Julio Cesar Wiederkehr

Hepatocyte transplantation for the low-density lipoprotein receptor-deficient state. A study in the Watanabe rabbit.

The Watanabe heritable hyperlipidemie (WHHL) rabbit reproduces human familial hypercholesterolemia due to a congenital low-density lipoprotein receptor deficiency and is characterized by elevated serum LDL. cholesterol levels and early atherosclerosis. We attempted to transplant normal allogeneic hepatocytes into WHHL rabbits without chronic immunosuppression to cure the LDL receptor—deficient state. Livers from normal New Zealand White (NZW) rabbits were digested by intraportal perfusion of collagenase solution. Pure hepatocytes (PH) were obtained by Percoll gradient separation and nonpareuchymal (NP) liver cells by pronase digestion. PH and NP were incubated with fluorescein isothiocyanate-monoclonal anti—rabbit class I, anti-ciass II, and anti-T cell antibodies and subjected to flow eytometry analysis. PH and NP were also used as stimulators in one way mixed lymphocyte-hepatoeyte cultures (MLHC), before and after ultraviolet B light (UVB) exposure. Intraportal and intrasplenic injection of allogeneic PH were also performed in homozygous WHHL rabbits. PH were attached to collagen-coated dextran microcarriers (mc-PH) for intraperitonealimjeetion. Recipient control and transplanted WHHL rabbits received a single dose of eyclosporine subcutaneously (10 mg/kg/s.e.) at the time of transplantation. PH were mainly class I-positive (77.6%) and class II-negative (5.9%), while 31.5% of NP cells were class II-positive, In MLHC, PH did not stimulate proliferation, (stimulation index: 0.97 ± 0.21), unlike NP (SI: 23.7). This latter response was abrogated by prior exposure of NP to UVB light. Intraportal injection of PH (n = 4) reduced serum LDL eholesterol to 60% of baseline, an effect lasting 2—3 weeks, and dose-dependent. Intraperitoneal mc-PH, 4 x 108 (n = 4), reduced serum LDL cholesterol levels to 45% of baseline more than 4 weeks posttransplant (P = 0.04). We conclude that transplantation of normal allogeneic NZW rabbit mc-PH reduces serum LDL cholesterol levels in homozygous WHHL rabbits without chronic immunosuppression. Longitudinal studies will establish if less atherosclerosis develops in mc-PH WHHL reeipients than sham controls.

The immunosuppressive properties of new oral prostaglandin E1 analogs

Prostaglandins play an important role in cell-mediated immune responses. Their clinical use has been limited by poor oral bioavailability, short half-lives, and significant toxicity profiles. We studied the immunosuppressive properties of new, synthetic, prostaglandin E1 (PGE1) methyl ester analogs (misoprostol, enisoprost) with oral bioavailability using an allogeneic in vitro immunoassay. Our results show that the PGE1 analogs suppress alloproliferative responses and supplement the immunosuppressive activity of cyclosporine and methylprednisolone. Moreover, we demonstrate that addition of recombinant interleukin-2 to the PGE1 analogs restores alloimmune responsiveness and the expression of surface class II antigen and IL-2 receptors on responder lymphocytes. These studies, together with preliminary in vivo data in rodents and man, suggest that the new synthetic oral PGE1 analogs may provide therapeutic efficacy in clinical transplantation and a variety of immunologically mediated diseases.

Complicações do tratamento laparoscópico da doença do refluxo gastroesofágico: experiência com 600 casos

The objective of the present study is to present the complications that occurred in 600 consecutive patients with gastroesophageal reflux disease who underwent laparoscopic fundoplication. A Nissen-Rosetti procedure (360° fundoplication) was performed in 587 patients (97.8%) and a Toupet procedure (2700 fundoplication) in 13 (2.2%). Eighty- one patients were also subjected to a concurrent cholecystectomy and one patient a concurrent cervical pharyngoesophageal diverticulectomy with cricopharyngeal myotomy. Thirty-nine patients had a previous upper abdominal operation. The period of hospitalization varied from 12 hours to 23 days, with an average of 1.2 days. The operation was converted to an open procedure in 10 patients (1,7%). The main cause of conversion was the presence of adhesions. The most frequent intraoperative complication was pneumothorax, that was observed in eight patients. All pneumothoraces occurred in the first 100 cases. Five patients had significant operative bleeding; two of them required laparotomy for bleeding control. Gastric ulcer was diagnosed in seven patients. One alcoholic patient died of acute pancreatitis and other with gastric perforation of multiple organ failure syndrome. Other major complications were two intrabdominal abscesses, one esophageal perforation, one sepsis due to gastric perforation, one hemorrhagic shock, and one gastric obstruction due to fundoplication herniation. It is concluded that complications of laparoscopic fundoplication are low and decrease significantly with the surgeons experience.

Autotransplante de fígado em Testemunha de Jeová portador de hepatocarcinoma

Hepatocellular carcinoma is one of the most frequent entities worldwide and partial hepatectomy has been the preferred option for treatment. We report the case of a 28-year-old Jehovahs Witness who came to us complaining about an abdominal mass. Angio-MRI showed a large heterogeneous mass in the left hepatic lobe. Ex situ liver resection followed by right hepatic lobe autotransplantation was performed, using extra-corporeal venous-venous bypass. He had an uneventful postoperative outcome and was discharged on the 10th postoperative day. The histology revealed hepatocellular carcinoma.

Gravidez após transplante hepático

The objective of the present study is to report a sucessful pregnancy in a 28 year-old female who underwent an orthotopic liver transplantation two years ago due to type I auto immune he patitis. Patient was taking cyclosporin, prednisone and azathioprine for maintenance immunossupression and had good graft function during all the pregnancy. The liver function tests were normal during the pregnancy. Fetal growth was monitored by ultrasonographic examination and showed normal development. At the end of the third trimester, she was subjected to a cesarean bearing a healthy girl weighting 2,320 kg. She was discharged with normal liver functions tests and no complications.