Haemophilus influenzae induces neutrophil necrosis: a role in chronic obstructive pulmonary disease?

Noncapsulate Haemophilus influenzae is commonly found in the airways of patients with chronic obstructive pulmonary disease (COPD), both during stable disease and during exacerbations. Neutrophils are also found in large numbers in sputum from patients with COPD, which also contains released neutrophil products such as elastase. Why H. influenzae colonizes the lungs of patients with COPD in the presence of such large numbers of infiltrating neutrophils is not known. We set out to determine if abnormal interactions between H. influenzae and neutrophils could impact on COPD pathology. Noncapsulate H. influenzae clinical isolates were incubated in vitro with neutrophils from healthy volunteers, and respiratory burst activity, cytokine and chemokine production, phagocytosis and killing of bacteria, and neutrophil apoptosis and necrosis were measured. Neutrophil morphology was determined in sputum samples. H. influenzae were phagocytosed by neutrophils, thereby activating a respiratory burst and the secretion of the neutrophil chemoattractant IL-8. However, rather than kill the bacteria, the neutrophils themselves were killed (largely via necrosis) and released their granule contents into the extracellular environment. Neutrophil-derived IL-8, generated after the interaction of H. influenzae with neutrophils, may result in the further infiltration of neutrophils into the lungs, thereby amplifying the inflammatory response. However, the infiltrating neutrophils fail to kill the bacteria and instead release tissue-damaging products into the lung as they undergo necrosis. These results may help to explain the clinical picture in COPD.     

Bone marrow transplantation for constitutional pure red cell aplasia

Constitutional pure red cell aplasia (CPRCA) is a syndrome of failed erythropoiesis usually diagnosed within the first year of life. Four patients with CPRCA received transplants with marrow from their HLA- identical, mixed lymphocyte culture-nonreactive siblings. All patients were resistant to corticosteroid therapy and were dependent on regular red cell transfusions for at least 5 years. Three patients were conditioned with procarbazine, antithymocyte globulin, cyclophosphamide, and busulfan, and one was conditioned with antithymocyte serum, cyclophosphamide, and busulfan. Three patients promptly had successful engraftments with establishment of donor hematopoiesis. One patient initially rejected his graft but received a successful retransplant. All patients are currently alive with Karnofsky performance scores of 100 and normal erythropoiesis of donor origin. Despite a history of multiple transfusions, bone marrow transplantation is a potentially curative therapy for patients with CPRCA.     

To Do No Good

Mrs F.W., a 57-year-old nursing home manager, presented witha polyarthritis and plantar fasciitis in association with psoriasisin 2003. She was already taking meloxicam and co-proxamol. HerESR was 51 and rheumatoid factor was 80. She was labelled assuffering from psoriatic arthritis. Because of indigestion shewas changed to celecoxib, which was ineffective and then valdecoxib(even though it was not specifically licensed for psoriaticarthritis), which     

Congenital hypoplastic anemia inhibition of erythropoiesis by sera from patients with congenital hypoplastic anemia

An in vitro marrow culture assay designed to measure erythropoietic capability was used to ascertain the presence of an inhibitor in the sera of patients with congenital hypoplastic anemia (CHA). Marrow cells from nine anemic CHA patients responded to the stimulatory effect of exogenous erythropoietin (EPO) by an increase in heme synthesis in the presence of normal serum. The effect on heme synthesis was less than that observed with normal marrow cells. CHA serum inhibited heme synthesis by both normal and CHA marrow cells. It is concluded that an in-inhibitor of erythropoiesis is present in serum from CHA patients. This inhibitor most likely blocks the EPO-sensitive stem cell receptor sites, causing decreased response to the hormone.     

Management of skin,mucosa and joint involvement of Behçet’s syndrome: A systematic review for update of the EULAR recommendations for the management of Behçet’s syndrome

Objectives

The aim of this systematic review was to inform the update of European League Against Rheumatism (EULAR) Recommendations for the management of Behçet’s syndrome (BS), on the evidence for the treatment of skin, mucosa and joint involvement of BS.