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1.
Phys Rev Lett ; 97(23): 235002, 2006 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-17280209

RESUMEN

Evidence of relaxation has appeared, for the first time, in the extremely high-beta, steady-state field-reversed configuration plasma states driven by rotating magnetic fields (RMF) in the translation, confinement, and sustainment experiment. The plasma self-organizes into a near-force-free state in the vicinity of the magnetic axis, with significant improvement in confinement. Associated with this change in magnetic topology is the appearance of an axial RMF component; this would, in turn, generate a current drive in the poloidal direction, thus sustaining the magnetic helicity. A newly developed two-dimensional "equilibrium-lite" model is employed to analyze the magnetic properties of the final high-confinement state, and shows a large q and a significant magnetic shear in the core.

2.
Phys Rev Lett ; 95(17): 175001, 2005 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-16383833

RESUMEN

An extremely high-beta (over 85%) self-organized field-reversed configuration (FRC) with a spherical-torus- (ST-)like core is produced in the translation, confinement, and sustainment experiment by highly super-Alfvénic translation of a spheromaklike plasmoid. Substantial flux conversion from toroidal into poloidal occurs during the capture process, resulting in the ST-like core. This plasma state exhibits a remarkable stabilizing property for the ubiquitous centrifugally driven interchange modes present in theta-pinch formed FRCs. This is explained, for the first time, by a simple model taking into account magnetic shear and centrifugal effects. The FRC-ST configuration has up to 4 times improvement in flux confinement times over the scaling of conventional theta-pinch formed FRCs and, thus, a significant improvement in the resistivity and transport.

3.
Phys Rev Lett ; 94(18): 185001, 2005 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-15904379

RESUMEN

Interchange modes have been a key limiting instability for many magnetic confinement fusion configurations. In previous studies intended to deal with these ubiquitous instabilities, complex, transport enhancing, minimum-B producing coils were added to the otherwise simple linear mirror plasma. Possible solutions for returning to a simple symmetric mirror configuration, such as ponderomotive fields, are weak and difficult to apply. A new method is demonstrated here for the first time, utilizing rotating magnetic fields that are simple to apply and highly effective. A simple and easily comprehensible theory has also been developed to explain the remarkable stabilizing properties. Although this work has been performed on field reversed configurations, it should have a wide application to other confinement schemes, and could become a cornerstone for high-beta plasma stability.

4.
Phys Rev Lett ; 92(24): 245001, 2004 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-15245090

RESUMEN

High-beta plasmoids can survive the violent dynamics of supersonic reflection off mirror structures, producing a stable high-beta field-reversed configuration (FRC). This shows both the robustness of FRCs and their tendency to assume a preferred plasma state, possibly conforming to a relaxation principle. The key observations are (1) approximate preservation of the magnetic helicity, (2) substantial conversion from toroidal to poloidal magnetic flux, (3) substantial toroidal flow, and (4) a high-beta quiescent final state. These results are from the Translation, Confinement, and Sustainment experiment where a disorganized plasmoid is injected at super-Alfvenic speed into a confinement chamber. After successive reflections from end mirrors, the plasmoid settled into a near-FRC state with high beta and low toroidal magnetic field. The flux conversion and helicity preservation are inferred by an interpretive model.

5.
Arch Surg ; 136(6): 664-9, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11387004

RESUMEN

BACKGROUND: Historically, surgical correction has been the treatment of choice for benign biliary strictures (BBS). Self-expandable metallic stents (MSs) have been useful for inoperable malignant biliary strictures; however, their use for BBS is controversial and their natural history unknown. HYPOTHESIS: To test our hypothesis that MSs provide only short-term benefit, we examined the long-term outcome of MSs for the treatment of BBS. Our goal was to develop a rational approach for treating BBS. DATA EXTRACTION: Between July 1990 and December 1995, 15 patients had MSs placed for BBS and have been followed up for a mean of 86.3 months (range, 55-120 months). The mean age of the patients was 66.6 years and 12 were women. Stents were placed for surgical injury in 5 patients and underlying disease in 10 patients (lithiasis, 7; pancreatitis, 2; and primary sclerosing cholangitis, 1). One or more MSs (Gianturco-Rosch "Z" for 4 patients and Wallstents for 11 patients) were placed by percutaneous, endoscopic, or combined approaches. We considered patients to have a good clinical outcome if the stent remained patent, they required 2 or fewer invasive interventions, and they had no biliary dilation on subsequent imaging. DATA SYNTHESIS: Metallic stents were successfully placed in all 15 patients, and the mean patency rate was 30.6 months (range, 7-120 months). Five patients (33%) had a good clinical result with stent patency from 55 to 120 months. Ten patients (67%) required more than 2 radiologic and/or endoscopic procedures for recurrent cholangitis and/or obstruction (range, 7-120 months). Five of the 10 patients developed complete stent obstruction at 8, 9, 10, 15, and 120 months and underwent surgical removal of the stent and bilioenteric anastomosis. Four of these 5 patients had strictures from surgical injuries. The patient who had surgical removal 10 years after MS placement developed cholangiocarcinoma. CONCLUSIONS: Surgical repair remains the treatment of choice for BBS. Metallic stents should only be considered for poor surgical candidates, intrahepatic biliary strictures, or failed attempts at surgical repair. Most patients with MSs will develop recurrent cholangitis or stent obstruction and require intervention. Chronic inflammation and obstruction may predispose the patient to cholangiocarcinoma.


Asunto(s)
Enfermedades de las Vías Biliares/cirugía , Stents , Adulto , Anciano , Anciano de 80 o más Años , Sistema Biliar/lesiones , Enfermedades de las Vías Biliares/clasificación , Enfermedades de las Vías Biliares/diagnóstico por imagen , Enfermedades de las Vías Biliares/etiología , Colangitis Esclerosante/complicaciones , Colelitiasis/complicaciones , Constricción Patológica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/complicaciones , Radiografía , Recurrencia , Estudios Retrospectivos , Stents/efectos adversos , Resultado del Tratamiento
6.
Am Surg ; 65(3): 218-21, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10075295

RESUMEN

An 82-year-old black woman with a history of hepatocellular carcinoma presented with gastrointestinal bleeding. Barium enema and fibrocolonoscopy revealed a 4-cm polypoid mass at the level of the ascending colon with evidence of active bleeding. Biopsies of the lesion proved it to be metastatic hepatocellular carcinoma. Exploratory laparotomy revealed no further dissemination of the tumor, and the patient underwent an ileocolectomy. The serosal side of the colonic lesion was free from tumor, and there was no peritoneal implantation, direct extension, or lymph node involvement. This case represents an extremely rare presentation of metastatic hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/secundario , Neoplasias del Colon/complicaciones , Neoplasias del Colon/secundario , Hemorragia Gastrointestinal/etiología , Neoplasias Hepáticas/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos
7.
Am Surg ; 63(10): 923-6, 1997 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9322674

RESUMEN

Acute liver failure has been reported as a frequent complication of transarterial chemoembolization (TACE). We prospectively evaluated the adverse effects and biochemical changes of TACE. From 10/95 to 9/96, 35 patients with hepatic malignancies were evaluated for TACE. Fifteen patients (9 male and 6 female) received 23 treatments. Ten of 15 patients had hepatocellular carcinoma, and 5 had metastatic tumors. Treatment exclusion criteria included advanced liver disease, hepatic vascular thrombosis, and severe comorbidity. TACE consisted of intra-arterial infusion of a mixture of doxorubicin, cisplatin, and mitomycin followed by embolization. Clinical symptoms and laboratory studies were monitored following treatment. Technical success was achieved in all patients. Adverse symptoms were transient, and most resolved within 1 week. Changes in hepatic, renal, and hematologic function were temporary and returned to pre-TACE levels by 1 month. None developed acute liver failure. The mean hospital stay was 3 days. Ten of 13 patients had a significant decrease in baseline tumor markers. The actual survival was 93 per cent with a median follow-up of 10 months. TACE can be performed safely in patients with hepatic tumors. The adverse effects can be anticipated and easily managed.


Asunto(s)
Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Adulto , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Biomarcadores de Tumor/análisis , Tumor Carcinoide/secundario , Tumor Carcinoide/terapia , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/efectos adversos , Cisplatino/administración & dosificación , Doxorrubicina/administración & dosificación , Estudios de Evaluación como Asunto , Femenino , Estudios de Seguimiento , Arteria Hepática , Humanos , Infusiones Intraarteriales , Riñón/fisiopatología , Tiempo de Internación , Hígado/irrigación sanguínea , Hígado/fisiopatología , Hepatopatías , Fallo Hepático Agudo/etiología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Mitomicinas/administración & dosificación , Selección de Paciente , Estudios Prospectivos , Inducción de Remisión , Seguridad , Tasa de Supervivencia , Trombosis
8.
Liver Transpl Surg ; 3(1): 46-53, 1997 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9377758

RESUMEN

Two case reports of hepatic angiomyolipoma, both originating in the caudate lobe, are reported with a review of the literature. The liver is the second most common site of angiomyolipoma, an uncommon benign tumor of mixed mesenchymal origin. It is commonly diagnosed following abdominal pain or as an asymptomatic mass discovered on abdominal ultrasound or computed tomography scan. Of 74 cases reported, the lesions ranged from 0.3 to 36 cm in diameter and are noted between the first and eighth decade, with predominant female predilection. The right lobe is the most common site, with lesions arising in the caudate lobe comprising only five cases. The natural history of the hepatic lesion is unknown. Malignant invasion or metastatic disease has not been documented. Hepatic and renal angiomyolipoma can occur concurrently (13 of 60 cases), although the majority are not biopsy proven. Multicentric hepatic disease occurs. The correlation between tuberous sclerosis and hepatic angiomyolipoma is not confirmed histologically and occurs rarely. These lesions have a characteristic radiographic appearance due to high fat content. Histologically, angiomyolipoma are characterized by an admixture of adipose tissue, blood vessels, and smooth muscle cells. These lesions cannot reliably be differentiated from a malignant lesion based on clinical history, radiologic examination, and/or pathologic interpretation. If clinical suspicion for malignancy is low, then careful observation with serial radiologic follow-up is performed. The treatment for a symptomatic or suspicious lesion is resection, if feasible. Liver transplantation may be considered for large or centrally located lesions not amenable to resection.


Asunto(s)
Angiomiolipoma/patología , Neoplasias Hepáticas/patología , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad
9.
Am Surg ; 62(10): 835-9, 1996 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8813166

RESUMEN

Variceal bleeding (VB) and ascites refractory to diuretics (RA) represent a significant cause of morbidity and mortality in patients with portal hypertension. Transjugular intrahepatic portosystemic shunts (TIPS) have been used effectively in patients with these complications, especially those individuals awaiting orthotopic liver transplantation (OLT). From April 1992 to July 1995, 41 adult patients underwent an attempt at TIPS placement for refractory VB or ascites at Cedars-Sinai Medical Center. Technical success was achieved in 37 of 41 cases (90.3%) with only two technical complications. Immediate control of hemorrhage and significant improvement of ascites was obtained in 91.9% and 83.5% of the patients, respectively. Six patients (16.2%) died within a week of TIPS placement due to uncontrollable ascites and multiorgan failure. Four of 31 patients (12.9%) developed mild to moderate grades of hepatic encephalopathy that was controlled with lactulose. Rebleeding from recurrent portal hypertension was noted in 5 of 31 cases (16.1%). Shunt stenosis or occlusion was seen in 7 of 31 cases (22.6%) at an average of 6.3 months following TIPS placement. Six patients underwent OLT within an average of 87 days after TIPS. These results indicate that TIPS appears to be an effective method for treatment of refractory VB and RA, especially for patients who are poor candidates for a surgical shunt or awaiting OLT. However, TIPS may not be considered a definitive solution for all patients with portal hypertension because of its current rate of shunt occlusion or stenosis.


Asunto(s)
Hipertensión Portal/cirugía , Trasplante de Hígado , Derivación Portosistémica Intrahepática Transyugular , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipertensión Portal/fisiopatología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Resultado del Tratamiento
10.
Pharmacotherapy ; 16(1): 59-65, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-8700793

RESUMEN

We evaluated the effect of Liqui-E, a water-soluble vitamin E preparation, on cyclosporin A (CyA) whole blood concentration in liver transplant recipients, and its impact on the cost of CyA. Patients were 26 liver transplant recipients (19 adults, 7 children) who were unable to achieve and maintain therapeutic CyA whole blood concentrations with the standard recommended oral daily dose in the early post-transplant period. Liqui-E 6.25 IU/kg orally was administered with CyA every 12 hours (median time of starting Liqui-E day 14.5). With Liqui-E, the daily oral CyA requirements (mean +/- SD) were decreased in adults from 22.6 +/- 8.9 to 16.2 +/- 7.3 mg/kg/day (p < 0.001) and in children from 78.6 +/- 34.1 to 53.7 +/- 35.0 mg/kg/day (p < 0.02); intravenous administration of CyA was unnecessary. The CyA trough concentrations (mean +/- SD) before and after Liqui-E were 670 +/- 186 and 1012 +/- 216 ng/ml, respectively, in adults (p < 0.001) and 732 +/- 187 and 1052 +/- 166 ng/ml, respectively, in children (p < 0.01). When given with Liqui-E, the daily cost of CyA decreased by 26% in both adults and children. No clinical or biochemical evidence of Liqui-E toxicity was observed. Thus its administration in the early post-transplantation period can enhance CyA absorption in adults and children who are unable to achieve adequate whole blood concentrations with the usual recommended oral dosages. In addition, a significant cost saving can be realized by coadministration.


Asunto(s)
Ciclosporina/farmacocinética , Inmunosupresores/farmacocinética , Trasplante de Hígado , Vitamina E/análogos & derivados , Absorción/efectos de los fármacos , Administración Oral , Adulto , Peso Corporal , Preescolar , Ciclosporina/administración & dosificación , Ciclosporina/sangre , Ciclosporina/economía , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/sangre , Inmunosupresores/economía , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Polietilenglicoles , Estudios Prospectivos , Vitamina E/administración & dosificación , Vitamina E/sangre , Vitamina E/farmacología
11.
Am Surg ; 61(10): 889-95, 1995 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7668463

RESUMEN

Although elderly patients are accounted for in all large series of major hepatic resections, the role of age as a determinant of outcome remains unclear. At Cedars-Sinai Medical Center, we review a series of 20 major hepatectomies for neoplasia performed in patients older than 66 years of age (4 of them > or = 80 years old) over a 5-year period. A retrospective comparison was conducted with a group of 22 hepatectomies for malignancy performed in 20 patients younger than 59 years of age during the same time period. The younger group had a significantly greater degree of liver resected (12 trisegmentectomies vs 3). Although one operative death (5% mortality) was observed in the elderly group, no statistically significant difference was noted, when compared to the younger group (Chi-square, P = 0.48). Likewise, no significant difference in the complication rate (20% vs 33%) was noticed (Chi-square, P = 0.8). Severe postoperative liver dysfunction was present in 2 cases (10%) in the elderly group and one (4%) in the younger group. These patients underwent a right trisegmentectomy (TS). Nine patients from each group were resected without red blood cell transfusion. We conclude that major hepatic resection in elderly patients without severe comorbid disease is a safe procedure that is not associated with an increased perioperative morbidity or mortality rate.


Asunto(s)
Hepatectomía , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias/epidemiología , Factores de Edad , Anciano , Comorbilidad , Hepatectomía/mortalidad , Humanos , Neoplasias Hepáticas/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia
12.
Psychiatr Serv ; 46(9): 945-7, 1995 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7583510

RESUMEN

A total of 771 professionals employed in alcohol treatment programs in Nebraska were surveyed to determine whether their personal alcohol and tobacco use status or characteristics of their treatment programs were related to whether they provided nicotine addiction counseling. About a third of respondents agreed that clients in active treatment should be urged to quit smoking. Compared with respondents who had never smoked, current smokers were one-half to one-third as likely to provide such counseling. Greater knowledge of the effects of nicotine addiction and employment in programs that provided nicotine addiction education or treatment increased the odds of counselors' providing nicotine counseling. Counselors' alcohol use status was not associated with nicotine counseling practices.


Asunto(s)
Consejo , Cese del Hábito de Fumar , Trastornos Relacionados con Sustancias/terapia , Tabaquismo/terapia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nicotina , Trastornos Relacionados con Sustancias/complicaciones , Tabaquismo/complicaciones
13.
Semin Liver Dis ; 14(2): 190-210, 1994 May.
Artículo en Inglés | MEDLINE | ID: mdl-8047902

RESUMEN

Liver regeneration occurs as a result of hepatic tissue loss or injury. The process of liver regeneration is carefully regulated in a controlled biologic scheme with closely interactive relationships between hormones, free neurotransmitters, and nutrients; protooncogenes; and polypeptide and glycolipid growth factors. These relationships are now being studied at the molecular and cellular levels and attempts are being made to reconstruct the complete intricate process. Although significant breakthroughs have occurred in understanding the effects and regulation of several subsystems (such as insulin and its receptors; TGF-alpha and TGF-beta; HGF and its receptors), the integral process remains a mystery. Improved comprehension of the regeneration process will lead to rational treatment algorithms for now dreaded hepatic diseases.


Asunto(s)
Regeneración Hepática , Inhibidores de Crecimiento/fisiología , Sustancias de Crecimiento/fisiología , Humanos , Hígado/citología , Hígado/fisiología , Hepatopatías/terapia , Regeneración Hepática/genética , Regeneración Hepática/fisiología , Biología Molecular , Proto-Oncogenes/genética
14.
J Subst Abuse Treat ; 10(2): 153-60, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8389896

RESUMEN

Traditionally, tobacco has been ignored as an issue in the treatment of addictions to alcohol and other drugs. Beginning in 1985, and especially since the publication of the 1988 Surgeon General's Report on nicotine addiction, a handful of treatment programs have worked at coming to terms with tobacco. This article explores the reasons for addressing nicotine in the course of managing other addictions and summarizes the lessons learned from the programs which have done pioneering work in this area. The reasons for addressing nicotine are compelling, and the accumulated experiences among the pioneering programs are consistently encouraging. Regional projects to help alcohol and drug treatment programs come to terms with tobacco are an appropriate next step.


Asunto(s)
Alcoholismo/rehabilitación , Drogas Ilícitas , Psicotrópicos , Cese del Hábito de Fumar , Trastornos Relacionados con Sustancias/rehabilitación , Cuidados Posteriores , Terapia Combinada , Comorbilidad , Estudios de Seguimiento , Humanos , Fumar/efectos adversos , Centros de Tratamiento de Abuso de Sustancias , Contaminación por Humo de Tabaco/efectos adversos , Contaminación por Humo de Tabaco/prevención & control
15.
J Subst Abuse ; 5(2): 131-43, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8400836

RESUMEN

This article reports two longitudinal prospective studies conducted sequentially to describe participants' maintenance of abstinence experiences up to 36 months posttreatment. Study 1 reports responses of 102 subjects who maintained alcohol abstinence following treatment and who were assessed for duration and intensity of symptoms associated with postacute withdrawal at baseline, 3, 6, and 12 months. A decreasing linear trend of symptoms was found as time of alcohol abstinence increased. Study 2 obtained interview and survey data from 23 successful abstainers from Study 1 at 12, 18, and 36 months posttreatment to describe coping strategies, perceptions of relapse risk, extent and duration of "aftercare," and substitute addictions as these phenomena developed and changed over time. Multiple occasions of data collection supported the description of three phases of maintenance: symptom stabilization/management accompanied by a cognitive paradigm shift, distancing self from alcohol-dependent behavior, and normalization of life processes.


Asunto(s)
Cuidados Posteriores/métodos , Alcoholismo/rehabilitación , Adulto , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Estudios Prospectivos
16.
Arch Psychiatr Nurs ; 6(1): 2-9, 1992 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-1567244

RESUMEN

Past and recent progress in theory development for psychiatric mental health nursing (PMHN) and its link to practice are reviewed. Results of a national survey of practitioners reflecting the current use of theory from the disciplines of nursing, psychiatry, and behavioral sciences are reported. Progress addressed in furthering the science of PMHN includes the taxonomy of nursing diagnoses and concept analysis. Case study methods are acknowledged as one approach to continue theory development. One paradigm, representative case research (RCR), is noted for its heuristic value for theory development and its potential for bridging the scientist-practitioner roles of mental health clinicians.


Asunto(s)
Teoría de Enfermería , Enfermería Psiquiátrica/tendencias , Humanos , Evaluación en Enfermería , Diagnóstico de Enfermería , Enfermería Psiquiátrica/educación
18.
Transplantation ; 49(3): 483-90, 1990 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1690469

RESUMEN

Small intestine allotransplantation in humans is not yet feasible due to the failure of the current methods of immunosuppression. FK-506, a powerful new immunosuppressive agent that is synergistic with cyclosporine, allows long-term survival of recipients of cardiac, renal, and hepatic allografts. This study compares the effects of FK-506 and cyclosporine on host survival, graft rejection, and graft-versus-host-disease in a rat small intestine transplantation model. Transplants between strongly histoincompatible ACI and Lewis (LEW) strain rats, and their F1 progeny are performed so that graft rejection alone is genetically permitted (F1----LEW) or GVHD alone permitted (LEW----F1) or that both immunologic processes are allowed to occur simultaneously (ACI----LEW). Specific doses of FK-506 result in prolonged graft and host survival in all genetic combinations tested. Furthermore, graft rejection is prevented (ACI----LEW model) or inhibited (rejection only model) and lethal acute GVHD is eliminated. Even at very high doses, cyclosporine did not prevent graft rejection or lethal GVHD, nor did it allow long-term survival of the intestinal graft or the host. Animals receiving low doses of cyclosporine have outcomes similar to the untreated control groups. No toxicity specific to FK-506 is noted, but earlier studies by other investigators suggest otherwise.


Asunto(s)
Antibacterianos/uso terapéutico , Inmunosupresores , Intestino Delgado/trasplante , Animales , Peso Corporal , Ciclosporinas/uso terapéutico , Rechazo de Injerto , Enfermedad Injerto contra Huésped/prevención & control , Intestino Delgado/citología , Masculino , Ratas , Ratas Endogámicas ACI , Ratas Endogámicas Lew , Análisis de Supervivencia , Tacrolimus
20.
Surgery ; 106(2): 354-63, 1989 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-2669198

RESUMEN

The goal of transplantation is the induction of immunologic tolerance. At present, nonspecific immunosuppression is used to prevent graft rejection and, commonly, graft-versus-host disease (GVHD). Nevertheless, nonspecific immunosuppressive therapy is frequently complicated by infection, malignant tumors, and drug toxicity. In order to examine whether hematopoietic chimerism can be used to induce specific allograft tolerance, we have reconstituted lethally irradiated Lewis rats with ACI bone marrow that has been depleted of T cells with use of immunomagnetic beads. This technique consists of binding OX-19, a mouse anti-rat pan-T lymphocyte monoclonal antibody, to magnetic polymer beads. Mixing of bone marrow or splenocytes with the bead/OX-19 complexes, followed by magnetic separation, results in significant depletion of T cells with minimal nonspecific cell loss. Immunomagnetic T-cell depletion of bone marrow, followed by reconstitution of a lethally irradiated host, allows for the development of stable, mixed hematopoietic chimerae without evidence of GVHD. These hosts are immunocompetent by clinical criteria. Recipients of untreated donor bone marrow that did or did not receive nonspecific immunosuppression demonstrated varying degrees of GVHD and reduced survival. The ability to rapidly and simply deplete T lymphocytes from bone marrow and produce stable, immunocompetent hematopoietic chimerae without GVHD may be an important method for tolerance induction to vascularized allografts.


Asunto(s)
Médula Ósea/patología , Quimera , Enfermedad Injerto contra Huésped/terapia , Depleción Linfocítica , Linfocitos T/patología , Animales , Enfermedad Injerto contra Huésped/patología , Técnicas Inmunológicas , Masculino , Microesferas , Ratas , Ratas Endogámicas Lew , Ratas Endogámicas
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