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Biomedical subjects

K Rentsch

Publications and source records attributed to K Rentsch.

14 recordsLinked to original sources
PubMed2006

Intrapleural topical application of cisplatin with the surgical carrier Vivostat increases the local drug concentration in an immune-competent rat model with malignant pleuromesothelioma.

OBJECTIVE: We sought to investigate whether intrapleural topical application of cisplatin with a surgical carrier has a prolonged local tissue level in comparison with cisplatin solution while reducing systemic toxicity. METHODS: Forty immune-competent Fischer rats were inoculated with 10(6) mesothelioma cells. Ten days later, left pneumonectomy with tumor debulking was performed. Twenty animals underwent local application of cisplatin solution (100 mg/m2), whereas the same quantity of cisplatin was topically applied as a gel with the Vivostat (Vivolution) system in 20 other animals. In each group 5 subgroups of 4 animals were defined according to the harvesting time of blood and tissue samples (2, 4, 24, and 72 hours and 1 week) after local therapy. Platinum concentrations in serum and tissue and systemic toxicity were analyzed. RESULTS: Platinum concentrations in tissue were significantly higher in the gel group (group 1) than in the solution group (group 2) at 1, 3, and 7 days after therapy (1510, 1224, and 1069 pg/mg for group 1 vs 598, 382, and 287 pg/mg for group 2; P = .007, P = .005, and P = .0002, respectively). Laboratory findings showed renal insufficiency in the animals of the solution group at 1 week, with values of 98 mmol/L versus 7.7 mmol/L for urea and 410 mumol/L versus 43 mumol/L for creatinine (P = .02 and P = .01, respectively), which was confirmed by means of pathologic analysis. CONCLUSIONS: Intrapleural administration of cisplatin with the carrier Vivostat significantly provides sustained higher platinum concentrations up to 1 week in tissue in comparison with application of cisplatin solution without conferring systemic toxicity in this model.

Administration, Topical↗
PubMed2004

Concentration of rocuronium in cerebrospinal fluid of patients undergoing cerebral aneurysm clipping.

BACKGROUND: This study assessed the concentration of rocuronium in the cerebrospinal fluid (CSF) of patients undergoing cerebral aneurysm clipping, and investigated whether the mode of administration (single bolus vs continuous infusion) influenced the CSF concentration. METHODS: Twenty patients with subarachnoid haemorrhage were randomly allocated to receive a bolus dose (bolus group), or a bolus followed by a continuous infusion of rocuronium (infusion group) (n=10 for each group). Arterial blood and ventricular CSF were sampled 2 h after the rocuronium bolus. Samples were analysed by liquid chromatography electrospray ionization-tandem mass spectrometry. RESULTS: Rocuronium could be detected in all the CSF samples. The mean (range) CSF concentration was 2.2 (0.9-4.6) ng x ml(-1) in the bolus group and 12.4 (2.4-34.6) ng x ml(-1) in the infusion group; P<0.01. CONCLUSIONS: This study demonstrated that rocuronium, normally not considered to cross the blood-brain barrier, is regularly found in the CSF of patients undergoing cerebral clipping; continuous infusion of the drug led to higher plasma and CSF concentrations than after a single bolus dose.

Adult↗
PubMed2001

[Fatal brain edema after ingestion of ecstasy and benzylpiperazine].

HISTORY AND ADMISSION FINDINGS: A 23-year-old woman was hospitalized with headache, malaise and somnolence 11 hours after ingestion of A2 (benzylpiperazine), 7 hours after ingestion of ecstasy (MDMA), and large volume of fluids. On admission she had bradycardia (heart rate 48/min), hypertension (blood pressure 154/95 mm Hg), and reduced consciousness with diminished tendon reflexes and non-reacting pupils (Glasgow Coma Score 6). INVESTIGATIONS: Serum sodium was markedly decreased (115 mmol/l [normal 135-145]) with low plasma osmolality (246 mosm/kg [normal 280-300]). Other laboratory findings were within normal limits. TREATMENT AND COURSE: The patient had severe hypervolaemic hypotonic hyponatraemia. 40 minutes after admission she seized twice and was intubated. Brain CT scan showed massive cerebral oedema with beginning tonsillar herniation. Serum sodium concentration returned to normal within 38 hours, but the patient deteriorated neurologically with increasing tonsillar herniation detected in a second brain CT scan. The patient died 57 hours after admission. CONCLUSION: 13 cases of MDMA-associated severe hyponatraemia are reported. Intake of fluids after MDMA ingestion may lead to potentially fatal hypervolaemic hypotonic hyponatraemia with cerebral oedema. Symptoms appear about 8 hours (range 4-18) after MDMA ingestion. Even low doses of MDMA and fluids may lead to a serious outcome. The only risk factor is female gender. Measurement of serum sodium and brain CT scan is recommended in all patients with altered mental status after MDMA consumption.

Adult↗
PubMed2001

Different patterns of mast cell activation by muscle relaxants in human skin.

BACKGROUND: Activation of mast cells and systemic release of histamine are major side effects of intravenously administered muscle relaxants. In the current study, dermal microdialysis was used for the investigation of mast cell activation by muscle relaxants. Dermal microdialysis enabled simultaneous assessment of mediator release, vascular reactions, and sensory effects induced by intradermal application of muscle relaxants without systemic side effects. METHODS: Succinylcholine, the isoquinolines cisatracurium, atracurium, and mivacurium, and the steroids pancuronium, vecuronium, rocuronium, and rapacuronium were tested in human volunteers (n = 6 each). After intradermal insertion of microdialysis capillaries (0.4 mm diameter, cutoff 3,000 kd) and a 60-min equilibration period, the muscle relaxants were delivered via the capillaries for 30 min, followed by a 30-min washout period. Dialysate was sampled at 15-min intervals, and histamine, mast cell tryptase, and protein extravasation were determined. Changes in skin blood flow were measured using a laser Doppler imager. Potency and efficacy were derived from nonlinear fittings of the dose-response curves. RESULTS: For succinylcholine and the isoquinolines, dose-response curves for the vascular and sensory effects paralleled the histamine and tryptase release. In contrast, aminosteroids evoked a rapid histamine release that was accompanied by a delayed increase in tryptase. CONCLUSIONS: Dermal microdialysis has been successfully used to simultaneously assess mediator release, vascular reactions, and sensory effects. The different pattern of tryptase release by isoquinolines and aminosteroids suggests different mechanisms of mast cell activation.

Adult↗
PubMed2000

Rapid detection of the CYP2D6*3, CYP2D6*4, and CYP2D6*6 alleles by tetra-primer PCR and of the CYP2D6*5 allele by multiplex long PCR.

BACKGROUND: Interindividual differences in CYP2D6 activity range from total absence of metabolism of certain drugs to ultrafast metabolism and can produce adverse effects or lack of therapeutic effect under standard therapy. Several mutations have been described in the CYP2D6 gene that abolish CYP2D6 activity. However, four mutations explain the majority of the poor metabolizers. We describe four single-tube assays to detect these mutations. METHODS: Three tetra-primer PCR assays were developed to detect the mutations in the CYP2D6*3, *4, and *6 alleles. In these single-tube assays, the CYP2D6 locus is amplified directly, followed by the allele-specific amplification on this new template. In addition, a multiplex long PCR was developed to genotype the CYP2D6*5 allele. Two long PCR amplifications for detection of the deletion of CYP2D6 (*5) and for detection of the CYP2D6 gene region were combined in one tube. RESULTS: Analysis of 114 alleles showed no CYP2D6*3 allele, and allele frequencies of 28.1% for CYP2D6*4, 2.6% for CYP2D6*5, and 0. 9% for CYP2D6*6. Re-analysis of the DNA samples by restriction fragment length polymorphism and sequencing analysis confirmed these results. Furthermore, re-analysis of sequenced genomic DNA by tetra-primer PCR analysis (7-11 times) always showed identical results. CONCLUSIONS: Our set of single-tube assays allows rapid and reproducible genotyping of the majority of CYP2D6 poor metabolizers.

Alleles↗
PubMed1996

Physiologic effects of anesthesia induced and maintained by intravenous administration of a climazolam-ketamine combination in ponies premedicated with acepromazine and xylazine.

OBJECTIVE: To examine the physiologic and pharmacokinetic effects of a technique of total intravenous anesthesia in ponies. ANIMALS: 6 healthy ponies. PROCEDURE: Ponies were premedicated with acepromazine (0.03 mg/kg of body weight, IV) and xylazine (1.0 mg/kg, IV). Two minutes later, anesthesia was induced with ketamine (2.0 mg/kg, IV) followed by climazolam (0.2 mg/kg, IV). Anesthesia was maintained for 120 minutes by an infusion of climazolam (0.4 mg/kg/h) and ketamine (6.0 mg/kg/h). Oxygen (5 L/min) was supplemented. 20 minutes after the infusion was stopped sarmazenil (0.04 mg/kg, IV) was administered. Cardiovascular and respiratory function measurements were taken before and after premedication, and during anesthesia. Plasma cortsol, ACTH, and catecholamine concentrations were used to assess adrenal and pituitary gland function Ketamine and climazolam kinetics were calculated, on the basis of plasma drug concentrations. RESULTS: There were no significant changes from pre-xylazine values in heart rate, respiratory rate, arterial blood pressure, cardiac index, systemic vascular resistance, or arterial PO2, PCO2, and pH. Plasma cortisol concentration decreased during anesthesia, but plasma ACTH and catecholamine concentrations did not change. Recovery was fairly smooth, but some excitement and ataxia were noted in 2 ponies. CONCLUSION: Ketamine-climazolan infusion appeared suitable for maintenance of anesthesia in ponies, although recovery was not ideal in 2 of 6 ponies.

Acepromazine↗
PubMed1995

Development of a gas chromatography-mass spectrometry method for determination of ketamine in plasma and its application to human samples.

A sensitive and precise gas chromatography-mass spectrometry method with selected ion monitoring has been developed for identification and quantification of the phencyclidine derivative ketamine in human plasma. The assay is based on an alkaline extraction from aqueous to organic solvent from plasma and an efficient gas chromatographic separation on a DB-5 capillary column. The analytical procedure has a coefficient of variation of 0.7-6.2% and from 1.3 to 8.7% within-day and from day-to-day analysis, respectively. The low level of sensitivity was 10 ng/ml. It was used to measure low plasma concentrations in volunteers during ketamine-induced experimental psychosis. The method is not enantio selective.

Adult↗
PubMed1994

Relation of cyclosporine blood levels to adverse effects on lipoproteins.

Hyperlipidemia is common in renal allograft recipients. To elucidate the role of cyclosporine in posttransplant hyperlipidemia, we measured lipids, lipoprotein lipids, and apolipoproteins of thirty-five renal allograft recipients and evaluated their relation to trough cyclosporine blood levels. All patients were on a triple immunosuppressive regimen with equal doses of prednisone and azathioprine, and had stable graft function. Cyclosporine blood levels were significantly correlated to total plasma cholesterol (P = 0.028), low-density lipoprotein cholesterol (P = 0.022), apolipoprotein B (P = 0.017), and the cholesterol/high-density lipoprotein cholesterol ratio (P < 0.002), but not to plasma triglycerides. Significant inverse correlations were found between cyclosporine blood levels and high-density lipoprotein cholesterol (P = 0.034), high-density lipoprotein3 cholesterol (P = 0.025), and apolipoprotein A-1 (P = 0.047), but not high-density lipoprotein2 cholesterol. The independent relation of cyclosporine blood levels to each of the measured lipid parameters was investigated by a stepwise regression model including age, body mass index, interval from transplantation, diabetes mellitus, plasma creatinine, and intake of diuretics and beta-blockers. After correction for these 7 variables, cyclosporine blood levels remained significantly associated with high-density lipoprotein cholesterol, high-density lipoprotein3 cholesterol, apolipoprotein A-1, apolipoprotein B, low-density lipoprotein cholesterol, and the cholesterol/high-density lipoprotein cholesterol ratio. These data suggest that cyclosporine causes atherogenic dyslipidemia.

Adult↗
PubMed1994

Plasma triglycerides and three lipoprotein cholesterol fractions are independent predictors of the extent of coronary atherosclerosis.

BACKGROUND: The lipoprotein system has manifold links to atherosclerotic disease. LDL cholesterol is related to lesion formation and growth. The cholesterol of HDLs is indicative of protection against atherosclerosis. The status of triglycerides and of subfractions of high-density lipoproteins as risk factors is less certain. Also, the magnitude of the atherogenic/protective power of these factors is not known. METHODS AND RESULTS: Five hundred patients (418 men and 82 women) were enrolled in an angiographic study. A total of 1006 coronary lesions with > or = 50% narrowing were recorded as study end points. By extent of atherosclerosis, defined as the number of > or = 50% lesions, the study subjects were allocated to one of four ordered categories with 0, 1 to 3, 4 to 6, or 7 to 10 lesions, respectively. Subfractions of HDL cholesterol were determined by a dual precipitation method. By a polychotomous logistic regression model, it was found that, besides age and sex, LDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, and triglycerides were independently predictive (P < .05) of the extent of coronary atherosclerosis. An increase in age by 10 years was associated with an increase of the odds ratio for falling into a higher-extent category by a factor of 1.64, and the same increase of the odds ratio was obtained by increasing LDL cholesterol by 0.92 mmol/L or triglycerides by 1.01 mmol/L and by decreasing HDL2 cholesterol by 0.20 mmol/L or HDL3 cholesterol by 0.46 mmol/L. The less sensitive coronary end point, presence of atherosclerosis (ie, observation of > or = 1 lesion of > or = 50%) depended significantly on age, sex, LDL cholesterol, and HDL2 cholesterol, but not on HDL3 cholesterol or triglycerides. CONCLUSIONS: In addition to LDL, HDL2, and HDL3 cholesterol, triglycerides also proved independently predictive of the extent of coronary atherosclerosis.

Cholesterol, HDL↗
PubMed1992

Relation of the level of high-density lipoprotein subfractions to the presence and extent of coronary artery disease.

Plasma lipid profiles, including high-density lipoprotein (HDL) subfractions HDL2 and HDL3, were obtained in 115 men undergoing coronary angiography to assess the relation of lipid levels to coronary artery disease (CAD). CAD was present in 87 patients (76%) and absent in 28 (24%). The largest difference between the 2 groups were observed for HDL2 cholesterol, with a mean of 0.13 mmol/liter (5 mg/dl) in patients with CAD compared with 0.25 mmol/liter (10 mg/dl) in those without CAD (p less than 0.005). Smaller differences were found for HDL3 (1.02 mmol/liter [39 mg/dl] vs 1.19 mmol/liter [46 mg/dl]; p less than 0.005) and HDL (1.15 vs 1.42 mmol/liter [45 vs 55 mg/dl]; p less than 0.001) cholesterol, and apolipoprotein A-1 (1.37 vs 1.50 g/liter; p less than 0.01) and plasma triglycerides (1.79 vs 1.38 mmol/liter [159 vs 122 mg/dl]; p less than 0.05). No significant difference was found for plasma and low-density lipoprotein cholesterol, and apolipoprotein B levels. Simple regression analysis revealed that the most powerful independent variable associated with the extent of CAD was HDL2 cholesterol (Spearman rho = 0.311; p less than 0.001). Stepwise multiple regression analysis proved HDL2 cholesterol and age to be the strongest predictors of extent of CAD. The level of HDL2 cholesterol was reasonably well correlated with HDL cholesterol (r2 = 0.6; p less than 0.0001), but less so with plasma apolipoprotein A-1 (r2 = 0.4; p less than 0.0001). The data add to the growing body of information demonstrating an important association of HDL (and more specifically HDL2) with CAD in men.

Age Factors↗