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Biomedical subjects

A F Lant

Publications and source records attributed to A F Lant.

At least 19 recordsLinked to original sources
PubMed1992

Erythrocyte sodium-lithium countertransport and blood pressure in identical twin pairs discordant for insulin dependent diabetes.

OBJECTIVE: To investigate whether insulin dependent diabetes is responsible for the abnormal behaviour of the carrier in sodium-lithium countertransport and whether the diabetic state is associated with rise in blood pressure. DESIGN: Case-control study. SETTING: London teaching hospital. SUBJECTS: 44 twin pairs discordant for insulin dependent diabetes living in United Kingdom and 44 healthy control subjects matched for age, sex, and body mass index. None of the twin pairs or the controls had evidence of microalbuminuria. MAIN OUTCOME MEASURES: Sodium-lithium countertransport activity in erythrocytes and arterial blood pressure. RESULTS: The mean (95% confidence interval) sodium-lithium countertransport activity (mmol Li per litre of red blood cells per h) of the diabetic twins (0.291 (0.244 to 0.338)) was similar to that of their non-diabetic cotwins (0.247 (0.204 to 0.290)); both values were significantly higher than that of the controls (0.187 (0.157 to 0.216); p < 0.05). In addition, systolic blood pressure was higher in those twins with diabetes (127 (122 to 133) mm Hg) than in the non-diabetic cotwins (122 (117 to 127) mm Hg; p < 0.01). There were no significant differences in mean diastolic blood pressure between any of the groups studied. CONCLUSIONS: The raised erythrocyte sodium-lithium countertransport activity in the diabetic twins compared with the controls seems to be inherited rather than a consequence of overt diabetes. The higher systolic blood pressure in diabetic twins than non-diabetic cotwins indicates that insulin dependent diabetes does exert a small influence on systolic blood pressure.

Adult↗
PubMed1992

Neuropsychological and psychiatric abnormalities in myalgic encephalomyelitis: a preliminary report.

Ten patients attending one general medical hospital clinic who fulfilled operational criteria for the diagnosis of myalgic encephalomyelitis (ME) and with a history longer than three months, underwent a series of standardized neuropsychological and psychiatric tests. Nine were able to complete the tests and were individually matched with a normal control group for age, sex, educational background and premorbid intelligence. The ME subjects showed inferior performance to the controls on two tests of verbal memory. Their personality scores displayed less extraversion and less psychoticism. This is the first report of objective neuropsychological abnormalities in patients with ME, suggesting a discrete deterioration of short-term memory. The findings may also suggest a concurrent psychiatric component of the condition, but the direction of causality remains to be clarified.

Anxiety Disorders↗
PubMed1992

Importance of routine measurement of HDL with total cholesterol in diabetic patients.

The prevalence of hypercholesterolaemia and the frequency of a reduced HDL-cholesterol (at different cholesterol concentrations) were evaluated in a group of 400 diabetic patients attending a single diabetic clinic. Despite regularly supervised diabetes, including dietary advice, over one quarter of the patients had a serum total cholesterol concentration greater than 6.5 mmol/l, while over a quarter of the non-insulin treated and one eighth of the insulin treated diabetic subjects had an HDL-cholesterol less than 0.9 mmol/l, with a greater prevalence in the males compared with the females. More than 60% of all the diabetic patients who had a reduced HDL-cholesterol less than 0.9 mmol/l also had a total cholesterol concentration less than 6.5 mmol/l. When the total/HDL-cholesterol ratio was calculated more non-insulin treated subjects had a value greater than 4.5 as compared with insulin treated diabetic patients. When comparisons were made between an age matched group of diabetic patients (n = 185) and a group of non-diabetic subjects attending for a health screen (n = 155), the frequencies of serum cholesterol concentrations greater than 5.2, 6.5, and 7.8 mmol/l were similar for both groups. Significantly greater numbers of diabetic patients had a reduced HDL-cholesterol less than 0.9 mmol/l (at any level of serum cholesterol) and a total/HDL cholesterol ratio greater than 4.5. This study has shown that the measurement of serum total cholesterol concentration alone will not characterize many subjects who are at risk of macrovascular complications due to a reduced HDL-cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Steroid trials in the assessment of reversibility of air flow limitation: a survey of current clinical practice of chest physicians.

To evaluate how steroid trials are currently used in the assessment of reversibility of air flow limitation, a postal questionnaire was sent to 355 consultant members of the British Thoracic Society working in England and Wales; 253 questionnaires were returned (71% response rate). Two respondents did not undertake steroid trials; of the remaining 251, 75% prescribed 30-40 mg oral prednisolone, with the commonest treatment period being 2 weeks. A high dose steroid inhaler was sometimes used as an alternative by 31% of respondents. Although 71% of respondents made lung function measurements on several occasions before starting steroids and 76% made measurements during treatment, 78% assessed patients on only one occasion at the end of the trials to ascertain its outcome. Weight, blood pressure and glycosuria were measured less frequently after the steroid treatment compared to the pre-trial period. Blood glucose and serum electrolytes were infrequently measured both before and after treatment. Wide variations exist in steroid trial regimens and current practice may neither provide definitive evidence of treatment benefit nor an adequate safeguard for patients against potential side-effects.

Chronic Disease↗
PubMed1991

Muzolimine: renal site of action and interaction with probenecid in humans.

Muzolimine (60 mg, administered orally) was administered to eight healthy volunteers, under conditions of altered fluid load, to elucidate its renal site of action. The duration of action and the effect of probenecid pretreatment on muzolimine response was also investigated. Muzolimine had a rapid onset of action, with the diuresis complete within 4 hours after dosing. At peak natriuresis, under hydrated conditions, fractional excretion of free water remained unaltered (9.72% +/- 0.59% versus 9.07% +/- 0.44%; difference not significant) but was accompanied by a significant increase in the delivery of sodium out of the proximal tubule, as measured by fractional excretion of lithium (22% +/- 2% to 31% +/- 1%; p less than 0.01). The fraction of sodium reabsorbed in the distal tubule also decreased from 94% +/- 1% to 67% +/- 1% (p less than 0.001) of the delivered load. The fractional reabsorption of free water during hydropenia decreased after muzolimine (5.63% +/- 0.26% to 2.00% +/- 0.81%; p less than 0.05). Pretreatment with probenecid resulted in a prominent decrease in urinary sodium excretion (246 +/- 25 mmol/24 hr for muzolimine alone 161 +/- 24 mmol/24 hr for muzolimine and probenecid; p less than 0.01). These findings suggest that muzolimine has a major site of action in the medullary portion of the thick ascending limb of Henle with additional inhibitory activity on the proximal tubule. It is likely that the active secretion of one or more of the acidic metabolites of muzolimine, by way of the probenecid sensitive organic acid pathway, is responsible for mediating the renal actions this basic drug.

Administration, Oral↗
PubMed1991

Analysis of the natriuretic action of a loop diuretic, piretanide, in man.

1. The renal responses to a loop diuretic, piretanide, were investigated in a group of fourteen healthy volunteers. The effect of fluid replacement on the drug-response relationship was evaluated in the absence and in the presence of probenecid pretreatment following both oral and intravenous administration of piretanide. 2. Urinary excretion of piretanide was greater when volume losses were replaced than in the absence of volume replacement (i.v. dose: 3.32 +/- 0.15 vs 2.55 +/- 0.23 mg 6 h-1, P less than 0.01; oral dose: 2.57 +/- 0.09 vs 1.87 +/- 0.27 mg 6 h-1, P less than 0.01). With intravenous piretanide urinary excretion of sodium was likewise greater in the fluid replaced group (198 +/- 4 vs 141 +/- 10 mmol 6 h-1, P less than 0.01); these differences caused by fluid replacement did not however occur after oral dosing of piretanide (181 +/- 12 vs 167 +/- 14 mmol 6 h-1). 3. Probenecid pretreatment significantly decreased the renal excretion of piretanide in all subjects and consistently decreased the natriuretic response with the exception of intravenous piretanide challenge in subjects not undergoing fluid replacement. In this situation, despite probenecid causing a decrease in the amount of drug excreted (2.55 +/- 0.23 vs 1.63 +/- 0.15 mg 6 h-1, P less than 0.05) the sodium output was unaltered (141 +/- 10 vs 152 +/- 16 mmol 6 h-1, NS). 4. Complete replacement of the induced fluid losses resulted in the enhancement of the renal response, without affecting the shape of the diuretic response curve, of either the intravenous or orally administered piretanide.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Management choices for hypertension with coexistent hypercholesterolaemia.

Guidelines for the management of either hypertension or hyperlipidaemia have been widely published. However, recent data have shown the high frequency of an abnormal lipid profile in hypertensive subjects. We have therefore surveyed 195 general practitioners throughout Britain to determine current community-based attitudes and management approaches to hypertension with coexistent hypercholesterolaemia. Routine screening for lipids in hypertensive subjects was recommended by 40% of respondents. First-line antihypertensive drug choices were influenced by the knowledge of a hypercholesterolaemia, with preference for drugs known to have no adverse effects on the lipid profile. When first-choice drug failed to effectively lower blood pressure, the additional drug or the substitute choices were not influenced by the metabolic profiles of the alternative selected. The current wide choice of antihypertensive drugs and the complexity of metabolic complications of treatment plus the relationship of risk factor clustering has made the formulation of management strategies very difficult. This was supported by the finding that 88% of respondents in our survey felt that there was a clear need for consensus management guidelines for the treatment of hypertension with coexistent hypercholesterolaemia.

Aged↗
PubMed1990

Pharmacokinetic and pharmacodynamic studies of glibenclamide in non-insulin dependent diabetes mellitus.

1. The pharmacokinetic and pharmacodynamic properties of oral glibenclamide have been studied in 31 hospitalised in-patients and 79 ambulant out-patients with diabetes mellitus. 2. Breakfast was found to have no significant influence on the kinetic behaviour of glibenclamide or on the effect of this drug on blood glucose utilisation. 3. The time course of glibenclamide kinetics after 20 mg dosing was adequately described by a two-compartment open model, yielding mean half-lives of 3.3 +/- 1.5 h (t1/2, lambda 1) and 9.7 +/- 1.2 (t1/2, z) for the initial and terminal elimination phases respectively. 4. No significant accumulation or change in kinetic profile occurred in patients who had normal renal and hepatic function, were treated continuously with glibenclamide, and then rechallenged after 8-12 weeks. 5. Despite inter-individual variations in drug absorption, peak plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC(0-24] were dose-dependent over the dose range 5-20 mg. No significant dose-response behaviour was observed in respect of glucose utilisation, suggesting that there is little clinical benefit in using doses of glibenclamide above 5 mg day-1. 6. Comparison of plasma glibenclamide concentrations at different time-bands following doses of 5 and 10 mg showed a wider range in ambulant out-patients than in age-, sex-matched in-patients treated with the same dosages of drug. Mean plasma drug concentrations attained at all time bands up to 8 h after dosing were higher in out-patients than in in-patients, suggesting a tendency to 'over-compliance' by patients in anticipation of attendance at clinic.

Administration, Oral↗
PubMed1990

Pharmacokinetic and pharmacodynamic actions of enalapril in humans: effect of probenecid pretreatment.

The pharmacokinetic and pharmacodynamic profiles of oral enalapril (20 mg), in absence and in presence of probenecid pretreatment (1 g twice daily for 5 days), were investigated in 12 healthy volunteers on normal salt intake (150 mmol/24 hr). Mean peak serum concentration of enalapril rose from 158 +/- 7 to 216 +/- 1 ng/ml (P less than .01), whereas that of its metabolite, enalaprilat, rose from 62 +/- 6 to 84 +/- 8 ng/ml (P less than .01) in the presence of probenecid pretreatment. Area under the curve of both enalapril and enalaprilat increased by 50% (P less than .001), which was accompanied by a reduction in renal excretion of both compounds. The renal clearance of enalapril decreased from 229 +/- 19 to 61 +/- 4 ml/min (P less than .001) and that of enalaprilat from 108 +/- 4 to 66 +/- 2 ml/min (P less than .001). The total drug recovery fell from 48 +/- 3 to 38 +/- 2% (P less than .01) of the administered dose with no accompanying changes in plasma elimination half-lives of the parent drug or metabolite. The pharmacodynamic response of enalapril such as fractional excretions of sodium, calcium, magnesium and urate were enhanced by probenecid pretreatment. Absolute urinary excretion of sodium increased from 51 +/- 5 to 91 +/- 8 mmol/6 hr (P less than .001) after enalapril and from 55 +/- 4 to 113 +/- 13 mmol/6 hr (P less than .01) after enalapril in presence of probenecid pretreatment, despite a significant decrease in the renal excretion of enalapril and enalaprilat over the same interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Renal responses and pharmacokinetics of piretanide in humans: effect of route of administration, state of hydration and probenecid pretreatment.

The influence of route of administration, state of hydration and transport inhibitor probenecid on the renal responses of a loop diuretic, piretanide, were investigated in 14 healthy volunteers. Maximally achieved plasma concentrations after i.v. and oral piretanide were higher in the nonhydrated state [+54% (i.v.); + 68% (oral)], accompanied by significant decreases in mean residence time, renal clearance and fraction of unchanged drug excreted with nonsignificant decreases in t1/2, steady-state volume of distribution and total clearance when compared with the hydrated state. Relative differences between the two hydrated states in maximal plasma concentrations of piretanide remained after probenecid [+26% (i.v.); +55% (oral)] but changes in kinetic parameters did not. Pretreatment with probenecid produced significant increases in absolute peak and plasma diuretic concentrations, t1/2 and mean residence time while decreasing steady-state volume of distribution, total clearance, renal clearance and fraction of unchanged drug excreted without affecting the bioavailability of piretanide. Urinary drug recovery was greater after i.v. than after oral piretanide, the recovery being consistently lower in nonhydrated state [iv: 2.78 (nonhydrated) versus 3.41 mg/24 h (hydrated); oral: 1.93 (nonhydrated) versus 2.76 mg/24 h (hydrated)]. Probenecid pretreatment reduced the overall urinary recovery of piretanide without altering the i.v./oral differences. Excretion of sodium paralleled piretanide excretion throughout the study except after i.v. dosing in the nonhydrated state where changes in drug excretion after probenecid (2.55 versus 1.63 mg/6 h) failed to influence sodium output (167 versus 152 mmol/6 h). These results demonstrate the importance of route of administration and state of hydration in determining the pharmacocological response of loop diuretics within the kidney.

Administration, Oral↗
PubMed1989

Effect of salt balance on the renal and hemodynamic actions of benazepril in normal men.

Renal and hemodynamic effects of diet alone and of single oral doses of the nonsulphydryl angiotensin converting enzyme (ACE) inhibitor, benazepril (10 mg), were investigated in eight healthy volunteers under stable conditions of high salt intake (300 mmol NaCl/day) and low salt intake (10 mmol NaCl/day), in a double blind, placebo controlled study. There were no changes in blood pressure between the two dietary extremes either during the run-in period or once sodium balance had been achieved. Mean renal plasma flow was higher, by approximately 10% and renal vascular resistance lower by 15%, on high salt diet compared to low salt diet. Glomerular filtration rates were found to be similar irrespective of the state of salt balance. Both plasma urate concentration and plasma renin activity were significantly elevated in the low salt compared to high salt state. Benazepril caused a greater fall in blood pressure in the sodium depleted state. Significant increases in the mean renal plasma flow, in the order of 15-20%, were seen over 6 h postbenazepril when compared with placebo response, regardless of the level of salt intake. Glomerular filtration rate over the same period remained unaltered. Benazepril doubled the urinary excretion of sodium over the first 4 hours after dosing whilst on the low salt diet; the equivalent increase during salt loading was approximately 20%. These results suggest that benazepril may exert direct effects on renal tubular function additional to those achieved through ACE blockade.

Adult↗
PubMed1989

Parasuicide in central London 1984-1988.

Experience of a central London unit dedicated to the care of patients following parasuicide between 1984 and 1988 is reviewed. There were 1160 admissions, which accounted for 11% of all acute adult medical admissions. The female to male ratio was 1.3, with a peak rate for females below 25 years and for males between 20 and 35. Unemployment was found to be a risk factor for parasuicide in men. Benzodiazepines were the most frequently used drug in parasuicide (35%), followed by paracetamol (13%) and aspirin (9%).

Acetaminophen↗
PubMed1988

Seventeen years' experience of a voluntarily based drug rationalisation programme in hospital.

A study was carried out analysing the operation of a drug rationalisation programme in a central London teaching district that had evolved from experience over 17 years. Creation of a limited list of about 700 drugs had been achieved by local consensus. Drug selection was based on appraisal of efficacy, safety, and cost and was undertaken by means of collaborative participation of most consultant specialists in the district. Educative and other non-restrictive strategies for reinforcing the rationalisation policy had achieved a consistently high rate of compliance in prescribing recommended drugs. The concept of selectivity in drug use and its continuous local reappraisal had a beneficial impact on the prescribing habits of doctors at all levels of seniority as well as on the training of medical undergraduates and nurses in the therapeutic use of medicines. Peer review and self audit were encouraged by use of an extensive monitoring system which incorporated continuous "facilitative" dialogue between ward pharmacists and prescribers. Two models of drug rationalisation programme were studied, the second of which together with other local initiatives had been associated with substantial and sustained reductions in drug spending each year over nine years since 1978. It is concluded that the second drug rationalisation programme model substantially improves the cost effective use of drugs in hospital and furthermore has the potential of being extended to general practice, especially in types of prescribing that are common to both forms of patient care.

Drug Prescriptions↗
PubMed1988

The influence of nonsteroidal anti-inflammatory drugs and probenecid on the renal response to and kinetics of piretanide in man.

The mechanism by which nonsteroidal antiinflammatory drugs interfere with the action of loop diuretics is not clear. We studied the renal response to an acute challenge of piretanide superimposed on pretreatment with either placebo, probenecid, indomethacin, or piroxicam in seven maximally hydrated subjects. No change was seen in glomerular filtration rate, as measured by creatinine clearance, throughout the experiments. When compared with responses to piretanide challenge after placebo pretreatment, probenecid reduced by 65% the peak fractional excretion of sodium (FENa), with a corresponding reduction in diuretic excretion. Pretreatment with indomethacin reduced peak FENa by 35%, but urinary delivery of piretanide was not altered. In contrast, piroxicam did not influence FENa but significantly reduced the delivery of both sodium and piretanide into urine. We conclude that the activity of nonsteroidal antiinflammatory drugs within the renal tubule varies among individual drugs and cannot be explained solely by their common mechanism of antiinflammatory action.

Administration, Oral↗
PubMed1988

Effect of maximal hydration on the renal responses to pretreatment with nonsteroidal anti-inflammatory drugs and probenecid in man.

The renal response to a challenge of maximal water diuresis has been studied in seven subjects pretreated over 48 h with either placebo, probenecid, indomethacin or piroxicam. Probenecid did not alter the excretion of water and sodium chloride when compared with placebo responses, but increased both phosphate and urate clearances. Indomethacin reduced significantly both water and sodium chloride clearances by approximately 40%. Piroxicam reduced water excretion to a similar extent but did not influence salt output. In parallel with these changes, both drugs caused significant phosphaturia. It is concluded that the renal actions of nonsteroidal anti-inflammatory drugs (NSAIDs) are individually distinct and involve direct effects on tubular transport of ions and water to differing extents within both the proximal and distal portions of the nephron.

Adult↗
PubMed1988

Acute and long-term renal and metabolic effects of piretanide in congestive cardiac failure.

1. The renal and metabolic effects of the sulphamoylbenzoic acid diuretic, piretanide, have been studied, under controlled dietary conditions, in 39 patients with congestive cardiac failure. 2. In acute studies, peak saluresis occurred within 4 h of oral piretanide administration; saluresis was complete within 6 h, after which a significant antidiuretic effect was observed. Addition of triamterene, 50 mg, blunted the 0-6 h kaliuretic effect of piretanide. Over 24 h, piretanide, alone, caused insignificant urinary losses of potassium when compared with control. 3. In comparative studies, the piretanide dose-response curve was found to be parallel to that of frusemide over the dose range studied. The 0-6 h saluretic responses of piretanide, 6, 12 and 18 mg, were found to be equivalent to frusemide, 40, 80 and 120 mg respectively. The collective mean ratios of all the saluretic responses to each dose of piretanide with the corresponding dose of frusemide was observed to be 0.99 +/- 0.12, over 0-6 h period, and 0.86 +/- 0.09 over the 24 h period. The relative potency of piretanide, when compared with frusemide was found to be 6.18 (95% confidence limits 4.87-8.33), over the 0-6 h period, and 4.73 (95% confidence limits 3.65-6.14), over 24 h period. 4. In 15 patients in severe cardiac failure, urinary recovery of piretanide, over first 6 h, at the start of treatment was 21.2 +/- 2.1% while efficiency of the diuretic (mmol Na/mg drug) was 47.3 +/- 4.1. Long-term piretanide therapy was continued in the same group for up to and in some cases over 3 years. No other diuretics or potassium supplements were given. Piretanide dosage ranged from 6 to 24 mg day-1 according to clinical need. Plasma potassium fell significantly at 12 and 24 months, though remaining within the normal range. At these same times, significant elevations in both plasma urate and total fasting cholesterol were observed. Two patients developed overt gout on high dose piretanide therapy (24 mg day-1). Piretanide was well tolerated, and effective in the management of congestive cardiac failure without any other recognized metabolic or electrolyte changes.

Adult↗
PubMed1988

The risks of staying in London: a review of overseas visitors admitted to a London hospital.

A retrospective review of 103 acute admissions of overseas visitors to a central London hospital was performed. Admissions were most commonly due to infection (43 admissions) and to recurrence of preexisting disease (40 admissions). Patients over 60 years were frequently admitted with new diagnoses. Groups at risk of admission were identified and strategies to reduce admissions discussed.

Adolescent↗