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Biomedical subjects

G D Murray

Publications and source records attributed to G D Murray.

At least 91 records · Page 5Linked to original sources
PubMed1994

Presentation, acute illness, and learning difficulties in salt wasting 21-hydroxylase deficiency.

The presentation, pattern of acute illness, and incidence of learning difficulties are described in 63 (33 boys, 30 girls) children with salt wasting 21-hydroxylase deficiency, drawn from a cohort study of congenital adrenal hyperplasia in the South West Region of England between 1968 and 1988. Thirty boys presented with a salt losing crisis from birth whereas the other three boys presented between 2 and 14 months of age with failure to thrive and hyponatraemia. Diagnostic uncertainty led to 13 (43%) of 30 girls developing a salt losing crisis. Five girls were misassigned as boys at birth. There were four deaths in the group, two due to salt losing crisis, one to complications of prematurity possibly compounded by 21-hydroxylase deficiency, and one from heart failure probably related to an excess of steroids. Acute admissions were common, especially during the first year of life, with convulsions in 7% of admissions. The 9% incidence of hypoglycaemia was considered to be an underestimate as blood glucose was measured in only 56 (22%) of 254 admissions. No convulsions occurred in the 38 (15%) admissions where the parents had given intramuscular hydrocortisone before bringing the child to hospital. A high incidence of learning difficulties was found among the 59 surviving children (9/30 (30%) boys and 6/29 (21%) girls), and in only two children could any factor other than 21-hydroxylase deficiency be invoked. Analysis of the subgroup with learning difficulties indicated that they were more ill at presentation with a significantly higher incidence of hypoglycaemia, and that growth in the first year was significantly worse. It is concluded that congenital adrenal hyperplasia remains a formidable disorder with an appreciable mortality and morbidity. The high incidence of learning difficulties seen in salt wasting 21-hydroxylase deficiency needs further attention. A prospective study is indicated to examine the effect of neonatal screening on morbidity from congenital adrenal hyperplasia, particularly the intellectual impairment seen in this study.

Acute Disease↗
PubMed1993

Does prediction of outcome alter patient management?

A patient's prognosis is a key factor for the clinicians involved in management. We set out to determine if provision of computer-based predictions of outcome after severe head injury resulted in measurable changes in patient management. In particular, we wondered whether introduction of the predictive system would alter the relation between severity of injury and "intensity" of management. 1025 patients admitted to four British neurosurgical units between 1986 and 1989 following a severe head injury, and who were either in coma for 6 h or had an operation for acute intracranial haematoma, were studied. Specified aspects of intensive management were recorded and all patients were followed up after six months. The study had three phases: a baseline period of at least one year before the introduction of computer-based outcome prediction, one year when predictions were provided at specified times, and a final six months when prediction was withdrawn. While predictions were being provided, there was an increase in the use of specified aspects of intensive care in patients predicted to have a good outcome, but a 39% reduction in the use of these same aspects of intensive care in patients predicted to have the worst outcome. There was no evidence that the provision of predictions affected overall outcome, length of stay, or the recording of explicit decisions to limit treatment. We have demonstrated that the introduction of a routine prediction service can alter patient management.

Adult↗
PubMed1993

Association of fibrinolytic tests with outcome of acute upper-gastrointestinal-tract bleeding.

Endogenous fibrinolysis may play a part in acute upper-gastrointestinal-tract bleeding by causing digestion of haemostatic plugs. We assessed the predictive value of fibrinolytic tests for hospital outcome in a prospective study of 122 patients with acute upper-gastrointestinal-tract bleeding who underwent endoscopy. Serum fibrin degradation products (FDP) were above the normal range in 32% (95% CI 21-44%) of patients who survived and did not require transfusion or surgery, in 53% (37-69%) of patients who survived without surgery but required transfusion, and in 100% (82-100%) of patients who required surgery or died. Multivariate analysis showed that after adjustment for the effects of established risk factors (age, pulse rate, blood pressure, haemoglobin, site of bleeding, and stigmata of active bleeding at endoscopy), serum FDP was a powerful independent predictor of outcome (p = 0.003). Doubling of serum FDP was associated with a 59% increase in the risk of a poor outcome (95% CI 14-120%). These findings are consistent with roles for endogenous fibrinolysis in gastrointestinal-tract bleeding, for fibrinolytic tests in prediction of adverse outcome, and for fibrinolytic inhibitors in treatment.

Acute Disease↗
PubMed1993

Expression of the pro-opiomelanocortin gene in lung neuroendocrine tumours: in situ hybridization and immunohistochemical studies.

Neuroendocrine tumours of the lung may be associated with the ectopic adrenocorticotrophin (ACTH) syndrome and may synthesize and secrete ACTH-related peptides in the absence of the syndrome. However, immunocytochemical analysis may not confirm these biochemical findings, particularly in small cell carcinoma, which is poorly granulated. To investigate further the morphological evidence for expression of the pro-opiomelanocortin (POMC) gene in neuroendocrine lung tumours, we have examined a series of 46 small cell carcinomas and 13 carcinoid tumours of the lung by in situ hybridization for POMC mRNA using a digoxigenin-labelled oligoprobe. We have compared the findings with the immunocytochemical detection of ACTH and beta-endorphin. In situ hybridization was positive in 15 of 46 small cell carcinomas (33 per cent) and in 8 of 13 carcinoid tumours (62 per cent). Immunocytochemical staining was positive in only one carcinoid tumour. These in situ hybridization studies have corroborated biochemical data indicating POMC gene expression in a high proportion of lung neuroendocrine tumours. This suggests that the low levels of expression detected by immunocytochemistry may be due to low levels of hormone storage. Multivariate analysis showed a weak negative association between POMC expression and survival in small cell carcinomas, although this did not reach statistical significance.

Adrenocorticotropic Hormone↗
PubMed1993

Dental disease, fibrinogen and white cell count; links with myocardial infarction?

Plasma fibrinogen and white blood cell count were compared in fifty patients aged 25-50 years with periodontal disease and in fifty age-matched controls with relatively healthy periodontal tissues. Patients had significantly higher levels of fibrinogen and white cell count, and dental indices correlated significantly with these two cardiovascular risk factors on multivariate analyses. We suggest that inflammatory dental disease may be a determinant of fibrinogen level and white cell count in the general population, and that fibrinogen and white cell count may be two mediators of the link between dental disease and myocardial infarction.

Adult↗
PubMed1993

Comparison of captopril, hydralazine and nifedipine as third drug in hypertensive patients.

The antihypertensive, biochemical and adverse effects of captopril, hydralazine, nifedipine and placebo were compared in 160 patients with BP inadequately controlled by atenolol 100 mg daily plus bendrofluazide 5 mg daily. Treatments were given for up to 12 weeks. Beta-blocker and thiazide were continued unchanged. All three active drugs reduced supine BP relative to placebo; mean BP changes attributable to active treatment (95% confidence intervals): captopril 13.4/10.3 mmHg (0.6/4.0 to 26.2/16.6), hydralazine 15.0/10.0 mmHg (1.7/3.4 to 28.3/16.6), nifedipine 16.8/8.1 mmHg (4.0/1.8 to 29.6/14.4). There were no significant differences between the agents. Results for erect BP were similar. Target BP (< 140/95 mmHg) was achieved more frequently on captopril (33%), hydralazine (29%) and nifedipine (17%) than on placebo (10%). Compared with the other treatments captopril increased serum potassium concentration (P = 0.01), and hydralazine reduced serum cholesterol concentration (median changes: captopril -0.2 mmol/l, hydralazine -0.8 mmol/l, nifedipine -0.2 mmol/l, and placebo +0.2 mmol/l, P < 0.001). Overall, side-effects did not differ significantly between the groups; withdrawals resulting from adverse reactions: captopril 15%, hydralazine 24%, nifedipine 22%, and placebo 3% (chi 2 = 8.2, P = 0.04). Captopril, hydralazine and nifedipine did not differ significantly in efficacy and tolerability when added to atenolol and bendrofluazide. However, there were trends in favour of captopril, on which drug the highest proportion of patients had their BP controlled and the lowest proportion were withdrawn because of side-effects. Thus, of the drugs tested, captopril appears to be the best option as third drug in hypertension.

Adrenergic beta-Antagonists↗
PubMed1993

Effects of atenolol withdrawal in patients on triple antihypertensive therapy.

The objective of this study was to examine the contribution of beta-blockade to antihypertensive treatment regimens including an angiotensin converting enzyme inhibitor or a calcium antagonist. The effects on BP control, adverse events, and plasma active renin concentration of removing atenolol from standard triple therapy (bendrofluazide and atenolol together with captopril or nifedipine) were assessed in a double-blind, randomised, parallel-group study, of eight weeks' duration in 46 patients from the Glasgow Blood Pressure Clinic. Blood pressures rose in patients randomised to placebo-atenolol compared with those who continued active-atenolol although the difference did not achieve statistical significance. However, the proportion of patients with controlled blood pressure (supine systolic BP < 140 mmHg plus supine diastolic BP < 95 mmHg) fell from 31% to 0% over the study period in patients given placebo-atenolol. There was a trend for BP control to deteriorate most when atenolol was withdrawn from nifedipine treated patients, but the 95% confidence intervals for the difference from captopril-treated patients were wide. Few side-effects were seen and these did not differ quantitatively between the study groups. Plasma active renin concentration was initially higher in captopril-treated patients, and increased on withdrawal of atenolol in both groups. Our findings suggest that beta-blockers make a clinically relevant contribution to treatment regimens including angiotensin converting enzyme inhibitors or calcium antagonists when given as part of standard triple antihypertensive therapy.

Adult↗
PubMed1992

Long-term prognostic significance of thymidine labelling index in primary breast cancer.

Tumour growth rates, as measured by incorporation of tritiated thymidine, have been reported as being of prognostic importance in breast cancer. We have measured the thymidine labelling index (TLI) of 185 early breast cancers, followed-up for a minimum of 8 years. Above median TLI was associated with higher tumour grade, but not with other prognostic factors. TLI was not predictive of survival in either univariate or multivariate analysis. The inter- and intra-observer reproducibilities of TLI measurements were poor, which may be a factor limiting its usefulness as a prognostic indicator in breast cancer.

Breast Neoplasms↗
PubMed1992

Lack of prognostic significance of DNA ploidy and S phase fraction in breast cancer.

DNA Ploidy and S phase fraction (SPF) were measured in Stage I and II breast cancers from patients with at least 8 years of follow-up, to assess the prognostic significance of these data. Disaggregated sections of formalin-fixed, paraffin-embedded tumour were analysed by flow cytometry. SPF was calculated using a rectangular model of S phase, after subtraction of background debris using an exponential model. 64% of tumours were DNA aneuploid. The median SPF was 4.5% for DNA diploid, and 10.9% for DNA aneuploid tumours. There were small reductions in survival at 10 years for DNA aneuploid tumours, and for tumours with above median SPF, but these were not statistically significant. The relative hazard for DNA aneuploid tumours was 1.20 (95% CI 0.81-1.76), and for high SPF was 1.31 (95% CI 0.87-1.98). Neither factor was statistically correlated with survival in multivariate analysis. Technical and theoretical factors limit the accuracy and reproducibility of flow cytometric data, and may explain the lack of prognostic information given.

Breast Neoplasms↗
PubMed1992

Timing of peak pressor response following endotracheal intubation.

The study was designed to measure the timing of the peak cardiovascular response following laryngoscopy and endotracheal intubation. Thirty patients ASA 1 or 2 were studied, with arterial pressure being continuously monitored using the Ohmeda 2300 Finapres. Patients were randomised to receive either propofol 2.5 mg.kg-1 (Group A) or thiopentone 4.5 mg.kg-1 (Group B). The mean time to complete laryngoscopy and intubation was 26 s in Group A and 20 s in Group B. The peak response occurred on average 31 s after the start of the stimulus in Group A and after 32 s in Group B. In 8 out of the 30 cases the peak response occurred during the period of stimulation. Systolic pressure fell on average by 2.6 kPa (20 mmHg) (range 0 to 5.9 (45 mmHg)) from its peak value to the value measured at the 1-min time mark in the propofol group, and by 2.3 kPa (17 mmHg) (range 0.4 (3 mmHg) to 3.8 (29 mmHg)) in the thiopentone group. We conclude that the use of slow arm-cuff-based arterial pressure measurement techniques may miss important hypertensive episodes during laryngoscopy and endotracheal intubation. The effectiveness of agents in obtunding the pressor response may thus be misinterpreted.

Adolescent↗
PubMed1992

Twenty-four-hour blood pressure in junior medical staff.

Circadian variations in blood pressure in junior medical staff were compared during routine working days and days receiving medical emergencies. The overnight work commitment of junior medical staff when receiving medical emergencies causes a loss in the normal circadian blood pressure rhythm, with overnight blood pressure falling 10/11 mmHg less than on routine working days. This supports the hypothesis that circadian blood-pressure changes are activity related rather than dependent upon hormonal variation. Long-term health effects of abolishing such normal circadian rhythms are not known.

Adult↗
PubMed1992

Psychological morbidity in the first year after breast surgery.

In this prospective study, the psychological morbidity associated with the treatment of breast cancer was assessed. The study population comprised all patients referred to one centre with a recently diagnosed breast lump, who were to undergo surgery. Psychological morbidity was assessed preoperatively and at 6 and 12 months postoperatively by modified Rotterdam Symptom Checklist. Three hundred and twenty patients completed all three questionnaires: 93 women undergoing mastectomy, 73 women having conservation therapy for breast cancer and 156 women having biopsy for benign breast disease. Patients with a breast malignancy smaller than 4 cm in diameter were treated by lumpectomy and radiotherapy, anti-oestrogen therapy or chemotherapy alone or in combination. Psychological morbidity among patients with malignant disease was significantly greater than that seen in the group with benign disease. Among cancer patients, a significant decrease in anxiety and depression occurred during the year following surgery. The study failed to demonstrate any psychological advantage associated with breast conservation.

Adaptation, Psychological↗
PubMed1991

Statistical aspects of research methodology.

Many reports in the medical literature are flawed through poor presentation of numerical results, or, more seriously, by the use of inadequate or inappropriate statistical methodology. This article expands on the more complex methodological issues. The main emphasis is on discussing key aspects of experimental design, and the idea of reporting results in terms of confidence intervals rather than P values.

Confidence Intervals↗
PubMed1991

Statistical guidelines for The British Journal of Surgery.

A set of statistical guidelines is presented which should be followed by authors preparing manuscripts for submission to The British Journal of Surgery. Simple points relating to presentation are explained in full, and more complex issues are highlighted and discussed in an accompanying review article.

Periodicals as Topic↗
PubMed1991

Anastomotic leaks in colorectal cancer surgery: a risk factor for recurrence?

This study examines anastomotic leaks as a potential influence on the long term outcome of patients with colorectal cancer. 167 patients were studied who had clinical and radiological assessment of anastomotic integrity in the post-operative period, following potentially curative resections for left-sided colonic or rectal cancer. There was no evidence of a leak in 135 of these patients, while the remaining 32 developed a clinical and/or a radiological leak. At the end of a mean follow-up of 25 months, 15 patients with leaks (46.9%) developed tumour recurrence, compared with 25 of those without any leak (18.5%; p less than 0.001). Cancer specific mortality at 24 months was also significantly higher for patients with leaks (36.9% +/- 9.7% versus 12.6% +/- 3.3%; p less than 0.001). The influence of anastomotic leaks on the outcome was independent of tumour stage. These results suggest that in patients undergoing surgery for colorectal cancer development of an anastomotic leak is significantly associated with a poorer long-term outcome.

Aged↗
PubMed1991

The fate of the claudicant--a prospective study of 1969 claudicants.

A prospective study of 1969 patients with intermittent claudication receiving placebo medication for a minimum of 1 year is reported. Patients were carefully monitored and only four patients were lost to follow-up. Annual mortality was 4.3%. Thirty-six patients developed a definite myocardial infarction, 27 a major stroke, 32 required a major amputation and 111 required surgical or radiological intervention for deteriorating ischaemia of the leg. The entry characteristics of the patients were analysed as a predictor of serious cardiovascular events. The most sensitive predictors of total mortality were age, history of coronary heart disease and an ankle/arm pressure ratio below 0.5. Of the laboratory measurements performed only the initial white cell count was a significant predictor of myocardial infarction, stroke and vascular deaths.

Amputation, Surgical↗
PubMed1991

The long term prognostic significance of c-erbB-2 in primary breast cancer.

The expression of the c-erbB-2 oncogene has been evaluated using an immunohistochemical technique with the 21N polyclonal antibody in paraffin embedded tissue from 465 patients treated between the years 1975-1981 for Stage I and II breast cancer. One hundred and four (22%) patients exhibited positive staining. This was not associated with any other variables. Expression of the oncogene was associated with significantly poorer survival which was independent of other tumour variables.

Breast Neoplasms↗