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William C Chapman

Publications and source records attributed to William C Chapman.

At least 37 records · Page 2Linked to original sources
PubMed2004

Natural antibodies prevent in vivo transmission of porcine islet-derived endogenous retrovirus to human cells.

The discovery of porcine endogenous retroviruses (PERV) has raised concerns regarding the safety of porcine xenotransplantation. However, transmission of PERV had not been observed in humans exposed to porcine tissue. We examined whether PERV derived from porcine pancreatic islet cells could infect human cells in vivo and the role of natural antibodies in inhibiting PERV infection. In vivo infective potential of PERV was studied in SCID mice reconstituted with human peripheral blood leucocytes. Porcine islets were transplanted under the kidney capsule. PERV infection was determined by analyzing PERV gene expression in graft infiltrating lymphocytes (GIL) harvested 21 days posttransplantation. Mice were administered normal human serum prior to and 2 days posttransplantation to study their role in protection of human cells against PERV infection. PERV genes were expressed in all porcine tissues examined, including purified porcine islets. PERV expression was detected in GILs from three of five human-SCID mice. Administration of human serum blocked PERV infection in GILs in five of five human-SCID mice. These results indicate that PERV from porcine islets can infect human cells in vivo. Normal human serum blocks transmission of retrovirus in vivo, suggesting that natural xenoreactive antibodies can prevent PERV infection.

Animals↗
PubMed2003

Multi-organ inflammation after hepatic cryoablation in BALB/c mice.

BACKGROUND: There is increasing evidence that injury to the liver can precipitate or exaggerate lung injury. We have previously shown that hepatic cryoablation (cryo) causes activation of nuclear factor (NF)-kappaB, cytokinemia (tumor necrosis factor-alpha, Mouse Macrophage Inflammatory Protein-2 [MIP-2]), and lung inflammation in transgenic HLL (5'HIV-LTR-Luciferase gene) mice and in Sprague-Dawley rats. It has been reported that BALB/c mice are susceptible to traumatic injury and are active immune responders. We tested whether activation of NF-kappaB and the development of multiple-organ inflammation in response to hepatic injury from 35% cryo were demonstrable in the BALB/c mouse. METHODS: BALB/c mice (n = 9) were anesthetized, and midline laparotomy was performed. Cryoablation was performed with careful isolation of adjacent structures to avoid inadvertent organ injury to the gastrointestinal tract. A freeze-thaw cycle of the left lobe of the liver was induced, encompassing approximately 35% (by weight). Animals were sacrificed at 1, 2, 4, and 24 h after cryoablation. Serum was collected via IVC puncture and liver, lungs, and kidneys were harvested and freeze-clamped. Two animals were sacrificed without undergoing cryo surgery to serve as a baseline control. NF-kappaB activity was monitored by electrophoretic mobility shift assays. MIP-2 levels and Mouse KC levels from tissue and serum were measured using enzyme-linked immunosorbent assay. Organs were submitted for histological review. We characterized lung inflammation induced by cryosurgery by measuring total and differential cell counts in lung lavage fluid 4 h after hepatic cryoablation. RESULTS: After cryo, NF-kappaB activation was demonstrated in the 1, 2, and 4-h time points by electrophoretic mobility shift assay in the liver and lungs. Mouse KC and MIP-2 levels increased from baseline, peaked at the 4-h time point, and returned to baseline after 24 h in both liver and lung. Lung lavage 4 h after cryoablation showed increased total cells and neutrophilic lung inflammation. CONCLUSIONS: BALB/c mice demonstrate evidence of multi-organ inflammation in response to 35% hepatic cryo. These data demonstrate that this model provides for assessment of liver-mediated multi-system inflammation after direct liver injury.

Animals↗
PubMed2003

Endotoxin potentiates lung injury in cerulein-induced pancreatitis.

BACKGROUND: In this study we examine the effect of endotoxin (lipopolysaccharide) on lung injury in the setting of acute pancreatitis (AP). METHODS: Twelve hourly injections of cerulein (50 microg/kg/h) were used to induce pancreatitis in mice. Intraperitoneal lipopolysaccharide (LPS [6 mg/kg]) was administered 24 hours after the initial cerulein injection. Twenty-four hours after LPS injection, myeloperoxidase (MPO) activity, nuclear factor (NF)-kappaB activation, and tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and chemokines MIP-2 and KC levels were measured in pancreas, liver, and lung tissues. Four groups of mice were studied: cerulein-LPS, cerulein-saline, saline-LPS, and saline-saline treated mice. RESULTS: Elevated serum lipase confirmed pancreatitis in cerulein treated mice. Lung MPO activity was significantly increased in the cerulein-LPS group. NF-kappaB was activated in the liver but not in pancreas and lung tissue. Chemokines MIP-2 and KC were elevated in pancreatic tissue only. CONCLUSIONS: These findings suggest that gram-negative infections may be an important predisposition for the development of adult respiratory distress syndrome in the setting of AP and that hepatic NF-kappaB may mediate multisystem injury.

Animals↗
PubMed2003

Systemic nf-kappaB activation in a transgenic mouse model of acute pancreatitis.

BACKGROUND: Transcription factor NF-kappaB has been implicated in numerous human inflammatory diseases. Acute pancreatitis can result in remote tissue injury, but the involved mechanisms are unknown. This study evaluates the role of systemic NF-kappaB activation in the pathogenesis of lung inflammation in a transgenic pancreatitis model. MATERIALS AND METHODS: Using transgenic mice expressing photinus luciferase controlled by an NF-kappaB-dependent promoter, luciferase activity was measured in pancreas, liver, and lung tissues as a surrogate marker of NF-kappaB activity. Luciferase activity was measured by in vivo bioluminescence and correlated to an in vitro luciferase assay of organ homogenates. Following measurement of luciferase activity in uninjured animals, these animals were fed a choline-deficient, ethionine supplemented diet for 48 h to induce pancreatitis, and luciferase activity was then measured at 48, 60, 72, and 96 h. Lung inflammation was determined by total nucleated cell counts in bronchoalveolar lavage (BAL) fluid. RESULTS: Bioluminescence detected increased luciferase activity over the upper abdominal region at 48 and 60 h (P < 0.05), and over the thorax at 60 and 72 h (P < 0.05). Luciferase assays showed significantly increased luciferase activity in both liver and lung tissue at 48 (liver = P < 0.005, lung = P < 0.05) and 60 h (liver = P < 0.05, lung = P < 0.05) compared to activity in uninjured controls. Total nucleated cell counts in BAL fluid were significantly increased at 72 h (P < 0.05) compared with controls. CONCLUSION: In this model, NF-kappaB binding activity is increased in the liver and lung. These data suggest that the liver modulates pancreatitis-induced systemic inflammatory response syndrome (SIRS) and suggest strategies to reduce multisystem injury.

Acute Disease↗
PubMed2003

Lack of optimal T-cell reactivity against the hepatitis C virus is associated with the development of fibrosis/cirrhosis during chronic hepatitis.

Chronic hepatitis C virus (HCV) infection develops in 85% of exposed individuals and 20% develop cirrhosis. However, the pathogenesis of this process is not well-understood. The objective of this study was to determine whether HCV-reactive T cells play a role in the process of development of cirrhosis during chronic HCV infection. We analyzed 21 human leukocyte antigen (HLA)-A2 patients with chronic HCV infection (9 with histology of inflammation and 12 with histology of fibrosis/cirrhosis). The frequency of CD8(+) T cells reactive to 12 HCV-derived epitopes was determined by an interferon-gamma enzyme-linked immunospot (ELISPOT) assay. The frequency of CD4(+) Th1 and Th2 cells reactive to the HCV core antigen was determined by interferon-gamma and interleukin-5 ELISPOT assays, respectively. Patients with histology of inflammation showed a significantly higher CD8(+) T-cell response to five HCV-derived epitopes (YLLPRRGPRL [core], CINGVCWTV [NS3], LLCPAGHAV [NS3], ILAGYGAGV [NS4B], and GLQDCTMLV [NS5B]) as compared with patients with histology of fibrosis/cirrhosis. Also, patients with histology of inflammation showed a significantly higher CD4(+) Th1 response to the HCV core antigen as compared to patients with histology of fibrosis/cirrhosis. These results indicate that a lack of an optimal T-cell response to HCV is associated with the development of cirrhosis during chronic HCV infection.

Adult↗
PubMed2003

Concomitant augmentation of type 1 CD4+ and CD8+ T-cell responses during successful interferon-alpha and ribavirin treatment for chronic hepatitis C virus infection.

The combined interferon-alpha (IFN-alpha) and ribavirin (IFN-alpha/ribavirin) therapy for chronic hepatitis C virus (HCV) infection results in sustained viral eradication in 31%-64% of the patients. Previous studies have strongly suggested that HCV-specific T-cell responses maybe modulated during this therapy. The objective of this study was to further define the effect of IFN-alpha/ribavirin therapy on type 1 and type 2 HCV-specific CD4(+) and CD8(+) T-cell responses during IFN-alpha/ribavirin therapy. Toward this, serial CD8(+) T-cell responses to HCV-derived epitopes and CD4(+) T-cell responses to the HCV core antigen were analyzed in four patients before (baseline), during (at 24 weeks), and at the end (at 48 weeks) of IFN-alpha/ribavirin therapy. Therapy-induced viral clearance in three patients was associated with a significant augmentation of HCV-specific type 1 CD4(+) and CD8(+) T-cell responses. In contrast, in a patient who did not respond to therapy, a significant HCV-specific CD4(+) Th2 cell reactivity was observed accompanied by a lack of augmentation of the HCV-specific CD8(+) T-cell reactivity. These results indicate that enhancement of HCV-specific CD4(+) and CD8(+) T-cell responses is an important factor in determining the response to the IFN-alpha/ribavirin therapy and the outcome of the HCV infection.

Antiviral Agents↗
PubMed2003

Indications and limitations of liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common cause of cancer-related death worldwide, yet remains difficult to treat, with dismal overall long-term survival rates. Recent strategies using liver transplantation for carefully selected patients with stage I and II HCC and cirrhosis have shown promising results, with 5-year survival rates comparable to survival rates for transplantation patients without malignancy. Currently, however, limited resources and a severe organ shortage make liver transplantation an option for only a limited number of patients with HCC in the United States. Future studies must document the long-term success of this therapy and improve methods for disease control before and after transplantation.

Carcinoma, Hepatocellular↗
PubMed2003

Incorporation of a laser range scanner into image-guided liver surgery: surface acquisition, registration, and tracking.

As image guided surgical procedures become increasingly diverse, there will be more scenarios where point-based fiducials cannot be accurately localized for registration and rigid body assumptions no longer hold. As a result, procedures will rely more frequently on anatomical surfaces for the basis of image alignment and will require intraoperative geometric data to measure and compensate for tissue deformation in the organ. In this paper we outline methods for which a laser range scanner may be used to accomplish these tasks intraoperatively. A laser range scanner based on the optical principle of triangulation acquires a dense set of three-dimensional point data in a very rapid, noncontact fashion. Phantom studies were performed to test the ability to link range scan data with traditional modes of image-guided surgery data through localization, registration, and tracking in physical space. The experiments demonstrate that the scanner is capable of localizing point-based fiducials to within 0.2 mm and capable of achieving point and surface based registrations with target registration error of less than 2.0 mm. Tracking points in physical space with the range scanning system yields an error of 1.4 +/- 0.8 mm. Surface deformation studies were performed with the range scanner in order to determine if this device was capable of acquiring enough information for compensation algorithms. In the surface deformation studies, the range scanner was able to detect changes in surface shape due to deformation comparable to those detected by tomographic image studies. Use of the range scanner has been approved for clinical trials, and an initial intraoperative range scan experiment is presented. In all of these studies, the primary source of error in range scan data is deterministically related to the position and orientation of the surface within the scanner's field of view. However, this systematic error can be corrected, allowing the range scanner to provide a rapid, robust method of acquiring anatomical surfaces intraoperatively.

Aged↗
PubMed2003

The role of [18F]fluorodeoxyglucose positron emission tomography imaging in the evaluation of hepatocellular carcinoma.

It has been well established that hepatocellular carcinomas (HCCs) accumulate [18F]fluorodeoxyglucose (FDG) to varying degrees; this is thought to be due to differing amounts of FDG-6-phosphatase activity. The purpose of this study was to evaluate the impact of FDG imaging on the management of patients diagnosed with hepatocellular carcinoma. We conducted a retrospective review of the clinical data of 91 consecutive patients diagnosed with HCC who underwent FDG-positron emission tomography (PET) imaging between August 1993 and March 2001. The patients were divided into two groups. In Group one 67 of 91 (74%) patients were evaluated for proven but untreated hepatic lesions using PET. In Group two the remaining 24 patients (26%) were referred for evaluation of HCC recurrence but did not have prior PET. The FDG images were acquired with two dedicated PET tomographs [Siemens ECAT 933, CTI (Knoxville, TN) and GE Advance, General Electric Medical Systems (Milwaukee, WI)] one hour after the intravenous administration of 10 mCi of FDG. Tumor biopsy or resection specimens were available for review from 34 patients and were evaluated for histologic grade, presence of cirrhosis, tumor necrosis, and intratumoral fibrosis. In group one 43 of 67 (64%) of the HCCs accumulated FDG. Sixteen of the 43 patients in whom FDG was accumulated had multiple subsequent FDG-PET scans either for monitoring therapy or for detection of recurrence. FDG-PET imaging had an impact on the management of 20 of these patients: by guiding the biopsy at the metabolically active site of a large necrotic tumor (one), by identifying distant metastases (five), by monitoring the response to treatment with hepatic chemoembolization and guiding additional regional therapy (12), and by detecting recurrence (two). In group two recurrence and/or metastases were demonstrated with FDG-PET imaging in six of 24 (25%) patients, three of whom had multiple subsequent FDG-PET scans to monitor their treatment. Higher histopathologic grade and intratumoral fibrosis but not necrosis or cirrhosis correlated with PET positivity. In this study only 64 per cent of HCCs accumulated FDG. Despite this limitation FDG-PET imaging remains a useful tool in the diagnosis and treatment of HCC. FDG-PET imaging had a clinically significant impact in 26 of 91 (28%) patients with HCC. This includes detection of unsuspected metastatic disease in high-risk patients-including liver transplant candidates-and monitoring response to hepatic-directed therapy. FDG-PET should be considered as part of the workup and management of selected patients with HCC.

Adult↗
PubMed2002

Water warming garment versus forced air warming system in prevention of intraoperative hypothermia during liver transplantation: a randomized controlled trial [ISRCTN32154832].

BACKGROUND: The authors compared two strategies for the maintenance of intraoperative normothermia during orthotopic liver transplantation (OLT): the routine forced-air warming system and the newly developed, whole body water garment. METHODS: In this prospective, randomized and open-labelled study, 24 adult patients were enrolled in one of two intraoperative temperature management groups during OLT. The water-garment group (N = 12) received warming with a body temperature (esophageal) set point of 36.8 degrees C. The forced air-warmer group (N = 12) received routine warming therapy using upper- and lower-body forced-air warming system. Body core temperature (primary outcome) was recorded intraoperatively and during the two hours after surgery in both groups. RESULTS: The mean core temperatures during incision, one hour after incision and during the skin closing were significantly higher (p < 0.05, t test with Bonferroni corrections for the individual tests) in the water warmer group compared to the control group (36.7 PlusMinus; 0.1, 36.7 PlusMinus; 0.2, 36.8 PlusMinus; 0.1 vs 36.1 PlusMinus; 0.4, 36.1 PlusMinus; 0.4, 36.07 PlusMinus; 0.4 degrees C, respectively). Moreover, significantly higher core temperatures were observed in the water warmer group than in the control group during the placement of cold liver allograft (36.75 PlusMinus; 0.17 vs 36.09 PlusMinus; 0.38 degrees C, respectively) and during the allograft reperfusion period (36.3 PlusMinus; 0.26 vs 35.52 PlusMinus; 0.42 degrees C, respectively). In addition, the core temperatures immediately after admission to the SICU (36.75 PlusMinus; 0.13 vs 36.22 PlusMinus; 0.3 degrees C, respectively) and at one hr (36.95 PlusMinus; 0.13 vs 36.46 PlusMinus; 0.2 degrees C, respectively) were significantly higher in the water warmer group, compared to the control group, whereas the core temperature did not differ significantly afte two hours in ICU in both groups. CONCLUSIONS: The investigated water warming system results in better maintenance of intraoperative normothermia than routine air forced warming applied to upper- and lower body.

Journal Article↗
PubMed2002

Modulation of endotoxin-induced NF-kappa B activation in lung and liver through TNF type 1 and IL-1 receptors.

We investigated the requirement for tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 receptors in the pathogenesis of the pulmonary and hepatic responses to Escherichia coli lipopolysaccharide (LPS) by studying wild-type mice and mice deficient in TNF type 1 receptor [TNFR1 knockout (KO)] or both TNF type 1 and IL-1 receptors (TNFR1/IL-1R KO). In lung tissue, NF-kappaB activation was similar among the groups after exposure to aerosolized LPS. After intraperitoneal injection of LPS, NF-kappaB activation in liver was attenuated in TNFR1 KO mice and further diminished in TNFR1/IL-1R KO mice; however, in lung tissue, no impairment in NF-kappaB activation was found in TNFR1 KO mice and only a modest decrease was found in TNFR1/IL-1R KO mice. Lung concentrations of KC and macrophage-inflammatory peptide 2 were lower in TNFR1 KO and TNFR1/IL-1R KO mice after aerosolized and intraperitoneal LPS. We conclude that LPS-induced NF-kappaB activation in liver is mediated through TNF-alpha- and IL-1 receptor-dependent pathways, but, in the lung, LPS-induced NF-kappaB activation is largely independent of these receptors.

Aerosols↗
PubMed2002

Disparate outcomes in patients with colorectal cancer: effect of race on long-term survival.

BACKGROUND: Increasing evidence suggests significant disparity in colorectal cancer outcomes between black and white patients. Contributing factors may include advanced tumor stage at diagnosis, differences in treatment, more aggressive tumor biology, access to care, and patient comorbidity. HYPOTHESIS: Disparities in colorectal cancer outcomes exist despite similar objective measures of treatment. DESIGN AND SETTING: Ten-year retrospective review of all patients with colorectal cancer using tumor registries at a city hospital (n = 83) and a university medical center (n = 585) in the same city. We assessed stage at diagnosis; curative surgical resection; use of adjuvant treatment; overall, disease-free, and stage-specific survival; and socioeconomic status. Patients with nonwhite, nonblack ethnicity (4% overall) were excluded. Differences in stage and treatments were compared using the chi(2) test, and median survival rates were compared using log-rank tests. RESULTS: Significantly more black patients were treated at the city hospital (53.0%) vs the university medical center (10.6%) (P<.001). No differences were identified in stage distribution or treatments received between hospitals or between black and white patients. Significantly worse survival was noted among patients treated at the city hospital (2.1 vs 5.3 years; P<.001) and among black patients treated at both institutions (city hospital: 1.4 vs 2.1 years, and university hospital: 3.2 vs 5.7 years; P<.001 for both). Disease-free survival rates showed similar significant reductions for black patients at both institutions. There was no association between survival and socioeconomic status at either institution. CONCLUSION: The marked reductions in overall and disease-free survival for black patients with colorectal cancer do not seem to be related to variation in treatment but may be due to biologic factors or non-cancer-related health conditions.

Black or African American↗
PubMed2002

Prevention of gallstone formation in morbidly obese patients undergoing rapid weight loss: results of a randomized controlled pilot study.

INTRODUCTION: An increased risk of gallstone (GS) formation has been linked to obesity and to episodes of rapid and significant weight loss. Previous reports have suggested that bile salt therapy (ursodeoxycholic acid) or prostaglandin inhibition (ibuprofen) may prevent gallstone formation in this high-risk group. The purpose of this study was to investigate GS prevention following bariatric surgery. DESIGN: Randomized double blind controlled trial. METHODS: Sixty patients without gallstones preoperatively (gender, 9 male, 51 female; average preop wt, 349.6 lb; mean age, 38 years) were randomly assigned to receive urso (600 mg/day, n = 20), ibuprofen (600 mg/d, n = 20), or placebo (n = 20). At the time of standard open gastric bypass, intraoperative ultrasonography confirmed the absence of stones or microcalculi, and bile samples were collected via puncture of the gallbladder for bile lipid analysis. Following recovery and resumption of a bariatric diet, study medication was prescribed for the first 6 months postop. Gallbladder emptying and GS formation were assessed using ultrasonograms preop and at 3, 6, 9, and 12 months postop (gallbladder emptying following a high-fat liquid test meal was assessed preop, and at 3 and 6 months postop). RESULTS: Forty-one (68.3%, 8 male, 33 female) of the original 60 patients completed all phases of the study (15 urso, 15 ibuprofen, 11 placebo). The average weight loss was 98.5 +/- 7.2 lb over the 12-month period following bariatric surgery. Twenty-nine (71%) of 41 patients who completed the study developed GS. Of those who formed stones, 12 (41%) developed symptomatic GS and 8/12 (67%) underwent cholecystectomy (4 refused operation). Preoperative gallbladder emptying studies showed no differences in emptying between groups (urso 29%, ibuprofen 32%, and placebo 30%). There was no correlation found between the cholesterol saturation index (CSI mean 205.15, range 67-360) and the incidence of GS. There was a statistical difference (P < 0.01) between the ursodeoxycholic acid group and the ibuprofen group with respect to the incidence of stone formation. There was correlation between weight loss (mean 99 lb, range 21-278 lb) and GS formation, in that patients who lost more weight had a greater tendency to form gallstones. Complete medical compliance was achieved in only 17/60 (28%) of patients originally enrolled. CONCLUSIONS: This pilot study confirms the high incidence of gallstone formation (71% of assessed patients) associated with rapid weight loss in patients undergoing gastric bypass. Despite active enrollment in a supervised prevention trial, the two therapies investigated to reduce gallstone formation were not efficacious, likely because compliance with medical therapy was poor. These findings highlight the significant risk of gallstone formation in this patient cohort even when prevention strategies are utilized.

Adult↗
PubMed2002

Biliary reconstruction is enhanced with a collagen-polyethylene glycol sealant.

Bile leaks occur in up to 27 per cent of liver transplant patients after biliary reconstruction. Synthetic sealants have not been investigated for these biliary procedures. We performed a randomized controlled study to evaluate a novel absorbable polyethylene glycol/collagen biopolymer sealant (CT3 Surgical Sealant) after incomplete end-to-end choledochocholedochostomy (CDCD) in pigs. Pigs (n = 18) underwent transection of the common bile duct and incomplete CDCD over a T-tube, leaving a one-sixth circumferential defect anteriorly. Animals were randomly assigned to treatment (CDCD with sealant, n = 9) or control (no sealant, n = 9). Drains were used to monitor leak volume and bilirubin (bili) concentration. Cholangiography was performed on postoperative day 3. Leaks were defined as drain bili/serum bill > 3, total drain output > 10 mL/kg, and/or extravasation on cholangiography. Animals sacrificed at 3 and 8 weeks (n = 4 and n = 5 from each group, respectively) underwent pathologic examination of the CDCD site. Statistical methods included Student's t test, chi2, linear regression, and analysis of variance procedures. The control group had a higher drain output rate over the first 4 postoperative days than the treatment group (P < 0.05, analysis of variance). Five of nine (56%) control and one of nine (11%) treatment animals had a bile leak (P < 0.05, chi2). There was no major inflammatory response to the sealant versus controls. We conclude that CT3 is effective in decreasing biliary leaks in an incomplete CDCD porcine model with no major adverse pathologic changes. This sealant should be considered for trials for biliary reconstruction in humans.

Anastomosis, Surgical↗
PubMed2002

Effective management of bleeding during tumor resection with a collagen-based hemostatic agent.

In a prospective controlled trial hemostatic effectiveness of a novel collagen-based composite (CoStasis) was compared with a collagen sponge applied with manual pressure at diffusely bleeding sites after surgical tumor resection. The proportion of subjects achieving complete cessation of bleeding within 10 minutes (i.e., hemostatic success) and the time to "complete hemostasis" were determined at raw surgical sites after tumor resection among 23 experimental and 30 control subjects. There was a similar distribution in tumor types (e.g., benign vs malignant) evaluated between treatment groups. A significantly greater proportion of experimental subjects achieved complete hemostasis within 10 minutes of observation compared with controls [23 of 23 (100%) vs 21 of 30 (70%); P = 0.003]. The median time required to achieve complete hemostasis was more than three times longer for subjects treated with the collagen sponge compared with subjects treated with CoStasis (243 vs 78 seconds; P = 0.0001). Approximately 80 per cent of experimental subjects achieved complete hemostasis within 2 minutes compared with only 35 per cent of controls. There were no adverse events related to the experimental treatment in this study. These results support the use of this novel hemostatic agent to control diffuse surgical site bleeding after tumor resection at diverse anatomical locations.

Abdominal Neoplasms↗
PubMedDate not supplied

Effects of hepatitis C virus infection and its recurrence after liver transplantation on functional performance and health-related quality of life.

Our aim was to examine the effects of hepatitis C virus (HCV) infection, a leading cause of end-stage liver disease, and its recurrence after liver transplantation on functional performance and health-related quality of life. Functional performance, liver function, and HCV recurrence were assessed longitudinally in 75 adult transplant recipients (28 with HCV). Quality of life was reported once after transplantation. Functional performance improved through year 2 (P < 0.001) and then declined in those with HCV, whereas the others remained stable (P = 0.05). Time had a positive effect (beta = 0.22, P = 0.05) and HCV infection had a negative effect (beta = -0.28, P = 0.01) on post-transplant functional performance. Educational level (beta = 0.24, P < 0.05) and recent functional performance (beta = 0.31, P = 0.01) had positive effects on quality of life. HCV recurrence was associated with relatively poorer pretransplant functional performance, a greater rate of improvement through month 3 (P < 0.05), and abnormal transaminase values between years 1 and 2 (P < 0.001). Rehospitalization for recurrent HCV was associated with reduced functional performance (P < 0.05). Functional performance improves with time following liver transplantation, but HCV infection exerts an opposing and comparably strong effect. Post-transplant functional performance, in turn, directly affects post-transplant quality of life. Severe, recurrent HCV illness is associated with reduced functional performance.

Cohort Studies↗
PubMedDate not supplied

Hepatic cryoablation-induced multisystem injury: bioluminescent detection of NF-kappaB activation in a transgenic mouse model.

Hepatic injury from cryoablation has been associated with multisystem injury, including adult respiratory distress syndrome, renal insufficiency, and coagulopathy; but the responsible mechanisms have not been well defined. In the present study we investigated the role of the transcription factor NF-kappaB in the multiorgan inflammatory response to hepatic cryoablation utilizing a novel in vivo system for determining NF-kappaB activity. Using transgenic mice expressing photinus luciferase under the control of the 5' HIV-LTR (an NF-kappaB-dependent promoter), we measured luciferase activity in the liver, lungs, and kidneys as a marker for NF-kappaB activity. Luciferase production was determined by in vivo bioluminescence and by luciferase assays of tissue homogenates. After measurement of basal luciferase activity, mice were treated with 35% hepatic cryoablation or sham laparotomy and injected with luciferin (0.75 mg/mouse). Photon emission from the liver, lungs, and kidneys was measured at multiple time points. Hepatic cryoablation induced a significant increase in photon emission by the liver, lungs, and kidneys, which correlated with markedly increased luciferase activity measured from each organ after death. Lung lavage 4 hours after cryoablation showed neutrophilic lung inflammation with increased MIP-2 levels compared with sham surgery. These findings demonstrate that 35% hepatic cryoablation is associated with NF-kappaB activation in the remnant liver and multiple distant sites, and may be causally related to the multisystem injury that is seen after direct liver injury.

Animals↗