PubMed Health⌕ Search

Biomedical subjects

Bernd Salzberger

Publications and source records attributed to Bernd Salzberger.

At least 19 recordsLinked to original sources

Influenza pandemic and professional duty: family or patients first? A survey of hospital employees.

BACKGROUND: Conflicts between professional duties and fear of influenza transmission to family members may arise among health care professionals (HCP). METHODS: We surveyed employees at our university hospital regarding ethical issues arising during the management of an influenza pandemic. RESULTS: Of 644 respondents, 182 (28%) agreed that it would be professionally acceptable for HCP to abandon their workplace during a pandemic in order to protect themselves and their families, 337 (52%) disagreed with this statement and 125 (19%) had no opinion, with a higher rate of disagreement among physicians (65%) and nurses (54%) compared with administrators (32%). Of all respondents, 375 (58%) did not believe that the decision to report to work during a pandemic should be left to the individual HCP and 496 (77%) disagreed with the statement that HCP should be permanently dismissed for not reporting to work during a pandemic. Only 136 (21%) respondents agreed that HCW without children should primarily care for the influenza patients. CONCLUSION: Our results suggest that a modest majority of HCP, but only a minority of hospital administrators, recognises the obligation to treat patients despite the potential risks. Professional ethical guidelines allowing for balancing the needs of society with personal risks are needed to help HCP fulfil their duties in the case of a pandemic influenza.

Absenteeism↗

An ultrastructural and molecular study of Tubulinosema kingi Kramer (Microsporidia: Tubulinosematidae) from Drosophila melanogaster (Diptera: Drosophilidae) and its parasitoid Asobara tabida (Hymenoptera: Braconidae).

Tubulinosema kingi is a pathogen of Drosophila spp. that was originally described 40 years ago. Although Drosophila melanogaster is widely used as a model organism for biological research, only limited data about microsporidia infecting Drosophila have been published so far and very little is known about the ultrastructure of T. kingi. In this study, we present the results of ultrastructural and molecular examinations of T. kingi. The whole life cycle took place in direct contact with the host cell cytoplasm and all examined life cycle stages contained a diplokaryon. Very few membrane elements were present in early merogonial stages, but their number and order of arrangement increased as the life cycle proceeded. The cell membrane of meronts had a surface coat of tubular elements that encircled the cell. Later, numerous electron-dense strands without any ornamentation accumulated on the plasma membrane, indicating that cells had entered sporogony. The cell membrane of sporonts was covered by electron-dense material. The polar filament in the spores was slightly anisofilar with the last three or four coils being smaller in diameter. The polar filament has 10 to 14 coils which were arranged predominantly in a single row, but in many spores, one winding of the coiled polar filament was located inside the outer coils. In some spores, the polar filament was irregularly arranged in two or even three rows. Molecular analysis showed that all Tubulinosema spp. are closely related and form a clade of their own that is distinct from the Nosema/Vairimorpha clade. All these ultrastructural and molecular features are in concordance with the family Tubulinosematidae and the genus Tubulinosema which reinforces the recent reclassification of this microsporidium.

Animals↗

[New developments in the diagnosis and therapy of acute bacterial meningitis].

BACKGROUND: Acute bacterial meningitis is a medical emergency. Despite advances in the diagnosis and treatment it continues to have a high case-fatality rate and high rates of long-term neurologic sequelae. ETIOLOGY: Since the widespread use of the vaccine for Haemophilus influenzae type B, Streptococcus pneumoniae has replaced it as the most common cause of acute community-acquired bacterial meningitis in industrialized countries. The rising incidence of beta-lactam-resistant pneumococci has to be considered when choosing a regimen for empiric antibiotic therapy. DIAGNOSIS: The clinical diagnosis remains difficult, as absent clinical meningeal signs do not exclude bacterial meningitis. If bacterial meningitis is considered a possible diagnosis, empiric antibiotic therapy should be initiated without any delay. Prior blood cultures and, if not contraindicated, a lumbar puncture should be performed. Based on new evidence, a screening cranial computed tomography to rule out raised intracranial pressure prior to lumbar puncture is recommended only for patients with defined risk factors (age > 60 years; preexisting immunodeficiency, immunosuppression, or neurologic diseases; recent seizures; any pathologic finding in the neurologic examination other than meningism). TREATMENT: Empiric antibiotic therapy should be initiated before cranial computed tomography. Adjuvant dexamethasone therapy initiated with or prior to the antibiotic therapy reduces mortality and morbidity for patients with pneumococcal meningitis without increasing the rate of side effects.

Acute Disease↗

Blockade of TNF does not alter oxygen burst and phagocytosis of human neutrophils in patients with rheumatoid arthritis.

Clinical trials evaluating tumor necrosis factor alpha (TNF-alpha) binding agents in patients with rheumatoid arthritis (RA) have demonstrated significant efficacy in reducing symptoms of disease and slowing radiographic progression. However, infectious complications are the most severe and common adverse effects of anti-TNF therapy. The functional capacities of neutrophils (PMNs) as the first line of defense in bacterial and fungal infections are enhanced by soluble TNF as a potent neutrophil primer. The aim of this study was to assess the influence of in vivo TNF blockade on oxygen burst (OB) and phagocytosis of human neutrophils. PMNs were derived from 20 patients with RA on anti-TNF-alpha therapy and 13 patients using conventional DMARDs. By flow cytometry we measured OB upon stimulation with Escherichia coli and N-formyl-1-methionyl-1-leucyl-phenylalanine (FMLP) with and without priming with granulocyte-colony stimulating factor (G-CSF) and/or TNF-alpha using dihydrorhodamine (DHR) 123. Phagocytosis of fluorescein isothiocyanate (FITC)-labeled E. coli was also assessed by flow cytometry. Thirty-three healthy volunteers served as controls. Upon stimulation with E. coli and FMLP, there was no significant difference in OB between the two patient groups and healthy controls. Priming was effective in all groups. Phagocytosis of E. coli by PMNs was equally effective in controls and patients independent from the treatment regimen. These data show that OB, phagocytosis and responsiveness to priming with TNF and G-CSF of PMNs are not impaired in patients with RA treated with anti-TNF agents in comparison with patients on conventional DMARDs or healthy controls. Thus, the infectious complications observed in patients with TNF blockade cannot be explained by functional impairment of PMNs; however, the neutralization of TNF as a potent primer of neutrophil response may increase the susceptibility for infections in these patients.

Adult↗

Preferences regarding medical and psychosocial support in HIV-infected patients.

Adherence to highly active antiretroviral therapy (HAART) is crucial for successful treatment of HIV-infected patients. Among other factors, meeting patients' preferences regarding medical and psychosocial support may have significant impact on adherence to HAART. But, systematic studies on HIV-infected patients' preferences regarding professional support are rare. We investigated preferences of German HIV-infected outpatients with HAART regarding medical and psychosocial support in a prospective study using qualitative and quantitative measures, e.g. semi-structured interviews and a questionnaire-based conjoint analysis (CA). CA was applied in 163 patients (93% male, 96% caucasians, age 42.2 +/- 10.3 years). Patients of our clinic predominately expect higher levels of personal support by their physicians, e.g. more flexible consultation time and telephone contacts, more disease related information by seminars or brochures, and additional counseling regarding psychosocial problems and dietary management, than applied in a German standard care setting. Prospective intervention studies are necessary to analyse whether meeting patients preferences regarding professional support can enhance adherence to HAART.

Adult↗

A designed TLR4/MD-2 complex to capture LPS.

The family of Toll-like receptors (TLRs) is involved in the defense of an organism to microbial attack. TLR4-induced signaling is involved in infectious diseases, chronic inflammatory diseases and sepsis; therefore, we aimed at modulating TLR4-signaling via ligand-binding soluble receptors. Because recognition of microbial structures shows some species-specific traits, we specifically selected the mouse model for later in vivo studies. We first prepared the N-terminally Flag-tagged mouse (m) recombinant (r) soluble (s) fusion proteins mrsTLR4-IgGFc (T4Fc) and mrsMD-2 in Drosophila melanogaster Schneider 2 (S2) cells. The function of these molecules was tested by inhibition of synthesis of pro-inflammatory cytokines after stimulation of mouse macrophage RAW 264.7 cells with purified lipopolysaccharide (LPS). T4Fc alone had no inhibitory activity; however, a T4Fc/MD-2 complex blocked LPS activity. By analogy with 'cytokine traps', we then prepared a designer molecule (LPS-Trap) by fusing MD-2 to the C-terminus of soluble TLR4 via a flexible linker. LPS-Trap significantly inhibited TNF production by LPS-stimulated RAW 264.7 cells. Thus, the T4Fc/MD-2 complex as well as the LPS-Trap blocked LPS activity in vitro and might thus represent a new therapeutic option in sepsis by neutralization of TLR4-activating ligands.

Animals↗

Uptake of Encephalitozoon spp. and Vittaforma corneae (Microsporidia) by different cells.

Microsporidia are obligate intracellular parasites infecting a broad range of vertebrates and invertebrates. Various microsporidian species induce different clinical pictures in humans. The reason for this is not clear. It has been speculated that the different microsporidian species are transmitted by various routes, thus causing infections in different organs. Another possibility is that the diverse microsporidia have different tropisms to organ-specific cells, thus causing various diseases. In this study, we investigated the uptake of microsporidian spores by different cells with an immunofluorescence staining technique to investigate whether there is a difference between microsporidian species as well as between different cells. Using this technique, we were able to distinguish between intra- and extracellular microsporidian spores. All examined cell lines were able to internalize microsporidian spores, but the extent of internalization differed significantly between the cells. Although the results showed some patterns that correlate with the distribution of the parasites in humans, the different clinical pictures cannot be sufficiently explained by this phenomenon, so it seems more likely that the various clinical manifestations caused by the different microsporidian species are a consequence of different infection routes rather than of different affinities of the microsporidian species to different cells.

Animals↗

Progressive multifocal leukencephalopathy in patients on highly active antiretroviral therapy: survival and risk factors of death.

OBJECTIVE: To describe the clinical course and risk factors of death in highly active antiretroviral therapy (HAART)-treated patients with progressive multifocal leukencephalopathy (PML); to evaluate the efficacy of cidofovir in addition to HAART. METHODS: Retrospective multicenter cohort study of PML in HIV-1-infected patients. Diagnosis of PML was confirmed by histology or by positive polymerase chain reaction for JC virus (JCV) in cerebrospinal fluid (CSF) or was made by typical radiologic and clinical findings. RESULTS: Thirty-five cases of PML were identified. The diagnosis was made by histology (9 cases), detection of JCV in CSF (17 cases), and by radiologic findings (9 cases). Upon manifestation of PML, 15/35 patients had never received HAART, and 11/35 were on HAART for >6 months (median 1126 days). In 9/35 cases, clinical manifestation of PML occurred within 6 months after initiation of HAART. All patients received HAART after PML diagnosis. After a median follow-up of 553 days (range 28-2694 days), the median survival time was not reached. In 12 patients who were treated concomitantly with cidofovir, cumulative survival was significantly shorter than in patients without cidofovir (P = 0.03). Patients in whom PML was diagnosed while on HAART demonstrated a trend toward a shorter survival than HAART-naive patients (P = 0.15). CONCLUSIONS: PML continues to occur in HIV-1-infected patients even when they are treated with HAART. Patients developing PML on HAART had a trend toward a shorter median survival compared with treatment-naive patients, and cidofovir therapy was not associated with improved survival in this cohort.

Acquired Immunodeficiency Syndrome↗

[Infectious diseases-Part II: New agents, resistances, and treatment strategies].

A number of new antimicrobial agents have been licensed in the last years, most prominently a number of new antiviral and antimycotic agents. The development of new antibacterial agents has slowed down, new agents are mainly targeted at a small but rapidly growing number of patients infected with bacteria resistant to the current antibiotics. The rates of resistance against antibiotics are rapidly rising, especially for gram-positive cocci and, in addition, for gram-negative nosocomial agents. Rising rates of resistances are further present in chronic viral infections, e. g., HIV infection. Instruments to monitor and minimize the rates of resistances are necessary. Important changes are to be found in a number of infectious complications. For patients with sepsis a new therapeutic principle, drocretogrin, has been found to reduce mortality. Additionally, low-dose corticosteroids in selected patients, close control of blood sugar and other interventions have shown to be effective. Corticosteroids have proven to be effective as well in the reduction of complications in adults with bacterial meningitis, most pronounced in pneumococcal meningitis. With new drugs licensed for the treatment of malaria and changes in the epidemiology, the guidelines for therapy and prevention have been reformulated.

Anti-Infective Agents↗

[Infectious diseases-part I: epidemiology].

The outstanding issue regarding recent trends in the epidemiology of infectious diseases is the epidemic occurrence of severe acute respiratory syndrome (SARS) in 2003. SARS is caused by a novel coronavirus, presumably originating from wild cats. This new agent was rapidly identified and characterized, the outbreak was terminated in early summer 2003 after implementation of strict infectious control measures. Especially the high rate of complications and nosocomial infections has caused severe public health problems in China and Canada. The number of persons infected with HIV is still rising rapidly globally. New regions with rapid spread include the countries of the former Soviet Union in East Europe and Central Asia. The introduction of modern antiretroviral therapy in countries with high prevalence is making slow progress, with no visible impact on transmission dynamics so far. The WHO has implemented a number of programs to eradicate or eliminate targeted infectious diseases. Polio eradication and elimination of neonatal tetanus are making slow progress, obstacles to the control of these diseases are ongoing armed conflicts in regions with high prevalence and under financing of programs. Lack of funding is especially obvious regarding programs for the control and therapy of malarial infections. The numbers of patients newly identified with new variant Creutzfeldt-Jakob disease are not rising, but rather constant or even declining, making a large epidemic of vCJD unlikely.

Communicable Disease Control↗

Quantitation of microsporidia in cultured cells by flow cytometry.

BACKGROUND: Microsporidia are obligate intracellular protozoan parasites that emerged as major opportunistic pathogens in humans since the onset of the AIDS pandemic. In the present study, we investigated whether FCM is a useful method for the quantitation of intracellular microsporidian spores in cultured cells. METHODS: Microsporidia (Encephalitozoon cuniculi) were grown in cell cultures and various cell-lines were coincubated with microsporidian spores at different multiplicities of infection, as well as for different periods of time. After permeabilization of the cells, intracellular spores were stained with a polyclonal anti-E. cuniculi serum and a FITC-labeled secondary antibody. Stained cells were analyzed on a flow cytometer and results were compared with those of fluorescence microscopy. RESULTS: Noninfected cells showed a lower fluorescence, while the relative fluorescence observed for infected cells was significantly higher. The cell population with the more intense fluorescence, representing cells with internalized microsporidian spores, increased with the multiplicity of infection as well as over time. Results of FCM and fluorescence microscopy were in excellent agreement for all experiments. CONCLUSIONS: We have developed a flow cytometric assay to detect and quantify cells with intracellular microsporidian spores. This method is easy to use, highly reproducible, and should be useful for future research.

Animals↗

Once-daily oral levofloxacin monotherapy versus piperacillin/tazobactam three times a day: a randomized controlled multicenter trial in patients with febrile neutropenia.

A prospective, randomized, controlled multicenter trial was performed to evaluate the efficacy and safety of once-daily oral monotherapy with 500 mg levofloxacin in comparison with 4.5 g piperacillin/tazobactam 3 times a day in patients with low-risk febrile neutropenia. Low risk was defined by oral temperature > or = 38.5 degrees C on one occasion or > or = 38.0 degrees C twice within 24 hours and granulocytopenia < or = 500/microL for less than 10 days. The primary end point was defined as defervescence after 72 hours followed by at least 7 afebrile days. Secondary end points were overall response, time to defervescence, survival on day 30, and toxicity. Thirty-four episodes were included. Fever of unknown origin accounted for 26 (76.5%) of the episodes, microbiologically defined infection for 5 (14.7%) of the episodes, and clinically defined infection for 3 (8.8%) of the episodes. On an intent-to-treat basis, all episodes were evaluable for the primary end point. Levofloxacin and piperacillin/tazobactam were successful after 72 hours of treatment in 76.5% and 88.3% of the episodes. Overall response was achieved in 94.1% and 100% of the episodes, respectively. One inpatient in the oral treatment group died of septic shock without identification of a causative pathogen. A larger phase III trial is warranted to further evaluate the lack of inferiority of the oral monotherapy regimen versus standard intravenous therapy.

Administration, Oral↗

Update on glycopeptide use in german university hospitals.

BACKGROUND: A previous study has shown considerable variation in glycopeptide use from 1992 through 1994 among four university hospitals in southern Germany. Active antimicrobial management in one of the hospitals was associated with the containment of glycopeptide consumption in the medical and surgical service at < 1.5 defined daily doses (DDD)/100 patient days in the subsequent period. In the present study, more recent data on comparative glycopeptide use in German university hospitals were analyzed. MATERIALS AND METHODS: Hospital pharmacy records from 1998 through 2000 were evaluated. The number of DDD (definition according to the World Health Organization [WHO]/Anatomic and Therapeutic Classification [ATC] index) per 100 patient days was calculated to compare glycopeptide use in different medical and surgical service areas between eight German university hospitals. RESULTS: The 3-year averages in recent glycopeptide use for the eight hospitals ranged between 1.3 and 8.8 DDD/100 patient days in the medical services, and between 0.7 and 1.8 DDD/100 patient days in the surgical services. Only one of the eight hospitals showed medical service glycopeptide use of < 1.5 DDD/100 patient days. In most hospitals, glycopeptide use was higher in the medical intensive care units (ICU) (median 8.6; range 4.3 to 12 DDD/100 patient days, data for the year 2000) than in the surgical ICUs (median 6.7; range 1.2 to 8.6 DDD/100 patient days, data for the year 2000). High use was also observed for hematology-oncology services (median 7.5; range 2.7 to 15.7 DDD/100 patient days, data for the year 2000). CONCLUSION: These recent data from a larger hospital sample confirm large variations in glycopeptide use, identify hematology-oncology services as a significant prescribing source along with ICUs, and indicate areas of probable overuse of glycopeptide antibiotics. The data may be useful as a benchmark for further focused drug use control interventions.

Anti-Bacterial Agents↗

Chemokine mRNA levels in mononucleated cells of HIV-infected patients before and after initiation of PI- versus NNRTI-containing HAART.

To compare CC chemokine mRNA levels from native peripheral blood mononucleated cells (PBMCs) before and 6 months after the initiation of two different regimens of highly active antiretroviral therapy (HAART), we treated group 1 (n = 11) with two nucleoside analogues and the protease inhibitor (PI) indinavir boosted by ritonavir (800/100 mg b.i.d.); group 2 (n = 8) was treated with the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz instead of PI. CC chemokine mRNA levels (regulated upon T cell activation expressed secreted [RANTES], macrophage inhibitory protein [MIP]-1alpha, MIP-1beta, monocyte chemotactic protein [MCP]-1, MCP-2) were quantified from PBMCs before and 6 months after the initiation of HAART using a reverse transcription/real-time polymerase chain reaction (PCR) assay. The mRNA levels of MCP-1 and MCP-2 were significantly decreased in both groups (P < 0.05), while MIP-1alpha and MIP-1beta were decreased significantly only in the PI-treated group, but not in the NNRTI group. A moderate decrease of RANTES was observed in both treatment groups. The data suggest that HAART regimens containing either NNRTI or PI are not equivalent with regard to modification of CC chemokine mRNA profiles.

Adult↗

Current treatment strategies for patients with Hodgkin's lymphoma and HIV infection.

Hodgkin's lymphoma is the most common non-AIDS-defining tumor diagnosed in HIV-infected patients. Although the introduction of highly active antiretroviral therapy (HAART) led to a decreased incidence of several malignancies among HIV-infected patients, the incidence of HIV-associated Hodgkin's lymphoma (HIV-HL) has been persistent in recent years. Its unusually aggressive tumor behavior includes a higher frequency of unfavorable histologic subtypes, high stage and extranodal involvement by the time of presentation and poor therapeutic outcome, in comparison with Hodgkin's lymphoma outside the HIV setting. Treatment of HIV-HL is challenging considering the underlying immunodeficiency caused by HIV itself and may increase the risk of opportunistic infections by inducing further immunosuppression. To address this delicate vulnerability of the HIV-infected host, tailored regimens, which are less aggressive than standard regimens for HIV-negative hosts, have been applied to achieve tumor control. The introduction of HAART has opened a new perspective in the treatment of HIV-associated malignancies. The improved control of HIV infection and the subsequently improved survival rates of HIV-infected patients has changed the goal from tumor control to cure and new treatment approaches with more potent regimens need to be evaluated to improve survival and quality of life in HIV-HL.

Anti-HIV Agents↗

Fatal outcome of constrictive pericarditis in rheumatoid arthritis.

This is a report of a 39-year-old patient diagnosed with seropositive rheumatoid arthritis at the age of 17. The patient died 2 years after the onset of extra-articular cardiac symptoms. This case demonstrates the devastating course of progressive constrictive pericarditis under sole medical therapy and emphasizes the importance of early radical pericardectomy to avoid progression of disease and secondary complications with fatal outcome. Further, we discuss risk factors, diagnostic caveats, diagnostic tests and therapy of hemodynamically relevant contrictive pericarditis.

Adult↗