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1.  Changes in anti-viral effectiveness of interferon after dose reduction in chronic hepatitis c patients: a case control study 
BMC Gastroenterology  2001;1:14.
Background
High dose interferon induction treatment of hepatitis C viral infection blocks viral production over 95%. Since dose reduction is often performed due to clinical considerations, the effect of dose reduction on hepatitis C virus kinetics was studied.
Methods
A new model that allowed longitudinal changes in the parameters of viral dynamics was used in a group of genotype-1 patients (N = 15) with dose reduction from 10 to 3 million units of interferon daily in combination with ribavirin, in comparison to a control group (N = 9) with no dose reduction.
Results
Dose reduction gave rise to a complex viral kinetic pattern, which could be only explained by a decrease in interferon effectiveness in blocking virion production. The benefit of the rapid initial viral decline following the high induction dose is lost after dose reduction. In addition, in some patients also the second phase viral decline slope, which is highly predictive of success of treatment, was impaired by the dose reduction resulting in smaller percentage of viral clearance in the dose reduction group.
Conclusions
These findings, while explaining the failure of many induction schedules, suggest that for genotype-1 patients induction therapy should be continued till HCVRNA negativity in serum in order to increase the sustained response rate for chronic hepatitis C.
doi:10.1186/1471-230X-1-14
PMCID: PMC64636  PMID: 11801193
2.  Early bronchopulmonary involvement in Crohn disease: a case report 
BMC Gastroenterology  2001;1:13.
Background
Bronchopulmonary manifestations of Crohn disease have been rarely described in children, including both subclinical pulmonary involvement and severe lung disease.
Case presentation
A 6.5-year-old girl is described with early recurrent bronchopulmonary symptoms both at presentation and in the quiescent phase of Crohn disease. Pulmonary function tests (lung volumes and flows, bronchial reactivity and carbon monoxide diffusing capacity) were normal. Bronchoalveolar cytology showed increased (30%) lymphocyte counts and bronchial biopsy revealed thickening of basal membrane and active chronic inflammation.
Conclusions
Clinical and histological findings in our young patient suggest involvement of both distal and central airways in an early phase of lung disease. The pathogenesis of Crohn disease-associated lung disorders is discussed with reference to the available literature. A low threshold for pulmonary evaluation seems to be advisable in all children with CD.
doi:10.1186/1471-230X-1-13
PMCID: PMC60654  PMID: 11734067
3.  The diagnostic value of liver biopsy 
BMC Gastroenterology  2001;1:12.
Background
Since the introduction of molecular diagnostic tools such as markers for hepatitis C and different autoimmune diseases, liver biopsy is thought to be useful mainly for staging but not for diagnostic purposes. The aim was to review the liver biopsies for 5 years after introduction of testing for hepatitis C, in order to evaluate what diagnostic insights – if any – remain after serologic testing.
Methods
Retrospective review of all liver biopsies performed between 1.1.1995 and 31.12.1999 at an academic outpatient hepatology department. The diagnoses suspected in the biopsy note were compared with the final diagnosis arrived at during a joint meeting with the responsible clinicians and a hepatopathologist.
Results
In 365 patients, 411 diagnoses were carried out before biopsy. 84.4 % were confirmed by biopsy but in 8.8 %, 6.8 % and 10.5 % the diagnosis was specified, changed or a diagnosis added, respectively. Additional diagnoses of clinical relevance were unrecognized biliary obstruction and additional alcoholic liver disease in patients with chronic hepatitis C. Liver biopsy led to change in management for 12.1 % of patients.
Conclusion
Even in the era of advanced virological, immunological and molecular genetic testing, liver biopsy remains a useful diagnostic tool. The yield is particularly high in marker negative patients but also in patients with a clear-cut prebiopsy diagnosis, liver biopsy can lead to changes in patient management.
doi:10.1186/1471-230X-1-12
PMCID: PMC59692  PMID: 11707153
4.  Do published guidelines for evaluation of Irritable Bowel Syndrome reflect practice? 
BMC Gastroenterology  2001;1:11.
Background
The only US guidelines listed in the National Guideline Warehouse for the diagnosis of Irritable Bowel Syndrome (IBS) are the expert opinion guidelines published by The American Gastroenterology Association. Although the listed target audience of these guidelines includes family physicians and general internists, the care recommended in the guidelines has not been compared to actual primary care practice. This study was designed to compare expert opinion guidelines with the actual primary care provided and to assess outcomes in the 3 years following the IBS diagnosis.
Methods
This is a retrospective medical record review study using a random sample of incident IBS cases from all Olmsted County, Minnesota providers diagnosed between January 1, 1993 and December 31, 1995. Data was collected on all care and testing provided to the subjects as well as 3-year outcomes related to the IBS diagnosis.
Results
Of the 149 IBS patients, 99 were women and the mean age was 47.6 years. No patient had all of the diagnostic tests recommended in the guidelines. 42% had the basic blood tests of CBC and a chemistry panel. Sedimentation rate (2%) and serum thyroxine level (3%) were uncommon. Colon imaging studies were done in 41% including 74% of those over the age of 50. In the 3 years following the diagnosis, only one person had a change in diagnosis and no diagnoses of gastro-intestinal malignancies were made in the cohort.
Conclusions
Primary care practice based diagnostic evaluations for IBS differ significantly from the specialty expert opinion-based guidelines. Implementation of the specialty guidelines in primary care practice would increase utilization with apparent limited improvement in diagnostic outcomes.
doi:10.1186/1471-230X-1-11
PMCID: PMC59674  PMID: 11701092
5.  Ileal mucosal bile acid absorption is increased in Cftr knockout mice 
BMC Gastroenterology  2001;1:10.
Background
Excessive loss of bile acids in stool has been reported in patients with cystic fibrosis. Some data suggest that a defect in mucosal bile acid transport may be the mechanism of bile acid malabsorption in these individuals. However, the molecular basis of this defect is unknown. This study examines the expression of the ileal bile acid transporter protein (IBAT) and rates of diffusional (sodium independent) and active (sodium dependent) uptake of the radiolabeled bile acid taurocholate in mice with targeted disruption of the cftr gene.
Methods
Wild-type, heterozygous cftr (+/-) and homozygous cftr (-/-) mice were studied. Five one-cm segments of terminal ileum were excised, everted and mounted onto thin stainless steel rods and incubated in buffer containing tracer 3H-taurocholate. Simultaneously, adjacent segments of terminal ileum were taken and processed for immunohistochemistry and Western blots using an antibody against the IBAT protein.
Results
In all ileal segments, taurocholate uptake rates were fourfold higher in cftr (-/-) and two-fold higher in cftr (+/-) mice compared to wild-type mice. Passive uptake was not significantly higher in cftr (-/-) mice than in controls. IBAT protein was comparably increased. Immuno-staining revealed that the greatest increases occurred in the crypts of cftr (-/-) animals.
Conclusions
In the ileum, IBAT protein densities and taurocholate uptake rates are elevated in cftr (-/-) mice > cftr (+/-) > wild-type mice. These findings indicate that bile acid malabsorption in cystic fibrosis is not caused by a decrease in IBAT activity at the brush border. Alternative mechanisms are proposed, such as impaired bile acid uptake caused by the thick mucus barrier in the distal small bowel, coupled with a direct negative regulatory role for cftr in IBAT function.
doi:10.1186/1471-230X-1-10
PMCID: PMC59644  PMID: 11696242
6.  Electrolytic ablation of the rat pancreas: a feasibility trial 
Background
Pancreatic cancer is a biologically aggressive disease with less than 20% of patients suitable for a "curative" surgical resection. This, combined with the poor 5-year survival indicates that effective palliative methods for symptom relief are required. Currently there are no ablative techniques to treat pancreatic cancer in clinical use. Tissue electrolysis is the delivery of a direct current between an anode and cathode to induce localised necrosis. Electrolysis has been shown to be safe and reliable in producing hepatic tissue and tumour ablation in animal models and in a limited number of patients. This study investigates the feasibility of using electrolysis to produce localised pancreatic necrosis in a healthy rat model.
Method
Ten rats were studied in total. Eight rats were treated with variable "doses" of coulombs, and the systemic and local effects were assessed; 2 rats were used as controls.
Results
Seven rats tolerated the procedure well without morbidity or mortality, and one died immediately post procedure. One control rat died on induction of anaesthesia. Serum amylase and glucose were not significantly affected.
Conclusion
Electrolysis in the rat pancreas produced localised necrosis and appears both safe, and reproducible. This novel technique could offer significant advantages for patients with unresectable pancreatic tumours. The next stage of the study is to assess pancreatic electrolysis in a pig model, prior to human pilot studies.
doi:10.1186/1471-230X-1-9
PMCID: PMC56592  PMID: 11570977
7.  Is it Crohn's disease? A severe systemic granulomatous reaction to sulfasalazine in patient with rheumatoid arthritis 
Background
Sulfasalazine is a widely used anti-inflammatory agent in the treatment of inflammatory bowel disease and several rheumatological disorders. Although as many as 20% of treated patients may experience reversible, dose-dependent side effects, less frequent but potentially severe, systemic reactions have also been reported.
Case Presentation
A severe systemic reaction to sulfasalazine developed in a 21-year old female with rheumatoid arthritis characterized by eosinophilia, granulomatous enteritis and myelotoxicity, cholestatic hepatitis, and seizures. The clinical course and management of this patient are presented as well as a review of the incidence and outcome of severe systemic reactions to sulfasalazine.
Conclusions
Granulomatous myelotoxicity and enteritis developed in a 21 year old female within 3 weeks of initiating sulfasalazine for rheumatoid arthritis. Following a short course of corticosteroids, the patient had resolution of her cholestatic hepatitis, rash, eosinophilia, and gastrointestinal symptoms with no residual manifestations at 7 months follow-up. Although severe reactions to sulfasalazine are rare and unpredictable, practicing physicians should be aware of unusual clinical presentations of toxicity when prescribing sulfasalazine.
doi:10.1186/1471-230X-1-8
PMCID: PMC56591  PMID: 11570976
8.  Efficacy of Helicobacter pylori eradication therapies: a single centre observational study 
Background
Many Helicobacter pylori eradication regimens have been described. There are little data reporting their efficacy or integration in routine clinical practice. The overall results of eradication therapy in a cohort of patients are described and an algorithm for management outlined.
Methods
469 patients receiving eradication therapy in routine clinical practice were evaluated. The successes of individual regimes as first, second and third line therapy were determined.
Results
Overall success after one, two and three courses of therapy were 73% (95% confidence intervals 69–77%), 94% (91–96%) and 98% (97–99%) respectively. 10 different regimens, including many non-recommended ones were used as primary therapy. Ranitidine bismuth citrate-amoxicillin-clarithromycin triple therapy (94.8%, 90–99%) was significantly more effective than any other combination as primary therapy, including all proton pump inhibitor based triple therapies. Quadruple therapy with bismuth chelate-proton pump inhibitor-tetracycline and a nitroimidazole (70%, 52–88%) and ranitidine bismuth citrate-based triple therapy (73%, 56–90%) where more effective second line combinations than proton pump inhibitor-triple therapies (37.5%, 12–58%). Third line therapy directed by the results of sensitivity testing improved eradication compared to further empirical antibiotics. The use of a proton pump inhibitor with clarithromycin and a nitroimidazole as initial therapy was associated with a significantly worse overall eradication rate than other combinations.
Conclusions
Helicobacter pylori eradication rates can be maximised by using ranitidine bismuth citrate-clarithromycin-amoxicillin containing triple therapy, followed by bismuth and nitroimidazle containing second-line therapy, with third line combinations directed by sensitivity testing. Proton pump inhibitor-clarithromycin-metronidazole combinations should be avoided.
doi:10.1186/1471-230X-1-7
PMCID: PMC55334  PMID: 11545677
9.  Physicians' preference values for hepatitis C health states and antiviral therapy: A survey 
Background
Physicians' perspectives regarding hepatitis C shape their approach to patient management. We used utility analysis to evaluate physicians' perceptions of hepatitis C-related health states (HS) and their threshold to recommend treatment.
Methods
A written questionnaire was administered to practicing physicians. They were asked to rate hepatitis C health states on a visual analog scale ranging from 0% (death) to 100% (health without hepatitis C). Physicians then judged quality of life associated with the side effects of antiviral therapy for hepatitis C and indicated the sustained virological response rate that they would require to recommend treatment.
Results
One hundred and thirteen physicians from five states were included. Median utility ratings for hepatitis C health states declined significantly with increasing severity of symptoms: HS1-No Symptoms, No Cirrhosis (88%; 12% reduction from good health), HS2-Mild Symptoms, No Cirrhosis (66%), HS3-Moderate Symptoms, No Cirrhosis (49%), HS4-Mild Symptoms, Cirrhosis (40%), HS5-Severe Symptoms, Cirrhosis (18%) [p < 0.001]. The median rating for life with side effects of antiviral therapy was 47%, suggesting a 53% reduction from good health. That was similar to the utility value for HS3-Moderate Symptoms, No Cirrhosis. The median threshold value for recommending treatment was a sustained response rate of 60%.
Conclusions
1) Physicians' utility ratings for hepatitis C health states were inversely related to the severity of disease manifestations described. 2) Physicians viewed side effects of therapy unfavorably and indicated that on average, they would require a 60% sustained response rate before recommending treatment, which far exceeds the efficacy of current antiviral therapy for hepatitis C in the majority of patients.
doi:10.1186/1471-230X-1-6
PMCID: PMC37537  PMID: 11513756
10.  TNF-α induced endothelial MAdCAM-1 expression is regulated by exogenous, not endogenous nitric oxide 
Background
MAdCAM-1 is an adhesion molecule expressed in Peyer's patches and lymphoid tissues which is mobilized by cytokines like TNF-α and is a major determinant of lymphocyte trafficking to the gut in human inflammatory bowel disease (IBD). It has been suggested that both reactive oxygen and nitrogen metabolites participate in regulating adhesion molecule expression in response to TNF-α.
Methods
To examine how exogenous and endogenous sources of NO modulate MAdCAM-1 induction by TNF-α, we pre-treated mouse lymphatic endothelial cells with either long or short acting NO donors prior to TNF-α-stimulation, and measured MAdCAM-1 induction at 24 h.
Results and Discussion
DETA-NO, a long-acting NO donor, and SperNO, a rapid releasing NO donor both inhibited TNF-α-stimulated MAdCAM-1 expression in a concentration dependent manner. Both NO donors also reduced a4b7-dependent lymphocyte endothelial adhesion. Inhibition of endogenous NO production by either L-NAME, a non-selective NOS inhibitor, or by 1400 w, a selective iNOS inhibitor failed to induce, or potentiate TNF-α regulated MAdCAM-1 expression.
Conclusions
Exogenous NO donors may be beneficial in the treatment of IBD, while endogenous nitric oxide synthases may be less effective in controlling adhesion molecule expression in response to cytokines.
doi:10.1186/1471-230X-1-5
PMCID: PMC35355  PMID: 11481030
11.  Low prevalence of liver-kidney microsomal autoantibodies of type 1 (LKM1) in hepatitis C seropositive subjects on Crete, Greece 
Background
Hepatitis C is a serious problem on the Greek island of Crete, where a high prevalence of antibodies against hepatitis C (anti-HCV) has recently been reported. This article reports the findings of a study carried out in Crete, which investigated the prevalence of serum autoantibodies in patients with chronic hepatitis C.
Patients and Methods
One hundred and forty two patients (59 men and 83 women), who were found anti-HCV seropositive in two hospitals and two Primary Health Care Centres in Crete, were eligible. Sixty healthy blood donors (46 men, 14 women), which were negative to anti-HCV, were used as the control group. They were randomly selected from those attending Rethymnon Hospital. Autoantibodies were identified using the indirect immunofluorescence (IFL) technique on human epithelial cells from larynx cancer (HEp-2 cells), rat liver-kidney-stomach substrate (CT3) and Chrithidia Luciliae (CL).
Results
Serum autoantibodies were detected in 104 HCV patients, yielding an overall prevalence of 73.2%. The most frequent autoantibodies were antinuclear antibodies (ANA), positive in 72 patients (50.7%). Anti-smooth muscle antibodies (ASMA) were detected in 33 patients (23.2%). Only one patient was positive for LKM1 autoantibodies. No autoantibodies were found in 38 patients (26.7%). Autoantibodies were also found in 5 out of the 60 examined healthy blood donors (8.3%).
Conclusions
Autoantibodies, mainly ANA and ASMA are very common in HCV seropositive patients from Crete. By contrast LKM1 autoantibodies are exceptionally rare in these patients.
doi:10.1186/1471-230X-1-4
PMCID: PMC33343  PMID: 11418082
12.  Intestinal parasitic infections in Thai HIV-infected patients with different immunity status 
Background
One of the major health problems among HIV seropositive patients is superimposed infection due to the defect of immunity. Furthermore, intestinal parasite infection, which is also one of the basic health problems in tropical region, is common in these patients. In this study, a cross sectional study to document the prevalence of intestinal parasitic infection in Thai HIV-infected patients with different immune status was performed.
Methods
A study of stool samples from 60 Thai HIV-infected patients with different immune status was performed at King Chulalongkorn Memorial Hospital, Thailand. Each patient was examined for CD4 count and screened for diarrheal symptoms.
Results
The prevalence of intestinal parasitic infection among the HIV-infected patients in this study was 50 %. Non- opportunistic intestinal parasite infections such as hookworms, Opisthorchis viverrini and Ascaris lumbricoides were commonly found in HIV-infected people regardless of immune status with or without diarrheal symptoms. Opportunistic intestinal parasites such as Cryptosporidium, Isospora belli, Microsporidia and Strongyloides stercoralis infection were significantly more frequent in the low immunity group with diarrhea.
Conclusion
Therefore, opportunistic intestinal parasite infection should be suspected in any HIV infected patient with advanced disease presenting with diarrhea. The importance of tropical epidemic non-opportunistic intestinal parasite infections among HIV-infected patients should not be neglected.
doi:10.1186/1471-230X-1-3
PMCID: PMC32247  PMID: 11394966
13.  Drug interaction: Omeprazole and Phenprocoumon 
Background
Oral anticoagulants like the coumarin derivatives are characterised by a particularly narrow therapeutic range. Any interfering co-medication can pose a challenge to establishing a stable anticoagulant dosage regimen and thus present a serious risk for the patient. Here we describe two cases of patients on anticoagulant therapy that suggest possible drug interactions between phenprocoumon and the proton pump inhibitor omeprazole.
Results
In both patients, the International Normalised Ratio (INR) increased beyond the therapeutic range after they were given omeprazole for the treatment of gastrointestinal symptoms. The INR returned to therapeutic levels after the phenprocoumon dose was reduced (Case 1) and omeprazole discontinued (Case 2).
Conclusions
The increased anticoagulant activity of phenprocoumon observed in the two described cases and the known interaction potential of omeprazole suggest that the clearance of phenprocoumon may have been reduced due to competitive inhibition of its degradation by omeprazole. Drug interactions may be one of the reasons for the difficulties encountered with some patients in establishing a stable anticoagulant therapy. Physicians should carefully review any concurrently used medication and if possible opt for drugs with a low interaction potential.
doi:10.1186/1471-230X-1-2
PMCID: PMC30938  PMID: 11313000
14.  Jejunogastric intussusception presented with hematemesis: a case presentation and review of the literature 
Background
Jejunogastric intussusception (JGI) is a rare but potentially very serious complication of gastrectomy or gastrojejunostomy. To avoid mortality early diagnosis and prompt surgical intervention is mandatory.
Case presentation
A young man presented with epigastric pain and bilous vomiting followed by hematemesis,10 years after vagotomy and gastrojejunostomy for a bleeding duodenal ulcer. Emergency endoscopy showed JGI and the CT scan of the abdomen was compatible with this diagnosis. At laparotomy a retrograde type II, JGI was confirmed and managed by reduction of JGI without intestinal resection. Postoperative recovery was uneventful.
Conclusions
JGI is a rare condition and less than 200 cases have been published since its first description in 1914. The clinical picture is almost diagnostic. Endoscopy performed by someone familiar with this rare entity is certainly diagnostic and CT-Scan of the abdomen could also help. There is no medical treatment for acute JGI and the correct treatment is surgical intervention as soon as possible.
doi:10.1186/1471-230X-1-1
PMCID: PMC29076  PMID: 11178112

Results 1-14 (14)