Macrophage phagocytosis and membrane fluidity in mice: the effect of age and dietary protein

Male C57BL/6NNia mice were used to investigate the effects of age and dietary protein intake on Fc and C3b receptor-mediated phagocytosis and on membrane fluidity. Six-month-old (adult) and 24-month-old (aged) mice were fed a 6% or 25% protein diet for 3, 5, or 6 weeks at which time thioglycollate elicited peritoneal macrophages were isolated. Both binding of IgG-coated sheep red blood cells to the macrophages and ingestion via the Fc-receptor were identical in all 4 groups after 3 and 6 weeks of feeding but were decreased at 5 weeks in the aged animals fed 6% protein. Phagocytosis via the C3b receptor was not depressed in either age group fed the low protein diet; it was, however, augmented significantly in the aged animals fed the 25% protein diet for 5 and 6 weeks. Membrane fluidity of the plasma membrane outer hemileaflet was monitored with an impermeant fluorescent probe. No changes were observed between adult and aged mice maintained up to 6 weeks on the diets.     

Serum osteoprotegerin is a predictor for incident cardiovascular disease and mortality in a general population: the Tromsø Study

Summary. Background: Osteoprotegerin (OPG) concentration in serum is associated with the presence and severity of atherosclerosis. Objective: To investigate the association between serum osteoprotegerin and the risk of a future myocardial infarction, ischemic stroke and mortality in a general population. Patients/methods: OPG was measured in serum collected from 6265 subjects recruited from a general population without a prior myocardial infarction and ischemic stroke (the Tromsø Study). Incident myocardial infarction, ischemic stroke and mortality were registered during follow‐up. Cox regression models were used to estimate crude and adjusted hazard ratios and 95% confidence intervals (HR; 95% CI). Results: There were 575 myocardial infarctions, 284 ischemic strokes and 824 deaths (146 deaths as a result of ischemic heart disease, 78 deaths because of stroke and 600 deaths due to other causes) in the cohort during a median of 10.6 years of follow‐up. Serum OPG (per SD [1.13 ng mL^?1] increase in OPG) was associated with an increased risk of a myocardial infarction (1.20; 1.11–1.31), ischemic stroke (1.32; 1.18–1.47), total mortality (1.34; 1.26–1.42), death because of ischemic heart disease, (1.35; 1.18–1.54), stroke (1.44; 1.19–1.75) and non‐vascular causes (1.31; 1.22–1.41) after adjustment for age, gender, current smoking, systolic blood pressure, body mass index, high density lipoprotein cholesterol, total cholesterol, creatinine, high sensitivity C‐reactive protein (CRP) and diabetes mellitus or HbA1c > 6.1%. No association was detected between OPG and incident hemorrhagic stroke (1.02; 0.73–1.43). Conclusions: Serum OPG was associated with future risk of myocardial infarction, ischemic stroke, total mortality, mortality of ischemic heart disease, stroke and of non‐vascular causes independent of traditional cardiovascular risk factors.     

Family history of myocardial infarction is an independent risk factor for venous thromboembolism: the Tromsø study

Summary. Background: Recent studies indicate that arterial cardiovascular diseases and venous thromboembolism (VTE) share common risk factors. A family history of myocardial infarction (MI) is a strong and independent risk factor for future MI. Objectives: The purpose of the present study was to determine the impact of cardiovascular risk factors, including family history of MI, on the incidence of VTE in a prospective, population‐based study. Patients and methods: Traditional cardiovascular risk factors and family history of MI were registered in 21 330 subjects, aged 25–96 years, enrolled in the Tromsø study in 1994–95. First‐lifetime VTE events during follow‐up were registered up to 1 September 2007. Results: There were 327 VTE events (1.40 per 1000 person‐years), 138 (42%) unprovoked, during a mean of 10.9 years of follow‐up. In age‐ and gender‐adjusted analysis, age [hazard ratio (HR) per decade, 1.97; 95% confidence interval (CI), 1.82–2.12], gender (men vs. women; HR, 1.25; 95% CI, 1.01–1.55), body mass index (BMI; HR per 3 kg m^?2, 1.21; 95% CI, 1.13–1.31), and family history of MI (HR, 1.31; 95% CI, 1.04–1.65) were significantly associated with VTE. Family history of MI remained a significant risk factor for total VTE (HR, 1.27; 95% CI, 1.01–1.60) and unprovoked VTE (HR, 1.46; 95% CI, 1.03–2.07) in multivariable analysis. Blood pressure, total cholesterol, HDL‐cholesterol, triglycerides, and smoking were not independently associated with total VTE. Conclusions: Family history of MI is a risk factor for both MI and VTE, and provides further evidence of a link between venous and arterial thrombosis.     

Quantitative liver function in patients with rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study

The objectives were to determine quantitative liver function prospectively in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX), to search for risk factors for a loss of quantitative liver function and to assess the relationship between quantitative liver function and histological staging. A total of 117 patients with RA (ACR criteria, 85 women, mean age 59 yr) had measurements of galactose elimination capacity (GEC), aminopyrine breath test (ABT) and liver enzymes [aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (AP), 7-glutamyl transferase (GGT), bile acids, bilirubin, albumin] before treatment with weekly i.m. MTX injections and every year thereafter. In 16 patients, liver biopsies were performed. Before the introduction of MTX, mean GEC was 6.6 mg/min/kg [5th to 95th percentile (5-95 PC) 5.1- 8.5; reference range 6.0-9.1] and mean ABT was 0.80% kg/mmol (5-95 PC 0.42-1.30: reference range 0.6-1.0). During treatment with MTX [mean weekly dose 11.8 mg (5-95 PC 5.4-20.2), mean observation period 3.8 yr (5-95 PC 0.4-6.9)], significant declines of GEC (-0.12 mg/min/kg per year. t = 3.30, P < 0.002) and ABT (-0.06% kg/mmol per year, t = 4.81, P < 0.001) were observed. Negative correlations were found between the annual change in GEC and GEC at baseline (Rs = -0.40, P < 0.0001), and the annual change in ABT and ABT at baseline (Rs = -0.43, P < 0.0001). No correlations were found between the annual change in GEC or ABT and weekly MTX dose, age or percentage of increased liver enzymes, and no effect of a history of alcohol consumption > 30 g/week became evident. Two patients with Roenigk grade III had impaired quantitative liver function, while 14 patients with Roenigk grades I and II exhibited a high variability of GEC and ABT from normal to abnormal values. The continuous declines in GEC and ABT observed deserve attention in patients with prolonged treatment. Patients with a low GEC or ABT at baseline seem not to be at increased risk for a further loss of quantitative liver function. An impaired GEC or ABT does not necessarily concur with hepatic fibrosis on histological examination.      

Acanthamoeba keratitis: a comprehensive photographic reference of common and uncommon signs

There has been a significant increase in the number of reported cases of Acanthamoeba keratitis reported internationally over the last 24 months. Diagnosing Acanthamoeba keratitis is often difficult and part of the difficulty is attributed to the variability of presentation. This article provides a comprehensive photographic reference of common and uncommon clinical signs of Acanthamoeba keratitis.     

Is there a national standard with respect to attitudes toward sexually explicit media material?

Surveys in 10 states conducted with probability samples of adults (N =4621) between 1976 and 1985 found that a statistically significant majority of the respondents in each state indicated acceptance of sexually explicit content in mass media. In each state, respondents felt that (i) standards have changed so that such material has become more acceptable; (ii) adults have the right to obtain such materials; and (iii) it is all right for adults to obtain and see materials containing exposure of the genitalia and every kind of sexual activity. Some factors contributing to what appears to be an emerging national consensus of acceptance are discussed. An earlier version of this paper was presented at the annual meeting of the American Association for Public Opinion Research, May 1988, in Toronto, Canada.     

The continuum of HIV care in Catalonia

The objective was to produce a cascade of care for Catalonia to gain a public health perspective on the overall quality of HIV services and allow comparison with other countries. It was constructed using the Integrated Epidemiological Surveillance System of HIV in Catalonia and data from the PISCIS Cohort. Estimates of the number of people living with HIV in Catalonia are modelled using Spectrum Projection Package 2011 (UNAIDS/WHO). Totals for each stage in the cascade are obtained by applying to the preceding stage a proportion estimated from available surveillance and cohort data. Undiagnosed HIV was estimated from the European literature. The proportions retained in care, on ART and virally suppressed were derived from the PISCIS cohort. Programmatic data on ART consumption was used to validate estimates. By the end of 2011 there were about 33,000 people living with HIV in Catalonia, 71% of which had been both diagnosed and linked to care. We estimate that 61% of all HIV infected persons were retained in care, 56% were on ART and 48% were virally suppressed. These figures data are comparable, although slightly lower, than that of France or the UK. The Cascade of HIV Care in Catalonia is similar to other western European countries such as France and the UK. Direct estimates of the undiagnosed HIV population and linkage to care are desirable but the contribution of cohort data to the cascade highlights their continued importance in HIV surveillance and design of evidence-based health strategies.     

An audit of consent refusals in clinical research at a tertiary care center in India

Background and Rationale:

Ensuring research participants’ autonomy is one of the core ethical obligations of researchers. This fundamental principle confers on every participant the right to refuse to take part in clinical research, and the measure of the number of consent refusals could be an important metric to evaluate the quality of the informed consent process. This audit examined consent refusals among Indian participants in clinical studies done at our center.

Materials and Methods:

The number of consent refusals and their reasons in 10 studies done at our center over a 5-year period were assessed. The studies were classified by the authors according to the type of participant (healthy vs patients), type of sponsor (investigator-initiated vs pharmaceutical industry), type of study (observational vs interventional), level of risk [based on the Indian Council of Medical Research (ICMR) “Ethical Guidelines for Biomedical Research on Human Participants”], available knowledge of the intervention being studied, and each patient''s disease condition.

Results:

The overall consent refusal rate was 21%. This rate was higher among patient participants [23.8% vs. healthy people (14.9%); P = 0.002], in interventional studies [33.6% vs observational studies (7.5%); P < 0.0001], in pharmaceutical industry-sponsored studies [34.7% vs investigator-initiated studies (7.2%); P < 0.0001], and in studies with greater risk (P < 0.0001). The most common reasons for consent refusals were multiple blood collections (28%), inability to comply with the study protocol (20%), and the risks involved (20%).

Conclusion:

Our audit suggests the adequacy and reasonable quality of the informed consent process using consent refusals as a metric.KEY WORDS: Autonomy, consent, India, reason, refusal, risk