Phase I trial and pharmacokinetic study of BMS-247550, an epothilone B analog, administered intravenously on a daily schedule for five days.

PURPOSE: The epothilones are a novel class of nontaxane microtubule-stabilizing agents. BMS-247550 is a semisynthetic analog of the natural product epothilone B. We conducted a phase I study administering BMS-247550 as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. PATIENTS AND METHODS: Twenty-one patients received BMS-247550 without filgrastim in the first cycle. An additional six patients were enrolled at a starting dose of 8 mg/m2/d with filgrastim support. Twenty-one of the 27 patients had received prior paclitaxel, docetaxel, or both. RESULTS: One hundred seven cycles were administered to 27 patients. The maximum-tolerated dose was 6 mg/m2 of BMS-247550 administered as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. Dose-limiting toxicity at a dose of 8 mg/m2/d was neutropenia with or without filgrastim support. Nonhematologic grade 3 toxicities included fatigue (seven cycles), stomatitis (two cycles), and anorexia (one cycle). The mean terminal half-life of BMS-247550 was 16.8 +/- 6.0 hours, the volume of distribution at steady-state was 798 +/- 375 L, and the clearance was 712 +/- 247 mL/min. Objective responses were observed in patients with breast, cervical, and basal cell cancer. Reductions in CA-125 levels were noted in patients with ovarian cancer. CONCLUSION: The recommended phase II dose of BMS-247550 on the daily schedule for 5 days is 6 mg/m2/d. Neutropenia was dose limiting, but higher doses were tolerated by a large fraction of patients with filgrastim support. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting.     

Predicting acute renal failure after coronary bypass surgery: cross-validation of two risk-stratification algorithms

BACKGROUND: Acute renal failure (ARF) requiring dialysis after coronary artery bypass grafting (CABG) occurs in 1 to 5% of patients and is independently associated with postoperative mortality, even after case-mix adjustment. A risk-stratification algorithm that could reliably identify patients at increased risk of ARF could help improve outcomes. METHODS: To assess the validity and generalizability of a previously published preoperative renal risk-stratification algorithm, we analyzed data from the Quality Measurement and Management Initiative (QMMI)1 patient cohort. The QMMI includes all adult patients (N = 9498) who underwent CABG at 1 of 12 academic tertiary care hospitals from August 1993 to October 1995. ARF requiring dialysis was the outcome of interest. Cross-validation of a recursive partitioning algorithm developed from the VA Continuous Improvement in Cardiac Surgery Program (CICSP) was performed on the QMMI. An additive severity score derived from logistic regression was also cross-validated on the QMMI. RESULTS: The CICSP recursive partitioning algorithm discriminated well (ARF vs. no ARF) in QMMI patients, even though the QMMI cohort was more diverse. Rates of ARF were similar among risk subgroups in the CICSP tree, as was the overall ranking of subgroups by risk. Using logistic regression, independent predictors of ARF in the QMMI cohort were similar to those found in the CICSP. The CICSP additive severity score performed well in the QMMI cohort, successfully stratifying patients into low-, medium-, high-, and very high-risk groups. CONCLUSIONS: The CICSP preoperative renal-risk algorithms are valid and generalizable across diverse populations.     

分娩期连续电子胎心监护用于胎儿评估

1背景 在美国，每4例孕妇中有3例在产群中及分娩时使用电子胎儿监护（EFM）（NCHS1993）。1989年，美国妇产科学院（ACOG1989）发表了一项声明，对于低危妊娠既可使用EFM，也可使用间断性胎心听诊；但是，美国预防保健委员会（USPSTF1989）和加拿大的定期健康检查委员会（CTFPHE1994）对高危妊娠仍保留使用EFM。尽管有人对EFM的效果和安全性表示担忧（Thacker 1987：Thacker 1995），     

Imaging spectrum in disseminated histoplasmosis: Case report and brief review

The clinical manifestations of chronic disseminated histoplasmosis are non-specific and resemble those of other chronic infections and malignancies. We report the radiographic, sonographic and contrast-enhanced CT appearances of histoplasmosis in an adult male with non-insulin dependent diabetes mellitus, who was HIV negative and presented with weight loss and pyrexia. Imaging studies simulated tuberculosis with mediastinal lymphadenopathy, bilateral fibrotic lung lesions, hepatomegaly and bilateral hypoattenuating adrenal enlargement, without clinical or laboratory evidence of hypoadrenalism. Computed tomography-guided fine-needle aspiration biopsy of adrenal glands revealed Histoplasma capsulatum. We report our experience to increase awareness of the imaging spectrum of disseminated histoplasmosis and its similarity to tuberculosis as, with increasing incidence of AIDS, the chances of these infections are likely to increase. Moreover, awareness of this entity is important because it is known that untreated disseminated histoplasmosis is fatal.     

The Effects of Maxillary MORA's on Strength and Muscle Efficiency Tests

The study described in this article tested mandibular orthopedic repositioning appliances (MORA's) on eleven athletes to determine changes in muscle strength and efficiency (power) during various exertions. In the vertical jump and grip tests, a significant increase in muscle efficiency was recorded. An average increase of 5% in vertical jump was noted for the eleven subjects. All of the subjects showed an increase in the grip test, with a mean of 17.3%. However, there was no significant increase in strength recorded for the maximum hip sled or the bench press test.