bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of different intragastric stimuli on triggering of transient lower oesophageal sphincter relaxation in the dog
Authors: STAKEBERG  , LEHMANN
Published: March 2003

Gastro‐oesophageal reflux in the dog is mainly caused by transient lower oesophageal sphincter relaxation (TLOSR), the major stimulus for which is distension of the stomach. The possibility that liquid and/or acid sensors in the proximal stomach reduce the incidence and/or shorten the duration of TLOSR was addressed in the present study. Manometric recordings of the pharynx, oesophagus, lower oesophageal sphincter and stomach were made in awake dogs equipped with an oesophagostomy. TLOSRs were induced by insufflation of air or infusion of liquid nutrients with varying pH. Intragastric distension with air provoked TLOSRs with a significantly shorter duration than those seen after distension with liquid (4.3 ± 0.5 vs 9.6 ± 0.3 sec; P < 0.05). There were fewer TLOSRs at high intragastric pH (pH 5.0: 3.1 ± 0.5/90 min) than at low pH (pH 1.5: 5.5 ± 0.9/90 min, P␣< 0.05). Successfully propagated peristalsis following a TLOSR was more common after stimulation with liquid than with air. It can be concluded that there are H+‐sensing mechanisms in the stomach which stimulate triggering of TLOSR. In addition, the reduced duration of TLOSR during air insufflation shows that the physical state of the distending stimulus can affect the patterning of TLOSR.
Neurotransmitter coding of enteric neurones in the submucous plexus is changed in non‐inflamed rectum of patients with Crohn’s disease
Authors: Schneider J. , Jehle E. C. , Starlinger M. J. , Neunlist M. , Michel K. , Hoppe S. , Schemann M.
Published: March 2003

Knowledge of the neurochemical coding of submucosal neurones in the human gut is important to assess neuronal changes under pathological conditions. We therefore investigated transmitter colocalization patterns in rectal submucosal neurones in normal tissue (n=11) and in noninflamed tissue of Crohn’s disease (CD) patients (n=17). Neurone‐specific enolase (NSE), choline acetyltransferase (ChAT), vasoactive intestinal polypeptide (VIP), substance P (SP), nitric oxide synthase (NOS) and calcitonin gene‐related peptide (CGRP) were detected immunohistochemically in whole‐mount preparations from rectal biopsies. The neuronal marker NSE revealed no differences in the number of cells per ganglion (controls 5.0; CD 5.1). Four cell populations with distinct neurochemical codes were identified. The sizes of the populations ChAT/VIP (58% vs. 55%), ChAT/SP (8% vs. 8%), and ChAT/– (22% vs. 22%) were similar in control and CD. The population VIP/– was significantly increased in CD (12% vs. 2% in controls). Unlike in controls, all NOS neurones colocalized ChAT in CD. Thickened CGRP‐fibres occurred in CD. We identified neurochemically distinct populations in the human submucous plexus. The increase in the VIP/– population, extensive colocalization of ChAT and NOS and hypertrophied CGRP fibres indicated adaptive changes in the enteric nervous system in noninflamed rectum of CD patients.
Do gap junctions couple interstitial cells of Cajal pacing and neurotransmission to gastrointestinal smooth muscle?
Authors: Daniel E. E. , Thomas J. , Ramnarain M. , Bowes T. J. , Jury J.
Published: March 2003

Interstitial cells of Cajal (ICC) pace gastrointestinal phasic activity and transmit nerve activity. Gap junctions may couple these cells to smooth muscle, but no functional evidence exists. The objective of this study was to use uncouplers of gap junctions, 18α‐glycyrrhetenic acid and its water‐soluble analogue carbenoxolone, to evaluate if gap junctions function in pacing and neurotransmission. After inhibition of nerve function with tetrodotoxin (TTX) and NG‐nitro‐L‐arginine (L‐NOARG), ionomycin‐ or carbachol‐initiated regular phasic activities of circular muscle strips from canine colon and ileum. In some cases, the primary ICC network responsible for pacing was removed. The effects of inhibitors of gap junction conductance (10–5–10–4 mol L–1) on frequencies and amplitudes of contraction were compared to appropriate time controls. Lower oesophageal sphincter (LOS) relaxations to nerve stimulation were studied before and after inhibition of gap junction functions. No major changes in LOS relaxations or frequencies of colonic or ileal contractions occurred, but amplitudes of contractions decreased from these agents. Similar results were obtained when the myenteric plexus–ICC network of ileum was removed. Regular phasic activity was not obtained after removal of the colon submuscular plexus ICC. These findings suggest that mechanisms other than gap junctions couple gut pacemaking activity and nerve transmission.
Effect of 2,4,6‐trinitrobenzenesulphonic acid (TNBS)‐induced ileitis on the motor function of non‐inflamed rat gastric fundus
Authors: Moreels T. G. , De Man J. G. , De Winter B. Y. , Timmermans J‐P. , Herman A. G. , Pelckmans P. A.
Published: March 2003

During intestinal inflammation, motility disturbances are not restricted to inflamed regions, but may also occur in remote non‐inflamed sites of the gastrointestinal tract. Our aim was to investigate the motor function of the gastric fundus after the induction of terminal ileitis in the rat. Ileal inflammation was induced by intraluminal installation of 2,4,6‐trinitrobenzenesulphonic acid (TNBS) into the ileum. Inflammation was assessed both histologically and biochemically. Contractions and relaxations of longitudinal muscle strips from the gastric fundus were studied 36 h and 1 week later. During the acute phase of ileal inflammation (36 h), the non‐inflamed stomach was distended. The contractility of longitudinal muscle strips of the gastric fundus was decreased due to a post‐receptor defect. In addition, nonadrenergic noncholinergic (NANC) relaxations were inhibited due to neuronal dysfunction. Aortic contractility remained normal and the mere presence of food in the stomach did not account for the disturbed neuromuscular function in the gastric fundus. Ablation of extrinsic primary afferent neurones by capsaicin further impaired gastric fundus contractility. Transection and re‐anastomosis of the jejunum reversed the effect of TNBS‐induced ileitis on the neuromuscular function of the gastric fundus. One week after TNBS, cholinergic neurotransmission was increased in the gastric fundus. During acute ileitis, smooth muscle cell contractility and inhibitory NANC neurotransmission are inhibited in the non‐inflamed gastric fundus. This phenomenon may be mediated by intrinsic connections within the enteric nervous system.
Serotonin type‐4 receptors modulate the sensitivity of intramural mechanoreceptive afferents of the cat rectum
Authors: Schikowski A. , Thewißen M. , Mathis C. , Ross H‐G. , Enck P.
Published: March 2003

Abstract
 
It has been suggested that serotonin (5‐hydroxytryptamine) type‐4 (5‐HT4) receptors modulate the sensitivity of intrinsic afferents of the intestinal mucosa. We studied the involvement of 5‐HT4receptors in the modulation of extrinsic afferent sensitivity of the intestinal wall. During distension ramps, mechanoreceptive rectal afferents in sacral dorsal roots were examined in decerebrate anaesthesia‐free cats using the selective 5‐HT4receptor partial agonist, tegaserod (HTF 919), and the 5‐HT4receptor antagonist, SB 203186. The static discharge rate of the afferents evoked by rectal distension decreased after intravenous (i.v.) administration of tegaserod at intraluminal pressures above 30 mmHg, with the most effective reduction occurring at 50 mmHg. The effect was dose‐dependent, with maximal reduction occurring at 1.2 mg kg−1bodyweight, and could be partly reversed by i.v. administration of SB 203186. Tegaserod did not alter the pressure–volume relationship (compliance) of the rectum. It is tentatively concluded that 5‐HT4receptor activation has an inhibitory effect on intramural mechanoreceptors in the cat's rectum. Our results are in line with the observation that tegaserod relieves the sensory symptoms of patients suffering from irritable bowel syndrome.
Immunohistochemical detection of vascular endothelial growth factor (VEGF) in the vasculature of oligodendrogliomas
Authors: Christov  , Christov  , Adle‐Biassette  , Adle‐Biassette  , Le Guerinel  , Le Guerinel  , Natchev  , Gherardi  , Gherardi
Published: March 2003

C. Christov, H. Adle‐Biassette, C. Le Guerinel, S. Natchev and R. K. Gherardi (1998) Neuropathology and Applied Neurobiology24, 29–35

Immunohistochemical detection of vascular endothelial growth factor (VEGF) in the vasculature of oligodendrogliomas

Vascular endothelial growth factor (VEGF) appears to be implicated in tumour angiogenesis. In the present study immunohistochemical expression of VEGF was evaluated in 34 oligodendrogliomas (13 grade II, 21 grade III [WHO]). VEGF immunoreactivity was found in 31 of 34 cases. Expression of VEGF was observed in endothelial cells and some vascular smooth muscle cells, but not in neoplastic oligodendrocytes. Vessel counts, percentages of VEGF‐positive vessels and vessels with vascular endothelial proliferation were assessed. The degree of VEGF labelling and vascular‐endothelial proliferation in each vessel were evaluated using a 3 degree intensity score. Expression of VEGF was higher in grade III than in grade II oligodendrogliomas as assessed by percentage of VEGF positive vessels (55.8 ± 29.2% vs 17.0 ± 19.0% [P < 0.001]) and by VEGF immunostaining intensity (1.90 ± 0.60 vs 0.90 ± 0.40 [P < 0.001]). VEGF expression did not correlate with vessel density. Intensity of VEGF expression correlated positively with that of vascular‐endothelial proliferation in grade III tumours (r=+0.47 [P < 0.05]). The percentage of VEGF positive vessels showed some degree of positive correlation with the percentage of vessels showing vascular‐endothelial proliferation (r=+408 [P < 0.10]). Within individual grade III tumours 67.5 ± 29.6% of all vessels with vascular‐endothelial proliferation were VEGF‐positive and 31.0 ± 20.5% of all VEGF‐positive vessels showed no evidence of vascular‐endothelial proliferation. We conclude that (i) expression of VEGF is observed in the vasculature of oligodendrogliomas; (ii) marked expression of VEGF is observed in grade III oligodendrogliomas; (iii) VEGF may be one of the interrelated causative stimuli acting in concert to induce vascular‐endothelial proliferation.
The influence of plasma proteins on the distribution of leucocytes within the brain parenchyma in a murine model of stroke
Authors: Brown  , Kristenssen  , Rothaul  , Perry
Published: March 2003

Inflammatory responses are thought to play an important role in the exacerbation of neuronal loss following stroke. Leucocyte recruitment following cerebral ischaemia has been demonstrated in experimental animals, and procedures which reduce the entry of leucocytes into the brain reduce neuronal loss and improve aspects of functional recovery in these models. In this study we investigate whether leakage of plasma proteins into the central nervous system (CNS) following ischaemia influences leucocyte adhesion within the parenchyma. Using an in vitro adhesion assay, we demonstrate that the addition of exogenous serum proteins increases macrophage adhesion to CNS tissue. Following permanent middle cerebral artery occlusion (MCAO) in mice, plasma proteins leak into the apparently healthy cortex surrounding the infarcted area. We show that there is increased macrophage adhesion to sections in the border region where endogenous plasma proteins are present within the parenchyma. Using immunohistochemistry, we co‐localize plasma protein distribution within the tissue with leucocyte recruitment following MCAO. We show that monocytes, not neutrophils, infiltrate the lesion border where plasma proteins are present in the parenchyma. This distribution is compatible with their contributing to neuropathology, whereas neutrophils are found in clusters in the lesion core. We conclude that leakage of plasma proteins into the brain could influence leucocyte adhesion within the parenchyma. Recruited monocytes may exacerbate neuropathology in situations such as permanent cerebral ischaemia, where disruption of the blood–brain barrier occurs.
Differential downregulation of vascular endothelial growth factor by dexamethasone in normoxic and hypoxic rat glioma cells
Authors: Machein  , Kullmer  , Rönicke  , Machein  , Krieg  , Damert  , Breier  , Risau  , Plate
Published: March 2003

Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is a mitogen and chemotactic factor for endothelial cells in vitro and an angiogenesis and vascular permeability factor in vivo. Due to its properties, VEGF is a candidate for both angiogenesis and vascular permeability/oedema induction which typically occur in glioblastomas. In this study we test the hypothesis that the antioedema effect of dexamethasone is mediated by downregulation of VEGF or VEGF receptor expression. VEGF mRNA and protein levels of two rat glioma cells lines, C6 and GS‐9L, were determined after incubation with dexamethasone under normoxic and hypoxic conditions. In normoxic C6 and GS9L cells, we observed 50–60% downregulation of VEGF mRNA by dexamethasone (P=0.015 and P=0.01, respectively). This effect was dependent on glucocorticoid‐receptor (GR) function. The inhibitory effect of dexamethasone on VEGF gene expression by tumour cells was markedly reduced by hypoxia which suggests that the upregulation of VEGF driven by hypoxia overcomes the effect of the dexamethasone. Dexamethasone did not alter VEGFR‐2 mRNA levels in human umbilical endothelial cells. In a subcutaneous glioma tumour model, we observed only a 15% decrease in VEGF mRNA expression in dexamethasone treated animals (n=12) compared with controls animals (P=0.24). We conclude that dexamethasone may decrease brain tumour‐associated oedema by reduction of VEGF expression in tumour cells. However, the highly reduced activity on hypoxic tumour cells suggests that dexamethasone efficacy may be limited by hypoxia in rapidly growing tumours.
Laminar distribution of Pick bodies, Pick cells and Alzheimer disease pathology in the frontal and temporal cortex in Pick’s disease
Authors: Armstrong  , Cairns  , Lantos
Published: March 2003

Lesions in Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) have distinct laminar distributions in the cortex. The objective of the present study was to test the hypothesis that the lesions characteristic of Pick’s disease (PD) and AD have distinctly different laminar distributions in cases of PD. Hence, the laminar distribution of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) was studied in the frontal and temporal cortex in nine patients with PD. In 57% of analyses of individual cortical areas, the density of PB was maximal in the upper cortex while in 25% of analyses, the distribution of PB was bimodal with density peaks in the upper and lower cortex. The density of PC was maximal in the lower cortex in 77% of analyses while a bimodal distribution was present in 5% of analyses. The density of NFT was maximal in the upper cortex in 50% of analyses, in the lower cortex in 15% of analyses, with a bimodal distribution in 4% of analyses. The density of SP did not vary significantly with cortical depth in 86% of analyses. The vertical densities of PB and PC were negatively correlated in 12/21 (57%) of brain areas. The maximum density of PB in the upper cortex was positively correlated with the maximum density of PC in the lower cortex. In 17/25 (68%) of brain areas, there was no significant correlation between the vertical densities of PB and NFT. The data suggest that the pathogenesis of PB may be related to that of the PC. In addition, although in many areas PB and NFT occur predominantly in the upper cortex, the two lesions appeared to affect different neuronal populations.
Neuronal accumulation of poly(ADP‐ribose) after brain ischaemia
Authors: Love  , Barber  , Wilcock
Published: March 2003

Animal and in vitro studies suggest that overactivation of poly(ADP‐ribose) polymerase (PARP) in response to oxidative DNA damage makes a substantial contribution to cell death after brain ischaemia. We have recently shown that global brain ischaemia due to cardiac arrest in man induces a rapid increase in the amount of neuronal and glial PARP that can be detected by immunohistochemistry. In the present study we sought evidence of a corresponding increase in the amount of poly(ADP‐ribose) within the brain, as this would confirm PARP activation and imply resulting consumption of NAD+ . We also studied the distribution of poly(ADP‐ribose) accumulation in relation to morphological evidence of ischaemic damage, and used double immunolabelling to investigate the types of cell that were affected. We found that global brain ischaemia did cause accumulation of poly(ADP‐ribose), particularly during the first 2 days after cardiac arrest. The distribution of cells with accumulation of poly(ADP‐ribose) corresponded in general to regions of ischaemic damage or immediately adjacent neocortex. Double immunolabelling for poly(ADP‐ribose) and MAP2 showed many of the cells with poly(ADP‐ribose) accumulation to be neurons. Our findings are in keeping with experimental evidence of a role for PARP in post‐ischaemic necrosis and of the potential for reducing ischaemic brain damage by the use of PARP inhibitors.
Inflammatory response and retinal ganglion cell degeneration following intraocular injection of ME7
Authors: Russelakis‐Carneiro  , Betmouni  , Perry
Published: March 2003

Scrapie is a prion disease which occurs naturally in sheep and which can be transmitted experimentally to rodents. After intracerebral injection of ME7 into mouse, an atypical inflammatory response, characterized by T‐lymphocytes and activated microglia is present early in the course of the disease. In the present work, we have investigated the relationship between this inflammatory response, astrocytosis and neuronal loss along the visual pathway after intraocular injection (intraocular) of ME7 in C57BL/6J mice. We have demonstrated that microglia activation and T‐lymphocyte recruitment accompanies the spread of prion pathology along the visual pathway and in the early stages of the disease is restricted to the subcortical visual pathway. Inflammation was also present in non‐visual areas in association with PrPsc deposition at late stages of the disease, possibily indicating that diffusion of the scrapie agent also contributes to the spread of the disease. After intraocular injection of the prion agent, the disease is believed to be transported into the brain via axons of retinal ganglion cells (RGCs). Despite the high levels of infectivity reported to be present in the retina early in the disease after intraocular injection of ME7, retinal pathology has not been extensively investigated. We have studied the RGCs response in whole mount retinas after intraocular injection of ME7. We have shown that RGCs degenerate after intraocular injection of ME7 whereas amacrine cells, retinal interneurones, are more resistant. Our results suggest that two distinct population of neurones, exposed in vivo at the same time to the same agent scrapie strain, show different susceptibility to the toxic effects of PrPsc .
Cell death and oxidative stress in gliomas
Authors: Tews
Published: March 2003

In gliomas, apoptosis and necrosis are determined by a number of promoting and inhibiting factors including oxidative cell stress mediated by nitric oxide synthases (NOS) and reduced by superoxide dismutases. Therefore, in 46 gliomas (including astrocytomas, oligodendrogliomas, oligo‐astrocytomas, and glioblastomas), the relationship of apoptosis and necrosis and the expression of apoptosis‐promoting (p53, bax, Fas, Fas‐L) and inhibiting (bcl‐2) factors as well as of different isoforms of NOS (NOSb, NOSe, NOSi) and manganese superoxide dismutase (MnSOD) were studied. Apoptosis was measured in situ by the TUNEL method while expression profiles of apoptosis‐related and oxidative stress‐associated factors were determined by immunohistochemistry. As a defining criterion, necrosis was restricted to glioblastomas while apoptosis increased with tumour malignancy (P=0.017) in all types of gliomas. Glial tumour cells displayed upregulation of bax, Fas, Fas‐L, p53, and bcl‐2 but with no significant correlation with malignancy. There was also a strong expression of NOS isoforms with upregulation of NOSe in all and of NOSb and NOSi in nearly 50% of the tumour specimens but only NOSb expression correlated significantly with tumour malignancy (P=0.004). Likewise, MnSOD was strongly expressed in all gliomas but was not correlated with tumour grade. There was a wide variability of expression in each tumour type without significant correlation between apoptosis and expression of apoptosis‐associated or oxidative stress‐related factors indicating that the network of regulating factors may be too complex for clear associations.
Insulin‐like growth factors and binding proteins in multiple sclerosis plaques
Authors: Gveric  , Cuzner  , Newcombe
Published: March 2003

Insulin‐like growth factors (IGFs) play an important role in development and myelination in the central nervous system (CNS) as well as in the proliferation and differentiation of cells of the immune system. To assess the influence of this growth factor family on demyelination and repair in multiple sclerosis (MS), the expression of IGF‐I, IGF‐II, insulin, IGF binding proteins (IGFBP) 1–3 and IGF‐I receptor (IGF‐IR) in CNS tissue from MS and normal control cases was studied by immunocytochemistry. In active MS lesions, the expression of IGF‐I, insulin and IGFBP1 was detected in hypertrophic astrocytes while that of IGF‐II and IGFBP2 and 3 was confined to foamy macrophages within lesions and activated microglia in adjacent white matter. IGF‐IR, the major IGF receptor, was immunolocalized in macrophages and an astrocyte subpopulation in plaques. Oligodendrocytes in normal‐appearing white matter expressed only IGFBP1, not IGFs or IGF‐IR. As the remyelinating capacity of oligodendrocytes could be impaired owing to the absence of IGF‐IR, the prevailing role of IGFs in inflammatory demyelination may be to promote phagocytosis of myelin and astrogliosis.
Phosphorylation of retinoblastoma protein in rat brain after transient middle cerebral artery occlusion
Authors: Hayashi T. , Sakai K. , Sasaki C. , Zhang W. R. , Abe K.
Published: March 2003

Although mature neurones do not replicate genomic DNA, some cell cycle‐related kinases are aberrantly activated in neurones after ischaemia. As hyper‐phosphorylation of retinoblastoma (Rb) protein is the common pathway in mitotic signal cascade, this study investigated the phosphorylation state of the Rb protein as well as its mRNA level in rat brain after transient middle cerebral artery (MCA) occlusion. Immunohisto‐chemical analysis revealed that neurones in the sham‐operated brain expressed Rb protein without the hyperphosphorylated form. Immunoreactivity for the hyperphosphorylated form of Rb protein progressively increased from 1 h to 3 days after ischaemia in neurones in the MCA territory. Western blot analysis demonstrated a similar change. However, reverse transcription‐polymerase chain reaction study revealed that Rb showed no definite change at the mRNA level. These results suggest that Rb protein is progressively hyper‐phosphorylated in the brain after ischaemia, which may activate apoptotic mechanisms in neuronal cells of the brain after ischaemia.
Expression of P‐selectin and intercellular adhesion molecule‐1 in human brain after focal infarction or cardiac arrest
Authors: Love S. , Barber R.
Published: March 2003

Data from experimental studies indicate that acute inflammation contributes to ischaemic brain damage. Tethering of neutrophils to brain endothelium is mediated by selectins, and subsequent adhesion and migration by endothelial intercellular adhesion molecule‐1 (ICAM‐1) and neutrophil CD18. In experimental studies of ischaemia‐reperfusion injury, brain damage has been ameliorated by administration of antibodies to these adhesion molecules. We studied the expression of P‐selectin and ICAM‐1 in sections of brain from patients who had experienced cardiac arrest or focal brain infarction, and who died 3.5 h to 9 days later. Endothelial immunopositivity for both adhesion molecules was maximal at about 2–3 days then declined. Between 1 day and 3 days, P‐selectin was also detected on platelets in blood vessels within infarcted tissue. Within infarcts, but not sections of brain from cardiac arrest patients, P‐selectin and ICAM‐1 were again detectable at 1 week, when hyperplastic endothelial cells were labelled in capillaries in and immediately adjacent to the infarcted tissue. The finding that P‐selectin and ICAM‐1 are upregulated within focally infarcted brain tissue supports the concept that blocking neutrophil adhesion may be of benefit in treating atherothrombotic strokes in man.
A population‐based study of abdominal wall defects in South Australia and Western Australia
Authors: Byron‐Scott Rosemary , Haan Eric , Chan Annabelle , Bower Carol , Scott Heather , Clark Kathryn
Published: March 2003

The purpose of this study was to determine the prevalence, clinical characteristics, prenatal diagnosis and occurrence of other birth defects with abdominal wall defects in births and terminations of pregnancy in South Australia (SA) and Western Australia (WA) over the period 1980–90. Cases of gastroschisis, exomphalos, bladder exstrophy, cloacal exstrophy and body stalk anomaly were ascertained from the WA Birth Defects Registry (1980–90) and the SA Birth Defects Register (1986–90). The registers are comparable population‐based data collections with information on livebirths and stillbirths of at least 400 g birthweight or 20 weeks’ gestation, and terminations of pregnancy for fetal abnormality. The prevalence of gastroschisis was 1.65/10 000 births (59 cases) and of exomphalos 2.90/10 000 births (104 cases). There was no significant difference in prevalence of exomphalos or gastroschisis between SA and WA for the years 1986–90. However, if data from WA for the years 1980–85 were included, SA had a significantly higher prevalence of exomphalos (prevalence ratio 1.71, confidence interval [CI] 1.16–2.55), although not of gastroschisis (prevalence ratio 1.35, CI 0.79–2.32). Exomphalos was significantly more common in mothers < 20 years (odds ratio [OR] 2.45, CI 1.22–4.86) and in mothers of 40 years or older (OR 5.65, CI 1.69–16.77). Gastroschisis was more common in younger mothers (OR 8.76, CI 4.02–19.32). Both exomphalos and gastroschisis were associated with low birthweight, prematurity, intrauterine growth retardation and caesarean section. The reason for the higher prevalence of exomphalos in SA than WA was not clear, but may be related to differences in prenatal diagnosis. The association between maternal age < 20 years and exomphalos raises the possibility of common factors in the aetiology of gastroschisis and exomphalos.
Air pollution and respiratory illness of children in São Paulo, Brazil
Authors: Lin  , Martins  , Farhat  , Pope  , Conceição  , Anastácio  , Hatanaka  , Andrade  , Hamaue  , Böhm  , Saldiva
Published: March 2003

This investigation reports the association between air pollution and paediatric respiratory emergency visits in São Paulo, Brazil, the largest city in South America. Daily records of emergency visits were obtained from the Children’s Institute of the University of São Paulo for the period from May 1991 to April 1993. Visits were classified as respiratory and non‐respiratory causes. Respiratory visits were further divided into three categories: upper respiratory illness, lower respiratory illness and wheezing. Daily records of SO2, CO, particulate matter (PM10), O3 and NO2 concentrations were obtained from the State Air Pollution Controlling Agency of São Paulo. Associations between respiratory emergency visits and air pollution were assessed by simple comparative statistics, simple correlation analysis and by estimating a variety of regression models. Significant associations between the increase of respiratory emergency visits and air pollution were observed. The most robust associations were observed with PM10, and to a lesser extent with O3. These associations were stable across different model specifications and several controlling variables. A significant increase in the counts of respiratory emergency visits – more than 20%– was observed on the most polluted days, indicating that air pollution is a substantial paediatric health concern in São Paulo.
Aetiology of childhood vision impairment, metropolitan Atlanta, 1991–93
Authors: Mervis Cynthia A. , Yeargin‐Allsopp Marshalyn , Winter Sarah , Boyle Coleen
Published: March 2003

Data from the population‐based Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP) were used to describe the underlying causes of vision impairment (VI; corrected visual acuity in the better eye of 20/70 or worse) in young children (n = 228) in metropolitan Atlanta in 1991–93. Children with VI were identified through record review at multiple educational and medical sources. Children were categorised as having isolated VI or multiple disabilities (i.e. VI plus one or more of four additional developmental disabilities) and as having low vision (visual acuity 20/70–20/400) or blindness (visual acuity worse than 20/400). Medical conditions abstracted from MADDSP sources were reviewed to determine the probable aetiology of a child’s VI. Aetiologies were assigned to one of three developmental time periods: prenatal, perinatal, or postnatal. Prenatal aetiologies were identified in 43% of the children; 38% of the prenatal aetiologies were genetic. Perinatal aetiologies were found in 27% of the children. Postnatal aetiologies were rare. Prenatal aetiologies were more common in children with isolated VI; perinatal and postnatal aetiologies were more common in children with multiple disabilities. Children with prenatal aetiologies tended to have less severe vision loss than did children with perinatal or postnatal aetiologies. The distribution varied by birthweight, but did not differ significantly by sex or race.
Maternal sociodemographic characteristics as risk factors for preterm birth in twins versus singletons
Authors: Rolett A. , Kiely J.L.
Published: March 2003

Many studies have examined associations between sociodemographic variables and preterm birth in singletons. However, almost no research has been published on whether variables such as maternal age, race, ethnicity, level of education and smoking are associated with preterm birth among twins in the same way. The purpose of this study was to examine such associations in twins and singletons comparatively. The study population consisted of all 567 796 twins and 23 297 909 singleton births recorded in the US birth records for 1990–95. Gestational age data were rigorously ‘cleaned’ to solve the problem of biologically implausible birthweight/gestation combinations in vital records. Preterm birth was defined as gestational age < 35 weeks. Some 25.8% of twins and 3.2% of singletons were preterm by this definition. Crude and adjusted relative risks (RR) were estimated using a modified Mantel–Haenszel procedure. We found several characteristics associated with preterm birth in both twins and singletons, e.g. for twins: race (black adjusted RR = 1.30 compared with white non‐Hispanic); marital status (unmarried adjusted RR = 1.15 compared with married); and age ( 17 years adjusted RR = 1.39 compared with 20–29 years). A similar analysis of singletons revealed stronger associations between the same characteristics and preterm birth, e.g. the adjusted RR for black race was 2.3. These differences in RRs suggest that sociodemographic characteristics have weaker effects on preterm birth among twins than among singletons. Care must be taken in interpreting differences in preterm birth in twins and singletons, as their gestational age distributions differ so markedly.
Identification of biological/biochemical marker(s) for preterm delivery
Authors: Thorsen Poul , Schendel Diana E. , Deshpande Anjali D. , Vogel Ida , Dudley Donald J. , Olsen Jørn
Published: March 2003

Fetal and neonatal mortality and morbidity rates are strongly associated with gestational age for delivery: the risk for poor outcome increases as gestational age decreases. Attempts to predict preterm delivery (PTD, spontaneous delivery before 37 weeks’ gestation) have been largely unsuccessful, and rates of PTD have not improved in recent decades. More recently, the reported associations between infections in pregnancy and PTD suggest preventive initiatives that could be taken.

The overall objective of the current study is to assess whether specific markers of infection (primarily interleukin (IL) 1β, tumour necrosis factor (TNF) α, IL‐6, and IL‐10) obtained from maternal blood during pregnancy, alone or in combination with other risk factors for PTD, permit identification of women at risk for spontaneous PTD. To achieve this objective, data are obtained from two Danish prospective cohort studies involving serial collection of maternal blood samples, newborn cord blood samples, and relevant confounders and other risk factors for PTD. The first study consists of a completed Danish regional cohort of 3000 pregnant women enrolled in a study of microbiological causes of PTD, upon which a nested case‐control study of PTD in 84 cases and 400 controls has been performed. The second study is a nested case‐control study of 675 PTD cases (equally divided into three gestational age categories of 24–29 weeks’ gestation, 30–33 weeks’ gestation, and 34–36 weeks’ gestation) and 675 controls drawn from the ongoing Danish National Birth Cohort study of 100 000 pregnant women enrolled during 1997–2001. The second study will provide the opportunity to refine and retest hypotheses from the first study, as well as to explore new hypotheses. Our preliminary work suggests that a single predictive marker effectively accounting for a large proportion of PTD is unlikely to be found. Rather, a search for multiple markers indicative of the multifactorial aetiology of PTD is likely to be more successful.

Knowledge gained from the proposed studies will be implemented in a third, clinical intervention study against PTD. The first phase of the clinical intervention study will be to establish a risk‐assessment model based on the ‘best’ combination of biological/biochemical measures and other factors associated with PTD in order to identify pregnant women at very high risk of PTD. The second phase will be to apply an intervention model of tailored obstetric care to the very high‐risk pregnant women for PTD identified in phase one. The intervention will be carried out against each specific risk factor associated with PTD identified for the individual. The aim is to reduce the risk for PTD attributed to the combination of risk factors included in the clinical intervention study.
Preterm labour at 34–36 weeks of gestation: should it be arrested?
Authors: Arnon Shmuel , Dolfin Tzipora , Litmanovitz Ita , Regev Rivka , Bauer Sofia , Fejgin Moshe
Published: March 2003

Currently, preterm labour is treated with tocolytic agents and prenatal steroids until the 34th week of gestation only. Our objective in this study was to assess this practice. Seven‐year records of all preterm infants born in our institution at 34–36 weeks of gestation, were evaluated retrospectively. All babies, born in singleton well‐dated pregnancies, without maternal, medical or obstetric complications, and by normal vaginal delivery, were included. Their length of hospital stay and perinatal complications were compared across gestational age groups of 34, 35 and 36 weeks. Of the 207 babies included, statistically significant reductions in the rates of respiratory distress syndrome (15.0% vs. 3.2%), nosocomial sepsis (5.0% vs. 0%) and apnoea of prematurity (11.7% vs. 2.2%), and consequently, in length of hospital stay (16 ± 2.7 vs. 4 ± 0.3 days) occurred between 34 and 36 weeks of gestation. The severity of respiratory distress syndrome also declined significantly. The changes were most noticeable after 35 weeks of gestation, and it was concluded that neonatal complications are still prevalent at 34 and 35 weeks. Therefore, we propose that labour should not be induced at 34 and 35 weeks of gestation and that tocolytic agents and maternal prenatal steroids may be considered in preterm labour during this period.
Psychomotor development in Argentinean children aged 0–5 years
Authors: Lejarraga Horacio , Pascucci María Cecilia , Krupitzky Sara , Kelmansky Diana , Bianco Ana , Martínez Elena , Tibaldi Fabián , Cameron Noel
Published: March 2003

In Argentina, there is no information on ages of attainment of developmental milestones and very few data about environmental factors that influence them. A national survey on the psychomotor development of children under 6 years of age was carried out with the help of 129 paediatricians. Logistic regression was applied to a final sample of 3573 healthy, normal children in order to estimate selected centiles (25th, 50th, 75th and 90th), together with their respective confidence intervals, of the ages of attainment of 78 developmental items belonging to the following areas: personal–social (18 items), fine motor (19), language (18) and gross motor (23). The 50th centile obtained for each of the 43 comparable items was compared with those obtained in previously standardised tests: DDST, Denver II, Bayley and Chilean scales. Neither significant nor systematic differences were found between our results and those described in the tests used for comparison. Multiple logistic regressions showed that social class, maternal education and sex (female) were associated with earlier attainment of some selected developmental items, achieved at ages later than 1 year. Selected items achieved before the first year of life were not affected by any of the independent environmental variables studied. The information is useful in helping paediatricians in their daily practice for surveillance of development, as baseline information for epidemiological studies on development in our country and for cross‐cultural analysis.
Is the timing of exposure to infection a major determinant of acute lymphoblastic leukaemia in Hong Kong?
Authors: Chan Li Chong , Lam Tai Hing , Li Chi Kong , Lau Yu Lung , Li Chi Keung , Yuen Hui Leung , Lee Chi Wai , Ha Shau Yin , Yuen Patrick M. P. , Leung Nai Kong , Patheal Sherry L. , Greaves Mel F. , Alexander Freda E.
Published: March 2003

The hypothesis that protection of infants from exposure to infectious agents with delayed first exposure to one or more specific agents together contribute to the aetiology of childhood leukaemia, especially common acute lymphoblastic leukaemia (cALL), has substantial indirect support from descriptive epidemiology and case–control studies in developed Western countries. A case–control study of childhood leukaemia diagnosed at ages 2–14 years has now been conducted in Hong Kong. Cases (n = 98) formed a consecutive series of Chinese children diagnosed with
acute leukaemia; controls (n = 228) were identified following a survey using random digit dialling and required to attend for medical examination by a paediatrician. Interviews with mothers were conducted in hospital by one trained interviewer using a structured questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) are reported for exposure variables capable of serving as proxies for exposure to infection in two critical time periods: first year of life, year before reference date (diagnosis for cases, corresponding date for controls). Analyses used logistic regression with adjustment for appropriate confounders.

Change of area of residence reduced risk if during the first time period (OR = 0.47 [95% CI 0.23, 0.98]) and increased risk if during the second (OR = 3.92, [95% CI 1.47, 10.46]). Reported roseola and/or fever and rash in the first year of life reduced risk (OR = 0.33 [95% CI 0.16, 0.68]) whereas tonsillitis in the period 3–12 months before reference date increased risk (OR = 2.56 [95% CI 1.22, 5.38]). Some other proxies for exposure to infection at the critical times were associated with predicted patterns of risk but day‐care attendance failed to show predicted associations. These results provide support for the delayed exposure hypothesis in an affluent geographical setting in which population exposure to infectious agents is quite distinct from the settings of previous case–control studies.
Impact of low birthweight on subsequent fertility: population‐based register study
Authors: Kristensen Petter , Irgens Lorentz M. , Bjerkedal Tor
Published: March 2003

Adverse birth outcomes may influence a family's wish for additional children. We investigated the influence of low birthweight in live births on subsequent fertility, and estimated secular trends of such an effect in a population‐based cohort study of births arranged in consecutive sibship records in the Medical Birth Registry of Norway. We included births of order one to seven to all 587 785 mothers in Norway who had a first singleton birth in 1967–91. Associations between birthweight in 1 158 072 surviving index births of order one to six, 1967–91, and subsequent fertility (probability of another birth), 1967–97, were estimated as fertility ratios in Cox regression analysis. Giving birth to a live infant weighing < 3000 g had a negative effect on subsequent fertility, increasingly strong for decreasing birthweight. Low birthweight (<2500 g) was associated with a fertility ratio of 0.88 [95% confidence interval 0.87, 0.89]. This negative impact was stronger if the mother had also given birth to surviving children of low birthweight previously, particularly if combined with caesarean section in the most recent birth. The negative fertility effect of low birthweight grew slightly stronger between 1967 and ≈ 1980, according to year of first birth. This trend paralleled reduced population fertility in the same period. The moderate negative impact of giving birth to a live infant of low birthweight on subsequent fertility could result from the combination of reduced wish for additional children and biological subfertility.
Evaluation of immunization with gut membrane glycoproteins of Ostertagia ostertagi against homologous challenge in calves and against Haemonchus contortus in sheep
Authors: Smith  , Smith  , Pettit
Published: March 2003

Peanut and ConA lectins were used as ligands to isolate glycoproteins from detergent extracts of adult Ostertagia ostertagi membranes. As judged by their profiles following SDS‐PAGE, these fractions closely resembled the equivalents from Haemonchus contortus which are derived from the nematode intestinal cell microvillar membranes and which are highly protective when used as antigens. Groups of calves were immunized with the peanut and ConA binding fractions of Ostertagia, either as separate or pooled antigens mixed with QuilA as adjuvant. All calves, including controls immunized with adjuvant only, were challenged with a single dose of infective Ostertagia larvae and faecal egg counts were monitored for 5 weeks. In two experiments where the antigen fractions were pooled, moderate (30–50%), but statistically significant reductions in egg output were observed, but the number of worms was not diminished. No significant protection was observed in a third trial where groups of calves were immunized with peanut or ConA binding proteins given separately. Two further trials were conducted in sheep immunized with the same Ostertagia fractions but challenged with Haemonchus. Irrespective of whether they were administered separately or together, the Ostertagia antigens cross protected efficiently against Haemonchus reducing egg counts by between 81% and 97% and worm numbers by between 57% and 84%.
The role of nitric oxide in the innate resistance to microfilariae of Litomosoides sigmodontis in mice
Authors: Pfaff Alexander W. , Schulz‐Key Hartwig , Soboslay Peter T. , Geiger Stefan M. , Hoffmann Wolfgang H.
Published: March 2003

Nitric oxide (NO) has been shown to be an important effector mechanism in the defence against various pathogens, including filariae. The production of NO, as well as H2O2, is induced by the Th1 cytokine IFN‐γ. Therefore, the microfilariae (mf) of filarial nematodes, which are known to elicit the release of IFN‐γ, may be a target of NO release. In this study, we found that mf of the filarial species Litomosoides sigmodontis were resistant to the attack of H2O2, but vulnerable to NO exposure in vitro by a chemical NO donor, as well as activated macrophages. Adult worms were considerably less affected by exposure to NO. In‐vivo production of NO following injection of mf, in this and previous studies, suggested a central role in the defence to filariae. However, neither pharmaceutical inhibition of nitric oxide synthesis, nor genetic knockout of the gene for inducible nitric oxide synthase (iNOS), abrogated resistance to circulating mf in mice. Interestingly, however, iNOS‐KO mice showed higher interleukin (IL)‐2 responses and lower IL‐10 production, compared to their wild‐type counterparts. In conclusion, despite its effectiveness in vitro and the observed production of NO by ex vivo cells following infection, nitric oxide seems not to be an important factor in elimination of mf of L. sigmodontis in vivo. However, it may have a regulatory role in the immune response.
Interleukin‐5 deficient mice exhibit impaired host defence against challenge Trichinella spiralis infections
Authors: Vallance B.A. , Matthaei K.I. , Sanovic S. , Young I.G. , Collins S.M.
Published: March 2003

Enteric nematode infections are characterized by both peripheral and tissue eosinophilia. The cytokine interleukin (IL)‐5 is considered a critical factor in the proliferation and recruitment of eosinophils, however, studies suggest it plays little role in host defence, at least during primary Trichinella spiralis infections. Less is known concerning its role in host defence or in the inflammatory response that develops against challenge infections with the same parasite. We examined these questions by infecting IL‐5 deficient and wild‐type mice, with T. spiralis parasites. Both strains expelled the primary infection by day 21. Forty days after the primary infection, we challenged the mice with a second T. spiralis infection and counted tissue eosinophils and worms in the intestine. While wild‐type mice developed a large tissue eosinophilia, IL‐5 deficient mice showed little increase in eosinophil numbers within the intestine. Throughout the challenge infection, significantly larger worm burdens were recovered from IL‐5 deficient mice, and worm expulsion was also significantly slower (day 21) compared to wild‐type mice (day 14). Thus, unlike in a primary infection, IL‐5 is not only essential for the onset of intestinal eosinophilia, but also makes a significant contribution to enteric host defence during challenge T. spiralis infections.