Citations

Biomechanical evaluation of the subsynovial connective tissue (SSCT) provides insight into the causes of carpal tunnel syndrome. Studies of carpal tunnel mechanics have been performed using fresh-frozen cadaver tissue. Freezing can affect mechanical properties of some tissues, but its effect on SSCT is unknown. A total of 16 rabbit paws were harvested from eight New Zealand rabbits and subjected to mechanical testing consisting of three repeated tendon excursions in sets of three different excursion magnitudes. One paw from each animal was unfrozen. The contralateral paw was frozen and thawed before testing. Force, energy and stiffness of the first cycle of each set were evaluated, as were ratios of the second to first cycle for each parameter. Two-factor ANOVA with repeated measures over both factors was performed. No significant interactions between factors were found. There were no significant differences between fresh and frozen paws for any parameters, though there were significant differences between excursion amplitudes. The damage threshold was not different between fresh and frozen paws. This study demonstrated that freezing rabbit subsynovial connective tissue does not significantly change its mechanical properties. The same may be true for human cadaver tissues. Results of cadaver mechanical testing may not be influenced by this preservation technique.

Background: In the presence of a competing risk of death, the Kaplan-Meier method is known to overestimate the probability of implant failure. To our knowledge, the magnitude of the competing risk of death in survivorship analyses in total knee arthroplasty has not been studied. The purpose of this study was to determine the extent of the competing risk of death in different age groups during a long-term follow-up of patients who had undergone primary total knee arthroplasty. Methods: The study population comprised 22,864 primary total knee arthroplasties at a large medical center in the United States. We compared the overall revision outcomes estimated using the Kaplan-Meier method and the cumulative incidence function over a mean follow-up of 7.8 years (range, 0.1 to 26.3 years). Results: The risk of death exceeded the risk of revision by a factor of 4 at twelve years following the surgical procedure. The Kaplan-Meier method overestimated the risk of revision by 3% at five years, 14% at ten years, 32% at fifteen years, and 57% at twenty years. At ten years after the surgical procedure, the risk of death exceeded the risk of revision by a factor of 15 in the all-polyethylene group and by a factor of 3.5 in the metal modular group. The Kaplan-Meier method overestimated the ten-year risk of revision by 18% in the all-polyethylene group and by 11% in the metal modular group. After accounting for the higher competing risk of death in the all-polyethylene group, the cumulative incidence of revision in the metal modular group was about 2.5 to three times higher than that in the all-polyethylene group at ten years. Conclusions: Although the Kaplan-Meier and cumulative incidence methods yielded different implant survival estimates beyond ten years (Kaplan-Meier overestimates implant failure), the size of the bias was small at earlier time points. The extent of overestimation depends on the duration of follow-up and the magnitude of the competing risk of death. Clinical Relevance: This study examines the clinical relevance of the competing risk of death in total knee arthroplasty.

Abstract Respiratory viruses cause asthma exacerbations. Because eosinophils are the prominent leukocytes in the airways of 60–70% of patients with asthma, we evaluated the effects of eosinophils on a common respiratory virus, parainfluenza 1, in the lung. Eosinophils recruited to the airways of wild-type mice after ovalbumin sensitization and challenge significantly decreased parainfluenza virus RNA in the lungs 4 days after infection compared with nonsensitized animals. This antiviral effect was also seen in IL-5 transgenic mice with an abundance of airway eosinophils (NJ.1726) but was lost in transgenic eosinophil-deficient mice (PHIL) and in IL-5 transgenic mice crossed with eosinophil-deficient mice (NJ.1726-PHIL). Loss of the eosinophil granule protein eosinophil peroxidase, using eosinophil peroxidase–deficient transgenic mice, did not reduce eosinophils’ antiviral effect. Eosinophil antiviral mechanisms were also explored in vitro. Isolated human eosinophils significantly reduced parainfluenza virus titers. This effect did not involve degradation of viral RNA by eosinophil granule RNases. However, eosinophils treated with a nitric oxide synthase inhibitor lost their antiviral activity, suggesting eosinophils attenuate viral infectivity through production of nitric oxide. Consequently, eosinophil nitric oxide production was measured with an intracellular fluorescent probe. Eosinophils produced nitric oxide in response to virus and to a synthetic agonist of the virus-sensing innate immune receptor, Toll-like receptor (TLR) 7. IFNγ increased expression of eosinophil TLR7 and potentiated TLR7-induced nitric oxide production. These results suggest that eosinophils promote viral clearance in the lung and contribute to innate immune responses against respiratory virus infections in humans.

Background: Numerous large-scale studies have found diverse risk factors for Parkinson’s disease (PD), including caffeine non-use, non-smoking, head injury, pesticide exposure, and family history. These studies assessed risk factors for PD overall; however, PD is a heterogeneous condition. One of the strongest identifiers of prognosis and disease subtype is the co-occurrence of rapid eye movement sleep behavior disorder (RBD). In previous studies, idiopathic RBD was associated with a different risk factor profile from PD and dementia with Lewy bodies, suggesting that the PD-RBD subtype may also have a different risk factor profile. Objective: To define risk factors for PD in patients with or without associated RBD. Methods: In a questionnaire, we assessed risk factors for PD, including demographic, medical, environmental, and lifestyle variables of 189 PD patients with or without associated polysomnography-confirmed RBD. The risk profile of patients with vs. without RBD was assessed with logistic regression, adjusting for age, sex, and disease duration. Results: PD-RBD patients were more likely to have been a welder (OR = 3.11 (1.05–9.223), and to have been regular smokers (OR = 1.96 (1.04–3.68)). There were no differences in use of caffeine or alcohol, other occupations, pesticide exposure, rural living, or well water use. Patients with RBD had a higher prevalence of the combined family history of both dementia and parkinsonism (13.3% vs. 5.5% , OR = 3.28 (1.07–10.0). Conclusion: The RBD-specific subtype of PD may also have a different risk factor profile.

Background: Clinical misdiagnosis, particularly at early disease stages, is a roadblock to finding new therapies for Lewy body disorders. Biopsy of a peripheral site might provide improved diagnostic accuracy. Previously, we reported, from both autopsy and needle biopsy, a high prevalence of submandibular gland synucleinopathy in Parkinson’s disease (PD). Here, we report on an extension of these studies to subjects with dementia with Lewy bodies (DLB) and other Lewy body disorders in 228 autopsied subjects from the Arizona Study of Aging and Neurodegenerative Disorders. Objective: To provide an estimate of the prevalence of histological synucleinopathy in the submandibular glands of subjects with PD and other Lewy body disorders. Methods: Submandibular gland sections from autopsied subjects were stained with an immunohistochemical method for α-synuclein phosphorylated at serine 129. Included were 146 cases with CNS Lewy-type synucleinopathy (LTS), composed of 46 PD, 28 DLB, 14 incidental Lewy body disease (ILBD), 33 Alzheimer’s disease with Lewy bodies (ADLB) and 2 with progressive supranuclear palsy and Lewy bodies (PSPLB). Control subjects included 79 normal elderly, 15 AD, 12 PSP, 2 conticobasal degeneration (CBD) and 2 multiple system atrophy (MSA). Results: Submandibular gland LTS was found in 42/47 (89%) of the PD subjects, 20/28 (71%) DLB, 4/33 (12%) ADLB and 1/9 (11%) ILBD subjects but none of the 110 control subjects. Conclusions: These results provide support for further clinical trials of in vivo submandibular gland diagnostic biopsy for PD and DLB. An accurate peripheral biopsy diagnosis would assist subject selection for clinical trials and could also be used to verify other biomarkers.