The aim of the present study was to explore the diagnostic value of the immunophenotypic analysis of bone marrow mast cells (BMMC) in indolent systemic mast cell disease (SMCD) patients. For that purpose, a total of 10 SMCD patients and 19 healthy controls were analyzed. Our results show that BMMC from SMCD are different from normal BMMC with regard to both their light scatter and immunophenotypic characteristics. Accordingly, forward light scatter (FSC), side (90°) light scatter (SSC), and baseline autofluorescence levels were higher in BMMC from indolent SMCD patients than they were in control subjects. From the immunophenotypic point of view, the most striking findings were the constant expression of CD2 (P = .0001), CD25 (P = .0001), and CD35 (P = .06) molecules by BMMC from SMCD patients, markers that were absent from all normal controls. In contrast, CD71, absent in BMMC from indolent SMCD, was positive in BMMC from normal subjects. Although, slight differences between BMMC from SMCD patients and normal controls were found in several other markers, they did not reach statistical significance. In conclusion, our results show that simultaneous assessment of FSC/SSC and reactivity for the CD117, CD2, CD25, CD33, and CD35 forms the basis for the immunophenotypic characterization of BMMC from SMCD in adults and should be integrated with clinical and morphologic studies for the diagnosis of the disease.
From 1987 to 1995, a retrospective case study was conducted at the Ramon y Cajal Hospital in Madrid, Spain, a public teaching hospital with 1,100 beds, to determine the clinicoepidemiologic characteristics, survival, and prognostic factors of patients with visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) infection. The prevalence of VL in HIVϩ patients compared with HIVϪ patients was studied. Epidemiologic, clinical, and parasitologic characteristics, as well as the effects of treatment, prognosis, and survival in 54 HIVϩ patients (90 episodes) with VL were defined. Comparative survival studies among patients with and without acquired immunodeficiency syndrome (AIDS)-defining criteria and multivariate analysis of survival risk factors were performed. The prevalence of VL in patients with AIDS was much higher than in immunocompetent individuals. In spite of a good initial response to treatment for VL, 60.6% of the patients had relapsed by the end of one year. Mortality from the first episode was 18.5%, and 24% died in the first month after diagnosis of any VL episode. The mean survival of the 29 patients who died was 10.27 months. Survival in patients with and without AIDS at the time of the first episode of VL was compared at 30 months: 53.7% versus 20.5% (P ϭ 0.00149). We found no significant difference (P ϭ 0.24) in the survival of HIVϩ patients who had died of VL without AIDS at the time of the first episode of VL compared with those of a control group of 413 dead patients with AIDS without VL. A diagnosis of AIDS at the time of the first episode of VL and thrombocytopenia were the only risk factors found related to survival. We conclude that in AIDS patients, VL is a recurrent disease that is highly prevalent and whose clinical course is modified by HIV.
In 2005, the oral iron chelator deferasirox was approved by the FDA for clinical use as a first-line therapy for blood-transfusion-related iron overload. Nephrotoxicity is the most serious and frequent adverse effect of deferasirox treatment. This nephrotoxicity can present as an acute or chronic decrease in glomerular filtration rate (GFR). Features of proximal tubular dysfunction might also be present. In clinical trials and observational studies, GFR is decreased in 30-100% of patients treated with deferasirox, depending on dose, method of assessment and population studied. Nephrotoxicity is usually nonprogressive and/or reversible and rapid iron depletion is one of several risk factors. Scarce data are available on the molecular mechanisms of nephrotoxicity and the reasons for the specific proximal tubular sensitivity to the drug. Although deferasirox promotes apoptosis of cultured proximal tubular cells, the trigger has not been well characterized. Observational studies are required to track current trends in deferasirox prescription, assess the epidemiology of deferasirox nephrotoxicity in routine clinical practice, explore the effect on outcomes of various monitoring and dose-adjustment protocols and elucidate the long-term consequences of the different features of nephrotoxicity. Deferasirox nephrotoxicity can be more common in the elderly; thus, specific efforts should be dedicated to investigate the effect of deferasirox use in this group of patients.
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