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.      

Early volatile depletion on planetesimals inferred from C–S systematics of iron meteorite parent bodies

During the formation of terrestrial planets, volatile loss may occur through nebular processing, planetesimal differentiation, and planetary accretion. We investigate iron meteorites as an archive of volatile loss during planetesimal processing. The carbon contents of the parent bodies of magmatic iron meteorites are reconstructed by thermodynamic modeling. Calculated solid/molten alloy partitioning of C increases greatly with liquid S concentration, and inferred parent body C concentrations range from 0.0004 to 0.11 wt%. Parent bodies fall into two compositional clusters characterized by cores with medium and low C/S. Both of these require significant planetesimal degassing, as metamorphic devolatilization on chondrite-like precursors is insufficient to account for their C depletions. Planetesimal core formation models, ranging from closed-system extraction to degassing of a wholly molten body, show that significant open-system silicate melting and volatile loss are required to match medium and low C/S parent body core compositions. Greater depletion in C relative to S is the hallmark of silicate degassing, indicating that parent body core compositions record processes that affect composite silicate/iron planetesimals. Degassing of bare cores stripped of their silicate mantles would deplete S with negligible C loss and could not account for inferred parent body core compositions. Devolatilization during small-body differentiation is thus a key process in shaping the volatile inventory of terrestrial planets derived from planetesimals and planetary embryos.

Major volatiles (H, C, N, and S) are inherently plentiful in the interstellar medium and abundant in primitive carbonaceous chondrites (CCs) (1, 2), but are scarce in terrestrial planets, which gained most of their mass from the inner parts of the solar nebula (3, 4). Formation of volatile-poor planets from a volatile-rich protoplanetary disk is a result of processes in the solar nebula, in accretion of precursor solids, and in interior differentiation. Addition of volatiles to nascent planets varies during accretion as protoplanetary systems become dynamically excited, contributing material originating from different heliocentric distances (3) and with different thermal histories. Much of this mass arrives in larger bodies (planetesimals or planetary embryos) that differentiated soon after formation (5). Key uncertainties include the nebular history of bulk materials that contributed volatiles to the rocky planets and how that affected their volatile cargos (6), and how planetesimal and planet formation influenced volatile distributions in accreted parent bodies.Processes responsible for volatile deficits in terrestrial planets (7, 8) can occur either in the nebular, planetesimal, or planetary environment. Nebular volatile depletion could result from chemical interactions between nebular gas and dust, chondrule formation, or the accretion of thermally processed solids (9–11), perhaps owing to the hotter conditions prevailing closer to the protosun (4). Li et al. (6) argue that the comparatively small C inventory of the bulk Earth requires that nebular materials experienced significant early (<1 Ma) heating, before the “soot line” moved inward of 1 AU. Planetesimal processes involve loss to space during differentiation or processing of intermediate-sized bodies of tens to hundreds of kilometers in diameter (e.g., refs. 12 and 13). Planetary loss processes occur on large (thousands of kilometers in diameter) bodies (14, 15) in which gravity plays an appreciable role—including loss from impacts (16). The sum of these is an important determinant for whether terrestrial planets form with volatiles sufficient for habitability but not so great as to become ocean worlds (17) or greenhouse hothouses (18).A key goal in the study of exoplanets and of young stellar systems is predicting environments and processes that could lead to habitable planets, including development of models that account for the distribution, acquisition, and loss of key volatile elements. Astronomical studies can reveal the architecture of other solar systems (19), the compositions of observable exoplanet atmospheres (ref. 20 and references therein), and the dust and volatile gas structure and composition of protoplanetary disks (ref. 21 and references therein), including interactions of the disk with gas- or ice-giant protoplanets. However, only limited astronomical observations can be made about conversion of disk materials (gas, dust, and pebbles) to planets in other solar systems. To understand this conversion, we must necessarily rely on planetesimals and their remnants (meteorites) as records of the processes that occurred. In this paper, we focus on volatile loss during planetesimal differentiation by examining evidence chiefly from iron meteorites. We note that ephemeral metal enrichments in white dwarf atmospheres confirm that differentiated planetesimals are common around other stars (22), and that our findings apply to how materials would have been processed during the assembly of other planetary systems.In classic oligarchic growth models of planetary origin, planets and embryos grow from accretion of planetesimals with characteristic radii of tens to a few hundreds of kilometers (3). In pebble accretion models of terrestrial planet formation, the fraction of planetesimals in accreting material varies with time and protoplanetary mass (23), but still remains significant. Thus, for understanding volatile delivery to growing planets, an important question is whether the volatile inventory of accreting planetesimals (or larger objects) remained similar to that of primitive materials, typically taken to be comparable to chondritic meteorites, or had diminished significantly from prior differentiation.^*Achondritic meteorites are fragments of differentiated planetesimals and provide direct evidence of processes on small bodies.^† Evidence for volatile loss on silicate achondritic parent bodies comes from elemental concentrations and from isotopes (24–27). However, the best-studied silicate achondritic suites, such as the eucrites and angrites, are igneous crustal rocks (28), and their compositions may not reflect average major volatile contents of their parent bodies. Volatile loss could have been locally enhanced by the igneous activity that produced the planetesimal crusts (29).Iron meteorites offer an additional record of volatile processing in planetesimals. Many, known as “magmatic” irons, originated as metallic cores of planetesimals (30) and potentially record volatile depletions in their parent planetesimals at the time of alloy–silicate separation. Iron meteorites contain measurable amounts both major (S, C, N) and moderately volatile (Ge, Ga) elements and represent the cores of at least 50 parent bodies (31). Thus, known parent body cores are likely survivors from a population of planetesimals that were mostly incorporated into larger bodies and planets. Additionally, isotopic evidence links iron meteorites with both carbonaceous (CC) and noncarbonaceous (NC) chondrites (32), thereby correlating the differentiated planetesimals to their primitive chondritic heritage.Here, we address the problem of planetesimal volatile loss by focusing on carbon and sulfur, two siderophile volatile elements that give important clues to the degassing history of metallic cores recorded iron meteorites and thereby their parent planetesimals.^‡ We begin by examination of C–S systematics in different classes of chondrites. Although chondritic parent bodies formed later than most parent bodies of iron meteorites (33), they provide the best available guide to undifferentiated materials in the early solar system. Their isotopic kinships to iron meteorites (32) suggest that they derive from similar, although not necessarily identical, reservoirs, and so they provide a basis for comparison to those estimated for parent body cores. They also reveal devolatilization processes associated with planetesimal metamorphism. We then examine iron meteorite groups and reconstruct the compositions of their respective parent cores. Finally, we consider a spectrum of simple planetesimal core-formation scenarios and model the resulting C and S distributions. Comparison of these to reconstructed parent core C and S places new constraints on the magnitude of degassing occurring from planetesimal interiors.     

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.     

Systematic review of enhanced recovery after gastro-oesophageal cancer surgery

Introduction

Fast track methodology or enhanced recovery schemes have gained increasing popularity in perioperative care. While evidence is strong for colorectal surgery, its importance in gastric and oesophageal surgery has yet to be established. This article reviews the evidence of enhanced recovery schemes on outcome for this type of surgery.

Methods

A systematic literature search was conducted up to March 2014. Studies were retrieved and analysed using predetermined criteria.

Results

From 34 articles reviewed, 18 eligible studies were identified: 7 on gastric and 11 on oesophageal resection. Three randomised controlled trials, five case-controlled studies and ten case series were identified. The reported protocols included changes to each stage of the patient journey from pre to postoperative care. The specific focus following oesophageal resections was on early mobilisation, a reduction in intensive care unit stay, early drain removal and early (or no) contrast swallow studies. Following gastric resections, the emphasis was on reducing epidural anaesthesia along with re-establishing oral intake in the first three postoperative days and early removal of nasogastric tubes.In the papers reviewed, mortality rates following fast track surgery were 0.8% (9/1,075) for oesophageal resection and 0% (0/329) for gastric resection. The reported morbidity rate was 16.5% (54/329) following gastric resection and 38.6% (396/1,075) following oesophageal resection. Length of stay was reduced in both groups compared with conventional recovery groups in comparative studies.

Conclusions

The evidence for enhanced recovery schemes following gastric and oesophageal resection is weak, with only three (low volume) published randomised controlled trials. However, the enhanced recovery approach appears safe and may be associated with a reduction in length of stay.     

Extracellular matrix of cultured bovine aortic endothelial cells contains functionally active type 1 plasminogen activator inhibitor

The extracellular matrix (ECM) of cultured bovine aortic endothelial cells (BAEs) was analyzed by immunoblotting and reverse fibrin autography and shown to contain type 1 plasminogen activator inhibitor (PAI-1). Most PAI-1 in the ECM formed complexes with exogenously added tissue-type plasminogen activator (tPA), demonstrating that this PAI-1 was functionally active. The resulting tPA/PAI-1 complexes were recovered in the reaction solution, indicating that the PAI-1 in such complexes no longer bound to ECM. The PAI-1 could not be removed by incubating ECM in high salt (2 mol/L NaCl), sugars (1 mol/L galactose, 1 mol/L mannose), glycosaminoglycans (10 mmol/L heparin, 10 mmol/L dermatan sulfate), or epsilon-aminocaproic acid (0.1 mol/L). However, PAI-1 could be extracted from ECM by treatment with either arginine (0.5 mol/L) or potassium thiocyanate (2 mol/L), or by incubation under acidic conditions (pH 2.5). ECM depleted of PAI-1 by acid extraction was able to bind both the active and latent forms of PAI-1. In this instance, most of the bound PAI-1 did not form complexes with tPA, indicating that the latent form was not activated as a consequence of binding to ECM. Although the PAI-1 activity in conditioned medium decayed with a half-life (t 1/2) of less than 3 hours, the t 1/2 of ECM- associated PAI-1 was greater than 24 hours. These data suggest that PAI- 1 is produced by cultured BAEs in an active form and is then either released into the medium where it is rapidly inactivated or into the subendothelium where it binds to ECM. The specific binding of PAI-1 to ECM protects it from this inactivation.