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Biomedical subjects

A Ward

Publications and source records attributed to A Ward.

At least 91 records · Page 5Linked to original sources
PubMed1996

Psychosocial influences on the use of health care by children.

A prospective cohort study examined the influence of psychosocial factors on the use of general practitioners over a six-month period by 271 children (aged four to nine years) and their mothers. The study was conducted in 10 general practices in the metropolitan area of Perth. The influences of psychosocial factors on use, nonuse and frequency of use by the children were examined, taking into account sociodemographic and morbidity factors. Physical health status, maternal use and financial factors were directly associated with the children's use or nonuse of general practitioners, while maternal stress, a mother's attitude towards her child and the child's psychosocial morbidity were indirectly related. Physical health status, doctor-initiated consultations, maternal stress, children's ages and birth order were directly associated with the children's frequency of use of general practitioners. Depression and anxiety in the mothers, measured with standardised instruments, were not associated with use by the children nor was a mother's level of social support. The results point to the importance of family relationships and illness behaviour in the family when considering use of general practitioners and the importance of using standardised measuring instruments and multivariate designs when studying such complex behaviours as the use of health care.

Attitude to Health↗
PubMed1996

Downgaze paresis following severe head trauma in a child.

A 4 1/2-year-old girl developed a downgaze paresis following severe head trauma. Magnetic resonance imaging showed evidence of peri-aqueductal lesions in the rostral midbrain in the region of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). Twenty five weeks following the injury, the downgaze paresis remained unchanged but she developed convergence retraction nystagmus on attempted upgaze. Repeat imaging did not show any change in the lesions in the rostral midbrain. This report provides further evidence for the riMLF in the control of downgaze, and a synkinesis is postulated for the development of the convergence retraction nystagmus.

Child, Preschool↗
PubMed1996

Arylamine N-acetyltransferase in erythrocytes of cystic fibrosis patients.

Sulphamethoxazole, a substrate of human arylamine N-acetyltransferase, is used in the treatment of cystic fibrosis patients, who metabolise the drug rapidly. Increased metabolic clearance of sulphamethoxazole has been suggested to account for this rapid metabolism. Arylamine N-acetyltransferase type 1 is expressed in erythrocytes and leucocytes and the activity in erythrocytes is shown to contribute approximately 99% of the activity of arylamine N-acetyltransferase type 1 in blood cells. Arylamine N-acetyltransferase type 1 activity in erythrocytes from 16 adult cystic fibrosis patients and 19 age-matched controls were compared. Although there is a variation in erythrocyte arylamine N-acetyltransferase type 1 activity within each group, no difference was found when the two groups were compared. All individuals from the cystic fibrosis and control groups were investigated for certain allelic variants of the arylamine N-acetyltransferase type 1 gene (NAT1). Only one copy of a mutant NAT1 allele (NAT1*11) was found. The heterozygous NAT1 individual is a cystic fibrosis patient with a low level of erythrocyte arylamine N-acetyltransferase type 1 activity. A second distinct arylamine N-acetyltransferase isozyme, arylamine N-acetyltransferase type 2, is encoded at the multi-allelic NAT2 locus. There was no correlation between erythrocyte arylamine N-acetyltransferase-1 activity and NAT2 alleles present in either the cystic fibrosis or control groups. The distribution of NAT2 alleles was very similar in the two groups. The increased clearance of sulphamethoxazole in cystic fibrosis patients appears unlikely to be due to erythrocyte arylamine N-acetyltransferase type 1 activity or to inheritance of alleles at either the NAT1 or NAT2 loci.

Adolescent↗
PubMed1996

To change or not to change--'how' is the question?

The objective was to apply the 'trans-theoretical' model of change to a group of patients with eating disorders. Patients were studied in an in-patient setting. Two sets of questionnaires were used, one to assess 'stage' of change, the other to measure the 'processes' used to achieve change. Three stages and eight processes were examined. Thirty-five patients completed the study. Highest scores were found in the contemplation, and lowest in the precontemplation stage. The most frequently used processes of change were self-reevaluation, helping relationships and consciousness raising, with different processes predominating at different stages. Covariance analysis supported an association between two latent variables 'stage' and 'process'. Despite the limitations of small numbers, our results are in broad agreement with others using the 'trans-theoretical' model, supporting its use in eating disorders. Although further work is necessary, the model suggests a way of thinking about helping this very ambivalent group of patients to institute and sustain change.

Adolescent↗
PubMed1996

Immunochemical detection of arylamine N-acetyltransferase in normal and neoplastic bladder.

The N-acetyltransferase (NAT) phenotype is an important determinant of individual susceptibility to occupational bladder cancer. N-Acetyltransferases arc known to metabolize aromatic amine bladder carcinogens, but the functional significance of NAT expression in the target organ is unclear. To resolve this issue, polygonal antisera against purified recombinant enzymes and C-terminal peptides of human NAT Type 1 (NAT1) and Type 2 (NAT2) were generated. Western blot analysis of exfoliated cells from human urine, pig bladder homogenate, and human bladder tumor-derived cell lines showed that NAT1 was expressed in all three systems, whereas NAT2 did not appear to be expressed in the bladder. Immunohistochemical analysis of human bladder tumor sections indicated that well-differentiated tumor cells expressed NAT1, with the highest level of expression being found in the umbrella cells that line the bladder lumen. Poorly differentiated tumor regions appeared to express NAT1 at lower levels than did well-differentiated areas. These findings support the hypothesis that aromatic amines are metabolized in the bladder epithelium by NAT1.

Amino Acid Sequence↗
PubMed1996

The demand for eating disorder care. An epidemiological study using the general practice research database.

BACKGROUND: An epidemiological study of anorexia nervosa and bulimia nervosa in primary care was performed using the General Practice Research Database (GPRD). METHOD: The GPRD was screened between 1988 and 1994 for newly diagnosed cases of anorexia nervosa and bulimia nervosa. The validity of the computer diagnosis was established by obtaining clinical details from a random sample of the general practitioners (GPs). RESULTS: Incidence rates for detection of cases by GPs in 1993 was 4.2 per 100,000 population for anorexia nervosa, and 12.2 per 100,000 for bulimia nervosa. The relative risks of females to males was 40:1 for anorexia nervosa and 47:1 for bulimia nervosa. A threefold increase in the recording of bulimia nervosa was found from 1988 to 1993. Eighty per cent of anorexia nervosa cases and 60% of bulimia nervosa cases were referred to secondary care. CONCLUSION: There is a continuing expansion of service need for bulimia nervosa. The majority of cases of eating disorders are referred to secondary services. There is scope for more effective management of bulimia nervosa in primary care.

Adolescent↗
PubMed1996

Physical measures of recovery from anorexia nervosa during hospitalised re-feeding.

OBJECTIVE: To examine the relationship between weight gain, changes in body composition and physiological characteristics of fitness during the recovery from anorexia nervosa. DESIGN: Longitudinal over eight weeks of intensive inpatient re-feeding (Wk 0-8). SETTING: The London Hospital Medical College. SUBJECTS: Ten female patients who agreed to participate. Seven completed the protocol. INTERVENTIONS: Dual-energy X-ray absorptiometry (dexa) and skinfold thickness measures at Wk 0 and 8. Weekly measures of peak expiratory flow rate and cycle ergometry (several variables relating to aerobic work recorded at rest and during cycling at low loads (0-60 W)). Blood samples for lactate and potassium measures, taken during cycling at Wk 0, 4 and 8 only. RESULTS: (1) Body composition: Mean weight gain over eight weeks was 9.6 kg, dexa and skinfold measures showing fat gain to contribute 62% and 54%, respectively. Both methods showed significant changes in percentage body fat with refeeding (P < 0.01 and P < 0.001, respectively), however there were significant differences in results between methods before (P < 0.01) but not after (P = 0.2) refeeding. (2) Physiological function: Between weeks 0 and 8, mean peak expiratory flow rate rose to 85% of predicted values, cycle ergometry performance improved in six subjects (three never reached 60 W load), mean respiratory exchange ratio (RER) during cycling fell at 0 W and 20 W loads (both P < 0.05), and oxygen pulse increased at rest and 0 W load cycling (both P < 0.05), Wk 8 values being well below normal. Oxygen uptake at rest and all loads increased in line with body weight gain only. No significant changes were seen in heart rate or blood lactate and potassium levels. CONCLUSIONS: (1) Lean body and fat mass increased significantly during eight weeks of refeeding. The methodological difference in initial body fat measurements requires further investigation. (2) The women had severely impaired physiological function. Variables studied were only slowly improving with refeeding, and work capacity was still well below normal.

Absorptiometry, Photon↗
PubMed1995

Repression of promoters for the mouse insulin-like growth factor II-encoding gene (Igf-2) by products of the Wilms' tumour suppressor gene wt1.

We have investigated actions of the Wilms' tumour suppressor zinc finger transcription factor, WT1, on promoters of the mouse insulin-like growth factor II-encoding gene (Igf-2). Two variant forms of WT1 repressed the two major Igf-2 promoters (P2 and P3) in transient transfection assays. WT1-binding sites were characterised in both these promoters and in the transcribed region downstream from P2, exon 2. In each of these regions, there was a pair of WT1-binding sites, and mutational analysis of the exon-2 sites indicated that both were required for full repression. Cooperative binding of WT1 to these sites might explain the dominant-negative mutations of WT1 observed in some Wilms' tumours and Denys-Drash syndrome cases.

Animals↗
PubMed1995

Human nicotinamide N-methyltransferase gene: molecular cloning, structural characterization and chromosomal localization.

Genomic DNA clones for nicotinamide N-methyltransferase (NNMT), an enzyme that catalyzes drug and xenobiotic metabolism, were isolated from a human chromosome 11-specific DNA library. Study of one of those clones, when combined with PCR-based experiments performed with human genomic DNA, made it possible to determine the structure of the human NNMT gene. The gene was approximately 16.5 kb in length and consisted of 3 exons and 2 introns. Transcription initiation for the NNMT gene occurred 105-109 nucleotides 5'-upstream from the cDNA translation initiation codon on the basis of the results of both primer extension and 5'-rapid amplification of cDNA ends. NNMT mapped to chromosome band 11q23.1 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1995

Purification of recombinant human N-acetyltransferase type 1 (NAT1) expressed in E. coli and characterization of its potential role in folate metabolism.

Human arylamine N-acetyltransferase type 1 (NAT1) has been cloned from human genomic DNA, into the vector pET(5a) and expressed in Escherichia coli. The recombinant protein has been purified to apparent homogeneity using anion exchange chromatography. The arylamine acceptor specificity, and the effect of potential NAT1 inhibitors has been investigated using purified recombinant protein. The Km of the recombinant NAT1 protein for the substrates para-aminobenzoate (p-aba) and 4-aminosalicylate are 14.3 and 11.8 microM, respectively. Folate and amethopterin were found to be potent competitive inhibitors of p-aba acetylation, with Ki values of 13.3 and 9.5 microM, respectively. The pteroate moiety of folate, in contrast is a poor inhibitor, with 100 microM pteroate inhibiting only 40% of NAT1 activity. A catabolite of folate para-aminobenzoly-L-glutamate has also been shown to be a NAT1 substrate with a Km value of 263 microM.

Arylamine N-Acetyltransferase↗
PubMed1995

Isolation and identification of a compound from avocado (Persea americana) leaves which causes necrosis of the acinar epithelium of the lactating mammary gland and the myocardium.

It is well known that when lactating livestock eat avocado (Persea americana) leaves they may develop non-infectious mastitis and agalactia. This is associated with extensive coagulation necrosis of the secretory acinar epithelium and interstitial oedema, congestion, and haemorrhage. Similar lesions have been produced in mammary glands of lactating mice fed a diet containing a small percentage of freeze-dried avocado leaf. Tests using these animals have been used to isolate the active principle, termed "persin," from avocado leaves. The purified persin was examined using IR, NMR, and UV spectroscopy and mass spectrometry, and identified as (Z,Z)-1-(acetyloxy)-2-hydroxy-12,15-heneicosadien-4-one. Persin has previously been isolated from avocado leaves and shown to have antifungal properties and to be toxic to silkworms. Our tests have shown that persin at the dose rate of 60-100 mg/kg has the same effect on mammary glands in lactating mice as leaves from avocado. Enantioselective syntheses of the R and the S isomers of persin and related derivatives were carried out. These compounds were tested for activity required to induce widespread lactating mammary gland necrosis in mice, and only the R isomer was found active. At doses of persin above 100 mg/kg necrosis of myocardial fibres may occur and hydrothorax may be present in severely affected animals. The mechanism of action of persin on both the mammary gland and the myocardium remain to be resolved.

Animals↗
PubMed1995

Mammary cancer in transgenic mice expressing insulin-like growth factor II (IGF-II)

The effect of insulin-like growth factor II (IGF-II) on tumour development in the mouse mammary gland was studied. To promote extra IGF-II expression in the mammary gland, sheep beta-lactoglobulin regulatory elements were attached to the coding regions of the mouse Igf-2 gene and injected into the pronuclei of mouse zygotes. Mammary tumours developed in each of the four independent lines of mice which expressed transgene IGF-II in the gland. Tumours from two of the lines grew after transplantation to both male and female hosts. Primary tumours contained stromal and epithelial regions, but the tumours were dominated by mammary adenocarcinoma after transplantation. The tumours expressed high levels of Igf-2 mRNA transcribed from the integrated transgenes.

Adenocarcinoma↗
PubMed1995

Doubly disabled: diabetes in combination with an eating disorder.

We present a series of patients with both an eating disorder and diabetes mellitus and compare these to a group of non-diabetic patients from the same clinic. Significantly more of the diabetic patients had previous attempts at treatment for their eating disorder. A high incidence of diabetic complications was noted with clear implications, both clinically and economically, for early intervention. The incidence of childhood trauma was lower in the diabetic than the non-diabetic group. In the majority of patients, diabetes developed before the eating disorder, suggesting that diabetes itself may provide the vulnerability and increase the risk of developing an eating disorder. Early intervention in diabetic clinics may prevent the development of serious eating disorders.

Adult↗
PubMed1995

Dapsone acetylation by human liver arylamine N-acetyltransferases and interaction with antiopportunistic infection drugs.

Dapsone is used in the treatment of Pneumocystis carinii pneumonia, an opportunistic infection that afflicts acquired immunodeficiency syndrome (AIDS) patients. Inhibition of N-acetyltransferase (NAT)-dependent acetylation of dapsone could increase peak plasma concentrations of dapsone and shift the biotransformation pathway to the P450-mediated formation of a toxic metabolite of dapsone, the hydroxylamine. Therefore, we have determined using human liver cytosol and bacterially expressed NATs, the NAT isoform responsible for acetylating dapsone and the potential for antiopportunistic infection drugs to inhibit this metabolic pathway. Formation of monoacetyldiaminodiphenylsulfone (MADDS) was quantitated by HPLC/UV detection at 270 nm after incubation of dapsone with 100 microM acetyl coenzyme A regenerating system and human liver cytosol. The mean +/- SD apparent KM for the formation of MADDS in three different human livers predicted to be fast acetylators based on genotyping was 98 +/- 17.6 microM, and the Vmax was 190 +/- 20 pmol/min/mg cytosol protein. Eadie-Hofstee transformation of the substrate velocity data was linear, indicating acetylation by a kinetically single enzyme. Sulfamethazine (250 microM) inhibited dapsone acetylation by 100% and 80%, respectively, at dapsone concentrations of 3 and 100 microM, in both fast- and slow-acetylating liver cytosol preparations, whereas para-amino-benzoic acid (100 microM) did not inhibit MADDS formation at either of these dapsone concentrations. Lineweaver-Burk plots of dapsone acetylation in the presence of 0, 25, and 50 microM sulfamethazine showed an increase in the apparent KM, with increase in sulfamethazine concentration with no change in the Vmax, indicating competitive inhibition of dapsone acetylation by sulfamethazine. The apparent KM of dapsone acetylation by bacterially expressed NAT1 and NAT2 enzymes was 687 and 136 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1995

Type 2 diabetes. Patient practices, and satisfaction with GP care.

OBJECTIVE: To document patients' practices and management of DM2, their satisfaction with diabetes care and their quality of life and functional status. DESIGN: Anonymous questionnaire completed by 467 patients recruited by 204 GPs in 124 practices in the Perth metropolitan area. RESULTS: Patients reported an adequate amount of monitoring for stable DM2. However, they lacked awareness of diabetes risk factors and complications from which they already suffered. Some 90% of patients reported a high level of satisfaction with GP care and only 2.4% of patients had more than a moderate degree of functional disability. CONCLUSION: Patients have a high level of satisfaction about the diabetes care received from their general practitioner. However, they lack awareness of their risk factors and complications of diabetes. A simple strategy is proposed to improve these deficits and to share the responsibility for diabetes care between patient and doctor.

Adult↗
PubMed1995

Chronic psychological effects of exercise and exercise plus cognitive strategies.

Psychological changes associated with 16-wk moderate and low intensity exercise training programs, two of which possessed a cognitive component, were evaluated. Subjects were healthy, sedentary adults, 69 women (mean age = 54.8 +/- 8.3 yr) and 66 men (mean age = 50.6 +/- 8.0 yr). Participants were randomly assigned to a control group (C), moderate intensity walking group (MW), low intensity walking group (LW), low intensity walking plus relaxation response group (LWR), or mindful exercise (ME) group-a Tai Chi type program. Women in the ME group experienced reductions in mood disturbance (tension, P < 0.01; depression, P < 0.05; anger, P < 0.008; confusion, P < 0.02; and total mood disturbance, P < 0.006) and an improvement in general mood (P < 0.04). Women in the MW group noted greater satisfaction with physical attributes (body cathexis, P < 0.03), and men in MW reported increased positive affect (P < 0.006). No other differences were observed between groups on measures of mood, self-esteem, personality, or life satisfaction. Equivocal support is provided for the hypothesis that exercise plus cognitive strategy training programs are more effective than exercise programs lacking a structured cognitive component in promoting psychological benefits.

Adaptation, Psychological↗