Showing papers in "BMJ in 1989"

Hay fever, hygiene, and household size.

Abstract: Hay fever has been described as a "post industrial revolution epidemic,"' and successive morbidity surveys from British general practice suggest that its prevalence has continued to increase over the past 30 years.) Other evidence suggests a recent increase in the prevalence of asthma2 and childhood eczema.3 This paper suggests a possible explanation for these trends over time.

Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease.

Abstract: In national samples of 9921 10 year olds and 3259 adults in Britain systolic blood pressure was inversely related to birth weight. The association was independent of gestational age and may therefore be attributed to reduced fetal growth. This suggests that the intrauterine environment influences blood pressure during adult life. It is further evidence that the geographical differences in average blood pressure and mortality from cardiovascular disease in Britain partly reflect past differences in the intrauterine environment. Within England and Wales 10 year olds living in areas with high cardiovascular mortality were shorter and had higher resting pulse rates than those living in other areas. Their mothers were also shorter and had higher diastolic blood pressures. This suggests that there are persisting geographical differences in the childhood environment that predispose to differences in cardiovascular mortality.

Meta-analysis of relation between cigarette smoking and stroke.

Abstract: There is a lack of consensus among studies on the possible risks of stroke from cigarette smoking; because of this a meta-analysis was conducted. All published data on the association were sought and the relative risk for each study obtained whenever possible. The pooled relative risks were calculated by using estimates of the precision of the individual relative risks to weight their contribution to the meta-analysis. Thirty two separate studies were analysed. The overall relative risk of stroke associated with cigarette smoking was 1.5 (95% confidence interval 1.4 to 1.6). Considerable differences were seen in relative risks among the subtypes: cerebral infarction 1.9, cerebral haemorrhage 0.7, and subarachnoid haemorrhage 2.9. An effect of age on the relative risk was also noted; less than 55 years 2.9, 55-74 years 1.8, and greater than or equal to 75 years 1.1. A dose response between the number of cigarettes smoked and relative risk was noted, and there was a small increased risk in women compared with men. Ex-smokers under the age of 75 seemed to retain an appreciably increased risk of stroke (1.5); for all ages the relative risk in ex-smokers was 1.2. The meta-analysis provides strong evidence of an excess risk of stroke among cigarette smokers. Stroke should therefore be added to the list of diseases related to smoking.

Association between dental health and acute myocardial infarction.

Abstract: Known risk factors for coronary heart disease do not explain all of the clinical and epidemiological features of the disease. To examine the role of chronic bacterial infections as risk factors for the disease the association between poor dental health and acute myocardial infarction was investigated in two separate case-control studies of a total of 100 patients with acute myocardial infarction and 102 controls selected from the community at random. Dental health was graded by using two indexes, one of which was assessed blind. Based on these indexes dental health was significantly worse in patients with acute myocardial infarction than in controls. The association remained valid after adjustment for age, social class, smoking, serum lipid concentrations, and the presence of diabetes. Further prospective studies are required in different populations to confirm the association and to elucidate its nature.

Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial.

Abstract: OBJECTIVE--To determine the efficacy of oral nimodipine in reducing cerebral infarction and poor outcomes (death and severe disability) after subarachnoid haemorrhage. DESIGN--Double blind, placebo controlled, randomised trial with three months of follow up and intention to treat analysis. To have an 80% chance with a significance level of 0.05 of detecting a 50% reduction in an incidence of cerebral infarction of 15% a minimum of 540 patients was required. SETTING--Four regional neurosurgical units in the United Kingdom. PATIENTS--In all 554 patients were recruited between June 1985 and September 1987 out of a population of 1115 patients admitted with subarachnoid haemorrhage proved by the results of lumbar puncture or computed tomography, or both. The main exclusion criterion was admission to the neurosurgical units more than 96 hours after subarachnoid haemorrhage. There were four breaks of code and no exclusions after entry. One patient was withdrawn and in 130 treatment was discontinued early. All patients were followed up for three months and were included in the analysis, except the patient who had been withdrawn. INTERVENTIONS--Placebo or nimodipine 60 mg was given orally every four hours for 21 days to 276 and 278 patients, respectively. Treatment was started within 96 hours after subarachnoid haemorrhage. END POINTS--Incidence of cerebral infarction and ischaemic neurological deficits and outcome three months after entry. MEASUREMENTS--Demographic and clinical data, including age, sex, history of hypertension and subarachnoid haemorrhage, severity of haemorrhage according to an adaptation of the Glasgow coma scale, number and site of aneurysms on angiography, and initial findings on computed tomography were measured at entry. Deterioration, defined as development of a focal sign or fall of more than one point on the Glasgow coma scale for more than six hours, was investigated by using clinical criteria and by computed tomography, by lumbar puncture, or at necropsy when appropriate. All episodes of deterioration and all patients with a three month outcome other than a good recovery were assessed by a review committee. MAIN RESULTS--Demographic and clinical data at entry were similar in the two groups. In patients given nimodipine the incidence of cerebral infarction was 22% (61/278) compared with 33% (92/276) in those given placebo, a significant reduction of 34% (95% confidence interval 13 to 50%). Poor outcomes were also significantly reduced by 40% (95% confidence interval 20 to 55%) with nimodipine (20% (55/278) in patients given nimodipine v 33% (91/278) in those given placebo). CONCLUSIONS--Oral nimodipine 60 mg four hourly is well tolerated and reduces cerebral infarction snd improves outcome after subarachnoid haemorrhage.

Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial.

Abstract: OBJECTIVE--To assess the safety and efficacy of a preparation of mesalazine (5-aminosalicylic acid) coated with a pH dependent resin (Eudragit L) as compared with sulphasalazine in patients with active mild to moderate ulcerative colitis. DESIGN--Eight week randomised double blind parallel group study. SETTING--Forty six gastroenterology outpatient clinics in seven countries. PATIENTS--Two hundred and twenty patients aged 18-70 who met the following criteria: clinical activity index greater than or equal to 6 and endoscopic index greater than or equal to 4; no concomitant treatment for ulcerative colitis; no hypersensitivity to salicylates or sulphonamides. Of the 164 patients eligible for efficacy analysis, 87 received the coated preparation of mesalazine and 77 sulphasalazine. Most of the remaining patients (28 in each group) were ineligible for the efficacy analysis because of treatment with steroid enemas. All pretrial characteristics were comparable in the two treatment groups. INTERVENTIONS--Coated mesalazine (Mesasal) 1.5 g daily or sulphasalazine 3.0 g daily for eight weeks. Compliance monitored by pill counts. END POINT--Clinical and endoscopic remission. MEASUREMENTS AND MAIN RESULTS--Clinical activity measured by daily diary cards, assessment by investigators, and laboratory findings. Endoscopic evaluation at week 8. After four weeks 50 of 70 patients (71%) taking coated mesalazine and 38 of 58 (66%) taking sulphasalazine had achieved remission of their disease by eight weeks remission rates were 74% (37/50 patients) and 81% (35/43) in the two treatment groups respectively. Endoscopic remission at eight weeks was recorded in 20 of 41 patients (49%) taking coated mesalazine and 18 of 38 (47%) taking sulphasalazine. There was a higher incidence of adverse events among patients taking sulphasalazine (25/105; 24%) than among those taking coated mesalazine (16/115; 14%). CONCLUSION--Mesalazine coated with Eudragit L is a safe, logical alternative to sulphasalazine.

Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data.

Abstract: To examine the association between cigarette smoking in adults and serum lipid and lipoprotein concentrations the results of 54 published studies were analysed. Overall, smokers had significantly higher serum concentrations of cholesterol (3.0%), triglycerides (9.1%), very low density lipoprotein cholesterol (10.4%), and low density lipoprotein cholesterol (1.7%) and lower serum concentrations of high density lipoprotein cholesterol (-5.7%) and apolipoprotein AI (-4.2%) compared with nonsmokers. Among non-smokers and light, moderate, and heavy smokers a significant dose response effect was present for cholesterol (0, 1.8, 4.3, and 4.5% respectively), triglycerides (0, 10.7, 11.5, and 18.0%), very low density lipoprotein cholesterol (0, 7.2, 44.4, and 39.0%), low density lipoprotein cholesterol (0, -1.1, 1.4, and 11.0%), high density lipoprotein cholesterol (0, -4.6, -6.3, and -8.9%), and apolipoprotein AI (0, -3.7 and -5.7% in non-smokers and light and heavy smokers). These dose response effects may provide new evidence for a causal relation between exposure to cigarette smoke and changes in serum lipid and lipoprotein concentrations whether as a direct result of physiological changes or of dietary changes induced by smoking. Adequate prospective data to estimate the excess risk of coronary artery disease existed only for cholesterol concentration. When that information was combined with data from the present study, and given that smokers as a group face an average overall excess risk of coronary artery disease of 70%, it was estimated that the observed increased serum cholesterol concentration in smokers may account for at least 9% of that excess risk. Furthermore, the dose response effect of smoking on serum cholesterol concentration suggests a gradient of increased absolute risk of coronary artery disease between light and heavy smokers.

Mental health, job satisfaction, and job stress among general practitioners.

Abstract: As early as 1968 Mechanic stated that “the average doctor responds to his growing practice and increasing demands on his time … by practising at a different pace and style. Such a pattern of work requires doctors to practise on an assembly line basis, which diminishes the unique satisfaction possible in general practice.”1 Since that time there has been a growing amount of published work on job dissatisfaction and stress among general practitioners.2

Deprivation: explaining differences in mortality between Scotland and England and Wales.

Abstract: To detect reasons for the difference in mortality between Scotland and England and Wales a measure of deprivation was studied, comprising overcrowding, unemployment of men, low social class, and not having a car. Data for Scotland for 1980-2 showed this measure to be strongly associated with mortality, with gradients being particularly steep in young adults. Deprivation was much severe in Scotland than in England and Wales. These findings suggest that much excess mortality may be ascribed to more adverse conditions. Standardising the mortality ratios to take account of the relative affluence and deprivation of the two populations led to the differentials observed being radically adjusted, while standardising for social class had little effect. Deprivation measures based on areas overcome many of the limitations associated with social class analysis and also show much greater discrimination between populations. Measures of deprivation apparently provide a powerful basis for explanation of health differences. Such measures should therefore form part of the 1991 census output to facilitate their use on a consistent basis.

Counselling in a general practice setting: controlled study of health visitor intervention in treatment of postnatal depression.

Abstract: OBJECTIVE--To determine whether counselling by health visitors is helpful in managing postnatal depression. DESIGN--Controlled, random order trial. SETTING--Health centres in Edinburgh and Livingston. PATIENTS--Sixty women identified as depressed by screening at six weeks post partum and by psychiatric interview at about 13 weeks post partum. Five women did not wish to participate, and a further five did not complete the trial. Age, social and obstetric factors, and diagnosis were similar in women who completed the trial and those who withdrew. INTERVENTION--Eight weekly counselling visits by health visitors who had been given a short training in counselling for postnatal depression. END POINT--Reduction of depression. MEASUREMENTS and main results--Standardised psychiatric interviews and a 10 point self report scale were used to identify depression before and after intervention. The psychiatrist was not told to which group women were allocated. After three months 18 (69%) of the 26 women in the treatment group had fully recovered compared with nine (38%) of the 24 in the control group. The difference between the groups was thus 32% (95% confidence interval 5 to 58). CONCLUSIONS--Counselling by health visitors is valuable in managing non-psychotic postnatal depression.

Patient preferences and randomised clinical trials.

Abstract: The child should be examined but not without the knowledge and agreement of a parent (or the order of a court). Mothers of pr?adolescent children should always be invited to be present, except in the most exceptional circumstances. Adolescent patients should be asked whether they wish a parent to be present. It is usually counterproductive to examine a resistant child, and if his or her cooperation cannot be obtained the examination should be deferred unless there are urgent medical reasons to proceed. The child should be examined as soon as optimal arrangements can be made. Few children require urgent examination. Repetitive examination is usually abusive and should be avoided. The examination should be conducted in absolute privacy and in an environment where the child can be comfortable?not behind screens in open wards or in police stations. There should be adequate equipment for any necessary diagnostic tests. Recording and photographic facilities are an advantage but their value is outweighed if they cause distress to the child or mean that another examination has to be conducted. Who should examine?

Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up.

Abstract: OBJECTIVE--Determination of the long term incidence of uraemia, hypertension, and toxaemia in pregnancy associated with non-obstructive focal renal scarring after pyelonephritis in childhood 25-35 years earlier. DESIGN--27 Year follow up of patients with non-obstructive focal scarring identified from a retrospective review of intravenous urograms performed in childhood between 1951 and 1967. SETTING--Paediatric primary referral centre and urological clinic in tertiary referral centre. PATIENTS--30 Patients (mean age 33 (range 22-41] with non-obstructive focal renal scarring first detected between 1951 and 1967 and a history of febrile urinary tract infection. MAIN OUTCOME MEASURE--Hypertension and complications of renal damage. RESULTS--Three patients had developed end stage renal disease, seven had developed hypertension, two of 16 women had a history of toxaemia during pregnancy, and seven patients had undergone renal surgery during follow up. Of the 20 patients who had neither had renal surgery nor had end stage renal disease, all had a significantly lower glomerular filtration rate and renal plasma flow and higher diastolic blood pressure, mean arterial blood pressure, plasma renin activity, and serum beta 2 microglobulin concentration than 13 healthy age matched controls. Diastolic blood pressure and plasma renin activity were positively correlated (r = 0.50, p less than 0.05) and so were fractional sodium excretion and both systolic and diastolic blood pressures (r = 0.54, p less than 0.01, r = 0.51, p less than 0.01 respectively). The progress of renal damage was unrelated to the incidence of recurrent infections. CONCLUSIONS--Children with focal renal scarring due to pyelonephritis are at high risk of serious long term consequences. It is essential that they are given adequate attention and care during adolescence and pregnancy.

Damp housing, mould growth, and symptomatic health state.

Abstract: OBJECTIVE--To examine the relation between damp and mould growth and symptomatic ill health. DESIGN--Cross-sectional study of random sample of households containing children; separate and independent assessments of housing conditions (by surveyor) and health (structured interview by trained researcher). SETTING--Subjects' homes (in selected areas of public housing in Glasgow, Edinburgh, and London). SUBJECTS--Adult respondents (94% women) and 1169 children living in 597 households. END POINTS--Specific health symptoms and general evaluation of health among respondents and children over two weeks before interview; and score on general health questionnaire (only respondents). MEASUREMENTS AND MAIN RESULTS--Damp was found in 184 (30.8%) dwellings and actual mould growth in 274 (45.9%). Adult respondents living in damp and mouldy dwellings were likely to report more symptoms overall, including nausea and vomiting, blocked nose, breathlessness, backache, fainting, and bad nerves, than respondents in dry dwellings. Children living in damp and mouldy dwellings had a greater prevalence of respiratory symptoms (wheeze, sore throat, runny nose) and headaches and fever compared with those living in dry dwellings. The mean number of symptoms was higher in damp and mouldy houses and positively associated with increasing severity of dampness and mould (dose response relation). All these differences persisted after controlling for possible confounding factors such as household income, cigarette smoking, unemployment, and overcrowding. Other possible sources of bias that might invalidate the assumption of a causal link between housing conditions and ill health--namely, investigator bias, respondent bias, and selection bias--were also considered and ruled out. CONCLUSION--Damp and mouldy living conditions have an adverse effect on symptomatic health, particularly among children.

Prevalence of symptoms of dyspepsia in the community.

Abstract: To study the prevalence of dyspepsia in the community a postal questionnaire was sent to 2697 patients who were selected at random from the lists of patients registered in two health centres in Hampshire. A total of 2066 returned questionnaires were suitable for analysis (response rate 77%). It was found that the six month prevalence of dyspepsia was 38%. There was considerable overlap between symptoms of heartburn and upper abdominal pain, with over half of patients with dyspepsia experiencing both. One in four of these patients had consulted their general practitioner during that time. The proportion of patients with dyspepsia who consulted their general practitioner varied widely among the eight doctors who participated in the study, from 17% to 45%. Frequency of symptoms tended to fall with age, particularly in men, while the proportion of patients with dyspepsia who sought medical advice increased with age. Almost one in five of the 2066 patients had been investigated with radiology or endoscopy at some time, and 143 (7%) of them claimed to have had a diagnosis of peptic ulcer.

Aspirin use and chronic diseases: a cohort study of the elderly.

Abstract: OBJECTIVE--To evaluate the associations between the use of aspirin and the incidences of cardiovascular diseases, cancers, and other chronic diseases. DESIGN--Postal questionnaire survey to elicit details of aspirin use. SETTING--Californian retirement community. SUBJECTS--All 22,781 residents of the community (white, affluent, and well educated) were sent a questionnaire that included questions on medical history and the use of drugs such as analgesics, laxatives, and vitamin supplements. In all 61% responded (13,987, 8881 women and 5106 men; median age 73). They formed the cohort that was followed up for 6 1/2 years using discharge summaries from three hospitals serving the area and death certificates from the health department. Only 13 respondents were lost to follow up but seemed not to have died. MAIN OUTCOME MEASURES--Incidences of cardiovascular diseases, cancers, gastrointestinal bleeding, ulcers, and cataracts were compared in participants who did and did not take aspirin daily. RESULTS--Age adjusted incidences were computed with an internal standard and five age groups. By 1 January 1988 there had been 25 incident cases of kidney cancer among all participants; 341 incident cases of stroke, 253 of acute myocardial infarction, 220 of ischaemic heart disease, and 317 of other heart disease were reported among respondents without a reported history of angina, myocardial infarction, or stroke. The incidence of kidney cancer was raised among those who took aspirin daily compared with those who did not take it, although the increase was significant only in men (relative risks = 6.3, 95% confidence interval 2.2 to 17, for men and 2.1, 0.53 to 8.5, for women). Those who took aspirin daily showed no increased risk of any other cancer, except colon cancer for both sexes combined (relative risk = 1.5, 1.1 to 2.2). The risk of acute myocardial infarction was reduced slightly among regular users of aspirin in men but not women. The risk of ischaemic heart disease was almost doubled in those who took aspirin daily compared with non-users (relative risks = 1.9, 1.1 to 3.1, for men and 1.7, 1.1 to 2.7, for women). Small, non-significant increased risks of stroke were observed in both sexes. CONCLUSION--The daily use of aspirin increased the risk of kidney cancer and ischaemic heart disease.

Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: results of a prospective study.

Abstract: OBJECTIVE: To determine the relative risk of developing endometrial neoplasia after treatment with oestrogens alone or in conjunction with progestogens. DESIGN: Prospective cohort follow up study, average observation period 5.7 years for each patient. To have a 90% chance of detecting a relative risk of 2.0 with 95% significance the study required 78,000 person years of observation. SETTING: Community based cohort. PATIENTS: Women aged over 35 who were prescribed non-contraceptive oestrogens in the Uppsala health care region during April 1977 to March 1980 were identified from pharmacy records. Of all prescriptions issued, 95% were identified. Patients from the cohort who developed endometrial neoplasia were identified from the cancer registry of the Uppsala health care region. Compliance, sociodemographic data, and lifetime exposures to oestrogen and cyclically added progestogen were assessed by questionnaire in a sample of the cohort. The final cohort consisted of 23,244 patients (133,373 person years). The prevalence of university education, oophorectomy, and hysterectomy was higher in the cohort than the general population; no other confounding factors were identified. MEASUREMENTS: The total number of person years was divided into exposure groups by inference from the data from the questionnaire. Compensation was made for the excess of hysterectomies. Specimens from all cases of endometrial neoplasia in the cohort and 90% of cases in the general population were studied blind histopathologically. Characteristics of treatment of all women who had endometrial neoplasia were assessed by questionnaire. Relative risks and 95% confidence intervals were calculated. RESULTS: Seventy four cases of carcinoma and 33 cases of premalignant lesions occurred in the cohort. The relative risk of endometrial carcinoma was 1.8 (95% confidence interval 1.1 to 3.2) after exposure to any oestrogen compound without progestogen for more than six years; 2.2 (1.2 to 4.4) after more than three years9 exposure to conjugated oestrogens without progestogen; and 2.7 (1.4 to 5.1) after more than three years9 exposure to oestradiol compounds without progestogen. When carcinoma and premalignant lesions were considered together the results were similar but the relative risk was higher. Risk of carcinoma did not increase when progestogens were cyclically added to oestrogens for the entire treatment period (relative risk 0.9 (0.4 to 2.0]. CONCLUSIONS: Use of oestrogens without progestogens is associated with a twofold to threefold increase in risk of endometrial neoplasia. Use of progestogens either removes this increased risk or delays its onset. A further follow up of the cohort is essential to analyse the risks with greater statistical power.

Effects on birth weight of smoking, alcohol, caffeine, socioeconomic factors, and psychosocial stress.

Abstract: OBJECTIVE--To investigate the effects of smoking, alcohol, and caffeine consumption and socio-economic factors and psychosocial stress on birth weight. DESIGN--Prospective population study. SETTING--District general hospital in inner London. PARTICIPANTS--A consecutive series of 1860 white women booking for delivery were approached. 136 Refused and 211 failed to complete the study for other reasons (moved, abortion, subsequent refusal), leaving a sample of 1513. Women who spoke no English, booked after 24 weeks, had insulin dependent diabetes, or had a multiple pregnancy were excluded. MEASUREMENTS--Data were obtained by research interviewers at booking (general health questionnaire, modified Paykel's interview, and Eysenck personality questionnaire) and at 17, 28, and 36 weeks' gestation and from the structured antenatal and obstetric record. Variables assessed included smoking, alcohol consumption, caffeine consumption, and over 40 indicators of socio-economic state and psychosocial stress, including social class, tenure of accommodations, education, employment, income, anxiety and depression, stressful life events, social stress, social support, personality, and attitudes to pregnancy. Birth weight was corrected for gestation and adjusted for maternal height, parity, and baby's sex. MAIN RESULTS--Smoking was the most important single factor (5% reduction in corrected birth weight). Passive smoking was not significant (0.5% reduction). After smoking was controlled for, alcohol had an effect only in smokers and the effects of caffeine became non-significant. Only four of the socioeconomic and stress factors significantly reduced birth weight and these effects became non-significant after smoking was controlled for. CONCLUSIONS--Social and psychological factors have little or no direct effect on birth weight corrected for gestational age (fetal growth), and the main environmental cause of its variation in this population was smoking.

Influence of past reproductive performance on risk of spontaneous abortion.

Abstract: OBJECTIVE--To investigate the incidence of spontaneous abortion in a population of women in order to establish their risk of spontaneous abortion and the obstetric factors predisposing to it. DESIGN--Prospective study of women recruited by radio and poster appeal and from hospital outpatient clinics. SETTING--English provincial community. PATIENTS--630 Women from the general population intending to become pregnant. INTERVENTIONS--The viability of the pregnancy was assessed by abdominal ultrasonography before completion of the eighth week, and the assessment was repeated if vaginal bleeding occurred. MAIN OUTCOME MEASURE--Spontaneous abortion or live births in women with or without a previous history of spontaneous abortion. RESULTS--The overall incidence of clinically recognisable spontaneous abortion before 20 weeks of gestation was 12% (50/407 pregnancies). The risk of spontaneous abortion in each category of patient was classified with respect to the patient's past reproductive performance and found to be influenced greatly by her previous obstetric history. In primigravidas and women with a history of consistently successful pregnancies the incidences of abortion were low (5% (4/87) and 4% (3/73) respectively), whereas women with only unsuccessful histories had a much greater risk of aborting the study pregnancy (24% (24/98)), even when their sole pregnancy had ended in abortion (20% (12/59)). The outcome of the last pregnancy also influenced the outcome of the study pregnancy; only 5% of women (5/95) whose previous pregnancy had been successful aborted, whereas the incidence of loss of pregnancy among women whose last pregnancy had aborted was 19% (40/214). CONCLUSIONS--A knowledge of the patient's reproductive history is essential for the clinical assessment of her risk of spontaneous abortion. As the most important predictive factor for spontaneous abortion is a previous abortion, the outcome of a woman's first pregnancy has profound consequences for all subsequent pregnancies.

Determinants of bone density in normal women: risk factors for future osteoporosis?

Abstract: Postmenopausal osteoporosis is an important public health problem in developed countries. Preventive treatment might effect a large reduction in the incidence, but this needs to be applied selectively to those women at increased risk. Loss of bone density results in an increased risk of fractures in the classical sites of vertebrae and proximal femur. A cross sectional study of bone density measurements was carried out in these sites in British women with a modern, precise densitometric technique. Possible predictors and risk factors for bone density were assessed in these women. Bone density was measured by dual photon absorptiometry in 284 apparently healthy women volunteers aged 21 to 68. The values obtained were similar to those obtained from equivalent studies performed in women in the United States. Peak adult bone density had been attained soon after the end of linear skeletal growth. Thereafter there was some decline with age in the proximal femur, but the major fall in bone density in all sites was related to the menopause. Other factors decreasing bone density, and hence increasing risk for osteoporosis, such as low body weight, alcohol and cigarette consumption, nulliparity, lack of previous use of oral contraceptives, and lack of regular exercise, seemed to be important. None, however, could predict satisfactorily women at future risk for osteoporosis. Direct measurements of bone density in the clinically relevant sites are necessary to determine which women should received preventive treatment for postmenopausal osteoporosis. This would help make such treatment more cost effective.

Calcium channel blockers in acute myocardial infarction and unstable angina: an overview.

Abstract: OBJECTIVE--To assess the effects of calcium channel blockers on development of infarcts, reinfarction, and mortality. DESIGN--A systematic overview of all randomised trials of calcium channel blockers in myocardial infarction and unstable angina. PATIENTS--19,000 Patients in 28 randomised trials. RESULTS--In the trials of myocardial infarction 873 deaths occurred among 8870 patients randomised to active treatment compared with 825 deaths among 8889 control patients (odds ratio of 1.06, 95% confidence interval of 0.96 to 1.18). There was no evidence of a beneficial effect on development and size of infarcts or rate of reinfarction. The results were similar in short term trials in which treatment was confined to the acute phase and those in which treatment was started some weeks later and continued for a year or two. There was no evidence of heterogeneity among different calcium channel blockers in their effects on any end point. The results were similar in the unstable angina trials (110 out of 561 patients treated with calcium channel blocker compared with 104 out of 548 controls developed a myocardial infarction; 14 out of 591 treated compared with nine out of 578 controls died). CONCLUSIONS--Calcium channel blockers do not reduce the risk of initial or recurrent infarction or death when given routinely to patients with acute myocardial infarction or unstable angina.

Lipid peroxides and atherosclerosis.

Abstract: Plasma lipid peroxide concentrations were measured in 100 patients with occlusive arterial disease proved angiographically (50 patients with ischaemic heart disease, 50 with peripheral arterial disease) and compared with values in 75 control patients with no clinical evidence of atherosclerosis. Lipid peroxide concentrations were significantly higher in patients both with ischaemic heart disease (median 4.37 mumol/l (interquartile range 3.85-5.75 mumol/l); p less than 0.001) and with peripheral arterial disease (median 4.37 mumol/l (3.88-5.21 mumol/l); p less than 0.001) than in controls (median 3.65 mumol/l (interquartile range 3.29-3.89 mumol/l). Overall there was a significant but weak correlation between plasma lipid peroxide and plasma triglyceride concentrations (rs = 0.25; p less than 0.001) but not between plasma lipid peroxide and plasma total cholesterol concentrations. Furthermore, hypertension, obesity, diabetes, smoking, positive family history, and intake of beta blockers and thiazide diuretics were not associated with significant differences in lipid peroxide values. This study provides clinical support to experimental data indicating that peroxidised lipids may be important in atherogenesis and its complications and also suggests that peroxidised lipids may provide an index of the severity of atherosclerosis.

Sensitivity to insulin during treatment with atenolol and metoprolol: a randomised, double blind study of effects on carbohydrate and lipoprotein metabolism in hypertensive patients.

Abstract: OBJECTIVE--To compare the effects of metoprolol and atenolol on carbohydrate and lipid metabolism and on insulin response to an intravenous glucose load. DESIGN--Randomised, double blind, double dummy, controlled crossover trial. SETTING--University Hospital, Uppsala, Sweden. PATIENTS--60 Patients with primary hypertension (diastolic blood pressure when resting supine 95-119 mm Hg on at least two occasions during four to six weeks of treatment with placebo) randomised to receive either metoprolol (n = 30) or atenolol (n = 30) during the first treatment period. INTERVENTIONS--Placebo was given for a run in period of four to six weeks. Metoprolol 100 mg twice daily or atenolol 25 mg twice daily was then given for 16 weeks. The two drugs were then exchanged and treatment continued for a further 16 weeks. END POINT--Evaluation of effects of treatment with metoprolol and atenolol on glucose, insulin, and lipid metabolism and glucose disposal mediated by insulin. MEASUREMENTS AND MAIN RESULTS--Reduction of blood pressure was similar and satisfactory during treatment with both drugs. Glucose uptake mediated by insulin was measured during a euglycaemic hyperinsulinaemic clamp to evaluate patients9 sensitivity to insulin. Glucose uptake decreased from 5.6 to 4.5 mg/kg/min when patients were taking metoprolol and from 5.6 to 4.9 mg/kg/min when they were taking atenolol. Both drugs caused a small increase in fasting plasma insulin and blood glucose concentrations and glycated haemoglobin concentration. Despite decreased sensitivity to insulin the increase in insulin concentration in response to an intravenous glucose tolerance test was small, suggesting inhibition of release of insulin. Very low density lipoprotein and low density lipoprotein triglyceride concentrations were increased with both drugs and high density lipoprotein cholesterol concentration was decreased. Low density lipoprotein cholesterol concentration was not affected. CONCLUSIONS--Long term use of metoprolol and atenolol causes metabolic abnormalities that may be related to the increased incidence of diabetes in patients with hypertension who are treated pharmacologically. These results may help to explain why the two drugs have failed consistently to reduce the incidence of coronary heart disease in several large scale studies.

Observer variation in histopathological diagnosis and grading of cervical intraepithelial neoplasia.

Abstract: To assess the variability among histopathologists in diagnosing and grading cervical intraepithelial neoplasia eight experienced histopathologists based at different hospitals examined the same set of 100 consecutive colposcopic cervical biopsy specimens and assigned them into one of six diagnostic categories. These were normal squamous epithelium, non-neoplastic squamous proliferations, cervical intraepithelial neoplasia grades I, II, and III, and other. The histopathologists were given currently accepted criteria for diagnosing and grading cervical intraepithelial neoplasia and asked to mark their degree of confidence about their decision on a visual linear analogue scale provided. The degree of agreement between the histopathologists was characterised by kappa statistics, which showed an overall poor agreement (unweighted kappa 0.358). Agreement between observers was excellent for invasive lesions, moderately good for cervical intraepithelial neoplasia grade III, and poor for cervical intraepithelial neoplasia grades I and II (unweighted kappa 0.832, 0.496, 0.172, and 0.175, respectively); the kappa value for all grades of cervical intraepithelial neoplasia taken together was 0.660. The most important source of disagreement lay in the distinction of reactive squamous proliferations from cervical intraepithelial neoplasia grade I. The histopathologists were confident in diagnosing cervical intraepithelial neoplasia grade III and invasive carcinoma (other) but not as confident in diagnosing cervical intraepithelial neoplasia grades I and II and glandular atypia (other). Experienced histopathologists show considerable interobserver variability in grading cervical intraepithelial neoplasia and more importantly in distinguishing between reactive squamous proliferations and cervical intraepithelial neoplasia grade I. It is suggested that the three grade division of cervical intraepithelial neoplasia should be abandoned and a borderline category introduced that entails follow up without treatment.

Risk factors for acute myocardial infarction in women: evidence from the Royal College of general practitioners' oral contraception study

Abstract: To determine the pattern of risk factors for acute myocardial infarction associated solely with women a nested case-control study was carried out on cohort data collected during the Royal College of General Practitioners' oral contraception study. Smoking (adjusted relative risk 1.7 for light smokers and 4.3 for heavy smokers), hypertension (2.4), toxaemia of pregnancy (2.8), and diabetes mellitus (6.9) were associated with a significantly increased risk of myocardial infarction. There was no significant trend of risk with social class. Current use of the pill increased the risk only among women who also smoked (relative risk 20.8 for heavy smokers). Previous use of the pill did not influence the risk of myocardial infarction. If heavy smokers also had a history of toxaemia of pregnancy their risk of myocardial infarction was further increased (relative risk 41.0). Other variables associated solely with women, such as parity, hysterectomy, and hormone replacement therapy, had little effect on the risk of having a myocardial infarction. Overall, smoking was the most important independent risk factor and had a strong influence on risks associated with other factors.

Breast feeding and lower respiratory tract illness in the first year of life.

Abstract: OBJECTIVE--To assess the relation between breast feeding and subsequent experience of lower respiratory tract illness. DESIGN--Prospective (from well child visits) and retrospective (from maternal recall) study of breast feeding and prospective assessment by paediatricians of lower respiratory tract illness in infants during first year of life. SETTING--Health maintenance organisation. PARTICIPANTS--Over 1000 infants who were healthy at birth and whose parents used the paediatricians of a local health maintenance organisation. MAIN OUTCOME MEASURES--Duration of breast feeding and type of lower respiratory tract illness (wheezing and non-wheezing) at different age intervals during the first year of life. RESULTS--Breast feeding was associated with a decreased incidence of wheezing illnesses only in the first four months of life. Interactions existed between breast feeding and sharing a room, being Mexican American, and being a boy. Multivariate techniques showed that after controlling for a variety of factors children who received minimal breast milk had a greater risk of early wheezing illnesses; the risk was further increased by simultaneous exposure to sharing a room. CONCLUSION--Breast feeding seems to protect against wheezing respiratory tract illnesses in the first four months of life, particularly when other risk factors are present.

Transvaginal colour flow imaging: a possible new screening technique for ovarian cancer.

Abstract: OBJECTIVE--To assess whether changes in the intraovarian vasculature or blood flow impedance can be used to identify potentially malignant masses. DESIGN--Open, non-comparative prospective study. SETTING--Ovarian screening clinics at King's College Hospital and the Hallam Medical Centre. SUBJECTS--50 Women selected on the basis of their medical history and the result of a previous transvaginal ultrasound scan. Thirty women (10 premenopausal (scan taken on days 1 to 8 of the menstrual cycle) and 20 postmenopausal) had normal ovaries, and 20 had at least one ovary with an abnormal morphology or volume, or both. INTERVENTIONS--Women with a positive result on screening were referred for laparotomy. MAIN OUTCOME MEASURES--Presence or absence of coloured areas (neovascularisation) and the pulsatility index within each ovary. The pulsatility index is a measure of the impedance to blood flow, a low value indicating decreased impedance and a high value increased impedance to blood flow. RESULTS--Two women with a positive result on screening had hydrosalpinges, 10 a benign tumour or a tumour-like condition, and eight primary ovarian cancers. No areas of neovascularisation were seen in the 30 women with morphologically normal ovaries and the two patients with hydrosalpinges; the pulsatility index ranged from 3.1 to 9.4. Similarly, nine patients (10 affected ovaries) with a non-malignant mass had no signs of neovascularisation and the pulsatility index varied from 3.2 to 7.0. One patient with bilateral dermoid cysts containing nests of thyroid-like cells had vascular changes and pulsatility index values of 0.4 and 0.8. Seven patients (eight ovaries) with primary ovarian cancer (one stage IV, four stage II, and two stage Ia) showed clear evidence of neovascularisation and pulsatility index values were from 0.3 to 1.0. One patient with an intraepithelial serous cystadenocarcinoma in a small ovary (less than 5 ml volume) had no signs of any vascular change and the pulsatility index was 5.5. CONCLUSION--Transvaginal colour flow imaging may be used to identify potentially malignant ovarian masses and help elucidate the early stages of tumorigenesis. The routine application of this technique may reduce the rate of false positive results of an ultrasonography based screening procedure.

Non-melanoma skin cancer.

Abstract: Multistep carcinogenesis: The transformation of normal to neoplastic cells is a process which lasts many years and takes place in a number of steps. Of these steps, many but not all are currently understood. Furthermore, exactly which steps need to take place in order to generate a certain type of tumor is even more unclear. According to our current understanding, the multistep carcinogenesis comprises the following stages.

Dietary calcium, physical activity, and risk of hip fracture: a prospective study.

Abstract: OBJECTIVE--To determine whether low dietary calcium intake and physical inactivity are risk factors for hip fracture among subjects aged 65 and over. DESIGN--Fifteen year follow up study of a large cohort of randomly selected elderly people living in the community, who had taken part in the 1973-4 survey of the Department of Health and Social Security, and for whom dietary and other data were recorded at initial interview and medical assessment. SETTING--Eight areas in Britain (England (five), Wales (one), and Scotland (two]. SUBJECTS--1688 Subjects living in the community, of whom 1419 subjects (720 men and 699 women) agreed to participate. 1356 Subjects completed a seven day dietary record and 983 (542 men and 441 women) agreed to be assessed by a geriatrician. RESULTS--Incidence of hip fracture increased with age and was higher in women than men. Comparison with matched controls showed no evidence that the risk of hip fracture was related to calcium intake: the odds ratio for the lowest third of dietary calcium compared with the highest was 0.7 (95% confidence interval 0.1 to 3.9) after adjustment for smoking and body mass index. The adjusted odds ratio for the lowest third of outdoor activity compared with the highest was 4.3 (0.7 to 26.8), and that for grip strength was 3.9 (0.7 to 23.0). CONCLUSIONS--Reduced intake of dietary calcium does not seem to be a risk factor for hip fracture. Further evidence is provided that physical activity in the elderly protects against hip fracture.

The polymerase chain reaction: a new epidemiological tool for investigating cervical human papillomavirus infection.

Abstract: The polymerase chain reaction is an in vitro method for primer directed enzymatic amplification of specific target DNA sequences. The technique was used to detect human papillomavirus types 11 and 16 simultaneously in cellular DNA recovered from cervical smears in 38 women referred for colposcopy to evaluate cytological abnormality and 10 women with no history of cytological abnormality. The polymerase chain reaction was shown to be both specific and sensitive in detecting human papillomavirus DNA such that a single human papillomavirus molecule was detected in 10(5) cells. Of the 38 women with cytological abnormality, all were positive for human papillomavirus on testing with the polymerase chain reaction; 36 were infected with human papillomavirus type 16 and 22 dually infected with human papillomavirus types 11 and 16. Seven of the 10 women with no cytological abnormality were also infected with human papillomavirus type 11 or 16. The use of the polymerase chain reaction will facilitate epidemiological investigation of the aetiological role of human papillomavirus in cervical neoplasia. This preliminary analysis suggests that the prevalence of human papillomavirus infection is greater than previously reported.

Transabdominal ultrasound screening for early ovarian cancer.

Abstract: OBJECTIVE--To assess the value of ultrasonography in a screening procedure for early ovarian cancer. DESIGN--Prospective study of at least 5000 self referred women without symptoms of ovarian cancer. Each woman was scheduled to undergo three annual screenings (consisting of one or more scans) to detect grossly abnormal ovaries or non-regressing masses. SETTING--The ovarian screening clinic at King9s College Hospital, London. SUBJECTS--5479 Self referred women without symptoms (aged 18-78, mean age 52). INTERVENTIONS--Women with a positive result on screening were referred for laparoscopy or laparotomy, or both. MAIN OUTCOME MEASURES--Findings at surgery and from histology of abnormal ovaries. RESULTS--A total of 14,594 screenings (15,977 scans) were performed. A positive result was obtained at 338 screens (2.3%) comprising 326 subjects (5.9%). Five patients with primary ovarian cancer (four stage Ia, one stage Ib; two at first screening three at second) were identified (prevalence 0.09%). An additional four patients had metastatic ovarian cancer (three at first screening, one at second). The apparent detection rate was 100%. It was not possible to differentiate between the ultrasonic appearance of early malignant and benign tumours. The rate of false positive results for primary ovarian cancer was 3.5% at the first screening, 1.8% at the second, and 1.2% at the third. Overall the rate of false positive results was 2.3%; the specificity was 97.7% and the predictive value of a positive result on screening was 1.5%. The odds that a positive result on screening indicated the presence of an ovarian tumour, any ovarian cancer, or primary ovarian cancer were about one to two, one to 37, and one to 67 respectively. CONCLUSION--Ultrasonography can be used to screen women without symptoms for persistent ovarian masses that will include early ovarian cancer.