D-penicillamine and retinopathy of prematurity.
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Biomedical subjects
Publications and source records attributed to L Lakatos.
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The pharmacokinetics of D-penicillamine in premature babies was studied. The metabolism of the drug was characterized by a long half-life (115 min) with a low plasma clearance (2.84 ml/min/kg body weight) in contrast to adults. The mean volume of distribution (649/ml/kg body weight) was similar to that of adults.
Serum ceruloplasmin activity in full term and premature neonates was measured on the first day of life. Preterm newborns were born more than 24 hours after antenatal corticosteroid treatment, had enzyme activity equivalent to that of the full term babies. Little or no ceruloplasmin activity was found in those prematures who were born without steroid prophylaxis. Highly significant correlation was observed between the initial ceruloplasmin activity and the morbidity and mortality of respiratory distress syndrome.
A prospective controlled trial has recently been reported to show the effectiveness of D-penicillamine (DPA) in the prevention of retinopathy of prematurity (ROP) among infants less than 2000 g birth-weight. The present paper is a comprehensive overview of a cohort of 204 prematures enrolled in the above study, with respect to mortality and outcome. Survival rate in the DPA treated group was the same as of those receiving conventional therapy. When the outcome of the DPA treated and the control infants was compared in terms of both major and minor impairments, the frequency of disabled and handicapped infants was higher in the control group. The same was observed with respect to the number of repeated hospital treatments, which was significantly higher among the control babies. The results suggest that DPA effectively prevents ROP among very-low-birth-weight infants, and also that the drug has no adverse effect on either mortality or late development.
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204 infants with birthweights between 751 and 2000 g and 26-35 weeks gestational age (100 treated and 104 control subjects) were enrolled in a prospective controlled trial of the effectiveness of D-penicillamine (DPA) in the prevention of retinopathy of prematurity (ROP). The two groups did not differ significantly in gestational age, birth weight, Apgar scores, the time of exposure to oxygen and in the incidence of PDA or in the number of exchange transfusions and RBTs. Of the treated infants 29, and of the control infants 34 died before the tenth week of life. These cases were not included in further analysis. Patients were subsequently examined and assessed by two ophthalmologists independently, who did not know which babies were receiving DPA. Six of the 70 surviving control infants and none of the 71 surviving treated infants had ROP stage II or graver. The results suggested that ROP may effectively be prevented with DPA in very low-birth-weight-infants, and that the drug has no serious adverse effects during the neonatal period.
The protecting effect of D-penicillamine against hydrogen peroxide and phenylhydrazine induced haemolysis and lipid peroxidation is discussed. It might represent a possible way of action of the drug in some neonatal disorders like hyperbilirubinaemia and retrolental fibroplasia.
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A 3-day D-penicillamine treatment of neonatal rats caused a significant decrease in heme oxygenase activity. This change was not observed in adult rats. The data indicate age-related differences in the effects of D-penicillamine.
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Explore the source record for details and available documents.
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D-Penicillamine, previously suspected to have a beneficial effect on the occurrence of severe retrolental fibroplasia among very low birth weight infants, was tested to determine the extent to which this drug modifies acute radiosensitivity on 3- to 4-day-old mice in comparison with adult animals. It was found that the radioprotective effect of penicillamine, given in doses of 3,000 mg/kg i.p. 60 min before whole-body exposure to 6-10 Gy of 60Co gamma rays, was greater in 3- to 4-day-old mice than in adult animals. These data seem to be compatible with the view that D-penicillamine, by virtue of its antioxidant action, may reduce the toxic effects associated with exposure of the newborn infant to hyperoxia, specifically retrolental fibroplasia and bronchopulmonary dysplasia.
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