Kinder und Jugendliche in der COVID-19-Pandemie – zur besonderen Betroffenheit einer vermeintlichen „low risk group“

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz -     

Universal HIV testing and treatment and HIV stigma reduction: a comparative thematic analysis of qualitative data from the HPTN 071 (PopART) trial in South Africa and Zambia

Despite continued development of effective HIV treatment, expanded access to care and advances in prevention modalities, HIV‐related stigma persists. We examine how, in the context of a universal HIV‐testing and treatment trial in South Africa and Zambia, increased availability of HIV services influenced conceptualisations of HIV. Using qualitative data, we explore people’s stigma‐related experiences of living in ‘intervention’ and ‘control’ study communities. We conducted exploratory data analysis from a qualitative cohort of 150 households in 13 study communities, collected between 2016 and 2018. We found that increased availability of HIV‐testing services influenced conceptualisations of HIV as normative (non‐exceptional) and the visibility of people living with HIV (PLHIV) in household and community spaces impacted opportunities for stigma. There was a shift in community narratives towards individual responsibility to take up (assumingly) widely available service – for PLHIV to take care of their own health and to prevent onward transmission. Based on empirical data, we show that, despite a growing acceptance of HIV‐related testing services, anticipated stigma persists through the mechanism of shifting responsibilisation. To mitigate the responsibilisation of PLHIV, heath implementers need to adapt anti‐stigma messaging and especially focus on anticipated stigma.     

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Monoclonal gammopathy after intense induction immunosuppression in renal transplant patients

OBJECTIVES.: Incidence and risk factors of post-transplant monoclonal gammopathywere studied in renal transplant patients who received theirgrafts between 1982 and 1992 (n=390 grafts). Immunoelectrophoresiswas performed at annual intervals after transplantation. RESULTS.: Forty-six cases of clonal gammopathy were detected: 35 monoclonal,11 bi- or triclonal, with a predominance of IgG and K light-chainsubtypes (IgG, 39; IgA, 3; IgM, 4; K, 35; , 19). Gammopathywas transient in 17 patients (37%). The 5-year cumulative incidenceof gammopathy was 10.7%, much higher than expected for a groupof similar age from the general population. Thirty of the 46gammopathies appeared within the first 2 years of transplantation.Gammopathy never progressed to multiple myeloma during follow-up(median 1 year; (range 0–10)); one patient subsequentlydeveloped Kaposi sarcoma. The 2-year incidence of gammopathywas much higher in patients transplanted in 1989–1991(23/142) than in 1982–1988 (7/248) (P<0.0001). Thiscoincided with the use of quadruple induction immunosuppression(cyclosporin A+azathioprine+prednisone plus either ATG-Fresenius(ATG-F) or OKT3) since 1989. The risk for acquiring gammopathywithin 2 years of transplantation was 14.7% (95% CI 9.2, 20.3%)in patients receiving quadruple induction therapy, but only3.0% (CI 1.2, 6.1%) without such therapy (P<0.0001). Therisk for patients receiving quadruple immunosuppression withOKT3 was 24.5%, significantly greater than with ATG-F (11.8%,P<0.05). Discriminant analysis revealed that the type ofimmunosuppression, but not age or year of transplantation, wereindependent risk factors for gammopathy. CONCLUSIONS.: Monoclonal gammopathy frequently occurs after renal transplantation.Risks are higher for patients receiving quadruple inductionimmunosuppression, particularly if it includes OKT3. Follow-upof these patients is warranted for the early detection of malignanttransformation.     

In vitro and in vivo down-regulation of human plateletα 2-adrenoceptors by clonidine

Summary The effect of clonidine on the number of ₂-adrenoceptors in human platelet membranes, determined by³H-yohimbine binding, was investigatedin vitro andin vivo. Incubation of platelet membranes with clonidine (1–100 µM) for 16 h at 25 °C led to a concentration-dependent decrease in the number of³H-yohimbine binding sites of 10–25%; the affinity of³H-yohimbine to the sites was not changed (K_D approximately 3–4 nM). In such desensitized membranes, inhibition of³H-yohimbine binding by clonidine resulted in steep, monophasic displacement curves, which in comparison to the curves from control membranes (IC₅₀ for clonidine 90 nM), were shifted to the right (IC₅₀: 321 nM) and were not affected by 10^–4M guanosine-5-triphosphate (GTP).Treatment of 3 hypertensive patients with clonidine (3×150 µg/d for 7 days) reduced blood pressure and heart rate. Simultaneously, both³H-yohimbine binding sites on platelet membranes and plasma catecholamine levels decreased within three days and remained at a reduced level during treatment. After abrupt cessation of clonidine treatment, blood pressure, heart rate and plasma catecholamines rapidly increased, reaching values after two days similar to or higher than those before treatment.³H-yohimbine binding sites, however, initially decreased further before returning to control values. In platelet membranes derived from hypertensive patients treated with clonidine for at least three weeks, GTP (10^–4M) had no influence on inhibition of³H-yohimbine binding by (—)-adrenaline and clonidine. It is concluded that clonidine desensitizes ₂-adrenoceptors in human platelet membranesin vitro andin vivo. An important step in the desensitization process is the uncoupling of receptor occupancy by agonists and adenylate cyclase activity, as indicated by loss of the regulatory activity of GTP on desensitized membranes. The clonidine withdrawal syndrome may be caused by enhanced release of endogenous catecholamines not adequately regulated by presynaptic ₂-adrenoceptors, which have become subsensitive after chronic clonidine treatment.     

Production of antivenom against detoxified taipoxin and immunochemical analysis of the alpha, beta and gamma subunits.

Taipoxin from the Australian taipan Oxyuranus s. scutellatus, was detoxified by reaction with p-bromophenacyl bromide and used for preparing antibodies in rabbits. Of its three subunits only the basic α-chain and the acidic γ-chain evoked antibody production, which may suggest that the neutral β-subunit is hidden in the complex. The antibodies did not cross-react with notexin from Notechis s. scutatus nor did taipoxin cross-react with antivenom against Bungarus multicinctus, in accordance with previous findings. Immunochemical studies show a strong interaction between α and γ, whereas α-β- and β-γ-interactions are weak. In animal experiments no protection was observed when antibodies (in excess) were injected i.v. 5 min after taipoxin. This confirms the irreversibility of the attack, perhaps enzymatic (phospholipase), on vital structures in the nerve terminal membranes and emphasizes the urgency of speedy antisera injections in cases of snake-bite in Australia. The modification with p-bromophenacyl bromide ought to be generally useful in the production of high-titre antibodies against snake venoms in a short time and with no ill effects in the antisera-producing animals.     

Characterization of human lymphocyte antigen class I antigen-processing machinery defects in renal cell carcinoma lesions with special emphasis on transporter-associated with antigen-processing down-regulation.

The HLA class I antigen-processing machinery (APM) plays a crucial role in the generation of peptides from endogenously synthesized proteins and in their presentation to cytotoxic T lymphocytes. The potential role of defects of APM components in immune escape mechanisms used by malignant cells has prompted us to analyze their expression in renal cell carcinoma (RCC) lesions with special emphasis on TAP because of its critical role in the loading of HLA class I antigens with peptides. Immunohistochemical staining of 51 formalin-fixed RCC lesions and autologous normal renal epithelium detected transporter associated with antigen processing (TAP)1 and tapasin deficiencies in 63 and 80% of the tumor lesions. Impaired low molecular weight protein (LMP)2 and LMP7 expression was found in 73 and 33% of the RCC lesions analyzed, respectively. In contrast to the high frequency of APM component down-regulation, HLA class I heavy chain and beta(2)-microglobulin defects were detected in only 12 and 10% of the lesions, respectively. Concomitant TAP1 and LMP2 deficiencies were found in approximately 57% of RCC lesions, whereas a coordinated down-regulation of all APM components occurred only in 5% of the tumor specimens analyzed. The presence of APM defects was independent of tumor stage and grade but varied significantly among the RCC subtypes. TAP abnormalities do not appear to be attributable to structural alterations because no mutations in TAP1 were detected in TAP1-deficient RCC lesions. These data suggest that TAP defects in RCC lesions are caused by regulatory abnormalities. Therefore, T-cell-based immunotherapy may benefit from the administration of cytokines that up-regulate TAP expression.