scholarly journals Features of self-tolerance loss in patients with different clinical phenotypes of myasthenia

2018 ◽  
Vol 9 (4) ◽  
pp. 561-567
Author(s):  
E. M. Klimova ◽  
D. V. Minuchin ◽  
L. A. Drozdova ◽  
E. V. Lavinskaya ◽  
T. I. Kordon ◽  
...  

The incidence of myasthenia gravis which is characterized by progressive muscular weakness on the background of structural disorders of the thymus, has increased. Myasthenia gravis is a multifactorial autoimmune disease, it has a pronounced clinical heterogeneity, and therefore the standard diagnostic and treatment protocol is not always effective. To substantiate an individual approach to the treatment of various clinical forms of myasthenia, we conducted a study of mechanisms and markers of loss of central and peripheral self-tolerance in thymus-independent myasthenia (M) and thymus-dependent myasthenia gravis with thymus hyperplasia (MH) and thymoma (MT), involving a total of 427 patients examined. In patients with different phenotypes of myasthenia, we used the methods of spectrophotometry, flow cytometry, enzyme immunoassay. In patients with MH on the background of lymphofollicular thymus hyperplasia we revealed a pronounced humoral sensitization in comparison with the reference values: the concentration of C4 complement, C-reactive protein, circulating immune complexes and the initiation of an indirect autoimmune reaction a reliable increase in autoantibodies (AAbs) to the α1 and α7 subunit of subunit of nicotinic receptors (nAChR). In M and MT groups a high similar titer of AAbs to other epitopes was revealed: DNA, β2-glycoprotein I, membranes of intestinal and stomach cells, lung, liver, kidney cells. A pronounced blast-transforming response to the presence of the mitogen PHA was revealed in the MT group. In the MT group, a decrease in the content of CD4+ CD28+ co-stimulatory molecules and in the MH group, a decrease in СD4+ CD25+ Treg lymphocytes was revealed. Individual methods for correcting the loss of self-tolerance in patients with different clinical phenotypes of myasthenia were justified taking into account the use of immunosuppression, specific viral-neutralizing immunoglobulins and massive IgG immunoglobulin therapy, and the application of anti-inflammatory recombinant interleukins.

Abstract. The aim of the study was to evaluate the presence of autoantibodies to different subunits of nAChR and nuclear antigens at different myasthenia phenotypes. The work has investigated the presence of antibodies to α1- and α7-subunits of nAChR, the repertoire and frequency of occurrence of antinuclear autoantibodies in different clinical phenotypes of myasthenia to understand the mechanisms of pathogenesis of various forms of the disease. Additional factors of autoimmunization were identified that affect certain mechanisms of pathogenesis in thymus-independent and thymus-dependent myasthenia gravis. Autoantibodies to α1 and α7 subunits of nAChR were detected in case of thymus-independent myasthenia gravis and thymus-dependent myasthenia gravis with thymus hyperplasia or locally spread thymoma, as well as the presence of antinuclear antibodies in case of thymoma on the background of myasthenia gravis. Autoantibodies to the α1 subunit of nAChR are available in all patients with thymus-independent and thymus-dependent myasthenia gravis; the maximum titer was in patients with myasthenia and thymus hyperplasia. The presence of autoimmune antibodies to another target – to the α7 subunit of nAChR was found in patients with thymus-independent myasthenia gravis and with myasthenia and thymus hyperplasia. Detected anti-nuclear antibodies (ANA) in patients with thymoma, are preferably antibodies to structures that are directly involved in mitotic cell division, that is to centromere, to centromeric protein F, to the centrosomal protein of achromatin spindle – NuMa and MSA-2 antigen mitotic spindle that affects the course of cell proliferation, reparative and regenerative processes in tissues. The selectivity of antibody damage by the subunit of NAHR in different myasthenia phenotypes and the presence of ANA in thymus-dependent myasthenia with thymoma has great diagnostic and prognostic value. The presence of specific autoantibodies to certain nuclear structures of the cell, along with other autoimmunization mechanisms, affects various metabolic mechanisms and can be used to select targeted therapy taking into account individual pathogenic targets of the autoimmune process.


2004 ◽  
Vol 101 (43) ◽  
pp. 15464-15469 ◽  
Author(s):  
C. Vandiedonck ◽  
G. Beaurain ◽  
M. Giraud ◽  
C. Hue-Beauvais ◽  
B. Eymard ◽  
...  

1997 ◽  
Vol 245 (1) ◽  
pp. 26-31 ◽  
Author(s):  
J. L. M. Jongen ◽  
P. A. van Doorn ◽  
Frans G. A. van der Meché

2020 ◽  
Vol 27 (09) ◽  
pp. 2007-2013
Author(s):  
Mohammad Umar ◽  
Jawad Ahmad Kundi ◽  
Muhammad Sulaiman ◽  
Muhammad Zaib Khan ◽  
Ali Altaf

Objectives: The aim of this study is to compare two plate fixation and one plate along with arch bar in the treatment of parasymphsis, and to analyze the advantages and disadvantages over one another. Study Design: Randomized Clinical Trial. Setting: Department of Oral and Maxillofacial Surgery Sardar Begam Dental College and Northwest General Hospital Peshawar. Period: Over a period of one year from June 2017 to August 2018. Material & Methods: 60 patients with parasymphysis fracture after diagnosis established on clinical and radiological examination were equally divided into two groups, 30 patients in each. Group (A) were treated with two miniplates, while Group (B) one miniplate along with arch  bar under general anesthesia with proper antibiotics coverage in the pre- and post-operative period. Results: The infection rate 4 (13.3%) patients in Group B while 0 in Group A. No Loosening /fracture of screw or plate occur in any subject in group A at any follow up visit, while it occurred in 4 subjects in group B at 15 days follow up period. 9 patients in Group A and 6 in Group B presented with immediate post of paresthesia, which was reduced to 7 patients in group A and 6 in group B at 15 days follow up, and to 4 patients in Group A and 5 in Group B at 1 month follow up. Similarly, no subject had inferior border misalignment in group A at any follow up period while 3 subjects have immediate post -op inferior border discrepancy in group B and 6 subjects in the same group shows inferior border discrepancy at 15 days , but the overall result of this variable was also statistically non-significant. Conclusion: Isolated mandibular parasymphysis fracture can be treated with either two miniplates or one miniplate along with arch bar for 6 weeks. Both treatment protocol shows advantages and disadvantages with the aim of achieving the best treatment outcome for the patients.


2018 ◽  
Vol 54 (5) ◽  
pp. 267-275 ◽  
Author(s):  
Sophie Palierne ◽  
Patricia Meynaud ◽  
Alexis Bilmont ◽  
Maxence Delverdier ◽  
Marie-Odile Semin ◽  
...  

ABSTRACT The objective of this study was to compare the clinical, biological, macroscopic, and histologic outcomes after resection of the soft palate by plasma-mediated bipolar radiofrequency ablation (PBRA) or traditional incisional techniques (incisional soft palate resection [INC]) in dogs. Ten dogs were divided in two groups. In the INC group, the soft palate was incised with scissors and the wound was sutured in a continuous pattern. In the PBRA group, a wand was used to ablate the desired portion of the soft palate, without suture. Clinical, biological, macroscopic, and histologic assessments were scheduled over 14 days. The duration of surgery was significantly shorter for the PBRA group. The C-reactive protein concentrations were significantly higher in the PBRA group at 6 hr and on day 3 (P < .05) but with values very close to the baseline. C-reactive protein concentrations were maximal, but with low values (<25 mg/L), at day 1 for both techniques. The irregularity scores for the soft palate caudal border on days 1, 3, and 14 were significantly higher in the INC group than in the PBRA group (P < .05). The main histopathologic changes were the presence of superficial granulomas and a significantly greater depth of tissue damage in the INC group (2.5 ± 0.3 mm) compared with the PBRA group (1.5 ± 0.1 mm; P < .05). PBRA compared favorably with the traditional technique in terms of ease, duration of surgery, and depth of tissue damage. Future studies are warranted to validate its effectiveness for treating brachycephalic airway obstruction syndrome in dogs.


PEDIATRICS ◽  
1979 ◽  
Vol 64 (6) ◽  
pp. 904-912
Author(s):  
Edward L. Kaplan ◽  
Robert Couser ◽  
Barbara Ballard Huwe ◽  
Carolyn Mckay ◽  
Lewis W. Wannamaker

One hundred ninety-six individuals, 86 with clinically overt pharyngotonsillitis and 110 of their clinically negative contacts were studied to evaluate the sensitivity and the specificity of quantitative saliva cultures for group A β-hemolytic streptococci. We also compared this technique with semiquantitative throat cultures as a means of isolating group A streptococci and of differentiating the streptococcal carrier state from patients with bona fide streptococcal upper respiratory tract infection as defmed by the presence of an antibody response. The data indicate that the throat culture is a more reliable means of identifying group A β-hemolytic streptococci in the upper respiratory tract than is the saliva culture. The converse is true for non-group A β-hemolytic streptococci; the saliva culture is a much better means for isolating these organisms. In individuals positive by both techniques we found good correlation between the degree of positivity of the saliva culture and the degree of positivity of the throat culture. Furthermore, while there was a definite trend for individuals with strongly positive cultures to demonstrate more often an antibody rise in either antistreptolysin O and/or antideoxynibonuclease B—indicating bona fide infection—this relationship was not sufficiently constant to provide a clear differentiation. This study also indicates that discordance (one positive, one negative) of simultaneous duplicate semiquantitative throat cultures is much more common among individuals who do not show an antibody response ("carriers") than among those with an antibody response (bona fide infection). This study confirms our previous observations suggesting that the presence of C-reactive protein in the serum of patients with a positive culture for group A streptococci and clinical signs and symptoms of pharyngitis is often an indication of true streptococcal upper respiratory tract infection, and that even with a positive saliva culture at the initial visit, a negative C-reactive protein is only infrequently (25%) associated with an antibody response.


2019 ◽  
Vol 13 (7) ◽  
pp. 949-953 ◽  
Author(s):  
Wolfgang Kruis ◽  
Phuong Nguyen ◽  
Julia Morgenstern ◽  
Wolfgang Ramlow ◽  
Axel Dignaß ◽  
...  

Abstract Background and Aims In active ulcerative colitis [UC] refractory to mesalazine, escalation to either steroids or immunosuppression is common practice. The efficacy and safety of alternative escalation therapy with a novel leukocyte apheresis device were studied. Methods This was a prospective, randomized, controlled multicentre pilot study comparing leukocyte apheresis with prednisolone in refractory UC (disease activity index [DAI] ≥ 4 and ≤8). Group A received weekly apheresis over five consecutive weeks. Group P received oral prednisolone 40 mg/day tapered to 0 mg at week 6. The primary end point was steroid-free clinical remission [DAI ≤ 2] at week 12. Clinical response was also analysed. Results Twenty-four patients were enrolled, 13 of whom were randomized into group A and 11 into group P. Clinical remission off steroids at week 12 was achieved in 3/12 patients [25.0%] with apheresis and 2/10 [20.0%] with prednisolone [p = 1.0]. The response rate after 12 weeks was 75.0% in group A and 50.0% in group P. Mean DAI scores improved in both treatment groups [p = 0.008]. C-reactive protein decreased from 6.0 ± 5.3 to 3.8 ± 3.7 mg/L at 12 weeks in group A and increased from 5.2 ± 6.0 to 6.3 ± 7.9 mg/mL in group P. Both treatments were well tolerated. No unexpected serious adverse events were seen in group A. In group P one symptomatic infection with Clostridium difficile occurred. Conclusions In patients with active UC refractory to mesalazine a novel leukocyte apheresis showed promising results. A comparison with prednisolone revealed similar therapeutic effectivity and excellent safety, providing the chance to escalate without systemic steroids.


Author(s):  
Maria Elizabeth Pereira Passos ◽  
Leandro Borges ◽  
Laiane Cristina dos Santos-Oliveira ◽  
Amanda Lins Alecrim-Zeza ◽  
Tiago Bertola Lobato ◽  
...  

AbstractThis study aimed to investigate the impact of a 16-week dance-based aerobic exercise program on lymphocyte function in healthy and type 2 diabetes mellitus (T2DM) women. We enrolled 23 women: 11 with T2DM and 12 non-diabetic controls. Initially, we performed anthropometry and body composition measurements, afterwards, plasma levels of C-reactive protein, lipids, and glucose were determined. We used flow cytometry to measure the CD25 and CD28 expression in circulating lymphocytes, T-regulatory (Treg) cell percentage, lymphocyte proliferation, and cytokines released by cultured lymphocytes. The T2DM group had a lower proportion of CD28+ cells and a higher percentage of Treg lymphocytes and proliferative capacity at the baseline compared with the control group. After 16 weeks of the program, differences in lymphocytes between the T2DM and the control groups disappeared. The dance program promoted IL-10 increase in both groups. We found decreased IL-4, IL-2, and IL-6 secretion in lymphocytes from the control group and increased IL-17 secretion and IL-10/IL-17 ratio in the T2DM group after the program. The program promoted marked changes in lymphocytes in diabetic women, leading to a balance between the different profiles.


2018 ◽  
Vol 7 (1) ◽  
pp. 56-59
Author(s):  
Meenakshi Basnet ◽  
Rajkumar Bedajit ◽  
Bijay Neupane ◽  
Bibek Ghimire

Background: The optimal conservative treatment protocol of parotid abscess in children is evaluated.Material and Methods: This is a randomized, prospective, cross-sectional study conducted between November 2013 and June 2017 in Nobel Medical College and Teaching Hospital. Thirty children (below 14 years age) suffering from parotid abscess diagnosed by ultrasonography were included in this study. Recurrent parotid abscess cases were excluded. The children were divided into 2 groups by computer assisted randomization into15 patients each. Group A were treated with intravenous Clindamycin while group B were given intravenous Ampicilin + Cloxacillin combination. Results: Five patients of group B did not respond to treatment and were then put on intravenous Clindamycin. Three of these patients responded to treatment but 2 developed multi-lobulated fluctuation and required incision + drainage. Remaining 10 patients in group B and all patients in Group A responded to medical treatment without recurrence. Five patients in group B developed severe diarrhea during antibiotic treatment but none of the patients in group A had this complaint. No patient developed any complications like parapharyngeal abscess or septicemia. Conclusion: Parotid abscess in children can be managed conservatively with intravenous Clindamycin without the need for incision and drainage. Journal of Nobel Medical College Volume 7, Number 1, Issue 12, January-June 2018, Page: 56-59 


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
N A Fahmy ◽  
S M Alfawal ◽  
H S Abdelsamie ◽  
A M Hassan

Abstract Background Atrial fibrillation (AF) is the most common sustained arrhythmia affecting humans. It is an electrical disturbance that leads to rapid, disorganized, and asynchronous contraction of the atrial muscle. In clinical practice, it accounts for approximately one-third of hospitalizations for cardiac rhythm disturbances. The incidence of AF increases from less than 0.1% per year in those under 40 years old to exceed 1.5% per year in women and 2% per year in men older than 80 years. Aim of the Work: to discuss the effect of variation in amiodarone use (including dosage and duration) on dysrhythmia recurrence in patients with new-onset AF in ICU. Patients and Methods This was a prospective observational study conducted over 6 months, 60 patients who fulfilled inclusion criteria were included in the study divided in two groups according to amiodarone dosage, each group is 30 patients: Group (A): received a loading dose of amiodarone followed by an infusion (1200mg amiodarone). Group (B): received a loading dose of amiodarone not followed by an infusion (300mg amiodarone). Results a significant positive correlation was observed between level of C-reactive protein (CRP) and the rate of AF recurrence. As regard effect of CRP on AF recurrence; in AF recurrent patients, mean is (191±77.3) with range from 15 to 352 which significantly differed from Non-recurrent AF patients, mean is (89±63) with range from 20 to 223 (p value <0.001). AF recurrence was higher in group (B) than group (A),. In group (A) 8 patients had recurrent AF representing 26.7 % and in group (B) 19 patients had AF recurrence representing 63.3% (p value =0.004). Conclusion Patients with new-onset AF in (ICU) who are treated with amiodarone should receive a loading dose, immediately followed by an infusion.


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