PubMed Health⌕ Search

Biomedical subjects

B Wiedenmann

Publications and source records attributed to B Wiedenmann.

At least 19 recordsLinked to original sources
PubMed2007

A phase IB, open-label dose-escalating study of the oral angiogenesis inhibitor PTK787/ZK 222584 (PTK/ZK), in combination with FOLFOX4 chemotherapy in patients with advanced colorectal cancer.

BACKGROUND: This open-label, phase IB study was undertaken to determine the safety/toxicity profile and recommended dose of oral once-daily PTK787/ZK 222584 (PTK/ZK) combined with oxaliplatin/5-fluorouracil (5-FU)/leucovorin (FOLFOX4) chemotherapy in patients with advanced colorectal cancer. Secondary objectives were to assess full pharmacokinetics and gather preliminary evidence of antitumor activity. PATIENTS AND METHODS: Thirty-five patients received escalating doses of PTK/ZK (range 500-2000 mg daily) continuously. Concurrent FOLFOX4 chemotherapy was administered on days 1 and 2 and repeated every 14 days. Dose escalation of PTK/ZK was continued until maximum tolerated dose (MTD) was established and additional patients were then enrolled at MTD dosage. RESULTS: Mean treatment duration of PTK/ZK was 9.5 months. The MTD was 1250 mg daily with dizziness being the most frequent dose-limiting toxicity (DLT). Hypertension (23%, grade 3) and neutropenia (37%, grades 3 + 4) were the most frequent grade 3 or 4 adverse events. Pharmacokinetic analyses found no evidence for interactions between PTK/ZK and the combination of 5-FU, leucovorin, and oxaliplatin during concomitant use. Median progression-free survival was 11.4 months. CONCLUSION: The MTD of PTK/ZK in combination with FOLFOX4 in this patient population is 1250 mg daily. The combination is feasible and safe and is not associated with significant pharmacokinetic interactions.

Adult↗
PubMed2006

Health-related quality of life in patients with pancreatic cancer.

BACKGROUND: Pancreatic cancer is an aggressive cancer with low survival time, with health-related quality of life (HRQoL) being of major importance. The aim of our study was to assess both generic and disease-specific HRQoL in patients with pancreatic cancer. METHODS: Patients with pancreatic cancer were consecutively included at admission to hospital. HRQoL was determined with the disease-specific European Organization for Research and Treatment of Cancer (EORTC) and generic EuroQoL (EQ-5D) health status instruments. Scores of patients were compared to those of norm populations. The association of symptoms with overall HRQoL was analysed using linear regression. RESULTS: A total of 45 patients with pancreatic cancer were included. The mean age was 64 years, 53% were females. Of all patients, 44% had metastases at the time of admission. HRQoL was significantly impaired for most EORTC and EQ-5D scales in comparison to norm populations. Symptoms of fatigue (-0.34 regression coefficient; 95% CI -0.63, -0.11) and pain (-0.21; 95% CI -0.39, -0.02) were significantly associated with impaired overall HRQoL. CONCLUSIONS: HRQoL was severely impaired in patients with pancreatic cancer. Symptom control and palliative care appear to be of particular importance.

Aged↗
PubMed2006

Impact of FDG-PET/MRI image fusion on the detection of pancreatic cancer.

BACKGROUND: This study assessed the value of image fusion with (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) in patients suspected of having pancreatic cancer. METHODS: 32 patients (12 women, 20 men; age 24-79 years; mean 56.6 years) were included. All patients underwent whole-body FDG-PET examinations and contrast-enhanced MRI. Image fusion used a semiautomatic voxel-based algorithm. Separate reading, side-by-side analysis and evaluation of fused PET/MRI images were performed. Results were correlated to histopathology (n = 30), or clinical follow-up (n = 2). RESULTS: 15/32 patients had pancreas cancer and 17/32 patients benign disease. The sensitivity and specificity for cancer detection by FDG-PET were 93 and 41% for visual and 86 and 58% for semiquantitative analysis whereas MRI achieved 100 and 76% respectively. Topographical assignment of PET foci by image fusion was superior to side-by-side analysis in 11/39 (28%) foci (in 8/32 patients). However, a true impact on therapeutic strategy was observed only in 1/8 patients as the presence of multiple metastases, irresectable primaries or medical reasons for inoperability prevented a curative setting. CONCLUSION: Compared to side-by-side analysis, PET/MRI image fusion improves the anatomical assignment and interpretation of FDG foci. The therapeutic benefit for the patient however is limited in patients with multiple lesions or incurable primaries.

Adenocarcinoma↗
PubMed2006

TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system.

The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor-node-metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients.

Biomarkers, Tumor↗
PubMed2006

Escherichia coli strain Nissle 1917 ameliorates experimental colitis via toll-like receptor 2- and toll-like receptor 4-dependent pathways.

Toll-like receptors (TLRs) are key components of the innate immune system that trigger antimicrobial host defense responses. The aim of the present study was to analyze the effects of probiotic Escherichia coli Nissle strain 1917 in experimental colitis induced in TLR-2 and TLR-4 knockout mice. Colitis was induced in wild-type (wt), TLR-2 knockout, and TLR-4 knockout mice via administration of 5% dextran sodium sulfate (DSS). Mice were treated with either 0.9% NaCl or 10(7) E. coli Nissle 1917 twice daily, followed by the determination of disease activity, mucosal damage, and cytokine secretion. wt and TLR-2 knockout mice exposed to DSS developed acute colitis, whereas TLR-4 knockout mice developed significantly less inflammation. In wt mice, but not TLR-2 or TLR-4 knockout mice, E. coli Nissle 1917 ameliorated colitis and decreased proinflammatory cytokine secretion. In TLR-2 knockout mice a selective reduction of gamma interferon secretion was observed after E. coli Nissle 1917 treatment. In TLR-4 knockout mice, cytokine secretion was almost undetectable and not modulated by E. coli Nissle 1917, indicating that TLR-4 knockout mice do not develop colitis similar to the wt mice. Coculture of E. coli Nissle 1917 and human T cells increased TLR-2 and TLR-4 protein expression in T cells and increased NF-kappaB activity via TLR-2 and TLR-4. In conclusion, our data provide evidence that E. coli Nissle 1917 ameliorates experimental induced colitis in mice via TLR-2- and TLR-4-dependent pathways.

Animals↗
PubMed2005

Direct and indirect costs in a prospective cohort of patients with pancreatic cancer.

BACKGROUND: Pancreatic cancer is an aggressive cancer with a low survival time. So far, there have been no studies assessing direct and indirect costs in individual patients. AIM: To assess prospectively the cost of illness in patients with pancreatic cancer. METHODS: Patients were consecutively included at first admission to hospital. Sociodemographic factors, medical resource use and employment status were assessed by patient interviews and from medical records in a standardized way. Costs were calculated from the perspectives of the hospital, social insurance and society. Linear regression analyses were used to determine factors associated with costs. RESULTS: A total of 57 patients were admitted with suspected pancreatic cancer. Of these patients, 45 (79%) had pancreatic cancer as final diagnosis, 11 (19%) pancreatitis and one patient cystadenoma. The median survival was 10.9 months in patients with pancreatic cancer. Per month of observation from societal perspective, total costs were 4075 for patients. Costs of hospitalizations were responsible for 75% of total costs. In multivariable analyses, surgery, a lower educational level, younger age, and the prevalence of metastases were significantly associated with higher total costs. CONCLUSIONS: Costs are considerable in patients with pancreatic cancer. Our results may facilitate further economic evaluations and aid health policy-makers in resource allocation.

Absenteeism↗
PubMed2005

Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats.

BACKGROUND AND AIMS: Ghrelin, the natural ligand of the growth hormone secretagogue receptor 1a, is the most powerful peripherally active orexigenic agent known. In rodents, ghrelin administration stimulates growth hormone release, food intake, and adiposity. Because of these effects, blocking of ghrelin has been widely discussed as a potential treatment for obesity. Spiegelmer NOX-B11 is a synthetic l-oligonucleotide, which was previously shown to bind ghrelin. We examined the effects of NOX-B11 on ghrelin induced neuronal activation and food intake in non-fasted rats. METHODS: Animals received various doses of NOX-B11, inactive control Spiegelmer, or vehicle intravenously. Ghrelin or vehicle was administered intraperitoneally 12 hours later and food intake was measured over four hours. Neuronal activation was assessed as c-Fos-like immunoreactivity in the arcuate nucleus. RESULTS: Treatment with NOX-B11 30 nmol suppressed ghrelin induced c-Fos-like immunoreactivity in the arcuate nucleus and blocked the ghrelin induced increase in food intake within the first half hour after ghrelin injection (mean 1.13 (SEM 0.59) g/kg body weight; 4.94 (0.63) g/kg body weight versus 0.58 (0.58) g/kg body weight; p<0.0001). Treatment with NOX-B11 1 nmol or control Spiegelmer had no effect whereas treatment with NOX-B11 10 nmol showed an intermediate effect on ghrelin induced food intake. CONCLUSIONS: Spiegelmer NOX-B11 suppresses ghrelin induced food intake and c-Fos induction in the arcuate nucleus in rats. The use of an anti-ghrelin Spiegelmer could be an innovative new approach to inhibit the biological action of circulating ghrelin. This may be of particular relevance to conditions associated with elevated plasma ghrelin, such as the Prader-Willi syndrome.

Animals↗
PubMed2005

[Endoscopic therapy of acute and chronic pancreatitis].

Endoscopic therapy is valuable for both acute and chronic pancreatitis. Early endoscopic papillotomy appears, in the case of a severe course of acute biliary pancreatitis, to be advantageous. Endoscopic drainage can be considered in cases of acute fluid retention and necrosis as well as subacute, non-healing pancreatitis or cyst development. By acute chronic pancreatitis with strictures or bile duct stones, papillotomy, dilation and stent insertion can lead to an improvement in pain symptoms. An improvement in endo- or exocrine function, however, is not expected. Studies on the endoscopic therapy of pancreatitis are still very limited, and recommendations can usually only be made based on retrospective case series.

Acute Disease↗
PubMed2005

Endocrine tumours of the gastrointestinal tract. Management of metastatic endocrine tumours.

Gastroenteropancreatic tumours are rare. They compromise a heterogenous class of neoplasm. If there is no hypersecretion syndrome, symptoms may be uncharacteristic and thus diagnosis occurs rather late after the first manifestations of the disease. The most important prognostic parameters are histological classification, the localisation of the primary, the tumour size and stage at diagnosis, and the presence or absence of metachronous or synchronous neoplasia. The article will focus on the importance of each of these parameters for the various treatment options in patients with metastatic disease.

Antineoplastic Agents↗
PubMed2005

Long-term failure of endoscopic suturing in the treatment of gastroesophageal reflux: a prospective follow-up study.

BACKGROUND AND STUDY AIMS: Several endoscopic antireflux therapies have been marketed, but long-term data on their objective and clinical efficacy are sparse. This report presents prospective 1-year follow-up results, including technical, clinical, and functional success rates, for the first of these treatments to be developed, endoscopic gastroplication (EGP). PATIENTS AND METHODS: A total of 43 EGP procedures were carried out in 38 patients with gastroesophageal reflux disease (GERD). Two or three EndoCinch gastroplications were constructed at the level of the gastric cardia in each patient; five patients were treated twice within 6 - 12 months. Each endoscopic suture joined two gastric folds to each other as a double fold, known as a "gastroplication", in order to narrow the esophagogastric junction. Postprocedure data after 2 months and after 1 year were compared with preoperative data, focusing on symptoms, medication requirements, endoscopic findings, and pH-metry results. RESULTS: In contrast to the findings at 2 months (which showed that 72 % of the sutures were present and that there was a reduction in the percentage of time when the esophageal pH was < 4 from 15.4 % to 8.7 %), the results 1 year after EGP were considered to indicate failure of the treatment in all 38 patients because none of them still had all of the initially placed gastroplications in situ (90 % of gastroplications were lost). The percentage of patients who did not require proton pump inhibitor medication decreased from 52 % at 2 months to only 20 % at 1 year and even more patients had evidence of reflux esophagitis at 1 year (56 %) than had initially demonstrated signs of this (41 %). CONCLUSIONS: EGP has some short-term beneficial effects on clinical symptoms and pH-metry. However, mainly due to the loss of the endoscopically placed sutures, these effects were not maintained at the 1-year follow-up. EGP cannot therefore be recommended for routine clinical use. Better endoscopic methods need to be developed, and they should be adequately tested before being marketed.

Adult↗
PubMed2005

Patients with active inflammatory bowel disease lack immature peripheral blood plasmacytoid and myeloid dendritic cells.

BACKGROUND: Breakdown of tolerance against the commensal microflora is believed to be a major factor in the pathogenesis of inflammatory bowel disease (IBD). Dendritic cells (DC) have been implicated in this process in various animal models, but data on human DC in IBD are very limited. AIM: To characterise plasmacytoid DC (PDC) and myeloid DC (MDC) in patients with active versus inactive IBD and healthy controls. PATIENTS AND METHODS: Peripheral blood was obtained from 106 patients (Crohn's disease (CD) n=49, ulcerative colitis (UC) n=57) and healthy controls (n=19). Disease activity was scored using the modified Truelove Witts (MTWSI) for UC and the Harvey Bradshaw severity indices (HBSI) for CD. Four colour flow cytometric analysis was used to identify, enumerate, and phenotype DC. DC from patients with acute flare ups and healthy controls were cultured and stimulated with CpG ODN 2006 or lipopolysaccharide (LPS). RESULTS: IBD patients in remission (PDC UC, 0.39%; CD, 0.35%; MDC-1 UC, 0.23%; CD, 0.22% of PBMC) have slightly lower numbers of circulating DC compared with healthy controls (PDC 0.41%, MDC-1 0.25% of PBMC). In acute flare ups IBD patients experience a significant drop of DC (PDC UC, 0.04%; CD, 0.11%; MDC-1 UC, 0.11%; CD, 0.14% of PBMC) that correlates with disease activity (correlation coefficients: PDC MTWSI, 0.93; HBSI, 0.79; MDC-1 MTWSI, 0.75; HBSI, 0.81). Moreover, both express alpha4beta7 integrin and display an immature phenotype. Freshly isolated PDC and MDC-1 from untreated flaring IBD patients express higher baseline levels of CD86 which increases further in culture and upon stimulation compared with healthy controls. CONCLUSION: IBD patients lack immature blood DC during flare ups which possibly migrate to the gut. An aberrant response to microbial surrogate stimuli suggests a disturbed interaction with commensals.

Acute Disease↗
PubMed2004

[Neuroendocrine tumours of the gastrointestinal tract].

Gastrointestinal neuroendocrine tumours are classified as functioning or non-functioning according to the presence or absence of a clinically evident hypersecretion syndrome. In foregut tumours the presence of autonomous hormone secretion and the respective hypersecretion syndrome indicate functionality. Abdominal ultrasound (US), computed tomography (CT), magnetic resonance tomography (MRT) and somatostatin receptor scintigraphy (SRS) are used for localisation of the primary tumour and metastasis. Invasive procedures such as endoscopic US, intraoperative US or intraoperative duodenal transillumination are useful to localise small (< 1 cm) tumours. For localised tumours surgery is the first line treatment. In metastatic disease symptomatic therapy, biotherapy and chemotherapy are available. Cytoreductive therapy such as embolisation, chemoembolisation, thermo- or cryotherapy, or radio-receptor therapy are additional options. The first symptom of most neuroendocrine midgut tumours is abdominal pain. An increased chromogranin-A plasma concentration or 5-hydroxyindoleacetic acid 24-h urinary excretion indicates the neuroendocrine origin of the tumour or the possibility of a carcinoid syndrome, respectively. Surgical therapy prolongs survival but is rarely curative. Biotherapy is effective as symptomatic therapy. However, its cytoreductive potency is low. Chemotherapy is less effective in midgut tumours compared to foregut tumours. Cytoreductive strategies (chemoembolisation, thermo- or cryotherapy, cytoreductive surgery) and radio-receptor therapy may offer new therapeutic options. However, their definitive value has yet to be defined.

Antineoplastic Agents↗
PubMed2004

Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system.

This consensus report gives a detailed description of the use of somatostatin analogs in the management of neuroendocrine tumors of the gastroenteropancreatic system. As background information we have outlined critical aspects of the pathology, the use of tumor markers, a definition of functional and non-functional digestive neuroendocrine tumors, different imaging modalities, surgical considerations, liver embolization and the use of cytotoxic drugs as well as interferon. Included in the report is an overview of somatostatin, somatostatin analogs and its receptor expression in different neuroendocrine tumors. It will also define the binding affinities of different somatostatin analogs to the five different subtypes of somatostatin receptor. We compare the efficacy of octreotide and lanreotide in reducing diarrhea and flushing. Side-effects are described and we provide practical information on somatostatin analog treatment.

Antineoplastic Agents, Hormonal↗
PubMed2004

Clinical relevance of transabdominal ultrasonography and magnetic resonance imaging in patients with inflammatory bowel disease of the terminal ileum and large bowel.

BACKGROUND: Ileocolonoscopy represents the diagnostic standard in the work-up of patients with inflammatory bowel diseases (IBD). Patients are often reluctant to be colonoscoped because of the invasiveness and pain sensation during colonoscopy. AIMS: To compare the usefulness oftransabdominal ultrasound (US) and magnetic resonance imaging (MRI) in assessing disease extension and activity in patients with IBD restricted to the terminal ileum and large bowel. PATIENTS AND METHODS: 61 patients with IBD [37 Crohn's disease (CD) and 24 ulcerative colitis (UC)] were prospectively studied. All patients underwent clinical and laboratory assessment, ileocolonoscopy, transabdominal sonography, and MRI within 5 days. Involved bowel segments were defined as those with bowel wall thickness >3 mm and increased Doppler signal on US or contrast enhancement of the bowel wall on MRI. To compare disease activity endoscopic, MRI and US findings were graded with newly developed scores. RESULTS: The segment-by-segment analysis revealed an overall accuracy of 89% for US and 73% for MRI in identifying active IBD. The accuracy was better in patients with UC than in patients with CD for both US and MRI. The endoscopic activity index (EAI) correlated stronger with the US activity index (r = 0.884) than with the MRI activity index (r = 0.344). The correlation of US and MRI activity indices with EAI was better in patients with UC compared with patients with CD. All three imaging methods showed a significant correlation with clinical disease activity in patients with UC but not in patients with CD. CONCLUSION: This study provides strong evidence that US should be considered as a first-choice method for follow-up of patients with IBD of the terminal ileum and large bowel.

Adult↗
PubMed2004

Oesophageal transport of solid dosage forms depends on body position, swallowing volume and pharyngeal propulsion velocity.

Knowledge about transit of solid dosage forms (SDF) in the gastrointestinal tract is incomplete. Detection of magnetically marked capsules (MMC) via superconducting quantum interference device (SQUID) allows monitoring of oesophageal transport of SDF with high tempospatial resolution. The aim of the study was to investigate the influence of body position, volume at swallowing, and oesophageal motility on orogastric transport of SDF. In 360 measurements we determined tempospatial characteristics of orogastric transit of SDFs by a SQUID device in six volunteers. They swallowed MMCs with various amounts of water in upright and supine position with and without simultaneous oesophageal manometry. Orogastric transit time, oesophageal transport velocity and rate of oesophageal retention of SDF depend on swallowing volume and body position at all experimental conditions. At 50 mL water bolus and in upright position, the retention rate depends on the pharyngeal propulsion velocity, and the transport velocity of MMCs in the oesophageal body are faster than the propulsive oesophageal contractions. Body position, swallowing volume and pharyngeal propulsion velocity markedly influence the oesophageal transport of SDF. They should be taken in upright body position with at least 50 mL of water to minimize entrapment in the oesophagus.

Adult↗