After treatment for primary or secondary syphilis, the HIV-infected patients responded less well serologically than the patients without HIV infection, but clinically defined failure was uncommon in both groups. Enhanced treatment with amoxicillin and probenecid did not improve the outcomes. Although T. pallidum was detected in cerebrospinal fluid before therapy in a quarter of the patients tested, such a finding did not predict treatment failure. The current recommendations for treating early syphilis appear adequate for most patients, whether or not they have HIV infection.
BACKGROUND
Because low grade serous carcinoma of the ovary is relatively chemo resistant disease, this study evaluated Selumetinib (AZD6244), an inhibitor of mitogen-activated protein kinase kinase (MEK-1/2), and explored associations between RAS, and RAF family mutations with clinical outcome.
METHODS
Women with recurrent low-grade serous ovarian or peritoneal carcinoma were eligible and received Selumetinib at 100 mg. orally b.i.d. until progression or toxicity were enrolled in Gynecologic Oncology protocol 239(NCT00551070). This trial has been completed and we are reporting the results. The primary endpoint of this trial was to examine tumor response rate to Selumetinib. The study used all-treated patients to determine response rate and overall survival.
FINDINGS
Fifty-two patients were enrolled over two years. Eight patients (15.4%) had complete (1) or partial (7) responses, and 34 (65%) had stable disease. There were no treatment-related deaths. There were three observed grade 4 toxicities and 46 grade 3 toxicities that occurred in more than one patient. Observed grade 4 toxicities were cardiac (1), pain (1), and pulmonary (1). Grade 3 toxicities that occurred included gastrointestinal (13), dermatologic (9), and metabolic (7).
CONCLUSIONS
Selumetinib is well tolerated, and is active in the treatment of recurrent low-grade serous carcinoma. In exploratory analyses, response to Selumetinib did not appear to be related to RAS/RAF mutational status. The 63% disease control is encouraging and worthy of further evaluation of MEK inhibitors in this population. This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group.
Associations between antioxidants and zinc and the 5-year incidence of early, age-related maculopathy (ARM) were investigated in a population-based cohort of middle-aged and older adults participating in the Beaver Dam Eye Study in Beaver Dam, Wisconsin. A food-frequency questionnaire was administered at baseline (1988-1990) to collect dietary information for that time period and a period of time 10 years earlier (1978-1980) from a 50 percent random sample of persons participating in this study. The incidence of the specific lesions of larger drusen (>125 microns) and pigmentary abnormalities and the incidence of any ARM were assessed by masked grading of stereoscopic color fundus photographs in 1,709 persons who participated in 5-year follow-up eye examinations. Significant, but modest, inverse associations (p < 0.05) were observed between intakes of pro-vitamin A carotenoids and dietary vitamin E and the incidence of large drusen and between zinc and the incidence of pigmentary abnormalities. No significant inverse associations were found between antioxidant or zinc intake and the incidence of overall early ARM. If ARM, which is characterized by a broad spectrum of lesions, involves a number of different underlying pathophysiologic processes, then associations between specific antioxidants and the incidence of distinct macular lesions may be biologically important. However, because there were too few incident late ARM cases in this cohort, the authors were unable to assess whether antioxidant intake is associated with the progression of early ARM to late-stage macular degeneration. Clinical trials and longer-term prospective studies are needed to elucidate further the impact of antioxidants and zinc on the development and progression of ARM.
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