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Biomedical subjects

S Staszewski

Publications and source records attributed to S Staszewski.

At least 73 records · Page 4Linked to original sources
PubMed1995

Seroprevalence of HCV, HAV, HBV, HDV, HCMV and HIV in high risk groups/Frankfurt a.M., Germany.

During the period from August 1991 to April 1993, serum samples originating from different risk groups were tested for antibodies against hepatitis C virus (HCV), using a second-generation ELISA. The highest HCV seroprevalence levels were observed in haemophiliacs (87.0%) and intravenous drug abusers (IVDA) (78.9%). The HCV-seropositivity rates of polytransfused and organ transplant recipients were nearly identical (18.4% vs. 16.8%). Significantly lower HCV-seroprevalence rates were determined in chronic haemodialysis patients (8.1%) and homo/bisexuals (10.0%). The lowest HCV seroprevalence levels were found in the groups of female prostitutes (1.4%) and health care staff (0.8%). A strong correlation between HCV seropositivity and the presence of antibodies against HIV-1, HBc and HCMV was observed. There was also an association between HCV seropositivity and HAV. The seroprevalence of HDV and the proportion of HBsAg and HBeAg carriers was not significantly influenced by HCV serostatus. The incidence of HCV infection in renal transplant recipients was 3.9%. In 10 (6.5%) patients, anti-HCV seroconversion was observed in the immediate post-transplantation period followed by a decrease of the index value and finally, disappearance of antibodies at the end of the study. Antibodies passively acquired through intravenous immunoglobulin (IVIG) donation may account for overestimation of HCV seroprevalence in retrospective seroepidemiological surveys as established by our findings.

Adolescent↗
PubMed1995

Combination therapy with zidovudine prevents selection of human immunodeficiency virus type 1 variants expressing high-level resistance to L-697,661, a nonnucleoside reverse transcriptase inhibitor.

L-697,661 is a human immunodeficiency virus type 1 (HIV-1)-specific nonnucleoside reverse transcriptase (RT) inhibitor. Its tolerability and activity in combination with zidovudine were evaluated in a 48-week double-blind study. One hundred nineteen zidovudine-naive HIV-1-infected patients with CD4 cell counts of 200-500/mm3 received either combination therapy, L-697,661 alone, or zidovudine alone. Activity was assessed by CD4 cell count changes. Selection for L-697,661-resistant virus was monitored by susceptibility testing of RT expressed by circulating viral RNA. Therapy was generally well tolerated. All groups receiving zidovudine exhibited transient increases in CD4 cell counts, while the L-697,661 monotherapy group showed a significant decline and yielded RT > 100-fold resistant to L-697,661 and associated with substitutions at RT residue 181. The RT from patients receiving combination therapy was maximally 15-fold less susceptible to L-697,661. Hence, cotreatment with zidovudine prevents selection of HIV-1 variants that are highly resistant to L-697,661 in patients naive to both compounds.

Adult↗
PubMed1995

Turnover of circulating virion RNA and of cell-associated viral DNA reflects active viral replication in human immunodeficiency virus type 1-infected individuals.

A quantitative assessment of human immunodeficiency virus type 1 turnover in patient cell-free virion and infected-cell compartments under the dynamic conditions imposed by an effective antiviral therapy was performed. The turnover was rapid, and following a temporal lag, the extent of viral population replacement was eventually similar in both compartments. Each compartment therefore reflects considerable active virus replication.

Antiviral Agents↗
PubMed1995

A dose comparison study of didanosine in patients with very advanced HIV infection who are intolerant to or clinically deteriorate on zidovudine. German ddI Trial Group.

OBJECTIVE: Zidovudine (ZDV) is the only antiretroviral drug which has been shown to reduce mortality in patients with symptomatic HIV disease, but its use is restricted by intolerance in a significant proportion of patients. Additionally, the efficacy of ZDV therapy appears to decrease after prolonged treatment particularly in the advanced stage of HIV disease. Therefore, alternative antiretroviral regimens for patients are needed. In this study, didanosine (ddI; 2',3'-dideoxyinosine), another HIV reverse transcriptase inhibitor, was evaluated. DESIGN: A total of 426 patients with AIDS or AIDS-related complex (ARC) who were intolerant to or clinically progressing on ZDV therapy and who had CD4+ cell counts < or = 150 x 10(6)/l were randomized to receive either a high (750 mg for bodyweight > or = 60 kg or 500 mg for bodyweight < 60 kg) or a low (200 mg and 134 mg, respectively) dose of ddI daily. SETTING: The patients were recruited from 31 German and Austrian AIDS clinical primary-care centres. RESULTS: The study was stopped after the second interim analysis due to a statistically significant difference in the incidence of pancreatitis (nine versus 26; relative risk, 2.92; P = 0.003) and neuropathy (28 versus 43; relative risk, 1.55; P = 0.05) in favour of the low dose. There was no difference between the low and high dosage groups in survival rate at 6 (80 versus 80%) and 12 months (61 versus 65%), number of deaths [82 (43.6 per 100 patient-years) versus 84 (44.4 per 100 patient-years)], progression from ARC to AIDS or to AIDS or death, or average number of new/recurrent opportunistic infections (2.8 versus 3.0 per patient). CONCLUSIONS: This study cannot conclude on ddI efficacy but it shows that in patients with advanced HIV disease for whom no alternative antiretroviral therapy is available and ddI therapy is considered, daily doses < 750 mg should be administered.

AIDS-Related Complex↗
PubMed1995

Zidovudine and lamivudine: results of phase III studies.

It has become apparent that the beneficial effects of zidovudine (AZT) and other antivirals will not continue indefinitely. However, synergistic activity of lamivudine (3TC) in combination with AZT, as well as reversal of phenotypic AZT resistance due to the presence of 3TC resistance-inducing mutations, has been documented in vitro. Two trials (NUCB 3001 and NUCB 3002) are therefore investigating the potential of the combination of 3TC with AZT. HIV-1-positive patients with CD4 cell counts of 100-400 cells/mm3 who had not previously received AZT were enrolled into study NUCB 3001 and treated with either AZT (200 mg t.i.d.) or 3TC (300 mg b.i.d.) plus AZT (200 mg t.i.d.) for 24 weeks. Open-label treatment with the combination regimen was offered for an additional 24 weeks. Both treatment groups experienced an initial increase in CD4 cell count. This increase was significantly greater and more sustained in the combination treatment group than in those receiving AZT monotherapy. Participants originally receiving AZT monotherapy, who changed to combination therapy after 24 weeks, experienced a rise in CD4 count. Those who began the study receiving combination therapy maintained their increased CD4 count for the duration of the study. A statistically significant difference in CD4 cell count between the two treatment groups was observed over the entire 48-week treatment period (p </= 0.0001) indicating that initial combination therapy was superior to monotherapy followed by a switch combination therapy after 24 weeks. Both treatment groups experienced a reduction in HIV-RNA levels and cellular viraemia, but these reductions were significantly greater in the combination treatment group than in those receiving AZT monotherapy. In addition, among patients initially randomized to AZT monotherapy, a significant reduction in the viral RNA concentration was observed after switching to combination therapy at week 24. There was an 80% reduction in p24 antigen levels from baseline in the combination treatment group compared with a 34% reduction from the baseline in the AZT monotherapy group, at 24 weeks. HIV-1-positive patients with CD4 cell counts of 100-400 cells/mm3 who had previously received a minimum of 24 weeks AZT treatment were enrolled into study NUCB 3002 and received either AZT monotherapy (200 mg t.i.d. plus placebo); AZT (200 mg t.i.d.) plus 3TC (300 mg b.i.d.) or AZT (200 mg t.i.d.) plus 3TC (150 mg b.i.d.) for 24 weeks. Open-label treatment with 3TC plus optional AZT was offered for a further 24 weeks (open-label phase). The study is still ongoing, but an initial increase in CD4 cell count was observed in the combination groups whereas, in the AZT monotherapy group, no discernible increase in CD4 cell count was observed at any time. The favorable effect of combination treatment with AZT and 3TC on CD4 cell count persisted throughout the open-label phase of the study. The addition of 3TC to the treatment regimens of patients who initially received AZT monotherapy had a favorable effect on CD4 cell count. Combination treatment with 3TC and AZT also resulted in a significantly greater reduction in viral load compared with AZT monotherapy. In conclusion, combination therapy with AZT plus 3TC produces beneficial effects on CD4 cell counts, HIV-1 RNA levels, and p24 antigen levels, which appear to be greater and more sustained than those produced by AZT monotherapy or any combination therapy to date. This combination appears to offer increased efficacy compared with AZT monotherapy without an increased risk of adverse experiences. Future studies to identify those patients most likely to benefit from such treatment and the optimum time for its initiation are therefore warranted.

Antiviral Agents↗
PubMed1994

Hepatitis C virus antibody prevalence among human immunodeficiency virus-1-infected individuals: analysis with different test systems.

Sera of 383 human immunodeficiency virus (HIV)-1-infected individuals from Frankfurt (Main)/Germany were assayed by two hepatitis C virus (HCV) screening tests (Abbott second generation, Ortho second generation). This population showed a prevalence for reactivity with both tests of 20.8% (80/383). Examination of all reactive sera (91/383) by a supplemental assay (Chiron RIBA 2) gave for 46 sera a positive, for 33 sera an indeterminate, and for 12 sera a negative result. Further analysis focussed on these RIBA 2-indeterminate and -negative samples. Analysis of the sera using an in-house Western blot with three different Escherichia coli-expressed HCV proteins revealed that none of the RIBA 2-negative, but 24 of the 33 RIBA 2-indeterminate sera, including 3 of 4 c33c (NS3)-reactive samples, were reactive with a recombinant core protein. Twenty-one of 22 c22-3 (core) indeterminates stained the core antigen in the in-house Western blot and 3 of them in addition a NS5 moiety. HCV-polymerase chain reaction (PCR) was positive for 14 of the 24 RIBA 2-indeterminate sera, but for none of the RIBA 2-negative or Western blot nonreactive samples. Discrepant results between the two screening tests could not be explained by differences in the antigen compositions (i.e., a NS3-NS4 moiety of 111 amino acids present in the Ortho enzyme-linked immunosorbent assay (ELISA), not present in the Abbott or RIBA 2 assays).

Acquired Immunodeficiency Syndrome↗
PubMed1994

AIDS-free survival and overall survival in HIV infection: the new CDC classification system (1993) for HIV disease and AIDS.

The clinical history of 1538 HIV positive patients was analyzed on the basis of the new CDC classification system of HIV disease and AIDS. This classification system combines three CD4 cell categories (1, 2, and 3) with three clinical categories (A, B, and C) into nine subgroups A1-C3. We examined the overall survival for all subgroups and the AIDS-free survival for subgroups A1-B3. AIDS-free survival for patients in subgroups A1, A2, and B1 was considerably longer than survival in patients from subgroups A3, B2, and B3 (P < 0.0001). According to these findings, the new CDC classification system could be simplified into three stages, stage I and II comprising the above mentioned six subgroups, and stage III comprising clinical AIDS defining categories C1, C2, and C3. These three stages correspond to different periods in the management of HIV positive patients, i.e., period of observation, period of prophylaxis, and period of treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1993

[Epidemiology of tuberculosis in patients with HIV infection of the Frankfurt University Clinic].

Frequency and risk of tuberculosis were studied among a large group of HIV-infected patients (n = 2556), 869 of whom had AIDS, over a period of ten years (February 1982 through February 1992) at the University Hospital Frankfurt. A total of 148 (5.8%) out of 2.556 patients had tuberculosis. With increasing immunodeficiency, the frequency of tuberculosis rose. The rate of tuberculosis in post-mortem was even higher, i.e. 17.3%. I.v. drug-addict AIDS patients were inflicted with 18.5% considerably more often than homo-/bisexual patients with 12.3%. The same holds true with 25% of tuberculosis infections for AIDS patients from endemic areas as compared with 13% for patients from countries with lower tuberculosis incidence. 18% of patients contracted tuberculosis already at > 200 CD4-positive cells/microliters before AIDS manifestation. Coming from endemic areas, drug addiction and lower number of T-cells signify a high risk for HIV-infected patients to acquire a post-primary or primary tuberculosis, respectively. HIV-infected patients represent a relevant danger of infection for partners and health-care personnel. In contrast to the United States, no increase in the tuberculosis incidence, except for some areas like Frankfurt, has been noted. Preventive measures, which include the IHN prophylaxis for patients with T-cell counts < 150/microliters, should be discussed.

AIDS-Related Opportunistic Infections↗
PubMed1991

[Intestinal permeability in patients with acquired immunodeficiency syndrome (AIDS)].

Intestinal permeability has been assessed as a parameter of the small intestinal barrier function in 33 patients with AIDS (WR 6), in 25 healthy volunteers, 32 patients with Crohn's disease, 18 patients with ulcerative colitis and in 12 patients with untreated coeliac disease. Permeability was measured by means of the 5 hour urinary excretion of lactulose and rhamnose after administration of these sugars (1 g rhamnose, 10 g lactulose) which allowed to calculate the urinary lactulose/rhamnose--ratio (L/R-r) as an index of intestinal permeability. Compared to the controls (L/R-r = 0.014 +/- 0.010) patients with AIDS had significantly increased lactulose/rhamnose--ratios (0.189 +/- 0.164; p less than 0.01) indicating abnormal permeation both of lactulose and rhamnose. This alteration of intestinal permeability was more pronounced than the significant increase of the L/R-r in the patients with either Crohn's disease or coeliac disease. However, intestinal permeability was not altered in the patients with ulcerative colitis. Among the patients with AIDS, the most abnormal permeability ratios were observed in two subjects with intestinal cryptosporidiosis. This investigation demonstrates by means of the "double sugar ratio", that intestinal permeability in patients with AIDS is highly abnormal, the impairment being even more abnormal than in patients with other small intestinal disease.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Fluconazole prophylaxis of recurrent oral candidiasis in HIV-positive patients.

In a randomized, open study, the efficacy of fluconazole as a prophylaxis of recurrent oral candidiasis in patients with advanced stages of HIV-infection (CD4 cell count less than 100/mm3) was studied. For this purpose, the frequency of episodes of oral candidiasis during two different prophylaxis regimens (50 mg/day vs. 100 mg/day) were compared to an untreated control group. Sixty-five HIV-positive patients were included in the study from May, 1989 to January, 1990. Of these, 58 were evaluated over an observation time of 137-215 days. Prophylaxis with fluconazole clearly reduced the occurrence of oral candidiasis. In 20 out of 21 patients in the untreated control group, a total of 60 relapses occurred. In the prophylaxis group receiving 50 mg/day (group 2), two out of 18 patients had four relapses. In the group receiving 100 mg/day (group 3), four out of 19 patients had nine relapses in total. Of 3575 observation days in the control group, treatment due to oral candidiasis was necessary on 393 days (28%). In group 2, on 57 of 3316 days (2%), fluconazole in a higher dosage was administered for treatment. In group 3, relapse treatment with fluconazole 200 mg/day, or treatment with ketoconazole, became necessary in 116 out of 3314 observation days (3%). In all relapses, Candida albicans cfu greater than 10(3)/ml were isolated in the oral wash-outs. As compared to the untreated control group, fluconazole prophylaxis in a daily dosage of 50 as well as 100 mg led to significantly less frequent relapses of oral candidiasis (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1990

Demonstration of cross-reactive antibodies able to elicit lysis of both HIV-1- and HIV-2-infected cells.

A total of 100% of sera from a large number of HIV-1-infected patients contained antibodies able to elicit Antibody-dependent cellular cytotoxicity lysis of cells infected with the HIV-1 isolates IIIB or RF. Levels of activity could not be correlated with activities in ELISA or neutralizing antibody assays nor with the clinical status of the patients. Surprisingly, 8 of 156 patients sera could additionally elicit lysis of HIV-2-infected cells, and cold target competition assays demonstrated that the cross-reactivity was apparently mediated via recognition of common epitope(s) expressed on the surface of cells infected with either group of HIV. The ADCC mechanism was shown to be mediated by a CD16+ lymphocyte. This demonstration of an effector mechanism able to attack and eliminate cells infected with a wide range of HIV strains has obvious implications for development of putative vaccines.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

[Comparison of the effect of 2 therapy concepts in the treatment of Pneumocystis carinii pneumonia. Cotrimoxazole for 21 days versus sequential therapy with cotrimoxazole followed by pentamidine inhalation].

Standard therapy of pneumocystis carinii pneumonia with cotrimoxazole and intravenous pentamidine second line therapy both have a response rate of 75 to 90%. As severe side effects, myelotoxicity and skin reaction have been observed which may occur from treatment day 7 on. In order to prevent such side effects as well as reduce hospitalization times, an open, randomized pilot study was designed. Object of this study was the comparison of efficacy and safety of two different treatment schemes: standard therapy versus sequential treatment. Twelve patients were treated according to study design: five patients with cotrimoxazole only, and seven patients with sequential therapy consisting of cotrimoxazole followed by pentamidine aerosol. All patients were treated for 21 days. Four out of five patients with cotrimoxazole, and two out of seven patients with sequential therapy, were successfully treated and had no pneumocystis carinii pneumonia relapses within four weeks after termination of treatment. Each group had one treatment failure. Four patients under sequential treatment were not evaluable. - In spite of the rather unfavourable preliminary results, the study should be continued. However, patients with secondary opportunistic infections respectively other severe diseases should not be included into the study.

Administration, Inhalation↗
PubMed1990

[Prospective study of primary and secondary prevention of Pneumocystis carinii pneumonia with pentamidine aerosol].

In an open prospective study in the AIDS Outpatient Department of the Frankfurt University Clinic the efficacy of pentamidine aerosol at a dosage of 200 mg every 14 days in the primary and secondary prophylaxis of pneumocystis carinii pneumonia was tested. The incidence of pneumocystis carinii pneumonia was reduced by more than 75% in the group of patients receiving pentamidine additionally by inhalation as compared with a historical cohort given azidothymidine alone. The results of the study suggest that a CD4-positive cell count of less than 50/microliters with a concomitant secondary lung infection promotes the development of pneumocystis carinii pneumonia. There was no correlation between the incidence of pneumocystis carinii pneumonia and the number of previous disease episodes. No systemic toxicity of pentamidine aerosol was established.

AIDS-Related Complex↗
PubMed1989

Inhibitory effect of azidothymidine, 2'-3'-dideoxyadenosine, and 2'-3'-dideoxycytidine on in vitro growth of hematopoietic progenitor cells from normal persons and from patients with AIDS.

Therapy of patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) with azidothymidine (AZT) and 2'-3'-dideoxycytidine (ddC) is complicated by severe anemia, neutropenia, and thrombocytopenia, the cause of which is unknown. We therefore tested the effect of AZT, ddC, and an additional 2'-3'-dideoxynucleoside analogue, 2'-3'-dideoxyadenosine (ddA), on the hematopoietic progenitor cells derived from the bone marrow of normal persons and patients with AIDS/ARC. All three substances dose-dependently inhibited the in vitro colony formation of the pluripotent (CFU-GEMM), as well as the erythroid (BFU-E) and granulocyte-macrophage progenitor cells (CFU-GM). The 50% inhibition of normal progenitors by AZT occurred at 0.13 microM for CFU-GEMM, 0.32 microM for BFU-E, and 1.9 microM for CFU-GM, by ddA at 15 microM for CFU-GEMM, 40 microM for BFU-E, and 140 microM for CFU-GM. ddC was the most toxic agent and already inhibited 71% +/- 16% (mean +/- standard error of the mean [SEM]) of CFU-GEMM and 52% +/- 22% of BFU-E at 0.1 microM, whereas the 50% inhibition of CFU-GM was reached at 0.3 microM. Hematotoxicity occurred at concentrations lower than necessary to inhibit the human immunodeficiency virus (HIV), except for ddA, which is 100 times less toxic than AZT whereas its antiviral effect is only 10 times less. The inhibition of progenitor cells from AIDS patients by the 2'-3'-dideoxynucleosides was comparable to normal progenitors, except for a higher sensitivity of AIDS-derived CFU-GEMM and BFU-E to AZT.

AIDS-Related Complex↗