What are we trying to measure? Rethinking approaches to health outcome assessment for the older person with cancer

The health burden of cancer within the older population is well recognized. For many of these patients, interventions and treatments will focus predominantly on improvements in health outcomes. There has been substantial interest in the development and application of health outcome assessments for use in cancer patients, yet in comparison, there has been less focus on the older person with cancer. This paper will review current perspectives on health outcome assessment in older people with cancer; the methodological challenges associated with this work and present recommendations for future work, including the potential application of a 'user-generated' approach to health outcome assessment in the older person with cancer.     

Brain injury case management: the potential and limitations of late-stage intervention--a pilot study

The focus of this study was to be upon case management intervention with the longer-term, often insidious cognitive and behavioural problems of brain injured patients, to effect a cohesive response towards improvement of function and social/community reintegration. Ten 'in depth' case management studies were developed. Age, sex, cause of injury, time post-injury, nature of brain injury,sequelae-and consequent intervention-differed widely. Three studies are précised in this paper. There was no attempt to match or compare such a diverse group, each was accepted on the basis of need and potential benefit. Available information for each was studied. Field assessment was by the case manager who then engaged whatever appropriate resources could be mustered on behalf of the individual client. For some, this permitted access to funding for further assessments or specific inputs, for others there was nothing available other than existing statutory or voluntary agencies. For field assessment purposes, the case manager developed informal ratings of a range of disabilities within the cognitive and behavioural realms and the handicaps resulting. The assessments and nature of interventions are described, discussed and conclusions offered.     

Human squamous cell carcinomas lose a mortality gene from chromosome 6q14.3 to q15

Normal human keratinocytes possess a finite replicative lifespan. Most advanced squamous cell carcinomas (SCCs), however, are immortal, a phenotype that is associated with p53 and INK4A dysfunction, high levels of telomerase and loss of heterozygosity (LOH) at several genetic loci, suggestive of the dysfunction of other mortality genes. We show here that human chromosome 6 specifically reduces the proliferation or viability of a human SCC line, BICR31, possessing LOH across the chromosome. This was determined by an 88% reduction in colony yield (P<0.001), following the reintroduction of an intact normal chromosome 6 by monochromosome transfer. Deletion analysis of immortal segregants using polymorphic markers revealed the loss of a 2.9 Mbp interval, centred on marker D6S1045 at 6q14.3-q15, in 6/19 segregants. Crucially, allelic losses of this region were not identified in control hybrids constructed between chromosome 6 and the BICR6 SCC cell line that is heterozygous for chromosome 6 and which showed no reduction in colony formation relative to the control chromosome transfers. This indicates that the minimally deleted region at D6S1045 is not the result of fragile sites, a recombination hot spot, or a feature of the monochromosome transfer technique. LOH of D6S1045 was found in 2/9 immortal SCC lines and was part of a minimally deleted region of line BICR19. Furthermore, allelic imbalance, consistent with LOH, was detected in 3/17 advanced SCCs of the tongue. These results suggest the existence of a suppressor of SCC immortality and tumour development at chromosome 6q14.3-q15, which is important to a subset of human SCCs.     

Combined effects of insulin-like growth factor-1 and transforming growth factor-beta1 on periosteal mesenchymal cells during chondrogenesis in vitro

OBJECTIVE: Periosteum contains undifferentiated mesenchymal stem cells that have both chondrogenic and osteogenic potential, and has been used to repair articular cartilage defects. During this process, the role of growth factors that stimulate the periosteal mesenchymal cells toward chondrogenesis to regenerate articular cartilage and maintain its phenotype is not yet fully understood. In this study, we examined the effects of insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta1 (TGF-beta1), alone and in combination, on periosteal chondrogenesis using an in vitro organ culture model. METHODS: Periosteal explants from the medial proximal tibia of 2-month-old rabbits were cultured in agarose under serum free conditions for up to 6 weeks. After culture the explants were weighed, assayed for cartilage production via Safranin O staining and histomorphometry, assessed for proliferation via proliferative cell nuclear antigen (PCNA) immunostaining, and assessed for type II collagen mRNA expression via in situ hybridization. RESULTS: IGF-1 significantly increased chondrogenesis in a dose-dependent manner when administered continuously throughout the culture period. Continuous IGF-1, in combination with TGF-beta1 for the first 2 days, further enhanced overall total cartilage growth. Immunohistochemistry for PCNA revealed that combining IGF-1 with TGF-beta1 gave the strongest proliferative stimulus early during chondrogenesis. In situ hybridization for type II collagen showed that continuous IGF-1 maintained type II collagen mRNA expression throughout the cambium layer from 2 to 6 weeks. CONCLUSION: The results of this study demonstrate that IGF-1 and TGF-beta1 can act in combination to regulate proliferation and differentiation of periosteal mesenchymal cells during chondrogenesis.     

Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients

The relationship between the dose of tacrolimus, trough tacrolimus blood concentration, and selected clinical endpoints (acute rejection, nephrotoxicity, and other toxicities) were examined in a prospective, multicenter clinical trial to validate the use of an enzyme-linked immunosorbent assay (ELISA) for monitoring whole-blood concentrations of tacrolimus in liver transplant patients. A total of 111 subjects from six transplant centers were evaluated over 12 weeks posttransplantation. In addition to trough tacrolimus blood concentrations, hematocrit, ALT, AST, GGTP, alkaline phosphatase, total bilirubin, serum creatinine, BUN, serum potassium, serum magnesium, blood glucose, and serum albumin were also measured. The relationship between trough tacrolimus blood concentrations and clinical endpoints was analyzed using both a logistic regression model and a Cox proportional hazard model. By logistic regression analysis, a statistically significant (p = 0.0465) relationship between increasing trough tacrolimus blood concentrations and decreasing risk of acute rejection was demonstrated over a 7-day time window. Nephrotoxicity and other toxicities also demonstrated statistically significant relationships with trough tacrolimus blood concentrations. The results of the Cox analysis were consistent with the logistic regression analysis. Using receiver operator characteristic curves, trough tacrolimus concentrations as measured by the ELISA method were able to differentiate the occurrence of nephrotoxicity and toxicity from nonevents. To minimize nephrotoxicity of tacrolimus, it is necessary to maintain trough blood concentrations below 15 ng/ml. This study demonstrates that the ELISA method used to measure tacrolimus blood concentrations in this study provides information of predictive value for managing the risk of nephrotoxicity, other toxicity, and rejection in liver transplant patients.     

The association of socioeconomic status with outcomes in cystic fibrosis patients in the United States

There is considerable variability in the clinical course of disease in cystic fibrosis (CF). Although currently unidentified modifier genes might explain some of this heterogeneity, other factors are probably contributory. Socioeconomic status (SES) is an important predictor of health status in many chronic polygenic diseases, but its role in CF has not been systematically evaluated. We performed a historical cohort analysis of pediatric CF patients in the United States using National Cystic Fibrosis Foundation Patient Registry (NCFPR) data for 1986 to 1994, and used Medicaid status as a proxy for low SES. The adjusted risk of death was 3.65 times higher (95% confidence interval [CI]: 3.03 to 4.40) for Medicaid patients than for those not receiving Medicaid. The percent predicted FEV(1) of surviving Medicaid patients was less by 9.1% (95% CI: 6.9 to 11.2). Medicaid patients were 2.19 times more likely to be below the 5th percentile for weight (95% CI: 1.91 to 2.51) and 2.22 times more likely to be below the 5th percentile for height (95% CI: 1.95 to 2.52) than were non-Medicaid patients. Medicaid patients were 1.60 times more likely to require treatment for a pulmonary exacerbation (95% CI: 1.29 to 1.98). There was no difference in the number of outpatient clinic visits for Medicaid and non-Medicaid patients. We conclude that low SES is associated with significantly poorer outcomes in children with CF. Barriers in access to specialty health care do not seem to explain this difference. Further study is indicated to determine what adverse environmental factors might cluster in CF patients of low SES to cause worse outcomes.     

氯喹对烟雾吸入伤大鼠肺细胞膜ATP酶活性和丙二醛含量的影响

目的：探讨氯喹对烟雾吸入伤大鼠肺细胞膜ＡＴＰ酶活性及丙二醛含量的影响,方法：８０只Ｗｉｓｔａｒ大鼠随机分成正常对照组,烟雾吸入伤１,３,６,１２和２４ｈ组以及氯喹治疗６ｈ和１２ｈ组,分别于各时相点活杀动物,取肺制备膜制剂,用生化比色法测定膜上Ｎａ＾＋,Ｋ＾＋－ＡＴＰ酶Ｍｇ＾２＋－ＡＴＰ酶和Ｃａ＾２＋－ＡＴＰ酶活性,用比色法测定膜上丙醛含量,并用定磷法测定膜总磷脂含量,结果：烟雾吸入伤后,肺细胞膜３     

An empirical assessment of the migraine personality type

The notion of a specific, measurable migraine personality type was empirically tested through the administration of the Jackson Personality Inventory (JPI) on 125 (103 female and 22 male) migraine subjects drawn from a biofeedback treatment/research project. A significant different (p less than 0.01) was identified between this group and the test norms on a simultaneous comparison of all 15 JPI variables (Hotelling T2 test). This difference was isolated along five variables (lower scores on the measures of Complexity, Risk Taking, and Social Participation and higher scores on the Responsibility and Value Orthodoxy scales). A post hoc profile analysis comparison of the female and male subjects revealed only a trend toward significance on one test, thereby supporting the assumption of no sex differences. While these findings are in line with some of the migraine personality literature support for many characteristics was not found (i.e. for the trait of anxiety).     

Simple overlay device for determining radial head and neck height

Background  

The purpose of this study was to test the hypothesis that a simple overlay device can be used on radiographs to measure radial head and neck height.     

The effect of hepatic enzyme inducers on busulfan neurotoxicity and myelotoxicity

Summary Anticonvulsants are commonly used empirically to prevent seizures in patients receiving high-dose busulfan in preparation for bone marrow transplantation. This study evaluates the effects of two anticonvulsants with enzyme-inductive properties, phenytoin and phenobarbital, and an enzyme inducer without anticonvulsant properties, Aroclor 1254, on the myelotoxicity and acute neurotoxicity of busulfan in a murine model. To assess the neuroprotective effects of these agents, we studied the effects of a single dose of 100 mg/kg i.p. busulfan, previously shown in this model to be uniformly lethal due to neurotoxicity. A significantly greater proportion of mice survived when pretreated with phenytoin or phenobarbital as compared with Aroclor 1254 pretreatment or an untreated control group. Busulfan myelotoxicity was studied in another group of mice treated with 135–150 mg/kg given in divided doses over 6 days. The proportion of animals surviving the otherwise myeloablative effects of this regimen were significantly improved by Aroclor 1254, high-dose phenytoin, and phenobarbital pretreatment. We conclude that anticonvulsants offer protection from the acute neurotoxicity of busulfan. However, these enzyme-inducing agents may reduce the myelosuppresive effects as well. These results suggest than an inducible enzyme system such as microsomal or glutathione S-transferases plays an important role in busulfan metabolism, warranting concern over concomitant administration of agents that either induce or inhibit these enzymes.