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Biomedical subjects

J K Rockstroh

Publications and source records attributed to J K Rockstroh.

At least 73 records · Page 4Linked to original sources
PubMed1998

In vitro cytopathogenicity of the human immunodeficiency virus (HIV)-1 predicts survival in HIV-infected hemophiliacs independent from CD4 cell count.

In addition to quantification of viral load the graded cytopathogenicity of the human immunodeficiency virus may provide prognostic information for the course of HIV infection. However, the prognostic value of graded cytopathogenicity in addition to the CD4 count has not been evaluated in a large longitudinal study. Therefore a total of 216 HIV-seropositive hemophiliacs have been followed up from 1985 to 1998 (mean follow-up 70.4 +/- SD 26 months, median 72, range: 12 to 120 months). In vitro virulence was determined according to cytopathic effects on freshly isolated PBMC of healthy donors and graded from A (strongest cytopathogenic effect) to D (no cytopathic isolate effect). Survival was analyzed among patients with different virus isolates by Kaplan-Meier statistics (log rank) and factors independently associated with decreased survival were analyzed by Cox hazard regression analysis. - A virus isolate A was found in 22 (10.2%) patients, a virus isolate B was found in 21 (9.3%) patients, a virus isolate C was found in 9 (4.2%) and a virus isolate D was found in 10 (4.2%) patients. Mean survival times were 48 months (95% Confidence Interval (CI) = 36 - 60) in patients with isolate A, 72 months (CI = 36 - 108) with isolate B, 84 months (CI = 48-120) with isolate C, 72 months (60 - 96) with isolate D and 96 months (CI = 96 - 108) in patients with a negative virus culture (p < 0.001). Cox regression analysis indicated significant associations with outcome for young age (p <0.001), positive virus culture (p < 0.0001) and CD4 count (p < 0.0001) as independent predictors of survival. The presence of an isolate A revealed the strongest odds ratio (6.3, 95% CI 2.9-13.2). Our data indicate that the presence of a virus isolate A represents a strong risk factor for mortality in the course of HIV infection. Besides quantification of viral load and CD4 count, the graded cytopathogenicity may provide additional information for early and aggressive antiretroviral treatment, since the mean survival in patients with cytopathogenic virus isolates is reduced significantly.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Changing role of invasive aspergillosis in AIDS--a case control study.

OBJECTIVE: From December 1993 until January 1996 we observed 10 cases of invasive aspergillosis in a cohort of 140 patients with AIDS (7%). By contrast, no invasive aspergillosis was diagnosed in a cohort of 278 patients with AIDS between 1986 until 1993. METHODS: Case controls were assigned randomly to each patient with invasive aspergillosis from the total pool of HIV-infected patients. Patients with invasive aspergillosis were studied retrospectively by matched-pairs analysis with respect to risk factors, radiological, microbiological and autopsy findings. RESULTS: Patients with aspergillosis had more AIDS-defining events (3.5 [2-5] vs. 2 [2-3], median [range], P < 0.05) and a longer median survival time with full-blown AIDS (31.5 [14-45] months vs. 20.5 [5-32] months, P < 0.005) than their case controls. Patients with invasive aspergillosis tended to have lower white blood cell counts and exhibited significantly decreased median CD4 counts (7 [0-44]/mm3 vs. 27 [8-57]/mm3, P < 0.05). CONCLUSIONS: Due to better management of opportunistic diseases and improved antiretroviral therapy, the lifespan of patients with full blown AIDS is prolonged. Patients who have survived four or more AIDS-defining events are at risk for invasive aspergillosis. This risk is associated with low white blood cell counts and CD4 cell counts.

AIDS-Related Opportunistic Infections↗
PubMed1998

Protein levels of interleukin-12 p70 holomer, its p40 chain and interferon-gamma during advancing HIV infection.

BACKGROUND: a switch from T helper 1 (TH1) to T helper 2 (TH2)-like cytokine production has been proposed for progressive HIV infection. OBJECTIVE: to study whether this hypothesis is reflected by altered IL-12 and IFN-gamma serum levels in HIV patients. METHODS: we measured serum levels of IL-12 p40 and p70 and IFN-gamma in 90 HIV seropositive patients at differing disease stages and in 10 healthy controls by radioimmunoassays. These cytokines were compared to established surrogate markers of immunodeficiency. RESULTS: IFN-gamma, as well as IL-12 p40 and p70, levels were significantly increased in HIV patients compared to controls. However, IFN-gamma and IL-12 showed no significant variations with progressive stages of immunodeficiency. IFN-gamma levels showed a significant positive correlation to the progression marker beta2-microglobulin and correlated negatively with CD4+ lymphocyte counts. In addition, IFN-gamma concentrations were related to sTNF-R p55 and p75 serum levels. Interestingly. IFN-gamma was related to IL-12 only with respect to p40, but not to p70. CONCLUSIONS: although our data do not necessarily reflect cytokine secretion at the single cell level or the cytokine milieu in the lymphoid microenvironment, our results from peripheral blood fail to demonstrate progressively decreased IL-12 and IFN-gamma serum levels in HIV infected patients.

Adult↗
PubMed1998

Reactivation of hepatitis B in a long-term anti-HBs-positive patient with AIDS following lamivudine withdrawal.

BACKGROUND/AIMS: In HIV-infected patients, who have recovered completely from an acute hepatitis B infection and become anti-HBs positive, hepatitis B infection may be reactivated after progression to AIDS. CASE REPORT: We present the case of a homosexual male patient with AIDS who developed clinical and serological reactivation of hepatitis B with detectable HBV-DNA 18 years after complete recovery from acute hepatitis B infection. Prior to reactivation, antiretroviral triple therapy including lamivudine was changed to therapy without lamivudine. After reintroduction of lamivudine in the triple therapy, HBV-DNA became undetectable and the patient lost HBsAg and again developed anti-HBs antibodies. CONCLUSION: The hepatitis B in this patient can be explained best by reactivation of persistent HBV infection, possibly because of transient decline in antibodies against HBs-antigen due to a reduction in CD4+ lymphocyte numbers and B cell dysfunction. This observation points to the clinical relevance of HBV persistence in serum and blood cells of anti-HBs-positive subjects for many years after recovery from acute hepatitis B infection. The possible role of lamivudine withdrawal which immediately preceded HBV breakthrough in our patient is noteworthy. Regular monitoring of markers of HBV infection, including HBV-DNA, in patients with AIDS appears justified after discontinuation of lamivudine.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Sodium selenite and N-acetylcysteine in antiretroviral-naive HIV-1-infected patients: a randomized, controlled pilot study.

BACKGROUND: The aim of this work was to study the effects of combined oral administration of N-acetylcysteine (NAC) and sodium selenite (Se) on plasma glutathione (GSH), lymphocyte subpopulations and viral load in asymptomatic human immunodeficiency virus (HIV)-infected patients. METHODS: We used a prospective, randomized and controlled therapy trial with partial crossover. Twenty-four antiretroviral-naive HIV-infected outpatients at Centers for Disease Control (CDC)'93 stages I and II were randomized to receive the antioxidant combination NAC 600 mg t.i.d. and Se 500 micrograms per day for either 24 weeks (group A, n = 13) or from the end of week 12 (group B, n = 11) until the end of week 24. Thus, group B served as untreated control during the first 12 weeks. RESULTS: There was (a) a trend towards an increase in the percentage of CD4+ lymphocytes after 6 weeks (P = 0.08); (b) an increase in the CD4/CD8 ratio after 6 and 12 weeks (P = 0.02 and P = 0.04 respectively); and (c) a decrease in the absolute CD8/CD38 count and percentage of lymphocytes after 6 weeks (P = 0.002 and P = 0.033 respectively) and 12 weeks (P = 0.033, P = 0.1 respectively) in group A compared with the control period of group B. The effects observed in group A were, however, not paralleled to the same extent by group B after crossing-over to treatment after 12 weeks. In addition, erythrocyte glutathione peroxidase (GSH-Px) activity and GSH, glutathionedisulphide (GSSG) concentrations and the reduced/total GSH ratio were not affected by the treatment. Serum selenium levels increased significantly (P < 0.001) upon treatment. Viral load was not altered. CONCLUSIONS: The changes in lymphocyte subsets after NAC/Se treatment were not comparable to those after standard antiretroviral drug therapy. This, however, does not preclude per se possible benefits of antioxidant supplementation in HIV disease.

Acetylcysteine↗
PubMed1998

Pharmacokinetics of azidothymidine and its major metabolite glucuronylazidothymidine in hemophiliacs coinfected with human immunodeficiency virus and chronic hepatitis C.

The increasingly reported cholestatic course of liver disease in hemophiliacs coinfected with human immunodeficiency virus (HIV) and hepatitis C (HCV) has been linked with impaired azidothymidine (AZT) metabolism in this patient group. Therefore, we compared the pharmacokinetics of AZT and its glucuronidated metabolite (glucuronylazidothymidine [GAZT]) in HIV/HCV-coinfected hemophiliacs without cirrhosis to HIV-infected patients without chronic hepatitis. Sixteen HIV/HCV-coinfected hemophiliacs without cirrhosis and six HIV-infected patients with negative hepatitis serology and normal liver transaminases received a single 100-mg oral dose of AZT. Subsequently, plasma concentrations of AZT and GAZT were measured during a 6-hour period by high-pressure liquid chromatography (HPLC). Blood samples were taken before and 30, 60, and 90 minutes and 2, 3, 6, and 8 hours after the intake of AZT. Pharmacokinetic parameters of AZT in HIV-infected patients with concomitant chronic hepatitis did not differ significantly as compared to patients without concomitant liver disease. GAZT half-life and mean residence time of GAZT, however, were significantly longer in HIV/HCV-coinfected hemophiliacs as compared to HIV-positive controls without hepatitis. In HIV-infected patients, underlying chronic hepatitis C does not require AZT dose adaptation. Yet despite normal oral clearance of AZT and GAZT, the increase of half-life and mean residence time of GAZT indicates a prolonged hepatic release of GAZT into the circulation of HIV-infected hemophiliacs with noncirrhotic hepatitis C.

Adult↗
PubMed1998

Role of HIV-1 phenotype in viral pathogenesis and its relation to viral load and CD4+ T-cell count.

The predictive value of HIV-1 phenotype in peripheral blood mononuclear cell (PBMC) coculture and the relation among viral phenotype, viral load, and CD4+ T-cell count were examined in two studies. In study A, 132 HIV-1-infected individuals were examined retrospectively for the relation between the result of their initial HIV cultivation in PBMC coculture and survival rate 6 years later. In study B, 176 patients were examined since 1994 for markers of HIV disease progression. HIV-1 phenotype was determined by PBMC cocultivation, viral load by NASBA HIV RNA QT System, and CD4+ T-cell count by flow cytometry. In study A, the percentage of survival for patients with initial negative virus culture was significantly higher (95%) than in patients with nonsyncytia-inducing (NSI) isolates (78%) and syncytia-inducing (SI) isolates (21%) (P < 0.05 and P< 0.0001, respectively). When SI phenotype was subdivided into moderately cytopathogenic and highly cytopathogenic, significant differences in the rate of survival between these subgroups could be observed (45% vs. 14%; P < 0.05). In study B, progression from negative virus culture to the isolation of NSI variants was associated with increasing viral load (P < 0.0001) but did not affect CD4+ T-cell count significantly (P> 0.07), whereas the switch from NSI to SI virus was accompanied by significant decline of CD4+ T-cells (P < 0.0001) but no change in viral load (P > 0.21). Thus, isolation and phenotyping of HIV represents an additional striking predictive marker for progression of HIV infection.

CD4 Lymphocyte Count↗
PubMed1997

Comparison of early target organ damage between blacks and whites with mild systemic arterial hypertension.

As greater mortality and morbidity from target organ damage in arterial hypertension have been reported for black than for white hypertensives, we examined in a matched-pair analysis whether race per se affected markers of early target organ damage at similar levels of blood pressure. After controlling for the confounding factors such as age, sex, weight, and arterial pressure that interact with hypertension-related target organ damage, no racial disparities could be detected between matched black and white hypertensive patients.

Adult↗
PubMed1997

Serum selenium versus lymphocyte subsets and markers of disease progression and inflammatory response in human immunodeficiency virus-1 infection.

Serum selenium levels were determined cross-sectionally in 57 HIV-infected patients who were classified according to the Centers for Disease Control (CDC) 1993 classification system. Mean serum selenium levels were lower in CDC stage II (58.7 +/- 12.2 micrograms/L; p < 0.01; n = 18) and stage III (47.6 +/- 11.3 micrograms/L; p < 0.01; n = 19) HIV-infected patients, than in healthy subjects (80.6 +/- 9.6 micrograms/L; n = 48) and stage I patients (73.6 +/- 16.5 micrograms/L; n = 20). Serum selenium levels were positively correlated with CD4 count, CD4/8 ratio, hematocrit, and serum albumin (r = 0.42; r = 0.39; r = 0.48; and r = 0.45; p < 0.01, respectively) and inversely with serum levels of thymidine kinase (r = -0.49; p < 0.01; n = 49) and beta 2-microglobulin (r = -0.46; p < 0.001; n = 49). In addition, serum selenium levels in 20 randomly selected AIDS-free individuals (CDC I: n = 10; CDC II: n = 10) were inversely correlated with serum concentrations of interleukin-8 (IL-8) and soluble tumor necrosis factor receptors (sTNFR) types I and II. There was no correlation with serum immuneglobulin A and total serum protein levels. The results show that the progressive deprivation of serum selenium in HIV-infection is associated with loss of CD(4+)-cells and with increased levels of markers of disease progression and inflammatory response.

Adult↗
PubMed1997

Renal and systemic hemodynamics in black and white hypertensive patients.

Greater mortality and morbidity for cardiovascular events and renal complications have been reported in black than in white hypertensive patients. In this study we examined whether race per se affected markers of early target organ damage in a population of black and white hypertensive patients in whom casual as well as ambulatory blood pressure measurements were obtained. We assessed renal and systemic hemodynamics by measuring mean arterial pressure invasively, renal blood flow by 131I-para-aminohippuric acid clearance, and cardiac output by the indocyanine dye dilution technique. Left ventricular structure was determined by two-dimensional guided M-mode echocardiography. No significant differences in cardiac output, total peripheral resistance, renal blood flow, and renal vascular resistance were found between the two racial populations. Indices of myocardial structure were also comparable between black and white hypertensive patients. This was true regardless whether all patients were analyzed, or male patients only, or only those with elevated ambulatory blood pressure measurements. When defining arterial pressure by 24-h ambulatory monitoring, no differences in early target organ damage can be found between black and white patients with mild essential hypertension.

Adult↗
PubMed1997

Serum selenium, plasma glutathione (GSH) and erythrocyte glutathione peroxidase (GSH-Px)-levels in asymptomatic versus symptomatic human immunodeficiency virus-1 (HIV-1)-infection.

OBJECTIVES: Antioxidant defense status was investigated in HIV-infected patients by measuring serum selenium, erythrocyte glutathione peroxidase (GSH-Px) activity, plasma thiol (-SH) and glutathione (GSH) concentrations along with the assessment of the clinical stage and surrogate markers of HIV-disease. DESIGN, SETTING AND SUBJECTS: Serum selenium levels were determined cross-sectionally in 104 sequentially selected HIV-infected patients (83 outpatients and 21 patients with ongoing AIDS defining events). The patients were classified into three stages of the disease, I, II and III according to the 1993 Centers For Disease Control (CDC) classification system for HIV-infection. GSH-Px activities, plasma SH and plasma GSH concentrations were determined in a subset of 24 patients at stage I and 12 patients at stage III with an active AIDS-defining disease. RESULTS: Mean serum selenium levels were lower in CDC stage II (68.7 +/- 20.9 micrograms/l; P < 0.01; n = 34) and stage III (51.4 +/- 14.7 micrograms/l; P < 0.01; n = 37) HIV-infected patients than in healthy subjects (89.2 +/- 20.9 micrograms/l; n = 72) and stage I patients (82.3 +/- 20.5; microgram/l; n = 33). Serum selenium levels were positively correlated with CD4-count (r = 0.42; P < 0.001; n = 104) and inversely with levels of soluble tumor necrosis factor receptors type II (r = -0.58; P < 0.01; n = 35), neopterin (r = -0.5; P < 0.001; n = 80) and beta 2-microglobulin (r = -0.4; P < 0.001; n = 94). Hepatitis C virus (HCV) and HIV-coinfected patients at CDC stages I and II showed markedly lower selenium concentrations compared to HIV-infected patients without concomitant HCV-infection. Serum selenium and GSH-Px activity in hospitalized AIDS patients was significantly lower as compared to asymptomatic patients and healthy subjects, whereas plasma SH and GSH concentrations were lower in both, asymptomatic -and AIDS-patients, than in the controls. CONCLUSION: The results show that stages I-III of HIV-disease are characterized by significant impairments of antioxidative defenses provided by selenium, GSH-Px, SH-groups and GSH.

Adult↗
PubMed1997

Inadequate erythropoietin response to anaemia in HIV patients: relationship to serum levels of tumour necrosis factor-alpha, interleukin-6 and their soluble receptors.

Severe anaemia is a frequent complication in advanced HIV infection. In our study we investigated the interaction between cytokine network, HIV infection and erythropoietin (Epo) response with increasing anaemia levels. No correlations could be established between circulating tumour necrosis factor (TNF)-alpha and any of the examined parameters. However, a negative correlation was found between haemoglobin values and soluble TNF receptor levels (sTNF-R-I: r = -0.54; P < 0.001; sTNF-R II: r = -0.47; P < 0.001) as well as interleukin-6 levels (r = -0.29; P < 0.01). In contrast, no significant increase in log[Epo], counterbalancing haemoglobin decline and paralleling the rise in sTNF receptors, was found. In patients classified as stage III, according to the Centers for Disease Control (CDC) classification, the erythropoietin response was significantly more impaired than in patients from CDC groups I and II (P < 0.01). The results of this study suggest that similar to its action in vitro, activation of the TNF/TNF-R system may impair erythropoietin production in HIV-associated anaemia. Due to the brief half-life of TNF-alpha, this activation is particularly reflected by elevations of soluble TNF receptor levels.

Adult↗
PubMed1997

The IL-1 system in HIV infection: peripheral concentrations of IL-1beta, IL-1 receptor antagonist and soluble IL-1 receptor type II.

The proinflammatory cytokine IL-1beta is thought to be involved in ongoing HIV disease. Furthermore, its naturally occurring inhibitors soluble IL-1 receptor type II (sIL-1RII) and IL-1 receptor antagonist (IL-1Ra) may play a pivotal role in regulating its biological action. To investigate the involvement of the IL-1 system we determined serum levels of IL-1beta, IL-1Ra and sIL-1RII in 90 HIV- patients. The obtained values were compared with markers of disease progression such as CD4+ count, 5'-neopterin. Beta2-microglobulin and soluble tumour necrosis factor receptors (sTNF-R) p55 and p75 and then compared with C-reactive protein (CRP), granulocyte count, IL-6 and TNF-alpha. While IL-1Ra concentrations increased significantly with progressive CDC disease stages, sIL-1RII and IL-1beta were not altered in our cohort. IL-1Ra showed statistical relation to decreasing CD4+ lymphocytes and increasing 5'-neopterin, beta2-microglobulin, sTNF-R p55, sTNF-R p75. Furthermore, IL-1Ra correlated positively with serum IL-6, TNF-alpha, CRP and granulocytes. In contrast, sIL-1RII and IL-1beta tended to show an inverse correlation or showed no significant relationship to all these parameters. IL-1beta was measurable only in a limited number of samples. IL-1Ra showed a clear relationship to acute inflammatory events as well as to the different disease stages. Our data suggest a dissociation between IL-1Ra and sIL-1RII serum levels which may indicate that the two IL-1 binding proteins have different pathophysiological roles in HIV infection.

Adult↗
PubMed1997

Blood pressure independent effects of nitrendipine on cardiac structure in patients after renal transplantation.

Left ventricular hypertrophy is well established as a blood pressure independent cardiovascular risk factor in patients on renal replacement therapy. The effects of antihypertensive treatment on myocardial structure and function in renal transplant recipients have been so far only rarely investigated. In a double-blind, placebo-controlled study patients were randomized to the calcium channel blocker nitrendipine or placebo if the transplanted kidney had developed a stable phase. Normotensive patients received nitrendipine 2 x 5 mg daily or placebo, hypertensive patients received 2 x 10 mg up to 2 x 20 mg nitrendipine daily or placebo. To achieve adequate blood pressure control, all patients with still elevated blood pressure on study medication received antihypertensive drugs other than calcium channels blockers. Ambulatory blood pressure recording and 2D-guided M-mode echocardiography were performed at baseline and upon completion of the study. In addition, laboratory workup (including serum creatinine and lipids) was done, and serum aldosterone, plasma renin activity, plasma angiotensin II and blood glucose levels were measured in all patients at baseline and after at least 12 months of therapy. Ambulatory blood pressure was almost identical between both groups at study baseline and follow-up. In renal transplant patients on nitrendipine, posterior wall thickness (-0.10 +/- 1.77 mm) and septal wall thickness (-0.83 +/- 2.23 mm) did not change significantly from baseline. In contrast, posterior wall thickness (0.71 +/- 0.92 mm, P < 0.01) and septal wall thickness (0.97 +/- 2.20 mm, P < 0.05) increased in patients on placebo, which differed from the observed changes on nitrendipine (ANOVA: P = 0.093 and P = 0.048, respectively). Relative wall thickness, a parameter for concentric left ventricular hypertrophy, became numerically smaller on nitrendipine therapy from 0.46 +/- 0.07 to 0.44 +/- 0.09 (-0.02 +/- 0.09, NS) but increased from 0.42 +/- 0.08 to 0.48 +/- 0.08 in the placebo arm (+0.04 +/- 0.08, P < 0.02), which was also significant between the two groups (ANOVA: P = 0.036). Endocrine parameters, lipids and blood glucose were not different between the two groups. We conclude from these data that the calcium channel blocker nitrendipine exerted beneficial effects on cardiac structure in patients after renal transplantation independent of blood pressure.

Adult↗