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A case of severe ulcerative colitis refractory to steroid therapy is reported. The authors look at cyclosporine use in this clinical setting and make a short review of cyclosporine usefulness and major side effects.

Endoscopic interventional techniques have created a wide new perspective for non-surgical treatment of chronic pancreatitis (CP). Surgery and endoscopy differ in their techniques, but are comparable with regard to tactics. The aim of methods in CP is to relieve pain and/or local complications. The preliminary results of endoscopic procedures in CP are promising and the methods appear safe in the hands of experienced endoscopists.

From September 1987 to April 1994, 144 biliary endoprostheses were introduced (81 male; 63 female; mean age 68.7 years) in patients presenting distal stricture of the common bile duct by pancreatic tumors. 135 plastic (10 and 12 French) and 9 metallic (30 French) prostheses were placed. The most common complication associated with plastic prostheses is clogging (16%); this problem was solved with the use of metallic prosthesis, which is limited by their high cost. The mortality and morbidity are lower and the time hospital discharge is shorter until, than the ones associated with bilio-digestive anastomosis; mean survival is similar with two procedures endoscopy/surgery.

The authors report a case of primary hypothyroidism where the main symptoms were caused by muscular lesions and disappeared after treatment with L-thyroxine. Based on this case study the authors then review both the clinical aspects and the diagnostical methods of hypothyroidism myopathy, noting its frequency, be it in terms of isolated laboratory changes or in terms of functional changes.

We conducted a prospective clinical trial of 154 patients with duodenal ulcer disease, which was divided in two different steps: healing phase and post-healing phase. In the first phase, the patients were randomly assigned to treatment with H2 blockers (Ranitidine 300 mg or Famotidine 40 mg), in a single bedtime dose. Endoscopy was performed after 4 and 12 weeks of treatment and the healing rate was 70% and 90%. There were no significant differences between the two drugs. After 12 weeks of treatment there were sixteen patients with non-healed duodenal ulcer, considered as refractory duodenal ulcer disease, in which we started therapy with a double dose of H2 receptor antagonists or sucralfate (4 gr/day). Endoscopic follow-up after 12 weeks of this regimen revealed ulcer healing in about half of them; the cummulative healing rate in 6 months was 96.4%. Persistent lesions after 6 months of follow-up were found in 5 patients. Omeprazole 40 mg, single dose, was given and all of them were healed during the first 4 weeks of treatment. In the second phase, 137 patients healed during the first 3 months of treatment, were followed for 12 months and randomized in two groups: 61, with maintenance therapy--ranitidine 150 mg or famotidine 20 mg; 76, without treatment. In the patients without maintenance therapy, the recurrence rate was significantly higher (p less than 0.55), than in the group with maintenance therapy. In this group several parameters were evaluated--clinical, biochemical and psychosocial--to try to identify some prognostic markers of healing, relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Despite the availability of a vaccine against hepatitis B virus (HBV), this infection still causes public health problems, particularly in susceptible populations. In Portugal, universal free vaccination started in 1994, and most HBV infections are diagnosed in immigrants from high-prevalence countries. Our aim was to assess the pattern of HBV genotypes/subgenotypes in samples collected between 2017 and 2021 from a convenience sample of 70 infected residents in Portugal. The HBV pol/HBsAg region was amplified and sequenced, allowing the analysis of RT sequences submitted to phylogenetic analysis and mutations assessment. A total of 37.1% of samples were from native Portuguese, aged 25-53 years (mean: 36.7 years), and the remaining samples were from individuals born outside of Portugal. A high diversity of HBV was identified: subgenotypes A1-A3 in 41.0% (16/39); D1, D3, and D4 in 30.7% (12/39); E in 23.1% (9/39); and F4 in 2.6% (1/39). Besides genotypes A and D, Portuguese were also infected with genotypes E and F, which are prevalent in Africa and South America, respectively. Resistance mutations in RT sequences were not found. The findings provide valuable insights for updating the HBV molecular epidemiology in Portugal. However, successful strategies to prevent and control the infection are still needed in the country, especially among susceptible and vulnerable populations.

Human T-cell lymphotropic virus type 1 (HTLV-1) prevalence in Portugal is low and mainly affects immigrants from endemic areas where human immunodeficiency virus (HIV) infection represents a public health problem. Despite the majority of HTLV-1-infected individuals remains asymptomatic, severe pathologies may develop after prolonged viral persistence, namely an aggressive form of leukemia. An increased mortality rate and faster progression to death is often related to HTLV-1/HIV coinfection. Nevertheless, studies showed that some antiretrovirals used in HIV treatment lead to a positive immune response against HTLV-1. This study aimed to analyze epidemiological and clinical data, and to assess the diversity of HTLV-1 strains circulating in infected residents diagnosed in the Portuguese national reference laboratory between 2010 and 2021. Long terminal repeat and env proviral sequences derived from 20 individuals were used to generate phylogenetic trees along with multiples reference sequences from different geographic origins retrieved from the database. Three samples belong to Portuguese natives and 17 belong to immigrants: 15 from several countries of Africa, 1 from South America, and 1 from Europe; 6 patients (30%, mean age 40.3 years) showed HTLV-1-related diseases, and 6 (30%, mean age 45.2 years) were coinfected with HIV/AIDS. The results show that the Cosmopolitan subtype is circulating in Portugal, with 10 sequences being classified as subgroup A, that include Portuguese and natives from S. Tomé and Príncipe with a mean age of 39.4 years, and 10 sequences that segregated into the Senegal cluster derived from natives born in Guinea-Bissau with a mean age of 43.5 years. A high proportion of HTLV-1-related diseases and HIV/AIDS coinfection was observed. Risk behavior practices and the absence of specific control measures, including diagnostic and treatment, may contribute to a silent dissemination of a broad diversity of HTLV-1 strains and, therefore, the increased rate of progression to debilitating diseases. In this manner, an early diagnostic and a molecular surveillance of HTLV-1 transmission remains necessary in Portugal.

Hepatitis C virus (HCV) is associated with liver damage and an increased progression rate to cirrhosis and hepatocellular carcinoma. In Portugal, it is prevalent in vulnerable populations such as injection drug users (IDU). HCV is characterized by a high intra-host variability, and the selecting driving forces could select variants containing resistance-associated substitutions (RAS) that reduce treatment effectiveness. The main goal of this study was to analyze the sequence variation of NS5A in treatment-naïve IDU. The epidemiological and clinical status of hepatitis C were analyzed, and samples were sequenced by Sanger and Next-Generation sequencing (NGS) to assess RAS and confirm HCV subtypes. Phylogenetic classification was concordant: 1a, 52.4%; 1b, 10.7%; 3a, 20.2%; 4a, 8.3%; 4d, 7.1%; and one 2k/1b recombinant. A 1a/3a mixed infection was detected by NGS. RAS were found in 34.5% (29/84) of samples using Sanger sequencing, while in 42.9% (36/84) using NGS. In sequences from subtypes 1a and 1b, RAS K24R, M28V, Q30H/R, H58D/P/Q/R, and RAS L31M and P58S were detected, respectively. In subtype 3a, RAS A30S/T, Y93H and polymorphisms in position 62 were identified. Additionally, RAS P58L was detected in genotype 4. The strategy used for the molecular survey of baseline HCV resistance is of particular importance to achieve treatment effectiveness and contribute to the elimination of hepatitis C.

Background: Current noninvasive tests to confirm the eradication of Helicobacter pylori must be performed 4 weeks or more after eradication therapy is completed., Objective: To determine whether the stool antigen test, a relatively new noninvasive test for H. pylori, administered at various times after eradication therapy correctly identifies persons with persistent H. pylori infection., Design: Prospective blinded study., Setting: Six clinical centers in the United States and Europe., Patients: 84 H. pylori --infected patients undergoing endoscopy for upper abdominal symptoms., Measurements: At baseline and on day 35 after the completion of triple eradication therapy, all patients underwent endoscopy with histologic examination, rapid urease test and culture, urea breath test, and a stool antigen test. The stool antigen test was also performed on days 3, 7, 15, 21, 28, and 35 after completion of therapy., Results: Compared with the gold-standard endoscopic tests on day 35 after antimicrobial therapy, the urea breath test had a sensitivity of 94% (95% CI, 71% to 100%) and a specificity of 100% (CI, 94% to 100%). The stool antigen test had a sensitivity of 94% (CI, 71% to 100%) and a specificity of 97% (CI, 89% to 100%). On day 7 after treatment, the stool antigen test was predictive of eradication (positive predictive value, 100% [CI, 69% to 100%]; negative predictive value, 91% [CI, 82% to 97%])., Conclusion: A positive result on the stool antigen test 7 days after completion of therapy identifies patients in whom eradication of H. pylori was unsuccessful.

Background: The accuracy of diagnostic tests to assess Helicobacter pylori eradication has rarely been performed., Aim: To compare the tests most commonly used for this purpose, i.e. histology, culture and (13)C urea breath test performed in centralized facilities., Methods: Prospective study where patients were included in four centres and diagnostic tests performed centrally by biologists experienced in the field. Gastric biopsies were obtained from antrum and corpus (two for histology, two for culture from each site) 4-6 weeks after an eradication treatment. The definition of a gold standard for H. pylori-positive patients was either a positive culture or both positive histology and urea breath test results., Results: Ninety-seven patients for whom data on histology, culture and (13)C urea breath test were available were included. The majority were females (60%) suffering from non-ulcer dyspepsia (52%) and having received proton-pump inhibitor-based triple therapy (62%). Forty-one per cent of the patients were H. pylori-positive according to the gold standard. The sensitivities were 90%, 95% and 92.5% and the specificities 100%, 98.2% and 100% for culture, histology and (13)C urea breath test, respectively., Conclusion: All the methods had excellent specificity but the sensitivity ranged between 90 and 95%. The combination of two techniques which increases the sensitivity to virtually 100% is recommended in situations where the eradication treatment requires a precise evaluation such as in clinical trials.

Objective: In a recently published multicenter study involving 501 patients undergoing esophagogastroduodenoscopy (EGD) throughout Europe, we showed the high accuracy of a recently developed simple test (HpSA) to detect Helicobacter pylori (H. pylori) antigens in stools of untreated patients. The aim of this study was to assess the diagnostic usefulness of HpSA compared with 13C UBT shortly after H. pylori eradication treatment., Methods: Of the 501 patients enrolled in the validation study, 279 were found to be H. pylori-positive. These patients were given H. pylori eradicating regimen and asked to return for follow-up EGD with biopsies, 13C UBT and HpSA testing 4 wk after therapy. Follow-up results were available for 235 patients. Of these, 162 consented to all testing and 73 consented only to 13C UBT and HpSA testing. We assessed sensitivity and specificity of both HpSA and 13C UBT compared with biopsy-based methods in the 162 patients, who accepted follow-up EGD. We also assessed sensitivity and specificity of HpSA compared with 13C UBT, arbitrarily chosen as the gold standard, in the whole population of 235 patients., Results: Sensitivity and specificity in 162 patients who consented to a second EGD were 93.8% (CI: 85.4-100%) and 96.9% (CI: 93.9-99.9%) for HpSA, and 90.6% (CI: 80.5-100%) and 99.2% (CI: 97.7-100%) for UBT. Using EGD-based methods as the gold standard, 130 of the 162 treated patients' H. pylori infection were eradicated (125 HpSA-negative, one borderline, and four false-positive; 129 13C UBT-negative, one false-positive), and 32 remained H. pylori-infected (30 HpSA-positive, two false-negative, 29 13C UBT-positive, three false negative). The overall eradication rate was 80.2%. The sensitivity and specificity of HpSA relative to UBT as the gold standard in the overall population (n = 235) were 95.6% (CI: 89.6-100%) and 94.7% (CI: 91.5-97.9%), respectively., Conclusions: HpSA has proven to be a useful method in posttreatment eradication testing for H. pylori. Its ease of use, speed, and noninvasive nature make HpSA testing an ideal method for post-treatment monitoring where a second EGD may not be justified.

The frequency of occurrence of Helicobacter pylori type I strains in isolates from Austria and Portugal and different polymerase chain reaction-based approaches to detect the cag pathogenicity island were assessed. Of the 41 Austrian strains, eight of 14 (57.2%) isolated from patients with gastritis, 14 of 19 (73.7%) from patients with peptic ulcer and eight of eight (100%) from patients with gastric cancer were type I strains. Among the Portuguese strains, eight of 14 (57.2%) isolated from patients with gastritis, ten of 12 (83.3%) from patients with peptic ulcer and five of 13 (38.5%) from patients with gastric cancer were classified as type I. Thus, Helicobacter pylori type I strains occur frequently in both populations but show no significant correlation with peptic ulcer disease. The prevalence of the type Igenotype in Austrian cancer patients, however, was significantly higher (P=0.007). The cagE-specific polymerase chain reaction was found to be a reliable and efficient method for detection of the cag pathogenicity island.

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.

A case of severe ulcerative colitis refractory to steroid therapy is reported. The authors look at cyclosporine use in this clinical setting and make a short review of cyclosporine usefulness and major side effects.

Background: DNA methylation and DNA cytometric parameters were evaluated in the rectal mucosa from patients with extensive and long-standing ulcerative colitis., Methods: Twenty-six patients with extensive disease for more than 7 years and 11 healthy controls were included. Global DNA methylation was assessed as the capacity of the DNA test to incorporate [3H]methyl groups from [3H]-S-adenosyl-methionine in the presence of Sss1 methylase. A higher incorporation reflects a lower state of intrinsic methylation. DNA ploidy, S-phase fraction, and proliferative index (PI = S + G2M) of the cell cycle were analyzed by flow cytometry., Results: Incorporation of the [3H]methyl groups into DNA was 10-fold higher in patients compared with controls (P < 0.001) and was significantly higher in patients with histologically active disease (P = 0.02). With regard to flow cytometry, all samples showed a diploid pattern, but S-phase fraction and the proliferative index values were significantly increased in patients compared with controls (P = 0.0007 and P = 0.003, respectively). A positive correlation was found between S-phase fraction and proliferative index and the number of exacerbations of the disease (P < 0.005), and there was a trend among those patients who had disease for longer than 20 years to present with increased cellular proliferation compared with those with a shorter evolution of disease (P > 0.05)., Conclusions: DNA hypomethylation and proliferative activity are increased in this group of patients, supporting the concept that their colonic mucosa undergoes epigenetic and kinetic changes that might predispose these individuals to develop colorectal neoplasms. However, it cannot be ruled out that these markers solely reflect hyperproliferation associated with active inflammation.

We describe the case of a localized lesion of African Histoplasmosis, presenting as a gastric ulcer, with radiological and endoscopic features suggesting malignancy, that was submitted to surgery. Histologic examination of the resected specimen revealed typical yeasts of Histoplasma duboisii. There where no clinical, radiological or endoscopic signs of disseminated disease and conventional antifungal therapy was not prescribed. The patient has been followed for 11 years now, without evidence of relapse. There are few reports of gastrointestinal Histoplasmosis, and even fewer specifically caused by H. Duboissii Previous descriptions of gastric ulcer in immunocompetent hosts are related to disseminated forms of American Histoplasmosis. Although focal digestive lesions have been found in African patients, there is no available data on the incidence of gastric ulcer as a presenting sign of the disease.

The mutagenic activity of glycine upon nitrosation was studied in the Ames tester strains TA98, TA100, TA102, and TA104. The results obtained show that glycine at acidic pH values and in the presence of Cl- can react with nitrite giving rise to genotoxic compounds to the tester strains used. When these experiments were carried out in the presence of gastric juice the genotoxicity observed was associated with the Cl- concentration in the different gastric juice samples. The nature and the mechanism of genetic lesion induced by the ultimate genotoxicant arising from the nitrosation of glycine are not fully understood. Primary amines (e.g., amino acids) have been described as potential alkylating agents after nitrosation. However, in our experimental conditions these alkylating activities were not detected, suggesting that other mechanisms could be involved in the genetic lesion induced by nitrosated glycine. The influence of Cl- in the genotoxic activity of glycine and other primary amines upon nitrosation and its possible involvement in the etiology of gastric cancer are discussed.

Endoscopic interventional techniques have created a wide new perspective for non-surgical treatment of chronic pancreatitis (CP). Surgery and endoscopy differ in their techniques, but are comparable with regard to tactics. The aim of methods in CP is to relieve pain and/or local complications. The preliminary results of endoscopic procedures in CP are promising and the methods appear safe in the hands of experienced endoscopists.

From September 1987 to April 1994, 144 biliary endoprostheses were introduced (81 male; 63 female; mean age 68.7 years) in patients presenting distal stricture of the common bile duct by pancreatic tumors. 135 plastic (10 and 12 French) and 9 metallic (30 French) prostheses were placed. The most common complication associated with plastic prostheses is clogging (16%); this problem was solved with the use of metallic prosthesis, which is limited by their high cost. The mortality and morbidity are lower and the time hospital discharge is shorter until, than the ones associated with bilio-digestive anastomosis; mean survival is similar with two procedures endoscopy/surgery.

The diagnosis of schistosomiasis is made by identification of Schistosoma in stool and urine, or by colonic or hepatic biopsies. The authors demonstrate in this paper, however, that it is also possible to suspect this disease by colonoscopy, i.e., by macroscopic observation of the vascular alterations in the mucous membrane of parasite infected patients. Out of 33 patients -21 with schistosomiasis and 12 with other intestinal parasitoses--the endoscopist correctly diagnosed Schistosomiasis in 18 (85.7%) patients, although he had no previous experience of the diagnosis. Since this infection is widespread throughout the world, these endoscopic findings are important; they may help the physician correctly diagnosis schistosomiasis in non-endemic areas where the diagnosis may not be suspected.

The authors report a case of primary hypothyroidism where the main symptoms were caused by muscular lesions and disappeared after treatment with L-thyroxine. Based on this case study the authors then review both the clinical aspects and the diagnostical methods of hypothyroidism myopathy, noting its frequency, be it in terms of isolated laboratory changes or in terms of functional changes.