Platelet-activating factor concentration in the stool of human newborns: effects of enteral feeding and neonatal necrotizing enterocolitis

Epidemiologic studies have identified enteral feedings as a risk factor for necrotizing enterocolitis (NEC). Enteral feedings provide the substrate for colonization of the newborn gut with gram-negative bacteria with endotoxin production, which may trigger the production of endogenous inflammatory mediators, including platelet-activating factor (PAF). In this prospective study, we examined the effect of enteral feeding on PAF concentration in the stool of preterm and full-term human newborns. The concentration of PAF levels in stool was measured at the following times: at passage of first meconium, within 24 h prior to the onset of feedings, at the 3rd and 14th day of feeding and at any time confirmed NEC developed. Stool samples also were analyzed for levels of acetylhydrolase, the PAF breakdown enzyme. Stool PAF concentration rose significantly following the start of enteral feedings. The mean PAF concentration for day 14 samples was significantly higher than the mean concentration of meconium samples (4.90 +/- 1.03 vs. 1.81 +/- 0.38 ng/g, p < 0.05) and day 0 samples (4.90 +/- 1.03 vs. 1.79 +/- 0.39 ng/g, p < 0.05). For the 7 patients diagnosed with definite NEC, the mean stool PAF concentration was 12.42 +/- 0.77 ng/g, significantly elevated compared to the mean PAF levels in stool from healthy infants at all sampling times (p < 0.01). There was no significant change in acetylhydrolase activity at any of the sampling times. Stool PAF concentration increases with the provision of enteral feedings and rises further with the development of NEC. Since stool acetylhydrolase activity remained unchanged, we speculate the increase of PAF in stool likely represents increased PAF production at the local level following the provision of enteral feedings or the development of neonatal necrotizing enterocolitis.     

Endotoxin and hypoxia-induced intestinal necrosis in rats: the role of platelet activating factor.

We have previously shown that intravascular platelet activating factor (PAF) causes ischemic bowel necrosis in rats morphologically similar to neonatal necrotizing enterocolitis (NEC). Because endotoxin (LPS) and hypoxia are risk factors for NEC, we studied their effect on PAF metabolism and the development of intestinal injury. Young male Sprague-Dawley rats were anesthetized with pentobarbital and divided into six experimental groups: 1) control, 2) LPS alone (2 mg/kg), 3) hypoxia alone (5% O2), 4) LPS+hypoxia, 5) WEB 2086 (PAF antagonist)+LPS+hypoxia, and 6) SRI 63-441 (PAF antagonist)+LPS+hypoxia. Evaluations included blood pressure recording, superior mesenteric artery blood flow, arterial blood gas, white blood cell count, hematocrit, plasma PAF, plasma acetylhydrolase, plasma tumor necrosis factor, intestinal perfusion, and intestinal injury at 3 h. We found that LPS+hypoxia synergistically contributed to hypotension (mean blood pressure 27 +/- 5.6% baseline versus 101 +/- 3.9% control), metabolic acidosis (pH 7.05, base deficit 24 mEq/L), hemoconcentration, decreased superior mesenteric artery blood flow (2.2 +/- 0.3 mL/min versus 5.8 +/- 0.2 mL/min control), and intestinal injury. The morbidities resulting from LPS+hypoxia were partially or completely prevented by PAF antagonists. In addition, animals treated with LPS+hypoxia had neutropenia, elevated plasma acetylhydrolase, and elevated plasma TNF. These results suggest that endogenous PAF may contribute to LPS+hypoxia-induced intestinal hypoperfusion and necrosis.     

Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis

We evaluated the response of preterm fetuses to maternal intravenous injection of 400 micrograms of thyrotropin releasing hormone (TRH) between 30 minutes and 5 hours before delivery (n = 12). An additional seven mothers received saline solution and served as control subjects. There were no statistically significant differences in gestational age, birth weight, or Apgar scores between groups. At delivery, concentrations of maternal thyrotropin were elevated in the TRH group compared with the control group (12.0 +/- 1.6 vs 5.6 +/- 0.5 mU/L; p less than 0.005); however, maternal triiodothyronine (T3) values remained unchanged. Significant elevations of fetal thyrotropin and T3 were observed after maternal administration of TRH compared with control subjects (45.8 +/- 7.7 vs 8.4 +/- 0.9 mU/L (p less than 0.002) and 1.3 +/- 0.07 vs 0.7 +/- 0.04 nmol/L or 87 +/- 5 vs 49 +/- 3 ng/dl (p less than 0.001), respectively). Fetal thyroxine (T4) and prolactin values were also elevated after exposure to TRH (135 +/- 5 vs 86 +/- 10 nmol/L or 10.5 +/- 0.4 vs 6.7 +/- 0.8 micrograms/dl (p less than 0.001) and 212 +/- 31 vs 105 +/- 28 micrograms/L (p less than 0.05), respectively). Two hours after birth, a significant increase in T3 but not T4 levels was observed in both groups of infants. These data indicate that fetal exposure to a single dose of TRH via maternal administration of this hormone results in marked stimulation of the preterm fetal pituitary-thyroid axis, as in the fetus at term, and that this treatment does not inhibit the early postnatal surge of T3.     

Acute polycythemia increases the disappearance rate of clottable fibrinogen in the newborn dog

To explore the pathophysiology of the necrotizing enterocolitis caused by polycythemia in the newborn dog, the effect of acute polycythemia on fibrinogen disappearance rate was studied in 38 puppies (3-14 days). All pups received an exchange transfusion removing 65 ml/kg of blood and transfusing 85 ml/kg of either whole blood (control, resulting hematocrit = 37), or packed red blood cells (polycythemia, resulting hematocrit = 68). Necrotizing enterocolitis was found in 15 of 19 polycythemic and four of 19 control pups (p less than 0.01). 125I fibrinogen and Evan's blue (an albumin marker) were injected 2 h after transfusion and the concentration of clottable labeled fibrinogen and albumin tracer were measured at 1/2 and 2 h after injection. The fraction of the tracer that disappeared over the 1 1/2-h period was calculated. In the polycythemic group 45 +/- 18 SD% of the clottable fibrinogen disappeared versus only 28 +/- 15% in the control group (p less than 0.01). In the polycythemic group 36 +/- 21% of the albumin tracer disappeared versus 31 +/- 12% in the control group (NS). Thus polycythemia in the newborn dog is associated with an increased disappearance rate of clottable fibrinogen not associated with a general increase in protein disappearance rate. Thus an intravascular coagulopathy is evident in the polycythemic animals. Whether this coagulopathy is the cause of the necrotizing enterocolitis or is secondary to the necrotizing enterocolitis seen in this animal model cannot be determined from this experiment.     

Reduced bone mineral density and increased bone turnover in Prader-Willi syndrome compared with controls matched for sex and body mass index--a cross-sectional study

OBJECTIVES: To study bone mineral status, body composition, and biochemical markers of bone turnover in Prader-Willi syndrome (PWS). STUDY DESIGN: Eight subjects with PWS (three males, five females; mean age, 24 years [range 16-41]) were included. Each subject was compared with an age-, sex- and body mass index-matched control randomly drawn from the background population. Bone mineral density (BMD), lean body mass, and fat mass were measured. Plasma PINP, PIIINP, osteocalcin, total alkaline phosphatase, bone-specific alkaline phosphatase, C-terminal telopeptide of type I collagen, and urine cross-linked N-terminal telopeptide of type I collagen were measured as biochemical markers of bone and collagen turnover. RESULTS: The PWS patients had significantly lower whole-body BMD (mean +/- SD, 1.020 +/- 0.041 vs 1.237 +/- 0.118 g/cm(2); 2p <.01) than controls due to lower bone mineral content (BMC: 2291 +/- 607 vs 2825 +/- 409 g; 2p=.02). Resorptive and formative bone markers were significantly elevated in patients compared with controls. Plasma testosterone was low in male patients (3.50 +/- 4.97 vs 19.2 +/- 8.78 nmol/L, 2p=.05), whereas no difference in plasma estradiol was present. CONCLUSIONS: The patients had a low BMD due to a high bone turnover. This high turnover was probably linked to sex steroid deficiency.     

Effect of polyunsaturated fatty acid (PUFA) supplementation on intestinal inflammation and necrotizing enterocolitis (NEC) in a neonatal rat model

Inasmuch as long-chain polyunsaturated fatty acids (PUFA, metabolites of the essential n-3 and n-6 fatty acids) are known to modulate inflammation, we hypothesized that supplementation of formula with these compounds would prevent necrotizing enterocolitis (NEC) and intestinal inflammation in our neonatal rat model. Newborn rats were stressed with asphyxia and formula feeding, and randomly assigned to control formula, control with PUFA supplementation, and PUFA with nucleotides. Animals were followed for 72--96 h and assessed for death, gross and histologic NEC, intestinal apoptosis, endotoxemia, and intestinal mRNA synthesis of phospholipase A(2)-II (rate-limiting enzyme for platelet activating factor production), platelet activating factor receptor, and inducible nitric oxide synthase. We found that PUFA reduced the incidence of death and NEC compared with the other groups (NEC 8 of 24 versus 17 of 24 control and 13 of 23 PUFA + nucleotides, p < 0.05). Furthermore, PUFA reduced plasma endotoxemia at 48 h (25 +/- 4 EU/mL versus 276 +/- 39 EU/mL in control and 170 +/- 28 EU/mL in PUFA + nucleotide), intestinal phospholipase A(2)-II expression at 24 h, and platelet activating factor receptor expression at 48 h. Formula supplementation had no effect on apoptosis of intestinal epithelium or intestinal inducible nitric oxide synthase expression. Addition of nucleotides with PUFA abrogated the beneficial effects of PUFA on intestinal inflammation. We conclude that PUFA reduces the incidence of NEC and intestinal inflammation in a neonatal rat model.     

Effect of early low-volume enteral substrate on subsequent feeding tolerance in very low birth weight infants

To determine the effect of small enteral feedings on small bowel function, 46 infants with birth weight less than 1500 g, selected on the basis of risk factors for feeding intolerance, were assigned randomly to one of two feeding groups. Group 1 received low-volume enteral feeds (12 ml/kg/day) in addition to parenteral alimentation for 10 days beginning on day 8 of life; group 2 received parenteral alimentation alone until day 18 of life. After this trial period feedings were increased by 15 ml/kg/day in all infants. Four infants (9%) developed necrotizing enterocolitis (one prior to any feeds, two in group 1, and one in group 2); two others were dropped from the study for reasons unrelated to feeding. The remaining 18 infants in group 1 had improved feeding tolerance compared with the 22 in group 2, as manifested by fewer days that gastric residuum totalled more than 10% of feedings (1.3 +/- 0.5 days vs 3.2 +/- 0.6 days, respectively, p less than 0.05) and fewer days that feedings were discontinued because of feeding intolerance (2.7 +/- 0.8 days vs 5.5 +/- 0.9 days, respectively, p less than 0.05). Consequently, 17 of 18 (94%) infants who had received the early low-volume enteral feedings achieved an enteral intake of 120 kcal/kg/day by 6 weeks of life, whereas only 14 of 22 (64%) infants in the delayed feeding group reached this intake (p less than 0.05). Peak total serum bilirubin concentrations were comparable in the two groups. The initiation of hypocaloric enteral substrate as an adjunct to parenteral nutrition improved subsequent feeding tolerance in sick infants with very low birth weight.     

Prevention of neonatal necrotizing enterocolitis

Small premature infants are often hypochlorhydric, and frequently their stomachs are colonized by enteric, gram-negative bacteria. We tested a hypothesis that gastric pH affected the colonization of the stomach with enteric bacteria and that this colonization was causally related to the risk or severity of necrotizing enterocolitis. A prospective, double-blind study was conducted that compared a group of infants supplemented with 0.01-0.02 ml of 1 N HCl/ml of milk to a group with a similar supplement of water. Gastric pH, gastric enteric bacteria counts, and the incidence and severity of necrotizing enterocolitis were monitored. The median gastric pH of the HCl-supplemented group was lower (3.0) than controls (4.0) throughout the study (p less than 0.001). The gastric enteric bacterial colonization rate and the quantitative bacterial counts were strongly correlated with gastric pH over 4 (p less than 0.001). Somatic growth rates in infants in the HCl-supplemented group were equal to, or exceeded, those in the control group. There was 1 case of necrotizing enterocolitis among the 34 infants in the HCl-supplemented group and 8 cases among the 34 in the control group (p = 0.02). It appears that acidifying the feedings of small premature infants to a pH low enough to inhibit bacterial proliferation in the stomach significantly lowers the risk of necrotizing enterocolitis.     

Pharmacokinetics of intravenous clindamycin in newborn infants

We studied 12 newborn infants (gestational ages 26-39 wk [mean +/- SD, 30.6 +/- 4.7]; birth weight 640-2700 g, [mean, 1,322 +/- 688]; postnatal age 1-24 days [mean, 9.6 +/- 8.5]) who received clindamycin phosphate for suspected or proven necrotizing enterocolitis (ten patients) or suspected anaerobic septicemia (two patients) in doses of 3.2-11 mg/kg every six hours. Range of mean serum concentration of clindamycin at steady state was between 12.7 and 40 micrograms/ml (therapeutic range = 2-10 micrograms/ml). High concentrations could be attributed to elimination T1/2 (6.3 +/- 2.1 hr) 100% longer than in older children or adults. Clindamycin clearance (61.6 +/- 31.6 hr ml/kg/hr) was lower than in older children or adults. Because of the observed prolongation in T1/2 and correspondingly lower clearance, the IV dose of clindamycin in newborn infants should be reduced to 15-20 mg/kg/day given in four daily doses.     

Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: implications for early recognition and therapy

AIM: The mechanism of pulmonary oedema, a life-threatening manifestation of enterovirus 71 (EV71) encephalitis, is unclear. Our aim was to assess the relationship of proinflammatory cytokines to EV71-related pulmonary oedema. METHODS: Proinflammatory responses in 33 EV71 patients with various complications and 21 normal healthy children were measured using an enzyme-linked immunosorbent assay. RESULTS: EV71 patients with both encephalitis and pulmonary oedema were found to have much higher levels of blood interleukin-6 (IL-6) (947 +/- 1239 vs 4.9 +/- 3.1 pg/ml, p = 0.0003), tumour necrosis factor-alpha (TNF-alpha) (22.4 +/- 29.5 vs 5.3 +/- 1.0 pg/ml, p = 0.0035), interleukin Ibeta (IL-1beta) (48.4 +/- 85.2 vs 4.9 +/- 10.1 pg/ml, p = 0.01), white blood cell count (28.3 +/- 7.6 vs 15.5 +/- 6.8 10(9)/L, p > or = 0.0001) and blood glucose (501 +/- 186 vs 165 +/- 117 mg/dL, p = 0.0009) than patients with EV71 encephalitis alone. In fact, the cytokine levels in patients with encephalitis only or in those without complications were not significantly different from the levels found in normal children. The sensitivity, specificity, positive and negative predictive values of IL-6 > 70 pg/ml for EV71 encephalitis with pulmonary oedema were all 100%. CONCLUSION: Patients with EV71-related encephalitis combined with pulmonary oedema were found to have significantly elevated levels of proinflammatory cytokines and the best predictor for this complicated condition was found to be the level of serum IL-6.     

Genetic variants of the tumour necrosis factor-alpha promoter gene do not influence the development of necrotizing enterocolitis

Previous studies indicated that elevated tumour necrosis factor-alpha (TNF-alpha) levels may play a role in the development of necrotizing enterocolitis (NEC). The A(-308) and A(-238) variants of the promoter region of the TNF-alpha gene are reportedly associated with altered TNF-alpha production. The aim of our study was to determine the impact of these gene polymorphisms on the development and course of NEC in very-low-birthweight (VLBW) infants. Dried blood samples from 46 VLBW neonates with NEC were analysed using the method of restriction fragment length polymorphism. Samples from 90 VLBW neonates without NEC were used as controls. The prevalence of alleles with guanine-adenine transition in the -308 and -238 positions was the same in NEC and control subjects (12% vs 10% and 3% vs 4%, respectively). CONCLUSION: The investigated genetic variants of the TNF-alpha gene promoter region have no influence on the risk and course of NEC in VLBW infants.     

Plasma cytokine levels in necrotizing enterocolitis

Plasma concentrations of tumour necrosis factor (TNF) and interleukin-6 (IL-6) were measured by ELISA in samples taken from 24 infants with necrotizing enterocolitis (NEC) between 0 and 306 h from diagnosis. TNF was detected (>10pg/ml) in 71% samples with a mean of 48pg/ml (95% CI 42 to 55 pg/ml) and did not vary with either time from diagnosis or severity of disease. IL-6 was raised during the first 48 h with a significant difference between stage II (mean 127 pg/ml, 95% CI 10 to 329 pg/ml) and stage HI (mean 3127 pg/ml, 95% CI 1809 to 4445 pg/ml, p = 0.001). Postoperative plasma IL-6 concentration fell to similar levels seen in stage II (mean 150 pg/ml, 95% CI 37 to 283 pg/ ml, p = 0.79). We conclude that plasma concentration of IL-6 rather than TNF reflects the clinical severity of necrotizing enterocolitis and that the relative level of these cytokines has important implications for the use of anti-cytokine therapy in NEC.     

Spontaneous tumor necrosis factor production in Kawasaki disease

Tumor necrosis factor production by peripheral blood mononuclear cells was measured in 18 patients with Kawasaki disease. In patients studied during the acute febrile phase of their disease, there was increased spontaneous TNF production (mean 26.9 +/- 40.3 U/ml) compared with that of control subjects (1.0 +/- .86 U/ml) (p less than or equal to 0.025). Spontaneous TNF production by patients tested in the subacute or convalescent phase of the illness was significantly lower than that in patients tested during the acute illness (p less than or equal to 0.025). In all patients studied with serial acute and subacute-convalescent samples, TNF production was normal in the follow-up samples. Because TNF is a potent mediator of inflammation and causes damage to vascular endothelial cells, we suggest that TNF may be important in the pathogenesis of both the immune activation and endothelial cell damage characteristic of this illness.     

Effect of season and vitamin D supplementation on plasma concentrations of 25-hydroxyvitamin D in Norwegian infants

Plasma concentrations of 25-hydroxyvitamin D (25OHD) were determined in 81 vitamin D supplemented or unsupplemented infants at the end of winter. The values were compared with maternal levels and with concentrations found in 22 unsupplemented infants at the end of summer. The 25OHD levels of the neonates were lower, but closely related to maternal values (r = 0.95, p less than 0.0005). Unsupplemented breast-fed infants had lower 25OHD levels at 6 weeks than at 4 days (16 +/- 7 vs. 32 +/- 15 nmol/l, mean +/- 1 SD, p less than 0.0005). The mean 25OHD level of vitamin D supplemented 6-12 months old infants was intermediate between those of the unsupplemented nursed groups and the unsupplemented children studied during summer (53 +/- 28 vs. 85 +/- 28 nmol/l, p less than 0.0005). Six weeks old infants who had received a milk formula containing 400 IU vitamin D3 per liter had levels similar to the latter group (92 +/- 21 nmol/l). The data suggest that the vitamin D stores acquired during fetal life, or from ultraviolet light exposure during the summer, may be inadequate to maintain safe levels of 25OHD throughout the winter, but that a daily supplement of 400 IU is adequate to establish concentrations in the summer range.     

Smoking during pregnancy--effects on the fetal thyroid function

Infants delivered at term by mothers smoking at least 10 cigarettes daily during pregnancy (n = 46) were found to be growth retarded compared to infants of non-smoking mothers (n = 49), birthweights 3,445 +/- 385 (SD) g and 3,667 +/- 392 g respectively (p less than 0.05) in the two groups. Cord serum thyrotropin (TSH) was significantly decreased (8.2 +/- 4.0 U/l vs. 10.3 +/- 4.9 U/l) and free thyroxine index (FT4I)/TSH ratio significantly increased (18.8 +/- 9.0 vs. 14.4 +/- 7.6) (p less than 0.05) in the smoking group compared to infants of non-smokers. Cord serum thyroxine (T4) and FT4I were higher in the smoking group (149.0 +/- 22.4 nmol/l and 125.5 +/- 14.9 respectively) compared to infants of non-smoking mothers (140.6 +/- 21.6 nmol/l and 120.0 +/- 16.5 respectively), with borderline statistical significance (0.05 less than p less than 0.10). The results indicate that infants of smoking mothers may have a hyperfunction of the thyroid gland at birth compared to infants of non-smokers, with a negative feed-back on TSH production from the pituitary gland. Increased metabolic rate and oxygen consumption caused by fetal thyroid hyperfunction may be pathogenetic factors for the fetal growth retardation caused by maternal smoking.     

Plasminogen activator inhibitor-1 and tissue-plasminogen activator in minority adolescents with type 2 diabetes and obesity

Increased plasminogen activator inhibitor-1 (PAI-1) and decreased tissue-plasminogen activator (t-PA) activities lead to impaired fibrinolysis, which is critical for cardiovascular disease. We studied these hemostatic factors at fasting state and after an oral fat load in 12 type 2 diabetic and 17 nondiabetic obese adolescents, matched for age, sex, body mass index, and sexual maturation. Plasma PAI-1, t-PA, and glucose as well as serum C-peptide, insulin, total cholesterol, triglyceride, and HDL and LDL cholesterol levels were measured at 0, 2, 4, and 6 h after the fat load. Metabolic responses were expressed as the area under the curve (AUC). PAI-1 activities were significantly greater in patients than in control subjects [fasting, 23.4 +/- 2.6 versus 12.9 +/- 2.0 U/mL (p < 0.004); AUC, 101.7 +/- 12.1 versus 57.6 +/- 6.5 U . h [corrected] . mL(-1) (p < 0.003)]. Fasting t-PA activities were significantly lower in the patients than in the control subjects (0.8 +/- 0.3 versus 6.5 +/- 2.7 U/mL; p < 0.001). Triglyceride was the only lipid parameter that was significantly different in the patients than in the control subjects [fasting, 1.5 +/- 0.2 versus 0.9 +/- 0.1 mM (p < 0.05); AUC, 15.7 +/- 2.9 versus 7.9 +/- 0.6 mmol . h(-1) . L(-1) (p < 0.02)]. The PAI-1 activities decreased significantly during the loading tests (p < 0.0001), whereas the t-PA activities did not change. Insulin resistance estimated by the homeostasis model assessment was greater in the patients than in the control subjects (14.4 +/- 2.8 versus 4.6 +/- 0.7; p < 0.0001). We conclude that elevated PAI-1 and diminished t-PA activities, suggestive of suppressed fibrinolysis, are present in our adolescents with type 2 diabetes; adding another risk factor for cardiovascular disease and acute high fat load does not further negatively affect this suppressed fibrinolysis.     

The relationship between carnitine and ketone body levels in diabetic children

Free carnitine was significantly (p less than 0.001) reduced both in the ketotic (29.7 +/- 3.4 nmol/ml) and in the ketoacidotic (24.6 +/- 1.4 nmol/ml) groups when compared to controls (50.0 +/- 2.4 nmol/ml). At the same time, acylcarnitine values in the ketotic (21.2 +/- 2.4 nmol/ml) and ketoacidotic (25.4 +/- 2.3 nmol/ml) groups were significantly above the control value (4.71 +/- 0.6 nmol/ml). There was no significant difference between the two ketotic groups in carnitine derivatives. The abnormal distribution of plasma free and acylcarnitines could be reversed by insulin treatment. There was an inverse correlation between ketone body levels and free carnitine in the ketotic (r = -0.71, p less than 0.02) and ketoacidotic group (r = -0.71, p less than 0.05). However, there was no correlation between ketone bodies and acylcarnitine and between free carnitine and acylcarnitines. We concluded that the increased acylation was only partly responsible for the reduction of free carnitine in diabetic ketosis.     

Neonatal interleukin-1 beta, interleukin-6, and tumor necrosis factor: cord blood levels and cellular production

In a prospective study, levels of interleukin-1 beta (IL-1 beta), interleukin-6) (IL-6), and tumor necrosis factor (TNF) were measured in a blind fashion in cord blood plasma from 92 neonates by specific immunoassays, and were correlated with the clinical courses of the infants, including type of delivery and perinatal complications. Plasma IL-1 beta concentration was undetectable in infants born by normal vaginal delivery or elective cesarean section but was significantly increased in infants born after induced vaginal deliveries (142 +/- 68 pg/ml) or urgent cesarean section (290 +/- 21 pg/ml; both p less than 0.05 compared with normal deliveries). The IL-1 beta levels were elevated in infants with severe perinatal complications (282 +/- 116 pg/ml; p less than 0.001), whereas TNF and IL-6 levels were not related to these complications. Infants with isolated perinatal infectious complications had elevated levels of plasma IL-6 compared with those of sick neonates without infection (p less than 0.001). In contrast, TNF plasma levels and IL-1 beta production by cord blood leukocytes were decreased in infants with infectious complications alone (both p less than 0.05). These studies suggest that the levels of IL-1 beta, IL-6, and TNF in the cord plasma relate differentially to clinical complications in the perinatal period.     

Decreased prolactin secretion in childhood obesity

Twelve obese patients and 7 control subjects, age and sex matched, whose weights were greater than 200% of ideal weight and 100% of ideal body weight, respectively, underwent intravenous insulin and thyroid releasing hormone (TRH) tests. Serial prolactin growth hormone, insulin, blood sugar, cortisol, glucagon, thyrotropin stimulating hormone, thyroxine, and triiodothyronine were obtained by RIA. Obese patients showed no significant differences from controls in basal and nadir glucose, basal and peak glucagon, cortisol, and thyroid responses to both tests. Basal insulin levels were higher (36 +/- 9.4 vs 10 +/- 2.3 microU/ml, P less than 0.05) and peak growth hormone responses after insulin were lower in the obese group (6.1 +/- 1.1 vs 12.7 +/- 3.7 ng/ml, P less than 0.05) than in controls. Whereas all control subjects had prolactin responses to both tests, five of 12 obese patients had no responses to insulin. Obese patients had lower prolactin responses at 30 minutes after insulin (5.4 +/- 0.7 vs 12.9 +/- 3.7 ng/ml, P less than 0.05) and lower prolactin responses at 60 minutes after TRH (9.9 +/- 1.7 vs 20.4 +/- 5.9 ng/ml, P less than 0.05). Maximum prolactin responses after TRH were lower in obese patients (9.9 +/- 2.0 vs 28.8 +/- 10.9 ng/ml, P less than 0.05). Maximum prolactin responses after insulin were lower in obese patients (6.2 +/- 4.1 vs 28.9 +/- 18.3 ng/ml). Thus prolactin secretion in childhood obesity is decreased after both stimuli, but more so after IV insulin that TRH, and suggests that, as in adult hypothalamic obesity, neuroendocrine regulation of prolactin release in obese children is impaired.     

Differences in thromboxane production between neonatal and adult platelets in response to arachidonic acid and epinephrine

In this study, we have investigated the possible role of the pro-aggregatory arachidonic acid (AA) metabolite thromboxane, in the impaired function of neonatal platelets. In platelet-rich plasma thromboxane production (measured by radioimmunoassay of thromboxane B2) was not different between neonates and adults when stimulated by thrombin (at 0.1 or 1.0 U/ml) or collagen (70 micrograms/ml) although neonatal platelets produced decreased thromboxane (TBX2) postepinephrine stimulation. In response to 1 U/ml thrombin, adult and neonatal platelet-rich plasmas produced mean values of 3.41 +/- 0.35 (SEM) and 3.11 +/- 0.49 pmol of TXB2/10(6) platelets, respectively. Production of TXB2 in response to 0.1 U/ml thrombin was not dissimilar between neonates (1.01 +/- 0.46 pmol) and adults (1.04 +/- 0.38 pmol). When collagen was used as the aggregating agent, TXB2 production was also not significantly different with values of 2.44 +/- 0.48 and 1.90 +/- 0.46 pmol/10(6) platelets produced by adult and neonatal platelet-rich plasma, respectively. In response to 200 microM epinephrine, adult platelets produced 1.03 +/- 0.39 pmol TXB2/10(6) platelets while neonatal platelet TXB2 production was significantly decreased (0.15 +/- 0.04; P less than 0.05). Thromboxane production in response to AA, however, was markedly elevated in neonatal platelet-rich plasma. When 200 and 400 microM concentrations of AA were used as the aggregating stimuli, neonatal platelet rich plasma produced 3.17 +/- 0.77 and 8.0 +/- 1.47 pmol TXB2/10(6) platelets, respectively. These values were significantly elevated P less than 0.02 and less than 0.005) when compared to mean values of 0.41 +/- 0.10 and 3.32 +/- 0.15 pmol in adult platelet-rich plasma.(ABSTRACT TRUNCATED AT 250 WORDS)