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ID PMID Title PublicationDate abstract
31101882 Histopathology and expression of the chemokines CXCL10, CXCL13, and CXCR3 and the endogeno 2019 May 17 Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease manifesting with a persistent high-spiking fever, a typical rash, and lymphadenopathy. Endogenous factors related to interleukin-1, such as S100A8/A9 and several chemokines including CXCL10, CXCR3, and CXCL13, potentially play roles in its pathogenesis. We describe the histopathological features and chemokine expression pattern in lymph nodes (LNs) of patients with AOSD. Formalin-fixed, paraffin-embedded excisional LN tissues from 48 patients with AOSD were histologically reviewed. CXCL10, CXCR3, CXCL13, and S100A8/A9 expression was evaluated immunohistochemically. The pathology of LN was characterized by paracortical hyperplasia with proliferation of histiocyte, immunoblast, CD8-positive lymphoid cell and blood vessel. Most cases required differential diagnosis from dermatopathic lymphadenitis (n = 16, 33.3%), T cell lymphoma (n = 11, 22.9%), and histiocytic necrotizing lymphadenitis (HNL) (n = 9, 18.8%). The expression levels of CXCL10 and CXCR3 were higher in patients with AOSD than in those with T cell lymphoma, HNL, tuberculous lymphadenitis, and reactive hyperplasia. It is important to recognize the aforementioned histopathologic findings of nodal involvement of AOSD because improper diagnosis and treatment can be avoided. Immunohistochemical staining for chemokines, CXCL10 and CXCR3, may aid in differentiating AOSD from other mimickers.
31541023 Identification of a Novel Role for Foxo3 Isoform2 in Osteoclastic Inhibition. 2019 Oct 15 Foxo3 acts as an important central regulator that integrates signaling pathways and coordinates cellular responses to environmental changes. Recent studies show the involvement of Foxo3 in osteoclastogenesis and rheumatoid arthritis, which prompted us to further investigate the FOXO3 locus. Several databases document FOXO3 isoform2, an N-terminal truncated mutation of the full-length FOXO3 However, the biological function of FOXO3 isoform2 is unclear. In this study, we established a conditional allele of Foxo3 in mice that deletes the full-length Foxo3 except isoform2, a close ortholog of the human FOXO3 isoform2. Expression of Foxo3 isoform2 specifically in macrophage/osteoclast lineage suppresses osteoclastogenesis and leads to the osteopetrotic phenotype in mice. Mechanistically, Foxo3 isoform2 enhances the expression of type I IFN response genes to RANKL stimulation and thus inhibits osteoclastogenesis via endogenous IFN-β-mediated feedback inhibition. Our findings identify, to our knowledge, the first known biological function of Foxo3 isoform2 that acts as a novel osteoclastic inhibitor in bone remodeling.
31539517 Achaete-Scute Homologue 2-Regulated Follicular Helper T Cells Promote Autoimmunity in a Mu 2019 Dec Follicular helper T (Tfh) cells contribute to various immune responses as well as to the pathogenesis of several immune diseases. However, the precise mechanism underlying the onset or development of autoimmunity via Tfh cells remains unclear. Herein, the detailed relationship between autoimmune disease and Tfh cells was analyzed using a murine model for Sjögren syndrome (SS) wherein the mice underwent neonatal thymectomy. Germinal center (GC) development was promoted in this SS model along with an increase of Tfh cells and GC B cells. The severity of the autoimmune lesions was correlated with the number of Tfh cells detected in the spleen of the SS model mice. In addition, treatment with an anti-CD20 monoclonal antibody effectively suppressed the autoimmune lesions with a reduction of Tfh cells and GC B cells. Comprehensive gene analysis revealed that several genes associated with Tfh cell differentiation, including achaete-scute homologue 2 (Ascl2), were up-regulated in peripheral CD25(-) CD4(+) T cells in SS model mice compared with those in control mice. Moreover, an experiment using CD4(Cre)Bcl6(fl/fl) mice that received neonatal thymectomy treatment demonstrated that Ascl2 contributes to the Tfh cell differentiation associated with autoimmunity during the early stages, independent of Bcl6. In conclusion, our results indicate that abnormal Tfh cell differentiation via Ascl2 regulation might contribute to the pathogenesis of autoimmunity.
31319889 Differential effects of specific cathepsin S inhibition in biocompartments from patients w 2019 Jul 18 OBJECTIVE: Primary Sjögren syndrome (pSS) is characterized by T and B cell infiltration of exocrine glands. The cysteine protease cathepsin S (CatS) is crucially involved in MHCII processing and T cell stimulation, and elevated levels have been found in patients with RA, psoriasis and pSS. However, little is known about the functional characteristics and mechanisms of SS-A- and SS-B-specific T cells in pSS patients. We herein investigated the inhibition of CatS activity in different biocompartments of pSS patients including antigen-specific T cell responses. METHODS: Ex vivo CatS activity was assessed in tears, plasma and saliva of 15 pSS patients and 13 healthy controls (HC) and in the presence or absence of the specific CatS inhibitor RO5459072. In addition, antigen (SS-A (60kD), SS-B, influenza H(3)N(2), tetanus toxoid and SEB)-specific T cell responses were examined using ex vivo IFN-γ/IL-17 Dual ELISPOT and Bromdesoxyuridin (BrdU) proliferation assays in the presence or absence of RO5459072. Supernatants were analysed for IL-1β, IL-6, IL-10, TNF-α, IL-21, IL-22 and IL-23, using conventional ELISA. RESULTS: CatS activity was significantly elevated in tear fluid, but not other biocompartments, was inversely associated with exocrinic function in pSS patients and could significantly be suppressed by RO5459072. Moreover, CatS inhibition by RO5459072 led to strong and dose-dependent suppression of SS-A/SS-B-specific T cell effector functions and cytokine secretion by CD14(+) monocytes. However, RO5459072 was incapable of suppressing SS-A/SS-B-induced secretion of cytokines in CD14(+) monocytes when T cells were absent, confirming a CatS/MHCII-mediated mechanism of suppression. CONCLUSION: CatS activity in tear fluid seems to be a relevant biomarker for pSS disease activity. Conversely, CatS inhibition diminishes T cell and associated monokine responses towards relevant autoantigens in pSS. Thus, CatS inhibition may represent a promising novel treatment strategy in pSS.
30338648 Influence of total glucosides of paeony on PD-1/PD-L1 expression in primary Sjögren's syn 2019 Feb AIM: To study the influence of total glucosides of paeony (TGP) on the expression of peripheral blood programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in patients with primary Sjögren's syndrome (pSS). METHOD: Ten patients with new-onset pSS were selected as the experimental group and were treated with 1.8 g of TGP (the main ingredient is Radix Paeoniae Alba) daily for 3 months; furthermore, 10 physically healthy individuals were selected as the control group. Peripheral blood mononuclear cells were isolated, and flow cytometry was used to detect PD-1 expression on the surface of CD4+ T and CD8+ T lymphocytes and PD-L1 expression on the surface of CD14+ monocytes and CD19+ B cells before and after treatment in the experimental and control groups. Furthermore, plasma levels of soluble PD-1 (sPD-1), interleukin (IL)-10, and IL-17A were also determined using enzyme-linked immunosorbent assay. RESULTS: The PD-1 expression on the surface of CD4+ T and CD8+ T lymphocytes in the peripheral blood of patients with pSS were significantly higher than in the control group (P < 0.001). However, PD-L1 expression on the surface of CD14+ monocytes declined but not significantly (P > 0.05), and PD-L1 expression on the surface of CD19+ B cells increased significantly (P < 0.001). Moreover, sPD-1 and IL-17A levels in the plasma of the experimental group were significantly higher than in the control group (P < 0.001), but the IL-10 level was significantly lower than in the control group (P < 0.001). After TGP treatment, PD-1 expression on the surface of CD4+ T and CD8+ lymphocytes in the peripheral blood of patients with pSS had decreased significantly (P < 0.001); the PD-L1 expression on the surface of CD19+ cells had decreased significantly (P < 0.001); and the PD-L1 expression on the surface of CD14+ monocytes did not differ significantly (P > 0.05). Furthermore, the levels of sPD-1 and IL-17A in plasma had decreased (P < 0.01) and IL-10 levels had increased after TGP treatment (P < 0.01). CONCLUSION: PD-1/PD-L1 molecules expressed on the surface of T cells, B cells, and monokaryon participated in the pathogenesis and development of SS through interactions. Therefore, TGP, which may increase the expression of PD-1 and its relevant ligand PD-L1 in the peripheral blood mononuclear cells, may play a role in the pathogenesis and development of SS through the PD-1/PD-L1 pathway by regulating regulatory T cells/T helper cell 17.
30269510 Lower Bone Density on Preoperative Computed Tomography Predicts Periprosthetic Fracture Ri 2019 Jan BACKGROUND: The effect of bone mineral density (BMD) on outcomes from total ankle arthroplasty (TAA) has not been studied. BMD can be estimated by measuring Hounsfield units (HU) on standard computed tomography (CT), which is frequently performed prior to TAA. We aimed to identify whether tibial and talar HU measured from preoperative CT scans were associated with periprosthetic fracture or revision risk in patients undergoing TAA. METHODS: A prospectively collected database was used to retrospectively screen all patients undergoing primary TAA. Only patients with a preoperative CT within 1 year of surgery were included. Primary outcomes were periprosthetic fracture and prosthetic revision. HU were measured on axial CT cuts in the distal tibia and talus. Additional patient factors analyzed included age, sex, weight, body mass index (BMI), tobacco use, presence of rheumatoid arthritis, and preoperative deformity. A total of 198 ankles were included, with a mean 2.4 years of follow-up. RESULTS: There were 7 intraoperative and 9 postoperative periprosthetic fractures (3.5% and 4.5%, respectively). Seven patients (3.5%) underwent prosthetic removal or revision. Lower tibial and talar HU, lower weight, and lower BMI were associated with periprosthetic fractures ( P < .05). After controlling for age, sex, and weight, only tibial HU was significantly associated with periprosthetic fracture ( P = .018). All intraoperative fractures occurred in patients with tibial HU less than 200. None of the patient factors analyzed were associated with revision. CONCLUSIONS: Lower tibial HU on preoperative CT was strongly associated with periprosthetic fracture risk with TAA. In patients with tibial HU less than 200, surgeons may consider prophylactic internal fixation of the medial malleolus. LEVEL OF EVIDENCE: Level III, retrospective cohort study.
30807586 Patterns of joint involvement in juvenile idiopathic arthritis and prediction of disease c 2019 Feb BACKGROUND: Joint inflammation is the common feature underlying juvenile idiopathic arthritis (JIA). Clinicians recognize patterns of joint involvement currently not part of the International League of Associations for Rheumatology (ILAR) classification. Using unsupervised machine learning, we sought to uncover data-driven joint patterns that predict clinical phenotype and disease trajectories. METHODS AND FINDINGS: We analyzed prospectively collected clinical data, including joint involvement using a standard 71-joint homunculus, for 640 discovery patients with newly diagnosed JIA enrolled in a Canada-wide study who were followed serially for five years, treatment-naïve except for nonsteroidal anti-inflammatory drugs (NSAIDs) and diagnosed within one year of symptom onset. Twenty-one patients had systemic arthritis, 300 oligoarthritis, 125 rheumatoid factor (RF)-negative polyarthritis, 16 RF-positive polyarthritis, 37 psoriatic arthritis, 78 enthesitis-related arthritis (ERA), and 63 undifferentiated arthritis. At diagnosis, we observed global hierarchical groups of co-involved joints. To characterize these patterns, we developed sparse multilayer non-negative matrix factorization (NMF). Model selection by internal bi-cross-validation identified seven joint patterns at presentation, to which all 640 discovery patients were assigned: pelvic girdle (57 patients), fingers (25), wrists (114), toes (48), ankles (106), knees (283), and indistinct (7). Patterns were distinct from clinical subtypes (P < 0.001 by χ2 test) and reproducible through external data set validation on a 119-patient, prospectively collected independent validation cohort (reconstruction accuracy Q2 = 0.55 for patterns; 0.35 for groups). Some patients matched multiple patterns. To determine whether their disease outcomes differed, we further subdivided the 640 discovery patients into three subgroups by degree of localization-the percentage of their active joints aligning with their assigned pattern: localized (≥90%; 359 patients), partially localized (60%-90%; 124), or extended (<60%; 157). Localized patients more often maintained their baseline patterns (P < 0.05 for five groups by permutation test) than nonlocalized patients (P < 0.05 for three groups by permutation test) over a five-year follow-up period. We modelled time to zero joints in the discovery cohort using a multivariate Cox proportional hazards model considering joint pattern, degree of localization, and ILAR subtype. Despite receiving more intense treatment, 50% of nonlocalized patients had zero joints at one year compared to six months for localized patients. Overall, localized patients required less time to reach zero joints (partial: P = 0.0018 versus localized by log-rank test; extended: P = 0.0057). Potential limitations include the requirement for patients to be treatment naïve (except NSAIDs), which may skew the patient cohorts towards milder disease, and the validation cohort size precluded multivariate analyses of disease trajectories. CONCLUSIONS: Multilayer NMF identified patterns of joint involvement that predicted disease trajectory in children with arthritis. Our hierarchical unsupervised approach identified a new clinical feature, degree of localization, which predicted outcomes in both cohorts. Detailed assessment of every joint is already part of every musculoskeletal exam for children with arthritis. Our study supports both the continued collection of detailed joint involvement and the inclusion of patterns and degrees of localization to stratify patients and inform treatment decisions. This will advance pediatric rheumatology from counting joints to realizing the potential of using data available from uncovering patterns of joint involvement.
31871683 Interstitial pneumonia with autoimmune features that met the proposed diagnostic criteria 2020 Mar We held a multidisciplinary discussion (MDD) about a 61-year-old woman who had an interstitial lung disease (ILD) without extrathoracic lesions that met the classification criteria for interstitial pneumonia with autoimmune features (IPAF) and the proposed diagnostic criteria for immunoglobulin G4 (IgG4)-related respiratory disease (IgG4-RRD). Clinically, the marked progression of lung-limited diffuse lesions was consistent with IPAF. Serum IgG4 and rheumatoid factor levels simultaneously increased and did not contribute to a diagnosis. Pathologically, the significant hyperplasia of lymphoid follicles was consistent with rheumatoid arthritis (RA)-associated ILD. Pulmonary venous occlusions by intimal fibrosis and intimal thickening were not important because these occlusions are found in IgG4-related lung disease (IgG4-RLD) and also in IPAF or ILDs related to connective tissue diseases (CTDs). Radiologically, fibrosing shadows that remained in the lung periphery after treatment were compatible with RA-associated chronic ILD. We concluded that the present case was IPAF that met the proposed diagnostic criteria for IgG4-RRD.
32743515 The immunobiology of humanized Anti-IL6 receptor antibody: From basic research to breakthr 2020 The clinical use of monoclonal antibodies is well established in human medicine and has been amongst the most important contributions of basic science to clinical disease. One such antibody, the humanized anti-human IL-6 receptor antibody, is used to treat a variety of autoimmune diseases, particularly rheumatoid arthritis. It is extremely difficult and a laborious process to go from a concept at the research bench, to government approval. Such approval implies not only efficacy but, more importantly, an appropriate safety profile. In this review, the history of anti-human IL-6 receptor antibody is discussed in depth beginning with the author's experience during a sabbatical visit at the University of California at Davis in 1978. At that time, it was discovered that B cell activation was at least one critical factor in the development of autoimmunity. Approximately six years later, the cDNA encoding for IL-6 was cloned as BSF-2 (B cell stimulatory factor 2) to differentiate B cells to produce antibody. Soon after, it was suggested that this cytokine plays an important role in the development of autoimmune diseases. Based on this evidence, the journey began to search for an IL-6 inhibitor. Although there were numerous obstacles in finding lead compounds, ultimately, basic science developed the methodology for high throughput readouts that would inhibit the biologic function of IL-6. It was finally concluded that a mouse monoclonal antibody against IL-6 receptor would be optimal. In 1991, this antibody was humanized by using CDR-grafting technology in collaboration with the MRC (Medical Research Council). The drug was named tocilizumab and launched as an innovative anti-rheumatic drug in 2008 in Japan. Subsequently, the drug has been used throughout the world and has achieved enormous success in helping patients who suffer from inflammatory arthropathies. The lessons learned in the development of this antibody have application to the study of biologics and their application to other human diseases.
32377090 Minimally Invasive Open Surgical Approach and Outcomes for Carpal Tunnel Syndrome. 2019 OBJECTIVES: The most common peripheral neuropathy is carpal tunnel syndrome. The present study aims to describe our minimally invasive open surgical approach for carpal tunnel syndrome and evaluate surgical outcomes. METHODS: We included 217 patients who were operated in our clinic for carpal tunnel syndrome by minimally invasive open surgical approach. Visual Analogue Scale and Functional Outcome Scale scores were obtained preoperative, postoperative at one month and three months to determine surgical outcomes. RESULTS: The mean age of the patients was 55.4±12.8 years (32 to 69), 175 (80.6%) were women and 42 (19.4%) were men. The assessment of carpal tunnel syndrome's etiology showed that 189 (%87.1%) of the cases were idiopathic, 19 (8.8%) had hypothyroidism, 5 (2.3%) had rheumatoid arthritis and 4 (1.8%) were due to pregnancy. The average improvement of VAS between preoperatively and late postoperatively was 5.41±1.05. The average improvement FOS was 17.44±3.06. They were statistically significant. CONCLUSION: The minimally invasive open surgical approach for carpal tunnel syndrome (an average of 1 cm skin incision) is performed with local anesthesia and successful surgical outcomes are achieved.
31993235 The Role of Interleukin-37 in the Pathogenesis of Allergic Diseases. 2019 Oct Cytokines of the interleukin-1 (IL-1) family play an important role in the realization of the protective functions of innate immunity and are the key mediators involved in the pathogenesis of a wide range of diseases, including various manifestations of allergy. The IL-1 family includes more than 11 members. However, the functions of many of them remain to be elucidated. Recently, new members of the IL-1 family have been discovered. In 2000, several independent research groups reported the discovery of a new interleukin of this family, which was named IL-37, or IL-1F7 (according to the new nomenclature). IL-37 was assigned to the IL-1 family based on its structural similarity with other members of this family. The study of its biological properties showed that its activity changes in inflammatory diseases, such as rheumatoid arthritis, psoriasis, as well as allergic diseases (allergic rhinitis, bronchial asthma, and atopic dermatitis). However, unlike most members of the IL-1 family, IL-37 acts as a negative regulator of inflammation. Activation of IL-37 suppresses inflammation, resulting in the suppression of inflammatory cytokines and chemokines, which in turn prevents infiltration of pro-inflammatory cells, mainly eosinophils and neutrophils. The exact molecular and cellular mechanisms of the anti-inflammatory effect of IL-37 in the development of allergic diseases (AD) have not been fully studied. This review summarizes and analyzes the accumulated experimental data on the role of IL-37 in the pathogenesis of AD, such as allergic rhinitis, bronchial asthma, and atopic dermatitis.
31801160 Evaluation of Phytochemical and Pharmacological Activity of Carissa carandas L. Fruits at 2020 Feb Inflammation plays an important role in various diseases with high prevalence within populations such as rheumatoid arthritis, ulcer, atherosclerosis and asthma. Many drugs are available in the market for inflammatory diseases but they exhibit several unwanted side effects. Therefore, alternative treatments with safer compounds are needed. The plant Carissa carandas L. plant is used traditionally for the treatment of various diseases. Hence to validate its traditional use, the present study has envisaged screening different solvents extract of Carissa carandas fruit for their phytochemical and pharmacological activity especially the anti-inflammatory activity of the fruits at 3 different stages of maturation. The n-hexane and chloroform extracts of immature, mature and ripe fruits showed positive tests for steroids and triterpenoids, whereas acetone extract showed positive tests for steroids, triterpenoids, alkaloids, tannins, sugar, saponins except for triterpenoids in immature fruits. The hydroalcoholic extract showed presence of alkaloids, tannins, sugars, saponin and flavonoids. The highest concentration of phenol, flavonoids and ascorbic acid were found to be more in acetone extract of mature fruits and of carbohydrates in ripe fruits. The hydroalcoholic extract also exhibited similar pattern. The anti-inflammatory property was evaluated by using different models like carrageenan induced paw edema in Wistar rats and cotton pellets induced granuloma. There was a consistent increase in % inhibition of inflammation at concentrations of 100 and 200 mg/kg up to 3 h. The highest activity was at 3 h with 200 mg/kg dose. Thus the present work has clearly proved that the acetone extract of mature fruits have considerable anti-inflammatory activity.
31717919 Staphylococcus aureus Nasal Carriage and Autoimmune Diseases: From Pathogenic Mechanisms t 2019 Nov 11 The role of infective agents in autoimmune diseases (ADs) development has been historically investigated, but in the last years has been strongly reconsidered due to the interest in the link between the microbiome and ADs. Together with the gut, the skin microbiome is characterized by the presence of several microorganisms, potentially influencing innate and adaptive immune response. S. aureus is one of the most important components of the skin microbiome that can colonize anterior nares without clinical manifestations. Data from the literature demonstrates a significantly higher prevalence of nasal colonization in ADs patients in comparison with healthy subjects, suggesting a possible role in terms of disease development and phenotypes. Thus, in the present narrative review we focused on the mechanisms by which S. aureus could influence the immune response and on its relationship with ADs, in particular granulomatosis with polyangiitis, rheumatoid arthritis, and systemic lupus erythematosus.
31680733 Prevalence of metal hypersensitivity in total knee replacement. 2019 Nov BACKGROUND: Cutaneous and local reactions to metals used in orthopaedic implants have been well documented. The prevalence of metal sensitivity in general population is 10%-15%. Nickel, Cobalt and Chromium are the most common allergen. The association between cutaneous reactions and implants has been less understood. Hence, this study was taken up with the aim to assess the prevalence of metal hypersensitivity in Total Knee Replacement (TKR) patients and find the most prevalent allergen. MATERIALS & METHODS: Longitudinal study conducted during January-December 2017. We enrolled 233 subjects who were at least three months postoperative. Radiological assessment was done. CREDISOL® kit was used for patch test. Results were recorded using ICDRG grading at 48 hours and five days. RESULTS: Mean age was 59.59 years; 12.01% were symptomatic. Pain followed by loss of function were the most common symptoms. However, loss of function and patient dissatisfaction towards procedure were significantly associated with metal hypersensitivity (χ(2) value > 3.84; p value < 0.05). In 66% subjects, pre-operative diagnosis was severe osteoarthritis, followed by rheumatoid arthritis (23%). None of the subjects had evidence of loosening on X-ray. Prevalence of Metal Hypersensitivity was found to be 15.87% (patch test positive). Chromium (11.58%) was found to be most common allergen followed by Nickel (8.58%) and then Cobalt (6.43%). CONCLUSIONS: Significant prevalence of metal hypersensitivity was found. Therefore, we recommend pre-operative patch test for detecting allergic reactions to implants. Alternatives like Titanium or Zirconium can be used to avoid complications.
31670985 PI3Kδ inhibitors for the treatment of cancer: a patent review (2015-present). 2019 Dec Introduction: PI3Kδ is an important subtype of PI3K kinases, which is mainly expressed in leukocytes and plays an important role in the proliferation, differentiation, maturation and self-reaction of B cells. It is an effective target in the treatment of hematological malignancies and autoimmune diseases such as rheumatoid arthritis. Therefore, many pharmaceutical companies and research institutions have focused on the PI3Kδ subtype in an attempt to develop potent and selective PI3Kδ inhibitors.Areas covered: This review aims to provide an overview of the patented selective PI3Kδ inhibitors in treating cancer from 2015 to present.Expert opinion: Due to the importance of PI3Kδ, the development of selective PI3Kδ inhibitors for the treatment of hematoma and autoimmune diseases is expected. On 23 July 2014, the world's first selective PI3Kδ inhibitor, idelalisib, was approved by the FDA for the treatment of CLL, FL and SLL. Moreover, there are still many small molecule selective PI3Kδ inhibitors at different stages of development. The future research effort for development of PI3Kδ inhibitors is to manage the toxicity and lower the side-effects.
31559208 A Study on Etiopathogenesis of Vocal Cord Paresis and Palsy in a Tertiary Centre. 2019 Sep To identify patients of vocal cord paresis and palsy and to establish an etiological diagnosis based on a study performed in a tertiary centre. Study was done prospectively in the Department of ENT in KIMS Hospital, Bangalore, for 1 year, from June 2016 to June 2017. 100 patients with vocal cord paresis and palsy were identified and examined by using various tests and investigations to establish the etiology. Most of the patients presented with complaints of change in voice (92%). Some of the other common presenting complaints included noisy breathing and difficulty in swallowing, difficulty in voice production and vocal fatigue and cough. Unilateral paralysis (82%) was found to be more common than bilateral paralysis (18%), of which left (52%) was more commonly affected than right (48%) vocal cord. The most common age group affected was 51-60 years (24%) followed by 61-70 years (19%). Males (60%) were affected more than females (40%) in a ratio of 3:2 and among the affected males 73% were known smokers. The most common cause of vocal cord paresis and palsy was found to be idiopathic (38%), followed by primary laryngeal growths (27%). Other causes included carcinomas of lung, thyroid and oesophagus, traumatic, inflammatory, systemic diseases like Rheumatoid arthritis, Hypertension leading to stroke. Identifying the exact etiopathogenesis of vocal cord paresis and palsy in patients has been difficult and is very important in order to establish a proper diagnostic and treatment protocol for these patients.
31518745 Transnasal and Transoral Approaches to Atlantoaxial Synovial Cysts: Report of 3 Cases and 2019 Dec BACKGROUND: Synovial cysts are cystic masses lined with pseudostratified columnar cells and containing clear or xanthochromic fluid. Although they are commonly encountered in the lumbar spine, synovial cysts infrequently occur in the cervical spine and rarely involve the odontoid process. The causes of synovial cysts of the odontoid process are unknown, but growth of synovial rests, proliferation of multipotent mesenchymal cells, atlantoaxial instability, and trauma are thought to play a role. CASE DESCRIPTION: We present 3 cases of atlantoaxial cysts with the associated radiographic features, surgical management, and clinical outcomes. No patient had rheumatoid arthritis. In all cases, preoperative differential diagnosis included neoplastic pathologic changes. Two patients underwent odontoidectomy through either an endonasal or a transoral approach, followed by posterior occipitocervical fusion. The third patient underwent an endoscopic transsphenoidal approach for cyst decompression. CONCLUSIONS: Tissue diagnosis is important in confirming pathologic analysis because synovial cysts have radiographic characteristics similar to those of a wide variety of neoplasms of the craniovertebral junction.
31449925 Primary Whipple disease of the Central Nervous System presenting with rhombencephalitis. 2019 Nov Primary Whipple disease of the Central Nervous System is a rare entity whose outcome might be fatal if not promptly diagnosed and treated. Few cases are reported in the literature with heterogeneous clinical and radiological presentations which often make the diagnosis extremely challenging. We report a case of primary Whipple disease of the Central Nervous System presenting with rhombencephalitis in a female patient in immunosuppressive treatment for rheumatoid arthritis. We describe the management of our patient and discuss the features of this rare clinical entity.
31389299 Probing the structural interactions between methotrexate and dexamethasone with muscle cys 2020 Jul Drug protein interactions have gained considerable attention over the past many years. In the current communication the association of muscle cystatin (MC) with anti-rheumatic drugs methotrexate and dexamethasone was studied by thiol proteinase inhibitor assay, ultra violet (UV) absorption, fluorescence spectroscopy, and fluorescence transform infra-red spectroscopy (FTIR). A static pattern of quenching was noticed between muscle cystatin and methotrexate (MTX). Binding constant (K(a)) of methotrexate to muscle cystatin was found to be 1 × 10(-7) M(-1) and the stoichiometry of binding was calculated to be one. Fluorescence measurement of the emission quenching reveals that the quenching process of cystatin by dexamethasone (DXN) was also static. The stoichiometry of binding and binding constant was also obtained. Additional evidence regarding MTX-MC and DXN-MC was obtained from UV spectroscopy and FTIR spectroscopic results. Such spectroscopic studies would help in modelling new candidate drugs for rheumatoid arthritis based on their cystatin binding profile.Communicated by Ramaswamy H. Sarma.
31351674 Clinical significance of altered collagen-receptor functioning in platelets with emphasis 2019 Nov Much interest surrounds the receptors α2β1 and glycoprotein VI (GPVI) whose synchronized action mediates the attachment and activation of platelets on collagen, essential for preventing blood loss but also the most thrombogenic component of the vessel wall. Subject to density variations on platelets through natural polymorphisms, the absence of α2β1 or GPVI uniquely leads to a substantial block of hemostasis without causing major bleeding. Specific to the megakaryocyte lineage, GPVI and its signaling pathways are most promising targets for anti-thrombotic therapy. This review looks at the clinical consequences of the loss of collagen receptor function with emphasis on both the inherited and acquired loss of GPVI with brief mention of mouse models when necessary. A detailed survey of rare case reports of patients with inherited disease-causing variants of the GP6 gene is followed by an assessment of the causes and clinical consequences of acquired GPVI deficiency, a more frequent finding most often due to antibody-induced platelet GPVI shedding. Release of soluble GPVI is brought about by platelet metalloproteinases; a process induced by ligand or antibody binding to GPVI or even high shear forces. Also included is an assessment of the clinical importance of GPVI-mediated platelet interactions with fibrin and of the promise shown by the pharmacological inhibition of GPVI in a cardiovascular context. The role for GPVI in platelet function in inflammation and in the evolution and treatment of major illnesses such as rheumatoid arthritis, cancer and sepsis is also discussed.