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Biomedical subjects

H T Schneider

Publications and source records attributed to H T Schneider.

At least 19 recordsLinked to original sources

Comparison of tree-based methods for prognostic stratification of survival data.

Tree-based methods can be used to generate rules for prognostic classification of patients that are expressed as logical combinations of covariate values. Several splitting algorithms have been proposed for generating trees from survival data. However, the choice of an appropriate algorithm is difficult and may also depend on clinical considerations. By means of a prognostic study of patients with gallbladder stones and of a simulation study, we compare the following splitting algorithms: log-rank statistic adjusted for measurement scale with (AP) and without (AU) pruning, exponential log-likelihood loss (EP), Kaplan-Meier (KP) distance of survival curves, unadjusted log-rank statistic (LP), martingale residuals (MP), and node impurity (ZP). With the exception of the AU algorithm (based on a Bonferroni-adjusted p-value driven stopping rule), trees are pruned using the measure of split-complexity, and optimally-sized trees are selected using cross-validation. The integrated Brier score is used for the evaluation of predictive models. According to the results of our simulation study and of the clinical example, we conclude that the AU, AP, EP, and LP algorithm may yield superior predictive accuracy. The choice among these four algorithms may be based on the required parsimonity and on medical considerations.

Algorithms↗

Quantitative testing of liver function in patients with cirrhosis due to chronic hepatitis C to assess disease severity.

BACKGROUND/AIMS: Quantitative testing of liver function (QTLF) may allow a prognostic assessment of patients with various liver diseases. However, there are insufficient data about patients with liver cirrhosis due to hepatitis C. PATIENTS/METHODS: 86 consecutive patients (58 males, 28 females, age: 48.3 +/- 11.7 years) with chronic hepatitis C (HCV RNA pos.) underwent sonographically guided liver biopsy to confirm the diagnosis of cirrhosis. QTLF included aminopyrine breath test (microsomal liver function), galactose elimination capacity (cytosolic liver function), sorbitol clearance (liver plasma flow) and indocyanine green clearance (liver perfusion). Values were correlated with the Child-Pugh classification. RESULTS: 55% of the patients (n=47) had cirrhosis of Child-Pugh grade A, 28% of grade B (n=24) and 17% of grade C (n=15). QTLF showed a steady decrease from Child-Pugh grade A to grade B and to grade C. Contrary to markedly reduced tests of metabolic liver function in Child-Pugh grade patients, surrogate tests of hepatic perfusion were at the lower normal limit. All QTLF were significantly reduced in Child-Pugh grade B and C patients compared to healthy controls. Differences between the three Child grades were significant. CONCLUSION: In patients with cirrhosis due to hepatitis C, QTLF correlated inversely with Child-Pugh grades. Since in cirrhosis of grade A, surrogate tests of hepatic perfusion remained at the lower normal limit, whereas those of metabolic function were decreased, QTLF may be a tool to predict prognosis or complications in early cirrhosis due to chronic hepatitis C.

Aminopyrine↗

Adverse drug reactions in patients with gastroenterological diseases: does age increase the risk?

BACKGROUND: It has been claimed that the risk of adverse drug reactions increases with age. However, only limited data exist for disease-group specific risks and none for patients with liver and gastrointestinal diseases. AIMS: To determine the incidence and characteristics of adverse drug reactions and the physicians' awareness of adverse drug reactions. METHODS: During a 7-month period, a prospective survey of 532 male patients (158 aged 65 years or older; 30%) was conducted on a hepatogastroenterological ward of a tertiary-care university hospital, using intensive bedside and computer-assisted drug surveillance methods. RESULTS: No difference was found in the overall rate of adverse drug reactions between older and younger patients (25.9% vs. 24.2%) during 6213 treatment days. However, a significantly higher risk for developing adverse drug reactions could be shown for the elderly with biliary tract diseases (P < 0.01). Independently of age, patients suffering from gastric ulcers, acute episodes of pancreatitis, cholangitis or inflammatory bowel diseases were at high risk of adverse drug reactions. Adverse drug reaction-associated mortality was encountered in four elderly and none of the younger patients. Secondary pharmacological effects and drug toxicity were the main types of adverse drug reactions for both age groups. Although 75.3% of the adverse drug reactions were predictable, only 37.5% of all adverse drug reactions were recognized by the staff physicians. CONCLUSION: In hepatogastroenterological patients, advancing age was not associated with an overall increased risk of adverse drug reactions except for patients with biliary tract diseases. In the elderly, adverse drug reactions were more severe and carried higher mortality. Guidelines and educational programs should be developed to increase the awareness of adverse drug reactions and their prevention, especially in high risk patients and, thus, to improve patient outcomes.

Age Factors↗

[Stimulation of immunoglobulin E formation in chronic pancreatitis by alcohol drinking and exocrine pancreatic insufficiency].

Many patients with chronic pancreatitis (CP) complain of several types of food intolerance despite elimination of fat and alcohol. Since there are no data on serum immunoglobulin E (IgE) concentrations in CP, IgE concentrations in serum were detected in 97 persons with CP and 50 controls. IgE was analyzed by the use of a highly sensitive fluoro-enzyme-immunoassay. In CP, a significantly raised IgE level (mean +/- SEM; 286.1 +/- 49 KU/L; p < 0.0001) was detected compared with controls (65.2 +/- 13 KU/L). CP-patients without alcohol consumption and normal exocrine pancreatic function were found to have only slightly elevated serum IgE values (120.2 +/- 54 KU/L), whereas patients with exocrine insufficiency treated with enzyme supplementation showed an IgE level of 153.7 +/- 51 and exocrine insufficient patients without treatment of 261.0 +/- 173 KU/L (p = 0.01). IgE levels were far more elevated in the corresponding groups with continued alcohol consumption (> 25 g/day). Alcohol consuming patients with CP and normal pancreatic function had a mean serum IgE of 295.0 +/- 114 KU/L, while patients with alcohol consumption and sufficiently treated exocrine pancreatic insufficiency showed a serum IgE of 393.7 +/- 147 KU/L (p = 0.03). Non-enzyme supplemented patients with CP and exocrine pancreatic insufficiency were characterized by approximately 10-fold increased serum IgE (1080.0 +/- 313 KU/L; p = 0.001). Non-allergic, alcohol consuming patients with CP have significantly increased serum IgE values. Since patients without alcohol consumption and normal pancreatic function or sufficiently treated exocrine insufficiency showed clearly lower IgE values than non-compliant patients with manifest exocrine pancreatic insufficiency, these results are compatible with the assumption that a reduced rate of antigen digestion in exocrine pancreatic insufficiency may lead to an increased intestinal antigen load, stimulating an abnormal humoral immune response with IgE production. Alcohol may further contribute to this by damaging the mucosal barrier.

Adult↗

Abdominal actinomycosis: complication of endoscopic stenting in chronic pancreatitis?

Pancreatic endotherapy is frequently performed in patients with chronic pancreatitis and stenoses of the main pancreatic duct. In a patient with long-standing chronic pancreatitis and treatment with pancreatic stents, metastatic pancreatic head carcinoma was suspected because of infiltration of the neighboring organs and hepatic lesions. Ultrasound-guided aspiration of one liver lesion revealed grains typical for actinomycosis. In the light of this case, an extracted pancreatic stent was microbiologically investigated for actinomycetes in another patient who had a suspicious lesion of the pancreatic head. Microbiological examination of the extracted pancreatic stent revealed colonization by Actinomyces meyeri, Klebsiella oxytoca, and mixed cultures of anaerobic and saprophytic Gram-positive bacteria. In the following weeks, she developed a septic clinical picture with multiple abscesses of the liver. Actinomyces meyeri, Corynebacterium species, Candida and Enterococcae were cultivated in the aspirates. It seems possible, that treatment with pancreatic stents could have caused invasion of actinomycetes into the parenchyma of the pancreas, which was already harmed by the chronic inflammation, followed by the typical infiltrative growth and hematologic or biliary seeding into the liver.

Actinomycosis↗

Faecal elastase-1: lyophilization of stool samples prevents false low results in diarrhoea.

BACKGROUND: In patients with diarrhoea, faecal elastase-1 is used to detect exocrine pancreatic insufficiency. Diarrhoea is defined as >85% stool water content. METHODS: We analysed elastase-1 in 519 stool samples from 310 patients unprocessed as well as after lyophilization in a standard laboratory lyophilizator. Stool water content was calculated by weight difference before and after lyophilization. RESULTS: 151 stool samples were classified as 'diarrhoea' (mean stool water content 88.8%); all others had a mean water content of 75.4%. In the 'diarrhoea' samples, elastase-1 levels were considerably higher after lyophilization--with a calculated normal water content of 75% (606 +/- 359 microg/g, mean +/- s)--compared to measurement when unprocessed (279 +/- 151 microg/g; P < 0.0001). In 16 of the 151 cases (11%), the abnormally low elastase-1 level below 200 microg/g found in unprocessed stools proved normal (>200 microg/g) after lyophilization and correction for stool water content. CONCLUSION: Diarrhoea can result in falsely decreased elastase-1 levels in a number of patients with non-pancreatogenic diarrhoea. Lyophilization is a simple measure by which to determine elastase-1 independently of stool water content. Lyophilization of stool samples can therefore help to prevent wrong positive elastase-1 test results.

Adolescent↗

Risperidone-induced cholestatic hepatitis.

Risperidone, a widely used atypical and potent neuroleptic drug, is assumed to induce fewer hepatic side-effects than phenothiazine anti-psychotics. Recently, we observed a case of risperidone-induced cholestatic hepatotoxicity. A 37-year-old male developed a rapid increase in liver enzymes and cholestatic parameters after starting treatment with risperidone for paranoid psychosis. Work-up for other potential aetiologies was negative. The results of a percutaneous liver biopsy were consistent with drug-induced liver injury and cholestasis. Over the course of one month after the discontinuance of all anti-psychotic agents, the liver function test results returned to near-normal values. This observation supports the need to monitor cholestatic parameters in addition to liver function enzymes during initiation and the first weeks of risperidone intake.

Adult↗

Parameters of microsomal and cytosolic liver function but not of liver perfusion predict portal vein velocity in noncirrhotic patients with chronic hepatitis C.

Our aim was to compare color-coded Doppler sonography (CCDS) and quantitative testing of liver function (QTLF) in patients with chronic hepatitis C. In all, 74 patients with chronic hepatitis C and mild fibrosis underwent QTLF, which included aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance (SC), and indocyanine green clearance (ICG). Hepatic artery velocity and resistance index (HA-V, HA-RI) as well as portal vein velocity (PV-V) were measured by CCDS. ABT, GEC, and PV-V were significantly reduced, whereas SC1, ICG, HA-V, and HA-RI showed normal levels. There was a significant correlation between reduction in PV-V only with GEC and ABT. QTLF did not correlate with HA-V and HA-RI. In conclusion, in hepatitis C patients with liver fibrosis, ABT and GEC are decreased significantly, which was paralleled by a reduction of PV-V. Unexpectedly SC1 and ICG, the classical hepatic perfusion parameters, do not correlate with the parameters measured by CCDS.

Aged↗

Analysis of the risk factors associated with endoscopic sphincterotomy techniques: preliminary results of a prospective study, with emphasis on the reduced risk of acute pancreatitis with low-dose anticoagulation treatment.

BACKGROUND AND STUDY AIMS: The aim of the present study was to analyze the risk factors associated with complications of endoscopic sphincterotomy (ES). PATIENTS AND METHODS: In all consecutive endoscopic sphincterotomies carried out between September 1994 and December 1996, the possible risk factors (12 patient-related factors and 12 procedure-related ones), as well as the concomitant medical treatment, indications, techniques, and success of endoscopic sphincterotomy were evaluated prospectively. Risk factors were analyzed on an exploratory basis using univariate methods. "Potential risk factors" (univariate, P<0.1) underwent multivariate analysis to determine independent "risk factors" (multivariate, P<0.05). In addition, the complication rate was calculated according to the number of potential risk factors present. RESULTS: A total of 438 patients who underwent ES were analyzed. Complications occurred in 7.5% (n = 33; acute pancreatitis 4.3%, hemorrhage 2.3 %, cholangitis 0.9%, technical 0.2%). Statistical analysis of the complications identified three independent risk factors (coagulopathy, patient age (< or =60 years, pancreas divisum), and one protective factor (pancreatic duct obstruction). The frequency of acute pancreatitis was increased by two independent risk factors (pancreas divisum, ES frequency <40 procedures/year) and was reduced if low-dose anticoagulation (unfractionated heparin or low molecular weight heparin) was administered (0.9%, one of 115 vs. 5.8%, 18 of 313; P<0.05). The effect of anticoagulation was not confounded by the presence or absence of other potential risk factors for acute pancreatitis. Neither the risk nor the severity of hemorrhage were increased by low-dose anticoagulation. Due to the low number of events, only potential risk factors for hemorrhage were identified (coagulopathy, intensive-care treatment). The overall complication rate and the incidence of pancreatitis and hemorrhage increased significantly depending on the number of simultaneous potential risk factors present (P<0.0001). CONCLUSIONS: Patients at risk for complications after endoscopic sphincterotomy can be identified by risk factor analysis. These data suggest the hypothesis that low-dose anticoagulation prior to endoscopic sphincterotomy reduces the risk of acute pancreatitis after sphincterotomy.

Acute Disease↗

Is endoscopic drainage of common bile duct stenoses in chronic pancreatitis up-to-date?

OBJECTIVE: Common bile duct (CBD) stenoses often complicate chronic pancreatitis (CP). Although endoscopic drainage is employed as a standard procedure in malignant CBD stenoses, it is not yet the approved standard therapy of CBD stenosis in CP. METHODS: The records of 31 patients with CBD stenosis in CP who had undergone endoscopic placement of plastic endoprostheses into the bile duct between January 1991 and February 1997 were analyzed retrospectively. In all, 18 patients suffered from jaundice and 13 patients exclusively showed serological cholestasis. Upstream dilation of the CBD (19 +/- 6.6 mm, 12-35 mm) was detected by ERCP in all patients. In total, 101 endoprostheses were implanted endoscopically, exchanged after 3 +/- 2 months, and removed after 10 +/- 8 months. RESULTS: All jaundiced patients showed immediate improvement of cholestasis after drainage. At the time of last exchange or after stent removal, prestenotic CBD dilation was reduced in 55% of all patients. Complete regression of stenosis and prestenotic dilation was accomplished only in 13%; dilation remained unchanged in 10%, and even showed progression in 22%. A total of 29 patients were followed-up over 24 months. Cholestatic parameters remained normal in all patients with complete normalization of the CBD, and were only moderately increased in another 10 patients, 7 and 28 months after stent removal, respectively. CONCLUSIONS: Technical and immediate clinical success of CBD stenting in patients with CBD stenoses due to CP is high; however, long-term complete normalization of the bile duct is rare. Endoscopic drainage of CBD-stenosis in patients with CP can be recommended to alleviate acute cholestasis, but not yet as a definite treatment.

Acute Disease↗

Incidence and costs of adverse drug reactions during hospitalisation: computerised monitoring versus stimulated spontaneous reporting.

OBJECTIVE: To implement a computer-based adverse drug reaction monitoring system and compare its results with those of stimulated spontaneous reporting, and to assess the excess lengths of stay and costs of patients with verified adverse drug reactions. DESIGN: A prospective cohort study was used to assess the efficacy of computer-based monitoring, and case-matching was used to assess excess length of stay and costs. SETTING: This was a study of all patients admitted to a medical ward of a university hospital in Germany between June and December 1997. PATIENTS AND PARTICIPANTS: 379 patients were included, most of whom had infectious, gastrointestinal or liver diseases, or sleep apnoea syndrome. Patients admitted because of adverse drug reactions were excluded. METHODS: All automatically generated laboratory signals and reports were evaluated by a team consisting of a clinical pharmacologist, a clinician and a pharmacist for their likelihood of being an adverse drug reaction. They were classified by severity and causality. For verified adverse drug reactions, control patients with similar primary diagnosis, age, gender and time of admission but without adverse drug reactions were matched to the cases in order to assess the excess length of hospitalisation caused by an adverse drug reaction. RESULTS: Adverse drug reactions were detected in 12% of patients by the computer-based monitoring system and stimulated spontaneous reporting together (46 adverse reactions in 45 patients) during 1718 treatment days. Computer-based monitoring identified adverse drug reactions in 34 cases, and stimulated spontaneous reporting in 17 cases. Only 5 adverse drug reactions were detected by both methods. The relative sensitivity of computer-based monitoring was 74% (relative specificity 75%), and that of stimulated spontaneous reporting was 37% (relative specificity 98%). All 3 serious adverse drug reactions were detected by computer-based monitoring, but only 2 out of the 3 were detected by stimulated spontaneous reporting. The percentage of automatically generated laboratory signals associated with an adverse drug reaction (positive predictive value) was 13%. The mean excess length of stay was 3.5 days per adverse drug reaction. 48% of adverse reactions were predictable and detected solely by computer-based monitoring. Therefore, the potential for savings on this ward from the introduction of computer-based monitoring can be calculated as EUR56 200/year ($US59 600/year) [ 1999 values]. CONCLUSION: Computer monitoring is an effective method for improving the detection of adverse drug reactions in inpatients. The excess length of stay and costs caused by adverse drug reactions are substantial and might be considerably reduced by earlier detection.

Adverse Drug Reaction Reporting Systems↗

Acute hepatitis induced by greater celandine (Chelidonium majus).

The hepatotoxic potential of conventional drugs is well known, but herbal medicines are often assumed to be harmless. In the last 2 years, we have observed 10 cases of acute hepatitis induced by preparations of greater celandine (Chelidonium majus), which are frequently prescribed to treat gastric and biliary disorders. The course of hepatitis was mild to severe. Marked cholestasis was observed in 5 patients, but liver failure did not occur. Other possible causes of liver disease (viral, autoimmune, hereditary, alcohol, and secondary biliary) were excluded by laboratory tests and imaging procedures, and liver biopsy specimens were consistent with drug-induced damage. After discontinuation of greater celandine, rapid recovery was observed in all patients and liver enzyme levels returned to normal in 2-6 months. Unintentional rechallenge led to a second flare of hepatic inflammation in 1 patient. Greater celandine has to be added to the list of herbs capable of inducing acute (cholestatic) hepatitis. A significant proportion of unexplained cases of hepatitis may be caused by greater celandine.

Acute Disease↗

Impact of skill and experience of the endoscopist on the outcome of endoscopic sphincterotomy techniques.

BACKGROUND: Our aim was to assess the influence of the skill and experience of the endoscopist on the success and risk of endoscopic sphincterotomy techniques. METHODS: The outcome of all endoscopic sphincterotomies (n = 1335) carried out between 1988 and 1995 were retrospectively analyzed with respect to the endoscopist performing the procedure. Endoscopists were differentiated according to whether they had previous experience with endoscopic sphincterotomy techniques (n > 100) and the frequency of endoscopic sphincterotomy during the study period (>40, 26 to 40, 10 to 25, <10 per year). RESULTS: Indications for endoscopic sphincterotomy techniques and technical execution had only a minor influence on the results of endoscopic sphincterotomy and were comparable for the individual endoscopists. The overall success rate of endoscopic sphincterotomy was 94.4% and did not significantly differ among the endoscopists. The overall complication rate of endoscopic sphincterotomy was 7.3%. Endoscopists learning endoscopic sphincterotomy techniques with a case frequency of less than 10 procedures per year had a consistently high complication rate (10.5%). Those learning endoscopic sphincterotomy techniques with a case frequency of more than 25 procedures per year had an above-average complication rate for their first 40 endoscopic sphincterotomy procedures and a significant decrease in complication rate as the number of procedures increased. The complication rate for experienced endoscopists was 7.7%. There were distinct and, in one case, significant differences in complication rates between individual endoscopists (11.5% vs. 4.8%, p = 0.01). However, when corrected for multiple testing, there were no significant differences at the p < 0. 05 level. The endoscopic sphincterotomy frequency of the endoscopist was the only significant risk factor for complications. Endoscopists with a frequency of more than 40 procedures per year had a significantly lower complication rate (5.6%) than endoscopists with a lower case frequency (9.3%, p < 0.05). CONCLUSIONS: A low endoscopic sphincterotomy frequency is, even for endoscopists with previous experience with the procedure, a risk factor for complications after endoscopic sphincterotomy. The learning of endoscopic sphincterotomy techniques requires a minimum of 40 procedures, but also after 100 procedures a further decrease of the complication rate can be expected.

Adult↗

Retrospective analysis of the frequency and recognition of adverse drug reactions by means of automatically recorded laboratory signals.

AIMS: To estimate the frequency of adverse drug reactions (ADRs) identified through the use of automatic signals generated from laboratory data (ALS) in hospitalised patients. To determine the frequency of spontaneous recognition of these ADRs by the attending physicians and to assess the potential value of ALS for detection of ADRs. METHODS: Laboratory results of patients hospitalised in a nine bed medical ward were automatically recorded over a period of 17 months. Values exceeding defined boundaries were used as ALS. Charts of every third patient were analysed retrospectively with regard to adverse drug related reactions and causality was evaluated as well as whether the ADR had been recognised during the period of hospitalisation. RESULTS: The charts and ALS of 98 patients were analysed. In 18 cases a drug-related adverse reaction was probable. Awareness to the reaction by the treating physicians was evident in 6 out of these 18 ADRs. Approximately 80% of the ADRs were considered predictable. Three ADRs were regarded as serious. CONCLUSIONS: Adverse drug reactions are common and often preventable. Only one third of ADRs which could have been detected through ALS were recognised by the attending physicians. An increased doctor's awareness of the frequency of drug related abnormal laboratory results by means of ALS is likely to increase the recognition rate of ADRs and might help to prevent them.

Adult↗

Effect of substance P on histamine secretion from gut mucosa in inflammatory bowel disease.

BACKGROUND: Mast cell hyperplasia in the gut is a feature of inflammatory bowel disease (IBD), but the role of mast cells in this disease is still unclear. Since mast cell-nerve interactions might have some impact on intestinal inflammation, the present study investigated whether the neuropeptide substance P causes histamine secretion from human gut mucosal mast cells. METHODS: Four hundred and eighteen colorectal endoscopic samples from 20 patients with IBD and 10 controls were studied. Colorectal biopsy samples were cultured in an oxygenated medium for spontaneous histamine release or were stimulated with substance P, anti-human immunoglobulin E, and a combination of substance P and anti-human immunoglobulin E. Histamine release was measured using a highly sensitive and specific radioimmunoassay. RESULTS: Substance P failed to induce mast cell activation in histologically normal mucosa from controls. In contrast, mucosal specimens taken from inflamed IBD tissue or from uninvolved Crohn disease tissue showed a considerably enhanced rate of histamine secretion towards substance P, alone or in combination with anti-IgE. Unaffected mucosa with ulcerative colitis appeared insensitive towards substance P. CONCLUSIONS: The neuropeptide substance P was shown to preferentially enhance mucosal mast cell mediator secretion in active IBD. Thus, it appears likely that mast cell-nerve interactions are involved in as yet uninvestigated neurovegetative histamine-releasing processes of the gut in IBD.

Adult↗