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Biomedical subjects

R Zangerle

Publications and source records attributed to R Zangerle.

At least 19 recordsLinked to original sources
PubMed2005

Kaposi sarcoma in solid organ transplant recipients: a single center report.

BACKGROUND: Human herpes virus (HHV8) is associated with Castleman's disease, primary effusion lymphoma, and the Kaposi's sarcoma (KS). PATIENTS AND METHODS: Among 3815 solid organ transplants performed at our center between 1977 and 2003, five patients (0.1%) were identified with KS. RESULTS: There were one cardiac, one liver, and three renal allograft recipients of median age of 52 (range 38 to 60) years, three of whom were females. Three patients were of Italian and one of Turkish descent; only one patient was a native Austrian. The onset of the disease was 2.0, 7.5, 7.8, 9.4 months, and 22 years posttransplant. Diagnosis of KS was based in all cases on histology. The heart recipient developed a tumor on the planta pedis; one renal recipient, on both legs. The liver and the two remaining renal recipients presented with disseminated disease. Treatment in all cases consisted of reduction in immunosuppression, together with surgery (n = 1), chemotherapy (n = 1), or irradiation (n = 2). Furthermore, immunosuppression was switched in two cases from Tacrolimus to Sirolimus. In the liver recipient a complete response was achieved; he died, however, due to noncompliance followed by graft failure. One renal recipient died without evidence of recurrent disease from myocardial infarction. The cardiac and two renal recipients are alive between 4 months and 17 years with well-functioning grafts and no evidence of recurrent disease. DISCUSSION: HHV8-associated lesions seem to be extremely rare in the Central European transplant population. Nevertheless, awareness of KS is important for early diagnosis and optimal treatment.

Adult↗
PubMed2003

Quality of life of HIV-infected patients: psychometric properties and validation of the German version of the MQOL-HIV.

OBJECTIVE: To determine the psychometric properties of the recently developed German version of the Multidimensional Quality of Life Questionnaire for HIV/AIDS (MQOL-HIV) and to test its performance in a sample of HIV-infected patients. METHODS: Two-hundred and seven outpatients with HIV/AIDS were interviewed with the German version of the MQOL-HIV; 109 patients were interviewed a second time approximately 2 weeks later. Patients also completed the Beck Depression Inventory (BDI) and the World Health Organization Disability Assessment Schedule II (WHODAS II). RESULTS: The German version of the MQOL-HIV showed satisfactory internal consistency (r: 0.74-0.85, sexual functioning: r = 0.61) and test-retest reliability in most subscales (r: 0.74-0.89, medical care: r = 0.67). Convergent validity with WHO-DAS II and BDI was satisfactory for most domains. Exploratory factor analysis yielded a seven-factor solution with separate factors for physical, emotional, cognitive, social and financial aspects, sexual functioning and medical care. CD4 count and source of infection were associated with most QOL domains, whereas age and gender showed no major impact on QOL. High rates of missing values were seen in the partnership domain and substantial ceiling effects in the area of medical care. CONCLUSIONS: Overall the German version of the MQOL-HIV showed satisfactory reliability and validity. However, the domains of partnership, sexuality and medical care should generally receive more emphasis in future research on QOL assessment in patients with HIV/AIDS and the MQOL-HIV may be improved in these domains.

Adult↗
PubMed2002

Extravascular necrotizing palisaded granulomas as the presenting skin sign of systemic lupus erythematosus.

We recently examined a patient who presented clinically with tender, erythematous papules associated with a febrile illness and polyarthralgias. Histopathological examination revealed extravascular palisaded neutrophilic granulomas, a skin reaction pattern originally described in Churg-Strauss disease but subsequently observed in a variety of other systemic disorders characterized by immune complex generation. A diagnosis of systemic lupus erythematosus (SLE) was established. To our knowledge, this is the first report of extravascular necrotizing palisaded granulomas as the presenting skin sign of SLE.

Adult↗
PubMed2001

Using phylogenetic analysis to trace HIV-1 migration among western European injecting drug users seroconverting from 1984 to 1997.

OBJECTIVE: To reconstruct the epidemiological relationships of the HIV epidemics among injecting drug users (IDU) in western Europe. METHODS: HIV env V3 sequences of and epidemiological data were obtained from 145 IDU who seroconverted in three sequential periods: 1984-1988, 1989-1992 and 1993-1997. The sequences were phylogenetically analysed and examined for signature patterns characteristic of northern European IDU, including the conserved GGC codon in the V3 loop. RESULTS: Subpopulations of genetically related HIV strains were observed in Italy, France, Scotland and Spain, in contrast to the Netherlands, Austria and Switzerland. This difference between the two groups of countries suggests that the HIV epidemics amongst IDU in the latter group was caused by multiple virus introductions. In Edinburgh and the surrounding area, most IDU were infected with the same GGC strain over the 12-year study period. The epidemic among IDU in north-western Europe started with GGC viruses, whereas in south-western Europe non-GGC viruses predominated. This geographical separation has faded during the course of the epidemic, most likely because of virus exchange among IDU populations.

Base Sequence↗
PubMed2000

Specific serum IgG, IgM and IgA antibodies to human papillomavirus types 6, 11, 16, 18 and 31 virus-like particles in human immunodeficiency virus-seropositive women.

To evaluate the humoral immune response to human papillomavirus (HPV) in women infected with human immunodeficiency virus (HIV), serum samples of 83 HIV-positive individuals were analysed by ELISA for specific antibodies of the isotypes IgG, IgA and IgM recognizing HPV-6, -11, -16, -18 and -31 L1 virus-like particles (VLPs). Papillomavirus-related lesions were present in 30 of 83 HIV-positive women. Twenty-one women (25%) presented with high-/intermediate-grade anogenital squamous intraepithelial lesions. PCR analysis and sequencing for HPV typing was done from biopsy specimens of 18 women; PCR-positive results were obtained in 90% of cases. In addition, HPV DNA hybrid capture assays were performed from cervical swabs of 58 HIV-positive women, 53% of whom had a positive result for high-risk HPV. Overall, positive IgG reactivity to HPV-6/-11 and HPV-16/-18/-31 was seen in 19%/31% and 49%/30%/24% of HIV-positive women, respectively. HPV-seropositivity was even higher than in 48 HIV-negative cervical intraepithelial neoplasia/cancer patients with percentages as follows: 8%/2% and 31%/15%/15%. This difference was significant for HPV-16 (P=0.046). IgA responses were comparable to IgG. IgM responses were low. The extraordinarily high rate of antibodies to the capsid protein L1 of high-risk HPVs (HPV-16, -18 and/or -31) in 58% of HIV-positive women compared to 19% (P=0.00001) of 102 healthy HIV-negative control women suggests a high lifetime cumulative exposure to HPV and increased expression of capsid proteins due to cellular immunodeficiency in HIV-infected women.

Adult↗
PubMed2000

Pyuria in patients treated with indinavir is associated with renal dysfunction.

BACKGROUND: Indinavir therapy is associated with a continuum of crystal-related syndromes, including nephrolithiasis, renal colic, flank pain without recognizable stone formation, dysuria and asymptomatic crystalluria. A frank nephropathy has been recognized recently as part of the spectrum. METHODS: A retrospective analysis of 72 HIV-infected individuals receiving indinavir was performed to identify the frequency and risk factors for indinavir-associated nephropathy and urinary complications. Individuals treated with nucleoside analogues alone served as controls. RESULTS: Mean serum creatinine levels rose from 1.03 +/- 0.16 mg/dl to 1.11 +/- 0.22 mg/dl at week 12 and 1.15 +/- 0.27 mg/dl at week 24 (both, p < 0.01). Thirteen individuals developed serum creatinine levels > or =1.4 mg/dl. Increased serum creatinine levels were found more frequently in women (p < 0.01) and were associated with pyuria and microhematuria (p < 0.01). Frank renal colic and/or nephrolithiasis (seven patients) and urinary pH were not associated with serum creatinine levels > or =1.4 mg/dl. The mean duration of indinavir treatment, until sterile pyuria occurred, were 22 weeks and 32 weeks until the first rise of serum creatinine levels to > or =1.4 mg/dl. Ten patients showed both findings, pyuria preceded the first rise in serum creatinine levels to > or = 1.4 mg/dl (18 vs. 27 weeks, p = 0.02). Renal biopsy, done in three patients, revealed tubulointerstitial disease with crystals in collecting ducts. In 21 patients, among them 11 with pyuria, indinavir was replaced for various reasons and pyuria disappeared in nine. In these patients mean serum creatinine levels decreased from 1.43 mg/dl at withdrawal of indinavir to 1.04 mg/dl three months later (p < 0.01). CONCLUSION: Indinavir therapy is associated with a decrease in renal function which is reversible after withdrawal. In addition, indinavir-associated tubulointerstitial disease does no in patients taking indinavir may help to identify patients being at risk for nephrotoxicity.

Adult↗
PubMed1999

Do gender differences in CD4 cell counts matter?

OBJECTIVE: To examine the effect of gender on disease progression and whether gender differences in CD4 lymphocyte counts persisted for the entire course from HIV seroconversion until (death from) AIDS. METHODS: CD4 lymphocyte counts were modelled in 221 female and 443 male seroconverters following seroconversion, backwards from AIDS and backwards from death using regression analysis for repeated measurements. RESULTS: In the period before use of highly active antiretroviral therapy (HAART), progression to AIDS and to death were marginally slower in women than in men as assessed by proportional hazards analysis. Women seroconverted for HIV, developed AIDS and died at higher CD4 cell counts than men (women: 815, 146 and 44 x 10(6) cells/l, respectively; men: 727, 49 and 22 x 10(6) cells/l, respectively), although differences were only statistically significant at AIDS onset. Declines in CD4 lymphocyte counts were not significantly affected by gender and absolute differences between men and women were stable, with exception for the trajectory close to AIDS when the decline became steeper for men than women. CONCLUSION: These gender differences in CD4 lymphocyte counts suggest a delay of initiation of therapy in women compared with men (our model predicted that women reach the threshold of starting HAART at about 12 months later than men). If this delay unfavourably influences progression, treatment guidelines should be revised so that women can benefit equally from HAART.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Human immunodeficiency virus type 1 protease inhibitor attenuates Candida albicans virulence properties in vitro.

The putative virulence factor secreted aspartyl proteinase (SAP) of Candida albicans and the human immunodeficiency virus type 1 (HIV-1) protease both belong to the aspartyl proteinase family. The present study demonstrates that the HIV-1 protease inhibitor Indinavir is a weak but specific inhibitor of SAP. In addition, Indinavir reduces the amount of cell bound as well as released SAP antigen from C. albicans. Furthermore, viability and growth of C. albicans are markedly reduced by Indinavir. These findings indicate that HIV-1 protease inhibitors may possess antifungal activity and we speculate that in vivo SAP inhibition may add to the resolution of mucosal candidiasis in HIV-1 infected subjects.

Amino Acid Sequence↗
PubMed1999

Longitudinal study of antibody reactivity against HIV-1 envelope and a peptide representing a conserved site on Gp41 in HIV-1-infected patients.

This study was designed to distinguish between antibodies in HIV-1-infected patients directed against epitopes accessible on the native HIV-1 envelope (Env) complex and non-native Env epitopes. Peptide p#13 (Env. aa642-673) containing the neutralising 2F5 epitope and recombinant soluble glycoprotein 160 (rsgp160) were used in ELISA to determine the antibody (Ab) reactivity in sera of 116 HIV-1-infected individuals and 18 HIV negative controls. The reactivity of sera classified CDC stage C against p#13 was significantly decreased in comparison to stage A sera, while staying constant against rsgp160. Accordingly, in 6 out of 8 individual patients tested over time the response against p#13 was declining at later time points of infection. The reactivity of patients' sera against p#13 corresponded directly to the recognition of infected T cells and largely also to the CD4 cell count. The causal relationships of these phenomena are not clear. It is conceivable that antibodies against epitopes on HIV are lost or escape mutants arise and consequently control of HIV is lost and virus load increases as it is known for CDC stage C. Alternatively, increasing virus load may affect B cells recognising native Env epitopes and turn antibody production down by some mechanism. In this latter scenario helper T cells might have a critical role.

Binding Sites↗
PubMed1999

Persistent flank pain, low-grade fever, and malaise in a woman treated with indinavir.

This case report describes a 32-year-old woman treated with indinavir who developed mild to moderate flank pain, malaise, and low-grade fever. Sterile pyuria preceded increased serum creatinine levels. Workup revealed persistent pyuria, normal-sized kidneys, a normal intravenous pyelography, and negative urinary cultures. Renal biopsy showed interstitial nephritis and chronic inflammation. Collecting ducts contained crystals. Two months after treatment with indinavir was discontinued, serum creatinine levels returned to normal and pyuria disappeared. Sterile pyuria in patients taking indinavir may help to identify patients at risk for renal dysfunction and interstitial nephritis. Markedly increasing the fluid intake above the recommended dosage may ameliorate or even reverse the process of tubulointerstitial disease.

Adult↗
PubMed1999

Geographical variation in disease progression in HIV-1 seroconverted injecting drug users in Europe?

BACKGROUND: Human immunodeficiency virus (HIV) disease progression might vary by geographical region due to differences in the spectrum of HIV-related illnesses and (access to) health care. Therefore, the effect of geographical region, next to the effect of other potential cofactors, on disease progression in 664 injecting drug users (IDU) with documented HIV seroconversion from eight cohorts in Europe was studied. METHODS: Kaplan-Meier methods and Cox proportional hazards analysis were performed to assess the effect of geographical region, other sociodemographics, drug use and repeated HIV exposure on progression from HIV seroconversion to immunosuppression, AIDS and death with AIDS. We considered the confounding effect of study-design related factors (e.g. setting of follow-up), and accounted for pre-AIDS death from natural causes by imputing when each endpoint would have occurred, had they not died without AIDS. RESULTS: Estimates of progression to AIDS and death with AIDS were substantially faster after taking pre-AIDS mortality into account. Median incubation time from seroconversion to the first CD4 count < 200 cells/microliter was 7.7 years (95% CI: 7.1-8.3) and to AIDS 10.4 years (95% CI: 9.8-infinity). The 10-year survival was 70.3% (95% CI: 62.8-76.6). The relative hazards (RH) of AIDS for IDU from central and southern Europe compared with IDU from northern Europe was 1.9 (95% CI: 1.2-3.0) and 1.2 (95% CI: 0.6-2.3), respectively, before, and 1.5 (95% CI: 0.7-3.2) and 1.1 (95% CI: 0.6-2.3) after taking differences in study-design related factors into account. Accounting for these factors, the RH of death with AIDS was 0.9 (95% CI: 0.3-2.5) for central and 1.2 (95% CI: 0.4-3.4) for southern Europe compared with northern Europe. For the first CD4 count < 200 cells/microliter these figures were 0.8 (95% CI: 0.5-1.4) and 0.8 (95% CI: 0.5-1.4). Age at seroconversion was the strongest predictor of disease progression. No statistically significant differences in disease progression were found by gender, foreign nationality, drug use and potential repeated HIV exposure. CONCLUSIONS: We found no evidence for regional variability in HIV disease progression among European IDU. Future studies evaluating geographical differences should consider the confounding effect of study-design related factors and differential non-AIDS mortality. As age is an important determinant of disease progression, it should be considered in recommending treatment.

Adult↗
PubMed1998

Serum HIV-1 RNA levels compared to soluble markers of immune activation to predict disease progression in HIV-1-infected individuals.

We assessed the value of HIV-1 RNA level compared to soluble immune activation markers, namely neopterin, beta2-microglobulin and soluble TNF receptor 75 (sTNFR-75), to predict the change in the number of CD4+ T cells over a 1-year period, the development of AIDS, and survival (median follow-up 54 months). The study population comprised a cohort of 47 individuals for the analysis of the change in CD4+ T cells and survival (20 died), and a subgroup of 31 individuals with a baseline CD4+ T cells above 200 x 10(6)/l for the development of AIDS (11 developed AIDS). HIV-1 RNA was measured from stored sera by quantitative PCR. The CD4+ T cell count obtained at study entry strongly correlated with baseline serum HIV-1 RNA levels (r=-0.47), and to a lesser extent with neopterin (r=-0.41) and beta2-microglobulin (r=-0.29). The percentage change in CD4+ T cells over a 1-year period correlated with HIV-1 RNA levels (r=-0.32, p=0.03), however, stronger correlations were found for neopterin, beta2-microglobulin and sTNFR-75 (r=-0.51, r=-0.41, r=-0.42; p< 0.01). No progression to AIDS or death was observed in individuals with baseline HIV-1 RNA levels below 20,000 copies/ml (10 of 31 and 15 of 47 individuals, respectively). A Cox's proportional hazard model to predict AIDS revealed that HIV-1 RNA, the change in CD4+ cells over a 1-year period and sTNFR-75 levels independently predict AIDS; the change in CD4+ cells, the absolute CD4+ T cell count and neopterin were jointly significant to predict death. All results were adjusted for nucleoside monotherapy. In conclusion, to improve the predictive power, quantitation of HIV-1 RNA as a 'natural history marker' may be supplemented by measurement of sTNFR-75 for 'early'-stage disease progression and neopterin for 'late'-stage disease progression.

Adult↗
PubMed1998

[Antiretroviral therapy 1998/1999: what is our current status?--Avoiding therapy failure instead of expecting it].

The stunning clinical benefit of antiretroviral therapy is associated with long-term viral suppression. Treatment failure has therefore been defined as incomplete suppression of viral replication, however, in clinical practice success is also seen in a substantial proportion of patients with ongoing viral replication, a phenomenon which is not understood at this time. The main reason for treatment failure is the development of resistance due to the inability of many patients to comply with the daunting challenge of the complex antiretroviral therapy. An "era of compliance" is now necessary to sustain and expand the benefits of these therapies.

Anti-HIV Agents↗
PubMed1998

[Guidelines for implementing antiretroviral therapy].

The rapid evolution of new information has introduced extraordinary complexity into the treatment of HIV-infected persons. Therefore it is recommended that care should be supervised by an expert. With regard to specific recommendations, treatment should be offered to all patients with the acute HIV syndrome and all patients with symptoms ascribed to HIV infection. The strength of the recommendation to treat asymptomatic patients should be based on the patient's willingness to accept therapy, the probability of adherence with the prescribed regimen, and the prognosis in term of time to an AIDS-defining disease as predicted by plasma HIV RNA levels and CD4+ T-cell counts. Once the decision has been made to initiate antiretroviral therapy, the goal is maximum viral suppression for as long as possible. Results of therapy are evaluated primarily with plasma HIV RNA levels: these are expected to show a one-log (10-fold) decrease at 8 weeks and no detectable virus at 4 to 6 months after initiation of treatment. Failure of therapy may be ascribed to nonadherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, resistance, and other factors that are poorly understood. Patient education and involvement in therapeutic decisions is important for all medical conditions but is considered especially critical for HIV-infection and its treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Pre-AIDS mortality from natural causes associated with HIV disease progression: evidence from the European Seroconverter Study among injecting drug users.

OBJECTIVES: To study differences in pre-AIDS mortality between European cohorts of injecting drug users (IDU) and to evaluate whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count. METHODS: The study population consisted of 664 IDU with documented intervals of HIV seroconversion from eight cohort studies. Differences in pre-AIDS mortality were studied between European sites; an evaluation of whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count was carried out using Poisson regression. RESULTS: One hundred and seven IDU died, of whom 57 did not have AIDS. Pre-AIDS causes of death were overdose/suicide (49%), natural causes such as bacterial infections/cirrhosis (40%), and unintentional injuries/unknown (11%). Considering pre-AIDS death and AIDS as competing risks, 14.7% were expected to have died without AIDS and 17.3% to have developed AIDS at 7 years from seroconversion. No statistically significant differences in pre-AIDS mortality were found between European regions, men and women, age categories and calendar time periods. Overall pre-AIDS mortality did not increase with time since seroconversion, but did increase with decreasing CD4 count. Evaluating cause-specific mortality, only pre-AIDS mortality from natural causes appeared to be associated with time since seroconversion as well as immunosuppression. For natural causes, the death rate per 100 person-years was 0.13 the first 2 years after seroconversion, 0.73 in years 2-4 [risk relative (RR) to years 0-2, 5.6], 1.83 in years 4-6 (RR, 14.0) and 1.54 for > or = 6 years (RR, 11.7). This rate was 0 for a CD4 cell count > or = 500 x 10(6)/l, 1.06 for 200-500 x 10(6)/l and 4.06 for < 200 x 10(6)/l (RR versus > or = 200 x 10(6)/l, 7.0). In multivariate analysis, both CD4 count and time since seroconversion appeared to be independently associated with death from natural causes; CD4 count appeared to be the strongest predictor (adjusted RR, 5.9). CONCLUSIONS: A high pre-AIDS mortality rate was observed among IDU. No significant differences were observed across European sites. Pre-AIDS mortality from natural causes but not from overdose and suicide was associated with HIV disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1997

trans-Activation of the HIV type 1 promoter by 7,8-dihydroneopterin in vitro.

Infection with human immunodeficiency virus type 1 and 2 is associated with elevated concentrations of neopterin, released in large quantities by human macrophages on stimulation with interferon gamma. Evidence has suggested a potential role of neopterin derivatives in oxygen radical-mediated processes. Here we show that the redox-sensitive transcription factors AP-1 and NF-kappaB are activated by 7,8-dihydroneopterin, either directly (AP-1), or by the synergistic action with tumor necrosis factor alpha (NF-kappaB). We could further demonstrate that 7,8-dihydroneopterin enhances HIV-1 expression as shown in transient transfection assays using HIV-1 CAT promoter-reporter gene constructs. In sera of HIV+ patients 7,8-dihydroneopterin significantly correlated with neopterin and HIV-1 p24 antigen. On the basis of our data we therefore assume that 7,8-dihydroneopterin might augment progression to higher stages of HIV-associated disease.

Biopterins↗