Ambrogio Capria

Peripheral Neurological Disturbances, Autonomic Dysfunction, and Antineuronal Antibodies in Adult Celiac Disease Before and After a Gluten-Free Diet

Thirty-two consecutive adult celiac disease (CD) patients (pts), complaining of peripheral neuropathy (12 pts), autonomic dysfunction (17 pts), or both (3 pts), were evaluated to assess the presence of neurological damage (by clinical neurological evaluation and electrophysiological study) and antineuronal antibodies and to assess the effect of a gluten-free diet (GFD) on the course of the neurological symptoms and on antineuronal antibodies. At entry, 12 of 32 (38%) pts showed signs and symptoms of neurological damage: 7 of 12 (58%), peripheral neurological damage; 3 of 12 (25%), autonomic dysfunction; and 2 (17%), both peripheral neurological damage and autonomic dysfunction. The overall TNS score was 105 at entry. Anti-GM1 antibodies were present in 5 of 12 (42%) pts: 3 showed peripheral neurological damage and 2 showed both peripheral neurological damage and autonomic dysfunction. One year after the GFD was started, histological lesions were still present in only 10 of 12 (83%) pts. TNS score was 99, 98, 98, and 101 at the 3rd, 6th, 9th, and 12th month after the GFD was started, so it did not improve throughout the follow-up. None of the pts showed disappearance of antineuronal antibodies throughout the follow-up. We conclude that adult CD patients may show neurological damage and presence of antineuronal antibodies. Unfortunately, these findings do not disappear with a GFD.

Regulatory T Cells in the Immunodiagnosis and Outcome of Kidney Allograft Rejection

Acute rejection (AR) is responsible for up to 12% of graft loss with the highest risk generally occurring during the first six months after transplantation. AR may be broadly classified into humoral as well as cellular rejection. Cellular rejection develops when donor alloantigens, presented by antigen-presenting cells (APCs) through class I or class II HLA molecules, activate the immune response against the allograft, resulting in activation of naive T cells that differentiate into subsets including cytotoxic CD8+ and helper CD4+ T cells type 1 (TH1) and TH2 cells or into cytoprotective immunoregulatory T cells (Tregs). The immune reaction directed against a renal allograft has been suggested to be characterized by two major components: a destructive one, mediated by CD4+ helper and CD8+ cytotoxic T cells, and a protective response, mediated by Tregs. The balance between these two opposite immune responses can significantly affect the graft survival. Many studies have been performed in order to define the role of Tregs either in the immunodiagnosis of transplant rejection or as predictor of the clinical outcome. However, information available from the literature shows a contradictory picture that deserves further investigation.

An Increased Endothelial-Independent Vasodilation Is the Hallmark of the Neurally Mediated Syncope

The neurally mediated syncope (NMS) is sustained by complex cardiac and vascular reflexes, acting on and amplified by central autonomic loops, resulting in bradycardia and hypotension.

Device monitoring of heart failure in cardiac resynchronization therapy device recipients: a single-center experience with a novel multivector impedance monitoring system.

Objectives We investigated the performance of a new intrathoracic multivector impedance monitoring system for the prediction of heart failure events in consecutive device-implanted patients. Methods Eighty heart failure patients implanted with biventricular defibrillators with multivector impedance monitoring capability were prospectively enrolled. Clinical heart failure status and impedance data were assessed during follow-up and if patients presented with an alert or heart failure deterioration. Results During follow-up (8.0 ± 4.4 months), 56 events of device alert for fluid index increase were identified in 29 patients, and a total of 39 heart failure events (defined by worsening of heart failure signs and symptoms) occurred in 23 patients. The sensitivity and positive predictive value (PPV) for heart failure deterioration was 61.5 and 42.9%, respectively. False-positive alerts occurred in 23 of 80 patients (28.8%), for an episode rate of 0.60 a year. Among all clinical heart failure events, decompensation caused hospitalization in 13 cases (33.3%), seven of them were preceded by an alert condition (53.8%) resulting in a sensitivity of 53.8% and a PPV of 17.9%. Conclusion The present study confirms the feasibility and clinical usefulness of this novel multivector impedance monitoring system. It would be worthwhile to perform larger studies to assess its actual clinical value in heart failure patients.

Endothelial dysfunction in rheumatoid arthritis is improved by anti-tumor necrosis factorα treatment

Rheumatoid arthritis (RA) is associated with excess cardiovascular morbidity and mortality. TNFα plays a pivotal role in causing both RA synovial damage and atherosclerosis, also by inducing endothelial dysfunction. The aim of the present study was to assess the occurrence of endothelial dysfunction and the effects of anti-TNFα antagonism on endothelial function in RA. Ten RA women with Disease Activity Score (DAS) ≥ 3.7 despite treatment with at least two disease-modifying antirheumatic drugs for 4 months underwent anti-TNFα treatment with infliximab or etanercept. Endothelium-dependent vasodilation was significantly lower than normal (3.8±3.7 % vs. 13.7 ±5.1, p≤0.05), thus demonstrating the presence of endothelial dysfunction in our RA patient population. Anti-TNF- treatment significantly improved flow-mediated vasodilation, which increased from baseline values of 3.8±3.7% to 10.9±6.6% (p<0.05) at day 1, to 13.4±5.4 % (p < 0.05) at week 1, to 12.7±5.3 % (p<0.05) at week 2 and to 15.5±5.2 % at week 6 (p≤0.05). There was no significant difference between two anti-TNFα treatments regarding mean percentage increase of flow-mediated vasodilation during treatment. RA clinical improvement was demonstrated by a significant decrease in the DAS score (from 6.26±1.6 to 5.26 1.38, p < 0.05) associated to a marked decrease of acute phase reactants serum levels. The present study supports the hypothesis of the pivotal role for TNFα as a mediator of systemic and vascular wall inflammation in RA.

Churg-Strauss syndrome development during asthma therapy with leukotriene receptor antagonists: just a coincidental association?

A report on our clinical experience based on 3 male patients who developed Churg-Strauss syndrome (CSS) after standard oral montelukast use. All patients affected by moderate asthma and chronic hyperplastic rhinosinusitis were treated with inhaled corticosteroids and ß2 agonists. Systemic corticosteroid treatment consisted in oral daily prednisone in case 1, in short courses of oral betamethasone in case 2, and in remote and isolated administrations of oral betamethasone and intramuscular methylprednisolone in case 3. Because of the improvement of the asthma symptoms after montelukast use, patient 1 decided to take half the dose of prednisone for 10 days and patient 2 decided to discontinue systemic and inhaled corticosteroids for 45 days. Overt CSS was heralded by vasculitic skin lesions and developed in each patient with severe organ damage, consisting in renal, myocardial and gastrointestinal involvement. Remission was obtained by standard CSS therapy after montelukast withdrawal. According to the unmasking hypothesis, antileukotriene treatment, by enabling the reduction in systemic corticosteroid therapy in case 1 and its discontinuation in case 2, might have only permitted the precipitation of the vasculitis. However antileukotriene-associated CSS reportedly occurred in systemic corticosteroid-naïve patients and relapsed in one patient after antileukotriene treatment. These observations lend support to the concept that the precipitation of the vasculitic phase may be associated with leukotriene modifier deleterious effects. In conclusion there is not enough evidence to prove that antileukotriene treatment plays a direct causative role in the pathogenesis of CSS. Further clinical and experimental research is required to clarify the antileukotriene associated CSS controversy.