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Biomedical subjects

R M Kliegman

Publications and source records attributed to R M Kliegman.

At least 19 recordsLinked to original sources
PubMed1991

The relationship of neonatal alimentation practices to the occurrence of endemic necrotizing enterocolitis.

Enteric alimentation has been one of several factors implicated in the development of necrotizing enterocolitis (NEC). To examine this relationship further, the alimentation records of 19 patients who developed NEC were each compared with two matched patients controlled for birthweight and time of admission to the intensive care nursery. Parameters compared included total fluids provided, rate of enteral feed volume advancement, milk selection, and medications given. In addition, because there were no marked day-to-day differences between the mean values of most parameters and because we noted a marked fluctuation of formula intake and volume increments, we analyzed the maximum differences between the two groups. Maximum total fluids intake occurred on day 5 of life for the NEC patients and was 180.7 +/- 44 ml/kg. The control group on this same day received 149.7 +/- 35 ml/kg (p less than 0.01). Maximum enteral intake occurred on day 8 for the NEC patients at 124.3 +/- 5.7 ml/kg, whereas the control group had consumed only 83.5 +/- 60 ml/kg (p less than 0.05) on this matched day. The feed increment rate from initiation of feeds to day of maximum feeds was 27.8 +/- 16 ml/kg/day for the NEC patients and 16.8 +/- 11 for the control patients (p less than 0.0005). Furthermore, during the entire study period patients who developed NEC had the greatest 1 day increment compared with the controls (56.7 +/- 19.4 vs 44.6 +/- 26.2 ml/kg, p less than 0.05). Very rapid advancement of enteral feedings and excessive fluid volumes may predispose premature infants to the development of NEC and should be discouraged.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies↗
PubMed1991

Insulin receptor number and binding affinity in newborn dogs.

The insulin resistance in newborn mammals may be caused by a receptor or postreceptor defect. Although liver and umbilical cord blood monocytes have increased numbers of insulin receptors, there is a paucity of information about other neonatal tissues. Glucose disposal takes place primarily in the skeletal muscle; therefore, it is important to evaluate this tissue for an insulin receptor defect. To determine the role of insulin receptors in neonatal insulin resistance, neonatal and adult canine skeletal muscle, heart, and liver were compared for numbers of insulin receptors and their affinity for insulin. Partially purified receptors from four animals in each group were obtained by wheat germ lectin affinity chromatography and used in competition binding studies. Specific binding (mean +/- SE) in the absence of cold insulin was increased in newborn skeletal muscle (9.7 +/- 0.8 versus 4.8 +/- 0.5%, p less than 0.001) and heart (8.1 +/- 1.2 versus 5.5 +/- 0.6%, p less than 0.05). High-affinity insulin receptor number (mean +/- SEM) was increased in newborn skeletal muscle (183 +/- 40 versus 120 +/- 29 pM, p less than 0.002) and heart (264 +/- 94 versus 157 +/- 51 pM, p less than 0.05) as estimated from the X intercept of the Scatchard plot. Using half-maximal binding to estimate affinity, there were no differences between adults and newborns among all tissues studied. High-affinity receptor number and percentage of specific binding were similar for newborn and adult liver tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1991

Rational principles for immunoglobulin prophylaxis and therapy of neonatal infections.

Immunotherapy was a common method of treating infectious diseases in the preantibiotic era. Serotherapy was a popular approach to serious infections and employed hyperimmune globulins harvested from various large animals. Such antisera needed to be administered early in the course of the disease and unfortunately was associated with significant risks of anaphylaxis and serum sickness. Because of the allergic risks associated with animal immunoglobulin preparations, the development of methods to isolate human immunoglobulins heralded a new era in immunotherapy. This article examines the uses of immunotherapy in the treatment of neonatal infections.

Bacterial Infections↗
PubMed1990

Pathology of neonatal necrotizing enterocolitis: a ten-year experience.

We reviewed pathology specimens from 84 patients seen during a 10-year period with neonatal necrotizing enterocolitis, and these findings were correlated with clinical features. Coagulation (ischemic) necrosis, inflammation, and bacterial overgrowth were all present in the intestine of nearly all patients but with individual variability in the severity of these findings. Overall, coagulation necrosis was more severe than any other finding in most infants, indicating the importance of ischemia in the pathophysiology of necrotizing enterocolitis. Reparative tissue changes such as epithelial regeneration, granulation tissue formation, and fibrosis, found in two thirds of cases, suggested ongoing tissue injury of at least several days' duration. Birth weight, Apgar score, age, feeding status, and the presence of respiratory distress syndrome were not correlated with any particular histologic feature. The pathologic changes of necrotizing enterocolitis suggest that its cause is multifactorial, with ischemia, inflammation, bacterial overgrowth, and reparative tissue changes all playing important roles.

Apgar Score↗
PubMed1990

Pharmacokinetics, outcome of treatment, and toxic effects of amphotericin B and 5-fluorocytosine in neonates.

To determine the pharmacokinetics of amphotericin B and 5-fluorocytosine in neonates, we measured serum concentrations at first dose and after 5 days of therapy by high-performance liquid chromatography in 13 neonates (mean birth weight 1.2 +/- 0.8 kg). The dose of amphotericin B was serially increased from 0.1 to 0.5 mg/kg/day in 10 infants but was decreased from 0.8 to 1.0 to 0.5 mg/kg/day in three infants. Amphotericin B concentrations were not detectable in infants receiving 0.1 mg/kg/day. Amphotericin B cerebrospinal fluid concentrations were 40% to 90% of serum values obtained simultaneously. Serum concentrations after oral administration of 5-fluorocytosine (dose 25 to 100 mg/kg/day) were detectable in all infants. We found extreme interindividual variability for the half-life, volume of distribution, and clearance for both drugs. Four infants had minimal elimination for both drugs between doses, a finding that correlates with rises in serum creatinine (greater than 0.4 mg/dl, 40 mumol/L) and blood urea nitrogen (greater than 10 mg/dl, 3.6 mmol/L). We recommend that the dose of amphotericin B given on the first day of treatment be greater than the usual testing dose of 0.1 mg/kg/day. We also recommend an initial 24-hour dosing interval for amphotericin B and 5-fluorocytosine. Serum drug concentrations may need to be monitored in high-risk, low birth weight infants.

Amphotericin B↗
PubMed1990

Clinical pharmacology of imipenem and cilastatin in premature infants during the first week of life.

The first-dose and multidose pharmacokinetics of imipenem and cilastatin were evaluated in 41 premature infants during their first week of life. Premature infants (gestational age, less than or equal to 37 weeks) were assigned to receive 10-, 15-, 20-, or 25-mg/kg doses of imipenem-cilastatin (1:1) as a single- or multiple-dose regimen. A total of 39 infants received a single dose, whereas 18 infants received multiple doses. No differences were observed in pharmacokinetic parameter estimates for either agent relative to the dose administered or infant body weight; thus, the data were pooled. Elimination half-life, steady-state volume of distribution, and body clearance averaged 2.5 h, 0.5 liter/kg, and 2.5 ml/min per kg, respectively, for imipenem and 9.1 h, 0.4 liter/kg, and 0.5 ml/min per kg, respectively, for cilastatin. Similar values for these parameter estimates were observed after multidose administration, although substantial accumulation of cilastatin in serum was observed. A total of 21% of the imipenem and 43% of the cilastatin were excreted unchanged in the urine over a 12-h collection period. Corresponding renal clearances averaged 0.4 and 0.2 ml/min per kg for imipenem and cilastatin, respectively. Substantial differences were observed in the route by which imipenem was cleared from the body compared with data from adult volunteers. These data suggest that infants should receive an imipenem dose of 20 mg/kg administered every 12 h for the treatment of bacterial infections outside the central nervous system.

Cilastatin↗
PubMed1990

Effects of maternal obesity on fasting metabolism in newborn rats.

Maternal obesity is a risk factor for subsequent fasting hypoglycemia in human infants after birth. To investigate further this problem, we employed an animal model of obesity to study neonatal extrauterine metabolic adaptations in pups of obese and lean rats. Female Sprague-Dawley rats were fed a 'cafeteria diet' to induce obesity prior to and during pregnancy. Prior to mating, the cafeteria fed rats were significantly heavier (449 v. 345 g, P less than 0.001) than the controls. Furthermore, weight gain during pregnancy and weight at term were also significantly greater in the obese rats even though they consumed less food during pregnancy. Pup weights and the number of pups per litter were similar between the two groups. Pups born to obese mothers demonstrated hypoglycemia after being fasted for 150 and 180 min when compared with control pups. Hepatic glycogen stores were increased in the fetus of pups born to obese mothers. Glycogen content in pups born to obese mothers declined minimally after birth and remained greater than hepatic glycogen values in control pups throughout the study. In addition to increased fetal storage of glycogen, fetal hepatic triglyceride content was augmented in pups of obese rats. These triglyceride stores declined and were mobilized during fasting after birth. In contrast, hepatic triglyceride content increased after birth among control rats. These results suggest that maternal obesity results in augmented fetal hepatic tissue stores of both glycogen and triglycerides. Hypoglycemia among pups of excessively obese mothers may be due to attenuated mobilization of hepatic glycogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Use of intravenously administered immune globulin to prevent nosocomial sepsis in low birth weight infants: report of a pilot study.

To evaluate the use of intravenously administered immune globulin (IVIG) for prevention of sepsis in preterm infants, we administered IVIG in a protocol designed to maintain a therapeutic serum "target level" of 700 mg/dl. The 200 patients who were eligible for the study (600 to 2000 gm birth weight) were monitored throughout their initial hospitalization. Of these, 115 patients were randomly assigned in a double-blind, controlled trial to treatment and placebo groups. The remaining 85 infants were not randomly assigned to a group, by parental request, but were followed and analyzed separately. In one patient who received IVIG, transient tachycardia and a decrease in blood pressure developed during an infusion; resolution occurred promptly after the infusion was discontinued. No persistent hepatic or renal abnormalities were noted in either the IVIG- or the placebo-treated group. There were seven episodes of sepsis in the placebo group and nine in the group whose parents refused consent to the study. No infant who received IVIG acquired nosocomial sepsis (p less than 0.01). All patients in the placebo group in whom sepsis developed had serum IgG levels less than 400 mg/dl at the time sepsis developed. Serum IgG levels were maintained near 700 mg/dl in patients who received IVIG. These data indicate that administration of sufficient IVIG to maintain target serum IgG levels throughout hospitalization may decrease the incidence of nosocomial sepsis in preterm infants.

Cross Infection↗
PubMed1989

Alterations of fasting glucose and fat metabolism in intrauterine growth-retarded newborn dogs.

Maternal nutritional deprivation resulted in reduced fetal weight at term gestation (251 +/- 7 vs. 277 +/- 7 g, P less than 0.01) in newborn dogs. Growth-retarded pups developed lower blood glucose levels after 3, 6, and 9 h of neonatal fasting, reduced plasma levels of free fatty acids (FFA) at 9 and 24 h, and lower ketone bodies at 24 h compared with age-matched newborn control pups. Systemic rates of palmitate and alanine turnover were not affected, but systemic glucose turnover was reduced for 3-9 h after birth. The rate of alanine incorporation into glucose from 3 to 9 h was also reduced in growth-retarded pups compared with timed controls. Paradoxically, the rate of incorporation of palmitate into triglycerides was augmented in the smaller growth-retarded pups. Hepatic glycogen content was reduced at every time in the study among growth-retarded pups, whereas the rates of glycogenolysis between birth and 24 h were equivalent in the two pup groups. In contrast, hepatic triglyceride levels were augmented throughout the study in pups with growth retardation. Maternal starvation and lower glucose levels resulted in a lower hepatic energy charge, and augmented cytoplasmic and mitochondrial NAD-to-NADH ratios in intrauterine growth-retarded pups. These data suggest that intrauterine growth retardation in dogs results in fasting neonatal hypoglycemia that is due in part to reduced systemic glucose production. We speculate that reduced rates of gluconeogenesis from alanine and reduced oxidation of alternate fuels such as FFA contribute to hypoglycemia. FFA recycling to triglyceride synthesis rather than oxidative pathways may contribute to the observed reduction of circulating glucose levels.

Aging↗
PubMed1989

Partitioning and extraction of glucose regulates cerebral glucose utilization in newborn dogs.

We investigated the amount of fasting steady-state systemic glucose production utilized by the neonatal canine cerebral cortex. The relationship of systemic glucose production and cerebral glucose utilization were analyzed as functions of cerebral blood flow, cerebral oxygen uptake, and indirect measures of alternate fuel utilization. Fasting arterial blood glucose was 3.36 mM and glucose production was 49.6 mumol/kg/min. Average cerebral blood flow was 0.83 ml/g/min, and cerebral glucose uptake was 0.60 +/- 0.15 mumol/g/min. 36.6% of systemic glucose production was utilized by the cerebral cortex. There were no correlations between systemic glucose production, cerebral blood flow, or cerebral glucose uptake with blood glucose concentration. Furthermore, total cerebral glucose uptake was static across a wide range of glucose levels. Nonetheless, the percent of glucose production used by the brain was an inverse function of systemic glucose production (r = -0.71, p less than 0.001). The cerebral extraction of glucose (27.6 +/- 4.1%) decreased as a function of increasing blood glucose levels (r = -0.51, p less than 0.05), while brain uptake index correlated with increasing systemic glucose production (r = 0.61, p less than 0.02). We can conclude that the canine neonatal cerebral cortex may utilize only 37% of systemic glucose production. At low rates of glucose turnover, a larger proportion of systemic glucose production is allotted to the brain. Mechanisms that may regulate total cerebral glucose influx may be glucose permeability, or the increased extraction of glucose at lower blood glucose levels.

Animals↗
PubMed1989

Assessment of insulin resistance in newborn beagles with the euglycemic hyperinsulinemic clamp.

The developmental response to the euglycemic hyperinsulinemic clamp was assessed among newborn and adult beagles to investigate neonatal insulin resistance. Both neonatal dogs and adults were clamped at euglycemic blood glucose concentrations while receiving insulin at a rate of 3.75, 15, 30, 60, 75 or 100 mU/kg/min to generate a dose-response curve. Blood glucose levels, plasma insulin concentrations and glucose turnover rates during the basal preclamp fasting period were similar in pups and adult dogs. During the clamp period, blood glucose levels were equivalent to the preclamp period whereas plasma insulin concentrations increased. Total glucose utilization increased from 28.7 +/- 18 to a plateau level of 114 +/- 52.3 mumol/kg/min in adult dogs and from 30.9 +/- 10.9 to 53.9 +/- 28.9 mumol/kg/min in newborn dogs. Suppression of endogenous glucose production during euglycemic hyperinsulinemia was close to 100% among adult dogs, whereas in the newborn pups, endogenous glucose production was suppressed 80%. To determine if the newborn was unable to increase glucose uptake because of a saturation effect on glucose utilization independent of insulin, another group of adult and newborn dogs received a hyperglycemic hyperinsulinemic clamp. In response to the hyperglycemic clamp, adults demonstrated an increase of glucose utilization to 261 +/- 83, and newborn dogs increased utilization to 227 +/- 76 mumol/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Severity of necrotizing enterocolitis: influence on outcome at 2 years of age.

The long-term outcome of very low birth weight (VLBW) infants with necrotizing enterocolitis has been reported to be similar to that of other VLBW infants. To examine the influence of disease severity on outcome, the growth and neurodevelopment of survivors of necrotizing enterocolitis were evaluated when the babies were 20 months' corrected age. Between 1975 and 1983, 1506 VLBW infants were admitted to the hospital, and necrotizing enterocolitis developed in 84 (5.6%). Forty infants (48%) survived to be 20 months' corrected age, and complete follow-up data were available for 36. Survivors were classified by modified Bell's criteria into four groups by increasing severity of disease; 13 had mild necrotizing enterocolitis (stage IIA, IIB), and 23 had severe necrotizing enterocolitis (stage IIIA, IIIB). The 36 survivors were compared with 766 surviving VLBW infants without necrotizing enterocolitis. There were no perinatal or socioeconomic differences between groups. Compared with infants with stage II necrotizing enterocolitis at 20 months, infants with stage III necrotizing enterocolitis had a higher rate of subnormal body weight (39% vs 15%) and subnormal head circumference (30% vs 0%). Thirty-three percent of necrotizing enterocolitis survivors had significant neurodevelopmental impairment; the majority of impaired infants (10 of 12) were survivors of stage III necrotizing enterocolitis. These findings highlight the importance of continued evaluations for medical and neurodevelopmental sequelae.

Child Development↗