Search PubMed⌕ Search

Biomedical subjects

H Stewart

Publications and source records attributed to H Stewart.

At least 37 records · Page 2Linked to original sources
PubMed1999

The obstetric and neonatal performance of teenage mothers in an Australian community.

A cohort of 7191 single births in Liverpool Hospital, New South Wales was studied to examine whether an association between young age and adverse obstetric and neonatal outcomes can be supported, and what factors if any could be related to poor outcomes. Women were classified into four groups according to their confinement age, under the age of 18 years, between 18 and 19 years, between 20 and 34 years and 35 years or over. Teenage mothers in this community, especially under the age of 18 years, were very much disadvantaged in terms of socioeconomic status. The overall obstetric performance of teenage mothers was comparable with that of adult mothers. The neonatal outcomes were found to be poor in some aspects. However, the reasons for the adverse neonatal outcomes among teenagers are not due to the young age itself, but other contributing factors, such as maternal smoking, parity, and unmarried status.

Journal Article↗
PubMed1999

Mutants of Escherichia coli heat-labile toxin act as effective mucosal adjuvants for nasal delivery of an acellular pertussis vaccine: differential effects of the nontoxic AB complex and enzyme activity on Th1 and Th2 cells.

Mucosal delivery of vaccines is dependent on the identification of safe and effective adjuvants that can enhance the immunogenicity of protein antigens administered by nasal or oral routes. In this study we demonstrate that two mutants of Escherichia coli heat-labile toxin (LT), LTK63, which lacks ADP-ribosylating activity, and LTR72, which has partial enzyme activity, act as potent mucosal adjuvants for the nasal delivery of an acellular pertussis (Pa) vaccine. Both LTK63 and LTR72 enhanced antigen-specific serum immunoglobulin G (IgG), secretory IgA, and local and systemic T-cell responses. Furthermore, using the murine respiratory challenge model for infection with Bordetella pertussis, we demonstrated that a nasally delivered diphtheria, tetanus, and acellular pertussis (DTPa) combination vaccine formulated with LTK63 as an adjuvant conferred a high level of protection, equivalent to that generated with a parenterally delivered DTPa vaccine formulated with alum. This study also provides significant new information on the roles of the binding and enzyme components of LT in the modulation of Th1 and Th2 responses. LTK63, which lacks enzyme activity, promoted T-cell responses with a mixed Th1-Th2 profile, but LTR72, which retains partial enzyme activity, and the wild-type toxin, especially at low dose, induced a more polarized Th2-type response and very high IgA and IgG antibody titers. Our findings suggest that the nontoxic AB complex has broad adjuvant activity for T-cell responses and that the ADP-ribosyltransferase activity of the A subunit also appears to modulate cytokine production, but its effect on T-cell subtypes, as well as enhancing, may be selectively suppressive.

Adjuvants, Immunologic↗
PubMed1998

Comparison of corticomotoneuronal EPSPs and macro-MUPs in amyotrophic lateral sclerosis.

We correlated the size of the corticomotoneuronal excitatory postsynaptic potential (CM-EPSP) arising in a single spinal motor neuron with the function of the target motor unit as measured by conventional and macro EMG in early amyotrophic lateral sclerosis (ALS). Macro motor unit potentials (macro-MUPs) were recorded from a surface electrode after spike-triggered averaging in the extensor digitorum communis muscle. The size of the CM-EPSP projecting to the same motor unit was measured from changes in the firing probability of single motor units induced by transcranial magnetic stimulation using peristimulus time histograms. In controls, the amplitudes of CM-EPSPs and macro-MUPs correlated inversely, probably reflecting a lower input resistance of larger spinal motoneurons. In ALS the amplitude of macro-MUPs did not correlate with that of CM-EPSPs and one third of normal ALS motor units had a reduced or temporally dispersed CM-EPSP. The findings indicate primary dysfunction of the corticomotoneuronal projection system in ALS that is independent of functional changes of spinal motoneurons.

Action Potentials↗
PubMed1998

The management of metformin overdose.

Only two cases of deliberate self-poisoning with metformin have been described in the literature. We report the management of three cases, all of which presented with severe lactic acidosis. Two cases had a fatal outcome. The options for treatment and previous cases reported in the literature are reviewed. Recommendations for the management of metformin overdose include early recognition, intensive support of the cardiovascular system, the correction of metabolic acidosis and the maintenance of body temperature. The use of venovenous haemofiltration against a non-lactate containing fluid may improve outcome when sodium bicarbonate alone fails to reverse severe systemic acidosis.

Acidosis, Lactic↗
PubMed1998

An audit of care provided for children with epilepsy in the South Tees area.

This study examined the knowledge carers of children with epilepsy have of the condition and its management. It also examined their experience of medical services for their child and the attitude of staff at their schools. A school nursing sister using a semi-structured technique interviewed 48 carers of 53 children. A majority expressed dissatisfaction with outpatient medical care, especially that outpatient visits did not improve their knowledge of the condition or its treatment. Twenty-eight carers were not satisfied with the attitude of staff at schools. Ways to improve the service are discussed, including the role of the specialist community children's nurse and the need to see children with epilepsy in a dedicated clinic.

Activities of Daily Living↗
PubMed1998

Molecular diagnosis of spinal muscular atrophy.

The frequency of deletions within the survival motor neurone (SMN) and neuronal apoptosis inhibitory protein (NAIP) genes in patients with spinal muscular atrophy (SMA), and the impact of this on the diagnosis and prenatal diagnosis of SMA, were investigated by molecular analysis of stored DNA and retrospective review of case notes. In type I SMA, 16 of 17 cases were homozygously deleted for exons 7 and 8 of SMN, 14 of 17 were homozygously deleted for exon 5 of NAIP, and 13 of 17 were deleted for both. In types II and III SMA, seven of nine cases were deleted for exons 7 and 8 of SMN. Deletions of SMN and NAIP occurred in four of nine cases. With one exception, the deletion genotypes of probands, affected siblings, and terminated fetuses were identical. Molecular studies are replacing conventional investigations for SMA and have a high uptake prenatally.

Cyclic AMP Response Element-Binding Protein↗
PubMed1997

Abnormalities of cortical inhibitory neurons in amyotrophic lateral sclerosis.

We have used peristimulus time histograms to study how paired, transcranial magnetic stimulation alters the firing of single motor units and the magnitude of unitary excitatory postsynaptic potentials (EPSPs) recorded from the extensor digitorum communis muscle. With stimulus intensity at threshold and an interstimulus interval of 30 ms, normal subjects (n = 20) demonstrated marked inhibition with a mean test/conditioning EPSP ratio of 13.8% (range 0-51%) and in 7 subjects the ratio was 0 (100% inhibition). In amyotrophic lateral sclerosis (ALS) the ratio was 133% (range 64-267%), P < 0.001. Fifty percent of patients had a test/conditioning EPSP ratio greater than 100% (0 inhibition). The abnormalities were independent of disease severity, bulbar versus spinal ALS, more prominent upper versus lower motor neuron findings, and disease duration. Normal inhibition occurred in 3 individuals, 1 each with multiple sclerosis, Kennedy's syndrome, and monomelic amyotrophy. We speculate that the marked loss of inhibition seen in all patients with ALS, which may be unique to this disorder, reflects loss of inhibitory modulation of the corticomotoneuron and could result in their chronic excitatory drive and eventual demise.

Adult↗
PubMed1997

Reversible paralysis with status asthmaticus, steroids, and pancuronium: clinical electrophysiological correlates.

Prolonged neuromuscular weakness has been identified after neuromuscular blockade in intensive care unit patients on mechanical ventilation. Previously reported electromyographic studies in these patients documented both neurogenic features and features consistent with a myopathy. We recorded sequential electrophysiological parameters during recovery from neuromuscular blockade in 5 patients with clinical weakness. An evolving pattern was identified. The early features were in keeping with previous reports of neurogenic changes, and this evolved into features consistent with a primary myopathy. Several potential underlying mechanisms are discussed.

Adult↗
PubMed1997

Diverse abnormalities of corticomotoneuronal projections in individual patients with amyotrophic lateral sclerosis.

Using peristimulus time histograms (PSTHs), abnormalities of composite excitatory postsynaptic potentials (EPSPs) induced by transcranial magnetic stimulation were studied in multiple motor units from individuals with amyotrophic lateral sclerosis (ALS) and normal subjects. We studied 97 motor units in the extensor digitorum communis muscle of 22 patients with sporadic ALS and 47 motor units of 10 healthy control subjects. Four or five motor units were studied in each patient and normal subject. For each unit, macro motor unit potentials (Macro-MUPs) were simultaneously recorded from a surface electrode after spike-triggered averaging. The composite EPSPs in ALS showed a generally bi-directional deviation from the normal curve, with small EPSPs at one end, and larger amplitude EPSPs with a prolonged rise time at the other end. The variability of EPSPs from adjacent motor units in the same individual was significantly larger in ALS than in controls. In normal subjects there is a significant negative correlation between the amplitude of composite EPSPs and the Macro-MUPs. In ALS, the trend is reversed (positive) suggesting that the abnormalities of composite EPSPs are supraspinal in origin. A combination of partial attrition of the corticomotoneuronal core and hyper-excitability of surviving corticomotoneurons projecting to a given spinal motoneuron pool best explains the diversity of the composite EPSP in individuals with ALS.

Adult↗
PubMed1997

Mapping ESTs to the TSC1 candidate interval by use of the 'Science 96' transcript map.

The transcription map of the human genome published by Schuler et al. (1996) is a valuable resource in which approximately one quarter of all human genes have been mapped with respect to genetic framework markers using radiation hybrids. We have taken information from this map to provide potential genes within the TSC1 candidate region on chromosome 9q34. In so doing we have been able to provide an independent assay of the quality of the radiation hybrid mapping by using somatic cell hybrids and a 2 Mb cosmid contig covering the TSC1 region as mapping tools. In addition, we have built sequence contigs of ESTs for 25 clusters. This has shown that about 20% of the relevant EST clusters in the Unigene resource (Boguski & Schuler 1995) contain chimaeric clones.

Animals↗
PubMed1997

A case of mosaic trisomy 2 diagnosed at amniocentesis in an abnormal fetus and confirmed in multiple fetal tissues.

Pseudomosaicism for trisomy 2 is a relatively common finding at amniocentesis. However, genuine trisomy 2 mosaicism is extremely rare. As a result, very few cases have been described and little information is available with which to counsel the parents of an affected fetus. We describe a case of mosaic trisomy 2 diagnosed at amniocentesis in a fetus with multiple anomalies on ultrasound scan. Following termination of pregnancy, the fetus was found to have mild dysmorphic features, together with an absent gall bladder, cystic left kidney, a 13th left rib and mild unilateral talipes. The presence of trisomy 2 cells was confirmed by both standard cytogenetic analysis and fluorescent in-situ hybridisation techniques in multiple fetal tissues, as well as in the cord and placenta.

Abortion, Induced↗
PubMed1996

A transgenic rat model of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy in humans and has been associated with a partial duplication of chromosome 17 (CMT type 1A). We have generated a transgenic rat model of this disease and provide experimental evidence that CMT1A is caused by increased expression of the gene for peripheral myelin protein-22 (PMP22, gas-3). PMP22-transgenic rats develop gait abnormalities caused by a peripheral hypomyelination, Schwann cell hypertrophy (onion bulb formation), and muscle weakness. Reduced nerve conduction velocities closely resemble recordings in human patients with CMT1A. When bred to homozygosity, transgenic animals completely fail to elaborate myelin. We anticipate that the CMT rat model will facilitate the identification of a cellular disease mechanism and serve in the evaluation of potential treatment strategies.

Animals↗
PubMed1996

Cortical projections to spinal motoneurons: changes with aging and amyotrophic lateral sclerosis.

Peristimulus time histograms (PSTHs) of discharging single motor units, recorded from the extensor digitorum communis (EDC) during randomly applied cortical magnetic stimulation, were obtained in 42 normal subjects aged 24 to 83 years and 42 patients with amyotrophic lateral sclerosis (ALS) aged 37 to 84 years. Normal subjects had an early period of increased firing probability occurring at about 20 msec poststimulus, reflecting an underlying compound excitatory postsynaptic potential (EPSP) induced by fast-conducting, descending volleys of the corticomotoneuronal core facilitating the single spinal motoneuron. There was an age-dependent, linear decline in the amplitude of the EPSP (r = 0.673). We estimated that by age 50 years about 35% of corticomotoneurons are lost or nonfunctioning in normal controls. Compared with age-matched controls, the EPSP in most patients with ALS was reduced, and it was unmeasurable in six. We postulate this reflects a loss of corticomotoneurons. Seven (16.7%) patients phenotypically the same as the others had EPSPs that were larger than age-predicted values. This may reflect glutamate-induced excitotoxicity in a subset of ALS. In a single patient with chronic spinal muscular atrophy the EPSP was normal.

Adult↗
PubMed1994

Cooperative breast cancer trials organized by the United Kingdom Co-ordinating Committee on Cancer Research.

The activities of the United Kingdom Co-ordinating Committee on Cancer Research in the area of breast cancer trials were reviewed. Current trials concern the management of ductal carcinoma in situ, the length of time tamoxifen should be given in the adjuvant setting, and trials of the use of chemotherapy. A trial of the use of tamoxifen to prevent breast cancer is being piloted in anticipation of a national study, and trials of the interval and age at which to undertake mammographic screening are also underway.

Breast Neoplasms↗