Sydney Louis

Diphenylhydantoin metabolism in uremia.

Abstract Diphenylhydantoin was administered orally or intravenously to 20 uremic and 20 nonuremic patients. In the former this drug and 5-phenyl-5-parahydroxyl-phenylhydantoin, its major metabolite, were measured in blood and urine. In the nonuremic patients, only diphenylhydantoin levels in plasma were measured. Regardless of the route of administration, diphenylhydantoin concentrations were uniformly lower in uremic than in nonuremic patients. In uremic patients, plasma concentrations of 5-phenyl-5-parahydroxyl-phenylhydantoin were higher than reported values in nonuremic subjects. After a single intravenous injection of 250 mg of diphenylhydantoin, its rate of elimination from plasma (half-life) was 8.1 hours in five uremic patients and 13.0 hours in three nonuremic subjects. These observations suggest an altered metabolic disposition of the drug in uremia.

The cardiocirculatory changes caused by intravenous Dilantin and its solvent

Abstract Disturbances of cardiac rhythm, blood pressure, and alterations of the ECG are produced by propylene glycol, the solvent for parenteral Dilantin. Many of these phenomena are prevented by the Dilantin itself. The proportion of Dilantin to solvent, the rate at which each acts upon the heart, and the rate of administration may determine the consequences in any particular patient. A unique change in the forms of the ECG, namely, augmentation of all amplitudes, is produced by propylene glycol. This phenomenon has not yet been explained.

Diphenylhydantoin: Efficacy, toxicity, and dose-serum level relationships in children

Fifty-three patients less than 20 years of age, who had seizures other than febrile types or petit mal, were treated with diphenylhydantoin. In 75 per cent the seizures were controlled; in 25 per cent clinical control was not achieved though this could be attributed to drug failure in only 11 per cent. In most patients the dose of the drug could be related to the serum level by a simple formula. A few patients had unusually high or unusually low levels relative to the dose. The serum levels associated with seizure control and clinical toxicity varied greatly but were individually consistent. The value of performing serum level determinations was demonstrated.

Stroke in Young Adults

Excerpt Identification of a stroke-prone individual before cerebral infarction is of great importance in solving the problem of prophylaxis of atherosclerotic cerebrovascular disease. The lesion un...

Seasonal variation of non-embolic cerebral infarction☆

IT IS well accepted today that the prevalence of diseases caused by microorganisms is altered by climatic fluctuations. The increased incidence of pulmonary infection [l] in the winter and of poliomyelitis and gastro-intestinal infections in the summer are the best examples of this and probably reflect a combination of variations in (1) the host’s susceptibilities; (2) bacterial or viral virulence; and (3) vector availability. Stroke should not have a seasonal variation unless the major causative factors underlying its precipitation, including for instance atherosclerosis and circulatory dynamics, are modified by climate and season. Such factors as eating and drinking habits vary with the temperature; summer dehydration may alter circulatory dynamics and lead to cerebral infarction. There are suggestions of a seasonal variation in cholesterol levels in a stable population of men aged 46-62. Cholesterol levels were found to be highest from November to March and lowest during the summer months, May through August [2, 31. In a similar study involving both sexes, males and females showed seasonal variations of cholesterol levels in opposite directions [4]. Protein bound iodine levels have been found to vary seasonally, the lowest values found during June, July and August with high values in September, October, February and March [4]. The gap between these suggestions of seasonal variation in serum cholesterol and PBI and the occurrence of stroke is too wide for any meaningful connection. Some evidence for a seasonal variation in atherosclerotic disease is found in studies of coronary heart disease. Death from cardiovascular disease in some parts of the United States has a peak during December to April with a low point in August and September [6, 71. The reduction of death rates during the summer months has been confirmed in studies in areas with a marked seasonal climatic variation but not in areas which are continuously warm [S]. In Australia cardiovascular deaths are higher during their winter months, June through September, and lowest during their summer months, January through April [9]. In the field of cerebrovascular disease Takakashi in Japan found that cerebral hemorrhage had a low incidence in the summer months, June to September, and a high incidence in the winter months [IO].

Diphenylhydantoin in children: Pharmacology and efficacy

Variability in anticonvulsant efficacy of diphenylhydantoin (DPH) in adults depends on variations in drug metabolism among individuals and differences in the type and “strength” of the epileptic process.’.’ Our studies of children have shown that DPH often is effective but that blood DPH levels and clinical response vary markedly.3 We have extended our observations of the relationships between drug administration and effect in children to elucidate ( I ) the relationship of total daily dosage to serum DPH levels, (2) the metabolism of DPH, and (3) the relation of serum and dosage levels to control of seizures.

A clinical trial of premarin in cerebrovascular disease

Abstract A double blind study was carried out in which patients with atherosclerotic cerebrovascular disease and cerebral infarction were randomly selected for treatment with 1.25 mg Premarin or placebo. No prophylactic effect in preventing the recurrence of cerebrovascular accidents or myocardial infarctions could be demonstrated when patients were followed from 6 months to 3 yr. The data from this study suggests that Premarin in this dosage, 1.25 mg, may have a harmful effect as the treated patients in general fared less well than the controls.

Modification of experimental seizures and anticonvulsant efficacy by peripheral stimulation

WE RECENTIY REPORTED upon the relationship between the amount of a convulsant-intracortical penicillin-needed to provoke focal epileptic seizures in the cat and the amount of anticonvulsant-intravenous diphenylhydantoin, or DPH ( DilantinB) -required to suppress these clinical seizures.192 Within certain limits, a linear relationship was demonstrated between the amount of penicillin needed to provoke the seizure and the amount of DPH required to suppress its clinical expression, namely, the clonic movements. No such relationship could be found for the electrical activity at the cortex which persisted long after cessation of the clinical attack. In a companion clinical study of status epilepticus, a similar finding was noted, namely, that a poor clinical response to DPH correlated with more severe brain damage and a higher mortality rate.3 In this clinical study, control of seizure manifestations could be related to DPH dosages but no such relationship could be established between cortical spikes and the DPH dose. It was suggested from these studies that the quantity of DPH needed to control the peripheral seizures might be used to measure the “strength” of an epileptic focus and, indirectly, the prognosis. Subsequent studies indicated that the relationship between the quantities of penicillin and DPH, required, respectively, to create and suppress seizures, could be fundamentally modified in our animal model. Alterations in this quantitative relationship could be induced by: [I] applying peripheral stimuli or [2] changing the anesthetic level. It was also noted that peripheral stimulation or an aItered anesthetic level could modify the severity of seizures in these experimental animals even before the use of anticonvulsant drugs. Observations made later on patients with status epilepticus indicated that afferent stimulation would similarly often precipitate seizures or modify their control by anticon\~ulsants. As these observations have obvious significance in the therapy of seizures in man and are of interest in understanding the mechanisms of seizure and anticonvulsant activity, they are reported in this paper.