Metabolisch-vaskuläres Syndrom – ein gesundheitspolitisches Problem

The identification of risk patients for diabetes is an important challenge in medicine and health economics. A model project is being carried out by general practitioners and diabetologists, in cooperation with prevention centers and health insurance companies in the region of Jena. Patients receive a find-the-risk questionnaire from their family physician, health insurance company or pharmacist. If indications for diabetes are present, an oral glucose tolerance test is carried out. Risk patients with impaired glucose tolerance are identified and sent to prevention centers where they are evaluated by prevention managers and offered an interdisciplinary, primary prevention program (lifestyle change). The patient is supervised for 3 years with quality control being carried out by the prevention center.     

Absence of structural alterations of the multidrug resistance genes in transitional cell carcinoma

Summary Tumor DNA from 27 patients with treated or untreated transitional cell carcinomas of the urinary tract was screened for genomic alterations of the multidrug resistance genes in order to determine whether structural changes of these genes are important in primary urothelial tumors. None of the tumors showed evidence of amplification or rearrangements of either mdr1 or mdr2. The lack of amplification or rearrangements observed in these tumors suggests that structural alterations of the mdr1 and mdr2 genes are not important mediators of drug resistance in TCC.Supported in part by grant CA-34775 from the National Institutes of Health and by a grant from the Heckscher Foundation for ChildrenDr. Klein is a fellow of the American Cancer Society     

Evaluation of filling materials in membrane‐protected bone defects. A comparative histomorphometric study in the mandible of miniature pigs.

In recent years, bone grafts and bone substitutes have been increasingly utilized underneath barrier membranes to optimize the treatment outcome of bone reconstructive therapy for defects in the alveolar process. In the present study, 4 different filling materials were evaluated in bone defects of similar dimensions in the mandible of miniature pigs. Blood clots and autografts were used as controls. The defects were covered with barrier membranes and allowed to heal for 4, 12 or 24 weeks. Histologic examination demonstrated that bone repair progressed through a programmed sequence of maturation steps closely resembling the pattern of bone development and growth regardless of whether bone grafts or substitutes were present or not. Histomorphometric analysis showed that autologous bone grafts (autografts) had the best osteoconductive properties during the initial healing period, with 39% of newly formed bone inside the membrane-covered defects at 4 weeks of healing. In addition, 87% of the graft surfaces were already covered by bone at this time. Both values were significantly higher for autografts than for the 4 alternative bone fillers (P < or = 0.05). At 12 weeks, these differences were no longer apparent, with all 5 filling materials showing similar values. Among the tested bone substitutes, tricalcium phosphate (TCP) showed a significantly higher percentage of bone fill at 24 weeks of healing. It can be concluded that sites filled with autografts clearly demonstrated the best results underneath barrier membranes in the early phase of healing. As far as degradation and substitution are concerned, TCP showed the most promising results. This filler, however, needs to be tested further in a more demanding animal model. Less favorable results were obtained for coral-derived hydroxyapatite granules and for demineralized freeze-dried bone allografts.     

The black hole effect in perimetry

Light-emitting diodes (LEDs), mounted in drilled holes in the perimeter bowl, are used as stimuli in several automated perimeters. A concern is that these "black holes" might interrupt the otherwise uniform background illumination and cause inconsistent test results. A Dicon perimeter was modified by covering some of the LEDs with diffusing plastic. One eye of 41 normal volunteers was tested repetitively within the central 5 degrees of the visual field at the same 12 locations with both covered and uncovered LED stimuli. Higher variances of multiple threshold determinations were observed, significant at the 0.0005 level, when testing was done with uncovered LEDs. On average, the black hole effect contributed 0.8 dB to short-term fluctuation. The black hole effect is probably of minor clinical importance except in exacting quantitative perimetry.     

Genotypic and phenotypic variability of 22q11.2 microduplications: An institutional experience

Duplications in the 22q11.2 region can cause 22q11.2 duplication syndrome and encompass a variety of phenotypes including developmental delays, facial abnormalities, cardiovascular defects, central nervous system delays, and other congenital abnormalities. However, the contribution of these contiguous duplicated regions to the clinical phenotypes has not been fully elucidated. In this study, we identified nine patients carrying different 22q11.2 microduplications detected by chromosomal microarray. Of these patients, seven pediatric patients presented with various clinical features including two neonate cases died shortly after birth, and two healthy adults. We examined region specific genotype–phenotype associations and found unpredictability associated with 22q11.2 duplications in these nine patients.     

Attenuated poxvirus expressing three immunodominant CMV antigens as a vaccine strategy for CMV infection.

BACKGROUND: Human cytomegalovirus (CMV) infection is an important risk factor in the post-transplant (Tx) recovery phase for both hematopoietic stem cell Tx (HSCT) and solid organ Tx (SOT) recipients. CMV infection may be prevented or controlled by simultaneously inducing both CMV-specific neutralizing antibody (nAb) and cellular immunity. Soluble (s) UL55 (surface glycoprotein), UL83 (tegument protein) and UL123/e4 (nuclear protein) are immunodominant in eliciting both CMV nAb and cellular immunity. An attenuated poxvirus, modified vaccinia Ankara (MVA) was selected to develop this vaccine strategy in Tx recipients, because of its clinical safety record, large foreign gene capacity, and capability to activate strong humoral and cellular immune responses against recombinant antigens. OBJECTIVES: A subunit vaccine that targets multiple CMV antigens will be used to gain maximal coverage and protective function against CMV infection. rMVA simultaneously expressing sUL55, UL83 and UL123/e4 will be generated, and humoral and cellular immunity it elicits will be characterized, after murine immunization and in vitro to amplify clinical recall responses. STUDY DESIGN: rMVA will be constructed in two steps using UL123/e4-pLW22 followed by sUL55-UL83-pLW51 transfer plasmids. Western blots will be used to characterize expression levels of each antigen. Primary immunity will be evaluated in mouse models, while recall responses to the virally expressed CMV antigens will be assessed in human peripheral blood. RESULTS: We generated CMV-MVA via homologous recombination, and demonstrated high expression levels of sUL55, UL83 and UL123/e4 by Western blot. CMV-MVA immunization potently induced both humoral and cellular immunity to sUL55, UL83 and UL123 after murine immunization, and cellular immunity to UL83 and UL123 by in vitro amplification of T cell recall responses in human PBMC. CONCLUSIONS: rMVA promotes high level expression of three immunodominant CMV antigens, which is reflected in results of immunization studies in which high titers of UL55-specific antibodies and CD4+ T-help are detected, as well as high levels of UL83-specific and moderate levels of UL123-specific CD8+ CTL.     

Elevated rubella antibodies in patients with chronic liver disease

Patients with autoimmune chronic active hepatitis (AICAH) and certain other chronic liver disorders often have very high titres of haemagglutination -inhibition (HI) antibodies to rubella virus. In this study it is shown, using floatation centrifugation, that the high rubella HI reactivity is not caused by nonspecific lipoprotein inhibitors but rather by antibodies specific for the rubella haemagglutinin (E1 glycoprotein). After sucrose density gradient ultracentrifugation of sera the major HI reactivity was recovered in the IgG containing fractions. The IgG antibody fraction was strongly reactive by an indirect enzyme-linked immunosorbent assay (ELISA). Higher prevalence and titres of rubella antibodies were also demonstrated by the complement fixation (CF) test using a haemagglutinin-free antigen, and by an indirect haemagglutination (IHA) test (Rubacell) using a cell-associated antigen which is distinct from the antigens used in the HI and CF tests. This high rubella antibody response is therefore demonstrated using three distinct antigen-antibody systems. By means of absorption experiments and radioimmunoprecipitation assays the coating antigen used in the IHA test was shown to reside in the E2 glycoprotein. The cause of this enhanced antibody response to rubella virus structural proteins remains elusive. © 1994 Wiley-Liss, Inc.     

The dual effect of L-proline on spreading depression in the chicken retina

Evidence was presented for a glutamate agonistic effect of L-proline which promotes K+-based spreading depressions (SD) in chick retinas at relatively high concentrations (5 mM), in addition to an antagonistic effect which inhibits glutamate-based SDs at lower (2 mM) concentrations. Together these effects explain the observed biphasic effect of L-proline on the incidence of SD in the retina.     

Isolation of Coccidioides immitis F antigen by immunoaffinity chromatography with monospecific antiserum.

Detection of antibody to Coccidioides immitis F antigen is of proved value in the diagnosis of coccidioidomycosis. This antibody is demonstrable by use of an immunodiffusion assay with reference coccidioidin antigen and antiserum to C. immitis. Using a combination of lectin affinity and immunoaffinity chromatography, we isolated the F antigen from coccidioidin and prepared monospecific antibody to the purified antigen. The availability of these reagents will enable the development of a sensitive and specific assay for detecting serologic reactivity to this antigen.     

Increased activation and oligoclonality of peripheral CD8(+) T cells in the chronic human helminth infection alveolar echinococcosis

Alveolar echinococcosis (AE) in humans is a chronic disease characterized by slowly expanding liver lesions. Cellular immunity restricts the spreading of the extracellular pathogen, but functional contributions of CD4(+) and CD8(+) T cells are not defined. Here we studied ex vivo the phenotype and function of circulating T-cell subsets in AE patients by means of flow cytometry, T-cell receptor spectratyping, and lymphocyte proliferation. AE patients with parasitic lesions displayed a significant increase of activation of predominantly CD8(+) T cells compared to healthy controls and AE patients without lesions. In vitro, proliferative T-cell responses to polyclonal stimulation with recall antigens and Echinococcus multilocularis vesicular fluid antigen were sustained during chronic persisting infection in all AE patients. Only in AE patients with parasitic lesions did T-cell receptor spectratyping reveal increased oligoclonality of CD8(+) but not CD4(+) T cells, suggesting a persistent antigenic drive for CD8(+) T cells with subsequent proliferation of selected clonotypes. Thus, our data provide strong evidence for an active role of CD8(+) T cells in AE.