Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen

Busulfan 16 mg/kg and cyclophosphamide 120 mg/kg were used as conditioning prior to allogeneic marrow transplantation in 50 adult patients with acute nonlymphocytic leukemia (ANLL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML). A standard risk group of 20 patients included those with acute leukemia in remission and CML in chronic phase. A high-risk group of 30 patients included individuals with refractory acute leukemia, acute leukemia in relapse, acute leukemia following preleukemia, and CML in accelerated and blastic phase. Complete remission and sustained complete engraftment were achieved in all evaluable patients. The duration of aplasia was remarkably short (median of 8 days), resulting in a low infection rate during the period of neutropenia, a reduced need for blood product support, and a short length of hospital stay. Three-year actuarial relapse-free survival in both standard-risk (88.9% +/- 10.5%) and high- risk (50.5% +/- 9.6%) groups compares favorably with that reported with total body irradiation (TBI) containing regimens.     

Membrane mechanical properties of ATP-depleted human erythrocytes

Although the relations between the metabolic state and the mechanical properties of human red blood cells (RBC) continue to be of current interest, literature reports in this area are not in agreement. The present investigation was designed to determine several intrinsic mechanical properties of human RBC membranes before and after metabolic depletion via incubation at 37 degrees C for 24 hr. Using micropipette and flow channel techniques, three properties were measured: (1) mu, surface shear modulus of elasticity; (2) K, elastic area compressibility modulus; (3) etap, shear viscosity in the plastic domain. Our results indicate no significant differences in these parameters between fresh and ATP-depleted human RBC membranes. These present data are thus in disagreement with other literature reports indicating large changes in membrane mechanical properties consequent to metabolic depletion. A brief discussion of the possible reasons for this disagreement is presented.     

A comparative study of the iron-clearing properties of desferrithiocin analogues with desferrioxamine B in a Cebus monkey model

A comparative study of the iron-clearing properties of subcutaneously administered desferrioxamine B (DFO) with those of orally administered desferrithiocin sodium salt (1), desmethyl desferrithiocin (2), desazadesmethyl desferrithiocin sodium salt (3), desazadesmethyl desferrithiocin pivaloyloxymethyl ester (4), and desazadesmethyl-5,5- dimethyl desferrithiocin (5) in an iron-loaded Cebus monkey model and a non-iron overloaded bile duct-cannulated rat model is presented. All six drugs, which performed well in rodent studies, demonstrated increased efficiency in the Cebus monkey model. When administered to rodents at a daily dosage of 384 mumol/kg over a period of 10 days, drug 1 demonstrated severe renal toxicity. whereas drugs 3, 4, and 5 exhibited severe gastrointestinal (GI) toxicity. Under the same experimental protocol, drug 2 did not show significant toxic side effects. In addition, to further evaluate the iron-clearing properties of analogue 2, a dose-response study was performed in the primates that showed that iron excretion increased in a dose-dependent fashion.     

Biologic properties in vitro of a recombinant human granulocyte- macrophage colony-stimulating factor

Recombinant human granulocyte-macrophage colony-stimulating factor (rH GM-CSF) was purified to homogeneity from medium conditioned by COS cells transfected with a cloned human GM-CSF cDNA and shown to be an effective proliferative stimulus in human marrow cultures for GM and eosinophil colony formation. The specific activity of purified rH GM- CSF in human marrow cultures was calculated to be at least 4 X 10(7) U/mg protein. Clone transfer experiments showed that this proliferation was due to direct stimulation of responding clonogenic cells. Acting alone, rH GM-CSF did not stimulate erythroid colony formation, but in combination with erythropoietin, increased erythroid and multipotential colony formation in cultures of peripheral blood cells. rH GM-CSF had no proliferative effects on adult or fetal murine hematopoietic cells, did not induce differentiation in murine myelomonocytic WEHI-3B cells, and was unable to stimulate the survival or proliferation of murine hematopoietic cell lines dependent on murine multi-CSF (IL 3). rH GM- CSF stimulated antibody-dependent cytolysis of tumor cells by both mature human neutrophils and eosinophils and increased eosinophil autofluorescence and phagocytosis by neutrophils. From a comparison of these effects with those of semipurified preparations of human CSF alpha and -beta, it was concluded that rH GM-CSF exhibited all the biologic activities previously noted for CSF alpha.     

Lipid hydroperoxides permit deformation-dependent leak of monovalent cation from erythrocytes

Subtle peroxidative perturbation of normal red blood cells (RBC) using t-butylhydroperoxide creates a leak pathway for monovalent cations that is reversibly activated by cell deformation. To determine what factor promotes expression of this unique membrane defect, we have dissected "peroxidation" into components that can be evaluated separately by comparing K leak from suitably modified RBC during elliptical deformation and parallel control incubation. Selective introduction of phospholipid hydroperoxides into normal RBC membranes successfully induces a deformation-dependent leak pathway having the same phenomenology as that previously documented for cells treated with t- butylhydroperoxide itself (fully recoverable; calcium-independent; inhibited at lower pH; K efflux balanced by Na influx). This leak pathway occurs in the absence of detectable secondary peroxidative change and appears to reflect a direct influence of lipid hydroperoxide. Using micropipette examination of vesicular bilayers reconstituted from RBC lipid extracts, we find that lipid from peroxidized RBC exhibits only a slight tendency to be less cohesive than normal lipid, apparently precluding isolated lipid properties as an explanation for altered permeability barrier function. However, addition of a hydrophobic membrane-spanning peptide to these same lipids significantly diminishes bilayer cohesion, an effect that is exacerbated further by the presence of peroxidized lipid. These observations suggest that lipid hydroperoxide is a necessary, but perhaps not sufficient, factor for induction of this unique leak pathway. Our results may be relevant to the abnormal cation homeostasis of sickle RBC in which deformation of an oxidatively perturbed membrane occurs during the sickling phenomenon.     

Inter-hospital transfers and outcomes of critically ill patients with severe acute kidney injury: a multicenter cohort study

Introduction

Patients with severe acute kidney injury (AKI) who are hospitalized at centers that do not provide renal replacement therapy (RRT) are frequently subjected to inter-hospital transfer for the provision of RRT. It is unclear whether such transfers are associated with worse patient outcomes as compared with the receipt of initial care in a center that provides RRT. This study examined the relationship between inter-hospital transfer and 30-day mortality among critically ill patients with AKI who received RRT.

Methods

We conducted a retrospective cohort study of all critically ill patients who commenced RRT for AKI at two academic hospitals in Toronto, Canada. The exposure of interest was inter-hospital transfer for the administration of RRT. We evaluated the relationship between transfer status and 30-day mortality (primary outcome) and RRT dependence at 30 days following RRT initiation (secondary outcome), by using multivariate logistic regression with adjustment for patient demographics, clinical factors, biochemical indices, and severity of illness.

Results

Of 370 patients who underwent RRT for AKI, 82 (22.2%) were transferred for this purpose from another hospital. Compared with non-transferred patients who started RRT, transferred patients were younger (61 ± 15 versus 65 ± 15 years, P = 0.03) and had a higher serum creatinine concentration at RRT initiation (474 ± 295 versus 365 ± 169 μmol/L, P = 0.002). Inter-hospital transfer was not associated with mortality (adjusted odds ratio 0.61, 95% confidence interval 0.33 to 1.12) or RRT-dependence (adjusted odds ratio 1.64, 95% confidence interval 0.70 to 3.81) at 30 days.

Conclusions

Within the limitations of this observational study and the potential for residual confounding, inter-hospital transfer of critically ill patients with AKI was not associated with a higher risk of death or dialysis dependence 30 days after the initiation of acute RRT.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0513-1) contains supplementary material, which is available to authorized users.     

Epidemiologic background of blood donors with antibody to human T-cell lymphotropic virus. Transfusion Safety Study Group

We interviewed 51 blood donors in four major US metropolitan areas subsequently found to have had antibodies to human T-cell lymphotropic virus (anti-HTLV) in late 1984-early 1985. Sixteen donors (31%) reported that they or a sexual contact had a history of blood transfusion. Twelve donors (24%) reported that they or a sexual contact used intravenous drugs. Ten donors (20%) were blacks born in the southeastern US. Four of the male donors (15%) reported homosexual contact. The most common characteristic was an association with Japan or the Caribbean basin (61%). These results show a broader variation of epidemiologic backgrounds than anticipated.     

EFFECT OF SUBCLINICAL LEAD INTOXICATION ON LARYNGEAL CANCER

SUMMARY In this study we investigated the possible relationship of laryngeal cancer and subclinical lead intoxication, using the depression of aminolevulinic acid dehydratase (ALAD) activity in blood as indicator. Twenty-six patients with laryngeal cancer and 53 normal controls met the criteria to enter the study. Blood ALAD activity values in the patients with laryngeal cancer ranged from 27.1 to 75.3 U/l with a mean of 50.79 U/l. The respective values in the control group ranged from 36.2 to 98 U/l with a mean of 59.76 U/l. There was a statistically significant difference between the two means (0.001 <p<0.01), whereas blood lead concentrations in all patients were within normal limits. These findings support the hypothesis that low level lead intoxication (subclinical blood lead levels), from cars, industries and products, may contribute to the risk of laryngeal cancer. Further investigation is needed to clarify the exact relationship between lead and cancer of the larynx.