Biomedical subjects

Hans-Ulrich Schulz

Publications and source records attributed to Hans-Ulrich Schulz.

28 records · Page 2Linked to original sources

PubMed2003

Drug interaction of spirapril hydrochloride monohydrate and hydrochlorothiazide. A clinical study to compare the pharmacokinetics after administration of spirapril hydrochloride monohydrate tablets, hydrochlorothiazide tablets and fixed combination bi-layer tablets.

The potential influence of concomitantly administered hydrochlorothiazide (CAS 58-93-5) on the pharmacokinetics of spirapril (CAS 94841-17-5)/spiraprilat (CAS 83602-05-5) and of concomitantly administered spirapril on the pharmacokinetics of hydrochlorothiazide was investigated in an open, randomised, 3-way crossover study in 12 healthy male subjects. The test drug was a newly developed bi-layer tablet containing a fixed combination of spirapril hydrochloride monohydrate and hydrochlorothiazide (Quadroplus). The reference formulations were tablets containing solely spirapril hydrochloride monohydrate (Quadropril) or hydrochlorothiazide (produced exclusively for study medication). For spirapril, spiraprilat and hydrochlorothiazide the 90% confidence intervals of the AUC(0-infinity) as a measure for the extent of absorption were entirely included within the equivalence range of 0.8 to 1.25 and the 90% confidence intervals of the Cmax as a measure for the rate of absorption were entirely included within the extended equivalence range of 0.7 to 1.43. Therefore, bioequivalence was concluded for the test and reference formulations. The results suggest that hydrochlorothiazide does not interact in the fixed combination with the pharmacokinetics of spirapril and vice versa.

Adult↗

PubMed2003

Analysis of tumour necrosis factor alpha and interleukin 10 promotor variants in patients with chronic pancreatitis.

OBJECTIVE: Cationic trypsinogen gene mutations are strong risk factors of hereditary pancreatitis. However, 20% of subjects with a trypsinogen mutation never get pancreatitis and the cause of this incomplete penetrance is unknown. We investigated the influence of interleukin 10 (IL10) and tumour necrosis factor alpha (TNFalpha) promotor variants on the manifestation of chronic pancreatitis of different underlying causes and in pancreatic cancer. METHODS: A total of 335 German patients with chronic pancreatitis were investigated. In 157 patients the disease was related to alcohol abuse; the other cases were of non-alcoholic origin. In the latter group, the serine protease inhibitor, Kazal type 1 (SPINK1) mutation N34S was found in 72 patients and the trypsinogen mutations N29I or R122H were present in 60 patients; in the remaining 46 patients no mutation was found. In addition, we studied 208 patients with pancreatic cancer. As controls, 116 healthy blood donors and 25 healthy carriers of the trypsinogen mutations N29I or R122H were investigated. After DNA extraction from blood leucocytes, genotyping for the cytokine polymorphisms was performed by induced heteroduplex generators and/or direct DNA sequencing of the IL10 and TNFalpha promotor regions. RESULTS: The frequencies of the promotor polymorphisms of IL10-627A, IL10-1117A, TNF-238A and TNF-308A in patients with alcoholic chronic pancreatitis, idiopathic pancreatitis, SPINK1-N34S-associated chronic pancreatitis and pancreatic cancer did not differ significantly from the control group. The variant TNF-238A was two to four times more frequent in index patients with trypsinogen mutations than in all other groups. The analysis of the allelic frequencies of whole families with trypsinogen mutations revealed that all subjects with the TNF-238A variant suffered from chronic pancreatitis, whereas all intrafamilial controls with wild-type TNF were unaffected. CONCLUSIONS: TNFalpha and IL10 promotor variants are not associated with a manifestation of chronic pancreatitis or pancreatic cancer. The variant TNF-238A, however, might be a relevant risk factor for disease manifestation in families with hereditary pancreatitis.

Case-Control Studies↗

PubMed2003

Risk factors for failure of endoscopic stenting of biliary strictures in chronic pancreatitis: a prospective follow-up study.

OBJECTIVES: The aims of this study were to investigate the value of interventional endoscopy in patients with strictures of the common bile duct (CBD) caused by chronic pancreatitis (CP), and to define the subset of patients who may be at risk for failure of endoscopic intervention, in a prospective follow-up study. METHODS: A total of 61 patients with symptomatic CBD strictures caused by alcoholic CP were treated by endoscopic stent insertion for 1 yr with scheduled stent changes every 3 months. After the treatment period, all patients entered a follow-up program. RESULTS: Initial endoscopic drainage was successful in all cases, with complete resolution of obstructive jaundice. After 1 yr from the initial stent insertion, in 19 patients (31.1%) the obstruction was resolved, and stents were removed without any need of additional procedures. During a median follow-up of 40 months (range 18-66 months), 16 patients had no recurrence of symptomatic CBD stricture (long term success rate 26.2%). Of 45 patients who needed definitive therapy, 12 patients (19.7%) were treated with repeated plastic stent insertion and three (4.9%) with insertion of a metal stent, and 30 patients (49.2%) underwent surgery. Among the variables tested, calcification of the pancreatic head was the only factor that was found to be of prognostic value. Of 39 patients with calcification of the pancreatic head, only three (7.7%) were successfully treated by a 1-yr period of plastic stent therapy, whereas in 13 of 22 patients (59.1%) without calcification, this treatment was successful (p<0.001). CONCLUSIONS: Endoscopic drainage of biliary obstruction provides excellent short term but only moderate long term results. Patients without calcifications of the pancreatic head benefit from biliary stenting. Patients with calcifications were identified to have a 17-fold (95% CI=4-74) increased risk of failure of a 12 month course of endoscopic stenting.

Adult↗

PubMed2003

N34S, a pancreatitis associated SPINK1 mutation, is not associated with sporadic pancreatic cancer.

BACKGROUND: The SPINK1 mutation N34S is associated to chronic pancreatitis of idiopathic, alcoholic and tropic origin. Our aim was to evaluate its prevalence in patients with sporadic pancreatic cancer. METHODS: The N34S allele of SPINK1 was analyzed by melting curve analysis using fluorescence resonance energy transfer (FRET) probes and the LightCycler in 159 German patients with sporadic pancreatic cancer (83 male, 76 female, median age of diagnosis 61 years, range 36-84 years) and 492 healthy controls. RESULTS: The N34S mutation was detected in 2 (1.3%) of the 159 patients with pancreatic cancer and in 8 (1.6%) of the 492 controls (not significant). CONCLUSION: The N34S mutation of SPINK1 appears not to be a distinct genetic risk factor in patients with sporadic pancreatic cancer.

Adult↗

PubMed2002

EUS in the diagnosis of early chronic pancreatitis: a prospective follow-up study.

BACKGROUND: The aim of this prospective, follow-up study was to investigate the value of EUS in the diagnosis of alcohol-induced chronic pancreatitis. METHODS: One hundred thirty patients with known (n = 51) or clinically suspected (n = 79) chronic pancreatitis were included. Patients with a history of chronic use of alcohol and recurrent abdominal pain underwent endoscopic retrograde pancreatography and EUS. The 38 patients with normal endoscopic retrograde pancreatography but signs of chronic pancreatitis on EUS were included in a follow-up program. RESULTS: All patients with chronic pancreatitis confirmed by retrograde pancreatography (n = 92; 70.8%) had ductal or parenchymal changes detectable with EUS. Among 38 patients (29.2%) with normal retrograde pancreatography, 32 (84.2%) presented with morphologic features consistent with chronic pancreatitis by EUS. During follow-up (median 18 months, range 6-25 months) chronic pancreatitis was confirmed by repeat endoscopic retrograde pancreatography in 22 of these 32 patients (68.8%). On the basis of these follow-up data, the sensitivities of EUS and endoscopic retrograde pancreatography at the time of the first examination were, respectively, 100% and 80.7% (p < 0.001). CONCLUSION: EUS detects chronic pancreatitis in all cases if endoscopic retrograde pancreatography was suggestive for chronic pancreatitis. However, EUS is more sensitive than endoscopic retrograde pancreatography in the detection of early morphologic changes of chronic pancreatitis in patients with abdominal pain and a history of chronic and continued ingestion of alcohol.

Adult↗

PubMed2002

Soluble thrombomodulin plasma levels are an early indication of a lethal course in human acute pancreatitis.

BACKGROUND: The potential to predict severe disease and lethality by using plasma soluble thrombomodulin (sTM) and C-reactive protein (CRP) levels in 73 patients with acute pancreatitis was analyzed in a prospective 5-year investigation performed at a single institution. METHODS: According to the Atlanta criteria, pancreatitis was classified as mild in 23 patients and as severe in 50 patients. Blood was collected on days 1, 3, 5, 7, 10, 14, 21, and 28 after the onset of pain and analyzed for sTM and CRP. RESULTS: During the period between days 3 and 10 of acute pancreatitis when most of the admissions occurred, sTM levels at a cutoff of 75 ng/mL on day 3 (sensitivity, 100%; specificity, 77%; positive predictive value, 38%; negative predictive value, 100%) and 71 ng/mL on day 10 (sensitivity, 100%; specificity, 77%; positive predictive value, 41%; negative predictive value, 100%) were predictive of a lethal outcome. With sTM levels, it was not possible to differentiate patients with mild pancreatitis from those with severe pancreatitis (Atlanta classification). In contrast, CRP levels at a cutoff of 113 mg/L on day 3 differentiated severe from mild courses with a diagnostic sensitivity of 84%, a specificity of 60%, a positive predictive value of 78%, and a negative predictive value of 69%. CRP levels at a cutoff of 122 mg/L on day 10 differentiated mild from severe courses (nonsurvivors) with a diagnostic sensitivity of 72%, a specificity of 72%, a positive predictive value of 86%, and a negative predictive value of 53%. In contrast, differentiation of mild forms of acute pancreatitis from severe pancreatitis (survivors) on day 10 was not possible. CONCLUSIONS: CRP is a valuable marker of disease severity in acute pancreatitis especially in the first period of pancreatitis, whereas sTM identifies early those patients with the most severe courses and a high risk of dying (negative predictive value, 100%). Determination of sTM in addition to CRP offers the opportunity of identifying early those patients who require intensive care most urgently. Of course, further investigations of sTM in acute pancreatitis are indicated to confirm our results.

Acute Disease↗

PubMed2002

Treatment of benign biliary strictures in chronic pancreatitis by self-expandable metal stents.

AIM: To determine the efficacy the value of self-expandable metal stents in patients with benign biliary strictures caused by chronic pancreatitis. METHOD: 61 patients with symptomatic common bile duct strictures caused by alcoholic chronic pancreatitis were treated by interventional endoscopy. RESULTS: Initial endoscopic drainage was successful in all cases, with complete resolution of obstructive jaundice. Of 45 patients who needed definitive therapy after a 12-months interval of interventional endoscopy, 12 patients were treated with repeated plastic stent insertion (19.7%) or by surgery (n = 30; 49.2%). In 3 patients a self-expandable metal stent was inserted into the common bile duct (4.9%). In patients treated with metal stents, no symptoms of biliary obstruction occurred during a mean follow-up period of 37 (range 18-53) months. The long-term success rate of treatment with metal stents was 100%. CONCLUSIONS: Endoscopic drainage of biliary obstruction by self-expandable metal stents provides excellent long-term results. To identify patients who benefit most from self-expandable metal stent insertion, further, prospective randomized studies are necessary.

Adult↗

PubMed2001

Reduced neutrophil sequestration in lung tissue after laparoscopic lavage in a rat peritonitis model.

Laparoscopy to treat abdominal infections is becoming more and more popular. The effects of the CO(2) pneumoperitoneum have not yet been completely clarified. In a rat peritonitis model, therefore, we investigated the influence of laparoscopic lavage in comparison with the conventional technique. A defined multibacterial fecal specimen was installed in the abdominal cavities of 80 rats. These animals were randomized to three groups: group 1 (n = 32), no intervention; group 2 (n = 24), conventional; group 3 (n = 24), laparoscopic lavage. At 1, 2, and 8 hours after the surgical intervention, animals were killed and autopsied. The main outcome measures were bacteremia, interleukin-6 (IL-6) in plasma and ascites, changes in the blood count, and myeloperoxidase (MPO) activity in lung, liver, kidney, and pancreas. Differences of bacteremia were not found. In the ascites a marked increase in IL-6 was observed after 8 hours, which was lower in the treatment groups than in the controls (p <0.025). MPO activity as a measure of the granulocytes present in the tissue showed significant changes only in lung tissue. Two hours after the surgical intervention, the MPO in the lung in the laparoscopy group was significantly lower than that in the controls and the laparotomy group. In conclusion, conventional and laparoscopic lavage reduce inflammation. In this model, laparoscopic lavage with a CO(2) pneumoperitoneum appeared to have no negative influence on the inflammatory reaction during the early postoperative phase. Reduced neutrophil sequestration in lung tissue following laparoscopic lavage reflects the lower level of trauma caused by laparoscopy.

Animals↗

PubMedDate not supplied

Bioavailability of beta-aescin from horse chestnut seed extract: comparative clinical studies of two Galenic formulations.

The bioavailability of beta-aescin--the main active constituent of horse chestnut seed extract--in a nonretarded test medication in comparison with that in a retarded reference formulation was evaluated in 2 randomized crossover clinical trials involving 18 healthy volunteers each. Serum concentration/time curves derived under steady-state conditions and pharmacokinetic parameters measured during both studies showed no significant difference between absorption rates for the retarded versus nonretarded preparation. In the first study, investigators found a test-to-reference ratio of 1.06 (90% confidence interval [CI] range: 99-113) for the area under the curve (AUC; the primary outcome measure). Absorption rates were diminished during the night compared with daytime rates for both study preparations. In the second study, using AUC and maximum concentration (Cmax) as the primary characteristics, investigators analyzed bioavailability based on the mean of 2 consecutive daytime periods and obtained estimates of 1.07 for AUC (90% CI range: 0.96-1.19) and 1.05 for Cmax (90% CI range: 0.90-1.21). Bioequivalence of the test and reference drug preparations was thus established according to the Note for Guidance on the Investigation of Bioavailability and Bioequivalence. Both treatments were equally well tolerated.

Adult↗

PubMedDate not supplied

Identification of gastric cancer patients by serum protein profiling.

Using surface-enhanced laser desorption ionization mass spectrometry (SELDI/TOF-MS) and ProteinChip technology, coupled with a pattern-matching algorithm and serum samples, we screened for protein patterns to differentiate gastric cancer patients from noncancer patients. A classifier ensemble, consisting of 50 decision trees, correctly classified all gastric cancers and all controls of a training set (100% sensitivity and 100% specificity). Eight of 9 stage I gastric cancers (88.9% sensitivity for stage I) were correctly classified. In addition, 28 sera from gastric cancer patients taken in different hospitals were correctly classified (100% sensitivity). Furthermore, all 11 control sera obtained from patients without gastric cancer (100% specificity) were classified correctly and 29 of 30 healthy blood-donors were classified as noncancerous. ProteinChip technology in conjunction with bioinformatics allows the highly sensitive and specific recognition of gastric cancer patients.

Algorithms↗