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991.
A phase 1B trial of humanized monoclonal antibody M195 (anti-CD33) in myeloid leukemia: specific targeting without immunogenicity 总被引:5,自引:1,他引:5
Caron PC; Jurcic JG; Scott AM; Finn RD; Divgi CR; Graham MC; Jureidini IM; Sgouros G; Tyson D; Old LJ 《Blood》1994,83(7):1760-1768
This trial studied the biodistribution, pharmacology, toxicity, immunogenicity, and biologic characteristics of a trace-labeled, anti- CD33, humanized monoclonal antibody M195 (Hu-M195) in patients with relapsed and refractory myeloid leukemia. Hu-M195 is a computer- modeled, "complementarity-determining region-grafted," IgG1, humanized version of M195. M195 is a murine monoclonal antibody that reacts with CD33, a 67-kD glycoprotein expressed on early myeloid progenitor cells and myeloid leukemia (acute myelogenous leukemia and chronic myelogenous leukemia) cells, but not normal stem cells. 131I-murine- M195 has already shown significant ability to cytoreduce patients with relapsed or refractory myeloid leukemias. Hu-M195 has higher avidity than the original mouse monoclonal antibody and, unlike murine M195, has the capability to mediate antibody-dependent cellular cytotoxicity against leukemia targets. Thirteen patients with relapsed or refractory myelogenous leukemia were treated with Hu-M195 at 4 levels of 0.5, 1.0, 3.0, and 10.0 mg/m2 in a phase I trial. Patients received a total of 6 doses per patient over 18 days. Two patients were retreated for a total of 12 doses. The first dose of Hu-M195 was trace-labeled with 131I to allow detailed pharmacokinetic and biodistribution studies by serial sampling of blood, radioimmunoassays of cells, and whole-body gamma- camera imaging. Cumulative total doses of up to 216 mg of Hu-M195 were administered safely. Reversible fever and rigors were observed after infusion at the highest dose levels. The entire bone marrow was specifically and clearly imaged within hours after infusion, with optimal biodistribution occurring at the 3 mg/m2 level. Adsorption of Hu-M195 onto targets in vivo was demonstrated by flow cytometry; near saturation of available sites occurred at the 3 mg/m2 dose level. Plasma and whole body half lives were 38 and 51 hours, respectively, which may reflect continual replenishment of target sites on new leukemia cells. 131I-Hu-M195 was rapidly internalized into the target cells in vivo within 1 hour. Human antihuman antibody responses were not observed. In conclusion, Hu-M195 can be administered safely in multiple doses, without significant toxicity or any evidence of immunogenicity, and can localize rapidly and efficiently to the bone marrow in patients with myeloid leukemias. Additional phase II trials with this agent alone or in combination with cytokines or isotopes are warranted at the optimal biologic dose. 相似文献
992.
Walters MC; Sullivan KM; Bernaudin F; Souillet G; Vannier JP; Johnson FL; Lenarsky C; Powars D; Bunin N; Ohene-Frempong K 《Blood》1995,85(4):879-884
Seven of 21 patients with sickle cell anemia developed neurologic complications 5 to 243 days (median, 33 days) after allogeneic marrow transplantation. Among these 7 patients, indications for transplantation included either a past history of stroke (4 patients) or recurrent severe vaso-occlusive events (3 patients). All received marrow from an HLA-identical sibling after preparation with busulfan and cyclophosphamide, and in 4 patients with antithymocyte globulin. Five of 6 patients developing seizures received anticonvulsant and supportive treatment with resolution of neurologic abnormalities. Three patients experienced intracranial bleeding, which was fatal in two. Of the 14 patients free of neurologic complications, 4 patients had experienced stroke before transplantation. However, among all patients with prior stroke, the incidence of intracranial hemorrhage was 38% (3/8), whereas none of the 13 patients without prior stroke developed posttransplant intracranial bleeding (P = .026). We conclude that patients with sickle cell anemia are at increased risk for neurologic complications after marrow ablative therapy and that patients with prior stroke are at increased risk for intracranial hemorrhage. Transplantation of patients before the onset of overt stroke may reduce this risk. 相似文献
993.
Sp alpha I/78: a mutation of the alpha I spectrin domain in a white kindred with HE and HPP phenotypes 总被引:5,自引:2,他引:5
Lecomte MC; Garbarz M; Grandchamp B; Feo C; Gautero H; Devaux I; Bournier O; Galand C; d'Auriol L; Galibert F 《Blood》1989,74(3):1126-1133
Limited tryptic digestion of spectrin (Sp) from seven related individuals manifesting hereditary elliptocytosis (HE) or hereditary pyropoikilocytosis (HPP) phenotypes revealed the presence of a novel peptide with a molecular weight of 78 Kd and a concomitant decrease in the alpha I domain (80-Kd peptide), which is the domain involved in the dimer self-association process. Sp from the normal members of this white family exhibited a normal peptide pattern, as compared with controls. The abnormal peptide pattern was associated with a decreased ability of Sp dimer to self-associate. In this kindred in which three generations were available for study, the clinical manifestations were quite variable and ranged from the asymptomatic HE carrier state to hemolytic HE or to severe anemia requiring splenectomy. The severity of the disease appeared to be correlated both with the amount of mutant spectrin (31% to 69%) and with the excess of the Sp dimer found in the membrane (26% to 60%, compared with a normal value of 5.6% +/- 2.2%). Partial amino acid sequencing showed that the alpha I/78-Kd peptide resulted from cleavage at lysine residue 10 of the alpha I/80-Kd domain. Knowledge of the exon/intron structure of cloned genomic DNA encoding the alpha I domain allowed us to amplify in vitro a DNA fragment containing the third exon of the alpha-spectrin gene. The amplified fragment was subcloned and sequenced. A G to T transversion was found in the 39th codon (AGT for AGG), which changed the normal arginine to a serine. Hybridization of amplified DNAs with allele- specific oligonucleotides corresponding to the normal and mutant sequences confirmed the presence of the mutation in three other HE members of the family (the propositus mother, brother, and sister). 相似文献
994.
John O. Simmons MD MPH MAJ MC Dr. Gordon L. Noel MD Louis F. Diehl MD LTC MC 《Journal of general internal medicine》1989,4(6):473-481
Sixty-five physicians were tested to determine the effect of their reviews of red blood cell morphology on their subsequent
diagnoses of and workup plans for common anemias. The subjects read clinical and laboratory data for six pairs of cases of
anemia, reviewing the blood smear for one case in each pair. They correctly identified the presence or absence of morphologic
features on the blood smears 82% of the time. In spite of excellent morphologic discrimination, the number of tests ordered
was not affected by blood smear review. In fact, the quality of the physicians’ workup plans, measured by numbers of tests
appropriately ordered and excluded, was slightly but significantly better when they did not review the smears (p<0.005). In
addition, smear review did not significantly improve diagnostic accuracy for any of the common anemias studied. Significantly
more correct diagnoses were made without smear review for vitamin B12-folate deficiency anemia (p<0.015) and thalassemia (p<0.0001). Although routine review of blood smears by physicians in the
management of common anemias may provide useful information, the authors were unable to demonstrate an improvement in the
number or appropriateness of tests ordered or diagnostic accuracy in spite of excellent morphologic discrimination.
Received from the Divisions of General Internal Medicine and Hematology, Department of Medicine, Walter Reed Army Medical
Center, Washington, DC, and the Uniformed Services University of the Health Sciences, Bethesda, Maryland. Dr. Simmons is now
Chief, Division of General Internal Medicine, Brooke Army Medical Center, San Antonio, Texas.
Presented in part at the annual meeting of the American Federation of Clinical Research, Washington, DC, May 3, 1986.
Supported by a grant from the Department of Clinical Investigation (WU 1013), Walter Reed Army Medical Center, Washington,
DC 20307-5001.
The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or
as reflecting the views of the Department of Defense, the Department of the Army, or the Uniformed Services University of
the Health Sciences. 相似文献
995.
Management of alloimmune thrombocytopenia: antenatal diagnosis and in utero transfusion of maternal platelets 总被引:2,自引:0,他引:2
Kaplan C; Daffos F; Forestier F; Cox WL; Lyon-Caen D; Dupuy-Montbrun MC; Salmon C 《Blood》1988,72(1):340-343
Neonatal alloimmune thrombocytopenia (NAIT) can cause severe bleeding in the central nervous system (CNS) and death or severe neurologic sequelae. The expression of the PLA1 antigen is detectable as early as 19 weeks of gestation. Alloimmunization can therefore lead to fetal thrombocytopenia very early in pregnancy. Until recently, we have had no means of detecting and assessing the severity of fetal thrombocytopenia during pregnancy. The level of the maternal antibody is not of a predictable value since 20% of the mothers had no circulating antibodies in our series. An alternative approach is to carry out investigations on fetal blood samplings. This management leads to an exact knowledge of the fetal status and antenatal diagnosis is feasible as early as the 21st week of gestation. Early diagnosis facilitates appropriate management and makes possible such therapeutic options as in utero maternal platelet transfusions. We report our experience in the antenatal diagnosis and management of nine cases with in utero transfusion in the six cases with severe thrombocytopenia. All neonates did well, with no signs of bleeding at birth. No side effects of therapy were noted after a period ranging from 6 months to 3 years. 相似文献
996.
Edward R. Gomez M.D. CPT MC Daniel Rosenthal M.D. COL MC 《Diseases of the colon and rectum》1984,27(10):651-653
Colostomy perforation is an infrequent but often diasastrous and lethal complication. In the majority of patients, the traumatic performation occurs during irrigation through the colostomy stoma. This case report reviews the clinical course of a patient with a subcutaneous colostomy perforation and the subsequent development of an extensive abscess. Aspects of the management included mobilization of the colostomy and thorough surgical debridement and drainage. In addition, the report introduces the use of the new semisynthetic biologic dressing, BioBrane®. This synthetic, semipermeable skin substitute served as a temporary dessing, provided good stability, and supported the application of a stoma appliance. 相似文献
997.
998.
999.
Dan A. Nelson Captain MC USAF Tracy L. Gustafson M.D. Richard L. Spielvogel Colonel MC USAF 《Journal of the American Academy of Dermatology》1985,12(6):985-992
Five patients with cutaneous leishmaniasis are described. Four of these patients acquired leishmaniasis in Texas. Four cases represent acute cutaneous leishmaniasis, and one case probably represents chronic cutaneous leishmaniasis. The classification and treatment of cutaneous leishmaniasis are reviewed. One patient in this report was successfully treated with topical antimony cream. Cutaneous leishmaniasis must be considered in the differential diagnosis of nonhealing ulcerated papules and nodules even in patients who do not have a foreign travel history. 相似文献
1000.
C Torti M Zazzi L Abenavoli F Trapasso F Cesario D Corigliano L Cosco C Costa RL Curia M De Rosa G Foti C Giraldi R Leone MC Liberto D Lucchino N Marascio R Masciari G Matera V Pisani N Serrao L Surace E Zicca F Castelli M Ciccozzi M Puoti A Focà SINERGIE Study Group 《BMC infectious diseases》2012,12(Z2):S9
The SINERGIE (South Italian Network for Rational Guidelines and International Epidemiology) project is intended to set up a collaborative network comprising virologists, clinicians and public health officials dealing with patients affected by HCV disease in the Calabria Region. A prospective observational data-base of HCV infection will be developed and used for studies on HCV natural history, response to treatment, pharmaco-economics, disease complications, and HCV epidemiology (including phylogenetic analysis). With this approach, we aim at improving the identification and care of patients, focusing on upcoming research questions. The final objective is to assist in improving care delivery and inform Public Health Authorities on how to optimize resource allocation in this area. 相似文献