Black Men Who Have Sex with Men and Lifetime HIV Testing: Characterizing the Reasons and Consequences of Having Never Tested for HIV

Prevention Science - HIV testing remains a critical point of entry to HIV treatment services and now biomedical prevention as well. Yet despite the high HIV prevalence among Black men who have sex...     

Phase II collaborative pilot study: preliminary analysis of central neural effects from exposure to volatile anesthetics in the PACU.

Nurses working in the PACU are occupationally exposed to volatile anesthetics that are exhaled by patients. Few studies have quantified this exposure using breath analysis or have characterized biological effects associated with this exposure. Isoflurane is a widely used anesthetic and is a strong respiratory depressant. Exposure to isoflurane has been shown to cause changes in breathing patterns at low doses. However, biological effects of isoflurane exposure have never been addressed in the occupational setting. This study investigates whether occupational exposure to anesthetic gases has a depressive effect on central neural control of breathing. In this study, concentrations of halogenated anesthetics were quantified in pre- and postshift breath samples of nurses working in the PACU on a Friday and the following Monday. After each breath sample was collected, an occlusion pressure measurement was taken as an indicator of central inspiratory drive. Cumulative nitrous oxide and halogenated anesthetics exposure was measured each day using personal sampling monitors placed close to the nurse's mouth. Exposure to nitrous oxide and isoflurane was significantly higher on Monday than on Friday (P <.001). Monday breath isoflurane concentrations (mean +/- SD) increased significantly from 43 +/- 30 parts per billion (ppb) in preshift breath samples to 124 +/- 57 ppb in postshift breath samples (P <.002). On Monday, there was a significant decrease in occlusion pressure from 1.2 +/- 0.37 cm H(2)O in preshift samples to 0.85 +/- 0.43 cm H(2)O in postshift samples (P =.05). There was no statistical difference in pre- versus postbreath isoflurane or occlusion pressure on Friday. These data indicate that after increased exposure to isoflurane, central neurorespiratory activity was depressed.     

Phase II trial of capecitabine and rHu-interferon-alpha-2a in patients with metastatic renal cell carcinoma, limited efficacy, and moderate toxicity

BACKGROUND: Capecitabine is an orally administered fluoropyrimidine that is converted to 5-fluorouracil by thymidine phosphorylase. In view of the recognized synergism of fluoropyrimidines with interferon-alpha (IFNalpha), a Phase II study to characterize the toxicity and efficacy of the combination of capecitabine and rHuIFNalpha-2a for the treatment of patients with renal cell carcinoma (RCC) was conducted. PATIENTS AND METHODS: Eligible patients had metastatic RCC, measurable disease, and no prior systemic therapy. A total of 32 patients were entered into the study. Histologic subtypes included clear cell (n = 28) and nonclear cell (n = 2). Histology was unknown for 2 patients. The first 14 patients were treated with capecitabine 1,000 mg/m(2) twice daily on days 1-14 and 22-36, combined with IFNalpha-2a 3.0 MU/m(2) subcutaneously 3 times weekly. Because of toxicity requiring dose reductions during the first cycle, the capecitabine dose was reduced to 825 mg/m(2) twice daily on days 1-14 and 22-36 in the subsequent 18 patients. RESULTS: Responses were seen in 4 of 32 patients (12%) (95% confidence interval 4% to 29%), with 1 complete response and 3 partial responses. There were 3 responses that occurred at the higher capecitabine starting dose level. Median response duration was 12 months (range 4.6-15.0). There were 12 patients (38%) who had stable disease for at least 2 cycles (duration 2.9 to 33.6+ months). One-year survival was 63%. Toxicity was moderate to severe and required dose reductions in 88% of patients. There were 23 patients who had grade > or =3 toxicity. CONCLUSION: The combination of capecitabine and IFNalpha-2a has limited activity in metastatic RCC and is associated with moderate-to-severe toxicity.     

Phase I trial of three-weekly Docetaxel,Carboplatin and oral lenalidomide (Revlimid®) in patients with advanced solid tumors

Summary Introduction: Lenalidomide is an immunomodulatory derivative of thalidomide with significantly greater in vitro activity and a different toxicity profile. In preclinical trials it has shown synergy with chemotherapy. Patients and methods: Primary objective of this study was to determine the maximum tolerated doses of docetaxel and carboplatin when combined with oral lenalidomide in a standard phase I study design. Between September 2004 and May 2005, 14 patients with pathologically proven solid tumors, ≤2 prior chemotherapy regimens, performance status ECOG 0/1, and adequate organ function were enrolled. Dose limiting toxicities (DLT) were defined as ≥ grade 3 non-hematological, or grade 4 hematological toxicity. No growth factors were used during cycle 1. Results: Three of four patients treated at dose level 1, docetaxel 60 mg/m² and carboplatin AUC 6 on Day 1, and lenalidomide 10 mg orally daily on Days 1–14 of a 21 day cycle experienced DLT (grade 3 electrolyte changes in two patients, and grade 4 neutropenia in one patient). Ten patients were treated at dose level −1, docetaxel 60 mg/m² and carboplatin AUC 6 on Day 1, and lenalidomide 5 mg orally daily on Days 1–14 of a 21 day cycle with one DLT (Grade 4 neutropenia). There were no treatment-related deaths or irreversible toxicities. Of the 14 response-evaluable patients, five achieved a partial response (5 out of 9 patients with non-small cell lung cancer. Conclusions: Docetaxel 60 mg/m² and carboplatin AUC 6 on Day 1, with lenalidomide 5 mg orally daily on Days 1–14 days of a 21 day cycle is the maximum tolerated dose without the use of prophylactic growth factors. This combination is active and further evaluation in a phase II trial is warranted. Revlimid? is a registered trademark of Celgene Corporation.     

The prognostic significance of epidermal growth factor receptor expression in clear-cell renal cell carcinoma: a call for standardized methods for immunohistochemical evaluation

Background

Epidermal growth factor receptor (EGFR) is overexpressed in the majority of clear-cell renal cell carcinomas (RCCs). The prognostic significance of EGFR overexpression after nephrectomy, however, is controversial because of different methods used in the immunohistochemical (IHC) evaluation of EGFR expression.

Patients and Methods

In this study, we evaluated EGFR expression and its prognostic significance using 3 IHC evaluation methods. A tissue microarray composed of 44 cases of clear-cell RCC was stained for the patterns of EGFR overexpression, including membranous, cytoplasmic (EGFR-c), and total (membranous and cytoplasmic), and the percentage of cells positive for EGFR overexpression were recorded. An EGFR composite score was calculated by multiplying the total EGFR overexpression score (0-3) and percentage of positive cells.

Results

Membranous EGFR overexpression was detected in 38 of 44 cases (93.2%), with moderate to strong staining (scores 2 and 3) in 35 cases (79.5%). EGFR-c was detected in 28 cases (63.6%), with moderate to strong staining (scores 2 and 3) in 16 cases (36.4%). EGFR-c was significantly associated with pathologic stage (P = 0.003) and Fuhrman nuclear grade (P = 0.042). Epidermal growth factor receptor composite score correlated with pathologic stage (P = 0.045) but not Fuhrman nuclear grade. However, EGFR expression did not correlate with overall survival or disease recurrence.

Conclusion

This study demonstrates that the prognostic value of EGFR overexpression differs significantly when different methods are used to evaluate EGFR expression by IHC. Future studies should use standardized methods to evaluate the EGFR staining pattern and intensity and the percentage of positive cells in order to clarify the prognostic significance of EGFR overexpression in clear-cell RCC.