A controlled trial of recombinant human erythropoietin after bone marrow transplantation

Recombinant human erythropoietin (rHuEPO) stimulates erythropoietic bone marrow cells and increases erythrocyte production. This prospective study was designed to evaluate the effects of rHuEPO on regeneration of erythropoiesis after allogeneic or autologous bone marrow transplantation (BMT). Seventeen centers participated in this randomized, double-blind, placebo-controlled multicenter trial. The randomization was performed centrally for each center and stratified according to allogeneic or autologous BMT and major ABO-blood group incompatibility. One hundred and six patients received rHuEPO after allogeneic BMT and 109 patients received placebo. After autologous BMT, 57 patients were treated with rHuEPO and 57 with placebo. Patients received either 150 IU/kg/day C127 mouse-cell-derived rHuEPO or placebo as continuous intravenous infusion. Therapy started after bone marrow infusion and lasted until independence from erythrocyte transfusions for 7 consecutive days with stable hemoglobin levels > or = 9 g/100 mL or until day 41. After allogeneic BMT, the reticulocyte counts were significantly higher with rHuEPO from day 21 to day 42 after BMT. The median time (95% confidence intervals) to erythrocyte transfusion independence was 19 days (range, 16.3 to 21.6) with rHuEPO and 27 days (range, 22.3 to > 42) with placebo (P < .003). The mean (+/- SD) numbers of erythrocyte transfusions until day 20 after BMT were 6.6 +/- 4.8 with rHuEPO and 6.0 +/- 3.8 with placebo. However, from day 21 to day 41, the rHuEPO-treated patients received 1.4 +/- 2.5 (median, 0) transfusions and the control group received 2.7 +/- 4.0 (median, 2) transfusions (P = .004). In the follow-up period from day 42 up to day 100, 2.4 +/- 5.6 transfusions were required with rHuEPO and 4.5 +/- 9.6 were required with placebo (P = .075). A multivariate analysis (ANOVA) showed that acute graft-versus-host disease (GVHD), major ABO-blood group incompatibility, age greater than 35 years, and hemorrhage significantly increased the number of transfusions. However, after day 20, rHuEPO significantly reduced the number of erythrocyte transfusions in these patient groups, as well as reducing incompatibility in the major ABO-blood group. For the whole study period, rHuEPO reduced the transfusion requirements in GVHD III and IV from 18.4 +/- 8.6 to 8.5 +/- 6.8 U (P = .05). After autologous BMT, there was no difference in the time to independence from erythrocyte transfusions and in the regeneration of reticulocytes. Marrow purging strongly increased the requirement for transfusions as well as the time to transfusion independence.     

Molecular cloning of human epsilon-globin gene.

Human beta-like globin genes were investigated by use of rabbit beta-globin cDNA plasmid as a cross-species hybridization probe. Normal and beta 0/delta beta 0 thalassemic DNA were compared by filter hybridization procedures. It proved possible to demonstrate that the rabbit probe detected G gamma, A gamma, delta, beta, beta 0, and delta beta 0 human globin genes as well as an additional unidentified beta-like globin gene. By use of an agarose gel elution procedure, fractions of HindIII-digested DNA enriched for beta-like globin genes were purified. One of these fractions, 8.0 kilobases in size, was clonedinto lambda 788, and EK2 lambda HindIII vector. A positive clone was obtained and characterized by restriction mapping and sequence analysis. The sequence data obtained predicted an amino acid sequence that exactly matches a part of human epsilon-globin. The human non-alpha-globin locus is now nearly complete. delta, beta, and gamma human globin genes have already been cloned and analyzed. We describe here the cloning of the remaining non-alpha-globin gene, epsilon.     

Effects of metoprolol on mortality and late infarction in diabetics with suspected acute myocardial infarction. Retrospective data from two large studies

From two large scale studies in patients with suspected acutemyocardial infarction we report the outcome in diabetics aftertreatment with either metoprolol or placebo. In the GoteborgMetoprolol Trial mortality at 3 months was reduced by metoprololfrom 17.9% to 7.5% and late infarction was reduced from 16.4%to 3.8%. In the MIAMI Trial, mortality was decreased by metoprololfrom 11.3% to 5.7% and the occcurence of late infarction wasdecreased from 4.5% to 31% during 15-day follow-up. Comparedwith the overall results, the effect of metoprolol on mortalityappears particularly impressive in diabetics.     

Functional and metabolic studies of polymorphonuclear leukocytes in the congenital Pelger-Huet anomaly

Polymorphonuclear leukocytes (PMNL) from two individuals with congenital Pelger-Huet anomaly (PHA) were examined to determine whether functional or metabolic defects accompanied the known morphological abnormality. No abnormalities of the PHA cells, as compared to normal control cells, were found when tested for quantitative leukocyte enzyme activities, nitroblue tetrazolium reduction, hexose monophosphate shunt activity, superoxide production, generation of chemiluminescence, or iodination. The PHA cells, as compared to normal PMNL, demonstrated normal chemotaxis and random migration, as well as bactericidal activity.     

Interaction of single-chain urokinase with its receptor induces the appearance and disappearance of binding epitopes within the resultant complex for other cell surface proteins

Binding of urokinase-type plasminogen activator (uPA) to its glycosylphosphatidylinositol-anchored receptor (uPAR) initiates signal transduction, adhesion, and migration in certain cell types. To determine whether some of these activities may be mediated by associations between the uPA/uPAR complex and other cell surface proteins, we studied the binding of complexes composed of recombinant, soluble uPA receptor (suPAR) and single chain uPA (scuPA) to a cell line (LM-TK- fibroblasts) that does not express glycosylphosphatidylinositol (GPI)-anchored proteins to eliminate potential competition by endogenous uPA receptors. scuPA induced the binding of suPAR to LM-TK- cells. Binding of labeled suPAR/scuPA was inhibited by unlabeled complex, but not by scuPA or suPAR added separately, indicating cellular binding sites had been formed that are not present in either component. Binding of the complex was inhibited by low molecular weight uPA (LMW-uPA) indicating exposure of an epitope found normally in the isolated B chain of two chain uPA (tcuPA), but hidden in soluble scuPA. Binding of LMW-uPA was independent of its catalytic site and was associated with retention of its enzymatic activity. Additional cell binding epitopes were generated within suPAR itself by the aminoterminal fragment of scuPA, which itself does not bind to LM-TK- cells. When scuPA bound to suPAR, a binding site for alpha 2-macroglobulin receptor/LDL receptor-related protein (alpha 2 MR/LRP) was lost, while binding sites for cell-associated vitronectin and thrombospondin were induced. In accord with this, the internalization and degradation of cell-associated tcuPA and tcuPA-PAI- 1 complexes proceeded less efficiently in the presence of suPAR. Further, little degradation of suPAR was detected, suggesting that cell- bound complex dissociated during the initial stages of endocytosis. Thus, the interaction of scuPA with its receptor causes multiple functional changes within the complex including the dis-appearance of an epitope in scuPA involved in its clearance from the cell surface and the generation of novel epitopes that promote its binding to proteins involved in cell adhesion and signal transduction.     

Helical advancement: Pearls and pitfalls

BACKGROUND:

Reconstruction of acquired auricular defects is a challenging procedure. Since its emergence, the helical advancement technique has proved to be an excellent method of repairing many auricle defects. This technique may occasionally result in an alteration in the dimensions of the neoauricle, with subsequent deformity. However, the advantages of this technique are well known, while the pitfalls are scarce.

OBJECTIVE:

To critically review the selection criteria of patients with acquired auricular defects to determine which are eligible for helical advancement technique without subsequent deformity.

METHODS:

From March 2004 to January 2006, 18 patients with three types of upper one-third auricle defects underwent the helical advancement procedure. All patients were male, with mean age of 33.5 years. The defects ranged from 1.2 cm to 4.3 cm in length. Two helical flaps (one on either side of the injury) were advanced along the helical margin to ensure closure. The vertical and horizontal auricular axes were measured before and after surgery, and the actual reduction in millimetres was calculated. Patients were followed up for three months postoperatively. Assessment of the surgical outcome was performed by surgeon (with patient feedback) in the final patient visit.

RESULTS:

The principle pitfall in the form of small neoauricle with or without cupping was reported in five patients (27.77%). The defects in these cases were >2.8 cm and the mean resultant reduction in vertical axes was >5 mm. Statistical analysis resulted in χ²=4.24 and P=0.04

CONCLUSION:

The three varieties of upper one-third auricle defects can best be corrected by the helical advancement technique when the defect is <2.8 cm. Furthermore, perioperative reduction in the vertical axis of the neoauricle >5 mm was an important predictive factor in the development of subsequent deformity.     

Absence of Asymptomatic Malaria Infection in Endemic Area of Bashagard District,Hormozgan Province,Iran

Background

A successful malaria elimination program calls for enough attention to parasite carriers, especially asymptomatic malaria, as well as the diagnosis and treatment of clinical cases. Asymptomatic malaria is an infection that patients do not show any symptom; thus, these patients play critical role in the concept of an elimination program. The current investigation was conducted to evaluate the presence of these cases in Bashagard District, formerly a high malaria transmission area in Hormozgan Province, Iran.

Methods

Blood samples (n = 500) were collected from symptomless individuals residing in Bashagard to evaluate Plasmodium infection by using microscopic, serological and nested-PCR techniques.

Results

Regarding the microscopic and nested-PCR analysis, no asymptomatic infection was detected among studied individuals. Totally, 1% of the studied population (5 of 500) had anti PvMSP-1₁₉-specific IgG antibody; however, only 0.2% (1 of 500) of the individuals was seropositive to recombinant PfMSP-1₁₉, using ELISA.

Conclusion

This study showed no asymptomatic malaria infection in the studied population; hence malaria elimination is feasible and can be successfully carried out in this region.