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Biomedical subjects

D Ball

Publications and source records attributed to D Ball.

At least 73 records · Page 4Linked to original sources
PubMed1999

Association analysis of sequence variants of GABA(A) alpha6, beta2, and gamma2 gene cluster and alcohol dependence.

Quantitative trait analyses in mice suggest a vulnerability locus for physiological alcohol withdrawal severity on a chromosomal segment that harbors the genes encoding the alpha1, alpha6, beta2, and gamma2 subunits of the gamma-aminobutyric acid type-A receptor (GABR). We tested whether genetic variation at the human GABA(A) alpha6, beta2, and gamma2 gene cluster on chromosome 5q33 confers vulnerability to alcohol dependence. The genotypes of three nucleotide substitution polymorphisms of the GABRA6, GABRB2, and GABRG2 genes were assessed in 349 German alcohol-dependent subjects and in 182 ethnically matched controls. To eliminate some of the genetic variance, three more homogeneous subgroups of alcoholics were formed by: (1) a history of alcohol withdrawal seizure or delirium (n = 106); (2) a history of parental alcoholism (n = 120); and (3) a comorbidity of dissocial personality disorder (n = 57). We found no evidence that any of the investigated allelic variants confers vulnerability to either alcohol dependence or severe physiological alcohol withdrawal symptoms or familial alcoholism (p > 0.05). The frequency of the T allele of the GABRA6 polymorphism was significantly increased in dissocial alcoholics [f(T) = 0.799] compared with the controls [f(T) = 0.658; p = 0.002; OR(T+) = 7.26]. Taking into account the high a priori risk of false-positive association findings due to multiple testing, further replication studies are necessary to examine the tentative phenotype-genotype relationship of GABRA6 gene variants and dissocial alcoholism.

Adult↗
PubMed1999

The use of a deuterium tracer technique to follow the fate of fluids ingested by human subjects: effects of drink volume and tracer concentration and content.

Deuterium oxide (2H2O) has been added to drinks as a tracer for water to estimate the availability to the body water pool of ingested fluids, but doubts have been raised as to the reliability of the method. The present investigation evaluated the effects of systematic variations in the volume of fluid consumed and the amount and concentration of added tracer on the rate of accumulation of tracer in arterialized blood after ingestion of a labelled drink. Three separate experiments were undertaken. In expt 1, six healthy men ingested on separate occasions 200, 400 and 800 ml of a dilute glucose-electrolyte solution: all test drinks contained the same concentration (40 g l-1) of 2H2O. In expt 2, six healthy men ingested 200, 400 and 800 ml of the same glucose-electrolyte drink: each drink contained 8 g of 2H2O so that the concentration, but not the amount, of 2H2O differed between treatments. In expt 3, six healthy men ingested 400 ml of the same drink on three separate occasions: each drink contained 8, 16 or 32 g of tracer so that amount and concentration of 2H2O both varied. Arterialized venous blood samples were collected for the determination of deuterium (2H) concentration before ingestion of the test drink and at intervals for 120 min after ingestion. All trials for each of the experiments were conducted in the morning after an overnight fast and trials were in randomized order and separated by 7 days. In expt 1, the blood 2H concentration at all time points from 2 min after ingestion of the test drink onwards was higher for the drink containing 32 g 2H2O than for the drink containing 16 g 2H2O, which in turn was higher than after ingestion of the drink containing 8 g of 2H2O. In expt 2, no significant differences between treatments were observed at any time. In expt 3, the rate of 2H accumulation was greater after ingestion of the drink containing 32 g of 2H2O than after either of the other two drinks, and the 2H accumulation rate was greater after ingestion of the drink containing 16 g of 2H2O than after the drink containing 8 g of 2H2O. When data from all three experiments were combined, significant correlations were observed between the rate of accumulation of 2H in the circulation (p.p.m. min-1) and the amount (rs = 0.75, P < 0001) and concentration (rs = 0.69, P < 0001) of 2H2O in the test drink, but there was no relationship (rs = 0.09, P = 0.5) between the rate of 2H accumulation in the blood and the volume of the drink consumed. The results suggest that the rate of tracer accumulation in the blood after ingestion of different volumes of test drinks is not a reliable indication of the availability of the ingested fluid, but that the method gives at least a qualitative measure of the sum of the effects of gastric emptying and intestinal water absorption.

Adult↗
PubMed1998

Results of treating primary tumors of the trachea with radiotherapy.

PURPOSE: To report the efficacy of treatment and to identify prognostic factors that were predictive of survival in primary tumors of the trachea treated with radiotherapy. METHODS AND MATERIALS: The medical records of patients treated at the Peter MacCallum Cancer Institute in the period 1962 to 1995 were reviewed. Forty-two patients were eligible for the study and were treated with radiotherapy. Squamous cell carcinoma (SCC) was the commonest subtype and patients generally presented with long-standing respiratory symptoms. Eleven patients were planned for treatment with at least 50 Gy to the primary, while the rest were treated with lower doses. RESULTS: The estimated median survival for all patients was 5.7 months, with 13% surviving at 2 years. Univariate analysis revealed performance status, weight loss, and lymph node or distant metastatic involvement as significant prognostic factors. Patients planned for treatment with at least 50 Gy survived longer than patients treated with less than 50 Gy, but this was probably due to selection of patients with better prognostic factors for higher dose treatment.

Adenocarcinoma↗
PubMed1998

Dopamine markers and general cognitive ability.

Because general cognitive ability (g) is among the most heritable behavioural traits, it is a reasonable target for a search for quantitative trait loci (QTLs). We used a selected-extremes design to test candidate genes for allelic association with g. Polymorphisms in four genes in the dopamine system (DRD2, DRD3, DRD4, DAT1) were genotyped for 51 high g children with IQ scores > 130 and for 51 average g control children. No significant allelic or genotypic differences were found between the high g and average g groups for these markers of the dopamine system, even though the selected-extremes design provides power to detect QTL associations that involve a relative risk of about 1.5.

Adolescent↗
PubMed1998

Adverse drug reaction reporting by general medical practitioners and retail pharmacists in Harare--a pilot study.

OBJECTIVE: The pilot study was undertaken to investigate whether doctors and pharmacists in the private sector are willing to undertake Adverse Drug Reaction (ADR) reporting, to analyse their perceptions with regard to ADR reporting and to determine whether the concept of sentinel reporters could be of value in Zimbabwe. DESIGN: An open, prospective study where a selected group of private general medical practitioners and community pharmacists were asked to report any suspected ADRs over a six month period and to complete a structured self administered questionnaire. SETTING: Private medical and pharmacy practices in Harare. SUBJECTS: General medical practitioners and community pharmacists. MAIN OUTCOME MEASURES: Number of ADR reports received at Medicines Control Authority (MCA) and questionnaire responses. RESULTS: 19 reports were received from participants (eight pharmacists and five doctors) accounting for 79.2% of ADR reports to the MCA, during the study period. Seventeen (89.5%) of the reports generated from the study came from doctors. The 19 reports involved 15 different drugs, three (20%) of which had been registered in the last three years. Twelve questionnaires were completed. Serious and unexpected reactions were more likely to be reported. Most respondents knew what was expected and were willing to report, although five (41.7%) felt they were too busy. Seventy five percent of the doctors had not known that a reporting scheme existed in Zimbabwe and none of the participants had ever sent in a report prior to the study. Medical journals and the drug manufacturers were the most important sources of information about ADRs. CONCLUSION: Simply having interested pharmacists and doctors on the look out for ADRs and increased reporting of ADRs to the MCA. There are willing health care personnel but there is a need for larger studies to see if sentinel reporting of ADRs is applicable on a country wide basis.

Adult↗
PubMed1997

No evidence for an association of affective disorders with high- or low-activity allele of catechol-o-methyltransferase gene.

Catechol-o-methyltransferase (COMT) is an enzyme that inactivates biologically active or toxic catechols. Previous studies have yielded inconsistent results on the relationship between erythrocyte COMT activity and affective disorders. Recently an amino acid change (Val-108-Met) of the COMT protein was shown to determine high- and low-activity alleles of the enzyme. Using polymerase chain reaction and the restriction enzyme NLaIII, we genotyped 107 patients with bipolar disorder, 62 with unipolar depression, and 121 controls. Neither bipolar nor unipolar patients differ significantly in the genotypic or allelic frequency from the control group. Even when the bipolar and unipolar patients were pooled into a single group, the distributions of both the genotypes and the alleles for the patient group were similar to those for the controls. We conclude that genetic variation that determines high and low activities of COMT does not have a major effect on the vulnerability to affective disorders in our sample.

Adult↗
PubMed1997

The serotonin transporter gene and peer-rated neuroticism.

Polymorphisms in the serotonin transporter gene (5HTT) have been reported to be associated with neuroticism (emotionality) and with depression. A recent report of an association between 5HTT and neuroticism involved unselected samples and self-report questionnaires. We attempted to extend these findings using a selected extremes design and peer ratings. From a sample of 2085 individuals, each assessed on neuroticism by two independent peers, we selected 52 individuals from the top 5% and 54 individuals from the bottom 5%. No association was found for either a functional 44 bp insertion/deletion polymorphism in 5HTT regulatory sequence (5HTTLPR) or for a non-functional variable number tandem repeat 5HTT polymorphism.

Adolescent↗
PubMed1997

5-HT2A receptor and bipolar affective disorder: association studies in affected patients.

The aim of this study was to investigate the possible involvement of genetic variation in serotonin receptors in the aetiology of bipolar affective disorder. The 5-HT2A receptor gene was systematically screened for genetic variants by single strand conformation polymorphism (SSCP) methods in subjects with bipolar affective disorder. Four polymorphisms (two structural changes, Thr25Asn and His4 M52Tyr, and two silent polymorphisms, 102-T/C and 516-C/T) which had previously been found in patients with schizophrenia and control subjects were detected. No novel polymorphisms were found in patients with bipolar affective disorder. These polymorphisms were genotyped in a sample of 129 patients and 252 controls of German origin and 176 patients and 182 controls of British origin. No strong associations were found between any of these polymorphisms and bipolar affective disorder. Genetic variation at the 5-HT2A receptor gene does not play a major role in the pathogenesis of the disorder.

Alleles↗
PubMed1997

DNA by mail: an inexpensive and noninvasive method for collecting DNA samples from widely dispersed populations.

As specific genes are identified that are associated with behavior, it becomes increasingly important for behavioral geneticists to be able to incorporate these genes in their research. Rather than using blood, DNA can be extracted from cheek swabs, which makes it possible to obtain DNA inexpensively by mail from large, widely dispersed individuals. The purpose of this paper is to recommend this technique to the behavioral genetics community and to present results of our use of this technique to obtain DNA by mail for 114 2-year-olds and 116 adults.

Adult↗
PubMed1997

A phase III study of radiotherapy with and without continuous-infusion fluorouracil as palliation for non-small-cell lung cancer.

This study assesses the effect of adding continuous-infusion fluorouracil to palliative thoracic radiation therapy (RT) on the rate and duration of symptom relief in patients with advanced non-small-cell lung cancer (NSCLC). Two hundred eligible patients with NSCLC were randomized to receive either 20 Gy in five daily fractions as palliation for intrathoracic disease or the same RT with concurrent continuous infusion of 1 g m(-2) day(-1) fluorouracil for 5 days. Survival, response and rates of symptom relief in the two groups were compared according to treatment intent, and toxicities were compared according to treatment received. The overall response rate was higher in patients randomized to the combination (29%) than in patients randomized to RT alone (16%) (P = 0.035). However, there were no significant differences between the treatment arms in terms of overall or progression-free survival or in palliation of symptoms. Patients treated with RT plus fluorouracil had significantly more acute toxicity, including nausea and vomiting (P = 0.01), oesophagitis (P = 0.0003), stomatitis (P = 0.0005) and skin reaction (P = 0.003). This study suggests for the first time an interaction between RT and infusional fluorouracil in NSCLC. Although RT plus fluorouracil resulted in a significantly higher response rate than achieved with RT alone, this did not translate into more effective palliation. Because the combination produced significantly more toxicity than RT alone, it is not recommended for the palliative treatment of NSCLC. Nevertheless, these results suggest that opportunities may exist for exploitation of the observed enhancement of antitumour effect in the setting of high-dose radical RT for NSCLC.

Adult↗
PubMed1997

Blood and urine acid-base status of premenopausal omnivorous and vegetarian women.

The effect of long-term differences in diet composition on whole-body acid-base status was examined in thirty-three young healthy females. The volunteers were recruited from two separate groups matched approximately for age, height and weight; one group regularly ate meat (omnivores; n 20) and one group did not (vegetarians; n 13). All subjects completed a 7 d weighed intake of food, and from their dietary records, total energy, carbohydrate (CHO), fat and protein content were estimated using computer-based food composition tables. During this week they reported to the laboratory on two occasions, following an overnight fast and separated by at least 48 h. Arterialized venous blood samples were obtained on each visit and these were analysed for blood acid-base status. Haemoglobin and packed cell volume, serum total cholesterol and HDL-cholesterol, serum albumin and total protein were also determined. Two 24 h urine collections were completed; the volume was recorded and samples were analysed for pH, titratable acid and Mg and Ca concentration. Total energy intake of the omnivores was greater (P = 0.0003) than that of the vegetarian group. Dietary intake of CHO (P = 0.024), fat (P = 0.0054) and protein (P = 0.0002) were higher in the omnivorous group than in the vegetarians. There were no differences between the two groups with respect to blood CO2 partial pressure, plasma HCO3- and blood base excess, but blood pH was slightly higher in the omnivores (P = 0.064). Measures of urine acid-base status suggested a lower pH in the omnivore group, but this difference was not statistically significant; a greater titratable acid output was observed with the omnivorous group compared with the vegetarians (48.9 (SE 20.3) v. 35.3 (SE 23.3) mEq/24h; P = 0.018). Although the dietary intake of Ca was not different between the two groups, urinary Ca excretion of the omnivores was significantly higher (3.87 (SD 1.34) v. 3.22 (SD 1.20) mmol/24 h) than that of the vegetarians (P = 0.014). It is suggested that the higher protein intake of the omnivores resulted in an increase in urinary total acid excretion, which may explain the higher rate of Ca excretion.

Acid-Base Equilibrium↗
PubMed1997

Diet composition and the performance of high-intensity exercise.

The crucial role of muscle glycogen as a fuel during prolonged exercise is well established, and the effects of acute changes in dietary carbohydrate intake on muscle glycogen content and on endurance capacity are equally well known. More recently, it has been recognized that diet can also affect the performance of high-intensity exercise of short (2-7 min) duration. If the muscle glycogen content is lowered by prolonged (1-1.5 h) exhausting cycle exercise, and is subsequently kept low for 3-4 days by consumption of a diet deficient in carbohydrate (< 5% of total energy intake), there is a dramatic (approximately 10-30%) reduction in exercise capacity during cycling sustainable for about 5 min. The same effect is observed if exercise is preceded by 3-4 days on a carbohydrate-restricted diet or by a 24 h total fast without prior depletion of the muscle glycogen. Consumption of a diet high in carbohydrate (70% of total energy intake from carbohydrate) for 3-4 days before exercise improves exercise capacity during high-intensity exercise, although this effect is less consistent. The blood lactate concentration is always lower at the point of fatigue after a diet low in carbohydrate and higher after a diet high in carbohydrate than after a normal diet. Even when the duration of the exercise task is kept constant, the blood lactate concentration is higher after exercise on a diet high in carbohydrate than on a diet low in carbohydrate. Consumption of a low-carbohydrate isoenergetic diet is achieved by an increased intake of protein and fat. A high-protein diet, particularly when combined with a low carbohydrate intake, results in metabolic acidosis, which ensues within 24 h and persists for at least 4 days. This appears to be the result of an increase in the circulating concentrations of strong organic acids, particularly free fatty acids and 3-hydroxybutyrate, together with an increase in the total plasma protein concentration. This acidosis, rather than any decrease in the muscle glycogen content, may be responsible for the reduced exercise capacity in high-intensity exercise; this may be due to a reduced rate of efflux of lactate and hydrogen ions from the working muscles. Alternatively, the accumulation of acetyl groups in the carbohydrate-deprived state may reduce substrate flux through the pyruvate dehydrogenase complex, thus reducing aerobic energy supply and accelerating the onset of fatigue.

Acidosis, Lactic↗