Recombinant gamma interferon induces hypertriglyceridemia and inhibits post-heparin lipase activity in cancer patients.

Animals suffering from malignancy or chronic infection develop characteristic metabolic abnormalities, including a well-defined hypertriglyceridemic state. These abnormalities have been attributed to release of one or more mediators from activated macrophages. We report that cancer patients receiving RIFN-gamma, a potent macrophage activator, at doses of greater than or equal to 0.25 mg/m2/d i.m. show marked increases in triglyceride but not in cholesterol levels (pretreatment triglyceride level of 180 +/- 190 mg/dl [mean +/- SD] vs. a day-14 level of 370 +/- 242 mg/dl, n = 23, p less than 0.001 by the paired t test). This hypertriglyceridemia was characterized by an increase in very low-density lipoproteins and a decrease in plasma post-heparin lipase activity, consistent with defective triglyceride clearance (mean pretreatment lipase level of 2.1 mumol/ml/h vs. a day-14 level of 1.2 mumol/ml/h, n = 6, p = 0.02 by the paired t test). rIFN-gamma did not directly inhibit lipoprotein lipase enzymatic activity in vitro. Other possible mechanisms of action, such as suppression of lipase by an rIFN-gamma-induced mediator released from activated macrophages, or a direct effect of interferon on lipase biosynthesis, require further investigation. Our observations provide evidence that factors produced by the immune system can regulate lipid metabolism in man

The ethics and politics of addressing health inequalities

Social determinants of health are responsible for a large proportion of disease which disproportionately affects deprived population groups, resulting in striking disparities in life expectancy and quality of life. Even systems with universal access to healthcare (such as the UK's NHS) can only mitigate some consequences of health inequalities. Instead substantial societal measures are required both to reduce harmful exposures and to improve standards of housing, education, work, nutrition and exercise. The case for such measures is widely accepted among healthcare professionals but, in wider discourse, scepticism has remained about the role of government and society in improving life chances along with the belief that responsibility for health and wellbeing should rest with individuals themselves. The stark inequalities exposed by the coronavirus pandemic could be an opportunity to challenge this thinking. This paper argues that doctors should do more to persuade others of the need to address health inequalities and that to achieve this, it is important to understand the ethical and philosophical perspectives that are sceptical of such measures. An approach to gaining greater support for interventions to address health inequalities is presented along with reflections on effective political advocacy which is consistent with physicians’ professional values

Blood, men and tears: keeping IUDs in place in Bangladesh.

The Intra-Uterine Device (IUD) is an effective method of contraception, but in Bangladesh is associated with high levels of discontinuation within the first year. This study involved data collection from a retrospective cohort of women who had an IUD inserted 12 months earlier. In the cohort, 330 women were interviewed to identify factors associated with discontinuation. Later, 20 women, of the 103 who reported discontinuing because of excessive menstrual bleeding, were interviewed again and in depth about these issues. Of 330 women who had an IUD inserted, 47.3% had discontinued use one year post-insertion. In univariate and multivariate analyses, IUD discontinuation was strongly associated with side-effects (heavier periods; abdominal pain) and spousal factors (not discussing IUD with husband pre-insertion), but not with service delivery factors. In-depth interviews with women who reported excessive blood loss as the main reason for discontinuation found a doubling of both menstrual days and blood loss after IUD insertion. In Bangladesh, women cannot pray, have sexual intercourse, perform household tasks or participate in community activities during menstruation. Thus, women with menstrual side-effects faced serious physical, social and psychological challenges that made continuation difficult. Among those who discontinued, spouses were generally unsupportive and sometimes abusive, particularly when not involved in the decision to use the IUD

Vulnerability re-assessed: the changing face of sex work in Guntur district, Andhra Pradesh.

We conducted a qualitative study to examine the impact of an HIV prevention programme on female sex workers' lives in Guntur district, Andhra Pradesh. The study found evidence that, in addition to the HIV prevention programme, structural and environmental factors had recently changed the way sex work was being practiced. Recent closure of the brothels and implementation of a late-night street curfew by the police meant sex work had become more hidden, with clients often solicited using mobile phones from home or their work place (e.g., in the fields or factories). Sex work had become safer, with violence by non-regular partners rarely reported. Women understood the risks of unprotected vaginal sex and reported using condoms with their clients. However, clients were more frequently requesting anal sex, possibly due to recent exposure to pornography following increased accessibility to modern technologies such as mobile phones and the Internet. Anal sex with clients was common but women were often unaware of the associated risks and reported unprotected anal sex. HIV positive and/or older women faced severe financial hardship and difficulty soliciting sufficient clients, and reported unprotected vaginal and anal sex to earn enough to survive. Taken together, the findings from this study suggest changing vulnerability to HIV in this setting. It will be important for HIV prevention programmes to be flexible and creative in their approaches if they are to continue to reach this target community effectively

What is the balance of benefits and harms for lung cancer screening with low-dose computed tomography?

After the National Lung Screening Trial (NLST)1 demonstrated improved lung cancer mortality almost a decade ago, hopes have been raised that low-dose computed tomography could be used to detect lung cancer in asymptomatic populations and improve outcomes by reducing the number of people diagnosed with advanced disease. The publication of the long-awaited Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) trial last year2 has provided further evidence of a lung cancer mortality benefit and has provoked further calls to implement national population-based screening programmes, but the case for lung cancer screening remains controversial

Early-stage lung cancer associated with higher frequency of chest x-ray up to three years prior to diagnosis

Objectives: Symptom awareness campaigns have contributed to improved early detection of lung cancer. Previous research suggests that this may have been achieved partly by diagnosing lung cancer in those who were not experiencing symptoms of their cancer. This study aimed to explore the relationship between frequency of chest x-ray in the three years prior to diagnosis and stage at diagnosis. Settings: Lung cancer service in a UK teaching hospital. Participants: Patients diagnosed with lung cancer between 2010 and 2013 were identified. The number of chest x-rays for each patient in the three years prior to diagnosis was recorded. Statistical analysis of chest x-ray frequency comparing patients with early- and late-stage disease was performed. Results: One-thousand seven-hundred fifty patients were included – 589 (33.7%) with stage I/II and 1,161 (66.3%) with stage III/IV disease. All patients had at least one chest x-ray in the six months prior to diagnosis. Those with early-stage disease had more chest x-rays in this period (1.32 vs 1.15 radiographs per patient, P = 0.009). In the period 36 months to six months prior to lung cancer diagnosis, this disparity was even greater (1.70 vs 0.92, radiographs per patient, P < 0.001). Conclusions: Increased rates of chest x-ray are likely to contribute to earlier detection. Given the known symptom lead time many patients diagnosed through chest x-ray may not have been experiencing symptoms caused by their cancer. The number of chest x-rays performed could reflect patient and/or clinician behaviours in response to symptoms

Graves-PCD: protocol for a randomised, dose-finding, adaptive trial of the plasma cell-depleting agent daratumumab in severe Graves\u27 disease

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ. INTRODUCTION: Severe Graves\u27 disease is a life-changing condition with poor outcomes from currently available treatments. It is caused by directly pathogenic thyroid-stimulating hormone receptor-stimulating antibodies (TRAb), which are secreted from plasma cells. The human anti-CD38 monoclonal antibody daratumumab was developed to target plasma cells which express high levels of CD38, and is currently licensed for treatment of the plasma cell malignancy, myeloma. However, it can also deplete benign plasma cells with the potential to reduce TRAb and alter the natural history of severe Graves\u27 disease. This study aims to establish proof of concept that daratumumab has efficacy in patients with severe Graves\u27 disease and will provide important data to inform a choice of dosing regimen for subsequent trials. METHODS AND ANALYSIS: The Graves-PCD trial aims to determine if daratumumab modulates the humoral immune response in patients with severe Graves\u27 disease, and if so, over what time period, and to find an optimal dose. It is a single-blinded, randomised, dose-finding, adaptive trial using four different doses of daratumumab or placebo in 30 adult patients. Part 1 of the trial is dose-finding and, following an interim analysis, in part 2, the remaining patients will be randomised between the chosen dose(s) from the interim analysis or placebo. The primary outcome is the percentage change in serum TRAb from baseline to 12 weeks. ETHICS AND DISSEMINATION: The trial received a favourable ethical opinion from London-Hampstead Research Ethics Committee (reference 21/LO/0449). The results of this trial will be disseminated at international meetings, in the peer-reviewed literature and through partner patient group newsletters and presentations at patient education events. TRIAL REGISTRATION NUMBER: ISRCTN81162400

Quasi-periodic vs. irreversible dynamics of an optically confined Bose-Einstein condensate

We consider the evolution of a dilute Bose-Einstein condensate in an optical trap formed by a doughnut laser mode. By solving a one dimensional Gross-Pitaevskii equation and looking at the variance and the statistical entropy associated with the position of the system we can study the dynamical behavior of the system. It is shown that for small condensates nonlinear revivals of the macroscopic wave function are expected. For sufficiently large and dense condensates irreversible dynamics takes place for which revivals of regular dynamics appear as predicted in [9]. These results are confirmed by a two dimensional simulation in which the scales of energy associated with the two different directions mimic the experimental situation.Comment: 10 page