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71.
Treatment of acute graft-versus-host disease with a nonmitogenic anti-CD3 monoclonal antibody. 总被引:2,自引:0,他引:2
C Anasetti P J Martin R Storb F R Appelbaum P G Beatty J Davis K Doney H F Hill P Stewart K M Sullivan 《Transplantation》1992,54(5):844-851
Treatment with the monoclonal antibody OKT3 specific for the CD3 complex associated with the T cell antigen receptor can reverse acute rejection of human renal allografts. However, efficacy of anti-CD3 antibodies for treatment of patients with acute graft-versus-host disease after marrow transplantation has not been established. The dose-limiting side effects resulting from T cell activation induced by some anti-CD3 antibodies in vivo have discouraged their use for this application. We now report a phase I-II study of GVHD treatment with the anti-CD3 antibody BC3, a monoclonal murine IgG2b that, unlike OKT3, does not activate T cells. Fourteen patients were treated with BC3 after progression of acute GVHD despite treatment with cyclosporine and corticosteroids, and three patients received BC3 as primary treatment for GVHD. BC3 was administered at a dose of 0.1 or 0.2 mg/kg/day for seven or eight days. Five patients achieved complete resolution of GVHD, eight patients had partial improvement, two patients had no change, and two patients had progression of GVHD on therapy. Responses were sustained in 8 of 13 patients. Mild chills, fever, hypertension, and chest discomfort occurred in various combinations following 6 of 17 (35%) initial infusions of BC3 and following 4 of 99 (4%) subsequent infusions. In each instance it was possible to continue BC3 therapy without adjusting the dose or treatment schedule. In each patient treated, the absolute count of peripheral blood lymphocytes decreased transiently but returned to baseline within 22 hr after the first infusion. Circulating T cells had surface CD3 molecules saturated by the infused antibody in all but one patient. Four patients survived longer than one year after treatment with antibody BC3, and 13 patients died of infection or organ failure. Administration of the nonmitogenic anti-CD3 antibody BC3 was associated with improvement in the clinical manifestations of GVHD with minimal acute toxicity. Efficacy of antibody treatment did not depend on depletion of circulating T cells. Therefore, antibody BC3 may be achieving therapeutic immunosuppression by modulating T cell function. Controlled studies in patients treated earlier in the course of GVHD should determine whether antibody BC3 can improve survival. 相似文献
72.
73.
Why should depression screening be conducted in chronically ill populations? Depression is a disabling illness and is very common among patients who have chronic illnesses. Despite its high prevalence in this patient population, depression often goes unrecognized. Having a plan for a population-based screening program for depression can not only identify patients who are at risk of depression, but can also help to foster early treatment and enhanced care for these patients. This article provides an overview of commonly-used depression screening tools and presents an example of how this might be carried out in a healthcare organization. 相似文献
74.
T lymphocytes expressing HECA-452 epitope are present in cutaneous acute graft-versus-host disease and erythema multiforme, but not in acute graft-versus-host disease in gut organs.
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Lymphocytes in formalin-fixed skin biopsies from patients with cutaneous acute graft-versus-host disease (aGVHD) were studied with HECA-452 (an antibody recognizing lymphocytes with skin-homing properties) and a panel of antibodies recognizing pan-B (L26 [CD20]), pan-T (L60 [CD43] and A6 [CD45RA]), and T-helper subset (OPD4) antigens in paraffin sections. Biopsies from patients with erythema multiforme (EM) were similarly studied for comparison. In both conditions, T lymphocytes stained by OPD4 were predominantly confined to the dermis, whereas those stained by HECA-452 were concentrated in the epidermis; however, there was considerable variation between cases, and overlap between findings in the dermis and epidermis. Lymphocytes similarly studied in paraffin sections of liver, salivary gland, and gut affected by aGVHD were essentially unreactive with HECA-452, although they were largely stained by pan-T markers and showed some comparable reactivity with OPD4. The findings suggest that aGVHD of the skin is mediated by a different set of lymphocytes than in gut organs, and may have a similar immunologic mechanism to EM. 相似文献
75.
R S Kahn M Davidson J Hirschowitz R G Stern B M Davis S Gabriel C Moore K L Davis 《Psychiatry research》1992,41(2):155-161
Plasma growth hormone concentrations were measured at hourly intervals between 10 p.m. and 8 a.m. the next morning in 15 drug-free chronic schizophrenic male inpatients and 14 healthy males. Growth hormone secretion was significantly lower in the patients as compared with the controls. Growth hormone release peaked around 1 a.m. in the controls, but a growth hormone peak was absent in the patient group. Increased dopamine activity, increased serotonin activity, or both could explain the absence of a nocturnal growth hormone surge in the schizophrenic patients. 相似文献
76.
Gary L. Davis MD 《Current hepatitis reports》2003,2(1):40-46
There has been considerable progress in the treatment of chronic hepatitis C since the first report that interferon (IFN)
monotherapy was effective in 1989. Early results were meager, with sustained loss of hepatitis C virus from blood in fewer
than 10% of cases. The combination of IFN with the oral nucleoside analogue ribavirin was a major breakthrough in clinical
hepatology; it led to dramatic increases in treatment responses, with 30% to 40% of patients clearing virus. Pegylated IFNs
that have prolonged activity and can be dosed once a week have now replaced standard IFNs. The combination of pegylated IFN
with ribavirin is the new standard of care; it causes sustained loss of virus in more than half of treated patients. Treatment
responses continue to be highly dependent on viral genotype. Patients with genotype 1, the most common type in the United
States, have a sustained clearance rate of 42% to 46%, whereas those with genotype 2 or 3 have a response rate approaching
80%. 相似文献
77.
78.
79.
D Rudy D A Sica T Comstock J Davis J Savory A C Schoolwerth 《The International journal of artificial organs》1991,14(10):625-629
The influence of a sodium citrate/citric acid mixture on the gastrointestinal (GI) absorption of aluminum (Al) from an Al(OH)3 preparation was evaluated in six stable maintenance hemodialysis patients. Plasma Al concentrations were determined serially after each of the following treatment sequences (I) Al(OH)3; (II) Al(OH)3 + sodium citrate/citric acid; (III) sodium citrate/citric acid; (IV) Al(OH)3 + NaHCO3. AUC0-8 for plasma Al from 0 to 8 hours was significantly greater (p less than 0.05) for Al(OH)3 + sodium citrate/citric acid (73 +/- 23 micrograms.hr/l; mean +/- SEM) than Al(OH)3 (16 +/- 30 micrograms.hr/l); sodium citrate/citric acid (-27 +/- 14 micrograms.hr/l); or Al(OH)3 + NaHCO3 (6 +/- 22 micrograms.hr/l). The 24 hour Al level remained above baseline (p less than 0.03) following Al(OH)3 + sodium citrate/citric acid (31 +/- 12 (pre) vs 54 +/- 14 micrograms/l (post), in contradistinction to study limb: l (34 +/- 14 vs 30 +/- 12 micrograms/l); III (79 +/- 40 vs 65 +/- 35 micrograms/l); and IV (71 +/- 37 vs 66 +/- 42 micrograms/l). We conclude that the GI absorption of Al from Al(OH)3 is enhanced by citrate in patients undergoing hemodialysis and that elevations of plasma Al persist longer. The concomitant administration of citrate and Al-containing phosphate (PO4) binders should be avoided in patients with end-stage renal disease (ESRD). NaHCO3 may serve as an alternative therapy for metabolic acidosis with less risk of enhancing Al absorption. 相似文献
80.
Specific interventional procedures have enjoyed widespread popularity in the United States in the routine management of low risk obstetric patients without the benefit of clinical studies attesting to their utility. A review of the literature was conducted to survey obstetric practice with regard to amniotomy, intravenous fluids, third stage administration of oxytocics, episiotomy and continuous fetal monitoring. 相似文献