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.

Expression of Thy-1 antigen by murine epidermal cells.

We report on the occurrence of a cell population within the murine epidermis which, by both morphologic and surface property criteria, is distinct from all other epidermal cell types known so far. These previously unrecognized cells are evenly distributed within the epidermis, display a primarily dendritic shape, exhibit a lobulated nucleus, contain large amounts of vimentin type intermediate-sized filaments, but lack desmosomes, melanosomes, Merkel cell granules, and Birbeck granules. As opposed to melanocytes, these cells fail to display tyrosinase activity. Surface marker analysis reveals these cells to uniformly express the Thy-1 antigen and to lack I-A and I-E/C antigen specificities. A major portion of these Thy-1-bearing cells are reactive with a monoclonal antibody to the Ly-5 determinant whereas attempts to demonstrate Lyt-1,2,3 antigens consistently yield negative results. These findings strongly suggest that Thy-1+ epidermal cells originate from the bone marrow; however, their precise relationship to distinct members of the hemopoietic differentiation pathway remains to be established.

Expression of the Ly-5 alloantigenic system on epidermal cells.

The expression of Ly-5 alloantigens is confined to hemopoietic cell types and is therefore considered a valuable indicator for the bone marrow derivation of a given cell. The further finding that different hemopoietic cell lineages express different molecular forms of the Ly-5 alloantigens prompted us to investigate (1) whether murine epidermal cells or subpopulations thereof express Ly-5 specificities and if so, (2) whether the expression of particular molecular configurations of Ly-5 antigens would allow us to gain a clue about the derivation of certain epidermal cell populations. When epidermal sheets from BALB/c, C57Bl/6, and C3H/He mice, were exposed to monoclonal anti Ly-5.1 antibody in an indirect immunofluorescence technique, a system of evenly distributed, dendritic cells was visualized. Allelic exclusion of the Ly-5 system was demonstrated by replacing anti-Ly-5.1 antibody by anti-Ly-5.2 reagent and by using epidermal sheets from SJL/J mice. Studies on epidermal cell (EC) suspensions revealed that about 1.6-5.2% of C3H/He EC were Ly-5-reactive and that approximately equal numbers of Ly-5-positive cells bore either Thy-1 or Ia antigens. Electron microscopic studies disclosed two morphologically different Ly-5-positive cell populations, i.e., cells of the Langerhans cell lineage and a recently defined cell system, whose most prominent feature is the expression of the Thy-1 antigen. We have termed these cells dendritic Thy-1+EC (dTHY-1+EC). In order to define the molecular configurations of the Ly-5 alloantigens, EC and spleen cells were internally labeled and--after immunoprecipitation of cell-membrane detergent extracts with anti-Ly-5.1--were analyzed on sodium dodecyl sulfate-polyacrylamide gels. Spleen cells yielded 3 bands with a molecular weight of 180,000, 195,000, and 215,000, respectively, as is characteristic for T lymphocytes, non-T/non-B cells, and B lymphocytes. In contrast, a single 195,000-200,000 dalton band was found in precipitates of both untreated and Langerhans cell-depleted (anti-Ia+C) EC. These data demonstrate the existence and active biosynthesis of the Ly-5 alloantigenic system on certain EC populations, i.e., Langerhans cells and dThy-1+EC, and therefore imply that both cell types originate from a bone marrow-derived precursor. The expression of the same molecular configuration of Ly-5 alloantigens on both LC and dThy-1+EC suggest that these two cell populations do not belong either to the T-cell or to the B-cell lineage and imply an ontogenetic relationship between dThy-1+EC and Ia-positive EC.

[Austrian AIDS counseling: responsibilities and strategies]. / Die Osterreichische AIDS-Hilfe: Aufgaben und Strategien.

The Austrian AIDS Foundation was founded in 1985 to satisfy the urgent needs of HIV-infected persons and those at increased risk of HIV infection, where such aid could not be met by existing medical institutions. Seven counselling centres with more than 100 members of staff provide services all over Austria. On the one hand the foundation offers help and support in all matters regarding HIV infection (counselling, social work, medical care). The second main task of the organization is the prevention of further spread of HIV through targeted information for the different groups (heterosexuals, homo/bi-sexual men, drug abusers, women, children and adolescents) to establish behaviour modification.

Neopterin as discriminating and prognostic parameter in healthy homosexuals, ARC and AIDS patients.

Urinary neopterin, a sensitive marker for activation of cell mediated immunity, is compared to clinical and laboratory data in 5 patients with AIDS, in 15 patients with ARC and in 40 male subjects without AIDS-related clinical signs attending an AIDS outpatient clinic. The sensitivity of neopterin for AIDS-related diseases was higher than that of the CD4+/CD8+ subset ratio. The differences in neopterin levels between the controls, ARC and AIDS patients were found to be more significant than the T-cell subset data. The observation that the 3 AIDS patients with the highest neopterin levels have died whereas the two others with the lower levels are still alive also underlines the prognostic potential of urinary neopterin level determinations. Measurement of urinary neopterin is thus recommended as an additional criterion for monitoring ARC and AIDS patients.

[AIDS therapy]. / AIDS-Therapie.

Therapy of AIDS comprises two aspects: (1) causative therapy, directed against HIV, and (2) symptomatic therapy of opportunistic infections and malignancies. The best results regarding antiretroviral therapy - both in vitro and in vivo - have been obtained, so far, with inhibitors of reverse transcriptase. We discuss the mechanism of action, the efficacy, and the side effects of AZT, a nucleoside analogue, and comment on combined therapies with acyclovir and immunomodulators. We report on the therapy of the most frequent opportunistic infection - i.e. Pneumocystis carinii pneumonia - with sulfamethoxazole/trimethoprim and pentamidine as well as the chemoprophylaxis of this disease. During the last few years, important progress has been made in the field of antiviral chemotherapy (HSV, CMV, VZV) and the therapy of gastrointestinal infections. Moreover, the therapy of Kaposi's sarcoma associated with AIDS and that of non-Hodgkin's lymphoma has been established by now.

[Cowden syndrome (multiple hamartoma syndrome)]. / Cowden-Syndrom (Multiple Hamartoma Syndrome).

This report deals with a female patient with multiple hamartoma syndrome (Cowden's disease) exhibiting characteristic cutaneous lesions and involvement of several inner organs.

[AIDS and the eye]. / AIDS und Auge.

The acquired immune deficiency syndrome (AIDS), is a recently described irreversible dysfunction of cell-mediated immunity in homosexuals, intravenous, drug abusers, and hemophiliacs, with subsequent development of potentially lethal opportunistic infections and/or unusual neoplasms, such as Kaposi's sarcoma. A prospective evaluation of ophthalmic findings in 14 patients with AIDS revealed that 8 patients had ophthalmoscopically and biomicroscopically significant ocular abnormalities, including peripapillary cotton-wool spots of changing frequency and diameter, retinal hemorrhages, progressive cytomegaly virus (CMV) retinitis, acute destructive retinal necrosis, periphlebitis, CMV conjunctivitis and keratitis, and in one patient a conjunctival Kaposi's sarcoma. All patients with AIDS and abnormal ocular findings carry a poor prognosis. Early detection of ocular manifestations is important, since most patients with AIDS are visually asymptomatic, and the ophthalmic presentation may be the primary one, and the initiating contact leading to diagnosis and permitting the prognosis to be assessed.

[South African tick bite fever]. / Südafrikanisches Zeckenbissfieber.

Two male patients developed South African tick bite fever after visits to South Africa. The clinical and laboratory findings in this condition, which is rarely seen in central Europe, are presented and its differential diagnosis to other rickettsial diseases is discussed.

[Serology in HIV infection: comparison of indirect immunofluorescence, Western blot and enzyme immunoassay]. / Serologie der HIV-Infektion: Vergleich von indirekter Immunfluoreszenz, Western Blot und Enzym Immunoassay.

145.990 sera obtained from AIDS-risks groups, hospitalized patients, blood donors etc. were tested for the presence of antibodies against the AIDS-Virus (HIV:Human Immunodeficiency Virus). All sera were submitted to ELISA screening. Sera with positive and questionable results were submitted to two independent confirmatory tests (Western Blot and immunofluorescence). In case of discordant confirmatory tests sera were additionally tested with the Abbott anti-HIV envelope/anti HIV core ELISA. The results of the present study demonstrate: 1. HIV serology has been definitely improved during the last year due to the development of high quality reagents. 2. Provided skilled and trained personnel the combined use of HIV confirmatory tests (Western Blot and immunofluorescence) does not give false negative or false positive results. 3. The results of both confirmatory assays may not always be interpretable ("problem sera"); this occurs more often with the Western Blot technique than with immunofluorescence. 4. Discrepant results in confirmatory tests necessitate the evaluation of many additional tests as possible. Such persons or patient should be further controlled serologically and clinically. 5. Checking the "problem sera" for antibodies against HTLV I gave only one single positive result in a Japanese.

[Hypereosinophilic dermatitis (Nir-Westfried). A variant in the spectrum of the hypereosinophilia syndrome]. / Die Hypereosinophile Dermatitis (Nir-Westfried). Eine Variante im Spektrum des Hypereosinophiliesyndroms.

Hypereosinophilic dermatitis represents a clinically distinct disorder in the spectrum of eosinophilic dermatoses. Its major clinical symptoms include pruriginous papular skin eruptions associated with blood eosinophilia. Histological examination reveals a diffuse, dense infiltration with eosinophils. We discuss the clinical picture, differential diagnosis, and therapy in the light of two cases.

Homozygous inheritance of the Machado-Joseph disease gene.

We report a patient presenting at age 16 years with postural instability and falls who developed severe generalized dystonia by the age of 20 years. He was the product of a consanguineous marriage. Maternal grandfather and paternal grandmother (brother and sister) living in the Azores were both affected by Machado-Joseph disease (MJD) beginning late in life. To date neither of the patient's parents are clinically affected. Linkage studies in this family and others of Azorean descent have confirmed the recent mapping of the MJD gene to chromosome 14q. Genotyping of the members of this pedigree provides strong genetic evidence that our patient is homozygous for the MJD gene. Our results combined with experience in 2 putative homozygotes previously reported in the literature suggest that gene dosage is an important determinant of age of onset and clinical phenotype in MJD. Other possible influencing factors are discussed.

Identification of individuals at increased risk for AIDS among clinically asymptomatic homosexuals and abusers of intravenous drugs.

Immunological parameters previously shown to constitute an increased risk for progression towards AIDS have been observed in clinically asymptomatic individuals considered to be at risk for this syndrome. These parameters include severely decreased numbers of T helper cells (count below 400/mm3 blood for CD4+ cells were detected in 7 our of 33 HIV antibody-positive, asymptomatic homosexuals and in 3 out of 29 HIV antibody-positive, asymptomatic drug abusers) and elevated serum IgA and IgM levels (found in 7 to 30 percent of these subjects). Furthermore, up to 60% of risk group members showed a decreased lymphoproliferative response to tetanus toxoid as compared to only 11% of so-called low responders in the simultaneously tested healthy controls. Finally, the capacity to mount an immune response to viral glycoproteins was found to be impaired in individuals at risk for AIDS, as indicated by a low serum level of antibodies to tick-borne meningoencephalitis virus antigen in recently vaccinated subjects.

Neopterin estimation compared with the ratio of T-cell subpopulations in persons infected with human immunodeficiency virus-1.

We measured neopterin, a biochemical indicator for the activation of cell-mediated immune reactions, in urines from 105 individuals at risk of infection with human immunodeficiency virus-1 (HIV-1), 83 of whom were seropositive for antibody to HIV-1. We compared absolute numbers of T-cell subsets (CD4+ helper/inducer T-cells, CD8+ suppressor/cytotoxic T-cells), and the ratio of CD4+ T-cells to CD8+ T-cells with the urinary neopterin concentrations. Concentrations of neopterin in urine were inversely correlated with absolute numbers of CD4+ T-cells and with CD4+/CD8+ ratios in anti-HIV-1 seropositive subjects but not in those seronegative. Various statistical comparisons of the data further demonstrated that neopterin concentrations showed larger differences between anti-HIV-1 seronegative and seropositive subjects than absolute numbers of CD4+ T-cells or CD4+/CD8+ ratios. These results seem to indicate that neopterin concentrations increase earlier in the course of HIV-1 infection, before effects on T-cell subpopulations are detectable, and may further support the suggestion that neopterin measurement could be of use for monitoring infected subjects or predicting the progression of disease.