Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study

Background

Patients with osteoarthritis (OA) take a variety of health supplements in an attempt to reduce pain and improve function. The aim of this study was to determine the efficacy of methylsulfonylmethane (MSM) in treating patients with knee OA.

Methods

This study was a prospective, randomized, double-blind, controlled clinical trial. Forty nine men and women 45-90 (mean 68 ± SD 7.3) years of age with knee OA according to the American College of Rheumatology clinical criteria for OA of the knee and with radiographic confirmed knee OA were enrolled in the study and randomly assigned into 2 groups: One received MSM in doses of 1.125 grams 3 times daily for 12 weeks and the other received a placebo in the same dosing frequency. The primary outcomes were the WOMAC Osteoarthritis Index for pain, stiffness and physical function, the Aggregated Locomotor Function (ALF) test that evaluates each patient's physical function, the SF-36 quality of life health survey and the visual-analogue-scale (VAS) for pain. The secondary outcomes were Knee Society Clinical Rating System for Knee Score (KSKS) and Function Score (KSFS). Patients were assessed at baseline, 6 weeks and 12 weeks. All continuous variables were tested by the Kolmogorov-Smirnov test for Normal distribution. Changes within the groups and differences between the groups were calculated by repeated measures of analysis (ANOVA) with one nested variable.

Results

There were significant differences between treatment groups over time in WOMAC physical function (14.6 mm [CI: 4.3, 25.0]; p = 0.04) and in WOMAC total score (15.0 mm [CI: 5.1, 24.9]; p = 0.03). Treatment groups did not differ significantly in WOMAC pain (12.4 mm [CI: 0.0, 24.8]); p = 0.08) or WOMAC stiffness (27.2 mm [CI: 8.2, 46.2]; p = 0.08). There was a non-significant difference in SF-36 total score between treatment groups (11.6 [CI: 1.0, 22.1]; p = 0.54). A significant difference was found between groups in VAS for pain (0.7 s [CI: -0.9, 2.4]; p = 0.05). Secondary outcomes showed non-significant differences between the two groups.

Conclusions

Patients with OA of the knee taking MSM for 12 weeks showed an improvement in pain and physical function. These improvements, however, are small and it is yet to be determined if they are of clinical significance.

Trial Registration

ClinicalTrials.gov: NCT01188213

     

FGFR1 over-expression in primary rhabdomyosarcoma tumors is associated with hypomethylation of a 5' CpG island and abnormal expression of the AKT1, NOG, and BMP4 genes

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma likely results from abnormal proliferation and differentiation during skeletal myogenesis. Multiple genetic alterations are associated with the three RMS histopathological subtypes, embryonal, alveolar, and pleomorphic adult variant. Recently, we reported the novel amplification of the FGFR1 gene in a RMS tumor. The involvement of FGFR1 in RMS was now further studied in primary tumors and RMS cell lines by mutation screening, quantitative RNA expression, and methylation analyses. No mutation was found by DHPLC and sequencing of the entire FGFR1 coding sequence and exon-intron boundaries. However, FGFR1 over-expression was detected in all primary RMS tumors and cell lines tested. A hypomethylation of a CpG island upstream to FGFR1 exon 1 was identified in the primary RMS tumors, using sodium bisulfite modification method, suggesting a molecular mechanism to FGFR1 over-expression. Expression analysis of additional genes, AKT1, NOG and its antagonist BMP4, which interact downstream to FGFR1, demonstrated expression differences between primary RMS tumors and normal skeletal muscles. Our data suggest an important role for FGFR1 and FGFR1-downstream genes in RMS tumorigenesis and a possible association with the deregulation of proliferation and differentiation of skeletal myoblasts in RMS.     

Familial Mediterranean fever gene and protection against asthma.

BACKGROUND: Asthma is an inflammatory airway disease caused by interaction between susceptibility genes and diverse environmental factors. In Israel, asthma seems to be familial and more severe in patients of Iraqi Jewish descent. On the other hand, asthma is less frequent in individuals with familial Mediterranean fever, an autoinflammatory disease prevalent in the Iraqi Jewish community and linked to mutations in the familial Mediterranean fever gene, designated MEFV. OBJECTIVES: To explore a possible role for mutated MEFV in the reduced susceptibility to asthma and to determine its expression in Israeli subjects of Iraqi origins. METHODS: Using a case-control approach, we studied the presence of the 3 most common MEFV mutations (M694V, V726A, and E148Q) in DNA samples from 75 patients with asthma and 45 asymptomatic first-degree relatives, all of Iraqi Jewish origin. The severity of asthma was evaluated using a published severity score. RESULTS: Eleven patients with asthma and 14 of their relatives carried 1 or 2 mutations in the MEFV gene, a carrier rate significantly lower in patients with asthma than in their first-degree relatives and in ethnically matched healthy individuals (P < .03 and P < .003, respectively). Carriers of MEFV mutations had less severe disease, compared with noncarriers (P < .002). CONCLUSION: These findings suggest that MEFV mutations may have a protective effect in the pathogenesis of asthma.     

Neuroimmunological function in parents of children suffering from cancer

The main aim of this study is to evaluate the relationship between depression and immunological function in parents of children with cancer. Thirty-two parents participated in the study. The parents completed the following assessments: a list of major stressful events in a Hemato-Oncology ward, beck depression inventory II (BDI-II), posttraumatic diagnostic scale (PDS) and quality of life (QOL) questionnaire. A single blood sample was drawn from parents for evaluation of cortisol levels and lymphocyte cell subgroups. The parents were divided into two groups: Those who suffered from depression as defined by BDI-II cutoff score of 14 (depressed parents (DP), n = 7), and non-depressed parents (non-DP, n = 25). In parents of children with cancer the DP group had statistically significantly higher stressful event scores, dysfunction scores (from the PDS) and CD8 percentage compared to the non-DP group. QOL, CD4 percentage and CD4/CD8 ratio were significantly lower in the DP group. The BDI scores significantly positively correlated with events and dysfunctional scores, and significantly negatively correlated with QOL scores and CD4/CD8 ratio. High psychiatric morbidity was found in parents of children with cancer. The findings of altered immunity in DP provide further evidence that the physiological response to stress and depression may alter immune functions.     

Vestibular evoked myogenic potentials and habituation to seasickness

Objective

Seasickness may impose severe limitations on the performance of ships’ crew. Cervical vestibular evoked myogenic potentials (cVEMP) assess the function of the saccule, the organ responsible for monitoring vertical linear acceleration, which has been found to be the most provocative motion stimulus in the evolution of motion sickness. We used the cVEMP test in a prospective evaluation of susceptibility and habituation to seasickness.

Methods

Forty-six naval recruits underwent the cVEMP test before exposure to sea conditions. After 6 months’ sailing experience, participants completed a questionnaire evaluating their initial and current seasickness severity. Based on their most recent experience, subjects were divided into three groups: non-vomiting non-habituating (NV-NH), vomiting (V), and non-vomiting habituating (NV-H).

Results

Statistically significant lower thresholds for cVEMP were found in subjects who habituated to sea conditions (NV-H), compared with those remaining severely susceptible (V) (77.0 dB HL vs. 84.9 dB HL; p < 0.01).

Conclusions

The ability to produce the cVEMP at lower thresholds represents a broader dynamic range, in which the reflex can respond to a wider array of stimuli amplitudes.

Significance

The present study demonstrates the potential of the cVEMP test for predicting future habituation to seasickness.     

Neurophysiologic monitoring and pharmacologic provocative testing for embolization of spinal cord arteriovenous malformations

BACKGROUND AND PURPOSE: Embolization of a spinal cord arteriovenous malformation (SCAVM) is still considered risky. We evaluated the efficacy and reliability of pharmacologic provocative testing with neurophysiologic monitoring in the embolization of SCAVMs. METHODS: We retrospectively analyzed results of 60 provocative tests during 84 angiographic procedures (in 52 patients) with intended endovascular embolization. Tests included 47 sodium amytal and 56 lidocaine injections. All procedures were performed with general anesthesia and monitoring of cortical somatosensory evoked potentials (SEPs) and transcranial motor evoked potentials (MEPs). For provocative testing, 50 mg of amytal and 40 mg of lidocaine were consecutively injected through a microcatheter placed at the position of intended embolization. If SEPs and MEPs did not change, embolization was performed with N-butyl-cyanoacrylate (NBCA). If SEPs or MEPs changed, NBCA embolization was not performed from that catheter position. RESULTS: One false-negative result occurred, with an increase in spasticity after embolization. Nineteen positive results occurred: four after amytal injection and 15 after lidocaine injections. Seven injections in a posterior spinal artery feeder resulted in loss of SEPs or MEPs. Eleven injections in the anterior spinal artery feeder and one in the posterior inferior cerebellar artery feeder resulted in loss of MEPs. CONCLUSION: Provocative testing with amytal and lidocaine combined with neurophysiologic monitoring had a high negative predictive value and was a useful adjunct for SCAVM embolization. Both amytal and lidocaine should be used as provocative agents, and both SEPs and MEPs should be monitored.     

Routine inclusion of level IV in neck dissection for squamous cell carcinoma of the larynx: Is it justified?

BACKGROUND: Dissection of levels II-IV as part of an elective or therapeutic neck dissection is common practice during laryngectomy for laryngeal squamous cell carcinoma (SCC). The necessity of routine dissection at level IV has recently been questioned. The purpose of this study was to find the incidence of level IV metastases in patients with transglottic and supraglottic SCC who underwent neck dissections. METHODS: The charts of 71 suitable patients were reviewed. Forty-two had supraglottic primary cancers, and 29 had transglottic primary tumors. Levels II-IV had been removed in them all, and their neck specimens were marked according to the levels of the neck. The surgical specimens were pathologically diagnosed. RESULTS: Of 43 patients who underwent elective lateral neck dissection, the only one (2.3%) with level IV metastases also showed metastases at level II. Nine (32%) of the other 28 patients with clinical adenopathy had level IV metastases. CONCLUSIONS: Dissection of level IV as part of a therapeutic neck dissection for supraglottic and transglottic SCC is recommended for patients with clinically enlarged lymph nodes, but its necessity in the absence of detectable adenopathy is challenged.     

Automated Computational Detection of Interstitial Fibrosis,Tubular Atrophy,and Glomerulosclerosis

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