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Biomedical subjects

G Roberts

Publications and source records attributed to G Roberts.

At least 109 records · Page 6Linked to original sources
PubMed1996

Analysis of a structural polymorphism in the 5-HT2A receptor and clinical response to clozapine.

Clozapine is an atypical antipsychotic with affinity for a broad range of receptors, including serotonin (5-HT) and dopamine receptors. It is successful in treating about 60% of patients refractory to other antipsychotic drugs. Since genetic variation in clozapine's neurotransmitter receptor targets may affect clinical response through altering drug binding or receptor expression, we have studied a His452Tyr polymorphism in the 5-HT2A receptor (HTR2A) in a sample of 153 schizophrenic patients undergoing clozapine treatment and 178 normal controls. An association was found between the allele Tyr452 and poor clinical response.

Alleles↗
PubMed1996

Complete analysis of the presenilin 1 gene in early onset Alzheimer's disease.

The presenilin 1 gene has recently been identified as the locus on chromosome 14 which is responsible for a large proportion of early onset, autosomal dominantly inherited Alzheimer's disease (AD). We have elucidated the intron/exon structure of the gene and designed intronic primers to enable direct sequencing of the entire coding region (10 exons) of the presenilin gene in a large number of families. This strategy has enabled us to find a further two novel mutations in the gene. We discuss the distribution of mutations and the proportions of autosomal dominant AD with a mean age of onset below 60 years caused by mutations in this gene.

Alzheimer Disease↗
PubMed1996

Racial and gender effects on the relaxation response: implications for the development of hypertension.

This study was designed to explore the effect of race and gender on the forehead muscle tension and finger temperature response to biofeedback-assisted relaxation training in individuals with normal blood pressure. Forty-five subjects-18 Black and 27 White, 25 males and 20 females-participated in eight sessions of autogenic relaxation training and thermal biofeedback. Multivariate analysis of variance of the variables measured at baseline (systolic BP diastolic BP sodium excretion, anxiety) was significant for gender Univariate analysis showed males different from females in DBP Na(+) excretion, and trait anxiety. Pretest values of muscle tension were similar by gender, but pretest temperatures were lower in males than females. Repeated measures ANOVA for muscle tension showed a significant effect of period. For temperature a significant effect of period, gender and gender x period was observed. Males increased temperature more than females. There was no effect of history of hypertension on the relaxation response. Multiple regression performed on change in muscle tension and change in temperature showed that pretest muscle tension predicted change in muscle tension. Four variables contributed to the variance in change in temperature: pretest temperature, sodium excretion, and state and trait anxiety.

Adult↗
PubMed1996

Prevalence of domestic violence among patients attending a hospital emergency department.

A cross-sectional study was conducted to determine the prevalence of domestic violence victims among patients using emergency services at Sydney's Royal North Shore Hospital, in an affluent urban area of New South Wales. This study used a self-administered questionnaire (used in a similar study at the Royal Brisbane Hospital) to investigate the history of domestic violence among patients attending the emergency department during 64 randomly selected nursing shifts in October-November 1994. Adult domestic violence was reported by 19.3 per cent of females and 8.5 per cent of males, confirming the results of the Brisbane study. Evidence for underreporting was found: 4 per cent of females and 6.3 per cent of males who did not report being victims revealed experiences of abuse on nine measures of types of violence, including six taken from the Conflict Tactics Scale. Results supported evidence from other studies suggesting that experience of abuse as a child is a risk factor for being in abusive relationships as an adult. In the past, comparison of results has been limited because of variation in definitions of domestic violence; this has been overcome by intentional replication of the Brisbane study. The study was enhanced by inclusion of patients from non-English-speaking backgrounds and a cohort of parents of children attending. Similar prevalence estimates were found in these groups. Results have implications for the detection and treatment of victims of domestic violence across all strata of society and have potential to raise awareness and affect attitudes towards this significant community problem.

Adolescent↗
PubMed1996

Community health workers' response to violence against women.

This paper reports on a qualitative study of community health workers from a predominantly rural based region in Queensland. The purpose of this study was to determine the community health worker barriers to identification, assessment and intervention on the issue of violence against women. The qualitative research method comprised five structured focus group interviews with 28 community health workers using open-ended questions to explore their perceptions. Analysis of the focus group data revealed that community health workers expressed reluctance to become involved in cases of violence against women. The reasons they provided are grouped under three main themes: barriers to identification; barriers to assessment; and barriers to intervention. Training programs offered to rural community health workers need to be aware of the barriers to identifying, assessing and intervening in cases of violence against women that are highlighted by this study. Further studies are needed to assess the wider relevance of these findings to other groups of community health workers in rural and non-rural settings.

Attitude of Health Personnel↗
PubMed1996

The role of presenilin 1 in the genetics of Alzheimer's disease.

Approximately 75% of AD patients have an onset of the disease after the age of 60 years, and 60% of AD patients have no family history of the disease. Some cases of EOAD are clearly inherited in an autosomal-dominant manner. The beta APP gene on chromosome 21, the PS-1 gene on chromosome 14, and the PS-2 gene on chromosome 1 have all been characterized as genes in which mutations lead to familial EOAD. For LOAD, the work on ApoE indicates that the epsilon 4 allele is a risk factor for developing AD. However, 35-50% of all AD patients do not have an epsilon 4 allele. Other loci contributing to LOAD remain to be mapped and characterized. As in other complex disorders, these additional loci may involve genetic interactions with the known AD loci. Identification of all susceptibility loci for AD is a major goal in resolving the pathogenesis of AD.

Alternative Splicing↗
PubMed1995

Association between clozapine response and allelic variation in 5-HT2A receptor gene.

We report allelic association between a polymorphism (T102C) within the coding region of the 5-HT2A gene (HTR2A, 13q14-21) and response to clozapine in schizophrenic patients. Homozygosity for the C102 allele was more frequent (30/57, 53%) among patients who did not respond to clozapine than in those who responded (23/92, 25%). This finding is evidence that allelic variation of genes which encode neurotransmitter receptors can influence clinical response to antipsychotic drugs.

Alleles↗
PubMed1995

Risk-adjusted analysis of surgeon performance: a 1-year study.

A 1-year prospective analysis was undertaken of all non-day-case general surgery in a district general hospital. Using the Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) scoring system 3004 patients were assessed. From the predictions of mortality and morbidity so obtained, a quality measure, the ratio of observed to expected numbers of deaths and complications (O:E ratio) was determined for each surgeon, both overall and within specialty zones. The present study demonstrates the serious hazard in using 'raw' uncorrected mortality and morbidity statistics to compare surgeon performance. Mortality rates varied from 1.0 to 4.9 per cent whereas O:E ratios ranged from 0.83 to 1.06; morbidity rates varied from 5.3 to 12.6 per cent with O:E ratios 0.86-1.02. Great misunderstanding may result from the publication of surgeon or hospital 'league tables'. The present study demonstrates a technique that might allow surgeon performance to be monitored adequately and accurately.

Day Care, Medical↗
PubMed1995

Unusual distribution of enamel hypoplasia in an 11-year-old child with Proteus syndrome.

An 11-year-old girl with Proteus syndrome attended our dental department because her teeth were sensitive to cold stimuli and because of the poor appearance of her anterior teeth. Extraoral examination revealed several of the previously reported craniofacial features of Proteus syndrome: facial and skull asymmetry, exostoses of the nasal bridge, and mandibular prognathism. Intraoral examination revealed enamel hypoplasia of primary and permanent teeth. The distribution of hypoplasia was unusual in that only teeth on the right side of the mouth were affected, and also in that only the distal half of the crown of the maxillary right permanent central incisor was affected. Behavioural problems necessitated treatment under general anaesthesia; the affected primary teeth were extracted and the hypoplastic permanent teeth were restored, relieving the patient's symptoms and greatly improving aesthetics.

Child↗
PubMed1995

Educational assessment of general practice experience for psychiatric trainees.

Eighteen psychiatric trainees spent 6 months each as general practice trainees. The educational impact of the experience was assessed by a self-assessment questionnaire, a semi-structured interview and a videotaped interview with a psychiatric patient. Each assessment was conducted at a baseline and after 12 months. A control group of 14 trainees was recruited from the same rotation. On the self-assessment questionnaire, the study registrars rated their abilities to solve general medical problems significantly improved compared to controls. They had also acquired greater understanding of the limitation of their knowledge and their legal responsibilities towards their patients. The semi-structured interview failed to distinguish between the two groups. Videotapes for rating at baseline and follow-up were available for only 17 of the trainees. Assessment of the tapes used the Maguire Scale and the Interview Behaviour Scale. Neither scale demonstrated any intervention effect. The interviews were all characterized by a preponderance of 'closed psychological' and 'checking-out' questions. It appears that psychiatric trainees' interviewing styles had not been influenced by the experience. This study suggests that psychiatric trainees gain greater confidence in their role as a doctor and greater understanding of the scope and nature of general practice by such an attachment. It is unclear whether or not supplementary interviewing skills had been acquired which were not utilized in the taped interview, which conforms very much to traditional psychiatric examination behaviour. Trainees were reassured that they had increased their knowledge without losing any of their specific professional skills.

Education, Medical, Continuing↗
PubMed1994

Senile dementia of the Lewy body type has an apolipoprotein E epsilon 4 allele frequency intermediate between controls and Alzheimer's disease.

We have examined the apolipoprotein E (ApoE) allele distributions in Alzheimer's disease, Parkinson's disease, senile dementia of the Lewy body type and neurologically normal controls. We have confirmed the strong genetic association between the epsilon 4 allele and Alzheimer's disease, shown that there is no association between the epsilon 4 allele and Parkinson's disease and shown that senile dementia of the Lewy body type has an epsilon 4 allele distribution intermediate between Alzheimer's disease and Parkinson's disease. On this basis, we suggest that senile dementia of the Lewy body type represents the co-occurrence of two syndromes.

Aged↗
PubMed1994

Plasminogen mutants activated by thrombin. Potential thrombus-selective thrombolytic agents.

Plasmin, the enzyme responsible for degradation of fibrin in blood clots and thus thrombolysis, is normally formed when its zymogen plasminogen is activated by cleavage of the Arg561-Val562 bond by specific plasminogen activators. We have altered the activation characteristics of plasminogen by substituting the P3, P2, and P1' cleavage site residues with sequences from thrombin-cleavable proteins to produce a novel thrombolytic agent which instead is activated by the blood clotting system. Plasminogen variants with thrombin cleavage sites from fibrinogen, the thrombin receptor, factor XIII, and factor XI were cleaved by thrombin with times to 50% cleavage of 28 h, 2.5 h, 5.7 min, and 3 min, respectively. In vitro clot lysis studies have shown that a variant in which the P3-P1' residues of plasminogen were substituted by the P7-P1' residues (Thr363-Ile370) from factor XI (T51) was sufficiently rapidly cleaved by thrombin to be activated by the endogenous thrombin produced by the coagulation cascade, resulting in rapid clot dissolution. Thrombin-activatable plasminogen therefore has the capacity to short circuit the physiological hemostatic mechanisms and produce fibrinolytic activity localized to the site of thrombin formation, that is, at the thrombus itself. The novel activation mechanism combined with the natural long circulating half-life of plasminogen gives this type of thrombolytic agent the potential for thrombus-selective plasmin generation and an extended duration of action.

Amino Acid Sequence↗
PubMed1994

Investigations of the 'active' edge of plaque psoriasis: vascular proliferation precedes changes in epidermal keratin.

We have investigated markers of epidermal proliferation and differentiation in terms of keratin expression, the morphology of the cutaneous vasculature, and numbers of cutaneous mast cells, in patients with chronic plaque psoriasis. Using the phenomenon of the 'active edge', we have studied these features in the psoriatic plaque itself, and in the clinically normal active and inactive edges of the same plaque. Our results confirm the anticipated changes in keratin profiles, mast cell numbers and psoriatic morphology of the vasculature within the plaque itself. They further indicate that the vascular changes precede the epidermal and mast cell features at the active edge, and that the inactive edge is inactive for all of these variables. Mediators responsible for the vascular proliferation and elongation must be present in increased amounts at the active edge when compared with the inactive, and include locally produced and circulating factors.

Cell Count↗
PubMed1994

The effect of low and high sodium diets on plasma atrial natriuretic factor, the renin-aldosterone system and blood pressure in subjects with essential hypertension.

OBJECTIVE: Increasing dietary sodium intake increases blood pressure in some subjects with essential hypertension. Atrial natriuretic factor (ANF) has a potential role in modifying these changes. The purpose of this study was to observe the blood pressure and plasma ANF responses to low and high sodium diets in subjects with essential hypertension to see if the plasma ANF and blood pressure responses were related. DESIGN: An in-patient study of subjects taking their normal diet (day 1), a 12 mmol sodium diet for 6 days and a 250 mmol diet for 6 days. PATIENTS: Seven men with essential hypertension. MEASUREMENTS: Continuous 24 hour urine collections were analysed for sodium excretion. Blood pressure was recorded at 0900, 1205 and 1700 h on days 1, 7 and 13. Blood was taken at 0900 h (fasting supine overnight) and at 1200 h (after 2 hours erect posture) on the above days for plasma ANF, plasma renin activity (PRA) and serum aldosterone. RESULTS: Urinary sodium excretion was (mean +/- SEM) 11 +/- 1 mmol on day 5 of the low sodium diet, and 294 +/- 17 mmol during the fifth day of the high sodium diet. Plasma ANF (supine and erect) was significantly lower (2.8 +/- 0.6, 1.6 +/- 0.2 pmol/l) on the low sodium diet when compared to the high sodium diet (8.6 +/- 2.4, 5.0 +/- 1.6 pmol/l (P < 0.05)). Supine and erect PRA and serum aldosterone were significantly higher on the low compared to the high sodium diet. Blood pressure responses were heterogeneous rather than bimodal. Mean arterial blood pressure was 107 +/- 3 mmHg on the low sodium diet and 111 +/- 4 mmHg on the high sodium diet (P < 0.05). Changes of blood pressure did not correlate with the changes of plasma ANF. CONCLUSIONS: Failure of plasma atrial natriuretic factor to rise with increasing dietary sodium did not therefore determine the blood pressure response to the change in dietary sodium. No link was established between plasma atrial natriuretic factor response and sodium sensitivity.

Adult↗
PubMed1994

Coagulopathy with piperacillin administration in cystic fibrosis: two case reports.

Two cases are reported of coagulopathy in association with the administration of piperacillin to patients with cystic fibrosis. In both cases the coagulopathy was associated with the development of a serum sickness-like illness with fever, rash and abnormal liver function tests occurring on day 12 and day 16 of treatment, respectively. On withdrawal of the piperacillin, both the serum sickness and the coagulopathy resolved rapidly, without sequelae.

Blood Coagulation Disorders↗
PubMed1994

Controlled trial of anti-tuberculous chemotherapy for two years in Crohn's disease.

One hundred and thirty patients with active symptoms of Crohn's disease were treated in a double blind randomised controlled trial with rifampicin, isoniazid, and ethambutol, or identical placebos for up to two years. All other treatment considered necessary was continued. Analyses were based on 126 patients, 63 in each treatment group. Thirty seven in the active and 30 in the placebo group had previous surgical procedures. There was no difference in concomitant treatment between the two groups. Thirty in the active and 46 in the placebo groups were taking corticosteroids at entry to the trial. Forty eight of 63 patients in the active and 49 of 63 in the placebo group, completed at least 12 months' therapy. Reasons for early withdrawal included pregnancy, adverse reaction, and failure to comply. There was no significant difference in the mean number of months completed between the two groups. Nineteen adverse reactions were recorded for 17 patients in the active group compared with three reactions in patients on placebo. All of the nine patients withdrawn early because of adverse reactions were in the active group. Fifteen patients on active treatment and 14 on placebo had surgery during the trial with no difference in the type of surgery required between the groups. Radiological assessments based on 98 patients at the end of the trial showed no significant differences between groups in changes of extent of disease. More patients developed strictures on placebo compared with active treatment but without a statistically significant difference. No differences were found between groups for the total prednisolone dose or the number of days on which prednisolone dose was 10 mg or above. Serial measurements of body weight and Crohn's disease activity index (CDAI) together with blood values for albumin, haemoglobin, white cell count, and platelets showed no consistent different differences between groups. There were occasional significant differences for some of these values between groups, which were not sustained. The trail provides little evidence of tangible benefit from the trail treatment.

Adolescent↗