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R H Perelman

Publications and source records attributed to R H Perelman.

13 recordsLinked to original sources
PubMed1996

Effects of maternal dexamethasone therapy on fetal lung development in the rhesus monkey.

A large body of evidence demonstrates that antenatal glucocorticoids can accelerate fetal lung maturation. The purpose of this study was to delineate the optimal dose of dexamethasone and to determine whether a single- or multiple-injection regimen of the same total dexamethasone dosage was more effective in accelerating pulmonary development. Pregnant rhesus monkeys were injected with varying doses of dexamethasone or vehicle as either a single-bolus injection or as four separate injections, each spaced 12 hours apart. All maternal treatments were begun exactly 72 hours prior to delivery, and all fetuses were delivered by cesarean section at 135 +/- 1 days gestation. When a single injection of dexamethasone was used, fetal liver weight increased in a dose-related fashion. Fetal and maternal cortisol and fetal blood glucose concentrations were also influenced by increasing dexamethasone dosages. Fetal pulmonary phospholipids, however, were unchanged at all steroid doses examined. Multiple injections of dexamethasone generally produced more pronounced effects, even though the total dexamethasone dose remained the same. Thus, liver weight and fetal and maternal cortisol, glucose, and insulin levels were significantly influenced by the multiple administration of dexamethasone. In addition, total lung phosphatidylcholine, surfactant phosphatidylcholine, the surfactant-phosphatidylcholine-to-total-phosphatidylcholine ratio, and the surfactant-disaturated-phosphatidylcholine-to-total-lung-disaturated- phosphatidylcholine ratio were elevated after the multiple-injection regimen. A total dose of 0.5 mg dexamethasone/kg maternal body weight given in four separate injections appeared to produce the most beneficial results. These data suggest that low-dose, antenatal glucocorticoid treatment can effectively accelerate the biochemical maturation of the fetal lung.

Animals↗
PubMed1986

Fetal lung development in male and female nonhuman primates.

Indices of lung maturation were assessed in 58 rhesus fetuses at five gestational ages during the last trimester of nonhuman primate pregnancy to determine whether fetal sex influences lung maturation. In addition to analysis of whole lung phospholipids, glycogen, protein, DNA, and pressure-volume curves surfactant fraction phosphatidylcholine (PC) was quantitated following isolation by sucrose gradient centrifugation and a combination of predictors were assessed by all possible subsets regression to attain a composite "maturity index." For the total population, there was a uniform progression in physical growth characteristics, lung destensibility and stability and phospholipids with advancing gestation. The quantitative change in surfactant fraction PC concentration for both sexes was considerably greater than that observed for whole lung PC between 135 days gestation and term. Further, the increase in surfactant PC occurred in association with improving lung destensibility and deflation stability prior to maximum changes in the whole lung PC or disaturated PC concentration. There were no statistically discernible differences in biochemical or physiological assessment between sexes at any gestational age. These data in nonhuman primates suggest that documented differences in survival from the respiratory distress syndrome between males and females do not result from a discordance in lung maturation as a function of time throughout the last trimester of gestation.

Animals↗
PubMed1986

Discordance between male and female deaths due to the respiratory distress syndrome.

General neonatal mortality statistics and those for the respiratory distress syndrome (RDS) were examined for the State of Wisconsin from 1979 through 1982. The objectives were to ascertain whether there are differences in total neonatal mortality related to sex and birth weight, to determine the veracity of reported gender differences in deaths due to RDS, and to assess the contribution of other risk factors for neonatal mortality to overall and sex-specific deaths occurring secondary to RDS. Additionally, a prospective analysis was performed at one perinatal center during a 5-year period in attempts to determine whether gender remained a significant factor in deaths due to RDS after adjusting for incidence. Overall, the most frequent diagnoses in those who died were RDS (15.6%), deaths due to complications of pregnancy (8%), immaturity (4.2%), and asphyxia (3.4%). The majority of fatalities for both sexes occur in neonates weighing less than 1 kg and the percentage of deaths attributable to RDS is greatest between 1 and 1.5 kg. The difference between sexes is also maximal in the latter weight group. Deaths secondary to RDS are greater for males regardless of Apgar score at one and five minutes, mode of delivery, maternal age, or ancillary diagnosis. These data suggest that deaths secondary to RDS are consistently greater in male neonates and that delivery within a limited "window" of time during gestation increases male susceptibility to fatal RDS.

Apgar Score↗
PubMed1985

Developmental aspects of lung lipids.

From this review, it is evident that multiple maternal/fetal endogenous or completely exogenous factors have been associated with the complex process regulating fetal lung development. Recent in vitro experiments with human fetal lung explants are especially noteworthy and may establish a perspective for future research. Snyder et al (108) and Medelson et al (74) have found that lung explants from 16-22-week abortuses show differentiated type II cells and augmented PC synthesis within 4 days of culture, rather than the minimum 10- to 15-week period expected in utero. Such a phenomenon is reminiscent of the usual time for clinical recovery from uncomplicated RDS (34). Thus, although expression of the genes influencing lung surfactant phospholipid synthesis and related biochemical processes normally occurs relatively late in gestation, the potential for biochemical differentiation is clearly present in earlier stages. It appears then that the "programming" of the fetal lung for maturation is not absolute but may be altered under certain influences. Whether the advent of lung biochemical maturation occurs as a result of release from inhibition, as the human lung explant data imply, or occurs in response to stimuli, as suggested by exogenous corticosteroid effects, remains to be clarified and is a very challenging scientific problem. It will also be of great interest to define further other biochemical regulators, such as fibroblast pneumocyte factor, that may play an important role in fetal lung maturation.

Androgens↗
PubMed1984

Changes in food intake during menstrual cycles and pregnancy of normal and diabetic rhesus monkeys.

Food intake of control and streptozotocin-diabetic rhesus monkeys was measured during menstrual cycles and pregnancy. Intake of control monkeys was lower at the time of ovulation than during other phases of the menstrual cycle. Intake of control monkeys was also low during most of pregnancy, but this was accompanied by normal fetal growth and net maternal weight gain. Diabetic monkeys ate more than controls in all conditions and their intake did not vary reliably according to reproductive status. It is suggested that (1) oestrogen normally inhibits food intake during menstrual cycles and pregnancy, (2) food energy is utilized more efficiently during pregnancy than during non-pregnant states, and (3) the influence of oestrogen on food intake is either attenuated by insulinopenia or is obscured by the hyperphagia typically exhibited by the diabetic monkeys.

Animals↗
PubMed1984

Relationship between the severity of experimental diabetes and altered lung phospholipid metabolism.

Glucose intolerance was induced in rats by iv infusion of streptozotocin (STZ) in doses of 30, 40, 50, and 100 mg/kg. Serum glucose concentrations were elevated versus controls and weight gains were reduced in a dose-dependent fashion up to 50 mg/kg. Urine outputs and blood urea nitrogen (BUN) values were higher than control values in the animals treated with 40 and 50 mg/kg and serum albumin concentrations were decreased after infusion with 50 mg STZ/kg. Lung phosphatidylcholine (PC) concentrations and dry-to-wet weight ratios were unchanged by STZ treatment, while lung protein and disaturated phosphatidylcholine (DSPC) concentrations were depressed in the 50-mg/kg group. Animals surviving treatment with 100 mg/kg demonstrated increased fasting blood glucose levels, BUN values, and 48-hr urine outputs, and decreased lung protein levels. However, these alterations were less than those found in the 50-mg/kg animals. Pulmonary concentrations of PC, DSPC, and lung dry-to-wet weight ratios were unchanged. It was found advantageous to express the results relative to fasting blood glucose levels. This demonstrated that urine output and BUN values increased and weight gain decreased with rising glucose concentrations, but serum albumin decreased only in moderate and severe hyperglycemia. Fasting glucose concentrations greater than 400 mg/dl were associated with reduced lung DSPC and protein levels, while pulmonary PC and dry-to-wet weight ratios demonstrated no change with increasing hyperglycemia.

Animals↗
PubMed1984

Saturated phospholipids in amniotic fluid of normal and diabetic pregnancies.

To assess fetal lung maturation in normal and diabetic pregnancies, the authors studied two phospholipids that are more specific for pulmonary surfactant than total phosphatidylcholine (lecithin), namely saturated phosphatidylcholine and phosphatidylglycerol. Results indicated that saturated phosphatidylcholine concentrations normally increase from 10 to 20 nmol/mL before 34 weeks to as high as 150 nmol/mL at term. Although the absolute concentration of saturated phosphatidylcholine could not be used to reliably identify pregnancies leading to respiratory distress syndrome, a saturated phosphatidylcholine level greater than 50% of total phosphatidylcholine was associated with satisfactory neonatal pulmonary function, whereas RDS often occurred in premature infants when less than half the phosphatidylcholine was saturated. Carefully regulated diabetic pregnancies at 36 to 42 weeks of gestation were not different from matched control subjects with respect to total phosphatidylcholine, its ratio to sphingomyelin, saturated phosphatidylcholine, or phosphatidylglycerol. Respiratory distress syndrome did not occur in any infant of the 40 diabetic mothers studied, nor were there any congenital anomalies or cases of symptomatic hypoglycemia.

Amniotic Fluid↗
PubMed1983

The infant of the diabetic mother. Pathophysiology and management.

Fetal complications such as macrosomia, hypoglycemia, respiratory distress, and congenital anomalies are associated with the diabetic pregnancy. However, strict control of maternal glucose during pregnancy, labor, and delivery has been shown to favorably influence the perinatal outcome.

Animals↗
PubMed1982

Comparative analysis of four methods for rapid glucose determination in neonates.

As an important aspect of newborn care, the rapid assessment of glucose homeostasis is often accomplished by a glucose oxidase-peroxidase chromagen test strip method, either alone or with a reflectance colorimeter. The precision of these techniques has been established, but few studies have determined accuracy in an intensive care setting. We performed the following study. During the time of routine heelstick blood sampling, the nurses collected 90 complete study sets for glucose analysis from 43 neonates. Dextrostix, Ames Meter, Chemstrip bG, and Stat Tek Meter determinations were performed according to manufacturers' instructions. Concurrent determination of blood glucose level by a glucose analyzer (Beckman) served as a standard for comparison. There was no significant difference in estimation of true blood glucose concentration among the rapid methods tested. The marked variability of results suggests only modest accuracy in estimating whole blood glucose concentration when employed in the routine neonatal clinical setting. These data indicate that the results from rapid blood glucose estimation techniques require confirmation by conventional laboratory methods prior to therapeutic intervention.

Blood Glucose↗
PubMed1982

Biochemical and physiological development of fetal rhesus lung.

Study of 17 fetal rhesus monkeys (Macaca mulatta) revealed a sequential rise in lung phosphatidylcholine (PC) concentration due to elevations in both disaturated (DSPC) and unsaturated constituents. The % DSPC in lung tissue clinical abruptly at 145 days of gestation prior to significant increases in PC or DSPC concentration but in association with improved lung deflation stability (% V10). This suggests that the DSPC-to-PC ratio may be a sensitive biochemical indicator of surfactant phospholipid production in lung parenchyma. Phosphatidyl-glycerol content did not increase significantly until after 155 days gestation, which was coincident with maximizing pulmonary distensibility (V max). Declining levels of phosphatidylethanolamine and sphingomyelin in lung tissue at 162 days support the hypothesis that preferential synthesis of PC occurs during late gestation. A serial decline in lung glycogen content with advancing gestation may reflect glycogen utilization as a substrate for lung phospholipid production. Comparison of biochemical and physiological data confirms the impression that discordances occur among lung maturational events. Lastly, a relationship between rising fetal blood cortisol levels and indices of fetal lung development was not demonstrated.

Animals↗
PubMed1982

Analysis of causes of neonatal death in the United States with specific emphasis on fatal hyaline membrane disease.

National mortality statistics for hyaline membrane disease (HMD) and the respiratory distress syndrome (RDS) and other major causalities were examined in this study for the years 1968 to 1978. A progressive reduction in total neonatal deaths began in 1971 such that only 56% as many newborn deaths occurred in 1978 as in 1968 (31,618 vs 66,456). In each of the 11 years surveyed, the majority of deaths occurred during the first four days of life, with more than half of the infants dying before 48 hours of age. HMD/RDS was the leading cause of death during nine of the 11 years analyzed, accounting for an average 19.5% of neonatal fatalities. Deaths associated with HMD/RDS increased for 1968 to 1971 plateaved and progressively decreased in the ensuing years between 1974 and 1978. Thus, the percent of all neonatal deaths attributable to HMD/RDS increased from 14.7% in 1968 to a maximum of 21.3% in 1974, before declining to 17.5% in 1978. The average contribution of other major causes of death to overall neonatal mortality were: perinatal asphyxia, 13.4%; immaturity, 13.4%; and complications of pregnancy, 11.1%. These data indicate that: (1) despite the declining incidence of fatal HMD/RDS the disorder accounted for an increasing percent of total deaths through the later part of the 11-year period; (2) prevention and/or improved management of asphyxia made the most significant (29%) contribution to reduced neonatal mortality; (3) less change occurred in fatal complications of pregnancy, implying a continuing need for improved maternal/fetal care. Comparing national mortality statistics with those of Wisconsin suggests that further reduction in HMD/RDS death rates should be possible and could have a marked influence on national neonatal mortality statistics.

Asphyxia Neonatorum↗
PubMedDate not supplied

An experimental model for studies of fetal maldevelopment in the diabetic pregnancy.

Values for plasma glucose and serum insulin in fasting conditions and glucose disappearance rates during an intravenous glucose tolerance test were obtained from 54 adult female rhesus monkeys. Some of these animals were subsequently made diabetic by intravenous infusion of streptozotocin (STZ). A single treatment with STZ (47.5 mg/kg) was consistently effective in ten animals for inducing severe hyperglycemia and diminished insulin response to glucose infusion. One of four additional animals became significantly glucose intolerant after a single treatment with STZ (30 mg/kg) and three of three animals became glucose intolerant after two treatments at this dosage. The greater effectiveness of STZ for inducing severe diabetes mellitus in the present study compared with previous investigations using nonhuman primates was attributed to rapid mixing and infusion of STZ with proven diabetogenic activity. Severely diabetic animals have been successfully maintained by daily subcutaneous injections of a combination of NPH and regular insulin. Fetuses of monkeys treated with STZ before conception were hyperglycemic and hyperinsulinemic, and four of these six fetuses were large for gestational age. Preliminary data suggest that fetal lung glycogen concentrations were elevated in these animals compared with controls at 145 days of gestation. It is concluded that the rhesus monkey treated with STZ before pregnancy represents a useful model for studies of fetal maldevelopment in pregnancies complicated by varying degrees of maternal diabetes.

Animals↗