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Biomedical subjects

C Wenisch

Publications and source records attributed to C Wenisch.

At least 55 records · Page 3Linked to original sources
PubMed1997

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↗
PubMed1997

Rapid susceptibility testing of fungi by flow cytometry using vital staining.

A 1-h assay for antifungal susceptibility testing measuring the impairment of fungal metabolic activity was developed. Yeast viability was analyzed by flow cytometry with a novel fluorescent probe, FUN-1, which emits a red fluorescence when the yeast is metabolically active. For nine Candida albicans strains tested, this method yielded results comparable to those obtained by the standard M27 procedure for amphotericin B, flucytosine, fluconazole, and ketoconazole. Whether the flow cytometry antifungal susceptibility test results correlate with the in vivo activities of the drugs remains to determined.

Candida albicans↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea.

We conducted a prospective, randomized study to compare the efficacy of oral fusidic acid, oral metronidazole, oral vancomycin, and oral teicoplanin for the treatment of Clostridium difficile-associated diarrhea. Treatment resulted in clinical cure for 94% of the patients who were treated with vancomycin, 96% of those treated with teicoplanin, 93% of those treated with fusidic acid, and 94% of those treated with metronidazole. Clinical symptoms recurred in 16% of patients treated with vancomycin, 7% of those treated with teicoplanin, 28% of those treated with fusidic acid, and 16% of those treated with metronidazole. There was asymptomatic carriage of C. difficile toxin in 13% of patients treated with vancomycin, 4% of those treated with teicoplanin, 24% of those treated with fusidic acid, and 16% of those treated with metronidazole. No adverse effects related to therapy with vancomycin or teicoplanin were observed. Considering the costs of treatment, our findings suggest that metronidazole is the drug of choice for C. difficile-associated diarrhea and that glycopeptides should be reserved for patients who cannot tolerate metronidazole or who do not respond to treatment with this drug.

Administration, Oral↗
PubMed1996

Big endothelin in patients with complicated Plasmodium falciparum malaria.

Plasma concentrations of big endothelin-1 were determined by ELISA in 18 patients with complicated Plasmodium falciparum malaria in Bangkok. Before therapy, elevated levels were recorded (21 +/- 12 vs. 2.9 +/- 1.1 pmol/L in age- and sex-matched healthy subjects; P < .001). Even 7 days after therapy, elevated concentrations were seen (25 +/- 14 pmol/L). Plasma endothelin levels were correlated with levels of tumor necrosis factor-alpha (r = .632, P < .01), and a negative correlation with platelet counts was seen (r = .783, P < .005). No relation between plasma endothelin concentrations and parasitemia, fever, or other indices of severe infection (hypotension, renal, hepatic or pulmonary impairment, cerebral malaria) existed. During and after complicated malaria, increased levels of plasma endothelin could contribute to malarial pathology or reflect endothelial damage or both.

Antimalarials↗
PubMed1996

Mild intraoperative hypothermia reduces production of reactive oxygen intermediates by polymorphonuclear leukocytes.

Mild hypothermia directly impairs numerous immune functions in vitro. However, the in vivo effects of mild hypothermia on neutrophil phagocytosis and oxidative killing remain unknown. We tested the hypothesis that mild intraoperative hypothermia decreases neutrophil phagocytic capacity and generation of reactive oxygen intermediates (a measure of oxidative killing). Additionally, we evaluated the effects of in vitro temperature manipulations on each function. Thermal management was randomly assigned in 10 surgical patients, causing intraoperative core temperatures to range from 33 to 37 degrees C. Production of reactive oxygen intermediates and neutrophil phagocytosis were evaluated using flow cytometry at ambient temperature. Phagocytic capacity was assessed by uptake of fluorescein isothiocyanate-labeled Escherichia coli. Reactive oxygen production was estimated by the intracellular conversion of dihydrorhodamine 123 to rhodamine 123. Blood samples were obtained preoperatively, 1 h after surgery started, and 2 h postoperatively. Blood was also obtained from 10 matched control subjects and tested at 32, 37, and 40 degrees C. Neutrophil oxidative and phagocytic capacities were significantly reduced intraoperatively, compared with preoperative and postoperative values. Intraoperative production of reactive oxygen species was linearly related to core temperature. In contrast, there was no correlation between core temperature and phagocytic activity. In vitro production of reactive oxygen intermediates increased sixfold from 32 to 40 degrees C. In vitro phagocytic capacity increased fourfold in this temperature range. Production of oxidative intermediates was most closely related to intraoperative core temperature, decreasing nearly fourfold over a 4 degree C range. This in vitro temperature dependence was matched in vitro. Impaired neutrophil oxidative killing may contribute to the observed hypothermia-induced reduction in resistance to infection.

Acute-Phase Proteins↗
PubMed1996

Dysregulation of the polymorphonuclear leukocyte--Candida spp. interaction in HIV-positive patients.

OBJECTIVE: In HIV-infected patients there is an increased frequency of fungal infections. Dysregulation of the response of phagocytic cells to fungal pathogens may be involved. DESIGN: Phagocytosis of Candida spp., consecutive intracellular production of reactive oxygen species, and candicidal activity were analysed in polymorphonuclear leukocytes (PML) from HIV-1-infected patients, who were at stage C3 of the 1993 revised Centers for Disease Control and Prevention classification system, by means of flow cytometry. METHODS: Phagocytic ability was assessed by measuring uptake of fluorescein isothiocyanate-labelled Candida albicans, C. krusei and C. glabrata. Reactive oxygen intermediate production was estimated by the quantity of dihydrorhodamine-123 converted to rhodamine-123 intracellularly. The candicidal effect was assessed by the propidium iodide uptake of killed yeast cells. RESULTS: As compared to PML of healthy, HIV-negative controls, PML of AIDS patients exhibited an increased phagocytic activity and a similar ability to generate reactive oxygen products. In contrast, PML of AIDS patients displayed a decreased candicidal activity (P < 0.05 compared to controls). CONCLUSION: These results suggest that in patients with advanced HIV-1 infection the impairment of non-oxidative killing mechanisms of phagocytic cells may contribute to the high incidence of fungal infections.

Adolescent↗
PubMed1996

Effect of single oral dose of azithromycin, clarithromycin, and roxithromycin on polymorphonuclear leukocyte function assessed ex vivo by flow cytometry.

Azithromycin was given as a single oral dose (20 mg/kg of body weight) to 12 volunteers in a crossover study with roxithromycin (8 to 12 mg/kg) and clarithromycin (8 to 12 mg/kg). Flow cytometry was used to study the phagocytic functions and the release of reactive oxygen products following phagocytosis by neutrophil granulocytes prior to administration of the three drugs, 16 h after azithromycin administration, and 3 h after clarithromycin and roxithromycin administration. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled bacteria. Reactive oxygen generation after phagocytosis of unlabeled bacteria was estimated by the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. Azithromycin resulted in decreased capacities of the cells to phagocytize Escherichia coli (median [range], 62% [27 to 91%] of the control values; P < 0.01) and generate reactive oxygen products (75% [34 to 26%] of the control values; P < 0.01). Clarithromycin resulted in reduced phagocytosis (82% [75 to 98%] of control values; P < 0.01) but did not alter reactive oxygen production (84% [63 to 113%] of the control values; P > 0.05). Roxithromycin treatment did not affect granulocyte phagocytosis (92% [62 to 118%] of the control values; P > 0.05) or reactive oxygen production (94% [66 to 128%] of the control value; P > 0.05). No relation between intra- and/or extracellular concentrations of azithromycin and/or roxithromycin and the polymorphonuclear phagocyte function and/or reactive oxygen production existed (P > 0.05 for all comparisons). These results demonstrate that the accumulation of macrolides in neutrophils can suppress the response of phagocytic cells to bacterial pathogens after a therapeutic dose.

Adult↗
PubMed1996

Detection of anti-neutrophil cytoplasmic antibodies after acute Plasmodium falciparum malaria.

Four of 30 patients with Plasmodium falciparum infection in Bangkok, Thailand, were positive for anti-neutrophil cytoplasmic antibodies by indirect immunofluorescence 1 month after antimalarial therapy. No myeloperoxidase, proteinase 3, lactoferrin, or elastase reactivity was found. Since no evidence of vasculitis was seen in these patients, anti-neutrophil cytoplasmic antibody production in malaria-infected susceptible patients probably represents a secondary response, indicating neutrophil activation.

Acute Disease↗
PubMed1996

High-dose catecholamine treatment decreases polymorphonuclear leukocyte phagocytic capacity and reactive oxygen production.

Flow cytometry was used to study phagocytic function (uptake of fluorescein isothiocyanate-labeled bacteria) and release of reactive oxygen products (dihydrorhodamine 123 converted to rhodamine 123) following phagocytosis by neutrophil granulocytes of heparinized whole blood treated with adrenaline, noradrenaline, dopamine, dobutamine, or orciprenaline. Reduced neutrophil phagocytosis and reactive oxygen production were seen at 12 micrograms of adrenaline per liter (72% each compared with control values); at 120 micrograms of noradrenaline (72% each), dobutamine (83 and 80%, respectively), and orciprenaline (81 and 80%, respectively) per liter; and at 100 micrograms of dopamine per liter (66 and 70%) (P < 0.05 for all). At these dosages, neutrophil chemotaxis was reduced to < 50% of control values for all catecholamines. Treatment with catecholamines at lower dosages had no significant effect on phagocytosis or generation of reactive oxygen products or chemotaxis. The phagocytic capacity of granulocytes was related to the generation of reactive oxygen products (r = 0.789; P < 0.05). The results demonstrate that catecholamines have a suppressive effect on the response of phagocytic cells to bacterial pathogens at high therapeutic levels in blood.

Adult↗
PubMed1995

Elevated serum levels of IL-10 and IFN-gamma in patients with acute Plasmodium falciparum malaria.

Serum levels of interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) were determined in 37 patients with acute Plasmodium falciparum malaria in Bangkok, Thailand. Serum levels of IL-10 and IFN-gamma were markedly elevated in patients with malaria prior to treatment (717 +/- 260 pg/ml versus 2.2 +/- 1.3 pg/ml in healthy controls; 123 +/- 71 pg/ml versus 29 +/- 9 pg/ml, respectively; mean +/- SD). Serum levels of IFN-gamma and IL-10 dropped significantly during treatment and were normal 14 and 21 days, respectively, after treatment was started. Prior to therapy a correlation between serum levels of IFN-gamma and IL-10 existed (r = 0.563). These results suggest that stimulatory and inhibitory cytokines for macrophage activation and/or antibody production (i.e., TH1- and TH2-type immunoreaction, respectively) are coexpressed during acute P. falciparum infection and stress the multifactorial network between host and parasite in malaria immunology.

Acute Disease↗
PubMed1995

Serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen and laminin are elevated in Graves' disease but not in toxic nodular goiter.

We determined serum levels of laminin, carboxy-terminal cross-linked telopeptide, and carboxy-terminal propeptide of type I collagen (ICTP and PICP) in 27 patients with Graves' disease (GD) and in 31 patients with toxic nodular goiter (TNG). Elevated levels of soluble laminin and ICTP were observed in patients with GD prior to treatment (mean +/- SD concentration 1444 +/- 404 and 8.6 +/- 3.5 ng/ml, respectively), compared to patients with TNG (476 +/- 103 and 4.2 +/- 1.5 ng/ml) and normal controls (492 +/- 112 and 3.1 +/- 1.3 ng/ml, n = 34). In contrast, serum PICP concentrations were not different between patients with GD or TNG and normal controls. In GD patients serum ICTP and laminin levels decreased during thiamazole treatment and normalized within 4 and 8 weeks of therapy. There was no correlation between serum ICTP and laminin levels and serum levels of thyroid hormones and/or autoantibodies, respectively. Serum ICTP and laminin could be markers for alterations of extracellular matrix during GD and release of matrix components in the circulation and/or reflect an impaired clearance.

Adult↗
PubMed1995

Serum concentrations of MIP-1 alpha and interleukin-8 in patients suffering from acute Plasmodium falciparum malaria.

The chemokines are a superfamily of small proteins secreted primarily by leukocytes and related by a conserved four-cystein motif. In the present study we investigated the serum levels of macrophage inflammatory protein 1 alpha (MIP-1 alpha) and interleukin-8 (IL-8). MIP-1 alpha is a neutrophil chemotactic protein important in acute and chronic inflammation. Recent studies demonstrated that MIP-1 alpha may also act as potent inhibitor of hemopoetic stem cell proliferation, which may be important in the development of prolonged anemia in patients suffering from Plasmodium falciparum malaria. IL-8 serum concentrations correlate with severity and outcome of infectious diseases. Moreover, recent reports indicate that IL-8 plays a major role in fatal gram-negative sepsis. It was the aim of this study to investigate the time course of MIP-1 alpha and IL-8 concentrations in patients suffering from acute P. falciparum infection. Blood samples of 20 patients suffering from severe P. falciparum malaria were investigated. MIP-1 alpha and IL-8 concentrations were determined using ELISA technique at admission, on Days 7, 14, 21, and 28. Maximal concentrations of MIP-1 alpha and IL-8 were found on Day 14, at a time when parasites were not detected in the smears. The serum levels of IL-8 on the day of admission were correlated to the parasite count. No correlation was seen between the hematokrit values and the MIP-1 alpha concentrations at any time.

Adolescent↗