Mapping a locus for susceptibility to HIV-1-associated nephropathy to mouse chromosome 3

HIV-1-associated nephropathy (HIVAN) is a major complication of HIV-1 infection with distinct pathologic features. Introduction of the HIV-1 genome into mice results in a renal disease with all of the histologic and clinical hallmarks of HIVAN on the FVB/N genetic background (TgFVB). We assessed the influence of genetic background on the development or progression of HIVAN by making F1 hybrids of TgFVB with five other inbred strains (CBA, DBA/2, CAST/Ei, C3H/He, BALB/c) and determining phenotypes relevant to renal failure among transgenic offspring (histology, blood urea nitrogen, proteinuria, serum albumin, and serum cholesterol). We found striking variation in phenotypes among F1s, ranging from severe renal disease to no renal disease whatsoever (P<0.001 for ANOVA across all groups). To map genes responsible for this variation, we produced a backcross of TgFVB/CAST F1 x TgFVB. By genome-wide analysis of linkage in 185 heterozygous transgenic backcross mice, we identified a locus on chromosome 3A1-3, HIVAN1, that showed highly significant linkage to renal disease [logarithm of odds (lod) score 4.9 at D3Mit203, accounting for 15% of the variance in renal disease]. Other loci on chromosomes 11, 14, and 16 were suggestive of linkage to renal disease, and a locus on chromosome 9 influenced serum cholesterol but not nephropathy. Interestingly, HIVAN1 is syntenic to human chromosome 3q25-27, an interval showing suggestive evidence of linkage to various nephropathies. These findings demonstrate a strong genetic influence on HIVAN and demonstrate a major renal disease susceptibility locus on mouse chromosome 3A1-3.     

WHO-ILAR COPCORD study (stage 1, urban study) in Sanandaj,Iran

Clinical Rheumatology - This study aims to conduct an urban Community Oriented Program for Control Of Rheumatic Diseases (COPCORD) study in Sanandaj (Kurdistan, Iran). Sanandaj with a population of...     

The Metastatic Spine Disease Multidisciplinary Working Group Algorithms

The Metastatic Spine Disease Multidisciplinary Working Group consists of medical and radiation oncologists, surgeons, and interventional radiologists from multiple comprehensive cancer centers who have developed evidence- and expert opinion-based algorithms for managing metastatic spine disease. The purpose of these algorithms is to facilitate interdisciplinary referrals by providing physicians with straightforward recommendations regarding the use of available treatment options, including emerging modalities such as stereotactic body radiation therapy and percutaneous tumor ablation. This consensus document details the evidence supporting the Working Group algorithms and includes illustrative cases to demonstrate how the algorithms may be applied.

Implications for Practice:

The Metastatic Spine Disease Multidisciplinary Working Group algorithms can facilitate interdisciplinary referrals by providing physicians with straightforward recommendations regarding available treatment options, including emerging modalities such as stereotactic body radiation therapy and percutaneous tumor ablation.     

Role of dietary therapies in the prevention and treatment of hypertension

Blood pressure naturally rises with increasing age. The rate of change in blood pressure with age is regulated in part by genetic factors, but can also be altered through sustained dietary modification. Dietary approaches to modify blood pressure remain an important part of cardiovascular health promotion, which is especially important given the aging of the general population coupled with the increasing prevalence of obesity and metabolic disturbances. Specific modification of dietary components such as macronutrients and micronutrients could be helpful to lower blood pressure and alter the slope of blood pressure change whereas nutritional supplements are less likely to have a substantial beneficial effect. Population-wide generalizations regarding diet are impractical as individualized strategies are more likely to be successful in facilitating long-term benefits in improving blood-pressure control. Consequently, more effort needs to be focused on evaluating data from large-scale observational and interventional studies and interpreting their information in a clinically relevant manner, which is likely to be helpful for individual patients. Providing education on the relationship between diet and blood pressure from an early age is most likely to produce tangible benefits.     

Inter-examiner reliability of diplomats in the mechanical diagnosis and therapy system in assessing patients with shoulder pain

Objective:

To investigate the inter-examiner reliability of Mechanical Diagnosis and Therapy (MDT)-trained diplomats in classifying patients with shoulder disorders. The MDT system has demonstrated acceptable reliability when used in patients with spinal disorders; however, little is known about its utility when used for appendicular conditions.

Methods:

Fifty-four clinical scenarios were created by a group of 11 MDT diploma holders based on their clinical experience with patients with shoulder pain. The vignettes were made anonymous, and their clinical diagnoses sections were left blank. The vignettes were sent to a second group of six international McKenzie Institute diploma holders who were asked to classify each vignette according to the MDT categories for upper extremity. Inter-examiner agreement was evaluated with kappa statistics.

Results:

There was ‘very good’ agreement among the six MDT diplomats for classifying the McKenzie syndromes in patients with shoulder pain (kappa = 0.90, SE = 0.018). The raw overall level of multi-rater agreement among the six clinicians in classifying the vignettes was 96%. After accounting for the actual MDT category for each vignette, kappa and the raw overall level of agreement decreased negligibly (0.89 and 95%, respectively).

Discussion:

Using clinical vignettes, the McKenzie system of MDT has very good reliability in classifying patients with shoulder pain. As an alternative, future reliability studies could use real patients instead of written vignettes.