The risk of polyomavirus-associated graft nephropathy is increased by a combined suppression of CD8 and CD4 cell-dependent immune effects.

Polyomavirus-associated graft nephropathy (PAN) has emerged as a significant risk factor for kidney graft loss. We analyzed intracellular cytokine responses for possible protective versus permissive immunologic effects on BK-virus replication. One hundred five renal transplant patients included in a prospective single-center study were randomized to receive cyclosporine mycophenolate mofetil (MMF) (CM: n = 31), tacrolimus (Tac)/MMF (TM: n = 32) or Tac/MMF with conversion to everolimus (TErl; n = 32). Ten patients were not randomized (NR) due to contraindications to MMF. The immunosuppressive therapy was monitored pre- and posttransplantation at 4, 12, and 24 months using triple fluorescence flow cytometry for intracellular interleukin (Il)-2 Il-4 and interferon (IFN)-γ production in phorbol myristate acetate- and lipopolysaccharide- stimulated lymphocyte cultures. BK viremia screening was performed by reverse-transcriptase polymerase chain reaction testing on days 0, 14, 30, 60, 90, 120, 180, 270, 360, and 720. Seven of 105 (6.7%) patients developed biopsy-proven PAN (CM: n = 1, TM: n = 3, TErl: n = 2, NR: n = 1), among whom 4 lost their grafts (TM: n = 1, TErl: n = 2, NR: n = 1). Twenty-one of 105 (20.0%) patients had documented BK viremia. BK viremia which preceded PAN in all cases, was significantly associated with TM immunosuppression: 4/31 (12.9%) CM: 11/32 (34.4%) TM; 5/32 (15.6%) TErl, and 1/10 (10.0%) NR patients (P = .034). BK-viremic patients showed significantly diminished CD8(+) T-cell Il-2 production at 120 days (P = .011) and 1 year posttransplantation (P = .014) compared with non-BK-viremic patients. Patients with PAN displayed significantly lower CD4(+) T-cell Il-4 responses at 1 and 2 years after transplantation (1 year: P = .007; 2 years: P = .001) with diminished IFN-γ responses at 1 year after transplantation (P = .011). Our analysis showed the incidence of BK viremia to be increased among patients with defective cytotoxic CD8(+) T-cell -dependent immune reactivity. Recipients who progressed from BK viremia to overt PAN showed an additional immunologic defect in CD4(+) T-cell function. Patients on a Tac- plus MMF-based immunosuppression were at higher risk to develop BK viremia.

Platelet autoantibodies (IgG, IgM, IgA) against glycoproteins IIb/IIIa and Ib/IX in patients with thrombocytopenia.

Autoimmune thrombocytopenic purpura (AITP) is most frequently induced by platelet-specific autoantibodies against epitopes on platelet GP Ib/IX or GP IIb/IIIa. These antibodies are reliably detected on the patients' autologous platelets. So far, studies on the characterization of platelet autoantibodies have been restricted to IgG antibodies. We used the monoclonal antibody immobilization of platelet antigens assay (MAIPA) in a modified version to detect GP-specific IgG, IgM, and IgA antibodies. Platelets of 46.2% of patients carried elevated amounts of IgG antibodies. IgM and IgA antibodies were observed less frequently and showed only weak OD signals in the MAIPA assay. Circulating IgG antibodies in serum were found in 11.5% of patients. Circulating IgM autoantibodies were observed in 8.9% and IgA antibodies in no patient with AITP. Results of direct MAIPA assay were compared with the reactivity of eluates in the platelet adhesion immunofluorescence assay and were found to be highly concordant. Patients with AITP in remission carried high percentages of anti-GP IIb/IIIa. Findings made in this study suggest that autoantibodies of the IgM and IgA classes play only a minor role in the pathogenesis of AITP.

[A retrospective analysis of the treatment results in Hodgkin's disease in a radiotherapy clinic]. / Retrospektive Analyse der Behandlungsergebnisse bei Morbus Hodgkin in einer strahlentherapeutischen Klinik.

PURPOSE: Treatment results were reviewed in a retrospective analysis and compared with literature data. Prognostic factors for freedom from relapse and overall survival were identified. PATIENTS AND METHODS: We analyzed the history of 183 patients treated for Hodgkin's disease between 1977 and 1989 at the Department of Radiation Therapy at the University of Würzburg. There were 100 males and 83 females between 16 and 86 years of age. 70.5% of patients presented with early stage Hodgkin's disease (23.5% stage I and 47.0% stage II) and 29.5% had advanced stages (25.1% stage III and 4.4% stage IV). All patients were treated initially with radiotherapy, 114 had radiotherapy alone and 69 patients received combined modality treatment. RESULTS: Hundred and sixty-one patients (88.0%) reached a complete remission. Freedom from relapse was 73.7% at 5 years and 70.3% at 10 years for these patients, overall survival was 74.3% and 62.8% at 5 and 10 years for all patients. Prognostic factors for freedom from relapse were stage IV, B symptoms, age greater than 35 years and more than 3 involved lymph node regions. These factors also were relevant for overall survival, in addition mixed cellularity or lymphocyte depleted subtype, high erythrocyte sedimentation rate, failure to achieve a complete remission following initial treatment and relapse of Hodgkin's disease were identified as negative prognostic factors. Laparotomy staged patients who received radiotherapy only for stage I and II Hodgkin's disease had better outcome than clinically staged patients. Our data suggest that adequate therapy is able to reduce the impact of unfavourable prognostic factors. The outcome for patients with bulky mediastinal disease was similar to that in patients without a mediastinal mass. CONCLUSIONS: The optimal choice of treatment for patients with early stage Hodgkin's disease--combined modality treatment/radiotherapy alone/chemotherapy alone?--and for patients with advanced stages--consolidation radiotherapy?--remains an unresolved issue and needs further testing in large randomized trials considering acute and late complications. Staging laparotomy may be used only for a small group of patients who would receive radiotherapy alone as definitive treatment. Modifications of therapy clearly reduce the impact of negative prognostic factors.

[Two modifications of MAIPA assays for the demonstration of platelet antibodies]. / Zwei Modifikationen des MAIPA-Assays zum Nachweis thrombozytärer Antikörper.

The monoclonal antibody immobilization of platelet antigens assay (MAIPA), published in 1987, is now used by many laboratories for detection of platelet antibodies. False-positive results were observed with sera containing anti-mouse IgG and in cases where MAIPA was employed to characterize platelet-specific antibodies of the IgM class. Modifications of MAIPA which completely eliminate these artifacts are described.

Marketing in home health care. A practical approach.

Home health marketing brings special problems and opportunities. One cannot rely on physical factors such as the physical plant and food service of a hospital or on the durability of a consumer product to judge home health. Opportunities exist within home health to identify activities that carry marketing value. Applying marketing principles to activities such as intake, customer service and public relations allows the home health agency to build referrals by meeting the wants and needs of the market. The home health organization needs to consider different wants and needs of those involved in the home health transaction: the decision maker, the purchaser, and the user. The success of the marketing function in meeting the organization's objectives will be aided by the placement of marketing at the senior management level.

[Study on the normal mercury concentrations of human organs (author's transl)]. / Untersuchung zur normalen Quecksilberkonzentration menschlicher Organe.

Organ samples of the right kidney the right and left lobe of liver, the cerebellum, and the left cerebrum (cortex and marrow separately) from 51 autopsies were analysed on their mercury content. A special high pressure-digestion was used for the sample preparation. The quantitative determination of the mercury concentrations was performed by the so-called cold vapour technique. In the organs the following median mercury concentrations were found: a) left lobe of liver: 58 microgram/kg b) right lobe of liver: 54 microgram/kg c) right kidney: 96 microgram/kg d) cerebellum: less than 5 microgram/kg e) cerebrum cortex: less than 5 microgram/kg f) cerebrum marrow: less than 5 microgram/kg. All values were below the internationally discussed range. No sex differences were detectable in the median mercury concentrations of the analysed organs. The positive correlation between age and the mercury concentration in the cerebellum could reflect an accumulation over the life. But most likely the concentrations still stay considerably below the critical limits. The negative correlations between age and the mercury concentrations of the liver lobes as well as of the kidneys indicates a change in the distribution of mercury in the body with increasing age.