The impact of alcohol on BCG-induced immunity against Mycobacterium tuberculosis.

BACKGROUND: Alcoholics are at heightened risk for developing active tuberculosis. This study evaluates chronic alcohol consumption in a murine model of vaccination with Mycobacterium bovis Bacille Calmette-Guèrin (BCG) and subsequent pulmonary infection with virulent Mycobacterium tuberculosis. METHODS: BALB/c mice were administered the Lieber-DeCarli liquid ethanol diet or pair-fed the liquid control diet for 3 weeks either before or after subcutaneous vaccination with M. bovis BCG. At least 3 weeks after BCG vaccination, groups of mice on the aforesaid diets were challenged with intratracheal infection with M. tuberculosis H37Rv. Lung mycobacterial burden, and lung and lung-associated lymph node CD4(+) lymphocyte production of tuberculosis-specific interferon (IFN)-γ were assayed. Popliteal lymph node lymphocytes from both dietary regimens undergoing BCG vaccination (in the absence of M. tuberculosis infection) were also evaluated for purified protein derivative-induced IFN-γ production by ELISpot assay. RESULTS: Mice begun on alcohol prior to vaccination with M. bovis BCG demonstrated impaired control of pulmonary challenge with virulent M. tuberculosis, as well as impaired lung CD4(+) and popliteal lymph node T-cell IFN-γ responses. If BCG vaccination was delivered prior to initiation of alcohol feeding, the mice remained protected against a subsequent challenge with M. tuberculosis, and BCG-induced immunity was not impaired in either the lung or the popliteal lymph nodes. CONCLUSIONS: Alcohol consumption blunts the development of the adaptive immune response to M. bovis BCG vaccination, which impairs the control of a secondary challenge with M. tuberculosis, but only if the alcohol exposure is begun prior to BCG vaccination. These results provide insight into mechanisms by which alcohol consumption impairs antimycobacterial immunity, including in response to vaccination and subsequent pathogenic challenge.

Niacin-a critical component to the management of atherosclerosis: contemporary management of dyslipidemia to prevent, reduce, or reverse atherosclerotic cardiovascular disease.

Niacin (nicotinic acid) is the most effective agent for raising high-density lipoprotein cholesterol levels and can improve the entire lipid panel in patients with dyslipidemia. Niacin-containing regimens are among the few treatments studied for dyslipidemia that have both elicited significant reductions in atherosclerotic progression (by angiography or imaging) and also significantly reduced (by approximately 90% vs control) the incidence of cardiovascular events in a single clinical trial. However, cutaneous flushing-an uncomfortable but typically transient adverse effect of niacin-often results in patient nonadherence with this potentially life-saving therapy. Effective counseling regarding the highly favorable benefit-risk ratio for niacin and management strategies such as careful dose escalation, follow-up monitoring, regimen adjustments, and the use of treatment adjuncts (eg, aspirin) can improve patient adherence with niacin therapy. Clinicians are uniquely positioned to provide such counseling to appropriate patients for niacin treatment and hence encourage wider use of this important and necessary cardioprotective medication.

Prescription omega-3s: an overview for nurse practitioners.

Nurse practitioners (NPs) often take a multidisciplinary approach when treating and educating patients. Collaboration with a registered dietitian is not uncommon when treating patients with severe hypertriglyceridemia (triglycerides [TGs] ≥500 mg/dL). Patients with severe hypertriglyceridemia should be treated and managed to normalize TG levels (TG level <150 mg/dL). Treatment for severe hypertriglyceridemia is often 3-fold, including lifestyle changes, diet modification, and pharmacotherapy. Therapeutic lifestyle changes are generally the first step in lowering TG levels. Registered dietitians promote a heart-healthy diet rich in fruits and vegetables. Evidence has been mounting to support consumption of eicosapentaenoic acid and docosahexaenoic acid to decrease TGs. When lifestyle and diet changes do not effectively decrease TGs, NPs will recommend pharmacological therapy as a next step. A viable pharmacological option includes prescription omega-3 (P-OM3) fatty acid ethyl esters. Each 4-g/d dose of P-OM3 provides 465 mg of eicosapentaenoic acid and 375 mg of docosahexaenoic acid. Clinical trials show that P-OM3 can safely and effectively decrease TGs by 45% in patients with severe hypertriglyceridemia. Nurse practitioners play an important role in the treatment of severe hypertriglyceridemia and in the education of patients about lifestyle and diet changes that can greatly impact patients' health.

Preventing coronary heart disease and stroke with aggressive statin therapy in older adults using a team management model.

PURPOSES: The purposes of this review were to highlight recent clinical trial results on the safety and efficacy of statin therapy in adults aged 65 years and older and to examine how nurse practitioners (NPs) and physician assistants (PAs) working together with physicians as a team can better serve the needs of this fastest growing subset of the U.S. population who are at high risk for cardiovascular events including stroke. DATA SOURCES: This report was compiled by reviewing the scientific literature on the safety and efficacy of statin therapy, including effects on cardiovascular, coronary, and stroke endpoints, with particular reference to clinical trial results in older patients. CONCLUSIONS: Recent guidelines emphasize that age alone is not a reason to withhold treatment with statin therapy in older adults. However, despite the evidence highlighted in this review demonstrating that older patients can safely achieve substantial benefit from statin therapy, studies have consistently shown an inverse relationship between age and treatment propensity. Often, older patients have multiple risk factors and many chronic comorbid conditions that seem to complicate and hinder treatment in many busy clinic practices. More extensive guidelines for the use of statin therapy in older patients, incorporating recommendations for treatment targets and developing a framework for the use of statins in stroke prevention, would assist care providers in the management of this high-risk population. Finally, NPs and PAs are both well educated and well placed to manage patients with chronic stable cardiovascular disease (CVD). IMPLICATIONS FOR PRACTICE: The implementation of a multidisciplinary team approach to identify at-risk individuals and provide them with education, counseling, and effective statin treatment will aid efforts to reduce the increased risk for morbidity and mortality associated with CVD in older adults.

Pulmonary interleukin-23 gene delivery increases local T-cell immunity and controls growth of Mycobacterium tuberculosis in the lungs.

Interleukin-23 (IL-23) is a heterodimeric cytokine that shares IL-12 p40 but contains a unique p19 subunit similar to IL-12 p35. Previous studies indicate a greater importance for intact IL-12/23 p40 expression than IL-12 p35 for immunity against Mycobacterium tuberculosis, suggesting a role for IL-23 in host defense. The effects of IL-23 on the outcome of pulmonary infection with M. tuberculosis have not been described. Here, we show that local delivery of replication-defective adenovirus vectors encoding IL-23 (AdIL-23) greatly stimulated expression of both gamma interferon (IFN-gamma) and IL-17 in lung tissues of otherwise normal mice. When given 72 h prior to infection with M. tuberculosis, AdIL-23 significantly reduced the bacterial burden at 14, 21, and 28 days. Markedly lower levels of lung inflammation were observed at 28 days than in control mice pretreated with control adenovirus (AdNull) or vehicle controls. AdIL-23 pretreatment resulted in increased numbers of CD4(+) CD25(+) activated T cells in lungs and draining lymph nodes compared to control groups and more CD4(+) T cells bearing surface memory markers in lung lymph nodes. IL-23 gene delivery also significantly enhanced host anti-mycobacterial T-cell responses, as shown by elevated levels of IFN-gamma and IL-17 secreted in vitro following restimulation with M. tuberculosis purified protein derivative. Overall, our data show that transient IL-23 gene delivery in the lung is well tolerated, and they provide the initial demonstration that this factor controls mycobacterial growth while augmenting early pulmonary T-cell immunity.

The nurse practitioner's role in helping patients achieve lipid goals with statin therapy.

PURPOSE: To discuss the merits of statins in achieving lipid goals and the role of nurse practitioners (NPs) in improving adherence to medical regimens with the goals of improving patient outcomes, reducing cardiovascular disease (CVD) risk within the population at large, and enhancing patients' ability to reach their individual goals. DATA SOURCES: Original research articles, journal articles, professional association practice guidelines. CONCLUSIONS: Despite extensive research clearly documenting the relation between lowering low-density lipoprotein cholesterol (LDL-C) and decreasing rates of cardiovascular events and deaths, lipid-lowering therapy is not being aggressively managed to achieve optimal lipid levels and CVDs remain the leading cause of death among adults in the United States. Contributing factors include lack of patient adherence with prescribed therapy, absence of dose titration when needed, and suboptimal follow-up. Two pathways to improving compliance are the following: first, use of a starting dose of a more efficacious statin to allow more patients to reach their LDL-C goal and, second, more effective primary care programs with NPs as team leaders who can assess and diagnose patients, then develop individual treatment plans and follow-up with patients to ensure that their lipid goals are met. IMPLICATIONS FOR PRACTICE: NPs are well suited to manage patients with hypercholesterolemia. The NP can bridge all aspects of care for the patient by overseeing assessment and treatment of cardiovascular risk factors, including elevated levels of LDL-C, initiating pharmacotherapy when needed, and establishing for each patient an individualized program that features education, support, and follow-up.

Pulmonary host defenses and factors predisposing to lung infection.

Hospital-acquired pneumonia remains a leading cause of nosocomial infections and is associated with significant rates of morbidity and mortality. Multiple host-, pathogen-, and intervention-related factors contribute to the development of pneumonia in this setting. Potentially deleterious impacts of illness or therapeutic modalities impair the host's ability to resist the development of pneumonia while in the hospital and predispose to a spectrum of pathogens of greater virulence than found in the community. Recognition of factors contributing to pneumonia in the hospital setting may offer the opportunity to intervene, minimizing, to the extent possible, the serious consequences of this nosocomial complication.

Alcohol exacerbates murine pulmonary tuberculosis.

Alcohol consumption has been described as a risk factor for infection with Mycobacterium tuberculosis, but its contribution to tuberculosis has been difficult to isolate from other adverse socioeconomic factors. Our objective was to evaluate the impact of alcohol consumption on pulmonary infection with M. tuberculosis in a murine model. BALB/c mice were maintained on the Lieber-DeCarli liquid ethanol diet or a liquid control diet and infected intratracheally with low-dose M. tuberculosis H37Rv. Lung organism burdens, lung and lung-associated lymph node CD4(+)- and CD8(+)- lymphocyte numbers and rates of proliferation, and CD4(+)-lymphocyte cytokine production levels were compared between the groups. The alcohol-consuming mice had significantly higher lung organism burdens than the control mice, and the CD4(+)- and CD8(+)-lymphocyte responses to pulmonary infection with M. tuberculosis were blunted in the alcohol group. Lymphocyte proliferation and production of gamma interferon were decreased in the CD4(+) lymphocytes from the alcohol-consuming mice. Additionally, lung granulomas were significantly smaller in the alcohol-consuming mice. In conclusion, murine alcohol consumption is associated with decreased control of pulmonary infection with M. tuberculosis, which is accompanied by alterations in the region-specific CD4(+)- and CD8(+)-lymphocyte responses and defective lung granuloma formation.

Immunity against mycobacteria.

Mycobacterium tuberculosis is the most prevalent infectious pathogen in the world, largely due to its unique interactions with the human immune system. Even in a normal host, a frequent outcome of infection with M. tuberculosis is failure to completely eradicate the organisms, despite the development of cell-mediated immunity. Viable organisms persist in a state in which they do not progressively replicate, leading to latent infection, which carries a risk of breakdown into active (reactivation) tuberculosis at some point later in life. Key features of the immune response against mycobacteria are reviewed here, and potential mechanisms by which the organisms may subvert these host defenses are discussed. Despite the multicellular nature of the host response to infecting mycobacteria, the organisms cannot be eradicated and contribute to the ongoing worldwide epidemic with tuberculosis.

Managing the spectrum of dyslipidemia in primary care.

Dyslipidemia, especially elevated low-density lipoprotein cholesterol (LDL-C), increases the risk of coronary heart disease and subsequent morbidity or mortality. For more than a decade, the National Cholesterol Education Program (NCEP) has endeavored to raise awareness of the dangers of dyslipidemia and to encourage the implementation of recommended treatment strategies. However, despite this initiative, previously published NCEP targets were not met. The recently released NCEP-Adult Treatment Panel III guidelines recommend more aggressive LDL-C reduction, elevation of categorical low high-density lipoprotein binding protein, and increased monitoring of moderate triglyceride elevations. Although the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are the most powerful medications available to reduce LDL-C, studies have shown that more than half of patients treated with these drugs do not achieve therapeutic targets and the resultant decrease in coronary heart disease events. There are a number of possible reasons for this, including potency of the statins and a lack of compliance on the part of patients and providers. Another concern with the available statins is the issue of drug-drug interactions. Some of these concerns may be addressed by newer agents in this drug class that are in development. They appear to have the potential to induce even greater reductions in LDL-C and to positively affect other lipoproteins. They also have the potential for less risk of drug-drug interactions. Nurse practitioners can play a pivotal role in improving the management of dyslipidemia by ensuring the proper implementation of current guidelines, helping patients adhere to treatment protocols, and remaining abreast of developments that may pave the way toward even more effective intervention in the future.

Ventilation-induced lung injury is associated with an increase in gut permeability.

Mechanical ventilation is associated with several harmful effects mainly related to high tidal volumes (Vt). Ventilator-induced lung injury can be responsible for an increased production of inflammatory mediators. We evaluated remote consequences on the gut of lung triggered inflammatory response, neutralizing anti-tumor necrosis factor (TNF) antibody was administered to assess the role of TNF in lung and gut permeability changes. Rats were anesthetized and ventilated for 2 h. A control group (Con: Vt = 10 mL/kg) was compared with a high Vt group (HV: Vt = 30 ml/kg). One microCi of I125-labeled human serum albumin was injected to measure extravascular albumin space. Gut permeability was evaluated by plasma-to-lumen ratio leakage of I125 human serum albumin. Extravascular albumin space increased in the HV group from 446 +/- 50 microL to 2783 +/- 887 microL. Gut index of permeability increased from 5.1 +/- 1.2 to 14.2 +/- 4.9. Anti-TNF antibody prevented both lung and gut increase in permeability. High tidal volume ventilation resulted in an increase in lung edema and gut permeability, antagonism of TNF with neutralizing antibodies abrogated the increase in gut permeability as well as lung edema.