Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures.

Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways.     

A case report and overview of organophosphate (OP) poisoning

A case of organophosphate (OP) poisoning who recovered after requiring almost 1000 mg of atropine, 10 gm of PAM and ventilatory support for 7 days is presented here. The overview of organophosphate poisoning and its management is given. With the approach adopted, the mortality reported in the general medicine unit in the central hospital in Nepal is 7.4%. The two important aspects of the management are vigilance of the atropine drip, especially at night, and other physical and psychological support care of the patients.     

Effect of air pollution on peak expiratory flow rate variability.

Exposure to air pollution affects pulmonary functions adversely. Effect of exposure to pollution on diurnal variation of peak flow was assessed in healthy students. Three hundred healthy age-matched nonsmoker students were studied. They were categorized into two groups on the basis of their residence: commuters and living on campus. Peak expiratory flow (PEF) recordings were made twice daily for 2 days with the Pink City Flow Meter. The measurement was then used to calculate for each subject the amplitude percentage mean, which is an index for expressing PEF variability for epidemiological purposes (Higgins BG, Britton JR, Chinns Jones TD, Jenkinson D, Burnery PG, Tattersfield AE. Distribution of peak expiratory flow variability in a population sample. Am Rev Respir Dis 1989; 140:1368-1372). Air pollution parameters were quantified by measurement of sulfur dioxide (SO2), oxides of nitrogen (NO2), carbon monoxide (CO), and respirable suspended particulate matter (RSPM) in the ambient air at the campus and on the roadside. The mean values of PEF variability (amplitude percent mean) in the students living on campus and in the commuters were 5.7 +/- 3.2 and 11 +/- 3.6, respectively (P < .05). Among the commuters, maximum number of subjects showed amplitude percentage mean PEFR at the higher end of variability distribution, as compared to the students living on campus, among whom the majority of subjects fell in the lower ranges of variability distribution. The ambient air quality parameters, namely SO2, NO2, CO, and RSPM were significantly lower on the campus. It can be concluded that long-term periodic exposure to air pollution can lead to increased PEF variability even in healthy subjects. Measurement of PEF variability may prove to be a simple test to measure effect of air pollution in healthy subjects.     

Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program Substudy.

OBJECTIVES: The purpose of this study was to determine quality of life (QOL) and exercise performance (EP) in patients with persistent atrial fibrillation (AF) converted to sinus rhythm (SR) compared with those remaining in or reverting to AF. BACKGROUND: Restoration of SR in patients with AF improving QOL and EP remains controversial. METHODS: Patients with persistent AF were randomized double-blind to amiodarone, sotalol, or placebo. Those not achieving SR at day 28 were cardioverted and classified into SR or AF groups at 8 weeks (n = 624) and 1 year (n = 556). The QOL (SF-36), symptom checklist (SCL), specific activity scale (SAS), AF severity scale (AFSS), and EP were assessed. RESULTS: Favorable changes were seen in SR patients at 8 weeks in physical functioning (p < 0.001), physical role limitations (p = 0.03), general health (p = 0.002), and vitality (p < 0.001), and at 1 year in general health (p = 0.007) and social functioning (p = 0.02). Changes in the scores for SCL severity (p = 0.01), functional capacity (p = 0.003), and AFSS symptom burden (p < 0.001) at 8 weeks and in SCL severity (p < 0.01) and AF symptom burden (p < 0.001) at 1 year showed significant improvements in SR versus AF. Symptomatic patients were more likely to have improvement. The EP in SR versus AF was greater from baseline to 8 weeks (p = 0.01) and to 1 year (p = 0.02). The EP correlated with physical functioning and functional capacity except in the AF group at 1 year. CONCLUSIONS: In patients with persistent AF, restoration and maintenance of SR was associated with improvements in QOL measures and EP. There was a strong correlation between QOL measures and EP.     

Decreased Risk of Renal Allograft Thrombosis Associated With Interleukin-2 Receptor Antagonists: A Report of the NAPRTCS

Graft thrombosis is the most common cause of first year graft failure in pediatric renal transplantation. The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database was analyzed for cases of graft failure due to thrombosis among patients transplanted from 1998 to 2004. The impact of interleukin-2 (IL-2) receptor antagonists as induction therapy was determined. There were a total of 51 graft failures due to thrombosis among the 2750 reported renal transplants (1.85%) (95% CI (1.39%, 2.41%)). This represents the most common cause of graft loss during the first year post-transplant accounting for 35% of first year losses and 18% of all graft losses. The incidence of thrombosis among patients who received IL-2 receptor antibodies was 1.07% (12/1126) compared to 2.40% (39/1624) among patients who did not (OR 0.44, 95% CI 0.23, 0.84, p = 0.014). Use of IL-2 receptor blockade was the only significant prognostic factor in a multivariate model with previously identified risk factors. Analysis of NAPRTCS data found that the use of IL-2 receptor antibodies as induction therapy is associated with a significantly decreased risk of graft failure due to thrombosis. This provocative finding requires further investigation to determine whether thrombotic failure can be decreased by this therapeutic strategy.     

An unusual case of mediastinal mass due to Fonsecaea pedrosoi.

Phaeohyphomycosis is a disease caused by dematiaceous fungi. Here, the first culture-proven case of mediastinal mass due to Fonsecaea pedrosoi is reported. The patient was a 40-yr-old male who had presented with history of dyspnoea and dysphagia. Computed tomography of the chest disclosed a mediastinal mass. Cultures of a specimen from the mediastinum grew Fonsecaea pedrosoi. The patient received amphotericin B and itraconazole and showed a remarkable recovery. Repeat computed tomography revealed a reduction in the mediastinal mass. The case highlights the need for a high degree of clinical suspicion and appropriate histopathological and mycological examination of clinical specimens.     

Leptomeninges as a site of relapse in locally controlled,diffuse pontine glioma with review of literature

Case report Leptomeningeal involvement in diffuse intrinsic brain stem gliomas is rarely diagnosed clinically and in majority of the instances diagnosed only on postmortem examination. We report two cases of diffuse pontine glioma diagnosed clinicoradiologically and treated with conventional radiotherapy.Observations On follow-up, both patients showed clinical features suggestive of meningeal spread although imaging for pontine tumor showed stable disease. Leptomeningeal disease in the spine was confirmed on imaging and in one case by cerebrospinal fluid examination also. During the follow-up of patients with pontine glioma, the possibility of leptomeningeal involvement must be borne in mind.