Differential susceptibility to experimental allergic encephalomyelitis (EAE) in genetically defined A+ and A- rabbits

Only one out of 57 A-/A- rabbits immunized with rat or guinea-pig myelin developed clinical signs suggestive of EAE. On the contrary, clinical signs of acute or chronic EAE were found in two thirds of the 102 A+/A+ and A+/A- rabbits immunized in the same way. About one third of the diseased animals had reversible acute EAE, another third died paralysed and the last third developed chronic progressive or relapsing EAE. Incidence and severity of EAE symptoms were positively correlated with age and no significant difference was observed between males and females. Cellular and humoral anti-myelin responses were stronger in A+ than in A- rabbits. Anti-A antibodies, on the contrary, were only detected in A- rabbits. The A+ rabbits did not make Anti-A at any time. Anti-A antibodies increased early, in A- rabbits, after immunization with myelin (11-30 days) and were later replaced by a low, but specific, anti-myelin response (60-90 days). The gene responsible for the susceptibility to EAE is autosomal and dominant over resistance. This gene must be closely linked to the A locus or might be the A gene itself. The low susceptibility of A- rabbits to the disease could be, in this last case, a consequence of the competition between the early anti-A and the normal anti-myelin immune responses, both induced by the injection of myelin.     

How to define intermediate stage in Hodgkin's lymphoma?

Abstract:  Background : Intermediate or unfavourable stage Hodgkin's lymphoma (HL) definition relies upon at least three different scoring systems defined by cooperative groups (EORTC, GHSG and Canadian-ECOG). We aimed to investigate their efficacy and their correlation with International Prognostic Score (IPS) for advanced HL. Patients and methods : We studied a population of 1156 patients with localized stage HL treated prospectively within GELA centres in H8 (518 patients) and H9 (638 patients) protocols. Median age: 30 yr, 18%, Female 50%; stage I: 25%; stage II: 75%. According to scoring systems 70% had 0–1 EORTC factors; 60% 0–1 GHSG factors and 82% 0–1 Canadian factors. The IPS for advanced stages was available only in H9 study with 64% 0–1 factor. Results : Survival curves according to each of the different scoring systems could significantly discriminate the subgroup populations. When a multivariate Cox analysis was performed for overall survival (OS) including all the scoring system variables: age >45 yr, sex male, Haemoglobin <10.5 g/dL, lymphocytes <600/ μ L, B symptoms with elevated ESR, extra nodal sites did retain an independent significant value. Probability of OS was 99%, 98%, 92%, 82% and 73% for patients with 1–5 factors, respectively P  < 0.0001. Conclusion : These factors are similar for most of them with those described in the IPS when stages III and IV are replaced by extra nodal localization. This new score should be validated in other prospective trials, as it will simplify the Hodgkin prognostic scoring systems for localized and advanced stages.     

Pulmonary nocardiosis in patients with COPD: characteristics and prognostic factors

IntroductionPulmonary nocardiosis (PN) is a severe infection with a high morbidity and mortality that mainly affects immunocompromised patients. In recent years, an increase in PN cases has been detected among patients with chronic obstructive pulmonary disease (COPD). The factors that are associated with its presence and determine its prognosis remain unknown.MethodsRetrospective study of COPD patients diagnosed with PN over the period from 1997 to 2009 at the Hospital de la Santa Creu i Sant Pau, in Barcelona (Spain). Demographic, clinical, microbiological and evolution data were evaluated in all cases.ResultsThirty patients were identified with PN and COPD. Mean age (standard deviation) was 76 (7) years and the mean FEV₁ was 40 (14)%. Chronic respiratory failure was observed in 56.7% patients and 51.7% had received systemic corticosteroid therapy previous to the PN diagnosis. The most common symptoms were cough and dyspnea (90%). Alveolar infiltrates were observed in 60% of the cases. The most frequently isolated Nocardia species was N. cyriacigeorgica (68%). The one-month mortality rate was 17%, while the one-year mortality rate was 33%. The factors associated with mortality within the first year included previous systemic corticosteroid treatment, less than three months of specific antibiotic therapy and active associated neoplasm.ConclusionsPN affects patients with moderate-severe COPD and has high short- and mid-term mortality rates. Previous corticosteroid treatment, specific antibiotic therapy for less than 3 months and active neoplasia were factors associated with mortality.     

Safety and efficacy of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab in patients with human immunodeficiency virus-associated diffuse large B-cell lymphoma: results of a phase II trial

Immunochemotherapy with cyclophosphamide, adriamycin, vincristine, prednisone and rituximab (R-CHOP) is the standard treatment in non-immunosuppressed patients with diffuse large B-cell lymphoma (DLBCL), but its adequacy has not been definitively established in patients with human immunodeficiency virus (HIV)-related lymphoma. This phase II trial aimed to evaluate the safety and efficacy of six cycles of R-CHOP in patients with HIV-related DLBCL and to determine whether response to highly active antiretroviral therapy (HAART) had prognostic impact. Patients were eligible if they had performance status <3 and absence of active opportunistic infections. Eighty-one patients were enrolled, 57 in stages III or IV, International Prognostic Index (IPI) 0 or 1 ( n  = 26), 2 ( n  = 19), 3 ( n  = 20) and 4 or 5 ( n  = 16), and median CD4 lymphocyte count of 0·158 × 10⁹/l. The main adverse events were neutropenia (48% of cycles) and infections (10% of cycles), which were fatal in seven patients. Complete response was achieved in 55 (69%) patients, with an estimated 3-year disease-free survival of 77% and 3-year overall survival of 56%. IPI score and virological response to HAART were the prognostic parameters for response and survival. In HIV-related DLBCL R-CHOP is feasible, safe and effective. The prognosis depends on lymphoma-related parameters and on the response to HAART.