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Biomedical subjects

W Trudeau

Publications and source records attributed to W Trudeau.

18 recordsLinked to original sources
PubMed1999

Activating SRC mutation in a subset of advanced human colon cancers.

The discovery of Rous sarcoma virus (RSV) led to the identification of cellular Src (c-Src), a non-receptor tyrosine kinase, which has since been implicated in the development of numerous human cancers. c-Src has been found to be highly activated in colon cancers, particularly in those metastatic to the liver. Studies of the mechanism of c-Src regulation have suggested that c-Src kinase activity is downregulated by phosphorylation of a critical carboxy-terminal tyrosine (Tyr 530 in human c-Src, equivalent to Tyr 527 in chicken Src) and have implied the existence of activating mutations in this C-terminal regulatory region. We report here the identification of a truncating mutation in SRC at codon 531 in 12% of cases of advanced human colon cancer tested and demonstrate that the mutation is activating, transforming, tumorigenic and promotes metastasis. These results provide, for the first time, genetic evidence that activating SRC mutations may have a role in the malignant progression of human colon cancer.

3T3 Cells↗
PubMed1999

Molecular staging for melanoma and breast cancer.

Despite increased sensitivity of PCR techniques, routine H&E histology and, in some cases, immunohistochemistry remain the gold standards for the detection of micrometastatic disease. Highly sensitive and specific molecular assays such as RT-PCR provide an ideal way to detect micrometastatic disease in tissues or blood at risk for metastases. RT-PCR has been shown to increase detection of micrometastases, especially in patients with breast cancer and melanoma. These assays have the potential to provide valuable tumor staging and progression information and thus determine the need for further surgery, adjuvant chemotherapy, and antigen-specific immunotherapy. As investigators gain more experience using molecular assays, the results of these assays will be more likely to guide clinical staging and decision making.

Breast Neoplasms↗
PubMed1996

Association of cocaine and methamphetamine use with giant gastroduodenal ulcers.

OBJECTIVES: Giant gastric and duodenal ulcers (>2-3 cm in greatest dimension) are reported to have higher rates of complication and mortality and to be associated with increasing age, renal failure, and use of nonsteroidal antiinflammatory drugs (NSAIDs). This study investigated the outcome and associations of gastric and duodenal ulcers >2.5 cm compared to ulcers of lesser size. METHODS: Records from all patients with gastric and duodenal ulcers >0.5 cm diagnosed by upper endoscopy between January 1994 and September 1995 were studied for evidence of concurrent use of aspirin, NSAIDs, methamphetamine, and cocaine, as well as for transfusion requirements, length of hospital stay, mortality, surgery, rebleeding, Helicobacter pylori infection, and malignancy. RESULTS: A logistic regression analysis of the 220 patients identified revealed that recent methamphetamine and/or cocaine use was significantly predictive of giant ulcer formation (p = 0.0002) with an odds ratio of 9.66. Also significant was younger age (p = 0.026) and aspirin or NSAID use (p = 0.046). H. pylori infection was significant only for giant gastric ulcers (p = 0.031). Ulcer size did not predict mortality, rate of rebleeding, requirement for surgery, transfusion requirements, or length of hospital stay. However, giant gastric ulcers were significantly more likely to be malignant (p = 0.002). CONCLUSIONS: Giant gastric and duodenal ulcers were strongly associated with stimulant abuse. They were also associated with younger age and use of aspirin or NSAIDs. Additionally, giant gastric ulcers were associated with malignancy and H. pylori infection. Ulcer size did not predict rate of complications or outcome.

Adolescent↗
PubMed1989

Use of continuous infusion of histamine2-receptor antagonists in critically ill patients.

Certain clinical situations require the use of a histamine2 (H2)-receptor antagonist to reduce gastric-acid volume and concentration or an antacid to act as a buffering agent. Presently, there are three H2-receptor antagonists available for iv use: cimetidine, ranitidine, and famotidine. Conventional therapy dictates that the H2-receptor antagonist be given by intermittent intravenous infusion, resulting in peaks and valleys of acid secretory control. Antacids, although capable of providing adequate gastric acidity control, must be administered frequently, often hourly, and thus require excessive nursing time. Presented here is a review of the rationale for the use of an H2-receptor antagonist by continuous infusion.

Critical Care↗
PubMed1987

Prognostic indicators in acute variceal hemorrhage after treatment by schlerotherapy.

The purpose of the study was to evaluate prognostic indicators in patients receiving endoscopic injection sclerosis for bleeding esophageal varices. The results below were obtained from a prospective nonrandomized study in which the patients were subdivided into the following groups (subsets): elective sclerotherapy--10, active variceal bleeding at endoscopy--47, active variceal bleeding with spontaneous resolution at the time of endoscopy--21, and gastric variceal bleeding--nine. The data were analyzed as follows: 14 variables possibly affecting 6-wk survival were evaluated by stepwise logistic regression analysis. Variables examined were subset, age, sex, Child's classification, ascites, comorbid conditions, SGOT, bilirubin, protime, albumin, volume of initial bleed, volume of rebleed, rebleed rate, and Blakemore tube use. Survival curves were also compared using the Kaplan-Meier methodology. The following results were obtained. First, the subsets above had significantly different survival curve patterns with the elective endoscopic injection sclerosis group having the best prognosis and the gastric variceal bleeders a significantly poorer survival. Second, stepwise logistic regression analysis revealed the following four significant variable prognostic indicators: comorbid factors, subset, Child's classification, and serum albumin. Although the latter two variables, Child's class (p = 0.03) and albumin (p = 0.1) had an impact on six week survival, this was no longer seen when subset (p = 0.0124) and comorbid factors (p = 0.003) were taken into account. We conclude that comorbid factors and subsets of variceal bleeding in themselves were the only two prognostic indicators showing a statistically significant association with 6-wk and long-term survival. In contrast, the more usual clinical prognostic parameters, i.e., the physical findings and biochemical test of liver function in patients with cirrhosis and acute variceal bleeding, were of lesser prognostic magnitude.

Acute Disease↗
PubMed1987

Colonoscopic therapy of acute pseudoobstruction of the colon.

All patients with the diagnosis of acute colonic pseudoobstruction at the University of California, Davis Medical Center from 1979-1985 were reviewed. These 25 patients were initially treated conservatively (nasogastric tube/rectal tube/enemas) and this was successful in eight of 25 patients (32%). The remaining 17 patients (68%) unresponsive to conservative therapy received endoscopic intervention, either colonoscopic suction decompression (CSD) or colonic suction decompression with proximal colonic tube placement (CDT) for continuous decompression. Of the endoscopic procedures performed, 13/17 (76%) resulted in successful acute decompression. Recurrences occurred in 6/13 (45%) (3/7 in the colonoscopic suction decompression group and three of six in the colonic tube placement group). In the 10 failures, six further procedures were attempted, but only one was successful. These patients were then treated conservatively. There were no instances of colonic perforation. Acute pseudoobstruction in our experience is a benign entity that can be safely and successfully treated nonsurgically. Colonoscopic suction decompression is often initially successful but has a high frequency of recurrence. Newer techniques to prevent recurrence, i.e., colonic tube placement, are of potential benefit but presently have technical problems.

Acute Disease↗
PubMed1986

Use of double spin-labeled histones to monitor histone-chromatin integration.

Tyrosine-specific nitroxide spin labels have been synthesized that utilize either deuterium or deuterium and [15N] isotopic substitution within the nitroxide ring. These probes have been used to differentially spin label and simultaneously monitor both histones H1 and H5, during the displacement of endogenous spin-labeled H1 from reconstituted chromatin by exogenously added spin-labeled H5.

Animals↗
PubMed1986

Effect of exogenous histone H5 on integration of histone H1 in rat liver chromatin. Correlations with aberrant epsilon-N-methylation of histone H1.

Binding modes of histones H1 and H5, and their competition for chromatin-binding sites in rat liver nuclei, were correlated with aberrant N-methylation of H1 histone lysine residues, induced by chicken erythrocyte histone H5, in order to gain more insight into the integration of lysine-rich histones in chromatin. Addition of approx. 2.5 molecules of histone H5 per nucleosome to rat liver nuclei increases the ratio of total basic residues in histones to DNA nucleotides (BR/NT) in the nuclear chromatin from 1.0 to 1.5. At this concentration, approx. 0.7 molecule of histone H5 is bound per nucleosome, and there is no displacement of histone H1 from the nuclear chromatin. If S-adenosyl[Me-3H]methionine is present in the incubation mixture, the aberrant incorporation of labeled methyl groups into histone H1 reaches a maximum at this concentration of histone H5. The radioactivity present in histone H1 from nuclei incubated with labeled AdoMet at a total BR/NT ratio of 1.5: resides mainly in a histone H1 subfraction tentatively identified by Bio-Rex 70 chromatography and acrylamide gel electrophoresis as histone H1c; presents as a single spot upon peptide mapping of tryptic hydrolysates by means of two-dimensional thin-layer chromatography; and elutes in the position of mono-N-methyllysine upon ion-exchange chromatography of histone H1 hydrolysates. Upon further increase of the BR/NT ratio, the following changes are produced: a gradual decrease in radioactive methyl uptake into histone H1; a gradual displacement of histone H1 from the chromatin; increased binding of histone H5 in chromatin, up to a maximum of 3.4 residues per nucleosome; and a slowly increasing uptake of label into histone H5. The combined data from histone H1/H5 binding and histone H1 methylation studies suggest that upon addition of exogenous histone H5 to rat liver nuclei the binding of two lysine-rich histones per nucleosome plays a significant role in the induction of specific changes in chromatin structure, which in vivo may have important functional implications in terms of chromatin condensation and suppression of transcription.

Animals↗
PubMed1986

Outpatient endoscopic injection sclerosis of esophageal varices.

We report our experience with outpatient endoscopic injection sclerosis (EIS). Fourteen patients receiving elective in patient EIS (30 patient sessions) were compared to 34 patients having elective outpatient EIS (133 patient sessions). The majority of the patients had Child's C alcoholic liver disease. There were two major complications in the 14 inpatients receiving elective EIS, one severe hemorrhage and one death, for a complication rate of 14%. There were no minor complications in this group. In the 34 patients undergoing outpatient EIS there was one major complication for a complication rate of 2.9% (bleeding) and no deaths. Minor complications in the outpatient group included chest pain in 9.0%, dysphagia without stricture in 6.0%, severe ulceration precluding EIS in 21.0%, and stricture of esophagus in 24.0%. The average cost for inpatient EIS was +1183.00 and for outpatient EIS, +339.00.

Ambulatory Care↗
PubMed1986

Endoscopic injection sclerosis in bleeding gastric varices.

Ninety-two consecutive, nonrandomized patients with bleeding varices were prospectively studied using sclerotherapy to control and prevent rebleeding. During this study, nine patients with gastric variceal bleeding were identified. A gastric variceal subset is defined and represents a 10% incidence in this series. All patients presented with indexed gastric bleeding varices that subsequently accounted for 34 bleeding sessions. The units of blood per rebleeding episode, hospital days, cost, and outcome were markedly different from the esophageal variceal groups. Initial management of indexed bleeding episodes by sclerotherapy and Sengstaken-Blakemore tubes were comparable; however, the number of rebleeding episodes was much higher. There was poor control of rebleeding with an associated higher rebleeding mortality and complications secondary to repeated sclerotherapy and Sengstaken-Blakemore tube use. In 37% of the patients, rebleeding was the direct result of gastric ulcerations at the endoscopic injection sclerotherapy site. The survival curve of this group was much lower than esophageal variceal bleeders. Endoscopic injection sclerotherapy in patients with bleeding gastric varices offers only temporary control of bleeding, and the high incidence of severe early rebleeding requires consideration of alternative methods for management or modified sclerotherapy techniques.

Esophageal and Gastric Varices↗
PubMed1986

A comparison of immediate versus delayed endoscopic injection sclerosis of bleeding esophageal varices.

The authors report their experience with immediate endoscopic injection sclerosis at the time of diagnosis of active bleeding esophageal varices compared to delayed sclerotherapy performed after control of variceal bleeding with vasopressin and Sengstaken-Blakemore tamponade. Twenty-eight active index bleeders and 20 active rebleeders were treated by immediate endoscopic injection sclerosis, which could technically be performed on all of the former and in 18 of the rebleeders (96%). Immediate control of active bleeding was achieved in all patients whose varices were injected (100%). Control at 48 hours was 89% for the index bleeding group and 80% for the rebleeding group. In the delayed sclerotherapy group of 19 patients, initial control (79%) and 48-hour control (64%) were significantly less. The rebleeding rate, complications, and death from exsanguination were greater in the delayed group, whereas longevity was similar in both groups. We conclude that immediate sclerotherapy effectively controls acutely bleeding esophageal varices with a lower complication rate than sclerotherapy performed after conventional medical therapy with vasopressin and Sengstaken-Blakemore tube tamponade.

Endoscopy↗
PubMed1985

Esophageal granular cell tumor removed by endoscopic polypectomy.

Granular cell tumors are rare neoplasms that are generally benign. They are usually found in the tongue, subcutaneous tissues, and breast. Since Abrikossof first described the histology of this tumor in 1926, there have been 86 cases involving the esophagus discussed in the literature. There is a low likelihood of these tumors becoming malignant and recurrence after resection is rare. However, these tumors can be confused with more malignant lesions. We report an additional case involving the esophagus and offer new management guidelines in the era of fiberoptic endoscopy.

Adult↗
PubMed1984

Megacolon and neurofibromatosis: a neuronal intestinal dysplasia. Case report and review of the literature.

This study presents the case of a patient with neurofibromatosis and megacolon. A diffuse, but patchy abnormality of neural tissue was present throughout the colon, especially in the myenteric plexus, but also in the submucosal plexus, smooth muscles, and lamina propria. This consisted of (a) a marked decrease in the number of argyrophilic neurons within the myenteric plexus, enlargement and deformity of those neurons present, and a marked increase of nerve fibers and nerve tract size in the myenteric plexus; (b) a proliferation of neurons and nerve fibers within the smooth muscle and submucosa; and (c) a proliferation of nerve fibers within focal areas of the lamina propria. The relationship of this case to previously reported cases of neuronal intestinal dysplasia and plexiform neurofibromatosis is discussed. Surgical treatment may be necessary and the surgical options are reviewed.

Colonic Neoplasms↗
PubMedDate not supplied

Bacterial peritonitis following esophageal injection sclerotherapy for variceal hemorrhage.

Patients presenting with ascites and upper gastrointestinal hemorrhage were studied prospectively. Five patients presenting with acute variceal hemorrhage were found not to have pre-existing spontaneous bacterial peritonitis on initial paracentesis. However, three of these five developed findings compatible with bacterial peritonitis after sclerotherapy. Although the number of cases is small, our results support the monitoring of ascitic fluid after sclerotherapy.

Adult↗
PubMedDate not supplied

Extraesophageal varices.

Esophageal varices are the most common site of variceal bleeding. However, bleeding from varices that are not located in the esophagus may account for up to 30% of all variceal bleeding. Significant varices can occur in the stomach, duodenum, jejunum, ileum, colon, rectum, and biliary tree. They can also occur at the site of a surgical ostomy. These types of varices bleed less commonly than esophageal varices, but they can also be far more difficult to diagnose and treat. The absence of stigmata of recent esophageal variceal bleeding and certain clues in the patient's history and clinical presentation should raise the clinician's suspicion of an extraesophageal site of variceal bleeding. Particularly, patients with extrahepatic causes of portal hypertension, cirrhotic patients with a prior history of gastrointestinal surgery, and patients who present with profound bleeding but without hematemesis need to be evaluated further if an obvious site of esophageal variceal bleeding is not seen on initial endoscopy. In this article, we review the features particular to extraesophageal varices as well as the diagnosis and management of bleeding from these varices. We use the term extraesophageal rather than ectopic because the term ectopic varices implies exclusion of both esophageal and gastric varices.

Digestive System↗