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Biomedical subjects

A F Lant

Publications and source records attributed to A F Lant.

At least 73 records · Page 4Linked to original sources
PubMed1984

Adult community-acquired pneumonia in central London.

Strep. pneumoniae was diagnosed as the cause of pneumonia in 40 (50%) of 80 consecutive adults admitted to St Stephen's Hospital with community-acquired pneumonia. None of the patients had evidence of Mycoplasma pneumoniae infection, and Legionella pneumophila serology was positive on only one occasion. In 29 patients (36%) no causative organism was demonstrated. The diagnosis of pneumococcal infection was obtained in 15 cases by isolating Strep. pneumoniae from the sputum, in 13 further cases by demonstrating pneumococcal capsular antigen in sputum, and in 12 other cases by detecting pneumococcal antigen in serum only. Only 2 cases with pneumococcal pneumonia were bacteraemic and 3 patients (7%), all aged more than 75 years, died. The relatively low bacteraemic and mortality rates suggest that community-acquired pneumococcal pneumonia currently seen in patients admitted to hospital in central London may not be so severe as in some other areas.

Adult↗
PubMed1984

Kinetic and metabolic aspects of enalapril action.

Enalapril is a long-acting, sulphydryl-free, ACE inhibitor whose humoral and hypotensive effects are maximal at 4-8 h and remain detectable at 24 h after a single dose. Serum profiles after chronic dosing of enalapril show little accumulation of the active diacid metabolite, enalaprilat. Comparison between the observed and predicted steady-state urinary recoveries of enalaprilat yields an effective accumulation half-life of approximately 11 h. In normotensive subjects, enalapril increases renal blood flow whilst leaving glomerular filtration unchanged irrespective of the state of sodium balance. Similarly under conditions of salt loading and salt depletion, a biphasic saluretic response is seen which parallels the excretory maxima for unchanged enalapril (1-2 h) and enalaprilat (4-8 h) suggesting direct interference by the drug moieties with tubular NaCl reabsorption. During the period of maximal enalapril action, uricosuria and phosphaturia are seen, supporting a direct action of enalaprilat on proximal tubular handling of these anions. Detailed documentation of the chronic metabolic effects of enalapril remains incomplete. A small rise in plasma potassium concentrations can occur but overt hyperkalaemia is unlikely in the absence of gross renal failure. Continued dosing is associated with a fall in plasma uric acid concentrations; plasma prolactin concentrations remain unaltered.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

The effect of enalapril on serum prolactin.

Twelve healthy male volunteers received single daily oral doses of enalapril (EN) 10 mg for 8 consecutive days. Serum samples for prolactin (PRL) assay were taken on day 0 (baseline) at 12.00 h and 16.00 h, and on days 1 and 8 at 08.00 h (pre-drug), 12.00 h and 16.00 h. The 08.00 h values on day 1 served as the pre-drug baseline. There were no significant changes from baseline in serum PRL levels on days 1 and 8. All mean serum PRL levels on day 8 were significantly (P less than 0.01) lower than the upper limit of the normal range (2-15 ng/ml) found for healthy males in this laboratory. It is concluded that therapeutic doses of EN (10 mg/day, p.o.) for 8 consecutive days do not raise mean serum PRL levels above the normal range in healthy male volunteers.

Adult↗
PubMed1980

Studies on the mechanism and characteristics of action of a uricosuric diuretic, indacrinone (MK-196).

1 The renal action of indacrinone (MK-196), a phenoxyacetic acid derivative with diuretic and uricosuric properties, has been studied in fifteen male subjects. 2 Increasing single doses of up to 60 mg of oral indacrinone produced a linear increase in urinary volume and excretion of Na+ and Cl-, whilst the responses of urinary K+, Ca2+, Mg2+ and uric acid excretion, rose to a plateau at the 40 mg dose. 3 Indacrinone evoked a rapid diuretic response which reached a maximum of 2-4 h and was largely complete at 8-12 h after administration. 4 During maximal hydration, indacrinone produced a substantial fall in fractional free water clearance (CH2O), from 8.89% to 5.83% of the filtered load of water, associated with an increase in osmolal clearance, from 1.38% to 5.78% of the filtered load of solute. The reduction in CH2O was of the same order as that produced by a dose of ethacrynic acid with comparable saluretic activity and significantly greater than that produced by an equi-saluretic dose of hydrochlorothiazide. These findings imply an action of indacrinone upon solute transport in the diluting segments of the distal tubule. 5 At the time of maximal indacrinone-induced saluresis, which amounted to an increase from 0.48% to 4.61% of the filtered load of NaCl, fractional urate clearance increased from 5.16% to 12.24% of the filtered load of uric acid. 6 Indacrinone is a long acting diuretic, sharing some properties in common with both loop diuretics and benzothiadiazines. The results are discussed in relation to structure-activity amongst derivatives of phenoxyacetic acid.

Diuresis↗
PubMed1979

Plasma levels of 5-fluorouracil after oral and intravenous administration in cancer patients.

1. Plasma levels of 5-fluorouracil (5FU) have been determined in eleven cancer patients after 0.5 g and 1.0 g intravenous doses, and in one patient after paired 1.0 g oral and intravenous doses. 2. The plasma half-life after the 0.5 g intravenous dose was relatively constant, irrespective of the stage and spread of the disease. 3. Plasma kinetics of the drug were dose dependent. Doubling of the intravenous dose produced a 1.5-fold increase in plasma half life, a two-fold increase in initial plasma drug concentration, and a three-fold increase in area under the concentration/time curve. 4. In one patient receiving paired 1.0 g intravenous and oral doses nine weeks apart, an increase in the bioavailability of the drug coincided with a marked clinical regression in palpable intra-abdominal metastases. 5. The significance of measuring plasma drug kinetics and their relationship to drug efficacy and toxicity are discussed.

Administration, Oral↗
PubMed1978

Use of a nitrogen detector for GLC determination of fluorouracil in plasma during single- and combined-agent chemotherapy.

A GLC assay for fluorouracil was developed and used to monitor plasma drug levels in patients on both single- and combined-agent chemotherapy. Fluorouracil is extracted from plasma, derivatized by flash methylation, and estimated using a thermionic nitrogen-phosphorus detector. The GLC determination was accurate at concentrations as low as Q.1 microgram/ml of human plasma. Other drugs commonly used in combination with fluorouracil did not interfere with the assay.

Antineoplastic Agents↗
PubMed1978

The use of the human erythrocyte as a model for studying the action of diuretics on sodium and chloride transport.

1. The Na+ and Cl- transport systems of human erythrocytes have been compared for their sensitivities to diuretics known to act in the ascending limb of Henle's loop. In addition, chemical analogues of 'loop' compounds and also diuretics which act in other areas of the nephron have been examined. 2. The Na+ transport system lacks specificity with respect to inhibition by 'loop' diuretics and also a related chemical analogue studied at equivalent concentrations. 3. The Cl- transport system is inhibited, at low concentrations, by diuretics known to act in the ascending limb of Henle's loop. 4. Erythrocyte Cl- transport offers a useful model with which to study the biochemical action of diuretics.

Biological Transport↗
PubMed1976

Comparative effects of acebutolol and practolol on the lipolytic response to isoprenaline.

1 The effects of beta-adrenoceptor blockade on the metabolic responses to isoprenaline have been studied in an in vitro system of isolated fat cells and in six normal subjects. 2 The inhibitory effects of varying concentrations of acebutolol, practolol and propranolol on free fatty acid (FFA) release produced by isoprenaline (10(-7) M) were compared in isolated fat cells prepared from rat epididymal adipose tissue. Acebutolol and practolol, at equimolar concentrations, showed a similar inhibitory effect whilst propranolol was approximately 100 times more potent then either drug. At 10(-5)M concentration of propranolol, lipolysis was virtually abolished whilst at the same molar concentration, acebutolol and practolol halved the response. 3 Six healthy volunteers received three successive 15 min intravenous isoprenaline challenges (0.03 mug kg-1 min-1) per individual experiment. The first acted as a control whilst the following two were given either after single oral doses of placebo, acebutolol or practolol. The mean (+/- s.e. mean) basal FFA level was 0.77 +/- 0.06 mE1/1 and subsequent resting values after the administration of placebo or beta-adrenoceptor blocker were not significantly different. 4 Acebutolol inhibited the respective mean rises in FFA, produced by both post-control isoprenaline challenges, by (mean +/- s.e. mean) 70 +/- 4% and 84% +/- 5%. The comparable figures for practolol were 33 +/- 15% and 24 +/- 20%. The higher serum concentration of acebutolol produced greater inhibition but correlation of log serum concentration of the drug with percentage inhibition of FFA rise did not achieve significance. 5 Administration of isoprenaline, acebutolol or practolol did not significantly alter serum glucose, triglyceride or cholesterol levels. 6 Acebutolol and practolol effectively blocked the isoprenaline-induced tachycardia. The degree of blockade produced by practolol was greater than its inhibitory effect on FFA release. The diatolic fall in blood pressure in response to isoprenaline was abolished by acebutolol suggesting that its beta-adrenoceptor blocking action encompasses peripheral vascular sites. The comparable effect with practolol was a partial inhibition of the diastolic fall.

Acebutolol↗
PubMed1975

Effects of intravenous and oral propantheline and metoclopramide on ethanol absorption.

The separate effects of propantheline, atropine, and metoclopramide on ethanol absorption have been studied in man. Intravenous propantheline lowered blood ethanol levels after ingestion of a standard ethanol load. Oral propantheline, at dose levels currently recommended for therapeutic use, was without significant effect on ethanol tolerance, whereas the tolerance was reduced by oral atropine. Propantheline bromide tablets have been shown to undergo significant hydrolysis at alkaline pH in vitro. Metoclopramide, given intravenously and orally, significant elevated blood ethanol levels soon after ingestion of a standard ethanol load. It is suggested that when propantheline is selected as an anticholinergic for clinical use, there is need for greater awareness of the marked reduction in bioavailablity that results when the drug is administered at conventional therapeutic dosage by the oral as opposed to the intravenous route.

Administration, Oral↗