Phase I trial of interleukin-2 after unmodified HLA-matched sibling bone marrow transplantation for children with acute leukemia

Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/d) for 10 days by CIV infusion. Levels I and II were well-tolerated, but, of 6 patients at level III, 1 developed pulmonary infiltrates, 1 developed hypotension (both resolved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. Ten patients remain in CR at 5+ to 67+ months. Thus, a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. Its clinical activity will be assessed in a phase II trial.     

Amelioration of Neurosensory Structure and Function in Animal and Cellular Models of a Congenital Blindness

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Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak,Tumbes, Peru, 2010–2012

During 2010–2012, an outbreak of 210 cases of malaria occurred in Tumbes, in the northern coast of Peru, where no Plasmodium falciparum malaria case had been reported since 2006. To identify the source of the parasite causing this outbreak, we conducted a molecular epidemiology investigation. Microsatellite typing showed an identical genotype in all 54 available isolates. This genotype was also identical to that of parasites isolated in 2010 in the Loreto region of the Peruvian Amazon and closely related to clonet B, a parasite lineage previously reported in the Amazon during 1998–2000. These findings are consistent with travel history of index case-patients. DNA sequencing revealed mutations in the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr1 loci, which are strongly associated with resistance to chloroquine and sulfadoxine/pyrimethamine, and deletion of the Pfhrp2 gene. These results highlight the need for timely molecular epidemiology investigations to trace the parasite source during malaria reintroduction events.     

Increasing of SIgA serum levels may reflect subclinical intestinal involvement in non-radiographic axial and peripheral spondyloarthritis

Clinical Rheumatology - The evidence shows that previous infection with enteric pathogens is a requirement to develop pSpA. Based on our previous results, variances on regulation of SIgA might...     

Valve Strain Quantitation in Normal Mitral Valves and Mitral Prolapse With Variable Degrees of Regurgitation

ObjectivesThe aim of this study was to quantitate patient-specific mitral valve (MV) strain in normal valves and in patients with mitral valve prolapse with and without significant mitral regurgitation (MR) and assess the determinants of MV strain.BackgroundFew data exist on MV deformation during systole in humans. Three-dimensional echocardiography allows for dynamic MV imaging, enabling digital modeling of MV function in health and disease.MethodsThree-dimensional transesophageal echocardiography was performed in 82 patients, 32 with normal MV and 50 with mitral valve prolapse (MVP): 12 with mild mitral regurgitation or less (MVP ? MR) and 38 with moderate MR or greater (MVP + MR). Three-dimensional MV models were generated, and the peak systolic strain of MV leaflets was computed on proprietary software.ResultsLeft ventricular ejection fraction was normal in all groups. MV annular dimensions were largest in MVP + MR (annular area: 13.8 ± 0.7 cm²) and comparable in MVP ? MR (10.6 ± 1 cm²) and normal valves (10.5 ± 0.3 cm²; analysis of variance: p < 0.001). Similarly, MV leaflet areas were largest in MVP + MR, particularly the posterior leaflet (8.7 ± 0.5 cm²); intermediate in MVP ? MR (6.5 ± 0.7 cm²); and smallest in normal valves (5.5 ± 0.2 cm²; p < 0.0001). Strain was overall highest in MVP + MR and lowest in normal valves. Patients with MVP ? MR had intermediate strain values that were higher than normal valves in the posterior leaflet (p = 0.001). On multivariable analysis, after adjustment for clinical and MV geometric parameters, leaflet thickness was the only parameter that was retained as being significantly correlated with mean MV strain (r = 0.34; p = 0.008).ConclusionsMVs that exhibit prolapse have higher strain compared to normal valves, particularly in the posterior leaflet. Although higher strain is observed with worsening MR and larger valves and annuli, mitral valve leaflet thickness—and, thus, underlying MV pathology—is the most significant independent determinant of valve deformation. Future studies are needed to assess the impact of MV strain determination on clinical outcome.     

Correlation study between prolactin and androgens in male patients with systemic lupus erythematosus

The hypothalamic-pituitary-gonadal axis was studied in 8 male patients with systemic lupus erythematosus (SLE), both before and after intravenous administration of luteinizing hormone-releasing hormone (LH-RH). We provide evidence herein that resting serum levels of estrone are increased and that resting serum testosterone (T) and dihydrotestosterone (DHT) levels are decreased in male patients with SLE. The decreased serum T levels were observed even after the IV administration of 25 micrograms of LH-RH. The high basal serum prolactin (PRL) levels observed in these patients with SLE is a novel finding not previously reported that could explain why serum T and DHT levels are low in this syndrome. We observed a decrease in the pituitary response to LH-RH stimulation; this low response could also be a hormonal manifestation of hyperprolactinemia. Furthermore, it has been suggested that PRL plays a role in immunocompetence, and therefore it could have influence either directly or indirectly in the altered immunoregulation observed in SLE.