Effect of the synthetic retinoid fenretinide on circulating free prostate-specific antigen, insulin-like growth factor-I, and insulin-like growth factor binding protein-3 levels in men with superficial bladder cancer.

PURPOSE: Fenretinide (4-HPR) is a synthetic retinoid that has shown a preventive activity in prostate cancer animal models. EXPERIMENTAL DESIGN: We measured the changes in total and free prostate-specific antigen (PSA) and its association with insulin-like growth factor I (IGF-I) and IGFBP-3 levels after 1 year of treatment in 24 subjects given 4-HPR and 24 control subjects enrolled in a randomized bladder cancer prevention trial. RESULTS: No significant effect of 4-HPR was observed on total and free fraction of PSA levels. The median percentage [95 confidence interval (95% CI)] change for % free PSA and total PSA in the 4-HPR and the control group were, respectively, 7.6 (95% CI, -4.0 to 69.3) versus 5.1 (95% CI, -21.4 to 59.8) and -7.8 (95% CI, -18.2 to 52.5) versus -12.3 (95% CI, -44.6 to 9.6). However, in patients ages <60 years, there was a trend to an increase of total free PSA and % free PSA after treatment with 4-HPR that was different from a trend to a decrease in the control group (P = 0.002 and 0.052, respectively). The interaction between age and treatment was statistically significant on free PSA (P = 0.001). A similar pattern was noted with smoking status (P = 0.011 for the interaction on free PSA). No association was observed between PSA levels and IGF-I or IGFBP-3 levels. CONCLUSIONS: We conclude that 4-HPR has no significant effect on circulating PSA, but it increases significantly free PSA levels in subjects younger than 60 years and in nonsmokers. These effects might support an activity in prostate cancer prevention but further studies are required.     

Radioquimioterapia de la enfermedad limitada del carcinoma pulmonar de célula pequeña. ¿Tratamiento concomitante en protocolos asistenciales?

Purpose We retrospectively reviewed our institution’s database to investigate the outcome and impact of combined radiochemotherapy (RT/CT; concomitant or in sequence) in localised small-cell lung cancer (L-SCLC). Material and methods Between January 1995 to November 1999, 79 patients with L-SCLC received combined RT/CT at our Institution. RT was delivered concurrently or sequentially following the CT. Patients with treatment response received additional prophylactic cranial irradiation (PCI). Results Of the patients treated, 54% had received concurrent CT/RT compared to 46% receiving RT following the CT. PCI was administered to 80% of the patients. Complete response was observed in 66% of patients. With a median follow up of 30 months, median overall survival was 15.9 months; 14.3 months for patients who received RT following CT and 21.6 months for those receiving concurrent CT/RT. The type of schedule of combined radiochemotherapy was an independent prognostic factor for survival free of local recurrence, as was additional PCI for distant metastasis-free survival. Conclusions Our results are similar to those reported previously in the literature. The main point of interest is that our patients were non-selected. We strongly support the use of concurrent CT/RT so as to achieve results comparable to the best in the literature.

     

Análisis coste-efectividad de samario-153 (Quadramet®) en el tratamiento del dolor en pacientes con cáncer de próstata y metástasis óseas

Objective. To evaluate the cost-effectiveness of samarium [¹⁵³Sm-EDTMP] (Quadramet®) compared to conventional therapy in the treatment of pain in patients with prostate cancer and bone metastases. Method. A decision tree model for the treatment of bone pain due to metastases was adapted to the Spanish context. The model represents the standard treatment patterns in Spain for the study population. The time-course of the model is 4 months and it computes an estimate for the cost of pain control per patient. The effectiveness data for the model derive from a randomised trial. The current treatment patterns have been established according to the consensus opinions of a group of medical experts. Results. The cost of pain control per patient is ? 12,515.39 for conventional therapy and ? 5,595.52 for samarium-153 (Quadramet®) therapy. The incremental cost-effectiveness analysis shows that samarium-153 (Quadramet®) is a dominant therapy. It presents lower costs and higher efficacy than the conventional strategy. The sensitivity analyses showed these results to be robust. Conclusion. Samarium-153 (Quadramet®) is costeffective in treating pain in patients with prostate cancer and bone metastases.     

二甲双胍治疗抗精神病药物引起的血脂异常:两项随机、安慰剂的对照研究

目的：验证二甲双胍治疗抗精神病药引起的血脂异常的疗效和安全性。方法：将两项随机、安慰剂的 对照研究纳入分析。共有201例服用抗精神病药物后出现血脂异常的首发精神分裂症患者,并将其分为1 000 mg/d 二甲双胍组(以下简称为二甲双胍组,n=103)和安慰剂组(n=98),观察24周。在基线、治疗后第12周和第24周进行 临床症状及体重、血糖、血脂等代谢指标的评估。结果：二甲双胍治疗后,二甲双胍组和安慰剂组之间低密度脂 蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)的平均差异从基线时的0.16 mmol/L,降低到第24周结束时的 –0.86 mmol/L,降低了1.02 mmol/L,差异有统计学意义(P<0.01)。而24周结束时,二甲双胍组LDL-C≥3.37 mmol/L的 患者有25.3%,显著低于安慰剂组24周结束时的64.8%(P<0.01)。与安慰剂组相比,二甲双胍组的体重、体重指数、 胰岛素、胰岛素抵抗指数、总胆固醇、三酰甘油和高密度脂蛋白胆固醇也有显著变化,差异均有统计学意义(均 P<0.05)。治疗对体重和胰岛素抵抗的影响出现在第12周,并且在第24周进一步改善,但对改善血脂异常的作用在第 24周结束时才出现。结论：二甲双胍治疗对于改善抗精神病药物引起的血脂异常和胰岛素抵抗是有效的,并且改善 抗精神病药物诱导的胰岛素抵抗出现的时间早于降低血脂异常的时间。     

Efectividad y seguridad de la terapia de rescate en pacientes VIH

IntroductionThe treatment used after failure of at least two lines of antiretroviral treatment in HIV patients is called salvage therapy. The study aims to describe the characteristics of HIV patients subjected to such a regimen, and determine the safety and effectiveness of treatment with tipranavir (TPV), darunavir (DRV), enfuvirtide (ENF) and etravirine (ETR) combined with an optimised antiretroviral regimen.Patients and methodsHIV patients treated with ENF, TPV, DRV or ETR in a tertiary hospital infectious diseases department subjected to at least 12 weeks treatment. The patient characteristics are described and the effectiveness, durability and adherence to the treatment analysed.ResultsThere were 28 patients studied, with an average of 10 treatment regimens prior to starting salvage therapy (SD = 3.5; 95 % CI, 8.9-11.1). A total of 85.7 % patients had treatment adherence > 90 %. For ENF, 70.8 % of the treatment lines were suspended during follow-up. After salvage therapy, the percentage of patients with viral load (VL) < 400 copies/ml doubled, and cases with undetectable CV (< 50 copies/ml) almost tripled. The treatments used did not change the liver or kidney profiles; however, they changed the lipid profile and increased the percentage of patients with hyperglycaemia.ConclusionsThe salvage therapy studied was effective. Good adherence to the therapy is critical for its effectiveness.     

Relevance of O-acetyl and phosphoglycerol groups for the antigenicity of Streptococcus pneumoniae serotype 18C capsular polysaccharide

Capsular polysaccharides are important virulence factors of Streptococcus pneumoniae. The polysaccharide has been used as a component of vaccines against pneumococcal diseases either as plain polysaccharide or better conjugated to a protein. The last one is the vaccine of choice to target child protection. The immune responses depend on several polysaccharide physicochemical properties that can be affected during either purification or modification in the case of conjugate vaccines. In serotype 18C, the repeating unit has a complex structure having a branched pentasaccharide with two apparently labile subtituents: glycerol-phosphate and O-acetyl group. The loss of these groups may potentially reduce the ability of the 18C polysaccharide to induce the desired immune response. Therefore, the relationship of both groups with the antigenicity and immunogenicity of 18C capsular polysaccharide is explored. It is shown that glycerol-phosphate must be preserved for conserving adequate antigenicity of the 18C capsular polysaccharide. At the same time, it was proved that O-acetyl groups do not play any role for the antigenicity and immunogenicity.     

Associations between surrogate measures of insulin resistance and waist circumference,cardiovascular risk and the metabolic syndrome across Hispanic and non‐Hispanic white populations

Aims We evaluated the relations between surrogate indices of insulin resistance and waist circumference, metabolic syndrome and coronary heart disease risk across Hispanic and non‐Hispanic white populations. Methods The study was a cross‐sectional analysis of participants without diabetes in the San Antonio Heart Study, Mexico City Diabetes Study and Spanish Insulin Resistance Study. We evaluated commonly used indices of insulin resistance, including homeostasis model assessment, McAuley’s index, Gutt’s insulin sensitivity index, Avignon’s insulin sensitivity index and the Stumvoll index with and without demographics, the modified Matsuda index and the product of the triglycerides and glucose index. The metabolic syndrome was defined by American Heart Association/National Heart, Lung, and Blood Institute criteria and coronary heart disease risk by Framingham risk scores. Results The Stumvoll index with demographics and the Avignon’s insulin sensitivity index had the strongest correlations with waist circumference across populations. The triglycerides and glucose and McAuley’s indices had the most robust correlations with Framingham risk score. The triglycerides and glucose index had the greatest ability to detect individuals with the metabolic syndrome and ≥ 10% coronary heart disease risk. Some indices display significant variability in the strength of the relationship with adiposity and coronary heart disease risk across populations. Conclusions There are significant differences between insulin resistance indices regarding the ability to detect the metabolic syndrome and coronary heart disease risk across populations. Studies may need to consider the index of insulin resistance that best suits the objectives.