Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long-Term Outcomes.

Interstitial fibrosis and tubular atrophy (IFTA) is found in approximately 25% of 1-year biopsies posttransplant. It is known that IFTA correlates with decreased graft survival when histological evidence of inflammation is present. Identifying the mechanistic etiology of IFTA is important to understanding why long-term graft survival has not changed as expected despite improved immunosuppression and dramatically reduced rates of clinical acute rejection (AR) (Services UDoHaH. http://www.ustransplant.org/annual_reports/current/509a_ki.htm). Gene expression profiles of 234 graft biopsy samples were obtained with matching clinical and outcome data. Eighty-one IFTA biopsies were divided into subphenotypes by degree of histological inflammation: IFTA with AR, IFTA with inflammation, and IFTA without inflammation. Samples with AR (n = 54) and normally functioning transplants (TX; n = 99) were used in comparisons. A novel analysis using gene coexpression networks revealed that all IFTA phenotypes were strongly enriched for dysregulated gene pathways and these were shared with the biopsy profiles of AR, including IFTA samples without histological evidence of inflammation. Thus, by molecular profiling we demonstrate that most IFTA samples have ongoing immune-mediated injury or chronic rejection that is more sensitively detected by gene expression profiling. These molecular biopsy profiles correlated with future graft loss in IFTA samples without inflammation.

Overweight and obesity associated with a missense polymorphism in fatty acid amide hydrolase (FAAH).

BACKGROUND: The brain endogenous cannabinoid system modulates reward and craving pathways and consequently may affect body weight. A naturally occurring missense polymorphism in the gene encoding fatty acid amide hydrolase (FAAH), the primary enzyme for inactivation of endocannabinoids, is associated with problem drug use. AIMS: To investigate the relationship between the FAAH cDNA 385 A/A (P129T) polymorphism and overweight disorders in subjects of multiple ethnic backgrounds attending a medical screening clinic. SUBJECTS: A total of 2667 subjects of white, black and Asian ancestry were genotyped and stratified by a standardized clinic-based assessment of body mass index (BMI, weight in kilograms/(height in meters)(2) or kg/m(2)). METHODS: Subjects were genotyped for the FAAH cDNA 385 C --> A polymorphism using allele-specific oligonucleotide hybridization methods by investigators blinded to all clinical information. BMI was calculated based on exact clinical measurements and World Health Organization ranges were used to stratify subjects. Statistical methods included the Fisher exact test, Mann-Whitney U-test and multivariable logistic regression analysis. RESULTS: The homozygous FAAH 385 A/A genotype was significantly associated with overweight and obesity in white subjects (P=0.005) and in black subjects (P=0.05) but not in a small group of Asians. The median BMI for all subjects was significantly greater in the FAAH 385 A/A genotype group compared to heterozygote and wild-type groups (P=0.0001). In white subjects, there was an increasing frequency of the FAAH 385 A/A genotype with increasing BMI categories of overweight (P=0.02) and obese (P=0.006) with the same trend in black subjects. CONCLUSIONS: These results suggest a role for the FAAH 385 A/A missense polymorphism as an endocannabinoid risk factor in overweight/obesity and may provide indirect evidence to support cannabinoid antagonist treatment strategies in overweight disorders.

Factor analytic properties of the Quality of Life Profile: examination of the nine subdomain Quality of Life Model.

The Quality of Life Profile is a 54-item multidimensional measure of quality of life. The measure is based upon a theoretical approach that considers quality of life to include satisfaction with nine subdomains of functioning. To date, the factor structure of this 54-item collection has not been examined. To do so, an examination was made of the factor structure that emerged from an administration to 219 gay men, half of whom were HIV+. Analysis indicated that seven subdomains were clearly represented in seven of the 11 factors that emerged. One subdomain was fractured into two factors and one subdomain did not appear in the factor structure. Two minor factors appeared to represent issues that may be especially important to gay men living in the HIV era. The study provides insights into the structure of quality of life among gay men living in Ontario.

Screening for intimate partner violence by health care providers. Barriers and interventions.

INTRODUCTION: Routine screening for intimate partner violence (IPV) is endorsed by numerous health professional organizations. Screening rates in health care settings, however, remain low. In this article, we present a review of studies focusing on provider-specific barriers to screening for IPV and interventions designed to increase IPV screening in clinical settings. METHODS: A review of published studies containing original research with a primary focus on screening for IPV by health professionals was completed. RESULTS: Twelve studies identifying barriers to IPV screening as perceived by health care providers yielded similar lists; top provider-related barriers included lack of provider education regarding IPV, lack of time, and lack of effective interventions. Patient-related factors (e.g., patient nondisclosure, fear of offending the patient) were also frequently mentioned. Twelve additional studies evaluating interventions designed to increase IPV screening by providers revealed that interventions limited to education of providers had no significant effect on screening or identification rates. However, most interventions that incorporated strategies in addition to education (e.g., providing specific screening questions) were associated with significant increases in identification rates. CONCLUSION: Barriers to screening for IPV are documented to be similar among health care providers across diverse specialties and settings. Interventions designed to overcome these barriers and increase IPV-screening rates in health care settings are likely to be more effective if they include strategies in addition to provider education.

Acitretin in psoriasis: an overview of adverse effects.

Oral retinoids are among the drugs of choice for pustular and erythrodermic psoriasis. In addition, retinoids are effective in combination with other topical and systemic agents for the treatment of plaque-type psoriasis. Acitretin, the active retinoid metabolite, has replaced etretinate in retinoid therapy of psoriasis because of its more favorable pharmacokinetic profile, including a significantly shorter half-life. Retinoids, including acitretin, are potent teratogens, leading to strict requirements for pregnancy prevention during and after their use. Other retinoid side effects are generally preventable or manageable through proper patient selection, dose adjustments, and routine monitoring. Mucocutaneous side effects such as cheilitis and hair loss are the most common dose-dependent side effects, requiring dose reduction in some patients. Less common effects such as hepatotoxicity, serum lipid alterations, pancreatitis, and possible skeletal effects are also discussed.

Psychometric properties of the neck disability index.

OBJECTIVES: To determine if a response set bias existed, to assess the factor structure and internal consistency, and to compare Neck Disability Index (NDI) scores with visual analogue scale (VAS) scores for pain intensity. SUMMARY OF BACKGROUND DATA: Although neck pain is a common problem, few instruments exist to assess the disability that accompanies it. The NDI is a 10 item paper-and-pencil measure of disability resulting from neck pain. STUDY DESIGN: A cross sectional study evaluating the psychometric properties of the NDI. METHODS: Seven modified versions of the original NDI were developed to assess the presence or absence of response set bias using a one-way analysis of variance. Internal consistency was measured by a Cronbach alpha, two factor analyses (exploratory and confirmatory) were conducted to examine the structure of the NDI and stepwise regression analysis was used to examine the variables most predictive of VAS scores. RESULTS: Results from 237 neck pain patients show that the responses given on the eight versions of the NDI are a function of the content and not of the format in which the items are presented. The NDI has stable psychometric characteristics, evidenced by high internal consistency (alpha = .92). In both factor analyses, one factor was extracted. CONCLUSIONS: The NDI possesses stable psychometric properties and provides an objective means of assessing the disability of patients suffering from neck pain.