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Biomedical subjects

J Blaser

Publications and source records attributed to J Blaser.

At least 19 recordsLinked to original sources
PubMed2002

[Speech recognition in clinical routine, a pilot trial at the Zurich University Hospital].

Two systems for continuous German speech recognition were evaluated in pilot installations in a Department of Medicine. Word recognition accuracies of 92-94% were achieved one month after implementation. For standardized text the performance increased to 97%. Speech recognition proved to be economical for physicians when producing short reports, whereas for comprehensive discharge summaries no significant time savings were observed. All reports could be made available much faster by using speech recognition. However, some particle difficulties may still limit the success of comprehensive installations in clinical settings. Adequate hardware, appropriate choice of areas of application, reasonably quiet working conditions and well motivated users are essential for successful implementations.

Hospital Information Systems↗
PubMed2001

Factors compromising antibiotic activity against biofilms of Staphylococcus epidermidis.

Several factors associated with bacterial biofilms were studied for their role in phenotypic resistance to antibiotics. These factors included bacterial slime extracted from biofilms, reduced growth rates of biofilm-embedded bacteria and high bacterial inocula. Antibiotic activity against suspended bacteria in the presence of these factors, either alone or combined, was compared with activity against adherent biofilms. All MICs, determined by standard susceptibility tests, were below the sensitivity breakpoints for Staphylococcus epidermidis strain V2. The addition of bacterial slime to suspended bacteria reduced the bactericidal activity of glycopeptides but had less or no effect on the activity of the other antibiotics tested. High bacterial inocula affected the activity of flucloxacillin and quinolones only moderately or not at all, though a more pronounced effect on glycopeptides was observed. In contrast, the bactericidal activity of most antibiotics was severely compromised when adherent bacterial biofilms were used as inocula. In conclusion, the presence of slime, slow growth rates and high bacterial counts may explain the poor activity of glycopeptides against biofilm-embedded organisms, but these factors, either alone or in combination, do not explain the lack of bactericidal activity of other drugs against biofilms. Thus, additional factors need to be identified.

Anti-Bacterial Agents↗
PubMed1999

Peripheral database module for clinical management and research in sleep medicine.

Hospital-wide information systems may provide economical solutions for communication processes or for documentation by means of centralized digital medical records. Within a large university hospital, however, there may be too many diverse subspecialties and too many special medical procedures to be supported comprehensively by a single database information system. A peripheral modular system has been tailored to the specific needs of a sleep disorder clinic as an adjunct to the main clinical information system. The client server application allows for automatic data acquisition by on-line devices and by a graphical user interface. It supports administrative tasks for patient management, specific encounter interactions and data retrieval for research. Performance and acceptance of the system was assessed during clinical use, revealing positive response by the users, also with respect to significant time savings. Our experience suggests that the concept of peripheral database modules as "satellites" to a main clinical system provides flexibility in design and implementation of the specialized databases while providing access to data of more general relevance via the main database.

Database Management Systems↗
PubMed1998

The association between telomerase, p53, and clinical staging in colorectal cancer.

BACKGROUND: A proposed etiology of tumor activation involves p53 mutations while telomerase may serve as a key enzyme for maintenance of tumor cell proliferation. METHODS: Telomerase activity levels were measured in colorectal adenocarcinomas and corresponding normal tissue using a modified telomeric repeat amplification protocol, and p53 mutations were identified using immunohistochemical staining. Results were compared with staging data using regression analysis. RESULTS: Telomerase activity was present in 23 of 23 (100%) of the tumors and only 2 (9%) of normal specimens (P <0.0001). The p53 mutations were present in 18 of 23 (78%) of the tumors. No significant correlation between p53 mutations, telomerase activity levels, and staging was found. CONCLUSIONS: Telomerase activity in 100% of the tumors suggests telomerase activation is a universal event in colorectal tumor progression; however, telomerase activity appears to be independent of p53 mutations and clinical staging.

Adenocarcinoma↗
PubMed1998

Bacterial concentrations in pus and infected peritoneal fluid--implications for bactericidal activity of antibiotics.

Little is known about how many bacteria are present at an infectious focus at the onset of antibiotic therapy. The number of cfu was determined in pus and infected peritoneal fluids obtained from 41 patients. Pathogens were detected in 71% of specimens. There were high concentrations of bacteria in culture-positive samples, in both soft-tissue and peritoneal infections, averaging 2 x 10(8) cfu/mL. These concentrations were much higher than the standard inoculum size used in in-vitro susceptibility tests, 5 x 10(5) cfu/mL. The impact of this discrepancy on antibacterial efficacy was studied with amikacin, ciprofloxacin, imipenem and piperacillin against Escherichia coli and Staphylococcus aureus. The inhibitory and bactericidal activities of amikacin and ciprofloxacin determined with high inocula were two to four times lower than with standard inocula, whereas the activity of piperacillin was diminished at least 128-fold. Similar activity was observed with these drugs in Mueller-Hinton broth and peritoneal fluid. The bactericidal activity of imipenem was reduced in peritoneal fluid. Thus, conditions prevailing at the infection site may compromise antibiotic activity determined in vitro.

Abdominal Abscess↗
PubMed1998

Impact of bacterial biofilm formation on in vitro and in vivo activities of antibiotics.

The impact of bacterial adherence on antibiotic activity was analyzed with two isogenic strains of Staphylococcus epidermidis that differ in the features of their in vitro biofilm formation. The eradication of bacteria adhering to glass beads by amikacin, levofloxacin, rifampin, or teicoplanin was studied in an animal model and in a pharmacokinetically matched in vitro model. The features of S. epidermidis RP62A that allowed it to grow on surfaces in multiple layers promoted phenotypic resistance to antibiotic treatment, whereas strain M7 failed to accumulate, despite initial adherence on surfaces and growth in suspension similar to those for RP62A. Biofilms of S. epidermidis M7 were better eradicated than those of strain RP62A in vitro (46 versus 31%; P < 0.05) as well as in the animal model (39 versus 9%; P < 0.01).

Animals↗
PubMed1997

Autosterilization of biodegradable implants by injection molding process.

Sterilization of degradable implants by standard procedures may damage the parts due to the labile chemical nature of the polymers. This study examined whether the injection molding process used for the production of polymeric parts may itself sterilize the implant due to high temperature, pressure, and shear forces applied. Poly-D,L-lactic acid (PDLLA) and poly-L-lactic acid (PLLA) granules were contaminated with thermoresistant spores of Bacillus stearothermophilus (>10(5) spores/g). Sterile and contaminated granules of both polymers were injection molded and tested for sterility. All 27 samples produced with sterile PDLLA and processed at 120 degrees C and all 18 samples produced with sterile PLLA at 200 degrees C remained sterile after injection molding and handling. However, in five out of 28 PDLLA samples and in one out of 26 PLLA samples produced with contaminated material, spores had survived the process. In conclusion, the injection molding process could not reliably sterilize parts produced with polylactic acid granules that were heavily contaminated with thermoresistant organisms. However, the number of viable spores was significantly reduced by more than 99.99%. Thus, the injection molding process might allow the autosterilization of parts produced with raw material that is not heavily contaminated.

Biocompatible Materials↗
PubMed1996

Determination of metalloproteinases, plasminogen-activators and their inhibitors in the synovial fluids of patients with rheumatoid arthritis during chemical synoviorthesis.

The concentrations of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-8 (MMP-8), matrix metalloproteinase-9 (MMP-9), lactoferrin and urokinase plasminogen activator (uPA), tissue-type plasminogen activator (tPA) and the inhibitors, tissue inhibitor of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor-1 (PAI-1), plasminogen activator inhibitor (PAI-2), and alpha2-macroglobulin in the synovial fluids of patients with rheumatoid arthritis was determined before and during chemical synoviorthesis with a sodium salt of the fatty acids from cod-liver oil (Varicocid). Synovial fluids were obtained before treatment from 37 patients with rheumatoid arthritis and, in most cases, at 8 and 24 h after injection of the agent. Well-established ELISAs were used to determine the amounts of all proteins. All patients with rheumatoid arthritis revealed very high levels of metalloproteinases (about 1-15 mu g/ml) in their synovial fluids. During the inflammation inducing treatment the granulocyte enzymes increased. In contrast to this, the level of MMP-1 decreased. All granulocyte-derived enzymes were strongly correlated with each other, whereas their dependence on the granulocyte count was only weak. uPA and PAI-2 showed good correlations with the granulocytes-derived enzymes, but were also only weakly correlating with the cell counts. t-PA was not detected by the ELISA used. The proteases, MMP-8, MMP-9 and uPA were increased 8 h after the treatment, whereas the specific inhibitors TIMP-1, PAI-1 and PAI-2 showed significant changes only 24 h after the injection. Matrix metalloproteinases are important factors in the pathogenesis of rheumatoid arthritis. The inflammatory activity in the joint could be better correlated to the granulocyte enzymes than to the granulocyte counts. The levels of uPA and PAI-2 are also parallel to the granulocyte enzyme levels and might underly the same regulatory mechanism.

Adult↗
PubMed1996

Once-versus thrice-daily netilmicin combined with amoxicillin, penicillin, or vancomycin against Enterococcus faecalis in a pharmacodynamic in vitro model.

Several in vitro and in vivo studies as well as clinical trials have demonstrated that once-daily aminoglycoside regimens are as effective as or more effective than multiple daily dosings. However, the most favorable aminoglycoside dosing regimen for treating enterococcal endocarditis remains controversial. The same total dose of netilmicin was administered as once-daily (24-micrograms/ml peaks) and thrice-daily (8 micrograms/ml) regimens in a pharmacodynamic in vitro model simulating exposure of Enterococcus faecalis to human serum kinetics. Netilmicin was administered in combination with continuous infusions of amoxicillin, vancomycin, or penicillin against a bacterial biofilm adhering to glass beads. No significant differences in bacterial killing were found after 24 or 48 h between the once- and thrice-daily regimens. Additional experiments considering animal kinetics (half-life of netilmicin, 20 min) instead of human kinetics (half-life, 2.5 h) in the pharmacodynamic model also revealed similar results. The addition of netilmicin synergistically increased the activity of vancomycin (P < 0.05). In contrast, amoxicillin alone was as effective as the combination with netilmicin. Thus, it could not be established in this model that once-daily dosing of aminoglycosides is contraindicated for treating infections caused by E. faecalis.

Amoxicillin↗
PubMed1996

[Dosing aminoglycosides once a day].

In the past few decades aminoglycosides have usually been administered as multiple daily dosing regimens. However, animal experiments have shown that nephrotoxicity can be reduced if, with the same total daily dose, the dosing interval is spread out. Further, several in-vitro and in-vivo studies suggest that once-daily dosing may be more effective. In 24 randomized, clinical trials, once- vs. multiple daily dosing regimens of amikacin, netilmicin and gentamicin have been compared in a total of 3181 patients. An analysis of these studies revealed significant advantages in favour of once-daily dosing for both clinical efficacy (89.5% vs. 84.7%, p < 0.001) and bacteriological efficacy (88.6% vs. 83.4%, p < 0.01). In addition, improved but not statistically significant results were obtained with once-daily dosing with regard to nephrotoxicity (4.5% for once-daily vs. 5.5% for multiple daily dosing) and ototoxicity (4.2% vs. 5.8%). Furthermore, once-daily dosing is cheaper, as less infusions are required and the expense of monitoring serum levels can be reduced. In conclusion, amikacin, netilmicin and gentamicin can be administered once a day.

Amikacin↗
PubMed1995

Once-daily dosing of aminoglycosides.

Since their introduction one or more decades ago, aminoglycosides have generally been administered in multiple daily (i.e. twice- or thrice-daily) dosing regimens. However, nephrotoxicity can be reduced in animal models by administering the same total daily dose as one large dose instead of as multiple small doses. In addition, in vitro and in vivo studies that considered the impact of dosing regimens on efficacy suggest that once-daily dosing is equally or more effective compared to multiple daily dosing. Once-daily versus multiple daily dosing regimens have been compared for amikacin, netilmicin, and gentamicin in 24 randomized, clinical trials including a total of 3,181 patients. An analysis of these studies revealed superior results for once-daily regimens with respect to clinical efficacy (89.5% vs. 84.7%, p < 0.001) as well as bacteriological efficacy (88.6% vs. 83.4%, p < 0.01). No statistically significant differences were noted for toxicity. Nevertheless, both nephrotoxicity and ototoxicity occurred less frequently during once-daily dosing (4.5% vs. 5.5% and 4.2% vs. 5.8%, respectively). Finally, once-daily dosing is more economical, since less nursing time and infusion material are required and the efforts for drug monitoring can be reduced. In conclusion, amikacin, netilmicin, and gentamicin can be administered once a day.

Aminoglycosides↗
PubMed1995

Assay of matrix metalloproteases types 8 and 9 by ELISA in human breast cancer.

Results from model tumour systems suggest that either increased levels of certain metalloproteases (MMPs) or decreased levels of their inhibitors correlate with metastatic potential. In this study, levels of two MMPs, i.e. MMP-8 and -9, and their inhibitor tissue inhibitor of metalloprotease type 1 (TIMP-1) were measured by enzyme-linked immunosorbent assay in human breast tumours. Levels of MMP-8 and -9 correlated significantly with each other, but neither MMP correlated with urokinase plasminogen activator. Levels of both MMP-8 and -9 were also significantly related to levels of TIMP-1. In contrast, neither MMP correlated with plasminogen activator inhibitor. No relationship was found between MMP-8, MMP-9 or TIMP-1 and either tumour size or metastasis to axillary nodes. MMP-8 and -9 levels were inversely related to levels of oestrogen receptors. MMP-8 but not MMP-9 levels were also inversely correlated with progesterone receptor levels. It is concluded that the assay for MMP-8 and -9 described here will permit the evaluation of these proteases as prognostic markers in cancer.

Biomarkers, Tumor↗
PubMed1995

The scid mouse as an experimental model for the evaluation of anti-Pneumocystis carinii therapy.

The usefulness of scid mice bearing endogenous Pneumocystis carinii infection as a model for experimental chemotherapy was examined using standard compounds known to be effective against P. carinii. Trimethoprim/sulphamethoxazole was able to reduce pulmonary P. carinii cysts in a dose-dependent manner within the dose range studied (10/50 to 100/500 TMP/SMX mg/kg/d, bd, po, 5 days per week for 30 treatments). However, alterations in associated symptoms of infection (reduced body weight, increased lung weight, increased blood leucocytes and erythrocytes), was apparently not linearly dose-dependent. Blood and lung lavage fluid levels of sulphamethoxazole one hour post administration of trimethoprim/sulphamethoxazole was dose-dependent, but not linear with dose, and was apparently correlated to cyst reduction; trimethoprim was below the limit of detection at this time. Treatment of mice with 100/500 mg/kg/day trimethoprim/sulphamethoxazole required 2 weeks (bd for 10 days of treatment) before changes in indices of infection became significant. Pentamidine (20 mg/kg, sc, three times per week for 3 weeks) was nearly as effective as high-dose trimethoprim/sulphamethoxazole in reducing cysts, whereas lower doses were ineffective. Despite being unable to reduce pulmonary P. carinii infection, even low doses of pentamidine (6 or 2 mg/kg, sc, three times per week for 3 weeks) were able to reduce lung weights and blood leucocyte levels. This model of pulmonary P. carinii infections is amenable to chemotherapeutic intervention in an apparently dose-dependent fashion, and can be used to evaluate the capacity of compounds to eradicate P. carinii and resolve signs of infection.

Animals↗
PubMed1995

Nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics of once versus thrice daily dosing of netilmicin in patients with serious infections.

The effect of dosing regimen on nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics was studied in a prospective, randomised clinical study. Therapy was started with total daily doses of 6 mg/kg given once (od) or thrice (tid) daily to 56 and 57 patients, respectively. Subsequent doses were adjusted according to serum levels. No major differences in toxicity or efficacy were noticed between od and tid regimens: clinical failures occurred in two and two patients, four and five patients suffered from a decrease of > or = 20 dB at least unilaterally at one frequency between 8 and 18 kHz, six and seven patients had a > 25 mumol/L or > 25% increase in serum creatinine, respectively. Serum creatinine or creatinine clearance did not change significantly during either therapy. Major differences between the two study groups were limited to pharmacokinetic parameters. Od dosing resulted in higher peak (mean of 21.6 vs 7.2 mg/L) and lower trough levels (0.5 vs 1.4 mg/L). Half-lives of netilmicin determined between 1 and 8 h increased significantly during therapy with tid (from a mean of 2.75 to a mean of 3.33 h, P < 0.01) but not significantly with od (rise from 2.8 to 3.03 h). Much longer half-lives were determined between 8 and 24 h in the od group (mean of 5.7 h, P < 0.01). In conclusion, only minimal differences in toxicity and efficacy were observed. Their clinical relevance appears to be minimal.

Adolescent↗
PubMed1995

Multicenter quality control study of amikacin assay for monitoring once-daily dosing regimens. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.

During once-daily dosing regimens of aminoglycosides, administration of large single doses results in high peak levels and low 24-h trough levels. However, commercial assays for monitoring aminoglycoside levels are designed to cover the smaller range of serum concentrations usually observed during multiple daily dosing regimens. The study assessed (a) the range of serum concentrations during once-daily dosing of amikacin and (b) the performance of a widely used assay system for measuring concentrations within this range. A total of 42 dosing intervals from eight patients receiving a once-daily regimen of amikacin (20 mg/kg) were monitored. Median (and range) of peak, 8- and 24-h trough levels were 61 (25-89), 5.9 (2.2-19), and 1.3 (< 0.8-6.2) mg/L, respectively. The accuracy of a fluorescence polarization immunoassay for measuring concentrations of amikacin during once-daily dosing regimens was assessed in an international multicenter study. The performance of the assay was excellent for peak and 8-h concentrations; median deviations from the target concentrations were < 5%. The majority of the trough levels (26 of 42) measured in patients during once-daily treatment were within the range of 1-2 mg/L and could also be determined with an accuracy sufficient for clinical monitoring (median deviations 14%).

Adult↗
PubMed1995

Monitoring of co-trimoxazole concentrations in serum during treatment of pneumocystis carinii pneumonia.

The purpose of this prospective randomized open trial was to investigate the impact of monitoring concentrations in serum on the efficacy and side effects of high-dose co-trimoxazole therapy. Forty consecutive patients with microscopically confirmed Pneumocystis carinii pneumonia were enrolled. Therapy was started with 5 and 25 mg of trimethoprim and sulfamethoxazole, respectively, per kg of body weight given every 6 h for 2 days and continued every 8 h either with (group A) or without (group B) monitoring and dose adjustments according to sulfamethoxazole levels in serum (target, 150 to 200 micrograms/ml) for a total of 21 days. Only 7 of 19 patients (83%). Patients who were treated for the full period and patients for whom co-trimoxazole was prematurely stopped had similar concentrations of sulfamethoxazole (157 +/- 52 versus 155 +/- 47 micrograms/ml) and trimethoprim (5.0 +/- 1.4 versus 5.6 +/- 1.0 microgram/ml). Concentrations of sulfamethoxazole and trimethoprim in group A (158 +/- 39 and 5.6 +/- 1.8 micrograms/ml, respectively) did not differ from those in group B (153 +/- 57 and 5.1 +/- 1.6 micrograms/ml, respectively), and the average daily maintenance doses for groups A (75.4 mg/kg plus 15.1 mg/kg) and B (76.4 mg/kg plus 15.3 mg/kg) were nearly identical. Although the average sulfamethoxazole concentrations were maintained within the target zone in the monitoring group (day 5, 160 +/- 44 micrograms/ml; day 10, 160 +/- 41 micrograms/ml; day 15, 168 +/- micrograms/ml; and day 21, 157 +/- 95 micrograms/ml), only 28% of the individual sulfamethoxazole levels were within the target range of 150 to 200 micrograms/ml after the dose adjustments (32% in group B without intervention). Response rates were similar in both groups. Complete response or improvement was observed in 18 of 19 (group A) and 19 of 21 (group B) patients. The method used for monitoring sulfamethoxazole levels with subsequent dose adjustment did not allow us to reliably achieve the target concentrations and did not significantly alter the incidence of side effects or the efficacy of the therapy.

AIDS-Related Complex↗