Biomedical subjects

C Kirsch

Publications and source records attributed to C Kirsch.

At least 19 recordsLinked to original sources

PubMed2006

Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin.

BACKGROUND: The clinical management of Helicobacter pylori infected patients who failed standard eradication therapies remains a challenge. AIM: To investigate the efficacy of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of H. pylori, and the correlation between cytochrome P450 2C19 (CYP2C19) polymorphisms and treatment outcome. METHODS: Patients infected with H. pylori resistant to both metronidazole and clarithromycin (n = 145) were randomized to either esomeprazole 20 mg, rifabutin 150 mg and amoxicillin 1 g, each given b.d. for 7 days (ERA), or to omeprazole 40 mg and amoxicillin 1000 mg, each given t.d.s. for 14 days (OA). Crossover therapy was offered in cases of persistent infection. CYP2C19 polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism. RESULTS: Intention-to-treat and per-protocol eradication rates were: ERA 74% (62.4-83.6) and 78% (66.7-87.3); high-dose OA 70% (57.5-79.7) and 75% (62.5-84.5). Crossover therapy was successful in seven of 10 patients with ERA and in eight of 10 patients with OA. Premature discontinuation of treatment occurred in 2% and 5% of patients, respectively. There was only a non-significant trend to lower eradication rates in homozygous extensive metabolizers. CONCLUSIONS: Triple therapy with esomeprazole, rifabutin and amoxicillin and high-dose omeprazole/amoxicillin are comparable and effective and safe for rescue therapy of H. pylori regardless of the patient's CYP2C19 genotype.

Adolescent↗

PubMed2005

Intragastric acidity during treatment with esomeprazole 40 mg twice daily or pantoprazole 40 mg twice daily--a randomized, two-way crossover study.

BACKGROUND: Patients with severe or complicated reflux disease may require higher than standard doses of a proton pump inhibitor for sufficient acid suppression. AIM: To test the hypothesis that esomeprazole 40 mg twice daily is superior to pantoprazole 40 mg twice daily in lowering intragastric acidity. METHODS: In a randomized, single-blinded, two-way crossover study, healthy subjects received esomeprazole 40 mg twice daily or pantoprazole 40 mg twice daily orally for five consecutive days. Continuous ambulatory 24-h intragastric pH was recorded on day 5 of each treatment. RESULTS: Thirty subjects were analysed. Esomeprazole provided significantly higher intragastric pH-values over the 24-h period [median intragastric pH 6.4 for esomeprazole and 5.1 for pantoprazole (P < 0.00005)]. Intragastric pH > 4 was maintained for 21.1 h with esomeprazole and 16.8 h with pantoprazole (P < 0.0001). An intragastric pH > 4 for more than 16 h was achieved in 96.7 and 56.7% of subjects, respectively (P = 0.0002). During night-time the proportion of time with intragastric pH > 4 was 85.4% with esomeprazole and 63.6% with pantoprazole (P = 0.0001). Nocturnal acid break through occurred less frequently on esomeprazole. CONCLUSIONS: Esomeprazole 40 mg twice daily provides better and more consistent intragastric acid control than pantoprazole 40 mg twice daily.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2003

Esomeprazole-based one-week triple therapy with clarithromycin and metronidazole is effective in eradicating Helicobacter pylori in the absence of antimicrobial resistance.

AIM: This study aimed to investigate the effectiveness of a one-week triple therapy with esomeprazole, clarithromycin and metronidazole for eradication of Helicobacter pylori infection in the absence of antimicrobial resistance. METHODS: Patients testing positive for H. pylori susceptible to metronidazole and clarithromycin (E-test) were randomized to receive a one-week regimen with either esomeprazole 2 x 20 mg or omeprazole 2 x 20 mg in combination with clarithromycin 2 x 250 mg and metronidazole 2 x 400 mg. Follow-up endoscopy with histology and culture and/or rapid urease test was performed 4-8 weeks after the end of treatment. RESULTS: Eighty patients were randomized. Helicobacter pylori infection was cured in 38/39 patients of the esomeprazole group and 31/33 patients of the omeprazole group (per protocol 97.4% (95% confidence interval [CI], 86.2-99.9), 93.7% (95% CI, 79.2-99.2), P=0.59); intention-to-treat 90.4% (95% CI: 77.4-97.3), 81.6% (95% CI: 65.7-92.3), respectively. No major side effects occurred. Minor side effects occurred in eight (20%) and six (23%) patients during esomeprazole and omeprazole therapy, respectively. Post-treatment susceptibility testing revealed resistance to both metronidazole and clarithromycin in two of the three patients who failed. CONCLUSION: We conclude that esomeprazole, clarithromycin and metronidazole as one-week triple therapy is effective for eradication of H. pylori in the absence of antimicrobial resistance.

Adult↗

PubMed2003

Brain cholesterol, statins and Alzheimer's Disease.

Growing evidence suggests that cellular cholesterol homeostasis is causally involved in different steps leading to pathological events in the brain of Alzheimer's Disease (AD) patients. It was previously demonstrated that the processing of the amyloid beta-peptide precursor protein (APP) is modulated by pronounced alterations in cellular cholesterol levels using statins or cholesterol extracting agents. However, a cholesterol-rich diet was found to enhance amyloid beta-peptide (Abeta) burden in the brain of transgenic mice without clearly affecting total brain cholesterol levels. Recent retrospective epidemiological studies have reported that the use of statins potentially suppresses the development of AD. Although some HMG-CoA reductase inhibitors seem to influence the central cholesterol pool in vivo, the above epidemiological findings are probably not linked to statin-induced changes in brain membrane cholesterol levels per se since not all statins active in preventing AD enter the central nervous system (CNS). Recently, we reported that different statins, regardless of their brain availability, induce alterations in cellular cholesterol distribution in the brain. Such pleiotropic, cholesterol-synthesis independent statin effects might be indirect and are possibly mediated at the blood-brain barrier (BBB) via nitric oxide (NO) or apolipoprotein E (ApoE).

Alzheimer Disease↗

PubMed2003

Brain-membrane cholesterol in Alzheimer's disease.

Cholesterol represents an important determinant of the physical state of biological membranes. Growing evidence indicate that changes in brain cholesterol and variations in neuronal membrane structure are involved in the development of Alzheimer's disease (AD). Cholesterol modulates the cleavage of the amyloid precursor protein and thus affect cellular production of beta-amyloid peptides (Ab). On the other hand, cholesterol seems to be protective against the neurotoxic and membrane disordering properties of Ab. Present review summarizes reports focusing on brain membrane changes in AD and the effects of Ab on these structures. Since it has been shown that these Ab effects are cholesterol dependent, recent findings are presented indicating that the modulation of membrane cholesterol refers to different cholesterol pools within the membranes. Further, consequences thereof for possible pharmacological strategies are discussed.

Aged↗

PubMed2002

Influence of the sagittal advancement of mandibulae on myofibrillar ATPase activity and myosin heavy chain content in the masticatory muscles of pigs.

Endurance muscle stress leads to polymorphic expression of myosin heavy chains (MyHC). Histochemical and electrophoretic analyses were performed on different masticatory muscles (masseter, temporal, geniohyoid and medial pterygoid) of 10 weeks old pigs after 28 days of chronic sagittal advancement of the mandibulae. The differentiation between fiber types was investigated histochemically with the myofibrillar ATPase (mATPase) method and by immunohistochemistry. Expression of different MyHC isoforms was also assessed by means of immunoblotting with monoclonal antibodies. The results of both methods were compared. Chronic sagittal advancement of the mandibulae led to an increase in the cross-sectional area of type I fibers and type I MyHC in the anterior part of the masseter, the distal part of the temporal and the medial pterygoid muscle. In the present study, clear differentiation between type I and type II muscle fibers in all histological analyses was possible. However, mATPase classification of subtypes of type II fibers may lead to misinterpretations. Additionally, a direct correlation between the type I MyHC concentration and the type I fibers was seen in enzyme histochemical and immunohistochemical staining. The defined cross section of fibers is important for the histological investigation in small muscles. The immunoblot method seems to be more sensitive and less subjective for measurement of muscle changes. It can be concluded that the immunoblot method used for measuring the MyHC content is a valid alternative for fiber typing in small muscles as it is less time-consuming and more sensitive than qualitative histochemistry.

Adenosine Triphosphatases↗

PubMed2001

Differential effects of lovastatin treatment on brain cholesterol levels in normal and apoE-deficient mice.

Growing evidence indicates that membrane cholesterol is involved in the development of Alzheimer's disease. Therefore, the availability of pharmacological strategies to modify brain cholesterol is of increasing importance. Accordingly, we investigated the effects of the HMG-CoA reductase inhibitor lovastatin on brain cholesterol levels in vivo. Brain cholesterol was significantly decreased by lovastatin treatment (100 mg/kg/day) in 1- and 12-month-old C57BL/6J mice. Reduced brain cholesterol was associated with decreased pyrene-excimer fluorescence, indicating altered membrane function. Lovastatin had no effect on brain cholesterol ApoE-/- mice. Peripheral cholesterol levels were not affected by lovastatin in all three groups of mice. We demonstrate for the first time that lovastatin represents a valid pharmacological tool to significantly modulate brain cholesterol levels.

Aging↗

PubMed2001

Anionic phospholipids are involved in membrane targeting of PI 3-kinase gamma.

Phosphoinositide 3-kinases (PI 3-kinases) have critical roles in diverse cellular signaling processes and in protein trafficking. In contrast to the class I PI 3-kinases alpha, beta, and delta which bind via src homology 2 (SH2) domains of adaptor proteins to tyrosine kinase receptors, the mechanism of recruitment of the PI 3-kinase gamma to membranes is unknown. We report in vitro experiments using immobilized proteins and small unilamellar vesicles which suggest an involvement of anionic phospholipids in membrane association of PI 3-kinase gamma. Furthermore we provide evidence that the enzyme displays beside the catalytic center a phospholipid binding domain which is essential for enzyme activity.

Animals↗

PubMed2001

Multiple PIP2 binding sites in Kir2.1 inwardly rectifying potassium channels.

Inwardly rectifying potassium channels require binding of phosphatidylinositol-4,5-bisphosphate (PIP2) for channel activity. Three independent sites (aa 175-206, aa 207-246, aa 324-365) were located in the C-terminal domain of Kir2.1 channels by assaying the binding of overlapping fragments to PIP2 containing liposomes. Mutations in the first site, which abolished channel activity, reduced PIP2 binding of this fragment but not of the complete C-terminus. Point mutations in the third site also reduced both, channel activity and PIP2 binding of this segment. The relevance of the third PIP2 binding site provides a basis for the understanding of constitutively active Kir2 channels.

Animals↗

PubMed2001

The role of hypertension in bromocriptine-related puerperal intracranial hemorrhage.

The spate of medicolegal inquiries following the disqualification of Parlodel (bromocriptine mesylate) by the Food and Drug Administration for postpartum ablactation, uncovered previously unreported side effects associated with its postpartum administration. In 1994, bromocriptine mesylate was withdrawn from the market as a milk suppressant. Since this time, over a dozen cases of postpartum intracranial hemorrhages associated with its use have been reported. We describe three additional cases of postpartum intracranial hemorrhage related to bromocriptine usage. One patient, previously normotensive, developed hypertension and a headache; initial CT was normal, but CT 24 h later demonstrated intracranial hemorrhage. This suggests that the blood-pressure elevation was drug-induced and was the cause, rather than the consequence, of bromocriptine-related intracranial hemorrhage.

Adult↗

PubMed2001

Membrane-disordering effects of beta-amyloid peptides.

beta-Amyloid (Abeta) protein is the major constituent of senile plaques and cerebrovascular deposits characteristic of Alzheimer's disease (AD). The causal relationship between Abeta and AD-specific lesions like neurodegeneration and atrophy is still not known. The present article summarizes our studies indicating that rather low concentrations of Abeta significantly alter the fluidity of cell membranes and subcellular fractions from different tissues and different species including humans, as a possible initial step of its biological effects. Using different fluorescent probes our data show clearly that Abeta peptides specifically disturb the acyl-chain layer of cell membranes in a very distinct fashion. By contrast, membrane properties at the level of the polar heads of the phospholipid bilayer at the interface with membrane proteins are much less affected.

Alzheimer Disease↗

PubMed2001

A highly specific pathogen-responsive promoter element from the immediate-early activated CMPG1 gene in Petroselinum crispum.

Within the complex signalling network from pathogen-derived elicitor perception to defense-related gene activation, some immediate-early responding genes may have pivotal roles in downstream transcriptional regulation. We have identified the parsley (Petroselinum crispum) ELI17 gene as a particularly fast-responding gene possessing a new type of W box-containing, elicitor-responsive promoter element, E17. Highly selective E17-mediated reporter gene expression at pathogen infection sites in transgenic Arabidopsis thaliana plants demonstrated the potential of this promoter element for designing new strategies in resistance breeding as well as for further analysis of the early components of defense-related gene activation mechanisms. The protein encoded by the ELI17 gene exhibits various structural characteristics of established transcription factors and is designated as a CMPG protein according to the first four strictly conserved amino acids defining a newly emerging class of plant-specific proteins.

Algal Proteins↗

PubMed2001

[Secondary high-grade MALT lymphoma of the stomach in a 69-year-old patient with gastrocolic fistula].

A 69-year-old man was referred to our department with an exorbitant foetor ex ore, dysphagia and dyspepsia. Upper endoscopy had been performed prior by an outpatient gastroenterologist and the patient had received an eradication therapy for a Helicobacter pylori-induced gastritis. At admission upper endoscopy showed a gastric ulcer which drained a stinking fluid. Endosonography, computed tomography and an upper gastrointestinal series with water soluble media revealed a gastrocolic fistula. Multiple biopsies showed a low-grade gastric MALT lymphoma. Therefore, a surgical reconstruction with Roux-en-Y esophagojejunostomy and transverso-descendostomy was performed. The histology of the completely removed stomach revealed a high-grade Non Hodgkin Lymphoma (NHL) with parts of a low-grade NHL. 3 weeks after surgery chemotherapy was started with the CHOP-regime which was well-tolerated by the patient.

Aged↗

PubMed2001

[Symptomatic cyst of the pancreas and asymptomatic bilateral phaeochromocytoma]

Symptomatic cyst of the pancreas and asymptomatic bilateral phaeochromocytoma. HISTORY AND CLINICAL FINDINGS: A 39-year-old woman was admitted to our department of gastroenterology with recurrent epigastrical pain. Ten years previously the diagnosis of von Hippel-Lindau (VHL)-syndrome has been established. Two years before a germ line mutation in exon 3 of the VHL-tumour suppressor gene has been detected. The patient has a healthy son with a normal VHL-gene and four healthy siblings who had refused a genetic blood test. INVESTIGATIONS: At abdominal ultrasound at the head of the pancreas three 4 2 cm large cysts and in the region of the left adrenal gland a 2,9 2,7 cm large tumor were visible. MRI of the abdomen revealed in addition a 2,2 1,5 cm large tumour of the right adrenal gland. An asymptomatic biadrenal phaeochromocytoma was detected by elevated urine catecholamines and 123I-MIBG-scintigraphy. TREATMENT AND COURSE: The cysts of the pancreas were punctured under endosonographical control and analysis of the cyst fluid was not suspicious of a malignant cystic tumour. The patient had no further abdominal complaints. After oral treatment with the alpha-blocker phentolamine the biadrenal phaeochromocytoma was treated by retroperitoneal laparoscopic surgery in an organ-sparing fashion. Postoperatively ACTH-stimulating test revealed a normal cortisol response. CONCLUSION: Adrenocortical function can be preserved by la-paroscopic adrenal-sparing surgery in bilateral phaeochromocytoma.

Journal Article↗

PubMed2001

Helicobacter pylori vacA, iceA, and cagA status and pattern of gastritis in patients with malignant and benign gastroduodenal disease.

OBJECTIVE: Both bacterial virulence factors and the pattern of Helicobacter pylori (H. pylori) gastritis may contribute to the development of clinically relevant gastroduodenal disease. The aim of our study was to investigate the frequency of H. pylori vacA alleles, iceA, and cagA, and the pattern of gastritis in patients with gastric cancer (GC), gastric lymphoma (MALT), duodenal ulcer (DU), and functional dyspepsia (FD). METHODS: H. pylori was cultured from 141 patients (34 GC, 26 MALT, 49 DU, 32 FD). Allelic variants of vacA and iceA, and cagA were identified by polymerase chain reaction. Antrum and corpus biopsies were obtained for assessment of gastritis according to the updated Sydney System. RESULTS: The vacA sl,ml genotype was more frequently detected in H. pylori from GC patients (70.6%) than from MALT, DU, and FD patients (p < 0.05). The frequency of iceA1 and cagA did not differ among the groups. The proportion of patients with severe gastritis in the corpus was significantly higher in patients with GC and MALT compared with patients with DU (p < 0.001). CONCLUSIONS: In a German patient population, only the vacA s1,m1 genotype of H. pylori is associated with GC, and therefore may be useful to identify infected patients being at an increased risk for GC.

Aged↗

PubMed2001

Helicobacter pylori and gastric cancer:current status of the Austrain Czech German gastric cancer prevention trial (PRISMA Study).

AIM: To test the hypothesis that Helicobacter pylori eradication alone can reduce the incidence of gastric cancer in a subgroup of individuals with an increased risk for this fatal disease. METHODS: It is a prospective, randomized, double blind, placebo controlled multinational multicenter trial. Men between 55 and 65 years of age with a gastric cancer phenotype of Helicobacter pylori gastritis are randomized to receive a 7 day course of omeprazole 2 X 20mg, clarithromycin 2 X 500mg, and amoxicillin 2 X 1g for 7 days, or omeprazole 2 X 20mg plus placebo. Follow-up endoscopy is scheduled 3 months after therapy, and thereafter in one-year intervals. Predefined study endpoints are gastric cancer, precancerous lesions (dysplasia, adenoma), other cancers, and death. RESULTS: Since March 1998, 1524 target patients have been screened, 279 patients (18.3%) had a corpus dominant type of H. pylori gastritis, and 167 of those were randomized (58.8%). In the active treatment group (r = 86), H. pylori infection infection was cured in 88.9% of patients. Currently, the cumulative follow-up time is 3046 months (253.38 patient years, median follow up 16 months). So far, none of the patients developed gastric cancer or any precancerous lesion. Three (1.8%) patients reached study endpoints other than gastric cancer. CONCLUSION: Among men between 55 and 65 years of age, the gastric cancer phenotype of H. pylori gastritis appears to be more common than expected. Further follow up and continuing recruitment are necessary to fulfil the main aim of the study.

Amoxicillin↗

PubMed2000

The Helicobacter pylori vacA s1, m1 genotype and cagA is associated with gastric carcinoma in Germany.

BACKGROUND: The H. pylori vacuolating cytotoxin encoded by vacA and the cytotoxin-associated protein encoded by cagA are considered to be important virulence determinants that have been implicated in the development of peptic ulcers and gastric carcinoma. However, conflicting results regarding the association between these virulence factors and clinical disease have been reported from different geographic regions. AIMS: To determine the frequency of vacA genotypes, vacuolating cytotoxin activity, and cagA in H. pylori isolates obtained from patients with gastric cancer in Germany. METHODS: H. pylori isolates were obtained from 34 patients with gastric cancer and from 35 subjects with asymptomatic H. pylori gastritis. vacA genotypes and cagA were identified by PCR. Cytotoxic activity was determined by HeLa cell assays. Gastritis was assessed according to the updated Sydney System. RESULTS: The H. pylori vacA s1,m1 genotype was significantly more frequent in patients with gastric cancer (24/34, 70.6%) as compared with controls (12/35, 34. 3%) (p = 0.005). Cytotoxic activity was detected in 24 (70.6%) and 15 (42.9%) H. pylori isolates from gastric cancer patients and controls, respectively (p = 0.03). The cagA gene was identified in 30 (88.2%) and 21 (60%) H. pylori isolates in the respective groups (p = 0.01). CONCLUSIONS: Our study suggests a significant association between the H. pylori vacA s1,m1 genotype, cytotoxic activity, cagA, and gastric cancer. Detection of H. pylori possessing these virulence determinants may help to identify patients being at an increased risk to develop gastric cancer in our population.

Adenocarcinoma↗

PubMed1998

Identification of 55 kDa phosphatidylinositol 4-kinase in HaCaT cells: comparison with the epithelial cell line A431.

Phosphatidylinositol kinases play a crucial role in signal transduction in many cell types. The 55 kDa isoform of phosphatidylinositol 4-kinases is a key enzyme in the metabolism of phosphoinositides, which work as regulators of cell function itself or as precursors of signal molecules. The experiments with HaCaT cells presented suggest that the phosphatidylinositol 4-kinase activity in this cell line corresponds to the 55 kDa isoform concerning kinetic parameters and specific activity in comparison with the malignant cell line A431. Km (for ATP and phosphatidyl-inositol) and Ki values (for Ca2+ and adenosine) are in good agreement with the parameters described for other cells. The findings support the idea that the 55 kDa phosphatidylinositol 4-kinase represents a key enzyme in the inositide signal transduction pathway.

1-Phosphatidylinositol 4-Kinase↗