Plasma HIV-1 RNA decline within the first two weeks of treatment is comparable for nevirapine, efavirenz, or both drugs combined and is not predictive of long-term virologic efficacy: A 2NN substudy

BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed as a marker of early efficacy of antiretroviral therapy (ART) and a possible predictor of late efficacy. We compared the rate of pVL decline in patients starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral decay constant (VDc) during the first 2 weeks of treatment in patients enrolled in the 2NN study who remained on allocated treatment. RESULTS: The median VDc (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25-0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3) times more likely to have a VDc >75th percentile. A high VDc was not associated with plasma drug concentration or with a decreased risk of virologic failure at week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2). CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar rates of pVL decline during the first 2 weeks of treatment. The VDc with these regimens is not predictive of late virologic efficacy.     

Antiangiogenic treatment with endostatin inhibits progression of AML in vivo.

Increased vessel density in the bone marrow of patients with acute myeloid leukemia as well as elevated expression of proangiogenic factors by leukemic cells implies a central role of angiogenesis in hematological malignancies. Endostatin (ES), a fragment of collagen XVIII, is an endogenous inhibitor of angiogenesis that has shown therapeutic activity in solid tumors in various preclinical models. Using microencapsulation technology, we studied the therapeutic effect of ES in AML. While ES had no effect on proliferation of M1 murine leukemic cells in vitro, ES producing microbeads significantly inhibited growth of subcutaneous chloromas in SCID mice as compared to controls. In a leukemia model using M1 cells the concomitant treatment of mice with ES microbeads prolonged median survival significantly. Histological analysis revealed a decreased microvessel density and a reduced number of CD31-positive single cells, putatively endothelial progenitor cells, in the bone marrow of treated animals. Taken together, ES has inhibitory effects on neo-angiogenesis in the bone marrow and on progression of leukemia in vivo. These experiments suggest a possible therapeutic role of antiangiogenic gene therapy with ES in AML.     

Docetaxel and carboplatin as second-line chemotherapy for metastatic non-small cell lung cancer

The aim of this pilot study was to evaluate the activity and toxicity of docetaxel plus carboplatin as second-line treatment in patients with metastatic non-small cell lung cancer (NSCLC). Patients received docetaxel 75 mg/m(2) followed by carboplatin AUC 5 on day 1 every 3 weeks in an out-patient setting. Twenty-six patients were enrolled; 23 patients were diagnosed stage IV disease and three patients had a IIIB disease with malignant pleural effusion. The median interval from first to second-line treatment was 3.5 months (range 1-13). Patients received a total of 101 cycles with a median number of four cycles per patient (range 1-6). Five patients achieved a partial remission (19.23%; 95% confidence interval (CI) 6.55-39.35%), 11 had stable disease (42.31%) and ten progressed (38.46%) after initiation of second-line therapy. Median survival was 243 days (95% CI 182-336 days), the median progression-free survival was 118 days (95% CI 89-170 days), and the 1-year survival rate was 25.98% (95% CI 6.33-45.63%). Moderate haematological and mild nonhaematological toxicities were observed. No treatment-related death occurred. In conclusion, docetaxel plus carboplatin as second-line regimen has a reasonable activity with good tolerance and encouraging survival data.     

Cognitive sequelae of brain radiation in adults

Radiotherapy (RT) is a proven curative and palliative therapeutic tool in the treatment of a wide variety of primary and metastatic brain tumors in adults. Recent advances in multimodality therapy have led to improvement in survival for many cancer patients. As survival has improved, more attention has been directed toward long-term treatment-related morbidity. Specifically, the effect of RT on the long-term cognitive performance of these patients is a major concern. This article reviews the neurocognitive effects of cranial RT on adult patients with brain tumors. Analyses of neurocognitive function are confounded by factors such as surgery, chemotherapy, tumor characteristics, tumor progression, concurrent medical illnesses, neurologic comorbidity, and medications that can contribute to neurocognitive deficits. Risk of deficits after cranial RT is associated with high RT dose, large fraction size, larger field size, and extremes of age at time of treatment. Using modern techniques with moderate total doses (50 to 54 Gy), conformal RT, conventional fractionation, and advanced planning imaging and software, the risks of neurocognitive deficits are quite small and greatly overshadowed by deficits caused by the tumor itself. Further studies need to be undertaken to elucidate the degree and cause of cognitive decline in adult patients undergoing multimodality therapy for cranial tumors.     

干细胞移植治疗时间窗与临床疗效的荟萃分析

目的:探讨寻找干细胞移植治疗急性心肌梗死的最佳移植治疗时间,指导临床应用,提高临床疗效。方法:应用计算机检索medline2000-01/2006-05文章,检索词为:"stem cell transplantation and/or acute myocardialinfarction(AMI)and/or chronic heart failure or ischemic cardiomyopathy",限定文章语言种类为English;同时计算机检索中国期刊全文数据库,相同时间的文章,检索词:"干细胞移植治疗,干细胞移植与急性心肌梗死,干细胞移植治疗与心力衰竭或慢性缺血性心肌病",限定文章语言种类为中文。共检索到300余篇与主题有关的文献,其中12篇有价值的文章见参考文献。移植时间取平均值,并按射血分数值和P值进行列表、作图。对干细胞移植时间与射血分数值之间的关系进行分析。结果:在急性心肌梗死后2～5d和9d以后进行干细胞移植治疗疗效较24h内及6～8d为好。结论:干细胞移植治疗急性心肌梗死的移植时间与临床疗效之间可能存在一定的相关性。经冠脉注入干细胞比经静脉或经心内膜下注入可以更好地改善左室功能,但还需要进一步的临床资料证实。     

A comparative histological analysis of human pulp following direct pulp capping with Propolis, mineral trioxide aggregate and Dycal

Background:  Permanent teeth pulp exposures have traditionally been treated with calcium hydroxide pulp capping. The aim of this study was to investigate the response of human pulp tissue which were mechanically exposed to a new material, Propolis and compare it with two existing and commonly used pulp capping agents (mineral trioxide aggregate and Dycal).
Methods:  Thirty-six intact human premolars were mechanically exposed. Teeth were divided into six groups of 6 teeth each and were capped with Propolis, mineral trioxide aggregate and Dycal. Final restoration was done with posterior composite resin using light cured glass ionomer cement as a liner. The teeth were then extracted on the 15th or the 45th day and processed for histological evaluation.
Results:  Differences in inflammatory response and dentine bridge formation of the exposed pulp to the three different materials were statistically calculated using chi-square test and were found to be non-significant. There was more pulp inflammation in teeth treated with Dycal than with Propolis and MTA on the 15th as well as on the 45th day. Propolis and MTA showed bridge formation in more teeth, and the bridges were in closer proximity to pulp capping material than teeth treated with Dycal on the 45th day.
Conclusions:  The response of pulps to Propolis as a pulp capping agent was comparable to MTA and Dycal.     

Entwicklung antiangiogener Kombinationstherapien zur Behandlung des Nierenzellkarzinoms

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