A comparison between two induction regimes for the interferon treatment of chronic hepatitis C. Response related factors.

Treatment of chronic hepatitis C with alfa interferon for 6 months achieves sustained responses in 15-25% of the patients. The initial induction with higher doses and the prolongation of treatment can improve the results. A randomized, prospective study was carried out to compare the efficacy of a short term induction schedule of interferon alfa-2b (group A) versus a long term one (group B). 106 patients with chronic hepatitis C were included: 54 received 5 megaunits tiw for 8 weeks and 52 for 16 weeks; afterwards, interferon was reduced to 3 megaunits up to 9 months. The percentage of sustained responses, transient responses and non responses were 18.5%, 24% and 57.4% in group A and 23.1%, 28.8% and 48.1% in group B (NS). The following factors were related to a poor response in the univariate analysis: an increase of serum iron levels, ferritin, Gamma-GT and bilirubin, anti-nuclear antibody positivity, presumed non-parenteral infection, an AST/ALT ratio greater than 0.75, a higher Knodell's index and a greater necrosis and fibrosis score. The multivariate analysis revealed that elevated serum iron and ferritin and anti-nuclear antibody positivity had an independent predictive value related to a non response. Our results appear to suggest that an induction with higher doses and the treatment over nine months are more efficient than the classic schedule. The prolongation of the induction period does not provide additional advantages.

Mutation analysis of the p53, APC, and p16 genes in the Barrett's oesophagus, dysplasia, and adenocarcinoma.

AIMS: To study the loss of heterozygosity and the presence of mutations at the p53, p16/CDKN2, and APC genes in Barrett's oesophagus, low grade dysplastic oesophageal epithelium, and adenocarcinoma of the oesophagus; to relate the presence of alterations at these genes with the progression from Barrett's oesophagus to adenocarcinoma. METHODS: DNA was extracted from paraffin blocks containing tissue from Barrett's oesophagus (12 samples), low grade dysplasia (15 cases), and adenocarcinoma (14 cases). Loss of heterozygosity (LOH) at the p53, p16, and APC genes was determined by comparing the autoradiographic patterns of several microsatellite markers between the normal tissue and the malignant tissue counterpart. SSCP was used to determine the presence of mutations at p53 (exons 5 to 8), p16 (exon 2), and APC. Homozygous deletion of the p16 gene was defined through polymerase chain reaction followed by Southern blot. RESULTS: LOH at the p53, p16, and APC genes was not observed in Barrett's oesophagus without dysplasia, and increased to 90% (p53), 89% (p16), and 60% (APC) in the adenocarcinomas. The p53 gene was mutated in only two adenocarcinomas (codons 175 and 245). In one case a mutation at the APC gene (codon 1297) was found. No patient had mutation at the second exon of p16. However, this gene was homozygously deleted in three of the 12 adenocarcinomas. CONCLUSIONS: The tumour suppressor genes p53, p16, and APC are often deleted in adenocarcinomas derived from Barrett's oesophagus. Mutations at these genes are also found in the adenocarcinomas, including the homozygous deletion of the p16 gene. However, the absence of genetic alterations in the Barrett's oesophagus and the low grade dysplastic epithelia suggest that mutations at these genes develop later in the progression from Barrett's oesophagus to adenocarcinoma.

Colonoscopic findings in patients with lower gastrointestinal bleeding send to a hospital for their study. Value of clinical data in predicting normal or pathological findings.

BACKGROUND: Lower gastrointestinal bleeding is a highly frequent clinical problem that may reflect serious pathology in the colon. Colonoscopy is generally accepted as the diagnostic procedure of choice. Decisions as to whether to carry out colonoscopy or not, are not well defined. METHODS: 536 colonoscopies, made to discover the cause of lower gastrointestinal bleeding were analyzed and a final 457 included in the study. All of these patients came to the hospital because they had presented at least in one occasion, one episode of rectal bleeding, and were send by the specialist of the zone, in order to achieve a correct diagnosis of its process. In all cases the following associated symptoms were analyzed: the presence of diarrhea, constipation, abdominal pain and rectal mass on examination. The characteristics of lower gastrointestinal bleeding were analyzed in a subset of 150 consecutive patients. RESULTS: Mean age was 59 +/- 16.9 years. 54.5% were male and 45.5% female. The exploration was normal until the cecum in 146 patients (32%). In the remaining 311, the findings were: polyps (25.1%), diverticular disease (24%), neoplasia (12.6%), inflammatory bowel disease (9.4%), unspecific proctitis (2.4%), ischemic colitis (2.4%), angiodysplasia (1.9%), infectious colitis (1.1%), and miscellaneous (0.7%). An age of less than 40 years and the existence of anal pathology were significantly more frequent among patients with a normal examination (p < 0.001), but with a sensitivity of only 66%. No differences were found among patients with disordered bowel frequency or abdominal pain in relation to the colonoscopic findings. Previous presence of a rectal mass when the examination proved abnormal (p=0.06). Intermittent bleeding and the presence of blood in the stools were more frequent in patients with normal examination (p= 0.07 and p< 0.05, respectively). No significant differences in relation to colour, duration of bleeding, or to whether toilet paper was stained with blood were found. CONCLUSIONS: 1) The more frequent endoscopic findings were polyps and diverticular disease. 2) Clinical data are of little value in predicting a normal examination. 3) Total colonoscopy appears to be the first procedure of choice in all patients with lower gastrointestinal bleeding, irrespective of the clinical data and the presence of anal pathology.

[An epidemiologic study on the prevalence of alcohol consumption in a rural area of Asturias (council of Somiedo)]. / Estudio epidemiológico sobre la prevalencia del consumo de alcohol en una zona rural asturiana (concejo de Somiedo).

AIMS: To determine the prevalence of alcoholism in a rural area of Asturias and the usefulness of others clinical and analytical parameters for a rapid detection of its related pathology. MATERIAL AND METHODS: We conducted a cross-sectional descriptive study on a sample of 198 persons, divided into two groups (Group I: Heavy-drinkers and Group II: Moderate and nondrinkers), according with alcohol daily intake. The limit for the classification was the consumption of 80 or more grams of ethanol/day in men, and 60 g/day or more in women. Data about physical findings and blood biochemistry were collected and compared into the two groups. RESULTS: The prevalence of alcoholism in group I, was of 16.5% and the mean age of 54.3 +/- 11.4 years with increased proportion of males over females with a ratio of 7.25/1. The main analytical parameters useful as indicators of heavy alcohol consumption were an increase of AST, ALT, GGT, Total Cholesterol, Uric acid and gammaglobulin levels. We found a significative relation between legal problems and alcohol consumption (p < 0.005) as well as an increased prevalence of chronic obstructive lung diseases (p < 0.005). Digestive diseases as a whole, were most frequently associated with heavy alcohol consumption. CONCLUSION: This paper confirms the finding of a increased alcohol consumption in this mainly agricultural area of Asturias (Spain) in 16.5% and also confirms the usefulness of the use of simple clinical and analytical parameters for its detection in order to permit an earlier diagnostic and better use of preventive measures.

[An epidemiologic study of the prevalence of alcohol consumption in the Council of Tineo (Asturias)]. / Estudio epidemiológico de la prevalencia del consumo de alcohol en el Concejo de Tineo (Asturias).

AIMS: To know the incidence and prevalence of alcohol consumption in the studied area and also the somatometric alterations and laboratory findings found. PATIENTS AND METHODS: One prospective study was performed in one-way, transversal in a sample of 216 people. With a protocol we collect the data of alcohol habits and also physical examination and biochemical findings. We divided the sample into two groups: Group I "heavy drinkers" (men with ethanol intake greater than 100 g/day, and women more than 50 g/day), and Group II composed by abstemics and slight drinkers. RESULTS: We found and excessive intake of alcohol in the 15.75%, the whole sample (11.6% males and 4.17% females). Mean age was of 41.7% +/- 12.1 y.o. Un group I we found slight jaundice in 32.3% spinders in 64.7%, hepatomegaly in 58.8%, palmar erythema in 29.4% gynecomastia in 29.4% and Dupuytren in 11.8% (p < 0.001). Of the symptoms we found matutinal cough in 52.9%, epigastric burning in 64.7%, nausea and vomiting in 41.2% and hands tremors in 29.4% (p < 0.001). Biochemical parameters elevated were found in TGC TGO/TGP, GGT and amylase. CONCLUSIONS: In this study we confirm the excessive alcohol consumption in this rural area of Tineo in Asturias. We also found an important increase of alcohol intake in last year in women. The utility of analytical and exploratory findings is also proved for the early diagnosis of this illness in the ambulatory study of these patients.

Clinical efficacy of intramuscular human interferon-beta vs interferon-alpha 2b for the treatment of chronic hepatitis C.

We have conducted a randomized study to compare the efficacy and tolerance of human interferon (IFN) beta vs recombinant IFN-alpha 2b in patients with chronic active hepatitis C. Forty patients were included: 21 received IFN-alpha (group A) and 19 IFN-beta (group B). IFN was administered intramuscularly at a dose of 6 MU three times a week (tiw) for 2 months (induction phase), followed by 3 MU tiw for 4 months. Clinical, epidemiological and pathological features were similar in the two groups. Normal alanine aminotransferase (ALT) values at the end of treatment was regarded as a response to therapy and the response rate was 57% (12/21) in group A and 5.2% (1/19) in group B (P < 0.01). Both types of IFN induced a significant decrease in mean ALT values by the end of the induction phase (P < 0.01). When the dose was reduced to 3 MU, a marked, but not significant increase in ALT, was seen in group B, whereas no increase was seen in group A. IFN-beta was better tolerated and haematological adverse effects (platelet and leucocyte decrease) were less pronounced with IFN-beta. Hence, human IFN-beta was less effective than IFN-alpha in treating chronic hepatitis C virus (HCV). Doses of IFN-beta of 3 MU intramuscular (IM) tiw were clearly insufficient and it remains to be established whether higher doses of intramuscularly IFN-beta can be useful.

[Esophageal carcinosarcoma: morphologic and cytometric study]. / Carcinosarcoma esofágico: estudio morfológico y citométrico.

Carcinosarcoma of the esophagus is a rare malignant neoplasm composed by both carcinomatous (epithelial) and sarcomatous (mesodermal) elements. We report a case, diagnosed by biopsy an endoscopic brushing. Cytometric analysis was also performed.