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Biomedical subjects

C Frampton

Publications and source records attributed to C Frampton.

51 records · Page 3Linked to original sources
PubMed1992

Effect of diet on posttransplant hyperlipidaemia.

Twenty-five patients with a renal transplant for 15 months to 19.4 years, hyperlipidaemia and stable graft function underwent three months of dietary management. Plasma lipid and apolipoprotein concentrations and lipoprotein electrophoresis were measured after a 12 hour fast at enrollment and after three months of diet. The aims of diet were to reduce energy intake in the overweight, restrict fat to 25-30% of total intake, reduce saturated fat content to less than 10% of total energy and cholesterol to less than 300 mg/d. After three months of diet there was a significant fall in mean cholesterol/HDL cholesterol risk ratio and a rise in mean HDL cholesterol concentration. Six patients reverted to a normal lipoprotein electrophoretic pattern with a significant reduction in mean total cholesterol, LDL cholesterol, cholesterol/HDL cholesterol ratio, apoprotein B and apoB/apo A-1 ratio. Most of the other patients who made dietary modifications showed some improvement in their lipid parameters. Dietary modification should be the initial approach to the management of posttransplant hyperlipidaemia.

Adult↗
PubMed1992

Prevalence of diabetes mellitus in an ambulant elderly New Zealand population.

The prevalence of diabetes mellitus (both known and previously undiagnosed) was studied in a population sample, predominantly Caucasoid and resident in the community with an age/sex distribution representative of the New Zealand population aged 65 + years, using WHO criteria. The population sample was randomly selected from the age/sex register of a large urban medical centre in Christchurch, New Zealand. Three hundred and sixty-nine subjects (participation rate 69.4%) were screened by casual glucose and glycated haemoglobin measurement, followed by oral glucose tolerance testing (OGTT) if one or both were elevated. The minimum prevalence rate of diabetes in the study sample was 17.2 +/- 3.3% in men and 12.5 +/- 2.2% in women (since not all patients underwent OGTT). The rate was only significantly higher in men than women in the 70-74 year age group (P less than 0.01). The combined age-adjusted prevalence rates for the New Zealand elderly are estimated to be 9.9% known diabetes, 5.0% previously undiagnosed, with the total prevalence rate 14.9%. Newly diagnosed subjects had a significantly higher body mass index than known diabetic or non-diabetic subjects (P less than 0.01). Eighty-two percent of newly diagnosed subjects had visited their general practitioner at least once during the previous 6 months. Measurement of glycated haemoglobin had a greater positive predictive value than casual blood glucose in the detection of new cases. There was no difference in frequency of attendance with general practitioners or in hospital admission rates between non-diabetic patients, or those with known or newly diagnosed diabetes. This study suggests that diabetes mellitus may be a prevalent disorder amongst the New Zealand elderly.

Age Factors↗
PubMed1992

Effect of inhibition of endopeptidase 24.11 on responses to angiotensin II in human volunteers.

The effects of endopeptidase 24.11 inhibition on angiotensin-induced changes in plasma angiotensin II, aldosterone, and atrial natriuretic factor concentrations and blood pressure were assessed in normal volunteers. Two groups, each consisting of eight normal volunteers, received stepwise infusions of angiotensin II (2, 4, and 8 ng/kg per minute) on day 5 of dose administration with 25 mg every 12 hours (group 1) or 100 mg every 12 hours (group 2) of an oral inhibitor of endopeptidase 24.11 (UK 79300, candoxatril) or placebo in balanced randomized, double-blind, placebo-controlled crossover studies. Both doses of candoxatril significantly enhanced achieved plasma angiotensin II concentrations during infusions (group 1, p < 0.001; group 2, p < 0.01; overall treatment effect for combined data, p < 0.001). This effect was most pronounced at the highest dose of angiotensin II (treatment-time interaction, p < 0.0001 for combined data) and tended to be more marked with the higher dose of candoxatril (treatment-group interaction, p = 0.08). The pressor response to angiotensin II was clearly enhanced by the lower dose of candoxatril; peak systolic and diastolic pressures exceeded placebo values by approximately 10 mm Hg (p < 0.001 and p < 0.05 for systolic and diastolic pressures, respectively). This effect of candoxatril was absent in group 2, which (unlike group 1) had exhibited a modest natriuretic response (sustained cumulative negative sodium balance, -70 +/- 21 mmol; p < 0.01) to the higher dose of inhibitor. Baseline plasma aldosterone concentrations and the incremental aldosterone response to angiotensin II infusions were not significantly altered by low-dose (group 1) candoxatril.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1992

Acute inhibition of endopeptidase 24.11 in essential hypertension: SCH 34826 enhances atrial natriuretic peptide and natriuresis without lowering blood pressure.

The acute renal, endocrine, and hemodynamic effects of the orally active endopeptidase inhibitor SCH 34826 (400 mg every 6 hours for five doses) were investigated in a group of 6 male patients [with established mild to moderate essential hypertension and left ventricular (LV) hypertrophy] in a balanced random-order double-blind, placebo-controlled cross-over study. Plasma atrial natriuretic factor (ANF) concentrations increased (p < 0.05) to fourfold control values after the first dose of inhibitor, but later postdose increments of ANF were less pronounced. Plasma cyclic GMP also increased significantly (p < 0.05). These effects were associated with a transient modest but significant (p < 0.05) increase in sodium excretion (50 mmol sodium in excess of placebo values) that was complete in 24 h. Mean 24-h urinary excretions of cyclic GMP and immunoreactive ANF were also significantly increased by 55 and 86%, respectively. Other urine indexes (including other electrolytes, volume, creatinine, aldosterone, and cortisol) and renal hemodynamics [including glomerular filtration rate (GFR) and effective renal plasma flow (RPF)] were unchanged. Renin-angiotensin-aldosterone system (RAAS) activity was not significantly altered. Plasma epinephrine increased after the initial three doses of SCH 34826. Systolic blood pressure (SBP) and heart rate (HR) were not altered by SCH 34826. Diastolic BP (DBP) increased slightly (p = 0.044). Acute inhibition of endopeptidase 24.11 by SCH 34826 in essential hypertension caused significant increments in plasma ANF and cyclic GMP together with modest natriuresis. No antihypertensive effect was observed in the first 30 h of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗
PubMed1991

Assessment of creatinine clearance in healthy subjects over 65 years of age.

Eighteen healthy people over 65 years of age were studied to compare the 99mTC-diethylenetriamine pentaacetic acid (DTPA) clearance, the measured 24-hour creatinine clearance and the assessed creatinine clearance using the Cockcroft and Gault (C-G) formula to measure their glomerular filtration rate. Significant correlations were found between the isotopic method and the measured creatinine clearance (r = 0.71; p less than 0.001); the measured creatinine clearance and the C-G formula (r = 0.81; p less than 0.001), and the isotopic method and the C-G formula (r = 0.70; p less than 0.001). The C-G formula correlated better with both the 99mTc-DTPA clearance and the measured creatinine clearance when the female correction factor was used. This study has shown that in healthy, elderly people, the C-G formula for assessing the creatinine clearance correlated extremely well with the standard clinical tests for measuring the glomerular filtration rate. Whilst the formula has clinical value and allows rapid and accurate assessment of renal function in the elderly, the clinician must be aware that the formula relatively underestimates the true renal clearance.

Aged↗
PubMed1991

EC 24.11 inhibition in man alters clearance of atrial natriuretic peptide.

Metabolic clearance and the biological effects of exogenous human atrial natriuretic factor (ANF) were assessed in two groups each of eight normal volunteers receiving 2-h iv infusions of ANF (2.5 pmol/kg.min) on the fifth day of dosing with the orally active inhibitor of endopeptidase 24.11, candoxatril (25 mg every 12 h in group 1 and 100 mg every 12 h in group 2), and placebo in balanced randomized, double blind, placebo-controlled, cross-over experiments. Although 4 days of pretreatment with the endopeptidase inhibitor did not affect basal plasma ANF, candoxatril enhanced mean ANF-induced increases in plasma ANF by 27 pmol/L (P = NS) and 42 pmol/L (P less than 0.002) in groups 1 and 2, respectively. Calculated MCRs for ANF were significantly reduced by both doses of candoxatril [group 1, 2.5 +/- 0.4 vs. 4.3 +/- 0.6 L/min (P less than 0.01); group 2, 2.3 +/- 0.4 vs. 5.6 +/- 0.8 L/min (P less than 0.001)]. ANF significantly enhanced urinary sodium excretion above preinfusion values in both study phases in both groups. Candoxatril significantly further augmented natriuresis in group 2 (P less than 0.01), but not group 1. Inulin clearance was minimally enhanced, and para-aminohippuran clearance was slightly decreased by candoxatril in both groups. Neither effect alone was statistically significant, but derived renal filtration fractions were significantly enhanced in both groups [group 1, 15.5 +/- 0.5% vs. 13.9 +/- 0.6% (P less than 0.01); group 2, 19.3 +/- 1.9% vs. 18.0 +/- 2.7% (P less than 0.01)]. Basal and stimulated cGMP concentrations in both plasma and urine were significantly enhanced by candoxatril in the two groups (P less than 0.001 and P less than 0.01, respectively, for combined data). Urinary ANF immunoreactivity was significantly enhanced by candoxatril in both groups (P less than 0.05 and P less than 0.01 in groups 1 and 2, respectively), with a more pronounced effect evident at the higher dose (P less than 0.01). These results show that chronic pretreatment with an endopeptidase inhibitor in normal man causes a dose-related reduction in the metabolic clearance of exogenous ANF, amplifies cGMP, and increases renal filtration and the natriuretic responses to infused ANF.

Adult↗
PubMed1991

Prolonged inhibition of endopeptidase 24.11 in normal man: renal, endocrine and haemodynamic effects.

The renal, hormonal and haemodynamic effects of chronic (4 days) dosing with an inhibitor of endopeptidase EC 3.4.24.11 (UK 79300) were assessed in two groups, each of eight normal volunteers, receiving 25 mg every 12 h (group 1) or 100 mg every 12 h (group 2) of UK 79300 in double-blind, balanced-randomized, placebo-controlled, crossover studies. Group 2 (but not group 1) exhibited a significant transient natriuresis (P less than 0.01) and a consequent sustained negative cumulative sodium balance (70 +/- 21 mmol) which was established within 48 h and remained for the duration of dosing with UK 79300. Urine and plasma cyclic guanosine monophosphate (cGMP) levels rose significantly above placebo values (P less than 0.01 and P less than 0.001, respectively) in both groups and the effect was sustained throughout the dosing period. Plasma atrial natriuretic factor (ANF) was slightly enhanced by UK 79300 in group 1 (P less than 0.05) but not significantly increased in group 2. Despite a significant increase in heart rate in both groups (P less than 0.001) and of natriuresis in group 2, there was minimal evidence of renin-aldosterone activation in either group. Trends towards lower systolic pressures, observed in both groups, did not attain statistical significance. These findings suggest chronic treatment with UK 79300 induces an increase in tissue ANF levels, with sustained enhancement of plasma and urine concentrations of ANF second messenger (cGMP) and increased heart rate.

Aldosterone↗
PubMed1990

Inhibition of endopeptidase EC 24.11 in humans. Renal and endocrine effects.

The effects of an orally active inhibitor (UK 79300) of the neutral metalloendopeptidase EC 3.4.24.11 were investigated in six healthy male volunteers maintained on a constant diet (150 mmol sodium/day and 80 mmol potassium/day). Subjects were studied in a random order, single-blind study on two occasions, each 48 hours in length, when they were given UK 79300 (25 or 50 mg p.o.) or placebo at 12-hour intervals (each agent for 24 hours). The endopeptidase inhibitor enhanced plasma concentrations of atrial natriuretic factor in association with suppression of both plasma renin activity and aldosterone concentrations. Twenty-four-hour urinary excretion of sodium was doubled by UK 79300, and the urinary excretion rates of phosphorus, atrial natriuretic factor immunoreactivity, and cyclic guanosine monophosphate were also significantly enhanced, whereas urinary aldosterone excretion was halved. The profile of biological effects closely paralleled those previously reported with low dose infusions of atrial natriuretic factor in humans and animals. Therapeutic trials of such inhibitors are now indicated for hypertension or heart failure together with further studies to clarify the underlying mechanisms of action.

Adult↗
PubMed1989

Competitive peptide antagonists of ANF-induced cyclic guanosine monophosphate production.

Atrial natriuretic factor (isoleucine ANF 101-126), cleaved ANF (isoleucine ANF 101-105/106-126) and des (Gln 18, Ser 19, Gly 20, Leu 21, Gly 22) ANF 4-23-NH2 (C-ANF 4-23) stimulated cyclic guanosine monophosphate production (cGMP) by rat aortic vascular smooth muscle cells (VSMC) in culture. Cleaved ANF and ANF C4-23 also antagonised or diminished the response to ANF 101-126. Agonist and antagonist actions of both peptides were dose-related. In contrast, prepro ANF (104-123), an ANF precursor fragment, exhibited no agonist or antagonist effect on cGMP production.

Animals↗
PubMed1987

Prospective, multi-centre trial of mortality following general or spinal anaesthesia for hip fracture surgery in the elderly.

In a prospective randomized multi-centre study, the mortality following internal fixation surgery for fracture of the upper femur was investigated in 538 elderly patients allocated to receive subarachnoid blockade or general (narcotic-relaxant) anaesthesia. The 28-day mortality was 6.6% with subarachnoid, and 5.9% with general, anaesthesia. The difference was not significant (95% confidence limits: -3.5 to +4.8). At 1 year following surgery, the mortality was 20.4%. Increasing age, ischaemic heart disease, cardiac failure, preoperative arrhythmias and poor ASA status were all associated with increases in early and long term mortality. A delay to surgery of more than 24 h from admission was also associated with an increased 28-day mortality. Senile dementia and admission other than from the patient's own home, were factors associated with a poorer long term outcome. From the point of view of mortality, subarachnoid anaesthesia did not appear to confer any advantages over general anaesthesia in non-prosthetic surgery for hip fracture in the elderly.

Aged↗
PubMed1976

An ECG telemetry system for physiological studies on swimmers.

A low frequency telemetry system is described which has been designed to allow high quality ECG measurements to be made on active swimmers. The transmitting antenna is a small loop worn by the swimmer whilst the receiver is fed from a single wire loop around the swimming pool. Both ECG electrodes and the transmitter case are made in a waterproof form which allows the swimmer complete freedom of action to dive and swim normally. The transmitter can be constructed from normal miniature components although the present version has been assembled using thick film techniques which combine high reliability with a reduction in overall volume.

Coronary Care Units↗