Lactase persistence/non-persistence variants, C/T_13910 and G/A_22018, as a diagnostic tool for lactose intolerance in IBS patients.

BACKGROUND: Irritable bowel syndrome (IBS) is a symptom-based disorder characterized by abdominal pain related to altered bowel habit. We evaluated the predictive power of 2 genetic markers of hypolactasia, C/T_13910 and G/A_22018, in IBS patients with and without lactose intolerance in order to gain insight into the role of lactose intolerance in IBS. METHODS: Seventy five patients (59F/16M, mean age: 49.6+/-14.2 years) with an IBS diagnosis based on Rome II criteria and 272 healthy individuals, where 74 (58F/16M, 54.1+/-10.9 years) were matched-controls, were evaluated. IBS and healthy individuals were genotyped for the C/T_13910 and G/A_22018 polymorphisms nearby the lactase-phlorizin hydrolase gene. Hydrogen breath test (HBT) with gas chromatography was performed in IBS patients to assess for lactose intolerance. RESULTS: Of the 75 IBS patients, 28 (37%) were defined as lactose intolerants. The grade/severity of symptoms after an oral lactose load were positively correlated to the expiratory H2 excretion (P<0.001). Alleles and genotypes frequencies from C/T_13910 and G/A_22018 were not significantly different between IBS patients and control individuals (P>0.05;NS). Presence of the C and G allele were positively associated with a higher expiratory hydrogen excretion and more intense gastrointestinal symptoms (P<0.001). Considering these polymorphisms as a diagnostic test for lactose intolerance in IBS patients, presence of the CC and GG genotypes were estimated to have, a sensitivity of 100% and 96%, respectively; and a specificity of 83% and 79%, positive predictive value of 76% and 73%, and negative predictive value of 100% and 97%. CONCLUSIONS: In IBS patients, genotyping of C/T_13910 and G/A_22018 polymorphisms predicts gastrointestinal symptoms after lactose ingestion and are a diagnostic tool for lactose intolerance.

Postoperative portal vein thrombosis in patients with hepatosplenic mansonic schistosomiasis: relationship with intraoperative portal pressure and flow. A prospective study.

BACKGROUND/AIMS: Portal vein thrombosis is a frequent postoperative complication after esophagogastric devascularization with splenectomy. The aim of this study was to analyze biochemical, hematological, coagulation blood tests and intraoperative portal vein hemodynamics after surgical treatment of hepatosplenic Mansonic schistosomal portal hypertension. METHODOLOGY: Forty patients with hepatosplenic schistosomiasis with indication for surgical treatment were prospectively studied. All patients underwent routine pre- and postoperative biochemical, hematologic, coagulation blood tests and intraoperative portal hemodynamic evaluation (portal pressure and portal flow) before and after esophagogastric devascularization and splenectomy using a 4-F thermodilution catheter introduced inside the portal vein. RESULTS: Portal vein thrombosis, diagnosed by routine postoperative Doppler ultrasonography was found in 22 patients (55%). It was partial in nineteen and total in three. In patients with postoperative portal thrombosis, we observed a reduction in portal flow of 971 +/- 592 mL/min (42 +/- 16%) at the end of the surgery, while this reduction was of 720 +/- 644mL/ min (33 +/- 30%) in those with postoperative pervious portal vein (p = 0.245). The decrease in portal pressure was the same in both groups: 7.2 +/- 3.0 mmHg (23 +/- 10%) and 7.6 +/- 3.8 mmHg (27 +/- 14%) with and without thrombosis respectively (p=0.759). There was also no significant difference between patients with and without portal vein thrombosis regarding pre- and postoperative hemoglobin level or platelet levels, coagulation tests, portal vein diameter and spleen's weight. CONCLUSIONS: Portal vein thrombosis was observed in 55% of the patients but this complication did not show any correlation with the decrease in portal flow or pressure or with biochemical, hematologic, coagulation blood tests, portal vein diameter or spleen's weight.

Different degrees of malnutrition and immunological alterations according to the aetiology of cirrhosis: a prospective and sequential study.

OBJECTIVES: In this work we investigated how immunological dysfunction and malnutrition interact in alcoholic and viral aetiologies of cirrhosis. METHODS: To investigate the matter, 77 cirrhotic patients divided in three aetiologies [Alcohol, HCV and Alcohol + HCV) and 32 controls were prospectivelly and sequentially studied. Parameters of humoral immunity (Components 3 and 4 of seric complement and immunoglobulins A M, G and E) and of cellular immunity (total leukocytes and lymphocytes in peripheral blood, T lymphocytes subpopulations, CD4+ and CD8+, CD4+/CD8+ ratio and intradermic tests of delayed hypersensitivity), as well as nutritional parameters: anthropometric measures, serum albumin and transferrin were evaluated. RESULTS: Multiple statistical comparisons showed that IgM was higher in HCV group; IgG was significantly elevated in both HCV and Alcohol + HCV, whereas for the Alcohol group, IgE was found at higher titles. The analysis of T- lymphocytes subpopulations showed no aetiologic differences, but intradermic tests of delayed hypersensitivity did show greater frequency of anergy in the Alcohol group. For anthropometric parameters, the Alcohol +HCV group displayed the lowest triceps skinfold whereas creatinine--height index evaluation was more preserved in the HCV group. Body mass index, arm muscle area and arm fat area showed that differently from alcohol group, the HCV group was similar to control. CONCLUSION: Significant differences were found among the main aetiologies of cirrhosis concerning immunological alterations and nutritional status: better nutrition and worse immunology for HCV and vice-versa for alcohol.

CFTR, PRSS1 and SPINK1 mutations in the development of pancreatitis in Brazilian patients.

CONTEXT: Mutations in cystic fibrosis transmembrane conductance regulator (CFTR), in cationic trypsinogen (PRSS1) and in serine protease inhibitor Kazal type 1 (SPINK1) genes have been associated with chronic pancreatitis (alcohol related, idiopathic and hereditary). However, the inheritance pattern is still not clear. PATIENTS: Eighty-two unrelated Brazilian patients with chronic pancreatitis (alcohol-related disease in 64, idiopathic disease in 16, and hereditary disease in 2). Two hundred unrelated individuals with an ethnic distribution comparable to the patients were studied as controls. MAIN OUTCOME MEASURE: Detection of mutations in CFTR, PRSS1, and SPINK1 genes. RESULTS: Mutations in the CFTR gene were found in 8 patients (9.8%) with chronic pancreatitis, 5 of them with idiopathic disease. Interestingly, the only clinical symptom in a male patient in the alcoholic group, who was a compound heterozygote (DeltaF508/R170C) for two CFTR mutations, was pancreatitis without infertility or pulmonary involvement. In the PRSS1 gene, the E79K change in exon 3 was found in one patient (1.2%) with alcohol-related chronic pancreatitis. Four different alterations were identified in the SPINK1 gene. CONCLUSIONS: Mutations in the CFTR gene represent the major cause of idiopathic chronic pancreatitis in Brazilian patients. No mutation was found in the PRSS1 gene among our patients suggesting further genetic heterogeneity for hereditary and idiopathic chronic pancreatitis. Interestingly, the most frequent SPINK1 N34S mutation was not present in patients or controls. Moreover, the -253C allele for the SPINK1 gene was significantly more frequent in patients than controls (P=0.004), suggesting that it might represent a risk factor for the development of pancreatitis in our population.

Prevalence of pulmonary hypertension in patients with hepatosplenic Mansonic schistosomiasis--prospective study.

BACKGROUND/AIMS: Thirty-four patients with portal hypertension and previous history of esophageal varices hemorrhage due to hepatosplenic Mansonic schistosomiasis were prospectively studied. METHODOLOGY: All patients underwent invasive hemodynamic monitoring with introduction of a pulmonary artery catheter. Hemodynamic evaluation was characterized by an increased cardiac index (4.90 +/- 1.27 L/min/m2) associated to a decrease in systemic vascular resistance index (1461 +/- 443.04 dynes.sec/cm5.m2). RESULTS: Mean pulmonary artery pressure (17.97 +/- 6.97 mmHg) and right atrial pressure (7.65 +/- 3.67 mmHg) were increased while pulmonary vascular resistance index was decreased (147.95 +/- 126.21 dynes.sec/cm5.m2). Twenty-four patients (70.5%) presented pulmonary hypertension (mean pulmonary artery pressure > 15 mmHg); in fifteen (44.1%) pulmonary pressure was between 15 and 20 mmHg, in three between 20 and 25 mmHg and, in four patients, pulmonary pressure was higher than 25 mmHg. CONCLUSIONS: In conclusion, pulmonary hypertension is a frequent complication in patients with portal hypertension due to hepatosplenic Mansonic schistosomiasis and, in 20.6% of the cases, it can be considered as moderate or severe. Our results suggest that shunt surgeries, which can aggravate pulmonary hypertension, should be employed very cautiously in the treatment of schistosomal portal hypertension.

Treatment by splenectomy of a portal vein aneurysm in hepatosplenic schistosomiasis.

Portal vein aneurysm is a rare medical entity that can be caused by chronic hepatic diseases with portal hypertension. We describe a 45-year-old man with variceal bleeding from hepatosplenic schistosomiasis and an incidentally found intrahepatic aneurysm. Diagnosis was confirmed with non-invasive imaging exams, arteriography and liver biopsy. Following splenectomy, the aneurysm diameter decreased substantially.

Therapeutic efficacy of ranitidine bismuth citrate with clarithromycin for seven days in the eradication of Helicobacter pylori in Brazilian peptic ulcer patients.

CONTEXT: The curative treatment of peptic ulcer is made available nowadays through the eradication of the bacterium Helicobacter pylori, which is associated with it, but the best therapeutic regimen is yet to be determined. OBJECTIVE: To assess the efficacy of a therapeutic regimen with 400 mg ranitidine bismuth citrate associated with 500 mg clarithromycin given twice a day for seven days in a cohort of Brazilian patients with peptic ulcer. TYPE OF STUDY: Cross-sectional study. SETTING: Tertiary-care hospital. PATIENTS: One hundred and twenty nine outpatients, with active or healed peptic ulcers infected by Helicobacter pylori, diagnosed via endoscopy with confirmation via the urease test and histological examination, who had never undergone a regimen for the eradication of the bacterium. PROCEDURE: Administration of 400 mg ranitidine-bismuth and 500 mg clarithromycin twice a day, for seven days. MAIN MEASUREMENTS: Efficacy of the treatment, with a check on the cure done via another endoscopy eight weeks after drug administration. The eradication of the bacterium was determined via the urease test and histological examination. Patients who were negative for both were considered to be cured. RESULTS: Eight patients failed to complete the study. The eradication rate according to intention to treat was 81% (104/129) and per protocol was 86% (104/121). CONCLUSION: The bismuth ranitidine compound associated with clarithromycin used for one week was shown to be a simple, effective and well-tolerated therapeutic regimen for the eradication of Helicobacter pylori.

The impact of Helicobacter pylori resistance on the efficacy of a short course pantoprazole based triple therapy.

BACKGROUND: Many of the currently used Helicobacter pylori eradication regimens fail to cure the infection due to either antimicrobial resistance or poor patient compliance. Those patients will remain at risk of developing potentially severe complications of peptic ulcer disease. AIM: We studied the impact of the antimicrobial resistance on the efficacy of a short course pantoprazole based triple therapy in a single-center pilot study. METHODS: Forty previously untreated adult patients (age range 20 to 75 years, 14 males) infected with Helicobacter pylori and with inactive or healing duodenal ulcer disease were assigned in this open cohort study to 1 week twice daily treatment with pantoprazole 40 mg, plus clarithromycin 250 mg and metronidazole 400 mg. Helicobacter pylori was assessed at entry and 50 3 days after the end of treatment by rapid urease test, culture and histology of gastric biopsies. The criteria for eradication was a negative result in the tests. Susceptibility of Helicobacter pylori to clarithromycin and metronidazole was determined before treatment with the disk diffusion test. RESULTS: One week treatment and follow up were complete in all patients. Eradication of Helicobacter pylori was achieved in 35/40 patients (87.5%) and was higher in patients with nitroimidazole-susceptible strains [susceptible: 20/20 (100%), resistant: 10/15 (67%)]. There were six (15%) mild adverse events reports. CONCLUSIONS: A short course of pantoprazole-based triple therapy is well tolerated and effective in eradicating Helicobacter pylori. The baseline metronidazole resistance may be a significant limiting factor in treatment success.

Histologic study of colonic mucosa in patients with chronic diarrhea and normal colonoscopic findings.

BACKGROUND: There are controversies about the importance of biopsies of normal colon mucosa in the investigation of patients with chronic diarrhea. STUDY: Colonic and terminal ileum biopsies of 167 patients were reviewed. In 5 patients, used as controls, colonoscopy was done due to family history of colon cancer. RESULTS: The 5 patients without symptoms had no histologic abnormalities. The histologic findings in 162 patients with chronic diarrhea were as follows: 110 patients (67.9%) with normal histology, microscopic colitis not otherwise specified, and isolated small granulomas; 17 (10.5%) patients had findings of borderline diagnostic significance, including possible collagenous colitis, some features of lymphocytic colitis and melanosis coli; and 35 (21.6%) patients, with diagnostic significant histologic findings as collagenous colitis, lymphocytic colitis, minimal change microscopic colitis, eosinophilic colitis, pericrypt eosinophilic enterocolitis, intestinal spirochetosis, schistosomiasis, and Crohn's disease. Of the 52 patients with either borderline or significant diagnostic abnormalities, in 8 (15.4%) the diagnosis was done only with a proximal study (ascending, transverse, or descending colons). CONCLUSIONS: Histologic lesions of possible diagnostic value could exist in 32.1% of chronic diarrhea patients with normal colonoscopy, which can justify, in certain cases, mucosa biopsies, which might contribute for a more precise etiologic diagnosis; also, the distribution of these histologic changes has pointed out the importance of having all colon segments biopsied.

Omeprazole, furazolidone, and tetracycline: an eradication treatment for resistant H. pylori in Brazilian patients with peptic ulcer disease.

OBJECTIVES: To determine the efficacy of a simple, short-term and low-cost eradication treatment for Helicobacter pylori (H. pylori) using omeprazole, tetracycline, and furazolidone in a Brazilian peptic ulcer population, divided into 2 subgroups: untreated and previously treated for the infection. PATIENTS AND METHODS: Patients with peptic ulcer disease diagnosed by endoscopic examination and infected by H. pylori diagnosed by the rapid urease test (RUT) and histological examination, untreated and previously unsuccessfully treated by macrolides and nitroimidazole, were medicated with omeprazole 20 mg daily dose and tetracycline 500 mg and furazolidone 200 mg given 3 times a day for 7 days. Another endoscopy or a breath test was performed 12 weeks after the end of treatment. Patients were considered cured of the infection if a RUT and histologic examination proved negative or a breath test was negative for the bacterium. RESULTS: Sixty-four patients were included in the study. The women were the predominant sex (58%); the mean age was 46 years. Thirty-three percent of the patients were tobacco users, and duodenal ulcer was identified in 80% of patients. For the 59 patients that underwent follow-up examinations, eradication was verified in 44 (75%). The eradication rate for the intention-to-treat group was 69%. The incidence of severe adverse effects was 15%. CONCLUSION: The treatment provides good efficacy for H. pylori eradication in patients who were previously treated without success, but it causes severe adverse effects that prevented adequate use of the medications in 15% of the patients.

Low efficacy of an ultra-short term, once-daily dose triple therapy with omeprazole, azithromycin, and secnidazole for Helicobacter pylori eradication in peptic ulcer.

PURPOSE: To determine the eradication rate of an ultra-short treatment schedule for Helicobacter pylori infection in a population with peptic ulcers, using omeprazole, secnidazole, and azithromycin in a once-daily dose for 3 days. METHODS: Thirty patients with peptic ulcer diagnosed by upper endoscopy and for Helicobacter pylori infection by rapid urease test and histologic examination received omeprazole 40 mg, secnidazole 1000 mg, and azithromycin 500 mg, administered once daily for 3 days. A follow-up exam was performed 12 weeks after the end of the treatment. Patients who were negative for Helicobacter pylori infection by rapid urease test and histologic examination were considered cured. RESULTS: Patients were predominantly female, and the mean age was 50 years. Duodenal peptic ulcer was found in 73% of the patients. Eradication was achieved in 9 of the 28 (32%) patients as determined from the follow-up endoscopic exam. The eradication rate by intention to treat was 30%. Side effects were present in 3% of the patients, and compliance to treatment was total. CONCLUSIONS: In spite of the low rate of side effects and good compliance, the eradication index was low. A possible drawback of this therapy is that it reduces the efficacy of macrolide and nitroimidazole compounds in subsequent treatments.

Preoperative serum levels of CA 72-4, CEA, CA 19-9, and alpha-fetoprotein in patients with gastric cancer.

INTRODUCTION: The clinical importance of preoperative serum levels of CA 72-4, carcinoembryonic antigen (CEA), CA 19-9, and alpha-fetoprotein (AFP) was prospectively evaluated in 44 patients with gastric cancer. METHOD: The serum tumor marker levels were determined by commercial radioimmunoassay kits. Positivity for CA 72-4 (>4 U/mL), CEA (>5 ng/mL), CA 19-9 (>37 U/mL), and AFP (>10 ng/mL) were correlated according to the stage, histology, and lymph node metastasis. RESULTS AND DISCUSSION: CA 72-4 showed a higher positivity rate for gastric cancer (47.7%) than CEA (25%), CA 19-9 (25%), and AFP (0%). The combination of CA 72-4 with CEA and CA 19-9 increased the sensitivity to 61.4%. The positivity rates of CA 72-4 in patients at stages I and II (initial disease) and in patients at stages III and IV (advanced disease) were 9% and 60.6%, respectively (P < 0.005). No correlation was found between CEA and CA 19-9 levels and the stage of gastric cancer. There was a tendency of positivity for CA 72-4 to suggest lymph node involvement, but it was not significant (P = 0.075). Serum levels of tumor markers did not show a correlation with the histological types of gastric cancer. CONCLUSION: Preoperative serum levels of CA 72-4 provided a predictive value in indicating advanced gastric cancer.

Cholestasis in a murine experimental model: lesions include hepatocyte ischemic necrosis.

OBJECTIVE: To establish a murine experimental model of bile duct obstruction that would enable controlled observations of the acute and subacute phases of cholestasis. METHODOLOGY: Adult male isogenic BALB/c mice underwent a bile duct ligation (22 animals) or a sham operation (10 animals). Fifteen days after surgery, or immediately after the animal's death, macroscopic findings were noted and histological study of the liver, biliary tree, and pancreas was performed (hematoxylin-eosin and Masson trichromic staining). RESULTS: Beginning 24 hours after surgery, all animals from the bile duct ligation group presented progressive generalized malaise. All animals presented jaundice in the parietal and visceral peritoneum, turgid and enlarged liver, and accentuated dilatation of gallbladder and common bile duct. Microscopic findings included marked dilatation and proliferation of bile ducts with accentuated collagen deposits, frequent areas of ischemic necrosis, hepatic microabscesses, and purulent cholangitis. Animals from the sham operation group presented no alterations. CONCLUSION: We established a murine experimental model of induced cholestasis, which made it possible to study acute and subacute tissue lesions. Our data suggests that in cholestasis, hepatic functional ischemia plays an important role in inducing hepatic lesions, and it also suggests that the infectious process is an important factor in morbidity and mortality.

Ultrastructural study of the pancreas in AIDS.

INTRODUCTION: Frequent histologic changes (90%) in the pancreas suggesting protein-energy malnutrition were found in a previous necropsy study of pancreas morphology in patients with AIDS. However, additional studies were required to clarify subcellular changes. AIM: To ultrastructurally analyze pancreas changes in AIDS patients through transmission electron microscopy. METHODOLOGY AND RESULTS: Pancreas specimens for necropsy were obtained from nine consecutive AIDS patients and four normal controls. A semiquantitative histologic and ultrastructural analysis of exocrine pancreas was carried out with the following findings: preserved pancreas structure with little autolysis, marked decrease in zymogen granules (100%), increased lipofuscin pigment (80%), augmented and dilated rough endoplasmic reticulum (100%), and increased number and size of mitochondria. The Golgi complex could be identified only in two cases. In all cases, acinar nuclei were decreased in size, with peripherally condensed chromatin and undulated membrane suggesting early apoptosis. In addition, immunohistochemical evaluation of the pancreas was carried out to detect opportunistic agents. CONCLUSION: Decreased zymogen granules, acinar atrophy, increased lipofuscin pigment, and rarefying Golgi complex represent the morphologic substrate of protein-energy malnutrition in AIDS patients. The combination of rough endoplasmic reticulum and mitochondria changes could be due to the need for supplying vital plasma proteins rather than exportation protein synthesis associated, or not, with the deleterious effects of inflammatory cytokines and/or therapy for disease.

Celiac disease in Brazilian adults.

UNLABELLED: Forty-eight adult patients with celiac disease between 15 and 68 years of age (mean, 41 years) were studied. Sixty-seven percent were female and 33% were male patients. Most of the patients were white (98%). The main clinical features were diarrhea (90%), weight loss (70%), and abdominal pain (56%). On physical examination, the main findings were pallor (40%), aphthous stomatitis (31%), and arthralgia (23%). Associated disorders included diabetes mellitus type I, osteoporosis, and atopy (6% each); dermatitis herpetiformis and depression (4% each); and hypothyroidism, hyperthyroidism, duodenal carcinoma, and Gilbert syndrome (2% each). The histologic results according to Marsh criteria (modified by Rostami) are as follows: type I, 10%; type II, 21%; type IIIa, 19%; type IIIb, 17%; and type IIIc, 33%. The sensitivity and specificity for the antiendomysium antibody-immunoglobulin A test were 92% and 100%, respectively, when considering the whole group of patients; however, the sensitivity (but not the specificity) decreased to 86% when taking into account only the group of patients with mild histologic alterations (Marsh type I, II, and IIIa). CONCLUSION: In general, the authors' results are similar to those described in developing countries, indicating that celiac disease might have the same spectrum of presentation regardless of the region studied.

Portal hyperflow in patients with hepatosplenic mansonic schistosomiasis.

PURPOSE: The purpose of this study was to assess portal hemodynamics in patients with portal hypertension due to hepatosplenic schistosomiasis as well as to assess the contribution of splanchnic hyperflow to the pathophysiology of the portal hypertension. METHODS: Sixteen patients with schistosomal portal hypertension and previous history of upper digestive bleeding due to esophageal varices rupture underwent elective esophagogastric devascularization and splenectomy and were prospectively studied. All patients underwent intraoperative invasive hemodynamic portal monitoring with a 4F-thermodilution catheter. The intraoperative portal hemodynamic assessment was conducted after laparotomy (initial) and after esophagogastric devascularization (final). RESULTS: The initial portal pressure was elevated (mean 28.5 +/- 4.5 mm Hg), and a significant drop of 25% was observed at the end of the surgery (21.9 +/- 4.9 mm Hg). The initial portal flow was elevated (mean 1766.9 +/- 686.6 mL/min). A significant fall (42%) occurred at the end of the surgical procedure (1025.62 +/- 338.7 mL/min). Fourteen patients (87.5%) presented a portal flow of more than 1200 mL/min, and in 5 cases, values greater than 2000 mL/min were observed. CONCLUSIONS: Esophagogastric devascularization and splenectomy promote a significant reduction of the elevated portal pressure and flow in schistosomal portal hypertension. These data favor the hypothesis of portal hyperflow in the physiopathology of portal hypertension of schistosomiasis.

Analysis of major histocompatibility complex and CTLA-4 alleles in Brazilian patients with primary biliary cirrhosis.

BACKGROUND AND AIMS: Predisposition to primary biliary cirrhosis (PBC) has been classically linked to HLA-DRB1 locus. However, the presence of the HLA-DRB1*08 antigen has been reported in less than one-third of PBC patients from Northern Europe and Japan. Recently, polymorphisms in the tumor necrosis factor alpha (TNFA) gene promoter at position -308 and in exon 1 of the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene at position 49 have been associated with susceptibility to PBC in Caucasians. In addition, the presence of HLA-DRB1*08 and the TNFA*1 allele was also linked to progression to end-stage liver disease. The aims of the present study were to investigate the frequencies of HLA-DR and DQ antigens and TNFA and CTLA-4 alleles in PBC patients from a different genetic background, as well as to assess the role of TNFA alleles and HLA-DR antigens in disease progression. METHODS: Determination of HLA-DRB1, DQB1, TNFA and CTLA-4 alleles was performed in patients with PBC and healthy controls using polymerase chain reaction-based techniques. RESULTS: Frequencies of HLA-DR and DQ antigens were similar in PBC patients and healthy controls. Accordingly, no association between TNFA and CTLA-4 alleles was observed in PBC patients. The histological stage at admission of patients with PBC also showed no correlation with HLA antigens and TNFA and CTLA-4 alleles. CONCLUSIONS: Susceptibility to PBC in Brazil is not associated with HLA-DR and DQ antigens and CTLA-4 genotypes. TNFA alleles were not shown to influence disease progression.

Prevalence of immune disturbances and chronic liver disease in family members of patients with primary biliary cirrhosis.

BACKGROUND AND AIMS: Primary biliary cirrhosis (PBC) has been reported in up to 4-6% of first degree relatives of patients with the disease. In addition, immune abnormalities, including hypergammaglobulinemia, autoantibodies and increased frequency of autoimmune disorders, were reported in family members of PBC patients. The aim of the present study was to investigate the prevalence of PBC in relatives of patients with PBC, and to investigate the occurrence of chronic liver disease (CLD) and immune abnormalities in these subjects. METHODS: One-hundred first degree relatives of 26 patients with PBC were interviewed and submitted to physical examination and determination of liver enzymes, gamma-globulin, bilirubin and auto-antibodies, including antinuclear (ANA), antismooth muscle (SMA), antimitochondrial antibodies (AMA) by indirect immunofluorescence (IIF) and anti-M2 antibody by immunoblotting (IB). RESULTS: Immune disturbances were rarely observed in relatives of PBC patients. Higher gamma-globulin levels, SMA and ANA were detected in four, eight and two family members, respectively. In most subjects, these autoantibodies were either in low titers or associated with concurrent diseases. Only four relatives had extrahepatic autoimmune diseases and another eight exhibited other CLD. Primary biliary cirrhosis was detected in a sister of one patient. Additionally, two other relatives of PBC patients who tested negative for AMA by IIF showed reactivity for anti-M2 by IB. CONCLUSIONS: Immune disturbances, including ANA and SMA, are uncommon in family members of PBC patients. Conversely, anti-M2 antibodies and overt PBC do occur in relatives of PBC patients, even in Brazil where the disease is quite rare.

Helicobacter pylori genotyping from positive clotests in patients with duodenal ulcer

Even though the seroprevalence of H. pylori may be high in the normal population, a minority develops peptic ulcer. Colonization of the gastric mucosa by more pathogenic vacA strains of H. pylori seems to be associated with enhanced gastric inflammation and duodenal ulcer. H. pylori genotyping from positive CLOtests was developed to determine the vacA genotypes and cagA status in 40 duodenal ulcer patients and for routine use. The pathogenic s1b/ m1/ cagA genotype was the most frequently occurring strain (17/42.5 per cent); only two (5 per cent) patients presented the s2/ m2 genotype, the less virulent strain. Multiple strains were also detected in 17 (42.5 per cent) patients. Multiple strains of H. pylori colonizing the human stomach have been underestimated, because genotyping has been performed from cultures of H. pylori. We concluded that genotyping of H. pylori from a positive CLOtest had the advantages of reducing the number of biopsies taken during endoscopy, eliminating the step of culturing H. pylori, and assuring the presence of H. pylori in the specimen being processed.

Validation of 14-C-urea breath test for diagnosis of Helicobacter pylori

The aim of this study was to validate the 14C-urea breath test for use in diagnosis of Helicobacter pylori infection. Thirty H. pylori positive patients, based on histologic test and thirty H. pylori negative patients by histology and anti-H. pylori IgG entered the study. Fasting patients drank 5 uCi of 14C-urea in 20 ml of water. Breath samples were collected at 0, 5, 10, 15, 20 and 30 min. The difference of cpm values between the two groups was significant at all the time intervals, besides time 0 (p<0.0001). At 20 min, the test gave 100 percent sensitivity and specificity with a cut-off value of 562 cpm. Females were higher expirers than males (p=0.005). 14C-urea breath test is highly accurate for Helicobacter pylori diagnosis. It is fast, simple and should be the non-invasive test used after treating Helicobacter pylori infection.