A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer. First report from the Scandinavian Prostatic Cancer Group Study No. 6

OBJECTIVES: To assess the efficacy and tolerability of bicalutamide 150 mg ('Casodex'(1)) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with early (T1b-T4, any N, M0) prostate cancer. METHODS: This randomised, double-blind study was conducted in the Nordic countries as part of the 'Casodex' Early Prostate Cancer programme. Patients received bicalutamide 150 mg (n=607) or placebo (n=611) in addition to standard care. RESULTS: More than 80% of patients had not received therapy of primary curative intent. Median follow-up in both groups was 3 years. Median exposure to study treatment in the bicalutamide and standard care alone groups was 2.5 and 2.3 years, respectively. Bicalutamide reduced the risk of objective disease progression by 57% compared with standard care alone (HR 0.43; 95% CI 0.34, 0.55; p<0.0001). Survival data were immature (11.4% deaths) with no difference between the two treatment groups. CONCLUSIONS: Bicalutamide 150 mg as immediate therapy, either alone or as adjuvant to treatment of curative intent, significantly reduces the risk of disease progression in patients with early prostate cancer. The trial is ongoing to assess whether the reduction in risk of objective progression translates into an overall survival benefit.     

Determination of cadmium and zinc in Alzheimer's brain tissue using inductively coupled plasma mass spectrometry

In this work, brain tissue was taken from Alzheimer's Disease (AD) subjects (n=11), 'normal' subjects (n=10) and from subjects with senile involutive cortical changes (SICC) (n=6). Concentrations of Cd and Zn were determined in all samples, using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The brain tissue was selected and obtained from the Netherlands Brain Bank. Samples were taken in each case, from both hemispheres of the superior frontal gyrus, the superior parietal gyrus, the medial temporal gyrus, the hippocampus and the thalamus of the same brain.Cd which is known to have no essential role in the brain was found to follow, as expected, a lognormal distribution of concentrations in 'normal' subjects (Shapiro-Wilk's test (0.98) (p<0.18)). For the Alzheimer's Disease subjects and SICC subjects, the data tends to follow a lognormal distribution, rather than a normal distribution, but is still significantly different from it (Shapiro-Wilk's test (0.97) (p<0.03); (0.93) (p<0.0067), respectively)).In the case of Zn concentrations, the data tends to follow a normal distribution for the 'normal' subject group, even though the data is significantly different from it (Shapiro-Wilk's test (0.95) (p<0.001)). Whereas in the Alzheimer's Disease and SICC subject groups, the data follows a normal distribution (Shapiro-Wilk's test (0.98) (p<0.21); (0.97) (p<0.2002), respectively)).When comparing age-matched groups, for all regions and both hemispheres, no significant differences (p>0.1) for Cd were found between 'normals' and Alzheimer's Disease subjects and Alzheimer's Disease subjects and SICC but at a low level of significance, lower concentrations of Cd were found in the SICC group compared to the 'normals'. For all regions and both hemispheres, Zn was found to be significantly decreased in the Alzheimer's Disease group, compared to the 'normal' and SICC groups. Zn concentrations were also found to be significantly decreased in the 'normals' compared to the SICC group.It is also of interest that Cd negatively correlates with the scale of tangles in both 'normals' (p<0.001) and Alzheimer's Disease subjects (p<0.01). In the SICC subjects Cd correlates negatively with the tangles but not significantly so (p>0.1).     

Endostatin reduces vascularization,blood flow,and growth in a rat gliosarcoma.

Endostatin, the 20-kDa C-terminal fragment of collagen XVIII, has previously been shown to inhibit growth and induce regression of different experimental tumors in rodents. In this study, we show that recombinant murine and human endostatin, produced in 293 EBNA cells and yeast, respectively, inhibit ectotopic as well as orthotopic growing BT4Cn gliosarcomas in BD-IX rats. In rats in which s.c. gliomas were grown for a total of 29 days, systemic treatment with recombinant murine endostatin induced about 50% reduction of intratumoral blood flow and tumor size after only 10 days of therapy. In contrast, the blood flow to irrelevant organs was unaffected by endostatin, indicating its specificity of action. Tumors were not observed to increase in size or regrow after cessation of therapy. Furthermore, endostatin-treated rats with i.c. tumors had significantly longer survival time than did untreated controls. In the treated rats, endostatin therapy resulted in a reduced tumor blood vessel volume and an increased tumor cell density with an increased apoptotic index within a given tumor volume, as verified by flow cytometry and by staining with deoxynucleotidyltransferase-mediated dUTP nick-end labeling. This work verifies the general anti-angiogenic and antitumor effects of endostatin and indicates that the protein may also be considered as a treatment strategy for malignant brain tumors.     

Bronchoscopy of symptom free patients infected with human immunodeficiency virus for detection of pneumocystosis.

No evidence of Pneumocystis carinii infection was found in eight symptom free patients who were positive for the human immunodeficiency virus and who underwent bronchoscopy, bronchoalveolar lavage, and brush biopsy. This suggests that the presence of Pneumocystis carinii in bronchoscopy material is likely to indicate pneumocystis infection.