Vibration-induced muscle fatigue,a possible contribution to musculoskeletal injury

Localized muscle fatigue resulting from 30-min sustained and intermittent grip exertions of 5% maximal voluntary contraction (MVC) with and without hand-vibration exposure (10 Hz, 7 mm displacement amplitude) was investigated. Muscle fatigue was quantified by the magnitude of the twitch force elicited in the right flexor digitorum superficialis muscle of the long finger using the low-frequency fatigue (LFF) method. The influence of vibration in the sustained grip exertion condition exacerbates fatigue as seen with the reduction in twitch force 30–60 min post-work task. Intermittent low grip force exertion conditions with and without vibration exposure show negligible fatigue, suggesting the benefit of rest in the work cycle. Perception of muscle fatigue was dissociated from the objective measure of twitch force, suggesting that LFF was not perceived. The presence of LFF and the lack of perception of LFF may increase the risk for the development of musculoskeletal disorders. The findings of this study may apply to the design of the work cycles and tasks that require the use of vibratory tools. Electronic Publication     

Body composition measured by dual-energy X-ray absorptiometry half-body scans in obese children

Aim: To perform a methods comparison of a left or right half‐body scan versus whole‐body scan for measuring body composition in a sample of obese children. Methods: A group of obese children (n = 58; ≥95th BMI percentile; 8–18 years) were required to undergo a dual‐energy X‐ray absorptiometry (DXA) body composition measurement as part of an ongoing cohort study; 34 fit within the imaging field of the DXA scanner and were eligible for inclusion in the present analysis. Percent fat, total mass, fat mass, lean mass and bone mineral content (BMC) were estimated from half‐body scans and compared with the whole‐body results. Assessment was completed using GE enCORE 11.40 software. Results: In comparing left‐ and right‐side scans to whole‐body scans, there was significant correlation for all body composition variables (p ≤ 0.005, R² = 0.996–1.0). Bland Altman analyses also showed high levels of agreement between half‐body estimates and whole‐body measurements. Conclusion: This study supports using a half‐body scan methodology for percent fat, total mass, fat mass, lean mass, and BMC as a valid alternative to full‐body analysis in obese children and youth.     

The pro-myogenic environment provided by whole organ scale acellular scaffolds from skeletal muscle

In the pursuit of a transplantable construct for the replacement of large skeletal muscle defects arising from traumatic or pathological conditions, several attempts have been made to obtain a highly oriented, vascularized and functional skeletal muscle. Acellular scaffolds derived from organ decellularization are promising, widely used biomaterials for tissue engineering. However, the acellular skeletal muscle extra cellular matrix (ECM) has been poorly characterized in terms of production, storage and host-donor interactions. We have produced acellular scaffolds at the whole organ scale from various skeletal muscles explanted from mice. The acellular scaffolds conserve chemical and architectural features of the tissue of origin, including the vascular bed. Scaffolds can be sterilely stored for weeks at?+4°C or?+37°C in tissue culture grade conditions. When transplanted in wt mice, the grafts are stable for several weeks, whilst being colonized by inflammatory and stem cells. We demonstrate that the acellular scaffold per se represents a pro-myogenic environment supporting de novo formation of muscle fibers, likely derived from host cells with myogenic potential. Myogenesis within the implant is enhanced by immunosuppressive treatment. Our work highlights the fundamental role of this niche in tissue engineering application and unveils the clinical potential of allografts based on decellularized tissue for regenerative medicine.     

Cerebellar binding of avian pancreatic polypeptide

Studies were carried out to determine the regional central nervous system and species specificity of the previously observed [125I]iodoavian pancreatic polypeptide ( [125I]iodo-APP) specific binding to chick brain membranes. The avian species examined were chicken, pigeon, duck, quail, chukar, and pheasant. In all species, the vast majority (greater than 90%) of APP binding was localized to the area of the cerebellum; other brain regions specifically bound small amounts of APP. Cerebellar hemisphere (folia) regions may have greater specific binding capacities than deep cerebellar nuclei, although all avian cerebellar preparations exhibited affinities for APP on the order of 10(-10) M and binding capacities from approximately 0.2-1.5 pmol/mg protein for the high affinity sites. The measured affinity for binding of APP to these cerebellar binding sites is consistent with normal plasma concentrations (3-6 ng/ml) of APP in all Aves examined. Mammalian (rat and beef) brain membranes, regardless of topographical region, showed low specific binding of [125I]iodo-APP and [125I]iodobovine PP. Preliminary experiments indicate that APP is neither contained in nor released from avian central nervous system synaptosomal elements.     

Amyloidosis and pleural disease

Pleural involvement with systemic amyloidosis has been reported rarely in the literature. Diagnosis of this entity by percutaneous needle biopsy of the pleura has been described only in two prior case reports. We describe five patients in whom the diagnosis of pleural amyloidosis was established by Cope needle biopsy during evaluation of pleural effusions of indeterminate cause. Three patients presented with a history suggestive of multiorgan disease and a pleural biopsy performed despite a transudative effusion demonstrated amyloid infiltration of the pleura, obviating the need for other organ biopsies. We conclude that in patients with pleural effusions, if history suggests multiorgan involvement and there is suspicion for amyloidosis, then a closed pleural biopsy with special stains for amyloid should be performed even if the effusions are transudative. This may be the diagnostic procedure of choice in such patients.     

Influence of methylprednisolone on plasma homocysteine levels in cadaveric renal transplant recipients

The aim of the present study was to investigate plasma homocysteine levels in renal transplant recipients in the course of steroid-based or steroid-free immunosuppression. Data from 32 patients were retrospectively analyzed according to the steroid immunosuppressive regimen. The 20 recipients on methylprednisolone (MP) plus cyclosporine (CyA) or tacrolimus (TRL) (n = 20) showed similar creatinine levels when compared with those on calcineurin inhibitors plus mycophenolate mofetil (MMF; n = 12), (1.6 +/- 1.5 vs 1.6 +/- 0.4 mg/dL; P = NS) but significantly higher total plasma homocysteine (tHcy) levels (28.5 +/- 12.5 vs 16.3 +/- 5.5 micromol/L; P < .05). No differences of tHcy levels have been observed when patients were analyzed according to CyA- or TRL-based immunosuppression regardless of MP or MMF associations. Our data suggest that recipients, particularly those on steroid-based immunosuppression, should receive homocysteine-lowering treatment early after transplantation.     

Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease

Infusions of large numbers (> 10(8)/kg) of donor leukocytes can induce remissions in patients with chronic myeloid leukemia (CML) who relapse after marrow transplantation. We wanted to determine if substantially lower numbers of donor leukocytes could induce remissions and, if so, whether this would reduce the 90% incidence of graft-versus-host disease (GVHD) associated with this therapy. Twenty-two patients with relapsed CML were studied: 2 in molecular relapse, 6 in cytogenetic relapse, 10 in chronic phase, and 4 in accelerated phase. Each patient received escalating doses of donor leukocytes at 4- to 33-week intervals. Leukocyte doses were calculated as T cells per kilogram of recipient weight. There were 8 dose levels between 1 x 10(5) and 5 x 10(8). Lineage-specific chimerism and residual leukemia detection were assessed using sensitive polymerase chain reaction (PCR) methodologies. Nineteen of the 22 patients achieved remission. Remissions were achieved at the following T-cell doses: 1 x 10(7) (n = 8), 5 x 10(7) (n = 4), 1 x 10(8) (n = 3), and 5 x 10(8) (n = 4). To date, 15 of the 17 evaluable patients have become BCR-ABL negative by PCR. The incidence of GVHD was correlated with the dose of T cells administered. Only 1 of the 8 patients who achieved remission at a T-cell dose of 1 x 10(7)/kg developed GVHD, whereas this complication developed in 8 of the 11 responders who received a T-cell dose of > or = 5 x 10(7)/kg. Three patients died in remission, 1 secondary to marrow aplasia, 1 of respiratory failure and 1 of complications of chronic GVHD. Sixteen patients who were mixed T-cell chimeras before treatment became full donor T-cell chimeras at the time of remission. Donor leukocytes with a T-cell content as low as 1 x 10(7)/kg can result in complete donor chimerism together with a potent graft-versus-leukemia (GVL) effect. The dose of donor leukocytes or T cells used may be important in determining both the GVL response and the incidence of GVHD. In many patients, this potent GVL effect can occur in the absence of clinical GVHD.     

TLR9 bone marrow chimeric mice define a role for cerebral TNF in neuroprotection induced by CpG preconditioning

Systemic preconditioning with the TLR9 ligand CpG induces neuroprotection against brain ischemic injury through a tumor necrosis factor (TNF)-dependent mechanism. It is unclear how systemic administration of CpG engages the brain to induce the protective phenotype. To address this, we created TLR9-deficient reciprocal bone marrow chimeric mice lacking TLR9 on either hematopoietic cells or radiation-resistant cells of nonhematopoietic origin. We report that wild-type mice reconstituted with TLR9-deficient hematopoietic cells failed to show neuroprotection after systemic CpG preconditioning. Further, while hematopoietic expression of TLR9 is required for CpG-induced neuroprotection it is not sufficient to restore protection to TLR9-deficient mice that are reconstituted with hematopoietic cells bearing TLR9. To determine whether the absence of protection was associated with TNF, we examined TNF levels in the systemic circulation and the brain. We found that although TNF is required for CpG preconditioning, systemic TNF levels did not correlate with the protective phenotype. However, induction of cerebral TNF mRNA required expression of TLR9 on both hematopoietic and nonhematopoietic cells and correlated with neuroprotection. In accordance with these results, we show the therapeutic potential of intranasal CpG preconditioning, which induces brain TNF mRNA and robust neuroprotection with no concomitant increase in systemic levels of TNF.