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Biomedical subjects

K Unertl

Publications and source records attributed to K Unertl.

At least 19 recordsLinked to original sources

Certain batches of albumin solutions influence the expression of endothelial cell adhesion molecules.

OBJECTIVE: Increased levels of soluble adhesion molecules, a decreased PO2/FIO2 ratio and a tendency to worsened outcome have been reported following the use of human albumin in critical illness. The reasons are not yet understood. Since albumin solutions have previously been shown to contain proinflammatory mediators, a direct upregulation of adhesion molecules by contaminated batches may explain these findings. To examine this, we studied the effects of different albumin preparations on endothelial cell adhesion molecules in vitro. DESIGN: Experimental study. SETTING: Laboratory for cell biology. METHODS: Human umbilical venous endothelial cell cultures (n = 4) were incubated for 6 h at 5 mg/ml with four different human albumin solutions (HA1-4) from different manufacturers. Medium served as the control. Using flow cytometry, the effects on E-selectin, ICAM-1 and VCAM-1 expression were determined on unstimulated cells and on cells stimulated with tumour necrosis factor alpha at 0.5 ng/ml for 4 h. MEASUREMENTS AND RESULTS: On unstimulated cells, HA1 and HA4, two different batches from the same manufacturer, increased ICAM-1 by 22% and 15%, respectively. After stimulation, both solutions resulted in a 19% increased expression of E-Selectin. In addition, HA4 decreased VCAM-1 on stimulated cells (p < or = 0.05). Two albumin preparations from other manufacturers did not produce significant effects. CONCLUSIONS: Some albumin solutions directly modulate adhesion molecule expression on endothelial cells. This may, at least in part, explain the previous finding of increased soluble adhesion molecules and a decreased PO2/FIO2 ratio in critically ill patients undergoing volume replacement with human albumin.

Albumins↗

Implementation of an interactive computer-assisted infection monitoring program at the bedside.

A new computer-assisted infection monitoring (CAI) software program has been developed for use in an intensive-care unit (ICU). By means of an interactive dialogue with physicians at the bedside, infection diagnoses and therapeutic decisions were recorded prospectively during a 3-month test period. By linking epidemiological data with information about therapeutic decisions, CAI could assess the quality of the therapeutic decisions. Antibiotics chosen empirically before the availability of any culture results, matched the antibiotic susceptibility patterns of the subsequently identified pathogens in 74% of the cases. Therapy chosen in collaboration with the computer after the pathogen was known, but before sensitivity results were available, corresponded with the eventual antibiograms of the microorganisms in 90% of the cases. Data analysis by CAI allowed us to assess critically the diagnostic and therapeutic habits in our ICU. Using the query-by-example method, CAI automatically calculated device-associated infection rates.

Adolescent↗

PCR and blood culture for detection of Escherichia coli bacteremia in rats.

Critically ill patients often develop symptoms of sepsis and therefore require microbiological tests for bacteremia that use conventional blood culture (BC) techniques. However, since these patients frequently receive early empirical antibiotic therapy before diagnostic procedures are completed, examination by BC can return false-negative results. We therefore hypothesized that PCR could improve the rate of detection of microbial pathogens over that of BC. To test this hypothesis, male Wistar rats were challenged intravenously with 10(6) CFU of Escherichia coli. Blood was then taken at several time points for detection of E. coli by BC and by PCR with E. coli-specific primers derived from the uidA gene, encoding beta-glucuronidase. In further experiments, cefotaxime (100 or 50 mg/kg of body weight) was administered intravenously to rats 10 min after E. coli challenge. Without this chemotherapy, the E. coli detection rate decreased at 15 min and at 210 min after challenge from 100% to 62% of the animals with PCR and from 100% to 54% of the animals with BC (P, >0.05). Chemotherapy decreased the E. coli detection rate at 25 min and at 55 min after challenge from 100% to 50% with PCR and from 100% to 0% with BC (P, <0.05). Thus, at clinically relevant serum antibiotic levels, PCR affords a significantly higher detection rate than BC in this rat model. The results suggest that PCR could be a useful adjunct tool supplementing conventional BC techniques in diagnosing bacteremia.

Animals↗

Elimination of meropenem by continuous hemo(dia) filtration: an in vitro one-compartment model.

Meropenem is a carbapenem antibiotic with a wide spectrum of activity against most gram positive and gram negative bacteria including anaerobes. Dose adjustments are necessary during continuous renal replacement therapies of acute renal failure. This in vitro study was conducted to investigate the influence of different filter materials, surface areas (AN-69 0.6 m2 and 0.9 m2, polysulfone 0.75 m2, polyamide 0.6 m2), and increasing flow rates (from 3.3 - 26.7 ml/min) on the elimination of meropenem in an in vitro continuous hemo(dia)filtration model. Meropenem was measured using HPLC with UV-detection. While the clearance increased proportionally to increasing dialysate flow rates in filters with a surface area of 0.9 m2, a peak clearance was reached in the small filters at flow rates of 10.0 ml/min (polyamide 0.6 m2) and 18.3 ml/min (AN-69 0.6 m2), when tested under the same conditions. This indicated incomplete dialysate saturation due to the diminished time available for meropenem to equilibrate with the dialysate solution. No adsorption to either of the tested membranes was detected. Dosage recommendations derived from clinical studies might be appropriate when different filter materials, but similar operational settings of the continuous replacement therapy, are applied. Reduction of the recommended dose might be necessary, when renal replacement therapies with lower flow rates and/or filters with smaller surface areas are carried out.

Anti-Bacterial Agents↗

Pharmacokinetics of meropenem in critically ill patients with acute renal failure treated by continuous hemodiafiltration.

The pharmacokinetics of meropenem were studied in nine anuric critically ill patients treated by continuous venovenous hemodiafiltration. Peak levels after infusion of 1,000 mg over 30 min amounted to 103.2 +/- 45.9 microgram/ml, and trough levels at 12 h were 9.6 +/- 3.8 microgram/ml. A dosage of 1,000 mg of meropenem twice a day provides plasma drug levels covering intermediately susceptible microorganisms. Further reductions of the dosage might be appropriate for highly susceptible bacteria or when renal replacement therapies with lower clearances are applied.

Acute Kidney Injury↗

Effects of regional anesthesia on phantom limb pain are mirrored in changes in cortical reorganization.

The causes underlying phantom limb pain are still unknown. Recent studies on the consequences of nervous system damage in animals and humans reported substantial reorganization of primary somatosensory cortex subsequent to amputation, and one study showed that cortical reorganization is positively correlated with phantom limb pain. This paper examined the hypothesis of a functional relationship between cortical reorganization and phantom limb pain. Neuroelectric source imaging was used to determine changes in cortical reorganization in somatosensory cortex after anesthesia of an amputation stump produced by brachial plexus blockade in six phantom limb pain patients and four pain-free amputees. Three of six phantom limb subjects experienced a virtual elimination of current phantom pain attributable to anesthesia (mean change: 3.8 on an 11-point scale; Z = -1.83; p < 0.05) that was mirrored by a very rapid elimination of cortical reorganization in somatosensory cortex (change = 19.8 mm; t(2) = 5.60; p < 0.05). Cortical reorganization remained unchanged (mean change = 1.6 mm) in three phantom limb pain amputees whose pain was not reduced by brachial plexus blockade and in the phantom pain-free amputation controls. These findings suggest that cortical reorganization and phantom limb pain might have a causal relationship. Methods designed to alter cortical reorganization should be examined for their efficacy in the treatment of phantom limb pain.

Adult↗

[Prognostic scores in intensive care].

Since the development of prognostic score systems in intensive care medicine in the 1980s score models have improved substantially and are now based on much larger databases. They have been validated in many multicenter and international studies all over the world. Prognostic scoring systems may be used for assessment of severity of illness, stratifying patients prior to randomization in clinical trials, evaluation and comparing outcome and survival (hospital mortality), quality assessment, cost-benefit analysis, and in clinical decision making. Validated time points for predicting hospital mortality of ICU patients are at admission and at 24 hours. The relationship of the observed hospital mortality rate to the estimated mortality provides the basis for clinical performance measurement. Since each ICU serves a different patient population, each score system must be calibrated in the individual hospital to ensure that the model is applicable. General scores covering more than one disease are Acute Physiology And Chronic Health Evaluation (APACHE II, APACHE III), Simplified Acute Physiology Score (SAPS) and Mortality Predicting Model (MPM). The Therapeutic Intervention Scoring System (TISS) and in part the Hannover Intensive Score (HIS) evaluate exclusively the amount of medical therapy required. The TISS-Score might serve as a possible measure of resource use for the ICU portion of the hospital stay. Disease (e.g. Trauma Score, Injury of Severity Score) and patient (e.g. PRISM = Pediatric Risk of Mortality) specific scores take into account the influence of disease and patient population in relation to outcome. They are not always of more predictive value than general score models. Score models have been criticized for a number of reasons. Outcome of ICU therapy should incorporate not only survival but should also take into account quality of life, morbidity and disability. Severity scores have no role in clinical decision making for an individual patient (e.g. patient triage for ICU admission, discharge criteria, withdrawal of life support). This is due to the current low sensitivity. Subsequent validation of variables could improve the sensitivity and the value of severity scoring in the future. Nevertheless, illness severity scores will never be indicative of absolute irreversibility of disease or impossibility of survival. Advances in computer technology should assist in achieving many of the future goals of prognostic scoring systems. Most of the physiological data are available from ICU monitors and computerized laboratory systems. By electronically interfacing with the ICU monitor an automated patient data entry is possible and will provide that prognostic scores can be made available to the clinician daily.

Critical Care↗

The prevention of anastomotic leakage after total gastrectomy with local decontamination. A prospective, randomized, double-blind, placebo-controlled multicenter trial.

OBJECTIVE: A prospective, randomized, double-blind, placebo controlled multicenter trial was undertaken in 205 patients treated with total gastrectomy for gastric malignancies to evaluate whether local antimicrobial measures reduce the incidence of esophagojejunal anastomotic leakage. SUMMARY BACKGROUND DATA: Anastomotic leakage of the esophagojejunostomy is always a septic complication of total gastrectomy for gastric malignancies, but it never has been attempted to prevent this complication with the administration of topical antimicrobial agents during the critical phase of anastomotic wound healing. METHODS: To evaluate the efficacy and safety of topical decontamination, the study was carried out as a prospective, randomized, double-blind and placebo-controlled clinical multicenter trial in patients with total gastrectomy for gastric cancer. Patients received either placebo or decontamination with polymyxin B (100 mg), tobramycin (80 mg), vancomycin (125 mg), and amphotericin B (500 mg) four times per day orally from the day before the operation until the seventh postoperative day. All patients received a perioperative intravenous prophylaxis with cefotaxime 2 x 2 g. Other interventions including the administration of antibiotics and fluids, were not affected by the study protocol. RESULTS: Of 260 patients who were randomized, total gastrectomy was not carried out in 55 patients. They dropped out of the study. Patients receiving an esophagojejunostomy were observed until day 42, when they were discharged from the clinic or died. An intention-to-treat analysis of the data was carried out. Among the 103 recipients of placebo, there were 11 (10.6%) with an anastomotic leakage of the esophagojejunostomy, and among the 102 recipients of decontamination, there were 3 (2.9%) with an anastomotic leakage of the esophagojejunostomy (p = 0.0492). Pulmonary infections were observed in 23 patients (22.3%) receiving placebo and in 9 patients (8.8%) who were decontaminated (p = 0.02). There were 11 deaths (10.6%) among the recipients of placebo and 5 deaths (4.9%) among the recipients of decontamination (p = 0.1). CONCLUSIONS: Decontamination with polymyxin, tobramycin, vancomycin, and amphotericin B during anastomotic wound healing is safe and effective in the prevention of esophagojejunal anastomotic leakage after total gastrectomy.

Aged↗

Influence of intravenously administered ciprofloxacin on aerobic intestinal microflora and fecal drug levels when administered simultaneously with sucralfate.

Ciprofloxacin, when given intravenously (i.v.), is secreted in significant amounts via the mucosa into the intestinal lumen. Sucralfate inhibits the antimicrobial activity of ciprofloxacin. The effect of combined therapy on the intestinal flora was investigated in 16 healthy volunteers. They were randomly assigned to two groups. Group A received 2 g of sucralfate orally three times a day for 7 days and 400 mg of ciprofloxacin i.v. twice a day (b.i.d.) starting 3 days after the sucralfate administration began. Group B was given only 400 mg of ciprofloxacin i.v. b.i.d. for 4 days. A total of 9 stool samples were collected from each subject beginning the week before ciprofloxacin was administered and on days -1, 1, 2, 3, 4, 7, 9, and 10 or 11 after commencement of the infusion period. The aerobic fecal flora was determined by standard microbiological methods. Measurements of fecal ciprofloxacin levels were based on high-performance liquid chromatography. Counts of bacteria of the family Enterobacteriaceae decreased in all subjects and were below 10(2) CFU/g in eight of eight subjects (group A) and six of eight subjects (group B) on day 4, but they returned to normal in all but one subject (group A) 10 days after the last infusion. The decreases in levels of bacteria of the family Enterobacteriaceae were not significantly different in groups A and B (Kaplan-Meier test). Staphylococci and nonfermenters responded variably, enterococci and lactobacilli remained unchanged, and candida levels increased transiently in four subjects (two in each group). Maximum fecal drug levels ranged from 251 to 811 microg/g. No significant difference could be found between the two groups. The i.v. application of ciprofloxacin eliminates intestinal bacteria of the family Enterobacteriaceae in a rapid and selective manner. This effect is not affected by simultaneous oral application of sucralfate.

Adult↗

[Potentialities and limitations of the score system in intensive medicine].

In intensive-care medicine, score systems serve to quantify the severity of diseases and to characterise patient groups on the basis of objective criteria. The principle is to describe the severity by adding up points. Objectives are to assess the prognosis, to establish the amount of treatment required and assist in clinical decision making. The most important examples of general scores covering more than one disease are Acute Physiology And Chronic Health Evaluation (APACHE-II, APACHE-III), Simplified Acute Physiology Score (SAPS) and Mortality Prediction Model (MPM). General scores assess the deviation of physiological parameters from the normal assuming that the degree of deviation reflects the severity of the disease. The Therapeutic Intervention Scoring System (TISS) constitutes a particular form which evaluates exclusively the amount of therapy required. Disease-specific scores (trauma scores, sepsis scores) take into account the fact that the nature and stage of specific disease determine the outcome in a typical way. Scores are adequately validated and suitable for evaluation of clinical studies or cost-benefit analyses by characterisation of patient populations. The use of score systems for individual prognosis is at present controversial. Their clinical significance might increase in that scores help to make medical decisions by contributing to early identification of endangered patients by systematic establishment and evaluation of investigation results. Scores are likely to be used increasingly in intensive-care medicine.

Critical Care↗