Detrusor instability associated with menstruation. Case report.
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Binding of several psychoactive, antiinflammatory, antihypertensive, and antiarrhythmic drugs to central and peripheral benzodiazepine (BZ) binding sites was studied in the brain, heart and kidneys of rats. Diazepam exhibited the highest affinity for all binding sites (Ki values at 0.01 microM level); another 1,4-BZ, oxazepam, had markedly lower affinity for peripheral binding sites (Ki 21-37 microM). Non-BZ compounds had low affinity for central BZ receptors; proquazone was the most potent (Ki 9.5 microM). The affinities of non-BZ compounds were higher for peripheral BZ binding sites. The Ki value for proquazone was approximately 0.1 microM; and many other antiinflammatory agents, and the vasodilators cyclandelate and nifedipine, produced Ki values in the micromolar level. beta-Blocking drugs, and several other antihypertensive and antiarrhythmic agents lacked affinity for both central and peripheral BZ binding sites. According to the results, the affinity for peripheral binding sites is independent of an affinity for central BZ receptors. Non-BZ compounds that bound to brain BZ receptors bound with equal affinity to both BZ1 and BZ2 subgroups of receptors. The compounds with affinity for peripheral BZ binding sites did not select between heart and kidneys, which suggests that these organs have similar binding sites. The role of the peripheral BZ binding sites has not yet been established. The findings of this study allow the selection of a more varied group of ligands to be used when investigating the physiological significance of these binding sites.
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A prospective controlled trial involving over 1000 patients did not reveal any difference between four drugs commonly used in accident and emergency departments for the relief of mild to moderate pain. There were no significant variations in therapeutic effect, side-effects or patient compliance. When considering the supply of analgesics which may be no more potent than those available without prescription from retail chemists, cost and safety are more important than analgesic effect. By restricting the choice of analgesics available, the accident and emergency department should be able to increase awareness among its staff of the actions and side-effects of a small number of prescribed drugs and to contain costs.
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The proposition that arteriolar constriction to increased intravascular pressure is mediated through either the increased local production of an eicosanoid constrictor factor or decreased production of a dilating factor was examined. The myogenic response of arterioles was studied by enclosing anesthetized rats in an airtight Plexiglas box with the cremaster muscle exteriorized into a tissue bath containing Krebs solution. Microvascular responses were observed by video microscopy. The arteriolar response to a 20-mmHg increase in intravascular pressure was examined in the absence or presence of cyclooxygenase inhibition. In the absence of cyclooxygenase inhibition, second-order arterioles (2As) responded passively to increased pressure by distending to 107 +/- 1% of control diameter. In the presence of the indomethacin, 2As constricted to 79 +/- 5% of control. Third-order arterioles (3As) constricted to 47 +/- 8% of control without indomethacin and similarly to 33 +/- 4% with indomethacin. To test whether inhibitors of endothelium-derived relaxation factor would potentiate the myogenic response of 3As, methylene blue or gossypol was topically applied to the cremaster muscle. Neither inhibitor was found to augment the myogenic vasoconstriction; however, these inhibitors were observed to significantly reduce basal vascular tone. In comparison, the tonic local production of dilating prostaglandins appears to attenuate myogenic activity as demonstrated by the appearance of myogenic activity in the normally passive 2As when exposed to cyclooxygenase inhibitors.
To determine whether angiotensin II and alpha-adrenergic activity contribute to the mechanism of impaired renal microvascular blood flow during hyperdynamic live Escherichia coli (E. coli) bacteremia, we used in vivo video microscopy in the chronic unilateral hydronephrotic kidney of decerebrate male Sprague-Dawley rats. Intravenous infusion of E. coli caused arteriolar constriction to 83 +/- 4% of baseline (BL) in cortical radial arteries (CRA), 82 +/- 3% of BL in afferent (AFF) arterioles, and decreased flow to 54 +/- 9% of BL. Subsequent local inhibition of renal prostaglandin synthesis with mefenamate increased preglomerular arteriolar constriction to 55 +/- 6% of BL in CRA and 51 +/- 6% of BL in AFF arterioles and decreased renal microvascular blood flow to 26 +/- 8% of BL values in E. coli animals but had no effect on control animals. Subsequent local renal angiotensin II receptor blockade with saralasin acetate increased renal microvascular blood flow in E. coli animals to 64 +/- 9% of BL by dilating CRA to 78 +/- 5% of BL and AFF arterioles to 89 +/- 5% of BL. Phentolamine caused further dilation of CRA to 104 +/- 7% BL and AFF arterioles to 116 +/- 109% and increased flow to 99 +/- 8% of BL. Acetylcholine increased diameters further to 110 +/- 3% of BL in CRA and 136 +/- 12% of BL in AFF arterioles. These data indicate that in our chronic hydronephrotic kidney model during E. coli bacteremia, renal microvascular tone is due to increased angiotensin II and alpha-adrenergic activity and some other, as yet, undefined factor.
BACKGROUND: In the absence of objective symptoms, it is difficult to assess an adverse reaction during drug provocation testing. We evaluated the value of serum tryptase levels to distinguish between positive, negative and, even more important, so-called 'hysterical' reactions (conversion symptoms). The latter are occasionally observed in drug provocation tests when the patient experiences ambiguous subjective symptoms. METHODS: In a prospective single-center study, 303 patients underwent 785 drug provocation tests. Blood was taken for tryptase measurement on each test day before and after drug challenge, and the changes in serum tryptase levels in patients with no reactions were compared with those who experienced immediate reactions to a drug. RESULTS: Thirty-four of 785 drug provocations were clinically judged as being positive. Despite objective symptoms, median serum tryptase values in the afternoon were even lower than baseline levels. However, this decrease was not statistically significant. In the 751 patients suffering no objective reactions, the median values of post-testing tryptase values were statistically significantly decreased as compared with pretesting values. CONCLUSIONS: The measurement of serum tryptase levels does not appear to be helpful to differentiate mild allergic or nonallergic reactions from 'hysterical' ones. The milder decrease in the group with objective drug reactions might indicate slight mast cell activation in some patients. More severe clinical drug reactions led to stronger mast cell degranulation. Mild reactions did not increase the tryptase levels consistently.
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