Absorption, metabolism and excretion of safrole in the rat and man.

The metabolic disposition of different doses of [14C] safrole were studied in rat and man. In both species, small amounts of orally administered safrole were absorbed rapidly and then excreted almost entirely within 24 h in the urine. In the rat, when the dose was raised from 0.6 to 750 mg/kg, a marked decrease in the rate of elimination occurred as only 25% of the dose was excreted in the urine in 24 h. Furthermore, at the high dose level, plasma and tissue concentrations of both unchanged safrole and its metabolites remained elevated for 48 h probably indicating impairment of the degradation/excretion pathways. The main urinary metabolite in both species was 1,2-dihydroxy-4-allylbenzene which was excreted in a conjugated form. Small amounts of eugenol or its isomer 1-methoxy-2-hydroxy-4-allylbenzene were also detected in rat and man. 1'-Hydroxysafrole, a proximate carcinogen of safrole, and 3'-hydroxyisosafrole were detected as conjugates in the urine of the rat. However, in these investigations we were unable to demonstrate the presence of the latter metabolites in man.     

The mechanism of midtrimester abortion induced by intra-amniotic instillation of hypertonic saline: A modification of Gustavii's lysosomal hypothesis

This modification of Gustavii's hypothesis recognizes the central role of saline-induced decidual cell necrosis and secondary prostaglandin release in the initiation of myometrial activity. In the absence of significant necrosis in the decidua basalis, passive stretching of the subplacental myometrium is considered to activate this region leading to secondary intervillous stasis and the reduction in progesterone delivery to the myometrium and systemic circulation. This drop in progesterone further sensitizes the myometrium to PGF_2α stimulation and helps the self-sustaining process of myometrial activity culminating in clinical abortion. A third hypothetical contributing factor may be the loss of some myometrial inhibitor normally present in the amniotic fluid.     

Active bronchial anaphylaxis in the rat: Inhibition by tiaramide

Intravenous administration of the benzothiazoline derivative tiaramide hydrochloride, to rats actively sensitized to ovalbumin, inhibited immunologic lung reactions in a dose-related manner. Methysergide also inhibited anaphylactic lung reactions. Serotonin, but not other chemical mediators, produced changes in pulmonary mechanics qualitatively similar to those produced by the sensitizing antigen. The bronchoconstrictive action of serotonin was blocked by methysergide and tiaramide. The latter drug also inhibited bronchoconstriction induced by methacholine. The results implicate serotonin as the primary mediator of the respiratory component of systemic anaphylaxis in the rat: however, the mechanism by which tiaramide inhibits anaphylactic bronchoconstriction remains to be elucidated.     

Synovial cysts of the hip joint and iliopsoas bursitis: A spectrum of imaging abnormalities

Synovium-related soft tissue disease around the hip constitutes a spectrum ranging from isolated iliopsoas bursitis to pure articular synovial herniations without bursal involvement. The clinical, pathologic, and radiographic features of these entities are discussed as they pertain to the variety of underlying disorders which predispose to their occurrence. Nine case reports are utilized to illustrate the variable clinical and radiographic presentations which may be encountered. Based upon these cases as well as those in the literature, an imaging algorithm has been developed which should eliminate unnecessary studies and allow prompt and accurate diagnosis.     

Criteria for selection of patients for emergency portacaval shunt

A computer program analysis of the effect on survival of 74 preoperative factors was performed as part of a prospective study of the emergency portacaval shunt in 146 unselected patients with bleeding esophageal varices due to alcoholic cirrhosis. Only ascites, a serum glutamic oxalacetic transaminase level of 100 units or more, and a requirement for 5,000 ml or more of blood transfusion were associated with a statistically significant decrease in survival. However, none of these factors are contraindications to operation because their presence permits a survival rate of 37 to 40 per cent. The only contraindication to emergency portacaval shunt is the combined presence of ascites, jaundice, encephalopathy, and severe muscle wasting, a constellation that was incompatible with survival beyond one year.     

Comparison of flunarizine (Sibelium®) and pizotifen (Sandomigran®) in migraine treatment: A double-blind study

In this double-blind, randomized multicenter study involving 75 patients, the calcium-entry blocker flunarizine (10 mg nocte) was compared with pizotifen (2–3 mg per day in three administrations). Duration of treatment was four months. The results suggest that, in the dosage used, flunarizine is at least as effective as pizotifen in both classical and common migraine as regards effect on attack frequency. Flunarizine might tend to more markedly suppress severity of the attack, though. The weight gain seen with both drugs might be slightly less with flunarizine. A practical advantage of flunarizine is its simple dosage schedule (one intake per day).     

Tissue distribution and hypotensive effect of prazosin in the conscious rat

We investigated the hypotensive effect and tissue distribution of prazosin (1 mg/kg i.v.) in conscious rats. This dose caused an immediate fall in blood pressure, associated with a nonsignificant increase in heart rate. Blood pressure then gradually rose to control over a 2-h period. Prazosin was measured in plasma and tissue samples by high-pressure liquid chromatography. Highest concentrations of drug were found in liver and kidney and the lowest in brain. The rate of decline of prazosin from plasma was similar to its decline from the tissues, indicating a rapid equilibrium. This rate of disappearance was also similar to the decay of the hypotensive response and suggests that prazosin in plasma may be in equilibrium with prazosin at its site of action.