The effects of paracetamol (acetaminophen) on hepatic tests in patients who chronically abuse alcohol – a randomized study

Aliment Pharmacol Ther 2010; 32: 478–486

Summary

Background Retrospective accounts suggest that therapeutic doses of paracetamol can produce severe hepatic injury in patients with putative high‐risk conditions, including alcoholism and infectious hepatitis. Metabolism of paracetamol to its hepatotoxic metabolite is enhanced in patients who abuse alcohol, who also have compromised liver defences from depressed hepatic glutathione. Aim To determine the effect of paracetamol on serum liver tests of newly abstinent subjects who abuse alcohol, including subjects with hepatitis C infection. Methods A randomized, double‐blind, placebo‐controlled study. Adult alcohol abusers with a current drinking episode longer than 7 days received either placebo or paracetamol 4 g/day for 5 days. Results Of 142 subjects enrolled, 74 received paracetamol and 68 received placebo. Mean ALT activity during treatment increased from 48 to 62 IU/L in the paracetamol group and from 47 to 49 IU/L in the placebo group. Maximum ALT was 238 and 249 IU/L in the paracetamol and control groups respectively. The INR remained unchanged and serum bilirubin decreased in both groups. Subgroup analyses for subjects with alcoholic hepatitis, hepatitis C virus antibody and other subgroups showed no statistical difference between groups. Conclusion Administration of paracetamol 4 g/day appears safe in newly abstinent patients who abuse alcohol.     

The human CD40 gene lies within chromosome 20q deletions associated with myeloid malignancies

Deletions of chromosome 20q are associated with myeloid malignancies and have been previously shown to arise in a multipotent progenitor of both myeloid and B cells. However, B-cell differentiation from the abnormal progenitor was impaired. The CD40 antigen is a surface glycoprotein which is expressed in B cells and haemopoietic stem cells and is important for B-cell growth and development. Following the recent mapping of CD40 to chromosome 20q we sought to determine its position relative to 20q deletions. Analysis of lymphoblastoid cell lines carrying 20q deletions placed CD40 within a 19–21 cM interval which is almost coincidental with the common deleted region defined by previous analysis of patient samples. Our results raise the possibility that genetic alteration of this locus may contribute to the pathogenesis of myeloid disorders associated with 20q deletions.     

The synthesis and antiallergy activity of 1-(aryloxy)-4-(4-arylpiperazinyl)-2-butanol derivatives

A series of 1-(aryloxy)-4-(4-arylpiperazinyl)-2-butanol derivatives were prepared and evaluated for antiallergy activity in the passive foot anaphylaxis (PFA) assay in rats. Twenty-seven derivatives had activity equal to or greater than the parent, alpha-(phenoxymethyl)-4-phenyl-1-piperazinepropanol. Six derivatives that possessed greater activity in the PFA than the parent compound were then tested in the guinea pig anaphylaxis (GPA) assay. Five of the derivatives were more potent than the parent (PD50 = 40 mg/kg) in the GPA with alpha-[(4-fluorophenoxy)methyl]-4-(4-fluorophenyl)-1-piperazinepropan ol (PD50 = 3 mg/kg) having the greatest potency.     

In situ breast carcinomas: A population-based study on frequency,growth pattern,and clinical aspects

This study comprises 78 consecutive women, within situ carcinoma of the breast and no evidence of invasion, who were diagnosed and treated surgically from October, 1979 to June, 1986. Lobular carcinoma in situ (LCIS) was found in 30 patients (38%) and ductal carcinoma in situ (DCIS) was identified in 48 patients (62%). The series is a study based in the county of Funen, which has a total female population of 230,028 inhabitants.Epidemiological calculations were carried out in 5 municipalities in the area of Odense University Hospital with 77,477 female inhabitants 20+ years of age according to a predetermined referral scheme and diagnostic procedures. This sub-study revealed a frequency of 9.0 cases ofin situ carcinomas per 10⁵ woman-years and a cumulated risk of 0.53% of havingin situ carcinoma demonstrated within the age range of 20–75 years.In situ lesions made up about 6% of all newly diagnosed breast carcinomas in the region. Furthermore, in about 3% of all breast biopsies and in about 0.3% of all women having mammography due to breast symptoms, anin situ finding was the only malignant change.Pathoanatomically, a distinction could be made between 3 different growth patterns: microfocal, tumor-forming, and diffuse growths. Microfocal lesions comprised a major part (60%) of in situ carcinomas. With one exception, the microfocal cases were chance findings in an otherwise benign breast biopsy, whereas the more aggressive growth patterns (tumor-forming and diffuse) were predominantly clinical and/or mammographic findings, all belonging to the DCIS type. Excisional biopsy or partial mastectomy was performed in 85% of the women with microfocal cases, while such breast preservation procedures were used in only 27% of patients with tumor-forming or diffuse growths.

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Resumen El presente estudio comprende 78 mujeres consecutivas con carcinoma mamarioin situ y sin evidencia de invasíon, quienes fueron diagnosticadas y tratadas quirúrgicamente durante el período 1979 a 1986. Se encontró carcinoma lobular in situ (CLIS) en 30 pacientes (38%) y carcinoma ductal in situ (CDIS) en 48 pacientes (62%). La serie proviene de la región de la isla de Funen, Dinamarca, con una población de 230,028 habitantes.Se realizaron determinaciones epidemiológicas en 5 municipalidades correspondientes a la región del Hospital de la Universidad de Odense, con 77,477 habitantes mujeres de acuerdo a un esquema predeterminado de referencia y a procedimientos de diagnóstico estandarizados. Este subanálisis reveló una frecuencia de 9.0 casos de carcinomasin situ por 10⁵ mujer-años y un riesgo de 0.53% de tener carcinomain situ para las mujeres entre los 20 y los 75 años. Las lesionesin situ representaron alrededor del 6% de la totalidad de los nuevos carcinomas mamarios diagnosticados en la región. Además, en alrededor de 3% de todas las biopsias mamarias y en alrededor de 0.3% de todas las mujeres sometidas a mamografía por razón de presentar síntomas mamarios, el hallazgoin situ fue el único hallazgo de malignidad.Se pudo hacer la diferenciación anatomopatológica entre 3 diferentes patrones de crecimiento: microfocal, formación tumoral, y crecimiento difuso. Las lesiones microfocales comprenden la mayor parte (60%) de los carcinomasin situ. Con una excepción, los casos del tipo microfocal fueron hallazgos fortuitos en biopsias mamarias por lo demás benignas, en tanto que los patrones de crecimiento de tipos más agresivos (formación tumoral y crecimiento difuso) fueron predominantemente hallazgos clínicos y/o mamográficos, todos CDIS. Se realizó biopsias excisional o mastectomía parcial en 85% de las mujeres con el tipo microfocal, en tanto que tales procedimientos de conservación mamaria fueron utilizados en solo 27% de las pacientes con los patrones de formación tumoral de crecimiento difuso.

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Résumé On a étudié les résultats de soixante-dix-huit cancersin situ du sein chez la femme, sans évidence d'envahissement, diagnostiqué et traités chirurgicalement entre octobre 1979 et juin 1986. Il y avait 30 cas (38%) de cancer lobulaire (CL) et 48 cas (62%) de cancer cannalaire (CC). Cette série de patientes provenait du comté de Funen, Danemark, dont la population féminine est de 230,028.L'épidémiologie a été étudiée dans 5 municipalités dans la région de l'Hôpital Universitaire d'Odense où la population féminine est de 77,477 selon une méthode de consultation et de diagnostic standardisée. Cette étude a montré que l'incidence était de 9 cas de cancerin situ pour 10⁵ femmes-années; le risque d'avoir un cancerin situ était de 0.53% entre les âges de 20–75 ans. Six pour cent des cancers diagnostiqués dans la région étaitin situ. Un cancer in situ a été trouvé dans 3% de toutes les biopsies du sein, et 0.3% des femmes ayant une mammographie motivée par une Symptomatologie au niveau du sein.Histologiquement, on pouvait distinguer 3 types de croissance: microfocale, tumorale, et diffuse. Les lésions microfocales étaient responsables de 60% des cancersin situ. A une exception près, les microfoyers de cancer ont tous été découverts par hasard, alors que les formes tumorales et diffuses ont tous été décelés grâce à des signes cliniques et/ou mammographiques. Il s'agissait toujours d'un cancer cannalaire. Une biopsie d'exérèse ou mastectomie partielle a été effectuée chez 85% des femmes ayant un microcancer, mais seulement chez 27% des femmes ayant une forme tumorale ou diffuse.

     

Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial

One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean ± SD of total stool output (g kg⁻¹) was 532 ± 476 vs 479 ± 354 and the duration (h) of diarrhoea was 108 ± 68 vs 103 ± 53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea.     

Branch retinal vein occlusion. A clinicopathologic case report

The eyes of a 72-year-old woman with a history of two branch retinal vein occlusions involving the left eye, were obtained postmortem and studied histopathologically. Prior to her death, she had been enrolled in the multicentered, prospective, randomized clinical trial on branch vein occlusion and treated with peripheral argon laser photocoagulation for disc neovascularization. Routine fluorescein angiograms and fundus photographs were available for clinical correlation. Despite photocoagulation, the patient had frequent recurrent episodes of vitreous hemorrhage. On histologic examination, both venous occlusions were found at arteriovenous crossings and associated with moderately sclerotic retinal arterioles. One occlusion was recanalized. Retinal inner ischemic atrophy was observed distal to the site of both venous occlusions and corresponded to areas of nonperfusion. Cystoid macular edema was not present. Three areas of neovascularization were found; one at the optic nerve head, one at the peripapillary retina, and one at the fovea. It is likely the patient's repeated vitreous hemorrhages were from one or all three areas of neovascularization demonstrated histopathologically.     

Intravenous 6-thioguanine or cisplatin, fluorouracil and leucovorin for advanced non-small cell lung cancer: a randomized phase II study of the cancer and leukemia group B.

This randomized phase II study was designed to evaluate the activity of intravenous 6-thioguanine (6-TG) as a single agent and the combination of cisplatin and 5-fluorouracil (5-Fu) modulated by oral leucovorin (PFL) in patients with advanced non-small cell lung cancer (NSCLC). Eligible patients had measurable or evaluable stage III B or IV NSCLC, had no received prior chemotherapy and had a performance status of 0-2. Patients were randomized to treatment with intravenous 6-TG at 55 mg/m2 administered over 30 minutes for 5 consecutive days and repeated every 35 days, or PFL chemotherapy with cisplatin 100 mg/m2 on day 1, 5-FU 800 mg/m2/day as a continuous intravenous infusion over 5 days and oral leucovorin administered at 100 mg every 4 hours during the entire duration of the cisplatin and 5-FU infusions. PFL was repeated every three weeks. Ninety-five eligible patients were randomized, 46 to 6-TG and 49 to PFL. Response rates were 4% for 6-TG (95% confidence interval 0.5%-14.8%, 1 partial, and 1 complete response) and 29% (16.6%-43.3%) for PFL (all partial). The median time to treatment failure was 2 and 4 months, respectively, and the median survival times were 6 and 10 months, respectively. Toxicities with 6-TG were, generally, mild to moderate but severe or life-threatening granulocytopenia was observed in 21% of patients. With PFL, mucositis was dose-limiting, and 78% of patients had severe or life-threatening mucositis. This led to dose reduction of 5-FU and leucovorin during subsequent cycles or treatment termination in 82% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)