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Biomedical subjects

L Rodrigo

Publications and source records attributed to L Rodrigo.

At least 73 records · Page 4Linked to original sources
PubMed1999

N-acetyltransferase-2, glutathione S-transferase M1, alcohol dehydrogenase, and cytochrome P450IIE1 genotypes in alcoholic liver cirrhosis: a case-control study.

BACKGROUND: Only a small percentage of long-term alcoholics develop liver cirrhosis. Genetic and non-genetic factors have been implicated in the risk of developing this disease. Among the genetic factors, case-control studies suggest an association with some polymorphisms at the alcohol dehydrogenase and cytochrome P450IIE1 genes. N-Acetyltransferase-2 metabolizes multiple compounds, transforming some of them to organ-toxic compounds and others into non-toxic molecules. Slow- and rapid-acetylator individuals exist in most human populations, and the mutations responsible for the slow-acetylator genotype have been determined. Slow acetylators, who should be at higher risk of developing breast cancer, and fast acetylators, who have an increased risk of developing colon cancer, can be characterized by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) genotyping. GSTM1 is another detoxifying enzyme for which functional interindividual differences, on the basis of gene polymorphisms, have been described. METHODS: We conducted a case-control study in which 120 alcoholic cirrhotics, 30 long-term non-cirrhotic alcoholics, and 200 healthy controls were genotyped for polymorphisms (RFLPs) at the ADH2, P450IIE1, and NAT2 genes. PCR, followed by restriction enzyme digestion, was performed. The homozygous deletion of the GSTM1 gene was also PCR-analyzed. Genotype frequencies were statistically compared. RESULTS: Frequencies for the ADH2, P450IIE1, and GSTM1 polymorphisms did not differ between patients and controls. Individuals homozygous for the NAT2*5 allele, which is the most frequent slow-acetylator (SA) allele and shows the lowest acetylator activity, were at a significantly decreased frequency among the cirrhotic patients compared with controls (9% versus 16%; P = 0.042). The frequency of this SA genotype was significantly increased (40%) in long-term alcoholics who did not develop cirrhosis (P = 0.0041 compared with controls; P= 0.000017 compared with cirrhotics). CONCLUSIONS: According to our results, NAT2 activity may be a factor that determines the risk of developing alcoholic liver cirrhosis, and slow acetylators would be protected.

Acetylation↗
PubMed1999

[Persistent leucocytosis as initial manifestation of Whipple's disease and development of gastric cancer in the follow up].

We report the case of a 57 year old male with Whipple's disease. The patient was asymptomatic and an unexplained peripheral leucocytosis was found in a routine examination. It persisted as the only abnormality for one year and then he developed articular symptoms, diarrhoea and weight loss. The diagnosis was confirmed by duodenal biopsy five years later. The leucocyte count ranged between 14,000 and 22,000 leuc/mm3. Response to cotrimoxazole was favourable with disappearance of all signs and symptoms, including leucocytosis. In the last endoscopic control, eight years after initial manifestations, an intramucosal gastric adenocarcinoma was diagnosed.

Adenocarcinoma↗
PubMed1999

[Liver involvement in coeliac disease].

Coeliac disease is a gluten-sensitive enteropathy in which, genetic, immunologic and environmental factors are implied. Several extradigestive diseases have been described in association with coeliac disease, which share most of the times an immunologic mechanism. The liver is damaged in coeliac disease, and it has been considered by some authors as an extraintestinal manifestation of the disease. In the present revision we discuss the different hepatic diseases related with the coeliac disease, as well as the best approach to diagnosis and therapy of choice. At diagnosis, it is very frequent to find an asymptomatic hipertransaminasemia, which frequently disappears after gluten suppression; the morphological substratum found in this alteration is a non-specific reactive hepatitis in the majority of cases. Coeliac disease is a demonstrated cause of cryptogenic hipertransaminasemia. In a small percentage of patient with coeliac disease an association has been found with other immunological liver diseases, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. Few studies exist that include a large number of patient, and the results on occasions are discordant. Nevertheless, the strongest association is with autoimmune hepatitis and with primary biliary cirrhosis. Several communications of isolated cases of rare hepatic diseases, which probably, only reflect a fortuitous association, have been cited in the literature.

Celiac Disease↗
PubMed1998

Human liver paraoxonase (PON1): subcellular distribution and characterization.

The subcellular localization and different biochemical properties of a human hepatic microsomal enzyme that hydrolyses paraoxon (paraoxonase, PON1) were studied and compared to the paraoxon hydrolase activity found in human plasma as well as in rat liver and plasma. Having evaluated the influence of the postmortem interval by a parallel experiment performed in rats, we conclude that the paraoxonase activity was preferentially localized in the microsomal fraction. The enzyme reaction was optimized according to temperature, pH, buffer, ionic strength, substrate concentration, and enzyme protein concentration. The characterization of human liver paraoxonase included the study of optimum pH, pH stability, heat inactivation assays, and kinetic parameters (K(m) and Vmax). In addition, the enzyme activity showed an absolute requirement for exogenous calcium. The activity was lost after incubation with EDTA and partially restored by the addition of calcium; however, other metals assayed were not able to activate the human liver enzyme as did calcium. Our results support the possible identity between human plasma and liver paraoxonases. In spite of the technical difficulties of this study and the possible interference of the postmortem changes in the results, this article represents the first systematic approach to the characterization of human liver paraoxonase.

Animals↗
PubMed1998

Metadoxine accelerates fatty liver recovery in alcoholic patients: results of a randomized double-blind, placebo-control trial. Spanish Group for the Study of Alcoholic Fatty Liver.

BACKGROUND/AIMS: Our aim was to investigate the effectiveness of metadoxine (pyridoxol L, 2 pyrrolidone-5-carboxylate) in the treatment of alcoholic fatty liver. METHODS: A double-blind randomized multicenter trial involving 136 chronic active alcoholic patients diagnosed with fatty liver by clinical, biochemical and ultrasonographic criteria was performed. Patients were treated with 1500 mg/day of metadoxine (n = 69) or placebo (n = 67) for 3 months. Patients were clinically and biochemically evaluated every month. Ultrasonography was performed before and after treatment. RESULTS: At the end of the study there was a significant improvement in the liver function tests in both groups. However, the changes were more rapid and greater in patients treated with metadoxine, in whom significant changes in serum levels of bilirubin, aminotransferases and gammaglutamyl transpeptidase were already observed after 1 month of treatment, and normalization of these parameters was observed at the end. After treatment, the percentage of patients with ultrasonographic signs of steatosis was significantly lower in the metadoxine group (28% vs 70%, p < 0.01) and the degree of steatosis was also lower in this group. Sixteen patients treated with metadoxine and 15 with placebo continued drinking. Alcohol intake was lower than initially, and similar in both groups. In the metadoxine group, the biochemical changes were similar in both the abstinent and the nonabstinent patients. In contrast, in the placebo group the improvement in the liver function tests was significantly higher in abstinents. Among patients who continued drinking, the prevalence (45% vs 92%, p < 0.05) and the degree of steatosis were also significantly lower in patients treated with metadoxine. CONCLUSIONS: In patients with alcoholic fatty liver, metadoxine accelerates the normalization of liver function tests and the ultrasonographic changes, even in those who do not completely abstain from alcohol intake. Thus, metadoxine could be useful in the treatment of the early stages of alcoholic liver disease.

Adult↗
PubMed1998

Omeprazole and ranitidine in long-term treatment of duodenal ulcer: a double-blind comparison of length of time in remission.

In most patients duodenal ulcer is a chronic relapsing disease. If no active maintenance treatment or eradication therapy is given after healing, around 70-100% of patients have a relapse during the first year. We conducted a double-blind multicenter study in 472 patients with duodenal ulcer. They were treated with omeprazole 20 mg every morning for four or eight weeks and when healed were randomly allocated to maintenance treatment with either omeprazole 20 mg every morning or ranitidine 150 mg at bedtime for up to six months. The patients were assessed by endoscopy at monthly intervals until healing occurred. Thereafter scheduled endoscopy was carried out after 1, 3, and 6 months of maintenance treatment or immediately in the event of a suspected relapse. Healing status (intention to treat approach) was 87% at four weeks and 93% at eight weeks. At six months the estimated remission rate was 90% for omeprazole and 82% for ranitidine (P = 0.03, 95% CI 1-15%). The incidence of adverse events was similar during the two maintenance treatments. Treatment with omeprazole 20 mg every morning maintained significantly more patients in remission than treatment with ranitidine 150 mg at bedtime.

Adult↗
PubMed1998

Tamoxifen does not improve survival of patients with advanced hepatocellular carcinoma.

To discover whether tamoxifen is able to extend the survival of patients with advanced hepatocellular carcinoma, we included 80 patients with cirrhosis and advanced hepatocellular carcinoma in a multicenter, double-blind, placebo-controlled trial in order to analyze the influence of treatment with tamoxifen on survival. The patients were randomized to receive tamoxifen, 40 mg/day (group 1), or placebo (group 2). Both groups were similar in age, sex, etiology of cirrhosis, biochemical, hematologic and hormonal parameters, morphology of the tumor (nodular vs multinodular or massive), Child-Pugh's score, and Okuda's stage. The 1-year survival rate was similar in both groups (30% in group 1 vs 37.8% in group 2; p = 0.31). Tamoxifen treatment was well tolerated by the patients. We conclude that tamoxifen does not extend the survival of patients with cirrhosis and advanced hepatocellular carcinoma.

Adult↗
PubMed1998

[Arterioportal fistula and hemobilia in a patient with hepatic transplant].

The case of a 36-year old male liver transplant recipient hospitalized for upper digestive hemorrhage, jaundice and pain in the right hypochondrium is herein reported. Two hepatic biopsies had been performed 60 and 7 days prior to admission. Bleeding was observed to be from the biliary tract by endoscopy and an arterioportal fistula in the right hepatic lobe by echo-doppler and arteriography was seen. Treatment with selective embolization by arteriography was satisfactory with biliary tract drainage not being required. Doppler echography was used to control the evolution of the patient.

Adult↗
PubMed1998

Ambulatory liver biopsy: complications and evolution in 264 cases.

AIM: To determine the safety and acceptance of outpatient liver biopsies. PATIENTS AND METHODS: Data from all liver biopsies were collected in a prospective way over a period of 18 months. Information was gathered on complications, evolution of patients outside the hospital and opinion relating to the test. All patients were required to previously present: platelet count > 60.000/mm3 prothrombin time within 4 seconds of control and absence of ascites or encephalopathy. Criteria for outpatient liver biopsy also included cooperative patient, a partner or friend who stayed with the patient during 12-24 hours following the test and easy access to the hospital. Out of a total of 378 biopsies, 264 (70%) were ambulatory. RESULTS: Five of the 264 outpatients were hospitalized (1.9%), due to a subcapsular hematoma in one case, persistent pain in 3 cases and sever hypotension in the other; all of them evolved favorably in the first 24 hours. Among the inpatients, 2 had complications (1.7%): one subcapsular hematoma resolved without treatment and one abdominal hemorrhage requiring transfusion. Of the ambulatory patients, 46 (18%) presented pain whilst at home, being more frequent in females than in males (30% vs 15%, p = 0.004) and in those who needed more than one attempt to obtain histological material compared with those of a single attempt (33% vs 17%; p = 0.008). Twenty four hours after the test, 83% of the patients had returned to their normal activities. Ninety five percent of the patients questioned considered that the test was not traumatic, and 88% stated a preference for liver biopsy as a day case procedure. CONCLUSIONS: Liver biopsy performed on an ambulatory basis is safe, well tolerated and acceptable by the majority of patients.

Adolescent↗
PubMed1997

Purification and characterization of paraoxon hydrolase from rat liver.

Paraoxonase (paraoxon hydrolase), an enzyme that hydrolyses paraoxon (O,O-diethyl O-p-nitrophenyl phosphate), is located in mammals primarily in the serum and liver. Although considerable information is available regarding serum paraoxonase, little is known about the hepatic form of this enzyme. The present work represents the first study on the purification of rat liver paraoxonase. This enzyme has been purified 415-fold to apparent homogeneity with a final specific activity of 1370 units/mg using a protocol consisting of five steps: solubilization of the microsomal fraction, hydroxyapatite adsorption, chromatography on DEAE-Sepharose CL-6B, non-specific affinity chromatography on Cibacron Blue 3GA and anion exchange on Mono Q HR 5/5. The presence of Ca2+ and Triton X-100 in the buffers throughout the purification procedure was essential for maintaining enzyme activity. SDS/PAGE of the final preparation indicated a single protein-staining band with an apparent Mr of 45 000. N-terminal and internal amino acid sequences were determined and compared with those of paraoxonases from human and rabbit serum and mouse liver, showing a high similarity. The pH profile showed optimum activity at pH 8.5. The pH stability and heat inactivation of the enzyme were also studied. The Km for liver paraoxonase was 1.69 mM.

Animals↗
PubMed1997

Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis.

BACKGROUND/AIMS: To investigate the possible role of HIV infection in the natural history of chronic parenterally-acquired hepatitis C. METHODS: A multicenter cross-sectional study was performed in 547 patients with chronic parenterally-acquired hepatitis C with or without HIV infection (116 HIV-positive and 431 HIV-negative). Approximate duration of HCV infection was estimated in all patients included, and histologic diagnoses made at different time intervals following HCV infection were analyzed in both groups. Factors related to serum HCV-RNA levels were also investigated. RESULTS: Histologic findings were similar in liver biopsies from both HIV-infected and noninfected patients. However, in the first 10 years, 13 out of 87 (14.9%) HIV-positive subjects developed cirrhosis, in comparison with 7 out of 272 (2.6%) in the HIV-negative group (p < 0.01). Similar results were found in the first 5 and 15 years, respectively, and most of the HIV-negative patients with cirrhosis (42 out of 56) developed cirrhosis in a time interval longer than 15 years. Consequently, mean interval from estimated time of HCV infection to cirrhosis was significantly longer in HIV-negative than HIV-positive patients (23.2 vs. 6.9 years; p < 0.001). Chronic active hepatitis (with and without cirrhosis) and long duration of HCV infection were significantly associated with higher HCV load (p < 0.05). Finally, HIV-positive patients with CD4+ cell counts > 500 cells/ml showed a lower HCV load than those with < 500 cells/ml (p < 0.05). CONCLUSIONS: HIV infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. HIV-related immunodeficiency may be a determinant of higher hepatitis C viremia levels and more severe liver damage.

Adult↗
PubMed1997

Short-course therapy with amoxycillin-clarithromycin triple therapy for 10 days (ACT-10) eradicates Helicobacter pylori and heals duodenal ulcer. ACT-10 Study Group.

BACKGROUND: Whilst the role of Helicobacter pylori eradication in managing duodenal ulcers has been established, consensus regarding the ideal regimen has not been achieved. METHODS: Patients with H. pylori-positive active duodenal ulcer were randomly assigned to receive triple therapy with amoxycillin 1000 mg b.d. + clarithromycin 500 mg b.d. + omeprazole 20 mg daily for 10 days (ACT-10) or dual therapy with clarithromycin 500 mg t.d.s. + omeprazole 40 mg daily for 14 days (Dual). No additional acid suppression was provided following eradication therapy. Endoscopy, with biopsy for culture and histology, as well as 13C-urea breath testing (13C-UBT) were performed pre-treatment to assess H. pylori infection. H. pylori eradication was established at 4-6 weeks follow-up with culture (2 antral, 1 corpus biopsies), histology (2 antral biopsies), and 13C-UBT. Ulcer healing by endoscopy and change in clinical symptoms were also assessed at 4-6 weeks. RESULTS: Two hundred and sixty-seven (267) patients were randomized to ACT-10 (n = 137) or Dual therapy (n = 130). By per-protocol and intention-to-treat analyses, H. pylori eradication at 4-6 weeks follow-up was 91% (115/127) and 88% (120/136), respectively, for ACT-10 patients and 59% (68/115) and 55% (72/130), respectively, for Dual therapy patients (P < 0.001 for both analyses). Ulcer healing was high in both treatment groups: ACT-10, 93% (118/127) and 90% (122/136), respectively; and Dual therapy, 91% (104/114) and 85% (111/130), respectively. Pre-treatment resistance to clarithromycin was low (4%, 8/214) as compared to metronidazole resistance which was over 40%. Emergence of resistance to clarithromycin was observed in 2% of patients receiving ACT-10 and in 25% of those receiving Dual therapy. ACT-10 and Dual therapy patients experienced similar rates of drug-related adverse events (33% vs. 32%, respectively) and discontinuation from therapy due to an adverse event (1.5% vs. 5%, respectively). More than 90% of patients were compliant with each prescribed medication. CONCLUSION: In patients with active duodenal ulcer, a 10-day course of amoxycillin-clarithromycin-based triple therapy without additional acid suppression is highly effective in eradicating H. pylori and healing duodenal ulcer.

Adult↗
PubMed1997

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.

Adenocarcinoma↗
PubMed1997

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.

Adolescent↗
PubMed1997

[Acute hepatitis associated with terbinafine].

Oral terbinafine is a recently introduced antifungal drug with slight side effects that rarely includes liver involvement. A case of toxic hepatitis secondary to terbinafine administration in a patient with no previous history of liver disease and in whom other possible causes of liver damage and histologic study were performed is reported. A mixed lesion was presented with predominance of cholestasis. The initial worsening following discontinuation of the drug is of note as are the prolonged course of the enzymatic alterations which normalized at one year. The precise mechanism by which terbinafine produced liver damage is unknown and is probably due to an idiosyncratic type reaction.

Acute Disease↗