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Biomedical subjects

J R Lawrence

Publications and source records attributed to J R Lawrence.

At least 55 records · Page 3Linked to original sources
PubMed1990

Metolazone in treatment of severe refractory congestive cardiac failure.

17 patients with New York Heart Association (NYHA) class IV congestive cardiac failure, refractory to conventional treatment, were additionally treated with oral metolazone (1.25-10 mg daily). 12 improved sufficiently to be discharged from hospital (NYHA class II or III, mean weight loss 8.3 kg), 1 of whom died at home 4 weeks later. The other 5 patients were treated with intravenous dobutamine for 72 h; 2 responded (average weight loss 4.4 kg), and 2 responded to subsequent reintroduction of metolazone. 4 of these 5 patients died, 2 in hospital of acute myocardial infarction. Overall, 15 patients with very severe refractory cardiac failure improved sufficiently to be discharged from hospital. Treatment was associated with mild transient hypokalaemia in 7 patients, and hyponatraemia and renal impairment in 1, for whom metolazone dosage had to be reduced. Failure to respond to the introduction of metolazone may indicate an especially poor prognosis.

Aged↗
PubMed1989

Micropuncture comparison of nephron function during acute and chronic ADH excess in the rat.

1. The aim of this study was to compare the effect of acute versus chronic ADH administration on the handling of sodium, potassium and water by the nephron. Simultaneous clearance and free-flow micropuncture experiments were performed on rats, infused with hypotonic Ringer solution, following either 1-3 h ('acute') or 10-12 days ('chronic') of continuous treatment with arginine vasopressin, 50 mU/h. A third group of animals receiving no exogenous ADH acted as controls. 2. Chronic ADH treatment led to more profound concentration of the urine and antidiuresis than acute treatment, due to enhanced extraction of water in the renal medulla. 3. Fractional sodium excretion during this protocol was increased after 'acute' but not 'chronic' ADH treatment. The acute natriuretic response was brought about principally along the length of the proximal tubule, probably due to volume expansion and increased arterial blood pressure. 4. Fractional excretion of potassium was also increased by 'acute' ADH, but this response was due to stimulation of potassium secretion in the late distal tubule. 5. It is concluded that acute and chronic exposure to ADH have different effects on nephron function, as a result of both direct and indirect actions.

Animals↗
PubMed1988

Anorexia tardive: a diagnosis of exclusion?

An elderly female patient is described in whom rapid severe weight loss appeared initially to be of psychogenic origin and self-induced. A diagnosis of late-onset anorexia nervosa or anorexia tardive was made when early investigations revealed no abnormality apart from changes that were consistent with malnutrition, and when typical behavioural and psychological factors together with putative psychodynamic issues were revealed. At first, nasogastric feeding was beneficial, but a stormy hospital course ensued. Further investigations revealed the presence of neoplastic disease which at post-mortem examination proved to be small-cell carcinoma of the lung.

Aged↗
PubMed1988

Iatrogenic Buschke's disease (Michelin man syndrome)

Scleredema [corrected] adultorum as originally described by Buschke in 1900, is cutaneous thickening of unknown aetiology. Since then several cases have been reported which have illustrated different aspects of the disease but the exact aetiology, pathogenesis and prognosis remain uncertain. Disease of possible iatrogenic origin appears not to have been described previously.

Blood Protein Electrophoresis↗
PubMed1987

Comparison of performance of final-year students from three Australian medical schools.

Between 1984 and 1986, 888 final-year medical students from The Universities of Sydney, Western Australia and Newcastle took part in trial examinations that comprised multiple-choice questions, modified essay questions and a patient management problem. Differences in student performance among the schools were small. In 1984 and 1985, Newcastle students performed less well than did Sydney students on multiple-choice questions that were prepared by The University of Sydney, but there was no difference between the schools in 1986. Sydney students performed better than did Newcastle students on the multiple-choice question paper that was prepared by The University of New South Wales in 1984, but in the last two years no differences have been detected between the schools in performance on this paper. The performance on modified essay questions in 1984 suggested that Newcastle students were stronger in behavioural sciences and weaker in pathological sciences than were Sydney students. Sydney students performed less well than did Newcastle students in the patient management problem in 1985, particularly in the area of the use of clinical investigations. On the one occasion of testing that involved students from The University of Western Australia (in 1985), these students performed best of the three schools in the patient management problem, and roughly equally with students from Sydney and Newcastle in the multiple-choice question papers. Differences among the schools usually amounted to less than 10% and might have been accounted for by differences in familiarity with test instruments. We conclude that medical students are likely to graduate from The University of Sydney, Western Australia and Newcastle with similar levels of knowledge of internal medicine. Possible differences in problem-solving ability require further study, particularly in the clinical setting.

Australia↗
PubMed1985

Correlation of the clinical pharmacodynamics of loprazolam with serum concentration.

Six healthy fasted volunteers each received oral doses of a placebo, 1 mg and 2 mg loprazolam with one week between treatments using a double-blind balanced crossover design. Serum samples were obtained at selected times after dosing for measurement of loprazolam using a combined high-performance liquid and gas chromatographic assay. Drug effect was also measured at the corresponding times using self-assessment scales and psychomotor tests. The serum levels of loprazolam followed a somewhat irregular shape with secondary and tertiary peaks possibly associated with food intake. The maximum serum levels of loprazolam following 1 mg and 2 mg doses of the drug (6.0 +/- 2.6 and 11.3 +/- 2.9 ng/ml, respectively) occurred at approximately one hour after dosing. Both the maximum serum levels and the area under the curve of loprazolam measured to six hours increased in direct proportion to dose. Statistically significant drug effects were seen after 2 mg loprazolam, although the subjects also appeared sedated after 1 mg doses. There appeared to be a good correlation between the logarithm of the serum concentration of loprazolam and effect which suggested that the hypnotic activity of the drug was not mediated via a long-lived metabolite. A threshold serum concentration associated with evident sedation was observed at approximately 3 ng/ml.

Adult↗
PubMed1982

The in vivo distribution of methotrexate between plasma and erythrocytes.

1. The concentration of methotrexate in whole blood, plasma and erythrocytes was measured in three patients receiving 250 mg methotrexate by continuous intravenous infusion over 12 h for different malignant diseases. 2. Methotrexate was measured using a double-antibody radioimmunoassay which facilitated drug monitoring for 1--2 weeks. 3. The concentration of methotrexate in plasma was much higher than that in whole blood and erythrocytes during the period of infusion, but this profile was reversed during the elimination phase. 4. The concentration in erythrocytes fell rapidly immediately after the infusion ended, but thereafter, in contrast to plasma levels, methotrexate concentrations in erythrocytes did not appear to decay during the elimination phase. In one patient the concentration/time profiles differed between treatment days. On the first occasion, at the initiation of chemotherapy, erythrocytes progressively accumulated methotrexate in the elimination phase against an apparent concentration gradient. On the second occasion this progressive increase was not observed, but as in the other two patients, methotrexate levels in red cells remained many times higher than drug levels in plasma throughout the period of observation. 5. Folinic acid administration did not appear to influence the distribution of methotrexate between red cells and plasma. 6. It was concluded that while the distribution between plasma and erythrocytes was probably mediated by complex mechanisms, the results were consistent with the erythrocyte mass behaving as a slowly exchanging kinetic compartment. Accumulation and persistence of a drug such as methotrexate in red cells might be expected to promote resistance and perhaps influence the expression of toxicity.

Erythrocytes↗
PubMed1982

The influence of protein binding on disopyramide clearance.

Individual disopyramide clearance is not constant and previous studies have suggested that this may be time and/or concentration dependent. Steady state disopyramide concentrations were achieved in six volunteer subjects at each of three infusion rates. Drug analysis was by HPLC and protein binding was determined by ultrafiltration. The disopyramide free fraction was concentration dependent and marked interindividual variability was observed. Disopyramide clearance was independent of time but dependent on total plasma concentration. This can be completely explained by non-linear protein binding since free disopyramide clearance was observed to be independent of free concentration.

Adult↗