Primary transplantation of allogeneic peripheral blood progenitor cells mobilized by filgrastim (granulocyte colony-stimulating factor) [see comments]

Transplantation of allogeneic peripheral blood progenitor cells (PBPCs) may have advantages over bone marrow transplantation (BMT) with regards to the speed of hematopoietic and immunologic recovery, which may then shorten the time spent in hospital and decrease costs. The recipient might also profit by an enhanced graft-versus-leukemia reaction exerted by the high number of natural killer cells contained in such grafts. The donor could be spared the discomfort and risks of general anesthesia and marrow harvesting. Primary transplantation of unmanipulated allogeneic PBPCs has not been reported so far because the vast amount of T cells contained in the collection product was thought to cause severe graft-versus-host disease. We present preliminary data on primary transplantation of allogeneic PBPCs in patients who either suffered from advanced leukemia or had a donor unable to undergo general anesthesia. Eight patients with a median age of 42 years suffering from acute myelogenous leukemia (AML) in first remission (n = 3), AML in third remission, AML in relapse (n = 2), acute lymphoblastic leukemia in second remission, or chronic myelogenous leukemia in accelerated phase received myeloablative therapy followed by transplantation of unmanipulated allogeneic PBPCs mobilized with granulocyte colony-stimulating factor (5 to 10 micrograms/kg of body weight of filgrastim administered for 5 to 6 days) in their HLA- identical donors. Hematopoietic reconstitution was achieved in all patients with a median of 15.5 (16.5) days after transplant needed to surpass an absolute neutrophil count of 0.5 (1.0) x 10(9)/L. The median time to an unsupported platelet count greater than 20 (> 50) x 10(9)/L was 19.5 (41) days after grafting. Three patients did not exhibit signs of acute graft-versus-host disease (GVHD), grade I disease was seen in one patient, and three patients experienced grade II disease limited to the skin. The only patient with severe acute GVHD (grade III) refused to take his oral cyclosporin regularly and had ineffective serum levels for most of the time until relapse. Six of eight patients are currently alive without evidence of disease between 61 and 533 days after grafting; two patients grafted for AML in relapse achieved a complete remission after transplantation but relapsed again and died of leukemia on days +48 and +70, respectively. Primary transplantation of unmanipulated allogeneic PBPCs is feasible and results in long-term engraftment without causing detrimental GVHD.     

Synergistic interaction between interleukin-12 and steel factor in support of proliferation of murine lymphohematopoietic progenitors in culture

We have investigated the effects of interleukin (IL)-12 (natural killer cell stimulatory factor/cytotoxic lymphocyte maturation factor) on the proliferation of murine myeloid and lymphohematopoietic progenitors in methylcellulose culture. In the presence of erythropoietin (Ep), IL-12 alone failed to support colony formation by mononuclear and enriched marrow cells of normal mice. Steel factor (SF) alone supported primarily formation of granulocyte/macrophage (GM) colony formation. However, the combination of the two cytokines yielded a significant number of multilineage colonies. When tested on marrow cells from 5- fluorouracil (5-FU)-treated mice, the combination of IL-12 and SF, but not the single factors, was effective in support of formation of various types of colonies. Approximately 25% of these colonies yielded pre-B-cell colonies when replated in secondary culture containing SF and IL-7, indicating that IL-12 can interact with SF in supporting the development of primitive lymphohematopoietic progenitors. These results demonstrate that IL-12, a cytokine believed to be involved in the development of cell-mediated immune responses, has a wider range of activity, including committed myeloid and multipotent lymphohematopoietic progenitors.     

Occlusion during iliac angioplasty: a salvageable complication

During transluminal dilation of the iliac artery, occlusion resulting from dissection occurred in four patients. In all four, the deteriorating clinical findings prompted surgical intervention. In three patients, Fogarty balloon catheters easily passed the occluded segments and specimens much the same as surgical endarterectomy specimens were retrieved. A clamp was used to retrieve the dissected portion of the vessel wall in the fourth patient. Three of four vessels have remained patent for 18 months, 18 months, and 6 months, respectively. One patient underwent bypass surgery 4 months after the occlusion episode for recurrent stenosis in a segment of vessel above the occluded segment, which had also been dilated during the same procedure. It is therefore possible in some cases to salvage vessels occluded during angioplasty, making it unnecessary to resort to aortofemoral or other type of bypass.     

Gynecologic imaging: comparison of transabdominal and transvaginal sonography

The sonographic findings in 200 patients who underwent concurrent transabdominal and transvaginal pelvic ultrasound were reviewed. The sonographic techniques were compared for image quality, completeness of anatomic detail depicted, and unique diagnostic information. Transvaginal image quality was better in 79%-87% of scans; transabdominal image quality was better in 3%-5% of scans; images of both techniques were equally good in 10%-18% of scans. The techniques provided equivalent diagnostic information in 60%-84% of cases. Transvaginal sonography was particularly helpful when exclusion of ectopic pregnancy was the clinical concern. Individual organs and fine structures were better seen transvaginally, but the regional survey offered by the transabdominal full-bladder approach remains necessary to provide anatomic orientation, particularly when the patient has not been studied previously.     

A noninvasive method for measuring portal venous/total hepatic blood flow by hepatosplenic radionuclide angiography

Radionuclide angiography was used to generate first-pass radioactivity vs. time curves for the left heart, right hepatic lobe, right lung, spleen, and both kidneys following rapid intravenous injection of 20 mCi (740 MBq) of 99mTc-pertechnetate. Seven normal subjects were examined as well as 57 cirrhotic patients, who also underwent angiographic grading of portal venous perfusion. For analysis, two time points were identified: (a) t0, when 99mTc first entered the liver (the initial rise of either curve); and (b)tc, when 99mTc was maximal in abdominal organs (the renal peak). Analysis was based on the slopes of the two phases of the hepatic curves t0 + 7 seconds and Tc + 7 seconds; this time selection permitted analysis of all curves. The hepatic perfusion index (HPI) = slope (tc + 7 secs)/slope (t0 + 7 secs) + slope (tc + 7 secs). The mean HPI for the normal subjects was 66% +/- 7; for the cirrhotic patients with angiographic Grades I, II, III, and IV, the HPI was 52% +/- 9, 37% +/- 6, 15% +/- 7, and 3% +/- 4, respectively. Correlation between HPI and angiography was significant (p less than 0.001). This method offers a readily available, rapid, relatively inexpensive, and quantitative method of grading the ratio of portal venous to total hepatic blood flow.     

Exploring recruitment,willingness to participate,and retention of low-SES women in stress and depression prevention

Background  

Recruitment, willingness to participate, and retention in interventions are indispensable for successful prevention. This study investigated the effectiveness of different strategies for recruiting and retaining low-SES women in depression prevention, and explored which sociodemographic characteristics and risk status factors within this specific target group are associated with successful recruitment and retention.     

Assessment of regional changes in skeletal metabolism following 3 and 18 months of teriparatide treatment

Teriparatide (TPTD) increases skeletal mass, bone turnover markers, and bone strength, but in vivo effects at individual skeletal sites have not been characterized. Quantitative radionuclide imaging studies reflect bone blood flow and osteoblast activity to assess regional changes in bone metabolism. Changes in bone plasma clearance using technetium‐99m methylene diphosphonate (^99mTc‐MDP) were quantified and correlated with changes in bone turnover markers in 10 postmenopausal women with osteoporosis. Subjects underwent bone scintigraphy at baseline and 3 and 18 months after initiating TPTD 20 µg/day subcutaneously. Subjects were injected with 600 MBq ^99mTc‐MDP, and whole‐body bone scan images were acquired at 10 minutes and 1, 2, 3, and 4 hours. Multiple blood samples were taken between 5 minutes and 4 hours after treatment, and free ^99mTc‐MDP was measured using ultrafiltration. The Patlak plot method was used to evaluate whole‐skeleton ^99mTc‐MDP plasma clearance (K_bone) and derive regional bone clearance for the calvarium, mandible, spine, pelvis, and upper and lower extremities using gamma camera counts. Bone turnover markers were measured at baseline and 3, 12, and 18 months. Median increases from baseline in whole‐skeleton K_bone were 22.3% (p = .004) and 33.7% (p = .002) at 3 and 18 months, respectively. Regional K_bone values were increased significantly in all six subregions at 3 months and in all subregions except the pelvis at 18 months. Bone markers were increased significantly from baseline at 3 and 18 months and correlated significantly with whole‐skeleton K_bone. This is the first study showing a direct metabolic effect of TPTD at different skeletal sites in vivo, as measured by tracer kinetics. © 2010 American Society for Bone and Mineral Research