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Tolerant Patients (tolerant + patient)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

Immunosuppressive drug-free operational immune tolerance in human kidney transplant recipients: Part I. blood gene expression statistical analysis

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2008
Christophe Braud
Abstract Survival of solid organ grafts depends on life-long immunosuppression, which results in increased rates of infection and malignancy. Induction of tolerance to allografts would represent the optimal solution for controlling both chronic rejection (CR) and side effects of immunosuppression. Although spontaneous "operational tolerance" can occur in human kidney transplantation, the lack of noninvasive peripheral blood biological markers of this rare phenomenon precludes the identification of potentially tolerant patients in whom immunosuppression could be tapered as well as the development of new tolerance inducing strategies. Here, the potential of high throughput microarray technology to decipher complex pathologies allowed us to study the peripheral blood specific gene expression profile and corresponding EASE molecular pathways associated to operational tolerance in a cohort of human kidney graft recipients. In comparison with patients with CR, tolerant patients displayed a set of 343 differentially expressed genes, mainly immune and defense genes, in their peripheral blood mononuclear cells (PBMC), of which 223 were also different from healthy volunteers. Using the expression pattern of these 343 genes, we were able to classify correctly >80% of the patients in a cross-validation experiment and classified correctly all of the samples over time. Collectively, this study identifies a unique PBMC gene signature associated with human operational tolerance in kidney transplantation by a classical statistical microarray analysis and, in the second part, by a nonstatistical analysis. J. Cell. Biochem. 103: 1681,1692, 2008. © 2007 Wiley-Liss, Inc. [source]

Mercaptopurine treatment should be considered in azathioprine intolerant patients with inflammatory bowel disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009
U. HINDORF
Summary Background, Adverse drug reactions are a significant reason for therapeutic failure during thiopurine treatment of inflammatory bowel disease. Some smaller series in this patient population have shown that a switch to mercaptopurine may be successful in many cases of azathioprine intolerance. Aim, To assess the long-term outcome of mercaptopurine treatment in a large patient population with azathioprine intolerance. Methods, We identified 135 patients (74 women; median age 40 years) with Crohn's disease (n = 88) or ulcerative colitis (n = 47) and reviewed their medical records. Results, A total of 70 patients (52%) tolerated mercaptopurine and were followed up for 736 (362,1080) days; 65 patients discontinued mercaptopurine due to adverse events after 25 (8,92) days. Mercaptopurine was tolerated in 71% (12/17) with hepatotoxicity and in 68% (13/19) with arthralgia/myalgia during azathioprine treatment. Previous abdominal surgery was more common in mercaptopurine intolerant patients [39/65 (60%) vs. 27/70 (39%); P = 0.02] and thiopurine methyltransferase activity was higher in mercaptopurine tolerant patients than in mercaptopurine intolerant patients [13.2 (11.4,15.3) vs. 11.8 (9.6,14.2) U/mL red blood cells; P = 0.04; n = 81]. Conclusions, A trial of mercaptopurine should be considered in azathioprine intolerance, as half of the patients tolerate a switch to mercaptopurine. Patients with hepatotoxicity or arthralgia/myalgia during azathioprine treatment might benefit more often than those with other types of adverse events. [source]

Casein-specific immunoglobulins in cow's milk allergic patient subgroups reveal a shift to IgA dominance in tolerant patients

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1 2007
Gaynour B. G. Sletten
Differences in casein-specific immunoglobulin (Ig) G-subclass and IgA serum levels between reactive and tolerant patients may hint at the immunopathogenesis during tolerance development in cow's milk allergy (CMA). , -, ,- and , -casein-specific IgG1, IgG4, IgE and IgA serum levels were compared in clinically reactive and tolerized IgE-mediated (n = 15) and non-IgE-mediated (n = 14) CMA with delayed gastrointestinal symptoms, using enzyme-linked immunosorbent assay (ELISA) and immunoblot techniques. The median anti-casein IgE levels in clinically reactive IgE-mediated CMA patients (n = 9) were 140- to 180-fold higher than in tolerized patients (n = 6) and 160- to 200-fold higher than in controls (n = 10). Median , -, ,- and , -casein-specific IgG1 and IgG4 levels were nine- to 60-fold higher in reactive patients and five- to 60-fold in tolerized patients. Clinical tolerance in IgE-mediated CMA was thus associated with decreased casein-specific IgE, IgG4 and IgG1, whereas serum IgA anti- , -, , - and , -casein remained practically unaltered. Tolerized cow's milk protein (CMP)-sensitive atopic dermatitis had, in particular, decreased , -casein-specific IgG1 levels, compared with clinically reactive patients. The ELISA levels to immunoblot correlation profile for the , -, , - and , -casein-specific IgE suggested that the IgE-mediated CMA patients predominantly reacted to tertiary , - and , -casein epitopes whereas the IgE in non-IgE-mediated patients reacted to linearized , -, , - and , -casein epitopes. Clinical tolerance in non-IgE-mediated CMA patients (n = 9) was associated with a four- to 10-fold decrease in casein-specific IgE levels, accompanied by a five- to eightfold decrease in IgG1 and five- to 60-fold decrease in IgG4 levels, whereas casein-specific IgA levels remained unaltered. Thus, tolerance in both patient groups was characterized by a generalized decreased humoral immune response to caseins, which induced a functional shift to IgA dominance. [source]

Impact of Aspirin Intolerance on Outcomes of Sinus Surgery,

THE LARYNGOSCOPE, Issue 5 2007
Jamie L. Robinson MD
Abstract Objectives: To compare objective and quality of life (QOL) outcomes after endoscopic sinus surgery (ESS) in aspirin (ASA)-tolerant patients and ASA-intolerant patients over intermediate and long-term follow-up. Study Design: Prospective analysis of a cohort of patients with chronic rhinosinusitis. Methods: Preoperative computed tomography (CT), pre- and postoperative endoscopy, and two validated disease specific QOL instruments, the Rhinosinusitis Disability Index (RSDI) and Chronic Sinusitis Survey (CSS), were collected. Differences in the proportions of patients who improved were analyzed using Pearson's chi-square and Fisher's exact test. Results: Nineteen ASA-intolerant patients and 104 ASA-tolerant patients were followed for a mean of 17.7 months. Patients with ASA intolerance had significantly worse preoperative CT (P < .0001) and endoscopy scores (P < .0001). After ESS, 57% to 74% of patients improved on endoscopy scores, 63% to 71% improved on the RSDI, and 58% to 73% improved on the CSS; improvement did not significantly differ by ASA status. Conclusions: Similar proportions of ASA-tolerant and ASA-intolerant patients showed improvement on endoscopy and QOL measures after ESS. [source]