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Biomedical subjects

A James

Publications and source records attributed to A James.

At least 19 recordsLinked to original sources
PubMed1999

Cell behaviour as a dynamic attractor in the intracellular signalling system.

We present a model of the cell signalling network based on the generic properties of interactions between protein kinases (PKs) and protein phosphatases (PPs) inside cells. The model is designed to examine the global properties and intrinsic dynamics of the phosphorylation system. A genetic algorithm (GA) is used to evolve populations of "cells". The GA selects cells and ranks them based on an analysis of the dynamics of the proteins within the networks from a series of different random starting conditions. The fittest cells are taken to be those which can generate a variety of different "behaviours" from a series of different initial conditions. During the GA, intracellular protein interactions evolve via mutation and an analogue of domain shuffling between protein types that is thought to occur during biological evolution. The dynamics of the simulated networks are presented and we discuss the hypothesis that changes in the behaviour of a cell may be interpretable as a switch between attractor basins in the intracellular signalling network.

Algorithms↗
PubMed1999

Segregation analysis of the specific response to allergens: a recessive major gene controls the specific IgE response to Timothy grass pollen.

Segregation analysis of the specific response to allergens (SRA) was performed in a sample of 234 randomly selected Australian families using the regressive models. Various SRA phenotypes were considered using broad and narrow definitions of these phenotypes, according to the type of test used, skin test or RAST test, and the specificity of the response to allergen. Strong evidence for familial dependencies among blood relatives was shown for most SRA phenotypes, especially when using a broad definition. There was no evidence for a Mendelian factor accounting for the familial transmission of these broadest phenotypes, which may involve multiple factors preventing the clear detection of a major effect with Mendelian transmission. However, segregation of a Mendelian recessive major gene was detected for one SRA sub-phenotype, the IgE response to a single allergen, Timothy grass pollen, measured by the RAST test. Identification of a specific SRA phenotype controlled by a major gene may have important implications for further linkage studies.

Adolescent↗
PubMed1998

Partial tetrasomy with triplication of chromosome (5) (p14-p15.33) in a patient with severe multiple congenital anomalies.

We report on a newborn infant with a de novo triplication of the distal segment of 5p: 46,XX,trp(5) (pter-->p14::p14-->p15.33::p15.33--> qter) and multiple congenital anomalies consistent with triplication of 5p. Partial triplication was documented by fluorescence in situ hybridization with a cosmid probe specific for 5p15.2 and microdissected probes obtained from "5pter." Partial duplication of the short arm of chromosome 5 is associated with a specific phenotype that appears to be dependent on the chromosomal region duplicated. Duplication of 5p with breakpoints proximal to band p14 is generally associated with distinct craniofacial malformations, cardiac, renal, intestinal, and limb defects, and mental retardation, whereas duplications with breakpoints distal to 5p14 result in a milder phenotype characterized by minor facial anomalies, developmental delay, and seizures. The most proximal breakpoints of the partial triplication in this patient was estimated to be 5p14, suggesting that a more severe phenotype can occur with triplication of the more distal segment.

Abnormalities, Multiple↗
PubMed1998

Epoxybutene-hemoglobin adducts in rats and mice: dose response for formation and persistence during and following long-term low-level exposure to butadiene.

Measurement of specific adducts to hemoglobin can be used to establish the dosimetry of electrophilic compounds and metabolites in experimental animals and in humans. The purpose of this study was to investigate the dose response for adduct formation and persistence in rats and mice during long-term low-level exposure to butadiene by inhalation. Adducts of 3,4-epoxy-1-butene, the primary metabolite of butadiene, with N-terminal valine in hemoglobin were determined in male B6C3F1 mice and male Sprague-Dawley rats following exposure to 0, 2, 10, or 100 ppm of 1,3-butadiene, 6 h/day, 5 days/week for 1, 2, 3, or 4 weeks. Blood samples were collected from groups of five mice and three rats at the end of each week during the 4 weeks of exposure and weekly for 3 weeks following the end of the 4-week exposure period. The increase and decrease, respectively, of the adduct levels during and following the end of the 4-week exposure followed closely the theoretical curve for adduct accumulation and removal for rats and mice, thereby demonstrating that the adducts are chemically stable in vivo and that the elimination follows the turnover of the red blood cells. The adduct level increased linearly with butadiene exposure concentration in the mice, whereas a deviation from linearity was observed in the rats. For example, after exposure to 100 ppm butadiene, the epoxybutene-hemoglobin adduct levels were about four times higher in mice than in rats; at lower concentrations of butadiene, the species difference was less pronounced. Blood concentrations of epoxybutene, estimated from hemoglobin adduct levels, were in general agreement with reported concentrations in mice and rats exposed by inhalation to 62.5 ppm. These studies show that adducts of epoxybutene with N-terminal valine in hemoglobin can be used to predict blood concentration of epoxybutene in experimental animals.

Algorithms↗
PubMed1998

A comparative study of the 1992 and 1997 recovery positions for use in the UK.

In April 1997 the ILCOR Basic Life Support advisory statements were announced in conjunction with changes to the recovery position for use in the UK. This study compared the new and old positions by using a questionnaire to assess how well each position satisfied the ILCOR statements. The study was carried out over six different hospital trusts by eight resuscitation training officers. Each tutor alternately taught the 1992 or 1997 recommended positions. After the practical session each student completed a questionnaire on ease of learning and use of the position, as well as other factors such as spinal stability. They were also asked to score the position when they were placed in recovery by other students. Their competency was assessed using the ALS criteria. Over the duration of the study 687 forms were suitable for analysis. For every question there was a significant trend in favour of the 92 position, with students finding the technique easier to learn and use, simpler for positioning for CPR and with less spinal movement during rolling. Possible sources of bias such as previous training, tutor or staff grade made no statistical difference to the results. When performed competently the 1997 position appears to cause less brachial compression, but other problems with learning or use of the 97 position outweigh this advantage. The 1992 position currently provides the best compromise between ease of use, spinal stability and other factors, and better satisfies the ILCOR advisory statements.

Attitude of Health Personnel↗
PubMed1998

The clinical skills of community psychiatric nurses working with patients who have severe and enduring mental health problems: an empirical analysis.

This study describes the use of reliable scales to rate the clinical skills of mental health nurses when working with individuals and families with severe mental health problems. The Cognitive Therapy Scale and the Schizophrenia Family Work Scale were adapted for the study and were shown to have good inter-rater reliability when assessing audio-taped interviews carried out by mental health nurses during their usual course of work with patients with severe mental health problems and their families. The sample of mental health nurses studied were shown to have significantly better general therapy skills than specific cognitive therapy technical skills. The implications for training are discussed.

Clinical Competence↗
PubMed1998

A genome scan for loci influencing total serum immunoglobulin levels: possible linkage of IgA to the chromosome 13 atopy locus.

Immunoglobulins play an essential part in the immune system, and immunoglobulin deficiencies can have profound medical consequences. The genetic control and regulation of the immunoglobulin response is therefore of interest. Previous investigations have identified a number of loci influencing total and specific IgE levels. In this study, 80 nuclear families have been examined for linkage of total serum IgA, IgG and IgM levels to a genome-wide panel of microsatellite markers. Potential quantitative trait loci influencing IgA levels have been identified on chromosomes 10 and 13, and possible loci influencing IgG levels were found on chromosomes 3 and 13. No significant linkages to IgM levels were found. The linkage of IgA on chromosome 13 was to a marker previously linked to IgE responses (atopy). Linkage to IgG was in the same region but to a more distal marker. None of the factors known to influence immunoglobulin expression map to the loci identified in the present study. These loci are therefore likely to contain previously unrecognized components of the immunoregulatory system.

Chromosomes, Human, Pair 13↗
PubMed1998

Comparative experience of a simple technique for laparoscopic chronic ambulatory peritoneal dialysis catheter placement.

BACKGROUND: Chronic ambulatory peritoneal dialysis (CAPD) is now an established technique for renal dialysis. Patients with renal failure cope poorly with major surgery and it is vital that the dialysis catheter tip is sited accurately in the pelvis if long-term catheter function is to be achieved. Laparoscopic placement of CAPD catheters may have potential advantages for renal patients by avoiding the morbidity of a laparotomy. METHODS: A retrospective audit was performed of all CAPD catheters inserted at the John Hunter Hospital over a 2-year period. Results of laparoscopically inserted catheters and those placed at laparotomy were compared. RESULTS: Sixty catheters were inserted, 30 laparoscopically and 30 at laparotomy. The mean operative time was 41 min in the laparoscopic patients and 57 min in the laparotomy patients (P = 0.0001). The mean total dose of narcotic administered postoperatively was significantly less in the laparoscopic group (5 mg vs 65 mg, P = 0.00002). There were three minor peri-operative complications in the laparoscopic group and seven peri-operative complications in the laparotomy group, three required reoperation and one resulted in the patient's death. There were no significant differences in the incidence of exit-site infection, catheter blockage, peritonitis, and overall catheter survival, although the laparoscopically placed catheters had been followed up for a shorter period (10 vs 16 months). CONCLUSIONS: This laparoscopic technique is safe and effective. Postoperative pain was less than for open placement. Laparoscopically placed catheters had a low incidence of peri-operative complications. Medium-term patency is similar to conventionally placed catheters. This procedure requires no additional equipment to that available for laparoscopic cholecystectomy and takes less time than the open operation.

Adult↗
PubMed1998

beta2-Adrenergic receptor haplotypes in mild, moderate and fatal/near fatal asthma.

Excess beta2-agonist use in asthmatics has been associated with increased mortality and morbidity. The mechanisms responsible for these observations are unknown. We hypothesized that polymorphisms of the beta2-adrenergic receptor (beta2AR) at amino acid positions 16, 27, and 164, which are known to alter receptor functions in vitro, may predispose asthmatics to fatal/near-fatal asthma and/or modify asthma severity. In preliminary studies we found significant differences in allele frequencies due to ethnic background: Caucasian, Black, Asian Gly16 = 0.61, 0.50, 0.40 and Gln27 = 0.57, 0. 73, 0.80, respectively. beta2AR genotyping was performed on DNA from Caucasians classified as nonasthmatic/nonatopic (n = 84), fatal/near-fatal asthmatics (n = 81) and mild/moderate asthmatics (n = 86). No polymorphism or haplotype was found to be associated with fatal/near-fatal asthma. However, the Gly16/Gln27 haplotype, which undergoes enhanced downregulation in vitro, was substantially more prevalent in moderate asthmatics than in mild asthmatics (p = 0.003, odds ratio = 3.1). We conclude that the beta2AR genotype is not a major determinant of fatal or near-fatal asthma. Furthermore, allele frequency variation among ethnic groups must be considered in clinical studies of beta2AR polymorphisms in asthma.

Adrenergic beta-Agonists↗
PubMed1998

Identification of novel factors that regulate GnRH gene expression and neuronal migration.

We used differential display PCR on two GnRH producing cell lines to identify genes involved in GnRH gene expression and neuronal migration. RNA from Gn10 cells (derived from a tumor in the olfactory area when GnRH neurons are migrating and make low levels of GnRH) and from GT1-7 cells (derived from a tumor in forebrain when GnRH neurons are postmigratory and make high levels of GnRH) was reverse transcribed into cDNA. The cDNA was amplified using three anchored primers and eight random primers from each cell line and products from duplicate reactions electrophoresed in parallel in a denaturing acrylamide gel. Differentially expressed cDNAs were excised, reamplified and used as probes in Northern analysis of total RNA from each cell line to confirm differentially expressed RNA. The cDNAs were sequenced and compared to the Genbank database. Four of five clones isolated from GT1-7 GnRH neurons are novel, while four of five clones isolated from Gn10 cells have homology to known DNA sequences. One clone, Gn8-01 encodes adhesion related kinase (Ark), a molecule that has an N-terminal domain characteristic of cell adhesion molecules and whose kinase domain may play a role in protection from apoptosis. Together these data support the usefulness of the technique to identify novel genes that play a role in the control of GnRH expression and neuronal migration.

Apoptosis↗
PubMed1998

Process-oriented critical pathways in inpatient psychiatry: our first year.

The critical pathway methodology of assigning and timing staff interventions and expected patient outcomes has developed worldwide recognition, but is less likely to be used in psychiatry than in other medical fields. At St. Mary's in Rochester, New York, an interdisciplinary team adapted the critical pathway concept to meet the needs of an acute inpatient population with relative success. Although staff education needs continue and plans to modify the pathway are in progress, all staff feel that the critical pathway is a viable tool for enhancing patient care and optimizing resources use. Benefits, obstacles, and suggestions are discussed.

Critical Pathways↗
PubMed1997

Attendance at an asthma educational intervention: characteristics of participants and non-participants.

As part of an evaluation of the patient education component of the Australian Asthma Management plan, a randomized, controlled trial of asthma education was conducted in 1994/95 at the outpatient asthma and allergy clinic of The Alfred Hospital, a tertiary referral hospital in Melbourne, Australia. The objective of the study was to investigate which demographic and clinical characteristics were associated with attendance at asthma educational session. A total of 125 asthmatics aged over 16 years agreed to participate in the programme, and full compliance with the programme was 43.2%. Allocation to immediate, rather than delayed, education and age were the only significant predictors of attendance. Subjects randomized to the intervention were approximately three times more likely to attend than control subjects (OR = 3.3, 95% CI 1.5-7.3). Asthmatics over 60 years old were approximately six times more likely to attend (OR = 6.6, 95% CI 2.2-19.8) than the age group 16-30 years. The increasing trend in attendance across age categories was highly significant (P < 0.001). There was no relationship between attendance and gender, medication, atopy, smoking status or the physical accessibility of the hospital. Despite offering incentives and conducting the education sessions at subjects' preferred times, their compliance in attending sessions was poor. Over half of the asthmatics, who had expressed interest, failed to attend for their educational sessions. An alternative strategy is required to improve participation by young and employed asthmatics at hospital-based asthma education programmes.

Adolescent↗
PubMed1997

Beyond the market in public service.

Critiques of the implementation of a market in health care have so far concentrated on conceptual, practical and ethical objections, it is not a real market, say the theorists; it is not delivering say the realists; it does not have public consent, say the moralists. Argues, from a more fundamental critique: the implementation of the market confuses means with ends. Problems lie not in the introduction of the market-which, is argued, has served well in breaking up the frozen paradigm of the welfare state-but in seeing it as an end state rather than a transition. Posits that this has left us trapped in a scenario about buildings, about restructuring and about contracts instead of resolving chronic human problems of ill health. Postulates that the issue is not to argue for or against the market, or indeed to set it against the alternative of the old welfare state: rather to ask how to learn from this transitional state and how to create the mixed economy which lies beyond both market and welfare state. Drawing on previous work on professional bureaucracies, markets and networks relocates the primary challenge not in managing the market but in meeting need within the remit of public consent.

Economic Competition↗
PubMed1997

Testing airway responsiveness using inhaled methacholine or histamine.

Airway responsiveness assessed using histamine and methacholine is safe, reproducible and relatively easily undertaken in adults and children. Results are similar for methacholine and histamine although methacholine is better tolerated. Responsiveness is increased in children and the elderly, and in women compared to men, possibly due to body size effects. Baseline lung function confounds the interpretation of airway responsiveness and may explain the effect of smoking in most studies. Results are most usefully expressed as the provocative dose producing a 20% fall in FEV1 (PD20FEV1) or the dose-response slope (DRS). When technical factors are controlled the reproducibility of the test is from one to two doubling doses. Measurements of airway responsiveness have been widely used in clinical and research practice. However, assessing their value in diagnosing asthma is limited by the lack of a gold standard for the definition of asthma. Using a cut-off value of 8 mg/mL or 8 mumol for PD20, the tests will discriminate asthmatic from non-asthmatic subjects (based on questionnaire definitions of asthma) with a sensitivity of around 60% and a specificity of around 90%. These properties of the test result in positive and negative predictive values of 86% and 69% when the prevalence of asthma is high (50%-as in the clinical setting) and 40% and 95% when the prevalence of asthma is low (10%, as in general population studies). In the usual clinical setting, assessing the significance of atypical or non-specific symptoms, the tests are of intermediate value in predicting the presence of asthma and less useful in excluding asthma. The additional benefit of testing airway responsiveness to measuring peak flows or to a trial of therapy has yet to be fully assessed. Testing of airway responsiveness may be of value in assessing occupational asthma, asthma severity and the effects of potential sensitizers or treatments. In research, tests of airway responsiveness are more useful for excluding cases of asthma. In population studies, they serve as an objective marker of abnormal airway function which may be genetically determined and, like allergy, are strongly associated with asthma. The predictive value of airway hyperresponsiveness for the development of airway disease is yet to be clearly established. In epidemiology the benefits of measuring airway responses must be weighed against the added inconvenience and cost that is incurred.

Adult↗
PubMed1997

The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics.

Airway inflammation in asthma consists of variably increased numbers of mononuclear and polymorphonuclear cells, and there is a growing body of evidence to suggest a primary role for lymphocytes and eosinophils in the pathogenesis of asthma. The aim of this study was to examine the distribution of lymphocytes and eosinophils in the bronchial tree of cases of mild and severe asthma. In cases of fatal asthma (n = 10), nonfatal asthma (sudden nonrespiratory death with a history of asthma n = 10), and control cases (sudden death with no history of respiratory illness, n = 10), lymphocytes and eosinophils were counted in transverse sections of large and small airways stained with haematoxylin and eosin. Cases of fatal asthma had longstanding severe asthma and nonfatal cases generally had mild asthma. Lymphocytes were increased in all airway size groups both in fatal and nonfatal cases of asthma compared to control cases (p < 0.001). Eosinophils were increased (p < 0.001) in all airway size groups in the cases of fatal asthma compared to the nonfatal asthma and control groups, which were similar. These differences between case groups were of similar magnitude, when only a random single airway section from each case in each size group was examined. The numbers of lymphocytes correlated with the number of eosinophils in the fatal asthma group (r = 0.60; p < 0.0001), and to a lesser extent in the nonfatal (r = 0.34; p = 0.001) and control groups (r = 0.32; p = 0.001). These findings suggest that increased numbers of lymphocytes are uniformly distributed in the large and small airways in cases of asthma, independently of asthma severity, and that eosinophil recruitment may be related to asthma severity. Hence, biopsy specimens of the proximal airways are likely to be representative of the cellular infiltrate in large and small airways in mild and severe asthma.

Adolescent↗