Impact of left ventricular filling properties on the benefit of exercise training in patients with advanced chronic heart failure secondary to ischemic or nonischemic cardiomyopathy

This study examined left ventricular (LV) filling properties and exercise hemodynamics noninvasively before and after an exercise training program in patients with chronic heart failure (HF). Although exercise training did not improve LV filling properties in patients with advanced HF, LV filling properties determined the hemodynamic benefit attainable from exercise in this patient group.     

Neuroendocrine Responses in Alcoholics to the Presentation and Consumption of a Perceived Alcoholic Beverage

Eight male alcoholic inpatients in their 2nd week of treatment were presented with, and instructed to consume, a beverage described at one session as containing alcohol and at another as not containing alcohol. The beverage on each occasion did not, in fact, contain alcohol. The results indicated that when subjects believed they had consumed alcohol, the change in insulin from baseline was significantly greater at 10, 20, and 30 min following consumption. The findings suggest that the insulin response of alcoholics following ingestion of a carbohydrate-containing beverage is enhanced by the anticipation of ethanol.     

The older patient with diabetes: a practical approach

Type 2 diabetes mellitus is very prevalent among persons aged 60–80 years old. This population is expected to increase in number and is characterized by the presence of comorbidities, long standing diabetes, frailty, high rate of cognitive impairment and limited life expectancy. These characteristics have a significant impact on diabetes and treatment among the elderly, much as diabetes predisposes to these conditions. In this article we will describe mechanisms that may lead to insulin resistance and diabetes among the elderly and also how these conditions contribute to the development of frailty and cognitive impairment. Hypoglycemia and it's consequences are important considerations when planning the treatment of diabetes. Treatment options in light of new goals and the danger of hypoglycemia will be detailed. Copyright © 2013 John Wiley & Sons, Ltd.     

Interleukin-1 receptor type-1 in non-hematopoietic cells is the target for the pro-atherogenic effects of interleukin-1 in apoE-deficient mice

ObjectiveRecent studies indicate that regulatory T cells (Tregs) attenuate murine atherosclerosis. Since interleukin (IL)-2 induces Tregs proliferation, we tested the impact of L19-IL2, a fusion antibody specific to extra-domain B of fibronectin (ED-B) containing an active human IL-2 molecule, in experimental atherosclerosis.Methods and resultsL19-IL2 or appropriate controls were given intravenously to 6 month old Western diet-fed apoE^?/? mice on day 1, 3, and 5. Human IL-2 was detected on day 7 within atherosclerotic plaques of L19-IL2-treated mice, and magnetic resonance imaging of the plaques showed a significant adventitial gadolinium enhancement on day 7 and 13, suggesting microvascular leakage as a result of the pharmacodynamic activity of L19-IL2. Treatment with L19-IL2 significantly reduced the size of pre-established atherosclerotic plaques at the thoracic aorta (Sudan III stained area) and in the aortic root area (microscopic, morphometric analysis) on day 7 as compared to controls (L19, D1.3-IL2, NaCl) as well as compared to baseline (day 0). Tregs markers Foxp3 and CTLA4 were highly increased in plaques after L19-IL2 treatment compared to controls (p < 0.01), whereas the macrophage marker Mac3 was significantly reduced (p < 0.03). Co-treatment with IL-2-receptor blocking antibody PC61 abrogated L19-IL2-induced plaque reduction compared with IgG control (p < 0.03).ConclusionL19-IL2 delivers functional IL-2 to pre-established atherosclerotic plaques of WD-fed apoE^?/? mice resulting in significant plaque size reduction mediated by local Tregs.     

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.     

Education on and prevention of dental trauma: it's time to act!

Dental trauma is, unfortunately, not uncommon and may be even more prevalent in high-risk populations. It should be emphasized and acknowledged that many cases of dental trauma are preventable. Appropriate management includes primary prevention, i.e. avoidance of pathology development, and secondary prevention, i.e. early diagnosing and treatment of the pathology before significant morbidity occurs. The aim of this article is to provide a review of the current dental trauma literature with regard to education and knowledge and with relevance to primary and secondary prevention. As the duty of providing the public with measures for the maintenance of proper oral health is of the dental profession, the responsibility of providing primary and secondary prevention of dental trauma is of dentists, dental hygienists, and dental nurses. They may, and should, educate other medical, paramedical, and non-medical professionals, taking into account that those non-dental professionals could not maintain a high level of knowledge and service regarding dental trauma without a continuous backing by the dental professionals. It should be remembered that as the prevalence of dental decay has reduced in the Western world during recent decades, dental trauma plays a significant part in causing dental morbidity and mortality (tooth loss). It seems that now is the time to act for the benefit of our community and move from 'treating' toward 'managing' risk factors and prevention.