hepatic elimination in the monkey, were efficacious in this species.

Animals↗