G. R. Avant

Gastric varices secondary to splenic vein occlusion: radiographic diagnosis and clinical significance.

The radiographic appearance and clinical significance of gastric varices in the absence of esophageal varices and secondary to splenic vein occlusion were studied. Eighteen patients were evaluated through medical records, angiography, and barium studies of the stomach and esophagus. The presence of splenic vein occlusion was determined by arteriography in 18 patients and its etiology confirmed by surgery in 17 patients. This condition should be suspected in patients with chronic abdominal pain, weight loss, and iron deficiency anemia who show fundal polypoid filling defects or prominent gastric folds on an upper GI series.

Infarction after embolization of the ileocolic artery

Treatment of colonic hemorrhage by therapeutic embolization of the involved artery may, rarely, result in bowel infarction. In one patient with angiodysplasia, bowel infarction resulted from a therapeutic embolization of the ileocolic artery. Because of the arterial anatomy of the cecum, occlusion of the cecal branches can result in devascularization of the cecum and appendix, even if the colic and ileal branches are not occluded. Thus, the ileocolic artery may not be a good candidate for therapeutic embolization.

The effect of cirrhosis on the disposition and elimination of clindamycin.

This study assessed the effect of alcoholic cirrhosis in man and of experimental liver injury in rats on the disposition and elimination of clindamycin. In 7 cirrhotics a statistically significant, although modest, prolongation of clindamycin half-life (T1/2β) was observed as compared to values in 7 agematched normal controls (mean ±SD: 4.46±0.93, hr vs 3.42±0.45 hr,P=0.02). This was primarily due to a decrease in clindamycin serum clearance in the cirrhotics, since the volume of distribution of the drug was similar in both groups (P<0.05). Serum protein binding of clindamycin was of the order of 79% and was comparable in both groups (P>0.05). There was a significant correlation between the T1/2β of the drug and both total serum bilirubin and SGOT. The T1/2β of clindamycin was also prolonged in rats with acute hepatic necrosis induced by administration of carbon tetrachloride and those with acute cholestasis caused by common bile duct ligation. These data suggest that liver damage, both chronic and acute, impairs the elimination of clindamycin but that this effect is small.

Physostigmine reversal of diazepam-induced hypnosis. A study in human volunteers

Under randomized double-blind conditions, 1.00 to 1.67 mg of intravenous physostigmine (Antilirium) reversed sleep induced by administration of 0.102 to 0.238 mg/kg body weight of intravenous diazepam in eight healthy human volunteers. Awakening occurred 330 to 740s after initiation of the physostigmine infusion at a rate of 0.5 mg/min every 4 min. Diazepam plasma levels were not significantly different at the start of either the physostigmine or placebo infusion. Physostigmine did not effect plasma binding of diazepam. Six subjects experienced nausea, and one subject developed an arrhythmia. Physostigmine reverses diazepam-induced hypnosis but causes side-effects requiring cautious administration.

Encainide disposition in patients with chronic cirrhosis

The antiarrhythmic agent encainide undergoes extensive first‐pass hepatic metabolism after oral dosing. The active metabolites O‐desmethylencainide and 3‐methoxy‐O‐desmethylencainide are formed in subjects who are extensive metabolizers (EMs), a phenotypic trait that cosegregates with that of debrisoquin. Because of the possibility that drug metabolism is altered by liver dysfunction, the disposition of encainide and its metabolites was studied in six such EMs with cirrhosis and compared with that in eight normal subjects of the same phenotype. Patients with cirrhosis had lower systemic and oral clearances of encainide, resulting in a threefold increase in oral bioavailability. The plasma concentration of encainide was significantly higher among the patients with cirrhosis, whereas the plasma levels of the respective metabolites were comparable with those in normal subjects, resulting in no change in the patients ECG intervals. Encainide is, therefore, an example of a drug in which cirrhosis causes a three‐ to fourfold increase in parent drug concentrations. However, because no change occurs in the levels of the pharmacologically active metabolites, dosage adjustment is probably not required in patients with cirrhosis.

Antagonism of benzodiazepine binding in rat and human brain by antiliriumR

Abstract Physostigmine (Antilirium R ) has been reported to reverse benzodiazepine- induced sleep or coma in man and prevent death in animals. Accordingly, we investigated the effect of Antilirium upon benzodiazepine binding to both rat and human brain. We report that Antilirium inhibits 3 H-diazepam and 3 H-flunitrazepam binding in a dose-dependent manner. The degree of inhibition of binding by Antilirium correlates with the affinity of benzodiazepine for its “receptor” such that diazepam is more affected than flunitrazepam. The inhibition is rapid but the kinetics are complex with only doses of Antilirium showing competitive inhibition when studied at equilibrium. These results may explain, at least in part, the effectiveness of Antilirium at reversing benzodiazepine-induced hypnosis without necessarily implicating a cholinergic mechanism.

Antagonism of Benzodiazepine Binding in Brain by Antilirium, Benzyl Alcohol, and Physostigmine

Abstract: Antilirium®, which contains eserine (physostigmine) and benzyl alcohol, is effective in reversing diazepam‐induced sleep in man and is capable in vitro of inhibiting the binding of labeled benzodiazepine to both rat and human brain homogenates in a dose‐dependent manner. We have examined the constituents of Antilirium and report that both benzyl alcohol and eserine inhibit [3HI‐diazepam binding to rat brain in a dose‐dependent manner. A major portion of the inhibition of binding found with Antilirium is accounted for by benzyl alcohol. Scatchard analysis of inhibition of benzodiazepine binding by benzyl alcohol reveals loss of binding sites and change in equilibrium dissociation constant. Methanol, ethanol, and butanol did not inhibit benzodiazepine binding. The inhibition by benzyl alcohol may be specific since there was no inhibition of labeled ligand binding to the γ‐aminobutyric acid, opiate, muscarinic acetylcholine, or β‐adrenergic receptors. The other constituent, eserine, is a competitive inhibitor. While eserine is a more potent inhibitor at the benzodiazepine receptor than is benzyl alcohol, it is also much less specific. Eserine inhibited binding of labeled ligand to the γ‐aminobutyric acid, opiate, and muscarinic acetylcholine receptors. The inhibition of benzodiazepine binding to brain in vitro by Antilirium and its constituents, eserine and benzyl alcohol, may be the explanation, at least in part, for the reversal by Antilirium of diazepam‐induced narcosis in viva, without postulating a cholinergic mechanism for the in vivo effect.

Conjugated sodium tyropanoate (Bilopaque) in the bowel: significance of its presence or absence after first-dose oral cholecystography.

Oral cholecystography following the ingestion of 4.5 g of sodium tyropanoate (Bilopaque) was performed in 1,053 patients. The radiographs of 89 patients in whom the gallbladder was either faintly visualized or nonvisualized were reviewed for the presence of conjugated contrast material in the bowel. All 89 of these patients underwent second-dose cholecystography. Oral cholecystography was found to be 100% accurate in the diagnosis of gallbladder disease when conjugated contrast media was found in the bowel in the presence of a faintly visualized or nonvisualized gallbladder. When this combination of findings is seen on the first-dose examination, a second-dose examination is unnecessary. When no conjugated contrast material is seen in the bowel after a first dose, a second dose is helpful only in those patients with normal biochemical liver function tests.