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O Epstein

Publications and source records attributed to O Epstein.

101 records · Page 6Linked to original sources

Effects of propranolol during pregnancy and development of rats. I. Adverse effects during pregnancy.

Pregnant rats, treated with high doses of propranolol, gave birth to small for dates neonates. Litter size was affected in daily doses of 100 and 150 mg/kg/day. Propranolol markedly influenced the gain in weight normally observed in pregnant rats. The placentas of the rats which received the higher doses of propranolol weighed about 30% less than normal placentas. Pregnant rats, treated with propranolol, gave birth to small for dates neonates. This effect is possibly the result of a drug-induced reduction in transport across cellular membranes, resulting in malnutrition. Since similar effects were reported in humans, treatment with propranolol during pregnancy should be further reevaluated in laboratory animals.

Animals↗

The effect of beta-adrenergic blocking agents on experimental porphyria induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) in vivo and in vitro.

The effect of DL-propranolol on 3',5'-diethoxycarbonyl-1,4-dihydrocollidine-induced experimental porphyria was studied. DL-Propranolol, a beta-adrenergic blocking agent with non-specific membrane effects, partially inhibited 3',5'-diethoxycarbonyl-1,4-dihydrocollidine-induced delta-aminolevulinate synthetase activity both in rats and in chick embryo liver cells in culture. In rats, DL-propranolol decreased urinary delta-aminolevulinate and porphobilinogen but no change occurred in the 24-h urinary excretion of total porphyrins and in the concentration of porphyrins in the liver. In cultured chick embryo liver cells treated with 3',5'-diethoxycarbonyl-1,4-dihydrocollidine, DL-propranolol decreased accumulation of porphyrins in the medium. D-Propranolol, oxprenolol and quinidine acted like DL-propranolol in chick embryo liver cells in culture treated with 3',5'-diethoxycarbonyl-1,4-dihydrocollidine. Pindolol, practolol and lidocaine had no effect. Phenobarbitone had a synergistic effect on the induction of delta-aminolevulinate synthetase by 3',5'-diethoxycarbonyl-1,4-dihydrocollidine in cultures of chick embryo liver cells. This induction was partially inhibited by propranolol. However, the increased accumulation of porphyrins in the medium caused by 3',5'-diethoxycarbonyl-1,4-dihydrocollidine was inhibited by the addition of phenobarbitone. This inhibited induction was further decreased by propranolol. Most of our results indicate that the drugs tested act mainly by their effects on membranes.

5-Aminolevulinate Synthetase↗

The ontogeny of liver copper metabolism in the guinea pig: clues to the etiology of Wilson's disease.

The normal human neonate has a copper profile indistinguishable from Wilson's disease, and we have previously postulated that this disease is caused by genetic failure to switch from the fetal to adult mode of copper metabolism. This study validates the developing guinea pig as a suitable animal in which to study copper ontogeny. At birth, liver copper concentrations are 7 times higher than in adults and serum copper and ceruloplasmin are 27 and 21% of adult values, respectively. A 53% fall in liver copper occurs in the 4 days after birth. This is associated with a marked increase in bile copper output, which does not parallel increasing bile flow. Liver copper falls, and serum copper and ceruloplasmin increase to near adult levels in the 30 days after birth. Until the sixtieth day of gestation, liver copper was significantly increased in copper-stressed littermates, although paradoxically at birth, concentrations were significantly lower. In copper-stressed fetal animals, bile copper output increased markedly before birth. Metallothionein was the dominant copper-binding protein in the fetal liver but a minor component in the adult. Superoxide dismutase activity only developed after birth. We conclude that the postnatal switch from the fetal to adult mode of copper metabolism involves activation of biliary excretion and ceruloplasmin export as well as changes in the association of copper with hepatic copper proteins. Similarities between the fetus and Wilson's disease suggest that this disease is caused by failure of this postnatal adaptation process.

Aging↗

Computerised biofeedback games: a new method for teaching stress management and its use in irritable bowel syndrome.

OBJECTIVES: To develop and test a computer biofeedback game designed to teach deep relaxation to patients with a stress related disorder and to assess whether relaxation can improve symptomatic episodes. STUDY DESIGN AND SETTING: An open, prospective, single centre study. Department of Gastroenterology, Royal Free Hospital, London. SUBJECTS: Forty patients with irritable bowel syndrome refractory to conventional medical treatment. MAIN OUTCOME MEASURES: Development of a computer aided biofeedback apparatus directed at the gut for teaching relaxation to patients with irritable bowel syndrome. The patients' ability to complete a computer game involving biofeedback modulated by a physiological loop that related changes in stress (monitored by electrodermal activity) to animated computer graphics. The degree to which deep relaxation was achieved was measured numerically by a progressive reduction in the sensitivity level of the biofeedback loop. The success of relaxation in ameliorating physical symptoms of irritable bowel syndrome was assessed by daily diaries in which global and weighted bowel symptom scores were entered. RESULTS: A computer biofeedback game based on animated gut imagery was successfully developed. Most patients learned to achieve progressively deeper levels of relaxation after four 30 minute biofeedback sessions (mean difference in sensitivity level 2.0 (95% confidence interval 0.96 to 2.93), p < 0.001). Use of 'dosed' relaxation when bowel symptoms were troublesome was helpful in 50% of patients. It reduced the global symptom score (mean difference 0.5 (0.02 to 0.32), p < 0.04) and the bowel symptom score (mean difference 0.8 (0.04 to 1.58), p < 0.04). At long term follow up, 64% of patients who had been helped by dosed relaxation continued to use the technique, although they had had no further contact with the hospital. CONCLUSIONS: This computer biofeedback game taught deep relaxation rapidly and effectively. Half the patients with refractory irritable bowel syndrome found the technique helpful on most occasions on which it was used. Computer biofeedback games may offer a simple, inexpensive strategy for managing other stress related medical disorders.

Adult↗