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1. The effects of antihypertensive drugs on lipids may also influence their effect on coronary artery disease (CAD). However, the clinical significance of these effects and the extent to which they persist during long-term therapy is uncertain. 2. We performed a meta-analysis on 23 randomized trials published between 1988 and 1994 that compared the effects of atenolol, celiprolol (a beta-blocker with beta 2-adrenoceptor intrinsic sympathomimetic activity), enalapril, nifedipine and doxazosin on plasma cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides and blood pressure (BP). 3. Predicted changes in CAD risk were calculated by incorporating the results for these parameters into the Framingham equations. 4. While there were no differences in antihypertensive efficacy between the drugs, atenolol significantly (P < 0.05) reduced HDL-C and increased total cholesterol, LDL-C and triglycerides compared with celiprolol, enalapril, doxazosin and nifedipine. 5. The magnitude of the effects on lipids was not significantly influenced by the duration of therapy (up to 3 years for atenolol and doxazosin and up to 2 years for celiprolol). 6. The improvement in Framingham equation point scores (systolic BP formula) was significantly (P < 0.05) less for atenolol (-0.54; confidence intervals (CI) -0.29-(-0.78)) than for celiprolol (-1.69; CI -0.68-2.70), doxazosin (-1.67; CI -1.11-(-2.23)), enalapril (-1.43; CI 0.23-(-3.07)) and nifedipine (-1.91; CI -1.22-(-2.59)). Similar results were obtained for the Framingham diastolic BP formula. 7. These results suggest that the adverse effects of atenolol ]on plasma lipids do not improve with prolonged therapy and are theoretically great enough to reduce its efficacy in reducing CAD by approximately two thirds compared with antihypertensive drugs that do not adversely affect plasma lipids. However it must be emphasized that these are theoretical effects. In order to determine the actual differences between these drugs on CAD end points, studies using these end points are required.

The elderly (age > 65 years) are more vulnerable to side-effects induced by non-steroidal anti-inflammatory drugs (NSAIDs). We therefore performed a double-blind comparative study of ketoprofen SR and sulindac in patients with active rheumatoid arthritis, 65 years of age or older. Sulindac was chosen because of its possible renal sparing effects, and ketoprofen SR because of its short half life and sustained release delivery system. Eighty patients were entered. More patients withdrew from the study due to side-effects in the sulindac group; both treatment groups had a high incidence of side-effects during this study and during previous exposure to other NSAIDs, demonstrating that the elderly are susceptible to side-effects from NSAIDs.

A retrospective review of 1900 road accident victims attending the emergency departments of two Melbourne hospitals was undertaken to identify Injury Severity Score levels which could distinguish between minor, moderate, severe and critical injury. Injuries scoring ISS 6 or below were designated 'minor' because they were associated with a low risk of requiring admission to hospital. Case notes of patients scoring above ISS 6 were then reviewed by a panel of clinicians, who independently rated each patient's overall injury severity as moderate, severe or critical according to what was recorded in the notes and their 'clinical' judgement. ISS values were compared with clinicians' ratings. Measures of each clinician's individual rating consistency, and correlation between pairs of clinicians with respect to inter-rater consistency, were made. By combining data from both hospitals it emerged that 'moderate' injury corresponded to ISS 8-13, 'severe' to ISS 14-20 and 'critical' to ISS 21 and above. These ISS breakpoints will be useful in selecting groups of injured patients for future trauma audit studies.

Sixteen patients who had essential hypertension were stabilized on either captopril or enalapril monotherapy and had 24-hour blood pressure profiles monitored by using one of two automatic, non-invasive ambulatory systems: Spacelabs 5300 (Squibb, Princeton, NJ) or PAR Physioport II (Kardiotec, Mannheim). In four subjects (group 1), ambulatory pressures were repeated 4 to 6 weeks later using the same equipment and the same drug. In four subjects (group 2), the drug was changed (dose ratio: captopril:enalapril, 5:1) after the first measurement, but the monitoring equipment was not changed. In four subjects (group 3), the drug was constant, but the equipment was changed for the second measurement of ambulatory pressure. In four subjects (group 4), both drug and equipment were reversed after the first measurement. The results showed that both drugs (given once daily) controlled blood pressure during the 24-hour period, with no clinically significant difference between them.

Over a five-year period, from 1976 to 1981, hormone-receptor assays were performed in breast cancer specimens from 1868 women and 10 men. Oestrogen, progesterone, and androgen receptor results were distributed from zero to high levels without any clear separation into identifiable groups, which suggests that the division of results into negative and positive is an arbitrary one. The number of positive results increased significantly during the course of the study, probably due to improved tissue handling and increasing experience with assays. Over-all results showed that 61% of primary breast cancers in women compared with only 49% of secondary cancers gave positive results for oestrogen receptor. The incidence of progesterone and androgen receptors was also higher in primary cancers than in secondary cancers. In women with primary cancers, 72% of cancers were women with primary cancers, 72% of cancers were oestrogen-receptor positive in women after menopause, whereas in those before menopause only 48% were positive. Oestrogen receptor was detected in nine out of 10 male breast cancers.

Generally, recent reports on the side effects of estrogen therapy for prostatic cancer have concerned mortality statistics, relatively little attention having been paid to the quality of life of individual patients. We herein propose an assessment of treatment regimens based on the concept of the time during which a patient remains free of tumor progression or serious side effects. A particular regimen has been examined in relation to the hormonal effects of endocrine ablation, and to the dosage and type of estrogen therapy used in 59 men with prostatic cancer. Although no significant difference among treatment methods has emerged in this small group (except for the more frequent occurrence of fluid retention with the stilbestrol dosage, 30 versus 15 mg. per day) and no correlation between the degree of testosterone suppression and length of remission has emerged so far, this method of assessment proved useful and should be applicable widely. It was confirmed that gonadotropin levels remained in the normal range in patients whose testosterone levels were suppressed with chlorotrianisene.

The clinical features and hormonal abnormalities were surveyed in 117 men with cirrhosis of the liver. Compared with healthy men of similar ages, the patients had significantly lower metabolic clearance rates, plasma production rates and total and free levels of testosterone, reduced testosterone responses to human chorionic gonadotrophin stimulation, higher oestradiol, luteinizing hormone and follicle stimulating hormone levels and higher binding capacities of sex steroid binding globulin. The peripheral conversion of testosterone to oestradiol was also found to be significantly increased. However, the metabolic clearance and plasma production rates of oestradiol were not significantly different from those of healthy men. Patients who were severely ill with liver failure and one with haemochromatosis had low levels of luteinizing hormone and follicle stimulating hormone and sub-normal responses to clomiphene and luteinizing hormone-releasing hormone. Higher plasma oestradiol levels were found in patients with gynaecomastia and spider naevi than in those without these signs. However, the clinical features of androgen deficiency--that is, testicular atrophy, impotence and loss of secondary sex hair--were only poorly related to the low testosterone levels, and production rates and longtitudinal studies indicated that the hormonal levels, endocrine features and severity of the liver disease could change independently. It is concluded that the clearance of oestradiol from plasma is not limited by liver disease in all patients, and that reduced degradation of oestrogens is not the initial event in the sequence leading to the hormonal abnormalities of cirrhosis. While gonadotrophin deficiency occurs with liver failure and in some patients with haemochromatosis, the more usual findings are of elevated gonadotrophin levels and a poor Leydig cell response to chorionic gonadotrophin. These suggest that the hypogonadism is primary in most patients with cirrhosis. The causes of the high oestradiol levels were not discovered. Increased peripheral conversion of precursors to oestradiol or increased testicular secretion of oestradiol are possibilities. The high binding capacities of sex steroid binding globulin were not significantly correlated with either the low testosterone or high oestradiol level and the cause of this abnormality remains uncertain. The low metabolic clearance rates of testosterone appeared to result from the increased plasma protein binding of testosterone. The discrepancies in the expected relationships between the hormone and clinical changes suggest that factors other than those studied are also involved in the genesis of the endocrine features of hepatic cirrhosis.

Survival data for 2006 women who had oestrogen receptor assay carried out on primary breast cancer tissue between 1976 and 1982 are presented. There was a significant trend to shorter survival in patients with low ER levels than in those with high ER levels (P less than 0.01). This trend was evident in both pre- and post-menopausal women. The point of maximum discrimination between prognostic groups occurred at 8 fm in premenopausal women and the four year survival rates of patients above and below this level were 84% and 48%, respectively. In post-menopausal women, maximum discrimination occurred at 90 fm, and the four year survival rates above and below this level were 82% and 64%, respectively.

Serum levels of the acid-ethanol soluble component of non-suppressible insulin-like activity (NSILA-S) have been measured by bioassay in patient with hyperprolactinaemia, hypothyroidism, thyrotoxicosis and diabetes mellitus, and in normal subjects administered prednisone, oestrogens of androgens. Hyperprolactinaemia per se did not influence serum NSILA-S, however when GH was deficient prolactin hypersecretion may have maintained serum NSILA-S. Thyroid hormones, insulin and steroids did not appear to influence serum NSILA-S. These results suggest that regulation of the serum concentration of NSILA-S is not a common effector mechanism by which these hormones influence statural growth in man.

Urinary oestrogen and pregnanediol excretion was measued daily ("daily monitoring") for a complete cycle in 20 normally menstruating women, in one patient with an anovulatory cycle and for 28 days in a patient with secondary amenorrhoea. The measurements were also performed on urine specimens collected at weekly intervals for 4 to 6 weeks ("weekly tracking") from 506 patients with evidence of abnormal ovarian function. These included 9 patients with primary amenorrhoea, 132 patients with secondary amenorrheoa, 138 patients with oligomenorrhoea and 227 patients with evidence of ovarian dysfunction and cycle lengths of 25 to 42 days. The results were subjected to statistical analysis. In the normal cycles, ovulation could be identified on the criteria of a rising pregnanediol value reaching or exceeding 2-0 mg. per 24 hours for a period of 7 days or more. Valid conclusions on the overall mean oestrogen and pregnanediol values for a complete cycle could be made from the results of weekly tracking, irrespective of which day the tracking commenced. Correlations were obtained by comparing the mean and maximum urinary oestrogen values and the variability of the values with the evidence of ovarian function indicated by the clinical classifications of the patients, the duration of the disorders and the subsequent occurrence of uterine bleeding. Mean oestrogen values of 10 mug. per 24 hours or less were associated with lack of ovarian function. For values higher than this a discriminant function based on both the mean oestrogen value and the variability of the oestrogen values was useful in predicting onset of spontaneous menstruation. A single urine specimen collected 4 to 8 days before onset of menstruation showing a raised pregnanediol value of 2-0 mg. per 24 hours or more provided a valid test for ovulation in women with regular cycles, and a single urine specimen giving an oestrogen value of 10 mug per 24 hours or less gave a valid indication of absent ovarian function in women with amenorrhoea for two years or more. In all other circumstances serial sampling at weekly intervals provided a valid assessment of ovarian activity. Application of these principles allows the greatest amount of information on ovarian function to be obtained with the greatest economy of effort.

Relationships between 51Cr platelet survival and plasma concentrations of beta-thromboglobulin (betaTG) and platelet factor 4 (PF4) were analyzed in 91 studies of patients with coronary artery disease. betaTG was significantly correlated with platelet life-span, turnover, and the number of hits in the multiple hit model. PF4 was significantly correlated with life-span and turnover. The most significant relationship involving platelet-specific protein concentrations and life-span estimates was between betaTG and life-span estimated using the multiple hit model (r = -0.39, p less than 0.001). There was a high correlation between betaTG and PF4 (r = 0.62, p less than 0.001), and no improvement could be obtained by combining the measurements of the two proteins in any regression with life-span or turnover. The results indicate that the patients with the shortest platelet survival time in this group tended to have the highest plasma concentration of betaTG and PF4 and thus probably increased in vivo release of betaTG and PF4. They strengthen the claim that these platelet-specific proteins may be indicators of platelet involvement in disease.

Although episodes of FSH values were similar in subjects with secondary amenorrhoea and oligomenorrhoea, but patients with oligomenorrhoea had significantly higher plasma LH secretion in four normal, fourteen anovulatory and one postmenopausal woman were confirmed by samples taken every 15 minutes for three hours, single plasma samples invariably provided a valid estimate of the current mean plasma FSH level, and of the current mean plasma LH level during the follicular phase of the ovulatory menstrual cycle and in anovulatory women with a mean plasma LH value of less than 0-8 mIU/ml. If the mean plasma LH value in anovulatory women exceeded 0-8 mIU/ml, the maximum difference between single and mean values was 28-3+/-4-7 per cent for four patients with oligomenorrhoea and 43-4+/-5-2 per cent for five patients with secondary amenorrhoea. Single plasma samples were collected from 26 patients with primary amenorrhoea, 95 patients with secondary amenorrhoea, 51 patients with oligomenorrhoea and 33 postmenopausal patients not on replacement therapy. In each group there were subjects with plasma FSH values in the postmenopausal range and they were unlikely to respond to ovulation induction. Those patients aside, plasma FSH values were similar in subjects with secondary amenorrhoea and oligomenorrhoea, but patients with oligomenorrhoea had significantly higher plasma LH values (p less than 0-001); mean levels of neither FSH nor LH showed a significant correlation with response to treatment with clomiphene but in patients with secondary amenorrhoea an ovulatory response to clomiphene did not occur unless the individual's plasma FSH value was in excess of 1-4 mIU/ml. In patients with oligomenorrhoea, plasma LH levels below 0-8 mIU/ml precluded successful treatment with clomiphene.

Unlabelled: Infertile men who had 3 or more semen analyses performed in one laboratory were placed in 2 groups (I) oligozoospermic group (n = 106), mean sperm concentration between 1 and 20 million/ml (II) asthenozoospermic group (n = 71), mean sperm concentration greater than 20 million/ml, and mean motility less than 60%. With increasing durations of abstinence from ejaculation before the tests there were significant increases in semen volume and sperm concentration. Semen volume increased over the first 4 days to a similar extent in both groups. Sperm concentrations increased over 15 days, but the effect of abstinence was much greater in the asthenozoospermic group than in the oligozoospermic group (14% compared with 1.4% of the within subject variation). Significant changes in results accompanied repeated testing, notably rises in sperm concentration and motility. Sperm motility was lower in winter and higher in summer in both groups and also, but to a lesser extent, in artificial insemination donors who collected semen in the laboratory., Conclusions: duration of abstinence, the elapse of time and seasonal temperature changes affect semen analysis results, and therefore controls for these variables must be incorporated in any therapeutic trial for male infertility. On the other hand, they only account for a small proportion of the total variability and thus routine correction of results would not greatly improve the value of semen analysis in the prediction of fertility. Furthermore because differences in the duration of abstinence have only a small effect on sperm concentration in oligozoospermic men, restricting sexual intercourse to the time of ovulation may not enhance fertility.

One hundred women underwent a 10-week sequential double-blind/crossover to compare conjugated equine oestrogen (Premarin, 0.625 mg and 1.25 mg) with one and two placebo tablets in the management of menopausal symptoms. Sixty-one subjects completed each of in the four regimens. Thirty-one of these continued with their own choice of regimen for a further nine months. Premarin 1.25 mg proved to be significantly more effective (P less than 0.01) in ameliorating menopausal symptoms than Premarin 0.625 mg and both levels of placebo. Premarin 1.25 mg was also preferred as the treatment of choice by the 31 women (P less than 0.001).

The effects on the serum levels of NSILA-S of the administration of human GH (hGH) or of hypophysectomy have been studied. hGH given im (5 mg daily for 3 days) raised the NSILA-S levels of three GH-deficient subjects into the normal range. Significant elevations of NSILA-S were also seen in three normal subjects given im GH. In the same groups of three normal and three GH-deficient subjects, 5 mg hGH administered iv induced an elevation of NSILA-S within 15-60 min. Hypophysectomy in three acromegalics and one subject with a chromophobe adenoma was followed by significant falls of serum NSILA-S. These studies provide further evidence of the dependence of NSILA-S levels on GH.

Eighty-one women who had received hormonal therapy for advanced disease were assessed for objective response to treatment. Another 73 patients who had received chemotherapy were similarly studied. Patients with ER - tumours had a significantly poorer response rate to hormonal therapy than those with ER + tumours (P less than 0.05) and a significant trend toward an increasing rate of response occurred with increasing quantitative levels of receptor (P less than 0.01). This trend was even more significant when the assay had been performed on recurrent tumour (P less than 0.001), suggesting that this provides a more accurate index of response to hormonal treatment than assays performed on the primary lesion. These results suggest that whilst the quantitative receptor level used to discriminate between 'negative' or 'positive' assays is appropriate, this division is an over-simplification. Oestrogen receptor was not helpful in predicting response to chemotherapy.

Sixty-six women who had received hormonal therapy for advanced disease were assessed for objective response to treatment. Another 51 patients who had received chemotherapy were similarly studied. Progesterone receptor was of no value as a predictor of patients unlikely to respond to hormone therapy, though it may have a role in predicting patients likely to respond favourably. The addition of progesterone receptor data to oestrogen receptor data may increase prediction of response in the ER+ range but clinicians should be cautious in their interpretation of progesterone receptor results in the ER- range. Progesterone receptor was of no value in predicting response to chemotherapy in this series. Analysis of survival data of 1731 women with primary breast cancer showed a highly significant trend toward longer survival in patients with progesterone receptor positive tumours than in those with receptor negative tumours (P less than 0.001). This trend was evident in both pre- and post-menopausal women. Even though the prognostic discrimination provided by progesterone receptor was correlated with that of oestrogen receptor, the addition of progesterone receptor data to oestrogen receptor data significantly improved prediction of survival (P less than 0.05).

The association between infertility and occupational group was examined using information collected from 1695 male patients. Although lack of detail in the nine occupational classifications may have diluted effects, mean sperm concentrations were significantly different, being highest in administrative and professional groups and lowest in farming and transport groups. Reported exposures to heat and chemicals were also significantly different between occupations. Greater occupational exposure to toxins may contribute to lower sperm concentrations in some groups such as farmers. More detailed research is needed to elucidate the association between occupation and infertility in men.

A longitudinal study of serum NSILA-S during normal human pregnancy and the puerperium has demonstrated that levels rose progressively during pregnancy and returned to nonpregnant values about 48 h after delivery. Low concentrations were defined within the feto-placental circulation at term. Cord arterial and venous levels were equivalent, but there was no significant correlation between these and matched maternal values.