DS Ramsay  MI Bendersky  M Lewis 《Canadian Metallurgical Quarterly》1996,21(6):833-840

Biologic data on benzene metabolite doses, cytotoxicity, and genotoxicity often show that these effects do not vary directly with cumulative benzene exposure (i.e., concentration times time, or c x t). To examine the effect of an alternate exposure metric, we analyzed cell-type specific leukemia mortality in Pliofilm workers. The work history of each Pliofilm worker was used to define each worker's maximally exposed job/department combination over time and the associated long-term average concentration associated with the maximally exposed job (LTA-MEJ). Using this measure, in conjunction with four job exposure estimates, we calculated SMRs for groups of workers with increasing LTA-MEJs. The analyses suggest that a critical concentration of benzene exposure must be reached in order for the risk of leukemia or, more specifically, AMML to be expressed. The minimum concentration is between 20 and 60 ppm depending on the exposure estimate and endpoint (all leukemias or AMMLs only). We believe these analyses are a useful adjunct to previous analyses of the Pliofilm data. They suggests that (a) AMML risk is shown only above a critical concentration of benzene exposure, measured as a long-term average and experienced for years, (b) the critical concentration is between 50 and 60 ppm when using a median exposure estimate derived from three previous exposure assessments, and is between 20 and 25 ppm using the lowest exposure estimates, and (c) risks for total leukemia are driven by risks for AMML, suggesting that AMML is the cell type related to benzene exposure.  相似文献   

    

B Jones  D Teather  J Wang  JA Lewis 《Canadian Metallurgical Quarterly》1998,17(15-16):1767-77; discussion 1799-800

When a clinical trial is conducted at more than one centre it is likely that the true treatment effect will not be identical at each centre. In other words there will be some degree of treatment-by-centre interaction. A number of alternative approaches for dealing with this have been suggested in the literature. These include frequentist approaches with a fixed or random effects model for the observed data and Bayesian approaches. In the fixed effects model, there are two common competing estimators of the treatment difference, based on weighted or unweighted estimates from individual centres. Which one of these should be used is the subject of some controversy and we do not intend to take a particular methodological position in this paper. Our intention is to provide some insight into the relative merits of the indicated range of possible estimators of the treatment effect. For the fixed effects model, we also look at the merits of using a preliminary test for interaction assuming a 10 per cent significance level for the test. In order to make comparisons we have simulated a 'typical' trial which compares an active drug with a placebo in the treatment of hypertension, using systolic blood pressure as the primary variable. As well as allowing the treatment effect to vary between centres, we have concentrated on the particular case where one centre is out of line with the others in terms of its true treatment difference. The various estimators that result from the different approaches are compared in terms of mean squared error and power to reject the null hypothesis of no treatment difference. Overall, the approach that uses the fixed effects weighted estimator of overall treatment difference is recommended as one that has much to offer.  相似文献   

    

AD Elias  C Wheeler  LJ Ayash  G Schwartz  J Ibrahim  L Mills  M McCauley  N Coleman  D Warren  L Schnipper  KH Antman  BA Teicher  E Frei 《Canadian Metallurgical Quarterly》1998,4(6):1443-1449

Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7. Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0. Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses) and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated. Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain, predominantly in stocking glove distribution, occurring between day -3 and day 0, and a sensory peripheral neuropathy with similar distribution peaking around day +60. The maximal achievable dose of etanidazole (16 g/m2 dose level) resulted in a mean serum level of 38 micrograms/ml (25-55 micrograms/ml). Etanidazole significantly enhanced host toxicity of high-dose ICE. Effective modulatory doses of etanidazole could not be given with acceptable toxicity using this schedule.  相似文献   

    

RD Lewis  CM Modlesky 《Canadian Metallurgical Quarterly》1998,8(3):250-284

Calcium and vitamin D can significantly impact bone mineral and fracture risk in women. Unfortunately, calcium intakes in women are low and many elderly have poor vitamin D status. Supplementation with calcium (approximately 1000 mg) can reduce bone loss in premenopausal and late postmenopausal women, especially at sites that have a high cortical bone composition. Vitamin D supplementation slows bone loss and reduces fracture rates in late postmenopausal women. While an excess of nutrients such as sodium and protein potentially affect bone mineral through increased calcium excretion, phytoestrogens in soy foods may attenuate bone loss through estrogenlike activity. Weight-bearing physical activity may reduce the risk of osteoporosis in women by augmenting bone mineral during the early adult years and reducing the loss of bone following menopause. High-load activities, such as resistance training, appear to provide the best stimulus for enhancing bone mineral; however, repetitive activities, such as walking, may have a positive impact on bone mineral when performed at higher intensities. Irrespective of changes in bone mineral, physical activities that improve muscular strength, endurance, and balance may reduce fracture risk by reducing the risk of falling. The combined effect of physical activity and calcium supplementation on bone mineral needs further investigation.  相似文献   

    

BA Elliott 《Canadian Metallurgical Quarterly》1993,20(2):277-288

Primary care physicians can easily incorporate efforts toward the primary and secondary prevention of family violence into their practices. By designing a preventive effort using the phases of the family life cycle, a developmentally appropriate system of prevention is created. The anticipatory guidance at each (annual) visit acknowledges family transitions and assures the family that abuse is a health issue and that the physician is a resource for issues of violence prevention. Using the FLC, the first phase is Coupling, when there is a risk of partner violence that continues as long as there is a partnership. Pregnancy and childbirth bring concerns of child neglect and battery. Older children are at additional risk for child sexual abuse. As families age, risks develop for elder abuse, too. The regular discussion of these issues raises the awareness that the potential for family violence continues over the life span and allows the physician opportunities to assess the risk of violence in that family and make appropriate preventive referrals. Primary care physicians are optimally positioned to address violence and its prevention in the office: they know and care for family units over time. Physicians are respected and trusted advisors who can become effective in preventing violence.  相似文献   

    

AP Evan  DP Henry  BA Connors  P Summerlin  WH Lee 《Canadian Metallurgical Quarterly》1995,48(5):1517-1529

Immunocytochemistry, in situ hybridization, and radioimmunoassay were employed to examine the cellular distribution of mRNAs and proteins for IGF-I, II, IGF-II/M6P receptor, IGFBP2 as well as the levels of IGF-I and II in normal and unilaterally nephrectomized (Nx) adult rat kidneys. A similar distribution of immunoreactive IGF-I, and -II as well as IGF-II/M6P receptor was found in the principal cells of the cortical collecting duct and in all cells of the inner medullary collecting duct. In addition, immunostainable IGF-I and IGF-II/M6P receptor were noted in some inner medullary loops of Henle, while IGFBP2 was seen in the collecting ducts and loops of Henle of the inner medullar and the renal vasculature of all animals. By comparison, in situ hybridization revealed IGF-I mRNA only in the medullary thick ascending limbs while IGF-II mRNA was localized to the wall of the renal microvasculature in all kidneys. IGFBP2 mRNA was localized to the renal corpuscle and to inner medullary interstitial cells of all kidneys. These data suggest that renal IGF-I and IGFBP2 are synthesized at upstream sites along the nephron and then transported downstream for interaction with IGF receptors. Following nephrectomy, the renal levels of IGF-I peptide and mRNA were elevated at both 5 and 33 days post-nephrectomy, supporting a potential functional role for IGF-I in stimulating the structural and functional recovery in compensatory hypertrophy.  相似文献   

    

TM Penning  JE Pawlowski  BP Schlegel  JM Jez  HK Lin  SS Hoog  MJ Bennett  M Lewis 《Canadian Metallurgical Quarterly》1997,62(5):455-456

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Lewis L. Osborne  Ronald W. Davies 《Water research》1987,21(8):913-921

Physico-chemical and biological samples were collected from 12 sampling stations over a 13-month period to assess the effects of a small town's chlorinated sewage discharge and a thermal discharge on the Sheep River's macroinvertebrate communities. During the study, the chlorinated effluent plume was restricted to the left third of the channel for approx. 0.5 km at which point the effluent was thoroughly mixed due to an abrupt change in channel direction. Within the concentrated 0.5 km chlorinated plume, total residual chlorine TRC concentrations periodically exceeded 5.0 mg l⁻¹. Stations were categorized into similar community assemblages on the basis of species abundance and composition using heirarchical cluster analysis. Stations immediately downstream of the thermal outfall and those within the chlorinated plume had distinctly different structure and were dominated by Oligochaeta. Multiple discriminant analysis indicated that temperature was the principle discriminating variable immediately below the thermal discharge while the chlorinated sewage (MCSE) variable was the most important discriminant function within the chlorinated effluent plume. Following complete mixing of the effluent plume within the stream channel (0.6 km downstream of outfall), macroinvertebrate structure and diversity improved, presumably due to nutrient enrichment and dilution of TRC below detectable levels.  相似文献   

    

SF Lewis  NM Jensen 《Canadian Metallurgical Quarterly》1996,11(9):542-544

Although screening sigmoidoscopy (SS) reduces colorectal cancer mortality, surveys indicate that fewer than half of primary care physicians routinely recommend SS and less than 10% of eligible patients receive this test. The purpose of this study was to explore barriers to compliance with SS through a cross-sectional survey of general medicine patients. Clinician advice, perceived benefit of the test, and having a family member who has had the test are associated with SS, while perceived pain is a barrier to compliance and can negate the positive effects of clinician advice. These factors can be targeted as part of efforts to improve compliance with SS.  相似文献   

    

AN Elgamasy  V Lewis  ME Hassouna  GM Ghoniem 《Canadian Metallurgical Quarterly》1996,16(4):127-130

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