Measurement of albumin and low molecular weight proteins in the urine of newborn infants using a cotton wool ball collection method

Objective : The aim of this study was to investigate the inter-relationship between urinary excretion of alpha-1-microglobulin (AIM), retinol-binding protein (RBP) and albumin in term and premature neonates, with urine collected into cotton wool balls and extracted by a novel method. Subjects and methods : Sixty-four infants were studied on the first day of life; 26 had been born at term (37–42 weeks gestation) and 38 prematurely (24–28 weeks n = 16, 29–36 weeks n = 22). Urine collected into cotton wool balls was analysed following a new detergent extraction method, which resulted in a recovery rate of 94–107% for albumin, AIM, RBP and creatinine. Results : Urinary protein excretion, expressed as a ratio to urinary creatinine, decreased significantly with increasing gestational age (24–28 weeks, 29–36 weeks, 37–42 weeks: albuminxreatinine ratio mg/mmol mean 96.9, 31.7, 19.3; AIM: creatinine ratio mg/mmol mean 99.3, 37.0, 7.8; RBP: creatinine ratio mg/mmol mean 16.2, 3.8, and <0.01, below the limit of detection, respectively). When results were corrected for birthweight, this gestation-associated effect was still present for A1M and RBP, but not for albumin. In premature infants there was a significant positive correlation between AIM: creatinine ratio and RBP: creatinine ratio ( r = 0.85), and also between albumin and both AIM and RBP ( r = 0.82 and 0.77). Conclusion : Increased excretion of AIM, RBP and albumin at earlier gestational ages is probably due to proximal tubular immaturity, although tubular damage and also glomerular dysfunction cannot be excluded as possible explanations.     

Delayed umbilical cord clamping in preterm infants: A feasibility study

Objectives: To assess: (i) the size of placental transfusion following a 30 s delay in cord clamping following vaginal and Caesarean births; and (ii) the feasibility of delaying cord clamping in the labour ward and particularly in the operating theatre.
Methods: Fourty-six infants born at 26–33 weeks gestation were randomized to having the umbilical cord clamped either immediately or 30 s after birth. The venous haematocrit was measured at 1 and at 4 h of age.
Results: There were trends towards higher mean haematocrits in the infants following delayed clamping, but these were not significant either at 1 h (55±7.7 vs 52.9±7) or at 4 h of age (55±7 vs 52.5±7). The trends were more marked in the infants born by Caesarean section, and in those born at 26–29 weeks gestation.
Conclusions: A 30 s delay in cord clamping is feasible at both vaginal and Caesarean births, but does not lead to the predicted difference in infant haematocrit. Although physiological studies suggest that a placental transfusion of 15–20 mL/kg occurs within 30 s of delivery, these data suggest that future trials should either delay cord clamping for more than 30 s, or should alter the position of the infant in relation to the uterus in order to facilitate the transfusion. Delayed cord clamping is feasible at Caesarean section.     

Incidence of apnoea and bradycardia in preterm infants following DTPw and Hib immunization: A prospective study

Objective: To evaluate the incidence and severity of apnoea and bradycardia in hospitalized preterm infants following immunization at 2 months of age, and identify risk factors.
Methodology: A prospective study of 98 preterm infants, of gestational age 24–31 weeks, immunized at approximately 2 months post natal age with diphtheria-tetanus-whole cell pertussis vaccine (DTP_w) in the neonatal intensive care unit (NICU) at King George V Hospital Sydney. Half the infants also received Haemophilus influenzae type b conjugate vaccine (Hib) simultaneously. All infants were monitored for apnoea and bradycardia in the 24 h periods pre- and post immunization.
Results: Only one infant had apnoea and/or bradycardia pre-immunization compared with 17 post immunization. For 12 infants these events were brief, self-limiting and not associated with desaturations (oxygen saturation <90%). However, for five infants (30%) these events were associated with oxygen desaturation and two of these infants required supplemental oxygen. The group that had apnoea and/or bradycardia and the group that did not were not significantly different in terms of gestational age, birth weight and other variables. Infants who received Hib together with DTP_w were less likely to have apnoea and/or bradycardia than those given DTP_w alone.
Conclusion: When considering immunization for preterm infants, the benefits of early immunization must be balanced against the risk of apnoea and bradycardia. We recommend that the cardio-respiratory function of hospitalized infants born at less than 31 weeks gestation be monitored for 48 h post immunization.     

Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994

OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age.     

Growth of Pakistani children in relation to the 1990 growth standards

This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background.     

The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children

OBJECTIVE: The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. METHODS: One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. RESULTS: The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. CONCLUSIONS: The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.     

A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-- >T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.      

In vivo hematopoietic effects of recombinant interleukin-1 alpha in mice: stimulation of granulocytic, monocytic, megakaryocytic, and early erythroid progenitors, suppression of late-stage erythropoiesis, and reversal of erythroid suppression with erythropoietin

Interleukin-1 alpha (IL-1 alpha) is a macrophage-derived, multifunctional cytokine that broadly potentiates myelopoiesis and induces the synthesis of hematopoietic colony-stimulating factors (CSF) in vitro and in vivo. To evaluate the possibility for use of IL-1 alpha in ameliorating in vivo bone marrow suppression induced by drugs or radiation, we examined the in vivo effects of the cytokine on erythropoietic and other hematopoietic progenitor cells. Normal mice were treated with a single intraperitoneal (IP) injection of recombinant human IL-1 alpha at varying doses and were assayed at various times post-treatment. By six hours postinjection, a significant suppression of mature erythroid progenitors (CFU-E) was observed in animals treated with IL-1 alpha (0.5 micrograms/mouse), with maximum suppression of CFU-E and peripheral blood reticulocyte counts occurring at 24 hours. Decreases in peripheral blood hematocrit did not occur after a single IL-1 alpha injection but were observed after multiple injections of the cytokine. The suppressive effects of IL-1 alpha on late-stage erythropoiesis were abrogated by simultaneous administration of erythropoietin (EPO). At 48 hours post-treatment, a marked stimulation was observed in the numbers of spleen and marrow immature erythroid (BFU-E), macrophage (CFU-M), granulocyte (CFU-G), granulocyte- macrophage (CFU-GM), and megakaryocyte (CFU-meg) progenitor cells. These results demonstrate the potential use of IL-1 alpha as a generalized stimulator of hematopoiesis and show that the cytokine- induced suppression of late-stage erythropoiesis can be prevented by EPO.     

Nitric oxide in ascitic fluid is an independent predictor of the development of renal impairment in patients with cirrhosis and spontaneous bacterial peritonitis

BACKGROUND/AIMS: Cirrhotic patients with spontaneous bacterial peritonitis show a marked activation of the cytokine cascade, and cytokines induce the synthesis of nitric oxide in vitro. Our aim was to assess whether patients with ascitic fluid infection show increased levels of nitric oxide, and whether this is related to the development of renal impairment. METHODS: Retrospective analysis of prospectively collected specimens from 168 patients with cirrhosis and presence of sterile or infected ascitic fluid. Routine biochemical data together with nitric oxide metabolites, tumour necrosis factor and interleukin-6 were measured. Univariate and multivariate analyses were performed to identify factors related to the development of renal impairment. RESULTS: Patients with infected ascites showed increased serum and ascitic-fluid levels of nitric oxide metabolites and cytokines compared with patients with sterile ascites. A significant direct correlation was observed between serum and ascitic fluid nitric oxide metabolite levels. Multivariate analysis identified ascitic-fluid nitric oxide metabolites as an independent predictor of renal impairment. CONCLUSIONS: The increased serum and ascitic fluid nitric oxide found in patients with infected ascites might induce a deterioration of the increased peripheral vasodilation found in this setting, leading to the development of renal impairment in a series of patients with spontaneous bacterial peritonitis.