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Biomedical subjects

R Thompson

Publications and source records attributed to R Thompson.

At least 55 records · Page 3Linked to original sources

Prescribing for childhood asthma in the Wellington area: comparison with international guidelines.

AIMS: An international paediatric asthma consensus group has outlined the rational approach to the treatment of childhood asthma. We have examined the prescription of asthma treatment to children in Wellington to assess to what extent these guidelines have been adopted by general practitioners. METHODS: During the period 1 May-11 June 1991, the prescriptions for 228 asthmatic children, dispensed at 30 randomly selected pharmacies in the greater Wellington area, were reviewed. RESULTS: Eighty-four per cent of the children were prescribed beta 2 adrenoceptor agonists. Of these, 80% of those under five years, and 27% over five years of age, received these agents by the oral route. In almost half, these drugs were prescribed on a regular basis. Fifty-two per cent of patients were prescribed some form of antiinflammatory therapy (inhaled or oral steroids, ketotifen or sodium cromoglycate). Only 2% received sodium cromoglycate. CONCLUSION: Although approximately half of these children received some form of antiinflammatory therapy, the minimal use of sodium cromoglycate, and high frequency of regular scheduled beta 2 adrenoceptor agonist use, suggests that the guidelines for asthma management in children may not have been widely adopted by primary care physicians in Wellington.

Adolescent

Functional expression of the transcriptional activator Opaque-2 of Zea mays in transformed yeast.

The aim of this research was to determine whether the structural homology between the O2 gene, a maize transcriptional activator, and the GCN4 gene, a yeast transcriptional factor, is reflected at the level of function. The O2 cDNA was cloned in the yeast expression vector pEMBLyex4 under the control of a hybrid inducible promoter, and used to transform the yeast Saccharomyces cerevisiae. Transformed yeast cells produced O2 mRNA and a polypeptide immunoreactive with anti-O2 antibodies during growth in galactose. The heterologous protein was correctly translocated into the yeast nuclei, as demonstrated by immunofluorescence, indicating that the nuclear targeting sequences of maize are recognized by yeast cells. Further experiments demonstrated the ability of O2 to rescue a gcn4 mutant grown in the presence of aminotriazole, an inhibitor of the HIS3 gene product, suggesting that O2 activates the HIS3 gene, gene normally under control of GCN4. It was shown that the O2 protein is able to trans-activate the HIS4 promoter in yeast cells and binds to it in vitro. The sequence protected by O2, TGACTC, is also the binding site for GCN4. Finally, the expression of O2 protein in yeast did not produce alterations during batch growth at 30 degrees C, while transformants expressing O2 protein showed a conditionally lethal phenotype when grown in galactose at 36 degrees C; this phenotype mimics the behaviour of gcd mutants. The results support the idea that basic mechanisms of transcription control have been highly conserved in eukaryotes.

Cloning, Molecular

Characteristic modifications of the breathing pattern of mice to evaluate the effects of airborne chemicals on the respiratory tract.

A system was developed for exposure of unanesthetized mice to airborne chemicals and for continuous measurement of their breathing pattern prior to, during and following exposure. By measuring inspiratory and expiratory airflows (VI and VE), and integration with time to yield tidal volume (VT), we obtained characteristic modifications to the normal breathing pattern. These permitted recognition that a specific portion of the respiratory tract was affected by the selected airborne chemicals. Following recognition, we also quantitated the degree of effect using one specific measurement in each case. An effect on the upper respiratory tract, induced by the sensory irritant, 2-chlorobenzylchloride, was quantitated by measuring a decrease in respiratory frequency. An effect on the conducting airways, induced by the airway constrictor, carbamylcholine, was quantitated by a decrease in VE at the mid-point of VT. An effect at the alveolar level, induced either by the vagal nerve ending stimulant, propranolol, or by the pulmonary irritant, machining fluid G, was quantitated by an increase in the length of a pause induced at the end of expiration. The system is easy to construct and operate and can be used to rapidly evaluate the effects of airborne chemicals on the respiratory tract.

Aerosols

Cost-effectiveness of neonatal screening for Duchenne muscular dystrophy--how does this compare to existing neonatal screening for metabolic disorders?

Costs of screening a series of 18,152 newborn males for Duchenne muscular dystrophy (DMD) in Canada were evaluated. The final aim of neonatal screening for DMD is the avoidance of additional cases in the families identified. Total costs to avoid one case of DMD were estimated at Cdn. $172,000, while the incremental costs were found to be $83,000. Reagent costs, test sensitivity, efficacy of screening and compliance with genetic advice were identified as factors crucial for cost-effectiveness. Costs of neonatal screening for DMD are compared with costs of neonatal screening for inborn metabolic disorders. It is found that the two programmes are similar in costs. Earlier predictions of inordinate costs of screening for DMD are refuted.

Cost-Benefit Analysis

Variation among individual White-Leghorn hens in the concentration of minerals in the albumen and yolk content of their eggs.

1. The mineral composition of the albumen and yolk was determined in several eggs from each of a number of individual hens from the same White-Leghorn strain. X-ray fluorescent spectrometry was used to undertake two independent series of analyses. A total of 8 minerals (calcium, chlorine, iron, magnesium, phosphorus, potassium, sodium, sulphur) were included in the analyses of the yolk and the same minerals, but excluding iron (which is present in only small amounts), in the albumen. 2. There was considerable variation between individuals in the mineral concentration in their eggs (coefficients of variation ranged between 3.8% for sodium to 19.9% for calcium in the albumen, and between 4.3% for phosphorus to 11.8% for iron in the yolk). 3. At the same time, the moderately high repeatability of mineral concentration (t = 0.4-0.6) in successive eggs from the same hen for several of the minerals analysed is indicative of some positive control by the hen of the mineral composition of her eggs. 4. There was a highly significant correlation (P < or = 0.001) between the mean concentration of potassium in the albumen and the hatchability of the eggs, supporting the claim that a deficiency of potassium in the egg could be the basis of some failures in hatchability. 5. The study also revealed variation among individual birds in the concentration of iron in the yolk which was negatively correlated (P < or = 0.01) with hatchability. No clear basis could be suggested for this variation among individual birds.

Animals

Clinical aspects of malignant mesothelioma in Australia.

Australia is currently experiencing an epidemic of malignant mesothelioma. The clinical aspects of malignant mesothelioma were investigated in 295 Australian patients as part of a national study of the disease. Most patients were male (91%), with the mean age at diagnosis being 64 years. The predominant cell type was epithelial (38%) and the majority of primary tumours arose from the pleura (94%). Mean survival was poor (17.6 months from first symptom; 11.8 months from diagnosis). Patients with a pleural primary tumour were more likely to present with dyspnoea, chest pain and cough; to have a pleural effusion diagnosed radiologically; and to have metastatic spread. Patients with a peritoneal primary tumour were more likely to present with weight loss, loss of appetite, abdominal pain and ascites; to have radiologic evidence of asbestos exposure; and to have spread along a needle track created during a diagnostic tap. A minority of patients had past thoracic conditions, or radiologic findings, specifically related to previous asbestos exposure. About one fifth of patients had no known asbestos exposure. Forty-one per cent of subjects received some form of chemotherapy, radiotherapy and/or surgery, but no formal disease staging had been documented for any patient. Proper controlled trials of secondary and tertiary treatments in malignant mesothelioma are now needed.

Aged

Na(+)-K(+)-2Cl- cotransport and Cl- secretion evoked by heat-stable enterotoxin is microfilament dependent in T84 cells.

We previously reported that adenosine 3',5'-cyclic monophosphate-mediated stimulation of Cl- secretion in the human intestinal epithelial cell line T84 is accompanied by significant remodeling of F-actin and that both the secretory and cytoskeletal responses may be inhibited by phalloidin derivatives, agents that polymerize actin and prevent dynamic reorganization of microfilaments. In contrast, the carbachol-elicited Cl- secretory response (Ca2+ mediated) was not attenuated by phalloidin (J. Clin. Invest. 87: 1903-1909, 1991). In the present study, we examine the effect of phalloidin on the Cl- secretory response elicited by the heat-stable enterotoxin of Escherichia coli (STa), which induces elevations in intracellular guanosine 3',5'-cyclic monophosphate. We find that apical administration of 1 microM STa results in a regionally restricted redistribution of F-actin confined to the basal pole of the cells. In monolayers pretreated with phalloidin, the Cl- secretory response to STa was inhibited by > 60%. Sequential treatment of phalloidin-loaded monolayers with STa followed by carbachol resulted in a synergistic secretory response that was not different from control (unloaded) monolayers. Examination of efflux/uptake through specific membrane transport pathways involved in STa-stimulated Cl- secretion indicated normal activation of apical Cl- and basolateral K+ channels under phalloidin-loaded conditions. The ability of STa-treated monolayers to pump Na+ in an absorptive direction was also unaffected by phalloidin. der phalloidin-loaded conditions, STa-stimulated Na(+)-K(+)-2Cl- cotransporter activity was reduced by approximately 60%, sufficient to account for the observed inhibition of net Cl- secretory response.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton

The pull-through procedure: technical factors in influencing outcome, with emphasis on pouchitis.

BACKGROUND: The purpose of the study was to review those features that we believed to be critical to the successful performance of the ileal pouch-anal anastomosis, or pull-through, procedure, and specifically the complication of pouchitis. METHODS: The charts of 205 patients who successfully underwent ileal pouch-anal anastomosis procedure were reviewed. No follow-up was available in five patients; therefore, the basis of this report and its analysis was based on 200 consecutive procedures in which at least two of the three surgeons participated. Particular emphasis was placed on continence, particularly nighttime continence. The incidence of pouchitis, either a single episode or intermittent episodes, was surveyed. Particular attention was paid to the level of rectal mucosectomy and anastomosis at the top of the columns of Morgagni, thus retaining the transitional zone. RESULTS: Only 5% of patients were incontinent in the absence of pouchitis. Twenty-five patients (13%) wore a pad at night, but only nine (5%) wore a pad during the day. Of those patients with pouchitis, 6% (12) have had a single episode and 12% (23) were intermittently on medication. Therapy of pouchitis was usually carried out with ciprofloxacin 500 mg by mouth everyday or twice a day. CONCLUSIONS: Ileal pouch-anal anastomosis is an excellent procedure, provided technical details are adhered to. Satisfactory outcome with respect to nighttime continence can be achieved with rectal mucosectomy with minimal manipulation and retaining the transitional epithelium, performing the pouch anastomosis at the top of the columns of Morgagni. The incidence of pouchitis is disappointing but need not be inhibiting of either patients or carrying out this life-saving procedure in patients with ulcerative colitis and familial polyposis.

Adolescent

Glutamate rich Plasmodium falciparum antigen (GLURP).

We have characterized a glutamate rich Plasmodium falciparum antigen, GLURP, which by immunoassays appears to be present in both the pre-erythrocytic and erythrocytic stages of the vertebrate life cycle. The gene, which is located on chromosome 10, encodes a polypeptide of 1271 residues with a predicted molecular mass of 145 kDa. Rabbit antiserum against a fusion protein expressing the C-terminal end of the molecule detects a protein with a molecular mass of 220 kDa. The sequence includes two hydrophobic regions: one consisting of 23 residues and located by the N-terminus which may act as signal peptide, and the second located at the C-terminus consisting of 33 predominantly hydrophobic residues. Except for these hydrophobic regions the protein is hydrophilic and highly charged. The sequence has two tandem repeats designated as R1 and R2. These regions were found to be conserved in isolates from different geographical areas. High levels of anti-GLURP antibodies have been shown to correlate with low parasite density. The indication of GLURP being present in all stages of the parasite in the human host raises significantly the prospects of the potential of this molecule.

Adult

Embolus in transit.

Since the advent of echocardiography, embolus in transit, historically found during surgical exploration or on postmortem examination, has been found with increasing frequency on antemortem examination. There is an inherent high mortality rate with this condition and awareness of the association between deep venous thrombosis and embolus in transit is paramount. On echocardiography the embolus is typically seen as a pleomorphic mass moving in a tumbling fashion. The most frequent symptoms are dyspnea and near syncopal episodes. The most common signs are diastolic "tumor plop" and a systolic ejection murmur heard on auscultation. Despite the success of some medical interventions, surgery should be strongly considered in patients with embolus in transit.

Aged

Estimation of changes in genetic parameters in selected lines of mice using REML with an animal model. 1. Lean mass.

Analysis was undertaken using Restricted Maximum Likelihood (REML) with an animal model of the results of selection for 20 generations for predicted lean mass in 10-week-old male mice. There were three replicates, each comprising high, low and unselected control lines. The overall estimates of heritability (h2) and common environmental correlations (c2) from results of the first seven generations were 0.51 +/- 0.03 and 0.21 +/- 0.01, respectively. Analyses of data from different lines and different numbers of generations were undertaken but with all pedigrees and data included, which enabled inferences to be drawn on changes in variance that were not due simply to inbreeding or short-term effects of selection. Estimates of h2 were lower in selected lines than the control, increasingly so in later generations, indicating departure from the infinitesimal model assumption of unlinked additive genes each of very small effect. In addition, values of c2 became higher in high than in control or low selected lines.

Analysis of Variance

Estimation of changes in genetic parameters in selected lines of mice using REML with an animal model. 2. Body weight, body composition and litter size.

Restricted Maximum Likelihood (REML) with an animal model was used to estimate genetic parameters of body weight, body consumption and litter size of lines of mice selected for 20 generations on an index of lean mass at 10 weeks in males, highly correlated with body weight, and for a further 18 generations on body weight at 10 weeks in males and females. Univariate and multivariate estimates of heritability were about 0.5 and those of common environment correlations were about 0.25 for both body weight and composition. Body weight and fat pad weight had genetic and phenotypic correlations of about 0.5. The heritability estimate of litter size was about 0.15 from univariate analysis, rather lower from multivariate, and the estimate of its genetic correlation with body weight was about 0.25. There were reductions in heritability of both body weight and litter size in later generations, even though full pedigrees were fitted and inferences made to the base population, but a plateau in response to selection for increased body weight could not be explained by a complete attenuation of genetic variance.

Animals

Methods of segregation analysis for animal breeding data: a comparison of power.

Maximum likelihood segregation analysis provides potentially the most powerful method for the detection of segregating major genes. Segregation analysis requires the comparison of the likelihood of the data under the combined model (allowing both polygenic and major gene genetic variation) with the likelihood of the data under the polygenic model (allowing only polygenic genetic variation). In this study three approximations to the combined model likelihood were compared using simulated data, both with and without a segregating major gene, containing observations on paternal half-sibs. The use of Hermite integration to replace the integration in the combined model likelihood provided the most powerful test for a major gene. Two approximations, based on extensions of linear-mixed-model theory and estimating transmitting abilities for sires, were also considered. These approximations were less powerful than the use of Hermite integration, although the approximation estimating a transmitting ability for each major genotype for the sires was an improvement over the approximation estimating a single transmitting ability. For each approximation the frequency of detection of a major gene depended on the proportion of the genetic variance explained by the simulated major gene and whether the major gene caused the distribution to be skewed.

Alleles

Methods of segregation analysis for animal breeding data: parameter estimates.

Three approximations to the combined model likelihood (including variation due to both polygenes and a major gene) used in segregation analysis were compared in their ability to estimate the parameters describing the model. Paternal half-sib data simulated under four different combined models were used. In general, when a combined model provides the best explanation of the data the parameter estimates from all three approximations investigated are, on average, in good agreement with the values simulated. The use of Hermite integration to replace the integration in the combined model likelihood provided the parameter estimates closest to those stimulated. The other two approximations, based on extensions of linear mixed-model theory, gave estimates further from the expected values, however, these latter two methods can estimate transmitting abilities for the sires directly from the analyses. The three approximations are similar in their ability to genotype sires at the major locus. On average, with the models studied here, about 65 per cent of sires can be successfully genotyped.

Alleles

A sequence-specific DNA-binding protein recognising a GA-rich element cooperates with Oct-1 at the herpes simplex virus type 1 IE3 promoter.

Herpes simplex virus immediate early (IE) gene transcription is regulated via the upstream TAATGARAT motif and involves the recruitment of the ubiquitous octamer-binding protein Oct-1 and a component of the virion Vmw65 into a multiprotein complex termed the immediate early complex (IEC). An upstream GA-rich element (GA-RE) has been postulated to mediate a response to Vmw65 independent of TAATGARAT. We have studied IEC formation in gel shift assays using DNA fragments containing these sequence elements from the HSV-1 IE gene 3 promoter in different combinations. The results show that a factor which footprints to the GA-RE cooperates with Oct-1 to increase IEC levels on a TAATGARAT motif located 5 bp 5' to the GA-RE. The factor alone is unable to promote IEC formation. We were unable to demonstrate any effect of this factor on a TAATGARAT motif located 16 bp from the GA-RE, suggesting that this effect is not universal for all TAATGARAT motifs.

Base Composition

Craniofacial form in class III cases.

Lateral skull cephalograms from 50 patients who subsequently had surgical correction of their Class III malocclusion were analysed using a complete linkage cluster analysis based on skull shape. Five subgroups were identified and are described. All subjects had a degree of mandibular prognathism while only 14 per cent had maxillary retrognathism. An increased lower face height was found in 58 per cent.

Adult