Search PubMedSearch

Biomedical subjects

P Malfertheiner

Publications and source records attributed to P Malfertheiner.

At least 19 recordsLinked to original sources

Is typing of metaplasia at the squamocolumnar junction revealing its aetiology?

Until recently, intestinal metaplasia (IM) at the squamocolumnar junction (SCJ) was ascribed to Barrett's mucosa (BM), which arises from gastro-oesophageal reflux. Recent studies, however, have shown that IM at the SCJ can also be induced, for example, by Helicobacter pylori (HP). The aim of this study was to investigate whether the type of IM might be helpful in the differentiation between these two aetiologies. Biopsies from the antrum, corpus and immediately below the Z-line were taken from 443 patients. Eighty-three of them showed IM below the Z-line. In these, the endoscopic aspect of the Z-line was classified as either unremarkable (n=49) or suspected of BM (n=34). Typing of IM was done using Gomori's aldehyde fuchsin-Alcian blue staining. Overall, age, HP status and erosive oesophagitis had no influence on the IM type. Type-III IM (n=24) was more frequent in men (P=0.0371) and related to endoscopic BM (P<0.0001). Type-I/II IM (n=59) was associated with an unremarkable Z-line (P<0.0001) and was linked to multifocal gastric IM (P=0.016) and HP (P=0.0011). In conclusion, it was shown that, in the presence of a normal Z-line, especially in the absence of HP, type-III IM is suggestive of BM. The diagnosis of short or ultra-short segment BM should therefore include endoscopic, histological and histochemical characteristics.

Adult

Cure of Helicobacter pylori-associated ulcer disease through eradication.

The eradication of Helicobacter pylori (H. pylori) infection has led to a dramatic benefit for patients with gastroduodenal ulcer disease, as the majority of these patients receive a lifelong cure. Relapses after successful H. pylori cure may be caused by either recrudescence or reinfection, both rare events nowadays, or be attributed to non-steroidal anti-inflammatory drugs or aspirin intake. In certain geographical areas, H. pylori-negative relapses are proposed as a new, pathophysiological and not yet elucidated entity. The cure of H. pylori infection in uncomplicated duodenal ulcer diseases consists of 7 days of proton pump inhibitor (PPI) based triple therapy, containing two antibiotics from clarithromycin, amoxicillin and metronidazole. In gastric ulcer, it is recommended that the PPI is continued for a further 3 weeks as these ulcers have a prolonged healing time. Rescue therapies after failure need to take into consideration the resistance pattern of the micro-organism and are offered in the form of quadruple therapy or a high-dose PPI with amoxicillin.

Anti-Bacterial Agents

Diagnosis of Helicobacter pylori infection with a new non-invasive antigen-based assay. HpSA European study group.

BACKGROUND: Helicobacter pylori is a common human pathogen implicated in certain gastrointestinal diseases. In the search for new non-invasive techniques to diagnose H. pylori infection, we evaluated an EIA for H. pylori antigen in stool (HpSA). METHODS: In a prospective multicentre study, stool specimens from 501 patients (276 men, 225 women; age range 17-88 years, mean 52) undergoing gastroscopy in 11 centres throughout Europe were tested with HpSA and the carbon-13-urea breath test. At endoscopy, four biopsy samples were taken for histology (haematoxylin and eosin) and H. pylori detection (giemsa in both antrum and corpus, culture and rapid urease test). Patients were defined as positive for H. pylori if histology (antrum, corpus, or both) and urease test were positive, or if culture was positive. Patients classified as having H. pylori infection received an eradication regimen; 107 were reassessed 4 weeks after therapy. FINDINGS: Of 272 patients with H. pylori infection by the predefined criteria, 256 were positive by HpSA (sensitivity 94.1% [95% CI 90.6-96.6]). Of 219 patients without infection, 201 were negative by HpSA (specificity 91.8% [87.3-95.1]). INTERPRETATION: The stool assay was a reliable and easy-to-use tool for diagnosis of H. pylori infection. The test was accurate even shortly after treatment.

Adolescent

Generalized AA-amyloidosis in a 58-year-old Caucasian woman with an 18-month history of gastrointestinal tuberculosis.

We report on a 58-year-old Caucasian woman who went to a general practitioner about recurrent abdominal pain, night sweats and weight loss of a few weeks' duration. Once gynaecological disease had been ruled out, the patient was admitted to hospital with severe abdominal pain and intestinal obstruction and a right-sided hemicolectomy was performed. Following the investigation of osteolytic lumbar vertebrae, 18 months after visiting the general practitioner the patient was finally found to be suffering from generalized AA-amyloidosis secondary to gastrointestinal tuberculosis. This had been misinterpreted as Crohn's disease. Re-examination of the specimens from the right-sided hemicolectomy demonstrated that scanty deposits of AA-amyloid were present 9 months after the first presentation. AA-amyloid can thus be present in serious inflammatory disease even during the first 9 months after the initial clinical presentation.

Amyloidosis

Gastric Helicobacter pylori infection accelerates healing of reflux esophagitis during treatment with the proton pump inhibitor pantoprazole.

BACKGROUND & AIMS: In previous studies an exaggerated effect of proton pump inhibitors (PPIs) on intragastric pH in Helicobacter pylori-infected patients was observed. Because healing and improvement of symptoms in patients with gastroesophageal reflux disease (GERD) is directly associated with an increase of intragastric pH during treatment, we hypothesized that the response to treatment with a PPI in patients with reflux esophagitis would be better in H. pylori-infected patients than in patients without H. pylori infection. METHODS: We recruited 971 patients with endoscopically verified reflux esophagitis grades II and III (Savary/Miller). At study entry, H. pylori status was assessed by a 13C-urea breath test and baseline characteristics were recorded. Physicians and patients were not notified about the results of the breath test until completion of the study. All patients underwent treatment with pantoprazole, 40 mg orally once daily for 4 weeks. Healing was verified by endoscopy after 4 or 8 weeks of treatment. If the esophagitis had not completely healed at this time, treatment was continued for a further 4-week period. Healing rates and symptom relief were compared for patients with and without H. pylori infection. RESULTS: The prevalence of H. pylori was 39.9% (95% confidence interval [CI], 36.9-42.9), and neither gender, smoking, nor alcohol consumption were associated with the H. pylori infection (P > 0.4). The trial was completed by 846 patients without protocol violation. Overall healing rates of reflux esophagitis were 80.4% (95% CI, 77.7-83.1) and 93.6% (95% CI, 91.8-95.2) after 4 and 8 weeks, respectively. In H. pylori-positive patients, healing rates were significantly higher after 4 (86.6% vs. 76.3%; P = 0.0005) and 8 weeks (96.4% vs. 91.8%; P < 0.004). Relief of symptoms after 4 weeks was also significantly (P < 0.05) better in H. pylori-infected patients than in uninfected patients. CONCLUSIONS: Patients with reflux esophagitis and H. pylori infection respond significantly better than H. pylori-negative patients to the PPI pantoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles

The GU-MACH study: the effect of 1-week omeprazole triple therapy on Helicobacter pylori infection in patients with gastric ulcer.

AIMS: To study the efficacy of omeprazole triple therapy in the eradication of Helicobacter pylori in patients with active gastric ulcer, and to assess healing and relapse of gastric ulcer. METHODS: A double-blind, randomized study was carried out in 18 centres in Germany, Hungary and Poland. Patients (n = 160) with gastric ulcer and a positive H. pylori screening test were randomized to a 7-day twice daily treatment with omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1000 mg (OAC) or omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg (OMC), or with omeprazole 20 mg once daily (O). After completion of this 1-week treatment, patients were treated with omeprazole until healing (maximum 12 weeks), and followed for 6 months. H. pylori was assessed by urea breath test (UBT) and histology. RESULTS: Eradication rates ITT were OAC 79% (95% CI: 65-90%), OMC 86% (95% CI: 73-94%) and O 4% (95% CI: 0-14%). Eradication rates PP were OAC 83% (95% CI: 68-93%), OMC 93% (95% CI: 80-98%) and O 3% (95% CI: 0-13%). Gastric ulcer relapses occurred in 5, 0 and 11 patients in the groups, respectively. CONCLUSIONS: The results from the study demonstrate that OMC and OAC 1-week regimens are safe and effective for eradication of H. pylori in gastric ulcer patients, and that ulcer relapse is infrequent after successful eradication.

Adult

Citric acid or orange juice for the 13C-urea breath test: the impact of pH and gastric emptying.

BACKGROUND: There is an ongoing debate about the optimal test drink to be used in the 13C-urea breath test (13C-UBT). We recently reported that a citric acid solution is the optimal test drink in the 13C-UBT, because it provides a high 13CO2 recovery and the excellent accuracy of the test appears optimal compared to other test meals. Orange juice, because of a better taste, is also propagated as a test drink in the 13C-UBT. AIM: To compare the diagnostic accuracy of the 13C-UBT with either orange juice or citric acid solution as a test drink. Furthermore, the effect of these test drinks on the gastric emptying rate was determined. METHODS: H. pylori status was assessed by histology, rapid urease test and culture in 50 consecutive dyspeptic patients. A 13C-UBT was performed on two consecutive days by giving 75 mg of 13C-urea randomly dissolved in 200 mL 0.1 M citric acid solution or 200 mL orange juice. The 13CO2/12CO2 ratio was measured in breath samples taken before and 15, 30, 45 and 60 min after administration of the test drink. The gastric emptying rate of orange juice and citric acid solution was compared to that of water in 10 healthy subjects on three consecutive days by means of a 13C-sodium acetate breath test; 50 mg of 13C-sodium acetate was dissolved in 200 mL of each solution and breath samples were collected before and every 10 min for 90 min after administration of the test drink. RESULTS: Twenty-six out of 50 patients (52%) were infected with H. pylori. Significantly higher values over baseline (35.7+/-5.2 per thousand vs. 23.2+/-3.4 per thousand, P<0.001) and higher area under the curve (1507+/-198 vs. 927+/-128, P<0.001) were observed in H. pylori-positive patients when citric acid solution was administered compared with orange juice. Sensitivity of the 13C-UBT was 100% when citric acid was used as a test drink and 88% with orange juice. Specificity was 100% with both test drinks. Gastric emptying of citric acid solution (t1/2 = 60.9+/-3.5 min) was significantly slower than that of orange juice (t1/2 = 49.7+/-3.1 min, P<0.001). CONCLUSION: 13C-UBT loses diagnostic accuracy when orange juice instead of citric acid is used as a test drink. The faster gastric emptying of orange juice might be responsible for the lower diagnostic accuracy of the 13C-UBT.

Adult

Role of aging in the expression of Helicobacter pylori gastritis in the antrum, corpus, and cardia.

BACKGROUND: Earlier studies identified a pylorocardial expansion of chronic gastritis. We investigated the age-dependent changes in grading and topography of Helicobacter pylori gastritis. METHODS: Antral, corpus, and cardial biopsy specimens from 216 H. pylori-positive patients with no peptic ulcer disease (PUD), malignancy, or Barrett's oesophagus were evaluated with haematoxylin and eosin and modified Giemsa. The patients were separated into four equal-sized age groups (1, < 46 years; II, 46-56 years; III, 57-68 years; IV, > 69 years). Sydney-system gradings of bacterial density and activity and degree of gastritis were used to calculate gastritis sum scores for age- and biopsy site-dependent comparisons. The prevalence of intestinal metaplasia (IM) and atrophy was also compared. RESULTS: Mean antral sum scores decreased slightly in group IV but were higher than those in the corpus or cardia in all groups (P < 0.05 each). In the corpus mean scores increased in groups II-IV versus group I (P < 0.05 each), and aging was associated with a significant increase in bacterial density and active inflammation. The cardia scores remained virtually constant in all groups and exceeded significantly that in the corpus in group I. IM and atrophy increased with age, occurring more frequently and earlier in the antrum and cardia than in the corpus. CONCLUSIONS: Progression of gastritis with age involves the corpus but not the cardia. Antral inflammation decreases slightly in patients of advanced age.

Adult

Alteration of fibroblast growth factor and receptor expression after acute pancreatitis in humans.

After an episode of acute pancreatitis (AP) in humans, the pancreas exhibits varying degrees of fibrosis, acinar cell regeneration, and the formation of tubular complexes. The mechanisms underlying these changes are unknown. By using Northern blot analysis and immunohistochemistry, we assessed the expression and distribution of fibroblast growth factors (FGFs) and their receptor in human pancreatic tissues obtained from patients with AP. By comparison with the normal pancreas, acidic FGF (aFGF) and FGF-receptor 1 (FGFR-1, flg), mRNA levels were significantly decreased in human pancreatic tissues, which were obtained approximately 8 days after onset of AP. In the normal pancreas, acidic FGF, basic FGF, and FGFR-1 immunoreactivity was present at low to moderate levels in a heterogeneous pattern in the cytoplasm of acinar and ductal cells. Two patterns of immunoreactivity were observed in the AP group. In regions that have undergone necrosis, there was complete loss of aFGF, bFGF, and FGFR-1 immunostaining. In contrast, in the regenerating areas, aFGF and bFGF were readily evident in exocrine-type cells, in association with a marked increase in FGFR-1 immunoreactivity. These findings indicate that FGF/receptor expression is altered after AP, and raise the possibility that FGFs may be involved in the process of pancreatic exocrine regeneration during recovery from AP.

Acute Disease

Hepatomegaly and cholestasis as primary clinical manifestations of an AL-kappa amyloidosis.

A 53-year-old man, who presented with weight loss over a period of 10 months, hepatomegaly, markedly raised cholestatic enzymes and Ca 19-9, was initially suspected of suffering from metastatic cholangio-carcinoma. Liver biopsy revealed depositions of AL-amyloid. Further investigations confirmed a generalized amyloidosis. Biopsies taken from the gastric, colonic, and bronchial mucosa all showed depositions of amyloid. A nephrotic syndrome was interpreted as being secondary to the renal involvement. Echocardiography identified changes which were consistent with cardiac involvement. A plasmacytoma or lymphoma was excluded. At the time of diagnosis the patient was in a good physical condition with normal renal function. Within a few weeks the renal function deteriorated and after 2 months the patient developed ascites and became jaundiced. Four months after initial presentation the patient died from cardiac failure.

Amyloid

The Maastricht recommendations and their impact on general practice.

At a meeting organized in Maastricht by the European Helicobacter Pylori Study Group, European consensus guidelines for the treatment of Helicobacter pylori were established by determining what relevant information from research could be translated into clinical practice. Many of the patients infected with H. pylori can be diagnosed and treated in the primary care setting. Dyspeptic patients under 45 years of age, with no alarm symptoms or risk of gastric or oesophageal malignancy, can be tested non-invasively and treated in the primary care setting. For diagnosis, a validated non-invasive method is recommended, such as the 13C-urea breath test or laboratory-based serology if properly validated in the region in which it is used. The meeting strongly recommended that all patients with peptic ulcer are treated with eradication therapy. Patients over the age of 45 years and those with alarm symptoms should be referred with no hesitation to the specialist After full consideration of the treatments used to date, it was strongly recommended that treatment should be with proton-pump inhibitor-based triple therapy, consisting of a proton-pump inhibitor and two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin. The evidence supporting the use of these therapies has been substantiated in large clinical trials that were recently completed.

Adult

Validity of a modified 13C-urea breath test for pre- and posttreatment diagnosis of Helicobacter pylori infection in the routine clinical setting.

OBJECTIVE: Citric acid meets the criteria of an optimal test drink for the 13C-urea breath test (13C-UBT) because it permits rapid, high level recovery of the 13C administered. In a previous study we reported that administration of 13C-urea dissolved in a citric acid solution provides results similar to those obtained with standard administration of the substrate 10 min after the test drink. The aim of this study was to evaluate the accuracy of this modified 13C-UBT for both primary and posttreatment diagnosis of Helicobacter pylori (H. pylori) infection in a large patient population in clinical practice. METHODS: The 13C-UBT was performed in 553 patients with dyspeptic symptoms by giving them 75 mg of 13C-urea either 10 min after administration of 200 ml of a test drink comprising 0.1 mol/L citric acid solution (protocol 1, n = 320) or dissolved in the same amount of this test drink (protocol 2, n = 233). All patients underwent an upper gastrointestinal endoscopy and the H. pylori-status was assessed by histology, rapid urease test, and culture. Sixty patients with proven H. pylori infection were reinvestigated by both endoscopy and 13C-UBT (protocol 2) 4 wk after completing eradication therapy. RESULTS: The accuracy of the two test protocols in the pretreatment diagnosis of H. pylori infection (95.6% and 96.6%), as well as of the modified 13C-UBT in the posttreatment evaluation of the infection (98.3%) was similar. More meaningful are the high PPV (>96%) and NPV (>93%) of the 13C-UBT under pre- and posttreatment conditions. CONCLUSIONS: The administration of 13C-urea dissolved in a citric acid solution simplifies the 13C-UBT, while preserving the high accuracy in the diagnosis of H. pylori infection. This modified 13C-UBT has equal accuracy in the pre- and the posttreatment situations.

Adolescent

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

A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis.

BACKGROUND: The pharmacological inhibition of exocrine pancreatic secretion with the somatostatin analogue octreotide has been advocated as a specific treatment of acute pancreatitis. AIM: To investigate the efficacy of octreotide in acute pancreatitis in a randomised, placebo controlled trial. METHODS: 302 patients from 32 hospitals, fulfilling the criteria for moderate to severe acute pancreatitis within 96 hours of the onset of symptoms, were randomly assigned to one of three treatment groups: group P (n=103) received placebo, while groups O1 (n=98) and O2 (n=101) received 100 and 200 microg of octreotide, respectively, by subcutaneous injection three times daily for seven days. The primary outcome variable was a score composed of mortality and 15 typical complications of acute pancreatitis. RESULTS: The three groups were well matched with respect to pretreatment characteristics. An intent to treat analysis of all 302 patients revealed no significant differences among treatment groups with respect to mortality (P: 16%; O1: 15%; O2: 12%), the rate of newly developed complications, the duration of pain, surgical interventions, or the length of the hospital stay. A valid for efficacy analysis (251 patients) also revealed no significant differences. CONCLUSIONS: This trial shows no benefit of octreotide in the treatment of acute pancreatitis.

Acute Disease