[BSE and vCJD. New infectious prion diseases].
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Animals↗
Biomedical subjects
B Salzberger
Publications and source records attributed to B Salzberger.
First-line ritonavir/indinavir 100/800 mg twice daily plus nucleoside reverse transcriptase inhibitors in a German multicentre study: 48-week results.
OBJECTIVES: To evaluate safety and efficacy of the protease inhibitor combination ritonavir/indinavir 100/800 mg twice daily plus 2-3 nucleoside reverse transcriptase inhibitors (NRTI) in antiretroviral-naive patients. METHODS: Within this open-label, uncontrolled multicentre trial, antiretroviral-naive patients (n = 57) with median baseline HIV-RNA of 308,000 copies/mL (range 170-3.01 million copies/mL) and median CD4 cell count of 50 cells/microL (range 0-853 cells/microL) were started on 2-3 NRTIs plus ritonavir/indinavir 100/800 mg twice daily. CD4 cell counts and HIV-RNA were determined at weeks 0, 4, 8, 12, 16, 20, 24 and 48. Statistical analysis was performed on treatment as well as intent-to-treat. RESULTS: Viral load decreased by a median of 3.79 log10 copies/mL (range 2.0-4.60 log10 copies/mL) until week 48. At week 48, 23/57 (40%, intent-to-treat) patients showed a viral load </= 80 copies/mL. In parallel, median CD4 cell counts increased by a median of 149 cells/microL (range -60-420 cells/microL). Median triglycerides and cholesterol increased from baseline 160 mg/dL (range 33-364 mg/dL) to 218 mg/dL (range 110-527 mg/dL) at week 48 and from 166 mg/dL (range 63-262 mg/dL) to 233 mg/dL (range 95-359 mg/dL), respectively. Twenty-seven of fifty-seven patients (47%) discontinued study medication, 19 (33%) due to nephrolithiasis. Two patients changed their antiretroviral regimen after failing virologically. CONCLUSION: Ritonavir/indinavir 100/800 mg twice daily appears to be effective up to 48 weeks despite high baseline viraemia and low CD4 cell count in antiretroviral-naive patients. However, discontinuation due to adverse events, especially nephrotoxicity, is frequent and limits treatment duration. Therefore, extra hydration appears inevitable with this combination.
Adult↗
T-cell non-Hodgkin's lymphoma in adults: clinicopathological characteristics, response to treatment and prognostic factors.
T-cell NHL represent 10-15% of all malignant lymphomas making systematic prospective clinical trials difficult. Therefore, the prognostic significance of the T-cell phenotype has been a matter of controversy in recent years. In a retrospective analysis of 681 patients (pts) with NHL accrued from 1992 to 1997 at a single institution, 66 patients with T-cell NHL were identified. According to the REAL classification, histologies were as follows: 28 peripheral T-cell lymphomas (PTCL), 19 large cell anaplastic lymphoma (LCAL), 12 precursor lymphoblastic lymphoma (Lb), and seven AILD. Multiagent anthracycline containing regimens were used as initial therapy in 91% of cases. T-cell NHL represent 9.8% of all NHL patients at our institution accrued over a 6-year period. Overall response rate was 76%, 21% had progressive disease and 3% died during first line treatment. Mean overall survival (OS) was 8.22 +/- 0.94 years. There was a significant difference in OS between the four different histological subgroups (log rank P=0.0288). LCAL: mean OS 11.05 +/- 1.55 years (95% CI 8.00-14.09); LB: mean OS 7.09 +/- 1.40 years (95% CI 4.33-9.84); PTCL: mean 6.62 +/- 1.17 years (95% CI 4.33-8.90); AILD: 1.54 +/- 0.44 years (95% CI 0.67-2.40). OS was also significantly different for patients classified according to the International Prognostic Index (IPI)-score (log rank P = 0.002). Mean OS for patients with low risk, intermediate low risk, intermediate high risk and high risk was 10.46 +/- 1.02, 6.46 +/- 1.79, 4.50 +/- 1.20 and 1.15 +/- 0.46 years, respectively. Univariate analysis (log-rank test) for prognostic factors also revealed elevated LDH, B-symptoms and extranodal involvement as significant factors for OS. The presence of bulky disease (>7.5 cm), advanced stage III/IV and bone marrow involvement did not influence OS. In conclusion, it is evident that histological subtype and IPI-score have a strong prognostic impact on OS in pts with T-cell NHL. Thus, the distribution of risk factors in patients with T-cell NHL may be more important for OS than T-cell histology per se.
Aged↗
A randomized monocentric trial in febrile neutropenic patients: ceftriaxone and gentamicin vs cefepime and gentamicin.
A prospective, randomized, controlled monocentric trial was performed to evaluate the efficacy and safety of once daily ceftriaxone 2 g plus gentamicin 5 mg/kg in comparison to cefepime 2 g t.i.d. plus gentamicin 5 mg/kg q.d. in the treatment of neutropenic fever. In case of fever (oral temperature > or =38.5 degrees C on one occasion or > or =38.0 degrees C twice within 24 h) and a granulocytopenia (neutrophil count below 500 or below 1000/microl when expected to fall below 500 within 72 h), patients with hematological malignancies or solid tumors were assigned to ceftriaxone or cefepime, each with gentamicin. The primary endpoint was defined as defervescence on day 4-6 followed by at least 7 afebrile days. Secondary endpoints were overall response, defined as defervescence on day 28 and toxicity. Two hundred eleven episodes were included. Fever of unknown origin (FUO) accounted for 124 episodes (58.8%), microbiologically defined infection (MDI) for 39 (18.5%), clinically defined infection (CDI) for 25 (11.8%), and both clinically and microbiologically defined infection (CMDI) for 19 episodes (9%). On an intent-to-treat basis 207 episodes were evaluable for the primary endpoint. Ceftriaxone plus gentamicin and cefepime plus gentamicin were successful in 49.5% and 51%, respectively. Overall response was achieved on study day 28 in 92.5% and 91%, respectively. Diarrhea was more frequent with ceftriaxone/gentamicin (6.5% vs 17%), while nausea/vomiting was less (12.1% vs 5%). Once-daily ceftriaxone plus gentamicin was not inferior to cefepime t.i.d. plus gentamicin q.d. in the empirical treatment of neutropenic fever.
Anti-Bacterial Agents↗
Pharmacokinetics of amprenavir and lopinavir in combination with nevirapine in highly pretreated HIV-infected patients.
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Anti-HIV Agents↗
Stavudine versus zidovudine and the development of lipodystrophy.
The pathogenesis of some components of the lipodystrophy (LD) syndrome might be linked to the use of nucleosides. Earlier reports did not compare treatment regimens according to the nucleoside backbone. We studied a cohort of individuals who did not switch between stavudine and zidovudine. LD was defined to be present if one of three criteria was met: self-report by the patient, observation by an investigator who had known the patient since commencement of highly active antiretroviral therapy (HAART), or examination by a physician masked to therapy. The mean duration of therapy was 101 weeks (range: 26-234 weeks). Overall prevalence of LD was 48.7%. Lipoatrophy and lipohypertrophy occurred in 33.9% and 28.7% of patients, respectively. Logistic regression showed four parameters to be significantly associated with lipoatrophy: HAART longer than 2 years (p =.002, odds ratio [OR] = 4.4, 95% confidence interval [CI]: 1.608-11.965), baseline viral load >100,000 copies/ml (p =.004, OR = 4.3, CI: 1.726-11.197), age >40 years (p =.016, OR = 3.2, CI: 1.247-8.373), and white ethnicity (p =.041, OR = 5.4, CI: 1.070-28.184). Cholesterol levels of >200 mg/dl at baseline were associated with a risk reduction (p =.047, OR = 0.36, CI: 0.130-0.987). Use of lipohypertrophy as a dependent variable resulted in a significant association with HAART duration (p = 0.028, OR = 2.7, CI: 1.2-6.5) and protease inhibitor use (p =.014, OR = 3.8, CI: 1.3-11.2). LD prevalence is similar with both backbones using stavudine or zidovudine. This is the first time that baseline cholesterol was shown to be significantly associated with lipoatrophy.
Adult↗
Avascular necrosis of both femoral heads in an HIV-infected patient receiving protease inhibitors.
Several adverse effects have been reported under antiretroviral therapy containing protease inhibitors. We report a further case of avascular necrosis of both femoral heads in an HIV-infected patient treated with protease inhibitor containing antiretroviral therapy.
Adult↗
Randomized controlled monocentric comparison of once daily ceftriaxone with tobramycin and cefotaxime three times daily with tobramycin in neutropenic fever.
A prospective, randomized, controlled monocentric trial was performed to evaluate the efficacy and safety of once daily ceftriaxone 2 g plus tobramycin 5 mg/kg in comparison to cefotaxime 2 g t.i.d. plus tobramycin 5 mg/kg qd in the treatment of neutropenic fever. In cases of fever > or = 38.5 degrees C and a neutrophil count below 1000/microliter, patients with hematological malignancies were assigned to ceftriaxone or cefotaxime, each with tobramycin. The primary endpoint was defined as defervescence < 37.5 degrees C on day 4-6 followed by at least 7 afebrile days. Secondary endpoints were overall response, defined as defervescence on day 25 and toxicity. There were 160 episodes of 114 patients included. Fever of unknown origin accounted for 79 episodes (51%), microbiologically defined infection for 36 (23%), clinically defined infection for 27 (17%), and both clinically and microbiologically defined infection for 14 episodes (9%). On an intent-to-treat basis 156 episodes could be evaluated for the primary endpoint. Ceftriaxone plus tobramycin and cefotaxime plus tobramycin resulted in a primary response in 46.9% and 45.3%, respectively. Overall response was achieved on study day 25 in 87.7% and 80%, respectively. No significant difference in toxicity was observed. Once-daily ceftriaxone plus tobramycin was not inferior to cefotaxime t.i.d. plus tobramycin qd in the empirical treatment of neutropenic fever.
Adult↗
Seroprevalence of human herpesvirus-8 in different patient groups in Cambodia and Germany.
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Antibodies, Viral↗
Detection of microsporidia in travelers with diarrhea.
We examined stool specimens of 148 returning travelers from an outpatient department for tropical diseases for the appearance of microsporidia using light microscopy and PCR. Intestinal microsporidiosis was diagnosed for five patients by light microscopy and for nine patients by PCR. Some cases were diagnosed only by PCR, indicating that the true prevalence has to be determined by highly sensitive techniques, such as PCR.
Animals↗
Risk factors for the HIV-associated lipodystrophy syndrome in a cross-sectional single-centre study.
OBJECTIVE: Risk factors for the HIV-associated lipodystrophy syndrome (HALS) were studied in a single-centre, cross-sectional study. - PATIENTS AND METHODS: 278 consecutive HIV-infected outpatients at a German tertiary care centre were enrolled. Changes in body shape were quantified using linear analogue scales. Cumulative treatment duration for each antiretroviral drug, CD4 cells, viral load and age were investigated as potential risk factors for a clinical diagnosis of lipodystrophy syndrome by logistic regression. RESULTS: HALS was diagnosed in 88 patients. The risk of HALS increased significantly with longer protease inhibitor treatment (relative risk 1.61 (95% confidence interval, 1. 24 to 2.09, per year); older age and a history of low CD4 cell counts were cofactors in this multivariate model, but nucleoside analogues did not contribute significantly. Neither pattern nor severity of disease were predicted by these risk factors. Treatment durations and other risk factors were highly correlated with each other. CONCLUSIONS: These findings support a pathogenetic role for protease inhibitor toxicity, advanced HIV disease, and ageing. No evidence for an additional effect of nucleoside analogues was found. The high correlation of potential risk factors indicates that this and other available studies may be too small to detect multiple risk factors without major confounding.
Acquired Immunodeficiency Syndrome↗
[Infectiology update. II: Diagnosis and therapy].
In this article, relevant recent changes in the diagnosis and therapy of infectious diseases are reviewed. Several new diagnostic tools for the quantification of viral DNA and RNA have been developed in the last years (PCR-based and related methods). A number of new antiviral agents has been licensed for the treatment of different viral infections. The clinical management of viral infections has dramatically changed with these tools and agents. Especially morbidity and mortality of HIV-infected patients have both been reduced by antiretroviral combination therapy. With rising rates of antibiotic resistance in gram-positive bacteria, therapy of infections with these agents has become increasingly difficult. A number of new antibiotic agents for the treatment of these infections have been developed and licensed.
Anti-Bacterial Agents↗
Spontaneous regression of HIV associated T-cell non-Hodgkin's lymphoma with highly active antiretroviral therapy.
A subcutaneous, T-phenotypic anaplastic large cell lymphoma (CD30/Ki1-positive, EBV positive) was diagnosed in a HIV-infected bisexual man. Without chemotherapy the patient had a sustained long-term remission of this tumor (more than three years) after the initiation of highly active antiretroviral therapy. By PCR analysis of T-cell receptor beta gene rearrangements the tumor was found to be oligoclonal. Improvement of cellular immune function by antiretroviral therapy is the only recognizable factor which may have led to tumor remission. This hypothesis is supported by parallels to EBV associated polyclonal lymphoproliferation in allogeneic transplantat recipients where regression of lymphoma can be induced by reducing immunosuppressive therapy.
Anti-HIV Agents↗
[Update in infectious diseases. Part I: epidemiology].
A number of infectious agents has been newly detected in the last 10 years. Climatic changes and migration have been the most important factors in the emergence of new and old infections. Additionally, new methods for the detection of DNA and RNA have played an important role in the detection of agents difficult to culture. Relevant new bacterial pathogens are Bartonella henselae (cat scratch disease, bacillary angiomatosis), Tropheryma whippeli (Whipple's disease) and new Rickettsiae. Newly detected viral pathogens include Sin-nombre virus (pulmonary Hanta virus syndrome), Nipah- and Hendra virus and avian influenza. Bovine spongiform encephalopathy has been transmitted to humans causing the newly described syndrome of variant Creuzfeldt-Jakob disease. The extent of this new epidemic is not yet clear. These trends from the last years clearly indicate, that further new infections and infectious agents will be detected in the future.
Bacterial Infections↗
[Dangerous tropics].
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Disease Transmission, Infectious↗
Taxonomic position of the human intestinal protozoan parasite Isospora belli as based on ribosomal RNA sequences.
The taxonomic positions of Isospora belli and other members of the genus Isospora are controversial. We determined the small-subunit ribosomal RNA of I. belli and used this sequence in combination with other coccidian RNA sequences for analysis of the taxonomic position of I. belli. The phylogenetic trees we obtained provide molecular evidence for three clades within a monophyletic group that represents the suborder Eimeriina. The clade containing I. belli consists of tissue-cyst-forming coccidia (Toxoplasma and Neospora) and members of the genus Isospora (I. ohioensis, I. suis, I. belli). The second clade, representing a sister clade of that containing the Isospora species, contains members of the genus Sarcocystis. The third one consists of members of the family Eimeriidae, including Eimeria and Cyclospora species. This shows that although I. belli as well as other members of the genus Isospora belong to the suborder Eimeriina, the family to which they belong is not Eimeriidae but rather Sarcocystidae. We suggest that the genus Isospora should be removed from the family Eimeriidae and placed into the family Sarcocystidae within the suborder Eimeriina.
Animals↗
Detection of Isospora belli by polymerase chain reaction using primers based on small-subunit ribosomal RNA sequences.
The aim of the present study was to use small-subunit (SSU)-rRNA sequences of Isospora belli to design specific primer pairs and a hybridization probe for the detection of Isospora belli in human samples by PCR and Southern blot hybridization. PCR amplification with the primer pairs produced correct DNA fragments with target DNA from samples of Isospora belli-infected patients and from cloned SSU-rRNA of Isospora belli. The nature of the PCR products was confirmed by Southern blot hybridization. No amplification was seen with template DNA extracted from other parasites. Although Isospora belli infections can be easily diagnosed using light microscopy, molecular-based techniques may prove useful as an additional diagnostic tool.
Animals↗
CMV sinusitis as the initial manifestation of AIDS.
Cytomegalovirus (CMV) disease is a typical late-stage complication of AIDS. Only six cases of CMV sinusitis have been reported in the literature. This is the first case of CMV sinusitis leading to the diagnosis of HIV and CMV retinitis. Diseases of the sinonasal tract may represent an initial manifestation of HIV or AIDS.
AIDS-Related Opportunistic Infections↗