Amyloid Myopathy as an Inclusion Body Myositis Mimic

Introduction: Amyloid myopathy is a rare presentation of systemic amyloidosis. Amyloid myopathy can be initially misdiagnosed as sporadic inclusion body myositis (IBM). Methods: We report 4 cases of amyloid myopathy clinically mimicking inclusion body myositis and initially thought to be phenotypically IBM by neuromuscular experts. Results: Case 1 is an 81-year-old woman who presented with distal arm and proximal leg asymmetric weakness (myopathy pattern 4). Case 2 is a 76-year-old man with primary systemic amyloidosis who presented with myopathy pattern 4 and progressive dysphagia for four years. Case 3 is an 82-year-old man with progressive myopathy pattern 4 weakness and swallowing difficulty. Case 4 is a 62-year-old man with progressive bilateral finger flexor weakness. Muscle biopsies in all 4 cases showed perivascular amyloid deposits Discussion: Amyloid myopathy may be clinically indistinguishable from IBM. Muscle biopsy is of critical importance in the evaluation of patients suspected to have IBM

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Chapitre 2. Imprimés et communautés

Les communautés amérindiennes CORNELIUS J. JAENEN Le XIXe siècle a été le théâtre d’un changement de perception des peuples autochtones. Jusque-là, les écrits européens les avaient plutôt dépeints avantageusement comme des personnes actives, indépendantes, parfois même comme des modèles de simplicité, de liberté, de fraternité et d’hospitalité. La poésie avait célébré comme des héros les chefs Kondiaronk, Pontiac et Tecumseh. Après 1840 cependant, les stéréotypes négatifs très répandus dans l..

Chapitre 9. Les périodiques

Les journaux et les magazines MERRILL DISTAD La presse périodique est le plus ancien média de masse national ; journaux et magazines ont joué un rôle crucial dans l’élaboration des cultures et de l’identité canadiennes. Après 1840, les journaux, déjà bien implantés dans toutes les colonies de l’Amérique du Nord britannique, gagnent en taille et en influence grâce à l’introduction de procédés d’impression adaptés aux grands tirages (voir illustration 9.1). Les magazines, au contraire, s’étiole..

Exogenous serotonin regulates proliferation of interstitial cells of Cajal in mouse jejunum through 5-HT2B receptors

BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) are required for normal gastrointestinal motility. Loss of ICC is associated with several motility disorders. The mechanisms modulating ICC survival and proliferation are poorly understood. This study aimed to establish whether 5-hydroxytryptamine (5-HT) plays a role in regulating ICC proliferation. METHODS: Expression of 5-HT receptor mRNA was investigated in muscle strips, in purified populations of ICC, and in identified single cells. The effect of 5-HT(2B) receptor ligands on ICC numbers was studied in primary cell cultures. Proliferation of ICC was determined by counting Ki67-positive cells in culture. RESULTS: Of the 5-HT receptors known to be involved in proliferation, 5-HT(2B) receptor mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in jejunal muscle, whereas 5-HT(1A), 5-HT(1D), and 5-HT(2C) receptor mRNAs were not. 5-HT(2B) receptor mRNA was found in single ICC and cells purified by flow cytometry. Exogenous 5-HT (1 micromol/L) increased (66% +/- 9%, P < .005) ICC numbers in culture. The 5-HT(2) receptor antagonist, ritanserin, and the 5-HT(2B) receptor antagonist, SB204741, inhibited the effect of 5-HT. The 5-HT(2B) receptor agonist BW 723C86 induced a concentration-dependent increase in ICC number (50% +/- 6% at 50 nM, P < .04) and increased ICC proliferation (25% +/- 3% vs 19 +/- 1% in controls, P < .03). CONCLUSIONS: These studies establish that 5-HT(2B) receptors are expressed on ICC. Exogenous 5-HT regulates ICC numbers through 5-HT(2B) receptors in part by increasing ICC proliferation. The 5-HT(2B) receptor may serve as a novel pathway to regulate ICC numbers.status: publishe

Potential contribution of the uterine microbiome in the development of endometrial cancer

Abstract Background Endometrial cancer studies have led to a number of well-defined but mechanistically unconnected genetic and environmental risk factors. One of the emerging modulators between environmental triggers and genetic expression is the microbiome. We set out to inquire about the composition of the uterine microbiome and its putative role in endometrial cancer. Methods We undertook a study of the microbiome in samples taken from different locations along the female reproductive tract in patients with endometrial cancer (n = 17), patients with endometrial hyperplasia (endometrial cancer precursor, n = 4), and patients afflicted with benign uterine conditions (n = 10). Vaginal, cervical, Fallopian, ovarian, peritoneal, and urine samples were collected aseptically both in the operating room and the pathology laboratory. DNA extraction was followed by amplification and high-throughput next generation sequencing (MiSeq) of the 16S rDNA V3-V5 region to identify the microbiota present. Microbiota data were summarized using both α-diversity to reflect species richness and evenness within bacterial populations and β-diversity to reflect the shared diversity between bacterial populations. Statistical significance was determined through the use of multiple testing, including the generalized mixed-effects model. Results The microbiome sequencing (16S rDNA V3-V5 region) revealed that the microbiomes of all organs (vagina, cervix, Fallopian tubes, and ovaries) are significantly correlated (p 4.5). Conclusions Our results suggest that the detection of A. vaginae and the identified Porphyromonas sp. in the gynecologic tract combined with a high vaginal pH is statistically associated with the presence of endometrial cancer. Given the documented association of the identified microorganisms with other pathologies, these findings raise the possibility of a microbiome role in the manifestation, etiology, or progression of endometrial cancer that should be further investigated