RESUMEN
The treatment of hepatocellular cancer (HCC) with transarterial chemoembolization (TACE) prior to orthotopic liver transplant (OLT) is of increasing importance due to the rise in HCC incidence and donor shortage. This single-center study examines 28 patients treated with TACE and 7 patients not treated with TACE, with HCC prior to OLT between 1999 and 2008. The overall 1- and 5-year survival of all transplanted patients with HCC was 94% (33 of 35) and 80% (28 of 35). There was no difference in survival (P = .99) between patients who underwent transplantation immediately (median 95 days) and patients who had significantly longer wait times (median 308 days) when treated with TACE. During extensive wait times for OLT, TACE can be used to keep patients with HCC on the waiting list by preventing tumor progression, with similar outcomes compared with those who underwent transplantation immediately.
Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Trasplante de Hígado , Listas de Espera , Adulto , Anciano , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Estudios de Cohortes , Aceite Etiodizado/administración & dosificación , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Surrogate consent is an accepted form of promoting patient autonomy when patients cannot consent, but it can lead to surrogate duress and may be unreliable. Since consent for liver transplantation in patients with fulminant hepatic failure (FHF) is typically performed by surrogates and these patients typically regain decisional capacity, we chose this population to query patients' opinion on the surrogate consent process. MATERIALS AND METHODS: We developed a questionnaire that queried transplanted patients' experience and opinion on surrogate consent, suitability of surrogates, and return of decisional capacity. This survey was then sent to consecutive survivors of liver transplantation for FHF at our institution. RESULTS: Eleven of 14 patients eligible to participate completed the questionnaire. The mean follow-up for all survivors was 41 mo, with a range of survival since transplant of 5 mo to 10 y. Although 10/11 respondents agreed with their surrogates to consent to liver transplantation, all 11 patients thought that surrogates should not be able to decline liver transplantation for this condition. In distinction, 3/11 patients believed patients could decline liver transplantation. CONCLUSIONS: This is the first study to demonstrate that liver transplant patients do not think surrogate decision-makers should be permitted to contravene physician recommendations regarding transplant. In clinical settings when patients cannot speak for themselves, it may be appropriate for surrogates and clinicians to act together according to the patients' best interest rather than attempt to determine what the patient would want. This approach might reduce surrogate distress, better represent patient preferences, and improve the decision-making process for affected patients.
Asunto(s)
Toma de Decisiones/ética , Fallo Hepático Agudo/cirugía , Trasplante de Hígado/ética , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Defensa del Paciente , Autonomía Personal , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Pain after shoulder surgery is often treated with interscalene nerve blocks. Single-injection blocks are effective, but time-limited. Adjuncts such as dexamethasone may help. We thus tested the hypothesis that adding dexamethasone significantly prolongs the duration of ropivacaine and bupivacaine analgesia and that the magnitude of the effect differs among the two local anaesthetics. METHODS: In a double-blinded trial utilizing single-injection interscalene block, patients were randomized to one of four groups: (i) ropivacaine: 0.5% ropivacaine; (ii) bupivacaine: 0.5% bupivacaine; (iii) ropivacaine and steroid: 0.5% ropivacaine mixed with dexamethasone 8 mg; and (iv) bupivacaine and steroid: 0.5% bupivacaine mixed with dexamethasone 8 mg. The primary outcome was time to first analgesic request after post-anaesthesia care unit discharge. The Kaplan-Meier survival density estimation and stratified Cox's proportional hazard regression were used to compare groups. RESULTS: Dexamethasone significantly prolonged the duration of analgesia of both ropivacaine [median (inter-quartile range) 11.8 (9.7, 13.8) vs 22.2 (18.0, 28.6) h, log-rank P<0.001] and bupivacaine [14.8 (11.8, 18.1) and 22.4 (20.5, 29.3) h, log-rank P<0.001]. Dexamethasone prolonged analgesia more with ropivacaine than bupivacaine (Cox's model interaction term P=0.0029). CONCLUSIONS: Dexamethasone prolongs analgesia from interscalene blocks using ropivacaine or bupivacaine, with the effect being stronger with ropivacaine. However, block duration was longer with plain bupivacaine than ropivacaine. Thus, although dexamethasone prolonged the action of ropivacaine more than that of bupivacaine, the combined effect of dexamethasone and either drug produced nearly the same 22 h of analgesia.
Asunto(s)
Amidas/farmacología , Anestésicos Locales/farmacología , Bupivacaína/farmacología , Dexametasona/farmacología , Bloqueo Nervioso , Dolor Postoperatorio/prevención & control , Hombro/cirugía , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Ropivacaína , Factores de TiempoRESUMEN
Three hundred forty-four human scapular bones (172 matched pairs) were measured for their glenoid height, width, inclination, and version. The sample consisted of 50 black men, 50 white men, 50 black women, and 22 white women, all of whom were aged 20 to 30 years at the time of death. The mean age of the study group was 25.6 years. No difference in glenoid size was noted between black and white patients. The overall glenoid version for the entire study group was 1.23 degrees of retroversion. The difference in glenoid version between black and white patients was statistically significant. The average glenoid version for black and white patients measured 0.20 degrees and 2.65 degrees of retroversion, respectively (P =.000014). Specifically, the glenoid version for black and white men measured 0.11 degrees and 2.87 degrees of retroversion, respectively (P =.00034). The glenoid version for black and white women measured 0.30 degrees and 2.16 degrees of retroversion, respectively (P =.034). No statistical difference in glenoid version was found between men and women of the same race. No difference was found between measuring the glenoid version based on the transverse axis of the scapula and measuring the glenoid version perpendicular to the glenohumeral joint. No statistical difference was found in the glenoid inclination based on race or sex. The relationships between glenoid size, inclination, and version are important to understand when a surgeon prepares to resurface the glenoid during total shoulder arthroplasty. The knowledge of these values, their variation, and racial differences should help reproduce a more anatomical result.
Asunto(s)
Inestabilidad de la Articulación/etiología , Escápula/anatomía & histología , Articulación del Hombro/anatomía & histología , Adulto , Antropometría , Artroplastia de Reemplazo/métodos , Población Negra , Femenino , Humanos , Masculino , Valores de Referencia , Factores Sexuales , Articulación del Hombro/cirugía , Población BlancaRESUMEN
Hepatic resection is the treatment of choice for many secondary and primary hepatic tumors. With improvement in surgical techniques and earlier recognition of hepatic tumors, there has been a renewed interest in performing hepatic resections. In this operative review, we will describe the techniques for performing right-sided and left-side hepatic resections. A major hepatic resection can be performed with less than 5% mortality and approximately a 5% to 15% morbidity. Special mention will be made of performing a hepatic resection without vascular inflow occlusion. This is necessary in performing a hepatic resection for use in live donor liver transplantation.
Asunto(s)
Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Humanos , Cuidados Intraoperatorios , Hígado/anatomía & histología , Neoplasias Hepáticas/secundario , Cuidados PosoperatoriosRESUMEN
Liver transplant patients were enrolled in a study designed to investigate correlations between plasma complement C3a or C4a levels and various postoperative complications. Longitudinal EDTA-plasma levels of C3a and C4a were measured by quantitative radioimmunoassay. Acute rejection gave a characteristic and marked increase in blood C3a, C4a and gamma-glutamyl transferase (gammaGT) levels, which rapidly resolved after high dose steroid treatment. Cytomegalovirus (CMV) infections in two of three patients gave an initial small increase only in C3a levels (i.e., alternative pathway activation) followed approximately 6 weeks later by a marked increase in C4a levels (i.e., classical or lectin pathway activation). In a third patient diagnosed for CMV infection, the complement activation profile was complicated by a coincident minor rejection episode. However, a late stage elevation in C4a was also noted. Two patients experiencing biopsy proven recurrent hepatitis C infections following transplantation exhibited increases in both gammaGT and C4a levels, without a significant increase in the level of C3a. Several hepatitis C and one hepatitis B patient had multiple late activation episodes involving marked elevation in both plasma C3a and C4a levels without detectable increases in the liver enzymes conventionally used to monitor organ function. We also showed that ex vivo activation of complement in EDTA plasma from all transplant patients was abnormally high. The classical or lectin pathway is believed to be responsible for this excessive ex vivo complement activation in the plasma of these patients. Therefore, subclinical rejection episodes and/or viral infections may be effectively detected or monitored by measuring C3a and C4a levels in plasma samples from liver transplant patients. Routine measurement of plasma complement products may provide an early non-invasive mode for detecting infections and also serve to monitor chronic or acute changes in the patient's immune system.
Asunto(s)
Complemento C3a/análisis , Complemento C4a/análisis , Trasplante de Hígado , Adulto , Anciano , Infecciones por Citomegalovirus/inmunología , Femenino , Hepatitis C/inmunología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana EdadRESUMEN
Previous studies have suggested that hepatic arterial flow in heterotopic partial liver transplants is necessary to ensure graft survival and regenerative capacity. This report presents findings in a syngeneic rat strain (Lewis) that partial liver transplants can be successfully heterotopically transplanted in the long term with the only inflow coming from the portal vein. When the host liver undergoes a nearly complete resection at 3-4 weeks, the transplanted liver regenerates to maintain the health of the host. Moderate to massive hepatocellular necrosis occurs in the first 3 months postoperatively, with recovery by 4-5 months. Liver transplants 8-10 months postoperatively appear architecturally normal. No host liver tissues were found to be regenerating after subtotal host liver resection. We conclude that portal vein reconstruction without hepatic arterial inflow can sustain a partial liver transplant in the long term, replacing the function of the host liver.
Asunto(s)
Trasplante de Hígado/métodos , Hígado/irrigación sanguínea , Vena Porta/fisiología , Trasplante Heterotópico/métodos , Anastomosis Quirúrgica/métodos , Animales , Hepatectomía , Hígado/patología , Regeneración Hepática , Trasplante de Hígado/patología , Masculino , Microcirugia/métodos , Vena Porta/cirugía , Periodo Posoperatorio , Ratas , Ratas Endogámicas Lew , Técnicas de Sutura , Factores de Tiempo , Trasplante Heterotópico/patología , Resultado del TratamientoRESUMEN
Multidirectional instability of the shoulder is a complex entity. Relatively few series of patients with this condition have been reported. Affected patients have global (anterior, inferior, and posterior) excessive laxity of the glenohumeral joint capsule and a rotator interval capsule defect. The onset of symptoms is frequently related to atraumatic events. The chief complaint is more often related to pain than to instability per se. Symptoms are mostly experienced within the midrange of glenohumeral motion. Because the contralateral shoulder is often equally lax and asymptomatic, it appears that factors in addition to excessive capsular laxity play a pathophysiologic role. These factors may include subtle losses of strength and/or neuromotor coordination of the rotator cuff and scapular stabilizing muscles, defective proprioceptive responses, and the absence of a limited joint volume. Most patients can be successfully treated nonoperatively with a specific exercise program. If a 6-month trial of nonoperative management fails, the patient is a candidate for surgical reconstruction. The most time-honored procedure is an open inferior capsular shift, which corrects excessive global laxity of the capsule and the rotator interval defect.
Asunto(s)
Inestabilidad de la Articulación , Articulación del Hombro , Artroscopía , Endoscopía , Humanos , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/fisiopatología , Inestabilidad de la Articulación/terapia , Modalidades de Fisioterapia , Rango del Movimiento Articular , Resultado del TratamientoRESUMEN
Arthritis of dislocation is a unique form of degenerative joint disease involving the shoulder. It seems that a larger number of patients who develop arthritis of dislocation have had prior instability repairs. In studying large numbers of patients, several factors seem to recur. Careful, repeated examinations of both symptomatic and asymptomatic shoulders may uncover subtle subluxations; examination of other peripheral joints may reveal evidence of hyperlaxity and multidirectional instability. With understanding of the nature, direction, and extent of the instability patterns, more appropriate stabilization procedures may diminish the incidence of arthritis of dislocation. Today's techniques and the surgical management of instabilities obviate the need for hardware, which has been shown to have a significant impact on the occurrence of this arthritis. Surgeons should realize the potentials and risks of arthroscopic stabilization procedures, and only after satisfactory analysis should these procedures be done by orthopedic surgeons in general. Many new techniques for shoulder stabilization are now in the armementarium of the arthroscopist, but more time is needed to see if they will influence the development of arthritis of instability. When arthritis of dislocation does develop, shoulder arthroplasty is reasonable, despite the young age of patients. In the technique of joint replacement for this condition, specific surgical principles must be kept in mind. Preservation of deltoid function is paramount. Restoration of muscle length and tension relationships are critical for successful functional outcomes. Component positioning and orientation must account for the bone loss and alterations in soft tissue tension and quality. No shoulder replacement, no matter how well performed, will be successful without adequate physician-directed rehabilitation.
Asunto(s)
Artritis/cirugía , Artroplastia de Reemplazo , Luxaciones Articulares/cirugía , Articulación del Hombro/cirugía , Factores de Edad , Artritis/etiología , Artritis/rehabilitación , Artroplastia de Reemplazo/métodos , Artroplastia de Reemplazo/rehabilitación , Artroscopía , Endoscopía , Humanos , Luxaciones Articulares/complicaciones , Inestabilidad de la Articulación/complicaciones , Inestabilidad de la Articulación/cirugía , Contracción Muscular/fisiología , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Recurrencia , Factores de Riesgo , Hombro/patología , Hombro/fisiopatología , Articulación del Hombro/patología , Articulación del Hombro/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Interscalene block can be chosen for complete anesthesia for shoulder surgery. Phrenic nerve block occurs with almost all interscalene blocks, but is well tolerated in most patients. This may not be the case in selected geriatric patients. METHODS: The patient is a 90-year-old female with osteoarthritis of the left shoulder scheduled for total shoulder anthroplasty. Past medical history revealed hypertension, mild mitral valve insufficiency, and a remote episode of congestive heart failure. She underwent interscalene block with 40 mL of 1.4% mepivacaine, 1:200,000 epinephrine freshly added, alkalinized with sodium bicarbonate. RESULTS: The onset of the block was rapid and complete. The patient had minimal intravenous sedation (0.5 mg midazolam) and was resting comfortably with a respiratory rate of 12-14 breaths/min. Approximately 5 minutes after the injection of local anesthetic, the patient was noted to be alert, cyanotic, denying dyspnea, with an oxygen saturation of 75-85%. A chest radiograph revealed elevation of the ipsilateral hemidiaphragm and no pneumothorax or other pathology. Despite supplemental oxygen by face mask, desaturation persisted and general anesthesia was induced. On emergence from anesthesia, the patient had a complete interscalene block. Repeat chest radiograph after resolution of the block revealed return of hemidiaphragm position and no other pathology. The patient was extubated in the recovery room without difficulty. Following extubation the patient demonstrated stable respirations and normal oxyhemoglobin saturation. CONCLUSIONS: Ipsilateral phrenic nerve paralysis caused significant respiratory compromise in an elderly patient without known significant pulmonary disease.
Asunto(s)
Bloqueo Nervioso/efectos adversos , Oxihemoglobinas/metabolismo , Anciano , Anciano de 80 o más Años , Anestesia General , Femenino , Humanos , Nervio Frénico , Articulación del Hombro/cirugíaAsunto(s)
Artropatía Neurógena/diagnóstico por imagen , Articulación del Hombro , Tomografía Computarizada por Rayos X , Malformación de Arnold-Chiari/complicaciones , Artropatía Neurógena/etiología , Artropatía Neurógena/patología , Progresión de la Enfermedad , Femenino , Humanos , Húmero/patología , Imagen por Resonancia Magnética , Persona de Mediana Edad , Lesiones del HombroRESUMEN
Successful outcome of total shoulder arthroplasty depends on a well-designed and a well-executed physical therapy program. For maximal benefit, the program is usually initiated immediately after surgery and follows a logical pattern of joint mobilization followed by muscle strengthening. The process proceeds through a series of well-defined phases. The patient must see himself or herself as the active agent in the program, a concept that is enhanced by a discussion and demonstration of the therapy goals before surgery. Because of a unique understanding of the therapy requirements, the surgeon should remain intimately involved with the patient and therapist, frequently evaluating progress and outcomes of the exercises. When a well-performed surgical procedure is supplemented with a well-designed and frequently monitored therapy program, an excellent outcome of shoulder replacement should be expected.
Asunto(s)
Terapia por Ejercicio/métodos , Prótesis Articulares/rehabilitación , Articulación del Hombro/cirugía , Artroplastia/rehabilitación , Humanos , Cooperación del Paciente , Educación del Paciente como Asunto , Rango del Movimiento Articular , Articulación del Hombro/fisiologíaAsunto(s)
Cateterismo/instrumentación , Migración de Cuerpo Extraño/terapia , Arteria Pulmonar , Stents , Síndrome de Budd-Chiari/terapia , Femenino , Migración de Cuerpo Extraño/diagnóstico por imagen , Humanos , Persona de Mediana Edad , Arteria Pulmonar/diagnóstico por imagen , Punciones , Radiografía Intervencional , Vena Cava Inferior/diagnóstico por imagenRESUMEN
The proliferative response of peripheral blood lymphocytes to the HBcAg was compared with serological, molecular and immunohistochemical parameters of hepatitis B virus infection and with biochemical and histological parameters of liver disease in a patient who received a completely human leukocyte antigen class I-mismatched liver allograft for fulminant hepatitis. The proliferative response increased progressively after transplantation, as hepatitis B virus infection became reestablished in the hepatic allograft. Strikingly, the HBcAg-specific T cells suddenly disappeared from the peripheral blood immediately before the acute onset of a severe necroinflammatory liver disease in which more than 80% of the hepatocytes expressed HBcAg. These observations are compatible with the hypothesis that human leukocyte antigen class I-independent hepatitis B virus-specific T cells might play a previously unsuspected role in the pathogenesis of hepatitis B virus-induced liver disease.
Asunto(s)
Antígenos del Núcleo de la Hepatitis B/análisis , Hepatitis B/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Trasplante de Hígado/inmunología , Adulto , Secuencia de Bases , Hepacivirus/inmunología , Anticuerpos Antihepatitis/análisis , Hepatitis B/fisiopatología , Antígenos de Superficie de la Hepatitis B/análisis , Antígenos e de la Hepatitis B/análisis , Anticuerpos contra la Hepatitis C , Prueba de Histocompatibilidad , Humanos , Trasplante de Hígado/patología , Activación de Linfocitos , Masculino , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos , Reacción en Cadena de la Polimerasa , Complicaciones Posoperatorias/inmunología , Trasplante Homólogo/inmunología , Trasplante Homólogo/patologíaRESUMEN
Reperfusion of the orthotopically transplanted liver can result in severe hemodynamic instability. This instability can result in the postreperfusion syndrome (PRS), which includes decreases in mean arterial pressure (MAP), systemic vascular resistance (SVR), and heart rate, and increases in central venous pressure and pulmonary capillary wedge pressure. This syndrome appears to be mediated by the left ventricular mechanoreceptor reflex (LVMRR), which can be activated by changes in preload, afterload, or left ventricular contractility, and by the infusion of alkaloids or potassium into the right atrium. In an attempt to prevent activation of the LVMRR and PRS, we have inserted a cannula into the retrohepatic vena cava and have allowed the initial 500-600 cc of portal blood reperfusing hepatic allografts to be discarded. We compared this nonsystemic reperfusion (NSRP) of livers with systemic reperfusion (SRP), in which the initial portal blood reperfusing livers is allowed to enter the systemic circulation. In the NSRP group (n = 14) there was no decrease in MAP, heart rate, or SVR, and the serum potassium did not increase after reperfusion. In the SRP group (n = 14), six patients (42%) developed PRS and there were statistically significant decreases in MAP and SVR, and increases in pulmonary capillary wedge pressure and serum potassium, as compared with the NSRP group. In conclusion, NSRP results in less hemodynamic instability during reperfusion, and should be considered the preferred method for reperfusion of the transplanted liver.
Asunto(s)
Trasplante de Hígado/fisiología , Reperfusión/métodos , Adulto , Presión Sanguínea , Femenino , Paro Cardíaco/etiología , Frecuencia Cardíaca , Humanos , Hiperpotasemia/complicaciones , Masculino , Potasio/sangre , Presión Esfenoidal Pulmonar , Resistencia VascularRESUMEN
A 44-year-old white female developed hepatic hemorrhage due to focal hepatic necrosis. This is the only reported case of its kind we have found. No other underlying processes were identified except for the chronic use of oral conjugated estrogens. The possible role of steroids and a possible relationship to the pathogenesis of peliosis hepatis is discussed.
Asunto(s)
Hemoperitoneo/etiología , Hemorragia/complicaciones , Hepatopatías/complicaciones , Adulto , Femenino , Humanos , Hepatopatías/patología , NecrosisRESUMEN
Thirty-eight patients (forty-three shoulders) who had disabling multidirectional instability of the shoulder were managed with an inferior capsular-shift procedure through an anterior approach. All of the patients were followed for a minimum of two years. The postoperative range of motion of the shoulders was well maintained. The mean forward elevation was 172 degrees; external rotation, 77 degrees; and internal rotation, to the level of the eighth thoracic vertebra. Four patients (four shoulders) had recurrence of symptomatic and disabling multidirectional instability, but thirty-nine (91 per cent) of the shoulders continued to function well with no instability. Nine patients (24 per cent) continued to have episodes of apprehension, which correlated with the residual inferior and posterior translations found at the postoperative physical examination. Thirty-four patients (thirty-nine shoulders) stated that they were subjectively satisfied with the status of the shoulder, but four patients, in whom the instability had recurred, were not satisfied. Thirty-seven (86 per cent) of the shoulders were judged to have been improved by the procedure, the initial postoperative stability had been maintained, and the result had not deteriorated with time. Six shoulders, however, including the four with recurrent instability, were thought by the patient to have deteriorated with the increased duration of follow-up. It was our experience that if non-operative treatment of multidirectional instability of the shoulder failed, the inferior capsular-shift procedure provided satisfactory objective and subjective results. Failures and recurrences of symptomatic instability occurred early in the postoperative period. There appeared to be no deterioration of the results with follow-up to seventy-one months.
Asunto(s)
Inestabilidad de la Articulación/cirugía , Articulación del Hombro/cirugía , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Rango del Movimiento Articular , Recurrencia , Articulación del Hombro/fisiologíaRESUMEN
Splenopneumopexy is intended to induce collateral circulation between the portal system and the pulmonary veins. It involves performing a parenchymatous anastomosis between the amputated superior pole of the spleen and the exposed pulmonary venous structures in the left lower lobe. This operative procedure was used to treat four patients with extended portal-splenic-mesenteric venous occlusion who did not respond satisfactorily to sclerotherapy. The patients underwent transfemoral embolization of their splenic arteries before splenopneumopexy. Following the operations, all patients have remained well, experiencing cessation of gastrointestinal bleeding for up to 48 months. Splenopneumopexy may be a therapeutic alternative in selected patients with portal hypertension, including those patients with widespread occlusion of the portal vein and its radicles.
Asunto(s)
Hipertensión Portal/etiología , Hipertensión Portal/cirugía , Pulmón/cirugía , Oclusión Vascular Mesentérica/complicaciones , Venas Mesentéricas/patología , Vena Porta/patología , Bazo/cirugía , Vena Esplénica/patología , Trombosis/complicaciones , Adulto , Circulación Colateral , Várices Esofágicas y Gástricas/cirugía , Várices Esofágicas y Gástricas/terapia , Femenino , Hemorragia Gastrointestinal/cirugía , Hemorragia Gastrointestinal/terapia , Humanos , Masculino , Oclusión Vascular Mesentérica/cirugía , Persona de Mediana Edad , Escleroterapia , Trombosis/cirugíaRESUMEN
The sulfate and glucuronide conjugation of acetaminophen (APAP) by hepatocytes cultured on Matrigel or type 1 collagen was compared to APAP metabolism in vivo. The metabolic fate of low (15 mg/kg), medium (125 mg/kg), and high (300 mg/kg) doses of APAP injected intraperitoneally were determined in male and female rats. Males excreted more APAP as the sulfate conjugate than females, which correlated with the twofold greater APAP sulfotransferase activity in the male vs. females (301 +/- 24 vs. 156 +/- 18 pmol.mg-1 protein.min-1). Also, as sulfate conjugation became saturated, there was a dose-related shift in APAP metabolism from sulfate to glucuronide conjugation in both sexes. After death, the livers of the same animals were perfused with collagenase and the hepatocytes cultured in modified Waymouth's medium on either Matrigel or rat-tail collagen, with various doses of APAP (0, 0.125, 0.25, 0.5, and 1.0 mM). Sex differences in APAP sulfation and glucuronidation persisted in culture for up to 4 days, with sulfation predominating in the male similar to in vivo. With increasing APAP concentration (dose), there was a saturation of sulfate conjugation and a shift to glucuronidation as observed in vivo. Sex differences in APAP sulfation and glucuronidation were no longer significant by Day 4 in culture. Sulfation, and to a lesser extent, glucuronidation, were more stable on Matrigel than collagen. We concluded that APAP metabolism of freshly isolated hepatocytes could replicate in vivo sex differences in conjugation, and that Matrigel was superior to collagen as substrate.