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To investigate the sociological, environmental, and economic impact of hormonally active contraceptives, a series of comprehensive literature surveys were employed. Sociological effects are discussed including abortion, exploitation of women, a weakening of marriage, and an increase in divorce with deleterious effects on children such as child poverty, poorer health, lower educational achievement, suicide risks, drug and alcohol abuse, criminality, and incarceration, among others. The environmental impact is discussed briefly and includes the feminization and trans-gendering of male fish downstream from the effluent of city wastewater treatment plants with declining fish populations. The potential economic impact of most of these side effects is estimated based on epidemiologic data and published estimates of costs of caring for the diseases which are linked to the use of hormonally active contraceptives. Hormonally active contraceptives appear to have a deleterious impact on multiple aspects of women’s health as well as negative economic and environmental impacts. These risks can be avoided through the use of nonhormonal methods and need to be more clearly conveyed to the public. Summary: Hormonal contraceptives have wide-ranging effects. The potential economic impact of the medical side effects is estimated. Sociological effects are discussed including abortion, exploitation of women, a weakening of marriage and an increase in divorce with negative effects on children such as child poverty, poorer health, lower educational achievement, suicide risks, drug and alcohol abuse, criminality and incarceration among others. The environmental impact includes hormonal effects on fish with declining fish populations. Women seeking birth control have a right to know about how to avoid these risks by using effective hormone-free methods like Fertility Awareness Methods.

Objective To describe a novel England-wide electronic health record (EHR) resource enabling whole population research on covid-19 and cardiovascular disease while ensuring data security and privacy and maintaining public trust. Design Data resource comprising linked person level records from national healthcare settings for the English population, accessible within NHS Digital’s new trusted research environment. Setting EHRs from primary care, hospital episodes, death registry, covid-19 laboratory test results, and community dispensing data, with further enrichment planned from specialist intensive care, cardiovascular, and covid-19 vaccination data. Participants 54.4 million people alive on 1 January 2020 and registered with an NHS general practitioner in England. Main outcome measures Confirmed and suspected covid-19 diagnoses, exemplar cardiovascular conditions (incident stroke or transient ischaemic attack and incident myocardial infarction) and all cause mortality between 1 January and 31 October 2020. Results The linked cohort includes more than 96% of the English population. By combining person level data across national healthcare settings, data on age, sex, and ethnicity are complete for around 95% of the population. Among 53.3 million people with no previous diagnosis of stroke or transient ischaemic attack, 98 721 had a first ever incident stroke or transient ischaemic attack between 1 January and 31 October 2020, of which 30% were recorded only in primary care and 4% only in death registry records. Among 53.2 million people with no previous diagnosis of myocardial infarction, 62 966 had an incident myocardial infarction during follow-up, of which 8% were recorded only in primary care and 12% only in death registry records. A total of 959 470 people had a confirmed or suspected covid-19 diagnosis (714 162 in primary care data, 126 349 in hospital admission records, 776 503 in covid-19 laboratory test data, and 50 504 in death registry records). Although 58% of these were recorded in both primary care and covid-19 laboratory test data, 15% and 18%, respectively, were recorded in only one. Conclusions This population-wide resource shows the importance of linking person level data across health settings to maximise completeness of key characteristics and to ascertain cardiovascular events and covid-19 diagnoses. Although this resource was initially established to support research on covid-19 and cardiovascular disease to benefit clinical care and public health and to inform healthcare policy, it can broaden further to enable a wide range of research.

Background: Treatment guidelines recommend a stepwise approach to primary biliary cholangitis: all patients begin treatment with ursodeoxycholic acid (UDCA) monotherapy and those with an inadequate biochemical response after 12 months are subsequently considered for second-line therapies. However, as a result, patients at the highest risk can wait the longest for effective treatment. We determined whether UDCA response can be accurately predicted using pretreatment clinical parameters. Methods: We did logistic regression analysis of pretreatment variables in a discovery cohort of patients in the UK with primary biliary cholangitis to derive the best-fitting model of UDCA response, defined as alkaline phosphatase less than 1·67 times the upper limit of normal (ULN), measured after 12 months of treatment with UDCA. We validated the model in an external cohort of patients with primary biliary cholangitis and treated with UDCA in Italy. Additionally, we assessed correlations between model predictions and key histological features, such as biliary injury and fibrosis, on liver biopsy samples. Findings: 2703 participants diagnosed with primary biliary cholangitis between Jan 1, 1998, and May 31, 2015, were included in the UK-PBC cohort for derivation of the model. The following pretreatment parameters were associated with lower probability of UDCA response: higher alkaline phosphatase concentration (p

Diets low in methionine extend lifespan of rodents, though through unknown mechanisms. Glycine can mitigate methionine toxicity, and a small prior study has suggested that supplemental glycine could extend lifespan of Fischer 344 rats. We therefore evaluated the effects of an 8% glycine diet on lifespan and pathology of genetically heterogeneous mice in the context of the Interventions Testing Program. Elevated glycine led to a small (4%–6%) but statistically significant lifespan increase, as well as an increase in maximum lifespan, in both males (p = 0.002) and females (p

The biochemical response to ursodeoxycholic acid (UDCA)—so-called “treatment response”—strongly predicts long-term outcome in primary biliary cholangitis (PBC). Several long-term prognostic models based solely on the treatment response have been developed that are widely used to risk stratify PBC patients and guide their management. However, they do not take other prognostic variables into account, such as the stage of the liver disease. We sought to improve existing long-term prognostic models of PBC using data from the UK-PBC Research Cohort. We performed Cox's proportional hazards regression analysis of diverse explanatory variables in a derivation cohort of 1,916 UDCA-treated participants. We used nonautomatic backward selection to derive the best-fitting Cox model, from which we derived a multivariable fractional polynomial model. We combined linear predictors and baseline survivor functions in equations to score the risk of a liver transplant or liver-related death occurring within 5, 10, or 15 years. We validated these risk scores in an independent cohort of 1,249 UDCA-treated participants. The best-fitting model consisted of the baseline albumin and platelet count, as well as the bilirubin, transaminases, and alkaline phosphatase, after 12 months of UDCA. In the validation cohort, the 5-, 10-, and 15-year risk scores were highly accurate (areas under the curve: >0.90). Conclusions: The prognosis of PBC patients can be accurately evaluated using the UK-PBC risk scores. They may be used to identify high-risk patients for closer monitoring and second-line therapies, as well as low-risk patients who could potentially be followed up in primary care. (Hepatology 2016;63:930–950)

The aim of this study was to review the incidence and type of central venous catheter-related bloodstream infection in children on treatment with home parenteral nutrition (PN) before and after the introduction of taurolidine. Taurolidine is a catheter lock solution that prevents biofilm formation and has broad-spectrum bactericidal and antifungal action. Its use in pediatric patients on PN has only been reported in case studies.A total of 19 children were reviewed, with the diagnoses of enteropathy (8 cases), short bowel syndrome (7 cases), and gastrointestinal dysmotility (4 cases). Incidence and type of sepsis were reviewed for 8 to 12 months pre- (when heparin was used) and 2 to 33 months postintroduction of the taurolidine catheter lock.There were 8.6 episodes of catheter-related bloodstream infections per 1000 catheter days with heparin and 1.1 episodes per 1000 catheter days with taurolidine (P=0.002). A total of 14 of the 19 patients (74%) had no infections for up to 33 months after changing to taurolidine. No reports of multiresistant organisms or adverse effects with taurolidine were found.Taurolidine line lock was associated with a decreased incidence of catheter-related bloodstream infections. This finding supports its use in patients with a history of septicemia on treatment with cyclical PN.

Drug-induced liver injury (DILI) accounts for 9.5% of all suspected adverse drug reactions (ADRs) and for a significant proportion of fatal ADRs. DILI may be a direct toxic effect or an immunological reaction to either the drug or an active metabolite. Drugs can cause a diverse array of liver injury, which may be acute or chronic. Adaptation to injurious effects, with only a transient increase in liver function, can occur. Inherited or acquired factors affect the risk of DILI. There is marked geographic variation in responsible agents; in the West antibiotics, anticonvulsants, psychotropic and recreational drugs are the most common offending agents, whereas in Asia, herbal and dietary supplements are more common. This contribution focuses on the pathogenesis and consequences of DILI, their investigation and management. Information on specific ADRs can be obtained from the British National Formulary, drug data sheets and other web-based databases (WHO Adverse Drug Reactions Monitoring; AERS and DIOGENES ® : Adverse Drug Events Database – FDA sites; Canada Vigilance Adverse Reaction Online Database; Drug Adverse Reaction Target Database (DART)).

This article aims to discuss problems with central venous catheters (CVCs) and offer strategies to assist in preventing their replacement. The article focuses on the most frequent complications of infection and obstruction. Traditional treatment options are presented and endoluminal brushing is introduced as an innovative treatment for retaining CVCs. The expert opinion that follows focuses on CVCs that are used for parenteral nutrition in paediatrics, but the evidence described can also be applied to larger adult catheters.

A 45-year-old HBsAg carrier (HBeAb positive with normal liver function tests) underwent renal transplantation for mesangioproliferative glomerulonephritis. Sixteen months later he developed jaundice. Investigations showed he remained HBeAb positive, but HBV-DNA levels were 99 pg/ml, indicating active replication of a HBV pre-core mutant. He was commenced on lamivudine therapy with a subsequent rapid fall in HBV-DNA levels to 2.8 pg/ml, but liver function tests continued to deteriorate and he developed hepatorenal failure. Liver biopsy showed fibrosing cholestatic hepatitis. He underwent liver transplantation, which was complicated by lactic acidosis. Lamivudine was withdrawn and HBV prophylaxis with HB immunoglobulin was commenced. Unfortunately he died 38 days post-transplant of surgical complications with no evidence of HBV recurrence. We discuss the use of nucleoside analogues in fibrosing cholestatic hepatitis and review the literature.

Alcoholic hepatitis is associated with a high short term mortality. We aimed to identify those factors associated with mortality and define a simple score which would predict outcome in our population.We identified 241 patients with alcoholic hepatitis. Clinical and laboratory data were recorded on the day of admission (day 1) and on days 6-9. Stepwise logistic regression was used to identify variables related to outcome at 28 days and 84 days after admission. These variables were included in the Glasgow alcoholic hepatitis score (GAHS) and its ability to predict outcome assessed. The GAHS was validated in a separate dataset of 195 patients.The GAHS was derived from five variables independently associated with outcome: age (p = 0.001) and, from day 1 results, serum bilirubin (p0.001), blood urea (p = 0.019) and, from day 6-9 results, serum bilirubin (p0.001), prothrombin time (p = 0.002), and peripheral blood white blood cell count (p = 0.001). The GAHS on day 1 had an overall accuracy of 81% when predicting 28 day outcome. In contrast, the modified discriminant function had an overall accuracy of 49%. Similar results were found using information at 6-9 days and when predicting 84 day outcome. The accuracy of the GAHS was confirmed by the validation study of 195 patients The GAHS was equally accurate irrespective of the use of the international normalised ratio or prothrombin time ratio, or if the diagnosis of alcoholic hepatitis was biopsy proven or on the basis of clinical assessment.Using variables associated with mortality we have derived and validated an accurate scoring system to assess outcome in alcoholic hepatitis. This score was able to identify patients at greatest risk of death throughout their admission.

Aims and Methods: Oxidant stress is proposed to be an important pathogenic factor in liver damage related to alcohol. The glutathione S-transferases (GSTs) are a group of polymorphic enzymes that are important in protection against oxidant stress. As there is evidence for genetic susceptibility to alcohol-related liver disease we have compared the frequency of polymorphisms of GSTM1, M3, P1, T1 and A1 by polymerase chain reaction (PCR) on leucocyte DNA in patients from North Staffordshire, Birmingham and Liverpool with alcohol-related chronic liver disease heavy drinking and normal local controls. Results: There were no significant differences in GSTM1, GSTM3 or GSTP1 genotype frequencies among patients, drinking and non-drinking controls from the three centres. There was a significant increase in the GSTT1 null Liverpool alcoholic liver disease (ALD) patients compared with corresponding non-drinking controls (26.3 and 14.6%, respectively; P = 0.044, odds ratio (OR) = 2.1, 95% CI = 1.1–4.7) though this was not repeated in the Birmingham and North Staffordshire cohorts. For GSTA1, the −69 CC genotype was associated with increased risk of ALD in the Liverpool group, but a reduced risk in the North Staffordshire group. Conclusions: We have failed to demonstrate within the limitation of a case–control study a reproducible significant association of GST polymorphisms with susceptibility to ALD but there are suggestions that GSTA1 and GSTT1 warrant further study. ( Received 13 July 2004; first review notified 28 August 2004; in revised form 29 September 2004; accepted 1 October 2004 )

BACKGROUND: Postnatal depression can be effectively treated by cognitive behavioural counselling (CBC), a simple intervention designed to be delivered by non-specialists in mental health. METHODS: Health visitors were trained in CBC and post-training changes in counselling skills, clinical practice and costs were assessed. RESULTS: Following training health visitors showed improved counselling skills, and they carried out more mental health assessments, recorded mental symptoms more often and treated more women themselves. However, their mean number of contacts with depressed women did not change; and the number of urgent contacts diminished. Referrals to general practitioners did not increase but there was an increase in referrals to mental health services. Costs to health visitor practice did not increase. LIMITATIONS: Assessment of clinical practice was based on health visitor records. The study uses a 'before and after' design rather than randomisation of subjects. CONCLUSIONS: Training health visitors in CBC leads to improved counselling skills and corresponding changes in clinical practice, without increasing the costs of health visitor practice.

The incidence of hepatitis E in the UK is increasing. We recommend measuring hepatitis E serology in those with an acute hepatitis.

Evidence that the metabolism of phospholipids and polyunsaturated fatty acids (PUFA) is abnormal in schizophrenia provided the rationale for intervention studies using PUFA supplementation. An initial open label study indicating efficacy for n-3 PUFA in schizophrenia led to two small double-blind pilot studies. The first study was designed to distinguish between the possible effects of two different n-3 PUFA: eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA). Forty-five schizophrenic patients on stable antipsychotic medication who were still symptomatic were treated with either EPA, DHA or placebo for 3 months. Improvement on EPA measured by the Positive and Negative Syndrome Scale (PANSS) was statistically superior to both DHA and placebo using changes in percentage scores on the total PANSS. EPA was significantly superior to DHA for positive symptoms using ANOVA for repeated measures. In the second placebo-controlled study, EPA was used as a sole treatment, though the use of antipsychotic drugs was still permitted if this was clinically imperative. By the end of the study, all 12 patients on placebo, but only eight out of 14 patients on EPA, were taking antipsychotic drugs. Despite this, patients taking EPA had significantly lower scores on the PANSS rating scale by the end of the study. It is concluded that EPA may represent a new treatment approach to schizophrenia, and this requires investigation by large-scale placebo-controlled trials.

The aim of this study was to determine the prevalence of infection with the newly described hepatitis G virus (HGV) in a liver transplant cohort, and to establish the frequency and nature of hepatitis in those with and without HGV infection. A reverse transcriptase-polymerase chain reaction technique was employed to determine viraemia in the patients, and liver biopsies taken at different times after transplantation were assessed histologically. Hepatitis G virus RNA was detected in 47% of the liver transplant recipients investigated. Those positive for HGV had received significantly more blood or blood products than the HGV-negative patients. The frequency of abnormal liver function tests was similar in HGV-positive and HGV-negative recipients. Bile duct epithelial cell damage was more frequently seen in those with HGV viraemia. This study indicates that almost half of the liver transplant recipients in Northern England are positive for HGV, and that infection is associated with exposure to blood and blood products. It appears that, in the immunosuppressed patient, HGV does not cause clinically significant liver disease, at least up to 2 years after transplantation. If HGV infection is associated with hepatitis outside this clinical setting, it is likely that the liver damage is immunopathologically mediated rather than as a result of direct viral cytotoxicity.

STUDY OBJECTIVE: To ascertain, from the published reports to date, whether or not a significantly increased risk of breast cancer is specifically attributable to a history of induced abortion, independent of spontaneous abortion and age at first full term pregnancy (or first live birth); to establish the relative magnitude of such risk increase as may be found, and to ascertain and quantify such risk increases as may pertain to particular subpopulations of women exposed to induced abortion; in particular, nulliparous women and parous women exposed before compared with after the first full term pregnancy. INCLUDED STUDIES: The meta-analysis includes all 28 published reports which include specific data on induced abortion and breast cancer incidence. Since some study data are presented in more than one report, the 28 reports were determined to constitute 23 independent studies. Overall induced abortion odds ratios and odds ratios for the different subpopulations were calculated using an average weighted according to the inverse of the variance. An overall unweighted average was also computed for comparison. No quality criteria were imposed, but a narrative review of all included studies is presented for the reader's use in assessing the quality of individual studies. EXCLUDED STUDIES: All 33 published reports including data on abortion and breast cancer incidence but either pertaining only to spontaneous abortion or to abortion without specification as to whether it was induced or spontaneous. These studies are listed for the reader's information. RESULTS: The overall odds ratio (for any induced abortion exposure; n = 21 studies) was 1.3 (95% confidence interval of 1.2, 1.4). For comparison, the unweighted overall odds ratio was 1.4 (1.3,1.6). The odds ratio for nulliparous women was 1.3 (1.0,1.6), that for abortion before the first term pregnancy in parous women was 1.5 (1.2,1.8), and that for abortion after the first term pregnancy was 1.3 (1.1,1.5). CONCLUSIONS: The results support the inclusion of induced abortion among significant independent risk factors for breast cancer, regardless of parity or timing of abortion relative to the first term pregnancy. Although the increase in risk was relatively low, the high incidence of both breast cancer and induced abortion suggest a substantial impact of thousands of excess cases per year currently, and a potentially much greater impact in the next century, as the first cohort of women exposed to legal induced abortion continues to age.

We studied hepatitis C virus (HCV)-related disease in older people because the treatment rationale for younger asymptomatic patients is based on the long-term prognosis of infection. Of the HCV-antibodypositive patients seen at Freeman Hospital 1990-1994, 25 were >65 years old ; 24 were Caucasian and one was Afro-Caribbean. Median age at presentation was 67 years, and five were female. Nine were asymptomatic at presentation, six presented with varices, five with malaise, three with abdominal pain, one with pruritis and one with oedema. Risk factors identified were : transfusion (7), haemodialysis (1), health care worker (dentist) (1), and tattoos (2). There was no recognized risk factor for infection in 14, but five of these had done military service in areas of high HCV prevalence. Liver biopsy in 20 showed chronic hepatitis in two, cirrhosis in 12, and cirrhosis and hepatocellular carcinoma in six. Three additional patients also developed hepatocellular carcinoma. HCV genotyping was done in 19 and all were type 1 (1a, 4 ; 1b, 14 ; 1 untypable, 1). Eleven died, at median age 71 years (range 65-94 years), five of HCV liver-related deaths and two from HCV-associated non-hepatic disorders (non-Hodgkin's lymphoma and fibrosing alveolitis).

Drugs that damage the liver account for 9.5% of all suspected adverse drug reactions (ADRs), are the main cause of fatal ADRs and are the most common reason for withdrawal of drugs from the market. Pre-market surveillance detects common ADRs, but those seen in clinical practice are rare (1 in 10,000–100,000). Their recognition depends on individual reports and post market surveillance. In the UK, the yellow card scheme is used to report all suspected ADRs with new drugs and serious ADRs with established drugs. Both under-reporting and over-reporting occur. Information on hepatotoxicity, therefore, is neither systematic or comprehensive. The liver is particularly affected as it is the central metabolizing organ through which all foreign compounds pass. Injury may be a direct toxic effect or immunological reaction to either the drug or an active metabolite formed by bio-activation (it was reported that for 62% of withdrawn drugs it is the metabolite that is toxic). Any type of liver injury can be reproduced by drugs and any drug can produce different types of liver injury. Injury may be acute or chronic and there can be adaptation to injurious effects with a transient increase in liver function in patients that have significant ongoing injury. Many factors interact to lead to injury and there is considerable variation in susceptibility which may be inherited and acquired. This contribution focuses on general principles of drug-induced liver disease. Information on specific ADRs can be obtained from the British National Formulary , drug datasheets and databases.

Dietary methionine (Met) restriction (MR) extends lifespan in rodents by 30–40% and inhibits growth. Since glycine is the vehicle for hepatic clearance of excess Met via glycine N-methyltransferase (GNMT), we hypothesized that dietary glycine supplementation (GS) might produce biochemical and endocrine changes similar to MR and also extend lifespan. Seven-week-old male Fisher 344 rats were fed diets containing 0.43% Met/2.3% glycine (control fed; CF) or 0.43% Met/4%, 8% or 12% glycine until natural death. In 8% or 12% GS rats, median lifespan increased from 88 weeks (w) to 113 w, and maximum lifespan increased from 91 w to 119 w v CF. Body growth reduction was less dramatic, and not even significant in the 8% GS group. Dose-dependent reductions in several serum markers were also observed. Long-term (50 w) 12% GS resulted in reductions in mean (±SD) fasting glucose (158 ± 13 v 179 ± 46 mg/dL), insulin (0.7 ± 0.4 v 0.8 ± 0.3 ng/mL), IGF-1 (1082 ± 128 v 1407 ± 142 ng/mL) and triglyceride (113 ± 31 v 221 ± 56...

Estriol-3-sulfate (E3S) is present in human breast cyst fluid (BCF) in median levels of 8.7-10.4 nmol/L, yet is barely detectable in the serum (less than 0.034 nmol/L). The source of this huge concentration of E3S is unknown. It may accumulate from blood by active transport or be synthesized and concentrated within the cyst. Since estrone sulfate (E1S) and its possible precursor, dehydroepiandrosterone sulfate (DHEAS) are elevated in BCF, E3S may originate via 16 alpha-hydroxylation of E1S. The present study examined the correlations between the levels of DHEAS and E1S with those of E3S in BCF. The sodium and potassium ions were also quantified and related to the steroid concentrations. By linear regression analysis of log-normalized data there was a highly significant correlation between the concentrations of E1S and E3S (n = 355, r = 0.690, P less than 0.001) and between DHEAS and E3S (n = 361, r = 0.577, P less than 0.001). The BCF were classified according to their K/Na ion ratios: type 1, greater than 1.0, type II, less than 0.25, and type III, 0.25-1.0. By Student's t test, the concentrations of E3S differed between each BCF Type (P less than 0.002). This was also true for E1S and DHEAS. Type 1 cysts were associated with the highest estrogen sulfate levels and type II with the lowest levels. The possible physiological importance of this observation resides in reports that the BCF type expressing the highest steroid concentrations has been related to an aporcine-like epithelial lining of the cyst wall and a somewhat higher risk for developing breast cancer. The results suggest that E3S in BCF may originate from E1S, but alternate mechanisms are not precluded.

A commercially available antidihydrotestosterone antiserum was used for the direct radioimmunoassay of androstenediol-3-sulfate (ADS) in human serum. Aliquots of 1 or 2 microliter male serum (mean age of 40 subjects, 38.2 +/- 5.0 years) were diluted and extracted with ethanol for assay. The tracer, [7-3H]ADS, was prepared by sodium borohydride reduction of [7-3H]dehydroepiandrosterone sulfate (DS). Significantly cross-reacting steroids were testosterone, DS, androsterone sulfate, and epiandrosterone sulfate, which combined to produce a mean overestimation of ADS of 4.3 micrograms/dl in male serum. Mean serum ADS was 23.6 +/- 10.0 micrograms/dl (SD) in 20 fresh-frozen sera versus 28.4 +/- 9.7 micrograms/dl (SD) in 20 long-term (24.4 +/- 1.2 years) frozen specimens, showing stability on long-term frozen storage. Androstenediol-3-sulfate also showed a strong correlation with serum DS (r = 0.75). The possible physiologic significance of ADS is discussed, particularly in terms of the known estrogenicity of unconjugated androstenediol.

Hannaford et al reported a significant 12% reduction in the risk of any cancer (adjusted relative risk 0.88, 95% confidence interval 0.83 to 0.94), which was widely cited in the popular media as reassuring evidence of the safety of oral contraceptives.1 But although it was prudent to exclude participants under age 38 at time of loss to follow-up, since use of oral …

Comparison of the Glasgow Alcoholic Hepatitis Score and the ABIC Score for the Assessment of Alcoholic Hepatitis

Dehydroepiandrosterone sulfate (DS) was measured by direct tritium RIA in longitudinal plasma specimens from 97 normal healthy male participants in the Baltimore Longitudinal Study of Aging. Fasting blood was collected at regular visits (approximately 1.5 yr apart) over an average 13 yr of adulthood (cumulative age range: 32-83 yr). DS was measured in 3-4 widely spaced specimens from each subject. A decline in DS was found in 65 (67%) subjects, 13 subjects (13%) showed no change, and increases were found in the 19 remaining subjects during the study period. A plot of individual data points revealed the same pattern we had obtained previously from a cross-sectional study of a different normal male population. A plot of DS values vs. age among subjects whose DS increased during the study also revealed an age-related decline. Thus, the longitudinal decrease in circulating DS, long inferred from cross-sectional data, is confirmed for normal men in the present study. A more detailed study of every specimen collected during the study period from 12 of the Baltimore Longitudinal Study of Aging subjects (4 whose values tended to be low, 4 whose values tended to be high, and 4 whose values were near the mean) failed to reveal any patterns of variation that could be correlated with changes in life circumstances, health status, or any other discernible factors. Hence, the wide variability seen in DS among individuals within normal populations remains unexplained.

Background: A review of biliary tract complications was performed in 32 patients who underwent liver transplantation by the Western Australian Liver Transplantation Service during a 2-year period. Methods: A review was made of patient data collected prospectively, and confirmed by retrospective casenote review. Results: A total of 30 patients (31 grafts) survived more than 2 days after transplantation, and of these 28 had an end-to-end biliary anastomosis. Analysis of these 28 patients found that eight of 17 patients with T-tubes had complications: three leaks at T-tube removal; two strictures and leaks; and three strictures. Six of 11 patients without a T-tube had complications: one leak; three strictures and leaks; and two strictures. Predisposing factors were present in eight of the 14 patients with biliary tract complications: hepatic artery stenosis in three; and one each with hepatic artery thrombosis; biliary calculi; donor–recipient bile duct mismatch; severe cellular rejection; and prolonged postoperative hypotension. Acute rejection, steroid-resistant rejection and cytomegalovirus infection were all significantly more common in those patients with biliary tract complications compared with those without. There was no difference in cold ischaemic time or donor age. Twelve of the 14 patients with biliary complications required endoscopic stenting with or without balloon dilation, and eight patients required radiological percutaneous drainage of bile collections. Only one patient required biliary reconstruction and two patients required re-transplantation. One patient died of uncontrolled infection. Of three patients who underwent choledochojejunostomy, biliary leak developed in two patients, both of whom required operative biliary and hepatic repair. One of the three patients died from disseminated Aspergillus infection. The median total hospital stay of patients with biliary complications was 61 days (range: 30–180 days) compared with 33.5 days (range: 22–70 days) for patients without. Of patients with end-to-end biliary anastomosis, 50% had biliary tract complications and more than half of these had predisposing factors. The majority of biliary complications were managed without the need for surgery. Conclusion: A total of 50% of patients with end-to-end biliary anastomosis had biliary tract complications. Biliary strictures presented later than leaks, and the majority of these complications were managed without the need for surgery.

Data were analyzed from 918 women aged 20-54 years at diagnosis with invasive breast cancer during 1986-89. The women had initially enrolled in a population-based case-control study investigating oral contraceptive use and the risk of breast cancer. Each case was pair-matched according to age and region of residence and cases and controls interviewed at home. Among parous women a history of induced abortion was associated with a 90% increased risk of breast cancer. Among nulliparous women no association was found between induced abortion and breast cancer. Neither among parous women nor nulliparous women was a history of spontaneous abortion related to the risk of breast cancer. The association between induced abortion and breast cancer was stronger in the southeastern regions of the country where there is a predominantly Roman Catholic population suggesting reporting bias. Support for reporting bias as an explanation for regional differences was also found in data supplied by study participants and their physicians on the use of oral contraception. The authors conclude that reporting bias is a real problem in case-control studies of induced abortion and breast cancer risk if study findings are based solely upon information from study subjects.

The epidemiology of hepatitis C virus (HCV) infection was studied in an English teaching hospital over an 18 month period. A total of 104 HCV antibody positive patients were referred for further investigation. They were divided into those diagnosed through screening (blood donors and intravenous drug abusers) and those diagnosed for other reasons, and their mean ages, known risk factors for HCV transmission, genotypes, and liver biopsy histology were analysed. Screened patients were significantly younger than the others. No significant difference in age was found between genotypes. Most patients genotyped (69%) were genotype 1. Intravenous drug abusers had a higher proportion of subtype 1a, and patients who acquired HCV through blood transfusion had a higher proportion of subtype 1b. Liver biopsy specimens were scored using a histological activity index for liver inflammation and fibrosis. Patients with subtype 1b had significantly more severe liver disease than other genotypes when the histological activity index scores for fibrosis were analysed (p

A 77-year-old Caucasian woman was referred for investigation of microcytic anaemia. She was known to have ischaemic heart disease and aortic valve disease. The patient complained of shortness of breath and lethargy with no other gastrointestinal specific symptoms. On examination, she had a systolic murmur in her aortic area and signs of mild heart failure with few crepitations in her chest and some lower limb oedema. Abdominal examination was normal. This woman …

Aims To review outcome in children with severe intestinal failure discharged home on parenteral nutrition (PN) treatment administered by parents. Methods All children discharged home on PN treatment since 1986 were reviewed. Primary diagnosis leading to intestinal failure, age, sex and outcome (1. recovered intestinal function and weaned off PN, 2. remained on treatment, 3. death) were recorded. Results 122 children, 63 male, 59 female were discharged home. Diagnoses were, short gut in 41 cases, enteropathy in 58 cases and motility disorder in 23. Children were aged from 2–27 years when reviewed and there were a total of 1150 years since start of treatment. Overall there was an 89% 1-year, 85% 2-year, 79% 5-year, 72% 10-year and 66% 20-year survival rate. 50% of children had weaned from PN within 5 years of commencing treatment. Children with short gut were more likely to regain intestinal function by 5 years in that 76% had weaned compared to 52% of those with other diagnoses. Conclusions Children with severe intestinal failure can survive for years on treatment with intravenous nutrition/PN with care by parents with a 72% 10 year survival rate. The best outcome was associated with short gut.

Serum dehydroepiandrosterone sulfate (DHEA-S) levels were measured in 270 men and 153 women who were experienced practitioners of the Transcendental Meditation (TM) and TM-Sidhi programs, mental techniques practiced twice daily, sitting quietly with the eyes closed. These were compared according to sex and 5-year age grouping to 799 male and 453 female nonmeditators. The mean DHEA-S levels in the TM group were higher in all 11 of the age groups measured in women and in 6 of 7 5-year age groups over 40 in men. There were no systematic differences in younger men. Simple regression using TM-group data revealed that this effect was independent of diet, body mass index, and exercise. The mean TM-group levels measured in all women and in the older men were generally comparable to those of nonmeditator groups 5 to 10 years younger. These findings suggest that some characteristics of TM practitioners are modifying the age-related deterioration in DHEA-S secretion by the adrenal cortex.

We have studied the clinical histories and liver biopsy findings in 1951 consecutive adult patients with suspected chronic liver disease, and in four known PiZ-homozygous alpha 1-antitrypsin-deficient patients with emphysema (candidates for lung transplant) and no known liver disease, in order to assess the importance of periportal alpha 1-antitrypsin granules in the liver and their possible causal role in liver disease, and to assess the value of possible screening tests. Periportal granules were found in 30 (1.5 per cent) of the 1951 liver biopsies and in all four known PiZ-homozygous subjects. They were the sole putative aetiological agent in eight of 85 patients (9.4 per cent) with otherwise cryptogenic cirrhosis and present in 2.5 per cent of patients with cirrhosis of known aetiology (alcohol, autoimmune etc.). All but one were Z phenotype (seven homozygotes, 22 heterozygotes). alpha 1-Antitrypsin granules were seen in 12 patients (including three of four lung transplant candidates) with no histological chronic liver disease. Determination of serum alpha 1-antitrypsin levels was quite unhelpful in identifying these patients. This study does not support the concept that periportal alpha 1-antitrypsin granules are necessarily pathogenic, but in some cases they may be causally related to otherwise cryptogenic liver disease. The presence of granules gave no important diagnostic, therapeutic or prognostic information.

The molecular genetics of five common single gene and one polygenic chronic liver disease is discussed. In two of the single gene disorders, alpha 1-antitrypsin deficiency and cystic fibrosis, the gene responsible is now known and the repertoire of different mutations underlying the disease is being defined. In the other three single gene defects (haemochromatosis, polycystic liver disease and Wilson's disease) the chromosomal location of the disease allele is known. It is anticipated that recombinant DNA techniques will enable the genes responsible for these diseases to be cloned in the near future, thus allowing the biochemical abnormalities to be defined through reverse genetics. In many chronic liver diseases the relative contribution of genetic and environmental factors remains unclear. Evidence suggests there is a definite genetic component in predisposition to alcoholic cirrhosis; the role of putative candidate genes is discussed. It is hoped that the definition of a genetic locus linked to alcoholic cirrhosis will ultimately teach us more about the basic pathogenesis of this disease.

The effects of selected hormones and drugs on freshly isolated mouse preputial gland cells have been studied. The steroid hormones, testosterone, DHT, androstanediol, androsterone and androstanedione all failed to stimulate and estradiol failed to inhibit, either DNA or lipid synthesis under the conditions studied. Thyroxine and insulin had no effect on lipogenesis but epinephrine and PGE 2 caused significant stimulation as did Bt 2 cAMP. The antilipemic drugs clofibrate, nicotinic acid and hydroxycitrate were all able to inhibit lipogenesis. Of the anti-acne drugs only L-DOPA was able to inhibit lipogenesis, neither tetracycline nor trans -retinoic acid showed any effect. Pyridoxine was unable to inhibit lipogenesis but DMSO caused dramatic stimulation though it was without effect on DNA synthesis. Evidence is presented which suggests that the lack of response to steroid hormones is not due to the inability of the cells to take up and metabolize the steroids but is due to the fact that the time-span of exposure is not long enough to elicit a cellular response. It is concluded that these freshly isolated cells are suitable for the study of those effects of hormones and drugs which occur within the first 3hr after exposure to the compound.