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Biomedical subjects

W Graninger

Publications and source records attributed to W Graninger.

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

Effects of parathyroid hormone and serum calcium on the phenotype and function of mononuclear cells in patients with primary hyperparathyroidism.

BACKGROUND: Several studies have demonstrated specific influence of parathyroid hormone (PTH) on immune parameters, especially on T- and B-cell function, migration of polymorphonuclear leucocytes (PMNLs) and antibody synthesis, in patients with secondary hyperparathyroidism and chronic renal failure and recently also in patients with primary hyperparathyroidism (pHPT). METHODS: We therefore examined 12 patients with pHPT before and 6 months after parathyroidectomy (PTX) and nine sex- and age-matched control subjects to determine the impact of PTH and serum calcium concentrations on several immune parameters, including (a) serum concentrations of immunoglobulins, (b) immunophenotype of peripheral blood lymphocytes, (c) phytohaemagglutinin (PHA)-induced lymphocyte proliferation and (d) monocytic surface marker expression. RESULTS: Serum concentrations of immunoglobulins (IgG, IgA, IgM) were unaffected by elevated serum PTH and calcium levels. T lymphocytes (CD3), B lymphocytes (CD19), NK cells (CD16/56) and monocytes (CD16) revealed a normal distribution and were not different before and after PTX in patients with pHPT when compared with the control group. CD4+ T-helper lymphocytes were significantly elevated pre- and post-operatively in patients with pHPT. The lymphocyte proliferation response to PHA in the highest concentration (12.5 micrograms L-1) tested was significantly suppressed in patients with pHPT preoperatively when compared with the patients post-operatively and the control group. In addition, both CD4+ and CD8+ lymphocytes showed a lower expression of activation markers, interleukin 2 (IL-2) receptor (CD25) and transferrin receptor (CD71), which could be partially restored 6 months after PTX, but did not reach normal values. CONCLUSION: In summary, in contrast to the findings in patients with secondary HPT, pHPT appears to be associated with less alterations of immune functions. Chronically elevated serum PTH and calcium concentrations in patients with pHPT induce a higher percentage of CD4+ helper T lymphocytes and a suppressed lymphocyte response to PHA as well as a reduced expression of activation markers on peripheral blood lymphocytes.

Adult↗
PubMed1998

Austrian national survey of prevalence of antimicrobial resistance among clinical isolates of Streptococcus pneumoniae 1994-96.

The antimicrobial susceptibilities of 1385 clinical isolates of Streptococcus pneumoniae obtained from 25 laboratories across Austria between December 1994 and January 1996 were tested. Minimal inhibitory concentration (MIC) values were determined in tests with penicillin, amoxycillin, amoxycillin/clavulanate, ceftriaxone, cefodizime, cefpirome, cefotaxime, cefpodoxime, cefadroxile, azithromycin, clarithromycin, josamycin and roxithromycin by the agar-dilution method. A total of 40 isolates (2.9%) demonstrated intermediate resistance (MIC 0.125-1 microg/ml) and 28 isolates (2.0%) had high-level resistance (MIC > or = 2 microg/ml) to penicillin. Excepting cefadroxil, with an MIC90 of 2 microg/ml, all other tested beta-lactams had MIC90s of 0.03-0.06 microg/ml. Penicillin-resistant strains were much more likely to be also resistant to the other beta-lactams. The macrolides proved to be very active compounds against pneumococci with MIC90s of 0.06 microg/ml (clarithromycin) and 0.25 microg/ml (all other macrolides). Regional differences within Austria with regard to antimicrobial resistance were not observed.

Anti-Bacterial Agents↗
PubMed1998

In-vitro selection of resistance to vancomycin and teicoplanin in Enterococcus faecium and Enterococcus faecalis compared with Staphylococcus epidermidis.

Clinical isolates of Enterococcus faecium, Enterococcus faecalis and Staphylococcus epidermidis were studied for their ability to develop resistance by two selection methods, one in broth and one on agar. The MICs for enterococci after exposure to vancomycin ranged from 0.5 mg/L to 4 mg/L, and those after exposure to teicoplanin ranged from 0.25 mg/L to 1 mg/L. No significant increases occurred for E. faecalis, whilst two isolates of E. faecium showed increases of up to eight-fold (from 0.125 mg/L to 1 mg/L). Vancomycin MICs ranged from 1 mg/L to 4 mg/L and teicoplanin MICs reached 32 mg/L for S. epidermidis. Pulsed-field gel electrophoresis analysis of SmaI-digested whole chromosomal DNA was performed to compare the genomic DNA of glycopeptide-exposed and wild-type strains. In-vitro exposure to vancomycin did not alter MICs significantly except in one S. epidermidis isolate for which the MIC reached 4 mg/L, whereas the teicoplanin-exposed cultures of S. epidermidis showed increases of up to 64 times the original MIC. Comparable results were achieved with the two selection methods.

Anti-Bacterial Agents↗
PubMed1998

Endothelial cell compatibility of glycopeptide antibiotics for intravenous use.

The use of human venous endothelial cells for testing antibiotic solutions for intravenous compatibility provides a valuable alternative to animal models. In order to evaluate the effect of vancomycin and teicoplanin on the viability of human umbilical venous endothelial cells, intracellular ATP levels were measured by a luciferin-luciferase assay. Prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined by direct radioimmunoassay. Vancomycin at concentrations of 5 and 10 mg/mL reduced the intracellular ATP content by 18.7% and 69.9%, respectively, within 60 min. In contrast, cellular energy charge remained significantly higher after incubation with teicoplanin at 5 and 10 mg/mL (reduction 8.7% and 15.5%, respectively). Neither vancomycin nor teicoplanin at a concentration of 2 mg/mL led to significant ATP decline. However, endothelial cells incubated with vancomycin resulted in significantly lower release of PGI2 and TXA2 compared with teicoplanin. These results show that teicoplanin is more compatible with endothelial cells than vancomycin, and that both antibiotics are well tolerated if diluted to a final concentration of 2 mg/mL.

Adenosine Triphosphate↗
PubMed1998

Benefit of 6 months long-term physical training in polymyositis/dermatomyositis patients.

OBJECTIVE: The benefit of long-term physical training in patients with chronic polymyositis or dermatomyositis (PM/DM) was studied prospectively. METHODS: Eight patients with chronic PM/DM participated in a training programme for 6 months. A group of five PM/DM patients without any physical training was observed for control purposes. RESULTS: While there was no significant change in serum creatine phosphokinase (CPK) levels, the 'activities of daily living (ADL)' score improved significantly (P < 0.03), peak isometric torque (PIT) generated by muscle groups in the lower extremities rose significantly (P < 0.03) and there was a statistically highly significant increase in peak oxygen uptake (VO2max) relative to body weight (P < 0.02) due to the long-term training. The patients improved their aerobic capacity by 28%, which is clinically significant. In the untrained patients, no improvement in these target parameters was observed. CONCLUSION: In clinically stable DM/PM patients, long-term physical training can safely be performed and is recommended as part of a comprehensive rehabilitation management, particularly in view of the cardiopulmonary risk in these patients.

Activities of Daily Living↗
PubMed1998

Improvement of physical fitness and muscle strength in polymyositis/dermatomyositis patients by a training programme.

In the present investigation, the benefit of physical training in patients with inflammatory myopathy was studied. In this prospective, randomized, controlled study, 14 patients with polymyositis (PM) or dermatomyositis (DM) were investigated. The training, consisting of bicycle exercise and step aerobics, took place over a 6 week period. Baseline and endpoint measurements included an 'activities of daily living' (ADL) score, peak isometric torque (PIT) generated by muscle groups in the lower extremities, peak oxygen consumption (VO2max), and creatine phosphokinase (CPK) levels. There was no significant rise in disease activity in the training group in comparison to the controls. The ADL score for the treatment group, in comparison to the control group, improved (P < 0.02), PIT rose (P < 0.05) and there was a statistically significant increase in oxygen uptake relative to body weight (P < 0.05). No rise in inflammatory activity, but significant improvement in muscle strength, oxygen uptake and well-being, were found in patients with inflammatory myopathy as a result of physical training. Besides medication, a physical training programme consisting mainly of concentric muscle contractions should therefore be an integral part of therapy, particularly in view of the cardiopulmonary risk of these patients.

Adult↗
PubMed1998

Reciprocal regulation of Th1- and Th2-cytokine-producing T cells during clearance of parasitemia in Plasmodium falciparum malaria.

Flow cytometry for the intracellular detection of T-cell cytokines was performed for 15 Gabonese patients during acute uncomplicated Plasmodium falciparum malaria. A striking expansion of CD4(+) and CD8(+) T cells producing gamma interferon (IFN-gamma) was found during drug-induced clearance of parasitemia, paralleled by a decrease of interleukin-2 (IL-2) production. The frequency of IL-4- and IL-13-producing CD4(+) cells gradually decreased, whereas the frequency of T cells producing IL-2(+)-IFN-gamma+, IL-4(-)-IL-5(+), and IL-4(+)-IL-5(+) cytokines as well as IL-4(+)-IFN-gamma+ and IL-13(+)-IFN-gamma+ cytokines was not significantly altered. The capacity for IL-10 production within the CD4(+) subset increased due to an expansion of both IL-10(+)-IFN-gamma- and IL-10(+)-IFN-gamma+ cytokine-expressing cells. Thus, a more pronounced Th2-driven immune response during acute untreated P. falciparum infection with a shift towards Th1 responsiveness induced by parasite clearance is suggested.

Acute Disease↗
PubMed1998

Effect of pentoxifylline on cytokine patterns in the therapy of complicated Plasmodium falciparum malaria.

The effect of pentoxifylline (PTX) was tested for its capacity to modulate cytokine responses during therapy of severe Plasmodium falciparum malaria in a placebo-controlled, randomized study in 45 adult patients in Bangkok, Thailand. The patients received standard antimalarial treatment with artesunate (120 mg intravenously given immediately, then 60 mg every 12 hr for a total dose of 600 mg). The patients received either low-dose PTX (20 mg/kg/day, n = 15), high-dose PTX (40 mg/kg/day, n = 15), or placebo (n = 15) as continuous infusion for the first three days of antimalarial treatment. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were markedly elevated in all patients prior to treatment. After 6 hr of high-dose PTX treatment, TNF and IL-6 levels significantly decreased while an increase in TNF and IL-6 levels was seen after 6 hr of low-dose PTX or placebo treatment (P < 0.01). After 12 and 24 hr of high-dose PTX infusion, TNF-receptor plasma concentrations were lower than in low-dose PTX- or placebo-treated patients (P < 0.01), whereas no differences between the groups with regard to IL-6 receptor levels were observed. We conclude that 40 mg/kg/day of PTX reduces plasma levels of TNF, IL-6, and TNF-receptor in patients with severe malaria. Whether this reduction improves clinical outcome remains to be determined.

Antimalarials↗
PubMed1998

Pentoxifylline as an ancillary treatment for severe falciparum malaria in Thailand.

Pentoxifylline, an inhibitor of tumor necrosis factor, has been evaluated as an antimalarial agent in combination with artesunate in 45 patients with severe falciparum malaria. Patients were admitted to the intensive care unit at the Hospital for Tropical Diseases in Bangkok, Thailand, and randomly assigned to treatment for 72 hr with a combination of intravenously administered artesunate and 1) placebo, 2) low-dose pentoxifylline (0.83 mg/kg/hr), or 3) high-dose pentoxifylline (1.67 mg/kg/hr). All 45 patients had one or more manifestations of severe malaria such as cerebral malaria (n = 18), renal failure requiring hemodialysis (n = 9), azotemia (n = 8), jaundice (n = 25), or hyperparasitemia (n = 30). The overall severity was comparable in the three groups. Clinical outcome was assessed with respect to the parasite clearance time and the fever clearance time in all patients. In addition, a number of subsidiary outcome variables were examined in specific subgroups, including the recovery time from coma for patients with cerebral malaria, the duration of intubation in patients with respiratory distress, the number of hemodialysis treatments needed for patients with acute renal failure, and the number of units of blood administered to patients requiring transfusion. Concentrations of tumor necrosis factor were reduced in all three groups at 48 hr after treatment. No significant differences among the three treatment groups were found for any of the outcome variables examined. We conclude that the addition of pentoxifylline to artesunate therapy for severe malaria produced no evident clinical benefit.

Adolescent↗
PubMed1998

Short report: total serum levels of the nitric oxide derivatives nitrite/nitrate during microfilarial clearance in human filarial disease.

Nitric oxide (NO) has recently been shown to be cytotoxic to both microfilariae and adult Brugia malayi in vitro and in a murine model, as well against Onchocerca lienalis microfilariae in vitro. We studied the kinetics of nitrite/nitrate, both stable end products of NO, by high-pressure liquid chromatography during microfilaricidal chemotherapy in four filariasis (three Loa loa, and one Onchocerca volvulus) patients. High serum levels of nitrite/nitrate were released during microfilarial clearance and sustained elevated levels were observed six months after chemotherapy, suggesting a role of NO in the elimination of microfilariae in human filariasis.

Adult↗
PubMed1997

Renal tolerability of four different once-daily dose regimen of netilmicin in critical care patients.

A prospective, randomized trial was conducted in a medical intensive care unit to assess safety and tolerability of four different dose regimens of intravenous netilmicin given once daily in the treatment of febrile episodes in critically ill patients. Eighty patients with febrile episodes during their stay in the intensive care unit were included in the study. The patients were randomized into four groups: Group 1 received a single daily dose of netilmicin based upon weight, age and renal function according to a dosage nomogram [13] (mean dose 298 +/- 29 mg, median 300 mg, range 250-350 mg), group 2 received 150% of this standard dose (mean 418 +/- 45 mg, median 400 mg, range 350-500 mg), group 3 200% (mean 525 +/- 41 mg, median 500 mg, range 400-550 mg) and group 4 250% (mean 710 +/- 39 mg, median 650 mg, range 600-750 mg). Duration of treatment was six days. Positive cultures were obtained in 29 patients. Serum creatinine and creatinine clearance, as well as netilmicin trough levels and levels of alpha 1-microglobulin showed no significant difference between the groups before, during, and after therapy. Our results indicate that with once daily dosing even high doses of netilmicin are well tolerated in patients with a creatinine clearance of > 70 ml/min before therapy. Necessary precautions include monitoring of drug trough levels (< 1 mg/L) and maintenance of adequate volume status.

Acute Kidney Injury↗
PubMed1997

Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria.

BACKGROUND: Routine antipyretic therapy in children with infectious diseases has long been the source of controversy. Each year, in addition to antimalarial medication, millions of children with Plasmodium falciparum malaria receive paracetamol to reduce fever. However, the usefulness of this practice has not been proven. METHODS: In a randomised trial in Lambaréné, Gabon, 50 children with P falciparum malaria were treated with intravenous quinine, and received either mechanical antipyresis alone, or in combination with paracetamol. Rectal body temperature and parasitaemia were recorded every 6 h for 4 days. Plasma concentrations and inducible concentrations of tumour necrosis factor (TNF) and interleukin-6 were measured every 24 h. In addition, production of oxygen radicals was measured in both groups. FINDINGS: The mean fever clearance time was 32 h for children treated with paracetamol and 43 h for those who received mechanical antipyresis alone; however, this 11 h difference was not significant (95% CI -2 to 24 h; p = 0.176). Parasite clearance time was significantly prolonged in patients who received paracetamol with a difference of 16 h (8-24 h; p = 0.004). Plasma concentrations of TNF and interleukin-6 were similar in both groups during the study. However, the induced concentrations of TNF, and the production of oxygen radicals, were significantly lower in children treated with paracetamol than those who received mechanical antipyresis alone. INTERPRETATION: These data suggest that paracetamol has no antipyretic benefits over mechanical antipyresis alone in P falciparum malaria. Moreover, paracetamol prolongs parasite clearance time, possibly by decreased production of TNF and oxygen radicals.

Acetaminophen↗
PubMed1997

Single-dose pharmacokinetics of teicoplanin during hemodialysis therapy using high-flux polysulfone membranes.

Teicoplanin is a new glycopeptide antibiotic with potent activity against Gram-positive bacteria. It has been considered to be non-dialyzable due to its high molecular weight (1875-1891 d) and high protein binding (89%). Therefore, a reduced dose was recommended for patients on hemodialysis therapy, with the loading dose being followed by a considerably lower maintenance dose and/or extension of the interval between doses. The present study was performed to evaluate the pharmacokinetics of teicoplanin during hemodialysis therapy using high flux membranes. The pharmacokinetic parameters of teicoplanin were studied in 15 patients with chronic renal failure on hemodialysis. A high flux polysulfone membrane (ultrafiltration coefficient of 40 ml/h/mmHg) was used. Teicoplanin was administered at a dosage of 10 mg.kg-1 body weight in 100 ml isotonic saline solution during the first 10 minutes of hemodialysis therapy. Pharmacokinetic analysis was performed using a three compartment analysis. After a single dose of teicoplanin plasma peak levels were 26.4 +/- 12.0 micrograms/mL (mean +/- SD) after 30 minutes. Teicoplanin concentrations rapidly declined to a nadir of 6.1 +/- 2.5 micrograms/mL at the end of the 3.5-hour session dialysis. Extracorporeal clearance was 39.7 +/- 24.5 mL/min. Removal of 19.3 +/- 7.7% of the drug was estimated if infused during hemodialysis. T 1/2 alpha were 0.37 +/- 0.25 hrs, t 1/2 beta 20.1 +/- 7.1 hrs, and t 1/2 gamma 549.7 +/- 210.5 hrs. We conclude that teicoplanin levels are reduced to a subtherapeutic range during one single high-flux dialysis session if the drug is administered during hemodialysis. Thus, in contrast to previous suggestions relevant amounts of teicoplanin are removed during hemodialysis and thus teicoplanin cannot be viewed as non-dialyzable drug. We recommend obligatory drug monitoring to achieve therapeutic plasma concentrations.

Adult↗
PubMed1997

Salmon calcitonin and calcium in the treatment of male osteoporosis: the effect on bone mineral density.

OBJECTIVE: To assess the effectiveness of salmon calcitonin in the therapy of male osteoporosis. METHODS: Nine male patients aged 20-73 years with vertebral osteoporosis were included in this study. Patients were prescribed 100 units of salmon calcitonin injected subcutaneously three times per week over a period of three months, followed by three months without salmon calcitonin treatment. Thereafter the patients received another salmon calcitonin cycle for three months as described above. All men received calcium supplementation of 1000 mg/day throughout the study period of 12 months. Bone mineral density of the lumbar spine and at the hip was measured at the beginning and the end of the treatment period using DXA (n = 7) or QCT (n = 2). RESULTS: Baseline evaluation revealed a bone mineral density of the lumbar spine of 0.78 +/- 0.09 g/cm2 and 0.62 +/- 0.09 g/cm2 at the hip. Treatment with salmon calcitonin resulted in a significant increase of vertebral bone mineral density to 0.80 +/- 0.09 g/cm2 (p < 0.015). Femoral bone mineral density also significantly increased after salmon calcitonin therapy to 0.64 +/- 0.11 g/cm2 (p < 0.05). CONCLUSION: These results show that calcium and salmon calcitonin increase bone mineral density in male patients with osteoporosis. Calcium and calcitonin may be useful in the treatment of male osteoporosis; however, further studies are necessary before definite recommendations can be made.

Adult↗
PubMed1997

Complement activation in severe Plasmodium falciparum malaria.

We determined indices of plasma complement activation (C3, C4, Bb, C4d, iC3b, and SC5b-9), levels of tumor necrosis factor (TNF) and interleukin-6, and the APACHE II score in 23 patients with complicated Plasmodium falciparum malaria. On admission, plasma concentrations of Bb, SC5b-9, and C4d were markedly increased compared to healthy control subjects (n = 24) (4.5 +/- 1.9 vs 1.5 +/- 0.6 mg/L; 1125.7 +/- 496.9 vs 183.2 +/- 76.5 microg/L; and 15.7 +/- 5.7 vs 7.2 +/- 1.4 mg/L, P < 0.01 for all). In contrast C3 and iC3b concentrations were decreased (631.4 +/- 247 vs 947.3 +/- 243.2 and 105 +/- 17.9 vs 151.3 +/- 14.5 mg/L; P < 0.01 for both). Plasma C4 concentrations in malaria were not different from normal controls. Plasma Bb, C3, and iC3b levels normalized on day 7 of treatment, whereas SC5b-9 and C4d levels remained elevated. A significant correlation between elevated TNF levels and Bb (r = 0.507) and SC5b-9 (r = 0.448, P < 0.01 for both) and a negative correlation between iC3b and SC5b-9 and TNF levels existed (r = -0.537 and r = -0.466, P < 0.01 for both). In addition, a significant correlation between C3 and iC3b (r = 0.689) and C4 and C4d (r = 0.737) existed. However, no relation between clinical disease severity and complement fragments existed. The results demonstrate that both the classical and the alternative pathways of the complement system are profoundly activated in complicated malaria.

Adult↗