Amifostine (WR-2721) shortens the engraftment period of 4-hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty-three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high-dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.     

Exact controllability for semilinear parabolic equations with Neumann boundary conditions

This paper studies the problem of exact boundary controllability of second-order semilinear parabolic equations when the control is under Neumann's boundary conditions. For a nonlinear term with a sublinear growth we prove the global null-controllability and for the superlinear growth case we prove the local exact controllability of the equations.     

Stress analysis of a cantilevered fixed partial denture with normal and reduced bone support

A two-dimensional finite element model was constructed to analyze the simulated mechanical behavior of a cantilevered fixed partial denture. The variations of the models were made by altering the degree of bone support, the number of splinted abutments, and the length of the pontics. High stress concentrations were observed around the connectors of the fixed prosthesis and the tooth closest to the cantilever. Reduced bone support increased the deflection and stress concentrations. There was reduction in displacement and stress concentration when the teeth were splinted together. To improve the prognosis of the fixed partial denture cantilever, the number of abutments should be increased and the number of pontics decreased.     

Perceptions of elder abuse and help-seeking patterns among African-American, Caucasian American, and Korean-American elderly women

Thirteen scenarios were used to measure and compare the perceptions of elder abuse and help-seeking behaviors of African-American, Caucasian American, and Korean-American elderly women. Significant group differences existed in their perceptions of elder abuse with regard to six scenarios, and the Korean-American women were substantially less likely to perceive a given situation as abusive than the other groups. The three groups also showed significant differences in their intended use of formal and informal sources of help in the case of elder abuse.     

Structures of sialylated oligosaccharides of human erythropoietin expressed in recombinant BHK-21 cells

The native structures of the Asn-linked oligosaccharides and the O-glycans at Ser126 of human erythropoietin expressed from recombinant BHK cells have been elucidated. Enzymatically released N-glycans were studied by methylation analyses, fast-atom-bombardment mass spectrometry as well as one- and two-dimensional 1H-NMR spectrometry at 600 MHz. Many (82.7%) were found to be tetraantennary N-acetyllactosamine-type (22.8% with one, 3.6% with two and 0.4% with three N-acetyllactosamine repeats) being tetrasialylated (41%), trisialylated (29.6%) and disialylated (12.2%). A few (9.7%; 4.1% 2,4-branched, 5.6%, 2,6-branched) of the chains were triantennary (5.4% trisialyl, 4.3% disialyl) and 4.6% were of the disialyl diantennary type. Almost all of the innermost GlcNAc residues were alpha 1-6 fucosylated and NeuAc was exclusively alpha 2-3 linked to Gal beta 1-4GlcNAc-R; 60% of the protein was found to be O-glycosylated at Ser126; structures were monosialylated (70%) or disialylated (30%) forms of the Gal beta 1-3GalNAc core type. Glycosylation patterns at individual Asn-Xaa-Thr/Ser sites were determined by analytical high-pH anion-exchange chromatography with pulsed amperometric detection. Only tetraantennary chains with 0-3 N-acetyllactosamine repeats were detected at Asn38 and Asn83, while almost all of the di- and triantennary oligosaccharides were attached to Asn24. Batch analysis of different preparations of recombinant erythropoietin revealed the high reproducibility of the production procedure. Structures containing terminal GalNAc-GlcNAc were detected in small amounts in a few batches.     

Border crossing for hospital care and its implications for the use of statewide data

A major concern of researchers using state data sets for population-based analyses and market share studies in the health care sector is the potential bias caused by 'border crossing'--patients receiving care out of state. By using the Health Care Financing Administration (HCFA) discharge abstract files for 1987 and 1988, we found that 'border crossing' is not a serious problem for the two large states we examined. Only 4.4% of New York patients and 2.15% of California patients received care out of state. At the county and zip code level, 'border crossing' is more frequent but tends to be concentrated in areas adjacent to other states. Even excluding all zips with more than 10% of patients crossing the 'border' results in a small loss of patients (2.2% for New York and 1.0% for California).     

Prediction of fatigue screw loosening in anterior spinal fixation using dual energy x-ray absorptiometry

STUDY DESIGN: A biomechanical study was performed to investigate a relation between the bone mineral density of the vertebral body and the number of loading cycles to induce fatigue loosening of an anterior vertebral screw. OBJECTIVES: The objective of this study was to investigate the potential usefulness of dual energy x-ray absorptiometry of measuring bone mineral density of the vertebral body in predicting the fatigue loosening of th anterior vertebral screw. SUMMARY OF BACKGROUND DATA: Loosening of the vertebral body screw is a well know failure in spinal instrumentation, and more commonly observed than pullout failure. The relation between bone mineral density and pullout strength of the screw has been investigated previously, but no studies are available on the fatigue loosening in anterior spinal fixation. METHODS: Bone mineral density was measured using dual energy x-ray absorptiometry and the screw loosening was produce by a cyclic loading in the cephalad-caudal direction. Screw loosening was defined as 1 mm displacement of the screw relative to bone, and the number of loading cycles to induce the screw loosening was obtained and statistically correlated with bone mineral density. RESULTS: There was a positive correlation between the number of loading cycles to induce screw loosening and bone mineral density (R = 0.8, P < 0.01). The average number of loading cycles to induce screw loosening was significantly less for specimens with bone mineral density < 0.45 g/cm2 compared to those with bone mineral density > or = g/cm2. CONCLUSIONS: These findings suggest that bone mineral density may be a good predictor of anterior vertebral screw loosening. Bone mineral density < 0.45 g/cm2 may be critical value of loosening of the anterior vertebral body screw. However, further biomechanical and clinical studies are required before using threshold value clinically.     

Precision and accuracy of total body bone mass and body composition measurements in the rat using x-ray-based dual photon absorptiometry

Lean body mass (LBM), total body bone mineral mass (BMC), total body bone areal density (BMD), and body fat mass (FM) were measured in rats by dual photon absorptiometry (DXA), using two different instruments. The coefficients of variation for repeated measurements of LBM and FM were about 0.4 and 2.5%, respectively, over an animal body weight range of 150 to 600 g. For BMC and BMD, the coefficients of variation were less than 2%. The correlation coefficients for LBM, FM, BMC, and BMD measured on the two densitometers were all greater than 0.94. The slope of the regression line relating LBM measured by DXA and LBM measured by carcass analysis was 0.999, and the correlation coefficient was 0.99. For FM the slope was 1.05, and the correlation coefficient was 0.98. BMC measures by DXA were falsely low in small animals. For larger animals, the correlation between BMC and ash weight was 0.93, but the slope of the regression line was 0.78. DXA measures of LBM and FM were accurate and reproducible for rats weighing between 150 and 600 g. There was a size-dependent error in BMC, which will be significant in longitudinal measurements of bone mass.