Showing papers in "BMJ in 1983"

Thrombosis, abortion, cerebral disease, and the lupus anticoagulant.

Abstract: employment the occupational medical officer should also be notified. Few diabetics register on the Disabled Persons Register, but those with disabling complications may find it advantageous to do so and to seek the advice of their local disablement resettlement officer. The present positive attitude towards the management of diabetes has ensured that most diabetics can be usefully and suitably employed, but the satisfactory care of the diabetic employee does require efficient medical support with good cooperation between the diabetic clinic, the family physician, and the occupational health service. JOHN LISTER Consultant Physician, East Berkshire Health District, Windsor SL4 3HH

Statistical guidelines for contributors to medical journals.

Abstract: Most papers published in medical journals contain analyses that have been carried out without any help from a statistician. Although nearly all medical researchers have some acquaintance with basic statistics, there is no easy way for them to acquire insight into important statistical concepts and principles. There is also little help available about how to design, analyse, and write up a whole project. Partly for these reasons much that is published in medical journals is statistically poor or even wrong.1 A high level of statistical errors has been noted in several reviews of journal articles and has caused much concern. Few journals offer even rudimentary statistical advice to contributors. It has been suggested1 2 that comprehensive statistical guidelines could help by making medical researchers more aware of important statistical principles, and by indicating what information ought to be supplied in a paper. We present below an attempt to do this. Deciding what to include in the guidelines, how much detail to give, and how to deal with topics where there is no consensus has been problematic. These guidelines should thus be seen as one view of what is important, rather than as a definitive docu? ment. We have not set out to provide a set of rules but rather to give general information and advice about important aspects of statistical design, analysis, and presentation. Those specific recommendations that we have made are mostly strong advice against certain practices. Some familiarity with statistical methods and ideas is assumed, since some knowledge of statistics is necessary before carrying out statistical analyses. For those with only a limited acquaintance with statistics, the guidelines should show that the subject is very much wider than mere significance testing and illustrate how important correct interpretation is. The lack of precise recommendations indicates that good statistical analysis re? quires common sense and judgment, as well as a repertoire of formal techniques, so that there is an art in statistics as well as in medicine. We hope that the guidelines present an uncontro versial view of the most frequently used and accepted statistical procedures. We have deliberately limited the scope of the guidelines to cover the more common statistical procedures. Readers may find that a relevant section presents information or advice that is unfamiliar or is not understood. In such circumstances, although almost all of the topics covered may be found in the more comprehensive medical statistics text? books,3 4 we strongly recommend that they should seek the advice of a statistician. The absence from the guidelines of specific references is intentional : it is better to get expert personal advice if further insight is needed. Moreover, because mistakes in design cannot later be rectified, professional advice should first be obtained when planning a research project rather than when analysing the data.

Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall study.

Abstract: In the Whitehall study of 18 403 male civil servants aged 40-64 years the 10 year mortality rates from coronary heart disease and stroke showed a non-linear relation to two hour blood glucose values, with a significantly increased risk for glucose intolerant subjects with concentrations above the 95th centile point (5.4-11.0 mmol/l; 96-199 mg/100 ml) and for diabetics (blood glucose greater than or equal to 11.1 mmol/l; greater than or equal to 200 mg/100 ml). Multiple logistic analysis showed that between one half and three quarters of the relative risks for deaths from coronary heart disease and stroke were "unexplained" by between group differences in risk factors such as age, blood pressure, obesity, smoking, cholesterol concentration, and electrocardiographic abnormalities. Within the glucose intolerant and diabetic groups the risk factors most strongly related to subsequent death from coronary heart disease were age and blood pressure, with less consistent relations for smoking, cholesterol concentration, and obesity. This study confirms the importance of hypertension as a cardiovascular risk factor in groups with glucose intolerance and diabetes, and this may have important preventive implications.

Underdiagnosis and undertreatment of asthma in childhood.

Abstract: A total of 179 Tyneside children who had suffered at least one episode of wheeze since school entry were seen at the age of 7. All but 14 had visited a doctor for chest symptoms, but a diagnosis of asthma had been offered to the parents of only 21 children, including three of the 56 children experiencing four to 12 wheezy episodes a year and 11 of the 31 children experiencing more than 12 episodes a year. Bronchodilator treatment was rarely offered in the absence of such a diagnosis, and two thirds of the children had never received a bronchodilator. Of the children experiencing four or more episodes a year, only a third had received bronchodilator drugs regularly, though half had lost more than 50 days from school because of wheeze. School absenteeism fell 10-fold in the 31 children finally offered continuous prophylactic treatment. Although many doctors had feared that use of the word "asthma" would cause anxiety, parents were uniformly relieved when given an explanation of their child's recurrent wheeze. This study uncovered a disturbing amount of ill health in children that was easily rectified. Probably this same problem exists in other areas.

Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating lupus anticoagulant.

Abstract: The lupus anticoagulant was found in the plasma of 31 of 60 patients with systemic lupus erythematosus and other connective tissue disorders (mixed connective tissue disease, systemic vasculitis, polyarteritis nodosa, primary sicca syndrome, discoid lupus, Behcet's syndrome, and systemic sclerosis). Strong associations were found with biological false positive seroreaction for syphilis and thrombocytopenia. The most striking association, however, was with the high prevalence of thrombosis. This tendency to thrombosis was independent of disease activity of systemic lupus erythematosus. The lupus anticoagulant appears to be a useful marker for a subset of patients with systemic lupus erythematosus at risk for the development of thromboembolic complications.

Benefits of supplementary tube feeding after fractured neck of femur: a randomised controlled trial.

Abstract: A total of 744 elderly women with fractured neck of femur were classified into three groups according to anthropometric measurements on admission: group 1, well nourished; group 2, thin; group 3, very thin. Group 1 ate well and had a low mortality and a short rehabilitation time. The thinner the patients the lower their voluntary food intake, the higher their mortality and the longer their rehabilitation time. A series of 122 patients from groups 2 and 3 were entered postoperatively into a randomised controlled trial of overnight supplementary nasogastric tube feeding (4.2 MJ (1000 kcal), including 28 g protein) in addition to their normal ward diet. This treatment was associated with improvements not only in anthropometric and plasma protein measurements but also in clinical outcome, especially in the very thin group 3 patients. Rehabilitation time and hospital stay were shortened. Mortality in group 3 was less in the tube fed patients (8%) than in the controls (22%) but this difference did not reach statistical significance. One in five patients could not tolerate the nasogastric tube, but in the remainder the treatment caused no side effects and did not seriously diminish voluntary oral food intake by day.

Family study of the major histocompatibility complex in patients with systemic lupus erythematosus: importance of null alleles of C4A and C4B in determining disease susceptibility.

Abstract: The families of 29 patients with systemic lupus erythematosus and 42 normal subjects were studied to determine the inheritance of the HLA-A, B, C, and DR antigens and also the complement polymorphisms for C2, C4A, C4B, and Bf, which are encoded in the same region of the sixth chromosome. Null (silent) alleles for C4A, C4B, or C2 were found in 24 of the 29 (83%) patients compared with 18 of the 42 (43%) normal controls. HLA-DR3 was present in 20 (69%) of the patients and seven out of 39 (18%) of the normal controls. There was strong linkage disequilibrium between DR3 and the null alleles for C4A and C4B. The data did not permit the relative contributions of DR3 and null factors of C4A and C4B as genetic risk factors to be distinguished. The known association of systemic lupus erythematosus with uncommon inherited and acquired deficiencies of complement components suggests, however, that the presence of null alleles for C4A and C4B, as well as C2, found in most of the patients, is relevant to their genetic susceptibility to this disease.

Pregnancy established in an infertile patient after transfer of a donated embryo fertilised in vitro.

Abstract: In vitro fertilisation after stimulation of the ovulatory cycle has led to successful pregnancy. If more oocytes are recovered than are needed they may be left unfertilised, preserved, or donated to a recipient couple from whom oocytes cannot be obtained. A case of human pregnancy initiated by transfer of a donated embryo fertilised in vitro is reported. The donor was a 42 year old woman with primary infertility from whom six follicles were aspirated after stimulation of the ovulatory cycle. The recipient was a 38 year old infertile woman who had undergone several unsuccessful attempts for artificial insemination from a donor. Five oocytes were recovered from the donor9s six follicles, four of which were inseminated with spermatozoa of the donor9s husband and the fifth with a frozen sample of semen. Three of the four embryos fertilised by her husband were returned to the donor and the fifth was transferred to the recipient. No pregnancy was recorded in the donor, but pregnancy was confirmed in the recipient, though spontaneous abortion occurred after 10 weeks. This case will give useful information for further study of in vitro fertilisation, but also raises many ethical issues.

The rising tide

Abstract: Special psychiatric services for the elderly now exist, some very well developed, in about half of all health districts, and over one tenth of all consultants in general psychiatry specialise in work with the elderly.' This development has taken place largely over the past decade, reflecting both progress in psychiatry and growing concern about how to cope with The Rising Tide2 of mental disorder in old age. The tide threatens to overwhelm the health and social services (where it has not already done so). Awful buildings, prehistoric thinking, and a vague hope that it will all go away or be dealt with by someone else have still too often nourished complacency, punctured only occasionally by media worthy scandals when the greatest deficiencies in this non-strategy have broken surface. It is to the credit of the director of the Health Advisory Service that he has made psychogeriatric services the special interest of his organisation in recent years, culminating in the publication of a document which brings together good sense and hard won experience in establishing such services. The Rising Tide should help particularly in those districts where people have not been able or willing to plan an effective response. People may turn also to a new textbook3 which devotes two detailed chapters to psychogeriatric services, and these also provide references to the already large volume of published work. A recent excellent personal review of issues and achievements has come from the Centre for Policy on Aging, which has chosen to launch its new series of policy studies with Alison Norman's Mental Illness in Old Age.4 The growing spate of publications itself reflects the urgency of the matter. Coupled with the appearance of The Rising Tide has been an announcement by the Minister for Health that an extra £6 million is to be made available over three years-about £130 000 per region a year.5 Not that this is a lot of money in relation to the scale of mental disorders in old age-for between half a million and a million old people suffer from dementia and about twice as many again from other mental disorders-but it is helpful both practically and symbolically. Much more investment will be needed ifthere is everywhere to be a minimum standard of decent services, but even relatively little cash can catalyse action, enable people to try new things, or help established services to do even better or …

Effect of magnesium on blood pressure.

Abstract: Twenty patients receiving long term diuretic treatment for arterial hypertension (18 patients) or congestive heart failure (two patients) received magnesium supplementation as aspartate hydrochloride 15 mmol/day for six months Both systolic and diastolic pressures decreased significantly, by a mean of 12/8 mm Hg No significant changes were recorded in plasma or urinary electrolytes except for magnesium, 24 hour urinary volumes, or body weight after treatment The effect of magnesium on blood pressure may be direct or through influences on the internal balance of potassium, sodium, and calcium

Long term correction of hyperglycaemia and progression of renal failure in insulin dependent diabetes

Abstract: The effect of long term correction of hyperglycaemia on the rate of deterioration of renal function was studied in six insulin dependent diabetics with proteinuria due to diabetic nephropathy. After a planned run in observation period of 10 to 24 months patients entered a programme of continuous subcutaneous insulin infusion for up to 24 months. Glycaemic control was promptly and significantly improved and optimal glycaemic values sustained throughout the study. Blood pressure was maintained stable. A control group of six nephropathic diabetics was studied receiving conventional insulin injection treatment but also with blood pressure control over the same period. Despite greatly improved metabolic control in the infusion treated group no significant change in the rate of decline of glomerular filtration rate could be shown, the plasma creatinine concentrations continued to increase, and the fractional clearance of albumin and IgG rose progressively, indicating progression of glomerular damage. The conventionally treated control group behaved similarly. In a single patient receiving the continuous infusion the rate of decline of the glomerular filtration rate slowed considerably, suggesting that the response to strict diabetic control may differ in some patients. These findings suggest that by the time glomerular function has started to fail in diabetic nephropathy the process culminating in end stage renal failure has become self perpetuating and is little influenced by the degree of metabolic control. A new definition of potential clinical diabetic nephropathy is proposed that will permit identification of patients at risk and earlier intervention by glycaemic correction in an attempt to arrest diabetic renal disease.

Change in risk factors for coronary heart disease during 10 years of a community intervention programme (North Karelia project).

Abstract: A comprehensive community based programme to control cardiovascular diseases was started in North Karelia, Finland, in 1972. Reductions in smoking, serum cholesterol concentrations, and blood pressure were among the central intermediate objectives. The effect of the programme during the 10 year period 1972-82 was evaluated by examining independent random population samples at the outset (1972) and five (1977) and 10 (1982) years later both in the programme and in a matched reference area. Over 10 000 subjects were studied in 1972 and 1977 (participation rate about 90%) and roughly 8000 subjects in 1982 (participation rate about 80%). Analyses were conducted of the estimated effect of the programme on the risk factor population means by comparing the baseline and five year and 10 year follow up results in the age range 30-59 years. The effect of the programme (net reduction in North Karelia) at 10 years among the middle aged male population was estimated to be a 28% reduction in smoking (p less than 0.001), a 3% reduction in mean serum cholesterol concentration (p less than 0.001), a 3% fall in mean systolic blood pressure (p less than 0.001), and a 1% fall in mean diastolic blood pressure (p less than 0.05). Among the female population the reductions were respectively, 14% (NS), 1% (NS), 5% (p less than 0.001), and 2% (p less than 0.05). During the first five years of the project (1972-7) the programme effectively reduced the population mean values of the major coronary risk factors. At 10 years the effects had persisted for serum cholesterol concentrations and blood pressure and were increased for smoking.

Bulimia nervosa, binge eating, and psychogenic vomiting: a controlled treatment study and long term outcome.

Abstract: An "epidemic" prevalence of binge eating and vomiting (bulimia nervosa) has been reported, and treatment has been claimed to be difficult. This paper describes a short term outpatient treatment programme of eclectic orientation capable of being conducted by non-specialist staff, under medical supervision, in local centres. The treatment programme was evaluated in a controlled trial and in long term follow up. In 30 women with severe bulimia the treatment programme significantly reduced their incidence of dietary manipulation without producing weight gain, weight disorder, or neurotic illness. After treatment all the women had fewer symptoms; 24 stopped binge eating and vomiting at the end of treatment, and a further four stopped shortly afterwards. During formal follow up 20 showed no dietary abuse and a further eight reduced their attacks to an average of three episodes a year: all judged treatment to be a success. Pretreatment indicators of poorer prognosis include alcohol abuse and a history of anorexia nervosa. Married patients experienced marital difficulties or illness in the spouse.

Prevalence and spectrum of asthma in childhood.

Abstract: All the 7 year old schoolchildren in North Tyneside were screened for wheeze with a questionnaire followed by selective clinical assessment: 9.3% of the children had had episodic wheeze within the past year and all those followed up subsequently responded to one or more of the drugs used for asthma. A further 1.8% had had similar symptoms since starting school, though they had not wheezed in the past year. Frequently of symptoms in the 11% of children with features of asthma varied widely and correlated with bronchial reactivity on histamine challenge, but it was not possible to separate children with frequent wheeze from asymptomatic controls by their response to histamine. It was concluded that all these wheezy children had symptoms of a common basic disorder and that they should all be treated as asthmatic.

Release of oxytocin and prolactin in response to suckling.

Abstract: The oxytocin and prolactin responses to suckling were measured in 10 women in early (n = 5) and established lactation (n = 5). Oxytocin was released in a pulsatile manner during suckling in all women, but the response was not related to milk volume, prolactin response, or parity of the mother. In all 10 women plasma oxytocin concentrations increased three to 10 minutes before suckling began. In five women this occurred in response to the baby crying, in three it coincided with the baby becoming restless in expectation of the feed, while in two it corresponded with the mother preparing for the feed. There was no prolactin response to stimuli other than stimulation of the nipple associated with suckling. These results clearly indicate that the milk ejection reflex, with release of oxytocin, occurs in most women before the tactile stimulus of suckling. A second release of oxytocin follows in response to the suckling stimulus itself. Thus it is important that care is taken to protect breast feeding mothers from stress not only during suckling but also immediately before nursing, when conditioned releases of oxytocin will occur.

Simple rule for calculating normal erythrocyte sedimentation rate.

Abstract: Measurement of the erythrocyte sedimentation rate is a commonly performed blood test, so it might be expected that the reference range would have been well established. Several surveysl-3 suggest that the upper limit of normal in a person aged under 50 may be as high as 15-20 mm in the first hour in men and 25-30 mm in the first hour in women, whereas a recent authoritative review4 recommended, on the basis of results \"derived from several publications,\" values of 10 and 12 mm in the first hour respectively. Even so, the haematology departments at 10 London teaching hospitals quote the reference ranges as only 0-5 and 0-7 mm in the first hour in men and women respectively, following a standard textbook.5 We set out to clarify the upper limit of the normal range on the basis of a wide survey.

Effect of nicotine chewing gum as an adjunct to general practitioners' advice against smoking

Abstract: This study was designed to see whether the offer and prescription of nicotine chewing gum would enhance the efficacy of general practitioners9 advice to stop smoking A sample of 1938 cigarette smokers who attended the surgeries of 34 general practitioners in six group practices were assigned by week of attendance (in a balanced design) to one of three groups: (a) non-intervention controls, (b) advice plus booklet, and (c) advice plus booklet plus the offer of nicotine gum Follow up was done after four months and one year The results show a clear advantage for those offered the nicotine gum (p less than 0001) After correction for those who refused or failed chemical validation and those who switched from cigarettes to a pipe or cigars, the proportions who were abstinent at four months and still abstinent at one year were 39%, 41%, and 88% in the three groups, respectively These percentages are based on all cigarette smokers who attended the surgeries including those who did not wish to stop and those in the gum group who did not try the gum (47%) The effect of the offer and prescription of gum was to motivate more smokers to try to stop, to increase the success rate among those who tried, and to reduce the relapse rate of those who stopped The self selected subgroup of 8% who used more than one box of 105 pieces of gum achieved a success rate of 24% It would be feasible and effective for general practitioners to include the offer of nicotine gum and brief instructions on its use as part of a minimal intervention routine with all cigarette smokers A general practitioner who adopts such a routine with similar success could expect to achieve about 35-40 long term ex-smokers a year and so save the lives of about 10 of them If replicated by all general practitioners throughout the country the yield of ex-smokers would be about one million a year

Clinical usefulness of estimation of serum fructosamine concentration as a screening test for diabetes mellitus.

Abstract: Fructosamine, a putative measure of serum glycosylated proteins, was measured in 74 subjects referred for oral glucose tolerance tests. A normal range (mean (2 SD] of 1.6 (0.4) mmol/l (40(10) mg/100 ml) derive from results obtained in 83 healthy non-diabetic volunteers permitted the detection of 15 out of 17 (88%) subjects with proved diabetes and yielded only five (9%) false positive diagnoses. Fructosamine concentrations correlated significantly (p less than 0.001) with fasting plasma glucose concentrations (r = 0.76) and glycosylated haemoglobin concentrations (r = 0.70). A longitudinal study suggested that fructosamine concentration was an index of intermediate term (one to three weeks) blood glucose control. Fructosamine concentration was not related to uraemia and did not depend on albumin or total protein concentrations, provided that serum albumin concentrations remained above 30 g/l. Estimation of fructosamine concentrations is a fully automated procedure and may provide a simple means of screening for diabetes mellitus.

Epileptic seizures in a population of 6000. I: Demography, diagnosis and classification, and role of the hospital services.

Abstract: A total of 122 patients with a history of non-febrile epileptic seizures were identified in a survey of 6000 persons from a single general practice. The lifetime prevalence was 20.3/1000 including single seizures and 17.0/1000 excluding single seizures; 5.3/1000 had active epilepsy. Diagnosis and classification of seizures in such a survey were difficult. Most patients were seen by a hospital specialist at some point, but hospital follow up was sporadic. Overall patient assessment and monitoring was poor. There is a place for specialised epilepsy clinics that could be organised along the lines of the clinics for diabetes. These provide facilities for initial diagnosis and assessment, for planning long term management, for the selected follow up of difficult cases, and for referral for specific problems. Such a system would improve the long term care of patients with epilepsy.

Neurological effects of recombinant human interferon.

Abstract: Ten women with advanced locally recurrent breast cancer who had failed to respond to radiation and hormonal and cytotoxic agents were given up to 12 weeks of recombinant leucocyte interferon 20 X 10(6) U/m2 daily or 50 X 10(6) U/m2 three times a week. Within one hour of administration influenza-like symptoms began, which one week later were superseded by lethargy, anorexia, and nausea, with a consequent loss of weight in most patients. Other side effects included profound somnolence, confusion, paraesthesia, and (in one patient) signs of an upper motor neurone lesion in the legs. All these effects together with increased slow wave activity in electroencephalograms from all patients during treatment disappeared when interferon was withdrawn and did not recur on reintroducing the drug at a lower dosage. Studies are continuing to determine the mechanisms of these effects.

Nifedipine in hypertensive emergencies.

Abstract: The effects and safety of using oral nifedipine 10-20 mg as acute antihypertensive treatment were studied in a single-blind placebo-controlled study of 25 consecutive patients with very high blood pressure requiring emergency reduction. In addition the effect of this treatment on cerebral blood flow was investigated using xenon-133 in 10 patients randomly allocated to receive oral nifedipine or intravenous clonidine. Whereas placebo did not alter the blood pressure, oral nifedipine significantly reduced the systolic and diastolic blood pressures in all 25 patients (from 221 +/- 22/126 +/- 14 mm Hg to 152 +/- 20/89 +/- 12 mm Hg after 30 minutes, p less than 0.001). Heart rate increased from 74 +/- 11 to 84 +/- 11 beats/minute (p less than 0.01); this effect was inversely related to age (r = -0.65, p less than 0.01). The falls in systolic and diastolic blood pressures were closely related to the blood pressures before treatment ) r = 0.67, p less than 0.001 for systolic, and r = -0.58, p less than 0.01 for diastolic values). No serious unwanted effects were observed. Measurement of cerebral blood flow after nifedipine showed an increase in flow in four out of five patients. Clonidine, by contrast, reduced cerebral blood flow in all patients by up to 28%. Nifedipine is a simple, effective, and safe alternative drug for managing hypertensive emergencies, especially when continuous monitoring of the patient cannot be guaranteed.

The critical attitude in medicine: the need for a new ethics.

Abstract: KIE: Challenging an attitude toward fallibility in medical practice which they see as outdated and detrimental to patient care, the authors suggest a new approach to self-evaluation and peer review by physicians. Arguing that knowledge grows from recognition of error, they submit ten proposals aimed at the development of a new professional ethics that would encourage physicians to admit and analyze their errors; improve the quality of their records; and accept the idea of mutual, nonpejorative criticism. Unlike those who fear that this open approach would destroy patients' faith in their doctors, the authors believe it would strengthen the physician patient relationship.

Sex hormones and skin collagen content in postmenopausal women.

Abstract: Skin biopsy specimens were taken from 29 postmenopausal women who had not been given hormone replacement therapy and from 26 women who had been treated with oestrogen and testosterone implants for two to 10 years. The mean hydroxyproline content and therefore the mean collagen content in the skin was found to be 48% greater in the treated than the untreated women, who were matched for age. This difference was significant (p less than 0.01). The implication of this finding is that oestrogen or testosterone, or both, prevents the decrease in skin collagen content that occurs with aging and protects skin in the same way as it protects bone in postmenopausal women.

Non-A non-B hepatitis after transfusion of factor VIII in infrequently treated patients.

Abstract: Thirty patients who had not previously received treatment with factor VIII concentrate or who had been treated only infrequently with factor VIII concentrate were studied after a transfusion of factor VIII. Tests of liver function were performed frequently. Four patients had evidence of chronic liver disease before transfusion. In 17 of the remaining 26 patients serum transaminase activities became raised and 10 patients developed jaundice. All of the nine patients who had not previously received factor VIII transfusion developed non-A non-B hepatitis. Four out of 10 patients followed up for a year had persisting abnormalities of liver function. The pattern of illness suggests that more than one serotype of non-A non-B hepatitis virus may be transmitted by factor VIII concentrate prepared by the National Health Service from volunteer donors in the United Kingdom.

Rifampicin reduces effectiveness and bioavailability of prednisolone.

Abstract: Rifampicin is an inducer of hepatic drug metabolising enzymes. This results in interactions with several drugs including oral anticoagulants, hypoglycaemics, and contraceptives. Concurrent treatment with prednisolone and rifampicin is given when tuberculosis coexists with a disease that is sensitive to steroids, when the diagnosis is uncertain, or occasionally in the treatment of severe tuberculosis. Two patients with respiratory disease were treated with both drugs: their condition improved considerably after rifampicin was withdrawn. Seven patients were then studied to assess the effect of rifampicin on the pharmacokinetics of prednisolone. Overall, rifampicin increased the plasma clearance of prednisolone by 45% and reduced the amount of drug available to the tissues (area under the plasma concentration time curve) by 66%. The effectiveness of prednisolone may be considerably reduced when rifampicin and prednisolone are used in combination.

Changes in volume and density of platelets in myocardial infarction.

Abstract: The distributions of platelet volume and density were measured in 15 men suffering myocardial infarction and in 22 healthy controls. The method used separated 93% of the total platelet population from whole blood. Mean platelet volume of the study group compared with that of controls was increased by a mean of 0.98 fl (p less than 0.001) in the first 12 hours after myocardial infarction, and by 1.24 fl six weeks later (p less than 0.001). Distribution of platelet volume remained log normal after myocardial infarction. Modal platelet density was increased by a mean of 25 g/l (p less than 0.05) after myocardial infarction. Platelet volume is probably chronically large in men suffering myocardial infarction and may be related to changes in megakaryocytes. It is suggested that the increase in platelet volume occurs before infarction.

Patterns of urine flow and electrolyte excretion in healthy elderly people.

Abstract: Twenty four young (mean age 29.2 years, range 25-35) and 21 elderly (mean age 66.5, range 60-80) healthy subjects collected their urine in timed aliquots over 24 hours. The elderly subjects had been selected for their fitness by clinical and laboratory examinations and all lived independently at home. Sodium and potassium excretions were reduced in the elderly subjects compared with the young subjects, potassium excretion considerably so. This was despite similar 24 hour urine volumes and total solute excretion by both groups. The ratios of rates of excretion of water, electrolytes, and solutes during the night to the rates of excretion during the day were found to be higher in the elderly than the young subjects. Reduced day to night ratios of urinary excretion may be partly responsible for complaints of nocturia and sleep disturbance in elderly people.

Effect of ethanol on vascular prostacyclin (prostaglandin I2) synthesis, platelet aggregation, and platelet thromboxane release

Abstract: A series of experiments with platelets from healthy volunteers showed a concentration related inhibitory effect of ethanol on platelet aggregation and release of thromboxane A2. This effect was observed at blood alcohol concentrations ranging between 66 and 132 mg/dl (14.3 and 28.6 mmol/l), which are commonly found in alcoholics. Investigations carried out by incubating ethanol with platelet rich plasma in vitro also showed an inverse linear correlation between ethanol concentration and platelet thromboxane synthesis. In contrast, the incubation of a wide range of concentrations of ethanol with human endothelial cells and rat aortic rings did not alter the ability of these systems to synthesise prostacyclin (prostaglandin I2). This finding of a selective inhibition of thromboxane A2 synthesis and platelet aggregation without an alteration of prostaglandin I2 synthesis may provide an explanation for the reported ethanol mediated protection against vascular disease. This effect of ethanol may also be relevant to the induction of acute gastrointestinal haemorrhage that occurs after bouts of excessive alcohol consumption.

Circadian variation of lymphocyte subpopulations: a study with monoclonal antibodies.

Abstract: Use of monoclonal antibodies to identify subpopulations of circulating lymphocytes in healthy adults showed pronounced circadian variations in total T cells, the two major T cell subsets, and HLA-DR+ lymphocytes. When the results for the T cell subsets were expressed as a ratio (helper:suppressor) no significant rhythmic variation was observed. Lymphocytes bearing a surface antigen identified by the HNK-1 antibody (a population containing the natural killer and antibody dependent killer activity) did not show significant rhythmic variation. There was an inverse relation between plasma cortisol concentration and numbers of T and B cells. These observations have therapeutic implications and should be considered in the course of immunological monitoring.