A phase HI comparative trial of tacrolimus- vs. cyclosporine-based graft-vs.-host disease (GVHD) prophylaxis for human leukocyte antigen (HLA)-identical sibling bone marrow transplantation showed ...less GVHD but poorer survival in the tacrolimus arm. To test the comparability of the two treatment arms with respect to baseline survival prognosis, a matched control study using exclusively cyclosporine-treated patients from the International Bone Marrow Transplant Registry (IBMTR) database was performed. Controls were matched (2:1) based on age (within 5 years), disease, and pretransplant disease status. Two-year survival for tacrolimus-treated clinical trial patients was similar to that of their cyclosporine-treated matched controls (27 and 24%, respectively), and 2-year survival of the cyclosporine-treated clinical trial patients was similar to that of their cyclosporine-treated matched IBMTR controls (42 and 45%, respectively). Consistent with the clinical trial results, the cyclosporine-treated IBMTR controls matched to the tacrolimus group had significantly poorer 2-year survival than the cyclosporine-treated IBMTR controls matched to the cyclosporine group (24 and 45%, respectively; p < 0.01). No significant difference was seen in GVHD between the cyclosporine-treated clinical trial patients and their matched controls; however, the tacrolimus-treated clinical trial patients had significantly less GVHD than their cyclosporine-treated IBMTR controls (p < 0.01). These results support the hypothesis that the survival difference in the phase III trial resulted from an imbalance in the underlying risk factors for death in the two groups rather than from the randomized immunosuppressive regimen.
Biol Blood Marrow Transplant 1999;5(3):180-6.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Epidemiological studies correlate adverse cardiovascular events with elevated exposure to ambient particulate matter, and reveal impairment of vasodilator mechanisms. The present study investigated ...the adenosine‐dependent vascular responsiveness of the thoracic aorta in a murine model which could exacerbate ischemic reperfusion injury following ultra fine particulate (UFPM) exposure. Mice were exposed to vehicle and 100 μg doses of UFPM by intratracheal instillation. 24 hrs later, aortas were isolated to evaluate vascular reactivity to adenosine. UFPM exposure increased the vasoconstrictor response of denuded thoracic aorta to 10 μM adenosine by nearly 50%. At 100 μM adenosine, the relaxation response of aorta from UFPM exposed animals was significantly impaired with a maximal relaxation of only 16%. UFPM exposure elevated constrictor response and sensitivity to the A1 receptor agonist CCPA. Minimal/moderate effects were observed with A2a or A3 receptor agonists NECA or CL‐IB‐MECA. UFPM exposure exaggerated the constrictor response to adenosine in aortas preincubated with the A3 receptor agonist MRS1523. These results are consistent with the hypothesis that particulate mater exposures can alter adenosine receptor activity in the vasculature. This of a proposed presentation does not necessarily reflect EPA policy.
Funding support impart by Phillip Morris US and International.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 0902 evaluated whether exercise and stress management training prior to hematopoietic cell transplantation (HCT) ...improved physical and mental functioning after HCT. Neither overall survival nor other patient-reported transplant outcomes were improved by the training intervention. In some animal studies of HCT, moderate intensity exercise for 8 weeks before HCT has been associated with positive effects on hematopoietic progenitors resulting in improved donor engraftment and improved survival. Accordingly, we performed a secondary analysis of data from BMT CTN 0902 to determine whether exercise engagement prior to HCT was associated with engraftment and survival. There were no significant associations between self-reported pre-HCT exercise levels and engraftment or survival. There was also no effect of pre-transplant exercise on either neutrophil or platelet engraftment. These findings do not support the observations in animal models but are limited by several shortcomings that do not refute the hypothesis that exercise before HCT may be beneficial.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The relationship between mental health status and longevity was examined in an archival prospective cohort study (
N
= 1,103) derived from work begun by Lewis Terman in the 1920s. Degree of ...psychological maladjustment, cumulatively rated by Terman and his colleagues as of 1950, was found to be related to higher risk of all-cause mortality over a 4-decade follow-up period. The differences among causes of death were nonsignificant, but there was some indication that mental health problems were more strongly related to deaths from injury and cardiovascular disease. The overall relationship was significant for men but weaker for women. The effect was not substantially mediated by alcohol consumption, obesity, or cigarette smoking.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Pairs of male Sprague-Dawley rats were administered mescaline, lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), 3,4-dimethoxyphenylethylamine (DMPEA), or 5-hydroxydopamine ...(5-OHDA) IP prior to being placed in a shock-elicited aggression situation. When foot shock was delivered, controls struck each other with their forepaws, but never engaged in either biting or injurious fighting. Mescaline-treated rats (50 or 250 mg) rarely struck each other, but engaged in nearly lethal biting. While LSD (25--400 micrograms/kg), psilocin (2.0 mg/kg), and DMT (5 mg/kg) produced some biting, this did not significantly differ from controls and never resulted in injuries. At higher doses, psilocin, DMT, and DMPEA decreased the amount and intensity of fighting. Rats treated with 5-OHDA (8--200 mg/kg) or LSD (25--400 micrograms/kg) did not differ from controls. These results suggest that mescaline's ability to induce pathological aggression in rats exposed to foot shock is not shared by other hallucinogens or nonhallucinogenic mescaline analogues.
BACKGROUND:Umbilical cord blood (UCB) is an acceptable source of hematopoietic cells for transplantation with success being associated with the nucleated cell count (NCC), CD34+ cells, and ...colony-forming unit-granulocyte-macrophage (CFU-GM) content infused. A total of 1033 UCB samples with neonatal and paternal characteristics that might influence hematopoietic content were examined. STUDY DESIGN AND METHODS:UCB samples were screened, processed, and reevaluated for the above cell counts. These parameters of engraftment potential were analyzed for associations with neonatal and parental characteristics. RESULTS:Postprocessed NCCs (median, 6.53 x 10 super(8) plus or minus 2.80 x 10 super(8) SD; mean 7.30 x 10 super(8)), CD34+ counts (median, 2.02 x 10 super(6) plus or minus 2.20 x 10 super(6) SD; mean, 2.65 x 10 super(6); r = 0.66; p < 0.001), and CFU-GM content (median, 2.65 x 10 super(5) plus or minus 3.16 x 10 super(5) SD; mean, 3.54 x 10 super(5); r = 0.61; p < 0.001) all were strongly interrelated. Both initial volume (median, 77.5 plus or minus 26.2 mL SD; mean, 81.9 mL) and initial NCC (median, 9.75 x 10 super(8) plus or minus 4.88 x 10 super(8) SD; mean, 10.9 x 10 super(8)) correlated well with postprocessed NCC (r = 0.60; r = 0.90; p < 0.01), CD34+ count (r = 0.40; r = 0.63; p < 0.01), and CFU-GM content (r = 0.38; r = 0.59; p < 0.01), with a stronger relationship seen with initial NCC. Infant birth weight (specifically, >3000 g), but not sex, gestational age, or cytomegalovirus status correlated strongly with collection volume and UCB cell counts. Units from minority volunteers contained relatively smaller volumes and hematopoietic content. CONCLUSION:UCB banks should emphasize selecting the heaviest infants and processing large-volume units with high NCCs to optimize hematopoietic potential. Minority recruitment should be encouraged with consideration given to inherent racial differences in cell counts. There does not appear to be a significant relationship between other neonatal and parental characteristics and that of engraftment potential.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Oral mucositis and hepatic veno-occlusive disease (HVOD) are common complications after bone marrow transplantation (BMT). Forty-seven patients were prospectively examined for development of ...ulcerative oral mucositis (UOM) and HVOD after allogeneic BMT. In 17 patients (36%) UOM developed between 2 days before and 18 days after transplant (median 4 days after BMT). In seven patients (15%) HVOD developed with onset between 3 and 21 days after transplant (median 18 days after BMT). In a time-dependent analysis, in patients given busulfan plus cyclophosphamide or busulfan, etoposide, and cyclophosphamide UOM was 19 times more likely to develop than in patients treated by cyclophosphamide plus total body irradiation or by cyclophosphamide alone (p less than 0.001). Patients in whom UOM developed were 6.5 times more likely to develop HVOD than those in whom UOM did not develop (p less than 0.03). The sensitivity (86%), specificity (73%), and negative predictive value (97%) of UOM to predict HVOD were high, but the positive predictive value (35%) was low. The association of UOM and HVOD support the concept that both are toxic effects of treatment. Patients with hepatic abnormalities but without UOM are unlikely to have HVOD, and other causes of the hepatic dysfunction should be investigated.
The aims of this study were to determine the extent to which hematopoietic cell transplantation (HCT) survivors adhere to the American Cancer Society recommendations for weekly physical activity and ...identify potential demographic and transplant characteristics associated with the lack of compliance.
This cross-sectional study included adults who had undergone HCT and were at least 1 year post transplantation. Physical activity was assessed using the screening tool of the Block 2014. The type of activity, frequency, and intensity were converted into the metabolic equivalent of task (MET) scores (0-499.0 MET min/week, inadequate activity; 500-1000 MET min/week, adequate activity; >1000 MET min/week, highly vigorous activity).
Participants (n = 81) reported a median MET score of 153 min/week, and 83% failed to reach the physical activity guideline of >500 MET min/week. Only 17.3% met the ACS recommendations, with three reporting above 1000 MET min/week. Median daily moderate and vigorous physical activity minute totals were 18.0 and 5.9 min/d, with 85.2% and 60.5% of participants involved, respectively. The median total physical activity energy expenditure was 744 kcal/d. Only race was associated with MET score, with Whites reporting higher MET scores.
Most HCT survivors assessed in this study did not meet the ACS physical activity recommendations. These findings reinforce the need to incorporate screening for physical activity into HCT survivorship care, offer counseling to those who do not meet the recommended levels, and encourage a physically active lifestyle among HCT survivors.
In 1986 the life expectancy at birth was 71.3 years for males and 78.3 years for females--providing a 7-year advantage for women. Although women live longer, it has been reported that they ...paradoxically experience more physical and psychological illnesses. In this article, we estimate the expected well-years or quality-adjusted life years for men and women in the general population. The data were obtained in a random sample of 1,034 residents of San Diego. The well-life expectancy uses standard life expectancies with adjustments for quality of life. The well-life expectancy for men was 59.8 years; for women, it was 62.7 years. Thus, the quality adjustment had significantly more impact on women (15.6 years) than on men (11.5 years). Age-specific estimates of health-related quality of life suggested a male advantage before age 45 and a female advantage after age 45. The benefits of well-years of life as a public health statistic are discussed.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
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