Citations

Clonal disorders of large granular lymphocytes (LGL) result in leukemia due to the expansion of a discrete subset of either CD3 + T cells or natural killer (NK) cells. It has been hypothesized that a viral antigen acts as the initial stimulus causing the expansion of these cells. The possible involvement of human T cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) in this disease has been studied but no conclusive evidence has linked either virus with LGL leukemia. In this study, we examined whether HTLV-3 or HTLV-4, two newly identified HTLV groups discovered in Central Africa in primate hunters, is involved in LGL leukemia. We developed two specific real-time PCR quantitative assays that are highly sensitive, capable of detecting 10 copies of HTLV-3 or HTLV-4 pol sequences in a background of 1 μ g of DNA from human peripheral blood lymphocytes (PBL). We tested PBL DNA samples from 40 LGL leukemia patients in the United States and found that all samples were negative for HTLV-3 or HTLV-4 infection. These results suggest that HTLV-3 and HTLV-4 are not the causative agent of LGL leukemia.

Between 1976 and 2004, 38 revision arthroplasties (35 patients) were performed for aseptic loosening of the humeral component. The mean interval from primary arthroplasty to revision was 7.1 years (0.4 to 16.6). A total of 35 shoulders (32 patients) were available for review at a mean follow-up of seven years (2 to 19.3). Pre-operatively, 34 patients (97%) had moderate or severe pain; at final follow-up, 29 (83%) had no or only mild pain (p < 0.0001). The mean active abduction improved from 88° to 107° (p < 0.01); and the mean external rotation from 37° to 46° (p = 0.27). Excellent or satisfactory results were achieved in 25 patients (71%) according to the modified Neer rating system. Humeral components were cemented in 29, with ingrowth implants used in nine cases. There were 19 of standard length and 17 were longer (two were custom replacements and are not included). Bone grafting was required for defects in 11 humeri. Only two glenoid components were left unrevised. Intra-operative complications included cement extrusion in eight cases, fracture of the shaft of the humerus is two and of the tuberosity in four. There were four re-operations, one for recurrent humeral loosening, with 89% survival free of re-operations at ten years. Revision surgery for aseptic loosening of the humeral component provides reliable pain relief and modest improvement of movement, although there is a substantial risk of intra-operative complications. Revision to a total shoulder replacement gives better results than to a hemiarthroplasty.

Abstract Background: How endogenous testosterone (Te), 5α-dihydrotestosterone (DHT), and estradiol (E2) regulate pulsatile GH secretion is not understood. Hypothesis: Conversion of Te to androgenic (Te→DHT) or estrogenic (Te→E2) products directs GH secretion. Subjects and Location: Healthy older men (N = 42, ages 50–79 yr) participated at an academic medical center. Methods: We inhibited 5α-reduction with dutasteride and aromatization with anastrozole during a pharmacological Te clamp and infused somatostatin (SS), GHRH, GH-releasing peptide-2 (GHRP-2), and l-arginine/GHRH/GHRP-2 (triple stimulus) to modulate GH secretion. Endpoints: Deconvolution-estimated basal and pulsatile GH secretion was assessed. Results: Administration of Te/placebo elevated Te by 2.8-fold, DHT by 2.6-fold, and E2 concentrations by 1.9-fold above placebo/placebo. Te/dutasteride and Te/anastrozole reduced stimulated DHT and E2 by 89 and 86%, respectively. Stepwise forward-selection regression analysis revealed that 1) Te positively determines mean (P = 0.017) and peak (P &lt; 0.001) GH concentrations, basal GH secretion (P = 0.015), and pulsatile GH secretion stimulated by GHRP-2 (P &lt; 0.001); 2) Te and E2 jointly predict GH responses to the triple stimulus (positively for Te, P = 0.006, and negatively for E2, P = 0.031); and 3) DHT correlates positively with pulsatile GH secretion during SS infusion (P = 0.011). These effects persisted when abdominal visceral fat was included in the regression. Conclusion: The present outcomes suggest a tetrapartite model of GH regulation in men, in which systemic concentrations of Te, DHT, and E2 along with abdominal visceral fat determine the selective actions of GH secretagogues and SS.

AbstractDo some patients benefit from an unrelated donor (URD) transplant because of a stronger graft-versus-leukemia (GVL) effect? We analyzed 4099 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) undergoing a myeloablative allogeneic hematopoietic cell transplantation (HCT) from an URD (8/8 human leukocyte antigen [HLA]–matched, n = 941) or HLA-identical sibling donor (n = 3158) between 1995 and 2004 reported to the CIBMTR. In the Cox regression model, acute and chronic GVHD were added as time-dependent variables. In multivariate analysis, URD transplant recipients had a higher risk for transplantation-related mortality (TRM; relative risk [RR], 2.76; P < .001) and relapse (RR, 1.50; P < .002) in patients with AML, but not ALL or CML. Chronic GVHD was associated with a lower relapse risk in all diagnoses. Leukemia-free survival (LFS) was decreased in patients with AML without acute GVHD receiving a URD transplant (RR, 2.02; P < .001) but was comparable to those receiving HLA-identical sibling transplants in patients with ALL and CML. In patients without GVHD, multivariate analysis showed similar risk of relapse but decreased LFS for URD transplants for all 3 diagnoses. In conclusion, risk of relapse was the same (ALL, CML) or worse (AML) in URD transplant recipients compared with HLA-identical sibling transplant recipients, suggesting a similar GVL effect.