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Biomedical subjects

T Shaw

Publications and source records attributed to T Shaw.

At least 55 records · Page 3Linked to original sources
PubMed1995

Action of diphenylamine carboxylate derivatives, a family of non-steroidal anti-inflammatory drugs, on [Ca2+]i and Ca(2+)-activated channels in neurons.

Ca(2+)-activated channels, including Ca(2+)-activated non-selective (CAN) channels and Ca(2+)-activated Cl- channels play important roles in regulating the electrical activity of neurons. No blockers of neuronal CAN channels have been previously reported. We used 2-electrode voltage clamping to measure membrane currents and fura-2 fluorescence imaging to measure [Ca2+]i in molluscan neurons. We show that the diphenylamine carboxylate derivative flufenamate (FFA), but not mefenamate or the parent compound, cause a transient increase in ICAN and a slow outward current, and a maintained increase in [Ca2+]i. We interpret this as a FFA-dependent release of Ca2+ from intracellular stores and Ca2+ influx, [Ca2+]i-dependent activation of the CAN and slow outward currents, and slow FFA-dependent channel block.

Animals↗
PubMed1995

Hepatic purine and pyrimidine metabolism: implications for antiviral chemotherapy of viral hepatitis.

The use of nucleoside analogues as antiviral agents is expanding. For most nucleoside analogues, intracellular phosphorylation is the major prerequisite for activity. Antiviral activity may be limited by poor uptake, absence of appropriate activating enzymes, catabolism, and competition from endogenous nucleotides. Appreciation of these factors, which are species-, tissue- and cell-specific is important in the understanding of the pharmacology and toxicology of nucleoside analogues. The use of nucleoside analogues against the agents of viral hepatitis is inherently problematic for many reasons including active hepatic nucleoside catabolism, probable absence of virus-specific activating enzymes, competition from endogenous nucleotides synthesised de novo or derived from RNA turnover, and factors related to mitochondrial toxicity. Despite these drawbacks, some nucleoside analogues have been found efficacious against hepatitis B virus and it is likely that as knowledge of their mechanism of action accumulates, their efficacy can be improved both by rational drug design and by use in combination with other drugs, including interferon.

Animals↗
PubMed1995

Inhibition of duck hepatitis B virus DNA replication by antiviral chemotherapy with ganciclovir-nalidixic acid.

The aim of this study was to examine the effects of ganciclovir and nalidixic acid either alone or in combination on duck hepatitis B virus DNA replication in vivo with particular reference to production of viral supercoiled DNA and RNA. The most effective antiviral response was observed in the livers of ducks treated by the combination therapy for 28 days, which resulted in a substantial decrease in the amounts of viral supercoiled DNA, relaxed circular and single-stranded DNA, and also viral RNA. This combination treatment was not hepatotoxic over the study period.

Animals↗
PubMed1995

Effect of immunosuppressive and antiviral agents on hepatitis B virus replication in vitro.

Hepatitis B virus (HBV) DNA-transfected hepatoma cells were incubated with the immunosuppressive agents prednisolone, azathioprine, and cyclosporin A (CsA) and the antiviral agents ganciclovir and foscarnet to investigate the effects of these compounds on HBV replication. Prednisolone and azathioprine increased intracellular viral DNA and RNA levels approximately twofold and fourfold, respectively. Treatment with CsA did not alter the levels of viral RNA or DNA. A combination of all three immunosuppressive agents increased the level of intracellular viral DNA eightfold, indicating an additive effect. Incubation of the cells in the presence of foscarnet decreased levels of both single-stranded and relaxed circular viral DNA, and in the presence of ganciclovir decreased the levels of relaxed circular viral DNA, predictable effects from their known mechanism of action. The stimulatory effect on viral replication induced by the combination of immunosuppressive agents was substantially inhibited by ganciclovir-foscarnet treatment. These observations could have implications for the management of recurrent HBV infection after liver transplantation.

Antiviral Agents↗
PubMed1995

HIV prevalence and risk factors in university students.

OBJECTIVE: To estimate HIV prevalence and risks in university students. DESIGN: Anonymous self-completion questionnaire and HIV survey with saliva samples. SETTING: University students at matriculation. PARTICIPANTS: All first and third year undergraduates and newly registering postgraduates at the University of Edinburgh, Scotland. MAIN OUTCOME MEASURES: HIV prevalence, sexual behaviour, condom use, drug use. RESULTS: The questionnaire responses were used to classify the 4665 respondents into four groups, ordered by risk of HIV positivity, and a sample of 2041 was selected for testing. All of the top two risk groups were tested (217 and 758 tests, respectively) as well as a random sample of the others. Five positive HIV-antibody tests were detected, all from the highest risk group. This gives an estimated rate of 1.2 per 1000 (95% confidence interval, 0.4-2.9) for all respondents. Only one of the five HIV-positives had been tested for HIV. The factors associated with HIV positivity were residence in Africa, intravenous drug use and male homosexuality. Overall, 74% of respondents reported ever having had sexual intercourse and this rate was the same for men and women. Reported intravenous drug use was very low: 0.5% for men and 0.1% for women. Condom use was more common for partners of short acquaintance, but unrelated to the number of sexual partners in the last year. CONCLUSIONS: There was no evidence of the spread of HIV infection beyond known high-risk groups in this population. This may be a result of relatively low levels of HIV risk-taking behaviour in the majority of respondents.

Adult↗
PubMed1994

A randomized study of telephone contact following completion of radiotherapy.

The hypothesis tested was that routine contact by telephone might significantly improve the adequacy of support for patients during the potentially stressful period between completing radiotherapy and the first follow-up visit. The study was a randomized controlled trial in which 100 patients were allocated either to telephone contact (intervention arm) or usual care (control arm). Adequacy of support was assessed by a questionnaire administered at the first follow-up visit. There were no significant differences in the perceived adequacy of support between the two arms. Of the 72 patients who completed questionnaires, 76% of those in the intervention arm versus 61% in the control arm rated their support after radiotherapy as 'extremely adequate'. The 95% confidence interval (CI) for this 15% rate difference was -6- +36. Analysis by intention to treat showed a rate difference of only 4% (95% CI -17-(+)25) in favour of intervention. We conclude that, given the limited resources currently available, it is not possible to justify a policy of routine contact by telephone for all patients completing radiotherapy.

Adult↗
PubMed1994

In vitro antiviral activity of penciclovir, a novel purine nucleoside, against duck hepatitis B virus.

The in vitro antihepadnavirus activities of the purine nucleoside analogs ganciclovir (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine) and penciclovir [9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine; BRL 39123] were compared in primary duck hepatocyte cultures congenitally infected with the duck hepatitis B virus (DHBV). Both compounds inhibited DHBV DNA replication to a comparable extent during continuous short-term treatment of the cultures. However penciclovir was more active both during longer-term continuous treatment (50% inhibitory concentrations: penciclovir, 0.7 +/- 0.1 microM; ganciclovir, 4.0 +/- 0.2 microM) and in washout experiments (50% inhibitory concentrations: penciclovir, 3.0 +/- 0.4 microM; ganciclovir, 46 +/- 1.5 microM) designed to compare the persistence of inhibitory activity after removal of the extracellular compound. The effects on viral protein synthesis were similar to the effects on viral DNA replication. These data suggest that penciclovir or its oral form, famciclovir, may have clinical utility in the treatment of chronic hepatitis B virus infection.

Acyclovir↗
PubMed1992

Left ventricular response to submaximal exercise in endurance-trained athletes and sedentary adults.

This investigation examines the hypothesis that athletes increase stroke volume with submaximal exercise through an augmentation of left ventricular (LV) end-diastolic volume and a reduction of LV end-systolic volume, whereas sedentary adults only increase stroke volume modestly, because LV end-diastolic volume does not increase. Upright bicycle exercise was performed by 17 endurance-trained male athletes and 15 sedentary men. M-mode echocardiograms were obtained during submaximal exercise at predetermined heart rates. Athletes, at a heart rate of 130 beats/min, increased their stroke volume 67% from 72 +/- 18 ml to 120 +/- 26 ml (p less than 0.001). This resulted from an increase of LV end-diastolic volume from 119 +/- 23 to 152 +/- 28 ml (p less than 0.001) and a reduction in LV end-systolic volume from 46 +/- 14 to 31 +/- 9 ml (p less than 0.001). Sedentary men at the same heart rate increased stroke volume 22% from 63 +/- 15 to 77 +/- 21 ml (p less than 0.05). LV end-diastolic volume did not change (96 +/- 20 vs 97 +/- 28 ml) (p = not significant), but LV end-systolic volume decreased (33 +/- 11 vs 20 +/- 9 ml) (p less than 0.001). In conclusion, athletes increased cardiac output through a more prominent augmentation of stroke volume than sedentary subjects at submaximal exercise. This was accomplished through an augmentation of LV end-diastolic volume. This may have a conserving effect on myocardial oxygen consumption at these levels of exercise.

Adult↗
PubMed1991

Staffing in cardiology in the United Kingdom 1990. Sixth biennial survey: with data on facilities in cardiology in England and Wales 1989.

The Sixth Biennial Survey of Staffing in Cardiology was conducted in July 1990. This report summarises the data that were collected, together with the results of a survey of facilities in cardiology made in 1989. The total number of cardiologists in the United Kingdom, defined as individuals trained in the specialty and spending at least 40% of their time working in it, is now 323. Six individuals work part time only, making 320 whole time posts. This number has increased over the two years from 1988 to 1990 by 32, of which 23 work only in the specialty and nine as general physicians with a major interest in cardiology. The rate of increase in numbers over the past decade has been reasonably consistent with an average of approximately 4.4% per year. Thirty one districts in England and Wales still have no cardiologist and 13 other districts have little provision with an average of three (visiting) sessions each per week. The population in these 44 districts is 8.3 million. Scotland also has an inadequate distribution of service in the specialty. If recommendations for cardiac surgery and angioplasty made in the Fourth Report of a Joint Cardiology Committee of the Royal College of Physicians of London and the Royal College of Surgeons of England are to be met, we calculate that we need 63 more cardiologists in our major centres. To provide one cardiologist in every district hospital and two for larger districts would require 94 more specialists, making a total shortfall of 157 individuals. We have no excess of senior registrars to provide for a major expansion at consultant level. Time spent within the senior registrar (or academic equivalent) grade has tended steadily to decline and very few now reach the end of their contracts. The need for more individuals to pass through the senior registrar grade will be met in part by a planned reduction in the training period to three years. This will be inadequate, however, because projected retirements show that the number of consultant vacancies will increase sharply from 1997. We believe that additional senior registrar posts must be created if a serious shortfall in service provision by consultants is to be avoided. The provision of non-invasive facilities in cardiology is reasonable. The need for additional equipment for invasive cardiology has not been assessed. The number of physiological measurement technicians varies considerably between regions and is generally inadequate.

Allied Health Personnel↗
PubMed1989

Sleep apnea syndrome after irradiation of the neck.

After irradiation of the neck for a squamous cell carcinoma of the tonsillar pillar and vocal cord, a 71-year-old man presented with a rapidly progressive sleep apnea syndrome. Previous reports describe the condition of patients with obstructive sleep apnea that developed after neck irradiation and secondary to supraglottic edema. Our patient had an obstructive component to his apnea similar to that described in previous cases, but, in addition, he had hypothyroidism. Myxedema is a well-described cause of both obstructive and central apnea. We believe both contributed to his condition. He was successfully treated by placement of a tracheostomy and by thyroid supplementation. In patients who present with sleep apnea after neck irradiation, especially with acute or severe symptoms, the differential diagnosis should include both a central cause from hypothyroidism as well as a peripheral obstructive cause from laryngeal edema.

Aged↗
PubMed1988

Suppression and induction of epileptic activity by neuronal grafts.

Fetal rat brain cell suspensions prepared from either the locus coeruleus region or hippocampus were implanted bilaterally into the subcortically denervated seizure-prone hippocampus of adult rats. Animals with locus coeruleus grafts were protected against picrotoxin-induced behavioral seizures and had significantly fewer interictal spikes. In contrast, in rats with fetal hippocampal grafts the incidence of interictal spikes was significantly higher than in lesion-only controls, and spontaneous behavioral seizures occurred in almost half of the animals. We suggest that neuronal grafting offers an alternative method for studying the mechanisms and control of epileptic brain activity.

Animals↗