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Biomedical subjects

P N Meier

Publications and source records attributed to P N Meier.

At least 19 recordsLinked to original sources
PubMed2006

Cholangioscopic characterization of dominant bile duct stenoses in patients with primary sclerosing cholangitis.

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is associated with the development of cholangiocarcinoma in up to 10 % of patients. Cholangiography or endoscopic tissue sampling does not reliably distinguish between cholangiocarcinoma and a benign dominant bile duct stenosis. The aim of the present study was to assess the value of cholangioscopy for distinguishing between benign and malignant dominant stenoses in PSC patients. PATIENTS AND METHODS: Fifty-three PSC patients with dominant bile duct stenoses were prospectively studied. Transpapillary cholangioscopy and endoscopic tissue sampling were carried out in addition to endoscopic retrograde cholangiography (ERC). The cholangiography and cholangioscopic findings were classified as malignant or benign by the investigators. A final diagnosis of malignant stenosis was based on positive histology and/or cytology, whereas a benign condition was assumed in cases of negative tissue sampling and uneventful extended clinical follow-up. RESULTS: Twelve PSC patients (23 %) had dominant bile duct stenoses caused by cholangiocarcinoma, whereas 41 of the 53 patients (77 %) had benign dominant bile duct stenoses. Cholangioscopy was significantly superior to ERC for detecting malignancy in terms of its sensitivity (92 % vs. 66 %; P = 0.25), specificity (93 % vs. 51 %; P < 0.001), accuracy (93 % vs. 55 %; P < 0.001), positive predictive value (79 % vs. 29 %; P < 0.001), and negative predictive value (97 % vs. 84 %; P < 0.001). Transpapillary cholangioscopy is more sensitive and specific for characterizing malignant bile duct stenosis in comparison with endoscopic brush cytology. CONCLUSIONS: Transpapillary cholangioscopy significantly increases the ability to distinguish between malignant and benign dominant bile duct stenoses in patients with PSC.

Adolescent↗
PubMed2006

[Advantages of endoscopic stenting for malignant gastrointestinal obstructions].

Self-expanding stents play a major role in the interdisciplinary treatment of gastrointestinal obstructions in patients with local nonresectable tumors, advanced metastasis, and pronounced comorbidity. Reinstenting the passage and sealing esophagotracheal fistulae is very effective as palliative treatment for esophageal tumor complications. In hepatobiliary occlusions, the success rate against cholestasis is also high. Enteral and colorectal stents are gaining favor. Required are an experienced endoscopy team and adequate equipment. The rate of procedural complications is generally low, but rare and severe complications such as perforation must be considered. Further improvements in the materials and construction of stents can be expected.

Constriction, Pathologic↗
PubMed2005

Selective expression of histamine receptors H1R, H2R, and H4R, but not H3R, in the human intestinal tract.

BACKGROUND AND AIMS: Histamine is known as a regulator of gastrointestinal functions, such as gastric acid production, intestinal motility, and mucosal ion secretion. Most of this knowledge has been obtained from animal studies. In contrast, in humans, expression and distribution of histamine receptors (HR) within the human gastrointestinal tract are unclear. METHODS: We analysed HR expression in human gastrointestinal tissue specimens by quantitative reverse transcription-polymerase chain reaction and immunostaining. RESULTS: We found that H1R, H2R, and H4R mRNA were expressed throughout the gastrointestinal tract, while H3R mRNA was absent. No significant differences in the distribution of HR were found between different anatomical sites (duodenum, ileum, colon, sigma, and rectum). Immunostaining of neurones and nerve fibres revealed that H3R was absent in the human enteric nervous system; however, H1R and H2R were found on ganglion cells of the myenteric plexus. Epithelial cells also expressed H1R, H2R and, to some extent, H4R. Intestinal fibroblasts exclusively expressed H1R while the muscular layers of human intestine stained positive for both H1R and H2R. Immune cells expressed mRNA and protein for H1R, H2R, and low levels of H4R. Analysis of endoscopic biopsies from patients with food allergy and irritable bowel syndrome revealed significantly elevated H1R and H2R mRNA levels compared with controls. CONCLUSIONS: We have demonstrated that H1R, H2R and, to some extent, H4R, are expressed in the human gastrointestinal tract, while H3R is absent, and we found that HR expression was altered in patients with gastrointestinal diseases.

Cells, Cultured↗
PubMed2004

[Lichen planus esophagitis without skin, genital or oral mucosa involvement].

Lichen ruber planus is a common skin and mucosal disease, with very rare involvement of the esophagus. We report on a 68-year-old patient suffering from dysphagia, with a reduced general condition and weight loss of 12 kg in the past 6 months due to lichen planus of the esophagus. Treatment by bougienage was very successful. This case report describes a lichen ruber planus of the esophagus without involvement of skin, genital or oral mucosa.

Aged↗
PubMed2004

Analysis of factors contributing to higher erythropoietin levels in patients with chronic liver disease.

BACKGROUND: Dysregulated erythropoietin (EPO) plasma levels may play a role in the pathophysiology of chronic liver disease (CLD) because chronic anaemia is frequently observed in patients with liver cirrhosis. We aimed to identify the factors contributing to EPO regulation in patients with CLD. METHODS: Plasma EPO concentrations were correlated with clinical and laboratory parameters in 111 CLD patients and 220 healthy controls. RESULTS: Anaemia, though generally mild, was common in CLD patients, and thrombocytopenia and previous bleeding episodes were observed in two-thirds of the patients. Plasma EPO levels were significantly elevated in CLD patients (P < 0.001). EPO increased according to Child's stages of cirrhosis, independently of the aetiology of CLD. EPO correlated with haemoglobin (r= -0.498, P < 0.001). Additionally, EPO independently correlated with markers of liver dysfunction, e.g. prothrombin time, albumin concentration or cholinesterase activity, and platelet count. EPO was also significantly elevated in patients with a current bleeding tendency and with prior gastrointestinal haemorrhages. EPO levels were increased in patients with impaired pulmonary function, e.g. decreased diffusion capacity, vital capacity or hyperventilation. Interestingly, plasma interleukin-6 (IL-6) concentrations positively correlated with EPO (r=0.277, P = 0.003), suggesting a possible mechanism of EPO upregulation in patients with CLD through IL-6 dependent pathways, e.g. binding of STAT transcription factors in the putative EPO promoter region. CONCLUSIONS: EPO is upregulated in patients with chronic liver diseases in response to anaemia, bleeding complications, impaired pulmonary function, thrombocytopenia and liver dysfunction. IL-6 dependent pathways could be involved in mediating elevated EPO levels in CLD patients.

Adolescent↗
PubMed2003

Telomere shortening of epithelial cells characterises the adenoma-carcinoma transition of human colorectal cancer.

BACKGROUND: and aims: Chromosomal instability is one of the most consistent markers of sporadic colorectal cancer in humans. There is growing evidence that telomere shortening is one of the mechanisms leading to chromosomal instability and cancer initiation. METHODS: To test this hypothesis, the telomere length of colorectal epithelial cells and cells from connective tissue was determined at the adenoma-carcinoma transition at the cellular level by quantitative fluorescence in situ hybridisation. RESULTS: Our study showed that the telomere fluorescence intensity of epithelial cells was significantly weaker at the earliest morphologically definable stage of carcinoma-high grade dysplasia with minimal invasive growth-compared with the surrounding adenoma. In contrast, cells from connective tissue had a similar telomere signal intensity at the carcinoma stage compared with the adenoma, and in turn cells from connective tissue had overall significantly stronger telomere fluorescence signals compared with epithelial cells. CONCLUSIONS: These results demonstrate that short telomeres of epithelial cells characterise the adenoma-carcinoma transition during human colorectal carcinogenesis, suggesting that carcinomas arise from cells with critical short telomeres within the adenoma. Since the adenoma-carcinoma transition in colorectal cancer is characterised by an increase in chromosomal instability and anaphase bridges, our data support the hypothesis that short telomeres initiate colorectal cancer by induction of chromosomal instability.

Adenoma↗
PubMed2002

Cystic echinococcosis with perforation into the biliary tract in an eight-year-old girl.

Cystic echinococcosis (CE) is a zoonotic infection caused by echinococcus granulosus and is still frequent in endemic areas. CE is predominantly localised in the liver. The therapy of choice is the surgical sanitation of the lesions, increasingly through interventional procedures such as percutaneous punctation of the cysts, aspiration of the cystic fluid, instillation of a protoscolicidal solution and reaspiration of this solution (PAIR). However, in some cases, such as perforation into the biliary tract, PAIR is not feasible. We report on an eight-year-old girl who suffered from CE with perforation of one cyst into the biliary tract. The diagnosis was confirmed by ERCP and cholangioscopy and a right hemihepatectomy was performed. The girl received adjuvant chemotherapy with albendazol perioperatively and is still asymptomatic with no indications of disease 10 months after the operation.

Albendazole↗
PubMed2002

Evaluation of endoscopic retrograde cholangiopancreatography under conscious sedation and general anesthesia.

BACKGROUND AND STUDY AIMS: In adults, general anesthesia is usually only provided during endoscopic retrograde cholangiopancreatography (ERCP) when prior attempts using conscious sedation have failed. It was hypothesized that in our hospital, other factors might be associated with general anesthesia for ERCP. The aim of this study was therefore to assess the indications for ERCP under general anesthesia, and to evaluate the underlying diseases, type, and efficacy of ERCP under general anesthesia in comparison with conscious sedation. PATIENTS AND METHODS: We retrospectively analyzed 1,056 ERCPs that had been carried out with the patients under general anesthesia or conscious sedation. The indications for general anesthesia were recorded, and the underlying diseases, the type and success of the interventions, and the causes of premature ERCP termination in both groups were assessed. RESULTS: Eighteen percent of the ERCPs were performed under general anesthesia and 82% under conscious sedation. The indications for general anesthesia were related to the type of procedure planned (46%), premature termination of ERCP under conscious sedation (28%), and other reasons. Patients with primary sclerosing cholangitis and liver transplant recipients received general anesthesia more frequently (general anesthesia vs. conscious sedation, 36% vs. 16%, P < 0.0001 and 22% vs. 13%, P = 0.003). Conscious sedation was provided more frequently in patients with neoplasms and cholelithiasis (21% vs. 12%, P = 0.004 and 13% vs. 3%, P < 0.001). Painful dilations were performed more frequently with the patients under general anesthesia (60% vs. 19%, P < 0.001), whereas major papillotomies were preferably performed with conscious sedation (34% vs. 21%, P = 0.006). More interventions per ERCP were performed with the patient under general anesthesia compared to conscious sedation (P < 0.001), during the same time (51 +/- 28 min vs. 52 +/- 26 min, P = 0.39). With conscious sedation, the ERCP failure rate was double that with general anesthesia (7% vs. 14%, P = 0.012), mainly due to inadequate conscious sedation (61%). CONCLUSIONS: The frequent use of general anesthesia for ERCP at our institution is related to the underlying diseases, which are frequently treated with complex and painful ERCP procedures. The efficacy of ERCP with general anesthesia supports a continued preference for general anesthesia rather than conscious sedation when complex and painful interventional ERCP procedures are planned.

Anesthesia, General↗
PubMed2001

Medical and endoscopic treatment in primary sclerosing cholangitis.

Primary sclerosing cholangitis is an important cause of chronic cholestatic liver disease. The aetiology is still unknown and an immunological basis is discussed. The disease results in diffuse narrowing and irregularities of intra- and extra-hepatic bile ducts that may lead to biliary cirrhosis. Progression of the disease is highly variable and fluctuating. An important issue is the risk for developing cholangiocarcinoma. For end-stage disease liver transplantation is the only therapeutic option. If strictures of the extra-hepatic bile ducts are demonstrable, endoscopic interventions are effective palliative treatment options. The use of immunosuppressive or anti-inflammatory drugs has been shown to have no influence on the course of primary sclerosing cholangitis.

Cholangitis, Sclerosing↗
PubMed2001

K-ras mutations in the bile of patients with primary sclerosing cholangitis.

BACKGROUND AND AIMS: The development of cholangiocarcinoma (CCC) is a complication of primary sclerosing cholangitis (PSC). To date, no reliable factors have been described which can define those PSC patients at high risk for the development of CCC and the clinical diagnosis of CCC in PSC patients is difficult. Therefore, molecular markers of cholangiocarcinogenesis, such as K-ras mutations, may improve the early diagnosis of CCC or the timing of liver transplantation. METHODS: K-ras mutations were analysed by enriched polymerase chain reaction/restriction fragment length polymorphism in the bile fluid of 56 PSC patients and 20 patients with other cholestatic diseases. To assess the value of K-ras mutations as a risk factor for cholangiocarcinogenesis, patients were prospectively investigated over a mean period of 31.5 months. RESULTS: In contrast with the control group, 17 (30%) patients with PSC revealed K-ras mutations in bile fluid. The mean Mayo score was not significantly different between PSC patients with (mean score 0.70) and without (mean score 0.13; p=0.2) K-ras mutations. In contrast with the group of PSC patients without K-ras mutations, four CCCs and two dysplasia were diagnosed in the group of patients with K-ras mutations during the follow up investigation (p<0.001). CONCLUSIONS: Our results indicate that K-ras mutations in bile fluid of PSC patients represent frequent early events during cholangiocarcinogenesis. However, most of the PSC patients with K-ras mutations remained tumour free after a long follow up investigation which is in agreement with the fact that these mutations are not specific for malignancy but may also occur in normal bile duct mucosa or in dysplasias. Therefore, analysis of K-ras mutations in bile should not be used for diagnosis of CCC in PSC patients. However, the results of our prospective follow up investigation indicate that K-ras mutations in bile fluid of PSC patients have to be considered as risk factors for the development of CCC which may have implications for the timing of liver transplantation.

Adult↗
PubMed1999

Reconstructive surgery for ischemic-type lesions at the bile duct bifurcation after liver transplantation.

OBJECTIVE: To assess the feasibility, morbidity, mortality, and clinical success rate of surgical reconstruction of the biliary system in patients with ischemic-type biliary lesions in their liver graft. SUMMARY BACKGROUND DATA: After liver transplantation, strictures in the biliary tree with secondary sludge formation can occur in the absence of vascular problems. Jaundice, pruritus, and recurrent cholangitis are predominant clinical features leading to considerable morbidity. Interventional measures are the first-line treatment but are frequently only of transient success. Retransplantation is usually considered when interventional treatment is not effective. METHODS: Surgical exploration and reconstruction was performed in 17 patients with ischemic-type biliary strictures at a median of 2 years after liver transplantation. Findings during surgery, surgical strategies, and postsurgical courses are described. Clinical symptoms and biochemical parameters of cholestasis and liver function were analyzed in the postsurgical course. RESULTS: During surgery, all 17 patients were found to have strictures or sclerotic changes involving the hepatic bifurcation and extrahepatic bile duct. Sludge or stones were present in nine patients. In 14 patients with viable bile ducts proximal to the bifurcation, surgical reconstruction was performed by resection of the bifurcation and hepaticojejunostomy. In three patients with more extensive biliary destruction, portoenterostomy with or without peripheral hepatojejunostomy was performed. The prevalence rate of biliary infection at surgery was 93%; the predominant organisms were Candida and enterococci. The perioperative mortality rate was 0%. Clinical symptoms and biochemical parameters became normal or were considerably improved in 14 of 16 patients (88%). CONCLUSIONS: The hepatic bifurcation seems to be a predominant site for ischemic-type biliary changes after liver transplantation. Surgical treatment by resection of the bifurcation and reconstruction by high hepaticojejunostomy is a safe and highly effective approach leading to cure or persistent major improvement in most patients.

Adult↗
PubMed1999

Enhanced production of monocyte chemotactic protein 3 in inflammatory bowel disease mucosa.

BACKGROUND: The beta chemokine monocyte chemotactic protein 3 (MCP-3) has chemoattractant and activating capabilities in monocytes, lymphocytes, eosinophils, and basophils. AIMS: To investigate MCP-3 expression in inflammatory conditions of the human intestinal mucosa. PATIENTS: Forty five colon biopsy specimens from 18 patients with inflammatory bowel disease (IBD; 16 specimens from inflamed and 10 from non-inflamed areas) and 19 control patients were examined. METHODS: Immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR) were used for MCP-3 detection in tissue sections. Intestinal epithelial cell lines (HT-29, Caco-2, T-84) were stimulated with interleukin (IL) 1beta, IL-6, and tumour necrosis factor alpha (TNF-alpha) and examined for MCP-3 protein and mRNA expression using immunocytochemistry and RT-PCR, respectively. RESULTS: In tissue sections, MCP-3 protein was detected predominantly in epithelial cells, both in patients with IBD and in controls. MCP-3 staining was particularly pronounced at sites of active mucosal inflammation. The intensity of MCP-3 staining was positively correlated with the extent of epithelial destruction. In intestinal epithelial cell lines, MCP-3 mRNA was expressed, whereas MCP-3 protein was not consistently detected. CONCLUSIONS: Our data show that MCP-3 protein is present in normal and inflamed intestinal tissue. MCP-3 production is substantially enhanced in areas of active inflammation, suggesting an immunoregulatory role of MCP-3 in intestinal inflammation.

Adult↗
PubMed1999

Malabsorption with progressive weight loss and multiple intestinal ulcers in a patient with T-cell lymphoma.

We describe a 52-year-old woman who presented with severe diarrhea, nausea, intermittent abdominal pain and weight loss of 18 kg within ten months. Jejunal and duodenal ulcers were detected by endoscopy and multiple biopsies revealed villous atrophy of the jejunum. However, neither gliadin nor endomysium antibodies were detected and no clinical and histological improvement was achieved after gluten withdrawal. Despite strong clinical suspicion for intestinal lymphoma many unrevealing biopsies were done. The patient developed intermittent septic fever and diagnostic laparotomy revealed jejunal perforation. Partial jejunal resection was performed and histology confirmed the diagnosis of an intestinal T-cell lymphoma without celiac disease. Malabsorption and all intestinal ulcers disappeared during the course of chemotherapy (six cycles CHOP) and the patient recovered remarkably.

Biopsy↗