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1.
Aliment Pharmacol Ther ; 34(2): 146-65, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21615439

ABSTRACT

BACKGROUND: Factors other than acid may play a role in gastro-oesophageal reflux disease (GERD) and its complications. AIM: To assessed the role of bile acids in the pathogenesis of GERD, Barrett's oesophagus and Barrett's-related neoplasia. METHODS: We conducted a systematic review of computerised bibliographic databases for original articles involving humans or human oesophageal tissue or cells that assessed exposure to or manipulation of bile acids. Outcomes assessed included GERD symptoms; gross oesophageal injury; Barrett's oesophagus and related neoplasia; and intermediate markers of inflammation, proliferation or neoplasia. RESULTS: Eighty-three original articles were included. In in vivo studies, bile acids concentrations were higher in the oesophageal aspirates of patients with GERD than controls, and bile acids infusions triggered GERD symptoms, especially in high concentrations or in combination with acid. In ex vivo/in vitro studies, bile acids stimulated squamous oesophageal cells and Barrett's epithelial cells to produce inflammatory mediators (e.g., IL-8 and COX-2) and caused oxidative stress, DNA damage and apoptosis. They also induced squamous cells to change their gene expression pattern to resemble intestinal-type cells and caused Barrett's cells to increase expression of intestinal-type genes. CONCLUSIONS: In aggregate, these studies suggest that bile acids may contribute to the pathogenesis of symptoms, oesophagitis and Barrett's metaplasia with related carcinogenesis in patients with GERD. However, all study results are not uniform and substantial differences in study parameters may explain at least some of this variation.


Subject(s)
Barrett Esophagus/etiology , Bile Acids and Salts/physiology , Esophageal Neoplasms/etiology , Gastroesophageal Reflux/etiology , Gastric Emptying/physiology , Humans , Hydrogen-Ion Concentration
2.
Lancet ; 365(9456): 305-11, 2005.
Article in English | MEDLINE | ID: mdl-15664225

ABSTRACT

BACKGROUND: The usefulness of currently available colon imaging tests, including air contrast barium enema (ACBE), computed tomographic colonography (CTC), and colonoscopy, to detect colon polyps and cancers is uncertain. We aimed to assess the sensitivity of these three imaging tests. METHODS: Patients with faecal occult blood, haematochezia, iron-deficiency anaemia, or a family history of colon cancer underwent three separate colon-imaging studies--ACBE, followed 7-14 days later by CTC and colonoscopy on the same day. The primary outcome was detection of colonic polyps and cancers. Outcomes were assessed by building an aggregate view of the colon, taking into account results of all three tests. FINDINGS: 614 patients completed all three imaging tests. When analysed on a per-patient basis, for lesions 10 mm or larger in size (n=63), the sensitivity of ACBE was 48% (95% CI 35-61), CTC 59% (46-71, p=0.1083 for CTC vs ACBE), and colonoscopy 98% (91-100, p<0.0001 for colonoscopy vs CTC). For lesions 6-9 mm in size (n=116), sensitivity was 35% for ACBE (27-45), 51% for CTC (41-60, p=0.0080 for CTC vs ACBE), and 99% for colonoscopy (95-100, p<0.0001 for colonoscopy vs CTC). For lesions of 10 mm or larger in size, the specificity was greater for colonoscopy (0.996) than for either ACBE (0.90) or CTC (0.96) and declined for ACBE and CTC when smaller lesions were considered. INTERPRETATION: Colonoscopy was more sensitive than other tests, as currently undertaken, for detection of colonic polyps and cancers. These data have important implications for diagnostic use of colon imaging tests.


Subject(s)
Barium Sulfate , Colon/diagnostic imaging , Colonic Neoplasms/diagnosis , Colonography, Computed Tomographic , Colonoscopy , Colonic Polyps/diagnosis , Enema , Female , Humans , Male , Middle Aged , Pneumoradiography , Sensitivity and Specificity
3.
Gastrointest Endosc ; 54(3): 310-5, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11522970

ABSTRACT

BACKGROUND: Virtual colonoscopy has excellent sensitivity for the detection of cancer and polyps greater than 1 cm in diameter. For virtual colonoscopy to succeed as a screening test for colorectal neoplasia, it must be well tolerated and accepted by patients. Patients' experiences with virtual colonoscopy and conventional colonoscopy were assessed and compared. METHODS: Patients referred to the GI clinic for colonoscopy for any indication were recruited to undergo virtual colonoscopy before conventional colonoscopy. Patients were asked to complete a questionnaire twice: after virtual colonoscopy and after completing both tests. Three variables, overall pain, discomfort, and lack of respect, were assessed by using a 7-point Liken scale with higher scores denoting a worse experience. Patients' preferences for virtual colonoscopy versus conventional colonoscopy were determined with a time tradeoff technique. To verify response stability, patients were asked to return an additional questionnaire by mail at 24 hours. RESULTS: Two hundred ninety-five patients completed the questionnaire immediately after the procedures, and 83 patients completed the questionnaire at 24 hours. At both 0 and 24 hours, patients reported more pain, discomfort, and less respect after virtual colonoscopy than conventional colonoscopy (p < 0.01). The overall agreement (Kappa statistic) between times 0 and 24 hours was fair. Patients reported that they preferred conventional colonoscopy and would wait longer for conventional colonoscopy (mean = 4.9 weeks) than undergo a virtual colonoscopy (p < 0.01). CONCLUSIONS: Patients tolerate both virtual colonoscopy and conventional colonoscopy, although they report more pain, discomfort, and less respect undergoing virtual colonoscopy. Efforts to improve patient experience during virtual colonoscopy need to be investigated.


Subject(s)
Colonic Neoplasms/diagnosis , Colonoscopy/methods , Colonoscopy/psychology , Patient Satisfaction , Abdominal Pain/etiology , Female , Humans , Male , Mass Screening/psychology , Middle Aged , Pain Measurement , Prospective Studies , Surveys and Questionnaires , User-Computer Interface
4.
Radiology ; 219(3): 685-92, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11376255

ABSTRACT

PURPOSE: To determine the sensitivity and specificity of computed tomographic (CT) colonography for colorectal polyp and cancer detection by using colonoscopy as the reference standard. MATERIALS AND METHODS: Three hundred patients underwent CT colonography followed by standard colonoscopy. Bowel preparation consisted of magnesium citrate and polyethylene glycol. After colonic air insufflation, patients underwent scanning in the supine and prone positions with 3-mm collimation during a single breath hold. The transverse CT images, sagittal and coronal reformations, and three-dimensional endoluminal images were interpreted by two radiologists independently, and then a consensus reading was performed. CT colonographic findings were correlated with standard colonoscopic and histologic findings. RESULTS: The overall sensitivity and specificity of CT colonography for polyp detection were 90.1% (164 of 182) and 72.0% (85 of 118), respectively. By using direct polyp matching, the overall sensitivity was 69.7% (365 of 524). The sensitivity was 90% (74 of 82) for the detection of polyps 10 mm or larger, 80.1% (113 of 141) for polyps 5.0-9.9 mm, and 59.1% (178 of 301) for polyps smaller than 5 mm. The sensitivity was 94% (64 of 68) for the detection of adenomas 10 mm or larger, 82% (72 of 88) for adenomas 5.0-9.9 mm, and 66.9% (95 of 142) for adenomas smaller than 5 mm. CT colonography was used to identify all eight carcinomas. CONCLUSION: CT colonography has excellent sensitivity for the detection of clinically important colorectal polyps and cancer.


Subject(s)
Colorectal Neoplasms/diagnostic imaging , Tomography, X-Ray Computed , Adenomatous Polyps/diagnostic imaging , Adenomatous Polyps/epidemiology , Case-Control Studies , Colonic Polyps/diagnostic imaging , Colonic Polyps/epidemiology , Colonoscopy , Colorectal Neoplasms/epidemiology , Female , Humans , Male , Mass Screening , Middle Aged , Prospective Studies , Sensitivity and Specificity
5.
Am J Gastroenterol ; 95(9): 2212-7, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11007220

ABSTRACT

OBJECTIVE: The aim of this study was to compare symptoms for patients with uninvestigated dyspepsia and a negative Helicobacter pylori serology who were treated with cisapride or placebo. METHODS: Helicobacter pylori-seronegative patients with chronic dyspepsia were randomized to receive cisapride 10 mg t.i.d. or placebo t.i.d. for 30 days. Symptom scores were performed 1 month and 3 months after randomization. Outcomes measured were dyspepsia symptom scores and a treatment "success" variable defined as absence of symptoms or decrease in the most severe individual symptom by two grades. RESULTS: A total of 60 patients were randomized; 56 completed the 1-month follow-up and 40 completed the 3-month follow-up interview. The mean score for all patients at the time of entry was 11.0 and declined to 8.3 and 8.2 at 1 and 3 months, respectively, after randomization. At 1 month and 3 months after randomization, there was no significant difference in the number of patients meeting the "success" variable for patients receiving cisapride as compared to placebo. The mean decline in symptom severity scores was not significantly different for patients receiving placebo or cisapride at 1 month (mean, -2.8 vs -3.1; difference = 0.3, p = 0.74) or 3 months (-3.1 vs -2.6, difference = -0.5, p = 0.58) after randomization. CONCLUSIONS: No significant difference in the severity of dyspeptic symptoms was found for patients receiving cisapride as compared to placebo in the setting of uninvestigated dyspepsia and a negative Helicobacter pylori serology.


Subject(s)
Antibodies, Bacterial/analysis , Cisapride/therapeutic use , Dyspepsia/drug therapy , Gastrointestinal Agents/therapeutic use , Helicobacter pylori/immunology , Administration, Oral , Adult , Cisapride/administration & dosage , Diagnosis, Differential , Dyspepsia/diagnosis , Dyspepsia/etiology , Female , Gastrointestinal Agents/administration & dosage , Helicobacter Infections/diagnosis , Helicobacter Infections/microbiology , Humans , Immunoglobulin G/immunology , Male , Severity of Illness Index
6.
Dig Dis Sci ; 45(4): 809-18, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10759254

ABSTRACT

The aim of this study was to determine the prevalence of upper gastrointestinal symptoms (UGIS) in a general population and quantify the relationship of those symptoms to healthcare utilization and quality of life. In-person interviews were conducted with 2056 United States and Canadian residents selected at random. Subjects reported frequency and severity for 11 symptoms, prescription and over-the-counter medication use, primary care and specialty physician visits in prior three months, and completed the Psychological General Well-Being Scale. For analyses, subjects were classified into four mutually exclusive symptom groups: gastroesophageal reflux disease (GERD) -like, GERD plus motility-like (GERD+), ulcerlike, and motility-like. Of the total sample, 51.4% reported the occurrence of at least one UGIS in the prior three months. Subjects in the GERD+ and ulcer groups used more prescription medications and were more likely to see a physician about the symptoms (P<0.001). Subjects with symptoms demonstrated poorer quality of life compared to subjects with no symptoms. The prevalence of UGIS in the general population is high and symptoms are associated with significant health-care utilization and poorer quality of life.


Subject(s)
Gastroesophageal Reflux/epidemiology , Health Services/statistics & numerical data , Peptic Ulcer/epidemiology , Quality of Life , Adult , Aged , Canada/epidemiology , Drug Prescriptions/statistics & numerical data , Drug Utilization/statistics & numerical data , Female , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/psychology , Gastrointestinal Motility , Humans , Male , Middle Aged , Nonprescription Drugs/therapeutic use , Office Visits/statistics & numerical data , Peptic Ulcer/complications , Peptic Ulcer/drug therapy , Peptic Ulcer/psychology , Prevalence , Severity of Illness Index , United States/epidemiology
7.
Int J Cancer ; 83(2): 162-6, 1999 Oct 08.
Article in English | MEDLINE | ID: mdl-10471521

ABSTRACT

Many colorectal cancers have high levels of cyclo-oxygenase 2 (COX-2), an enzyme that metabolizes the essential fatty acids into prostaglandins. Since the low-density lipoprotein receptor (LDLr) is involved in the uptake of essential fatty acids, we studied the effect of LDL on growth and gene regulation in colorectal cancer cells. DiFi cells grown in lipoprotein-deficient sera (LPDS) grew more slowly than cells with LDL. LDLr antibody caused significant inhibition of tumor cell growth but did not affect controls. In addition, LDL uptake did not change in the presence of excess LDL, suggesting that ldlr mRNA lacks normal feedback regulation in some colorectal cancers. Analysis of the ldlr mRNA showed that excess LDL in the medium did not cause down-regulation of the message even after 24 hr. The second portion of the study examined the mRNA expression of ldlr and its co-regulation with cox-2 in normal and tumor specimens from patients with colorectal adenocarcinomas. The ratio of tumor:paired normal mucosa of mRNA expression of ldlr and of cox-2 was measured in specimens taken during colonoscopy. ldlr and cox-2 transcripts were apparent in 11 of 11 carcinomas. There was significant coordinate up-regulation both of ldlr and of cox-2 in 6 of 11 (55%) tumors compared with normal colonic mucosa. There was no up-regulation of cox-2 without concomitant up-regulation of ldlr. These data suggest that the LDLr is abnormally regulated in some colorectal tumors and may play a role in the up-regulation of cox-2.


Subject(s)
Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Isoenzymes/biosynthesis , Prostaglandin-Endoperoxide Synthases/biosynthesis , Receptors, LDL/biosynthesis , Adenocarcinoma/enzymology , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Biopsy , Cell Division/genetics , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/pathology , Cyclooxygenase 2 , Feedback , Gene Expression Regulation, Enzymologic , Humans , Isoenzymes/genetics , Lipoproteins, LDL/pharmacology , Male , Membrane Proteins , Middle Aged , Prostaglandin-Endoperoxide Synthases/genetics , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, LDL/genetics , Tumor Cells, Cultured , Up-Regulation/genetics
8.
Am J Gastroenterol ; 93(7): 1060-3, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9672330

ABSTRACT

OBJECTIVE: The aim of this study was to determine if omeprazole improves pulmonary function and quality of life in asthmatics with gastroesophageal reflux. METHODS: This was a double blind, randomized, placebo-controlled cross-over trial. After a 4-wk lead-in period, nine patients with documented asthma and gastroesophageal reflux, were prescribed either omeprazole 20 mg, daily or placebo for 8 wk and then crossed over to the alternate treatment. Outcome measurements included: forced expiratory volume at 1 s (FEV1), peak expiratory flow rate (PEFR), and responses on the Asthma Quality of Life Questionnaire, a validated disease specific measure of functional status. RESULTS: After omeprazole treatment, compared with placebo, patients had higher mean morning and evening PEFR, mean absolute difference (95% CI): morning: 37.8 L/min. (10.9-64.6), evening: 31.2 (3.2-59.2). Omeprazole treatment led to higher mean overall scores on the Asthma Quality of Life Questionnaire, and on the subdomains of activity limitation, symptoms, and emotions (p = 0.039, 0.049, 0.024, 0.040). A trend toward higher FEV1 (mean: 15.6% difference) with omeprazole failed to reach statistical significance (p > 0.2). CONCLUSIONS: After taking omeprazole for 8 wk, asthmatics with GER have better PEFR and quality of life than after placebo.


Subject(s)
Anti-Ulcer Agents/therapeutic use , Asthma/physiopathology , Gastroesophageal Reflux/drug therapy , Omeprazole/therapeutic use , Peak Expiratory Flow Rate/drug effects , Quality of Life , Activities of Daily Living , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Ulcer Agents/administration & dosage , Asthma/complications , Asthma/psychology , Circadian Rhythm , Cross-Over Studies , Double-Blind Method , Emotions , Female , Forced Expiratory Volume/drug effects , Gastroesophageal Reflux/complications , Health Status , Humans , Male , Middle Aged , Omeprazole/administration & dosage , Placebos , Reproducibility of Results , Treatment Outcome
9.
N Engl J Med ; 339(3): 153-9, 1998 Jul 16.
Article in English | MEDLINE | ID: mdl-9664091

ABSTRACT

BACKGROUND: Although bleeding lesions anywhere in the gastrointestinal tract can cause a positive reaction on guaiac-based fecal occult-blood tests, the relative frequency of upper gastrointestinal and colonic lesions is unknown. METHODS: During a period of 30 months, we prospectively studied all patients with at least one stool specimen containing fecal occult blood who were referred for further evaluation. Fecal occult blood was detected by standard guaiac-based tests of stool specimens obtained as part of routine screening or of stool obtained by digital rectal examination. Patients with documented iron-deficiency anemia or active gastrointestinal bleeding were excluded from the study. All participants had a detailed history taken and underwent colonoscopy, followed by esophagogastroduodenoscopy. RESULTS: Of the 409 patients with fecal occult blood who were referred, 310 were potentially eligible to participate, and 248 (mean age, 61 years; range, 40 to 89) were studied; 40 percent were women. We identified lesions consistent with occult bleeding in 119 patients (48 percent); in 71 bleeding lesions were found in the upper gastrointestinal tract, and in 54 they were identified in the colon. Six patients had abnormalities in both areas. The most common upper gastrointestinal lesions were esophagitis (23 patients), gastric ulcer (14), gastritis (12), and duodenal ulcer (10). Thirty patients with lesions in the upper gastrointestinal tract were long-term users of aspirin, ethanol, nonsteroidal antiinflammatory drugs, or a combination of these substances. The most common colonic lesions were adenomas more than 1.0 cm in diameter (29 patients), carcinoma (13), colitis (5), and vascular ectasia (5). Although the overall sensitivity of symptoms for the detection of gastrointestinal lesions was low, logistic-regression analysis demonstrated that the presence of symptoms in the upper gastrointestinal tract was associated with the detection of lesions in the upper gastrointestinal tract (odds ratio, 2.6; 95 percent confidence interval, 1.4 to 4.7). In both patients with symptoms and those without symptoms, the prevalence of lesions in the upper gastrointestinal tract was greater than or equal to that of colonic lesions. CONCLUSIONS: In a group of patients with positive fecal occult-blood tests who were referred for further evaluation, from which those with iron-deficiency anemia and active bleeding had been excluded, upper gastrointestinal lesions were identified more frequently than colonic lesions.


Subject(s)
Colonic Diseases/diagnosis , Gastrointestinal Diseases/diagnosis , Occult Blood , Aged , Colonic Diseases/epidemiology , Endoscopy, Digestive System , False Positive Reactions , Female , Gastrointestinal Diseases/epidemiology , Humans , Logistic Models , Male , Middle Aged , Prevalence , Prospective Studies , Sensitivity and Specificity
10.
CLAO J ; 24(1): 36-40, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9474452

ABSTRACT

PURPOSE: The purpose of this study was to describe and evaluate the frequent parameter changes required in aphakic infants fit with rigid gas permeable (RGP) contact lenses. METHODS: Twenty-five eyes from 18 patients with congenital cataracts were fit postoperatively with RGP lenses and followed for an average of 19 months. The original lens specifications were determined by keratometer readings, corneal diameter, and axial length or retinoscopy obtained under sedation just prior to or after cataract extraction surgery. The frequency of changes in contact lens power, base curve, and diameter was recorded and analyzed. RESULTS: Due to rapid growth and/or difficulty in achieving accurate measurements, repeated contact lens adjustments were needed to ensure proper power and fit. CONCLUSIONS: The data contained in this study indicates a relatively stable period--from 6 to 12 months postoperatively--where the likelihood that contact lenses will need to be modified falls below 50%.


Subject(s)
Acrylic Resins , Aphakia, Postcataract/therapy , Contact Lenses , Silicones , Aging , Cataract/congenital , Cataract/diagnosis , Cataract Extraction , Follow-Up Studies , Humans , Infant , Infant, Newborn , Patient Satisfaction , Prosthesis Fitting , Refraction, Ocular
11.
Am J Gastroenterol ; 93(2): 179-82, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9468237

ABSTRACT

OBJECTIVE: The objective of this study was to determine whether specific clinical symptoms associated with hematochezia are predictive of important GI pathology and whether full colonoscopic examination is necessary. METHODS: A total of 103 outpatients (> or = 45 yr) with hematochezia, defined as the passage of bright red blood per rectum, underwent anoscopy and colonoscopy. Before endoscopy, patients completed a detailed interview, quantitating the amount and frequency of bleeding, weight loss, use of aspirin/NSAIDs, change in bowel habits, family history, and prior GI illnesses. Based on this information, physicians were asked to predict whether the bleeding was from a perianal or more proximal site. At colonoscopy, pathology was stratified as either proximal or distal to the sigmoid/descending junction. Substantial pathology was defined as one or more adenomas > 8 mm, carcinoma, or colitis. RESULTS: Anoscopy demonstrated internal and external hemorrhoids in 78 and 29 patients, respectively. On colonoscopy, 36 patients had 43 substantial lesions. Thirty-seven of these lesions were distal to the junction of the descending and sigmoid colons and six were proximal lesions. Four patients had cancer; all were distal lesions. Patients with substantial lesions were more likely to give a history of blood mixed within their stool (p = 0.03), to have more episodes of hematochezia per month (p = 0.008), and to have a significantly shorter duration of bleeding before medical evaluation (p = 0.02) than did patients without such lesions. However, the physician's clinical assessment did not predict reliably which patients were likely to have substantial pathology. CONCLUSIONS: In patients with hematochezia, clinicians were unable to distinguish between those patients with and those without significant colonic lesions by history alone. Flexible sigmoidoscopy would have demonstrated most (95%) substantial lesions. The lesions that flexible sigmoidoscopy missed were an unlikely cause of bleeding in this small group of patients.


Subject(s)
Gastrointestinal Hemorrhage/etiology , Ambulatory Care , Colitis/complications , Colitis/diagnosis , Colonoscopy , Colorectal Neoplasms/complications , Colorectal Neoplasms/diagnosis , Diagnosis, Differential , Gastrointestinal Hemorrhage/diagnosis , Hemorrhoids/complications , Hemorrhoids/diagnosis , Humans , Middle Aged
12.
Ann Intern Med ; 126(11): 858-65, 1997 Jun 01.
Article in English | MEDLINE | ID: mdl-9163286

ABSTRACT

BACKGROUND: Hemorrhage from esophageal varices remains a substantial management problem. Endoscopic sclerotherapy was preferred for more than a decade, but fluoroscopically placed intrahepatic portosystemic stents have recently been used with increasing frequency. OBJECTIVE: To compare sclerotherapy with transjugular intrahepatic portosystemic shunt (TIPS) in patients with bleeding from esophageal varices. DESIGN: Randomized, controlled clinical trial. SETTING: Three teaching hospitals. PATIENTS: 49 adults hospitalized with acute variceal hemorrhage from November 1991 to December 1995: 25 assigned to sclerotherapy and 24 assigned to TIPS. INTERVENTION: Patients assigned to repeated sclerotherapy had the procedure weekly. In those assigned to TIPS, an expandable mesh stent was fluoroscopically placed between an intrahepatic portal vein and an adjacent hepatic vein. MEASUREMENTS: Pretreatment measures included demographic and laboratory data. Postrandomization data included index hospitalization survival, duration of follow-up, successful obliteration of varices, rebleeding from varices, number of variceal rebleeding events, total days of hospitalization for variceal bleeding, blood transfusion requirements after randomization, prevalence of encephalopathy, and total health care costs. RESULTS: Mean follow-up (+/-SE) was 567 +/- 104 days in the sclerotherapy group and 575 +/- 109 days in the TIPS group. Varices were obliterated more reliably by TIPS than by sclerotherapy (P < 0.001). Patients having TIPS were significantly less likely to rebleed from esophageal varices than patients receiving sclerotherapy (3 of 24 compared with 12 of 25; P = 0.012). No other follow-up measures differed significantly between groups. A trend toward improved survival, which was not statistically significant, was noted in the TIPS group (hazard ratio, 0.53 [95% CI, 0.18 to 1.5]). CONCLUSIONS: In obliterating varices and reducing rebleeding events from esophageal varies, TIPS was more effective than sclerotherapy. However, TIPS did not decrease morbidity after randomization or improve health care costs. It seemed to produce better survival, but the increase in survival was not statistically significant.


Subject(s)
Esophageal and Gastric Varices/complications , Gastrointestinal Hemorrhage/prevention & control , Portasystemic Shunt, Transjugular Intrahepatic , Sclerotherapy , Adult , Endoscopy , Female , Follow-Up Studies , Gastrointestinal Hemorrhage/mortality , Humans , Length of Stay , Male , Middle Aged , Proportional Hazards Models , Recurrence , Survival Analysis , Treatment Outcome
13.
Exp Physiol ; 82(2): 369-76, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9129951

ABSTRACT

Endothelial dysfunction has an important role to play in the pathophysiology of human vascular disease. The maintenance of barrier function is critical to the role of vascular endothelium in cardiovascular haemostasis and this function can be compromised by inflammatory mediators, cytokines or oxidants. Under conditions of oxidative stress a variety of reactive oxygen species (ROS) may be generated, which increase the permeability of the endothelial monolayer to fluid, macromolecules and inflammatory cells. The endothelium-derived nitric oxide radical (NO), whose physiological actions include effects on vascular smooth muscle, is normally inactivated by the superoxide radical anion. While large amounts of NO have cytotoxic potential, it is now becoming clear that combinations of NO with ROS can produce either cytotoxic or cytoprotective effects, depending on the relative amounts of each which are present in the target cell or its environment at a particular time. The contribution of NO to oxidant-mediated endothelial barrier dysfunction can be assessed in vitro in endothelial monolayers grown on porous membrane supports. In this model, using hydrogen peroxide (H2O2) as the oxidant, H2O2-induced losses of barrier function can be enhanced or partially offset by NO donor drugs, depending on the concentration of NO donor used. Furthermore, the injurious or cytoprotective effects of these agents appear to be determined by the quantity of NO generated. Since NO is administered clinically by inhalation in conditions such as pulmonary hypertension or the adult respiratory distress syndrome, which are themselves associated with generation of ROS, it is likely that low concentrations of NO may protect the pulmonary vascular endothelium while high concentrations might be expected to combine with ROS to yield intermediates capable of causing further endothelial injury or loss of barrier function.


Subject(s)
Blood-Air Barrier/physiology , Endothelium, Vascular/physiopathology , Nitric Oxide/physiology , Oxidative Stress/physiology , Vascular Diseases/physiopathology , Animals , Endothelium, Vascular/cytology , Humans , Oxidants/metabolism , Vascular Diseases/metabolism , Vascular Diseases/pathology
14.
Gastrointest Endosc Clin N Am ; 7(4): 657-70, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9376956

ABSTRACT

The majority of patients who present with acute upper gastrointestinal hemorrhage are found to be bleeding from acid peptic disease including ulcer, esophagitis and gastritis, and variceal disease. Mallory-Weiss tear, Dieulafoy's lesion, cancer, and other rare lesions account for the bleeding source in the remaining patients. Endoscopic hemostasis may be effective in many of the conditions, but only Mallory-Weiss tear and Dieulafoy's lesion are encountered frequently enough to be clinically significant.


Subject(s)
Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/therapy , Hemostasis, Endoscopic/instrumentation , Hemostasis, Endoscopic/methods , Mallory-Weiss Syndrome/therapy , Acute Disease , Humans , Mallory-Weiss Syndrome/complications , Peptic Ulcer Hemorrhage/therapy , Randomized Controlled Trials as Topic , Treatment Outcome
15.
Eur J Pharmacol ; 307(2): 233-41, 1996 Jun 27.
Article in English | MEDLINE | ID: mdl-8832226

ABSTRACT

Acute effects of the nitric oxide (NO) donors sodium nitroprusside and glyceryl trinitrate on hydrogen peroxide (H2O2)-induced increases in endothelial monolayer permeability to trypan blue-labelled bovine serum albumin have been investigated in vitro. Exposure of bovine pulmonary artery endothelial cell monolayers to 0.2 mM H2O2 for 20 min caused a significant increase in percentage trypan blue-labelled albumin transfer from the lumenal to the ablumenal compartment (basal 6.0 +/- 0.6 to 25.4 +/- 0.9%, n = 4, P < 0.0005). In separate experiments 100 microM sodium nitroprusside significantly enhanced the effect of 0.2 mM H2O2 (from 7.4 +/- 1.4 to 11.9 +/- 1.5%, n = 9, P < 0.0001) but did not alter albumin transfer in the absence of H2O2. This additive effect appeared to be due to NO release from sodium nitroprusside, since nitrite concentration in the medium overlying cells treated with 100 microM sodium nitroprusside was 19.9 +/- 1.8 microM (n = 12). Significantly less nitrite (3.5 +/- 0.5 microM, n = 12, P < 0.0001) was found in the medium overlying cells treated with 100 microM glyceryl trinitrate, which in contrast to sodium nitroprusside, inhibited the permeability increase caused by H2O2 (from 15.6 +/- 3.3 to 13.8 +/- 3.1%, n = 6, P < 0.001). Furthermore 10 microM sodium nitroprusside, which released comparable amount of nitrite (4.5 +/- 0.4 microM, n = 6) to 100 microM glyceryl trinitrate, also inhibited the permeability increase caused by H2O2 (from 20.7 +/- 0.4 to 19.4 +/- 0.3%, n = 9, P < 0.01). We conclude that relatively large amounts of NO released from 100 microM sodium nitroprusside exacerbate the barrier dysfunction caused by H2O2, while lower amounts of NO give a small amount of cytoprotection.


Subject(s)
Endothelium/physiopathology , Hydrogen Peroxide/adverse effects , Nitric Oxide/physiology , Animals , Cattle , Cell Survival , Cells, Cultured , Endothelium/drug effects , Endothelium/metabolism , In Vitro Techniques , Microscopy, Electron , Nitrites/metabolism , Nitroglycerin/pharmacology , Nitroprusside/pharmacology , Pulmonary Artery/cytology , Serum Albumin, Bovine/metabolism , Spectrophotometry, Ultraviolet , Trypan Blue
16.
Surg Endosc ; 9(7): 820-3, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7482193

ABSTRACT

We report a case of metastatic lobular breast carcinoma with extrahepatic gastrointestinal disease. On the basis of clinical findings, radiologic investigations, computerized axial tomography, gastrointestinal endoscopy, and gastric biopsy, the diagnosis of gastric and ileal Crohn's disease was made. The correct diagnosis of peritoneal carcinomatosis was made at laparoscopy. This case exemplifies the utility of laparoscopy in establishing the diagnosis and staging for abdominal disease of uncertain etiology.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Lobular/diagnosis , Carcinoma, Lobular/secondary , Crohn Disease/diagnosis , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/secondary , Laparoscopy , Aged , Female , Humans , Neoplasm Staging
17.
N Engl J Med ; 331(25): 1685-8, 1994 Dec 22.
Article in English | MEDLINE | ID: mdl-7969359

ABSTRACT

BACKGROUND: Hydrocolonic ultrasonography--abdominal ultrasonography in conjunction with the retrograde instillation of water into the colon--has been advocated as an alternative to colonoscopy for detecting colorectal polyps and cancer. We conducted a prospective, blinded trial to evaluate the procedure further. METHODS: Fifty-two consecutive patients (50 men and 2 women; average age, 62 years) who were referred for colonoscopy underwent hydrocolonic ultrasonography followed by colonoscopy. The physicians performing colonoscopy were blinded to the ultrasound results. Patients who had a history of colonic polyps or tumors or who had previously undergone flexible sigmoidoscopy or colonoscopy were excluded. RESULTS: Twenty-two patients had normal results on colonoscopy, 26 had polyps, 3 had cancer and polyps, and 1 had cancer alone. Twenty patients had polyps less than 7 mm in diameter, eight had polyps 7 mm or more in diameter, and one had a polyp of unknown size. Hydrocolonic ultrasonography did not detect any cancers and detected only one polyp > or = 7 mm and one polyp < 7 mm in diameter. The overall sensitivity of ultrasonography for identifying any polyp was 6.9 percent, and for identifying a polyp > or = 7 mm, it was 12.5 percent. Ultrasonography suggested the presence of five masses and five polyps that were not confirmed by colonoscopy. Six patients had incomplete ultrasound studies because of discomfort or the inability to retain water. There were two complications: one patient had two vasovagal episodes, and another had diaphoresis. CONCLUSIONS: Hydrocolonic ultrasonography was less useful than colonoscopy for detecting colorectal polyps and cancers. The usefulness of the technique in screening for colonic polyps and tumors appears to be limited.


Subject(s)
Colonic Neoplasms/diagnostic imaging , Colonic Polyps/diagnostic imaging , Ultrasonography, Interventional , Colonic Polyps/diagnosis , Colonic Polyps/surgery , Colonoscopy , False Positive Reactions , Female , Humans , Male , Middle Aged , Prospective Studies
19.
Aliment Pharmacol Ther ; 7(5): 537-41, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8280822

ABSTRACT

It has been proposed that famotidine may be effective in maintaining intragastric pH > or = 4 for up to 12 h with a single i.v. 20 mg bolus injection and thereby prevent acute stress-related mucosal haemorrhage. The present study was designed to compare a ranitidine continuous i.v. infusion (6.25 mg/h) vs. famotidine bolus injection (20 mg every 12 h) on 24-h intragastric pH and gastric acid secretion. Twenty-eight healthy volunteers (15 males, 13 females; 20-56 years) participated in two 24-h treatment periods; each test was in random order separated by 7-10 days. After an overnight fast, subjects were intubated and gastric pH and acid secretion measured hourly. Whereas ranitidine maintained gastric pH above 4 for the entire 24-h period, mean pH steadily decreased to a nadir of 2.9 and 3.7, respectively, 12 h after each famotidine injection (P < 0.01 vs. ranitidine). Furthermore, gastric acid secretion increased to 4.4 +/- 1.2 mmol/h 12 h after famotidine injection compared to 1.1 +/- 0.3 mmol/h with ranitidine (P < 0.01). We conclude that ranitidine delivered as a continuous i.v. infusion (6.25 mg/h) is superior to bolus famotidine injections (20 mg) at 12-h intervals in suppressing gastric acid secretion and maintaining an intragastric pH > or = 4. More frequent famotidine dosing, or delivery by continuous i.v. infusion, may be required to provide prolonged acid suppression.


Subject(s)
Famotidine/pharmacology , Gastric Acid/metabolism , Ranitidine/pharmacology , Adult , Famotidine/administration & dosage , Female , Gastric Acidity Determination , Humans , Hydrogen-Ion Concentration , Infusions, Intravenous , Injections, Intravenous , Male , Middle Aged , Ranitidine/administration & dosage
20.
J Clin Gastroenterol ; 17(2): 97-100, 1993 Sep.
Article in English | MEDLINE | ID: mdl-8409329

ABSTRACT

Nonulcer dyspepsia (NUD) is an enigmatic disorder which likely has heterogeneous etiologies. Helicobacter pylori-associated gastritis has been identified in a large number of patients with NUD, raising speculation that chronic infection with this organism may cause dyspepsia in some patients. Prospective case-control and cohort studies however do not suggest that H. pylori prevalence is greater in NUD than in asymptomatic controls. Limited therapeutic trials of H. pylori-eradication therapy have not shown a convincing symptomatic improvement compared with placebo treatment. Definition of the role of H. pylori in NUD awaits further well-designed, well-controlled epidemiologic and therapeutic studies. Until such information is available, routine endoscopic gastric biopsies looking for H. pylori in patients with NUD should be abandoned.


Subject(s)
Dyspepsia/etiology , Dyspepsia/pathology , Biopsy , Dyspepsia/microbiology , Gastroscopy , Helicobacter Infections/complications , Helicobacter pylori , Humans
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