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Biomedical subjects

H U Schulz

Publications and source records attributed to H U Schulz.

At least 37 records · Page 2Linked to original sources
PubMed1999

Bioavailability of trospium chloride after intravesical instillation in patients with neurogenic lower urinary tract dysfunction: A pilot study.

Oral drug treatment of detrusor overactivity often causes undesirable side effects in other organs. For some patients, in particular those with neurogenically induced detrusor overactivity (detrusor hyperreflexia), the tolerance level for adverse effects is low and oral treatment may become ineffective. Intravesical administration of the drug can diminish the side effects or increase treatment effectivity in patients who are (partially) refractory to oral treatment because the relative concentration of the drug is increased in the target organ and decreased in the circulation. Six men (19-34 years old) with traumatic spinal cord lesions between C2 and Th11 were randomized to intravesical instillation with 15 or 30 mg trospium chloride in 40 ml saline into the empty bladder. Catheterization was postponed until at least 3 h after instillation, and fluid intake was not allowed during the first 4 h. Blood samples were taken before and 11 times after instillation; the last sample 12 h post instillation. Four positive samples were found in three patients: 0.10 ng/ml after 1 h and 0.13 ng/ml after 2(1/2) h in two patients with 15 mg, and 0.24 ng/ml after 30 min and 0.70 ng/ml after 6 h in one patient with 30 mg instilled trospium chloride. Three adverse effects were reported and were rated as probably not related to the drug. It is concluded that intravesically instilled trospium chloride is not absorbed into the circulation in significant amounts and, thus, it may be expected that this mode of administration will improve the efficacy of trospium chloride therapy by reducing the side effects. Neurourol. Urodynam. 18:447-453, 1999.

Adult↗
PubMed1999

[Gastrointestinal stromal tumors--problems in diagnosis and therapy].

Gastrointestinal stromal tumors (GIST), which form a rare group of neoplasias of the gastrointestinal tract, have not yet been fully investigated. Although good progress has been made in their diagnosis, classification of these lesions with regard to their histogenesis and biological behavior remains problematic. Between 1994 and 1998, 18 GIST patients underwere operation in the Department of Surgery. Twelve of these patients (67%) had stromal tumors in the stomach, and six (33%) had intestinal stromal tumors. The primary tumor could be removed in all patients with R0 resection. Six patients developed hematogenous liver metastasis, with the size of their primary tumor exceeding 10 cm. Extrahepatic distant metastases were not found in any case. Lymphadenectomy showed that lymph node metastases did not occur. Histological evaluation was made according to the guidelines of Lewin, Weinstein and Riddell. Currently established therapy is limited to complete surgical resection of the primary tumor and its metastases. Adjuvant or neoadjuvant chemotherapy approaches have failed.

Adult↗
PubMed1999

Pharmacokinetic properties of tramadol sustained release capsules. 1st communication: investigation of dose linearity.

The relationship between the dose and the pharmacokinetic characteristics. AUC(0-infinity) and Cmax was investigated with respect to linearity in 12 healthy male volunteers. Single doses of 50 mg, 100 mg and 200 mg tramadol (CAS 27203-92-5) hydrochloride were administered as sustained release capsules in an open, randomized three-period crossover study. Tramadol plasma concentrations were determined by a validated gas chromatography method. Statistical analysis after logarithmic transformation of the dose-adjusted characteristics mentioned above yielded bioequivalence for all doses applied. Therefore, dose linearity for the range investigated could be concluded.

Adult↗
PubMed1999

Pharmacokinetic properties of tramadol sustained release capsules. 2nd communication: investigation of relative bioavailability and food interaction.

In an open, randomized four-period crossover study in 24 healthy male volunteers a newly developed tramadol (CAS 27203-92-5) sustained release capsule with and without concomitant food intake and an instant release formulation were administered. Additionally, a sustained release tablet was applied as further reference substance. Statistical analysis of AUC(0-infinity) and Cmax after logarithmic transformation yielded bioequivalence of tramadol sustained release capsules with and without concomitant food intake. Therefore, lack of food interaction could be concluded. The investigation also showed an only slightly diminished bioavailability of the tramadol sustained release capsules compared to the instant release formulation. Furthermore, the sustained release capsules investigated showed enhanced retardation at almost identical bioavailability compared with the sustained release competitor drug.

Adult↗
PubMed1999

Pharmacokinetic properties of tramadol sustained release capsules. 3rd communication: investigation of relative bioavailability under steady state conditions.

In an open, randomized two-period crossover study in 24 healthy male volunteers multiple doses of tramadol (CAS 27203-92-5) test and reference medication were administered as follows: Test: sustained release capsules containing 100 mg tramadol hydrochloride, a total of 6 capsules at intervals of 12 h; Reference: instant release capsules containing 50 mg tramadol hydrochloride, a total of 12 capsules at intervals of 6 h. As a result of the statistical analysis of AUCss(48-72 h) after logarithmic transformation a bioavailability of 100% for the sustained release capsules compared with the instant release capsules was obtained. As expected statistical analysis of the peak trough fluctuation at steady state PTFss(48-72 h) yielded a distinct diminution of the fluctuation.

Adult↗
PubMed1999

Induction of TFF1 gene expression in pancreas overexpressing transforming growth factor alpha.

BACKGROUND/AIMS: Chronic pancreatitis is an inflammatory disease of the exocrine pancreas associated with extensive fibrosis, enlarged pancreatic ducts, acinar cell degeneration, and the formation of tubular complexes. The molecular and biochemical alterations associated with these histological changes are not kown. Generally, the new family of TFF peptides (formerly known as P-domain peptides or trefoil factors) is aberrantly expressed during chronic inflammatory diseases of the gastrointestinal tract. METHODS: Using human pancreatic tissues obtained from patients with chronic pancreatitis and murine pancreatic tissues obtained from transgenic mice overexpressing transforming growth factor alpha (TGF-alpha), the expression and cellular distribution of TFF1 was analysed using northern blot analysis, polymerase chain reaction (PCR), and immunohistochemistry. RESULTS: In the normal human pancreas, TFF1 was scarce, with only a few ducts exhibiting cytoplasmic TFF1 immunoreactivity. In contrast, human chronic pancreatitis tissue specimens exhibited strong TFF1 immunoreactivity in ductal cells, areas of ductal hyperplasia, and tubular complexes. Semiquantitative PCR analysis of TFF1 mRNA levels showed enhanced expression of TFF1 in the pancreas of patients with chronic pancreatitis. Furthermore, TFF1 mRNA levels were detectable in the pancreas in four of five transgenic mice overexpressing TGF-alpha. In contrast, four of five wild type mice did not exhibit a TFF1 mRNA transcript. In addition, while no specific TFF1 immunoreactivity was present in the pancreas of the wild type mice, ductal epithelial cells and duct-like tubular complexes in the pancreas of the transgenic mice overexpressing TGF-alpha exhibited pronounced TFF1 immunoreactivity. CONCLUSIONS: Ductal cells and tubular complexes in pancreatic fibrosis express TFF1. As the 5'-flanking region of TFF1 contains an epidermal growth factor responsive enhancer region and the expression of epidermal growth factor and TGF-alpha is enhanced in pancreatic fibrosis, the enhanced expression of TFF1 in pancreatic fibrosis may be mediated by TGF-alpha.

Adolescent↗
PubMed1999

Multimodal treatment of neuroendocrine tumors of the pancreas and the ampulla of Vater.

Neuroendocrine tumors are not seen frequently. They are most commonly located in the small bowel including the vermiform appendix. Neuroendocrine tumors of pancreatic origin are extremely rare. Symptoms caused by excessive hormone production by large liver metastases often lead to their diagnosis. Preoperative diagnostics include analysis of specific hormones in serum and urine, ultrasound, CT and somatostatin receptor scintigraphy. Liver metastases of neuroendocrine tumors of the pancreas are common at the time of diagnosis. Curative resection should be performed whenever possible, although patients often benefit from debulking procedures, too. Liver metastases can be subjected to surgical resection, embolization, regional chemotherapy or local procedures such as alcohol injection or cryoablation. As an exception, liver transplantation can be considered in selected cases where radical surgery for the primary tumor could be performed and extrahepatic metastases are not present. Supplementary or alternative options include octreotide and/or interferon-alpha administration. In this article, we report on 6 patients suffering from primary neuroendocrine tumors of the pancreas or the ampulla of Vater who were treated at our department over the past 5 years. In addition, we discuss our own experience with this rare condition in the light of the recent literature.

Adult↗
PubMed1999

[Peritonitis models in the rat with special reference to laparoscopic therapy options].

With ongoing development of minimally invasive surgery the laparoscopic techniques are increasingly used also in patients with intra-abdominal inflammatory diseases. The systemic sequelae of laparoscopy are not yet clear. In this study, we investigated three experimental models of peritonitis in rats (cecal ligation and puncture n = 14, cecal stent peritonitis n = 14, implantation of a standardized fecal inoculum n = 18) concerning the therapeutic potential of laparoscopy, reproducibility of the results and clinical relevance (elimination of the inflammatory focus, intraperitoneal modulation of inflammation). The peritonitis model of implantation of a standardized fecal inoculum was shown to be the experimental model with the closest clinical relevance. In this technically simple, reproducible model, the primary inflammatory focus can be eliminated by laparoscopic lavage. A significant difference (p < 0.002) of survival between the groups with and without laparoscopic lavage was found. In addition, the intraperitoneal application of drugs is possible in order to modulate peritoneal and systemic inflammation.

Animals↗
PubMed1999

[Aorto-duodenal fistula--a rare cause of upper gastrointestinal hemorrhage].

Upper gastrointestinal hemorrhage is the most frequent indication for emergency endoscopy. In most of the cases the bleeding is primarily treated endoscopically. The duodenal penetration of an aortic graft implant is a rare condition, only accidentally diagnosed by endoscopy. This condition represents a difficult situation for the endoscopist since it is usually not included in the differential diagnosis. Additionally hemostasis can not be achieved by endoscopic intervention. Therefore the instant realization of this dangerous diagnosis is extremely important, because only surgical therapy in a center of vascular surgery may save the live of the patient.

Aged↗
PubMed1998

Occurrence of oxidatively modified proteins: an early event in experimental acute pancreatitis.

Free radical-mediated injury is believed to play a key role in the pathogenesis of acute pancreatitis (AP). Therefore, oxidative damage of proteins may be an important event in the development of AP. The present study was performed to investigate oxidative protein modification, quantified as 2,4-dinitrophenylhydrazine-reactive protein-carbonyls, during the time course of taurocholate-induced pancreatitis of the rat and to analyze oxidatively modified proteins by Western blotting. Protein modification in pancreatic homogenates was found as early as 30 min after induction of severe AP with 3% taurocholate preceding the elevation of serum amylase activity and the increase of malondialdehyde in the tissue. A correlation of protein-carbonyl contents to a score of pancreatic macroscopic alterations (r = .69) and to the wet weight/dry weight ratio (r = .65) was found. Infusion of 5% taurocholate resulted in fulminant AP with high lethality during the 24 h of the experiment. However, rats surviving showed significantly lower level of protein-carbonyls than animals that died between 20-24 h after AP induction. The quantitative data were confirmed by the intensity of immunostained protein-carbonyls. The present data show a rather uniform increase in the staining pattern not revealing single, selectively damaged proteins. The aldehydic product of lipid peroxidation 4-hydroxynonenal (HNE) is known for its reactivity towards proteins. Interestingly, an antibody raised against protein-bound HNE did not indicate an increased protein modification by this aldehyde. In conclusion, experimental AP is characterized by an early oxidative protein modification, possibly contributing to functional impairment of the pancreas. This protein alteration may not be mediated by HNE.

Acute Disease↗
PubMed1998

Diagnostic relevance of interleukin pattern, acute-phase proteins, and procalcitonin in early phase of post-ERCP pancreatitis.

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has been suggested as a model for acute pancreatitis (AP), which allows evaluation of early alterations in the time course of the disease. The influence of the clinical course on procalcitonin (PCT), serum amyloid A (SAA), and several proinflammatory and inhibitory cytokines was evaluated in patients with AP following ERCP. Blood samples were prospectively collected from patients undergoing ERCP. The incidence of ERCP-induced pancreatic damage, defined as abdominal complaints, a threefold increase of serum lipase, and elevation of CRP from <10 to >20 mg/liter was 12.8% (12/94). Only mild clinical courses of acute pancreatitis were observed. PCT significantly increased in subjects with post-ERCP pancreatitis after 24 hr. However, PCT levels did not exceed 0.5 ng/ml in any patient. Interleukin-1 receptor antagonist (IL-1RA) began to differ from baseline 2 hr after ERCP, followed by interleukin-6 (IL-6, 6 hr), solubilized tumor necrosis factor-alpha receptor II (sTNF-alphaRII, 24 hr) and SAA (24 hr). Interleukin 10 (IL-10) showed marked interindividual variations with no obvious peak. Among all parameters evaluated, only peak values of IL-6 and IL-10 showed significant correlations with the reported pain score (r2 = 0.62/0.78), degree of ampullar irritation (r2 = NS/0.87), and the duration of ERCP (r2 = 0.58/0.76). No correlation was found with the volume of the injected contrast agent. We conclude that IL-10 and IL-6 appear to be useful to monitor patients after ERCP. The absence of any PCT elevation in the present study is in accordance with the clinical course of the patients who suffered from mild pancreatic damage without systemic or infectious complications.

Acute Disease↗
PubMed1998

Effect of supramaximal cerulein stimulation on mitochondrial energy metabolism in rat pancreas.

Hyperstimulation with the cholecystokinin analogue cerulein induces mild edematous pancreatitis in rats. It is believed that an impaired energy metabolism diminishes the cellular defense capacity in the inflamed pancreatic tissue and, therefore, contributes to the injuries in acinar cells. In the present study, changes in the capacity of oxidative phosphorylation were quantified within the first 24 h after subcutaneous cerulein injections. Serum amylase level and pancreatic water content were maximally elevated 5 h after the first injection. The capacity of mitochondrial respiration was reduced in isolated acinar cells to 69 and 44% at 5 and 24 h, respectively, compared to that in saline controls. Simultaneously, glutamate dehydrogenase (GLDH) activity dropped to 70 and 46%. The respiration rates of acinar cells and of isolated mitochondria related to GLDH activities were not different from controls. This suggests that the major portion of the mitochondrial population within the acinar cell is inactivated in the course of cerulein treatment. After 24 h, the reduced population of functionally intact mitochondria restricted the rate of phosphorylating respiration in acinar cells (52%), which resulted in a diminution of cellular ATP to 57%. It is concluded that cerulein hyperstimulation induces a drastic and long-lasting reduction of the capacity for mitochondrial ATP production which may adversely affect energy-requiring reactions of the gland during regeneration.

Adenosine Triphosphate↗
PubMed1998

Analysis of K-ras gene mutations in rare pancreatic and ampullary tumours.

OBJECTIVE: Mutation of the K-ras oncogene is a frequent event in pancreatic ductal carcinogenesis and it is believed to occur at an early stage in the development of pancreatic cancer. However, little is known of the role of K-ras mutations in rare pancreatic epithelial neoplasms, endocrine tumours or other non-epithelial tumours of the pancreas. Furthermore, limited data are available regarding the role of K-ras mutations in the pathogenesis of ampullary tumours. DESIGN AND METHODS: Using single-strand conformation polymorphism (SSCP) and direct sequencing of polymerase chain reaction (PCR)-amplified fragments, we analysed codons 12 and 13 for the presence of oncogenic mutations of the K-ras oncogene. Tissues were obtained from patients undergoing tumour resection for various rare pancreatic or ampullary neoplasms (number of cases in brackets): ampullary adenoma (1), neuro-endocrine tumour (3), malignant fibrous histiocytoma of the pancreas (1), pancreatic cystadenocarcinoma (1), serous cystadenoma (1), and primary and metastatic adenocarcinoma of the ampulla (5) and pancreas (3). RESULTS: K-ras gene mutations at codon 12 were detected in both pancreatic adenocarcinomas and in the metastatic lesion, whereas two ampullary cancers harboured a point mutation at codon 13: GGC-->GGG and GGC-->GGT. None of the other tumours exhibited a K-ras gene mutation at codons 12 or 13. CONCLUSION: Pancreatic tumours other than ductal adenocarcinoma of the pancreas do not harbour mutations of the K-ras oncogene. In addition, ampullary adenocarcinomas may present with codon 13 mutations; however, these mutations were not associated with amino acid substitution. Therefore, K-ras gene mutations seem to be a specific genetic alteration contributing to the pathogenesis of pancreatic ductal adenocarcinoma.

Adenocarcinoma↗
PubMed1998

[The plasma level of the neurotoxin 1-trichloromethyl-1,2,4,5-tetrahydro-beta-carboline (TaClo) in man after oral administration of chloral hydrate].

Chloral hydrate (CAS 302-17-0) is a widely used hypnotic and sedative agent. It was recently reported in the literature that a neurotoxin, TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline), may be formed in vitro from tryptamine (Ta) and chloral (Clo). Intraperitoneal administration of TaClo led to parkinson-like symptoms in the rat. Hence, the plasma levels of TaClo were determined at various time-points in 18 healthy volunteers in two periods each during a bioavailability study of several chloral hydrate preparations. The limit of quantitation for TaClo was 5 ng/ml. No TaClo could be determined in the plasma of the various volunteers following administration of human therapeutic doses of chloral hydrate. Hence, it is unlikely that TaClo will be formed in man after application of therapeutic doses of chloral hydrate to patients.

Adult↗
PubMed1998

[The relative bioavailability and pharmacokinetics of chloral hydrate and its metabolites].

Two open, randomized cross-over trials were performed in 18 healthy volunteers each to evaluate the relative bioavailability and the pharmacokinetics of chloral hydrate (CAS 302-17-0), the active ingredient of Chloraldurat 500 (immediate release capsules, CH), Chloraldurat rot (immediate release capsules, CR) and Chloraldurat blau (enteric-coated modified release capsules, CB). In the first study the male subjects, aged 21 to 31 years, were randomly given one capsule of CH or 500 mg of chloral hydrate as drinking solution. In the second study the volunteers, aged 20 to 28 years, received either one capsule of CR or one capsule of CB or 250 mg of chloral hydrate as drinking solution. The time of administration was between 6:30 and 7:30 a.m. and the capsules had to be swallowed with 150 ml water. The reference medication consisted of 150 ml drinking solution. The wash out time in both studies was 4 weeks. Prior to the administration and (2, 4, 6, only for CH) 8, 10, 15, 20, 40, 60 min and 1.5, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 192, 240 (and 408 only for CR/CB) h afterwards blood samples of 4.5 ml were taken from the antecubital vein. Additional 4.5 ml were drawn before and 10, 20, 40 and 60 min after administration to detect unchanged chloral hydrate. In the second study times of blood sampling were modified up to 4 h after administration due to the estimated later onset of release from CB in comparison to CR. Blood samples were centrifuged within 20 min, the plasma was separated and immediately frozen at -20 degrees C. Due to the extremely short terminal half-life of chloral hydrate its active metabolite trichloroethanol is regarded as the pharmacokinetically relevant parameter for the assessment of the bioavailability of the parent substance. Compared to the reference formulation (drinking solution) the bioavailability of trichloroethanol was 94.8% (CH), 100.7% (CR) and 101.6 (CB), respectively. The maximum plasma concentrations (Cmax) of trichloroethanol were 5176 ng/ml after intake of CH (reference 6131 ng/ml), after intake of CR 3241 ng/ml and CB 3279 ng/ml (reference 2993 ng/ml). Maximum plasma concentrations (tmax) of trichloroethanol were reached after 0.67 h (reference) and after 0.98 (CH), 0.76 (CR) and 2.38 h (CB), respectively. The terminal half-life for trichloroethanol was calculated to be 9.3 to 10.2 h, for the inactive metabolite trichloracetic acid the half-life ranged from 89 to 94 h. Chloral hydrate itself could be detected only 8 to 60 min after application at very low concentrations in some of the plasma samples. It is justified to characterize its bioavailability by the active metabolite trichloroethanol due to the extremely short terminal half-life and high variability of the parent substance.

Adult↗
PubMed1997

Trypsinogen activation in rat pancreatic acinar cells hyperstimulated by caerulein.

Inappropriate trypsinogen activation is discussed as an early intracellular event in the secretagogue-induced model of acute pancreatitis. However, the mechanisms by which trypsinogen is activated are not well characterized. In the present work, trypsinogen activation was studied in intact acinar cells using bis-(CBZ-arginyl)-Rhodamine 110 [(CBZ-Arg)2-Rho 110] as a cell-permeant substrate for trypsin and also independently via the formation of trypsinogen activation peptide (TAP). Preincubation with 10 nM caerulein increased the Rho 110-substrate cleavage more than threefold. This proteolytic activity was fully sensitive to a benzamidine (BA)-type serine protease inhibitor. The appearance of enzymatic activity was paralleled by the formation of TAP. The lack of effect of the high-molecular soybean trypsin inhibitor indicates an intracellular substrate cleavage. The cathepsin B inhibitor CA-074 prevented neither the caerulein-induced formation of TAP nor the (CBZ-Arg)2-Rho 110-cleaving activity. BA inhibited the Rho 110-substrate cleavage and significantly reduced the TAP formation. These results show that trypsinogen activation in caerulein-hyperstimulated acinar cells may occur independently of the activity of cathepsin B. On the contrary, the effect of BA suggests the role of a serine protease in trypsinogen activation.

Animals↗
PubMed1997

Effect of oxidative stress on cellular functions and cytosolic free calcium of rat pancreatic acinar cells.

The present study evaluates the effect of free radicals generated by xanthine oxidase-catalyzed oxidation of hypoxanthine on cellular function of isolated rat pancreatic acinar cells. The results show that a rapid and sustained increase in intracellular Ca2+ concentration ([Ca2+]i) preceded all other morphological and functional alterations investigated. Radical-induced [Ca2+]i increase was largely inhibited by 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, which prevents Ca2+ release from intracellular stores, but not by Ca2(+)-depleted medium. Radicals released Ca2+ from thapsigargin-insensitive, ryanodine-sensitive intracellular stores, whereas the secretagogue caerulein at physiological concentrations mainly released Ca2+ from thapsigargin-sensitive stores. In contrast to effects of the secretagogue, radical-induced Ca2+ changes did not cause luminal protein secretion but cell death. In single-cell measurements, both secretagogue and radicals induced oscillations of [Ca2+]i. Radical-induced oscillations had a lower frequency but similar amplitude when compared with caerulein-induced oscillations. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and ryanodine, which prevented the radical-induced Ca2+ increase without altering the generation of radicals, markedly reduced the radical-induced cell damage. These results suggest that the Ca2+ increase mediates the radical-induced cell injury. The studies also indicate that not only the extent and duration but also the origin of [Ca2+]i release as well as the frequency of Ca2+ oscillations may determine whether a pancreatic acinar cell will secrete or die.

Adenosine Triphosphate↗