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ID PMID Title PublicationDate abstract
24289832 Patient initiated clinics for patients with chronic or recurrent conditions managed in sec 2013 Dec 1 BACKGROUND: The cost to the NHS of missed or inappropriate hospital appointments is considerable. Alternative methods of appointment scheduling might be more flexible to patients' needs without jeopardising health and service quality. The objective was to systematically review evidence of patient initiated clinics in secondary care on patient reported outcomes among patients with chronic/recurrent conditions. METHODS: Seven databases were searched from inception to June 2013. Hand searching of included studies references was also conducted. Studies comparing the effects of patient initiated clinics with traditional consultant led clinics in secondary care for patients with long term chronic or recurrent diseases on health related quality of life and/or patient satisfaction were included. Data was extracted by one reviewer and checked by a second. Results were synthesised narratively. RESULTS: Seven studies were included in the review, these covered a total of 1,655 participants across three conditions: breast cancer, inflammatory bowel disease and rheumatoid arthritis. Quality of reporting was variable. Results showed no significant differences between the intervention and control groups for psychological and health related quality of life outcomes indicating no evidence of harm. Some patients reported significantly more satisfaction using patient-initiated clinics than usual care (p < 0.001). CONCLUSIONS: The results show potential for patient initiated clinics to result in greater patient and clinician satisfaction. The patient-consultant relationship appeared to play an important part in patient satisfaction and should be considered an important area of future research as should the presence or absence of a guidebook to aid self-management. Patient initiated clinics fit the models of care suggested by policy makers and so further research into long term outcomes for patients and service use in this area of practice is both relevant and timely.
24048363 Combined arthroscopic synovectomy and radiosynoviorthesis in the treatment of chronic non- 2013 Nov INTRODUCTION: Chronic non-specific synovitis has a higher recurrence rate with arthroscopic synovectomy due to the insufficient removal of all pathological tissues. Neither has radiosynoviorthesis been sufficiently effective in treatment in contrast to cases of chronic specific synovitis such as rheumatoid arthritis. This study aimed to investigate the efficiency of combined arthroscopic and radionuclide synovectomy in chronic non-specific synovitis of the knee with the evaluation of clinical and radiological results. MATERIALS AND METHODS: 14 knees of 14 patients (11 female, 3 male) diagnosed as chronic non-specific synovitis were treated with arthroscopic subtotal synovectomy combined with radiosynoviorthesis. The efficiency was evaluated retrospectively by comparing preoperative and postoperative modified cincinnati knee score, Visual Analogue Scale, joint USG and MRI. The mean age was 29.2 ± 10.3 years and the mean follow-up period was 30.3 ± 3.7 months. RESULTS: Clinical parameters such as pain, limitation of motion and effusion were regressed. Daily activities at the final follow-up were significantly better than in the preoperative period. The mean modified cincinnati knee score of the patients increased from 25.8 ± 8.7 preoperatively to 67.8 ± 13.4 postoperatively (p = 0.002). The mean VAS score was 7.2 ± 1.1 preoperatively and 1.3 ± 0.8 postoperatively (p = 0.003). Clinically and radiologically on MRI there was no recurrence. Mean synovial membrane thickness was 4.5 ± 2.4 mm in the preoperative period. At the final follow-up, noticeable regression of synovial membrane thickness (2.1 ± 0.5 mm) was recorded in the knee joint USG (p = 0.015). No complications were observed. CONCLUSION: The combination of arthroscopic subtotal synovectomy and radiosynoviorthesis can be an effective treatment modality for chronic non-specific synovitis of the knee.
23990947 Association of STAT4 polymorphisms with susceptibility to type-1 autoimmune hepatitis in t 2013 BACKGROUND/AIMS: Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study. METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44) or without liver cirrhosis (n = 186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies). CONCLUSIONS/SIGNIFICANCE: This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.
23906180 Functional profiling of the gut microbiome in disease-associated inflammation. 2013 The microbial residents of the human gut are a major factor in the development and lifelong maintenance of health. The gut microbiota differs to a large degree from person to person and has an important influence on health and disease due to its interaction with the human immune system. Its overall composition and microbial ecology have been implicated in many autoimmune diseases, and it represents a particularly important area for translational research as a new target for diagnostics and therapeutics in complex inflammatory conditions. Determining the biomolecular mechanisms by which altered microbial communities contribute to human disease will be an important outcome of current functional studies of the human microbiome. In this review, we discuss functional profiling of the human microbiome using metagenomic and metatranscriptomic approaches, focusing on the implications for inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis. Common themes in gut microbial ecology have emerged among these diverse diseases, but they have not yet been linked to targetable mechanisms such as microbial gene and genome composition, pathway and transcript activity, and metabolism. Combining these microbial activities with host gene, transcript and metabolic information will be necessary to understand how and why these complex interacting systems are altered in disease-associated inflammation.
23792584 Anti-inflammatory activity of Markhamia tomentosa (Benth.) K. Schum. Ex Engl. ethanolic le 2013 Aug 26 ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Markhamia tomentosa (Benth.) K. Schum (Bignoniaceae) are used traditionally for the treatment of oedema and rheumatoid arthritis in Nigeria. AIM OF THE STUDY: The aim of the work was to investigate the anti-inflammatory activity of the ethanolic leaf extract of Markhamia tomentosa. MATERIALS AND METHODS: The extract was screened using the carrageenan-induced paw oedema in rats, xylene-induced oedema in mice and the formalin-induced oedema in mice at 50, 100, 200mg/kg doses p.o respectively. The mechanism by which the extract mediated the anti-inflammatory activity was assessed using the histamine-induced rat paw oedema and serotonin-induced rat paw oedema at the highest dose (200mg/kg). RESULTS: The results showed that the extract produced a significant dose-dependent inhibition in carrageenan-induced, xylene-induced and the formalin tests. The extract exerted a significant inhibition of 54.55% (P<0.0001) and 42.11% (P<0.01) at 90 min in the histamine-induced and serotonin-induced rat paw oedema models respectively. CONCLUSIONS: These findings suggest that the ethanolic leaf extract of Markhamia tomentosa possesses anti-inflammatory activity possibly mediated by histamine. The results justify the use of the plant in the preparation of ethno medicines used in the treatment of ailments associated with inflammation.
23532673 Mid term results of LCS knee: The Indian experience. 2013 Jan BACKGROUND: The low contact stress rotating platform (LCS RP) knee (DePuy Orthopedics, Inc, Warsaw, Indiana), in use for last four decades in Western population, is reported to have a survival of more than 95% at 15 to 20 years. The reported Indian experience of this knee is limited to 5 years. Our aim was to report the clinical and radiological results of the LCS RP TKA design in the Indian population with a minimum followup of 10 years. MATERIALS AND METHODS: Fifty-five LCS knees (45 patients) operated between February 1997 and October 2001 were evaluated retrospectively. LCS design was generally selected if the patient was young (≤65 years of age), active and had no severe deformity. There were 40 female (88.9%) and 5 male (11.1%) patients; 47 knees had osteoarthritis (85.5%) and 8 knees had rheumatoid arthritis (14.5%). Knee Society Scores (KSS) and outcome questionnaire were filled at followup and radiographs were analyzed using Knee Society radiographic evaluation and scoring system. RESULTS: Of 45 patients (55 knees) enrolled, 37 patients (44 knees; 80%) were available for followup at 10 years. Average age was 59.6 years (range 40 to 77). Minimum followup was 10 years (average 12.3 years; range 10 to 15.3 years.). Three knees (6.8%) had been revised, one each for aseptic loosening, bearing dislocation and infection. Mean preoperative KSS of 33 improved to 91 postoperatively. Mean preoperative functional score of 45 improved to 76 postoperatively. Mean preoperative flexion of 113° (90°-140°) reduced to 102° (80°-135°) postoperatively. Erratic femoral rollback and tighter flexion gap to prevent spin out are the probable factors for decreased postoperative range of motion. Five (12%) patients could sit cross-legged and sit on the floor. Anterior knee pain was present in 4.6% (2/44 knees). The survival was 93.2% at 12.3 years. One patient (1.8%) had spin-out of the rotating bearing. No knee had osteolysis or progressive radiolucent lines on X-rays. CONCLUSION: LCS implant has given good survival (93.2% at 12.3 years) with low rates of spin-out and anterior knee pain and no incidence of osteolysis. Limited flexion post surgery (104°) with only 12% managing to sit cross legged on the floor is a drawback.
23485647 A rapid and reliable method for the quantitation of hydroxychloroquine in serum using turb 2013 Jun 5 BACKGROUND: Hydroxychloroquine is routinely used in managing systemic lupus erythematosus and rheumatoid arthritis. Whole blood levels are currently measured in the laboratory but at least one study suggests that serum levels may be equally useful. Moreover, serum samples are the preferred matrix type in the clinical laboratory as a result of their reduced complexity compared to whole blood. These observations suggest that the clinical utility of serum hydroxychloroquine levels needs to be reevaluated using larger studies and more robust assays. We report a turbulent flow LC-MS/MS method we developed for this purpose. METHODS: After protein precipitation from serum with 0.33 mol/l perchloric acid, hydroxychloroquine and its deuterated analog were injected onto a Cyclone turbulent flow column for sample cleanup. Analytical separation was accomplished on a HypersilGold C8 column with a gradient of water and methanol, each containing 0.1% formic acid and 10 mmol/l ammonium formate. Analytes were ionized and detected by electrospray ionization mass spectrometry with multiple reaction monitoring. RESULTS: Our method was linear from 15.7 to 2000 ng/ml. Total imprecision at multiple levels was <5% and accuracy was within ±15%. The method showed minimal carryover. Our extraction efficiency was 103% and the matrix factor was 101%. Comparison with a reference laboratory method identified constant bias but good correlation between the 2 methods. CONCLUSIONS: We present a novel turbulent flow liquid chromatography-tandem mass spectrometry method for quantification of hydroxychloroquine in serum. Our method has comparable sensitivity, selectivity, precision, accuracy, and linearity to previously reported methods. However, it offers simpler sample processing, shorter overall analysis time, and minimal carryover. These characteristics make our method well-suited for efficient analysis of the large number of samples necessary for studies on the clinical utility of serum HQ levels.
23085014 Vitamin D: health panacea or false prophet? 2013 Jan Vitamin D deficiency, diagnosed when the serum 25-hydroxyvitamin D (25-OHD(3)) concentration is less than 20 ng/mL, has joined vitamin A deficiency as two of the most common nutrition-responsive medical conditions worldwide. There have been more scientific articles published about vitamin D in the 21st century than about any other vitamin, reflecting the massive expansion of the field of vitamin D research. Adequate vitamin D status has been linked to decreased risks of developing specific cancers, including cancers of the esophagus, stomach, colon, rectum, gallbladder, pancreas, lung, breast, uterus, ovary, prostate, urinary bladder, kidney, skin, thyroid, and hematopoietic system (e.g., Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma); bacterial infections; rheumatoid arthritis; Crohn's disease; periodontal disease; multiple sclerosis; asthma; type 2 diabetes; cardiovascular disease; stroke; peripheral artery disease; hypertension; chronic kidney disease; muscle weakness; cognitive impairment; Alzheimer's disease; clinical depression; and premature death. On the other hand, inadequate vitamin D status during human pregnancy may be associated with increased risk for the development of type 1 diabetes in the offspring. However, this point of view may be excessively optimistic. There also is evidence that despite the current heavy reliance on serum 25-OHD(3) concentration for the diagnosis of an individual's vitamin D status, local tissue vitamin D intoxication may be present in individuals with much lower serum 25-OHD(3) concentrations than are currently appreciated. Only rarely are the symptoms of local tissue vitamin D intoxication associated with vitamin D status or intake. An individual's serum 25-OHD(3) concentration may appear to be "low" for reasons totally independent of sunlight exposure or vitamin D intake. Serum 25-OHD(3) concentration is only poorly responsive to increases in vitamin D intake, and the prolonged routine consumption of thousands of international units of vitamin D may interfere with the regulation of phosphate homeostasis by fibroblast growth factor-23 (FGF23) and the Klotho gene product, with consequences that are detrimental to human health. In light of these counterbalancing observations, curbing excessive enthusiasm for universally increasing vitamin D intake recommendations may be in order.
25134436 Simple finite element models for use in the design of therapeutic footwear. 2014 Sep 22 Therapeutic footwear is frequently prescribed in cases of rheumatoid arthritis and diabetes to relieve or redistribute high plantar pressures in the region of the metatarsal heads. Few guidelines exist as to how these interventions should be designed and what effect such interventions actually have on the plantar pressure distribution. Finite element analysis has the potential to assist in the design process by refining a given intervention or identifying an optimal intervention without having to actually build and test each condition. However, complete and detailed foot models based on medical image segmentation have proven time consuming to build and computationally expensive to solve, hindering their utility in practice. Therefore, the goal of the current work was to determine if a simplified patient-specific model could be used to assist in the design of foot orthoses to reduce the plantar pressure in the metatarsal head region. The approach is illustrated by a case study of a diabetic patient experiencing high pressures and pain over the fifth metatarsal head. The simple foot model was initially calibrated by adjusting the individual loads on the metatarsals to approximate measured peak plantar pressure distributions in the barefoot condition to within 3%. This loading was used in various shod conditions to identify an effective orthosis. Model results for metatarsal pads were considerably higher than measured values but predictions for uniform surfaces were generally within 16% of measured values. The approach enabled virtual prototyping of the orthoses, identifying the most favorable approach to redistribute the patient's plantar pressures.
24917676 Novel cartilage oligomeric matrix protein (COMP) neoepitopes identified in synovial fluids 2014 Jul 25 To identify patients at risk for progressive joint damage, there is a need for early diagnostic tools to detect molecular events leading to cartilage destruction. Isolation and characterization of distinct cartilage oligomeric matrix protein (COMP) fragments derived from cartilage and released into synovial fluid will allow discrimination between different pathological conditions and monitoring of disease progression. Early detection of disease and processes in the tissue as well as an understanding of the pathologic mechanisms will also open the way for novel treatment strategies. Disease-specific COMP fragments were isolated by affinity chromatography of synovial fluids from patients with rheumatoid arthritis, osteoarthritis, or acute trauma. Enriched COMP fragments were separated by SDSPAGE followed by in-gel digestion and mass spectrometric identification and characterization.Using the enzymes trypsin, chymotrypsin, and Asp-N for the digestions, an extensive analysis of the enriched fragments could be accomplished. Twelve different neoepitopes were identified and characterized within the enriched COMP fragments. For one of the neoepitopes, Ser77, an inhibition ELISA was developed. This ELISA quantifies COMP fragments clearly distinguishable from total COMP. Furthermore, fragments containing the neoepitope Ser77 were released into the culture medium of cytokine (TNF-α and IL-6/soluble IL-6 receptor)-stimulated human cartilage explants. The identified neoepitopes provide a complement to the currently available commercial assays for cartilage markers. Through neoepitope assays, tools to pinpoint disease progression, evaluation methods for therapy, and means to elucidate disease mechanisms will be provided.
24800865 Clinical, microbiologic, and outcome analysis of mycotic aortic aneurysm: the role of endo 2014 Jun BACKGROUND: Mycotic aortic aneurysm (MAA) is an infrequent but devastating form of vascular disease. METHODS: We conducted a retrospective cohort study at a major medical center to identify independent risk factors for MAA and to provide opinions about treating it. The study population consisted of 43 patients who had had 44 MAAs over a period of 15 y. RESULTS: All of the patients had positive blood cultures, radiologic findings typical of MAA, and clinical signs of infection (leukocytosis, fever, and elevated C-reactive protein). The mean age of the patients was 63.8±10.6 y and the mean period of their follow up was 35.7±39.3 mo. Twenty-nine patients with MAAs underwent traditional open surgery, 11 others received endovascular stent grafts, and four MAAs were managed conservatively. The most frequent causative pathogens were Salmonella (36/44 patients [81.8%]), in whom organisms of Salmonella serogroup C (consisting mainly of S. choleraesuis) were identified in 14 patients, organisms of Salmonella serogroup D were identified in 13 patients, and species without serogroup information were identified in nine patients. The overall mortality in the study population was 43.2% (with an aneurysm-related mortality of 18.2%, surgically related mortality of 13.6%, and in-hospital mortality of 22.7%). CONCLUSIONS: Shock is a risk factor for operative mortality. Misdiagnosis and treatment of MAA as low back pain, co-existing connective-tissue disease such as systemic lupus erythematosus and rheumatoid arthritis, and Salmonella serogroup C-associated bacteremia are risk factors for aneurysm-related death. Endovascular repair should be considered as an alternative option to the open repair of MAA.
24668548 Susceptibility to hepatocellular carcinoma in the Chinese population--associations with in 2014 Jul Hepatocellular carcinoma (HCC) is one of the most deadly malignant diseases in the world. Genetic variations in cytokine genes may have an effect on the immune and inflammatory responses which are associated with HBV-HCC. The interleukin-6 (IL-6) receptor is known to be mainly expressed by hepatocytes, neutrophils, monocytes/macrophages, and some lymphocytes, which have been used as prognostic markers in a variety of inflammatory diseases such as rheumatoid arthritis, asthma, and Crohn's disease. To determine the association of IL-6 receptor (IL-6R) polymorphism with the risk of hepatocellular carcinoma (HCC) development in the Chinese population, a hospital based case-control study was designed consisting of 192 subjects with HCC and 192 healthy control subjects. Our results revealed no risk associations (p = 0.064) with rs6684439 CT genotypes. However, rs6684439 TT genotypes were associated with a significantly decreased risk of HBV-related HCC compared with the CC genotype (odds ratio (OR) = 0.469, 95 % confidence interval (CI) 0.228-0.967, p = 0.040). The data also revealed that subjects with the T allele appeared to have a lower susceptibility to HBV-related HCC than those with the C allele (OR = 0.657, 95 % CI 0.476-0.907, p = 0.011). The present study supports the view that variants in the rs6684439 SNP of IL-6R is associated with a lower risk of HBV-related HCC, and this could provide valuable clues to understanding the mechanisms underlying susceptibility to this malignant disease. Replication and further functional studies should be carried out in the future using larger samples.
24572879 Expression of follicle-stimulating hormone receptor in vascular anomalies. 2014 Mar BACKGROUND: The mechanism for the growth of infantile hemangioma and vascular malformations is unknown. Follicle-stimulating hormone secretion mirrors the life cycle of infantile hemangioma and increases during adolescence, when vascular malformations often progress. The purpose of this study was to determine whether vascular anomalies express the receptor for follicle-stimulating hormone. METHODS: Human vascular tumors (i.e., infantile hemangioma, congenital hemangioma, kaposiform hemangioendothelioma, and pyogenic granuloma) and vascular malformations (i.e., capillary, lymphatic, venous, and arteriovenous) were subjected to immunofluorescence for follicle-stimulating hormone receptor. Control specimens included normal skin/subcutis, mucosa, liver, spleen, Crohn disease, granulation, pancreatitis, rheumatoid arthritis, and synovitis. Receptor and microvessel density were quantified using imaging software. RESULTS: Follicle-stimulating hormone receptor was found in the endothelium of all vascular anomalies but was not present in control specimens. Expression was greater in proliferating infantile hemangioma (6.0 percent) compared with other vascular tumors (congenital hemangioma, 0.61 percent; kaposiform hemangioendothelioma, 0.55 percent; pyogenic granuloma, 0.56 percent; p < 0.0001), despite similar microvessel density (p = 0.1). Follicle-stimulating hormone receptor was elevated in arteriovenous malformations (2.65 percent) compared with other types of vascular malformations (capillary, 1.02 percent; lymphatic, 0.38 percent; venous, 0.76 percent; p < 0.0001). CONCLUSIONS: Vascular anomalies express follicle-stimulating hormone receptor on their endothelium, in contrast to vascular control tissues. Vascular anomalies are the only benign, pathologic tissue known to express this receptor. Because the secretion of follicle-stimulating hormone correlates with the growth pattern of infantile hemangioma and vascular malformations, follicle-stimulating hormone might be involved in the pathogenesis of these lesions.
24397399 Matrix-assisted refolding and purification of placenta-derived recombinant human interleuk 2014 Sep Biological activity of human interleukin-6 (IL-6) is associated with a vast number of diseases such as rheumatoid arthritis, sepsis, and severe inflammatory diseases. In this study, human IL-6 cDNA was isolated from a cDNA library that was constructed with mRNA derived from human placental tissues. Subsequently, the complete human IL-6 cDNA was cloned and expressed in BL21DE3 cells. The recombinant human IL-6 (rhIL-6) protein was expressed in a form of an insoluble inclusion body. Inclusion bodies were solubilized under denaturing conditions and purified by immobilized metal affinity chromatography with gradual on-column refolding by the gradient elution method (from 6 to 0 M urea). The protein was purified to apparent homogeneity of about 99% with a yield of 50 mg/L. The purity was assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), size exclusion high-performance liquid chromatography, and Western blotting analysis. The bioactivity was assessed by proliferation assay of TF-1 cells in a dose-dependent manner. The present study confirms the expression of the placenta-derived IL-6 gene in a prokaryotic expression system and matrix-assisted on-column refolding and purification of rhIL-6 by immobilized metal affinity chromatography.
24343531 Daphnetin, a natural coumarin derivative, provides the neuroprotection against glutamate-i 2014 Feb Daphnetin (DAP), a coumarin derivative, has been reported to have multiple pharmacological actions including analgesia, antimalarial, anti-arthritic, and anti-pyretic properties. It is unclear whether DAP has neuroprotective effects on ischemic brain injury. In this study, we found that DAP treatment (i.c.v.) reduced the infarct volume at 24 h after ischemia/reperfusion injury and improved neurological behaviors in a middle cerebral artery occlusion mouse model. Moreover, we provided evidences that DAP had protective effects on infarct volume in neonate rats even it was administrated at 4 h after cerebral hypoxia/ischemia injury. To explore its neuroprotective mechanisms of DAP, we examined the protection of DAP on glutamate toxicity-induced cell death in hippocampal HT-22 cells. Our results demonstrated that DAP protected against glutamate toxicity in HT-22 cells in a concentration-dependent manner. Further, we found that DAP maintained the cellular levels of glutathione and superoxide dismutase activity, suggesting the anti-oxidatant activity of DAP. Since DAP has been used for the treatment of coagulation disorder and rheumatoid arthritis for long time with a safety profile, DAP will be a promising agent for the treatment of stroke.
24333456 Revision surgery after cervical laminoplasty: report of five cases and literature review. 2015 Jun 1 BACKGROUND CONTEXT: Revision surgery after laminoplasty is rarely performed, and there are few reports of this procedure in the English literature. PURPOSE: To evaluate the reasons why patients underwent revision surgery after laminoplasty and to discuss methods of preventing the need for revision surgery. A literature review with a comparative analysis between previous reports and present cases was also performed. STUDY DESIGN: Case report and literature review. PATIENT SAMPLE: Five patients who underwent revision surgery after laminoplasty. OUTCOME MEASURES: Diagnosis was based on the preoperative computed tomography and magnetic resonance imaging findings. Neurologic findings were evaluated using the Japanese Orthopedic Association score. METHODS: A total of 237 patients who underwent cervical laminoplasty for cervical spondylotic myelopathy from 1990 to 2010 were reviewed. Patients with ossification of the posterior longitudinal ligament, renal dialysis, infection, tumor, or rheumatoid arthritis were excluded. Five patients who underwent revision surgery for symptoms of recurrent myelopathy or radiculopathy were identified, and the clinical courses and radiological findings of these patients were retrospectively reviewed. RESULTS: The average interval from the initial surgery to revision surgery was 15.0 (range 9-19) years. The patients were four men and one woman with an average age at the time of the initial operation of 49.8 (range 34-65) years. Four patients developed symptoms of recurrent myelopathy after their initial surgery, for the following reasons: adjacent segment canal stenosis, restenosis after inadequate opening of the lamina with degenerative changes, and trauma after inadequate opening of the lamina. One patient developed new radiculopathy symptoms because of foraminal stenosis secondary to osteoarthritis at the Luschka and zygapophyseal joints. All patients experienced resolution of their symptoms after revision surgery. CONCLUSIONS: Revision surgery after laminoplasty is rare. Inadequate opening of the lamina is one of the important reasons for needing revision surgery. Degenerative changes after laminoplasty may also result in a need for revision surgery. Surgeons should be aware of the degenerative changes that can cause neurologic deterioration after laminoplasty.
24128781 A systematic literature review on the application of Rasch analysis in musculoskeletal dis 2014 Jan OBJECTIVE: The Rasch measurement model provides robust analysis of the internal construct validity of outcome measures. We reviewed the application of Rasch analysis in musculoskeletal medicine as part of the work leading to discussion in a Special Interest Group in Rasch Analysis at Outcome Measures in Rheumatology 11. METHODS: A systematic literature review of SCOPUS and MEDLINE was performed (January 1, 1985, to February 29, 2012. Original research reports in English using "Rasch" or "Item Response Theory" in musculoskeletal diseases were assessed by 2 independent reviewers. The topics of focus and analysis methodology details were recorded. RESULTS: Of 212 articles reviewed, 114 were included. The number of publications rose from 1 in 1991-1992 to 23 in 2011-February 2012. Disease areas included rheumatoid arthritis (28%), osteoarthritis (16.6%), and general musculoskeletal disorders (43%). Sixty-six reports (57.9%) evaluated psychometric properties of existing scales and 35 (30.7%) involved development of new scales. Nine articles (7.9%) were on methodology illustration. Four articles were on item banking and computer adaptive testing. A majority of the articles reported fit statistics, while the basic Rasch model assumption (i.e., unidimensionality) was examined in only 57.2% of the articles. An improvement in reporting qualities with Rasch articles was noted over time. In addition, only 11.4% of the articles provided a transformation table for interval scale measurement in clinical practice. CONCLUSION: The Rasch model has been increasingly used in rheumatology over the last 2 decades in a wide range of applications. The majority of the articles demonstrated reasonable quality of reporting. Improvements in quality of reporting over time were revealed.
24084731 Radical roles for RAGE in the pathogenesis of oxidative stress in cardiovascular diseases 2013 Oct 1 Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE) mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS) and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplification mechanisms in the mitochondria may further drive ROS production. Recent studies indicating that the cytoplasmic domain of RAGE binds to the formin mDia1 provide further support for the critical roles of this pathway in oxidative stress; mDia1 was required for activation of rac1 and NADPH oxidase in primary murine aortic smooth muscle cells treated with RAGE ligand S100B. In vivo, in multiple distinct disease models in animals, RAGE action generates oxidative stress and modulates cellular/tissue fate in range of disorders, such as in myocardial ischemia, atherosclerosis, and aneurysm formation. Blockade or genetic deletion of RAGE was shown to be protective in these settings. Indeed, beyond cardiovascular disease, evidence is accruing in human subjects linking levels of RAGE ligands and soluble RAGE to oxidative stress in disorders such as doxorubicin toxicity, acetaminophen toxicity, neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis and pulmonary fibrosis. Blockade of RAGE signal transduction may be a key strategy for the prevention of the deleterious consequences of oxidative stress, particularly in chronic disease.
24029553 Quantification of the 5-lipoxygenase inhibitor zileuton in human plasma using high perform 2013 Oct 15 Zileuton is an orally active, selective inhibitor of 5-lipoxygenase, which catalyzes the first step in the conversion of arachadonic acid into leukotrienes. Given the important role of leukotrienes in inflammation and cell signaling, multiple studies have investigated the efficacy of zileuton in the treatment of human disease. Examples of disease targets include asthma, ulcerative colitis, rheumatoid arthritis, and more recently, acne, ischemic/reperfusion injury, inflammatory pain, and sickle cell anemia. Zileuton is currently approved for the prophylaxis and chronic treatment of asthma. We report the development and validation of a sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the quantification of zileuton in human EDTA plasma. The range of reliable response was 3.05-20,000ng/mL in human plasma. The calibration curves had a correlation coefficient of r(2)>0.99. The intra-day precision was 3.4-5.3%. The inter-day precision ranged from 4.5% to 7.3% and inter-day accuracy from 100% to 107%. No matrix interferences, ion suppression/enhancement, or carry-over was observed. The assay met all predefined acceptance criteria and was subsequently employed to measure plasma zileuton concentrations in a clinical trial.
28748127 Gender-biased regulation of human IL-17-producing cells in vitro by peptides corresponding 2013 Jul Susceptibility to rheumatoid arthritis (RA) is associated with HLA-DRB1 alleles coding a 5-amino acid sequence motif called the shared epitope (SE). To explore the potential mechanisms that lead to RA susceptibility, we analyze the in vitro effect of peptides bearing different HLA-DR4 sequences on human peripheral blood-derived cells. Three 15-mer peptides were used: 65-79*0401 (an HLA-DRB1*04:01-coded sequence carrying the SE motif, QKRAA); 65-79*0402 (an HLA-DRB1*04:02-coded sequence carrying a SE-negative motif, DERAA); 65-79*0403 (an HLA-DRB1*04:03-coded sequence carrying a SE-negative motif, QRRAE). We found that CD4 TH17 cells are regulated by peptide treatment with gender bias. In male-derived T cells, all peptide treatments significantly reduced TH17 cell differentiation in vitro when compared to no peptide treatment, and to female samples. TH17 differentiation in samples not treated with peptides, either in the presence or absence of TH17-polarizing cytokines, was higher in males than in females; however, in unfractionated PBMC after treatment with TH17 polarizing cytokines, IL-17A positive cells were more abundant in females than in males. In addition, SE-positive females showed a significantly higher percentage of IL-17A-positive cells compared to SE-negative females. In conclusion, donor's SE status and gender may both influence TH17 immune polarization.