Citations

Objectives: To assess the clinical effectiveness of Low Level Laser Therapy (LLLT) in the treatment of tendinopathy. Secondary objectives were to determine the relevance of irradiation parameters to outcomes, and the validity of current dosage recommendations for the treatment of tendinopathy. Background: LLLT is proposed as a possible treatment for tendon injuries. However, the clinical effectiveness of this modality remains controversial, with limited agreement on the most efficacious dosage and parameter choices. Method: The following databases were searched from inception to 1 st August 2008: MEDLINE, PubMed, CINAHL, AMED, EMBASE, All EBM reviews, PEDro (Physiotherapy Evidence Database), SCOPUS. Controlled clinical trials evaluating LLLT as a primary intervention for any tendinopathy were included in the review. Methodological quality was classified as: high (≥6 out of 10 on the PEDro scale) or low (<6) to grade the strength of evidence. Accuracy and clinical appropriateness of treatment parameters were assessed using established recommendations and guidelines. Results: Twenty-five controlled clinical trials met the inclusion criteria. There were conflicting findings from multiple trials: 12 showed positive effects and 13 were inconclusive or showed no effect. Dosages used in the 12 positive studies would support the existence of an effective dosage window that closely resembled current recommended guidelines. In two instances where pooling of data was possible, LLLT showed a positive effect size; in studies of lateral epicondylitis that scored ≥6 on the PEDro scale, participants' grip strength was 9.59 kg higher than that of the control group; for participants with Achilles tendinopathy, the effect was 13.6 mm less pain on a 100 mm visual analogue scale. Conclusion: LLLT can potentially be effective in treating tendinopathy when recommended dosages are used. The 12 positive studies provide strong evidence that positive outcomes are associated with the use of current dosage recommendations for the treatment of tendinopathy.

ABSTRACTEosinophils are best known as the predominant cellular infiltrate associated with asthma and parasitic infections. Recently, numerous studies have documented the presence of Toll-like receptors (TLRs) on the surfaces of eosinophils, suggesting that these leukocytes may participate in the recognition and killing of viruses and bacteria. However, the significance of this role in the innate immune response to bacterial infection is largely unknown. Here we report a novel role for eosinophils as antibacterial defenders in the host response. Isolated mouse eosinophils possessed antipseudomonal properties in vitro. In vivo, interleukin-5 transgenic mice, which have profound eosinophilia, demonstrated improved clearance ofPseudomonas aeruginosaintroduced into the peritoneal cavity. The findings of improved bacterial clearance following adoptive transfer of eosinophils, and impaired bacterial clearance in mice with a congenital eosinophil deficiency, established that this effect was eosinophil specific. The data presented also demonstrate that eosinophils mediate this antibacterial effect in part through the release of cationic secondary granule proteins. Specifically, isolated eosinophil granules had antibacterial properties in vitro, and administration of eosinophil granule extracts significantly improved bacterial clearance in vivo. These data suggest a potent yet underappreciated antibacterial role for eosinophils in vivo, specifically for eosinophil granules. Moreover, the data suggest that the administration of eosinophil-derived products may represent a viable adjuvant therapy for septic or bacteremic patients in the intensive care unit.

Background Golf provides an opportunity for relatively low-impact exercise for nearly all age groups and is considered a recommended activity for patients after total knee arthroplasty. Hypothesis We hypothesized that total knee arthroplasty would afford patients increased ability to participate in and enjoy golf, allowing a large percentage of these patients to walk the golf course. Study Design Case series; Level of evidence, 4. Methods Surveys were sent to 151 golfers who had undergone primary total knee arthroplasty from 1995 to 2000. The detailed survey included 33 questions specific to the patients’ golf performance, enjoyment of golf, frequency of participation, timing of return to play, presence of pain, use of a cart, and related golf-specific issues. Results We received and evaluated 93 responses (62%). Fifty-seven percent reported they had returned to golf within 6 months after total knee arthroplasty. Eighty-one percent of respondents reported golfing as frequently, or more frequently, than before knee replacement. Notably, golfers reported less pain while golfing after total knee arthroplasty than before (13% vs 83%; P < .0001), and 94% of respondents reported currently enjoying golf as much as or more than before surgery. Twenty-eight percent of respondents stated that they walked the course, rather than using a motorized golf cart, before surgery, while only 14% walked the course after surgery ( P = .02). Conclusion In this population of golfers, total knee arthroplasty reliably relieved pain that had been previously experienced while golfing, and increased or maintained this group’s enjoyment of playing golf. However, 86% of these patients reported using a cart while golfing. Further patient education is needed regarding the potential health benefits of walking during golf after total knee arthroplasty.

Abstract Purpose: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder associated primarily with bilateral schwannomas seen on the superior vestibular branches of the eighth cranial nerves. Significant morbidity can result from surgical treatment of these tumors. Meningiomas, ependymomas, and other benign central nervous system tumors are also common in NF2. The lack of effective treatments for NF2 marks an unmet medical need. Experimental Design: Here, we provide recommendations from a workshop, cochaired by Drs. D. Gareth Evans and Marco Giovannini, of 36 international researchers, physicians, representatives of the biotechnology industry, and patient advocates on how to accelerate progress toward NF2 clinical trials. Results: Workshop participants reached a consensus that, based on current knowledge, the time is right to plan and implement NF2 clinical trials. Obstacles impeding NF2 clinical trials and how to address them were discussed, as well as the candidate therapeutic pipeline for NF2. Conclusions: Both phase 0 and phase II NF2 trials are near-term options for NF2 clinical trials. The number of NF2 patients in the population remains limited, and successful recruitment will require ongoing collaboration efforts between NF2 clinics. (Clin Cancer Res 2009;15(16):5032–9)

Unilateral renal artery stenosis (RAS) leads to atrophy of the stenotic kidney and compensatory enlargement of the contralateral kidney. Although the two-kidney, one-clip (2K1C) model has been extensively used to model human RAS, the cellular responses in the stenotic and contralateral kidneys, particularly in the murine model, have received relatively little attention. We studied mice 2, 5, and 11 wk after unilateral RAS. These mice became hypertensive within 1 wk. The contralateral kidney increased in size within 2 wk after surgery. This enlargement was associated with a transient increase in expression of phospho-extracellular signal-regulated kinase (p-ERK), the proliferation markers proliferating cell nuclear antigen and Ki-67, the cell cycle inhibitors p21 and p27, and transforming growth factor-β, with return to baseline levels by 11 wk. The size of the stenotic kidney was unchanged at 2 wk but progressively decreased between 5 and 11 wk. Unlike the contralateral kidney, which showed minimal histopathological alterations, the stenotic kidney developed progressive interstitial fibrosis, tubular atrophy, and interstitial inflammation. Surprisingly, the stenotic kidney showed a proliferative response, which involved largely tubular epithelial cells. The atrophic kidney had little evidence of apoptosis, despite persistent upregulation of p53; expression of cell cycle regulatory proteins in the stenotic kidney was persistently increased through 11 wk. These studies indicate that in the 2K1C model, the stenotic kidney and contralateral, enlarged kidney exhibit a distinct temporal expression of proteins involved in cell growth, cell survival, apoptosis, inflammation, and fibrosis. Notably, an unexpected proliferative response occurs in the stenotic kidney that undergoes atrophy.

Abstract Inherited BRCA1/2 mutations confer elevated ovarian cancer risk. Knowledge of factors that can improve ovarian cancer risk assessment in BRCA1/2 mutation carriers is important because no effective early detection for ovarian cancers exists. A cohort of 1,575 BRCA1 and 856 BRCA2 mutation carriers was used to evaluate haplotypes at ATM, BARD1, BRIP1, CTIP, MRE11, NBS1, RAD50, RAD51, and TOPBP1 in ovarian cancer risk. In BRCA1 carriers, no associations were observed with ATM, BARD1, CTIP, RAD50, RAD51, or TOPBP1. At BRIP1, an association was observed for one haplotype with a multiple testing corrected P (Pcorr) = 0.012, although no individual haplotype was significant. At MRE11, statistically significant associations were observed for one haplotype (Pcorr = 0.007). At NBS1, we observed a Pcorr = 0.024 for haplotypes. In BRCA2 carriers, no associations were observed with CTIP, NBS1, RAD50, or TOPBP1. Rare haplotypes at ATM (Pcorr = 0.044) and BARD1 (Pcorr = 0.012) were associated with ovarian cancer risk. At BRIP1, two common haplotypes were significantly associated with ovarian cancer risk (Pcorr = 0.011). At MRE11, we observed a significant haplotype association (Pcorr = 0.012), and at RAD51, one common haplotype was significantly associated with ovarian cancer risk (Pcorr = 0.026). Variants in genes that interact biologically withBRCA1 and/or BRCA2 may be associated with modified ovarian cancer risk in women who carry BRCA1/2 mutations. [Cancer Res 2009;69(14):5801–10]