Developmental failure of chimeric embryos expressing high levels of H-2Dd transplantation antigens.

The absence of expression of class I products of the major histocompatibility complex at early stages of development is thought to play a key role in maternal tolerance of the fetal allograft. To test this, we developed a strategy that would allow us to describe the consequences of overexpression of the H-2Dd transplantation antigen in the developing embryo. A construct containing the H-2Dd gene under control of the human beta-actin promoter was transfected into pluripotent embryonic stem (ES) cells. Particularly in this case, since overexpression of major histocompatibility complex class I gene products may profoundly affect embryonic development, an important advantage of the ES cell system is the ability to analyze gene expression and study effects on cell growth and differentiation in vitro. ES cells do not constitutively express beta 2-microglobulin. Consistent with this, H-2Dd H chains expressed by ES cell transformants were not associated with beta 2-microglobulin or transported to the cell surface. Significant levels of beta 2-microglobulin and H-2Dd membrane glycoproteins were expressed following differentiation in vitro. H-2Dd-transfected ES cells gave rise to a wide range of differentiated cell types, and there was no evidence to suggest that expression of the introduced H-2Dd gene affects the differentiation abilities of ES cells in vitro. When introduced into blastocysts, H-2Dd-transfected ES cells extensively contribute to embryonic and extraembryonic tissues, but this results in the failure of chimeric conceptuses at midgestation. Considering that transgenic chimeras cannot be rescued by transfer into syngeneic foster females, it seems likely that nonimmunological mechanisms are responsible for these prenatal lethalities.     

Immunoblastic sarcoma with features of Sj?gren's syndrome and systemic lupus erythematosus in a patient with immunoblastic lymphadenopathy.

A patient with immunoblastic lymphadenopathy and features of Sj?gren's syndrome and systemic lupus erythematosus is presented. Clinical features included generalized lymphadenopathy, rash, alopecia, and synovitis, with associated laboratory abnormalities of a positive antinuclear factor and double-stranded DNA antibodies, positive lupus band test, and hemolytic anemia. Symptoms of Sj?gren's syndrome included dry eyes and mouth and swollen parotid gland; biopsy results of the accessory salivary glands were positive. At autopsy immunoblastic sarcoma was found that involved the myocardium, which stained for both kappa and lambda light chains by immunoperoxidase techniques.     

Food Insecurity and Cost-Related Medication Underuse Among Nonelderly Adults in a Nationally Representative Sample

Objectives. We investigated whether nonelderly US adults (aged 18–64 years) in food-insecure households are more likely to report cost-related medication underuse than the food-secure, and whether the relationship between food insecurity and cost-related medication underuse differs by gender, chronic disease, and health insurance status.Methods. We analyzed data from the 2011 and 2012 National Health Interview Survey (n = 67 539). We examined the relationship between food insecurity and cost-related medication underuse with the χ² test and multivariate logistic regression with interaction terms.Results. Bivariate and multivariate analyses showed a dose–response relationship between food insecurity and cost-related medication underuse, with an increasing likelihood of cost-related medication underuse with increasing severity of food insecurity (P < .001). This association was conditional on health insurance status, but not substantially different by gender or chronic disease status. Being female, low-income, having no or partial health insurance, chronic conditions, functional limitations, or severe mental illness were positively associated with cost-related medication underuse.Conclusions. Using food insecurity as a risk factor to assess cost-related medication underuse could help increase identification of individuals who may need assistance purchasing medications and improve health for those in food-insecure households.Food insecurity refers to “limited or uncertain availability of nutritionally adequate and safe foods or limited or uncertain ability to acquire acceptable foods in socially acceptable ways.”1^(p6) Food insecurity is associated with poor health status and risk factors such as obesity, metabolic conditions, and chronic diseases, potentially attributable to intake of poor-quality diets, which increase the risk for obesity and cardiometabolic diseases.2–5 Studies of diabetic patients living in food-insecure households have shown poor outcomes such as poor glycemic control and increased physician use.6,7 Moreover, there is evidence that people living in food-insecure households are more likely to have poor mental health outcomes,8,9 use alcohol,10 and smoke cigarettes11—factors also associated with poor health status.Recent research suggests that people living in food-insecure households may adjust their behaviors in ways that are potentially detrimental to their health. Ivers and Cullen suggest that the vulnerability of food insecurity puts individuals at risk for engaging in coping strategies (e.g., withdrawal of children from school, theft, and risky sexual behaviors), particularly among women who tend to be children’s primary caregivers.12 One set of behaviors that has received relatively little attention as a potential coping mechanism for food insecurity until recently is reducing, skipping, delaying, or using lower-cost medications to compensate for lack of household resources to purchase food. These behaviors have been described as cost-related medication underuse.13,14Studies have demonstrated the relationship between cost-related medication underuse and poor health outcomes,15–19 but, to our knowledge, only 1 study has examined the relationship between food insecurity and cost-related medication underuse in the United States in a nationally representative sample.13 This study, which was restricted to individuals with chronic diseases, found that those living in food-insecure households were more likely to report cost-related medication underuse. Similar findings have been demonstrated from smaller studies in different parts of the country among people with diabetes, people with HIV/AIDS, and patients presenting at emergency departments.20–24We extend the literature on behaviors individuals living in food-insecure households may adopt to save money for food by examining the relationships between food insecurity and cost-related medication underuse in a nationally representative sample of nonelderly adults living in the United States. The objective of this analysis was to determine whether nonelderly adults (aged 18–64 years) living in food-insecure households in the United States are more likely to report cost-related medication underuse. We also examined whether the relationship between food insecurity and cost-related medication underuse differs by gender, chronic disease status, and health insurance status.     

A Low Pulse Food Intake May Contribute to the Poor Nutritional Status and Low Dietary Intakes of Adolescent Girls in Rural Southern Ethiopia

Poor nutrition in adolescent girls poses critical health risks on future pregnancy and birth outcomes especially in developing countries. Our purpose was to assess nutritional status and dietary intake of rural adolescent girls and determine pulse and food intake patterns associated with poor nutritional status. A cross-sectional community-based study was conducted in a traditional pulse growing region of southern Ethiopia on 188 girls between 15 to 19 years of age, with 70% being from food insecure families. Prevalence of stunting (30.9%) and underweight (13.3%) were associated with low food and nutrient intake. Diets were cereal-based, with both animal source foods and pulses rarely consumed. Improving dietary intakes of female adolescents with nutrient dense foods would ensure better health for themselves and for the next generation.     

Venous pressure and exercise tolerance.

Compared to the number of contractions obtained when a blood pressure cuff on the upper arm was at zero pressure, inflation of the cuff to pressures ranging between 5 and 40 mm Hg resulted in an augmentation of the number of hand contractions that could be performed prior to the development of ipsilateral severe fatigue or intolerable pain. Cuff pressures of 60 mm Hg reduced the number of contractions below the control level. These results are consistent with the concept that exercise during venous congestion facilitates the washout of the toxic catabolite presumed to be produced during muscular contraction.     

Lower rather than higher levels of B-type natriuretic peptides (NT-pro-BNP and BNP) predict short-term mortality in end-stage heart failure patients treated with nesiritide

Elevated plasma natriuretic peptides in heart failure (HF) usually indicate a poor outcome and low levels a compensated state. In advanced chronic HF, however, low levels may reflect an impaired neurohormonal response. To assess this hypothesis, this study analyzed whether N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) and B-type natriuretic peptide (BNP) levels were related to mortality in 40 patients treated for decompensated chronic HF. Cardiovascular mortality during follow-up (10 +/- 1 months) was 40%. BNP levels were lower in patients who died (487 +/- 60 vs 836 +/- 99 pg/ml, p <0.02), as were NT-pro-BNP levels (9,507 +/- 1,178 vs 17,611 +/- 4,338 pg/ml, p <0.05). These data support the hypothesis that patients with end-stage HF and poor short-term survival have lower natriuretic peptide levels than those who survive. These findings suggest that the natriuretic peptide system can no longer contribute adequately to neurohormonal compensation and that paradoxically low peptide levels are an adverse prognostic marker in advanced HF.