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Biomedical subjects

W Graninger

Publications and source records attributed to W Graninger.

At least 55 records · Page 3Linked to original sources
PubMed2000

Stimulatory effects of cartilage-derived morphogenetic proteins 1 and 2 on osteogenic differentiation of bone marrow stromal cells.

Cartilage-derived morphogenetic proteins 1 and 2 (CDMP-1 and CDMP-2) are members of the bone morphogenetic protein (BMP) family which play an important role in embryonic skeletal development. Throughout adult life, bone marrow-derived precursor cells maintain their ability to differentiate into osteoblasts in response to local growth factors. This study examines the osteogenic potential of CDMP-1, CDMP-2, BMP-6 and osteogenic protein 1 (OP-1) in bone marrow stromal cells (BMSC) and investigates the endogenous expression of CDMPs/BMPs and their respective activin receptor-like kinase (ALK) receptors. A 4-day exposure of BMSC to CDMP-1, CDMP-2, BMP-6, and OP-1 under serum-free conditions stimulated the progression of the osteogenic lineage in a dose-dependent manner as evaluated by alkaline phosphatase activity and osteocalcin synthesis. In contrast to the BMPs, CDMP-1 and especially CDMP-2 were significantly less osteogenic, as confirmed by Northern blot analysis. Moreover, BMSC were shown to express endogenously CDMP-2, BMP-2 to -6 and ALK-1, -2, -3, -5 and -6. Phenotypic characterization of BMSC by RT-PCR showed transcripts of the fat marker adipsin and the prechondrocytic marker procollagen type IIA; however, we were unable to detect the mature cartilage markers, procollagen type IIB and aggrecan, even after growth factor treatment. Our data indicate that CDMP-1, CDMP-2, BMP-6 and OP-1 enhance the osteogenic phenotype in BMSC, with CDMPs being clearly less osteogenic than BMPs. The endogenous expression of a variety of CDMPs/BMPs and their respective ALK receptors, suggests a possible involvement of these growth factors in the osteogenic differentiation of bone marrow progenitor cells.

Activin Receptors↗
PubMed2000

In vitro diffusion of mitomycin-C into human sclera after episcleral application: impact of diffusion time.

The purpose of this study was to investigate the impact of different diffusion times of mitomycin-C (MMC) on the intrascleral concentration vs depth profile of MMC in an experimental model. Scleral quadrants of eight human donor eyes were exposed to sponges soaked with MMC for an application time of 1 min. After irrigation with 40 ml saline, we allowed further diffusion of MMC in the sclera for 1, 5, 14 and 29 min until the specimens were further processed. A central 8 mm diameter scleral disk was horizontally dissected with a kryotome at -20 degrees C. MMC concentrations of six layers of 140 microm thickness were analysed by means of high-performance liquid chromatography. The MMC concentrations (microg g(-1)) of layer 1 were: 13.45+/- 5.9 (mean +/- S.D. at 2 min diffusion time), 7.6+/-2.5 (6 min diffusion), 5.6+/-3.1 (15 min diffusion) and 3.6+/-1.7 (30 min diffusion). The corresponding MMC concentrations of layer 6 were: 0.61+/-0.48, 1.47 +/-0.66, 1.83+/-0.42 and 2.98+/-0.97 microg g(-1). The superficial concentration of intrascleral MMC decreased with increasing diffusion time, the deep concentrations increased. After 30 min of diffusion time, equal concentrations of MMC were found in all layers. Even with current low-dose application regimens of MMC the concentrations in the inner side of the sclera rapidly increase beyond the limits of the therapeutic range. Owing to this fast diffusion of MMC, the only means of reducing ciliary body concentrations of MMC is to reduce the dose.

Administration, Topical↗
PubMed2000

Aerobic capacity in adult dermatomyositis/polymyositis patients and healthy controls.

OBJECTIVE: Assessment of myositis patients has relied on symptoms, strength testing, and serum muscle enzyme activity. Recently, functional assessments and evaluation of strength by dynamometry and of disease activity by magnetic resonance imaging have also been added. Aerobic testing in selected patients has been considered useful. DESIGN: Case-control study. SETTING: University Hospital, Vienna, Austria. PATIENTS: Twenty-two subjects (8 outpatients with chronic dermatomyositis and 3 outpatients with chronic polymyositis, and 11 healthy controls) participated, allowing the identification of 11 case-control pairs matched by age (+/-3 years) and gender (mean age, 48+/-14 yrs; ratio of women to men, 18/4). MAIN OUTCOME MEASURES: Target parameters were peak oxygen uptake (peak VO2) to estimate aerobic exercise capacity and peak isometric torque for muscle strength. Creatine phosphokinase (CPK) was measured to assess elevation of muscle enzymes. RESULTS: The mean peak VO2 in patients with dermatomyositis/polymyositis was 15.3 mL/min/kg (SD = 5.8) and in the healthy controls 28.7 mL/min/kg (SD = 7.8). Cardiorespiratory capacity expressed as peak VO2 was thus significantly reduced at 53% (p = .0001) of the control value. Muscle strength expressed as peak isometric torque was significantly lower (p = .01) in patients (mean 148+/-73 Nm) when compared to the control group (mean 261+/-99 Nm). In myositis patients peak VO2 and peak isometric torque correlate well with each other (r = .7631; p = .0001), but not at all with serum CPK levels (r = .056; p = .869). CONCLUSION: Peak VO2 is significantly diminished in patients with dermatomyositis/polymyositis, compared with age- and sex-matched controls. Serum CPK did not significantly correlate with VO2. Aerobic exercise testing may be a useful assessment parameter in selected patients with dermatomyositis/ polymyositis.

Case-Control Studies↗
PubMed2000

Teicoplanin in the treatment of serious infection.

The merits and dosing regimens for teicoplanin in the treatment of endocarditis, bacteremia, bone and joint infections, pediatric use, non in-patient use and in the ICU are discussed. Teicoplanin has several advantages over vancomycin in the treatment of serious infections: long half-life, lower nephrotoxicity, and lack of requirement for serum assays. The recommended regimen for teicoplanin is three loading doses of 6 mg/kg (400 mg) q12h, then 6 mg/kg (400 mg) q24h. There is no significant difference in efficacy between teicoplanin and vancomycin when at least 6 mg/kg teicoplanin is used or, in the case of staphylococcal endocarditis, it is given in combination with another antimicrobial. Teicoplanin is effective and safe in staphylococcal infections including endocarditis, osteomyelitis and septic arthritis. The once daily or alternate daily dosage allows home administration of treatment of infections caused by Staphylococcus aureus, including methicillin-resistant strains and enterococci with appreciable savings in hospital costs and improvement in the quality of life.

Anti-Bacterial Agents↗
PubMed2000

Ventricular cerebrospinal fluid and serum concentrations of sTNFR-I, IL-1ra, and IL-6 after aneurysmal subarachnoid hemorrhage.

Postsubarachnoid hemorrhage, systemic inflammatory response syndrome and associated organ system failure are more frequently found in patients in poor neurologic condition. Since subarachnoid hemorrhage causes a profound intrathecal inflammatory response with production of proinflammatory cytokines TNFalpha, IL-1beta, and IL-6, a possible explanation for this association is that brain-derived cytokines may enter the systemic circulation in the presence of postsubarachnoid hemorrhage blood brain barrier disruption to systemically activate inflammatory cascades and thereby contribute to the development of postsubarachnoid hemorrhage systemic inflammatory response syndrome and extracerebral organ system failures. In 44 patients with aneurysmal subarachnoid hemorrhage admitted within 3 days of the initial bleed, extracerebral organ system functions were assessed individually and in aggregate using the modified Multiple Organ Dysfunction Score. Serum and cerebrospinal fluid concentrations of soluble tumor necrosis factor-alpha receptor-I, interleukin-1beta receptor antagonist, and IL-6 were determined during the first 2 weeks after subarachnoid hemorrhage and tested for correlation with (1) admission Hunt-Hess grade, (2) development of systemic inflammatory response syndrome and extracerebral organ system failures, and (3) neurologic outcome. The development of postsubarachnoid hemorrhage systemic inflammatory response syndrome and extracerebral organ system failures was paralleled by a significant increase in serum but not in cerebrospinal fluid levels of soluble tumor necrosis factor-alpha receptor-I and IL-1ra, that is, patients with and without extracerebral organ system failures did not differ in pattern and time course of cerebrospinal fluid cytokine concentrations. In contrast, increasing soluble tumor necrosis factor-alpha receptor-I and interleukin-1beta receptor antagonist serum levels correlated with a higher Multiple Organ Dysfunction score and with individual organ system dysfunctions. Postsubarachnoid hemorrhage, systemic inflammatory response syndrome and extracerebral organ system failures could therefore not be linked to changes in cerebrospinal fluid cytokine concentration profiles.

Adult↗
PubMed2000

National and local antibiotic policies in Central and Eastern Europe.

To assess the antibiotic policies of Central European countries, we performed an overview of antibiotic stewardship, prescription habits and antibiotic prescription regulatory procedures. Since most Central European countries have had centralized health care and drug policies, the situation 10 years after decentralization is surprising. Only 3 of 10 Central European countries have some regulation of prescription of antibiotics, only 4 restrict some antibiotics, only 5 have hospital and only 3 national antibiotic policies. In all but 3 countries physicians can prescribe quinolones and/or 3rd generation oral cephalosporins as first-line antibiotics. Information on local and national antibiotic policies in Central and Eastern European countries is given including prescription guidelines for antibiotic use in community and hospital.

Anti-Bacterial Agents↗
PubMed2000

DNase I induced DNA degradation is inhibited by neomycin.

Preparations of antimicrobials from biotechnological sources containing nucleic acids may serve as vector for the dissemination of resistance genes. An essential prerequisite for the acquisition of a new resistance phenotype in a transformational scenario is the availability of physically intact DNA molecules capable of transforming competent microorganisms. DNA is thought to be an easy target for catabolic processes when present in the natural habitat of bacteria (e.g. gastrointestinal tract, soil) due to the overall presence of nucleolytic enzymes. Aminoglycoside antibiotics are known to display a strong affinity to nucleic acids rendering these compounds to be primary candidates for exerting DNA protective functions in the gastrointestinal tract when applied orally during antibiotic chemotherapy. Using a DNase I protection assay it could be demonstrated that neomycin B at a concentration of 2 mM completely inhibited degradation of plasmid DNA in vitro. No inhibition of degradation was observed with streptomycin and kanamycin and the non-aminoglycoside antibiotics oxytetracycline and ampicillin under identical assay conditions. Thus, neomycin preparations may be able to promote structural integrity of contaminating DNA-fragments in DNase-rich environments.

Ampicillin↗
PubMed2000

Serum concentrations of granulocyte-colony stimulating factor in complicated Plasmodium falciparum malaria.

Involvement of neutrophils in the control of blood parasites in malaria has been reported. Both, mononuclear phagocytes and neutrophils are known to be stimulated by cytokines such as TNF-alpha in order to augment the defence potency against the parasites. Previously, it has been shown that serum-G-CSF concentrations are increased in patients with bacterial sepsis. In vitro studies have shown that P. falciparum - infected erythrocytes induce the release of G-CSF by several cells such as endothelial cells and monocytes, however, nothing is known about G-CSF serum concentrations during the clinical course of severe P. falciparum malaria. Thus, it was the aim of the present study to investigate the time course for G-CSF serum concentrations in patients with complicated P. falciparum malaria, and to correlate these values with other mediators of inflammation and hematopoesis. Twenty-six patients suffering from complicated P. falciparum malaria were included in the study, and 20, age and sex matched, healthy volunteers were used as the negative control group. Serum samples for determination of G-CSF were taken on day 0, 7 and 14, and measured by ELISA. We found significantly increased serum concentrations of G-CSF in patients with complicated P. falciparum malaria on day 0, values decreasing to within the normal range by day 7. A significant correlation was found between G-CSF (d0) and procalcitonin, the parasite count, erythropoietin and macrophage inflammatory protein, however no correlation could be shown for the neutrophil count. In conclusion, on the day of hospital admission, elevated serum concentrations of G-CSF were detected in patients with complicated P. falciparum malaria, which might indicate a role of G-CSF in the acute defence mechanism against the parasites.

Adolescent↗
PubMed2000

[Reciprocal modification of Fas activation and stress protein response decides apoptosis or resistance development of cells].

Activation of heat shock factor (HSF)-1 DNA binding and heat shock protein (hsp)-70 expression enable resistance of cells to various forms of stress and maintain cell survival. Fas, a membrane-bound protein, is a central pro-apoptotic factor. Its activation leads to a cascade of events resulting in programmed cell death. Herein, these two mechanisms with contrary functions, promoting either cell survival or death, were addressed for their potential to inhibit each other's activation. Induction of Fas-mediated signalling was followed by a rapid decrease of HSF1 DNA binding and inducible hsp70 expression. Inhibition of HSF1 DNA binding was demonstrated to be based on absent hyperphosphorylation of HSF1 during FAS-signalling. These effects of Fas-activation on the HSF1/hsp70 stress response were blocked by ICE (caspase 1)-inhibitors, suggesting an ICE-mediated process. Furthermore, inhibition of HSF1/hsp70 was accompanied by an increase of apoptosis rates from 20% to 50% in response to heat stress. When analyzing Fas-mediated apoptosis in the presence of HSF1/hsp70 activation, decreased apoptosis rates were detected with induced expression of hsp70 but not with activation of HSF1-DNA binding alone. Thus, we conclude that inhibition of the HSF1/hsp70 stress response during Fas-mediated apoptosis and vice versa may facilitate a cell to pass a previously chosen pathway, stress resistance or apoptosis.

Animals↗
PubMed1999

Intestinal tuberculosis presenting as fever of unknown origin in a heart transplant patient.

Patients undergoing transplantation have an increased risk of developing infections such as tuberculosis, Pneumocystis carinii pneumonia, Candida infections or cytomegalovirus infections because of their immunosuppressive therapy with cyclosporin A, azathioprine and steroids. Mycobacterial infection is well recognized as a complication in the immunocompromised host but diagnosis and therapy are very difficult.

Antitubercular Agents↗
PubMed1999

Persistent functional and social benefit 5 years after a multidisciplinary arthritis training program.

OBJECTIVE: To assess the sustainable benefits of a professional, multidisciplinary training program for patients with rheumatoid arthritis. DESIGN: Two studies with different observation periods. Study I was a prospective, randomized trial for 1 year. Study II was a noncontrolled observation over 5 years. SETTING: The 9-day program for eight patient groups encompassed a multidisciplinary cooperation between rheumatologists, orthopedists, physicotherapists, psychologists and social workers. PATIENTS: Sixty-eight consecutive patients with rheumatoid arthritis participated in an arthritis training program either immediately after enrollment in the program or after 1 year. INTERVENTIONS: The program covered the following fields: pathogenesis of rheumatoid arthritis, drug therapy, physicotherapy, practical exercise in remedial gymnastics, use of joint protection devices, orthopedic perspectives, psychological counseling, dietetics, information about unproven cures and social assistance. MAIN OUTCOME MEASURES: Clinical outcome was assessed by self-report questionnaires: (1) Stanford Health Assessment Questionnaire, (2) Freiburg Questionnaire of Coping with Illness, (3) Beck Depression Inventory, and (4) a 21-point scale to evaluate cognitive-behavioral and environmental impact. RESULTS: A significant and persistent improvement of all investigated parameters was demonstrated in the 1-year controlled trial. Between the end-point of the 1-year study and the 5-year evaluation, this improvement increased even more for functional status and coping with illness, whereas depression returned to baseline values. These effects were seen even without reinforcement of the training. CONCLUSION: A professional, multidisciplinary approach to educate patients with rheumatoid arthritis leads to a significant and sustained improvement of the clinical outcome and is an approach that should be established as a part of conventional therapy.

Activities of Daily Living↗
PubMed1999

The role of glycopeptide antibiotics in the treatment of infective endocarditis.

There are several sets of guidelines for the treatment of infective endocarditis, reflecting the need for differing treatment in various countries and times. This review considers the need for differing treatment modalities and in particular the utility of the glycopeptide antibiotics vancomycin and teicoplanin. Specific recommendations are offered as to when to consider the use of glycopeptides, appropriate dosage, length of treatment course and whether to use monotherapy or combined therapy. Used judiciously, the glycopeptides give results as good as can be achieved with other antimicrobial agents without exceptional toxicity. The potential of teicoplanin for use in the outpatient treatment of infective endocarditis is considered.

Anti-Bacterial Agents↗
PubMed1999

High serum laminin concentrations in patients with Candida sepsis.

BACKGROUND: Laminin, a major component of the basement membrane, plays a critical role in normal cell adhesion and also during tissue invasion of pathogenic microorganisms. MATERIALS AND METHODS: Serum laminin concentrations were determined in 19 patients with Candida albicans sepsis, in 13 patients with bacterial sepsis and in 20 noninfectious controls. RESULTS: Serum laminin concentrations of both, patients with candidal and bacterial sepsis, were significantly elevated compared to the controls (486 ng mL-1 [155-924], median [range]; P < 0.01). Laminin concentrations were significantly higher in patients with Candida sepsis than in patients with bacterial sepsis on day 1 (2565 ng mL-1 [659-6064] vs. 994 ng mL-1 [386-2064]; P < 0.01), day 7 (1594 ng mL-1 [607-4611] vs. 684 ng mL-1 [284-1920]; P < 0.05) and day 14 (1444 ng mL-1 [202-2131] vs. 386 ng mL-1 [180-1658]; P < 0.05). CONCLUSIONS: Laminin serum concentrations might be useful to differentiate nonbacterial, bacterial and fungal etiology.

APACHE↗
PubMed1999

Frequency of cytokine-producing T cells in patients of different age groups with Plasmodium falciparum malaria.

The frequency of cytokine-producing T cells was assessed in patients of different age groups (29 infants, aged 1-5 years; 30 schoolchildren, aged 6-14 years; 26 adults, aged >15 years) with acute Plasmodium falciparum malaria from Gabon. By using flow cytometry for the intracellular detection of cytokines, a striking expansion was seen, in adults compared with children, of CD4+ and CD8+ T cells with the following profiles of type 1 cytokine production: interleukin (IL)-2-/interferon (IFN)-gamma+, IL-2+/IFN-gamma+, and IL-2+/IFN-gamma-. Patients with hyperparasitemia had a significantly lower frequency of IL-2-/IFN-gamma+ CD4+ cells. Type 2 cytokine expression (IL-4+/IFN-gamma-, IL-13+/IFN-gamma-) and type 0 cytokine expression (IL-4+/IFN-gamma+, IL-13+/IFN-gamma+) were also increased in adults within the CD4+ subset. Frequencies of IL-5+/IL-4+, IL-10+/IFN-gamma-, and IL-10+/IFN-gamma+ cells were similar in all groups. The increased frequency of both type 1 and type 2 cytokine-producing T cells in adults is likely to be of significance in the protection against P. falciparum malaria.

Acute Disease↗
PubMed1999

Penetration and decay of meropenem into the human aqueous humor and vitreous.

The aim of this study was to determine the penetration of intravenously administered meropenem into the human aqueous humor and vitreous. Thirty patients about to undergo cataract surgery and fourteen patients about to undergo vitrectomy received a 2 g dose of meropenem before surgery. Specimens of aqueous humor or vitreous and blood were obtained intraoperatively and analyzed by high performance liquid chromatography (HPLC). The study was designed as a non-randomized prospective trial. Thirty min to 12 hr after administration, mean aqueous humor levels of 13.4 and 1.1 mg/l and vitreous levels between 8.94 and 1.08 mg/l were found, respectively. The peak concentrations are distinctly above the in vitro measured minimum inhibitory concentration of meropenem for 90% (MIC90) of almost all relevant gram-positive and gram-negative organisms, including Pseudomonas aeruginosa and Enterobacteriaceae. With regard to its broad spectrum, high antibacterial activity, and good penetration into ocular fluids, meropenem seems to be an alternative to currently used systemic drugs. Its usefulness in perioperative prophylaxis, as initial therapy after perforating or penetrating injuries, or in the therapy of bacterial endophthalmitis has yet to be proved.

Aqueous Humor↗
PubMed1999

Efficacy of beta-lactam and inhibitor combinations in a diffusion chamber model in rabbits.

Using a diffusion chamber in rabbits, we evaluated therapy with the combination of ceftriaxone plus the beta-lactamase inhibitor tazobactam in comparison with ceftriaxone alone. One sensitive and one resistant strain of Escherichia coli, Enterobacter cloacae and Klebsiella pneumoniae were inoculated into one of the six diffusion chambers, implanted in the same animal. In order to simulate pharmacokinetics in humans, both substances were administered in decreasing doses. Ceftriaxone was given 0, 2, 4 and 6 h after infection in dosages of 45, 35, 25 and 15 mg/kg of body weight, while tazobactam was administered either in one dose at 0 h, or divided into two doses at 0 and 1 h or 0 and 4 h, or divided into three doses at 0, 1 and 4 h after infection. The ratio of ceftriaxone:tazobactam was fixed at 8:1. Ceftriaxone, in combination with tazobactam, given in one dose immediately after infection showed a significant reduction in bacterial count. All other combinations of ceftriaxone and tazobactam did not differ from ceftriaxone in monotherapy. Co-administration of the beta-lactamase inhibitor tazobactam significantly enhanced the activity of ceftriaxone against all three tested species.

Animals↗
PubMed1999

Comparative susceptibility to penicillin and quinolones of 1385 Streptococcus pneumoniae isolates. Austrian Bacterial Surveillance Network.

Antibiotic resistance among Streptococcus pneumoniae isolates has spread rapidly throughout the world since the first description of a strain with diminished susceptibility to penicillin in Australia in 1967. A total of 1385 strains of S. pneumoniae, collected in several centres throughout Austria, were assessed for their sensitivity to moxifloxacin, trovafloxacin, ciprofloxacin, ofloxacin, levofloxacin and lomefloxacin. The MICs were determined using the agar dilution method, according to NCCLS guidelines. Both moxlfloxacin and trovafloxacin showed good anti-pneumococcal activity in terms of MIC50 (both 0.125 mg/L) and MIC90 (both 0.25 mg/L). Less active, but with similar activity to each other, were ciprofloxacin and levofloxacin, each with an MIC50 of 1 mg/L and an MIC90 of 2 mg/L. Ofloxacin showed only moderate activity (MIC50, 1 mg/L; MIC90, 2 mg/L) and lomefloxacin was the least active compound (MIC50, 4 mg/L; MIC90, 8 mg/L). Both moxifloxacin and trovafloxacin at a concentration of < or = 0.5 mg/L inhibited all of the S. pneumoniae strains tested.

Anti-Infective Agents↗