PubMed Health⌕ Search

Biomedical subjects

Andrew S Klein

Publications and source records attributed to Andrew S Klein.

At least 19 recordsLinked to original sources
PubMed2006

Successful transplantation of cadaveric polycystic liver: case report and review of the literature.

The number of candidates awaiting liver transplantation continues to exceed the available donor organ pool. This steadily increasing donor organ shortage calls for the widening of selection criteria for potential donor organs. Strategies to increase the number of liver allografts include liver splitting, use of donors over 70 years, use of steatotic donor livers, and reutilization of liver allografts after brain death of the first recipient. We report the successful use of a polycystic donor liver and review the experience with this donor population. We propose that the selective use of polycystic donor livers containing small (<5 cm) cysts with preserved liver parenchyma is safe and appropriate.

Cadaver↗
PubMed2006

Management of Budd-Chiari syndrome.

KEY CONCEPTS: 1. Medical therapy alone is rarely sufficient for long-term management of patients with hepatic vein thrombosis. 2. Enthusiasm for intravascular stents (transjugular intrahepatic portosystemic shunt [TIPS] or vena caval stents) for the management of Budd-Chiari syndrome must be tempered by the limited interval of expected utility, the likelihood of stent occlusion/revisions, and the potential complications that stent migration would impose upon a subsequent liver transplant. 3. Both decompressive shunts and liver transplantation provide excellent long-term survival for patients with the Budd-Chiari syndrome. The determination of which surgical procedure is most appropriate is aided by assessment of the etiology of hepatic vein thrombosis, hepatic reserve, liver histology, and splanchnic venous anatomy. 4. Progressive hepatic damage may develop in patients with Budd-Chiari syndrome who have patent surgical shunts or TIPS. Lifelong follow-up and tracking of hepatic function are indicated. Some patients with shunts will require salvage with liver transplantation. 5. Long-term anticoagulation should be considered after transplantation, even in patients who do not have an identifiable coagulation disorder.

Budd-Chiari Syndrome↗
PubMed2006

Diaphragmatic hernia after right donor and hepatectomy: a rare donor complication of partial hepatectomy for transplantation.

BACKGROUND: Because of the critical worldwide shortage of cadaveric organ donors, transplant professionals have increasingly turned to living donors. Partial hepatectomy for adult living donor liver transplantation has been performed since the late 1990s. Most often, the complications of living donor hepatectomy have been related to the biliary tract, specifically biliary leaks. METHODS: A 54-year-old man underwent donor right hepatectomy for living donor liver transplantation. Three years after liver donation he presented with upper abdominal pain and fullness. Radiographic workup revealed a diaphragmatic hernia of the right hemithorax. RESULTS: After thoracoscopic evaluation of the right hemithorax, diaphragmatic hernia was repaired. Currently the patient remains well several months after the repair with complete resolution of abdominal pain, normal chest X-ray examination demonstrating no recurrence of diaphragmatic hernia, and normal liver functions tests. CONCLUSIONS: Multiple complications of living donor liver transplantation have been described the transplant literature. Diaphragmatic hernia is a formerly-undescribed complication of right donor hepatectomy for transplantation.

Hepatectomy↗
PubMed2005

Oxidative mitochondrial DNA damage and deletion in hepatocytes of rejecting liver allografts in rats: role of TNF-alpha.

An orthotopic liver transplant model in the rat was used to evaluate the role of tumor necrosis factor alpha (TNF-alpha) in liver transplant rejection. There were significantly increased levels of TNF-alpha mRNA and parallel increases in 8-hydroxy-2' deoxyguanosine (8-OHdG) indicative of oxidative DNA damage present 7 to 12 days after transplantation. Cells staining positively for 8-OHdG were localized to the cytoplasm of hepatocytes adjacent to the TNF-alpha expressing inflammatory cells in the portal areas or in patches surrounded by inflammatory cells in the hepatic sinusoids. Significantly more cells staining for 8-OHdG were found in the allogeneic grafts that were strongly rejected than in the syngeneic controls or in the grafts placed in species that accepted the allograft permanently after a rejection episode. TUNEL reactivity lagged 2 days behind peak reactivity for 8-OHdG. On day 12 after transplantation, many cells stained for both 8-OHdG and TUNEL, indicating that the cells suffering oxidative DNA injury were undergoing apoptosis or death. Oxidative injury resulted in mtDNA deletion consisting of 4,834 base-pairs. Studies of hepatocytes cultured from normal rats displayed dose-dependent relationships between TNF-alpha concentration and 8-OHdG and mtDNA mutation. Repetitive intraperitoneal injection of Enbrel, a TNF receptor blocker, significantly decreased hepatocyte 8-OHdG levels and the frequency of deleted mtDNA while greatly extending graft survival time. In conclusion, the data presented implicate TNF-alpha as being capable of causing oxidative DNA damage and mtDNA mutation in hepatocytes.

Animals↗
PubMed2005

The utility of TIPS in the management of Budd-Chiari syndrome.

BACKGROUND AND AIM: Budd-Chiari syndrome (BCS) is a rare condition associated with hepatic venous outflow obstruction classically treated with portosystemic shunts or liver transplantation. Recent reports indicate promising results with the use of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of these patients. PATIENTS AND METHODS: We reviewed a 10-year single-institution experience with TIPS in patients diagnosed with BCS. RESULTS: Eleven patients with BCS underwent TIPS procedures, 3 of whom carried a diagnosis of paroxysmal nocturnal hemoglobinuria, a relative contraindication for liver transplantation. One TIPS procedure was unsuccessful for technical reasons. No patient suffered mortality or major morbidity related to the TIPS procedure. The mean reduction of portal venous pressures was 43.7%, with a mean decrease of 73% in the pressure gradient. Of the 7 patients where long-term follow-up was available, 57% had shunts which remained patent but required several nonsurgical revisions for occlusion, with an average assisted patency of 37.5 months. CONCLUSIONS: TIPS is an effective modality in the treatment of patients with BCS, especially for those who are not candidates for liver transplantation. TIPS can be successfully used as a bridge to surgical portosystemic shunting, as well as liver transplantation, but may cause technical difficulties when performing transplantation.

Budd-Chiari Syndrome↗
PubMed2005

Reactive oxygen species are essential mediators in antigen presentation by Kupffer cells.

Kupffer cells (KC) act as APC in the liver and play a major role in the clearance of gut-derived antigens and pathogens entering the liver with portal venous blood. Antigen presentation by KC has been implicated in regulation of the local and systemic immune responses. In this study, modulation of KC antigen presentation by antioxidants and the role of reactive oxygen species (ROS) as essential mediators of antigen presentation in KC were investigated. Co-culture of KC with ovalbumin (OVA) antigens resulted in upstream intracellular endogenous ROS generation and increased expression of MHC class II and costimulator molecules, and consequent OVA-specific CD4(+) T-cell proliferation in response to antigen presentation by KC. Scavenging of KC ROS by antioxidants, or blocking of KC ROS generation by specific inhibitors of NADPH oxidase and/or xanthine oxidase, or by specific inhibitors of the mitochondrial electron transport chain, significantly decreased OVA-specific T-cell proliferation in response to antigen presentation by KC. Increased expression of MHC class II and costimulatory molecules in KC pulsed with OVA antigens was blocked by inhibiting ROS generation enzymatically. Intracellular endogenous ROS generation during antigen processing may therefore provide essential secondary signalling for KC antigen presentation.

Animals↗
PubMed2005

Attitudes, psychology, and risk taking of potential live kidney donors: strangers, relatives, and the general public.

It is unclear whether potential living kidney donors and the general public differ in attitudes and psychological characteristics. We performed a case-control study to explore differences in these groups using a standardized questionnaire (analyzed using conditional logistic regression). Strangers (N = 42) were more willing than controls (N = 126) to incur risks: 64% strangers versus 35% controls accepting >50% medical complications (MC) risk; 90% strangers versus 61% controls accepting >8 days hospitalization; 71% strangers versus 43% controls accepting >3 months unpaid; 55% strangers versus 16% controls accepting 100% kidney failure (KF) risk; 70% strangers versus 34% controls accepting < or =10% likelihood of successful transplant (all p < 0.01). Relatives (N = 251) were also more willing than controls (N = 251) to incur risks. Strangers were most willing to incur MC, KF and transplant failure. Groups did not differ in attitudes, depression or anxiety. Potential stranger and related donors are willing to undergo greater risks with donation than the general public, but do not differ in other attitudes, depression or anxiety. This should help reassure transplant centers and the public that both forms of live donation do not necessarily involve increased ethical risks of donor coercion or irrational thought processes. Still, careful attention to communication of all risks of donation is warranted.

Adult↗
PubMed2004

Procurement of liver and pancreas allografts in donors with replaced/accessory right hepatic arteries.

Anatomic variants in the origin of the right hepatic artery have led to various approaches at the time of organ procurement for transplantation. Of special relevance is the presence of a replaced or accessory right hepatic artery arising independently from the superior mesenteric artery. On the basis of an estimated combined experience of almost 2,000 organ procurements and implantations, we propose a technique in which dissection is kept to a minimum, with the goal of preventing procurement-associated injuries.

Hepatectomy↗
PubMed2004

Lipopolysaccharides induced increases in Fas ligand expression by Kupffer cells via mechanisms dependent on reactive oxygen species.

Fas-Fas ligand (FasL)-dependent pathways exert a suppressive effect on inflammatory responses in immune-privileged organs. FasL expression in hepatic Kupffer cells (KC) has been implicated in hepatic immunoregulation. In this study, modulation of FasL expression of KC by endogenous gut-derived bacterial LPS and the role of reactive oxygen species (ROS) as potential mediators of FasL expression in KC were investigated. LPS stimulation of KC resulted in upstream ROS generation and, subsequently, increased FasL expression and consequent Jurkat cell (Fas-positive) apoptosis. The NADPH oxidase and xanthine oxidase enzymatic pathways appear to be major sources of this upstream ROS generation. Increased FasL expression was blocked by antioxidants and by enzymatic blocking of ROS generation. Exogenous administration of H2O2 stimulated KC FasL expression and subsequent Jurkat cell apoptosis. Intracellular endogenous ROS generation may therefore represent an important signal transduction pathway for FasL expression in KC.

Animals↗
PubMed2004

Urethral stricture after pancreas-kidney transplantation due to polypoid urethritis.

Urologic complications are common after pancreas-kidney transplantation using bladder drainage. We report a case of urethral stricture caused by polypoid urethritis occurring 4 years after simultaneous pancreas-kidney transplantation. Endoscopic exploration revealed irregular, ragged-appearing urethral mucosa. The diagnosis of polypoid urethritis was confirmed histopathologically.

Adult↗
PubMed2004

Over-expression of AIF-1 in liver allografts and peripheral blood correlates with acute rejection after transplantation in rats.

Early and accurate detection of acute cellular rejection (ACR) is important in the management of liver allograft recipients. We hypothesized that expression of allograft inflammatory factor (AIF)-1 would be associated with liver allograft rejection as previous studies have shown that a relationship exists between kidney and heart transplantation. Indeed using rat orthotopic transplant models we found that the expression of allograft inflammatory factor-1 (AIF-1) can be detected in both allograft and peripheral blood leukocytes with peak levels detected 7 days following liver transplantation. Interestingly, AIF-1 expression increased 2-fold in acutely rejecting liver allografts compared to chronically accepted livers on days 5, 7 and 10 after transplantation. AIF-1 expression in peripheral blood leukocytes was also significantly greater in the rejection model than in the acceptance model. Flow cytometric analysis of peripheral blood leukocytes demonstrated that AIF-1 was expressed in ED2-positive cells, a marker for Kupffer cells. In vitro studies showed that AIF-1 expression in Kupffer cells was up-regulated by coculture with Th1 cytokines. However, neither LPS nor Escherichia coli (E. coli) administration had an affect on AIF-1 expression. These data indicate that high levels of AIF-1 expression reflect aggressive liver allograft rejection and suggest a role for monitoring AIF-1 in peripheral blood leukocytes as a monitor for increased immunosuppression.

Animals↗
PubMed2003

In vitro interleukin-6 treatment prevents mortality associated with fatty liver transplants in rats.

BACKGROUND & AIMS: Orthotopic liver transplantation is currently the only curative therapy for chronic end-stage liver disease and acute liver failure. However, a scarcity of cadaveric donors has led to a critical shortage of organs available for transplant. This is further complicated by the prevalence of steatosis in about 13%-50% of donor livers, which is associated with a high risk of dysfunction and primary nonfunction. METHODS: Steatotic Zucker rat livers and livers from alcohol-fed rats were transplanted into lean control rats. Liver injury, activation of survival signals, and hepatic microcirculation were compared in nontreated and interleukin-6 (IL-6)-treated steatotic isografts. RESULTS: IL-6 pretreatment of steatotic Zucker rat liver isografts dramatically reduces mortality and liver injury following transplantation. Reperfusion after transplantation induces significant sinusoidal endothelial cell necrapoptosis in steatotic Zucker rat liver isografts, which is prevented by in vitro IL-6 pretreatment. IL-6 treatment activates cell survival signal transducer and activator of transcription factor 3 (STAT3) in hepatocytes and sinusoidal endothelial cells. Laser Doppler imaging and microsphere analyses demonstrate that IL-6 treatment markedly improves hepatic microcirculation, which is impaired in steatotic Zucker rat liver transplants. Finally, in vitro IL-6 treatment of donor livers also markedly reduces mortality associated with fatty liver transplants from alcohol-fed rats. CONCLUSIONS: IL-6 induces hepatoprotection of steatotic liver isografts via preventing sinusoidal endothelial cell necrapoptosis and consequent amelioration of hepatic microcirculation, and protecting against hepatocyte death. IL-6 pretreatment of steatotic livers may render such allografts useable for clinical transplantation.

Animals↗
PubMed2003

Laparoscopic procurement model for living donor liver transplantation.

BACKGROUND/AIMS: Noting the contribution to renal transplantation by the introduction of the laparoscopic approach to donor nephrectomy, we investigated the possibility of performing a laparoscopic hepatic lobe procurement with the goal of performing a live donor liver transplantation. We describe our technique and determine its feasibility for such a goal. METHODS: The surgical technique was developed over a series of 12 adult female pigs and adapted in two human cadavers. The technique included pneumoperitoneum with CO2, mobilization of the liver, and transection of the parenchyma into right and left lobes with a laparoscopic cavitron ultrasonic aspirator. The vascular inflow and outflow structures (hepatic artery, portal vein, hepatic veins) of the anatomical specimen being procured were preserved undisturbed during the hepatic transection. No temporary vascular occlusion techniques were utilized. The vascular structures were stapled and sectioned just prior to removal of the specimen. RESULTS: Hepatic lobectomies were successfully performed laparoscopically. Vascular and biliary structures were preserved to allow for subsequent transplantation. Operative time from establishment of pneumoperitoneum to lobe procurement was under 4 h. CONCLUSIONS: This study demonstrates the feasibility of laparoscopic living donor procurement for liver transplantation, from both a technical and a physiological perspective.

Animals↗
PubMed2003

Normal and variant arterial supply of the liver and gallbladder.

The vascular supply of the liver and gallbladder is characterized by a striking degree of polymorphism. The occurrence of variants that differ from the usual pattern is both surprisingly common and unpredictable. Knowledge of this variable anatomy is particularly important during surgical interventions in which preoperative imaging studies are not available, such as in organ procurements. In this report we consider various anatomical arterial configurations, and describe an unusual variant.

Arteries↗
PubMed2003

Concomitant surgery with laparoscopic live donor nephrectomy.

Routine live donor evaluations reveal unexpected silent pathologies. Herein, we describe our experience treating such pathologies at the time of laparoscopic donor nephrectomy. We have not encountered any previous reports of such an approach. We prospectively collected data on 321 donors. Concomitant surgeries at the time of procurement included two laparoscopic adrenalectomies, one colposuspension, one laparoscopic cholecystectomy, and one liver biopsy. Mean operative time was 321 min (range 230-380), with a mean blood loss of 280 mL (range 150-500). No blood transfusions were required. The left kidney was procured in four cases. The right kidney was obtained on one occasion. Mean hospital stay was 3 days (median 3, range 2-4). No short- or long-term complications have been identified. Mean follow-up time was 2.63 years (median 2.76, range 2.23-2.99). Four of the five kidney recipients were first-time transplants who had not yet started dialysis. Simultaneous surgical interventions at the time of laparoscopic live kidney donation are safe and can be undertaken in selected cases. This practice is beneficial to both the donor and the recipient, and is likely to become more commonplace with changing practice patterns involving donor evaluation and management.

Adenoma↗
PubMed2003

Hepatic allograft-derived Kupffer cells regulate T cell response in rats.

In liver transplantation, the development of tolerance is associated with an increased rate of apoptosis of T lymphocytes in the portal inflammatory infiltrate and the presence of an intragraft Th2-like T cell population. Underlying mechanisms are poorly understood. Kupffer cells (KC), which reside in the hepatic sinosoids, can directly interact with circulating T lymphocytes and thus are uniquely positioned to play a role in immunomodulation. In this study, the immunoregulatory effects of KC were investigated. We show that KC can significantly suppress T cell proliferation in mixed leukocyte reaction (MLR). Furthermore, KC express functional Fas ligand (FasL) and can induce apoptosis of Fas+ cells. This process can be blocked by addition of neutralizing anti-FasL antibody. Moreover, using an allogeneic liver transplant model we have determined that 1. KC recovered from chronically accepted hepatic allografts have increased FasL messenger RNA (mRNA) and protein expression and a greater ability to induce apoptosis of alloreactive T cells compared with KC recovered from an acute rejection model; 2. KC not only induce apoptosis of T cells, but also regulate cytokine production and Th2/Th3-like cytokine (interleukin [IL]-10 / transforming growth factor [TGF]-beta) mRNA expression in allogeneic MLR in vitro; and 3. administration of KC derived from chronically accepted liver allografts significantly prolongs the survival of hepatic allografts in an acute rejection model in an alloantigen-specific manner. In conclusion, these data implicate the possible role of KC-mediated regulation of T cell response in the induction of immune tolerance in liver allografts.

Animals↗