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Biomedical subjects

J L Mendoza

Publications and source records attributed to J L Mendoza.

12 recordsLinked to original sources
PubMed2001

[Rate and risk factors of liver toxicity in patients receiving antiretroviral therapy].

BACKGROUND: The benefit of highly active antiretroviral therapy (HAART) may be limited by the development of liver toxicity. The prevalence and risk factors of this complication using different antiretroviral drug combinations are not well known. PATIENTS AND METHOD: Clinical charts of HIV-infected patients, previously naive for antiretroviral drugs, starting HAART between January 1997 and January 2000 were reviewed. Liver toxicity was scored according to increases in liver enzymes. RESULTS: HIV infection had been acquired by intravenous drug use in 36 (40%) of 91 subjects recruited in the study. The rest had been infected through homosexual (38%) or heterosexual contact (22%). Overall, 43 patients (47%) were coinfected with hepatitis C (42%) and/or B (8%) viruses. Antiretroviral therapy included protease inhibitors (PI) plus two nucleosides in 48 individuals and non-nucleosides in 50. Baseline characteristics were similar across the different treatment groups. Liver toxicity was recorded in 30 (31%) subjects, and it was severe in 10 (11%). Cytolysis was the predominant pattern (28), while only one case of cholestasis and one with a mixed pattern were recorded. Coinfection with hepatitis B and/or C viruses was associated with liver toxicity (RR: 10.36; 95% CI, 1.38-77.56; p = 0.03) as was a high alcohol intake (RR: 3.35; 95% CI, 2.43-4.62; p = 0.01). No differences in the rate of hepatotoxicity were found when comparing PI and non-nucleoside containing regimens. The development of isolated hyperbilirubinemia (27%) was strongly associated with the use of indinavir (RR: 3.61; 95% CI, 1.81-7.21; p < 0.001). CONCLUSIONS: Liver toxicity occurs in about one third of HIV-infected patients after initiating HAART, regardless of the drugs used, yet it is commonly mild and transient. A high alcohol intake and a coinfection with HCV/HBV constitute the most important predictive factors.

Adult↗
PubMed2001

Risk factors for severe hepatic injury after introduction of highly active antiretroviral therapy.

OBJECTIVES: Treatment of HIV infection with highly antiretroviral therapy (HAART) may be limited by liver toxicity. Its incidence and risk factors are not well known. PATIENTS AND METHODS: Retrospective chart review. Naive patients beginning HAART between January 1997 and January 2000. Severe transaminase elevation was defined as fivefold or higher rise over upper normal limits, or as > or =3.5-fold rise above abnormal baseline values. RESULTS: Of 222 study subjects, 38%, 5%, and 2% were coinfected with hepatitis C virus (HCV), hepatitis B virus, and hepatitis D virus, respectively. Besides two nucleoside reverse transcriptase inhibitors (NRTIs), 96 patients received protease inhibitors (PIs), 90 received nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 35 received a PI + NNRTI combination. Severe hepatic injury developed in 21 (9%): 10% PI, 9%, and 9% PI + NNRTI. Both univariate and multivariate analyses identified alcohol abuse, HCV coinfection, and older age as independent risk factors. Predictor variables in the final multivariate model were: alcohol abuse (risk ratio [RR], 5.87; 95% confidence interval [CI], 1.49-23.15; p =.01], positive HCV serology (RR, 3.99; 95% CI, 1.32-12.10; p =.01], and older age (RR, 1.11; 95% CI, 1.04-1.18; p = 0.001). CONCLUSIONS: Nearly 10% of study subjects who start HAART experience severe transaminase elevation, irrespective of the treatment. Avoidance of alcohol abuse, especially in study subjects coinfected with HCV, will reduce the risk of hepatic injury after HAART. When possible, prior treatment for chronic HCV infection should be considered.

Adult↗
PubMed2000

Presence of a protective allele for achalasia on the central region of the major histocompatibility complex.

Idiopathic achalasia is a motility disorder of the esophagus whose etiology is unknown. An association between HLA genes and susceptibility to achalasia which suggests a possible immunogenetic mechanism has been reported recently. This study was designed to examine the HLA class II association in a large group of achalasia patients further and to investigate the distribution of TNFa and TNFb microsatellites in these patients. The study population, all Spanish, white and unrelated, consisted of 115 consecutive patients and 339 healthy controls. All of the patients had been diagnosed with primary achalasia of the esophagus with manometric, radiographic and endoscopic studies. All studies were performed on DNA samples after locus-specific amplification with the polymerase chain reaction: HLA-DRB1, DQA1 and DQB1 were typed by dot-blot hybridization and the size of the TNFa and TNFb microsatellites was measured using a semiautomatic method. The broad allele HLA-DQ1 was seen to be weakly associated with achalasia. The TNFa11 allele and the DRB1*1501-DQA1*0102-DQB1*0602 haplotype were reduced in achalasia patients but the stratified analyses showed that this was true only when both were present in the same individual. These results confirm the association between achalasia and HLA-DQ1 allele and suggest that TNFa11 is a marker for a protective allele for the disease, present on the B7-DRB1*1501 (7.1) ancestral haplotype in our population.

Alleles↗
PubMed2000

Large-sample confidence intervals for validity and reliability coefficients.

Large-sample confidence intervals (CI) for reliability, validity, and unattenuated validity are presented. The CI for unattenuated validity is based on the Bonferroni inequality, which relies on one CI for test-retest reliability and one for validity. Covered are four reliability-validity situations: (a) both estimates were from random samples; (b) reliability was from a random sample but validity was from a selected sample; (c) validity was from a random sample but reliability was from a selected sample; and (d) both estimates were from selected samples. All CIs were evaluated by using a simulation. CIs on reliability, validity, or unattenuated validity are accurate as long as selection ratio is at least 20% and selected sample size is 100 or larger. When selection ratio is less than 20%, estimators tend to underestimate their parameters.

Confidence Intervals↗
PubMed2000

[Diagnosis of hemochromatosis with magnetic resonance].

Hemochromatosis is a disorder of parenchymal iron overload. The diagnosis is based upon clinical manifestations, laboratory findings and iron concentration in liver. Magnetic resonance imaging (MRI) shows a decrease in liver signal intensity. Its role has not been already defined. Nonetheless, ratio of liver to muscle proton density (LMPD) shows a significant correlation with hepatic iron. One patient with a long-standing cirrhosis with data of hemochromatosis whose coagulation study did not allow to perform a liver biopsy was diagnosed with this method. Hepatic iron concentration was calculated based upon: microgram/g of hepatic iron = (-5.174* LMPD) + 9.932. MRI can be useful in the evaluation of hemochromatosis among patients who refuse or have contraindication to liver biopsy.

Aged↗
PubMed1999

Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of a humanized monoclonal antibody against vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and in pathological processes such as tumor growth, rheumatoid arthritis, and ocular neovascularization. A recombinant humanized monoclonal antibody (rhuMAb), rhuMAb VEGF, has been developed to inhibit the effects of VEGF in the treatment of solid tumors. Intravenous and s.c. pharmacokinetic studies were conducted in mice, rats, and cynomolgus monkeys. In addition, the tissue distribution of i.v. 125I-rhuMAb VEGF was investigated in rabbits. At a dose of approximately 10 mg/kg, the clearance of rhuMAb VEGF from the serum was 15.7 ml/day/kg in mice, 4.83 ml/day/kg in rats, and 5.59 ml/day/kg in cynomolgus monkeys, and the terminal half-life ranged from 6 to 12 days in all species. After s.c. administration, rhuMAb VEGF had a bioavailability of 69% in rats and 100% in mice and cynomolgus monkeys. Pharmacokinetic data in mice, rats, and cynomolgus monkeys were used to predict the pharmacokinetics of rhuMAb VEGF using allometric scaling in humans. The predicted serum clearance of rhuMAb VEGF in humans was 2.4 ml/day/kg and the terminal half-life was 12 days. Two hours after i.v. bolus administration of 125I-rhuMAb VEGF in rabbits, trichloroacetic acid-precipitable radioactivity was noted primarily in the plasma, with lesser amounts in highly perfused tissues such as kidneys, testes, spleen, heart, and lungs. At 48 h after dosing, trichloroacetic acid-precipitable radioactivity was noted in plasma with minimal distribution to testes, bladder, heart, lungs, and kidneys. Tissue distribution and pharmacokinetic data indicate that rhuMAb VEGF is cleared slowly and distributes to specific sites in the body.

Animals↗
PubMed1998

Contribution of HLA class II genes to susceptibility in achalasia.

Achalasia is a motor disorder of the esophagus resulting in functional obstruction. The cause of the lesion is unknown although genetic and immunologic factors have been suggested. An association with serological HLA epitopes has been previously reported. In this study, we have further examined this HLA class II association with susceptibility to achalasia by DNA based methods. Achalasia patients (n=40) and healthy controls (n=275), all Caucasians and unrelated, were included in the analysis. The strongest associations were with HLA-DQA1*0101 and two HLA-DQ alphabeta heterodimers having their alpha chain encoded by this allele. Moreover, relative risk was significantly higher in DQA1*0101 homozygotes as compared to heterozygotes and results suggested that DQB1*02 may have a protective role.

Alleles↗
PubMed1998

[Carcinoma of the gastroesophageal junction following variceal sclerosis: more than a coincidence?].

In the last decade, several cases of patients with esophageal varices treated with endoscopic sclerotherapy who posteriorly developed carcinoma of the gastroesophageal junction have been reported in the literature. This may only be a coincidence, although the existence of an undemonstrated relationship direct cannot be discarded. The case of a patient diagnosed with alcoholic liver cirrhosis with portal hypertension and esophageal varices who underwent several sessions of endoscopic sclerotherapy with ethanolamine oleate is presented. During follow-up dysphagia was observed due to adenocarcinoma of the lower third of the esophagus. Carcinoma of the esophagus should be taken into account as a rare diagnostic possibility in a patient with dysphagia of recent appearance with a history of esophageal varix sclerotherapy.

Adenocarcinoma↗
PubMed1998

[Acute pancreatitis induced by isoniazid, a casual association].

We describe the case of a 68 years-old who developed 2 attacks of acute pancreatitis during the treatment with isoniazid used as a chemoprophylactic. There was not recurrence of symptoms for the last year after isoniazid was withdrawn. This report suggest that isoniazid can induce acute pancreatitis.

Acute Disease↗
PubMed1996

The role of sonography in the early diagnosis of biliopancreatic Ascaris infestation.

Acute pancreatitis due to ascaris lumbricoides infestation is extraordinarily uncommon in Europe. The diagnosis can be difficult because of the low index of suspicion in our area, and this may lead to death. The case of a Columbian patient living in Spain who developed an acute pancreatitis is discussed. He had no history of alcohol abuse, gallstones, or drug abuse. The sonography showed a longitudinal structure with inner parallel linear bands and undulant movements inside the gallbladder and a hypoechogenic pancreas. These features are compatible with acute pancreatitis secondary to Ascaris lumbricoides infestation. The patient was treated with mebendazole and his evolution was excellent. Sonography was useful as an assessment modality during follow-up. We conclude that Ascaris lumbricoides should be recalled as a rare cause of acute pancreatitis in Western countries. Sonography allows early diagnosis and prompt treatment.

Acute Disease↗