In vitro effects of bisantrene on fresh clonogenic leukemia cells: a preliminary study on 15 cases

In vitro clonogenic assays may be useful for determining the sensitivity of leukemic cells to chemotherapeutic agents. We evaluated the antileukemic effect of Bisantrene (an anthracene derivative now undergoing phase II clinical trials in relapsed/resistant acute non lymphoid leukemias-ANLL) using the ANLL cell clonogenic assay. Fifteen cases were studied (9 newly diagnosed, 5 relapsed and 1 refractory ANLL). Normal CFU-GM sensitivity was tested in a subset of 10 normal controls. A wide range of concentrations (from 0.01 to 10 micrograms/ml) at 3 durations of exposure (30 min, 120 min, continuous) was employed. Bisantrene proved effective in 12 out of 15 ANLL cases, inhibiting blast colony growth (50% at 1 micrograms/ml; nearly 100% at 10 micrograms/ml) in a dose-dependent, time-independent way. Three cases were unresponsive both in vitro and in vivo. Normal CFU-GM were inhibited at lower doses (50% at 0.5 micrograms/ml; 100% at 5 micrograms/ml). We conclude that: 1) Bisantrene is active in vitro on leukemic clonogenic cells at doses corresponding to plasmatic levels achievable in patients, with a parallel activity in vivo in 3 relapsed cases. It should be tested in vitro before therapeutic use in order to avoid, if possible, improper use in resistant patients. 2) Normal CFU-GM are more sensitive than clonogenic leukemic cells. This must be taken into account, in view of possible prolonged neutropenias after therapy. 3) The time-independent effect of the drug should be evaluated in the design of new therapeutic schedules.     

Behçet’s disease: an immune-mediated vasculitis involving vessels of all sizes

Behçet’s disease is an immune-mediated vasculitis affecting both small and large vessels. Small-vessel vasculitis is the pathological basis of the multiorgan involvement that results in protean clinical features. However, relapsing aphthous ulcers in the mouth are considered the clinical hallmark and are often also observed over the genitalia. Both manifestations, in association with uveitis, form the typical clinical triad. In addition, skeletal muscles, joints, gastrointestinal, cardiopulmonary, and central nervous systems can be involved. Heterogeneity in incidence, clinical manifestations, course, and seventy are observed according to ethnic background. The natural course is chronic with relapses and remissions, gradually abating over the years, but the illness can also be life or sight threatening. Its origin and cause are still obscure: genetic, infectious, environmental, and immunological factors have been proposed. Owing to the lack of a specific test, diagnosis still relies on recognition of the typical clinical pattern. Treatment usually includes corticosteroids and immunosuppressive drugs. A better understanding of the pathogenesis will hopefully improve both diagnosis and therapy. In addition, the development of tests aimed at monitoring disease activity and response to therapy is certainly desirable.     

The survival of metallic residues from gunshot wounds in cremated bone: a SEM–EDX study

The research and analysis of gunshot residues has a relevant role in the examination of gunshot wounds. Nevertheless, very little literature exists concerning gunshot wounds on charred material. In this study, 16 adult bovine ribs (eight still with soft tissues and eight totally skeletonized) underwent a shooting test with two types of projectiles (9?mm full metal-jacketed bullet and 9?mm unjacketed bullet). Each rib then underwent a charring process in an electric oven, reaching the stage of complete calcination at 800°C. The area of each entrance wound was analyzed before and after the carbonization process via a scanning electron microscope (SEM) equipped with an energy dispersive X-ray analyzer (EDX). In each sample, metallic residues composed of lead, barium, and antimony were found. These metallic residues were thus preserved also after exposure to the extremely high temperatures reached within the oven, especially with unjacketed bullets, although the particles seem to be more irregular in shape as a result of the heating process. In conclusion, this study proved that gunshot residues survive extremely high temperatures and can be detected via SEM/EDX even in cases of charred tissues.     

A technique for the flow cytometric analysis of lymphocytes bearing histamine receptors

Histamine receptors have been demonstrated on lymphocyte membranes by a variety of techniques. We now report a method that allows for the flow cytometric analysis of histamine receptors on human peripheral T cells. Histamine is conjugated to fluoresceinated human albumin by the coupling agent ECDI. This conjugated histamine compound (FHA-his) binds to approximately 45% of T cells. Fluoresceinated human albumin alone (FHA), not conjugated to histamine, does not bind to T cells. In addition, unconjugated histamine can inhibit completely the binding seen with FHA-his. We conclude that this technique demonstrates specific FHA-his binding to histamine receptors on T cells and can be used to determine the number of cells bearing such receptors. In addition, the reagent could be used with a cell sorter to isolate distinct histamine-receptor-bearing (HR+) cells for further immunologic study.     

Natural interferon-alpha versus its combination with 6-methyl- prednisolone in the therapy of type II mixed cryoglobulinemia: a long- term, randomized, controlled study

Type II mixed cryoglobulinemia (MC) is an often progressive vasculitis characterized by circulating cold-precipitable proteins that usually consists of polyclonal IgG and monoclonal IgM kappa with rheumatoid factor (RF) activity. Its etiology is unknown, although recent evidence strongly suggests that hepatitis C virus (HCV) plays a major role. Plasmapheresis, corticosteroids, and cytotoxic drugs have been used in the therapy of MC patients. Recently, favorable results with recombinant interferon-alpha (rIFN alpha) have been reported. To further assess its effectiveness, we studied the effects of natural human interferon-alpha (nIFN alpha), alone and in combination with 6- methyl-prednisolone (PDN), in a prospective, randomized, controlled trial in patients with symptomatic MC. Sixty-five patients were enrolled onto the trial, 52 (80%) of whom presented serum anti-HCV antibodies and specific genomic RNA sequences. Fifteen patients received nIFN alpha (3 MU) intramuscularly (IM) three times weekly, whereas 17 patients also received 16 mg/d of PDN orally on non-IFN days. Moreover, 18 patients received 16 mg/d of PDN only, and 15 were untreated. Treatment was discontinued after 1 year and patients were monitored for 8 to 17 months (mean, 13). A complete response was achieved in eight of 15 patients (53.3%) treated with nIFN alpha and nine of 17 (52.9%) treated with nIFN alpha plus PDN, as compared with three of 18 patients (16.7%) who received PDN only (P < .05) and one of 15 (6.7%) untreated controls (P < .01). Partial response occurred in two of 15 (13.3%) patients treated with nIFN alpha, three of 17 (17.6%) who received nIFN alpha plus PDN, one of 18 (5.5%) who received PDN only, and one of 15 (6.7%) controls. A complete response in six patients (66.7%) was achieved within 3 months in the group that received nIFN alpha plus PDN, as compared with two patients (25%) of those who received nIFN alpha alone (P < .02). In anti-HCV-positive patients, the clinical response occurred in step with reduced or undetectable levels of HCV RNA and transaminase normalization. Quantification of circulating HCV RNA represented a good predictive response marker. The probability of relapse within 3 months after treatment was 100% (three of three patients) and 75% (six of eight patients), respectively, in patients who received PDN alone or nIFN alpha alone as compared with none of those who received nIFN alpha plus PDN (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)