You are here

Actualités Médicales

Relationship of MR Imaging of Submandibular Glands to Hyposalivation in Sjögren's Syndrome.

Actualités En Médecine Interne - dim, 15/07/2018 - 13:31

Relationship of MR Imaging of Submandibular Glands to Hyposalivation in Sjögren's Syndrome.

Oral Dis. 2018 Jul 14;:

Authors: Kojima I, Sakamoto M, Iikubo M, Shimada Y, Nishioka T, Sasano T

Abstract
OBJECTIVE: We analysed the correlation between magnetic resonance images of the parotid and submandibular glands and the salivary flow rate in patients with Sjögren's syndrome.
METHODS: We retrospectively reviewed magnetic resonance images (heterogeneous signal-intensity distribution and gland volume on T1- and fat-suppressed T2-weighted images, and multiple high-signal-intensity spots on magnetic resonance sialograms in the parotid and submandibular glands) obtained from 66 patients who were diagnosed with Sjögren's syndrome. We evaluated the relationship between these imaging features and their salivary flow rates in stimulated and unstimulated conditions.
RESULTS: We found that, as the disease progressed, both the heterogeneous signal-intensity distribution and the volumes of the parotid and the submandibular glands were significantly related to the stimulated and the unstimulated salivary flow rate. These imaging features were more highly correlated in assessments of the submandibular gland than in those of the parotid gland for both stimulated and unstimulated salivary flow rates.
CONCLUSIONS: Magnetic resonance image features of heterogeneity and smaller volume in the submandibular gland are reliable for predicting hyposalivation related to the progression of Sjögren's syndrome. This article is protected by copyright. All rights reserved.

PMID: 30007097 [PubMed - as supplied by publisher]

Up-regulation of IL-6 expression in human salivary gland cell line by IL-17 via activation of p38 MAPK, ERK, PI3K/Akt, and NF-κB pathways.

Actualités En Médecine Interne - dim, 15/07/2018 - 13:31

Up-regulation of IL-6 expression in human salivary gland cell line by IL-17 via activation of p38 MAPK, ERK, PI3K/Akt, and NF-κB pathways.

J Oral Pathol Med. 2018 Jul 14;:

Authors: Wei L, Xiong H, Li W, Li B, Cheng Y

Abstract
BACKGROUND: The human salivary gland cell line (HSG) has so far been used as in vitro models for study of the influence of cytokines and pharmacologic agents on salivary glands, as well as a model system for inflammation in Sjögren's syndrome (SS). This study aimed to determine the effect of IL-17 on IL-6 production and the underlying molecular mechanism regulated by the HSG cell line.
METHODS: Immunofluorescence analyses, RT-PCR, and Western blot were conducted to evaluate the IL-17 receptor (IL-17R) expression in cultured HSG cells. Real-time PCR and ELISA were then utilized to establish the mRNA and protein levels of IL-6 in IL-17-stimulated HSG cells. Western blot, flow cytometry, immunofluorescence and inhibitor analyses were conducted to elucidate the involved signaling pathways.
RESULTS: The HSG cells reliably expressed the IL-17R mRNA and its encoded surface-bound protein. The expression of IL-6 mRNA and protein was upregulated by stimulation of HSG cells with IL-17; this effect was impeded by IL-17 or IL-17R-neutralizing antibodies. IL-17 stimulation ended up with the fast phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), Akt, and translocation of nuclear factor-kappaB (NF-κB) in the HSG cells. p38 MAPK, Akt, and NF-κB inhibitors significantly subdued IL-6 generation in HSG cells stimulated by IL-17. PD98059, an ERK inhibitor, decreased IL-6 generation under low-dose of IL-17 but not with high-dose.
CONCLUSIONS: The HSG cells expressed IL-17R and reacted to IL-17 to generate IL-6 via the stimulation of ERK, p38 MAPK, Akt, and NF-κB signaling pathways. This article is protected by copyright. All rights reserved.

PMID: 30007092 [PubMed - as supplied by publisher]

Prevalence of overlap of antineutrophil cytoplasmic antibody associated vasculitis with systemic autoimmune diseases: an unrecognized example of poliautoimmunity.

Actualités En Médecine Interne - dim, 15/07/2018 - 13:31
Related Articles

Prevalence of overlap of antineutrophil cytoplasmic antibody associated vasculitis with systemic autoimmune diseases: an unrecognized example of poliautoimmunity.

Clin Rheumatol. 2018 Jul 14;:

Authors: Martín-Nares E, Zuñiga-Tamayo D, Hinojosa-Azaola A

Abstract
We aimed to estimate the frequency of overlap of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with systemic autoimmune diseases. Retrospective single-center study to identify patients with AAV diagnosis and concomitant autoimmune systemic diseases, simultaneously, before or after the diagnosis of AAV. Sociodemographic characteristics, such as comorbidities; follow-up time; type of AAV; disease duration; relapses; treatment and response; clinical, serological, and histological characteristics; disease activity and damage; prognosis; dialysis requirements, and death were assessed. Twenty-eight of two hundred and forty-seven patients (11.3%) with AAV had a concomitant diagnosis of autoimmune disease. The predominant AAV type was renal-limited vasculitis (39%), followed by granulomatosis with polyangiitis (29%), mycroscopic polyangiitis (25%), and eosinophilic granulomatosis with polyangiitis (7%). Mean age at AAV diagnosis was 50 ± 17 years and 24/28 were ANCA positive. The main clinical manifestations were renal (79%), otorhinolaryngologic (43%), and pulmonary and peripheral neuropathy (32%). Sixteen patients (57%) experienced partial or total remission at a median follow-up of 34 months, and four patients (14%) died. The most frequent autoimmune disease overlapped was rheumatoid arthritis (39%), followed by Sjögren's syndrome and systemic sclerosis (14%), mixed connective tissue disease (11%), systemic lupus erythematosus and juvenile idiopathic arthritis (7%), and ankylosing spondylitis and IgG4-related disease (4%). In nine patients (32%), both diagnoses were simultaneous; in the rest, median time elapsed between the autoimmune disease and AAV diagnosis was 173 months. The prevalence of overlap AAV with other autoimmune diseases was low. The most common AAV phenotype was renal-limited vasculitis, and the most frequent overlap disease was rheumatoid arthritis.

PMID: 30006919 [PubMed - as supplied by publisher]

Long-term follow-up of nailfold videocapillaroscopic changes in dermatomyositis versus systemic sclerosis patients.

Actualités En Médecine Interne - dim, 15/07/2018 - 13:31
Related Articles

Long-term follow-up of nailfold videocapillaroscopic changes in dermatomyositis versus systemic sclerosis patients.

Clin Rheumatol. 2018 Jul 13;:

Authors: Pizzorni C, Cutolo M, Sulli A, Ruaro B, Trombetta AC, Ferrari G, Pesce G, Smith V, Paolino S

Abstract
To identify nailfold videocapillaroscopy (NVC) changes in patients with dermatomyositis (DM) during a 3-year follow-up and to compare the NVC findings between DM and systemic sclerosis (SSc) patients at their first visit. Retrospective study of 24 DM and 24 SSc patients, matched for age and disease duration at first NVC. Capillaroscopic patterns/scores and clinical parameters had been yearly assessed. Nineteen out of 24 DM patients (79%) showed a NVC "scleroderma-like pattern." No statistically significant variation of all the capillaroscopic scores was observed during the 3-year follow-up. By comparing DM patients with or without anti-Jo-1 positivity, no statistically significant difference of the scores of the main capillary parameters was observed at baseline between the groups. Comparing at baseline DM with SSc patients, the giant capillary and microhemorrhage scores were significantly higher in SSc than those in DM patients (p = 0.04 and p = 0.05, respectively), while capillary density, ramification (abnormally shaped capillaries, expression of angiogenesis), and disorganization scores were higher in DM patients (p = 0.05, p = 0.002, p = 0.004, respectively). The absolute number of ramified capillaries was significantly higher in DM patients (p = 0.002), while the absolute capillary number was significantly higher in SSc patients (p = 0.05) at baseline. This pilot study demonstrates, for the first time, over long-term, that the capillaroscopic manifestations of DM persist in contrast to the progressive changes described in SSc patients, and the anti-Jo-1 positivity does not seem to modify the NVC pattern.

PMID: 30006917 [PubMed - as supplied by publisher]

Calcium signaling defects underlying salivary gland dysfunction.

Actualités En Médecine Interne - dim, 15/07/2018 - 13:31
Related Articles

Calcium signaling defects underlying salivary gland dysfunction.

Biochim Biophys Acta. 2018 Jul 10;:

Authors: Ambudkar I

Abstract
Salivary glands secrete saliva, a mixture of proteins and fluids, which plays an extremely important role in the maintenance of oral health. Loss of salivary secretion causes a dry mouth condition, xerostomia, which has numerous deleterious consequences including opportunistic infections within the oral cavity, difficulties in eating and swallowing food, and problems with speech. Saliva secretion is regulated by stimulation of specific signaling mechanisms within the acinar cells of the gland. Neurotransmitter-stimulated increase in cytosolic [Ca2+] ([Ca2+]i) in acinar cells is the primary trigger for salivary fluid secretion from salivary glands, the loss of which is a critical factor underlying dry mouth conditions in patients. The increase in [Ca2+]i regulates multiple ion channel and transport activities that together generate the osmotic gradient which drives fluid secretion across the apical membrane. Ca2+ entry mediated by the Store-Operated Ca2+ Entry (SOCE) mechanism provides the essential [Ca2+]i signals to trigger salivary gland fluid secretion. Under physiological conditions depletion of ER-Ca2+ stores is caused by activation of IP3R by IP3 and this provides the stimulus for SOCE. Core components of SOCE in salivary gland acinar cells are the plasma membrane Ca2+ channels, Orai1 and TRPC1, and STIM1, a Ca2+-sensor protein in the ER, which regulates both channels. In addition, STIM2 likely enhances the sensitivity of cells to ER-Ca2+ depletion thereby tuning the cellular response to agonist stimulation. Two major, clinically relevant, conditions which cause irreversible salivary gland dysfunction are radiation treatment for head-and-neck cancers and the autoimmune exocrinopathy, Sjögren's syndrome (pSS). However, the exact mechanism(s) that causes the loss of fluid secretion, in either condition, is not clearly understood. A number of recent studies have identified that defects in critical Ca2+ signaling mechanisms underlie salivary gland dysfunction caused by radiation treatment or Sjögren's syndrome (pSS). This chapter will discuss these very interesting and important studies.

PMID: 30006140 [PubMed - as supplied by publisher]

Therapy of scleroderma renal crisis: State of the art.

Actualités En Médecine Interne - dim, 15/07/2018 - 13:31
Related Articles

Therapy of scleroderma renal crisis: State of the art.

Autoimmun Rev. 2018 Jul 10;:

Authors: Zanatta E, Polito P, Favaro M, Larosa M, Marson P, Cozzi F, Doria A

Abstract
Scleroderma renal crisis (SRC) is an uncommon but still life-threatening manifestation of systemic sclerosis (SSc). The incidence of SRC has decreased in the last few decades, probably due to a widespread use of vasodilators in SSc patients. It is well-recognized that exposure to different drugs can trigger SRC (corticosteroids, cyclosporine) or prevent its occurrence (iloprost, calcium channel blockers). The prognosis of this life-threatening manifestation has not substantially improved since 1980s, when ACE-inhibitors were introduced in its treatment. ACE-inhibitors remain the mainstay in the therapy of SRC due to their efficacy in controlling malignant hypertension; indeed, the prognosis largely depends on the rapid improvement of the ongoing renal ischemia. Calcium-channel blockers and in third line diuretics and alpha-blockers should be used as additional therapy if blood pressure control remains suboptimal despite maximum tolerated doses of ACE-inhibitors. Given the growing evidence on the role of complement activation and endothelin-1 in the pathogenesis of SRC, recent case-series and case reports have suggested the use of C5-inhibitors and endothelin receptor antagonists in the therapy of SRC, mainly in the refractory cases. Plasma-exchange seems to give some benefits in patients with SRC and microangiopathy or intolerant to ACE-inhibitors. Renal transplantation is the last treatment option and its outcome is similar to that reported in other connective tissue disorders, with a 5-year patient survival rate of about 82%. In this review we summarize the current knowledge in the treatment of SRC.

PMID: 30005860 [PubMed - as supplied by publisher]

Subclinical cardiovascular disease and Systemic Sclerosis: A comparison between risk charts, quantification of coronary calcium and carotid ultrasonography.

Actualités En Médecine Interne - dim, 15/07/2018 - 13:31
Related Articles

Subclinical cardiovascular disease and Systemic Sclerosis: A comparison between risk charts, quantification of coronary calcium and carotid ultrasonography.

Autoimmun Rev. 2018 Jul 10;:

Authors: Sanz Pérez I, Martínez Valle F, Guillén Del Castillo A, Roque Pérez A, Cuéllar Calàbria H, Pizzi MN, Fernández Codina A, Callejas Moragas E, Orozco Gálvez O, Fonollosa Pla V, Simeón Aznar CP

Abstract
BACKGROUND AND OBJECTIVES: Recently published population-based cohort studies have shown a high prevalence of cardiovascular disease in Systemic Sclerosis (SSc) patients. The aim of this study is to compare three different methods to measure cardiovascular risk in patients with scleroderma.
METHODS: Forty-three SSc patients were included. A prospective study was performed for evaluation of cardiovascular risk and subclinical atheromatosis using 3 non-invasive methods: cardiovascular risk tables, carotid Doppler ultrasonography and quantification of coronary calcium by computerized tomography (CT).
RESULTS: The cardiovascular risk charts for the Spanish population did not identify patients at high cardiovascular risk. Framingham-REGICOR identified 13 intermediate-risk patients. Twenty-two patients (51.2%) had plaques on carotid ultrasonography. We performed a ROC curve to identify the best cutoff point for the quantification of coronary artery calcium (CACscore), the value of CACscore > 28 AU (Agatston Units) had the highest sensitivity (73%) and specificity (81%) for the diagnosis of subclinical atheromatosis. In the multiple regression study, age and decreased HDL cholesterol levels were identified as independent factors for subclinical atherosclerotic disease. No disease-related factors were associated with increased subclinical arteriosclerosis.
CONCLUSION: Carotid ultrasound and CACscore are useful for identifying subclinical atheromatosis in patients with SSc and are superior compared to risk charts used for general population. HDL cholesterol and age were independent factors for the presence of subclinical atherosclerotic disease. A carotid ultrasound or CT should be performed for early detection of subclinical atheromatosis if these factors are present.

PMID: 30005858 [PubMed - as supplied by publisher]

((((((thrombophlebitis) OR takayasu) OR temporal arteritis) OR sarcoidosis) OR myositis) OR scleroderma) OR sjogren's disease; +17 new citations

Actualités En Médecine Interne - sam, 14/07/2018 - 14:48

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

((((((thrombophlebitis) OR takayasu) OR temporal arteritis) OR sarcoidosis) OR myositis) OR scleroderma) OR sjogren's disease

These pubmed results were generated on 2018/07/14

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Does early seronegative arthritis develop into rheumatoid arthritis? A 10-year observational study.

Actualités En Médecine Interne - ven, 13/07/2018 - 12:06
Related Articles

Does early seronegative arthritis develop into rheumatoid arthritis? A 10-year observational study.

Clin Exp Rheumatol. 2018 Jun 07;

Authors: Paalanen K, Rannio K, Rannio T, Asikainen J, Hannonen P, Sokka T

Abstract
OBJECTIVES: To investigate the 10-year clinical course of patients with seronegative arthritis with the emphasis of reclassification of diagnoses when applicable.
METHODS: A total of 1030 patients including 435 seronegative cases were classified as early RA in 1997-2005 at Jyväskylä Rheumatology Centre and prospectively scheduled for a ten-year follow-up. Clinical data from the follow-up visits and the case-reports until and including the 10-year visit or death, whichever happened earlier, were retrospectively collected and reviewed with re-classification of the cases when applicable. Descriptive statistics were used.
RESULTS: Among the 435 seronegative cases (69 % women, baseline mean age was 59 years), 13 (13/435 [3%]) could be reclassified as seropositive or erosive RA: 4 turned seropositive (2 for ACPA and 2 for RF [> 2x reference level]) and 9 developed erosions typical for RA. Reclassification revealed 68 (16%) cases of polymyalgia rheumatica, 46 (11%) psoriatic arthritis, 45 (10%) osteoarthritis, 38 (8.7%) spondyloarthritis, 15 (3.4%) plausible reactive arthritis, 10 (2.3%) gout, 17 (3.9%) pseudogout, 6 (1.4%) paraneoplastic arthritis, 6 (1.4%) juvenile arthritis, 2 (0.5%) haemochromatosis, 3 (0.7%) ankylosing spondylitis, 2 (0.5%) giant cell arteritis, and 8 miscellaneous diagnoses. The other 140 patients (32%) could not be reclassified in any clear-cut diagnosis and had features of transient arthritis (n=41), seronegative spondyloarthritis (n=47), while 49 remained unspecified.
CONCLUSIONS: Over a 10-year follow-up period, reclassification revealed significant heterogeneity in the diagnosis of seronegative RA. Therefore, seronegative arthritis should not be studied as a homogenous entity.

PMID: 29998832 [PubMed - as supplied by publisher]

Limited efficacy of targeted treatments in Sjögren's syndrome: why?

Actualités En Médecine Interne - ven, 13/07/2018 - 12:06
Related Articles

Limited efficacy of targeted treatments in Sjögren's syndrome: why?

Clin Exp Rheumatol. 2018 Jun 21;

Authors: Tzioufas AG, Goules AV

PMID: 29998826 [PubMed - as supplied by publisher]

The prevalence and relevance of traditional cardiovascular risk factors in primary Sjögren's syndrome.

Actualités En Médecine Interne - ven, 13/07/2018 - 12:06
Related Articles

The prevalence and relevance of traditional cardiovascular risk factors in primary Sjögren's syndrome.

Clin Exp Rheumatol. 2018 May 30;

Authors: Bartoloni E, Alunno A, Valentini V, Valentini E, La Paglia GMC, Leone MC, Cafaro G, Marcucci E, Bonifacio AF, Luccioli F, Gerli R

Abstract
Accelerated atherosclerosis is a distinct feature of some inflammatory and autoimmune disorders and several specific autoimmune mechanisms and persistent inflammation have been identified to exert a pivotal role in precocious atherosclerotic damage in these disorders. Although increased atherosclerotic risk has been well established in some rheumatic autoimmune systemic diseases, such as systemic lupus erythematosus and rheumatoid arthritis, reliable data regarding the prevalence and pathogenetic mechanisms associated with increased atherosclerotic damage in primary Sjögren's syndrome are scarse. Indeed, primary Sjögren's syndrome is an autoimmune disorder characterised by chronic inflammation and autoimmune dysregulation that shares many pathogenic mechanisms and clinical features with systemic lupus erythematosus and rheumatoid arthitis. Higher prevalence of subclinical atherosclerosis has been observed in primary Sjögren's syndrome patients and recent population-based studies demonstrated an increased risk of cardiovascular events in these patients in comparison to general population. Among mechanisms associated with atherosclerotic damage, the prevalence and the role of traditional cardiovascular risk factors have been poorly investigated. In particular, the issue of whether the presence of these cardiovascular risk factors is associated with an increased risk of cardiovascular events needs to be further explored.

PMID: 29998823 [PubMed - as supplied by publisher]

Salivary S100A8/A9 in Sjögren's syndrome accompanied by lymphoma.

Actualités En Médecine Interne - ven, 13/07/2018 - 12:06
Related Articles

Salivary S100A8/A9 in Sjögren's syndrome accompanied by lymphoma.

J Oral Pathol Med. 2018 Jul 12;:

Authors: Jazzar A, Shirlaw PJ, Carpenter GH, Challacombe SJ, Proctor GB

Abstract
BACKGROUND: Sjögren's syndrome (SS) is an autoimmune inflammatory disease that affects the exocrine glands. The absence of early diagnostic markers contributes to delays in its diagnosis. Identification of changes in the protein profile of saliva is considered one of the promising strategies for the discovery of new biomarkers for SS.
OBJECTIVE: To identify salivary protein biomarkers with potential for use in discriminating between different lymphoma risk sub-groups of SS.
METHOD: Parotid and whole mouth saliva samples were collected from SS patients, including those in sub-groups at higher risk of developing or with confirmed lymphoma, non-SS sicca disease controls and healthy subjects. An initial proteomics analysis by mass spectrometry (LCMSMS) identified S100A8/A9 as a biomarker and was followed by validation with an enzyme linked immunosorbent assay (ELISA).
RESULTS: Significant differences were found in levels of S100A8/A9 in parotid saliva but not whole mouth saliva between SS patients compared with healthy and disease control subjects (p=0.001 and 0.031respectively). Sub-groups of SS patients based on lymphoma risk showed significant differences in salivary levels of S100A8/A9.
CONCLUSION: The results suggest that salivary levels of S100A8/A9 can aid in differentiating between SS, disease control and healthy control subjects, especially the sub-groups of SS with lymphoma or at higher risk of lymphoma. This article is protected by copyright. All rights reserved.

PMID: 29998578 [PubMed - as supplied by publisher]

Serum BAFF and APRIL levels in Indian patients with Takayasu arteritis.

Actualités En Médecine Interne - ven, 13/07/2018 - 12:06
Related Articles

Serum BAFF and APRIL levels in Indian patients with Takayasu arteritis.

Clin Rheumatol. 2018 Jul 11;:

Authors: Zanwar A, Jain A, Gupta L, Chaurasia S, Kumar S, Misra DP, Misra R

Abstract
Despite many studies focused on involvement of T cell in pathogenesis of Takayasu arteritis (TaK), very few have explored the role of B cells. Hence, we sought evidence of B cell involvement in a large cohort of TaK by measuring serum levels of B cell survival factors activation factor (BAFF) and A proliferation inducing ligand (APRIL). Serum BAFF and APRIL levels were measured by ELISA in 50 patients and 48 healthy individuals, and further assessed for correlation with outcome measures, such as Indian Takayasu Clinical Activity Score-ESR (ITAS-ESR) and Takayasu arteritis Damage score (TADS). Forty women and ten men of median age 26 (11-52) and disease duration of 3 years (0.1-22) were studied. Type V disease was the most common subset (n = 31), while type I, II, III, and IV was seen in ten, four, three, and two patients respectively. Serum APRIL levels were raised in patients as compared to healthy controls [2087.5 pg/ml (1480.0-2279.0) vs. 1288.64 pg/ml, (844.2-1632.9) p = 0.01]. Median serum APRIL level was also raised in patients with active disease (n = 24) as compared to inactive disease (n = 26) 2098.79 pg/ml, (1930.75-2768.75) vs. 1802.5 pg/ml, (1066.75-2098); p = 0.03). Serum BAFF levels were not raised in patients with TaK when compared to healthy Individuals. Neither BAFF, nor APRIL levels correlated with disease activity (ITAS-ESR) or TADS. Elevated APRIL levels in active TaK suggest probable role of B cells in pathogenesis.

PMID: 29998368 [PubMed - as supplied by publisher]

Enhancement of the aesthetic outcome of scleroderma en coup de sabre with botulinum toxin injection.

Actualités En Médecine Interne - ven, 13/07/2018 - 12:06
Related Articles

Enhancement of the aesthetic outcome of scleroderma en coup de sabre with botulinum toxin injection.

JAAD Case Rep. 2018 Jul;4(6):579-581

Authors: Turkmani MG, Alnomair N

PMID: 29998179 [PubMed]

A typical case of giant cell arteritis with vision loss due to delayed diagnosis.

Actualités En Médecine Interne - ven, 13/07/2018 - 12:06
Related Articles

A typical case of giant cell arteritis with vision loss due to delayed diagnosis.

J Gen Fam Med. 2018 Jul;19(4):139-140

Authors: Watanabe A, Isono H, Shimada K, Chino Y

Abstract
A 75-year-old woman lost vision because of delayed recognition of GCA. Early diagnosis and treatment of GCA are important for preventing visual complications. Physicians must remember to evaluate the entire body, not just a single organ/system.

PMID: 29998045 [PubMed]

The Diagnostic Value of MRI Pattern Recognition in Distal Myopathies.

Actualités En Médecine Interne - ven, 13/07/2018 - 12:06
Related Articles

The Diagnostic Value of MRI Pattern Recognition in Distal Myopathies.

Front Neurol. 2018;9:456

Authors: Bugiardini E, Morrow JM, Shah S, Wood CL, Lynch DS, Pitmann AM, Reilly MM, Houlden H, Matthews E, Parton M, Hanna MG, Straub V, Yousry TA

Abstract
Objective: Distal myopathies are a diagnostically challenging group of diseases. We wanted to understand the value of MRI in the current clinical setting and explore the potential for optimizing its clinical application. Methods: We retrospectively audited the diagnostic workup in a distal myopathy patient cohort, reassessing the diagnosis, whilst documenting the usage of MRI. We established a literature based distal myopathies MRI pattern template and assessed its diagnostic utility in terms of sensitivity, specificity, and potential impact on the diagnostic workup. Results: Fifty-five patients were included; in 38 with a comprehensive set of data the diagnostic work-up was audited. The median time from symptoms onset to diagnosis was 12.1 years. The initial genetic diagnostic rate was 39%; 18% were misdiagnosed as neuropathies and 13% as inclusion body myositis (IBM). Based on 21 publications we established a MRI pattern template. Its overall sensitivity (50%) and specificity (32%) were low. However in some diseases (e.g., MYOT-related myopathy, TTN-HMERF) MRI correctly identified the causative gene. The number of genes suggested by MRI pattern analysis was smaller compared to clinical work up (median 1 vs. 9, p < 0.0001) but fewer genes were correctly predicted (5/10 vs. 7/10). MRI analysis ruled out IBM in all cases. Conclusion: In the diagnostic work-up of distal myopathies, MRI is useful in assisting genetic testing and avoiding misdiagnosis (IBM). The overall low sensitivity and specificity limits its generalized use when traditional single gene test methods are applied. However, in the context of next generation sequencing MRI may represent a valuable tool for interpreting complex genetic results.

PMID: 29997562 [PubMed]

TRP Channel Involvement in Salivary Glands-Some Good, Some Bad.

Actualités En Médecine Interne - ven, 13/07/2018 - 12:06
Related Articles

TRP Channel Involvement in Salivary Glands-Some Good, Some Bad.

Cells. 2018 Jul 11;7(7):

Authors: Liu X, Ong HL, Ambudkar I

Abstract
Salivary glands secrete saliva, a mixture of proteins and fluids, which plays an extremely important role in the maintenance of oral health. Loss of salivary secretion causes a dry mouth condition, xerostomia, which has numerous deleterious consequences including opportunistic infections within the oral cavity, difficulties in eating and swallowing food, and problems with speech. Secretion of fluid by salivary glands is stimulated by activation of specific receptors on acinar cell plasma membrane and is mediated by an increase in cytosolic [Ca2+] ([Ca2+]i). The increase in [Ca2+]i regulates a number of ion channels and transporters that are required for establishing an osmotic gradient that drives water flow via aquaporin water channels in the apical membrane. The Store-Operated Ca2+ Entry (SOCE) mechanism, which is regulated in response to depletion of ER-Ca2+, determines the sustained [Ca2+]i increase required for prolonged fluid secretion. Core components of SOCE in salivary gland acinar cells are Orai1 and STIM1. In addition, TRPC1 is a major and non-redundant contributor to SOCE and fluid secretion in salivary gland acinar and ductal cells. Other TRP channels that contribute to salivary flow are TRPC3 and TRPV4, while presence of others, including TRPM8, TRPA1, TRPV1, and TRPV3, have been identified in the gland. Loss of salivary gland function leads to dry mouth conditions, or xerostomia, which is clinically seen in patients who have undergone radiation treatment for head-and-neck cancers, and those with the autoimmune exocrinopathy, Sjögren's syndrome (pSS). TRPM2 is a unique TRP channel that acts as a sensor for intracellular ROS. We will discuss recent studies reported by us that demonstrate a key role for TRPM2 in radiation-induced salivary gland dysfunction. Further, there is increasing evidence that TRPM2 might be involved in inflammatory processes. These interesting findings point to the possible involvement of TRPM2 in Sjögren's Syndrome, although further studies will be required to identify the exact role of TRPM2 in this disease.

PMID: 29997338 [PubMed]

TLR4-dependent fibroblast activation drives persistent organ fibrosis in skin and lung.

Actualités En Médecine Interne - ven, 13/07/2018 - 12:06
Related Articles

TLR4-dependent fibroblast activation drives persistent organ fibrosis in skin and lung.

JCI Insight. 2018 Jul 12;3(13):

Authors: Bhattacharyya S, Wang W, Qin W, Cheng K, Coulup S, Chavez S, Jiang S, Raparia K, De Almeida LMV, Stehlik C, Tamaki Z, Yin H, Varga J

Abstract
Persistent fibrosis in multiple organs is the hallmark of systemic sclerosis (SSc). Recent genetic and genomic studies implicate TLRs and their damage-associated molecular pattern (DAMP) endogenous ligands in fibrosis. To test the hypothesis that TLR4 and its coreceptor myeloid differentiation 2 (MD2) drive fibrosis persistence, we measured MD2/TLR4 signaling in tissues from patients with fibrotic SSc, and we examined the impact of MD2 targeting using a potentially novel small molecule. Levels of MD2 and TLR4, and a TLR4-responsive gene signature, were enhanced in SSc skin biopsies. We developed a small molecule that selectively blocks MD2, which is uniquely required for TLR4 signaling. Targeting MD2/TLR4 abrogated inducible and constitutive myofibroblast transformation and matrix remodeling in fibroblast monolayers, as well as in 3-D scleroderma skin equivalents and human skin explants. Moreover, the selective TLR4 inhibitor prevented organ fibrosis in several preclinical disease models and mouse strains, and it reversed preexisting fibrosis. Fibroblast-specific deletion of TLR4 in mice afforded substantial protection from skin and lung fibrosis. By comparing experimentally generated fibroblast TLR4 gene signatures with SSc skin biopsy gene expression datasets, we identified a subset of SSc patients displaying an activated TLR4 signature. Together, results from these human and mouse studies implicate MD2/TLR4-dependent fibroblast activation as a key driver of persistent organ fibrosis. The results suggest that SSc patients with high TLR4 activity might show optimal therapeutic response to selective inhibitors of MD2/TLR4 complex formation.

PMID: 29997297 [PubMed - as supplied by publisher]

Serial observation of electrocardiographic responses to corticosteroid therapy in a patient with right ventricular-predominant cardiac sarcoidosis.

Actualités En Médecine Interne - ven, 13/07/2018 - 12:06
Related Articles

Serial observation of electrocardiographic responses to corticosteroid therapy in a patient with right ventricular-predominant cardiac sarcoidosis.

J Electrocardiol. 2018 Jul - Aug;51(4):658-662

Authors: Toh H, Mori S, Keno M, Yokota S, Shinkura Y, Izawa Y, Nagamatsu Y, Shimoyama S, Fukuzawa K, Doi T, Hirata KI

Abstract
Predominant or isolated right ventricular involvement in cardiac sarcoidosis is uncommon, but should always be considered in a case of right ventricular hypertrophy combined with ventricular arrhythmia and/or conduction disturbance. Although improvement in right ventricular hypertrophy and atrioventricular conduction disturbance following corticosteroid therapy has been reported, the detailed serial electrocardiographic responses during corticosteroid therapy, as well as temporal changes in the electrocardiographic, biochemical, and morphological responses, have not been reported. We describe the clinical course and supportive imaging findings of reversible right ventricular hypertrophy and cardiac conduction disturbance in a case of right ventricular-predominant cardiac sarcoidosis.

PMID: 29997007 [PubMed - in process]

Extravascular manifestations of Takayasu arteritis: focusing on the features shared with spondyloarthritis.

Actualités En Médecine Interne - ven, 13/07/2018 - 12:06
Related Articles

Extravascular manifestations of Takayasu arteritis: focusing on the features shared with spondyloarthritis.

Arthritis Res Ther. 2018 Jul 11;20(1):142

Authors: Kwon OC, Lee SW, Park YB, Oh JS, Lee SH, Hong S, Lee CK, Yoo B, Kim YG

Abstract
BACKGROUND: Takayasu arteritis (TAK) is a systemic disease characterized by large vessel involvement. Although the vascular characteristics of TAK are well characterized, there is no well-organized study demonstrating the extravascular manifestations of TAK. We aimed to evaluate the characteristics of extravascular manifestations of TAK, and to identify the association between vascular and extravascular manifestations of TAK.
METHODS: TAK patients from two independent cohorts between January 2012 and October 2017 were included in the study. Patient characteristics were retrospectively collected from the electronic dataset. The computed tomography scans of all subjects were reviewed to evaluate the pattern of vascular involvement and presence of sacroiliitis. Clinical findings including uveitis, skin lesions, oral ulcers, arthritis, and inflammatory bowel disease (IBD) were reviewed. Logistic regression analysis was performed to evaluate the association between vascular and extravascular manifestations.
RESULTS: For the 268 TAK patients, the mean age at diagnosis was 41.2 ± 14.2 years and 88.1% were female. The extravascular manifestation of TAK was observed in 19.0% of patients, the most common being arthritis including sacroiliitis (11.9%) followed by recurrent oral ulcers (8.6%) and IBD (2.6%). A multivariate logistic regression analysis revealed type IIB vascular involvement (adjusted odds ratio (OR) 2.956, 95% confidence interval (CI) 1.337-6.537, p = 0.007) and the erythrocyte sedimentation rate (ESR) (adjusted OR 1.014, 95% CI 1.003-1.025, p = 0.012) as significantly associated with the presence of axial and peripheral arthritis.
CONCLUSIONS: Extravascular manifestations of TAK were observed in up to one-fifth of patients. The most common extravascular manifestation was arthritis, which was associated with a type IIB vascular involvement pattern and a high ESR.

PMID: 29996949 [PubMed - in process]

Pages

Subscribe to La Libre Pensée  agrégateur - Actualités Médecine Interne