A 7-month-old male infant with extra- and intrahepatic biliary cysts.
Explore the source record for details and available documents.
Caroli Disease↗
Biomedical subjects
S Emre
Publications and source records attributed to S Emre.
Cytokine profiles in early rejection following OKT3 treatment in liver transplant patients.
OKT3 , a murine monoclonal antibody specific to the human CD3 complex, induces immunosuppression by depletion of T cells. Administration of OKT3 results in significant release of proinflammatory cytokines, such as TNFalpha and IL1beta. Liver recipients who experience rejection within 3 weeks after transplantation with OKT3 prophylaxis recover their T cells by postoperative day 10 despite complete initial clearance. We sought to analyze the role of proinflammatory and Th-1 cytokines in T cell recovery and rejection after liver transplantation with OKT3 prophylaxis. In plasma samples from 32 patients, we measured TNFalpha, IL1beta and IL6 (before transplant and on postoperative days 1, 2 and 3) and IL2, IFNgamma, sIL2R and slCAM (postoperative days 5, 7 and 10) and examined possible correlations with T-cell recovery and occurrence of rejection within 3 weeks. TNFalpha, IL1beta, and IL6 did not correlate with T-cell recovery. In patients who rejected, IL2 and IFNgamma on postoperative days 5 and 7 correlated with degree of T-cell recovery by day 10; a significant rise in sIL2R over time also correlated with T-cell recovery in this group. Our results emphasize the role of Th-1 cytokines in rejection following OKT3 induction and suggest that markers of T cell activation may predict risk.
Animals↗
Th1/Th2 cytokines and ICAM-1 levels post-liver transplant do not predict early rejection.
Th1 derived cytokines IFN-gamma and IL-2, Th2 cytokine IL-4, and ICAM-1 have been implicated in liver allograft rejection. In order to determine whether monitoring of cytokine profiles during the first days post-liver transplant can predict early rejection we measured IFN-gg, IL-2, sIL-2 receptor, IL-4 and ICAM-1 in 22 patients, in plasma samples obtained within 4 h after liver perfusion (baseline) and between postoperative days (POD) 3-6. ICAM-1 and sIL-2R levels at POD 3-6 were significantly higher than at baseline but did not differ in presence or absence of rejection. Mean percentage increase of ICAM-1 levels was significantly lower in patients with Muromonab-C3 Orthoclone OKT3 (J.C. Health Care) (OKT3) whereas percentage increase of sIL-2R levels was higher in OKT3-treated patients. IFN-gamma levels at POD 3-6 increased from baseline while IL-4 levels were unchanged. Levels of IFN-gamma, IL-4 and their ratios did not correlate with rejection or immunosuppressive therapy. Thus, Th1/Th2 cytokine monitoring during the first week post-transplant does not predict early rejection and immunosuppressive therapy is the predominant factor affecting ICAM and sIL-2R levels after liver transplantation.
Female↗
Two new loci for autosomal recessive ichthyosis on chromosomes 3p21 and 19p12-q12 and evidence for further genetic heterogeneity.
Autosomal recessive ichthyosis (ARI) includes a heterogeneous group of disorders of keratinization characterized by desquamation over the whole body. Two forms largely limited to the skin have been defined: lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE). A first gene for LI, transglutaminase TGM1, has been identified on chromosome 14, and a second one has been localized on chromosome 2. In a genomewide scan of nine large consanguineous families, using homozygosity mapping, two new loci for ARI were found, one for a lamellar form in a 6-cM interval on chromosome 19 and a second for an erythrodermic form in a 7.7-cM interval on chromosome 3. Linkage to one of the four loci could be demonstrated in more than half of 51 consanguineous families, most of them from the Mediterranean basin. All four loci could be excluded in the others, implying further genetic heterogeneity in this disorder. Multipoint linkage analysis gave maximal LOD scores of 11.25 at locus D19S566 and 8.53 at locus D3S3564.
Chromosome Mapping↗
A pilot study of posttraumatic stress and nonadherence in pediatric liver transplant recipients.
BACKGROUND: Symptoms of posttraumatic stress disorder (PTSD) were described in survivors of life-threatening diseases, the trauma being the experiences associated with the disease or its treatment. Their prevalence in liver transplant recipients is unknown. Based on clinical observations, we hypothesize that a significant proportion of pediatric liver transplant recipients suffers from PTSD symptoms. We further hypothesize that nonadherence (noncompliance) to medical management may, in some cases, be associated with these symptoms. Traumatized patients, according to this hypothesis, will avoid taking their medications, because these serve as painful reminders of the disease. OBJECTIVES: To determine the prevalence of PTSD symptoms in a sample of pediatric liver transplant recipients. To determine whether symptoms of PTSD are associated with nonadherence in these patients. To describe the clinical presentation of PTSD and the management of severe nonadherence in patients who suffer from this disorder. METHODS: Nineteen pediatric liver transplant recipients and their caretakers were interviewed, using the UCLA Post Traumatic Stress Disorder Reaction Index (PTSRI). Data were obtained on a few demographic parameters and perception of disease threat. Adherence was evaluated by 2 methods: 1) a clinician panel (taking into account the clinical sequelae of severe nonadherence); and 2) computation of the standard deviations (SDs) of consecutive determinations of blood levels of Tacrolimus (a higher SD means higher variability between individual measures and is therefore an indicator of nonadherence). As an illustration of the general phenomenon, we describe 3 cases of liver transplant recipients who were nonadherent and who suffered from PTSD. RESULTS: Six of 19 patients had positive scores on all 3 components of the PTSRI (PTSD patients). Three of these, and none of the others, were considered significantly nonadherent by the panel. Therefore, nonadherence was significantly associated with the existence of symptoms from all 3 domains of PTSD (Fisher's exact test) in our sample. In particular, a high avoidance score on the PTSRI was highly correlated with panel-determined nonadherence. Further, SD of medication levels were significantly higher in PTSD patients, compared with the rest of our sample. No significant differences were found in perception of disease threat or demographic variables between PTSD patients and the rest of our sample. The 3 cases that we describe became adherent to their medications when symptoms of PTSD subsided during the course of therapy. CONCLUSIONS: Clinically significant nonadherence, determined by 2 different methods, was associated with the full spectrum of PTSD symptoms in this sample. It was especially associated with a high avoidance score, which suggests that avoidance of reminders of the disease (eg, medications) may be a mechanism of nonadherence. Screening for and management of these symptoms, therefore, may improve adherence. This novel concept may be applicable to other patient populations. However, more data are needed before any definite conclusions can be drawn.
Adolescent↗
Hepatocellular carcinoma and non-Hodgkin lymphoma in a patient with chronic hepatitis C and cirrhosis.
Hepatitis C virus (HCV) is a hepatotropic virus, but its genome and replicative intermediates also have been detected in peripheral blood mononuclear cells in patients with chronic hepatitis C. Chronic HCV infection may lead to hepatocellular carcinoma and, in a small percentage of cases, to B-cell non-Hodgkin lymphoma. To our knowledge, coexistence of these 2 tumors has not been reported previously. We describe a case of chronic hepatitis C and cirrhosis with 2 small hepatocellular carcinomas and incidental non-Hodgkin lymphoma of a hilar lymph node found during liver transplantation. Although the mechanisms of HCV oncogenesis in hepatocellular carcinoma and in lymphoma are unclear, the presence of these 2 tumors in a single patient are in agreement with the tropism of HCV and its role in oncogenesis.
Carcinoma, Hepatocellular↗
Echocardiographic findings of pericardial involvement in patients with malignant pleural mesothelioma with a history of environmental exposure to asbestos and erionite.
OBJECTIVE: The aim of the present study was to evaluate the pericardial involvement in patients with malignant mesothelioma caused by exposure to different minerals. METHODOLOGY: Forty-two patients (mean age of 52 +/- 12 years) with malignant mesothelioma were examined with transthoracic echocardiography. Thirty-three (78.9%) patients had a history of environmental exposure to asbestos and nine (21.4%) had a history of environmental exposure to erionite. RESULTS: In 19 (45.2%) patients with malignant pericardial mesothelioma, pericardial involvement was determined by echocardiography. The other 23 (54.8%) patients had no pericardial involvement. Pericardial effusion was detected in nine (64.3%) patients and pericardial effusion was small in six (14.3%) patients, moderate in one (2.4%) patient and large in two patients. Thickening of the pericardium was observed in eight (19%) patients. In another two (7.1%) patients pericardial calcification was observed. Among the 33 patients who had been exposed to asbestos, 15 (45.5%) had pericardial involvement, and among the nine patients with a history of exposure to erionite, four (44.4%) had pericardial involvement. There was no difference in terms of pericardial involvement in different stages of the tumour (P > 0.05). CONCLUSIONS: Pericardial involvement is commonly seen in patients with malignant mesothelioma. Among patients exposed to asbestos or zeolite there was no difference in terms of pericardial involvement. Furthermore, pericardial involvement was not related with the stage of the tumour.
Adult↗
Liver transplantation at Mount Sinai.
Nearly 2000 liver transplants have been performed over the past 12 years at Mount Sinai, with a recent exponential growth in living donor surgeries. Living-donor liver transplantation has emerged as an important option for our patients with end-stage liver disease. We are only beginning to recognize fully the advantages that 'scheduled' liver transplantation can offer. In this era of severe cadaver organ shortages, living donation offers patients the option of liver replacement in a timely fashion, before life-threatening complications of hepatic failure and/or carcinoma progression prohibit transplantation. The next era of transplantation at Mount Sinai will bring significant increases in the number of transplants performed with living donors, with projections of over 50% of the total transplants each year expected to involve living donations. We are committed to offering this option while recognizing that donor safety remains paramount and cannot be overemphasized. Proper donor and recipient selection, as well as surgical experience are imperative to success with this technically demanding procedure. Recurrent disease after transplantation, particularly with hepatitis C, remains a challenge clinically. Further investigations into the pathogenesis of the rapid progression of recurrent hepatitis C need to be addressed. Living donor transplantation could be an important option for these patients and would allow timely transplantation and the potential for improved survival in patients with hepatocellular carcinoma.
Adult↗
Prospective longitudinal analysis of quantitative Epstein-Barr virus polymerase chain reaction in pediatric liver transplant recipients.
BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) remains a significant cause of morbidity and mortality in pediatric liver transplant recipients. Epstein-Barr Virus (EBV) mismatch associated with more prevalent use of split-liver, reduced size, and living-related transplants has increased the risk of primary EBV infection and subsequent PTLD. Early identification of EBV viremia may reduce the risk of PTLD, because it allows for early adjustment of immunosuppression and antiviral therapy. METHODS: EBV viral load was measured monthly by quantitative competitive polymerase chain reactions in three pediatric liver transplant recipients. RESULTS: Onset of EBV viremia was documented in one recipient. Established EBV viremia was followed in the other two recipients (one with chronic rejection and one with PTLD) who were initially tested once monitoring was initiated in our program. CONCLUSIONS: EBV quantitative competitive polymerase chain reactions may represent a promising way to follow EBV viral load and potentially prevent the development of PTLD.
Epstein-Barr Virus Infections↗
Safe transplantation of blood type A2 livers to blood type O recipients.
BACKGROUND: Transplantation of blood type A subgroup 2 (A2) livers into non-A recipients has not been reported previously. A2 to O renal transplantation has been reported, with early results including some accelerated rejections and graft losses. This has led some to selectively offer A2 renal transplantation only for patients with low anti-A titers. Given the different clinical behavior of liver allografts to preformed antibody, we felt that such restriction was unnecessary. METHODS: We performed six cases of A2 to O liver transplantation with no augmented immunomodulation or restriction with regard to antibody titers. Clinical courses, anti-A titers, rejection rates, and graft and patient survival were evaluated. RESULTS: All six patients had high pretransplant anti-A titers (>1:8), and all six grafts functioned normally. There were nine rejections in the six patients, of which three were severe (steroid-resistant) and five were late (>90 days). No rejection was vascular, and no grafts were lost, with mean follow-up of 665 days. In one patient who had anti-A antibody measured at the time of rejection IGM titers increased from baseline. Currently all patients are home with normal function. CONCLUSIONS: We found that transplantation of blood group A2 livers into blood group O recipients is safe and can be performed without graft loss and without regard to anti-A titer level. The rate of acute cellular rejection is high in this small series, and a significant proportion of these events were late or required OKT-3. We did not rely on plasmapheresis or anti-A titer determinations. However, the potential for late rejection prompts us to consider the addition of a third immunosuppressive agent. The transplantation of A2 livers into O recipients can partially compensate for the more frequent use of O livers in recipients from other blood groups.
ABO Blood-Group System↗
Unsuspected bile duct paucity in donors for living-related liver transplantation: two case reports.
Alagille's syndrome is a common cause of liver disease in children and may lead to the need for orthotopic liver transplantation. Alagille's syndrome is inherited in an autosomal dominant manner, with variable penetration, and may also be present in patients' parents, who may be considered potential donors for living-related transplantation. We report here on two cases in which the living-related donors for children with Alagille's syndrome had no liver function abnormalities or characteristic features of Alagille's syndrome. In both cases, the operation for living-related donation had to be aborted because of a paucity of bile ducts discovered intraoperatively. Given the variable presentation of Alagille's syndrome, we believe that it is necessary preoperatively to evaluate the biliary system of family members who are potential living-related donors for patients with this condition.
Adult↗
De novo hepatocellular carcinoma in a hepatic allograft with recurrent hepatitis C cirrhosis.
We report a case of de novo hepatocellular carcinoma (HCC) in a patient with recurrent hepatitis C (HCV) and cirrhosis 7 years after orthotopic liver transplantation (OLT). This is a previously unreported observation in the natural history of posttransplantantion HCV infection and reiterates the strong oncogenic potential of HCV.
Carcinoma, Hepatocellular↗
Living related liver transplantation for acute liver failure in children.
The mortality rate among children with acute liver failure (ALF) on the waiting list for liver transplantation is high. We present our experience with living related donor liver transplantation (LRD-LT) in children who required urgent transplantation for ALF. Between December 1995 and July 1997, 6 children underwent LRD-LT for ALF. Cause of liver failure, recipient and donor demographics, clinical and laboratory data, surgical details, complications, and 6-month and 2-year graft and patient survival were recorded. Five boys and 1 girl received left lateral segment grafts from their parents. The mean age was 4 +/- 2.8 years (range, 1 to 9 years). ALF was caused by Wilson's disease in 1 patient and sickle cell intrahepatic cholestasis syndrome in 1 patient; in 4 patients, the cause was unknown. All patients had mental status changes; 2 were on life support. Mean pretransplantation liver function test values were: alanine aminotransferase, 972 +/- 565 U/L (normal, 1 to 53 U/L), total bilirubin, 31.3 +/- 12.4 mg/dL (normal, 0.1 to 1.2 mg/dL), prothrombin time, 34.3 +/- 12.4 seconds (normal, 10.8 to 13.3 seconds), international normalized ratio, 8.46 +/- 5.4 (normal < 2), and fibrinogen, 109 +/- 23.9 mg/dL (normal, 175 to 400 mg/dL). The donors were 5 mothers and 1 father. The mean donor age was 32.5 +/- 7.6 years (range, 19 to 40 years). No donor required blood transfusion, and no donor had any early or late postoperative complications. The donors' mean hospital length of stay was 5 days. In five cases, grafts were blood group-compatible; 1 child received a blood group-incompatible graft. All grafts functioned immediately. No patient had hepatic artery or portal vein thrombosis or biliary complications. The child who received a mismatched graft died of infection of the brain caused by Aspergillus spp at 22 days posttransplantation with a functioning graft. The child with ALF caused by sickle cell intrahepatic cholestasis syndrome developed outflow obstruction 3 months posttransplantation and required retransplantation; he eventually died of vascular complications related to his primary disease. Four children are alive at a mean follow-up of 27 months (range, 14 to 36 months). LRD-LT for children with ALF facilitates timely transplantation without drawing on cadaveric donor resources. The established safety record of LRD-LT made this option appealing to both physicians and parental donors.
Adult↗
Successful liver transplantation from a donor with brodifacoum intoxication.
We describe our use of a liver allograft from a donor who died of intracranial hemorrhage after brodifacoum ingestion. Because brodifacoum can remain in the human body for months, the recipient's posttransplantation coagulation profiles and serum brodifacoum levels were monitored closely. Her posttransplantation course was excellent, with no coagulation problem. At 15 months posttransplantation, she is well, with normal liver function and coagulation profile. We conclude that brodifacoum toxicity is not a strict contraindication to liver donation.
4-Hydroxycoumarins↗
Hepatic epithelioid hemangioendothelioma: resection or transplantation, which and when?
Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor with an unpredictable course and prognosis. The aim of this study is to describe our experience with liver resection, as well as transplantation, in the treatment of this tumor. We retrospectively analyzed the clinical features, pathological findings, and postoperative results in a series of 11 patients presenting between 1990 and 1998. Five patients (45%) presented with abdominal pain, 3 patients (27%) with jaundice and ascites, and the rest were asymptomatic. Computed tomography or magnetic resonance imaging showed localized lesions in 2 patients (18%) and multifocal disease in the others. Seven patients (64%) had extrahepatic lesions, detected either by preoperative imaging or discovered at exploration. Two resections of apparently localized lesions were followed by rapid and aggressive recurrence. Five patients were treated with transplantation, including 1 patient who had previously undergone resection. Of these 5 patients, 2 patients are currently free of detectable disease, 1 patient who had severe ascites and jaundice is now asymptomatic with stable extrahepatic lesions, and 2 patients (including 1 who had previously undergone a resection) died of tumor recurrence. One patient with advanced tumor died while waiting for transplantation. The remaining 4 patients are free of symptoms and have stable hepatic and extrahepatic disease. HEHE is nearly always multifocal, and our results with resection were dismal. Because of the unpredictable nature of the tumor, the indications for transplantation in patients without liver-related symptoms should be carefully evaluated. Nevertheless, extrahepatic disease should not be an absolute contraindication for liver transplantation in patients with severe liver dysfunction.
Female↗
Transmission of factor VII deficiency through liver transplantation.
The liver is the primary site of synthesis for the majority of coagulation factors. There are published accounts of liver donor-to-recipient transmission of protein C deficiency with dysfibrinogenemia and factor XI deficiency. In this article, we report what we believe to be the first observation, of transmission of factor VII deficiency, a rare, autosomal recessive coagulation disorder, from an affected liver donor to a naive liver recipient. At 300 days after transplantation, the recipient remains with an isolated prolongation of the prothrombin time and a below-normal level of factor VII, and has had no bleeding complications.
Adult↗
The relaxation induced by nicotine in the rat isolated renal artery.
The mechanism of nicotine-induced relaxation was investigated in the rat isolated renal artery. Nicotine (10(-3) M) produced a relaxation when preparations were precontracted by phenylephrine (3 x 10(-6) M). Nicotine-induced relaxation was 27.3 +/- 2.5% of phenylephrine contraction and was not affected by atropine (10(-5) M), guanethidine (10(-5) M), hexamethonium (10(-4) M), indomethacin (10(-5) M), N(G)-nitro-L-arginine (10(-4) M), methylene blue (10(-5) M), glibenclamide (10(-5) M), quinacrine (3 x 10(-6) M), tetrodotoxin (10(-6) M), capsaicin (10(-6) M), tetraethylammonium (10(-3) M), 4-aminopyridine (10(-3) M), and ouabain (10(-6) M) (n = 6, Mann-Whitney U-test). A calcium antagonizing effect of nicotine was not observed. Therefore, it appears that nicotine relaxes rat isolated renal artery by a nonspecific action on the vascular smooth muscle.
Animals↗
Analysis of three mutations in Turkish children with Gaucher disease.
Explore the source record for details and available documents.
Gaucher Disease↗