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991.
Evaluation of a CD5-specific immunotoxin for treatment of acute graft- versus-host disease after allogeneic marrow transplantation 总被引:3,自引:4,他引:3
Martin PJ; Nelson BJ; Appelbaum FR; Anasetti C; Deeg HJ; Hansen JA; McDonald GB; Nash RA; Sullivan KM; Witherspoon RP; Scannon PJ; Friedmann N; Storb R 《Blood》1996,88(3):824-830
Acute graft-versus-host disease (GVHD) is most often treated with high dose glucocorticoids, but less than half of patients have durable overall improvement. Previous phase I and phase II studies suggested that treatment with a CD5-specific immunotoxin (XomaZyme-CD5 Plus) could ameliorate symptoms of GVHD. In a randomized, double-blind trial, we compared XomaZyme-CD5 Plus and glucocorticoids versus placebo and glucocorticoids as initial therapy for 243 patients who developed acute GVHD after allogeneic marrow transplantation. The study drug (XomaZyme. CD5-Plus or an identical appearing placebo) was administered at a dose of 0.1 mg/kg body weight on each of 14 consecutive days. All patients were treated concomitantly with a standard regimen of methylprednisolone. At the time of entry on study, 94% of patients had a rash, 56% had hyperbilirubinemia, 61% had diarrhea, and 84% had nausea and vomiting. At 3, 4, and 5 weeks after starting treatment, symptom severity was less in the CD5 group than in the placebo group. At 4 weeks, 40% of patients assigned to the CD5 group had complete response compared with 25% of those assigned to the control group (P = .019). At 6 weeks, 44% of patients assigned to the CD5 group had complete response as compared with 38% in the placebo group (P = .36). Clinical extensive chronic GVHD developed in 65% of patients in the CD5 group compared with 72% in the control group (P = .35). Survival at 1 year after treatment was 49% in the CD5 group and 45% in the control group (P = .68). Side effects required close monitoring and appropriate adjustment of treatment. The combined administration of a CD5-specific immunotoxin and glucocorticoids controls GVHD manifestations more effectively than treatment with glucocorticoids alone during the first 5 weeks after starting treatment. Use of this immunotoxin does not result in any long-term clinical benefit for patients with acute GVHD. 相似文献
992.
The role of HLA-DPB1 disparity in the development of acute graft-versus- host disease following unrelated donor marrow transplantation 总被引:3,自引:5,他引:3
Petersdorf EW; Smith AG; Mickelson EM; Longton GM; Anasetti C; Choo SY; Martin PJ; Hansen JA 《Blood》1993,81(7):1923-1932
The role of HLA-DPB1 disparity in the development of acute graft-versus- host disease (GVHD) following unrelated donor (URD) marrow transplantation is unknown. We studied 129 patients who underwent marrow transplantation from HLA-A, -B, -DRB, and -DQB matched URDs to determine whether matching for HLA-DPB1 alleles significantly decreased the risk of developing acute GVHD. HLA-DPB1 alleles were determined by sequence-specific oligonucleotide hybridization and by the number of patient DPB1 alleles not shared by the donor scored. The Kaplan-Meier probability of developing grades II to IV acute GVHD was determined for patients incompatible for zero (group A), one (group B), or two (group C) DPB1 alleles. Of the 129 pairs, there was no recipient DPB1 incompatibility in 28 (22%), one DPB1 mismatch in 72 (56%), and two DPB1 mismatches in 29 (22%). The probability of grades II to IV acute GVHD was 0.69 (0.50, 0.86) for group A, 0.83 (0.73, 0.91) for group B, and 0.72 (0.56, 0.87) for group C (P = .63). These results indicate that matching patients and unrelated donors for HLA-A, -B, -DRB, and - DQB does not predict for matching at DPB1. However, recipient incompatibility for DPB1 alleles does not detectably influence the risk of acute GVHD. Therefore, HLA-DP disparity should not be used as an exclusion criterion for donor selection in unrelated marrow transplantation. 相似文献
993.
A neutrophil membrane marker reveals two groups of chronic myelogenous leukemia and its absence may be a marker of disease progression 总被引:1,自引:0,他引:1
Gallin JI; Jacobson RJ; Seligmann BE; Metcalf JA; McKay JH; Sacher RA; Malech HL 《Blood》1986,68(2):343-346
An IgG1 monoclonal antibody, 31D8, that recognizes normal neutrophil (PMN) membranes, was used to study PMN from patients with chronic myelogenous leukemia (CML). Nineteen patients with Philadelphia chromosome positive CML were followed over a ten-month period and compared with 23 normals, six patients with leukemoid reactions, and eight patients with phagocytic cell defects. The percentage of PMN binding of 31D8 among normal subjects was variable about a normal distribution with an average of 95 +/- 2% of cells binding 31D8. In contrast, there were two groups of CML patients: in 14 patients 88 +/- 3% PMN bound 31D8 while in the remaining five patients only 6 +/- 6% PMN bound 31D8. PMN 31D8 binding was normal in the control patient groups. Control antibodies 7C3 (binds to PMN precursors) and OKM1 (binds to the CR3 (iC3b) receptor) bound normally to CML neutrophils. Functionally, CML cells had normal chemotaxis to several stimuli and normal superoxide generation to phorbol myristate acetate. However, superoxide production in response to fmet-leu-phe was significantly less in 31D8 negative CML PMN than both 31D8 positive CML PMN and normal PMN which contained 85% 31D8 positive and 15% 31D8 negative PMN. Clinically, 2 of 14 CML patients with 31D8 positive PMN were in blast crisis (one extramedullary) at the time of study and the other 12 patients remained clinically stable in the chronic phase during the ten months of study. In contrast, one of five patients with 31D8 negative PMN was in blast crisis at the time of study and all four of the remaining patients progressed to either the accelerated phase or blast crisis. Three of these patients died of their disease eight to ten months after their initial study. Thus, failure of CML cells to bind 31D8 may be useful for predicting which patients are likely to progress to the accelerated phase or blast crisis. 相似文献
994.
Double-balloon enteroscopy and capsule endoscopy have comparable diagnostic yield in small-bowel disease: a meta-analysis 总被引:1,自引:0,他引:1
SF Pasha JA Leighton A Das ME Harrison GA Decker DE Fleischer VK Sharma 《Clinical gastroenterology and hepatology》2008,6(6):671-676
BACKGROUND & AIMS: The aim of this study was to compare the diagnostic yield of capsule endoscopy (CE) with double-balloon enteroscopy (DBE) in small-bowel (SB) disease using meta-analysis. METHODS: We performed a search of studies comparing CE with DBE in SB disease. Data on diagnostic yield of CE and DBE were extracted, pooled, and analyzed. The weighted incremental yield (IY(W)) (yield of CE--yield of DBE) of CE over DBE and 95% confidence intervals (95% CIs) for pooled data were calculated using a fixed-effect model (FEM) for analyses without, and a random-effect model (REM) for analyses with, significant heterogeneity. RESULTS: Eleven studies compared CE and DBE; the pooled overall yield for CE and DBE was 60% (n = 397) and 57% (n = 360), respectively (IY(W), 3%; 95% CI, -4% to 10%; P = .42; FEM). Ten studies reported vascular findings; the pooled yield for CE and DBE was 24% (n = 371) and 24% (n = 364), respectively (IY(W), 0%; 95% CI, -5% to 6%; P = .88; REM). Nine studies reported inflammatory findings; the pooled yield for CE and DBE was 18% (n = 343) and 16% (n = 336), respectively (IY(W), 0%; 95% CI, -5% to 6%; P = .89; FEM). Nine studies reported polyps/tumors; the pooled yield for CE and DBE was 11% (n = 343) and 11% (n = 336), respectively (IY(W), -1%; 95% CI, -5% to 4%; P = .76; FEM). CONCLUSIONS: CE and DBE have comparable diagnostic yield in SB disease, including obscure gastrointestinal bleeding. CE should be the initial diagnostic test because of its noninvasive quality, tolerance, ability to view the entire SB, and for determining the initial route of DBE. Because of its therapeutic capabilities, DBE may be indicated in patients with a positive finding on CE requiring a biopsy or therapeutic intervention, if suspicion for a SB lesion is high despite a negative CE, and in patients with active bleeding. 相似文献
995.
Miller GJ; Martin JC; Mitropoulos KA; Esnouf MP; Cooper JA; Morrissey JH; Howarth DJ; Tuddenham EG 《Blood》1996,87(10):4187-4196
Factor VII activity (FVIIc), a risk marker for coronary heart disease, is increased during postprandial lipemia. Factor VII activation accompanies lipolysis of triglyceride-rich lipoproteins, but the nature of this association and whether it is causal remain uncertain. To explore this issue, four patients with homozygous factor XII deficiency, four with complete factor XI deficiency, six with factor IX deficiency, and their respective age- and sex-matched controls were given two isocaloric dietary regimens, one providing on average 136 g fat and the other 19 g fat. Blood was taken before breakfast, immediately before lunch at 195 minutes, and at completion of the study at 390 minutes. All samples for each subject and matched control were assayed as one batch for FVIIc, activated factor VII, and factor VII antigen (FVIIag). Activation of factor VII was observed with the high- fat regimen but not with the low-fat regimen in all controls, factor XII-deficient patients, and factor XI-deficient patients. No factor VII activation was observed during either regimen in factor IX-deficient patients, but a normal postprandial responsiveness of factor VII to dietary fat was restored in one patient who replicated the study after factor IX therapy. Plasma FVIIag was not altered postprandially in either regimen in any group of patients or controls. Factor IX apparently plays an obligatory role in the postprandial activation of factor VII, although the mechanism remains to be determined. 相似文献
996.
van Dijk TB; Bracke M; Caldenhoven E; Raaijmakers JA; Lammers JW; Koenderman L; de Groot RP 《Blood》1996,88(11):4229-4238
The Fc receptor for IgA (Fc alpha R, CD89) is a transmembrane glycoprotein found on monocytes, macrophages, neutrophils, and eosinophils. Here we describe the characterization of a novel isoform of the Fc alpha R cloned from a human eosinophil cDNA library. This clone, Fc alpha Rb, lacks the exon encoding the transmembrane/intracellular region of wild type Fc alpha R, which is replaced by 23 new amino acids. Expression of Fc alpha Rb mRNA could be detected in eosinophils and neutrophils. IIA1.6 murine pro-B cells transfected with Fc alpha Rb cDNA secrete high levels of the protein, but also a substantial amount of Fc alpha Rb is expressed at the cell membrane. Membrane-bound Fc alpha Rb binds IgA-coated beads equally well as wild type Fc alpha R. Surface expression is not affected by phosphatidyl inositol phospholipase C, indicating that glycosyl phosphatidyl inositol-linkage of Fc alpha Rb is not likely. In IIA1.6 cells expressing Fc alpha Rb and FcR gamma, which is necessary for signal transduction by wild type Fc alpha R, no tyrosine phosphorylation or Ca(2+)-mobilization could be observed after receptor cross-linking. These results indicate that Fc alpha Rb is likely to have a different function than wild-type Fc alpha R receptor. 相似文献
997.
Narvaez J; Narvaez JA; Sanchez-Marquez A; Clavaguera MT; Rodriguez-Moreno J; Gil M 《Rheumatology (Oxford, England)》1997,36(1):136-139
Dysfunction of the posterior tibial tendon is the most common cause of
acquired flatfoot in adults; despite this, the condition is not commonly
recognized. We report three cases with flatfoot secondary to spontaneous
tendon rupture, in whom magnetic resonance imaging (MRI) was a helpful
non-invasive technique to confirm the suspected diagnosis. This disabling
entity, and the usefulness of MRI in the diagnosis and planning the
appropriate treatment, are reviewed.
相似文献
998.
Carrier detection in the Wiskott Aldrich syndrome 总被引:13,自引:1,他引:13
The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease characterized by immunodeficiency and severe thrombocytopenia in affected males, but no demonstrable clinical abnormalities in carrier females. Through analysis of the methylation patterns of X-linked genes that display restriction fragment length polymorphisms (RFLPs), we studied the pattern of X-chromosome inactivation in various cell populations from female relatives of patients with WAS. The peripheral blood T cells, granulocytes, and B cells of eight obligate WAS carriers were found to display specific patterns of X-chromosome inactivation clearly different from these of normal controls. Thus, carriers of WAS could be accurately identified using this analysis. 相似文献
999.
Erythrocytes from heterozygous carriers of the high oxygen affinity mutant hemoglobin, Hb Wood, demonstrate lower rates of methemoglobin reduction than normal human red cells when incubated in the in vitro system of Beutler and Baluda. The rate of methemoglobin reduction in red cells from an individual who is heterozygous for both NADH- methoglobin reductase deficiency and Hb Wood shows the combined effects of the two mutations. 相似文献
1000.
Ragni MV; Tegtmeier GE; Levy JA; Kaminsky LS; Lewis JH; Spero JA; Bontempo FA; Handwerk-Leber C; Bayer WL; Zimmerman DH 《Blood》1986,67(3):592-595
Antibodies to the AIDS retrovirus, specifically to human T cell lymphotropic virus, type III, and AIDS-associated retrovirus, were detected with increasing prevalence in a population of 190 hemophiliacs from western Pennsylvania between 1981 and 1984: 7.7% in 1981, 20.0% in 1982, 45.5% in 1983, and 62.5% in 1984. The seropositive included approximately three fourths of those receiving factor VIII concentrate, nearly one third of those receiving factor IX concentrate, nearly one fifth of those receiving cryoprecipitate, and none of those receiving fresh frozen plasma. The seroconversion rate, determined on 43 seropositive hemophiliacs from this group who were serially sampled, was 0% in 1977, 4.7% in 1978, 4.9% in 1979, 2.6% in 1980, 10.5% in 1981, 52.9% in 1982, 87.5% in 1983, and 100% in 1984. Of 27 seropositive for three or more years (since 1982 or before), four (15%) have developed AIDS and seven (26%), diffuse lymphadenopathy (ARC); of 16 seropositive for less than three years, none has developed AIDS and three (19%) have developed ARC. The mean time from seroconversion to onset of ARC, 0.8 +/- 0.2 years (SEM), was shorter (P less than .001) than the time to onset of AIDS, 4.1 +/- 0.6 years. These findings confirm the widespread presence of AIDS retrovirus and support the association of these retroviruses with the acquired immunodeficiency syndrome and related conditions. 相似文献