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Nancy Brown

Publications and source records attributed to Nancy Brown.

9 recordsLinked to original sources

Pathogenomic sequence analysis of Bacillus cereus and Bacillus thuringiensis isolates closely related to Bacillus anthracis.

Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis are closely related gram-positive, spore-forming bacteria of the B. cereus sensu lato group. While independently derived strains of B. anthracis reveal conspicuous sequence homogeneity, environmental isolates of B. cereus and B. thuringiensis exhibit extensive genetic diversity. Here we report the sequencing and comparative analysis of the genomes of two members of the B. cereus group, B. thuringiensis 97-27 subsp. konkukian serotype H34, isolated from a necrotic human wound, and B. cereus E33L, which was isolated from a swab of a zebra carcass in Namibia. These two strains, when analyzed by amplified fragment length polymorphism within a collection of over 300 of B. cereus, B. thuringiensis, and B. anthracis isolates, appear closely related to B. anthracis. The B. cereus E33L isolate appears to be the nearest relative to B. anthracis identified thus far. Whole-genome sequencing of B. thuringiensis 97-27and B. cereus E33L was undertaken to identify shared and unique genes among these isolates in comparison to the genomes of pathogenic strains B. anthracis Ames and B. cereus G9241 and nonpathogenic strains B. cereus ATCC 10987 and B. cereus ATCC 14579. Comparison of these genomes revealed differences in terms of virulence, metabolic competence, structural components, and regulatory mechanisms.

Amino Acids↗

Pancreas-sparing duodenectomy is effective management for familial adenomatous polyposis.

Duodenal adenocarcinoma remains the leading cause of cancer death in familial adenomatous polyposis patients following colectomy. Stratification based on Spigelman's criteria provides a means for determining therapy. Spigelman stage IV patients have been selected for pancreas-sparing duodenectomy. Twenty-one patients underwent resection between 1992 and 2004, with a mean age of 58 +/- 11 years. The mean time from colectomy to duodenectomy was 27 +/- 13 years. Invasive cancer was found in the distal duodenum in one patient. Operative time averaged 327 +/- 61 minutes with a mean blood loss of 503 +/- 266 ml. There was no mortality, and eight patients (38%) had 14 complications: six (29%) with delayed gastric emptying, four (19%) with biliary/pancreatic anastomotic leak, one with pancreatitis, and one with wound infection. There were two reoperations: one for delayed gastric emptying and one for an early biliary leak. Mean length of stay was 15 +/- 10 days. Two late complications occurred: a stomal ulcer and an intestinal obstruction at 48 and 24 months, respectively. Mean follow-up was 79 months (range, 3-152 months). Two patients developed polyps in the advanced jejunal limb and were endoscopically treated. Pancreas-sparing duodenectomy represents a definitive treatment for advanced duodenal polyposis and can obviate the need for pancreaticoduodenectomy.

Adenomatous Polyposis Coli↗

Natural history of indeterminate pancreatic cysts.

BACKGROUND: The optimal treatment for incidental asymptomatic pancreatic cysts is not known. The purpose of this study was to determine whether nonmucinous cysts by cyst-aspiration analysis can be observed safely. METHODS: A prospective protocol was initiated in September of 1999 for all suspected cystic neoplasms. Asymptomatic patients with negative cyst aspirates (no extracellular mucin, and concentration of carcinoembryonic antigen in the cyst fluid <200 ng/mL) were followed-up clinically and radiographically. RESULTS: Through December 2004, 221 patients have been evaluated, and 80 (36%) initially were operated. There were 141 (64%) patients with indeterminate cysts, 98 have been followed-up for more than 12 months. Compared with resected patients, observed patients were older (62 vs 56 y, P < .006), and had smaller cysts (2.4 vs 4.0, P = .001). At a mean follow-up period of 24 months, 4 patients (4%) were resected. The indication, time to resection, and pathology were as follows: 2 patients for symptoms (abdominal pain and obstructive jaundice) at 24 and 72 months, respectively: mucinous and serous cystadenomas; 1 patient for an increase in size (6.6 to 7.8 cm) at 18 months: lymphoepithelial cyst; and 1 patient for abdominal pain and increase in size (2.0 to 3.7 cm) at 41 months: pseudocyst. The only patient resected for a mucinous neoplasm had a cyst fluid carcinoembryonic antigen level of 896 ng/mL. In the remaining observed patients, 20 (23%) showed a decrease in cyst size, and 16 (19%) showed an increase in size (mean diameter change, 21%). CONCLUSIONS: Initial follow-up evaluation indicates that asymptomatic patients without evidence of a mucinous neoplasm by cyst aspiration can be followed clinically and with interval imaging.

Carcinoembryonic Antigen↗

A training program for certified asthma educators: assessing performance.

BACKGROUND: Evidence-based asthma guidelines identify asthma education as an essential element of care. In Canada, a process for certifying asthma educators was established to help provide asthma education to patients. A critical component to certifying asthma educators is their training and evaluation. The purpose of the study was to identify an approach to evaluate participants and to determine if specific characteristics influenced participants' success. METHODS: Participants completed a questionnaire that collected demographic, practice, and learner characteristics. Assessment strategies and criteria used to determine the level of success included 1) a written asthma knowledge score; 2) a written educational theory score, and 3) a practice teaching skill score based on three encounters with standardized patients. Standardized patient encounters were scored by using a standard checklist of essential teaching functions. RESULTS: Participants (n = 73) represented a broad range of health professions (respiratory therapists, nurses, pharmacists, and physiotherapists). The average score for written asthma knowledge, educational theory, and practice skill assessment was 82.0 +/- 8.0%, 68.6 +/- 16.2%, and 80.3 +/- 9.7%, respectively. Moderate interrelationships were observed between the practice teaching skills score and years of practice in asthma (r = 0.35; p < 0.01) and percentage of workdays dedicated to asthma care (r = 0.30; p < 0.05). Moderately strong relationships were observed among the three standardized patient encounters. However, there were no associations between participant scores on the written asthma or educational theory examination and the practice skill assessment scores. CONCLUSIONS: Participants of an asthma educator training program represent a wide range of disciplines, practice settings, and experience. It is important that asthma educator training programs assess both written knowledge and practice assessments to evaluate participants.

Adult↗

Management of failed biliary repairs for major bile duct injuries after laparoscopic cholecystectomy.

BACKGROUND: Many bile injuries are managed without referral to tertiary centers. Management of patients referred for a primary repair, or after a failed repair, was reviewed to compare outcomes. STUDY DESIGN: Retrospective review of data collected in prospective database. RESULTS: A total of 133 patients had been treated over 12 years ending in December 2002. Forty-six (35%) were treated for failed earlier repairs and 40 (30%) had their primary surgical repair at our institution. Patients with a failed repair were referred at a longer interval (165 versus 9 days, p < 0.001), were more often diagnosed intraoperatively (28 [61%] versus 13 [33%], p = 0.009), and presented with biliary obstruction (41 [89%] versus 13 [33%], p < 0.001). Of the failed repairs, 26 patients (56%) had an earlier biliary-enteric anastomosis and 20 had primary end-to-end repair. One-third of failed repairs was successfully treated with stenting and was significantly more successful after a biliary-enteric anastomosis. Surgical revision of failed repairs was required in 27 patients (59%) and was more likely in earlier primary repairs. At a mean followup of 64 months, recurrent biliary strictures occurred in 5 patients (6%). CONCLUSIONS: Management of a failed major bile duct repair requires multiple modalities, but eventually the majority of repairs require surgical revision. Good results can be expected for all surgical biliary repairs at tertiary centers.

Adult↗

Environmentally determined genetic expression: clinical correlates with molecular variants of carbamyl phosphate synthetase I.

Carbamyl phosphate synthetase I (CPSI) determines the rate-limiting entry of free ammonia into the urea cycle. Disruption of CPSI affects the liver's ability to remove waste nitrogen and produce arginine, citrulline, and urea. Arginine is the necessary precursor for the critical biomolecule, nitric oxide (NO). We have studied the classic model of CPSI deficiency, which results in severe hyperammonemia, and identified a large number of molecular defects. A number of CPSI polymorphisms have been found that appear to result in functional consequences. We have examined the association of these polymorphisms with various environmental stress conditions and found that certain CPSI alleles are associated with clinical outcome. We refer to these associations as environmentally determined genetic expression (EDGE) affects. In addition to studies of classic CPSI deficiency, we have developed data for the EDGE concept in post-cardiac surgery-related pulmonary hypertension, hepatic veno-occlusive disease after bone marrow transplantation, and persistent pulmonary hypertension of the newborn. We have linked these outcomes and genotypes to the availability of the urea cycle intermediates, citrulline and arginine, and their role in NO synthesis. We hypothesize that these polymorphisms affect the functional efficiency of CPSI and thus the entire urea cycle and as such, the availability of the NO substrates. By piecing together the various functional aspects of the urea cycle changes we have seen, we can better understand the clinical vulnerabilities of patients in environmentally stressful situations. This knowledge should allow us to design intervention strategies to either predict or modify the associated adverse outcomes.

Bone Marrow Transplantation↗

Purification of a modified form of bovine antithrombin III as an HIV-1 CD8+ T-cell antiviral factor.

CD8(+) T-cells secrete soluble factor(s) capable of inhibiting both R5- and X4-tropic strains of human immunodeficiency virus type 1 (HIV-1). CCR5 chemokine ligands, released from activated CD8(+) T-cells, contribute to the antiviral activity of these cells. These CC-chemokines, however, do not account for all CD8(+) T-cell antiviral factor(s) (CAF) released from these cells, particularly because the elusive CAF can inhibit the replication of X4 HIV-1 strains that use CXCR4 and not CCR5 as a coreceptor. Here we demonstrate that activated CD8(+) T-cells of HIV-1-seropositive individuals modify serum bovine antithrombin III into an HIV-1 inhibitory factor capable of suppressing the replication of X4 HIV-1. These data indicate that antithrombin III may play a role in the progression of HIV-1 disease.

Animals↗

Prospective preoperative determination of mucinous pancreatic cystic neoplasms.

BACKGROUND: Optimal management of pancreatic cystic neoplasms includes identification and resection of mucinous neoplasms. This study was performed to assess the accuracy of preoperative variables in determining a mucinous lesion. METHODS: Patients referred for a cystic neoplasm were prospectively assessed by presenting symptoms, blinded radiologic review, and endoscopic ultrasound-guided cyst aspirate analysis. Patients who were symptomatic, or had aspirate findings of a mucinous neoplasm were resected. RESULTS: Eighty-seven patients were enrolled over a 22-month period ending in December 2001. There were 56 (64%) women and 31 (36%) men, with a mean age of 63 (27-86) years. Thirty-five (40%) patients were resected including 24 (69%) women and 11 (31%) men with a mean age of 58 years. Twenty-eight (80%) patients who had resection were symptomatic. Specimen histology included 18 (51%) mucinous neoplasms, 8 (23%) serous neoplasms, 4 (11%) ductal or neuroendocrine carcinomas, and 3 (9%) pseudocysts. The positive predictive value (PPV) for cyst-aspirate extracellular mucin (83%) was significant in predicting a mucinous neoplasm (P =.009). No other aspirate variables (amylase, carcinoembryonic antigen, CA15-3, viscosity), or patient characteristics were predictive of final histology. Diagnostic agreement between all 3 radiologists was 8% (P =.98). At a median follow-up of 12 months, no patients who were observed required resection. CONCLUSIONS: Patients with suspected pancreatic cystic neoplasms can be selectively treated on the basis of symptoms and cyst-aspirate mucin analysis. Symptomatic and mucin containing lesions should be resected.

Adenocarcinoma, Mucinous↗