Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel

PURPOSE: Topotecan, a topoisomerase I inhibitor, was evaluated in a multicenter, phase II study of women with epithelial ovarian carcinoma who relapsed after one or two prior regimens that included platinum and paclitaxel. PATIENTS AND METHODS: Topotecan 1.5 mg/m2 daily was administered as a 30-minute infusion for 5 consecutive days on a 21-day cycle. Eligibility criteria included bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of 2 or less, and adequate bone marrow, liver, and renal function. Efficacy was assessed by independent radiologic review. RESULTS: One hundred thirty-nine patients were treated; 81% were platinum resistant. Sixty-two patients had received one prior regimen and 77 patients had received two prior regimens. Nine patients were not assessable for response; however, all patients were included in the response analysis. The overall response rate was 13.7%; 12.4% in platinum-resistant and 19.2% in platinum-sensitive patients. Stable disease lasted at least 8 weeks in 27.3% of the patients. The median duration of response and time to progression were 18.1 and 12.1 weeks, respectively. The median survival was 47.0 weeks. Grade 4 neutropenia occurred in 82% of the patients (34% of the courses) and thrombocytopenia in 30% of the patients (9% of the courses). Infectious complications occurred in 6% of the courses. Nonhematologic toxicities were mild. There were no drug-related toxic deaths. CONCLUSION: As a single agent, topotecan has modest activity in women with advanced epithelial ovarian carcinoma who have progressed or not responded after one or two prior regimens with platinum and paclitaxel. Further investigation of combination regimens is indicated in the primary therapy for ovarian cancer based on the mechanism of action and tolerability.     

Estrogen modulation: tiered testing for human hazard evaluation. American Industrial Health Council, Reproductive and Developmental Effects Subcommittee

Recent concerns about the potential of certain chemicals to modulate estrogen-regulated processes have led to questions as to how chemicals should be tested for such effects. Therefore, AIHC has developed a comprehensive, resource-efficient, and flexible tiered strategy for estrogen modulation (EM) testing. Levels of evaluation include Tier 0, in which exposure, along with alerts based on structure-activity, persistence, bioaccumulation, and other data, are assessed to prioritize chemicals for preliminary testing. In Tier I, short term in vitro, ex vivo, and/or in vivo assays are used to obtain a preliminary indication of EM potential. Among these, an in vivo response assay is considered the most reliable at this time. However, none of these tests are intended for risk assessment, but rather to aid in choosing chemicals for further testing and in guiding the extent of that testing. Tier II is aimed at risk assessment and involves whole animal tests that contain EM-sensitive end points (e.g., two-generation reproduction study). Tier III consists of hypothesis-driven research reserved for situations where targeted research can reduce levels of uncertainty. This tiered approach provides a framework for the strategic and effective application of EM test methods to address specific information needs on a case by case basis.     

Intestinal hemorrhage from exposure to pulsed ultrasound

Threshold exposures for producing intestinal hemorrhage in mice were determined using focused sources operating at 0.7, 1.1, 2.4 and 3.6 MHz. The choice of pulse length (10 microseconds) and pulse repetition frequency (100 Hz) made the exposures diagnostically relevant, while at the same time, minimized possible thermal contributions to the mechanism of action of the ultrasound. Each animal was irradiated at four to five abdominal sites for 5 min per site. Suprathreshold lesions ranged from small petechiae to hemorrhagic regions extending 4 mm or more along the intestine, depending upon the exposure levels. Higher frequencies were less effective in producing intestinal hemorrhage than lower frequencies. Thermocouple measurements of temperature rise in the intestine during ultrasound exposure revealed temperature increments between 1 degrees and 2 degrees C at the highest exposure levels. The frequency dependence of the production of intestinal hemorrhage together with the observed limited heating is consistent with a cavitation-related mechanism of action of pulsed ultrasound.     

Purification of enolase and phosphoglycerate mutase from human brain and formation of a bienzymatic complex from them

Neuron-specific enolase and phosphoglycerate mutase with specific activities of 106 and 215 U/mg, respectively, have been purified from human brain. Hydrophobic chromatography for enolase and blue Sepharose affinity chromatography for phosphoglycerate mutase were used as the last steps of purification. A heterobifunctional complex with fully preserved enolase and phosphoglycerate mutase activities was synthesized with the use of a bifunctional reagent, N-succinimidyl 3-(2-pyridyldithio)propionate. Autoantibodies to the conjugate will be used for identifying the bienzymatic complex in vivo.     

Nursing of surgical closure of cerebrospinal rhinorrhea from sella turcica by the extranasal ethmoidal approach

The expression of estrogen receptor (ER) and progesterone receptor (PR) in 200 breast cancer specimens were imvestigated by monoclonal antibody with S-P staining to evaluate and standardize the criteria for positive staining. The results revealed that the incidence of ER and PR were 73.5% and 65.5% respectively. The authors concluded that the immunostaining could demonstrate in situ ER and PR, the results were stable, highly sensitive, consistent and comparable with the well established and recognized techniques home and abroad. The authors further pointed out that the crucial point of the staining is antigen retrieval and reported the optimal temperature and the time of sodium citrate buffer treatment. In this report, the criteria for positive staining were discussed intensively. The observations indicated that the percentage of the positive cells is more reliable, representative and practical than that of positive staining intensity index.     

Spectrum of disease among HIV-infected adults hospitalised in a respiratory medicine unit in Abidjan, C?te d'Ivoire

SETTING: Respiratory medicine wards of the University Teaching Hospital, Abidjan, C?te d'Ivoire. OBJECTIVES: To describe the spectrum of opportunistic infection among human immunodeficiency virus (HIV) infected adults hospitalised in the respiratory medicine unit in Abidjan, and the level of immunosuppression at which these diseases occur. DESIGN: Cross-sectional study. RESULTS: Overall, 75% of patients were HIV-positive: among these patients, the most frequent diagnosis was tuberculosis, in 61%, followed by bacterial pneumonia (15%), Gram-negative septicaemia (particularly non-typhoid Salmonella) (9%) and empyema (5%). Atypical pneumonias appeared to be rare. Most HIV-positive patients had CD4 counts indicative of advanced immunosuppression: 36% had CD4 counts below 100 x 10(6)/l, 19% between 100 and 199 x 10(6)/l, 29% between 200 and 499 x 10(6)/l, and 16% above 500 x 10(6)/l. Overall in-hospital mortality was 27% for HIV-positive patients and 22% for HIV-negative patients (P = 0.5). In a multivariate analysis, the strongest independent risk factors for death were cachexia (odds ratio [OR] 7.4, 95% confidence interval [CI] 2.1-26.3), male sex (OR 4.5, 95% CI 1.2-17.4) and age over 40 (OR 4.1, 95% CI 1.0-17.2). CONCLUSIONS: Tuberculosis and bacterial infections are the major causes of respiratory morbidity in immunosuppressed HIV-infected adults in this population. Efforts to improve the management of HIV-related disease need to focus on prevention and treatment of these infections.