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Biomedical subjects

William C Chapman

Publications and source records attributed to William C Chapman.

At least 19 recordsLinked to original sources
PubMed2006

Elevated soluble CD30 correlates with development of bronchiolitis obliterans syndrome following lung transplantation.

BACKGROUND: The long-term function of lung transplants is limited by chronic rejection (bronchiolitis obliterans syndrome, BOS). Due to lack of specific markers, BOS is diagnosed clinically. Because there is strong evidence that alloimmunity plays a significant role in the pathogenesis of BOS, we investigated whether soluble CD30 (sCD30), a T-cell activation marker, would correlate with BOS. METHODS: Sera collected serially from BOS+ (n = 20) and matched BOS- (n = 20) lung transplant (LT) patients were analyzed for sCD30 by enzyme-linked immunosorbent assay. Pretransplant sera and sera from normal donors were also analyzed. RESULTS: PreLT levels were comparable to normal subjects. However, posttransplant there was a significant elevation in sCD30 levels during BOS development in all BOS+ patients, compared to BOS- (mean 139.8+/-10.7 vs. 14.8+/-2.7 U/ml, P < 0.001). sCD30 levels declined in the BOS+ patients but were still elevated compared to BOS- (48.52+/-5.04 vs. 7.19+/-2.9, P < 0.0001). CONCLUSIONS: We conclude that sCD30 may represent a novel marker to monitor the development of BOS.

Adult↗
PubMed2006

Pre-liver transplantation locoregional adjuvant therapy for hepatocellular carcinoma as a strategy to improve longterm survival.

BACKGROUND: Preorthotopic liver transplantation locoregional therapy (LRT) for hepatocellular carcinoma (HCC) reduces drop-out rates in patients awaiting orthotopic liver transplantation (OLT). In this study, we investigated the efficacy of LRT as a strategy to improve longterm survival after transplantation. STUDY DESIGN: A retrospective analysis of prospectively collected data identified 100 patients with HCC who underwent OLT between 1985 and 2005. Of these, 46 received LRT in the form of transarterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or a combination of these. RESULTS: The 1-, 3-, and 5-year survivals, regardless of LRT, were 81.3%, 66.1%, and 61.3%, respectively. Demographic data and waiting time for OLT were similar between LRT and untreated groups. Pre-OLT radiologic stage was comparable (LRT: 2.11 +/- 0.74 versus Untreated: 2.39 +/- 0.94; p = 0.16). At the time of transplantation, the LRT group had notable tumor downstaging (1.50 +/- 1.34 versus 2.49 +/- 1.17; p = 0.008). The LRT group had better 5-year survival (82.4% versus 51.8%; p = 0.01), but this improvement was observed in patients with HCC stages II, III, and IV (77.6% versus 37.4%; p = 0.016). Sixteen LRT patients, and none untreated, revealed complete tumor necrosis with no viable tumor cells on explant pathology (pT0). These patients did not experience any longterm recurrence, in contrast to those with similar pre-OLT tumors. CONCLUSIONS: OLT is a viable treatment option for primary HCC. LRT substantially downstages the primary tumor and improves longterm survival in patients with advanced disease. Complete tumor necrosis with LRT is associated with excellent longterm recurrence-free survival.

Adult↗
PubMed2006

CpG island methylation of genes accumulates during the adenoma progression step of the multistep pathogenesis of colorectal cancer.

Genetic alterations occur during the adenoma-carcinoma sequence of colon cancer formation and drive the initiation and progression of colon cancer formation. The aberrant methylation of genes is an alternate, epigenetic mechanism for silencing tumor suppressor genes in colon cancer. The aim of this study was to determine on a global and gene-specific level the role of CpG island methylation in the initiation and progression of colon cancer. Consequently, we assessed the frequency of gene methylation in tumors representative of the commonly recognized histological steps of the adenoma-carcinoma progression sequence through the analysis of eight genes previously identified to be methylated in colon cancer, MGMT, HLTF, MLH1, p14(ARF), CDKN2A, TIMP3, THBS1, and CDH1. We observed that the proportion of tumors carrying methylated alleles increased from adenomas to adenocarcinomas but that the proportion of tumors with methylated alleles was not different between adenocarcinomas and metastases (69% versus 90%, P = 0.01 and 90% versus 81%, P > 0.05). The most substantial difference occurred between early and advanced adenomas (47% versus 84%, P = 0.018). Furthermore, we observed that the frequency of gene methylation at the different steps of the progression sequence varied between genes. Thus, the aberrant methylation of genes appears to increase most significantly during the progression of early adenomas to advanced adenomas, and the frequency of specific gene methylation at the different steps of the adenoma-carcinoma progression sequence varies in a gene-specific fashion.

Adenocarcinoma↗
PubMed2006

Complement depletion enhances pulmonary inflammatory response after liver injury.

Hepatic cryoablation can produce acute lung injury, with activation of nuclear factor (NF)-kappaB in the remnant liver and lungs, production of C-X-C chemokines, and neutrophil infiltration of the lungs. Activated complement stimulates NF-kappaB and cytokine secretion from Kupffer cells. The role of complement in the development of acute lung injury after cryoablation was examined using HLL transgenic mice (5'HIV-LTR-Luciferase gene; 5' HIV-LTR is an NF-kappaB-dependent promoter). Total complement depletion was achieved with preoperative administration of cobra venom factor (CVF). After hepatic cryoablation, bioluminescent NF-kappaB activity increased in the nonablated liver remnant by 4 hours in both control (119,093 +/- 22,808 net RLU/mg protein) and CVF-treated mice (117,722 +/- 14,932) from cumulative baseline (657 +/- 90, P < 0.0001). In the lung, complement-depletion induced significantly greater increases in NF-kappaB activation at both early and later times. Likewise, chemokines were higher in complement-depleted mice relative to controls (KC: 493 +/- 43 versus 269 +/- 29 pg/mg protein, P < 0.001; MIP-2: 171 +/- 29 versus 64 +/- 13 pg/mg protein, P < 0.0001). Pulmonary myeloperoxidase activity was equivalent at 24 hours, but complement-depletion caused a significantly more rapid influx of neutrophils. Complement depletion results in increased pulmonary inflammation following liver cryo injury via relative upregulation of NF-kappaB activity. Activated complement is not the initiator of the systemic inflammatory response; in fact, downstream components of the complement cascade may diminish subsequent inflammation.

Analysis of Variance↗
PubMed2006

Activation of nuclear factor kappa B and severe hepatic necrosis may mediate systemic inflammation in choline-deficient/ethionine-supplemented diet-induced pancreatitis.

OBJECTIVES: We hypothesized that hepatic injury is associated with severe acute pancreatitis (SAP) and may result in lung injury through nuclear factor kappa B (NF-kappaB)-dependent inflammatory mediators. The study characterizes the timing and determines the involvement of selected cytokines and chemokines in the pathogenesis of hepatocellular injury associated with SAP. METHODS: The SAP was induced in C57BL/6 mice by feeding a choline-deficient/ethionine-supplemented diet. The mice were killed at 12-hour intervals for 96 hours. Terminal deoxynucleotidyl transferase-mediated nick-end labeling staining was used to determine the extent of hepatic apoptosis. The NF-kappaB activation in nuclear protein extracts from liver tissue was measured using a sensitive RelA enzyme-linked immunoadsorbent assay. Tumor necrosis factor alpha, interleukin 6, macrophage inflammatory protein (MIP) 2, and keratinocyte-derived chemokine (KC) levels in homogenates of liver and lung tissues were measured by enzyme-linked immunoadsorbent assay. The SAP-associated neutrophil lung inflammation was measured as tissue myeloperoxidase activity. RESULTS: The SAP and subsequent liver injury were confirmed by histological analysis and rises in plasma amylase and transaminase levels. Severe hepatocellular apoptosis was detected at 36 and 48 hours after the diet initiation by terminal deoxynucleotidyl transferase-mediated nick-end labeling staining (P < 0.05) and subsequently progressed to hepatic necrosis. Liver NF-kappaB activation was detected at 36 hours (P < 0.05) and followed by a sharp increase in hepatocellular levels of interleukin 6, MIP-2, and KC at 72 hours and thereafter (P < 0.05). Levels of MIP-2 and KC in lung tissue were also elevated at 72 hours (P < 0.05) and closely correlated with increased myeloperoxidase activity and increased inflammatory cell infiltrate in the lung. CONCLUSIONS: Choline-deficient/ethionine-supplemented diet-induced SAP is accompanied with hepatocellular apoptosis and eventual necrosis. This injury is associated with the hepatic NF-kappaB activation leading to the production of NF-kappaB-dependent cytokines and chemokines in the liver, which may mediate the lung injury.

Animals↗
PubMed2006

Rapid growth in infancy: balancing the interests of the child.

Low birth weight is associated with a number of immediate adverse consequences, and it has been assumed that "catch-up" growth is a "good thing" because "better" nutritional status is associated with greater childhood health and survival. The same thinking applies to infants who suffer malnutrition and growth faltering during weaning. Recent studies suggest that the rapid postnatal growth of babies is associated with an enhanced risk for obesity, diabetes, hypertension, cardiovascular disease and osteopenia in later life. If this is true, it has implications for our recommendations for infant feeding. Insights from evolutionary biology, life cycle theory, animal husbandry, epidemiology and comparative zoology suggest that the energetic feeding of underweight infants should be considered in the context of the whole life cycle and balance the interests of the child with its likely fortunes in adulthood. Before we revise our current recommendations, we must consider the meaning of catch-up growth, what it involves in terms of tissues gained (fat, muscle and bone) and to what degree association represents causation. In the meantime, it will be prudent to balance the short- and long-term interests of the child by endeavoring to (1) optimize maternal nutrition and health, to avoid low birth weight, (2) breast-feed ideally, (3) consider birth weight, gestation and future "nutritional environment" when making decisions about infant feeding, (4) use appropriate growth charts, (5) avoid excessive postnatal weight gain, (6) think about the whole life span and (7) extrapolate from animal studies cautiously.

Bottle Feeding↗
PubMed2006

Do adverse histopathologic findings in colorectal cancer patients explain disparate outcomes?

We have previously reported reduced overall and disease-free survival in black patients from a 10-year retrospective review of 668 patients from tumor registry data. This study of 213 patients reports the analysis of available archived tissue from a city hospital (n=44 patients, 53% black) and from a university medical center (n=169, 10.6% black). Two senior pathologists independently reviewed slides for predetermined histologic criteria reported to correlate with survival: tumor type, stage at diagnosis, character of invasion, vascular or perineural invasion, the presence of residual adenoma, the presence of a Crohn's-like reaction and number of nodes resected. Differences in discrete variables were compared using the Chi-squared test. Differences in continuous variables were analyzed using independent t tests. No statistically significant differences were identified in tumor stage or type by institution or race. In patients treated at the city hospital, there was a higher incidence of infiltrating tumors (85% vs. 61%, p<0.001), vascular invasion (70% vs. 36%, p<0.05) and residual adenoma (84% vs. 39%, p<0.05); however, no differences by race were identified. Blacks at both hospitals had significantly more perineural invasion (81% vs. 30%, p<0.05) and Crohn's-like reaction (64% vs. 30%, p<0.05) when compared to white patients, although there was no difference between hospitals. The total number of lymph nodes resected was higher at the university hospital (17.0 vs. 8.9, p<0.001). There were no differences in number of nodes resected at either institution by race. Histopathologic findings did not explain the apparent disparity in survival. The differences in number of nodes harvested may suggest inadequate resection or insufficient recovery of nodes by the pathologist.

Black People↗
PubMed2005

Liver transplantation for hepatocellular carcinoma: expanding special priority to include stage III disease.

HYPOTHESIS: After liver transplantation, patients with stage III hepatocellular carcinoma (HCC) experience survivals similar to those of patients with less advanced disease and of matched control subjects. DESIGN: Retrospective review of prospectively collected database. SETTING: University hospital. PATIENTS: Fifty-one adults with HCC and 153 matched adults without HCC who underwent orthotopic liver transplantation. MAIN OUTCOME MEASURES: One-, 3-, and 5-year survivals for all groups. After matching for year of transplantation, age, sex, and underlying liver disease, long-term survival was compared between groups. Rates of recurrence were also measured in the HCC groups. RESULTS: From August 1, 1985, to February 28, 2002, we performed 635 adult liver transplantations, including 51 (8%) in patients with HCC. One hundred fifty-one patients without HCC who underwent transplantation were selected as controls. Patient demographic features were similar between case-control groups. The overall 5-year survival trend was worse for patients with HCC vs their matched controls (48% vs 65%; P = .07); however, this survival disadvantage was eliminated when patients with stages I through III HCC were combined and compared with their matched controls (59% vs 63%; P = .96). Survival of patients with stage III disease was comparable to that of matched controls (65% vs 59%; P = .44). CONCLUSIONS: For patients with stages I through III disease, long-term survival is comparable to that of matched controls, and only patients with stage IV disease experience poorer survival. Consideration should be given to granting exception points to patients with stage III disease.

Carcinoma, Hepatocellular↗
PubMed2005

Interleukin-1beta is prominent in the early pulmonary inflammatory response after hepatic injury.

BACKGROUND: Acute lung injury and inflammation can occur after hepatic ischemia/reperfusion or cryoablation. The etiology of this response is uncertain although it involves NF-kappaB-mediated cytokine release from the liver. METHODS: Inflammation-specific complementary DNA microarrays were utilized to evaluate cytokine upregulation in mouse lung at 4 hours after partial-volume hepatic cryoablation with a recirculating liquid N(2) probe. Hierarchical cluster analysis was performed to identify candidate genes. On the basis of these results, an enzyme-linked immunosorbent assay for interleukin-1beta (IL-1beta) was conducted on serum and pulmonary parenchymal specimens. The time course of IL-1beta transcriptional upregulation in the liver and lungs was evaluated by quantitative reverse transcription/real-time polymerase chain reaction. RESULTS: Starting with a pool of 35 genes generated from normalization and variation filtration, unsupervised hierarchical clustering clearly distinguished lungs of hepatic cryo-injured mice from controls. Genes from the IL-1-family were prominent in the signature. IL-1beta was demonstrable in serum within 2 hours postinjury (218 +/- 89 pg/mL vs 0 at baseline, P = .01). In the lung, IL-1beta was more than 4-fold greater at 4 hours than at baseline. Real-time polymerase chain reaction showed a transcription peak of IL-1beta at 30 minutes in the liver, whereas expression in the lungs remained low until 60 minutes, then continued to increase through 4 hours. CONCLUSIONS: Microarray analysis identified cytokines of the IL-1 family as central components of acute lung injury after hepatic cryoablation. IL-1beta levels increased in both serum and lung tissue over 4 hours after liver injury. Expression of IL-1beta peaked early in the injured liver remnant, followed by subsequent increases in the lungs. Targeted intervention against IL-1beta may ameliorate liver-mediated lung injury.

Animals↗
PubMed2005

Hepatic arterial chemoembolization for hepatocellular carcinoma: comparison of survival rates with different embolic agents.

PURPOSE: The optimal embolic agent for transhepatic arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) has not been identified. This study reports outcomes of TACE for HCC with Gelfoam powder and polyvinyl alcohol (PVA). MATERIALS AND METHODS: Eighty-one patients underwent 152 TACE sessions with Gelfoam powder (n = 41) or polyvinyl alcohol (PVA) and Ethiodol (n = 40) as the embolic agent. Chemotherapeutic drugs were the same for all patients (50 mg cisplatin, 20 mg doxorubicin, 10 mg mitomycin-c). The groups were compared based on number of TACE sessions, maximum tumor size, bilirubin level, aspartate and alanine aminotransferase levels, Child-Pugh score, Model for End-stage Liver Disease score, and hepatitis B or C virus positivity. The number of cases of each Child class in each group was also evaluated. Survival starting from the first TACE session was calculated according to Kaplan-Meier analysis. Forty-eight patients died during the study period, 19 received transplants, and 14 were alive at the end of the study period. RESULTS: The groups were statistically similar in all categories regarding liver function, Child-Pugh score, tumor size, hepatitis status, and percentage of patients with Child class A, B, and C disease. The number of TACE sessions was significantly greater for the Gelfoam powder group (mean, 2.2) versus the PVA group (mean, 1.6; P = .01). Overall survival was similar between groups whether patients who received transplants were included in the analysis (mean, 659 days +/- 83 with Gelfoam powder vs 565 days +/- 71 with PVA; P = .42) or were excluded (mean, 519 days +/- 80 with Gelfoam powder vs 511 days +/- 75 with PVA; P = .93). CONCLUSION: In similar patient groups, survival after treatment of HCC with TACE with Gelfoam powder or PVA and Ethiodol was similar.

Antineoplastic Agents↗
PubMed2005

Compensating for intraoperative soft-tissue deformations using incomplete surface data and finite elements.

Image-guided liver surgery requires the ability to identify and compensate for soft tissue deformation in the organ. The predeformed state is represented as a complete three-dimensional surface of the organ, while the intraoperative data is a range scan point cloud acquired from the exposed liver surface. The first step is to rigidly align the coordinate systems of the intraoperative and preoperative data. Most traditional rigid registration methods minimize an error metric over the entire data set. In this paper, a new deformation-identifying rigid registration (DIRR) is reported that identifies and aligns minimally deformed regions of the data using a modified closest point distance cost function. Once a rigid alignment has been established, deformation is accounted for using a linearly elastic finite element model (FEM) and implemented using an incremental framework to resolve geometric nonlinearities. Boundary conditions for the incremental formulation are generated from intraoperatively acquired range scan surfaces of the exposed liver surface. A series of phantom experiments is presented to assess the fidelity of the DIRR and the combined DIRR/FEM approaches separately. The DIRR approach identified deforming regions in 90% of cases under conditions of realistic surgical exposure. With respect to the DIRR/FEM algorithm, subsurface target errors were correctly located to within 4 mm in phantom experiments.

Algorithms↗
PubMed2004

Human immune responses to porcine endogenous retrovirus-derived peptides presented naturally in the context of porcine and human major histocompatibility complex class I molecules: implications in xenotransplantation of porcine organs.

BACKGROUND: Porcine endogenous retroviruses (PERV) have been shown to infect human cells, raising concerns regarding safety of xenotransplantation. In patients exposed to porcine tissues, no PERV infection has been observed. This study was designed to develop human CD8+ cytotoxic T lymphocytes (CTL) against PERV-derived peptides presented in the context of human leukocyte antigen (HLA) or swine leukocyte antigen (SLA) class I molecules and to define dominant epitopes contributed by PERV. METHODS: Human CD8+ CTL were generated against porcine aortic endothelial cells (PAEC). Peptides presented on SLA class I molecules were acid eluted and fractionated by reverse-phase high-performance liquid chromatography. Peptide fractions that restored lysis of acid-stripped PAEC were sequenced by tandem mass spectrometry. Human CD8+ CTL were generated against PERV envelope-derived peptides and PERV-infected human cells to identify immunodominant PERV-derived epitopes. RESULTS: We identified two peptides derived from retroviral transactivating regulatory protein (AHQDPLPEQP) and retroviral transcription factor (PQKPFVT) recognized by human CD8+ CTL in the context of SLA class I. Computer-assisted analysis identified nine PERV-envelope-derived 9-mer peptides with high affinity for the HLA-A2 molecule (Env-1-9). PERV-specific CD8+ CTL generated in vitro identified the immunodominant Env-5 peptide (303-311, KLFSLIQGA) and demonstrated HLA-A2-restricted cytotoxicity against PERV-infected human cells. CONCLUSIONS: Our results indicate that PERV-derived peptides are presented naturally on porcine and human major histocompatibility complex class I molecules. CD8+ CTL responses elicited against dominant SLA and HLA class I-restricted PERV-derived epitopes may play an important role in xenograft rejection and in containment of PERV infection of human cells after xenotransplantation.

Animals↗
PubMed2004

Predicting outcome after liver transplantation: utility of the model for end-stage liver disease and a newly derived discrimination function.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) has been found to accurately predict pretransplant mortality and is a valuable system for ranking patients in greatest need of liver transplantation. It is unknown whether a higher MELD score also predicts decreased posttransplant survival. METHODS: We examined a cohort of patients from the United Network for Organ Sharing (UNOS) database for whom the critical pretransplant recipient values needed to calculate the MELD score were available (international normalized ratio of prothrombin time, total bilirubin, and creatinine). In these 2,565 patients, we analyzed whether the MELD score predicted graft and patient survival and length of posttransplant hospitalization. RESULTS: In contrast with its ability to predict survival in patients with chronic liver disease awaiting liver transplant, the MELD score was found to be poor at predicting posttransplant outcome except for patients with the highest 20% of MELD scores. We developed a model with four variables not included in MELD that had greater ability to predict 3-month posttransplant patient survival, with a c-statistic of 0.65, compared with 0.54 for the pretransplant MELD score. These pretransplant variables were recipient age, mechanical ventilation, dialysis, and retransplantation. Recipients with any two of the three latter variables showed a markedly diminished posttransplant survival rate. CONCLUSIONS: The MELD score is a relatively poor predictor of posttransplant outcome. In contrast, a model based on four pretransplant variables (recipient age, mechanical ventilation, dialysis, and retransplantation) had a better ability to predict outcome. Our results support the use of MELD for liver allocation and indicate that statistical modeling, such as reported in this article, can be used to identify futile cases in which expected outcome is too poor to justify transplantation.

Adult↗
PubMed2004

Fluorodeoxyglucose PET imaging in the evaluation of gallbladder carcinoma and cholangiocarcinoma.

Our goal was to evaluate fluorodeoxyglucose (FDG) positron emission tomography (PET) in staging patients with biliary tract cancers. Fifty consecutive patients who underwent FDG-PET for suspected cholangiocarcinoma (n=36) or gallbladder carcinoma (n=14) were reviewed. Patients with cholangiocarcinoma were divided into two groups: group 1 had nodular type (mass=1 cm) (n=22) and group 2 had infiltrating type (n=14) cholangiocarcinoma. Thirty-one of 36 patients evaluated for cholangiocarcinoma had cholangiocarcinoma and five did not. Sensitivity was 85% for nodular morphology but only 18% for infiltrating morphology. Sensitivity for metastases was 65% but false negative for carcinomatosis in three of three patients. One false positive result occurred in a patient with primary sclerosing cholangitis who had acute cholangitis. Seven (58%) of 12 patients had FDG uptake along the tract of a biliary stent. FDG-PET led to a change in surgical management in 30% (11 of 36) of patients evaluated for cholangiocarcinoma because of detection of unsuspected metastases. Eleven of 14 patients with gallbladder carcinoma were newly diagnosed by cholecystectomy or another type of exploratory procedure, whereas three patients were undergoing follow-up. Nine had residual gallbladder carcinoma at the time of PET. Sensitivity for gallbladder carcinoma was 78%. Sensitivity for extrahepatic metastases was 50% in eight patients; six of them had carcinomatosis. These data suggest that PET is accurate in predicting the presence of nodular cholangiocarcinoma (mass>1cm) but was not helpful for the infiltrating type. PET was also helpful for detecting residual gallbladder carcinoma following cholecystectomy, but was not helpful in patients with carcinomatosis. Although FDG-PET led to a change in management in 30% of patients with cholangiocarcinoma, it must be interpreted with caution in patients with primary sclerosing cholangitis and with stents in place, as well as in those with known granulomatous disease.

Adult↗
PubMed2004

Registration of medical images using an interpolated closest point transform: method and validation.

Image registration is an important procedure for medical diagnosis. Since the large inter-site retrospective validation study led by Fitzpatrick at Vanderbilt University, voxel-based methods and more specifically mutual information-based registration methods (see for instance [IEEE Trans. Med. Imag. 22 (8) (2003) 986] for a review on these methods) have been regarded as the method of choice for rigid-body intra-subject registration problems. In this study we propose a method that is based on the Iterative Closest Point algorithm and a pre-computed closest point map obtained with a slight modification of the fast marching method proposed by Sethian. Pre-computing the closest point map speeds up the process because at each iteration point correspondence can be established by table lookup. We also show that because the closest point map is defined on a regular grid it introduces a registration error and we propose an interpolation scheme that addresses this issue. The method has been tested both on synthetic and real images, and registration results have been assessed quantitatively using the data set provided by the Retrospective Registration Evaluation Project. For these volumes, MR and CT head surfaces were extracted automatically using a level-set technique. Results show that on these data sets this registration method leads to accuracy numbers that are comparable to those obtained with voxel-based methods.

Algorithms↗