The essential role of t cells in multiple sclerosis: A reappraisal
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Cris S Constantinescu, Bruno Gran DOI:10.4103/2319-4170.128746 PMID:24732657
Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system in which destruction of myelin and nerve axons has been shown to be mediated by immune mechanisms. Although the focus of research has been traditionally on T cells as key mediators of the immunopathology, more recent efforts at understanding this complex disorder have been directed increasingly at other cellular and humoral elements of the immune response. This review is a reappraisal of the crucial role of T cells, in particular the CD4+ helper T-cell subset, in multiple sclerosis. Recent evidence is discussed underlining the predominant contribution of T-cell-associated genes to the genome-wide association study results of multiple sclerosis susceptibility, the loss of T-cell quiescence in the conversion from clinically isolated syndrome to clinically definite multiple sclerosis, and the fact that T cells represent the main target of effective immunomodulatory and immunosuppressive treatments in multiple sclerosis.
Advances in the treatment of relapsing - Remitting multiple sclerosis
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Radu Tanasescu, Carolina Ionete, I-Jun Chou, Cris S Constantinescu DOI:10.4103/2319-4170.130440 PMID:24732658
This article reviews and discusses the approved and emerging therapies for multiple sclerosis (MS). MS is a chronic and disabling immune-mediated disease of the central nervous system (CNS) that affects mainly young adults. MS imposes a huge economic burden on healthcare systems and the society. Although the last 20 years have brought a continuous expansion in therapeutic options, there are still unmet needs in MS management. Available MS drugs have varying degrees of efficacy in reducing relapse risk. The long-term term effects of these treatments are incompletely known. New therapies, along with variations of currently available treatments, may prove more effective and tolerable than the available drugs. Treatments for MS differ with respect to the mode of administration, tolerability and likelihood of treatment adherence, side effects, and risk of major toxicity. The armamentarium of approved disease-modifying therapies in MS and those in development include: (1) the first approved, moderately effective, injectable interferon-β and glatiramer acetate; (2) oral drugs (fingolimod, laquinimod, teriflunomide, dimethyl fumarate); (3) monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab); and (4) immunosuppressive agents (e.g. mitoxantrone). The place of each drug in the therapeutic algorithm is dependent on its specific risk-benefit profile. Patients' clinical and paraclinical phenotypes and biomarker profile may help to elucidate disease subtypes and response to therapy in the future, thus allowing treatment individualization.
Diagnostic modalities in multiple sclerosis: Perspectives in children
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I-Jun Chou, William P Whitehouse, Huei-Shyong Wang, Radu Tanasescu, Cris S Constantinescu DOI:10.4103/2319-4170.129269 PMID:24732659
Pediatric multiple sclerosis (MS) represents only 2-5% of the MS population, but children with MS have a higher relapse rate and reach permanent disability at a younger age than adult-onset MS. Early and accurate diagnosis of pediatric MS is vital for prompt treatment to mitigate ongoing neuroinflammation and irreversible neurodegeneration. However, it is difficult to differentiate MS from acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica (NMO) in pediatric patients, even considering the clinical, magnetic resonance imaging (MRI), and paraclinical findings, because the first presentation of inflammatory demyelination in children is often atypical. The purpose of this review is to summarize the clinical, neuroimaging, and paraclinical key differences between pediatric patients with MS, ADEM, and NMO and to discuss novel biomarkers, such as antibodies to aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG), which may help in making a diagnosis.
Background: Obstructive sleep apnea (OSA) syndrome is a complicated disease involving several pathogenic mechanisms. Microarray technology provides a high-throughput means of identifying differentially expressed genes in patients with OSA.
Methods: An Affymetrix U133A gene chip was used to globally analyze the transcriptome of peripheral blood mononuclear cells (PBMC) in patients with OSA and nonapneic control participants after overnight polysomnography.
Results: Several genes were differentially expressed in patients with OSA compared with control participants. These genes included disintegrin and metalloproteinase domain 29 (ADAM29), solute carrier family 18 (vesicular acetylcholine) member 3 (SLC18A3), cyclin-dependent kinase inhibitor 2C (CDKN2C), and fibronectin-like domain-containing leucine-rich transmembrane protein 2 (FLRT2). Among these genes, the expression levels of ADAM29 (p = 0.00003), FLRT2 (p < 0.0001), and SLC18A3 (p = 0.0006) were found to be possible markers of severe OSA [respiratory disturbance index (RDI) > 30].
Conclusion: Our data suggest that PCMC expression of ADAM29, FLRT2, and SLC18A3 could be assessed as part of a routine screen to help identify individuals at risk of severe OSA in Asian populations.
Nutritional status assessed by scored patient-generated subjective global assessment associated with length of hospital stay in adult patients receiving an appendectomy
Background: Malnutrition has been associated with poor health outcomes in hospitalized patients. This study assessed the validity of the scored patient-generated subjective global assessment (PG-SGA) in adult patients who had undergone an open appendectomy, and examined the association of this assessment tool with length of hospital stay.
Methods: Nutritional status was determined by using the scored PG-SGA in adult patients (n = 86) who had undergone an open appendectomy within 24 hours of admission. Variables were compared between well-nourished and malnourished participants. Regression analysis was used to identify potential predictors for length of hospital stay. Receiver operator characteristic (ROC) analysis was used to examine the validity of the PG-SGA score to predict the nutritional status.
Results: On admission, 17% of the study subjects were malnourished and associated with a significantly older age (53.0 vs. 39.5), greater PG-SGA score (8 vs. 2), higher comorbidity (67% vs. 27%), and longer length of hospital stay (6.9 d vs. 4.1 d). The PG-SGA score and comorbidity were the determined risk factors for length of hospital stay after performing multiple regression analysis. Furthermore, the PG-SGA score had a significantly positive correlation with length of hospital stay (Spearman's rho = 0.378, p < 0.001). The area under the ROC curve indicating the PG-SGA score, compared with nutritional status, is 0.9751.
Conclusions: The scored PG-SGA in adults receiving an appendectomy is significantly associated with length of hospital stay, and is an effective tool for assessing the nutritional status of patients with cancer and chronic illness, as well as of patients with acute surgical abdomen.
Background: Lumbar spine facet joints are arranged sagittally and mainly provide forward flexibility. Rotation of the lumbar vertebral body and coronal plane deformity may influence the function of lumbar forward flexibility. We hypothesize that the more advanced axial and coronal plane deformity could cause more limitation on forward flexibility in patients with idiopathic scoliosis.
Methods: Between January 2011 and August 2011, 85 patients with adolescent idiopathic scoliosis were enrolled in this study. The proximal thoracic, major thoracic, thoracolumbar/lumbar (TL/L), and lumbar (L1/L5) curves were measured by Cobb's method. Lumbar apical rotation was graded using the Nash-Moe score. Lumbar forward flexibility was measured using the sit and reach (S and R) test. Statistical analysis was performed using one-way analysis of variance (ANOVA), Spearman's and Pearson's correlation coefficients.
Results: The mean age was 16.1 ± 2.84 years. The mean proximal thoracic, major thoracic, TL/L, and L1/L5 curves were 17.61° ± 8.92, 25.56° ± 11.61, 26.09° ± 8.6, and 15.10° ± 7.85, respectively. The mean S and R measurement was 25.56 ± 12.33 cm. The magnitude of the TL/L and L1/L5 curves was statistically positively related to vertebral rotation (rs = 0.580 and 0.649, respectively). The correlation between the S and R test and both the TL/L and L1/L5 curves was negative (rp = –0.371 and –0.595, respectively). Besides, the S and R test also demonstrated a significant negative relationship with vertebral rotation (rs = –0.768).
Conclusion: In patients with idiopathic scoliosis, spinal deformity can diminish lumbar forward flexibility. Higher lumbar curvature and rotation lead to greater restriction of lumbar flexion.
Total knee arthroplasty in patients with dialysis: Early complications and mortality
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Jen-Hung Chen, Feng-Chih Kuo, Jun-Wen Wang DOI:10.4103/2319-4170.117897 PMID:24732663
Background: Total hip arthroplasty (THA) in patients on long-term hemodialysis may result in a high prevalence of complications which related to nature of the disease, and associated cardiovascular conditions. However, the result of total knee artrhopalsty (TKA) in those patients is not clear. The purpose of this study was to retrospectively evaluate the early mortality and complications of TKA performed in patients with dialysis.
Methods: We retrospectively evaluated 15 dialysis patients (18 knees) who underwent TKA using antibiotic-loaded cement fixation. Fourteen patients had maintained hemodialysis and one patient had continuous ambulatory peritoneal dialysis. The function of the knee was evaluated before operation and postoperatively using Knee Society evaluating system. Postoperative complications and mortality were recorded for all patients. The average follow up period was 25 months (6 to 59 months).
Results: There were no mortalities including short-term (≤90 days) or long-term (>90 days) follow up. The mean knee and function scores improved from preoperative 36 points (27~46) and 19.4 points (10~35) to 79 points (68~87) and 81 points (70~95) respectively at the latest follow up. One (6.7%) patient had early postoperative pneumonia (≤90 days). The late (>90 days) complica-tion rate was 20% including 1 sepsis with toe gangrene, 1 recurrent stroke and 1 acute myocardiac infarction. There was no deep prosthetic joint infection or loosening of the components.
Conclusion: TKA with antibiotic-loaded cement resulted in a substantial low short-term mortality and deep infections in 15 patients with dialysis. However, a longer term follow up is necessary.
Serum levels of melatonin and cytokines in multiple sclerosis
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Naser Farhadi, Shahrbanoo Oryan, Mohammad Nabiuni DOI:10.4103/2319-4170.125885 PMID:24732664
Cytokines are important factors of the immune system in autoimmune diseases such as multiple sclerosis (MS) in which damage caused by oxidants plays a major role in the pathology. Melatonin secreted by the pineal gland has recently been considered as an antioxidant. The purpose of this study was to determine the relationship between melatonin and cytokines in patients with MS. Thirty patients with MS and 30 healthy controls were selected. Serum levels of melatonin and cytokines, including interleukin-4, interferon-γ, and tumor necrosis factor alpha (TNF-α), were detected in all participants by the enzyme-linked immunosorbent assay (ELISA) method. There was a significant difference between patient and control groups in the levels of melatonin and TNF-α. Also, no significant correlation between the serum levels of melatonin and cytokines in both patient and control groups was seen. We concluded that decrease of melatonin and subsequent increase of pro-inflammatory cytokine, TNF-α, could be a factor in the inflammatory reactions in the pathologic process of MS.