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Biomedical subjects

W Graninger

Publications and source records attributed to W Graninger.

At least 37 records · Page 2Linked to original sources

Effects of ciprofloxacin and ofloxacin on adult human cartilage in vitro.

Chondrocyte toxicity and necrosis were seen with electron microscopy after incubation of human adult cartilage biopsy specimens in ciprofloxacin or ofloxacin. In vitro exposure of chondrocytes to fluoroquinolones did not affect apoptosis as determined by flow cytometry. While the immediate clinical significance of this finding remains unclear, the possibility of long-term cartilage damage after fluoroquinolone treatment cannot be excluded.

Adult

Prospective randomized comparison of cefodizime versus cefuroxime for perioperative prophylaxis in patients undergoing coronary artery bypass grafting.

The effects of cefodizime and cefuroxime on neutrophil phagocytosis and reactive oxygen production in 54 patients undergoing elective coronary artery bypass grafting were studied. Both drugs were administered twice at a dosage of 40 mg/kg of body weight (pre- and intraoperative). Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled Escherichia coli and Staphylococcus aureus by flow cytometry. Reactive oxygen generation after phagocytosis was estimated by determining the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. In both groups the mean phagocytic ability for E. coli and S. aureus decreased during surgery (-21 and -8%, respectively, for the cefodizime group and -39 and -38%, respectively, for the cefuroxime group; P < 0.05 for all). In the cefodizime group a normalization of mean E. coli and S. aureus neutrophil phagocytosis was seen on day 5 (+9 and -4% compared to preoperative values; P > 0.35 for both), whereas in cefuroxime-treated patients phagocytic ability remained depressed (-37 and -31%; P < 0.04 for both). In both groups mean neutrophil reactive oxygen intermediate (ROI) production after E. coli and S. aureus phagocytosis increased during cardiopulmonary bypass (+44 and +83%, respectively, in the cefodizime group and +58 and +73%, respectively, in the cefuroxime group; P < 0.05 for all). One day after surgery E. coli- and S. aureus-driven neutrophil ROI production was not different from the preoperative values (-2 and +12%, respectively, for the cefodizime group and +7 and +15%, respectively, for the cefuroxime group; P > 0.15 for all). Postoperative serum levels of the C-reactive protein on days 2 and 7 were lower in cefodizime-treated patients (19 +/- 6 and 4 +/- 2 mg/liter versus 23 +/- 6 and 11 +/- 5 mg/liter; P < 0.05 for both). In addition to cefodizime's antimicrobial activity during perioperative prophylaxis, its use in coronary artery bypass grafting can prevent procedure-related prolonged postoperative neutrophil phagocytosis impairment.

Aged

Levels of stem cell factor and interleukin-3 in serum in acute Plasmodium falciparum malaria.

The purpose of the present study was to measure serum concentrations of stem cell factor (SCF) and interleukin-3 (IL-3) in patients with acute Plasmodium falciparum malaria. Serum samples from 15 patients were taken on day of admission and days 7, 14, 21, and 28. Anemia developed in 80% of patients. A transient increase in IL-3 could be observed at the beginning of the disease. It remains controversial whether the measured concentrations of IL-3 and SCF correlate with the grade of anemia. The possibly suppressed IL-3 and SCF production may contribute to the prolonged anemia in P. falciparum malaria, as has been shown for erythropoietin.

Adolescent

Cytokine profile and correlation to the APACHE III and MPM II scores in patients with sepsis.

In 35 patients fulfilling the criteria of systemic inflammatory response syndrome (SIRS) of infectious origin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), tumor necrosis factor-soluble receptor (TNF-sR), and interleukin-12 (IL-12), C-reactive protein (CRP) levels and the Acute Physiology, and Chronic Health Evaluation III score (APACHE III) were determined on days 1 to 7, 14, 21, and 28. The Mortality Probability Models (MPM) II sepsis score was assessed at the time of admission into the study. The MPM II sepsis score correlated with IL-6 plasma levels on day 1. The APACHE III scores correlated with plasma levels of TNF-sR on days 2-7, with IL-6 levels on days 3-7, and with CRP levels on days 4-7 (p < 0.01). The MPM II sepsis score, the APACHE III score, and the IL-6, TNF-sR, and CRP levels were significantly different between survivors and nonsurvivors and between patients with and without shock (p < 0.05). A significant decrease of the APACHE III scores, IL-6, and CRP levels was observed over the study period in the survivor group only (p < 0.05), while neither the dynamics of TNF-alpha nor IL-12 plasma levels contributed to the risk estimation of mortality.

APACHE

Management of serious staphylococcal infections in the outpatient setting.

Patients with serious staphylococcal infections, e.g. endocarditis and osteomyelitis, need prompt and prolonged parenteral antibiotic treatment to ensure eradication of the causative pathogen. The major cost in the treatment of these infections is the long period of hospitalisation required for the administration of intravenous antibiotics. To shorten the hospitalisation period, outpatient treatment can be given to some patients. In this study, patients with acute exacerbations of chronic osteomyelitis (n = 44) or endocarditis (n = 10) were treated with intravenous teicoplanin. The pathogens were Staphylococcus aureus (n = 41, 13 of which were methicillin resistant) and coagulase-negative staphylococci (n = 13, one of which was methicillin resistant). After a mean loading dose of 15 mg/kg for 3 to 10 days, patients received teicoplanin 3 times a week at a dose (mean 15 mg/kg) individualised to achieve serum trough concentrations of approximately 10 mg/L for osteomyelitis and 20 mg/L for endocarditis. Treatment duration ranged from 28 to 150 (mean 62) days for patients with osteomyelitis and from 28 to 88 (mean 49) days for patients with endocarditis. 37 (84%) patients with osteomyelitis and 8 (80%) patients with endocarditis were treated successfully. Adverse events were observed in 9 patients and included rash (n = 3), thrombocytopenia (n = 3), and drug fever, pseudomembranous colitis, nausea, leucopenia and transient hearing impairment (one patient each). In conclusion, this study demonstrates that teicoplanin can be administered successfully in an outpatient setting according to a 3-times weekly schedule for the treatment of patients with staphylococcal osteomyelitis and endocarditis.

Adolescent

Endothelial cell compatibility of fluoroquinolone solutions for intravenous use.

One local side-effect closely related to the use of parenteral fluoroquinolones is phlebitis. The occurrence of this phenomenon is largely thought due to the damage of endothelial cells with subsequent inflammation. In order to evaluate the effect of ciprofloxacin, fleroxacin, and ofloxacin on the viability of human umbilical venous endothelial cells (HUVEC), intracellular ATP levels were measured by a luciferin-luciferase assay. Prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined by means of direct radioimmunoassay. Commercially available preparations of ciprofloxacin (2 mg/ml) and fleroxacin (4 mg/ml) reduced the intracellular ATP content by 75.9 +/- 1.9% and 82.1 +/- 0.6%, respectively, within 20 minutes, indicating severe damage of endothelial cells. Incubation with ofloxacin (2 mg/ml) did not have any detrimental effect. All fluoroquinolones were tolerated well by endothelial cells at low concentrations up to 20 micrograms/ml. Concentrations between 100-200 micrograms/ml gradually led to functional alterations such as increased PGI2 release. The tolerance of intravenously applied antibiotics has been tested in animal models. Use of human venous endothelial cells for testing antibiotic solutions for intravenous application provides a valuable alternate model for tolerability.

6-Ketoprostaglandin F1 alpha

Tissue concentration of clindamycin and gentamicin near ischaemic ulcers with transvenous injection in Bier's arterial arrest.

BACKGROUND: In the treatment of patients with inflamed ischaemic ulcers in peripheral arterial occlusive disease, high tissue concentrations of antibiotics (TCA) are important. With local transvenous pressure injection in Biers' arterial arrest (TVA-Bier) higher TCAs are assumed to be obtained but they have not been measured. METHODS: Two groups of 16 patients each with ischaemic foot ulcers were studied. In one group, patients received a mean of 284 (SD 116) mg gentamicin and in the other, 1200 mg clindamycin. The antibiotics were given intravenously, intra-arterially, and by TVA-Bier in a randomised order at intervals of 48 hours. Biopsy samples were taken from the edge of the ulcers 20 minutes and 3 hours after TVA-Bier, and 1 hour and 3 hours after intravenous and intra-arterial injection. At the same times blood samples were taken. FINDINGS: TCAs of gentamicin and clindamycin with TVA-Bier were significantly higher compared with intravenous or intra-arterial injection. Median TCA-enhancing factor of clindamycin achieved by TVA-Bier at 20 min 1 hour was 18.3 and 14.1 versus intravenous and intra-arterial infusion, respectively, and at 3 hours 7.3 and 5.6, respectively. The median TCA-enhancing factor for gentamicin by TVA-Bier versus intravenous and intra-arterial application was, at 1 hour 20 min, 9.4 and 9.7, respectively, and at 3 hours 1.2 and 1.7, respectively. INTERPRETATION: Higher TCAs could be achieved with TVA-Bier than with intravenous or intra-arterial infusion. TCAs were lower when using gentamicin and higher with clindamycin.

Aged

Increased serum concentrations of the carboxy-terminal-cross-linked telopeptide of collagen type I in patients with acute Plasmodium falciparum malaria.

We determined serum levels of the carboxy-terminal-cross-linked telopeptide and carboxy-terminal propeptide of type I collagen (ICTP and PICP) in 24 patients with acute complicated Plasmodium falciparum malaria prior to and 7, 14, 21, and 28 days after therapy by radioimmunoassay in Bangkok, Thailand. Elevated levels of ICTP were observed in patients (mean +/- SD concentration 16.7 +/- 5.8 ng/ml), compared with normal controls (3.1 +/- 1.3 ng/ml), during the acute phase of the disease. In contrast, serum concentrations PICP were not different between patients and controls (168 +/- 63 and 144 +/- 57 ng/ml, respectively). After therapy serum ICTP concentrations decreased but remained elevated even 28 days after the malaria attack (10.3 +/- 2.9 ng/ml). These findings suggest an increased production or release of ICTP in P. falciparum malaria, which could implicate an alteration of extracellular matrix during P. falciparum malaria.

Acute Disease

Increased serum concentration of soluble CD14 is a prognostic marker in gram-positive sepsis.

Increased serum sCD14 concentrations are associated with poor outcome in Gram-negative sepsis and trauma patients. In the present study serum sCD14 concentrations were measured in patients with Gram-positive sepsis and compared with Gram-negative septic and nonseptic intensive care unit patients. Furthermore, serum sCD14 concentration was correlated with patient's outcome. Serum samples of 28 Gram-positive (8 nonsurvivors/20 survivors) and 10 Gram-negative bacteriemic patients (3 nonsurvivors/7 survivors) were obtained at the day they met the sepsis criteria defined by Bone et al. (Day 0) and at Days 4 and 7 and compared with 10 nonseptic ICU patients and 10 healthy volunteers. Serum concentrations of sCD14 were measured by ELISA. Significantly higher sCD14 serum concentrations were found on Days 4 and 7 in Gram-positive nonsurvivors than in Gram-positive survivors (Day 4: 5.85 +/- 0.48 vs 4.07 +/- 0.43 microgram/ml, P < 0.05; Day 7: 6.12 +/- 0.46 vs 3.53 +/- 0.33 microgram/ml, P < 0.01). In addition, sCD14 concentrations of Gram-positive nonsurvivors were significantly higher than those of nonseptic ICU patients and healthy volunteers at any time of observation. However, no significant difference was calculated between Gram-positive and Gram-negative patients. Summarizing our results, the serum level of sCD14 could be proven to be a good prognostic marker in the course of Gram-positive sepsis. Increased levels are associated with a high mortality.

Adult

Serum laminin and basic fibroblast growth factor concentrations in patients with complicated Plasmodium falciparum malaria.

Serum concentrations of laminin and basic fibroblast growth factor (FGF) were measured in 20 patients suffering from complicated Plasmodium falciparum malaria in Bangkok. Significant higher mean serum concentrations of laminin were determined prior to treatment (1973 ng/ml) and 7 days after starting medication (1025 ng/ml) in comparison to the control (412 ng/ml). The values remained numerically higher for at least 21 days. With regard to serum basic FGF concentrations, a peak was found 7 day after starting treatment (35.61 pg/ml). In addition, a significant correlation was found for parasite clearance time and basic FGF concentration on day 7 (P < 0.01). These increased values of laminin and basic FGF may be the consequence of endothelial and basement membrane damage induced by sequestration of the parasites. Furthermore, basic FGF might play a role in endothelial repair mechanisms after the clearance of the parasites.

Adolescent

Influence of pentoxifylline on cytokine levels and inflammatory parameters in septic shock.

OBJECTIVE: To evaluate the influence of pentoxifylline (PTX), a phosphodiesterase inhibitor, on cytokines and inflammatory proteins in patients suffering from septic shock. DESIGN: Prospective study comparing a therapy group to a matched control group. SETTING: Medical intensive care unit at a university hospital. PATIENTS: Twenty four patients fulfilling the criteria of septic shock were included in this study. Twelve patients received PTX (therapy group) and 12 patients matched for diagnosis, age and gender served as the control group. INTERVENTIONS: Pentoxifylline at 1 mg/kg per hour over 24 h in the therapy group. MEASUREMENTS AND RESULTS: Cytokine levels [tumor necrosis factor-alpha (TNF)], soluble TNF receptor [TNF-R], and interleukin-6 [IL-6] and inflammatory proteins [C-reactive protein, alpha-1-antitrypsin (AAT), fibronectin, and haptoglobin], as well as hemodynamic parameters and the APACHE III score were evaluated before initiation of therapy and 24 h-later. After 24 h, TNF levels were significantly lower in the therapy group (p = 0.013), while IL-6 levels were significantly higher in the therapy group (p = 0.030). Within the 24 h TNF declined significantly in the therapy group (p = 0.006), while IL-6 showed a significant increase (p = 0.043). AAT and the APACHE III score tended to differ significantly after 24 h between the groups [AAT levels higher in the therapy group (p = 0.05), APACHE III score lower (p = 0.05)]. In the therapy group, the systemic vascular resistance index was significantly higher after 24 h (p = 0.0026) whereas the cardiac index declined (p = 0.035). CONCLUSIONS: PTX does influence TNF levels in septic shock patients. Nevertheless, inhibiting a single mediator in severe septic shock cannot stop the inflammatory overreaction.

APACHE

[MRI and ultrasound in rheumatology].

Technical innovations and software improvements in magnetic resonance imaging (MRI) and high-resolution sonography (US) have definitely influenced the diagnostic imaging of rheumatic diseases. For MRI, improvements in surface coils, dedicated low-field systems (0.2 T), and software improvements (shorter acquisition times and refinements of fat suppressing techniques) must be mentioned. For sonography, the main innovations concern the development of higher transducer frequencies (7-15 Mhz) and power Doppler imaging. Clinical evaluations have shown that MRI and US are most useful in cases of suspected rheumatic disease with negative plain film radiographs and for documenting the course of the disease, diagnosing of early rheumatoid arthritis, making a differential diagnosis in clinically unclear rheumatic diseases, investigating vascularization, and quantifying pannus formation. In order to improve diagnostic efficacy the role of MRI and US in the management of patients with rheumatic disease should be reconsidered.

Arthritis, Rheumatoid

[Primary chronic polyarthritis of the knee joint].

Rheumatoid arthritis is a chronic, multisystemic disease. The characteristic feature is persistent inflammatory synovitis. The knee joint is commonly involved with synovial hypertrophy, chronic effusion, and frequently ligamentous laxity. Pain and swelling behind the knee may be caused by extension of inflamed synovium into the popliteal space (Baker's cyst). Plain radiographs of the knee joint remain the basic radiological procedure, although early in the disease they might not provide significant changes. Sonography sufficiently reveals synovial fluid and Baker cysts, but cannot be recommended for evaluation of synovial proliferations or pannus formation. Computer tomography has only limited indications and may be used for the evaluation of subtle erosive lesions or the quantitation of osteoporotic changes. Magnetic resonance imaging has shown excellent visualization of cartilage, fluid, synovium and soft tissues and is the method of choice for the demonstration of early affection and the evaluation of pannus activity and therapy control. With administration of contrast agents (gadolinium), dynamic studies may demonstrate inflammatory activity. Modern MR sequences, such as T1 SE "fat sat" or magnetization transfer, further improve the discrimination of cartilage, pannus and synovial fluid.

Arthritis, Rheumatoid

Multiple-dose pharmacokinetics of cefpirome in long-term hemodialysis with high-flux membranes.

Cefpirome is a cephalosporin eliminated primarily by kidneys that requires dosage reduction in patients with renal failure. The pharmacokinetic parameters were studied in 10 patients with end-stage renal disease who were receiving hemodialysis. Repeated intravenous administration of 2 gm cefpirome three times a week resulted in trough levels of 12.2 +/- 5.4 micrograms/ml and peak serum concentrations of 99.6 +/- 82.1 micrograms/ml. After 3 1/2 hours of hemodialysis with polysulfone high-flux membranes, 62.3% +/- 23.3% of cefpirome was removed. The interdialytic half-life was 9.35 +/- 0.99 hours, and the intradialytic half-life was 2.02 +/- 0.7 hours.

Adult

Elevated levels of soluble CD14 in serum of patients with acute Plasmodium falciparum malaria.

Serum sCD14, tumour necrosis factor-alpha (TNF-alpha), IL-6, and endotoxin were analysed in 45 patients with complicated malaria, in 14 patients with Gram-negative septicaemia and in 24 healthy subjects by ELISA. Malaria patients with renal failure (n = 16) had higher levels than patients without renal failure (n = 29) (8116 + 1440 micrograms/l versus 9453 + 1017 micrograms/l; P < 0.05) and both had higher levels than patients with septicaemia (6155 + 1635 micrograms/l) and normal subjects (2776 + 747 micrograms/l). A significant correlation between sCD14 and IL-6 (r = 0.756) and TNF (r = 0.822) existed. However, no relation between sCD14 and serum endotoxin or indices of clinical disease severity (parasitaemia, fever, parasite or fever clearance time) was seen. Although the role of sCD14 in malaria remains to be determined, elevated levels may participate in the inflammatory response in complicated malaria.

Acute Disease

Increased serum concentrations of the carboxy-terminal cross-linked telopeptide of collagen type I in patients with Gram-negative septicaemia.

The authors determined serum levels of the carboxy-terminal cross-linked telopeptide and the carboxy-terminal propeptide of type I collagen (ICTP and PICP) in 18 patients with Gramnegative septicaemia before (day 0) and 28 days after therapy and in 18 age- and sex-matched controls by radioimmunoassay. Elevated levels of ICTP were observed in septicaemic patients [median (range): 15 (7-49) mu g L-1 before therapy and 14 (6-45) mu g L-1 28 days after therapy vs. 2 center dot 1 (1 center dot 4-4 center dot 3) mu g L-1 in normal subjects; P < 0 center dot 01 for both], whereas PICP levels were not different between patients and controls [median (range): 119 (52-275) mu g L-1 (day 0) and 133 (79-288) mu g L-1 (day 28) vs. 91 (54-213) mu g L-1 in normal subjects, P > 0 center dot 05 for all]. The findings suggest an increased production or release of ICTP in Gram-negative septicaemia, presumably owing to an alteration of extracellular matrix during septicaemia-related vascular inflammation.

Adolescent

The effect of age on the transendothelial migration of human T lymphocytes.

Since the migration of immunologically active cells into perivascular tissue is an important step in acute and chronic inflammation, the authors studied the possible influence of age on the transendothelial migration of T cells in an in vitro model. After incubation on collagen gels coated with human endothelial cells, three populations of T cells of elderly and young subjects were harvested: non-adherent (NAD), bound (BND) and migrated (MIG) cells. The percentages of the BND and MIG fractions were similar in the young and elderly groups. Phenotypic analysis showed that in the starting population of the elderly subjects T-cell subpopulations that have an increased capacity of transendothelial migration (e.g., CD4+ memory cells, CD8+/CD57+ cells) were enriched: nevertheless ageing was not associated with an increase in the transendothelial migration of T cells.

Adult