A phase I study of paclitaxel for mobilization of peripheral blood progenitor cells.

We conducted a phase I trial to determine the dose and schedule of paclitaxel, when given together with filgrastim, which would optimally promote mobilization of stem cells with tolerable toxicity. Dose escalation began at 275 mg/m2 3 h infusion. Dose-limiting neuropathy was observed at the 300 mg/m2 dose level. A second dose escalation was conducted utilizing 24 h infusion schedules, beginning at 225 mg/m2. Dose escalation was continued by 25 mg/m2 increments to 300 mg/m2, at which dose neuropathy was again dose-limiting. The recommended dose and schedule of paclitaxel for the purpose of mobilization of stem cells, when given together with filgrastim, are 275 mg/m2 as a 24 h infusion. The median stem cell yield after this dose of paclitaxel was 6.6 x 10(6) CD34+ cells/kg/apheresis (range 3.6 x 10(6)-7.7 x 10(6)).

Second primary malignancies associated with primary female breast cancer: a review of the Danbury Hospital experience.

Second primary tumors associated with breast cancer are well known. The purpose of this retrospective study is to review the Danbury Hospital experience with second primary tumors following or concurrent with a diagnosis of breast cancer. Eighty-three women with an initial diagnosis of breast cancer between 1970 and 1986 developed second primary malignancies, most commonly in the contralateral breast, followed by colon or rectum. The median time to second diagnosis was shorter for the colorectal group than for the other sites. The occurrence of a second primary malignancy in general seemed to be more likely in the postmenopausal group, and the presence of a family history of breast cancer in a first degree relative was more often associated with second primary malignancy located in the contralateral breast. Patients who had had systemic therapy showed a shorter mean interval to second diagnosis than those who had received local therapy alone among the subset of patients with a second malignancy in the contralateral breast. Additionally, there was no tendency to discover the second primary breast cancer at an earlier stage than the first. These results suggest the importance of bowel surveillance once a diagnosis of breast cancer is made. They also suggest the importance of contralateral breast surveillance, especially with a positive family history, and that current methods of surveillance need to be reevaluated.

Mechanism for binding of fatty acids to hepatocyte plasma membranes.

The purpose of this study was to examine the interaction between fatty acids and plasma membranes from liver cells. We were unable to reproduce the reported effect of heating on the capacity of these membranes to bind [3H]oleate (Stremmel et al. 1985 Proc. Natl. Acad. Sci. USA. 82: 4-8). In fact, the distribution of [3H]oleate between plasma membranes and unilamellar vesicles of lipids extracted from these membranes was in favor of the lipids, indicating the absence of a detectable amount of binding to a putative fatty acid binding protein in plasma membranes. Radius of curvature of vesicles (125 A vs 475 A) had no effect on the partitioning of fatty acid. In addition, the distribution of [3H]oleate between plasma membranes and other phases had the properties of a partition coefficient over a 200-fold range of [3H]oleate. There was no evidence in this experiment for a binding isotherm, i.e., binding of [3H]oleate at a specific site, superimposed on the nonspecific partitioning of [3H]oleate into the lipids of the plasma membrane. There was no competition between [14C]oleate and [3H]palmitate for entry into plasma membranes. Finally, rates of uptake of [14C]oleate and [3H]palmitate by perfused rat liver were not affected by the presence of the other fatty acid in perfusates. These data indicate that the avidity of hepatocyte plasma membranes for [3H]oleate is a simple consequence of the physical chemical properties of oleate, lipids, and water. The data exclude the idea that the uptake of fatty acids into cells is the result of binding proteins and/or catalyzed reactions at the water-membrane interface of the cell or within the plane of the plasma membrane.

The physical-chemical basis for sex-related differences in uptake of fatty acids by the liver.

The uptake of fatty acids by the liver was shown previously to be a non-catalyzed process, and rates of uptake were correlated to the affinity of the plasma membranes of liver cells for fatty acids. The experiments in this paper were designed to test whether the known differences in uptake and metabolism of free fatty acids by the livers of male and female rats could be understood based on differences in the affinities of the corresponding plasma membranes for these substrates. The relative affinities for palmitate and oleate of 'male' plasma membranes were found to be lower versus 'female' membranes. Measurements of uptake of palmitate from albumin-palmitate complexes by 'male' and 'female' perfused livers showed higher uptake rates by the latter when correlated with the concentration of the complex. However, the rates of uptake were identical when the concentrations of the fatty acid in the plasma membranes of male and female liver cells were the same.

Comparison of continuous positive airway pressure, incentive spirometry, and conservative therapy after cardiac operations.

Of 38 patients undergoing median sternotomy for cardiac operations all developed profound restrictive defects in pulmonary function during the first 72 h after tracheal extubation. Although decreased lung volumes were refractory to correction by vigorous, aggressive pulmonary therapy during this period, frequent and supervised treatment may prevent further deterioration in pulmonary function. The overall incidence of pneumonia was only 3% (1/38). Continuous positive airway pressure delivered by mask proved to be a nearly effortless form of postoperative respiratory therapy that was less painful than incentive spirometry or coughing and deep breathing, and therefore may be preferable.

A linear programming model for determining efficient combinations of 8-, 10-, and 12-hour shifts.

I have formulated a linear programming model to determine changes in efficiency and productivity that would result from scheduling personnel to work combinations of 8-, 10-, and 12-hour shifts in a section of our pulmonary medicine department. My objective was to minimize the number of staff hours worked each day, subject to the constraints imposed by the levels of staffing required during each hour of the day. I found that a combination of 8-, 10- and 12-hour shifts could increase productivity 8.1% and reduce personnel requirements by one full-time equivalent. Salary expenses would decrease 7.5% if overtime were not paid for the extended hours of the 10- and 12-hour shifts. Two considerations in implementing the proposed schedule are the willingness of staff to work extended hours and the necessity of developing a format for communication between therapists who work discontinuous shifts.

Effect of cigarette smoke exposure on maturation of the antibody response in spleens of newborn mice.

Balb/c mice were exposed to smoke from Kentucky Reference IRI cigarettes within 24 hr after birth on a Prototype Mark II Walton Horizontal Smoke Exposure Machine for various periods of time up to 10 wk of age. There was no difference in the magnitude of the splenic plaque-forming cells (PFC) response in smoke-exposed and untreated control animals immunized with sheep red blood cells (SRBC) on sequential days up to day 9 postpartum. However, beginning at day 10 and for each subsequent time period assayed thereafter, there was a statistically significant reduction in the number of splenic PFC observed in the smoke-exposed animals. On day 10, the PFC response of smoke-exposed mice was reduced by 33%, on day 14, there was a 60% reduction, whereas animals exposed to smoke from 4-10 wk showed a 90% reduction of the splenic PFC response.