What does the cryotherapy preliminary report mean?
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Biomedical subjects
Publications and source records attributed to D L Phelps.
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The human infant is born with low body stores of vitamin E. Thus, the infant requires an adequate intake of vitamin E soon after birth. If adequate sources of tocopherol are not provided, a clearly defined deficiency state characterized by hemolytic anemia and, after a period of years, spinocerebellar degeneration results. However, the benefit of pharmacologic doses of vitamin E given as prophylaxis against diseases believed to be related to oxygen toxicity (bronchopulmonary dysplasia, retinopathy of prematurity, and periventricular-intraventricular hemorrhage) is not clear. Possible benefits must be balanced against the potential for serious toxicity. Few data are available on the pharmacokinetics of tocopherols in infants, particularly with respect to esterified forms of tocopherol, and little is known about the toxicity associated with parenteral administration of the vitamin.
The effects of two types of prolonged oxygen supplementation were tested in the kitten model of oxygen induced retinopathy. Thirty-one litters were placed in 80% oxygen for 65 h starting the 3rd day after birth to initiate a moderately severe retinopathy. One-half of each litter thereafter served as controls, remaining in room air during the development of the retinopathy. In the remaining half, the retinopathy was allowed to develop in either a variably hyperoxic/hypoxic environment (one-half of each of 16 litters) or in an oxygen environment that was gradually reduced to room air by 4 wk (one-half of each of 15 litters). The retinopathy scores in the controls were comparable in both studies and the same as in previous experience with this model. Kittens exposed to the variable oxygen recovery environment had significantly less severe retinopathy than their room air recovery littermates (p less than 0.05). The retinopathy scores in the group with gradually withdrawn oxygen did not differ from the littermate controls (power greater than 80%). These data support the hypothesis that conditions of oxygenation during the recovery process from an acute oxygen-induced vascular injury have a significant effect on the healing process.
This article reviews the progress being made into the prevention or arrest of this complex respiratory disease. The key elements in the pathophysiology are reviewed; the current problems in defining, classifying, and predicting the development of this disorder are discussed and potentially useful interventions also are introduced.
To test the efficacy and safety of vitamin E in preventing retinopathy of prematurity, 287 infants with birth weights of less than 1.5 kg or gestational ages of less than 33 weeks were enrolled within 24 hours of birth in a randomized, double-masked trial of IV, followed by oral, placebo v tocopherol (adjusted to plasma levels of 3 to 3.5 mg/dL). In the 196 infants completing ophthalmic follow-up, tocopherol did not prevent retinopathy of prematurity of any stage (28% placebo treated v 26% tocopherol treated) or moderately severe retinopathy of prematurity (8% placebo treated v 11% tocopherol treated). Cicatricial sequelae were not significantly different (1/97 placebo treated v 3/99 tocopherol treated), with one placebo-treated infant and one tocopherol-treated infant having retinal detachments. Among all 232 infants examined, those treated with tocopherol had more retinal hemorrhage than placebo-treated infants (8/121 placebo treated v 16/111 tocopherol treated), and retinal hemorrhage correlated positively (P less than .01) with plasma levels of tocopherol after the first 2 weeks of age. Prospective monitoring of morbidity including late-onset sepsis, necrotizing enterocolitis, etc revealed no differences between groups except that grades 3 and 4 intraventricular hemorrhage occurred more frequently in infants weighing less than 1 kg at birth who had received tocopherol (14/42, 33%) v those who had received placebo (4/43, 9%) (P less than .02). Our data do not support the use of tocopherol for prophylaxis against retinopathy of prematurity in premature infants and suggest that IV tocopherol treatment starting on day 1 may increase the incidence of hemorrhagic complications of prematurity, particularly in infants with birth weights of less than 1 kg.
Two hundred eighty-seven infants were enrolled in a double masked, randomized, placebo controlled trial of early parenteral tocopherol given from day one. Among the 232 survivors with ophthalmologic follow-up, retinal hemorrhages occurred more frequently in the tocopherol group (16/111; 14.4%) than in the placebo group (8/121; 6.6%). The development of retinal hemorrhages correlated strongly with plasma tocopherol levels from three weeks to three months (P less than 0.05). Future studies of tocopherol should be aware of potential bleeding diatheses, and study this prospectively.
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Prolonged oxygen administration in premature infants is the most predictive variable for severe retinopathy of prematurity, after degree of prematurity itself. It was noted that infants receiving prolonged oxygen supplementation are probably hypoxemic relative to their healthy counterparts. Therefore, hypoxemia during recovery from a hyperoxic-induced retinal vascular injury was tested in the kitten model of oxygen-induced retinopathy. Twelve litters were exposed to 80% inspired O2 for 65 hours on day 3, and recovered in room air, 13% or 17% oxygen. The retinas were scored at 4 weeks, and 13% oxygen recovery (PO2 = 39 +/- 18 torr) was found to worsen significantly the retinopathy compared with that in room air-recovered littermates (P less than .01). Hemorrhages occurred more frequently in the retinas from the hypoxemic-recovered kittens. Clinical trials of this hypothesis are indicated in humans.
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Six immature infants were given oral feedings of 10% preservative-free human immune serum globulin ranging from 1 to 8 ml/kg/day. A seventh infant served as a control. Undigested and partially digested IgG was detected in the stools in significant quantities in all but the control infant. This coproantibody retained significant opsonic activity for type III group B streptococci as determined by a chemiluminescence assay, but lost most of its tetanus antibody activity. The newborn infants' enzymatic immaturity or rapid transit time permits the passage of intact IgG or partially digested IgG to pass throughout the gastrointestinal tract.
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A 20-year-old white women with cystic fibrosis who breast-fed her normal infant is described. Extensive breast milk analysis revealed normal sodium and chloride concentrations but elevated total protein and low total fat content; IgG and IgM levels were low to absent. The infant tolerated breast-feeding well, with normal growth and without infections, but the nutritional status of the mother appeared to be adversely affected. This case illustrates that breast-feeding by a mother with cystic fibrosis appears to be feasible but is fraught with difficulties.
Significant systemic toxicity has been observed in kittens daily with 50-1,000 mg/kg/day parenteral vitamin E for 3 weeks. The toxicity was dose-related and resulted in significant mortality at doses over 100-200 mg/kg daily. Local reactions to the injections could be eliminated by using the drugs intravenously or intraarterially as tested in acute and chronic preparation in the rat, rabbit and lamb.