RESUMEN
The continual improvement in outcome with highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection and visceral transplantation for gut failure stimulated our interest in lifting HIV infection as a contraindication for intestinal and multivisceral transplantation. This report is the first to describe visceral transplantation in a patient with HIV infection. A HAART regimen was introduced in the setting of short-gut syndrome with successful suppression of HIV viral load. The indication for en bloc multivisceral and kidney transplantation was end-stage liver failure with portomesenteric venous thrombosis and chronic renal insufficiency. The underlying hepatic pathology was alcoholic and home parenteral nutrition-associated cirrhosis. Surgery was complicated due to technical difficulties with excessive blood loss and long operative time. The complex posttransplant course included multiple exploratory laparotomies due to serious intra-abdominal and systemic infections. Heavy immunosuppression was required to treat recurrent episodes of severe allograft rejection. Posttransplant oral HAART successfully sustained undetectable viral load. Unfortunately, the patient succumbed to sepsis 3 months posttransplant. With new insights into the biology of gut immunity, mechanisms of allograft tolerance, and HIV-associated immune dysregulation, successful outcome is anticipated, particularly in patients who are in need of isolated intestinal and less-organ-contained visceral allografts.
Asunto(s)
Rechazo de Injerto/diagnóstico , Infecciones por VIH/complicaciones , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Fallo Hepático/cirugía , Complicaciones Posoperatorias , Vísceras/trasplante , Adulto , Femenino , Rechazo de Injerto/etiología , Supervivencia de Injerto , VIH/patogenicidad , Infecciones por VIH/virología , Humanos , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/etiología , Fallo Hepático/etiología , Masculino , Persona de Mediana Edad , Trasplante de Órganos , Pronóstico , Adulto JovenRESUMEN
The utilization of normothermic machine perfusion (NMP) may be an effective strategy to resuscitate livers from donation after circulatory death (DCD). There is no consensus regarding the efficacy of different perfusates on graft and bile duct viability. The aim of this study was to compare, in an NMP porcine DCD model, the preservation potential of three different perfusates. Twenty porcine livers with 60 min of warm ischemia were separated into four preservation groups: cold storage (CS), NMP with Steen solution (Steen; XVIVO Perfusion Inc., Denver, CO), Steen plus red blood cells (RBCs), or whole blood (WB). All livers were preserved for 10 h and reperfused to simulate transplantation for 24 h. During preservation, the NMP with Steen group presented the highest hepatocellular injury. At reperfusion, the CS group had the lowest bile production and the worst hepatocellular injury compared with all other groups, followed by NMP with Steen; the Steen plus RBC and WB groups presented the best functional and hepatocellular injury outcomes, with WB livers showing lower aspartate aminotransferase release and a trend toward better results for most parameters. Based on our results, a perfusate that contains an oxygen carrier is most effective in a model of NMP porcine DCD livers compared with Steen solution. Specifically, WB-perfused livers showed a trend toward better outcomes compared with Steen plus RBCs.
Asunto(s)
Muerte Súbita Cardíaca , Hígado/fisiología , Preservación de Órganos/métodos , Donantes de Tejidos , Obtención de Tejidos y Órganos/métodos , Animales , Hemodinámica , Trasplante de Hígado , Consumo de Oxígeno , Perfusión , Regeneración , Porcinos , Isquemia TibiaRESUMEN
The Registry has gathered information on intestine transplantation (IT) since 1985. During this time, individual centers have reported progress but small case volumes potentially limit the generalizability of this information. The present study was undertaken to examine recent global IT activity. Activity was assessed with descriptive statistics, Kaplan-Meier survival curves and a multiple variable analysis. Eighty-two programs reported 2887 transplants in 2699 patients. Regional practices and outcomes are now similar worldwide. Current actuarial patient survival rates are 76%, 56% and 43% at 1, 5 and 10 years, respectively. Rates of graft loss beyond 1 year have not improved. Grafts that included a colon segment had better function. Waiting at home for IT, the use of induction immune-suppression therapy, inclusion of a liver component and maintenance therapy with rapamycin were associated with better graft survival. Outcomes of IT have modestly improved over the past decade. Case volumes have recently declined. Identifying the root reasons for late graft loss is difficult due to the low case volumes at most centers. The high participation rate in the Registry provides unique opportunities to study these issues.
Asunto(s)
Salud Global , Rechazo de Injerto/mortalidad , Enfermedades Intestinales/cirugía , Intestinos/trasplante , Sistema de Registros , Trasplante de Tejidos/normas , Trasplante de Tejidos/tendencias , Obtención de Tejidos y Órganos/organización & administración , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Terapia de Inmunosupresión , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Donantes de Tejidos , Adulto JovenRESUMEN
Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis characterized by fibrosis and calcification of the intestine that, in severe cases, can progress to intestinal failure and total parenteral nutrition dependency. Medical and surgical interventions carry a poor prognosis in these patients. We describe a case of a 36-year-old female with end-stage kidney disease and severe EPS not amenable to surgical intervention who underwent a combined intestinal and kidney transplantation. At 3 years posttransplantation, the patient has normal intestinal and kidney function. This represents, to our knowledge, the first report of severe EPS and end-stage kidney disease treated with a combined transplant.
Asunto(s)
Intestinos/trasplante , Trasplante de Riñón/métodos , Fibrosis Peritoneal/terapia , Adulto , Femenino , Fibrosis , Humanos , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/terapia , Donadores Vivos , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , Resultado del TratamientoRESUMEN
Since the introduction of tacrolimus, small-bowel and multivisceral transplantion has increased to 100-200/year in the United States. The intestine carries more passenger lymphocytes than other organs, and bidirectional trafficking of lymphocytes and other immunocytes begins as soon as the vascular clamp is released. Because of ischemia-reperfusion injury and exposure to ligands for Toll-like receptors from the lumen, the innate immune system of the graft is activated, causing inflammation which must be brought under control by regulatory cells. Inclusion of the liver in the allograft favors graft acceptance, but the mechanism of this effect has not been determined. Anti-HLA and other anti-donor antibodies clearly play a major role in determining the long-term fate of the graft, as reflected in 5-year graft survival. Development of new (de novo) HLA antibodies and/or increases in their titers or function-especially the ability to bind C1q and activate complement increase the risk of graft loss. Monitoring antidonor antibody production and the use of new therapies including complement inhibitors will contribute to increasing success of SBT.
Asunto(s)
Inmunidad Innata/inmunología , Terapia de Inmunosupresión/métodos , Intestino Delgado/trasplante , Trasplante de Órganos/fisiología , Anticuerpos/sangre , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Antígenos HLA/inmunología , Humanos , Donantes de TejidosRESUMEN
Despite improvement in early outcome, rejection particularly chronic allograft enteropathy continues to be a major barrier to long-term visceral engraftment. The potential role of donor specific antibodies (DSA) was examined in 194 primary adult recipients. All underwent complement-dependent lymphocytotoxic crossmatch (CDC-XM) with pre- and posttransplant solid phase HLA-DSA assay in 156 (80%). Grafts were ABO-identical with random HLA-match. Liver was included in 71 (37%) allografts. Immunosuppression was tacrolimus-based with antilymphocyte recipient pretreatment in 150 (77%). CDC-XM was positive in 55 (28%). HLA-DSA was detectable before transplant in 49 (31%) recipients with 19 continuing to have circulating antibodies. Another 19 (18%) developed de novo DSA. Ninety percent of patients with preformed DSA harbored HLA Class-I whereas 74% of recipients with de novo antibodies had Class-II. Gender, age, ABO blood-type, cold ischemia, splenectomy and allograft type were significant DSA predictors. Preformed DSA significantly (p < 0.05) increased risk of acute rejection. Persistent and de novo HLA-DSA significantly (p < 0.001) increased risk of chronic rejection and associated graft loss. Inclusion of the liver was a significant predictor of better outcome (p = 0.004, HR = 0.347) with significant clearance of preformed antibodies (p = 0.04, OR = 56) and lower induction of de novo DSA (p = 0.07, OR = 24). Innovative multifaceted anti-DSA strategies are required to further improve long-term survival particularly of liver-free allografts.
Asunto(s)
Antígenos HLA/inmunología , Intestinos/trasplante , Trasplante de Hígado/inmunología , Adulto , Análisis de Varianza , Biopsia con Aguja , Estudios Transversales , Femenino , Estudios de Seguimiento , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Prueba de Histocompatibilidad , Humanos , Inmunohistoquímica , Isoanticuerpos/inmunología , Trasplante de Hígado/métodos , Masculino , Persona de Mediana Edad , Trasplante de Órganos/métodos , Valores de Referencia , Medición de Riesgo , Factores de Tiempo , Donantes de Tejidos , Trasplante Homólogo/inmunología , Resultado del TratamientoRESUMEN
Clinical evidence suggests that recurrent acute cellular rejection (ACR) may trigger chronic rejection and impair outcome after intestinal transplantation. To test this hypothesis and clarify underlying molecular mechanisms, orthotopic/allogenic intestinal transplantation was performed in rats. ACR was allowed to occur in a MHC-disparate combination (BN-LEW) and two rescue strategies (FK506monotherapy vs. FK506+infliximab) were tested against continuous immunosuppression without ACR, with observation for 7/14 and 21 days after transplantation. Both, FK506 and FK506+infliximab rescue therapy reversed ACR and resulted in improved histology and less cellular infiltration. Proinflammatory cytokines and chemotactic mediators in the muscle layer were significantly reduced in FK506 treated groups. Increased levels of CD4, FOXP3 and IL-17 (mRNA) were observed with infliximab. Contractile function improved significantly after FK506 rescue therapy, with a slight benefit from additional infliximab, but did not reach nontransplanted controls. Fibrosis onset was detected in both rescue groups by Sirius-Red staining with concomitant increase of the fibrogenic mediator VEGF. Recovery from ACR could be attained by both rescue therapy regimens, progressing steadily after initiation of immunosuppression. Reversal of ACR, however, resulted in early stage graft fibrosis. Additional infliximab treatment may enhance physiological recovery of the muscle layer and enteric nervous system independent of inflammatory reactions.
Asunto(s)
Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Intestino Delgado/fisiología , Intestino Delgado/trasplante , Trasplante de Órganos/fisiología , Regeneración/fisiología , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Citocinas/metabolismo , Quimioterapia Combinada , Fibrosis , Inmunosupresores/farmacología , Infliximab , Intestino Delgado/patología , Macrófagos/patología , Masculino , Modelos Animales , Neutrófilos/patología , Ratas , Ratas Endogámicas BN , Ratas Endogámicas Lew , Regeneración/efectos de los fármacos , Tacrolimus/farmacología , Tacrolimus/uso terapéutico , Trasplante Homólogo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
BACKGROUND: Venous access is crucial in intestinal transplantation, but a thrombosed venous system may prevent the use of central veins of the upper body. The incidence of venous thrombosis and the necessity to perform alternative vascular access (AVA) in intestinal transplant recipients have not been fully investigated. METHODS: Records of adult patients who underwent intestinal transplantation between January 1, 2001, and December 31, 2009, were reviewed. Contrast venography was performed as pre-transplantation screening. Vascular accesses at the transplantation were categorized as I (percutaneous line via the upper body veins), II (percutaneous line via the lower body veins), and III (vascular accesses secured surgically, with interventional radiology, or using non-venous sites). Categories II and III were defined as AVA. Risk factors for central venous thrombosis and those for requiring AVA were analysed, respectively. RESULTS: Among 173 patients, central venous obstruction or stenosis (<50% of normal diameter) was found in 82% (141 patients). AVA was required in 4.6% (eight patients: four in each category II and III). Large-bore infusion lines were placed via the femoral arteries in all category III patients without complications. Existing inferior vena cava filter and hypercoagulable states were identified as the risk factors for the use of AVA, but not for central venous thrombosis. Outcomes of patients who underwent AVA were similar to those of patients without AVA. CONCLUSIONS: The majority of adult patients undergoing intestinal transplantation had at least one central venous stenosis or obstruction. The recipient outcomes were comparable when either standard vascular access or AVA was used for transplantation.
Asunto(s)
Cateterismo Venoso Central , Intestino Delgado/trasplante , Atención Perioperativa/métodos , Trombosis de la Vena/complicaciones , Adulto , Contraindicaciones , Femenino , Humanos , Infusiones Intraarteriales/métodos , Masculino , Persona de Mediana Edad , Flebografía/métodos , Periodo Preoperatorio , Estudios Retrospectivos , Factores de Riesgo , Síndrome del Intestino Corto/complicaciones , Síndrome del Intestino Corto/cirugía , Resultado del Tratamiento , Trombosis de la Vena/diagnóstico por imagenRESUMEN
PURPOSE: Ischemia-reperfusion injury leads to impaired smooth muscle function and inflammatory reactions after intestinal transplantation. In previous studies, infliximab has been shown to effectively protect allogenic intestinal grafts in the early phase after transplantation with resulting improved contractility. This study was designed to reveal protective effects of infliximab on ischemia-reperfusion injury in isogenic transplantation. METHODS: Isogenic, orthotopic small bowel transplantation was performed in Lewis rats (3 h cold ischemia). Five groups were defined: non-transplanted animals with no treatment (group 1), isogenic transplanted animals with vehicle treatment (groups 2/3) or with infliximab treatment (5 mg/kg body weight intravenously, directly after reperfusion; groups 4/5). The treated animals were sacrificed after 3 (group 2/4) or 24 h (group 3/5). Histological and immunohistochemical analysis, TUNEL staining, real-time RT-PCR, and contractility measurements in a standard organ bath were used for determination of ischemia-reperfusion injury. RESULTS: All transplanted animals showed reduced smooth muscle function, while no significant advantage of infliximab treatment was observed. Reduced infiltration of neutrophils was noted in the early phase in animals treated with infliximab. The structural integrity of the bowel and infiltration of ED1-positive monocytes and macrophages did not improve with infliximab treatment. At 3 h after reperfusion, mRNA expression of interleukin (IL)-6, TNF-α, IL-10, and iNOS and MCP-1 displayed increased activation in the infliximab group. CONCLUSION: The protective effects of infliximab in the early phase after experimental small bowel transplantation seem to be unrelated to ischemia-reperfusion injury. The promising effects in allogenic transplantation indicate the need for further experiments with infliximab as complementary treatment under standard immunosuppressive therapy. Further experiments should focus on additional infliximab treatment in the setting of acute rejection.
Asunto(s)
Antiinflamatorios/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Intestino Delgado/trasplante , Daño por Reperfusión/prevención & control , Animales , Apoptosis , Técnicas In Vitro , Infliximab , Intestino Delgado/irrigación sanguínea , Intestino Delgado/patología , Intestino Delgado/fisiopatología , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso/patología , Ratas , Ratas Endogámicas Lew , Daño por Reperfusión/etiología , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Trasplante IsogénicoRESUMEN
Rotavirus enteritis (RVE) is increasingly recognized as a cause of small bowel allograft dysfunction but its significance in adult patients is unknown. We have studied 23 adult small bowel transplant patients aged 19.8-59 years (mean = 38.2 years), who were presented with diarrhea and tested positive for rotavirus by enzyme-linked immunosorbent assay methods. Serial follow-up biopsies, as well as clinical data, are documented and analyzed. These patients were followed up for an average of 168 days (range 33-534 days). Mean time of rotavirus diagnosis from transplant day was 794 days (range 38-2907 days). Self-limited diarrhea lasting 6-13 days (mean = 9 days) was the main presentation. Sixteen (69.6%) patients developed acute cellular rejection either concurrently with (i.e. six patients) or after (10 patients) RVE, often characterized by prominent mucosal plasmacytosis at an average of 22 days (range 0-94 days) from the day RVE was diagnosed. One-third of patients with acute rejection (i.e. five out of 16) required muromonab-CD3 rescue therapy. Two patients experienced graft loss (one from chronic rejection, another from sepsis). Rotavirus infection is a cause of diarrhea in adult small bowel transplant patients. The infection appeared to trigger cellular rejection that was associated with mucosal plasmacytosis, and sometimes required aggressive rescue therapy.
Asunto(s)
Rechazo de Injerto/virología , Intestino Delgado/trasplante , Infecciones por Rotavirus/patología , Adulto , Anciano , Estudios de Cohortes , Femenino , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/patología , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Muromonab-CD3/uso terapéuticoRESUMEN
This report describes a new innovative pull-through technique of hindgut reconstruction with en bloc small bowel and colon transplantation in a Crohn's disease patient with irreversible intestinal failure. The approach was intersphincteric and the anastomosis was established between the allograft colon and the recipient anal verge with achievement of full nutritional autonomy and anal continence.
Asunto(s)
Canal Anal/cirugía , Colon/trasplante , Enfermedad de Crohn/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Intestino Delgado/trasplante , Adulto , Anastomosis Quirúrgica , Femenino , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias/cirugía , Resultado del TratamientoRESUMEN
In small bowel transplantation (SBTx), graft manipulation, ischemia/reperfusion injury and acute rejection initiate a severe cellular and molecular inflammatory response in the muscularis propria leading to impaired motility of the graft. This study examined and compared the effect of tacrolimus and sirolimus on inflammation in graft muscularis. After allogeneic orthotopic SBTx, recipient rats were treated with tacrolimus or sirolimus. Tacrolimus and sirolimus attenuated neutrophilic, macrophage and T-cell infiltration in graft muscularis, which was associated with reduced apoptotic cell death. Nonspecific inflammatory mediators (IL-6, MCP-1) and T-cell activation markers (IL-2, IFN-gamma) were highly upregulated in allogeneic control graft muscularis 24 h and 7 days after SBTx, and tacrolimus and sirolimus significantly suppressed upregulation of these mediators. In vitro organ bath method demonstrated a severe decrease in graft smooth muscle contractility in allogeneic control (22% of normal control). Correlating with attenuated upregulation of iNOS, tacrolimus and sirolimus treatment significantly improved contractility (64% and 72%, respectively). Although sirolimus reduced cellular and molecular inflammatory response more efficiently after 24 h, contrary tacrolimus prevented acute rejection more efficiently. In conclusion, tacrolimus and sirolimus attenuate cellular and molecular inflammatory response in graft muscularis and subsequent dysmotility of the graft after allogeneic SBTx.
Asunto(s)
Terapia de Inmunosupresión/métodos , Inflamación/fisiopatología , Intestino Delgado/trasplante , Contracción Muscular/fisiología , Animales , Antígenos CD/genética , Apoptosis/efectos de los fármacos , Inmunosupresores/uso terapéutico , Inflamación/prevención & control , Intestino Delgado/fisiología , Intestino Delgado/fisiopatología , Masculino , Ratas , Ratas Endogámicas BN , Ratas Endogámicas Lew , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sirolimus/uso terapéutico , Linfocitos T/inmunología , Tacrolimus/uso terapéutico , Trasplante Homólogo/inmunología , Trasplante Isogénico/inmunologíaRESUMEN
Despite continuous improvement in long-term survival, there is no knowledge about risk of bone health impairment and management strategies before and after intestinal transplantation. Therefore, 147 adults were retrospectively studied via chart review; 70 long-term survivors, 53 candidates and 24 recipients with longitudinal follow-up. Evaluation process included measurement of bone mineral density (BMD) and allied biochemical markers. Both long-term survivors and candidates showed low bone mass with lower (p < 0.05) z-scores at hip, femoral neck and spine. Vitamin D deficiency and secondary hyperparathyroidism were observed in both groups. Prevalence of osteoporosis was 44% among long-term survivors and 36% in candidates with age, BMD, duration of parenteral nutrition, type of immunosuppression and rejection being significant risk factors. Fragility fractures occurred at a higher (p = 0.02) rate among long-term survivors (20%) compared to candidates (6%). The longitudinal study documented acceleration (p = 0.025) of bone loss after transplantation with a decline of 13.4% (femoral neck), 12.7% (hip) and 2.1% (spine). Alendronate reduced (p < 0.05) but did not prevent bone loss. In conclusion, intestinal transplant recipients are at risk of osteoporosis secondary to bone loss before and after transplantation. Accordingly, current management includes comprehensive preventive measures with prompt therapeutic intervention utilizing intravenous bisphosphonates or subcutaneous human PTH.
Asunto(s)
Densidad Ósea , Intestinos/trasplante , Trasplante de Hígado , Adulto , Alendronato/uso terapéutico , Biomarcadores/análisis , Femenino , Fracturas Óseas/etiología , Humanos , Hiperparatiroidismo Secundario , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Osteoporosis/epidemiología , Osteoporosis/etiología , Nutrición Parenteral en el Domicilio/efectos adversos , Pennsylvania/epidemiología , Estudios Retrospectivos , Sobrevivientes , Deficiencia de Vitamina D/complicacionesRESUMEN
As we have shown in the past, acute rejection-related TNF-α upregulation in resident macrophages in the tunica muscularis after small bowel transplantation (SBTx) results in local amplification of inflammation, decisively contributing to graft dysmotility. Therefore, the aim of this study is to investigate the effectiveness of the chimeric-monoclonal-anti-TNF-α antibody infliximab as perioperative single shot treatment addressing inflammatory processes during acute rejection early after transplantation. Orthotopic, isogenic and allogenic SBTx was performed in rats (BN-Lewis/BN-BN) with infliximab treatment. Vehicle and IV-immunoglobulin-treated animals served as controls. Animals were sacrificed after 24 and 168 h. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry, mediator mRNA expression by Real-Time-RT-PCR, apoptosis by TUNEL and smooth muscle contractility in a standard organ bath. Both, infliximab and Sandoglobulin® revealed antiinflammatory effects. Infliximab resulted in significantly less leukocyte infiltration compared to allogenic controls and IV-immunoglobulin, which was accompanied by lower gene expression of MCP-1 (24 h), IFN-γ (168 h) and infiltration of CD8-positive cells. Smooth muscle contractility improved significantly after 24 h compared to all controls in infliximab treated animals accompanied by lower iNOS expression. Perioperative treatment with infliximab is a possible pharmaceutical approach to overcome graft dysmotility early after SBTx.
Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Rechazo de Injerto/prevención & control , Inflamación/prevención & control , Intestino Delgado/trasplante , Animales , Apoptosis , Betanecol/farmacología , Motilidad Gastrointestinal , Inmunoglobulinas Intravenosas/uso terapéutico , Infliximab , Interleucina-10/biosíntesis , Interleucina-1beta/biosíntesis , Infiltración Neutrófila , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Atención Perioperativa , Ratas , Ratas Endogámicas BN , Ratas Endogámicas Lew , Trasplante Homólogo/inmunología , Trasplante Isogénico/inmunología , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
OBJECTIVE: To describe successful treatment of tardive dyskinesia with levetiracetam. BACKGROUND: Tardive dyskinesia is a late-onset movement disorder caused by exposure to dopamine receptor blocking agents, most commonly neuroleptics. Metoclopramide is frequently used to treat gastrointestinal dysmotility. It has antidopaminergic properties, and is estimated to be responsible for two-thirds of drug-related movement disorders. DESIGN/METHODS: Case report. RESULTS: A 68-year-old woman presented with a history of intestinal transplantation (12 years ago; short gut syndrome related to bowel resection for rectal carcinoma) and renal transplantation (1 year ago; diabetes). She developed involuntary movements with stereotypic oro-buccal-lingual dyskinesias and right-sided choreiform movements. Her Abnormal Involuntary Movement Scale score (AIMS) score was 27. She has been treated with metoclopramide for gastrointestinal dysmotility for more than 10 years and was diagnosed with tardive dyskinesia. Treatment with levetiracetam 250 mg orally b.i.d. led to a significant improvement of abnormal movements within a week. Her AIMS score decreased to 8. DISCUSSION: Tardive dyskinesia may be quite disabling and options include withdrawal of offending medication, or use of tetrabenazine or reserpine. Several reports also suggested improvement of tardive movement disorders with levetiracetam. In our patient, levetiracetam relieved symptoms of tardive dyskinesia and allowed continuous use of metoclopramide. Larger studies are needed to confirm its efficacy.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Piracetam/análogos & derivados , Anciano , Antieméticos/efectos adversos , Discinesia Inducida por Medicamentos/etiología , Femenino , Humanos , Levetiracetam , Metoclopramida/efectos adversos , Piracetam/uso terapéuticoRESUMEN
To further enhance chimerism, 229 primary allograft recipients have received perioperative intravenous infusion of a single dose of 3 to 6 X 10(8) unmodified donor bone marrow (BM) cells/kg body weight. In addition, 42 patients have been accrued in a concurrent protocol involving multiple (up to three) sequential perioperative infusions of 2 x 10(8) BM cells/kg/day from day 0-2 posttransplantation (PTx). Organ recipients (n = 133) for whom BM was not available were monitored as controls. The infusion of BM was safe and except for 50 (18%), all study patients have optimal graft function. Of the control patients, allografts in 30 (23%) have been lost during the course of follow-up. The cumulative risk of acute cellular rejection (ACR) was statistically lower in the study patients compared with that of controls. It is interesting that, 62% of BM-augmented heart recipients were free of ACR (Grade > or = 3A) in the first 6 months PTx compared to controls. The incidence of obliterative bronchiolitis was also statistically lower in study lung recipients (3.8%) compared with the contemporaneously acquired controls (31%). The levels of donor cell chimerism were at least a log higher in the peripheral blood of majority of the study patients compared with that of controls. The incidence of donor-specific hyporeactivity, as determined by one-way mixed leukocyte reaction, was also higher in those BM-augmented liver, kidney, and lung recipients that could be evaluated compared to controls.
Asunto(s)
Células de la Médula Ósea/inmunología , Trasplante de Médula Ósea/inmunología , Tolerancia Inmunológica/inmunología , Transfusión de Leucocitos , Leucocitos/inmunología , Trasplante de Órganos , Femenino , Estudios de Seguimiento , Rechazo de Injerto/inmunología , Trasplante de Corazón/inmunología , Herpesvirus Humano 4/inmunología , Humanos , Incidencia , Trasplante de Riñón/inmunología , Trasplante de Hígado/inmunología , Trasplante de Pulmón/inmunología , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/inmunología , Quimera por Trasplante/inmunología , Trasplante Homólogo/inmunologíaRESUMEN
Hepatitis C virus (HCV) infection remains a leading indication for orthotopic liver transplantation (OLT) worldwide. Recurrence of HCV following OLT is universal. There is scarcity of data on the post-OLT treatment of HCV genotype-4-the predominant genotype in North Africa and the Middle East. Herein, we present three patients who have experienced HCV genotype-4 recurrence post-OLT. All three patients were interferon-naive and were treated with simeprivir (SIM) and sofosbuvir (SOF) combination therapy for 12-24 weeks. The data from this case series show that SIM+SOF are well-tolerated and effective for achieving viral clearance in HCV genotype-4 post-OLT patients. Given the limited nature of a case series, further research must be pursued regarding post-OLT HCV genotype-4 responses to direct-acting anti-viral therapy.
RESUMEN
A composite graft consisting of a reduced left lateral hepatic segment in continuity with the small intestine was procured from an adult cadaveric donor using a modified in situ split technique. The primary recipient was a 3-year-old boy with hepatointestinal failure. The right side of the liver was transplanted into a 63-year-old man with a central hepatoma and hepatitis C cirrhosis. This was accomplished with center-to-center sharing of the liver portion of the allograft. The in situ split technique was feasible, with good initial allograft function. However, both grafts failed subsequently because of peri-operative recipient-related complications. The adult patient died of an infected pseudoaneurysm of the arterial graft, and the pediatric patient required repeat transplantation as a result of the late diagnosis of a native pancreatic fistula with cholestatic damage to the reduced liver allograft. The child is currently alive 8 months after repeat transplantation.
Asunto(s)
Intestino Delgado/trasplante , Trasplante de Hígado/métodos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Trasplante de Órganos/métodosRESUMEN
BACKGROUND: Bacterial translocation (BT) has been suggested to be responsible for the high incidence of infections occurring after small bowel transplantation (SBTx). Bacterial overgrowth, alteration of the mucosal barrier function as a consequence of preservation injury or acute rejection (AR), and potent immunosuppression are all associated with BT. The aim of this study was to evaluate and quantify the correlation of BT with these events. METHODS: Fifty pediatric SBTx recipients on tacrolimus and prednisone immunosuppression were analyzed. Blood, stool, and liver biopsies and peritoneal fluid were cultured (circa 4000 total specimens) when infection was clinically suspected or as part of follow-up. BT episodes were considered when microorganisms were found simultaneously in blood or liver biopsy and stool. RESULTS: BT (average of 2.0 episodes/patient) was evident in 44% of patients and was most frequently caused by Enterococcus, Staphylococcus, Enterobacter, and Klebsiella. The presence of a colon allograft was associated with a higher rate of BT (75% vs. 33.3%). Furthermore, the transplantation procedure (colon vs. no colon) affected the rate of BT: SBTx=40% vs. 25%, combined liver and SBTx=100% vs. 30%, multivisceral transplantation=25% vs. 50%. AR was associated with 39% of BT episodes. BT followed AR in 9.6% of the cases. In 5.2% of the cases, positive blood cultures without stool confirmation of the bacteria were seen. Prolonged cold ischemia time (CIT) affected BT rate significantly (CIT>9 hr 76% vs. CIT<9 hr 20.8%). CONCLUSIONS: This study shows that 1) a substantial percentage of, but not all, BT is associated with AR, 2) the presence of a colon allograft increases the risk for BT, and 3) a long CIT is associated with a high incidence of BT after SBTx.
Asunto(s)
Traslocación Bacteriana/fisiología , Intestino Delgado/microbiología , Intestino Delgado/trasplante , Enfermedad Aguda , Infecciones Bacterianas/complicaciones , Candidiasis/complicaciones , Niño , Colon/microbiología , Colon/trasplante , Criopreservación , Rechazo de Injerto/microbiología , Humanos , Factores de Tiempo , Virosis/complicacionesRESUMEN
BACKGROUND: Bacteremia occurs frequently after intestinal transplantation (ITx) in children. During our initial experience with this procedure, we noted that bacteremic episodes tended to occur simultaneously with the presence of rejection and/or gastrointestinal (GI) posttransplant lymphoproliferative disease (PTLD). AIM: To document the association of bacteremia with rejection and GI PTLD in pediatric ITx recipients. METHODS: Retrospective analysis of all medical records from 62 children who underwent ITx between July 1990 and January 1998 at Children's Hospital of Pittsburgh. A bacteremic episode was defined as two positive blood cultures from different sites at the same time or from the same site at different times. Rejection and PTLD were defined using previously published criteria. RESULTS: A total of 39/62 ITx recipients had 133 blood stream infections (2.1 episodes/patient) including 121 episodes of bacteremia and 12 of fungemia. Enteric organisms were the most frequently recovered pathogens (Gram negative rods, n=76; enterococci, n=36). Enteric organisms were recovered as a single organism (n=57), with another enteric bacteria (n=23), or with coagulase negative staphylococci (CONS) (n=24). CONS were recovered as a single organism on 21 occasions. An obvious source of bacteremia was not found for 115/121 episodes. Endoscopy was performed for 107 of the 115 bacteremia episodes; an abnormal histology was identified in 74 revealing rejection (n=36), GI PTLD (n=21), or both (n=17). When endoscopy showed GI pathology, enteric organisms alone or in combination with CONS were recovered on 63/107 occasions, although CONS were recovered alone only 11 times. CONCLUSIONS: Bacteremia accompanies GI rejection and intestinal PTLD in ITx recipients. Endoscopy should be performed to inspect the allograft when bacteremia occurs without an obvious source in these patients. This is especially true for patients with bacteremia due to enteric organisms.