ABSTRACT
INTRODUCTION: For 7 years we gained experience of how asthma and chronic rhinosinusitis with nasal polyposis respond to biologics. In contrast, it is much less known, how ASA/NSAID intolerance (Widal's disease) behaves under biologicals. We therefore describe the case of a patient with both clinical conditions who reacted with a severe intolerance reaction under perioperative metamizole administration.
Subject(s)
Asthma, Aspirin-Induced , Nasal Polyps , Humans , Nasal Polyps/drug therapy , Asthma, Aspirin-Induced/drug therapy , Asthma, Aspirin-Induced/diagnosis , Sinusitis/drug therapy , Dipyrone/adverse effects , Dipyrone/therapeutic use , Female , Middle Aged , Asthma/drug therapy , Male , Rhinitis/drug therapy , Anti-Asthmatic Agents/adverse effects , Anti-Asthmatic Agents/therapeutic use , Diagnosis, Differential , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , UndertreatmentSubject(s)
Heart Failure/therapy , Adult , Cardiovascular Agents/therapeutic use , Combined Modality Therapy , Continuous Positive Airway Pressure , Electrocardiography , Extracorporeal Membrane Oxygenation , Female , Heart Failure/diagnosis , Heart Failure/physiopathology , Hemodynamics/physiology , Humans , Influenza B virus , Influenza, Human/complications , Influenza, Human/diagnosis , Pacemaker, Artificial , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/physiopathology , Shock, Cardiogenic/therapy , Signal Processing, Computer-AssistedABSTRACT
The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV(H) gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood. Here, we evaluated AID protein expression compared with known molecular and immunohistochemical prognostic indicators in 71 chronic lymphocytic leukemia/small lymphocytic lymphoma patients using a tissue microarray approach. We found AID heterogeneously expressed in tumor cells as shown by colocalization analysis for CD5 and CD23. Ki-67 positive paraimmunoblasts of the proliferation centers displayed the highest expression. This observation is reflected by a significant association of AID positivity with a high proliferation rate (P=0.012). ATM deletion was detected in 10% (6/63) of patients and p53 deletion in 19% (13/67) of patients. Moreover, both ATM (P=0.002) and p53 deletion (P=0.004) were significantly associated with AID. IgV(H) gene mutation was seen in 45% (27/60) of patients. Twenty-five percent (17/69) of patients with AID-positive chronic lymphocytic leukemia/small lymphocytic lymphoma displayed a shorter survival than AID-negative chronic lymphocytic leukemia/small lymphocytic lymphoma patients (61 vs 130 months, P=0.001). Although there was a trend, we could not show an association with the IgV(H) gene mutation status. Taken together, our study shows that AID expression is an indicator of an unfavorable prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma patients, although it is not a surrogate marker for the IgV(H) status. Furthermore, the microenvironment of proliferation centers seems to influence AID regulation and might be an initiating factor in its transformation.
