Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

冠状动脉粥样硬化ADAMTS7新位点的发现和冠状动脉粥样硬化中ABO位点与心肌梗死的相关性:两项全基因组关联研究

<正>背景:该研究旨在评价在现有的冠状动脉粥样硬化的病变中,遗传因素对粥样硬化斑块进展及特异性心肌梗死是否存在显著作用。方法:对欧洲后裔参与者冠状动脉造影表型进行了两项全基因组关联研究(GWAS),为寻找冠状动脉疾病(CAD)易感性基因位点,研究比较了有异常(n=12393)和无异常的(对照组n=7383)个体;为寻找心肌梗死易感性基因位点,也同时比较了造影证实存在CAD并且有心肌梗死的个体(n=5783)与虽有CAD但无心肌梗死的个体(n=3644)。     

Immunophenotypic aspects of cylindroma and nodular hidradenoma

Background Some adnexal tumours have many controversies about their histogenesis. Objectives To evaluate the eccrine and/or apocrine differentiation phenotype in cases of cylindroma and clear cell hidradenoma with CD15 and p63 antibodies. Methodology Slides and blocks of six cases of cylindroma and seven cases of nodular hidradenoma (clear cells) were analyzed by the technique of immunohistochemistry with CD15 and p63 antibodies. Results In all cases of cylindroma we obtained negative results for CD15 antibody and positive for p63 antibody. In five of seven cases of nodular hidradenoma (clear cell), we could easily observe clear cells between 20% and 50% of tumour cells. In the two other cases, cystic lesions were present and occasional clear cells could be seen. The reaction with CD15 antibody was positive in granular and cytoplasmic pattern in six of seven cases, especially in cells with suggestive clear cytoplasm in lower proportion than this clear cells could be seen in haematoxylin and eosin. The positivity for p63 antibody, nuclear pattern, was observed in six of seven cases, in the major part of tumour cells. In only one case, the positivity was in 20% of cells. Limitation Samples are in small number because these are relatively rare tumours. Conclusions The present study suggests eccrine origin for both tumours: cylindroma and clear cell hidradenoma.     

Otoacoustic emissions as a screening test for hearing impairment in children

Transient evoked otoacoustic emissions (TEOAEs) are low amplitude sound waves produced by the healthy cochlea. They can be recorded with a microphone in the external ear. TEOAEs are abolished by hearing losses of 30 dB or more. The feasibility of using TEOAEs as a screening test for hearing loss in children was studied. TEOAE recordings were attempted in 56 children attending an audiology clinic. Recordings were possible from both ears in 52 children; of these 104 ears, 32 had hearing deficits of 30 dB or more. Hearing status was compared with the results of six TEOAE screening criteria. All criteria had a sensitivity of 1.00. Four standard TEOAE criteria yielded specificities of 0.46-0.58. Two new criteria derived from analysis of limited frequencies from the TEOAE waveform gave specificities of 0.76 and 0.82. It can be concluded that, when appropriate pass/fail criteria are employed, TEOAEs are a feasible screening test in children.     

Effects of N-acetylcysteine on myoglobinuric-acute renal failure in rats

Oxygen metabolites play an important role in renal injury during myoglobinuric acute renal failure (ARF). This study was designed to determine the protective influence of N-acetylcysteine (NAC), a hydroxyl radical scavenger, and treatment in an experimental model of myoglobinuric-ARF induced by intramuscular injection of hypertonic glycerol in rats. The rats were randomly distributed into five groups: Group 0 (n = 10), was assigned to receive 2mL saline (0,9%) intraperitoneally (ip); Group 1 (n = 10), NAC ip in a dose of 0 mg/100 g of body weight 30 min before the intramuscular (im) injection of 50% glycerol (10 mg/kg); Group 2 (n = 10), received saline 0,9% ip in a equivalent volume of NAC in Group I before the im injection of glycerol; Group 3 (n = 10), received NAC ip in a dose of 10 mg/100 g after im injection of glycerol; Group 4 (n = 10), saline 0,9% ip in a equivalent volume of NAC of the Group 3 after im administration of glycerol. After 24 h rats were sacrificed and kidney morphology and renal function were determined. A severe renal failure was produced by glycerol injection in the Groups 1, 2, 3, and 4, with significant tubular proximal necrosis and cast formation, and creatinine and urea concentrations were elevated in these groups without significant differences among groups, but Group 0 where the values were significantly lower. The results of this study suggests that ip administration of NAC in rats before or after glycerol injection do not confer protection against impairment of renal function under these conditions in this model of myoglobinuric-ARF.     

Comparison of the efficacy,safety and predictive value of HIV genotyping using distinct ritonavir-boosted protease inhibitors

The pharmacokinetic profile of protease inhibitors (PI) is improved significantly by adding low doses of ritonavir (rit). The use of rit-boosted PI allows the reduction of pill burden, improves dosing schedules and enhances drug exposure, all factors that have been associated with a greater benefit of antiretroviral therapy. All patients receiving rit 100 mg bid together with saquinavir (SQV) soft gel 1000 mg bid, indinavir (IDV) 800 mg bid or lopinavir (LPV) 400 mg bid, as part of a salvage regimen, were retrospectively analyzed in a reference institution. Only subjects who had failed all three antiretroviral drug families in the past were included. A total of 299 patients were included in the study (121 on SQV, 62 on IDV and 116 on LPV). Mean plasma HIV-RNA and CD4 lymphocyte counts at baseline were less favourable in the LPV group (4.4 logs, 275 cells/μl) with respect to SQV (4.3 logs, 355 cells/μl) and IDV (3.7 logs, 409 cells/μl) groups (P<0.05). The proportion of subjects experiencing virological success (attainment of either <500 HIV-RNA copies/ml or >1 log reduction) in an intent-to-treat analysis at 24 weeks was 61% with LPV, 49% with SQV and 48% with IDV. The CD4 count increased 48% with SQV, 45% with IDV and 37% with LPV. The proportion of subjects discontinuing therapy due to adverse events was higher using IDV (27%) than using either SQV (11%) or LPV (6%) (P<0.05). The presence of <5 or >5 PI resistance mutations at baseline discriminated significantly better who would respond to therapy in all instances: 90 vs. 48% with LPV, 95 vs. 21% with SQV and 90 vs. 23% with IDV. The efficacy of rit-boosted PI combinations is greatly influenced by the extent of baseline PI resistance. Differences, not only in potency, but mainly in tolerance may favour the selection of one dual PI combination over others.