bluuebunny/crossref_metadata_2025 huggingface dataset:
Blocking of cloned and native delayed rectifier K+ channels from visceral smooth muscles by phencyclidine
Authors: Frey B. W. , Lynch F. T. , Kinsella J. M. , Horowitz B. , Sanders K. M. , Carl A.
Published: March 2003

We investigated the effect of phencyclidine (PCP) on three native delayed rectifier K+ currents and three channels cloned from canine and human circular colonic myocytes using voltage‐clamp techniques. Native delayed rectifier K+ current in canine circular colon is composed of at least three components: (i) a rapidly activating, 4‐aminopyridine‐sensitive component (termed IdK(f)); (ii) a slowly activating, tetraethylammonium (TEA)‐sensitive component (IdK(s)); and (iii) a rapidly activating, TEA‐sensitive component, which has a steady‐state inactivation curve shifted towards more negative potentials (IdK(n)). PCP blocked all three components with EC50 values of 45, 27 and 59 μmol L–1, respectively. Blocking was neither use‐dependent nor voltage‐dependent. Delayed rectifier K+ channels cloned from canine (Kv1.2, Kv1.5) and from human (Kv2.2) colon were expressed in Xenopus oocytes. PCP blocked all three currents with similar potency. In contrast, PCP (up to 10–4 mol L–1) did not reduce the magnitude of Ca2+‐dependent outward current of large conductance Ca2+‐activated K+ channels (BK channels).
Prolonged recording of oesophageal and lower oesophageal sphincter pressure using a portable water‐perfused manometric system
Authors: Van Herwaarden M. A. , Samsom M. , Akkermans L. M. A. , Smout A. J. P. M.
Published: March 2003

The aim of our study was to investigate the recording fidelity of a water‐perfused micromanometric catheter with incorporated sleeve combined with a newly developed portable water‐perfused manometric system for pharyngeal, oesophageal and lower oesophageal sphincter (LOS) pressure recording. The system’s performance was assessed in prolonged recordings in ambulant gastro‐oesophageal reflux disease (GORD) patients. Eighty 24‐h studies in GORD patients, carried out with the perfused portable manometric system, were evaluated. Twelve of these recordings were analysed in detail in order to compare oesophageal and LOS motor patterns with those described previously. Paired 2‐h manometric recordings of the pharynx, oesophagus, LOS and stomach, using the new system and a conventional perfused stationary manometric system, were performed in eight healthy subjects. With the portable manometric system oesophageal contractions, transient LOS relaxations, swallow‐associated prolonged LOS relaxations and LOS pressures were recorded with equal fidelity to the conventional manometric system. Recordings obtained with the portable system showed meal‐related and diurnal variations in oesophageal and LOS variables that were similar to these found in studies using conventional equipment. The new manometric system, consisting of a perfused micromanometric catheter with incorporated sleeve and a portable perfusion system, enables prolonged studies on oesophageal and LOS motor patterns in ambulant subjects.
Antral motility measurements by magnetic resonance imaging
Authors: Marciani L. , Young P. , Wright J. , Moore R. , Coleman N. , Gowland P. A. , Spiller R. C.
Published: March 2003

Magnetic resonance imaging has been recently proposed as a promising, noninvasive technique to assess the motility of the gastric antrum. However, so far the reproducibility and dependence on test meal composition has not been evaluated. In this study, snapshot echo‐planar magnetic resonance imaging was used to measure the frequency, propagation speed and percentage occlusion of antral contractions in 28 healthy volunteers. They were fed either liquid (n=12), mixed liquid/solid (n=8) or mixed viscous/solid (n=8) nutrient (1350 kJ) test meals, and a total of 208 motility measurements were performed. No effect of meal type on antral motility parameters was observed. Antral contraction frequency was 3.0 ± 0.2 min−1 (mean ± SD, n=164), propagation speed was 1.6 ± 0.2 mm s−1 (n=164) and the percentage occlusion was 58 ± 14% (n=76). Overall, 21% of measurements did not provide useful antral motility data, because, in the supine position, the antrum was not filled by the test meal. Simple methods to overcome this and reduce scanning time to a minimum are proposed. The results show that the noninvasive magnetic resonance imaging evaluation of antral motility is accurate and reproducible and has potential to become a standard tool for such investigations.
Matrix metalloproteinases MMP‐2 and MMP‐9 in denervated muscle and injured nerve
Authors: Kherif  , Dehaupas  , Lafuma  , Fardeau  , Alameddine
Published: March 2003

Nerve crush or axotomy results in a transient or long‐term denervation accompanied by remodelling in nerve, muscle and neuromuscular junctions. These changes include an increased turnover of several extracellular matrix molecules and proliferation of Schwann cells in injured nerves. Given the role of matrix degrading metalloproteinases MMP‐2 and MMP‐9 (gelatinases‐type IV collagenases) in extracellular matrix remodelling, we investigated their regulation and activation in denervated muscles and injured nerves in mice. For this, immunofluorescence using MMP‐2 and MMP‐9 antibodies was carried concomitantly with gelatin zymography and quantification of gelatinase activity using [3H]‐gelatin substrate. Results show that in normal mouse muscles MMP‐2 and MMP‐9 are localized at the neuromuscular junctions, in Schwann cells and the perineurium of the intramuscular nerves. In denervated mouse muscles, MMP‐2 immunolabelling persists at the neuromuscular junctions but decreases in the nerves whereas MMP‐9 immunolabelling persists at the neuromuscular junctions but is enhanced in degenerated intramuscular nerves. Denervated muscles did not show any significant change of gelatinolytic activity or expression pattern, while injured nerves exhibited a transient increase of MMP‐9 and activation of MMP‐2. In conclusion, this study demonstrates that MMP‐2 and MMP‐9 are expressed at mouse neuromuscular junctions and that their localization and expression pattern appear not to be modified by denervation. Their modulation in injured nerves suggests they are involved in axonal degeneration and regeneration.
Morphological correlates of neurological dysfunction in macaques infected with neurovirulent simian immunodeficiency virus
Authors: Raghavan  , Cheney  , Raymond  , Joag  , Stephens  , Adany  , Pinson  , Li  , Marcario  , Jia  , Wang  , Foresman  , Berman  , Narayan
Published: March 2003

The pattern of neurological disease caused by human immunodeficiency virus (HIV) infection of the central nervous system (CNS) was investigated using a macaque model of acquired immune defiency syndrome (AIDS). Seven of nine macaques inoculated with neurovirulent simian imunodeficiency virus (SIVmac ) developed AIDS within 3 months. Four of these had clinically obvious neurological disease and extensive conduction defects in the form of latency increases in evoked potential (EP) responses. Neuropathologically, all four animals had disseminated white matter disease in the form of multifocal, perivascular and nodular parenchymal mononuclear cell infiltrates, along with extensive involvement of the cortical grey matter, leptomeninges and intracranial portions of cranial nerves. A brisk multinucleated giant cell (MGC) response was a frequent accompaniment in the affected areas. Three of the animals in this group also showed spongiform vacuolation in the occipital grey matter, a lesion described only rarely in HIV encephalitis. In the remaining three animals, there was only minimal evidence of overt neurological impairment or conduction defects. These animals had only mild to moderate neuropathological changes and lesions were virtually confined to the white matter regions of the brain. MGC responses were rare or absent in the CNS of these animals. Neuropathological findings in this SIVmac model have therefore shown good correlation with the severity of clinical and neurophysiological changes, and are reminiscent of HIV‐1 encephalitis. More importantly, white matter involvement was a consistent finding in the affected macaques, regardless of the duration and severity of disease, or type of virus inoculated, suggesting an unusual susceptibility for lentiviral infection in these regions of the macaque CNS.
Changes in expression of NMDA receptor subunits in the rat lumbar spinal cord following neonatal nerve injury
Authors: Virgo L. , Dekkers J. , Mentis G. Z. , Navarrete R. , De Belleroche J.
Published: March 2003

The vulnerability of motoneurones to glutamate has been implicated in neurological disorders such as amyotrophic lateral sclerosis but it is not known whether specific receptor subtypes mediate this effect. In order to investigate this further, the expression of N‐methyl‐ d‐aspartate (NMDA) receptor subunits was studied during the first three post‐natal weeks when motoneurones are differentially vulnerable to injury following neonatal nerve crush compared to the adult. Unilateral nerve crush was carried out at day 2 after birth (P2) which causes a decrease of 66% in motoneurone number by 14 days (P14). To study receptor expression in identified motoneurones, serial section analysis was carried out on retrogradely labelled common peroneal (CP) motoneurones by combined immunocytochemistry and in situ hybridization (ISH). mRNA levels were also quantified in homogenates from lumbar spinal cords in which the side ipsilateral to the crush was separated from the contralateral side. The NR1 subunit of the NMDA receptor was widely distributed in the spinal cord being expressed most strongly in motoneurone somata particularly during the neonatal period (P3–P7). The NR2 subunits were also expressed at higher levels in the somata and dendrites of neonatal motoneurones compared to older animals. NR2B mRNA was expressed at low to moderate levels throughout the studied period whereas NR2A mRNA levels were low until P21. Following unilateral nerve crush, an initial decrease in NR1 mRNA occurred at one day after nerve crush (P3) in labelled CP motoneurones ipsilateral to the crush which was followed by a significant increase in NR1 subunit expression at 5 days post‐injury. This increase was bilateral although reaching greater significance ipsilateral to the crush compared with sham‐operated animals. A significant increase in NR1 and NR2B mRNA post injury was also detected in spinal cord homogenates. In addition, the changes in levels of NR1 and NR2B mRNA were reflected by comparable bilateral changes at P7 in receptor protein determined by quantitative immunocytochemical analysis of NR1 and NR2 subunit expression in identified CP motoneurones indicating a co‐ordinated regulation of receptor subunits in response to injury.
A comparison of two methods of follow‐up in a trial of prophylactic volume expansion in preterm babies
Authors: Fooks Jean , Fritz Susan , Tin Win , Yudkin Patricia , Johnson Ann , Elbourne Diana , Hey Edmund
Published: March 2003

The outcome at age 2 years of preterm babies recruited into a three‐arm randomised controlled trial of prophylactic volume expansion was ascertained in two ways: from a neurodevelopmental assessment performed by a paediatrician and from responses on a brief questionnaire completed by the child's personal health visitor. Of 776 babies recruited into the trial, 604 survived to the age of 2 years and the findings of a paediatric assessment were available for all survivors. Questionnaires were sent to the health visitors of 601 of the survivors; 513 (85.4%) were returned. There was sufficient information on the returned questionnaires to categorise 449 of the children as normal, impaired, moderately disabled or severely disabled. We were unable to detect a response bias by severity of disability. Agreement on individual questions ranged between 86.3% and 98.4%. There was some mismatch in the reporting of vision (weighted kappa = 0.71) and hearing (weighted kappa = 0.73), with differences in perception of level of severity of sensory loss. Health visitors tended to underestimate the child's functional level compared with the paediatrician. However, of 56 children classified as severely disabled by the paediatrician, 48 were classified similarly and eight as moderately disabled on the basis of the questionnaire. The end point of the trial was death or severe disability at 2 years of age. There was close similarity in the trial results whether based on the paediatric assessment or on the questionnaire. Further refinement of the questionnaire is needed, but this methodology may be useful in ascertaining the frequency of severe disability in large cohorts of babies.
Visual impairment in children: prevalence, aetiology and care, 1976–85
Authors: Arnaud Catherine , Baille Marie‐Florence , Grandjean Hélène , Cans Christine , Du Mazaubrun Christiane , Rumeau‐Rouquette Claude
Published: March 2003

Visual impairment (corrected visual acuity in the best eye < 0.3) was evaluated in a retrospective study of 296 children born between 1976 and 1985 and recruited from three French departments. For children younger than 9 years, the overall prevalence was 0.80 per 1000 and that of blindness was 0.28 per 1000. No decrease in prevalence was noted over this decade. The most common aetiologies were antenatal factors (48%), which were observed mainly in the cases of poor vision, and perinatal factors (27%), which were more common in the cases of blindness. Fifty‐six per cent of the children had an additional severe handicap. The most common association was with motor impairment and mental retardation. The mean age of first medical care (3.1 years) did not change over the decade: 2.0 years for children with an associated handicap, 2.9 years for cases of isolated blindness and 5.1 years for cases of isolated poor vision. Among children with isolated visual impairment, there was a significantly higher percentage of scholastic underachievers in those presenting after the age of 5 years (39.3% vs. 14.6%).
New epidemiological problem in Poland: vertical transmission of human immunodeficiency virus
Authors: Lech  , Szczepanska‐Putz
Published: March 2003

New diagnostic, prophylactic and treatment perspectives in HIV infection of the fetus and newborn is a challenge for health services in Poland. In view of these advances, the ascertainment of HIV status of all pregnant women is important both for individuals and for the health services. By law, laboratory HIV testing in Poland can be performed only on a voluntary basis. All newly diagnosed cases of AIDS and HIV infections are anonymously reported to the National Institute of Hygiene in Warsaw. There are no clear data about vertical transmission of HIV infection in Poland mostly because of the unknown number of women who are positive at delivery. Almost all our data were collected from Polish Regional AIDS/HIV Diagnostic and Therapeutic Centres. During the period 1986–95, 88 children were delivered by HIV‐positive women and vertical transmission occurred in 15 cases.
Breast feeding and later psychosocial adjustment
Authors: Fergusson  , Woodward
Published: March 2003

The relationship between the duration of breast feeding and psychosocial outcomes measured between the ages of 15 and 18 years was examined in a birth cohort of 999 New Zealand children. During the period from birth to 1 year, information was collected on maternal breast‐feeding practices. Between the ages of 15 and 18 years, sample members were assessed using a range of psychosocial measures, including measures of the quality of parent–child relationships, juvenile delinquency, substance abuse and mental health. Children who were breast fed for a longer duration were more likely to report higher levels of parental attachment and tended to perceive their mothers as being more caring and less overprotective towards them compared with bottle‐fed children. No association was found between the extent of breast feeding and subsequent rates of juvenile offending, substance use and mental health in later life. Mothers who elected to breast feed were also more likely to be older, better educated, living with a partner, less likely to smoke during pregnancy, and to come from advantaged socio‐economic backgrounds characterised by better living standards and a higher family income. Rates of breast feeding were also greater among mothers who gave birth to a first‐born child of higher birthweight. After adjustment for these maternal and perinatal factors, the duration of breast feeding remained significantly associated with adolescent perceptions of maternal care, with increasing duration of breast feeding being associated with higher levels of perceived maternal care during childhood. It is concluded that: (a) it is unlikely that breast feeding is associated with reduced risks of psychiatric disorder in later life; (b) breast feeding may lead to closer parent–child relationships; and (c) it is unlikely that the association between breast feeding and cognitive development is mediated by intervening processes relating to improved psychosocial adjustment in breast‐fed children.
The relationship between Caesarean section and neonatal mortality in very‐low‐birthweight infants born in Washington State, USA
Authors: Jonas  , Khalid  , Schwartz
Published: March 2003

We examined the associations between Caesarean section and neonatal mortality in singleton liveborn very‐low‐birthweight (VLBW) infants (500–1499 g) born during 1984–95 in Washington State, USA, using data from the Washington State birth certificate files. The infants included in this study had no life‐threatening congenital malformations and had not been delivered by a repeat Caesarean without a trial of labour (n = 5182). For infants weighing 500–749, 750–999, 1000–1249 and 1250–1499 g, the neonatal mortality rates were 57.8%, 18.6%, 9.7% and 4.7%, respectively, and the Caesarean section rates were 28.4%, 47.8%, 48.0% and 44.6%. The adjusted odds ratios (ORs) for neonatal death associated with Caesarean section were 0.55 [95% confidence interval 0.38, 0.78] for the 500–749 g infants (n = 1059), and 1.15 [0.91, 1.45] for the larger (750–1499 g) infants, after adjustment for birth year, type of hospital, birthweight, presence or absence of labour, breech/malpresentation, and other obstetric indications for Caesarean section (prolapsed cord, placenta praevia, eclampsia, pre‐eclampsia and chronic hypertension). However, when the larger (750–1499 g) vertex‐presenting (n = 3248) and breech/malpresenting (n = 809) infants were considered separately, the adjusted ORs were 1.42 [1.05, 1.91] and 0.37 [0.23, 0.58] respectively. In contrast, among infants weighing 500–749 g, the ORs were not modified by presentation. The results were similar when we restricted analyses to infants without the above obstetric indications for Caesarean section. Because such an observational study is liable to unmeasurable biases and incomplete reporting of obstetric complications, these OR estimates may be subject to residual confounding. In their present state, these recent population‐based data support the view that Caesarean sections do not enhance the neonatal survival of larger (> 750 g) VLBW babies when obstetric complications are absent. The possibility of a protective effect of Caesarean section on the survival of breech/malpresenting infants and infants weighing 500–749 g deserves further studies.
Study methodology. Using genetic epidemiology to study Rett syndrome: the design of a case–control study
Authors: Leonard Helen , Fyfe Susan , Dye Danielle , Leonard Seonaid
Published: March 2003

Rett syndrome is a neurological disorder that is seen almost exclusively in females. Although generally considered to have a genetic basis, the underlying mechanism remains obscure. One favoured hypothesis is that the syndrome is an X‐linked dominant disorder, lethal or non‐expressed in males. Genealogical research has also suggested that the mode of transmission in Rett syndrome may involve a pre‐mutation which over several generations is converted to a full mutation. Geographical clustering has been reported, and it has also been proposed that Rett syndrome is a clinically variable condition and that other neurological disorders may be occurring more commonly in families with Rett syndrome. Other studies have found an apparent increase in intellectual disability and seizures in the extended families of girls with Rett syndrome. The science of genetic epidemiology can be used to identify familial aggregation, which is the clustering of a disorder within a family. We have used a case–control study design to investigate both fetal wastage and familial aggregation of other disorders in families of girls with Rett syndrome. The Australian Rett Syndrome Database provided the source of cases, and control probands were girls of a similar age with normal development. This paper describes the methodology for a case–control study of this rare condition using pedigree data and discusses issues in the collection and evaluation of such data. The use of a control population is an important feature. Both the strengths and the shortcomings of our design are identified, and recommendations are made for future research.
Birthweight and infant mortality in Bulgaria’s transition crisis
Authors: Carlson Elwood , Tsvetarsky Sergey
Published: March 2003

Between 1988 and 1991, years of political and economic crisis, Bulgaria reported a 25% increase in infant mortality. From 1991 to 1995, the rate then dropped slightly. Analysis of detailed unpublished vital statistics shows that the reported increase could not have been a result of more complete reporting of early neonatal mortality for very low‐weight births. Old reporting practices continue unchanged. Rather, these statistics reveal an increase in the proportion of low‐weight births, combined with rising death rates, particularly for low‐weight births in the postneonatal period, but also for normal‐weight babies.
Seasonal variation in the prevalence of persistent otitis media with effusion in one‐year‐old infants
Authors: Rovers M.M. , Straatman H. , Zielhuis G.A. , Ingels K. , Van Der Wilt G‐J.
Published: March 2003

The objective of this population‐based cohort study was to evaluate the prevalence of persistent otitis media with effusion (OME) and its seasonal variation in 12‐month‐old infants. All 30 099 infants born in the eastern part of The Netherlands between 1 January 1996 and 1 April 1997 were invited for hearing screening, comprising a protocol of three possible tests. Those who failed all three screening tests were referred to an ENT clinic for examination. Prevalences (i.e. the probability that a child would fail all the screening tests) were calculated by searching for the best logistic model for the first, second and third screening test as well as for the visit to an ENT department. By multiplying the prevalences found by the different models with each other, a prevalence was calculated that accounted for increasing age and the timing of the successive hearing tests. Furthermore, 95% confidence intervals were calculated for this age‐season‐corrected prevalence. When all the children attended the hearing tests at 9, 10, 11 and 12 months of age and when the number of births was the same in all months, the overall prevalence was 4.8%[95% CI 4.3, 5.2]. The highest prevalence (8.0%) was found in April, and the lowest (1.5%) in October. Rates of bilateral OME during the late winter months were twice as high as those during the late summer.
Tocolytic therapy for preterm labour: assessing its potential for reducing preterm delivery
Authors: West Suzanne L. , Yawn Barbara P. , Thorp John M. , Korhonen Maarit J. H. , Savitz David A. , Guess Harry A.
Published: March 2003

Preterm labour (PTL) is a major contributor to preterm delivery (PTD) but delivery is often not preventable by current therapies. We conducted this study to determine the proportion of women with PTL who were and who were not candidates for tocolytic therapy. The cohort comprised residents of Olmsted County, Minnesota who delivered at >20 weeks’ gestation in 1985–94 and who experienced PTL. Medical records were abstracted to identify episodes of PTL, its treatment and outcome. We developed an algorithm that accounted for gestation at delivery and pregnancy complications to determine the proportion of pregnancies complicated by PTL that were candidates for tocolytic therapy. Of 651 pregnancies complicated by PTL, a 50% probability sample, stratified by delivery year, were selected and abstracted. The cumulative incidence of PTL ranged from 3.6 to 6.4 per 100 deliveries of live or stillborn infants. Tocolysis was not contraindicated for 49.4% of all women with PTL and for a third of women with only one PTL episode. Delivery was delayed to >35 weeks in 53.8% of candidates for tocolysis. Only an additional 11.7% of women with one or more PTL episodes could have had their PTD delayed beyond 35 weeks if a perfect tocolytic therapy had been available. Many pregnancies complicated by PTL occurred at ≥35 weeks or involved maternal or obstetric factors that contraindicated tocolytic medications. The maximum incremental benefit that could be expected of a new safe and efficacious tocolytic therapy would be to reduce current PTD rates resulting from PTL by about 12%.
Delivery method and self‐reported postpartum general health status among primiparous women
Authors: Lydon‐Rochelle Mona T. , Holt Victoria L. , Martin Diane P.
Published: March 2003

Despite nearly four million deliveries in the United States each year, minimal information exists on unintended health consequences following childbirth, particularly in relation to delivery method. The purpose of this study was to assess the association between method of delivery and the general health status, sexual, bowel and urinary functioning of primiparous women as measured at 7 weeks postpartum. Data from the Statewide Obstetrical Review of Quality System (StORQS) Survey of Maternity Care in Washington State were analysed. Participants included all primiparous women with a delivery of a singleton infant discharged alive between August and December 1991 from 10 non‐federal short‐stay hospitals who responded to the StORQS Survey of Maternity Care (n = 971). The main outcome measures included the modified Medical Outcomes Study 36‐Item Short‐Form Health Survey and self‐reported sexual, bowel and urinary functioning. At 7 weeks postpartum, women who had caesarean or assisted vaginal deliveries reported significantly lower postpartum general health status scores than women with unassisted vaginal delivery. Additionally, women with assisted vaginal delivery reported significantly worse sexual, bowel and urinary functioning. Our results suggest that more careful attention to the postpartum general health and sexual functioning of women with caesarean and assisted vaginal delivery may be merited.
Atmospheric pressure and sudden infant death syndrome in Cook County, Chicago
Authors: Campbell Michael J. , Julious Steven A. , Peterson Charles K. , Tobias Aurelio
Published: March 2003

We investigated daily deaths from sudden infant death syndrome (SIDS) in Cook County, Chicago, from 1 January 1986 to 31 December 1990. The daily SIDS rate was 0.54 deaths/day. Mean daily atmospheric pressure ranged from 952 to 1007 mb. We found a weak link with barometric pressure, whereby an increase of 10 mb was associated with an increased risk of 12% [95% CI 0.1%, 24%]. Cross‐tabulation revealed that the highest SIDS rates were associated with a drop from high to low pressure. Possible reasons for this are discussed.
The reliability of perinatal and neonatal mortality rates: differential under‐reporting in linked professional registers vs. Dutch civil registers
Authors: Anthony Sabine , Bruin Karin M. van der Pal‐de , Graafmans Wilco C. , Dorrepaal Caroline A. , Borkent‐Polet Marion , Hemel Oscar J. S. van , Jansen Frans H. M. , Ouden A. Lya den
Published: March 2003

Official Dutch perinatal mortality rates are based on birth and death certificates. These civil registration data are not detailed enough for international comparisons or extensive epidemiological research. In this study, we linked and extrapolated three national, incomplete, professional registers from midwives, obstetricians and paediatricians, containing detailed perinatal information. This linkage and extrapolation resulted in one detailed professional database which is representative of all Dutch births and from which gestational age‐specific perinatal mortality rates could be calculated. The reliability of these calculated mortality rates was established by comparing them with the rates derived from the national civil registers. The professional database reported more perinatal deaths and fewer late neonatal deaths than the civil registers. The under‐reporting in the civil registers amounted to 1.2 fewer perinatal deaths per 1000 births and was most apparent in immature newborns. We concluded that under‐reporting of perinatal and neonatal deaths depends on the data source used. Mortality rates for the purpose of national and international comparison should, therefore, be defined with caution. This study also demonstrated that combining different incomplete professional registers can result in a more reliable database containing detailed perinatal information. Such databases can be used as the basis for extensive perinatal epidemiological research.
The increase in very‐low‐birthweight infants in Germany: artefact or reality?
Authors: Nolte Ellen , Koupilová Ilona , McKee Martin
Published: March 2003

Earlier findings have shown that after unification with the Federal Republic of Germany (FRG) in October 1990 the proportion of very‐low‐birthweight infants in the former German Democratic Republic (GDR) increased. This study seeks to explore this observation in more detail at the regional level. The analysis of aggregate data of live births in Germany between 1991 and 1997 shows an increasing proportion of very‐low‐birthweight infants as well as a general trend towards heavier babies in both east and west. The growing proportion of live born infants at very low birthweights in the east, however, seems to be due, in part, to increased registration, most likely reflecting the introduction of the more comprehensive (western) definition of a live birth with unification in October 1990. A fairly distinct east–west pattern in the birthweight distribution present in 1991 had almost disappeared by 1997 and given way to a north–south one.
Growth parameters in newborns with hyperphenylalaninaemia
Authors: Zaffanello Marco , Zamboni Giorgio , Tatò Luciano
Published: March 2003

To understand the effects of hyperphenylalaninaemia on fetal growth, we studied growth parameters (weight, length and head circumference) of 23 phenylketonuric (PKU) and 60 hyperphenylalaninaemic (HPA) newborns from healthy mothers and of 1853 healthy neonates from north‐east Italy.

A comparison of the growth parameters for both PKU and HPA newborns, as well as for controls, showed a statistically significant higher percentage of PKU and HPA patients with reduced body length and cranial circumference (P < 0.05 for both parameters in affected neonates). The z‐scores for all growth parameters regarding both PKU and HPA newborns and controls, and between PKU and HPA newborns according to the Mann–Whitney non‐parametric test, were statistically significantly lower in PKU newborns than in controls; in contrast, only body length was significantly lower in HPA newborns than in controls (P < 0.01). A comparison of growth parameter z‐scores using the Kruskal–Wallis test for PKU, HPA and control newborns showed that both body length (P < 0.01) and cranial circumference (P < 0.05) were significantly lower in both groups of affected neonates.

Our results showed intrauterine growth retardation for both PKU and HPA newborns. Body length and cranial circumference appeared to be more important than birthweight in evaluating growth of PKU and HPA newborns.
Down's syndrome and paternal age in Norway
Authors: Kazaura Method R. , Lie Rolv T.
Published: March 2003

There is strong evidence for an effect of maternal age on the risk of Down's syndrome. An effect of paternal age has been suspected, but so far neither confirmed nor completely excluded. Large population‐based data that allow detailed adjustment for maternal age are needed for a definitive analysis of the paternal age effect. We used data from the Medical Birth Registry of Norway recorded from 1967 to 1998. A total of 1 738 852 children were included in the analysis. A total of 10.3 per 10 000 newborns had Down's syndrome. The data were fitted to logistic regression models with careful control for maternal age, birth calendar year and place of birth. When maternal age was adjusted for using categories of 5‐year intervals, residual confounding still resulted in a strong effect of paternal age. However, when the shape of the effect of maternal age was well captured by the model, the estimated effect of paternal age was weak (1.11‐fold increased risk per 10 years of paternal age, 95% CI of odds ratio 0.99, 1.22) and not statistically significant.
A DNA vaccine protects mice against the rickettsial agent Cowdria ruminantium
Authors: NYIKA  , MAHAN  , BURRIDGE  , MCGUIRE  , RURANGIRWA  , BARBET
Published: March 2003

A DNA vaccine (VCL1010/MAP1) containing the major antigenic protein 1 (MAP1) gene of Cowdria ruminantium, driven by the human cytomegalovirus (HCMV) enhancer‐promoter, was injected intramuscularly into 8–10 week‐old female DBA/2 mice after treating them with 50 μl/muscle of 0.5% bupivacaine three days previously. Up to 75% of the immunized mice seroconverted and reacted with C. ruminantium antigen blots. Splenocytes from immunized mice, but not from control mice, proliferated in response to the recombinant MAP1 and to C. ruminantium antigens in in vitro lymphocyte proliferation tests. These proliferating cells secreted IFN‐gamma and IL‐2 at concentrations ranging from 610 pg/ml to 1290 pg/ml and from 152 pg/ml to 310 pg/ml, respectively. Only up to 45 pg/ml and 42 pg/ml of IFN‐gamma and IL‐2, respectively, were detected in supernatants of splenocytes from control mice. In experiments testing different VCL1010/MAP1 DNA vaccine dose regimens (25–100 μg/dose, two or four immunizations), survival rates of 23% to 88% (35/92 survivors/total in all VCL1010/MAP1 immunized groups) were observed on challenge with a lethal dose of cell culture‐derived C. ruminantium organisms. In contrast, survival rates of 0% to 3% (1/144 survivors/total in all control groups) were recorded for control mice. This study demonstrates that MAP1 is a protective antigen and validates the concept of DNA vaccines against heartwater.
Toxocara infestations in humans: symptomatic course of toxocarosis correlates significantly with levels of IgE/anti‐IgE immune complexes
Authors: OBWALLER A. , JENSEN‐JAROLIM E. , AUER H. , HUBER A. , KRAFT D. , ASPÖCK H.
Published: March 2003

Infestations of humans with the parasitic nematode T. canis are common in both developing and industrialized countries. Most infestations induce a clinically inapparent course of infection, however, severe clinical manifestations, i.e. visceral larva migrans (VLM) or ocular larva migrans (OLM) syndromes are observed. To find an explanation for the different courses of toxocarosis we examined several serological parameters: the expression of (i) specific IgE (Immunoblot, IB), (ii) specific IgG subclasses (IgG1–4, ELISA) and the formation of (iii) IgE/anti‐IgE immune complexes. Serum samples were obtained from persons with symptomatic (VLM, OLM) and asymptomatic course (AS) of the infestation. As antigen, T. canis excretory/secretory (TES) antigen from L3 larvae was used. Reactivity of IgE against SDS‐PAGE separated TES antigens was marginally higher in toxocarosis patients (35%) than in asymptomatics (24%), but without statistical significance. TES‐specific IgG (1–4), predominant subclass in all three groups was IgG1, followed by IgG2, IgG4 and IgG3. Subclasses IgG1, 2, 4 showed significant differences between patients with VLM associated symptoms and asymptomatic persons (P < 0.001) but not between patients with OLM associated symptoms and asymptomatics. Significantly elevated levels of IgE/anti‐IgE immune complexes were detected in sera of patients with symptomatic course of the disease, both VLM and OLM (P < 0.001). Whereas specific IgG may act via antibody dependent cell‐mediated cytotoxicity mechanisms, IgE/anti‐IgE immune complexes might possibly participate in VLM and OLM by inducing type III hypersensitivity.
The immune response and immunopathology in infection with Schistosoma mansoni: a key role of major egg antigen Sm‐p40
Authors: STADECKER MIGUEL J. , HERNANDEZ HECTOR J.
Published: March 2003

The immune response and related granulomatous inflammation in infection with Schistosoma mansoni are ultimately dependent on SEA‐sensitized CD4+ Th cells and comprise multiple pathways variously involving the activation and recruitment of different cell populations and the production of different inflammatory cytokines, all under the influence of regulatory genetic factors. The spontaneous down‐regulation of granuloma formation (immunomodulation), in turn, is a well‐known phenomenon, but the full extent of its precipitating factors is still uncertain. This review describes a pathway leading to immunomodulation that features at its centre the down‐regulatory cytokine IL‐10. This mechanism is attractive because it offers a cogent correlation between findings in the laboratory and those displayed by patients affected with the disease. The Sm‐p40 antigen, a major component of schistosome eggs, elicits a strong CD4+ Th cell response in H‐2k mice that correlates with intense granuloma formation; in contrast, its immunogenicity is relatively minor during infection of other mouse strains that develop smaller granulomas. Of great interest is that the Sm‐p40 antigen only elicits a Th‐1 type cytokine response, a phenotype that remains constant even as the overall response to SEA shifts to a Th‐2 type. The Sm‐p40 molecule has a dominant epitope that is the target of CD4+ Th cells from infected H‐2k mice; indeed, a minimal peptide that bears the epitope binds to I‐Ak. The importance of pursuing a systematic elucidation of the major egg antigens, resides in the exciting possibility of specifically desensitizing the CD4+ Th cells that mediate granuloma formation, which may achieve meaningful prevention or amelioration of clinical disease.
Immunoregulation in experimental murine Trypanosoma congolense infection: anti‐IL‐10 antibodies reverse trypanosome‐mediated suppression of lymphocyte proliferation in vitro and moderately prolong the lifespan of genetically susceptible BALB/c mice
Authors: UZONNA  , KAUSHIK  , GORDON  , TABEL
Published: March 2003

We infected highly susceptible BALB/c and relatively resistant C57BL/6 mice with cloned Trypanosoma congolense and followed the effects of these infections on the circulating parasite numbers, mouse mortality and cytokine expression. C57BL/6 mice controlled their parasitaemia and survived for up to 163 ± 12 days, while BALB/c mice could not control their parasitaemia and succumbed to the infection within 8.4 ± 0.5 days. Susceptible BALB/c mice had dramatically higher plasma levels of IL‐10 than the resistant C57BL/6 mice from day 7 forward. This was preceded by an earlier and higher level induction of splenic IL‐10 messenger RNA (mRNA) expression in the infected BALB/c mice. There was a strong negative correlation between the splenocyte proliferative responses to Concanavalin‐A (Con‐A) and their production of IL‐10 in these infected BALB/c mice. Co‐treatment of the Con‐A‐stimulated spleen cell cultures with monoclonal anti‐IL‐10 antibodies, but not isotype‐matched control antibodies, could completely reverse this suppression of the splenocyte proliferative response. Finally, in three experiments, anti‐IL‐10 antibody treatment in vivo reduced the peak circulating parasitaemia of infected BALB/c mice by 43% and increased their median survival periods by 38% relative to isotype‐matched control antibody‐treated mice.
Nitric oxide production in vervet monkeys (Cercopithecus aethiops) infected with Trypanosoma brucei
Authors: STERNBERG  , NJOGU MAINA  , GICKHUKI  , NDUNG'U
Published: March 2003

A retrospective study of nitrate concentration in serum and cerebrospinal fluid (CSF) from vervet monkeys (Cercopithecus aethiops) infected with Trypanosoma brucei was undertaken. Serum nitrate was significantly elevated in parasitaemic animals. CSF nitrate detection correlated with the presence of parasites in the CNS. The results provide evidence for the production of nitric oxide (NO) in response to infection in a primate model of human African trypanosomiasis and provide the basis for the use of such a model in studies of the immunopathological effects of NO in human trypanosomiasis.
Amelioration of virulent Babesia bovis infection in calves by administration of the nitric oxide synthase inhibitor aminoguanidine
Authors: GALE  , WALTISBUHL  , BOWDEN  , JORGENSEN  , MATHESON  , EAST  , ZAKRZEWSKI  , LEATCH
Published: March 2003

Calves undergoing initial infection with a virulent strain of the haemoprotozoan parasite Babesia bovis were treated with aminoguanidine (AG), an inhibitor of the inducible form of nitric oxide synthase (iNOS). The mean maximum parasitaemia of the AG treated calves was significantly lower than that of the control cattle. In addition, the febrile response and decrease in packed cell volume (PCV) observed during acute infection were significantly ameliorated in the AG treated cattle relative to the controls. However, AG had no effect on the multiplication of B. bovis in the microaerophilous stationary‐phase (MASP) in‐vitro culture system. These results provide evidence of a role for nitric oxide (NO) produced in response to acute infection in the pathology of bovine babesiosis.
T cell responses in coinfection with Onchocerca volvulus and the human immunodeficiency virus Type 1
Authors: SENTONGO  , RUBAALE  , BÜTTNER  , BRATTIG
Published: March 2003

Onchocerca volvulus and the human immunodeficiency virus (HIV) are two immunocompromising infectious agents of major public health concern in Uganda. To examine the effect of coinfection with O. volvulus and HIV on cellular immune responses, lymphocyte proliferative responses and cytokine production of peripheral blood mononuclear cells (PBMC) from persons infected with O. volvulus with and without HIV type 1 infection were compared. Proliferation of PBMC to PHA and tuberculin (PPD) in coinfection was less (P = 0.08, P < 0.01) than in O. volvulus infection. O. volvulus extract stimulated lymphocyte proliferation in microfilaria‐negative and HIV‐negative O. volvulus infection while only an inconspicuous response was observed in microfilaria‐negative coinfection. After stimulation of PBMC with PPD, the production of interferon‐γ (IFN‐γ), interleukin (IL)‐4 and IL‐5—demonstrated in O. volvulus infection—were reduced in coinfection with HIV (P < 0.01). While both groups failed to produce IFN‐γ in response to O. volvulus extract, only O. volvulus infected persons generated pronounced IL‐5 and low IL‐4 levels (0.01 > P = 0.02). The cellular immune responses in coinfection suggested an HIV‐related lack of specific reactivity to O. volvulus antigen and impairment of IL‐4 and IL‐5 production in addition to the lack of IFN‐γ response on antigenic stimulation.
Immunoblot analysis of a 10 kDa antigen in cyst fluid ofTaenia soliummetacestodes
Authors: YANG  , CHUNG  , YUN  , KONG  , ITO  , MA  , LIU  , LEE  , KANG  , CHO
Published: March 2003

The diagnostic value of a 10 kDa subunit of 150 kDa protein in cyst fluid (CF) ofTaenia soliummetacestodes was evaluated. Immunoblot analysis revealed that most sera from patients with neurocysticercosis recognized the 10 kDa subunit strongly (209/217 cases, 84.6%), while a few sera from individuals with other parasitic diseases including alveolar echinococcosis (AE, 2/20, 10%) and cystic echinococcosis (CE, 2/25, 8%) showed faint reactions. Sera of cases with other parasitic diseases, especially AE and CE, exhibited cross reactions against other bands in CF. Both differential immunoblot and immunoprecipitation analyses showed that the 10 kDa subunit was the most specific to cysticercosis and highly antigenic, whereas other components at 20–40, 64, 95 and 106 kDa in CF were cross‐reactive. IgG subclass ELISA and immunoblot demonstrated that both IgG4 and IgG1 reactions were predominant in neurocysticercosis and recognized the 10 kDa.
Schistosoma japonicum myosin: cloning, expression and vaccination studies with the homologue of the S. mansoni myosin fragment IrV‐5
Authors: ZHANG YAOBI , TAYLOR MARTIN G. , BICKLE QUENTIN D.
Published: March 2003

The Schistosoma japonicum homologue of the 62 kDa fragment of S. mansoni myosin (SmIrV‐5), which has proved highly protective against S. mansoni infection in mice and rats, has been cloned and expressed as the full length 62 kDa equivalent, Sj62, and a truncated 44 kDa version, Sj44. DNA sequencing showed the Sj62 sequence to be 88.4% identical at the nucleic acid level and 96% identical in deduced amino acid sequence to that of SmIrV‐5. The recombinant proteins (rSj44 and rSj62) were strongly recognized in Western blotting by sera from mice multiply vaccinated with UV‐irradiated S. japonicum cercariae and weakly recognized by S. japonicum chronic infection mouse sera. Unlike SmIrV‐5, mouse antisera against the recombinant S. japonicum proteins did not give positive recognition in immunofluorescence assay with the surface of newly transformed schistosomula of the homologous species, S. japonicum, nor did they react with S. mansoni schistosomula. However, the anti‐rSj62 sera clearly localized the native antigen to the subtegumental muscle layers in male adult worm sections by immunoelectron microscopy. Vaccination of several groups of mice and/or rats with rSj44 and rSj62 incorporated into different adjuvants induced high titres of specific IgG but in only one experimental group was there a significant reduction in worm burden (27%, P < 0.05). The possible reasons for the disparity between the vaccination results presented here and those demonstrated in experiments using rSm62 (IrV‐5) are discussed.
Vaccination of mice with γ‐irradiated Schistosoma japonicum cercariae
Authors: ZHANG YAOBI , TAYLOR MARTIN G. , BICKLE QUENTIN D. , WANG HAO , GE JIHUA
Published: March 2003

γ‐irradiated cercarial vaccines induce high levels of protection in mice against Schistosoma mansoni infection, however, the same has not been well established for S. japonicum. Here we describe vaccination studies in mice with γ‐irradiated S. japonicum cercariae testing the effectiveness of different irradiation doses, number of vaccinations, and mouse strains. In CBA/Ca mice, a single percutaneous exposure to 500 S. japonicum cercariae previously attenuated by 10, 20, 30, 40 or 50 krad γ‐irradiation induced significant, but comparable levels of protection (34–46%) against challenge infection. In a repeat experiment in C57Bl/6 mice, only groups vaccinated with 10 or 20 krad γ‐irradiated cercariae showed statistically significant, but lower levels of resistance (20–24%). Multiple vaccination of CBA/Ca mice with 500 20 krad γ‐irradiated cercariae did not improve the resistance level (40%). Analysis of IgG responses showed no clear correlation between antibody levels and levels of protection. Western blot analysis suggested that recognition of a 200‐kDa antigen might be correlated with protection, that antigens of 42 and 50 kDa may be involved in the protection induced by single vaccination, but that different antigens might be protective in single vs multiple vaccinations. Sera from mice vaccinated with γ‐irradiated cercariae recognized many fewer antigens than more protective sera from mice vaccinated with UV‐attenuated cercariae. These results suggest that the mouse may not be a suitable host for studies involving γ‐irradiated S. japonicum vaccines.