[Pulmonary Immune Mechanisms in Tuberculosis]. / Pulmonale Immunität bei Tuberkulose.

Tuberculosis is transmitted by inhalation of Mycobacterium tuberculosis-containing aerosols; 75 % of all patients show pulmonary manifestation. Immune responses after exposure that lead to clinical symptoms occur mainly in the respiratory tract and are only poorly understood. In most cases, cells of the innate immune system are believed to control the growth of or eradicate inhaled mycobacteria. However, this cannot be verified in vivo using standard methods. Subsequently, CD4+ and CD8+ T cell-driven adaptive immune responses are induced that attempt to control bacterial growth. The humoral defence appears to be less important. This article gives an overview of the current understanding of pulmonary immune mechanisms during exposure, latent infection, active disease and therapy of tuberculosis.

Therapy and prophylaxis of opportunistic infections in HIV-infected patients: a guideline by the German and Austrian AIDS societies (DAIG/ÖAG) (AWMF 055/066).

INTRODUCTION: There was a growing need for practical guidelines for the most common OIs in Germany and Austria under consideration of the local epidemiological conditions. MATERIALS AND METHODS: The German and Austrian AIDS societies developed these guidelines between March 2010 and November 2011. A structured Medline research was performed for 12 diseases, namely Immune reconstitution inflammatory syndrome, Pneumocystis jiroveci pneumonia, cerebral toxoplasmosis, cytomegalovirus manifestations, candidiasis, herpes simplex virus infections, varizella zoster virus infections, progressive multifocal leucencephalopathy, cryptosporidiosis, cryptococcosis, nontuberculosis mycobacteria infections and tuberculosis. Due to the lack of evidence by randomized controlled trials, part of the guidelines reflects expert opinions. The German version was accepted by the German and Austrian AIDS Societies and was previously published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF; German Association of the Scientific Medical Societies). CONCLUSION: The review presented here is a translation of a short version of the German-Austrian Guidelines of opportunistic infections in HIV patients. These guidelines are well-accepted in a clinical setting in both Germany and Austria. They lead to a similar treatment of a heterogeneous group of patients in these countries.

[Tuberculosis]. / Tuberkulose.

Tuberculosis is still one of the most important infectious disease worldwide. In Germany the tuberculosis incidence has been declining for decades to currently about 4500 new cases per year. A new challenge poses the rising number tuberculosis cases with drug resistant strains of Mycobacterium tuberculosis. Substantiell progress has been achieved in the diagnosis of tuberculosis with new molecular techniques that can lead to a much faster and more reliable identification of cases with acid-fast bacilli smear-negative tuberculosis and in the identification of drug-resistant strains of M. tuberculosis. Tuberculosis caused by drug resistant strains of M. tuberculosis is difficult to treat with the currently available medications and is related to very high costs of care. New therapeutic approaches and drugs are urgently needed. Interferon-γ tests have made the diagnosis of latent infection with M. tuberculosis more specific, but hardly contribute to the diagnosis of active tuberculosis.This article presents a brief summary of current knowledge concerning the epidemiology, risk factors, diagnosis and treatment of active tuberculosis and latent infection with M. tuberculosis. Moreover, current treatment approaches and economic aspects of care are discussed.

[Infections with non-tuberculous mycobacteria in HIV-infected patients]. / Infektionen mit nichttuberkulösen Mykobakterien bei HIV-infizierten Patienten.

Disseminated infections with non-tuberculous mycobacteria (NTM) are a life-threatening AIDS-defining illness. Localized infections include pulmonary and extra-pulmonary disease as well as the immune reconstitution inflammatory syndrome (IRIS). Furthermore cutaneous and subcutaneous manifestations of systemic NTM-Infections have been reported. Skin infections without involvement of other anatomical regions are predominantly caused by M. marinum and M. ulcerans. No association with HIV is proven for these two species. This article summarizes the diseases caused by this heterogeneous group of bacteria. The focus is on disseminated disease, dermatological manifestations and extra-pulmonary localized infections. Diagnostic challenges, therapeutic strategies and prognosis of NTM-infections are discussed.

[Infections with non-tuberculous mycobacteria and HIV]. / Nicht-tuberkulöse Mykobakteriosen bei der HIV-Infektion.

Infections with non-tuberculous mycobacteria (NTM) belong to the AIDS-defining illnesses of HIV infection. Severe immunosuppression with CD4+ lymphocyte counts lower than 50 cells/microl is a risk factor for the acquaintance of NTM infections. More than 90% of NTM infections in HIV-seropositive individuals are caused by bacteria of the M. avium complex. The manifestations of the disease are heterogeneous and not specific for the causative mycobacterial species. Furthermore, the differentiation between infection and colonisation can be challenging, especially when NTM are isolated from respiratory specimen. Diagnosis and therapy are recommended according to the guidelines of the American Thoracic Society and the Infectious Diseases Society of America (ATS/IDSA). The treatment success relies on the effects of antiretroviral therapy and a combination of 2 - 4 antimycobacterial antibiotics tailored to the NTM species. In vitro resistance testing often does not predict the clinical response. Interactions with antiretroviral medications are common. The complexity of HIV/NTM co-infection is discussed from an epidemiological, microbiological and clinical perspective.

Pharmacokinetics of acetyl-L-carnitine given in single or multiple doses to HIV-1 Infected patients with toxic peripheral polyneuropathy.

The use of nucleoside reverse transcriptase inhibitors in the treatment of HIV infection is associated with antiretroviral toxic polyneuropathy (ATN). Previous studies suggest that long term treatment with Acetyl-L-carnitine (ALCAR) 1.5 gram twice daily improves symptoms and promotes nerve regeneration. It is unknown whether the drug's pharmacokinetic profile would allow for a once daily administration. Twenty three HIV-1 infected subjects taking ALCAR for ATN were enrolled in a cross over trial and switched from twice to once daily dosing. Their regimen was changed from 1.5 g twice daily to 1g (4 patients), 2g (7), and 3g (12) once daily, respectively. Twelve healthy volunteers served as control. Plasma levels of ALCAR and its metabolite L-carnitine were measured. Patients receiving ALCAR had higher pre-dose levels than control subjects. Post dose levels were not significantly higher than pre dose levels in any treatment group. The pre / post dose ALCAR concentrations were 7.6 / 7.7, 7.1 / 6.8, 7.7 / 6.8, and 7.1 / 7.5 micromol/l for 1.5 g twice daily, 1g once daily, 2g once daily, and 3g once daily, respectively. All values were significantly higher than the mean concentration in the control group (4.3 micromol/l). For ALCAR and L-carnitine, measurements for once daily regimens did not differ from the twice daily regimen. Once daily dosing of ALCAR can achieve similar plasma levels as twice daily dosing but intra-mitochondrial levels remain unknown. The pharmacokinetic profile of orally administered ALCAR is complex and likely to be highly affected by endogenous concentrations.

Long-term clinical and surrogate marker effects of subcutaneous intermittent interleukin-2 without antiretroviral therapy in HIV-infected patients.

OBJECTIVES: Subcutaneous administration of interleukin-2 (IL-2) has been shown to increase CD4 counts in HIV-infected patients. It remains unclear whether this effect is associated with a clinical benefit. PATIENTS AND METHODS: We conducted a long-term follow-up in the cohort of the UK-Vanguard study in which three groups of 12 antiretroviral-naive subjects with CD4 cell counts >350 cells/mm(3) received no treatment or IL-2 at either 4.5 or 7.5 MIU twice daily in 5 day cycles, respectively. RESULTS: Mean follow-up was 376 weeks. IL-2 therapy was associated with a higher area under the curve of CD4 cell count change from baseline at week 48 but not thereafter. HIV-RNA levels were unaffected. Highly active antiretroviral therapy (HAART) was initiated after a mean of 172, 175 and 152 weeks in the control group, low-dose and high-dose IL-2 treatment group, respectively, a statistically non-significant difference. There was a tendency to start HAART soon after discontinuation of IL-2 therapy which may have been triggered by the steep decay of CD4 counts. There were two serious adverse events in the control group, seven in the low-dose IL-2 group and eight in the high-dose IL-2 group. No pattern of disease was detected, making an association with IL-2 therapy unlikely. CONCLUSIONS: We could detect neither a benefit of IL-2 therapy after week 48 nor delayed initiation of HAART. This is currently the longest follow-up data comparing IL-2 therapy with no therapy in antiretroviral-naive HIV-infected patients and does not show a persistent benefit of the intervention.

Safety, pharmacokinetics, and efficacy of (+/-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine with efavirenz and stavudine in antiretroviral-naïve human immunodeficiency virus-infected patients.

Racivir [RCV; (+/-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine], a 50:50 racemic mixture of the two beta nucleoside enantiomers, is currently in development for the treatment of human immunodeficiency virus type 1 (HIV-1) infections. RCV was administered once a day orally for 14 days at doses of 200, 400, or 600 mg in combination with stavudine and efavirenz to HIV-1-infected treatment-naïve male volunteers in a phase Ib/IIa study. Six volunteers at each dose were monitored for a total of 35 days for tolerance, pharmacokinetics, and plasma HIV RNA levels. RCV in combination with stavudine and efavirenz was well tolerated at all doses tested. Pharmacokinetic parameters were dose proportional, and the maximum concentration of drug in serum at all doses exceeded the 90% effective concentration for wild-type HIV-1. Viral loads dropped as expected in all dosage groups, with mean reductions from 1.13 to 1.42 log10 by day 4 and 2.02 to 2.43 log10 by day 14. HIV RNA levels remained suppressed for more than 2 weeks in the absence of any additional therapy, with mean viral loads ranging from 2.1 to 2.6 log10 below baseline through day 28. By day 35, HIV RNA levels began to increase but still remained >1 log10 below baseline levels.

[The cardiotropic effect of antidepressants in aging patients (author's transl)]. / Zur frage der kardiotropen Wirkung von Antidepressiva insbesondere bei Alterspatienten.

All antidepressants now used have a cardiotropic, for some instances also cardiotoxic effect. This quinidine-like effect prolongs the QT-interval of ECG and can induce reentry and ventricular fibrillation. When quinidine and antidepressants are combined in the same patient the risk of such cardiac complications increases.

Viability of Bacillus popilliae after lyophilization of liquid nitrogen frozen cells.

The per cent viability of Bacillus popilliae after lyophilization of liquid nitrogen frozen cells was determined. Lyophilization of 9- to 12-hr cells which had been suspended in 5% sodium glutamate plus 0.5% gum tragacanth, frozen in liquid nitrogen vapor, and dried 4 to 5 hr with the ampoules exposed to room temperature resulted in survival of 64.6% of the original cells. After storage of these lyophilized preparations for 6 months at room temperature, 10.5% of the original cells were still viable.