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Biomedical subjects

C M Miller

Publications and source records attributed to C M Miller.

At least 73 records · Page 4Linked to original sources
PubMed1998

Dissecting the molecular details of prokaryotic transcriptional control by surface plasmon resonance: the methionine and arginine repressor proteins.

The commercial surface plasmon resonance (SPR) biosensors, BIACORE, have been used to investigate the molecular details of macromolecular interactions at prokaryotic promoter-operators. For the Escherichia coli methionine repressor, MetJ, we have quantitated the interaction of the protein with synthetic and natural operator sites and shown that the SPR response is directly related to the stoichiometry of the complexes being formed. The utility of a continuous flow system has also been exploited to investigate transcription from an immobilised promoter-operator fragment; with transcripts collected and subsequently characterised by RT-PCR. This technique has enabled us to investigate how repressor binding affects (i) the interaction of the RNA polymerase (RNAP) with the promoter and (ii) the ability of RNAP to initiate transcription. Remarkably, the repression complex appears to stabilise binding of RNAP, whilst having the expected effects on the levels of transcripts produced. This may well be a general mechanism allowing rapid transcription initiation to occur as soon as the repression complex dissociates. These techniques have also been used to examine protein-DNA interactions in the E. coli and Bacillus subtilis arginine repressor systems. The repressors are the products of the argR and ahrC genes, respectively. Both proteins form hexamers in rapid equilibrium with smaller subunits believed to be trimers. There are three types of operator in these systems, autoregulatory, biosynthetic and catabolic (B. subtilis only). Sensorgrams show that each protein recognises the three types of immobilised operator differently and that binding is stimulated over 100-fold by the presence of L-arginine.

Bacterial Proteins↗
PubMed1998

Differential in vivo recovery of sinusoidal endothelial cells, hepatocytes, and Kupffer cells after cold preservation and liver transplantation in rats.

BACKGROUND: The injury resulting from cold preservation/reperfusion primarily affects sinusoidal endothelial cells, while hepatocytes are thought to be less vulnerable; morphological changes and increased cytokine release suggest that Kupffer cells are activated. We evaluated the extent of functional damage to the different cell types in the liver after cold preservation and transplantation. Additionally, we analyzed in vivo the patterns of functional recovery of all three cell types over the first week after transplantation in Lewis rats. METHODS: We evaluated the in vivo uptake of hyaluronic acid, indocyanine green, and radio-labeled sulphur colloid to assess the function of sinusoidal endothelial cells, hepatocytes, and Kupffer cells, respectively. Measurements were performed immediately after transplantation using syngeneic grafts preserved in University of Wisconsin solution for different periods. Functional recovery was monitored in animals receiving grafts preserved for 24 hr over the first postoperative week. RESULTS: We found that hepatocyte were less affected compared with the profoundly damaged endothelial cells. The phagocytic ability of Kupffer cells was, however, also seriously compromised, which suggests a selective down-regulation. Functional recovery occurs in a differential manner during the first postoperative week starting with hepatocytes followed by sinusoidal endothelial cells. Phagocytic function further deteriorates after transplantation before showing improvement. CONCLUSIONS: In viable liver grafts, all cell types recover from preservation/reperfusion injury by the end of the first week after transplantation. The differential time courses of the recovery suggest that successful sinusoidal endothelial cell recovery may depend upon prior hepatocyte regeneration and may involve a paracrine interaction, via cytokines and growth factors.

Alanine Transaminase↗
PubMed1998

Liver transplant recipients are not at increased risk for nonlymphoid solid organ tumors.

BACKGROUND: Organ transplant recipients are at higher risk for developing lymphoid tumors, skin carcinomas, and sarcomas. Whether liver transplant recipients are at higher risk for developing more common cancers is unclear. METHODS: All patients with a history of malignancy prior to liver transplantation and those who developed malignancy, either de novo or recurrent, after transplantation were identified retrospectively. The following parameters were examined: age at diagnosis; indication for transplant; interval from transplant to tumor diagnosis; tumor treatment received; predisposing factors for the development of cancer; immunosuppression regimen, including the use of OKT3; number and treatment of rejection episodes; and survival. RESULTS: Of 888 patients, 29 (3.2%) had 31 previous malignancies; of these 29 patients, 4 developed a recurrence in the posttransplant period. Thirty-nine patients (4.3%) developed 43 de novo nonlymphoid malignancies. Alcoholic cirrhotic patients had a significantly higher incidence of de novo carcinomas. Except for skin carcinomas, tumors did not occur with greater frequency than in the general population, and recurrent tumors were not more aggressive than reported for that disease. One patient had an unrecognized renal cell carcinoma at the time of transplant that progressed rapidly; this patient died 64 days after transplantation. CONCLUSIONS: With current immunosuppressive regimens, liver transplant patients do not appear to be at an increased risk for developing nonlymphoid solid organ tumors. However, longer follow-up will be necessary to confirm these results.

Adult↗
PubMed1998

Amino acid availability regulates p70 S6 kinase and multiple translation factors.

Incubation of Chinese hamster ovary cells without amino acids for up to 60 min caused a rapid marked decrease in p70 S6 kinase activity and increased binding of initiation factor eIF4E to its inhibitory regulator protein 4E-BP1. This was associated with dephosphorylation of 4E-BP1 and eIF4E and dissociation of eIF4E from eIF4G. All these effects were rapidly reversed by resupplying a mixture of amino acids and this was blocked by rapamycin and by inhibitors of phosphatidylinositol 3-kinase, implying a role for phosphatidylinositol 3-kinase in the signalling pathway linking amino acids with the control of p70 S6 kinase activity and the phosphorylation of these translation factors. Amino acid withdrawal also led to changes in the phosphorylation of other translation factors; phosphorylation of eIF4E decreased whereas elongation factor eEF2 became more heavily phosphorylated, each of these changes being associated with decreased activity of the factor in question. Earlier studies have suggested that protein kinase B (PKB) may act upstream of p70 S6 kinase. However, amino acids did not affect the activity of PKB, indicating that amino acids activate p70 S6 kinase through a pathway independent of this enzyme. Studies with individual amino acids suggested that the effects on p70 S6 kinase activity and translation-factor phosphorylation were independent of cell swelling. The data show that amino acid supply regulates multiple translation factors in mammalian cells.

Amino Acids↗
PubMed1998

Effect of topographical aspect and farm system on the population dynamics of Trichostrongylus larvae on a hill pasture.

The population dynamics of Trichostrongylus colubriformis larvae were compared over two years on contrasting topographical aspects north (warm and dry) and south-facing (cool and moist) hill slopes) on paddocks which form part of the 'non-chemical' and conventional' farm systems at the AgResearch Ballantrae Hill Country Station located in a summer-moist region of New Zealand. Sheep faeces containing 50,000 Trichostrongylus eggs were incubated for 4 days at 25 degrees C and then deposited on each of 36 sub-plots in each of 8 plots in a 2 x 2 factorial design in the summer (summer trial) and again in autumn (autumn trial). Pasture was removed to ground level and larvae extracted from six sub-plots from each plot 2, 4, 6, 8, 11 and 14 weeks after contamination in all trials. Larvae were recovered from two strata, 0-5 cm above the soil surface and > 5 cm above the soil surface. Fewer (p < 0.001) larvae were recovered from herbage (47 vs. 118) and residual faeces (28 vs. 246) from the autumn than from the summer trials. This coincided with more rapid (p < 0.001) faecal disappearance in the autumn trials. In the summer trials, fewer (p < 0.003) larvae were recovered from the herbage (101 vs. 182) and residual faeces (140 vs. 352) from plots on the south than the north facing aspect. In the autumn trials there was a rapid (p < 0.0001) faecal disappearance from the south-facing aspect. In the autumn trials there was a non-significant (p < 0.10) trend for fewer larvae to be recovered from the south-facing aspect (2 vs. 54). This also coincided with more rapid faecal disappearance from the south-facing aspect. There was no effect of farm system on the number of larvae recovered. Despite greater (p < 0.0001) numbers of larvae recovered from the bottom stratum of herbage, the density of larvae (L3/kg DM) tended (p < 0.12) to be higher in the top stratum of herbage. It was concluded that season and aspect have a marked effect on the number of larvae recovered from herbage and that this was inversely related to the rate of faecal disappearance.

Agrochemicals↗
PubMed1998

Hyperosmolarity associated with diabetes insipidus alters hepatocyte structure and function but not survival after orthotopic liver transplantation in rats.

BACKGROUND: This study was designed to evaluate the effect of donor hyperosmolarity secondary to diabetes insipidus, an almost universal occurrence among brain-dead patients, on hepatic function. METHODS: In vitro (isolated liver perfusion) and in vivo (hyaluronic acid and indocyanine green uptake, arterial ketone body ratio, orthotopic liver transplantation) experiments were conducted using Brattleboro rats, with hereditary hypothalamic diabetes insipidus, and Sprague-Dawley rats, with normal pituitary function. ATP content and recovery after cold preservation were measured during the perfusion. RESULTS: Cold-preserved livers from hyperosmolar rats were observed to have elevated hepatic enzyme release and decreased bile production compared with normosmolar controls. Moreover, in these livers, the recovery of ATP after cold preservation was completely absent. Transmission electron microscopy of liver biopsies collected from hyperosmolar rats demonstrated profound ultrastructural changes, particularly in the mitochondria, that were not evident in the biopsies from normosmolar rats. All the experimental groups demonstrated similar hyaluronic acid uptake, whereas indocyanine green uptake was markedly impaired in the hyperosmolar group, suggesting that hepatocyte and not sinusoidal endothelial cell function is adversely affected by hyperosmolarity. The arterial ketone body ratio was profoundly compromised by chronic and, to an even greater degree, by acute hyperosmolarity. Survival after transplantation using hyperosmolar donors was not affected in this study. CONCLUSIONS: These results are an important step toward understanding the mechanism whereby brain death, a complicated pathophysiologic phenomenon, adversely affects the hepatic allograft.

Adenosine Triphosphate↗
PubMed1998

Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin.

Eukaryotic initiation factor eIF2B catalyses a key regulatory step in mRNA translation. eIF2B and total protein synthesis are acutely activated by insulin, and this requires phosphatidylinositol 3-kinase (PI 3-kinase). The epsilon-subunit of eIF2B is phosphorylated by glycogen synthase kinase-3 (GSK-3), which is inactivated by insulin in a PI 3-kinase-dependent manner. Here we identify the phosphorylation site in eIF2Bepsilon as Ser540 and show that treatment of eIF2B with GSK-3 inhibits its activity. Ser540 is phosphorylated in intact cells and undergoes dephosphorylation in response to insulin. This is blocked by PI 3-kinase inhibitors. Insulin-induced dephosphorylation of this inhibitory site in eIF2B seems likely to be important in the overall activation of translation by this hormone.

Amino Acid Sequence↗
PubMed1998

The efficacy of prophylactic interferon alfa-2b in preventing recurrent hepatitis C after liver transplantation.

Clinical recurrence of hepatitis C after liver transplantation can lead to cirrhosis, liver failure, and death. In patients undergoing liver transplantation for hepatitis C, we assessed the efficacy of interferon alfa-2b (IFN) in preventing recurrent hepatitis. We randomized 86 patients to either an IFN group (3 MU three times a week starting within 2 weeks after transplantation and continued for 1 year) or a control (no IFN) group. Recurrence, the primary end point, was diagnosed on biopsy performed at 1 year or for abnormal biochemistries. HCV RNA levels were measured by branched-chain DNA (bcDNA) assay and arbitrarily defined as low, moderate, or high (< 10 x 10(5), 10-100 x 10(5), or > 100 x 10(5) Eq/mL, respectively). Data on 30 IFN patients and 41 no-IFN patients who survived > or = 3 months were reviewed. Mean follow-up was 669 +/- 228 days for IFN patients and 594 +/- 254 days for no-IFN patients. IFN patients were less likely to develop recurrent hepatitis (8 IFN vs. 22 no-IFN patients, P = .017, log rank analysis). IFN and 1-month HCV RNA level were independent predictors of recurrence. IFN reduced the risk of recurrence by a factor of 0.4 (P = .04, Cox proportional hazards model); HCV RNA level > 100 x 10(5) Eq/mL at 1 month after transplantation increased the risk by a factor of 3.1 (P = .01). Low, moderate, and high viral levels at 1 and 3 months were associated with significantly different rates of recurrence in IFN patients (P = .05 at 1 month and P = .003 at 3 months) but not in untreated patients (P = .28 at 1 month and P = .25 at 3 months). In patients with two or more rejections, the risk of recurrence was increased by a factor of 2.17 (P = .05). On 47 1-year biopsies (24 IFN; 23 no IFN), piecemeal necrosis was more common in untreated patients (P < .02). One- and 2-year patient survival, respectively, was 96% and 96% with IFN and 91.2% and 87.2% without (P = NS). Prophylactic IFN reduced the incidence of recurrent hepatitis after transplant. Although IFN was most effective in patients with low HCV RNA levels, we also noted an effect in patients with moderate levels. IFN did not prevent viremia, suggesting that it may work through alternative mechanisms.

Adult↗
PubMed1998

The impact of cyclosporine dose and level on acute rejection and patient and graft survival in liver transplant recipients.

A multicenter, retrospective analysis of 623 liver transplant recipients was performed to define safe and effective cyclosporine doses and blood levels at various times after transplantation. Patient and graft survival were assessed as efficacy parameters, and serum creatinine and cholesterol levels as safety parameters. The mean daily cyclosporine dose was 12.1 mg/kg/d at 1 month posttransplantation and 5.5 mg/kg/d after 1 year. After 4 years, the mean cyclosporine dose was maintained at 4.0 mg/kg/d. Mean cyclosporine blood levels showed a similar trend. Patient and graft survival after 4 years of cyclosporine maintenance therapy were 72% and 67%, respectively. Both serum creatinine and cholesterol levels were stable over the study period, and neither correlated with cyclosporine dose. The cumulative incidence of biopsy-proven acute cellular rejection was 59% for early (< 6 months) episodes and 21% for late (> or = 6 months) episodes. Patient and graft survival did not differ significantly between patients experiencing early or late acute rejection episodes and those who did using univariate analysis. The high patient and graft survival, low rejection rates, and lack of significant renal dysfunction or hypercholesterolemia suggest that the cyclosporine doses and blood levels described are safe and therapeutically effective.

Adult↗
PubMed1998

Donor des-gamma-carboxy prothrombin positivity is a risk factor for poor early graft function in liver transplantation.

Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin that lacks coagulating activity. The aim of this study was to determine if the presence of DCP in the donor could be used as a marker of post-transplant graft function. We collected data and serum samples on 90 organ donors. DCP level was correlated with donor-specific factors and with graft function intraoperatively and in the early post-transplant period. Twenty-seven donors (30.0%) had positive DCP levels before harvesting. Although recipients were similar in demographics, preoperative liver function, and primary disease distribution, patients transplanted with livers from DCP-positive donors needed significantly more intraoperative transfusion. Furthermore, donor DCP positivity was identified as a preoperative risk factor for poor early graft function based on multivariate analysis (odds ratio = 6.58, P = 0.0032). Our findings suggest that DCP is another valuable marker for evaluating the quality of donor livers.

Adolescent↗
PubMed1998

Effect of plant species on the larvae of gastrointestinal nematodes which parasitise sheep.

Faeces containing Trichostrongylus colubriformis and/or Ostertagia circumcincta eggs were used to provide four contaminations in each of 2 years on plots of browntop, Yorkshire fog, ryegrass, tall fescue, lucerne, chicory, cocksfoot, white clover, and prairie grass and in the second year a mixed sward of ryegrass/white clover. Third stage larvae were recovered from faeces and from four strata of herbage, 0-2.5, 2.5-5, 5-7.5 and > 7.5 cm above the soil surface at 2, 4, 6, 8, 11, and 14 weeks after faeces were deposited on the swards. Herbage species had a significant (P < 0.0001) effect on the number of larvae recovered. Greatest numbers of larvae, as indicated by ranking analysis, were recovered from Yorkshire fog, ryegrass, and cocksfoot and lowest numbers from white clover and lucerne. The difference between herbages in numbers of larvae recovered was due to the "development success", the ability of larvae to develop to the infective stage and migrate on to herbage, rather than "survival", the rate of population decline once on the herbage. Faecal degradation was most rapid from white clover and browntop, intermediate from tall fescue, lucerne, prairie grass, cocksfoot, and ryegrass, and slowest from Yorkshire fog swards. The numbers of larvae recovered from herbages were related (r2 = 0.59, P < 0.05) with the faecal mass remaining. A greater proportion of the total larvae recovered from the herbage was recovered from the bottom stratum of Yorkshire fog and prairie grass than from white clover, with the other herbages intermediate, indicating that larvae had greater difficulty migrating up Yorkshire fog and prairie grass than the other herbage species. In most herbage species, despite more larvae being recovered from the lowest stratum, larval density (L3/kg herbage DM) was highest in the top stratum. This study has demonstrated that herbage species can have a significant impact on the population dynamics and vertical migration of T. colubriformis and O. circumcincta larvae.

Animals↗
PubMed1998

Aggressive surgical treatment of intrahepatic cholangiocarcinoma: predictors of outcomes.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and constitutes 10% of primary liver malignancies. Surgery is the optimal therapy; the majority of the patients will require extensive resections that are associated with significant morbidity. METHODS: We retrospectively studied the records of 26 patients who underwent exploratory laparotomy for intrahepatic cholangiocarcinoma between June 1991 and December 1997 at the Mount Sinai Hospital. Patients with perihilar (Klatskin) tumors were excluded. All patients were considered resectable based on CT or MRI findings. Patients with positive margins or nodal invasion received adjuvant chemotherapy and radiation. RESULTS: Sixteen patients underwent 18 resections; in 10 patients the tumors were unresectable at laparotomy and only biopsy was performed. The mean age (62 versus 53 years) was significantly higher, and the mean total bilirubin level (0.71 versus 6.17 mg/dL) was significantly lower in the resected group (p=0.031 and 0.017, respectively). No patient with a total bilirubin over 1.2 mg/dL was found to be resectable. Median actuarial survivals were 42.9+/-8.9 months for resectable and 6.7+/-3.6 months for unresectable patients (p=0.005). Positive margins were associated with significantly shorter disease-free survival. But resected patients with positive margins survived significantly longer than those who were unresectable. Tumor size, presence of satellite nodules, and degree of tumor necrosis on histologic examination were significant predictors of outcomes. Survival among patients receiving adjuvant therapy was not significantly altered. CONCLUSIONS: We conclude that an aggressive surgical approach is warranted in patients with ICC because resection offers the only hope for longterm survival. Our findings emphasize the importance of achieving tumor-free margins. Noncurative resection offers a survival advantage over no resection. Histologic examination of resected specimens can help select patients with poor prognoses.

Actuarial Analysis↗
PubMed1998

The effect of continuous drug exposure on the immune response of lambs challenged with drug-susceptible or drug-resistant nematode larvae.

Groups of lambs either with or without controlled-release albendazole (ABZ) capsules (CRCs) were challenged twice weekly for 6 weeks with either drug-susceptible or drug-resistant Ostertagia circumcincta and Trichostrongylus colubriformis. Groups with and without CRCs remained unchallenged as controls. There was minimal establishment of drug-susceptible parasites of either species in those lambs with CRCs. However, drug-resistant parasites of both species established adult worm burdens in the presence of the capsules. The humoral immune response, as measured by the serum antilarval (L3) antibody (Ab) titre, was pooled for weeks 4-6 and compared for each group. With the exception of anti-T. colubriformis Ab in group 2, anti-L3 Ab titres were significantly higher in all the parasite-challenged groups as compared to the control animals. Also, with the exception of anti-resistant O. circumcincta Ab levels in the CRC-treated animals (group 5), no significant difference was observed in Ab titres between the four groups challenged with either resistant or susceptible larvae. The results demonstrate the inability of CRCs to prevent establishment of drug-resistant parasites and that immune stimulation is not inhibited by the capsules.

Albendazole↗
PubMed1998

Ecomycins, unique antimycotics from Pseudomonas viridiflava.

A novel family of peptide antimycotics, termed ecomycins, is described from Pseudomonas viridiflava, a plant-associated bacterium. Ecomycins B and C have molecular masses of 1153 and 1181. They contain equimolar amounts of a beta hydroxyaspartic acid, homoserine, threonine, serine, alanine, glycine and one unknown amino acid. Fatty acids were detectable after hydrolysis, methylation and gas chromatography and mass spectroscopy. The ecomycins have significant bioactivities against a wide range of human and plant pathogenic fungi. The minimum inhibitory concentration values for ecomycin B were 4.0 micrograms ml-1 against Cryptococcus neoformans and 31 micrograms ml-1 against Candida albicans. Pseudomonas viridiflava also produces what appears to be syringotoxin, an antifungal lipopeptide previously described from Ps. syringae.

Amino Acids↗
PubMed1997

ErbB kinases and NDF signaling in human prostate cancer cells.

Prostate carcinoma (PCA) is the most commonly diagnosed malignancy in American men. Our knowledge of PCA growth regulation lags behind that of other cancers, such as breast and colon carcinomas. Among receptor tyrosine kinases, the ErbB family is most frequently implicated in neoplasia. We report here the expression of ErbB family kinases and their ligands in PCA cell lines and a xenograft. While ErbB1/EGFR, ErbB2/NEU, and ErbB3 were always observed in a distinct pattern, ErbB4 was not observed. Interestingly, while TGF-alpha was expressed in the majority of PCA lines, the ligand Neu Differentiation Factor/Heregulin (NDF) was expressed only in an immortalized, non-transformed prostate epithelial line. Concomitantly, there was a significant difference in biological response to these ligands. NDF inhibited LNCaP growth and induced an epithelial-like morphological change, in contrast to TGF-alpha, which accelerated cell growth. We also performed the first comprehensive analysis of NDF signaling in a prostate line. LNCaP stimulated with NDF demonstrated crosstalk between ErbB3 and ErbB2 which did not involve ErbB1. NDF also turned on several cascades, including those of PI3-K, ERK/MAPK, mHOG/p38 and JNK/SAPK, but not those of PLCgamma or the STAT family. This signaling pattern is distinct from that of TGF-alpha. The activation of mHOG by ErbB2 or ErbB3 has not been reported, and may contribute to the unusual phenotype. PI3-K activation is characterized by the formation of a striking 'activation complex' with multiple tyrosine-phosphorylated species, including ErbB3. Our studies provide a framework in which to dissect the growth and differentiation signals of prostate cancer cells.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1997

Persistent hypersplenism early after liver transplant: the role of splenectomy.

BACKGROUND: Transient thrombocytopenia is common after liver transplantation, but persisting thrombocytopenia worsens the prognosis after transplant. METHODS: Two patients underwent splenectomy for persistent thrombocytopenia early after liver transplantation. The first patient had a platelet count of 17,000/mm3 on postoperative day (POD) 6; her hemoglobin and white blood cell counts were normal. Work-ups including bone marrow aspiration, Coombs test, and antiplatelet antibody test were negative. On POD 9, she had abdominal bleeding with a platelet count of 17,000/mm3 despite repeated platelet transfusions, and splenectomy was done. The second patient had a platelet count of 3000/mm3 on POD 14, white blood cell was 1600/mm3, and hemoglobin was 7.7 g/dl. Bone marrow biopsy revealed hypercellular marrow. Because his platelet count remained at 2000/mm3 despite empiric treatment with intravenous immune globulin and methylprednisolone, splenectomy was performed. RESULTS: The first patient's platelet count rose to 155,000/mm3 by POD 8. The second patient's platelet count reached 210,000/mm3 on POD 5. Neither patient has had an episode of thrombocytopenia at 36 and 32 months after splenectomy. CONCLUSIONS: Splenectomy can be used after liver transplantation for severe, persistent thrombocytopenic states that cannot be attributed to sepsis, intravascular coagulation, immunological causes, or drug effects.

Adolescent↗
PubMed1997

Selective revascularization of hepatic artery thromboses after liver transplantation improves patient and graft survival.

BACKGROUND: Hepatic artery thrombosis (HAT) can be a devastating complication of orthotopic liver transplantation (OLT), but early diagnosis may allow successful revascularization and graft salvage. METHODS: We reviewed data on 1,026 liver transplants at our institution. For patients in whom HAT was diagnosed within 30 days after OLT, we recorded indications for ultrasonography and liver function tests at diagnosis, management of HAT, and graft and patient survival. RESULTS: Thirty-two patients (3.1%) developed HAT at 6.8+/-6.6 days (range, 1-29 days) after OLT. Twelve patients (37.5%) were asymptomatic at diagnosis. In 11 of these 12, HAT was diagnosed on routine duplex at 2.0+/-1.55 days after OLT; in the 12th patient, HAT was noted during re-exploration for unrelated bleeding on postoperative day 3. Eleven of 12 patients (91.6%) were revascularized; one patient (8.4%) received no treatment with no sequelae. Of the 11 who were revascularized, 9 (81.8%) had graft salvage and 2 (18.2%) received a second transplant, with one death. Twenty patients (62.5%) were symptomatic. In these 20, HAT was diagnosed at 9.85+/-6.93 days after OLT. Symptoms were: elevated liver function test results (serum glutamic oxaloacetic transaminase: 722+/-1792 U/ml, serum glutamic pyruvic transaminase: 678+/-963 U/ml, and bilirubin: 10.2+/-6.2 mg/dl) in 13 patients (65%); bile leak in 4 patients (20%), and sepsis in 3 (15%). Five of the 20 patients (25%) were revascularized; of these 5, 2 (40%) had graft salvage, 2 (40%) received a second transplant with 1 death, and 1 (20%) died of a liver abscess. Twelve symptomatic patients (60%) had immediate re-OLT; 10/12 are alive, 1 died of sepsis, and 1 died late of unrelated causes. Three symptomatic patients had no treatment; two died of biliary sepsis and one survived. Overall graft salvage was 83.3% in asymptomatic patients and 15% in patients with symptoms (P<0.001). Graft salvage in asymptomatic patients undergoing revascularization was 81.8%, versus 40% in symptomatic patients (P=NS). One-year patient survival was 91.7% in asymptomatic patients and 65% in symptomatic patients (with one late death excluded) (P=NS). CONCLUSIONS: Routine postoperative duplex ultrasonography should be performed early after liver transplantation. We believe that emergent revascularization of hepatic artery thrombosis in asymptomatic patients and retransplantation in symptomatic patients lead to improved graft salvage and patient survival with a relatively low incidence of late biliary complications.

Acute Disease↗