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Previous studies of the maturation of periodic breathing cycle duration (PCD) with postnatal age in infants have yielded conflicting results. PCD is reported to fall in term infants over the first 6 mo postnatally, whereas in preterm infants PCD is reported either not to change or to fall. Contrary to measured values, use of a theoretical respiratory control model predicts PCD should increase with postnatal age. We re-examined this issue in a longitudinal study of 17 term and 22 preterm infants. PCD decreased exponentially from birth in both groups, reaching a plateau between 4 and 6 mo of age. In preterm infants, PCD fell from a mean of 18.3 s to 9.8 s [95% confidence interval (CI) is +/- 3.2 s]. In term infants, PCD fell from 15.4 s to 10.1 s (95% CI is +/- 3.1 s). The higher PCD at birth in preterm infants, and the similar PCD value at 6 mo in the two groups, suggest a more rapid maturation of PCD in preterm infants. This study confirms that PCD declines after birth. The disagreement between our data and theoretical predictions of PCD may point to important differences between the respiratory controller of the infant and adult.

The clinical value of lymph node immunohistochemistry was assessed in 343 consecutive patients with apparently node-negative breast cancer using antimucin monoclonal antibodies BC2, BC3 and 3E1.2. Occult metastases were detected in 41 patients (12 per cent). Although most of these were micrometastatic (< 2 mm in diameter), larger or diffuse deposits were found in ten patients. Blind assessment of repeat haematoxylin and eosin stained sections detected metastases in ten of the 41 patients with occult metastases. After a median follow-up of 79 months, patients with occult metastases had a shorter time to disease recurrence (P < 0.05) but not to death. After adjustment for other prognostic factors, the presence of occult metastases in two or more nodes was the most significant predictor of both disease recurrence (P < 0.01) and death (P < 0.01). When the ten patients with positive haematoxylin and eosin sections were excluded from the analysis, the presence of occult metastases in two or more nodes was still associated with a reduced disease-free interval (P < 0.05) and survival (P < 0.05). Lymph node immunohistochemistry is a simple technique affording more accurate definition of nodal involvement than conventional methods.

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.

Sixty-five patients with operable breast cancer were studied to assess the reliability of immunocytochemical analysis of oestrogen receptor (ER-ICA) in specimens obtained by percutaneous fine needle aspiration. Results obtained with the commercially available ER-ICA kit were compared with those obtained by the routine biochemical radioligand assay of oestrogen receptor (ER) on excised tumour specimens. Fifty-two of 65 percutaneous aspirates were evaluable. Of these, thirty-five (67%) were ER positive by the radioligand method. ER-ICA was found to be a reliable method for oestrogen receptor assay, with a high concordance (90.4%) between it and the radioligand essay. The ER-ICA assay had a sensitivity of 89%, specificity of 94%, positive predictive value of 97% and negative predictive value of 80%. ER-ICA assay performed on material obtained by fine-needle aspiration is a reliable method of ER assay. It can replace formal biopsy for patients with inoperable primary tumours or accessible metastases.

Androgen receptor assays have been performed on 1371 specimens of histologically confirmed primary and recurrent breast cancer. Forty-two patients who had received tamoxifen as treatment for advanced disease were assessed for objective response. Another 42 patients who had received chemotherapy were similarly studied. Patients with androgen receptor-negative tumors had a significantly poorer response rate to hormone therapy than those with receptor-positive tumors (P less than 0.05). This clinical correlation is supported by survival data of 1181 patients with primary breast cancer which showed that patients with androgen receptor-negative tumors had a highly significant trend toward shorter overall survival than those with receptor-positive tumors (P less than 0.001). Androgen receptor data added significantly to the information provided by estrogen receptor data both in terms of response to hormone treatment and survival.

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.

The validation of a prognostic index for patients with primary breast cancer is described. The actual survival data in a group of 383 patients was compared with expected survival predicted by an index based on axillary lymph node status, oestrogen receptor, progesterone receptor and age. There was no significant difference between actual and predicted deaths for five ranges of index value at 2 years and for the three highest ranges of index value at 5 years. However, in the two lowest ranges, the index significantly underpredicted deaths at 5 years. The Cox proportional hazards model was used to determine if there was any significantly better combination of coefficients and covariates to predict survival in the test group. The original index--1 = N + E + P + A, where N = 0 if no nodes are involved, 13 if one to three nodes are involved, and 31 if more than three nodes are involved; E = 15 if oestrogen receptor value is less than 10 fmol/mg cytosol protein and 0 otherwise; P = 12.5 if progesterone receptor value is less than 10 fmol/mg cytosol protein and 0 otherwise; and A = number of years over age 65--was as good as any competing model in ranking survival prospects in the test group. However, it was a less sensitive predictor in this group than in the original set of patients. A second index based on tumour size, hormone receptor status and age, for use when lymph node status was unavailable, was tested by the same method and validated.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet survival and plasma concentrations of beta thromboglobulin and platelet factor 4 were measured in 44 patients before and 6 months after coronary artery bypass grafting. Postoperatively, patients were randomized to receive sulfinpyrazone, 800 mg/day, or placebo. Preoperatively, platelet survival was significantly shorter than normal, and plasma concentrations of both platelet-specific proteins were significantly elevated. Postoperatively, all three indexes of platelet function tended to become normal, but these changes were statistically significant only in patients treated with sulfinpyrazone. Postoperative exercise testing correlated significantly with plasma concentrations of beta thromboglobulin and platelet factor 4 measured preoperative and postoperative. These results are consistent with reports of the effects of sulfinpyrazine on platelet involvement in other conditions, and suggest that the drug reduces platelet activation and inhibits actual destruction. The results also show a relationship between abnormalities of platelet function and an index of postoperative myocardial ischemia.

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.

A practical bioassay for the acid-ethanol soluble non-suppressible insulin-like activity (NSILA-S) of individual serum samples has been developed utilizing the incorporation of 14C-glucose into the lipid faction of isolated adipocytes. NSILA-S activity was correlated with somatotropin status. Thus, the mean potencies (+/-SD) relative to an extract of pooled normal human serum were: normal samples 1.11 +/- 0.14, acromegalic 2.91 +/- 0.72, and somatotropin deficient 0.13 +/- 0.06. This variation in NSILA-S was not due to variability in extraction recoveries. The within assay precision was 9% (coefficient of variation) and the between assay 23%. This method allows the simultaneous extraction and processing of relatively large numbers of samples, and compares favorably with other more complex methods. Because of the evidence that NSILA-S may be related to the somatomedins, the present method should provide a simpler and more reliable alternative to the cartilage bioassays used to measure somatomedin activity.

Streptozotocin-diabetic rats suffered growth failure and had reduced serum levels of the acid--ethanol soluble component of non-suppressible insulin-like activity (NSILA-S) compared with normal rats. Chronic insulin substitution (6 weeks) resulted in a normalization of serum levels of NSILA-S; this was accompanied by a normal increase in weight. Insulin therapy for 3 days resulted in a partial recovery of serum levels of NSILA-S and a slight but significant accompanying gain in weight. Short-term administration of GH also resulted in a partial recovery of the serum level of NSILA-S, in spite of continued uncontrolled diabetes. These results demonstrate that, in the rat, insulin as well as GH contributes to the regulation of serum levels of NSILA-S.

We studied the karyotype in 81 consecutively diagnosed children with acute lymphocytic leukemia (ALL) treated at one institution on a randomized treatment protocol. In 75 patients (93%), a morphological cytogenetic result was obtained, and 57 (65%) were successfully G-banded. Of the 75 patients, 46 (61%) showed abnormal chromosomes, mainly hyperdiploidy and pseudodiploidy, and 29 had no detectable abnormality. Our findings confirmed that the karyotype has prognostic significance. Duration of complete remission was 93% at 42 months for patients with high hyperdiploidy (greater than 50). For patients with an apparently normal karyotype, it was 58%; and for patients with structural abnormalities it was 15%. The significance of these findings was confirmed by multivariate analysis, which showed age and karyotype to be the most important determinants of duration of remission.

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.

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).

In order to provide a comprehensive account of pituitary-testicular function in man, 466 subjects, ranging in age from 2 to 101 years, were studied to examine blood levels of the pituitary gonadotrophins (LH and FSH), the sex steroids testosterone and oestradiol, the binding capacity of the sex hormone binding globulin (SHBG), the free testosterone and oestradiol fractions, and the transfer constant for the peripheral conversion of testosterone to oestradiol. The results were compared with clinical indices of testicular size, sexual function and secondary sex hair distribution. Serum LH and FSH were low before puberty, increased in pubertal adolescents to levels somewhat above those of adults and subsequently increased progressively over the age of 40 years. Testosterone levels fell slowly after the age of 40, while there was a slight rise in plasma oestradiol with increasing age. FSH and testosterone showed small seasonal variations in young adult men, the lowest values being seen in winter. SHBG binding capacity was high in two prepubertal boys, fell in adult men, but increased in old age. Free testosterone and oestradiol levels fell in old age. The metabolic clearance rates (MCR) of testosterone and oestradiol also fell in old age, while the conversion of testosterone to oestradiol was increased. Many correlations were observed between various hormonal and clincial measurements. The evidence is consistent with a primary decrease in testicular function over the age of 40 years.

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.

Pregnancy rates in 651 subfertile couples in which the man had a varicocele were analysed by life table methods and were not found to be significantly different before and after testicular vein ligation performed in 283 patients. Estimated proportions of couples conceiving were roughly 30% by one year and 45% by two years in both groups. The operation was also not associated with improvement in results of semen analysis. These findings suggest that testicular vein ligation for varicoceles does not improve fertility.

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).

We conducted a double-blind crossover study to determine which patient characteristics best predict a beneficial response to combined insulin-glyburide therapy. Glyburide (15 mg/day) or placebo was added to the treatment regimen of 31 insulin-treated type II (non-insulin-dependent) diabetic subjects. During glyburide therapy, there was a significant improvement in glycemic control with a reduction in glycosylated hemoglobin from 9.9 +/- 1.3 to 9.1 +/- 1.3% (P less than .001). Patients who responded had higher fasting C-peptide levels (P less than .001) and shorter durations of insulin therapy (P less than .01) than those who did not respond. Glyburide withdrawal was associated with a greater than expected deterioration in glycemic control. Patients on insulin therapy for greater than 8 yr are unlikely to benefit significantly from the addition of glyburide to their treatment regimen.

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.

Studies were undertaken to determine the effects of intravenous infusions of bovine testicular extracts on plasma levels of FSH and LH in castrate male sheep. Decapsulated bovine testes were homogenized with phosphate buffer, the homogenates centrifuged at 30,000 X g for 30 min, and the supernatants extracted with diethyl ether. The aqueous extracts were filtered using Diaflo XM-100 membranes and the ultra-filtrates lyophilized. The extracts were infused over 24 hours, and plasma FSH and LH were measured prior to, during, and after the infusion. Control studies using infusions of saline and liver extracts demonstrated no decrease in FSH levels in 6 out of 7 controls, while LH levels tended to rise. Following infusions with the testicular extracts, the levels of FSH were selectively decreased to between 42% and 85% of baseline levels, and they subsequently remained suppressed for at least 24 hours. These results suggest that the testis is the site of production of a water-soluble, non-steroidal substance which exerts an inhibitory effect on the production and/or release of FSH.

A number of different factors are known to be correlated with survival of patients with breast cancer. Among these are lymph node status, tumour size, oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) status. The purpose of this study was to investigate the relative significance of these factors and use this information to construct a prognostic index capable of predicting survival. These factors together with age and menopausal status were studied and correlated with prognosis in 796 women with primary breast cancer. The data were analysed in a stepwise manner by the Cox proportional hazards regression technique. Statistically, greater than 3 nodes involved gave the worst prognosis (P less than 0.001). This was followed by ER if less than 10 fmol/mg cytosol protein (P less than 0.001), PR if less than 10 fmol (P less than 0.01), greater than 0 lymph nodes involved (P less than 0.01) and the number of years over age 65 (P less than 0.01). When these factors were accounted for, tumour size, menopausal status and AR did not significantly improve prediction of survival. The significant factors were incorporated into a prognostic index: I = N + E + P + A, where N = 0 if no nodes involved, 13 (if 1-3 nodes involved and 31 if greater than 3 nodes involved, E = 15 if ER less than 10 fmol, P = 12.5 if PR less than 10 fmol and A = number of years over 65. Using this index five year survival curves were constructed corresponding to groups of patients with widely differing prognoses. Predicted five year survival ranged from 96 to 12 per cent.