HRAS1-selected, chromosome-mediated transformants vary in phenotype in vitro and tumorigenic potential in vivo

Transfection of mouse C127 cells with mitotic chromosomes isolated from a human EJ bladder carcinoma cell line gave rise, at high frequency, to foci of transformed cells. Independent, HRAS1-selected chromosome-mediated transformants displayed distinctive cellular morphologies in monolayer culture and colony-forming abilities in low-melting-point agarose. Subcutaneous inoculation of neonatally thymectomized, Ara-C-protected, total-body-irradiated CBA mice was used to compare the tumorigenic potential of each transformant. Significant quantitative and qualitative differences in tumorigenicity were found between transformants which correlated with differences in malignant phenotype observed in vitro. The sensitivity of the tumorigenicity assay is such that rare transformation events can be selected directly in vivo.     

Evaluating the impact of human papillomavirus vaccines

While two prophylactic HPV vaccines have been proven notably efficacious in clinical trials, the effectiveness of these vaccines at the population level remains to be evaluated. To lay the foundation for understanding the strengths and limitations of different endpoints for future effectiveness research, we present a comprehensive review of HPV-related clinical outcomes, including: (i) HPV type-specific positivity and persistence, (ii) Pap diagnoses (ASC-US, LSIL, and HSIL), (iii) histologic cervical cancer precursor lesions (i.e., CIN1, CIN2, and CIN3), (iv) invasive cervical cancer (ICC), (v) anogenital warts, (vi) recurrent respiratory papillomatosis (RRP), and (vii) other HPV-associated cancers (vulvar, vaginal, anal, penile, and oropharyngeal). While research on the vaccines’ effects on these HPV clinical outcomes in the general population is presently limited, numerous large trials will soon be completed, making a priori discussion of these potential outcomes especially urgent. Furthermore, population level systems to track HPV-associated clinical outcomes may need to be developed for HPV vaccine effectiveness evaluation.     

Coronary artery fistula presenting as bacterial endocarditis

Coronary artery fistula is often considered to be a benign and rare congenital anomaly. It is usually an incidental finding encountered during routine cardiac catheterization. We report a case of a patient presenting with endocarditis involving a large coronary artery fistula connecting an aneurysmal circumflex coronary artery to the coronary sinus. The diagnosis was initially made by echocardiography and confirmed by cardiac catheterization. In addition, we briefly discuss the literature on management of this coronary anomaly.     

Three years of alendronate treatment results in similar levels of vertebral microdamage as after one year of treatment.

Three years of daily alendronate treatment increases microdamage in vertebral bone but does not significantly increase it beyond levels of microdamage found after 1 yr of treatment. This suggests microdamage accumulation peaks during the early period of bisphosphonate treatment and does not continue to accumulate with longer periods of treatment. INTRODUCTION: Clinically relevant doses of alendronate increase vertebral microdamage by 4- to 5-fold in skeletally mature beagles after 1 yr of treatment. The goal of this study was to determine whether microdamage would continue to accumulate with 3 yr of alendronate treatment in an intact beagle dog model. MATERIALS AND METHODS: One-year-old female beagles were treated with daily oral doses of vehicle (VEH, 1 ml/kg/d) or alendronate (ALN, 0.2 or 1.0 mg/kg/d) for 3 yr. These ALN doses were chosen to approximate, on a milligram per kilogram basis, those used to treat osteoporosis (ALN0.2) and Paget's disease (ALN1.0). Microdamage accumulation, static and dynamic histomorphometry, densitometry, and mechanical properties of lumbar vertebrae were assessed. Comparisons were made among the three groups treated for 3 yr and also within each treatment group to animals treated under the same conditions for 1 yr. RESULTS: Overall microdamage accumulation (crack surface density) was not significantly higher in animals treated for 3 yr with either dose of ALN, whereas crack density increased significantly (100%; p < 0.05) with the higher dose of ALN compared with VEH. Both ALN doses significantly suppressed the rate of bone turnover (-60% versus VEH). There was no difference among groups for any of the structural biomechanical properties-ultimate load, stiffness, or energy absorption. However, when adjusted for areal BMD, ALN-treated animals had significantly lower energy absorption (-20%) compared with VEH. Toughness, the energy absorption capacity of the bone tissue, was significantly lower than VEH for both ALN0.2 (-27%) and ALN1.0 (-33%). Compared with animals treated for 1 yr, there was no significant difference in microdamage accumulation for either ALN dose. VEH-treated animals had significantly lower bone turnover (-58%) and significantly higher levels of microdamage (+300%) compared with values in 1-yr animals. Toughness was significantly lower in animals treated for 3 yr with ALN1.0 (-18%) compared with animals treated for 1 yr, whereas there was no difference in toughness between the two treatment durations for either VEH or ALN0.2. CONCLUSIONS: Although 3 yr of ALN treatment resulted in higher microcrack density in vertebral trabecular bone compared with control dogs, the amount of microdamage was not significantly higher than animals treated for 1 yr with similar doses. This suggests that bisphosphonate-associated increases in microdamage occur early in treatment. Because toughness continued to decline significantly over 3 yr of treatment at the higher ALN dose, decreases in toughness are probably not dependent on damage accumulation.     

Screening for type 2 diabetes mellitus in children and adolescents: attitudes, barriers, and practices among pediatric clinicians.

OBJECTIVE: The American Diabetes Association (ADA) recommends screening children at risk for type 2 diabetes with a fasting plasma glucose test or an oral glucose tolerance test. The purpose of this study was to describe attitudes, barriers, and practices related to type 2 diabetes screening in children among pediatric clinicians. METHODS: Pediatricians, nurse practitioners and physician assistants from a multispecialty, group practice in Eastern Massachusetts completed a mailed survey. To assess screening practice, three vignettes were presented representing pediatric patients with low, moderately high, and high risk for type 2 diabetes. The moderately high-risk and high-risk patients met ADA criteria for screening. ADA-consistent practice was defined as only screening the moderately high-risk and high-risk patients; lower-threshold practice was defined as also screening the low-risk patient; and higher threshold practice was screening only the high-risk patient. RESULTS: Sixty-two of 90 clinicians responded (69%). Based on intent to screen in the 3 vignettes, 21% of respondents reported ADA-consistent screening practice, 39% lower-threshold, and 35% higher-threshold screening practice. Five percent had incomplete or nonclassifiable responses. Many clinicians ordered screening tests other than those recommended by the ADA; few (< or =8% in any vignette) ordered only an ADA-recommended test. Preferences for nonfasting tests were influenced by nonmedical factors such as access to or cost of transportation. Inadequate patient education materials and unclear recommendations for appropriate screening methods were the most frequently reported moderate/strong barriers to screening. CONCLUSIONS: Most respondents reported type 2 diabetes screening practices that differed from current ADA recommendations. Our findings suggest that type 2 diabetes screening tests must be practical for clinicians and patients if they are to be used in pediatric practice. Further study of the benefits and cost-effectiveness of type 2 diabetes screening in children is warranted to clarify the role and optimal methods for screening in pediatric primary care.     

A framework for systematically improving occupational therapy expert opinions on work capacity

Aim:  To present an evidence-based framework to improve the quality of occupational therapy expert opinions on work capacity for litigation, compensation and insurance purposes.
Methods:  Grounded theory methodology was used to collect and analyse data from a sample of 31 participants, comprising 19 occupational therapists, 6 medical specialists and 6 lawyers. A focused semistructured interview was completed with each participant. In addition, 20 participants verified the key findings.
Results:  The framework is contextualised within a medicolegal system requiring increasing expertise. The framework consists of (i) broad professional development strategies and principles, and (ii) specific strategies and principles for improving opinions through reporting and assessment practices.
Conclusions:  The synthesis of the participants' recommendations provides systematic guidelines for improving occupational therapy expert opinion on work capacity.     

Predictors, costs and characteristics of out of area placement for people with intellectual disability and challenging behaviour

Background Out of area placements for people with challenging behaviour represent an expensive and often ineffective strategy for meeting the needs of this service user group. Methods More than 800 agencies and service settings in a large area of South Wales were screened to identify children and adults with challenging behaviour against a number of defined operational criteria. Detailed data on identified individuals and the services they received were collected by interviewing key informants. Univariate and multivariate statistics were employed to identify predictors of out of area placement. Results In total, 1458 people were identified. Full data were available for 901 participants, 97 of whom were placed out of area. Predictors of out of area placement included behaviours resulting in physical injury and exclusion from service settings, a history of formal detention under the mental health act, the presence of mental health problems, a diagnosis of autism and higher total score on the Adaptive Behaviour Scale. Out of area placements were typically of high cost, and associated with only limited evidence of improved service quality. Conclusions Identifying predictors for out of area placement can be used to highlight deficiencies in local services and individuals at increased risk of exclusion from local services.