Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases.

PURPOSE: This phase III randomized trial evaluated survival as well as neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd). PATIENTS AND METHODS: Patients were randomly assigned to 30 Gy of WBRT +/- 5 mg/kg/d MGd. Survival and time to neurologic progression determined by a blinded events review committee (ERC) were coprimary end points. Standardized investigator neurologic assessment and neurocognitive testing were evaluated. RESULTS: Four hundred one (251 non-small-cell lung cancer) patients were enrolled. There was no significant difference by treatment arm in survival (median, 5.2 months for MGd v 4.9 months for WBRT; P =.48) or time to neurologic progression (median, 9.5 months for MGd v 8.3 months for WBRT; P =.95). Treatment with MGd improved time to neurologic progression in patients with lung cancer (median, not reached for MGd v 7.4 months for WBRT; P =.048, unadjusted). By investigator, MGd improved time to neurologic progression in all patients (median, 4.3 months for MGd v 3.8 months for WBRT; P =.018) and in lung cancer patients (median, 5.5 months for MGd v 3.7 months for WBRT; P =.025). MGd improved neurocognitive function in lung cancer patients. CONCLUSION: The overall results did not demonstrate significant differences by treatment arm for survival and ERC time to neurologic progression. Investigator neurologic assessments demonstrated an MGd treatment benefit in all patients. In lung cancer patients, ERC- and investigator-determined time to neurologic progression demonstrated an MGd treatment benefit. MGd may improve time to neurologic and neurocognitive progression in lung cancer.     

Improved freedom from PSA failure with whole pelvic irradiation for high-risk prostate cancer

Purpose: To determine the impact of whole pelvic irradiation on the risk of PSA failure in prostate cancer patients, at high predicted risk for lymph node involvement, receiving definitive radiotherapy.

Materials and Methods: Between October 1987 and December 1995, 506 patients with clinically localized prostate cancer were treated with definitive radiotherapy at UCSF and affiliated institutions. Treatment consisted of 4-field whole pelvic irradiation followed by a prostate-only boost, or prostate-only treatment (median follow-up was 35 months and 30 months, respectively). PSA failure was defined as: 1. a PSA value ≥ 1 ng/ml; or 2. a PSA value that rose ≥ 0.5 ng/ml in ≤ 1 year posttreatment on two consecutive measurements, with the first rise defined as the time of failure. The calculated risk of lymph node positivity (%rLN+) was defined as (iPSA) + 10(GS-6), and high risk was defined as %rLN+ ≥ 15%. Univariate and multivariate analyses were performed.

Results: A total of 201 high-risk patients were identified. High-risk patients who received whole pelvic irradiation had significantly improved freedom from PSA failure compared to those who received prostate-only treatment (median PFS = 34.3 months vs. 21.0 months; p = 0.0001). Potential confounding variables, including initial PSA, Gleason score, T stage, radiation dose, year of treatment, use of three-dimensional (3D) conformal techniques, and use of hormone therapy, did not account for the observed difference in time to PSA failure. Multivariate analysis revealed type of radiation treatment to be the most significant independent predictor of outcome.

Conclusion: Whole pelvic radiotherapy significantly improves the PSA failure-free survival in patients with a high calculated risk of lymph node positivity.     

Neural response to emotional salience in schizophrenia.

Neuroimaging probes of brain regions implicated in emotion represent an important research strategy for understanding emotional dysfunction in schizophrenia. Anterior limbic structures, such as the ventral striatum and the amygdala, have been implicated in the pathophysiology of schizophrenia and the generation of emotional responses, although few studies to date have used emotion probes to target these areas in schizophrenia. With this goal in mind, emotionally salient visual images were used in a simple, nondemanding task. In all, 13 medicated, schizophrenic patients, five unmedicated patients, and 10 healthy volunteers viewed complex visual pictures and a nonsalient, blank screen while regional cerebral blood flow was measured with the [O-15] water technique. Pictures consisted of real world scenes with aversive, positive, and nonaversive content. Eye movements were recorded simultaneous with scan acquisition. Positron emission tomography images were analyzed for baseline, tonic activity, in addition to phasic changes ('activation') to salient stimuli. Lateral eye movement measures and on-line ratings showed good behavioral compliance with the task. Patients with schizophrenia showed impaired neural responses to salient stimuli in the right ventral striatum (VS), and they exhibited elevated tonic activity levels in the right VS and bilateral amygdala, inversely correlated with overall symptom severity. The patients also showed reduced modulation of visual cortex by salient stimuli. The results show that patients with schizophrenia exhibit impaired neural responses to emotionally salient stimuli in the VS, supporting a role for this structure in the pathophysiology of the illness. Reduced modulation of visual cortex by emotionally salient stimuli also suggests a failure to organize cerebral activity at a global level.     

妇女健康研究进展与机遇

与当代生物医学及行为研究的某些挑战比较，近年来，妇女健康研究概念的延伸和扩展是平行甚至超前的。15年前，妇女健康研究主要集中在生殖健康方面。尽管女性并非总被排除于生殖系统之外的临床研究，但是在同时涉及女性和男性的临床试验并未常规确定女性与男性的差别。为了拓宽女性健康的概念，加之认识到绝经后妇女的增多，研究的倡导者强调需要阐明女性一生的健康状态，包括正常衰老的影响。     

流式细胞仪交叉配型对移植肾1年存活率的影响

目的：探讨流式细胞仪交叉配型（flow cytometry crossmatch, FCXM）对移植肾一年存活率的影响。方法:应用χ2检验比较FCXM阳性与阴性组间1年移植肾死亡有无差异。以“移植后1年肾脏的存活状况(是/否)”为应变量，以移植后早期排斥反应（移植后1月内发生）、血管性排斥反应、移植肾功能延迟（移植后1周内需做血液透析）、FCXM、群体抗原反应抗体(PRA)、 HLA A,B配型、HLA DR配型、供者类型（尸肾/活体供肾）、既往移植次数、免疫抑制药物的使用、血清巨细胞病毒状态、冷缺血时间、供者和受者年龄等可疑影响因素为自变量建立Logistic回归模型，探讨流式细胞仪交叉配型对移植肾1年存活有无影响。结果:258例患者平均随访时间为25个月（12～60个月），期间30例移植肾死亡，其中23例发生在移植后1年内。 χ2检验显示，FCXM阳性与阴性组间1年移植肾死亡无统计学差异（P=0.157?0）。 Logistic 回归显示，对移植肾1年死亡有影响的因素包括移植肾功能延迟（OR=8.00, P=0.001?4），供者类型为尸肾（OR=9.30, P=0.001?7）和血管排斥反应（OR=5.05, P=0.021?9）。FCXM的结果不会影响移植肾一年存活率（OR=1.60, P=0.534?6）。结论: FCXM对移植肾1年后存活尚无肯定的影响。     

Lung bullae and pulmonary fibrosis associated with marijuana smoking

A 26‐year‐old man with a history of heavy marijuana and minimal tobacco use was found to have extensive bilateral lung bullae and interstitial fibrosis, heavily infiltrated by pigmented macrophages. These features can be associated with marijuana smoking. The differential diagnoses in this patient are also discussed.