A thermodynamic approach to problems of drug antagonism. Measurements of the parameters of affinity (pA2) of antihistaminics and a beta-haloalkylamine under varying experimental conditions

Two measurements of pA₂ (in equilibrium and at the receptor site) are described for both diphenhydramine (Benadryl) and phenoxybenzamine (Dibenzyline). For diphenhydramine, after washing out the preparation, there is a spontaneous recovery with a rapid decrease of pA₂ (at the receptor site) to 0, though for phenoxybenzamine the preparation remains at a high level of inhibition for several hours, provided the temperature is kept at 37°C. Such a conditioned allowed a measurement of the affinity parameter (pA₂ = ?log K_i) at different temperatures, from 40°C down to 2–4°C. By using a classical Arrhenius plot it was possible to calculate enthalpies (?ΔH) and entropies (ΔS) of formation of the alleged bindings of phenoxybenzamine with the histamine H₁-receptor which was found to depend strongly upon temperature. Above 20°C the enthalpy ΔH = ?21,494.8 cal/°K was significant and large enough to suggest a covalent or ionic binding, with a negative entropy of formation. Below 20°CΔH = ?3,461.04 e.u. was low and non-significant, with a positive entropy of formation. The conclusion was drawn that at low temperature the binding is probably entropy driven and depends more upon hydrophobic interactions of the antagonist with the receptor site.     

The management of intractable vasomotor rhinorrhoea by transnasal vidian neurectomy

The performance of transnasal vidian neurectomy in cases of intractable vasomotor rhinorrhoea is described. Of the 66 patients who underwent the procedure, 58 have been followed up and 96% of these reported total or marked improvement in nasal obstruction, 87% reported total or marked improvement in rhinorrhoea and sneezing and 90% reported improvement in post-nasal drip. The procedure is recommended for patients in whom medical treatment has failed.     

Comparison of timegadine and naproxen in rheumatoid arthritis. A placebo controlled trial

A double blind, cross-over design was used to compare the acute effects of timegadine, naproxen and placebo in rheumatoid arthritis. Timegadine appeared to be more effective than naproxen in those variables related to disease activity although there were no statistically significant differences (apart from morning stiffness) where variables were examined individually. There was a tendency to a rise in alkaline phosphatase, and possibly gamma glutamyl transpeptidase, during the 2-week timegadine treatment period. No other biochemical or haematological abnormality was observed.     

Physiopathology of arterial hypertension. Significance of the renin-angiotensin-aldosterone system and structural changes

It is presented a review of some recent aspects of the hypertension's physiopathology, namely those related with the renin-angiotensin-aldosterone system and with the cardiovascular structural changes. The large action range of the angiotensin is pointed out, in particular those actions related with the heart's and vessel's adaptation to a chronic load of pressure. In the end, the author stresses some recent references about the genetic's role on the pathogenesis of the structural changes.     

Spontaneous and antibody-dependent cell-mediated cytotoxicity by human T cell subpopulations.

Human peripheral blood non-T cells, T cells and their subpopulations (Tmu, Tgamma, Tphi, Tgamma-depleted cells, and Tmu-depleted cells) were assayed for their capacity to mediated spontaneous lymphocyte-mediated cytotoxicity (SLMC) or natural killer activity against K562 tumor cell line and antibody-dependent cellular cytotoxicity (ADCC) against chicken erythrocytes coated with antibody. Non-T cells, unseparated T cells, Tgamma cells, and Tmu-depleted (Tgamma-enriched) cells were found to have both SLMC (NK activity) and ADCC. Tmu, Tphi, and Tgamma-depleted cells had minimal or no SLMC and ADCC activity. This study demonstrates that SLMC and ADCC activity in T cells is mediated by Tgamma cell subpopulations. These two cytotoxic reactions were either mediated by two distinct subsets of Tgamma cells or by a single effector cell using two different mechanisms.     

Two decades of experience with testicular tumors in children at St Jude Children's Research Hospital

From 1968 to 1988, 24 children and adolescents with malignant testicular tumors were treated at St Jude Children's Research Hospital. Pure yolk sac tumors (YST) were present in 13 cases; 11 patients had other types of nonseminomatous malignant germ cell tumors. Children with localized and totally resectable disease (stage I) were treated by orchiectomy alone; all others also received chemotherapy. Five of ten patients treated before the implementation of a multiagent chemotherapy protocol in 1979 have died. By contrast, all of the 14 patients treated on this protocol are alive. The improved survival during the past decade is attributable to better diagnostic imaging techniques, the availability of serum tumor markers to monitor disease activity, and more effective chemotherapy. Orchiectomy alone is sufficient treatment for patients with clinical stage I disease who show appropriate reductions in tumor marker levels after surgery. Modern platinum-based chemotherapy provides disease control in patients with higher stage disease.