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Biomedical subjects

K Erdmann

Publications and source records attributed to K Erdmann.

At least 19 recordsLinked to original sources

Rosuvastatin upregulates the antioxidant defense protein heme oxygenase-1.

Cholesterol-independent, pleiotropic actions of HMG-CoA reductase inhibitors (statins) lead to anti-inflammatory and antioxidant actions by as yet unidentified mechanisms. This study explores the role of heme oxygenase-1 (HO-1) as target and potential mediator of rosuvastatin. In cultured human endothelial cells (ECV 304), rosuvastatin increased HO-1 mRNA and protein levels in a concentration-dependent fashion. HO-1 induction by rosuvastatin remained unaffected by mevalonate and N-nitro-L-arginine-methylester, showing that isoprenoid- and NO-dependent pathways were not involved. Pretreatment of endothelial cells with rosuvastatin reduced NADPH-dependent production of oxygen radicals. The HO-1 metabolite bilirubin, when added exogenously to the cells, virtually abolished NADPH-dependent oxidative stress. Rosuvastatin-induced inhibition of free radical formation was rescued in the presence of the HO inhibitor, tin protoporphyrin-IX. Our results demonstrate that HO-1 is a target site and antioxidant mediator of rosuvastatin in endothelial cells. This novel pathway may contribute to and partially explain the pleiotropic antiatherogenic actions of rosuvastatin.

Antioxidants↗

Does bile of patients with acute gallstone pancreatitis cause pancreatic inflammatory lesions? A study of the pancreatic toxicity of choledochal secretions collected at ERCP.

BACKGROUND: Bile flow into the pancreatic duct has been proposed as the cause of acute biliary pancreatitis. However, the pancreatic toxicity of choledochal bile from patients with acute gallstone pancreatitis has not been studied. METHODS: Bile was collected endoscopically from the common bile ducts of 21 patients with acute gallstone pancreatitis within 72 hours after the onset of disease. The bile samples were instilled into the pancreatic duct of rabbits, and light microscopic examination of the pancreas morphology was performed to assess the toxicity of human bile. Microbiologic quantitative analysis of the aerobic and anaerobic bacterial bile flora was performed. RESULTS: Bile of six patients with acute gallstone pancreatitis (29%) induced interstitial inflammation in the rabbit pancreas. Choledochal bile of these patients harbored more than 10(4) CFU/mL bacteria (Proteus vulgaris, n = 1; Klebsiella pneumoniae, n = 1; Escherichia coli, n = 2; enterococci, n = 2). After sterilization, the bile samples did not induce acute pancreatitis. In 15 patients (71%), bile did not cause acute pancreatitis in the rabbit pancreas. These choledochal secretions were sterile or contained less than 10(4) CFU/mL. CONCLUSIONS: Reflux of infected bile may be a potential cause of acute pancreatitis in the minority of patients with bacterobilia. In most patients with gallstone pancreatitis, bile is neither infected nor harmful to the pancreas, and its flow into the gland is unlikely to be the cause of inflammation.

Acute Disease↗

Vancomycin dosing in haemodialysis patients and Bayesian estimate of individual pharmacokinetic parameters.

A dose reduction of vancomycin to 1000 mg once a week usually is recommended for haemodialysis patients. Our modified dosing schedule consists of a loading dose of 1000 mg and a maintenance dose of 500 mg administered 3 times a week after haemodialysis. Different vancomycin regimens were retrospectively evaluated by therapeutic drug monitoring and bayesian parameter estimates in 39 dialysis patients. The mean (+/- SD) trough level in 7 patients receiving only the conventional dosage regimen was significantly lower than in 17 patients strictly treated by the modified schedule (7 +/- 4 versus 17 +/- 8 mg/L; p = 0.001). The corresponding peaks were low in both groups and no different (23 +/- 10 versus 27 +/- 12 mg/L). The one week average vancomycin clearance was significantly lower in the conventional dosage group compared to the modified dosage group (6 +/- 3 versus 10 +/- 3 ml/min; p = 0.001). High-flux dialysers were not used in the conventional dosage group but for 30 percent of the procedures in the modified dosage group, where the vancomycin one week average elimination half-life was 66 hours (+/- 18) and the volume of distribution 50 litres (+/- 5). As compared to the bayesian programme, NONMEM calculated comparable pharmacokinetic parameters but could be applied only in 5 cases with a sufficient number of concentration measurements. Ototoxicity occurred in 1 patient, whereas vancomycin treatment was judged as ineffective against infection in 5 of the 39 patients. Their troughs were below 15 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Nonlinear kinetics and the 1-exp function in nephropharmacology.

The basic law in nephropharmacology states that pharmacokinetic parameters depend linearly on renal function. Few exceptions to linear dependence have been reported, e.g. substances with saturable tubular reabsorption or secretion. A further example is cyclosporin, which was found to be eliminated according to log-concave nonlinear kinetics in 3 patients with hepatotoxicity after kidney transplantation. The nonlinear cyclosporin kinetics were computer-fitted to the integrated forms of the 1-exp function and the Michaelis-Menten equation by nonlinear regression analysis. The same maximal velocity (Vmax = 23 ng ml-1 h-1) and Michaelis constant (Km = 686 ng ml-1) were calculated for cyclosporin when applying either the 1-exp function or the Michaelis-Menten equation. The nonlinear elimination of cyclosporin, however, was described even more closely by the 1-exp function than by the Michaelis-Menten equation.

Humans↗

Median nerve blockade during diagnostic intravenous regional anesthesia as measured by somatosensory evoked potentials.

Intravenous regional anesthesia (IVRA) may be used as a diagnostic method in patients suffering from chronic pain in the forearm or hand to differentiate the origin of pain within the anesthetic area from that above. For this purpose it needs to be proven that all nerve fibers are blocked and that conduction blockade induced by IVRA takes place within the nerve trunks. Therefore the transmission of impulses in a nerve trunk to the central nervous system has been studied. Diagnostic intravenous regional anesthesia (5 mg/kg mepivacaine 1%) of the arm was performed in eight patients for 30 min. Short-latency somatosensory evoked potentials (SSEPs) induced by median nerve stimulation at the wrist were recorded from the scalp at 5-min intervals before, during, and after IVRA. In five patients, sensory nerve action potentials (SNAPs) of the median nerve, at the elbow and axilla, and SSEPs at spinous processus C-7 were recorded simultaneously. During IVRA the function of the nerve fibers which are assumed to mediate pain was tested by the patient's sensation following median nerve stimulation at an intensity which evoked pain before IVRA. During IVRA, peak latencies of the scalp recorded SSEPs (N20) increased progressively and interpeak amplitudes (N20/P25) decreased. After 20 min, SSEPs could no longer be recorded, and median nerve stimulation no longer evoked any sensation at all. After deflation of the cuff, both peak latency (N20) and interpeak amplitude (N20/P25) of SSEPs recovered. The changes in latency and amplitude of SSEPs from the scalp as well as SNAPs and SSEPs from the neck were similar. Because SSEPs, SNAPs, and the pain sensation following median nerve stimulation disappeared during IVRA, it may be concluded that the thick and thin myelinated nerve fibers of the median nerve have been blocked. For diagnostic use, IVRA is superior to peripheral nerve blockade, which has been shown previously to not abolish SSEPs.

Adult↗

Nonparametric meta-analysis of published data on kidney-function dependence of pharmacokinetic parameters for the aminoglycoside netilmicin.

The distribution and elimination of various drugs depend on kidney function. This dependence is published either as a linear regression equation or as the discrete extreme values for normal kidney function and anuria. A meta-analysis of the published pharmacokinetic data is required to build up a knowledge-based computer system for dosage adjustment in renal failure. A sample comparison of 4 statistical methods for meta-analysis was performed by applying them to 13 publications about the aminoglycoside netilmicin. Parametric meta-analytical methods I and II are based on regression equations alone (Z-transformation, maximum likelihood) and yield unreliable data, especially with regard to extreme values for anuria. The parametric meta-analytical method III is based on means of extreme values (standard 2-stage approach) and does not permit a decision as to whether linear interpolation of a parameter (e.g. volume of distribution) can be used for all degrees of renal insufficiency. In contrast, the nonparametric median (meta-analytical method IV) is based on the extreme values calculated from regression equations and empirical extreme values combined into 1 group of data on normal kidney function and another on anuria. For netilmicin, the meta-analytical median with the 95% confidence interval (95% CI) yields a significant increase in the dominant elimination half-life from 2h (95% CI 1.9h, 2.6h) in patients with normal kidney function to 45h (95% CI 41h, 301h) in those with anuria (p = 0.001). For a normal bodyweight of 65kg, the volume of distribution also increases significantly from 13L (95% CI 9L, 15L) to 20L (95% CI 14L, 21L) in patients with anuria (p = 0.04). Thus, drug dosage adjustment according to therapeutic peak and trough concentrations requires knowledge of the distribution and elimination parameters, since they can both be independently altered in renal failure. We conclude that the most robust meta-analysis of these alterations is achieved with the nonparametric median of extreme values.

Creatinine↗

[The potentialities of EEG analysis using the Lifescan in anesthesiology].

In 87 patients a new computerized EEG monitor was used in clinical anesthesia. Following aperiodic analysis, the Lifescan shows the computerized EEG in a striking color visualization allowing recognition of changes in the course of the EEG and of interhemispheric differences. The computerized EEG can be read after a brief training period. The changes caused by different clinical situations are visualized in detail. Different changes were observed with the anesthetics used. During induction with thiopentone a sudden increase in activity was obvious. During a lighter level of anesthesia with thiopentone beta activity was easily recognizable. During induction with high-dose fentanyl frequency was slowed over a long period and activity was increased. The monitor shows the changes in the lower frequency range in detail. A bimodal pattern occurred with a higher dosage of enflurane. During lightening of anesthesia with enflurane a typical pattern indicated return to consciousness. When nitrous oxide was administered during anesthesia with halothane, and to a lesser degree during anesthesia with enflurane or isoflurane, remarkable slowing and decrease in activity occurred. The monitor allowed detailed recognition of the different patterns obtained with the various anesthetics. In some cases it was possible to say what dosage of the anesthetic used had been given or what depth of anesthesia had been achieved. The effect of combined anesthesia, however, was difficult to judge. In carotid artery surgery a quick unilateral decrease in activity and slowing of frequency indicated cerebral ischemia and quickly disappeared after insertion of a shunt. This change was particularly obvious with the new monitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

High spinal anesthesia does not depress central nervous system function as measured by central conduction time and somatosensory evoked potentials.

Short-latency somatosensory evoked potentials (SSEPs) in response to median nerve stimulation were recorded from the neck and the scalp before and during diagnostic high spinal anesthesia (touch T3, pinprick C8) in six patients with chronic pain. The central conduction time--the time difference between the neck-recorded N13 and the scalp-recorded N20--and the amplitudes of the SSEPs did not change in a statistically significant way during high spinal anesthesia. However, latencies of the neck-recorded N13 and the scalp-recorded N20 and P25 increased slightly. This may have been due to a local anesthetic effect on those spinal roots of the median nerve in which segmental pinprick analgesia occurred. Because high spinal anesthesia did not depress central nervous function, as measured by central conduction time, and SSEP amplitudes, it is concluded that scalp-recorded SSEPs during high spinal anesthesia measure the effects of local anesthetics in the cerebrospinal fluid on neuronal pathways outside the brain.

Adult↗

[Transpapillary endoprostheses in malignant and benign bile duct diseases].

During the last years the non-surgical drainage of the bile ducts developed to an efficient treatment method and is a real enrichment in the concept of treatment of the malignant obstruction of the bile ducts. In no more radically operable carcinomas in the area of the bile ducts, the pancreas or the porta of the liver it is to be preferred to a palliative drainage operation. In case the drainage of the bile ducts shall not be used therapeutically (through-drainage), an inner drainage in form of an endoprosthesis should always be preferred. As a procedure of the 1st choice the endoscopic retrograde technique is recommended, as procedure of 2nd choice the percutaneous transhepatic technique. Benign basic diseases are more infrequently the reason for the insert of a bile duct drainage. The main indications are general inoperability in non-extractable calculi in the common bile duct. In our own cases patients could be followed up up to 3.5 years. No complications were observed. The occlusion of prostheses does apparently not play a role.

Ampulla of Vater↗

[Clinical aspects, diagnosis and therapy of cancer of Vater's ampulla].

The carcinoma of the papilla occupies a special position among the periampullary carcinomas by its favourable prognosis. Responsible for this are the early appearance of symptoms due to the close neighbourhood to the common bile duct and the restriction of the metastasation to the first stage of lymphatic nodes in the majority of cases. Symptoms are jaundice, epigastric pain and decrease of weight. In the carcinoma of the papilla the duodenoscopy with biopsy and ERCP is the method of choice. The reliability of the biopsy is larger, when it is performed after an endoscopic sphincterotomy. For the delimitation of the carcinoma of the papilla against other causes can further be used the hypotensive duodenography, the abdominal computerd tomography, the sonography and the PTC. A curative treatment is possible only surgically. On account of the better long-term results the partial duodenopancreatectomy is to be preferred to the local exstirpation of the papilla. Endoscopic drainages of the biliary tract carried out preoperatively may reduce the lethality of operations. A palliative drainage of the biliary tract on the endoscopic or percutaneous transhepatic way as well as the endoscopic sphincterotomy may improve the patients' quality of life and prolong the survival time, when there are non-resectable tumours or a general inoperability.

Ampulla of Vater↗

[Biliary pancreatitis--pathogenesis, therapy, results].

According to current knowledge biliary (gallstone-associated) acute pancreatitis is induced by transient obstruction of the papilla by migrating gall stones. It seems, therefore, rational to remove the occluding stone as early as possible by endoscopic papillotomy (EPT). Uncontrolled studies have shown that patients with acute pancreatitis are not more endangered by EPT than those without pancreatitis and that the intervention seems to beneficially influence the course of the pancreatic disease. Early endoscopy (within 48 h), however, revealed incarcerated papillary stones only in 10% but common bile ducts free of stones in 24%. There seems to be only a small subgroup with acute biliary pancreatitis who might benefit from early EPT. This subgroup should be characterized more precisely. Early EPT indiscriminately performed in any kind of acute pancreatitis has little rational ground and is, up to now, not justified.

Acute Disease↗

[Does the duration of work disability in patients with uncomplicated duodenal ulcer affect risk of recurrence the following year? A multicenter study].

At present there is no therapeutic approach conducive to success, with the help of which the inclination to recidivation of duodenal ulcer might be restricted. In a prospective multicentric study with the help of two randomized groups of patients (group A: 13 days of disablement, group B: 37 days of disablement) was tried to prove a possible influence of the duration of the disablement on the inclination to recidivation in ulceration. In comparable groups of patients out of 99 evaluable documentations of patients in group A were found 62.5% of recidivations, in group B 68.6%. The difference was not significant. No connection could be found between duration of the disablement in ulceration and inclination to recidivation. Smokers have a distinctly higher inclination to recidivation than non-smokers.

Absenteeism↗

'Anestheticography': on-line monitoring and documentation of inhalational anesthesia.

The safe practice of inhalational anesthesia requires control over the amount of volatile anesthetic delivered to the patient. With minimal fresh gas flow this is facilitated by continuous monitoring and recording of the agent's concentration ('Anestheticography'). Alterations brought about by routine clinical maneuvers become visible. We recorded the course of the inspiratory and expiratory concentration of volatile anesthetic (Isoflurane) by infrared absorption and a trend recorder. Changing the carrier gas composition during high flow from 75% to 25% nitrous oxide in oxygen resulted in a 10% increase of the inspiratory isoflurane concentration. Activating the oxygen bypass or exchanging the soda lime canisters was followed by a prolonged disturbance of concentrations, most pronounced with minimal flow. Initiating emergence by closing the vaporizer during minimal flow led to a slow decrease in concentration whilst at a flow of 61/min the inspiratory isoflurane concentration rapidly decreased to subanesthetic levels. Insertion of a charcoal filter into the inspiratory limb of the breathing circuit immediately dropped the inspiratory concentration to undetectable levels. 'Anestheticography' is a useful means of monitoring and documentation of inhalational anesthetic. With the use of a charcoal filter all advantages of minimal flow anesthesia can be realized throughout the entire anesthetic, including emergence.

Anesthesia, Inhalation↗

[Coincidence of chronic pancreatitis and duodenitis].

Biopsies taken from various regions of the duodenal mucosa were investigated with a quantitative histological method with a view to frequency, quantity, and localisation of the duodenitis in clinically proven chronic pancreatitis. The histologic classification of duodenitis was made according to Whitehead et al. Out of 46 patients suffering from a chronic pancreatitis, 19 had a duodenitis grade 1 in the pars superior and pars descendens. A more frequent occurrence of duodenitis with concomitant chronic gastritis or a pathologic condition of the bile duct or a chronic alcohol abuse could not be proved statistically.

Aged↗

[Bupivacaine-CO2 and bupivacaine-HCl at various injection temperatures in peridural anesthesia for extracorporeal shock wave lithotripsy].

INTRODUCTION: The effect of different injection temperatures on carbonated anesthetics has been controversial since 1965. The current study was undertaken to determine onset times of sensory and motor blockade after epidural anesthesia with 0.5% bupivacaine-CO2 and 0.5% bupivacaine-HCl at various injection temperatures. MATERIALS AND METHODS: The study was performed on 90 ASA class I-II urologic patients during extracorporeal shock wave lithotripsy. The patients were randomized in six groups to receive either 0.5% bupivacaine-CO2 or 0.5% bupivacaine-HCl at temperatures of 4 degrees, 20 degrees, or 36 degrees C. The six groups were comparable in age, height, and weight. Epidural anesthesia was performed at the L2-3 interspace with an 18-gauge Tuohy needle using loss of resistance. A catheter was advanced 4 cm in the epidural space and 4 ml 0.5% bupivacaine with adrenaline 1:200,000 was given as a test dose. After 4 min the full anesthetic dose, based on body size, was injected with the patient supine. Sensory blockade was determined by the pinprick method and motor blockade by the Bromage method at 2-min intervals for the first 20 min, at 5-min intervals for the next 10 min, and then every 15 min to a total of 240 min. Statistical analysis was done by the Mann-Whitney test, with P less than 0.05 considered significant. RESULTS: Spread of sensory blockade was significantly faster with bupivacaine-CO2 and -HCl at a temperature of 36 degrees C as compared to 4 degrees or 20 degrees C (P less than 0.05) (Figs. 1, 2 and Table 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗

Malignant hyperthermia susceptibility--successful management with a "stressfree" technique.

The pathogenesis of the malignant hyperthermia syndrome is not yet completely understood. There is evidence of involvement of the sympathoadrenergic system. We describe the anesthetic management of two patients considered to be MH-susceptible. Management in the theater included an infusion of dantrolene 2.5 mg/kg prior to induction of anesthesia. In addition, the first patient was given a peroral prophylaxis with dantrolene; in subsequent cases this route of administration was abandoned. Anesthesia was performed with a drug combination devoid of sympathomimetic effects (diazepam, flunitrazepam, midazolam,--methohexital,--fentanyl, alfentanil,--vecuronium). Monitoring should include ECG, blood pressure, body temperature and end-tidal CO2-concentration.

Administration, Oral↗