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Using the General Practice Research Database, the authors performed (1) a cohort analysis comparing the incidence of liver dysfunction in new users of minocycline with new users of oxytetracycline/tetracycline and (2) a case control study assessing antibiotic exposure in new cases of liver dysfunction and controls without liver dysfunction. In new users, the incidence of liver dysfunction in those exposed to minocycline was 1.04 cases/10,000 exposed person months (EPM) and 0.69 cases/10,000 EPM in those exposed to oxytetracycline/tetracycline (relative risk 1.51 [CI95: 0.63, 3.65]). The risk in both groups was greatest in the first month of use. The adjusted odds ratio (ORadj) of liver dysfunction associated with exposure to minocycline compared with nonuse was 2.10 (CI95: 1.30, 3.40); for oxytetracycline/tetracycline, the ORadj was 1.46 (CI95: 0.81, 2.64); and for exposure to erythromycin, the ORadj was 1.64 (CI95: 0.71, 3.80). The authors thus support a weak association between the use of oral antibiotics and liver dysfunction in patients with acne. The risk associated with exposure to minocycline appears to be very small. The cohort analysis demonstrated that any risk associated with minocycline was not significantly greater than that associated with oxytetracycline/tetracycline exposure.

Following high-dose chemotherapy patients need to undergo bone marrow rescue through stem cell transplantation. Patients who received stem cell transplantation at home expressed satisfaction with this form of therapy. Performing stem cell transplantation in the home can reduce both costs and the risk of infection.

Peripherally inserted central catheters benefit many patients requiring repeated intravenous treatment. This study investigated the effect of using a hand-held Doppler to aid insertion where a patient's veins are not visible or palpable.

Guidelines on the management of chronic obstructive pulmonary disease (COPD) issued by the European Respiratory Society (ERS), British Thoracic Society (BTS), American Thoracic Society (ATS), and Department of Health for England and Wales (DoH) suggest differing values of forced expiratory volume in 1 s (FEV1) below which arterial blood gas analysis should be performed to determine the presence of severe hypoxaemia and possible long-term oxygen therapy (LTOT) requirement. This study aimed to determine the value of FEV1 at these different levels in screening for LTOT requirement defined as PaO2 < 7.3 kPa in subjects with stable COPD. Comparative measures were taken against other lung function tests of volume and diffusing capacity. A retrospective analysis of paired lung function and arterial oxygen measurements in 491 subjects was made. The positive and negative predictive values, sensitivity and specificity of FEV1 < 70% predicted (ERS), FEV1 < 50% predicted (ATS), FEV1 < 40% predicted (BTS) and FEV1 < 1.51 (DoH) were determined for fulfilling LTOT criteria (PaO2 < 7.3 kPa). The correlation between lung function variables and PaO2 was established. Logistic regression analysis was used to classify subjects with PaO2 < 7.3 kPa and PaO2 > or = 7.3 kPa. Using FEV1 to screen for LTOT requirement produced a high negative predictive value at all four suggested limits (FEV1 < 70% 100%, FEV1 < 50% 96%, FEV1 < 40% 95%, FEV1 < 1.51 97%). However, the positive predictive values were low (FEV1 < 70% 13%, FEV1 < 50% 16%, FEV1 < 40% 19%, FEV1 < 1.51 15%) as were sensitivities. No single lung function variable was a strong determinant of PaO2. FEV1 % pred (r = 0.40), FVC % pred (r = 0.34) and TLCO % pred (r = 0.27) had the strongest relationships. Logistic regression also placed FEV1 % pred and TLCO % pred as the best predictors of PaO2 < 7.3 kPa. We conclude no lung function variable correlates well with PaO2 in subjects with stable COPD. The best predictor of PaO2 < 7.3 kPa was FEV1 % pred. Whilst a low FEV1 is a poor predictor of LTOT requirement in an individual, PaO2 < 7.3 kPa is only found in subjects with a low FEV1. A high FEV1 may be used to exclude subjects from further investigation for LTOT and prevent unnecessary arterial sampling.

The effect of thyrotrophin suppression on bone mineral density (BMD) and serum cholesterol concentration was assessed in 31 treated hypothyroid women. Measurements of the BMD of the lumbar spine and femoral neck were repeated in seven of those with the lowest value after an average period of 22.7 months. Final cholesterol concentrations were compared with values before thyroxine was started. The dose of thyroxine was based on clinical assessment, serum triiodothyronine concentrations kept within the normal range, and thyrotrophin values within the normal range or suppressed. The patients had taken thyroxine replacement for a mean of 12.7 years. Two-thirds (21 subjects) had suppressed thyrotrophin concentrations, and it was normal in one-third (10). Fifteen subjects had a past history of thyrotoxicosis. BMD and cholesterol concentrations were compared between those with suppressed and normal thyrotrophin concentrations and between those with and without a past history of thyrotoxicosis. No patient had a pathological fracture. One had a Z value for the femoral neck of -1.6, denoting early but definite osteoporosis, and five had borderline osteoporosis with Z values for one or other site between -1.1 and -1.5. None of the seven with the lowest BMDs had any significant change when measurements were repeated. The difference in Z values between subjects with suppressed and normal thyrotrophin concentrations was not significant for either the lumbar spine (p = 0.68) or the femoral neck (p = 0.28). A past history of thyrotoxicosis had a greater effect on BMD for both sites than thyrotrophin suppression, but again the difference between those with and without a past history of thyrotoxicosis was significant neither for the lumbar spine (p = 0.18) nor for the femoral neck (p = 0.34). The combination of thyrotrophin suppression and a past history of thyrotoxicosis also failed significantly to reduce the BMD of the lumbar spine (p = 0.38) or femoral neck (p = 0.30) in comparison with those who had neither thyrotrophin suppression nor a past history of thyrotoxicosis. The mean fall in serum cholesterol concentration was 2.1 mmol/l (SD 1.78) (p = 0.001) in those with a suppressed thyrotrophin concentration taking a mean daily dose of thyroxine of 171 micrograms (SD: 34.7), compared with a fall of 0.89 mmol/l (SD: 1.04) (p = 0.065) in those whose thyrotrophin concentration was not suppressed on a mean daily thyroxine dose of 140 micrograms (SD: 50). No patient had atrial fibrillation or cardiographic evidence of coronary artery disease (CAD). The serum cholesterol concentration should play at least as important a part in influencing the dose of thyroxine as a fear of osteoporosis. Fractures are not a feature in the natural history of treated hypothyroidism, whereas CAD is a common cause of death in these patients.

Objective: To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of venous thromboembolism., Design: Matched case-control study., Setting: 10 centres in Germany and United Kingdom., Subjects: Cases were 471 women aged 16-44 who had a venous thromboembolism. Controls were 1772 women (at least 3 controls per case) unaffected by venous thromboembolism who were matched with corresponding case for age and for hospital or community setting., Main Outcome Measures: Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables., Results: Odds ratios (95% confidence intervals) for venous thromboembolism were: for any oral contraceptives versus no use, 4.0 (3.1 to 5.3); for second generation products (low dose ethinyl-oestradiol, no gestodene or desogestrel) versus no use, 3.2 (2.3 to 4.3); for third generation products (low dose ethinyloestradiol, gestodene or desogestrel) versus no use, 4.8 (3.4 to 6.7); for third generation products versus second generation products, 1.5 (1.1 to 2.1); for products containing gestodene versus second generation products, 1.5 (1.0 to 2.2); and for products containing desogestrel versus second generation products, 1.5 (1.1 to 2.2). Probability of death due to venous thromboembolism for women using third generation products is about 20 per million users per year, for women using second generation products it is about 14 per million users per year, and for non-users it is five per million per year., Conclusions: Risk of venous thromboembolism was slightly increased in users of third generation oral contraceptives compared with users of second generation products.

Objective: To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of myocardial infarction., Design: Matched case-control study., Setting: 16 centres in Austria, France, Germany, Switzerland, and the United Kingdom., Subjects: Cases were 153 women aged 16-44 with a myocardial infarction event. Controls were 498 women (at least 3 controls per case) unaffected by myocardial infarction who were matched with their corresponding case for age and for hospital or community setting within four months of the index infarction., Main Outcome Measures: Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables., Results: The estimated odds ratio for myocardial infarction of third compared with second generation oral contraceptives among all 651 study subjects was 0.36 (95% confidence interval 0.1 to 1.2) (P = 0.11). The odds ratio for the United Kingdom and Germany alone was 0.45 (0.1 to 1.8) (P = 0.26). Other odds ratios for the five countries were 3.1 (1.5 to 6.3) (P = 0.003) for use of second generation products v no current use and 1.1 (0.4 to 3.4) (P = 0.9) for use of third generation products v no current use. Among the confounding variables the independent contribution of smoking (for which adjustment was made in the above estimates) proved to be important (10.1 (5.7 to 17.9), P < 0.001)., Conclusion: An odds ratio of 0.45 with wide confidence intervals shows that third generation oral contraceptives compared with second generation products are associated with a reduced risk of myocardial infarction or with no difference. This finding from an interim analysis should be interpreted with extreme caution. However, the excess risk of venous thromboembolism associated with the use of third generation products may be balanced by the reduced risk of myocardial infarction associated with the same products.

Objective: To measure changes in female sexual behaviour, including condom use, and their relationship with the incidence of sexually transmitted and other genital diseases in women during the decade 1982-92., Design: A prospective series of cross-sectional surveys of sexual behaviour reported by a standardised self-administered questionnaire in new patients who presented for screening and diagnosis., Setting: A genitourinary medicine clinic in West London., Subjects: 4089 consecutive newly attending patients who completed sexual behaviour questionnaires during 1982, 1987, 1989 and 1992., Main Outcome Measures: Trends in socio-demographic status, sexual behaviour, condom-use, sexually transmitted diseases and other genital infections diagnosed by routine clinical and laboratory methods., Results: Women reported significantly increasing condom use (from 3.6% to 20.7%) and decreasing oral contraception (from 51.2% to 40.1%), but the proportion who used no contraception (23.6% to 24.7%) and the proportion who had never been pregnant (58.3% to 59.9%) remained similar. Numbers of sexual partners in the preceding year decreased (p < 0.001) and an increasing proportion of women practised oral intercourse (p < 0.001). During the same period, there was a progressive decline (p < 0.001) in the incidence of gonorrhoea, chlamydial infection and trichomoniasis by approximately two-thirds. However, the incidence of vaginal candidosis (p < 0.001), bacterial vaginosis (p < 0.001) and genital warts (p < 0.01) increased., Conclusions: Increasing use of condoms for vaginal intercourse with both regular and non-regular partners has been associated with a decrease in the incidence of gonorrhoea, chlamydial infection and trichomoniasis. There was also an increase in the practice of fellatio and a change in the spectrum of STD and other genital infections with little net reduction in morbidity. HIV infection showed no evidence of heterosexual spread.

Objectives: To examine the effect of patient-defined non-regular heterosexual relationships on the incidence of sexually transmitted diseases and other genital infections in women and the role of condom use in the prevention of their spread., Design: A cross-sectional study of sexual behaviour reported by a standardised self-administered questionnaire in new patients who presented for screening and diagnosis., Setting: A genitourinary medicine clinic in West London., Subjects: 938 consecutive newly attending women who completed a sexual behaviour questionnaire in 1992., Main Outcome Measures: Variables relating to socio-demographic status, sexual behaviour, condom use, sexually transmitted diseases and other genital infections stratified by the reporting of non-regular partners., Results: We found that women who reported non-regular sexual partners were more likely to be single (p = 0.0001), white (p < 0.0001), have had coitarche before 17 years of age (p = 0.003) and many more sexual partners both in the last year and in their life-time (p < 0.0001) and were more likely to practise fellatio (p < 0.0001), anal penetration (p = 0.004) and to be smokers (p < 0.0001). Paradoxically, the incidence of sexually transmitted diseases and other genital infections was no higher in this group than in the group of women who did not have non-regular partners. Increasing condom use with regular partners correlated with decreasing incidence of gonorrhoea (p < 0.001), chlamydial infection (p < 0.01) and trichomoniasis (p < 0.02), but increasing condom use with non-regular partners did not show this trend., Conclusions: Regular heterosexual partners play the major role in transmission of bacterial sexually transmitted diseases to women. This is significantly influenced by use of condoms.

Background: This report is a study of prognostic factors, including adjuvant chemotherapy, that influence survival of patients with malignant melanoma who have clinical and pathologic involvement of regional lymph nodes., Methods: A total of 169 evaluable patients with malignant melanoma metastatic to regional lymph nodes were registered consecutively and prospectively between June 1977 and December 1986 in the computerized data base of the melanoma registry at Westminster Hospital. Eighty-seven of these patients received adjuvant chemotherapy with vindesine after resection of palpable metastatic lymph nodes, and 82 had no systemic treatment after surgery. All were followed up for at least 2 years (median, 8 years) after involvement of regional lymph nodes was noted or until death. Statistical analyses included simple life-table comparisons, unadjusted for covariates. In addition, Breslow's thickness, ulceration of the primary lesion, its anatomical location, number of regional lymph nodes histologically involved, dissection site, patient age and sex, and adjuvant vindesine therapy were included as covariates in Cox regression models., Results: The disease-free interval (P = 0.0001), time to dissemination from lymph node metastases (P < 0.0001), survival time after lymph node dissection (P = 0.0227) and overall survival time after initial diagnosis of malignant melanoma (P = 0.0095, log-rank chi-square test) were superior for the 87 patients who received adjuvant chemotherapy with vindesine. Cox regression analysis confirmed adjuvant vindesine as a highly significant variable influencing all of these outcomes, including overall survival time after first diagnosis (P = 0.003)., Conclusions: The apparent effect of adjuvant vindesine on overall survival in this study is large (hazard ratio, 0.52) and highly statistically significant. Adjuvant vindesine therapy merits consideration for malignant melanoma metastatic to regional lymph nodes. However, these results observed in concurrent, but nonrandomized, patients clearly require confirmation.

Between July 1985 and December 1987, 87 patients with advanced breast carcinoma were randomized to receive single agent doxorubicin (70 mg/m2), epirubicin (70 mg/m2) or mitozantrone (14 mg/m2) at 3-weekly intervals. The patients had received no previous chemotherapy for their advanced disease but 91% had received prior hormonal therapy. The response rates were 36% with doxorubicin, 32% with epirubicin and 26% with mitozantrone, but these differences did not reach statistical significance. The median survival of all patients was 8.3 months. There was no significant difference in response rates or survival according to menopausal status. The toxicities of the three agents are compared. Nausea, vomiting and alopecia were more severe in patients treated with doxorubicin or epirubicin than those treated with mitozantrone. Myelosuppression and infective episodes occurred more frequently with mitozantrone. Two cardiac complications were reported. This study shows that the toxicity and low efficacy of all three agents limit their use as single agents in advanced breast carcinoma. The role of single agent chemotherapy and the relative toxicities of these drugs are discussed.

Testicular feminization syndrome was diagnosed in a mare with aggressive, stallion like behavior and a history of infertility. She was found to have a high baseline testosterone concentration suggesting that testicular tissue was present, and ovarian-like structures examined by use of transrectal ultrasonography had the appearance typical of testicular tissue. Although her external female genitalia appeared normal, her vagina ended in a blind sac, and no cervix or uterus were identified. Surgery was performed, and structures removed from the abdominal cavity were determined to be hypoplastic testicles. Removal of the testicular tissue resulted in complete resolution of her aggressive behavior. Chromosomal evaluation revealed that the mare had 64X,Y (normal male) karyotype. Testicular feminization syndrome is a condition characterized by insensitivity of reproductive tissues to androgens during development because of an abnormality in androgen receptors. This androgen insensitivity results in development of normal external female genitalia, with high testosterone concentrations being released from developing testicles. Testicular feminization syndrome has not been commonly diagnosed in horses, but should be considered as a differential diagnosis for overly aggressive mares with a history of infertility.

The hand radiographs of 422 patients with end-stage renal failure were graded for severity of subperiosteal resorption. Two hundred and seventy-three patients (64.7%) had no evidence of resorption; 114 (27.0%) showed resorption, in 32 of whom it was severe (7.6% of the total). Thirty-five patients (8.3%) were assessed as having doubtful evidence of subperiosteal resorption. Age, gender, race, renal diagnosis, duration of renal failure and vitamin D status were assessed as potential risk factors for the development of subperiosteal resorption. Duration of renal failure, female gender, young age, and certain renal diagnostic groups namely obstructive uropathy, unknown diagnosis, presumed glomerulonephritis and tubulointerstitial disease emerged as independent risk factors. Diabetic patients appeared to be least at risk of developing subperiosteal resorption. Patients whose renal failure was of unknown duration showed a degree of risk similar to those whose duration was < 2 years. In order to identify prospectively patients likely to develop subperiosteal resorption by the time they reach renal replacement therapy, the relative risks were used to create a risk index. Use of such an index might allow prophylactic treatment to be given to those particularly at risk. The concept of a risk index requires testing by a prospective study, which is in progress.

The main objective of the present study was to test the hypothesis that patients with cardiopulmonary disease can reliably identify different sensory qualities of their experience of breathlessness. A secondary aim was to examine whether there was any relationship between such specific descriptors of the sensation of breathlessness and a patient's clinical diagnosis. A randomly ordered list of 45 descriptors of breathing discomfort related to exertion was administered on two occasions to 208 patients with cardiopulmonary disease; patients identified the descriptors that applied to their own experience. A total of 169 patients were considered reliable in that their responses were repeatable between questionnaires; there was evidence that an individual's reliability could be assessed by asking repeat questions within a questionnaire. With these patients, individual descriptors generated different degrees of yes and no response and were answered with a variable consistency, suggesting that some questions may be more useful than others in discriminating between the quality of patients' sensations. Overall, patients with obstructive disorders (asthma and chronic obstructive airways disease [COAD]) answered yes more often than those with restrictive or cardiac conditions, possibly reflecting differences in severity of disease. A cluster analysis separated the descriptors into 12 groups which appeared to describe different aspects of breathing discomfort. Relative to their response to other clusters, COAD patients were more inclined to identify distress, asthma patients to indicate wheeziness, restrictive patients to report rapid breathing, and the cardiac group to describe a need to sign. A second cluster analysis separated patients into 12 groups based on responses for the descriptor clusters.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction equations for normal lung function have been derived from tests on 179 healthy, non-smoking, white urban dwellers. The subjects, 96 women (height 1.46-1.77 m) and 83 men (height 1.61-1.96 m) aged 18-86 years, underwent measurements of spirometric flow and volume, multi-breath helium dilution lung volumes, and single breath carbon monoxide transfer factor and the single breath nitrogen washout test. Regression analysis using height, age, and weight as independent variables was used to provide predicted values for both sexes. Correlation coefficients were similar to those found in previous studies but normal ranges for spirometic measurements were narrower than in many previous studies, and spirometric flow and volume measurements were higher than those obtained in studies that included cigarette smokers, reflecting our more stringent criteria for selecting subjects and the newer standardised technical methods adopted. Multi-breath helium dilution values for total lung capacity were similar to those found in previous studies but the inspiratory vital capacity was larger and the residual volume reduced. Values for carbon monoxide transfer factor and the single breath nitrogen washout did not differ significantly from existing values. A complete set of lung function reference values and prediction equations for both sexes has been derived from a single population. The exclusion of cigarette smokers and subjects with respiratory symptoms has produced values that should have a greater sensitivity in the detection of mild lung disease.

1. In order to document the characteristics of the renal vascular response to blood losses of varying severity, Inactin-anaesthetized rats were subjected to a haemorrhage of 5, 10, 15 or 20 ml (kg body weight)-1, while a fifth group (control rats) remained unbled. Radioactive microspheres (diameter 10 microns) were used to determine cardiac output, total renal blood flow and the distribution of blood flow within the kidneys; measurements were made before and 5-120 min after haemorrhage. 2. In control animals none of the variables studied changed significantly during the experimental period. 3. Immediately after haemorrhage there were reductions in arterial pressure and cardiac output which were roughly proportional to the severity of haemorrhage. Arterial pressure recovered to some extent during the next 30 min, then stabilized; cardiac output recovered only slightly. 4. Total renal blood flow fell to an extent dependent on the degree of haemorrhage, with no evidence of subsequent recovery. The approximate reductions in renal blood flow were 2% (n.s.), 15%, 30% and 50% after bleeds of 5, 10, 15 and 20 ml kg-1, respectively. Renal vascular resistance increased consistently only in the groups bled 15 and 20 ml kg-1. When renal blood flow was expressed as a fraction of cardiac output, it increased during the period immediately after haemorrhage, indicating some degree of 'protection' of the renal circulation in the face of hypotension. 5. Measurements of intrarenal blood flow indicated a significantly reduced flow to the superficial cortex after every degree of haemorrhage. Inner cortical flow was less affected and fell significantly only in the groups bled 15 and 20 ml kg-1; blood flow to the mid-cortex was intermediate.

A total of 771 individuals with end-stage renal disease treated at one centre from 1964 to 1990 were studied. Data on racial origin, gender, age, and primary renal diagnosis were analysed. The male: female ratio (468:303) and proportions of individuals in different diagnostic groups (renal diagnosis based on European Dialysis and Transplant Association (EDTA) groups) were similar to EDTA data for the UK as a whole. Racial distribution was Caucasian 79.0%, Indian subcontinent (Is-c) 12.7%, Caribbean, 5.6%, African 1.6% and other Asian 1.2%. In Britain individuals from the Is-c constitute 2.2% of the general population and those from the Caribbean 1.0%. We found differences in the distribution of primary renal disease among patients from different racial groups. Adult polycystic kidney disease was almost entirely confined to Caucasians (75 to 79 patients). Diabetic nephropathy was relatively more common in individuals (especially males) from the Is-c. Hypertensive renal disease was relatively more common in those of Caribbean descent and in Africans, whilst 'Unknown diagnosis' was most common in patients from the Is-c.

A statistical overview of published results on correlations between various prognostic factors in breast cancer was undertaken. A distinction was made between clinical (or anatomical) prognostic factors--namely, axillary lymph node status and tumour size--and eight different biological prognostic factors. The latter included: tumour grade, oestrogen and progesterone receptor status, thymidine labelling index, DNA ploidy, S-phase fraction, epidermal growth factor receptor expression and c-erbB-2 gene amplification (or overexpression). 139 articles were eligible for review which reported a total of 432 individual correlations. A simple form of meta-analysis was employed: the counting method, in which the number of studies achieving a statistically significant correlation or not were counted. For each possible correlation examined, the proportion of studies showing a statistically significant correlation was calculated and an exact binomial 99% confidence interval determined for that proportion. If the 99% confidence interval included 5% (the proportion of correlations that would be expected to be statistically significant if the null hypothesis was true), it was taken as failing to exclude the null hypothesis of a zero correlation, while if it excluded 5% it was taken as rejecting the null hypothesis of a zero correlation. A broad agreement was found among published reports on the existence of a statistically significant correlation between the various biological prognostic factors in breast cancer. Of the 20 correlations examined, 18 had a 99% confidence interval excluding 5%, thus rejecting the null hypothesis of a zero correlation. On the other hand, a completely different result was obtained when reports on possible correlations between lymph node status and tumour size on the one hand and the eight biological prognostic factors on the other were analysed. Of the 16 correlations examined, 13 had a 99% confidence interval including 5%, failing to reject the null hypothesis of a zero correlation. These observations suggest the hypothesis that the prognostic influence of node status and tumour size cannot be explained by an analysis of the biology of breast cancer; and is compatible with the contention that axillary node status is merely a reflection of the relative chronological age of breast cancer.

Total lung capacity (TLC) and residual volume (RV) measurements derived from multi-breath and single breath helium dilution methods were combined to produce four indices of gas mixing: single breath volume/multi-breath volume ratio (TLCr, RVr) or multi-breath volume minus single breath volume difference (TLCd, RVd). The reproducibility of these indices and their sensitivity and specificity in discriminating between normal subjects and those with mild asthma and severe chronic obstructive pulmonary disease (COPD) was assessed. The total lung capacity ratio (TLCr) was the superior variable overall, providing a single range for both sexes with a specificity and sensitivity similar to that of the forced expiratory volume in one second (FEV1) in the diagnosis of airflow obstruction. Despite the similar sensitivity, correlation between TLCr and FEV1 was only moderate (r = 0.56). This may reflect greater influence of peripheral rather than central airflow obstruction on TLCr. Combining both tests improved sensitivity in the detection of airways obstruction in the asthmatic and COPD groups studied.

Inheritance of the Blotchy allele at the X-chromosomal Mottled locus of mice results in changes in the lung which resemble emphysema. Previous studies using measurements of mean linear intercept have recognized emphysema in the hemizygous, Blo/Y, male and homozygous, Blo/Blo, female, but not in the heterozygous, Blo/+, female. The aim of this study was to develop a rapid, accurate method for analysis of emphysema and to establish whether it would identify emphysema in the heterozygote. Lungs from wild type and outbred Blo mice were inflated with fixative at a pressure of 25 cm and then sectioned and stained. Transect lengths across air spaces were measured using computerized image analysis and the results were plotted as histograms. Data were also expressed as cumulative frequencies (ogives) and subjected to statistical analysis by the non-parametric Kolmogorov-Smirnov test. Emphysema was shown by significantly increased (P less than 0.001) transect lengths in the Blo/Blo female and Blo/Y male compared with the wild type controls. The heterozygous Blo/+ mice form an intermediate group significantly different (P less than 0.001) from the wild and blotchy mice. The sensitivity of the method is illustrated by the fact that the Blo/+ female formed an intermediate group between wild type and the Blo/Y male and Blo/Blo female.

The results of 5-day cyclical combined chemotherapy for advanced breast cancer were compared in two trials with the less demanding 1-day and 2-day regimens. At all stages, except at 3 months, 5-day treatment was significantly more successful in providing regression and remission of tumours than the 1-day regimen. However, although the differences are not statistically significant, data from the second trial indicated that the 2-day regimen tended to be more effective than the 5-day regimen. The lower 95% confidence limit for the success of the 2-day treatment was 56.2% at 3 months.

Fifty-two patients with rheumatoid arthritis were studied in a single blind trial comparing aurothioglucose and auranofin. The duration of the study was 52 weeks. Twenty-six patients, 13 in each treatment group, dropped out during the first year of treatment. The main reason for discontinuing treatment with aurothioglucose was adverse reactions and, in the auranofin group, lack of efficacy. In those patients who continued therapy the results of treatment were comparable; patients on aurothioglucose improved slightly more than auranofin treated patients, although the difference was not statistically significant.

A prospective, multicentre trial was conducted in 262 patients with advanced breast cancer randomized to receive every 3 weeks either: (i) a single five-drug combination of adriamycin (50 mg), vincristine (1.5 mg) and 5-fluorouracil (750 mg) given intravenously; with methotrexate (50 mg) intramuscularly and chlorambucil (10 mg) orally all at time zero, followed by three further doses of chlorambucil (10 mg) at 6-h intervals, or (ii) one course of two alternating three-drug combinations consisting of regimen A--vincristine (1.5 mg), adriamycin (70 mg) and methotrexate (50 mg) and regimen B--5-fluorouracil (750 mg) and vindesine (5 mg) intravenously with cyclophosphamide (50 mg) orally at time zero, followed by three further doses of cyclophosphamide (50 mg) at 6-h intervals. Results show that overall response rates to chemotherapy were comparable in the two arms of this study being 63% (83 of 131 patients) for the single combination and 64% (84 of 131 patients) for the alternating combinations. Response rates according to menopausal status indicate no significant difference for the two arms of this study. However overall, combining all patients treated with either the single or the alternating combinations, post-menopausal patients had a significantly lower response rate (57%) compared with pre-menopausal patients (76%), P less than 0.05. Overall serious side-effects were minimal and were similar in both treatment groups. Response durations and overall survival data, which are essentially similar for the two treatment groups, proved disappointing with a median response duration of only approx. 6 months and overall median survival only slightly in excess of 1 year. Alternative treatment approaches are needed to maintain the remissions initially achieved in metastatic breast cancer.

A single-blind, randomised, placebo-controlled trial of superficial acupuncture in the treatment of low back pain was carried out by comparing 8 patients treated by acupuncture with 9 patients treated by placebo. In all five measures of efficacy chosen for study the acupuncture group achieved better responses than the placebo group; four of the five inter-group differences were statistically significant. In addition, an overall mean for all five measures combined showed significant superiority of acupuncture over placebo.

Previous studies of the effects of moderate drinking on the outcome of pregnancy are assessed. The results of a prospective study of the association between alcohol consumption in pregnancy and birthweight, length of baby, head circumference and premature delivery are described. Consumption of more than 10 g alcohol per day in very early pregnancy or even before conception approximately doubled the risk that the infant would have a low birthweight. Cigarette smoking was also a risk factor for low birthweight. It may therefore be beneficial for women to reduce their alcohol consumption to one drink a day or less from before conception and give up smoking as well.

A randomized prospective controlled trial compared a policy of bladder catheterization with no catheterization in patients undergoing laparoscopy. Of the 41 patients randomized to receive no catheterization, seven were actually catheterized on the judgement of the surgeon, but only one of them had greater than 50 ml of urine. Midstream urine obtained 6 days after laparoscopy was infected in 9 (21%) of the 42 patients allocated to receive catheterization and in only five (12%) of those allocated to the no-catheter group. Four of these five were actually not catheterized, giving an infection rate of 12% in the 34 patients not catheterized. The differences are statistically significant. A routine policy of catheterization for patients undergoing laparoscopy is questionable. All patients who are catheterized should be investigated for urinary tract infections after operation.

A summary of the symptoms, prevalence and history of premenstrual syndrome (PMS) is presented. The legal implications of PMS, particularly its use as a defence in criminal prosecutions and as an implicit factor in specific offences, are discussed by means of an analysis of Canadian legal cases, with reference to those in England and the United States. The authors offer suggestions on how physicians can make use of PMS in a courtroom more reliable. They conclude that PMS is unlikely to become a substantive criminal defence until the medical community more fully recognizes its significance. Although the role of PMS as a mitigating factor in sentencing may be illogical, the courts now recognize the syndrome in a legally and practically important manner.