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Biomedical subjects

N Bishop

Publications and source records attributed to N Bishop.

At least 37 records · Page 2Linked to original sources
PubMed1990

Antiviral strategies in chronic hepatitis B virus infection: I. Establishment of an in vitro system using the duck hepatitis B virus model.

Primary duck hepatocyte (PDH) cultures were established from ducklings congenitally infected with the duck hepatitis B virus (DHBV), plated onto feeder cell layers of irradiated human embryonic lung fibroblasts, and observed for 2 to 3 weeks. This system permitted the survival of the PDH in a differentiated form free of fibroblastic overgrowth for at least 3 weeks. The hepatocytes were shown to contain all the replicative DNA intermediates found during DHBV replication as well as the DHBV structural proteins PRE-S1, PRE-S2, and S of duck hepatitis B surface antigen (DHBsAg). The pool of supercoiled (SC) DHBV DNA increased dramatically from days 10 to 14 postplating. This PDH-feeder cell layer cell culture model provides a convenient system to study the effects of conventional inhibitors of DHBV replication and compounds targeted at the supercoiled form of DHBV DNA. This approach should allow the evaluation of a variety of strategies for treating chronic carriers of hepadnaviruses.

Animals↗
PubMed1990

Antiviral strategies in chronic hepatitis B virus infection: II. Inhibition of duck hepatitis B virus in vitro using conventional antiviral agents and supercoiled-DNA active compounds.

Primary duck hepatocyte (PDH) cultures, congenitally infected with the duck hepatitis B virus (DHBV), were grown on feeder cell layers of irradiated human embryonic lung fibroblasts and then exposed to a number of compounds with recognized or potential antiviral activity. These compounds included conventional antiviral agents, reverse transcriptase inhibitors, compounds with activity to supercoiled-DNA, and DNA-binding agents. Twenty-three compounds were evaluated, and 13 were found to inhibit significantly viral DNA replication. Seven of these compounds (ellipticine, amsacrine, coumermycin A1, Adriamycin, mitozantrone, chloroquine, and neocarzinostatin) acted at the level of viral SC DNA and significantly inhibited production of duck hepatitis B surface antigen (DHBsAg). Conventional agents that inhibited DHBV DNA replication included ganciclovir, acyclovir, bromovinyldeoxyuridine, ribavirin, phosphonoformate, and dideoxyadenosine. Except for dideoxyadenosine, these inhibitors of viral DNA synthesis did not significantly inhibit DHBsAg production. Two additional compounds, novobiocin and nalidixic acid, altered the pattern of viral DNA replication, especially the generation and processing of viral SC DNA, and also inhibited the production of DHBsAg. Several compounds acting at the level of viral SC DNA have now been identified and may offer potential for the management of chronic hepatitis B virus infection.

Animals↗
PubMed1989

High alkaline phosphatase activity and growth in preterm neonates.

In a study on 857 infants born preterm, high peak plasma alkaline phosphatase activity was independently related to slower growth rate in the neonatal period, and to a highly significant reduction in attained length at 9 months and 18 months post term. At 18 months the deficit in body length associated with peak neonatal plasma alkaline phosphase activity of 1200 IU/l or more was 1.6 cm (95% confidence interval 0.9 to 2.3 cm) after adjusting for confounding factors. The strength and magnitude of this association between high plasma alkaline phosphase activity and body length was greater than that for any other factor identified, including the infant's sex and the presence of fetal growth retardation. Data are presented that support the view that the high plasma alkaline phosphatase activity reflected early bone mineral substrate deficiency resulting in metabolic bone disease. We speculate that even silent early bone disease may interfere with the control of subsequent linear growth and emphasise the potential importance of providing preterm infants, especially those fed human milk, with adequate substrate for bone mineralisation.

Alkaline Phosphatase↗
PubMed1989

Forearm blood flow measurements using technetium-99m human serum albumin following brachial arteriotomy.

A simple, low cost method for measuring forearm blood flow during reactive hyperemia has been developed. Subjects are seated with hands and forearms over a large field-of-view gamma camera. Blood pressure cuffs inflated above the elbows isolate the blood in the forearms and hands and induce a hyperemic response. The remaining blood pool is labeled with technetium. The rate of increase of activity following release of the cuffs is measured from the gradient of time-activity curves and is calibrated for flow by counting a venous blood sample. The technique has been applied to a group of normal controls and to symptomatic and asymptomatic patients following right brachial arteriotomy. Forearm blood flow in normal subjects was 32.9 +/- 6.4 ml/100 ml/min and for subjects with occlusion of the brachial artery was 6.4 +/- 2.1 ml/100 ml/min. The method is simple, widely available, and reproducible. The good signal to noise ratio allows it to be used in cases of very low flow either as an aid to diagnosis or to measure treatment response.

Adult↗
PubMed1988

Changes in myocardial ischaemia during isosorbide dinitrate or indoramin therapy in patients with stable angina using relations between the ST segment and heart rate.

The effect of isosorbide dinitrate or indoramin on myocardial ischaemia was examined in patients with stable angina pectoris. In a prospective trial, randomization resulted in 8 and 9 patients, respectively, given isosorbide dinitrate in a dose of 30-90 mg daily, and indoramin in a dose of 75-225 mg daily; 2 of these patients were serially examined during the two types of therapy. Changes in myocardial ischaemia were assessed by exercise testing using 12 standard electrocardiographic leads and a bipolar lead CM5. Individual and group comparisons showed that isosorbide dinitrate resulted in an increase in ST segment depression, the maximal ST/heart rate slope and the ratio of net ST segment depression to increases in heart rate (at least P less than 0.01). In contrast, with indoramin therapy there were no significant changes in these indices. The results in these patients suggest that isosorbide dinitrate leads more consistently to increases in the severity of myocardial ischaemia than indoramin, although this effect on ischaemia is apparently less than the benefit of these agents on exercise performance.

Adult↗
PubMed1988

Aortic valve disease and the ST segment/heart rate relationship: a longitudinal study before and after aortic valve replacement.

The ST segment/heart rate relationship or maximal ST/HR slope has been validated as an index of myocardial ischemia in selected populations of patients with angina pectoris. The present study involved patients selected as having aortic valve disease unaccompanied by angiographic coronary artery narrowing. In each of seven patients, so far examined, a slope value and ST segment depression of greater than 1 mm were obtained which, according to previous experience, indicated myocardial ischemia equivalent to coronary heart disease. After aortic valve replacement, there was a significant reduction in heart size as assessed using the cardiothoracic ratio, and the amplitude of QRS complex on the electrocardiogram. The slope was abolished (two patients) or markedly reduced (five patients), and the decrease in the seven patients was statistically significant. ST segment depression could be obtained in one patient. This study has shown the occurrence of maximal ST/HR slope in patients without large coronary artery disease who have aortic valve disease and cardiac enlargement.

Aortic Valve↗
PubMed1988

Blood vitamin C concentrations in patients with diabetes mellitus.

Plasma and buffy layer vitamin C concentrations have been measured in insulin dependent and non-insulin dependent diabetic patients and the results compared with age and gender matched non-diabetic controls. No differences were found between the controls and the diabetics nor between the different types of diabetes, although patients who had had clinical diabetes for longer had higher plasma vitamin C values than patients in whom the disease was not long standing. There were no significant changes in the distribution of vitamin C between plasma and white cells in the diabetic nor in patients with marked hyperglycaemia. We conclude that the vitamin C intakes of the majority of diabetic patients we studied, who are probably typical of diabetics receiving hospital treatment in the United Kingdom, are adequate and are sufficient to maintain satisfactory plasma and buffy layer vitamin C concentrations. These findings are discussed in the light of reports which have shown lower levels of vitamin C in the blood of diabetic patients and competition between vitamin C and glucose for transport across the cell membrane.

Adult↗
PubMed1987

Use of the maximal ST/HR slope to estimate myocardial ischaemia after recent myocardial infarction.

Fifty two patients were examined 4-6 weeks after myocardial infarction to assess whether factors other than coronary artery narrowing affect the maximal ST/HR slope which is used as an index of myocardial ischaemia. The slope was compared with indices of myocardial scarring or cardiac enlargement derived from x ray and echocardiographic and angio-cardiographic investigations. In 35 (67%) patients the slope failed to predict the severity of myocardial ischaemia attributable to coronary artery narrowing: in 14 (27%) patients the slope overestimated the findings of coronary angiography and in 21 (40%) patients the slope underestimated the findings of coronary angiography. In the remaining 17 (33%) patients the slope accorded with the assessment of myocardial ischaemia by coronary angiography. Underestimation by the slope was associated with significantly poorer left ventricular function and a lower ejection fraction, indicating a greater degree of myocardial scarring. To assess whether overestimation was related to cardiac enlargement with better preservation of ventricular function a follow up examination was performed six months after infarction. In the overestimated group 11 patients were followed up and seven of them showed a reduction in the maximal ST/HR slope which correlated with a reduction in the cardiothoracic ratio. This suggested that cardiac enlargement had contributed to myocardial ischaemia. The results suggest that if the maximal ST/HR slope is an index of exercise induced myocardial ischaemia after recent infarction, it is subject to the influences of coronary artery narrowing as well as those of scarring and cardiac enlargement.

Adult↗
PubMed1986

Assessment of the effect of nifedipine on myocardial ischaemia by using the ST segment/heart rate slope.

Nifedipine is used in patients with stable angina of effort and any resulting change in symptoms is attributed to several effects of nifedipine. However, there have been indications in such patients that one effect of nifedipine could be an increase in the severity of myocardial ischaemia, and the present report involves a trial the results of which could explain this effect. In the present trial, the effect of nifedipine on myocardial ischaemia was assessed by using the maximal ST/heart rate slope. This slope was used as an index of myocardial ischaemia because, in our hands in patients with angina, an increase or a decrease in the value of the slope respectively indicated an increase or a decrease in the severity of myocardial ischaemia as assessed by coronary arteriography. The maximal ST/heart rate slope was obtained at least twice in each of 23 patients with stable angina, with and without nifedipine; two patients were examined twice and three other patients were examined after an increased dose. Nifedipine resulted in an increase in the slope in 24 of the 28 comparisons, no change in three and a decrease in one comparison; there was a statistically significant (P less than 0.005; n = 28; paired t-test) increase in the maximal ST/heart rate slope. A further increase in the slope was obtained by increasing the dose of nifedipine in two out of three patients. The increase in the maximal ST/heart rate slope occurred in the absence of any effect of nifedipine on the initial level of ST segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The effect of indoramin on exercise performance in mild hypertension.

The alpha 1-adrenoceptor antagonist indoramin is proposed to reduce arterial blood pressure without a concomitantly significant increase in heart rate (HR). The present study involves assessment of the effect of alpha 1-adrenoceptor antagonism in patients with mild hypertension on the HR/oxygen consumption (Vo2) relationship, which has previously been shown to indicate improvement in cardiorespiratory fitness following exercise training. A total of 16 patients with a systolic blood pressure of 140-200 mm Hg and diastolic blood pressure of 95-110 mm Hg were examined. A double-blind, placebo-controlled study design was utilized. Following initial observations, the patients were randomized into one group (a) of seven patients who were given a placebo, indoramin, and finally placebo, and a second group (b) of nine patients who were given the two agents in the reverse order, i.e., indoramin, placebo, indoramin; each intervention lasted for 2 weeks and indoramin was given in a dose of 75 mg/day. Indoramin caused a reduction in the elevation of the computed regression line relating HR to Vo2 (a shift to the right), such that at the same HR a greater Vo2 was attained in 11 of the 16 patients in comparison with the baseline exercise test. Pooled results showed a shift of the HR/Vo2 regression line to the right when indoramin was compared with baseline (p less than 0.05) or placebo. In the same patients, indoramin caused a decrease in arterial blood pressure during exercise relative to baseline or placebo periods, and a decrease in the HR during exercise relative to baseline period, but not when compared with placebo periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗