Shaping Skeletal Growth by Modular Regulatory Elements in the Bmp5 Gene

Cartilage and bone are formed into a remarkable range of shapes and sizes that underlie many anatomical adaptations to different lifestyles in vertebrates. Although the morphological blueprints for individual cartilage and bony structures must somehow be encoded in the genome, we currently know little about the detailed genomic mechanisms that direct precise growth patterns for particular bones. We have carried out large-scale enhancer surveys to identify the regulatory architecture controlling developmental expression of the mouse Bmp5 gene, which encodes a secreted signaling molecule required for normal morphology of specific skeletal features. Although Bmp5 is expressed in many skeletal precursors, different enhancers control expression in individual bones. Remarkably, we show here that different enhancers also exist for highly restricted spatial subdomains along the surface of individual skeletal structures, including ribs and nasal cartilages. Transgenic, null, and regulatory mutations confirm that these anatomy-specific sequences are sufficient to trigger local changes in skeletal morphology and are required for establishing normal growth rates on separate bone surfaces. Our findings suggest that individual bones are composite structures whose detailed growth patterns are built from many smaller lineage and gene expression domains. Individual enhancers in BMP genes provide a genomic mechanism for controlling precise growth domains in particular cartilages and bones, making it possible to separately regulate skeletal anatomy at highly specific locations in the body

Analysis of a Panel of 48 Cytokines in BAL Fluids Specifically Identifies IL-8 Levels as the Only Cytokine that Distinguishes Controlled Asthma from Uncontrolled Asthma, and Correlates Inversely with FEV1

We sought to identify cells and cytokines in bronchoalveolar lavage (BAL) fluids that distinguish asthma from healthy control subjects and those that distinguish controlled asthma from uncontrolled asthma. Following informed consent, 36 human subjects were recruited for this study. These included 11 healthy control subjects, 15 subjects with controlled asthma with FEV1≥80% predicted and 10 subjects with uncontrolled asthma with FEV1 2.4%) were a higher BAL fluid IL-8 levels, and a lower FEV1 in the latter group. By contrast, compared to eosinophil-normal asthma (eosinophils≤0.3%), eosinophil-high asthma (eosinophils>0.3%) had higher levels of IL-5, IL-13, IL-16, and PDGF-bb, but same neutrophil percentage, IL-8, and FEV1. Our results identify neutrophils and IL-8 are the only inflammatory components in BAL fluids that distinguish controlled asthma from uncontrolled asthma, and both correlate inversely with FEV1

The epidemiology of total hip replacement in the Netherlands and Sweden - Present status and future needs

By combining data from the Discharge registers and the census bureaus in The Netherlands and Sweden, we calculated the age-specific incidences of primary total hip replacement (THR), studied the demographic profile of the population receiving THR and predicted demands. In the period 1986-1997, the number of THRs increased by 20% in Sweden to 10,000 operations (1131100,000 inhabitants) and by 68% to 17,400 operations (112/100,000 inhabitants) in The Netherlands. Of this increase 3% and 15% could be explained by changes in the age-profile and size of the population, respectively. Although the overall incidence of THR was similar in both countries in 1997, we found that, after correction for differences in population structure, the incidence of THR was 20% higher in The Netherlands. In Sweden, relatively more men were operated on than in The Netherlands. We also found that in Sweden, but not in the Netherlands, relatively more older people were operated on in 1997 than in 1987. Assuming no further change in the age- and sex-specific arthroplasty rates, the predicted annual number of total hip replacements by the year 2020 will increase by at least one fourth in Sweden and almost one half in The Netherlands

Clinical benefit of joint distraction in the treatment of severe osteoarthritis of the ankle

Objective. Osteoarthritis, (OA) is a degenerative, disabling joint disease that affects >10% of the adult population. No effective disease-modifying treatment is available. In the present study, we used joint distraction, a relatively new treatment in Which mechanical contact between the articular surfaces is avoided while intraarticular intermittent fluid pressure is maintained, to treat patients with severe OA of the ankle. Methods. Patients with severe ankle OA (n = 57) who were being considered for joint fusion (arthrodesis) were treated with joint distraction in an open prospective study. In addition, a randomized trial was performed in 17 patients to determine whether joint distraction had a better outcome than debridement. A standardized evaluation protocol (physical examination, assessment of pain, mobility, and functional ability) was used, and changes in radiographic joint space width and subchondral sclerosis were measured. Thirty-eight patients in the open study have been followed up for >1 year, with up to 5 years of followup in 7 of them (mean +/- SD followup 2.8 +/- 0.3 years). Patients in the randomized study have been followed up for 1 year. Results. Significant clinical benefit was found in three-fourths of the 57 patients in the open prospective study. Most interestingly, the improvement increased over time. Radiographic evaluation showed increased joint space width and decreased subchondral sclerosis. Moreover, joint distraction showed significantly better results than debridement. Conclusion. The clinical benefit of joint distraction in the treatment of severe OA is proof of the concept. Although the followup remains relatively short and effects over time remain unpredictable, our study creates possibilities for the treatment of severe OA in general. Considering the high prevalence of OA and the lack of a cure for it, joint distraction as a treatment of severe OA may have great medical, social, and economic impact