Search

The statistical adequacy of all papers published in the period 1976-80 describing clinical trials of five non-steroidal anti-inflammatory and two analgesic drugs introduced into the UK market in 1978 and 1979 has been assessed using a checklist of simple criteria. Most trials were reported to be randomised and double-blind. Trial designs were less satisfactory in other important respects; the sample size of most trials was inadequate to demonstrate superiority of the new drug compared with an active control therapy. The period of treatment assessment was short in view of the likelihood of prolonged prescription of drugs in these classes. It is suggested that licensing authorities should demand higher standards of clinical trial evidence offered in support of new drugs. [ABSTRACT FROM AUTHOR]

Familial clustering of microalbuminuria with cardiovascular disease suggests a possible common genetic antecedent. We have tested the hypothesis that the angiotensin-converting enzyme (ACE) DD genotype and the angiotensin II type I receptor (AT1R) gene C allele represent the common link between microalbuminuria and coronary heart disease. The frequency of polymorphisms of the ACE and AT1R genes were investigated in 509 nondiabetic white subjects and in 86 non-insulin-dependent diabetic white patients. There was no significant difference in albumin excretion rate between the genotypes in nondiabetic subjects on either a daytime or an overnight sample or in diabetic subjects expressed as a normalized albumin concentration on an untimed morning urine collection. We have found no evidence for an association between polymorphism of the ACE or AT1R genes and microalbuminuria in two groups of subjects without insulin-dependent diabetes.

Elevated concentrations of proinsulin-like molecules, other than insulin, may be associated with abnormalities of cardiovascular risk factors, promoting atherogenesis and thrombosis. Using specific assays we examined the relationship of levels of insulin, intact proinsulin and des-31,32 proinsulin to blood pressure, lipids, fibrinogen, factor VII and albumin excretion rate in 270 europids with normal glucose tolerance. After correcting for age and body mass index, fasting and 2-h insulin concentrations were significantly associated with those of total and LDL-cholesterol (r = 0.18-0.22), HDL-cholesterol (both r = -0.20) and triglycerides (r = 0.21 and 0.18), but not with blood pressure. Concentrations of intact and des-31,32 proinsulin showed significant associations with those of total and LDL-cholesterol (r = 0.20-0.23), HDL-cholesterol (r = -0.31 and -0.32) and triglycerides (r = 0.22 and 0.26). Fasting insulin and intact proinsulin concentrations were significantly associated with fibrinogen (r = -0.15 and 0.18). Concentrations of proinsulin-like molecules comprised less than 10% of all insulin-like molecules, and so were calculated not to influence previously described relationships between insulin concentrations and cardiovascular risk factors measured using non-specific assays. In multiple regression analyses des-31,32 proinsulin concentration was more strongly associated with those of HDL-cholesterol (negatively), LDL-cholesterol and triglycerides than fasting insulin concentrations, while intact proinsulin replaced insulin concentrations in their relationships with fibrinogen. Our results show correlations between dyslipidaemia and proinsulin-like molecules at concentrations at which biological, insulin-like, activity appears unlikely. We also show relationships between LDL-cholesterol and fibrinogen and the proinsulin-like molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Microalbuminuria and its association with vascular disease has previously been reported in nondiabetic individuals. The aims of this study were to determine whether there is a cross-sectional relationship between urinary albumin excretion rate and cardiovascular disease in nondiabetic subjects and to investigate hereditary predisposition to microalbuminuria by studying offspring of the main study population. Europid patients, aged 40-70 years, were randomly selected from a large inner-city general practice; there was a 62.6% attendance rate, and a study population of 959 remained after exclusions. Blood pressure, ankle systolic pressure, height, and weight were measured. Albumin excretion rate was calculated from overnight and morning urine collections. Venous blood was taken for lipids, fibrinogen, and factor VII; and resting electrocardiograms were carried out. Offspring (aged 15-40 years) of those found to be microalbuminuric were invited to attend for the same tests, and controls were selected by age and sex matching the parents. There was no association between parents' albumin excretion rate with that of their offspring, and there were no significant differences in albumin excretion rate between offspring subjects and their controls. There were no statistically significant associations of prevalent coronary heart disease (CHD) with albumin excretion rate or microalbuminuria in either sex [CHD in women: odds ratio (OR) 1.85; 95% confidence interval (CI) 0.19,9.0] [CHD in men: OR 2.13; 95% CI (0.64, 6.59)]. In women, there were significant associations between albumin excretion rate and peripheral vascular disease (positive) and fibrinogen (negative). Because established risk factors may not be as strongly associated with CHD in cross-sectional studies, we intend to follow this group prospectively.

Objectives: To study the association(s) between microalbuminuria and cardiovascular risk factors in non-diabetic subjects., Design: Patients aged 40-75 years were randomly selected from a general practice list and invited to participate., Setting: Health centre in inner city London., Subjects: Of those invited, 1046 out of 1671 (62.6%) attended. Subjects were excluded for the following reasons: not being white (44); urinary albumin excretion rate > 200 micrograms/min (3); having a urinary infection (5); taking penicillamine or angiotensin converting enzyme inhibitors (7); older than 75 (2); having diabetes (25); missing data on glucose concentration (1)., Main Outcome Measures: Glucose tolerance test results, albumin excretion rate from overnight and timed morning collections of urine; blood pressure; height., Results: Mean albumin excretion rate was significantly lower in women than men (mean ratio 0.8, 95% confidence interval (0.69 to 0.91)). Mean albumin excretion rate was significantly associated with age, blood pressure, and blood glucose concentration (fasting, 1 hour, and 2 hour) in men and inversely with height. Men who had microalbuminuria in both samples were significantly shorter (by 5 cm (1.3 to 9.3 cm)) than those who had no microalbuminuria in either sample when age was taken into account. In the case of women only systolic pressure was significantly associated with albumin excretion rate., Conclusions: Microalbuminuria and short stature in men are associated. Cardiovascular risk has been associated with both of these factors and with lower birth weight. The inverse association of microalbuminuria with height is compatible with the suggestion that factors operating in utero or early childhood are implicated in cardiovascular disease. The higher prevalence of microalbuminuria in men compared with women may indicate that sex differences in cardiovascular risk are reflected in differences in albumin excretion rate.

Sex steroids and dietary fat intake have been implicated in the growth of breast tumours. We have previously shown that the plasma free oestradiol fraction is increased in women with breast cancer and that the addition of free fatty acids (FFA) to plasma can increase the free oestradiol fraction in vitro. In the present study we have examined the distribution of oestradiol and testosterone in serum obtained from European women (EW) and Asian (Gujarati) women (GW) living in north-west London. Fat intake by these women is similar but GW, who are vegetarians, consume a greater proportion of unsaturated fats. In serum from perimenopausal GW, the free testosterone concentration was significantly higher than for EW (11.1 +/- 3.6 pmol/l vs 8.7 +/- 3.4 pmol/l, p < 0.05). Although a significant correlation was found between the free testosterone and FFA concentrations for GW (r = 0.49, p < 0.05), concentrations of sex-hormone binding globulin (SHBG) were significantly lower in GW than EW. The finding of lower SHBG concentration in GW was confirmed in a second study in postmenopausal women (EW, 60.1 +/- 34.1 nmol/l; GW, 37.8 +/- 20.5 nmol/l, p < 0.05). However, no difference in the free oestradiol fraction or concentration was detected for EW and GW and no correlations with total or individual FFA were found. It is concluded from this study that while dietary fats may have an important role in the development of breast tumours, it is unlikely to be mediated by FFA inhibiting the binding of sex steroids to plasma proteins.

Objective: To determine the prevalence of visual disability and common eye disease among elderly people in inner London., Design: Cross sectional random sample survey., Setting: Inner London health centre., Subjects: Random sample of people aged 65 and over taken from practice's computerised age-sex register., Main Outcome Measures: Presenting binocular Snellen 6 m distance acuity and best monocular 3 m Sonksen-Silver acuity to classify prevalence of blindness by World Health Organisation criteria (less than 3/60 in better eye) and American criteria for legal blindness (better eye equal to 6/60 or less) and of low vision by WHO criteria (best acuity 6/18) and visual impairment by American criteria (less than 6/12 or 20/40 but greater than 6/60 or 20/200 in better eye). Principal cause of visual loss by diagnosis, referral indication by cause to hospital eye service, and proportion of cases known to primary care., Results: 207 of 288 (72%) eligible people were examined. 17 (8%) housebound subjects were examined at home. The prevalence of blindness was 1% by WHO criteria and 3.9% by American criteria. The prevalence of low vision (WHO criteria) was 7.7%. The prevalence of visual impairment (American criteria) was 10.6%. Cataract accounted for 75% of cases of low vision. Only eight out of 16 patients with low vision were known by their general practitioner to have an eye problem. 56 subjects (27%) would probably have benefited from refraction. Comparisons with studies in the United States and Finland suggested higher rates in this sample, mainly due to the prevalence of disabling cataract., Conclusion: There seems to be a considerable amount of undetected ocular disease in elderly people in the community.

Forty-two students kept a log diary of all activities during their general surgical firms at a main university hospital in London. The students saw on average 35 patients per week on whom physical aspects were discussed by the consultant with the student after the consultation in 58%, psychological aspects in 4% and social aspects in 1.6%. Students spent an average of 11.2 hours per week with patients. In outpatients students spent most of their time as passive observers, but there were opportunities for more active involvement on the wards. Here the students spent on average 1.5 hours per week personally examining patients and 1 hour per week taking histories. Each student performed on average two short and one long examination per week and 0.5 short and 2.25 long histories per week. The students received on average 2.9 hours per week of consultant teaching in small groups, junior medical staff teaching at 2.2 hours and non-medical staff teaching of 1.1 hour per week. Students spent almost 4 hours per week attending formal traditional lectures in large groups. Some areas identified for improvement were: the relatively little feedback and supervision students received when personally examining patients and taking histories; the passive involvement of students in most educational settings; the small amount of time devoted to discussing social and psychologically relevant factors in the history; the few practical procedures personally performed by students; the relatively large amount of time students reported as unproductive and the small amount of time spent on self-education.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood group and secretor status were determined in 89 heavy drinkers receiving outpatient treatment at a district general hospital in north-west London, and compared with 89 age-, sex- and ethnic origin-matched controls drawn from a panel of 1700 patients from a contiguous general practice. There were no significant differences in the distribution of ABO types and secretor status in the two groups. Differences in salivary mucins were investigated by assaying levels of sialylated and non-sialylated Lewis antigens and blood group antigens ABH in both patients and controls. Although there were no differences in the mean antigen levels for H, A, B Le(a) and Le(b) antigens, using the monoclonal antibody 19.9 (to sialylated Lewis(a) antigen), higher levels were found for groups O and B/AB non-secretors and for group A secretors in alcoholics compared with controls. In addition, inappropriate Le(a) and 19.9 immuno-reactivities were detected in the saliva samples of a group O Le(a)-b- secretor alcoholic and a group A Le(a)-b- secretor alcoholic, respectively. It is suggested that these changes in glycosylation of salivary proteins relate to the increased parotid gland cell proliferation known to occur in chronic alcoholics.

The aim of this study was to evaluate the effects of a fish oil preparation (MaxEPA) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic (NIDDM) subjects. Eighty NIDDM outpatients aged 55.9 yr (mean SD 11.5 yr) participated in a prospective double-blind placebo-controlled study of MaxEPA capsules (10 g/day) or olive oil (control) treatment over 6 wk. Patients received either MaxEPA or olive oil in addition to preexisting therapy. Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk. Platelet membrane eicosapentaenoic acid (EPA) content increased in the treatment group (P less than 0.001). MaxEPA supplementation was associated with a significant fall in total triglycerides (P less than 0.001) but did not affect total cholesterol (P = 0.7) compared with control treatment. Fasting plasma glucose increased after 3 wk (P = 0.01) but not after 6 wk (P = 0.17) treatment with MaxEPA. Spontaneous platelet aggregation in whole blood fell in the MaxEPA group (P less than 0.02) after 6 wk, but there were no changes in agonist-induced platelet aggregation, thromboxane generation in platelet-rich plasma, or plasma beta-thromboglobulin and platelet factor IV levels. An increase in clotting factor VII (P = 0.02), without changes in fibrinogen or factor X levels, occurred in the MaxEPA group. Similar reductions in blood pressure were observed in both groups. Dietary supplementation with MaxEPA capsules (10 g/day) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels. Most indices of platelet function are unaffected by this therapy.

Forty-eight students kept a log diary of activities during their central London general practice teaching attachments associated with the Department of Primary Health Care of University College and Middlesex School of Medicine. The students each saw on average 96 patients per week, of whom 69% were discussed by the general practitioner with the student after the consultation. Students spent an average of 21.5 hours a week sitting in with the general practitioner. While most of this time was as a passive observer, the students were also able to participate more actively, personally taking histories for a median of 1.25 hours a week and personally examining patients for a median of 1.7 hours a week. During these periods of active involvement each student personally took a mean of 10 short and 2.5 long histories per week and performed a mean of 25.5 short and 1.2 long examinations per week. General practitioners to whom the students were attached spent a mean of 4 hours a week on (patient-oriented) teaching. The tuition was highly rated by the students in terms of both usefulness and stimulation. Students also received a mean of 2.3 hours a week of teaching from other members of the primary health care team, which was somewhat less well received. Areas for improvement were: the relatively few home visits (median of 6 per week) per student; the limited time students spent on self-education (average of 65 minutes per week); and the few practical procedures performed by the students. Students could also be encouraged to play a more active role in examining and interviewing patients.

Although there has been growing interest in general practitioners' participation in promoting health, little is known about the attitudes of their patients. Thus we sent a copy of a self administered questionnaire (the Health Survey Questionnaire) to 3452 patients aged 17-70 who were registered with two practices in north west London. Questions about attitudes to and perceptions of general practitioners' interest in weight, smoking, drinking, and fitness problems were included. The patients were also asked whether they thought that they had a problem in any of these areas. The response rate was 72%. Of those who responded, the proportions who thought that their general practitioners should be interested ranged from 72% in the case of fitness to 83% for weight, but only 38% thought that general practitioners had in fact been interested in fitness and only 48% thought so about weight. Forty one per cent of the respondents thought that they had a fitness problem, 42% a weight problem, and 59% of the smokers thought that they had a smoking problem. Four per cent of respondents stated that they had a drinking problem. Of those patients who said that they had a problem, the proportions who thought that their general practitioners had seemed interested ranged from 43% for fitness to 69% for smoking. The findings of this study suggest that greater participation by general practitioners in health promotion would be well received by most patients and that currently there may be considerable discrepancies between patients' expectations and their perception of their general practitioner's interest in these areas of preventive medicine.

Medication record cards were kept for 1,366 patients over a three-year period at a neighbourhood pharmacy in north-west London. Eighty-six potential adverse drug reactions were detected. In 53 cases the general practitioner changed the prescription after being contacted by the pharmacist. In a further 15 cases advice intended to reduce the likelihood of an adverse drug reaction was given to the patients by the pharmacist. Seventy-six errors on prescriptions were also detected; these were mainly unintended changes in dose or strength of medication. Pharmacists could have a useful role to play in monitoring for potential drug reactions in general practice. Closer collaboration between the two professions would be of mutual benefit.

The serum concentrations of prolactin (PRL), follicle stimulating hormone (FSH) and luteinizing hormone (LH) and the plasma concentrations of testosterone, 5-alpha-dihydrotestosterone (DHT) and oestradiol were measured in 80 infertile men and 38 men of known fertility. The infertile men had a lower mean concentration of prolactin and a higher mean concentration of FSH than the fertile controls. The mean FSH was particularly high in infertile men without antisperm antibodies but with oligospermia (sperm density up to 20 million/ml), who also had a higher mean serum LH level than the fertile controls. Both FSH and LH showed an inverse relationship with sperm density. There were no significant differences in plasma testosterone, DHT or oestradiol between fertile and infertile men. In both the fertile and infertile groups strong positive associations were found between the concentrations of FSH and LH, and between testosterone and DHT. Weaker relationships were found between DHT and oestradiol, and between testosterone and PRL. In the fertile men, positive associations were also found between LH and testosterone, and between oestradiol and both FSH and LH. Testosterone and oestradiol were associated only in infertile men. The relevance of these findings to the aetiology of male infertility is discussed.

Among current cigarette smokers in the Northwick Park Heart Study in N.W. London, England, secretors of ABH antigen had a higher mean peak expiratory flow rate than did nonsecretors. The relationship was independent of other factors known to affect peak expiratory flow rate. No significant differences in peak expiratory flow rate by secretor status were detected in nonsmokers or in pipe and cigar smokers, although a smaller difference was seen among secretors and nonsecretors who were ex-cigarette smokers than among those who were current cigarette smokers. It is concluded that secretion of ABH antigen into the respiratory tract may have a protective effect against pulmonary damage by noxious agents.

An examination of the practice notes and attached correspondence of 900 patients aged 30 to 65 years in a random sample of 18 general practice in north west London showed that 340 (47%) of 716 patients consulting in a 10 year period had no blood pressure readings in their records. The blood pressure was equal to or above 160 mm Hg systolic or 95 mm Hg diastolic, or both, in 115 (31%) of those whose blood pressures were recorded; 18 (16%) of these were not followed up. Seventy four patients were being treated for hypertension. Diuretics were the most commonly prescribed drugs. Treatment was started after one blood pressure reading in 34 (46%). Nine of those who had an initial raised blood pressure reading were normotensive on follow up. A further 14 patients had subsequent raised blood pressure readings but were not treated. Sixty one (69%) of the 88 patients with hypertension did not have a blood pressure recording after diagnosis for one or more periods exceeding 12 months. Of 84 hypertensive patients with complete records, 62 (74%) apparently had had no physical examination performed by the general practitioner and 61 (72%) did not seem to have had any investigations initiated by the general practitioners. Fifteen (35%) of 43 patients taking oral contraceptive pills apparently had no blood pressure recordings during the time they were taking these. The results of this study suggest that there are still deficiencies in the detection and management of hypertension in general practice.

The birthweights of 664 Hindu and 132 Moslem babies were compared with those of 486 European babies born at the same hospital. The mean birthweight of the Europeans was 3362 g, compared with 3146 g for the Moslems and 2960 g for the Hindus. The Asian women were smaller than the European and tended to have a shorter length of gestation. Forty-four per cent of the Asians and 46% of the European mothers were of social classes I and II; 28% of the Europeans and 2% of the Asians smoked. There were no significant differences between Asians and Europeans in the effects of maternal size, parity, gestational age and fetal sex on birthweight. After adjustment for these variables and for cigarette smoking there was no significant difference in birthweight between the Moslems and the Europeans, but the mean birthweight of the Hindus was about 190 g lighter than that of the Europeans. Hindus from East Africa had lighter babies than those from India.

In a study of breath methane concentration 43 percent of males and 49 percent of females produced detectable amounts. The proportion of methane producers increased significantly with age in males but not in females. Obesity as measured by the sum of triceps, forearm, suprailiac and subscapular skinfolds was significantly less in producers than non-producers. Amongst methane producers there was also an inverse relationship between skinfold thickness and the breath methane concentration. Breath methane concentrations were lower in males than females. In addition, a higher proportion of methane producers was found amongst secretors of blood group substances (ABH antigen) than non-secretors.

The health survey questionnaire was used to collect information about cigarette smoking, alcohol consumption, physical exercise, and dieting and weight. Completed questionnaires were received from 25,496 men and 36,657 women registered with 47 group practices in England and Scotland. The proportions of respondents who stated that they had a problem ranged from 1% (women and drinking, n = 406) to 34% (women and weight, n = 12,526). Between 49% (women and drinking, n = 18,048) and 67% (men (n = 17,095) and women (n = 24,550) and weight) thought that their general practitioners should be interested in their lifestyle. The proportions who could recall having received relevant advice ranged from 2% (women and drinking, n = 591) to 24% (women and weight, n = 8946). Advice about smoking had been given to 4055 (40%) of the women and 2941 (39%) of the men who smoked. Only 96 (10%) of the 989 women and 331 (17%) of the 1948 men who drank excessively could recall having received advice about alcohol consumption. These results suggest that patients are concerned about their lifestyle, that most would welcome relevant counselling, and that doctors should become more concerned with prevention of this kind.

The incidence of ischaemic heart disease (IHD) is higher in postmenopausal women than in premenopausal women of the same age. The difference may be partly explicable in terms of differences between premenopausal and postmenopausal women in haemostatic function. This possibility has been studied in 833 White women in the Northwick Park Heart Study (NPHS). Mean levels of factor VIIC, fibrinogen, and cholesterol were between 6% and 10% higher in postmenopausal women than in premenopausal women of the same age. When allowances were made for associations between these variables, the difference between the two groups in cholesterol was no longer evident. By analogy with NPHS data on men, the differences in factor VIIC, fibrinogen, and cholesterol would increase the risk of fatal IHD in postmenopausal women by about 40% compared with the risk in premenopausal women of the same age.

Study Objective: To determine the relationship between obesity and subsequent incidence of ischaemic heart disease (IHD)., Design: Prospective cohort survey., Setting: Study of three occupational groups, with follow up examinations., Subjects: 3500 people recruited between 1972 and 1978 (80% response rate), and followed up between 1978 and 1984. This report is based on subgroup of 1511 white men aged 40-64 at entry., Measurements and Main Results: Information was obtained on smoking and family history of IHD. Blood pressure, weight, height, skinfold thickness at four sites, fibrinogen, factor VII activity and cholesterol were measured during follow up. Body mass index (BMI) was used as an index of obesity. BMI was found to be more strongly correlated with IHD than any of the skinfold measurements, none of which was significantly associated with IHD when BMI was allowed for. Increase in BMI by 1 SD (approximately 8 kg) was associated with a 44% increase in the risk of IHD. Of the four skinfolds, subscapular was the most closely associated with risk, confirming the relevance of central obesity. The association between obesity and IHD remained when possible mechanisms for its effects were taken into account, and its strength may increase with time: for 1 SD increase in BMI, risk of events within 5 years was increased by 28%, while risk of events after longer than 5 years was increased by 65%., Conclusions: Preventive strategies for IHD should include avoidance of obesity.

In 92 Hindu Asians, 59% of them vegetarian, and 51 Europeans longitudinal measurements were made during pregnancy of the zinc and copper concentrations in plasma and hair together with urinary zinc excretion, as indices of their zinc and copper status. Maternal diets were assessed once at booking. Zinc intakes ranged from 3.1 to 16.9 mg/day, with average intakes least in vegetarian Hindus and most in Europeans. Average copper intakes ranged between 1.48 and 1.80 mg/day and were similar in the three patient groups. Both ethnic groups showed the pregnancy-associated fall in the plasma concentration of zinc and rise in that of copper but throughout the study Hindus had statistically significant lower levels of zinc and higher levels of copper than Europeans. Urinary zinc excretion was not only significantly lower throughout the study in Hindus than in Europeans but the increase in excretion which occurred after 20 weeks gestation was smaller. There were no ethnic differences in the zinc content of hair. Urinary zinc excretion correlated with both plasma zinc levels and dietary zinc. Mean birthweight in the Hindus was 2912 g and 34% of infants were below the 10th centile, using the Aberdeen standards, compared with 6% of the European babies (mean birthweight 3349 g). No association was found between crude or adjusted birthweight and any of the measures of zinc or copper status in either ethnic group. The Hindus had an apparently lower average zinc status than the Europeans, but there was no evidence that this had acted as a nutritional constraint and was the cause of their slower rate of intrauterine growth.

In 15 women on oral contraceptives containing 30 microgram oestrogen, mean values for factors II, VII, and X, fibrinogen, fibrinolytic activity, antithrombin III, cholesterol, and fasting triglycerides were intermediate between values for 63 women on preparations containing 50 microgram oestrogen and those for 243 premenopausal women not on oral contraceptives. Mean blood-pressure levels, however, were higher in women on 30 microgram than in those on 50 microgram preparations. In 28 women on 50 microgram preparations containing 3 mg or 4 mg norethisterone, mean values of factor VII, fibrinogen, fibrinolytic activity, cholesterol, fasting triglycerides, and systolic blood-pressure were higher than in 15 women whose preparations contained only 1 mg of norethisterone. A less consistent picture was found in women on 30 microgram oestrogen preparations containing either 250 microgram (10 women) or 150 microgram (5 women) d-norgestrel. It is concluded that 30 microgram oestrogen preparations probably result in smaller hemostatic and lipid changes than 50 microgram preparations but that they may have a blood-pressure-raising effect attributable to the particular progestagen, d-norgestrel, used in 30 microgram preparations. The safety of these 30 microgram oestrogen preparations may thus depend partly on the balance between these two sets of effects. It is also concluded that norethisterone may have effects similar to those attributed to oestrogens.

1. Twelve healthy male subjects took a daily supplement of 20 ml of cod-liver oil for 6 weeks. This provided 1.8 g of eicosapentaenoic acid (20:5 omega 3) and 2.2 g of docosahexaenoic acid (22:6 omega 3). The effects of the supplement on blood lipids, haemostatic variables, bleeding time and plasma vitamin A and carotene were studied. In seven subjects platelet aggregation induced by adenosine 5'-pyrophosphate (ADP) was also studied. 2. The proportions of 20: 5 omega 3 and 22: 6 omega 3 in platelet and erythrocyte phosphoglycerides were substantially increased by the supplement mainly at the expense of omega 6 polyunsaturated fatty acids. 3. Mean plasma triglyceride concentrations were reduced and those of high-density-lipoprotein (HDL) cholesterol were increased by the supplement. 4. The mean bleeding time was significantly prolonged after 3 weeks of taking the supplement, but had returned to the presupplementation value 5 weeks after withdrawal of the supplement. 5. The maximum estimated response to platelet aggregation induced by ADP was increased by the supplement. 6. The mean levels of antithrombin III (immunological) and blood pressure were lower at the end of the period of supplementation and remained so 5 weeks after withdrawal of the supplement. No significant changes in other variables were noted.

The hospital records of 60 female and 56 male pancreatic cancer patients and 232 age-, race-, sex-, and hospital-matched controls were reviewed for evidence of prior thyroid disease, cholecystectomy, appendectomy, alcohol consumption and among females, for diseases for the endometrium and ovary. No statistically significant differences were detected between case and control groups. It may be of interest, however, that there were four patients with a history of thyrotoxicosis among the pancreatic cancer patients and only one in the control group. In females, a history of thyroidectomy was somewhat more common among the patients than the controls.

A prospective study of the relation between scores on the six subscales of the Crown-Crisp experiential index and subsequent incidence of ischaemic heart disease was undertaken among participants in the Northwick Park heart study. Results from 1457 white men aged 40-64 at recruitment showed that phobic anxiety was strongly related to subsequent major ischaemic heart disease (fatal and non-fatal events combined) when other associated variables were taken into account. The phobic anxiety score alone remained significantly associated with ischaemic heart disease when scores on all the subscales were included in the analysis. Phobic anxiety seemed to be particularly associated with fatal ischaemic heart disease but was not associated with deaths from other causes and was no higher in those with a pre-existing myocardial infarction at recruitment than in those without. There was a consistent increase in risk of fatal ischaemic heart disease with score on the phobic anxiety subscale. The relative risk for those whose score was 5 and above was 3.77 (95% confidence interval 1.64 to 8.64) compared with those whose score was 0 or 1. The 49 participants with evidence of myocardial infarction at recruitment had higher scores on the subscales for free floating anxiety and functional somatic complaint. The Crown-Crisp experiential index is simple to fill out and acceptable to patients. When the results are combined with other known risk factors it may be of use in defining high risk subjects and in planning strategies for prevention.

As part of a study to determine the extent to which the haemostatic system is implicated in the onset of clinically manifest ischaemic heart disease, characteristics influencing fibrinolytic activity (FA) and plasma fibrinogen concentrations were examined in 1601 men aged 18-64 and 707 women aged 18-59 in several occupational groups in North-west London. In men FA noticeably decreased till the age of about 58, when there was a small rise. In women a small increase in FA between 18 and about 40 was followed by a slightly larger fall between 40 and 59. There was a pronounced negative association of FA with obesity. FA was significantly less in smokers than non-smokers, though the effect was not large. FA increased with alcohol consumption. FA in men appeared to be greatest in the lower social classes, and men on night shift had poorer FA than those on day work. FA was greater in women using oral contraceptives than in those not using these preparations. In both sexes FA increased with exercise, but there were no associations between any of the characteristics studied and the increase. Plasma fibrinogen concentrations increase with age and obesity, are higher in smokers than non-smokers, and fall with alcohol consumption. In women the concentrations are higher in those using oral contraceptives. The general epidemiology of FA and plasma fibrinogen concentrations suggests that they may well be implicated in the pathogenesis of ischaemic heart disease.

A random sample of the records of patients having barium meal examinations at a district general hospital was reviewed. In both males and females, there was no significant difference in the proportions of abnormalities between referrals from hospital doctors and general practitioners. Younger males were less likely to show abnormalities than older males, but there was no age difference in the proportions of abnormal barium meals in females. There was a smaller proportion of major abnormalities (19 per cent) in female than male patients (28 per cent). This study does not suggest that any reduction of direct access barium meal examinations for general practitioners is necessary.

Patients from 47 group practices recruited from the Medical Research Council's general practice research framework participated in a study involving the collection of information about smoking, drinking, exercise and dieting and weight. This paper is concerned with the data on alcohol consumption obtained in the first stage of the study in which a self-administered questionnaire, the health survey questionnaire, was distributed by hand or by post to patients registered with the participating practices.Of the 25496 men who completed the questionnaire, 83.6% stated that they had been drinking in the previous three months compared with 69.2% of the 36657 women. For both sexes, abstinence rates were significantly lower in the younger age groups (P

A comparison of blood pressure (BP), smoking, alcohol consumption and obesity between whites and blacks of Caribbean origin aged 17-70 was undertaken in a general practice in North West London. Mean systolic and diastolic blood pressures (DBP) showed no consistent overall differences between the two ethnic groups, though DBP rose significantly more with age in black males than white males. Somewhat higher proportions of the black patients were receiving anti-hyper-tensive treatment compared with the whites, the difference was statistically significant in the case of males (P less than 0.02). This observation did not appear to be due to more effective detection of hypertension amongst black males. Overall, fewer than one-third of black females were current cigarette smokers compared with around one-half of white females (P less than 0.001). Amongst males, however, the proportions of never, ex and current smokers were similar in the two ethnic groups. Young black patients of both sexes were more likely to smoke than older blacks. Blacks who smoked tended to smoke fewer cigarettes than white smokers. Eleven of 190 (5.8%) black males had consumed 35 units or more of alcohol within the last week compared with 87 of 452 (19.2%) of white males, (P less than .001). Amongst females the differences were smaller, 5 of 227 (2.2%) of black females had consumed 21 units or more in the last week compared with 23 of 490 (4.7%) of white females (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The epidemiological characteristics of platelet aggregability were established in 958 participants in the Northwick Park Heart Study. The main analyses were based on the dose of adenosine diphosphate at which primary aggregation occurred at half its maximum velocity. Aggregability increased with age in both sexes, was greater in whites than blacks (particularly among men), and tended to decrease with the level of habitual alcohol consumption. Aggregability was, however, greater in women than men and in nonsmokers than smokers. There was no relation between aggregability on the one hand and obesity, current or past oral contraceptive use, menopausal state, or blood cholesterol and triglyceride concentrations on the other. Aggregability was somewhat, though not significantly, higher in men with a history of ischaemic heart disease and in those with electrocardiographic evidence of ischaemia than in those without. There was a strong association between the plasma fibrinogen concentration and aggregability. The widely held concept of platelet aggregability and its implications is probably an oversimplification. In the prevention of thrombosis it may be as useful to consider modifying external influences on platelet behaviour, such as plasma fibrinogen concentration or thrombin production, as it is to rely solely on platelet active agents.

Eighty infertile men and 38 men of known fertility were studied for investigation of both the importance of zinc, copper, cadmium, and lead to fertility and the possible interrelationships between these trace elements. The infertile men had higher mean concentrations of plasma copper than those of proven fertility. The difference was statistically significant (P less than 0.01) but was of small magnitude (approximately 1.5 mumol mean difference). The concentrations of plasma zinc, erythrocyte zinc, whole blood lead and cadmium, and seminal plasma zinc and copper did not differ significantly between infertile and fertile men. There was a significant positive relationship between sperm density and seminal plasma zinc concentration in the fertile, but not in the infertile, men. The infertile men with antisperm antibodies or counts greater than 20 million/ml had significantly higher mean levels of seminal plasma zinc than infertile men with oligospermia. The higher semen zinc in these two groups may reflect an abnormal fragility of the spermatozoa, resulting in the release of zinc, but the absence of significant overall differences between fertile and infertile men suggests that measurement of the concentration of zinc in plasma or zinc and copper in seminal plasma has little value in the routine investigation of infertility.

In a study of 272 patients with myocardial infarction (MI) the 68 who died within 1 year had significantly higher levels of factor VIIIR:Ag, factor VIII:C, fibrinogen, alpha 1 antitrypsin and alpha 2 macroglobulin than those who survived. The mean white cell count (WCC) and peak creatine kinase (CK) were also significantly higher in those who died compared with the survivors. There was considerable intercorrelation between many of the haemostatic variables, WCC and CK as well as between many of the clinical predictors of outcome and the laboratory variables. The differences in haemostatic variables between those who died and those who survived may merely reflect the size of the infarct; alternatively, the haemostatic system may influence prognosis following an MI.

Components of the haemostatic system which may be involved in the pathogenesis of ischaemic heart disease (IHD) were measured in the Northwick Park Heart Study. Of 1510 white men aged 40-64 at recruitment, 49 have since died. 27 died from cardiovascular disease (IHD in all but 3), 18 from cancer, and 4 from other causes. The mean recruitment levels of factor VIIc, factor VIIIc, and fibrinogen were significantly higher in those who died of cardiovascular disease than in those who survived. The independent associations of factor VIIc and fibrinogen with cardiovascular death were at least as strong as the association of blood cholesterol with cardiovascular death. A clustering of two or three high clotting-factor values (factor VIIc, factor VIIIc, and fibrinogen) was present at recruitment in 63% of those who died of cardiovascular disease, compared with 23% of those who survived. The clotting-factor results appeared to be specific for cardiovascular disease: there was no evidence that high levels of factor VIIc, factor VIIIc, and fibrinogen were associated with death from cancer. The general epidemiology of factor VIIc, factor VIIIc, and fibrinogen is consistent with their having a role in the pathogenesis of IHD.

A self-administered questionnaire, the Health Survey Questionnaire (HSQ) was distributed to patients registered with 47 group general practices. The HSQ assesses alcohol consumption using a quantity frequency scale and includes the four CAGE questions and a question on whether respondents think they have an alcohol problem. A random stratified sample of those patients who returned an HSQ (2666 men and 1537 women) were subsequently invited to attend their general practice for an interview with the practice nurse, where weekly alcohol consumption was estimated using both a quantity frequency scale and a systematic enquiry about alcohol consumption for the week immediately preceding the interview. The latter method was taken as the 'gold standard'. Excessive drinkers were defined as men whose weekly consumption by this method was not less than 35 units per week and women drinking at least 21 units per week. After weighing the results to take account of the sampling bias in favour of the excessive drinkers, 11.7% of men and 2.9% of women were excessive drinkers according to the estimate of alcohol consumption at interview. This compares with the 7.6% of men and 2.7% of women who were heavy drinkers by the HSQ quantity frequency scale. The two interview estimates were comparable but in general the HSQ tended to underestimate consumption compared with these estimates. The questionnaire was found to be most effective in screening for excessive drinkers if all the patients who indicated concern about their drinking (i.e. those who were with CAGE positive or had a self-assessed drinking problem), as well as all of those who were above the limits for the trial on the quantity frequency scale, were selected as being potentially excessive drinkers. In the weighted sample, 14.8% of men and 6.9% of women were in this group. Using these selection criteria and taking the interview as the standard for determining the excessive drinkers a sensitivity of 58.6% and specificity of 91.08% was obtained for men, with a positive predictive value of 46.1% and a negative predictive value of 94.3%. For women the test was more sensitive (69.7%) and more specific (95.0%) and had a better negative predictive value (99.1%) than for men. The positive predictive value for women at 29.6% was not as good as that obtained for men. This analysis shows that the HSQ is a fairly effective tool for detecting excessive drinkers in general practices with a small proportion of false positive results. It is both economical and acceptable to patients in a wide range of practice settings.