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Biomedical subjects

A Shaked

Publications and source records attributed to A Shaked.

At least 109 records · Page 6Linked to original sources
PubMed1993

Resection of the caudate lobe through "bloody gultch".

Isolated resection of the caudate lobe for primary or metastatic neoplasms is an uncommon operation. Our experience with mobilization of the liver in more than 700 hepatic transplants has led us to a simplified technique for caudate lobe resection. Herein we describe our technique and report our experience with three patients.

Adult↗
PubMed1992

Correlation of hepatic injury, synthetic function, and mitochondria energy level in orthotopic liver transplantation.

UNLABELLED: The arterial ketone blood ratio (AKBR) of acetoacetate to b-hydroxybutyrate was previously shown to reflect hepatic mitochondria oxidation/reduction (redox) state and energy level. In this study we correlated AKBR to the degree of liver injury immediately following orthotopic liver transplantation (OLT). Serial measurements of AKBR in 209 patients undergoing OLT, during the anhepatic phase, and up to 60 hr following reperfusion demonstrated direct correlation between mitochondria Redox state (AKBR), hepatocyte injury (SGOT), and hepatic synthetic function (prothrombin time). AKBR levels less than 0.7 were seen in primary nonfunction grafts and were associated with raising SGOT (greater than 1000) and prolonged PT (greater than 18). Acute occlusion of arterial blood supply to the graft was seen in conjunction with low AKBR (less than 0.7). However, hepatic synthetic function and serum enzyme were stabilized or returned to normal within 24-48 hr postreperfusion. IN CONCLUSION: (1) AKBR measurements are useful in predicting graft survival, (2) reduction in liver mitochondria Redox state is seen in primary hepatocyte dysfunction and correlates well to synthetic function, and (3) acute occlusion of the arterial supply to the liver graft is associated with decreased redox state. However, with intact portal blood flow, it is still possible to preserve adequate hepatic synthetic function.

Adult↗
PubMed1992

The interrelation between sclerosing cholangitis and ulcerative colitis in patients undergoing liver transplantation.

Thirty-six patients underwent orthotopic liver transplantation (OLT) for primary sclerosing cholangitis under cyclosporine, azathioprine, and steroid immunosuppression. Of these patients, 29 suffered from chronic ulcerative colitis. The purpose of this study is to determine (1) whether replacement of the diseased liver and the altered immunocompetence suppresses the manifestation of chronic ulcerative colitis, and (2) if active colonic disease alters allograft function. Thirty of 36 patients survived OLT. After OLT, seven of 14 patients with symptomatic colon disease at the time of transplantation continue to suffer from active chronic ulcerative colitis, and three of 13 who were asymptomatic developed clinically active disease. Intractable colonic disease was the indication for post-OLT proctocolectomy in three patients, and one refused an indicated colectomy. Despite the long duration of the disease, none developed colonic malignancy. Long-term graft assessment showed good hepatocyte synthetic function in patients suffering from either active or inactive disease. Liver alkaline phosphatase, however, was significantly higher in patients suffering from active colonic disease. Furthermore, the alkaline phosphatase in symptomatic patients was higher than that seen in a matched cohort undergoing OLT for chronic active hepatitis or primary biliary cirrhosis. These results suggest that (1) liver replacement and immunosuppression in patients suffering from sclerosing cholangitis and ulcerative colitis do not alter the course of the colon disease, and (2) active chronic ulcerative colitis does not adversely affect allograft function, although elevation of alkaline phosphatase may be the harbinger of recurrence over the long term.

Adult↗
PubMed1992

Biliary strictures complicating liver transplantation. Incidence, pathogenesis, management, and outcome.

Six hundred sixty-six patients received 792 liver transplants between February 1, 1984 and September 30, 1991. Biliary reconstruction was by choledochocholedochostomy (CDCD) with T-tube (n = 509) or Roux-en-Y choledochojejunostomy (CDJ) (n = 283). Twenty-five patients (4%) developed biliary strictures. Anastomotic strictures were more common after CDJ (n = 10, 3.5%) than for CDCD (n = 3, 0.6%). Intrahepatic strictures developed in 12 patients. Six patients had occult hepatic artery thrombosis (HAT). The other six patients received grafts in which cold ischemia time exceeded 12 hours. Anastomotic strictures were successfully managed by percutaneous dilation (PD) in five patients (n = 10), operation in three (n = 6), with retransplantation required in two patients. Intrahepatic strictures were managed by PD in seven, retransplantation in one, and expectantly in four patients. Of 25 patients, 19 (76%) are alive with good graft function. In three of six deaths, the biliary stricture was a significant factor to the development of sepsis and allograft failure. The authors conclude that (1) anastomotic strictures are rare after LT; (2) the development of biliary strictures may signify occult HAT; (3) PD is effective for most strictures; and (4) extended cold graft ischemia (less than 12 hours) may be injurious to the biliary epithelium, resulting in intrahepatic stricture formation.

Adult↗
PubMed1992

The role of differential class II antigen expression in stimulation of allogeneic mixed lymphocyte reactions by human monocyte hybridomas.

The recognition of foreign class II antigens on accessory cells is the crux of an alloreactive immune response. This phenomenon is clearly demonstrated in the primary mixed lymphocyte reaction, which correlates with the type and density of expressed gene products of the HLA-D region. We have generated a series of human monocyte hybridomas by fusing monocytes with the hypoxanthine guanine phosphoribosyl transferase (HGPRT)-deficient, HLA-D antigen-negative U937 histiocytic cell line. Clones bearing combination of HLA-DQ, -DP with or without HLA-DR have been isolated, allowing for the functional assessment of these molecules. In contrast to the U937 cells, the HLA-DR+DQ+DP+ clone 16.1 was capable of stimulating a primary allogeneic MLR. Interestingly, the DR- but DP+DQ+ clones 13 and 15 were also capable of stimulating alloreactive T cells, and the addition of anti-DQ or -DP but not -DR was associated with significant inhibition of the MLR response. Furthermore, gamma-IFN was found to have diverse effects on class II antigen expression in the U937 cells and the hybrids. gamma-IFN down-regulated the expression of HLA-DQ, -DP without altering -DR on clone 16.1, and this was associated with a significant reduction in its MLR stimulatory capacity. The MLR generated by this gamma-IFN-stimulated hybridoma (HLA-DR+DQ-DP-) was now unaffected by the addition of anti-DQ or -DP mAbs. In contrast, up-regulation of DQ and DP antigens on the U937 cells by gamma-IFN now rendered these cells stimulatory in MLR. These data are consistent with the concept that DQ and DP are both important allostimulatory determinants. Our results stress the potential importance of all D-region molecules in acute allograft rejection or successful engraftment.

Antibodies↗
PubMed1992

Hepatic artery thrombosis resulting in gas gangrene of the transplanted liver.

Early hepatic artery thrombosis after orthotopic liver transplantation results in massive injury to hepatocytes and the bile duct epithelium. In the fulminate form, impaired liver synthetic function is expressed by encephalopathy and coagulopathy. Ischemic bile duct injury is associated with the disruption of the biliary anastomosis, bile duct strictures, and intrahepatic bilomas. The inability of the liver macrophages to clear translocated portal blood intestinal pathogens results in persistent bacteremia and sepsis. The major radiologic finding is the radiographic evidence of gas gangrene of the liver graft. Early recognition and correct interpretation of the radiologic findings, immediate removal of the liver graft, and placement of the patient on venous-venous bypass or total hepatic devascularization while a new liver is being procured and retransplantation are the only hope for survival.

Adult↗
PubMed1992

Portosystemic shunt versus orthotopic liver transplantation for the Budd-Chiari syndrome.

We have analyzed the indications and results of shunt operation versus orthotopic liver transplantation (OLT) in 22 patients with Budd-Chiari syndrome (BCS). The underlying cause of the syndrome was similar between the two groups and was related to myeloproliferative disorders or the use of birth control pills in 18 of 22 patients. The results of biopsies of the liver showed centrilobular congestion and necrosis in all candidates who underwent shunting and the presence of fibrosis and cirrhosis in the OLT candidates. The indications for shunts included symptoms related to portal hypertension only and well-preserved synthetic hepatic function. Ten patients were treated with 12 shunt procedures, including mesoatrial (eight patients) and side to side portacaval shunt (four patients). Significant complications after shunt procedure included fulminant (one of ten patients) and progressive (one of ten patients) hepatic failure requiring urgent OLT; one death occurred because of pulmonary sepsis. Indications for OLT were signs of end stage liver expressed by severe portal hypertension and variceal bleeding (four of 14 patients), progressive encephalopathy (seven of 14 patients) and poor synthetic function (bilirubin greater than 3 milligrams per deciliter in eight of 14 patients and albumin less than 3.0 grams per liter, or both, in ten of 14 patients). Fourteen patients were treated with 16 OLT, three patients had retransplantation for primary nonfunction graft (two of 14 patients) or chronic rejection (one of 14 patients). There were two early deaths in the group. With a follow-up period between two months to five years, 12 of 14 patients undergoing OLT are alive, fully functional and have normal liver function tests. Seven of ten patients who had shunts are alive, six are able to maintain normal activity and one has progressive end stage hepatic disease and is not a candidate for OLT. However, the hepatic function continues progressively to be abnormal. Various options are available for the treatment of the syndrome. Portosystemic decompression is effective and should be considered at the early stage of the disease, prior to the development of significant hepatic failure. However, few of the patients will continue to have slow, but progressive hepatic failure and may require OLT. The only effective treatment for end stage hepatic disease secondary to the BCS is OLT.

Actuarial Analysis↗
PubMed1991

The generation and characterization of human monocyte hybridomas.

Fusion of interferon-gamma activated peripheral blood monocytes to a mutagenized hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient U937 parent line was performed resulting in the generation of a series of unique cloned monocyte hybridomas. These cell lines were proven to be true hybrids by the acquisition of donor class I antigens as well as other donor derived chromosomes. In addition, novel functional characteristics were observed including secretion of specific monokines and the acquisition of phagocytic capabilities. The ability to generate immortalized human monocyte hybridomas will allow for more in depth analysis of monocyte subpopulations and dissection of specific monocyte functions.

Analysis of Variance↗
PubMed1991

Safety of surgical procedures performed by residents.

The outcome of surgical procedures on the gallbladder performed by surgical residents in a university hospital was compared with the outcome of those performed by the attending staff. More than 60% of the operations (643/1084) were done by residents under the direct supervision of the attending surgeon. We found no differences in the rate of technical complications, postoperative morbidity and mortality, or length of hospitalization between the two groups. Thus, resident surgery under appropriate guidance is safe and does not compromise the quality of patient care or operative outcome.

Cholecystectomy↗
PubMed1991

Liver transplantation in patients with portal vein thrombosis and central portacaval shunts.

The authors have analyzed the impact of pre-existing portal vein pathology on the outcome of orthotopic liver transplantation. The incidence was high in patients suffering from chronic active hepatitis, hypercoagulable states, trauma or previous dissection of the porta hepatis, and splenectomy. The existence of portal vein thrombosis (23 patients) or surgical central portosystemic shunt (10 patients) was documented by preoperative Doppler sonogram or angiography (26/33), or operative findings of occluded vein (7/33). Successful thrombectomy and dismantling of portacaval shunts were achieved in most cases (24/33). Only nine patients required the placement of an interposition vein graft to the superior mesenteric vein. The intraoperative course was characterized by increased blood loss and coagulopathy, significantly higher than in patients with a patent portal vein. When compared with all liver transplants, the immediate postoperative complication rate was higher for primary nonfunction (33% versus 8%), re-exploration for intraperitoneal bleeding and hematomas, and morbid infections. Rethrombosis rate of thrombectomized veins or vein graft was low (2/33). The mortality rate was 35% in the presence of portal vein thrombosis (PVT) and 30% for portacaval shuct (PCS), both significantly higher than the 12% for other orthotopic liver transplant (OLT) patients. These results are expected to improve with better patient selection, surgical experience, and anticipation of the complex postoperative course. The authors conclude that PVT or the presence of PCS are not contraindications to orthotopic liver transplantation.

Blood Loss, Surgical↗
PubMed1991

Stimulation of distinct T cell subsets in MLR using human macrophage hybridomas differentially expressing class II antigens.

Recognition of class II antigens by alloreactive T cells is thought to be the major mechanism by which tissues undergo rejection. However, the specific role of the various class II antigens in the stimulation of these alloreactive cells remains to be elucidated. We have recently generated a series of human monocyte hybridomas that express distinct patterns of class II antigen expression. HLA-DR+ as well as HLA-DR-DP+DQ+ hybrids were capable of promoting T cell proliferation in a unidirectional mixed lymphocyte reaction. T cells stimulated by the HLA-DR+ clone 16.1 were predominantly of the CD4 (helper/inducer) phenotype. In contrast, T cells stimulated by the HLA-DR-DP+DQ+ clone 13 appear to reside in the CD8+ T cell subpopulation. Functional assessment of the T cell blasts generated in these cultures demonstrated a predominant helper T cell effect by those T cells stimulated by the HLA-DR+ clone 16.1, while suppressor cell activity was exhibited by T cells stimulated with the HLA-DR-DP+DQ+ clone 13. These data suggest that there may be a differential role for distinct class II molecules in the stimulation of T cell subpopulations.

Antibodies, Monoclonal↗
PubMed1991

The hepatorenal syndrome in liver transplant recipients.

The hepatorenal syndrome (HRS) is a well-known complication of liver failure, and medical treatment is usually not successful unless liver function can be improved. The authors review their experience with 130 adults undergoing orthotopic liver transplantation (OLT) over a 20-month period to determine the incidence of HRS and its effects on patient outcome, need for hemodialysis (HD), and the degree of recovery of renal function. The clinical diagnosis of HRS preoperatively was made by using criteria to exclude prerenal azotemia, acute tubular necrosis, and primary renal diseases. Nineteen patients were identified as having the HRS for a preoperative incidence of 15.1 per cent. Overall, 41 of the 126 patients reviewed required postoperative HD, and the mortality in this group was 54 per cent. Fifty-eight per cent of the HRS patients were dialyzed postoperatively vs 28 per cent of non-HRS patients. The mean posttransplant creatinine improved over time in the HRS patients while it worsened slightly in the non-HRS group. At 12 weeks posttransplant, there was a significant difference in the mean creatinine levels (1.8 +/- 0.3 mg/dl vs 1.2 +/- 0.04 mg/dl, P = .001). However, at 24 weeks the small difference was not statistically significant between the two groups (1.6 +/- 0.15 mg/dl vs 1.3 +/- 0.06 mg/dl, P = NS). The current survival of the hepatorenal group is comparable to the nonhepatorenal patients at a follow-up of 6 to 25 months: 68 per cent vs 78 per cent, P = NS. The authors conclude that liver transplantation reverses the HRS, and that hepatorenal patients can undergo liver transplantation with outcomes comparable to nonhepatorenal patients.

Cause of Death↗
PubMed1991

Liver transplantation at UCLA: report of clinical activities.

Liver transplantation remains the treatment of choice for many forms of end-stage liver disease. In most large series, 5-year actuarial survival is greater than 70%. The majority of the morbidity and mortality occurs in the first 6 months posttransplant; as these figures have improved, so have overall survival rates. Infants under 1 year of age have a survival rate below that of older patients; in addition, a severe organ shortage for these patients continues. The use of reduced grafts has ameliorated the problem to a certain extent; however, further expansion of the donor pool is still necessary. Progress has also been made in the postoperative management of transplant patients. We currently follow AKBR and TNF levels in all patients to aid in the diagnosis of primary nonfunction and acute rejection, respectively. The introduction of additional immunosuppressive agents has instigated several large clinical trials. CsA, however, remains the gold standard to which these drugs must be compared.

Actuarial Analysis↗
PubMed1990

Surface expression of CD-4 does not predict susceptibility to infection with HIV-1 in human monocyte hybridomas.

In contrast to T-cell lines, where CD-4 expression may predict susceptibility to HIV infection, in monocyte hybridomas, presence or absence of surface CD-4 does not appear to be the determining factor of susceptibility to HIV infection. One clone, 20, was documented to be CD-4 negative by surface immunofluorescence as well as by immunoprecipitation. Both CD-4+ and CD-4- human monocyte hybridomas, representative of peripheral blood monocytes were readily infected with HIV (strains IIIB and BR-1 and a variety of patient isolates) as assessed by p24 Ag secretion reverse transcriptase activity and in situ hybridization. Infection occurred in the absence of antibody to HIV suggesting a non Fc mediated process as had been previously described. These data suggest that alternative mechanisms, such as non-specific phagocytosis, may exist for entry of HIV into peripheral blood monocytes. Given these findings, treatment for AIDS, such as the use of soluble CD-4, may not be effective long term, as monocyte infection may still occur and serve as a reservoir for subsequent viral infection of T cells.

CD4 Antigens↗