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Biomedical subjects

G D Murray

Publications and source records attributed to G D Murray.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

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

Comparison of two methods for predicting difficult intubation.

Two methods of predicting difficult laryngoscopy were compared prospectively. Mallampati class and Wilson risk-sum were determined before operation and laryngeal view graded in 675 patients. Both tests identified five of 12 difficult laryngoscopies; twice as many patients were predicted to be difficult by Mallampati classification than by Wilson risk-sum. Inter-observer variation was minimal using Wilson risk-sum, but considerable for Mallampati classification. We prefer the Wilson risk-sum for assessment of the airway, while noting that both tests have poor sensitivities.

Adolescent

Evaluation of potential pharmacodynamic and pharmacokinetic interactions between verapamil and propranolol in normal subjects.

1. Potential pharmacodynamic and pharmacokinetic interactions between verapamil and propranolol were evaluated in two double-blind, randomised, balanced, crossover studies employing the same six healthy males. 2. The first study examined the effect of repeated propranolol administration on the pharmacodynamics and pharmacokinetics of verapamil after single oral and intravenous doses. The second explored the pharmacodynamics and pharmacokinetics of verapamil and propranolol alone and in combination after single and repeated oral doses. 3. The magnitude of the prolongation of PR interval induced by oral and intravenous verapamil was not affected by pre-treatment with propranolol. When verapamil and propranolol were co-administered as single doses, effects on PR interval were additive but, following repeated doses, a trend towards greater than additive prolongation was seen. The arithmetic sum of the effects of the two drugs was 23% (95% C.I. 8-38%) but the measured increase after the combination was 40% (95% C.I. 26-54%). 4. The extent of reduction in heart rate and blood pressure at rest and after exercise following repeated doses of propranolol was not influenced by single oral or intravenous doses of verapamil. The heart rate and blood pressure responses to single and repeated oral doses of verapamil and propranolol in combination were significantly greater than those after either drug alone and approximated to the arithmetic sum of the individual responses. 5. Although repeated administration of propranolol reduced hepatic blood flow as assessed by indocyanine green clearance, there was no evidence of an interaction between the drugs at this level. 6. The pharmacokinetics of verapamil and norverapamil were not significantly affected by prior propranolol. After single doses of verapamil and propranolol in combination, the maximum plasma concentration of propranolol was increased and the oral clearance of verapamil reduced. No pharmacokinetic interaction was observed after repeated doses. 7. These findings provide little evidence of a pharmacodynamic or pharmacokinetic interaction between verapamil and propranolol in normal subjects. Most of the haemodynamic responses to these drugs in combination can be explained by additive drug effects but an interaction affecting AV conduction after repeated doses cannot be excluded. The minor pharmacokinetic interaction between the drugs is unlikely to be relevant to the pharmacodynamic changes.

Adult

Cross-sectional assessment of caries and periodontitis risk within the same subject.

Dental caries and chronic periodontitis may be synergistically associated, negatively associated, or completely independent. The present report examines this relationship by comparing the susceptibility to chronic periodontitis and caries within the same individual. From an 800-patient sample, a periodontitis risk score was derived by radiographic assessment of bone loss in quarters of optimum bone height and obtaining for each subject a mean score based on all measurable surfaces. Similarly the caries risk was determined radiographically from the total decayed and filled teeth (DFT), as a percentage of the total teeth measured. The Mantel-Haenszel technique was used for analysis of the relationship between periodontitis and caries and data was stratified on four categories of age, sex, and numbers of teeth present. This analysis revealed no systematic patterns, indicating that the risks of caries and periodontal diseases are unrelated (chi 2 = 0.00; 1 df; P greater than 0.50). In addition, a regression analysis, which was controlled for sex and age, indicated a marked lack of association between caries and periodontitis (P = 0.94). Thus, although these common diseases share putative etiologic factors such as oral hygiene practices and dental attendance pattern, the major risk factors are probably quite different.

Adolescent

Hemodynamic effects of a single moderate dose of alcohol in elderly subjects.

The effects of 0.5 g ethanol/kg body weight and of an iso-volumic control drink were compared in eight normotensive subjects aged 70-96 years. Blood alcohol concentration reached a mean (+/- SEM) maximum of 44.4 +/- 5.0 mg/dl at 50 minutes after the start of drinking. Compared to control, alcohol increased mean sitting and standing heart rates by 3.4 +/- 1.3 (p = .08) and 5.4 +/- 1.9 (p less than .05) beats/minute, respectively; mean venous haematocrit rose by 3.9 +/- 1.3% (p less than .05). There were no significant changes in sitting or standing systolic or diastolic blood pressures after alcohol compared to the control drink. A single moderate dose of alcohol has only minor haemodynamic effects in normotensive elderly subjects. The rise in heart rate after alcohol may be a reflex response that helps to maintain blood pressure in the face of reduced circulating plasma volume due to alcohol-induced diuresis.

Aged

The Acute Infarction Ramipril Efficacy (AIRE) Study: rationale, design, organization, and outcome definitions.

The rationale, design, organization, and outcome definitions of the Acute Infarction Ramipril Efficacy (AIRE) Study are described prospectively. A total of 2,000 patients (1,000 per treatment group) will be recruited to this multicenter, multinational, double-blind, randomized, placebo-controlled study investigating the effect of oral treatment with ramipril (2.5 or 5 mg twice daily) on the total mortality of survivors of an acute myocardial infarction (AMI) with early clinical evidence of heart failure. Secondary outcomes of the study include progression to severe/resistant heart failure (at which time the patient will be withdrawn from the study treatment), reinfarction, and stroke. Treatment will be initiated in hospital between day 3 and day 10 following AMI, and follow-up continued for an average of 15 months and a minimum of 6 months. The study data will be analyzed on an intention-to-treat basis: a single formal interim analysis will be conducted after 175 deaths. An Independent Adjudicating Panel will act as the overall ethical supervisory body for the study and will retain the randomization code. An International Steering Committee will be responsible for the clinical definitions of the secondary study outcomes, and will regularly review progress of the study. We believe that early treatment with ramipril may reduce the total mortality of patients surviving an AMI with clinical evidence of heart failure.

Acute Disease

Meta-analysis.

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Humans

Statistical comparison of two methods of clinical measurement.

The comparison of two measurement techniques, neither of which can be regarded as being a 'gold standard', is fundamental to much basic research. This apparently simple problem raises many statistical difficulties, which are reviewed in this paper in the context of anorectal manometry. It is concluded that a recently developed approach focusing on the agreement between the two techniques is far superior to the more conventional approach based on correlation. However, until the benefits of the new analysis are more widely recognized (and it is hoped that this paper is a step towards that goal), it is argued that it is useful to present both analyses in such comparisons of measurement techniques.

Air

How we should approach the future.

There is little doubt that there are still major problems with the statistical aspects of published medical research. This paper argues that it is not sufficient to teach statistics to medical undergraduates, when the bulk of their courses are being taught by the very same individuals who continue to undertake and publish substandard research. Instead, any undergraduate teaching needs to advance in parallel with courses given to the clinical staff within medical schools.

Computer-Assisted Instruction