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Audrey J Lazenby

Publications and source records attributed to Audrey J Lazenby.

15 recordsLinked to original sources
PubMed2006

Diagnostic quality of: polyps resected by snare polypectomy: does the type of electrosurgical current used matter?

BACKGROUND: Traditionally, snare polypectomy is performed using blended, coagulation, or pure cutting electrical current (EC). The aim of this study was to assess and compare the diagnostic quality of polyps obtained by snare polypectomy using two different electrosurgical currents. METHODS: Consecutive patients undergoing colonoscopy underwent polypectomy using either blended EC with a conventional electrosurgical generator (ESG) or using an ESG with a microprocessor that automatically controls cutting and coagulation (Endocut). An experienced blinded gastrointestinal (GI) pathologist evaluated the specimens for diameter, cautery damage (amount and degree), margin evaluability, architecture, and general histologic diagnostic quality. RESULTS: One hundred sixteen patients (69% men, mean age 63.8 +/- 15 yr) underwent 148 polypectomies (78 using blended current and 70 using Endocut). We found that the cautery degree was less with the Endocut than with the blended current (p < 0.02). Cautery amount was also higher in polyps resected using blended current (56%) than Endocut (51%) but this difference did not reach statistical significance (p= 0.1). Polyps resected using Endocut had better margin evaluability (75.7% to 60.3%, p= 0.046). The overall tissue architecture was similar in both groups. Polyps removed with blended current had less overall quality as compared to polyps removed by Endocut (p= 0.024). CONCLUSIONS: More extensive tissue damage occurred using blended EC with the conventional ESG than when using Endocut. The quality of the polypectomy specimens was overall better using Endocut. Finally, the ability to evaluate resected polyp margins and overall tissue histology was better with the microprocessor-controlled ESG than with the conventional ESG.

Aged↗
PubMed2006

Signal transduction cross-talk during colorectal tumorigenesis.

Colorectal carcinoma (CRC) is the second leading cause of cancer-related death in the United States in the general population (men and women combined). Epidemiologic data obtained over the last several decades shows convincing evidence for the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in the reduction of risk of CRC through the inhibition of cycloxygenase (COX). Recent research has also demonstrated that prostaglandin E2 (PGE2), a predominant product of COX, plays a critical role in tumorigenesis of CRCs through its guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs), EP2, and EP4. Molecular analysis of CRC and its precursor lesions have shown that mutation of Adenomatous Polyposis Coli (APC), a gene involved in the wingless type signaling pathway, is an early event during the neoplastic progression in the majority of sporadic CRCs. The fundamental questions are: why is wild type APC so important in adult colorectal tissues in preventing this tumorigenesis, and what are the mechanisms by which NSAIDs prevent colorectal tumorigenesis? We reviewed the recent literature concerning the PGE2-GPCR signaling pathway and the APC-beta-catenin (wingless type) pathway in CRC cells and propose a unifying schema regarding the tumorigenesis of CRC. Colorectal epithelia are continuously exposed to various extracellular agonists (including low levels of PGE2). The binding of these agonists to their corresponding GPCRs leads to formation of activated Galphas, which in turn activates beta-catenin. In normal colorectal epithelia, wild type APC blocks the Galphas-induced activation of beta-catenin, and therefore maintains homeostasis and prevents tumorigenesis. In contrast, in the absence of functional APC, continuous formation of activated Galphas by the binding of various extracellular agonists to their receptors leads to the activation and nuclear accumulation of beta-catenin. This elevated nuclear beta-catenin in turn increases transcription of many genes (COX-2, C-myc, Cyclin D1, vascular endothelial growth factor, T cell factor, etc.) involved in tumorigenesis. Increased transcription of COX-2 also leads to excessive production of PGE2 that in turn forms a stimulatory loop with many biologic functions (proliferation, migration, invasion, angiogenesis, and inhibition of apoptosis), which may result in the development of CRC. Because NSAIDs inhibit COX and decrease the production of PGE2, interruption of the cycle helps prevent colorectal tumorigenesis.

Adult↗
PubMed2006

Cytomegalovirus blocks intestinal stroma-induced down-regulation of macrophage HIV-1 infection.

Intestinal macrophages, unlike macrophages from other tissues, do not support HIV-1 infection or produce proinflammatory cytokines. In vitro studies suggest this unique, functional phenotype is a result of the exposure of newly recruited blood monocytes to intestinal stromal products. However, in AIDS-related CMV colitis, mucosal macrophages express HIV-1 and proinflammatory cytokines. Therefore, we investigated the mechanism by which CMV confers permissiveness to HIV-1 and cytokine production on intestinal macrophages. We show that intestinal stroma-conditioned media (S-CM) down-regulated monocyte-derived macrophage infection by HIV-1 (pseudotyped with YU2 envelope or vesicular stomatitis virus glycoprotein) and production of TNF-alpha, but preinfection of the cells with CMV reversed this down-regulation, enhancing HIV-1 infection, p24 production, and TNF-alpha release. The ability of CMV to reverse S-CM down-regulation of macrophage HIV-1 infection was blocked by anti-TNF-alpha antibodies and over-ridden by exogenous TNF-alpha. Immunohistochemical analysis of monocyte-derived macrophages exposed to CMV and HIV-1 (YU2 pseudotype) revealed that the cells infrequently contained CMV and HIV-1 viral proteins. In addition, analysis of colon tissue sections from HIV-1-infected patients with CMV colitis showed that some macrophage-like cells contained CMV and TNF-alpha proteins, others contained HIV-1 and TNF-alpha proteins, but cells infrequently contained CMV and HIV-1 proteins. These results indicate that CMV blocks stromal product inhibition of HIV-1 infection in macrophages, and this inhibition is mediated, at least in part, by CMV-induced TNF-alpha acting in trans to enhance HIV-1 infection.

Cells, Cultured↗
PubMed2006

The prevalence of nonalcoholic steatohepatitis is greater in morbidly obese men compared to women.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a form of liver injury that is common in morbidly obese subjects. It has been shown that gender differences exist in the spectrum of nonalcoholic fatty liver disease (NAFLD). The focus of this study was to further characterize these gender differences based on ATP III criteria used to diagnose the metabolic syndrome (MS). METHODS: We retrospectively assessed NAFLD 58 men and 307 women who underwent gastric bypass, for the presence of NASH, MS, and positive predictors of NASH. RESULTS: There was no statistical difference in age, gender, or the presence of diabetes. The prevalence of NASH in men and women was 60.3% and 30.9%, respectively (P<0.001). Multivariate logistic analysis showed an association of male gender with NASH (2.7; 95% CI, 1.3-5.6, P=0.006) as well as age, AST, and diabetes. MS was diagnosed in 91.4% and 76.2% of men and women (P=0.008), and men tended to have more criteria for MS compared to women. The only positive predictor of MS that was statistically significant between genders was high triglycerides (P=0.003). Controlling for BMI and excess body weight produced similar results. CONCLUSIONS: Gender differences do exist within NAFLD and MS, that may be associated with free fatty acid flow to the liver.

Adult↗
PubMed2005

Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT in obese women.

The upper limit of normal for ALT activity has been recommended to be lowered to < or = 30 U/L in men and < or = 19 U/L in women. These changes have been suggested to be diagnostically useful in subjects with nonalcoholic fatty liver disease (NAFLD). Our aim was to investigate the prevalence and spectrum of NAFLD with regard to the new ALT guidelines in 233 women with class II/III obesity. We compared our prior reference range for ALT (ULN < or = 30 U/L in women) with the new standard. Our study demonstrates that only 86 patients (36.9%) would be classified as having normal ALT levels compared with 169 patients (72.5%) by the new and old standards, respectively. In patients with normal ALT activity (new vs. old standard), the prevalence of fatty liver (FL: 39.5% vs 40.2%), portal fibrosis, and steatosis (IPF: 37.2% vs. 33.7%) and nonalcoholic steatohepatitis (NASH: 23.3% vs. 26%) were similar. In comparison, newly defined patients with elevated ALT levels (>19 U/L) demonstrated an increased prevalence of FL (36%) and IPF (11.6%) but a 23.8% decrease in the prevalence of NASH as compared with the old standard. The sensitivity and specificity for NASH were 42% and 80% (ALT > 30 U/L) compared with 74% and 42% (ALT > 19 U/L). In conclusion, a significant increase in the prevalence of FL and IPF is detected in subjects with elevated ALT levels with the application of the new standard. However, the diagnostic utility for ALT to identify NASH or IPF remains poor, and significant healthcare expenditures may be incurred if this standard is adopted.

Adult↗
PubMed2005

Occurrence of gastrointestinal opportunistic disorders in AIDS despite the use of highly active antiretroviral therapy.

Since the introduction of highly active antiretroviral therapy (HAART), the frequency of opportunistic disorders (ODs) of the gastrointestinal (GI) tract in human immunodeficiency virus (HIV)-infected patients has fallen dramatically. We have found, however, that despite the use of HAART, HIV-infected patients can still present with GI ODs. To evaluate the prevalence of GI ODs in HIV-infected patients on HAART who were undergoing endoscopic evaluation for GI-related symptoms. From January 1996 through February 2002, all HIV-infected patients undergoing GI endoscopy were prospectively identified; mucosal biopsies were obtained in a standardized fashion and histologic specimens were examined by a single GI pathologist. All the patients on HAART presenting with a GI OD are described. Results showed that 294 patients (88% men; mean age, 36.5 +/- 10 years; median CD4 lymphocyte count, 64 cells/microl; range, 1-884; median viral RNA level, 40,357 copies/ml; range, 0-7,721,715) underwent 401 upper and/or lower endoscopies during the study period. The use of HAART increased from 10% in early 1996 to 85% in 2002. Nevertheless we found that 27 patients (9%) presented with a GI OD despite HAART. Forty percent of the patients with a GI OD were noncompliant with HAART. We conclude that GI ODs can occur despite HAART and normal CD4 counts. The prevalence of GI ODs in HIV-infected patients taking HAART is 9%. The reasons for this are multifactorial and likely include noncompliance with medications, viral resistance to the drugs, and decreased drug bioavailability. Although the use of HAART has led to a decreased incidence of GI ODs in AIDS, the gastroenterologist evaluating these patients should not discard the possibility that the GI symptoms in HIV-infected patients taking HAART may be secondary to an OD, even when the CD4 count is normal and the viral load is low.

AIDS-Related Opportunistic Infections↗
PubMed2005

Collagenous and lymphocytic colitis.

Collagenous and lymphocytic colitis have been recognized as chronic intestinal inflammatory disorders causing watery diarrhea, which have been recognized in the past three to two decades, respectively. Collagenous colitis is primarily a disorder of middle-aged women and is characterized on biopsy by increased subepithelial collagen as well as increased inflammatory cells in the lamina propria and increased intraepithelial lymphocytes. Key to the correct diagnosis in this condition is recognizing that there are two words in this diagnostic entity, and colitis is, by definition, present. Focusing solely on the collagen band can result in both over- and underdiagnosis. Newer therapeutic options are available in this condition, and patients are now frequently being treated either with budesonide or with high dose bismuth preparations. Whereas collagenous colitis is a tightly coherent clinical pathologic entity, lymphocytic colitis has a more varied clinical picture. Lymphocytic colitis is also seen in middle-aged patients but has a more equal female-to-male ratio. Lymphocytic colitis is defined by increased intraepithelial lymphocytes, with the median being 30 lymphocytes per 100 epithelial cells. There are also an increase in inflammatory cells in the lamina propria, but the increase may be milder than in collagenous colitis and there are usually minimal eosinophils. Although numerous studies have described lymphocytic colitis causing a chronic diarrhea, more recent studies suggest that patients may have a single attack in approximately 60% of cases. Although most cases of lymphocytic colitis are idiopathic, there is a clear association with multiple drugs, celiac disease, and there may be an infectious trigger. Approximately 10% of lymphocytic colitis patients have a positive family history of some type of inflammatory intestinal disease, including ulcerative colitis, Crohn's disease, collagenous colitis, and celiac disease. Therapy in lymphocytic colitis is less well studied, but the same medications are used with success, including budesonide and high dose bismuth.

Colitis, Collagenous↗
PubMed2005

Rab11a immunohistochemical analysis does not distinguish indefinite, low-, and high-grade dysplasia in Barrett esophagus.

Our aim was to determine whether p53 and Rab11a immunoreactivity enhance diagnostic assessment of esophageal dysplasia. Histologic sections from 68 cases of Barrett esophagus obtained as part of a 12-institution study were stained with antibodies to p53 and Rab11a, randomized, and coded. The mucosal surface layer and deeper glands were scored blindly on a semiquantitative scale. The correlations between p53 and Rab11a scoring with the consensus diagnosis of dysplasia were analyzed. The histologic scale was as follows: no dysplasia, indefinite, low-grade dysplasia, high-grade dysplasia, intramucosal carcinoma, and invasive carcinoma. Rab11a staining was most prominent in epithelia negative for dysplasia but with regenerative features. There was an inverse relationship between Rab11a staining and findings of surface dysplasia (P < .02, chi(2)). However, statistical significance largely reflected loss of Rab11a immunoreactivity in intramucosal and invasive carcinoma, which was not a diagnostic dilemma. There was a strong positive correlation of p53 immunoreactivity with an increasing degree of epithelial dysplasia and carcinoma (P < .03, chi(2)). Rab11a immunoreactivity did not enhance the diagnostic assessment of dysplasia in Barrett esophagus. The previously reported positive correlation of p53 immunoreactivity with the presence of dysplasia in Barrett esophagus was confirmed.

Adenocarcinoma↗
PubMed2004

Portal fibrosis and hepatic steatosis in morbidly obese subjects: A spectrum of nonalcoholic fatty liver disease.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can lead to hepatic fibrosis and cirrhosis. Portal fibrosis in the absence of NASH, called isolated portal fibrosis (IPF), has received less attention and has not been classified as a spectrum of NAFLD. The aims of this study were to determine the prevalence of IPF in subjects undergoing gastric bypass surgery, to identify biochemical variables associated with IPF, and to assess the metabolic syndrome as defined by the AdultTreatment Panel III criteria. We analyzed liver biopsies from 195 morbidly obese subjects after excluding all other causes of liver disease. The prevalence of fatty liver (FL) only, IPF, and NASH was 30.3%, 33.3%, and 36.4%, respectively. Several biochemical parameters significantly trended across the 3 groups, with IPF falling between FL and NASH. Hyperglycemia was the only metabolic parameter associated with NASH (OR, 5.4; 95% CI, 2.4-12; P < .0001) and IPF (OR, 2.8; 95% CI, 1.2-6.5; P = .01). Subjects with diabetes had the greatest risk for NASH (OR, 8; 95% CI, 3.3-19.7; P < .0001) and IPF (OR, 4.3; 95% CI, 1.6-11.6; P = .003). The metabolic syndrome was identified in 78.5% of subjects, and a significant trend for the number of metabolic criteria was observed across the spectrum of FL, IPF, and NASH. In conclusion, a significant subset of morbidly obese individuals has portal fibrosis in the absence of NASH that is associated with glycemic dysregulation. Therefore, IPF should be considered a spectrum of NAFLD that may prelude NASH in morbid obesity.

Adult↗
PubMed2004

Whipple's disease.

Explore the source record for details and available documents.

Endoscopy, Gastrointestinal↗
PubMed2004

The spectrum of GI strongyloidiasis: an endoscopic-pathologic study.

BACKGROUND: The aim of this study was a detailed endoscopic-pathologic assessment of patients with various forms of GI strongyloidiasis. METHODS: Six patients with a diagnosis of GI strongyloidiasis who underwent endoscopic evaluation during a 3-year period (January 1998-January 2001) were included. Published information was reviewed in detail, focusing on the endoscopic features and the diagnostic approach to this parasitosis. OBSERVATIONS: Strongyloidiasis has a broad range of endoscopic features. In the duodenum, the findings included edema, brown discoloration of the mucosa, erythematous spots, subepithelial hemorrhages, and megaduodenum. In the colon, the findings included loss of vascular pattern, edema, aphthous ulcers, erosions, serpiginous ulcerations, and xanthoma-like lesions, and, in the stomach, thickened folds and mucosal erosions. A histopathologic diagnosis of strongyloidiasis was made in all cases. CONCLUSIONS: Strongyloidiasis can involve any segment of the GI tract. EGD with procurement of biopsy specimens from the duodenum was the most accurate method of diagnosis in this case series.

Adult↗
PubMed2002

A 38-year-old African-American woman with an unusually rapid progression of "Primary Biliary Cirrhosis": a missed opportunity!

The case discussed is of a 38-year-old African-American woman who developed upper abdominal symptoms and liver test abnormalities. She underwent cholecystectomy for presumed gallstone disease. This was followed by a worsening of her condition, with the development of jaundice in the next 2 weeks. Results of reevaluation included transaminases around 1000 IU/L with minimal elevation of alkaline phosphatase (ALP), an antimitochondrial antibody (AMA) titer of 1:320, and an elevated immunoglobulin M (IgM). The antinuclear antibodies (ANA) level was positive, but titers were not obtained. There was no suggestion of bile duct obstruction. Liver biopsy findings were believed to be consistent with primary biliary cirrhosis (PBC). She was therefore started on, but failed treatment with, ursodeoxycholic acid. She was transferred to a transplant center 8 weeks later after a brief episode of encephalopathy and hypoglycemia. The clinical findings were consistent with subfulminant hepatic failure secondary to autoimmune hepatitis (AIH) with an ANA titer of 1:1280, an anti-smooth muscle antibody (SMA) titer of 1:40, and an elevated IgG. Review of the biopsy showed panlobular inflammation and bridging necrosis consistent with severe AIH. On imaging, she had ascites and a nodular appearance of the liver. An immediate drop in transaminases followed corticosteroid therapy, but her disease was already irreversible, and she underwent successful liver transplantation. The explanted liver was shrunken and noncirrhotic with massive hepatocellular collapse and contained multiple regenerating nodules, explaining the ultrasonographic appearances. The inflammatory component had greatly diminished compared with the earlier biopsy. The case illustrates the importance of knowledge of the natural course of a specific disease and the careful interpretation of clinical data, including autoimmune markers. PBC would rarely cause liver failure in a young woman; it is not a rapidly progressive disease. The original clinical diagnosis was unduly swayed by a positive AMA, which can be seen in up to 20% of patients with AIH. Markedly elevated transaminases with minimal elevation of ALP and positive ANA in a young woman should have pointed toward AIH at an earlier stage. The academic discussion of AMA-positive AIH versus PBC/AIH overlap syndrome remains intriguing, but prompt institution of aggressive immunosuppressive therapy aimed at the AIH component should not be deferred. In retrospect, an opportunity was missed.

Adult↗
PubMed2002

Are ulcers a marker for invasive carcinoma in Barrett's esophagus? Data from a diagnostic variability study with clinical follow-up.

OBJECTIVES: We correlated follow-up information from 138 patients with Barrett's esophagus and varying degrees of dysplasia with the presence of ulcers. METHODS: A group of pathologist participants were asked to contribute patients' initial biopsy slides showing Barrett's esophagus (BE) without dysplasia and with epithelial changes indefinite for dysplasia, low grade dysplasia (LGD), high grade dysplasia (HGD), and adenocarcinoma. From the initial 250 cases used for a diagnostic reproducibility study, follow-up information was available for 138 patients. RESULTS: There were 44 cases submitted as BE, 22 as BE with epithelial changes indefinite for dysplasia, 26 as BE with LGD, 33 as BE with HGD, and 13 as BE with adenocarcinoma. Ulcers were present in 35/138 cases (25%), including 3/44 cases of BE without dysplasia (7%), 2/22 cases of BE with epithelial changes indefinite for dysplasia (9%), 0/26 cases of BE with LGD (0%), 10/33 cases of BE with HGD (30%), and 7/13 cases of BE with adenocarcinoma (54%). On follow-up, there were no invasive carcinomas detected among the BE without dysplasia group (median follow-up = 38.5 months). Adenocarcinomas were detected in 4/22 cases (18%) submitted as BE with epithelial changes indefinite for dysplasia at 19, 55, 60, and 62 months and in 4/26 cases (15%) of BE with LGD at 9, 9, 11, and 60 months. None of these carcinomas occurred in cases in which an ulcer was present in the initial biopsy specimen. Among the 33 HGD cases, 20 (60%) were found to have adenocarcinoma on subsequent resection specimens. The presence of an ulcer with HGD increased the likelihood of finding carcinoma in the resection specimen, as 8/10 biopsies (80%) of HGD patients with ulcers had carcinoma, compared to 12/23 biopsies (52%) of HGD patients without ulcers. All of the cases interpreted as adenocarcinomas on biopsy were found either to have invasive carcinoma on esophageal resection or to have metastases that were demonstrated in unresectable patients. CONCLUSION: If an ulcer accompanies HGD in a biopsy specimen from a patient with BE, it is likely that invasive carcinoma is also present at that time.

Adenocarcinoma↗