APC gene alterations in Barrett's metaplasia are implicated at an early stage in the carcinogenesis of esophageal adenocarcinoma.
Explore the source record for details and available documents.
Adenocarcinoma↗
Biomedical subjects
M Fein
Publications and source records attributed to M Fein.
Can the combination of symptoms and endoscopy confirm the presence of gastroesophageal reflux disease?
The aim of this study was to evaluate the accuracy of symptomatology and esophagogastroduodenoscopy (EGD) in the diagnosis of proven gastroesophageal reflux disease (GERD). We evaluated the symptoms and EGD findings of 100 consecutive patients presenting with symptoms suggestive of GERD. Patients' symptoms were scored at their first visit with a standardized symptom scoring system (grades 0-3). Grade 3 symptoms were the most severe. EGD findings were classified according to the modified Savary-Miller scale. Esophageal acid exposure was quantified using 24-hour esophageal pH monitoring; a positive composite score was considered evidence of GERD. Fifty-seven patients had positive pH scores, and 43 were negative. The combination of grade 2 or 3 heartburn and/or regurgitation with erosive esophagitis or Barrett's esophagus on EGD had a 97 per cent specificity and 64 per cent sensitivity for accurately diagnosing GERD. It is concluded that, in the presence of moderate to severe symptoms and endoscopic injury, the diagnosis of GERD can be made without further studies. However, 24-hour esophageal pH monitoring is still indicated in patients with mild typical symptoms, atypical symptoms, or when the combination of heartburn and regurgitation, regardless of their severity, occurs in the absence of severe mucosal damage.
Adolescent↗
Fiberoptic technique for 24-hour bile reflux monitoring. Standards and normal values for gastric monitoring.
Physiologic bile reflux was assessed in 27 in vivo test with healthy volunteers to define a standardized protocol and normal values for 24-hour enterogastric bile reflux monitoring (protocol with supine, upright, and meal phases and a free diet avoiding alcohol, smoking, and coffee, evaluation with different thresholds of absorbance units: 0.14, 0.25). In vitro tests with bile-sodium solutions demonstrated a linear dependence of absorbance for bilirubin up to 600 mumol/liter (range of the fiberoptic device: 0.0-1.0). Fluids and food might interfere with absorbances below 0.25 (exception: coffee). In vivo bile often remains in the stomach for more than 1 hr; these events were defined as reflux episodes. The upper limits for physiologic bile reflux are a percentage of total time of bile reflux of 28.2% and an average absorbance during a reflux episode of 0.62 (95th percentile with threshold 0.25). Comparing bile with pH monitoring (absorbance > 0.25 and/or pH > 4), an increase of bilirubin was found most frequently with constant pH (45%) or an increase of pH with constant bilirubin (36%). The hypothesis was drawn that bile and duodenal or pancreatic secretions may separately contribute to duodenogastric reflux.
Adult↗
Duodenogastroesophageal reflux parallels acid and not alkaline exposure in the esophagus and contributes to complications of reflux disease.
Explore the source record for details and available documents.
Barrett Esophagus↗
Quantification of color Doppler for the evaluation of tissue vascularization.
Assessment of tissue vascularization with color Doppler (CD) can improve differential diagnosis of tumors. Until now, measurement of flow velocities is restricted to conventional duplex ultrasound of single vessels or semiquantitative scoring of the vessel distribution in CD. We developed a new method for quantification of CD data in organs or tumors by statistical image analysis. Based on standardized image recording, data is acquired from the video output of any ultrasound scanner using a 24-bit color framegrabber in a personal computer. The digitized colors are recognized according to their position in the CD palette bar resulting in an 8-bit color image (number of identified pixels > 99.9%). Within the region of interest, statistics of the detected flow patterns are calculated. The color pixel density and the mean color value varies between recordings of the same image during subsequent systolic peaks with a SD of 10% and 2%, respectively, and within different sections of the same organ or tumor with 25% and 10-50%. This analysis can be used for comparative or longitudinal studies and an objective evaluation of CD in complex vascular formations such as tumors. Its diagnostic impact has already been demonstrated in clinical studies.
Blood Flow Velocity↗
Current aspects of gastroduodenal ulcer disease: diagnosis of pathophysiologic background and indications for operative therapy.
The management of gastroduodenal ulcer disease has changed because of new evidence of its pathophysiologic background and the introduction of new medication and operative techniques. Proximal gastric vagotomy (PGV) was abandoned by some as the treatment of choice because of high recurrence rates. With the advent of minimally invasive surgery, laparoscopic vagotomy has renewed interest in vagotomy as a treatment option for gastroduodenal ulcer disease. In view of this development, a study was performed to investigate the incidence of abnormal gastric hyperacidity in a population of ulcer patients in order to select those patients for operative acid reduction who will benefit most from operation. Sixty-eight patients with gastroduodenal ulcer disease underwent 24-hour-gastric-pH monitoring, 29 of these patients subsequently underwent proximal gastric vagotomy. The study demonstrates that it is possible to identify patients with hyperacidity. It revealed a variation of intraluminal gastric acidity in patients with different ulcer locations. On the basis of the opinion that gastric hyperacidity is the main indication for PGV, it is emphasized that the choice of surgery should depend on the functional defect and that the indication for operation should be based on therapy-resistant symptoms.
Duodenogastric Reflux↗
Lateral mobility of lipid analogues and GPI-anchored proteins in supported bilayers determined by fluorescent bead tracking.
Lipid analogues and glycosylphosphatidylinositol (GPI)-anchored proteins incorporated in glass-supported phospholipid bilayers (SBL) were coupled to small (30 nm diameter) fluorescent beads whose motion in the liquid phase was tracked by intensified fluorescence video microscopy. Streptavidin (St), covalently attached to the carboxyl modified surface of the polystyrene bead, bound either the biotinylated membrane component, or a biotinylated monoclonal antibody (mAb) directed against a specific membrane constituent. The positions of the beads tethered to randomly diffusing membrane molecules were recorded at 0.2 sec intervals for about 1 min. The mean square displacement (rho) of the beads was found to be a linear function of diffusion time t, and the diffusion coefficient, D, was derived from the relation, rho(t) = 4Dt. The values of D for biotinylated phosphatidylethanolamine (Bi-PE) dispersed in an egg lecithin:cholesterol (80:20%) bilayer obtained by this methodology range from 0.05 to 0.6 micron 2/sec with an average of mean value of D = 0.26 micron 2/sec, similar to the value of mean value of D = 0.24 micron 2/sec for fluorescein-conjugated phosphatidylethanolamine (Fl-PE) linked to St-coupled beads by the anti-fluorescein mAb 4-4-20 or its Fab fragment. These values of D are comparable to those reported for Fl-PE linked to 30 nm gold particles but are several times lower than that of Fl-PE in the same planar bilayer as measured by fluorescence photobleaching recovery, D = 1.3 microns 2/sec. The mobilities of two GPI-anchored proteins in similar SBL were also determined by use of the appropriate biotinylated mAb and were found to be mean value of D = 0.25 and 0.56 micron 2/sec for the decay accelerating factor (DAF, CD55) and the human Fc gamma RIIIB (CD16) receptors, respectively. The methodology described here is suitable for tracking any accessible membrane component.
Animals↗
New method of estimating the ultrasonic beam ratio parameter for characterizing sound propagation in tissue.
The backscattered ultrasonic signal from soft tissue can be considered to consist of two parts: a spatially fluctuating component due to coherent scattering from randomly distributed scattering centers and a relatively constant component related to structural ordering. The relationship between these, which has been termed the "beam ratio parameter" influences the speckle pattern of an ultrasound image. First-order image statistics for this special speckle pattern are characterized by the Rician distribution. Changes of second-order statistics have also been derived as a function of the beam ratio parameter. A new method for the estimation of the beam ratio parameter from the intensity distribution of the ultrasonic signal is described in this paper. This method was used to measure the parameter in ultrasonic images from phantoms and liver tissue yielding values of about 0.1. The measured changes of the second-order statistics were not correlated to this parameter. The results indicate that the relatively constant intensity component related to structural ordering has only a small influence on the speckle pattern.
Biopsy↗
Direct radioimmunoassay procedure for plasma dexamethasone with a sensitivity at the picogram level.
A simple radioimmunoassay (RIA) for the direct quantitation of plasma dexamethasone (DEX) at the picogram level has been developed. An antiserum with high specificity and avidity was obtained by the immunization of a carefully synthesized dexamethasone-21-succinyl-thyroglobulin with a high incorporation ratio. As little as 1 pg of DEX in 50 microL of plasma sample can be detected directly by this RIA without extraction and other purification procedures. Intra- and interassay coefficients of variation were 2.1 and 3.3% for plasma levels at 2.93 ng/mL or 2.3 and 7.2% for plasma levels at 0.88 ng/mL. Blank values for plasma of normal or pre-DEX patients were always under the detection limit (20 pg/mL). Excellent linearity (r = 0.9991-0.9999) was demonstrated between the serial dilutions of six plasma samples and their corresponding DEX concentrations. In single-dose DEX (0.25-1 mg) pharmacokinetic studies, plasma DEX was consistently detectable up to 24 h post dose. Compared with existing methods, this direct RIA demonstrates superior performance with regard to simplicity, sensitivity, specificity, and reproducibility. It also enables high sample throughput and has proven robust in our hands. This assay should be readily transferable to other laboratories for clinical or research purposes.
Animals↗
A highly sensitive and specific radioimmunoassay for quantitation of plasma fluphenazine.
Antisera of high sensitivity and selectivity were obtained from rabbits immunized with conjugates of hemisuccinylated fluphenazine and porcine thyroglobulin. The antiserum selected (titer 1:6000) for the development of the RIA was obtained after a priming dose and a single iv booster injection three months later. This antiserum had negligible crossreactivity with known available metabolites of fluphenazine (FPZ) and an affinity constant of 2 X 10(10) L/mol. Tritiated FPZ was further purified by HPLC and used as a ligand. The method detects as little as 20 pg/mL of plasma (4 pg/RIA tube) after 1 mL of plasma is extracted. The extraction was performed at a basic pH with heptane: isoamyl alcohol (99:1); the solvent was then back extracted using an acetic phosphate buffer. Recoveries were uniformly high (88.6 +/- 2.1%), and this aqueous buffer extract was used directly in the RIA procedure. The assay has intra- and interassay coefficients of variation of 5.8 and 8.2%, respectively, in a plasma concentration of 95 pg/mL. Results using this procedure have been cross validated against an HPLC procedure (r = 0.952, slope = 1.032, intercept = 0.009, n = 18). In a single-dose FPZ study (10 mg, po), plasma FPZ levels in 25 normal volunteers could be monitored greater than 48 h post dose. Single plasma level profiles, after an initial injection of 12.5 mg of FPZ decanoate, could be measured greater than 36 d, and, in some cases, up to 100 d post dose.
Administration, Oral↗
Growth hormone secretion in prepubertal children with major depression. II. Sleep-related plasma concentrations during a depressive episode.
Plasma growth hormone (GH) concentrations were determined every 20 minutes during sleep in 71 prepubertal children: 22 had endogenous major depressive disorder, 20 had nonendogenous major depressive disorder, 21 had nondepressed neurotic disorders, and eight were normal. Both depressive groups secreted significantly more GH during sleep than did controls. Measures included maximal GH plasma peak and area under the curve (AUC) during the total sleep period, during the first three hours after sleep onset, and during the first five hours after sleep onset. An AUC cutoff of 2,000 ng X min/mL identified positively half the prepubertal children with major depression; with a specificity of 78% (v neurotics) and 100% (v normal children). Increased GH secretion during sleep may be a marker of illness, a past episode, or trait for prepubertal major depression regardless of endogenicity.
Affective Symptoms↗
Prolactin levels in schizophrenia: relation to platelet monoamine oxidase, plasma amine oxidase, plasma dopamine-beta-hydroxylase, and erythrocyte catechol-O-methyltransferase activity.
Explore the source record for details and available documents.
Adolescent↗
Quantitative characterization of color Doppler images: reproducibility, accuracy, and limitations.
A computer-based quantitative analysis for color Doppler images of complex vascular formations is presented. The red-green-blue-signal from an Acuson XP10 is frame-grabbed and digitized. By matching each image pixel with the color bar, color pixels are identified and assigned to the corresponding flow velocity (color value). Data analysis consists of delineation of a region of interest and calculation of the relative number of color pixels in this region (color pixel density) as well as the mean color value. The mean color value was compared to flow velocities in a flow phantom. The thyroid and carotid artery in a volunteer were repeatedly examined by a single examiner to assess intra-observer variability. The thyroids in five healthy controls were examined by three experienced physicians to assess the extent of inter-observer variability and observer bias. The correlation between the mean color value and flow velocity ranged from 0.94 to 0.96 for a range of velocities determined by pulse repetition frequency. The average deviation of the mean color value from the flow velocity was 22% to 41%, depending on the selected pulse repetition frequency (range of deviations, -46% to +66%). Flow velocity was underestimated with inadequately low pulse repetition frequency, or inadequately high reject threshold. An overestimation occurred with inadequately high pulse repetition frequency. The highest intra-observer variability was 22% (relative standard deviation) for the color pixel density, and 9.1% for the mean color value. The inter-observer variation was approximately 30% for the color pixel density, and 20% for the mean color value. In conclusion, computer assisted image analysis permits an objective description of color Doppler images. However, the user must be aware that image acquisition under in vivo conditions as well as physical and instrumental factors may considerably influence the results.
Algorithms↗
Duodenogastric reflux potentiates the injurious effects of gastroesophageal reflux.
Experimental studies have shown that the severity of esophageal mucosal injury in gastroesophageal reflux disease is related to the reflux of both gastric and duodenal juice. The purpose of this study was to determine whether duodenal juice potentiates esophageal injury in patients with reflux disease or, in fact, causes no harm allowing acid and pepsin to do the damage. A total of 148 consecutive patients who had no previous gastric or esophageal surgery underwent endoscopy and biopsy, manometry, and 24-hour esophageal pH and bilirubin monitoring. Esophageal injury was defined by the presence of erosive esophagitis, stricture, or biopsy-proved Barrett's esophagus. Exposure to duodenal juice, identified by the absorbance of bilirubin, was defined as an exposure time exceeding the ninety-fifth percentile measured in 35 volunteers. To separate the effects of gastric and duodenal juice, patients were stratified according to their acid exposure time. One hundred patients had documented acid reflux on pH monitoring, and in 63 of them it was combined with reflux of duodenal juice. Patients with combined reflux (50 of 63) were more likely to have injury than patients without combined reflux (22 of 37; P < 0.05). When the acid exposure time was greater than 10%, patients with injury (n = 40) had a greater exposure to duodenal juice (median exposure time 17.2% vs. 1.1%, P = 0.006) than patients without injury (n = 5), but there was no difference in their acid exposure (16.9% vs. 13.4%). Patients with dysplasia of Barrett's epithelium (n = 9) had a greater exposure to duodenal juice (median exposure time 30.2% vs. 7.2%, P = 0.04) compared to patients without complications (n = 25), whereas acid exposure was the same (16.4% vs. 15%). Duodenal juice adds a noxious component to the refluxed gastric juice and potentiates the injurious effects of gastric juice on the esophageal mucosa.
Adult↗
Combination of endoscopic argon plasma coagulation and antireflux surgery for treatment of Barrett's esophagus.
Columnar-lined epithelium with specialized intestinal metaplasia of the esophagus (i.e., Barrett's esophagus) is a premalignant condition caused by chronic gastroesophageal reflux disease. Progression of intestinal metaplasia may be avoided by antireflux surgery, whereas regeneration of esophageal mucosa could be achieved by endoscopic argon plasma coagulation (EAPC). The aim of this prospective study was to show the early results of a combination of EAPC and antireflux surgery. Thirty patients with Barrett's esophagus were treated between August 1996 and December 1999. Regeneration of esophageal mucosa was achieved with several sessions of EAPC under general anesthesia. All patients were receiving a double dose of proton pump inhibitors. Endoscopic follow-up was performed 6 to 8 weeks after the last session. Antireflux surgery (Nissen [n = 26] or Toupet [n = 4] fundoplication) followed complete regeneration of the squamous epithelium in the esophagus. One year after laparoscopic fundoplication and EAPC follow-up with endoscopy and quadrant biopsies of the esophagus, 24-hour pH monitoring and esophageal manometry were performed. All 30 patients showed complete regeneration of the squamous epithelium after a median of two sessions (range 1 to 7) of EAPC. Twenty-two patients underwent 1-year follow-up studies. All showed endoscopically an intact fundic wrap. Recurrence of a 1 cm segment of Barrett's epithelium without dysplasia was present in two patients, both of whom had recurrent acid reflux due to failure of their antireflux procedure. Our results indicate that the combination of EAPC and antireflux surgery is an effective treatment option in patients with Barrett's esophagus with gastroesophageal reflux disease. Long-term follow-up of this therapy is necessary to evaluate its effect on cancer risk in Barrett's esophagus.
Adult↗
Quality of life following laparoscopic gastric banding in patients with morbid obesity.
In a prospective study of 188 patients with morbid obesity, the time-dependent changes in the quality of life of individual patients were analyzed following laparoscopic gastric banding (LGB). These 188 patients (148 females and 40 males; age 19 to 59 years; body mass index 33 to 72 kg/m(2)) underwent evaluation of the LGB according to a strict protocol that included psychological testing using standardized instruments, detailed medical evaluation, upper gastrointestinal function studies, and evaluation of quality of life using the Gastrointestinal Quality of Life Index (GIQLI). Following this evaluation, 73 patients (57 females and 16 males; age 37 years [range 19 to 59 years]; body mass index 48 kg/m(2) [range 37 to 72 kg/m(2)]) underwent LGB and were followed up for 2 years focusing on weight loss, postoperative morbidity, weight-related comorbidity, and quality of life. The results demonstrate that LGB is well able to allow for a significant loss of excess weight and a significant improvement in patients' quality of life, both after a rather short period of time after surgery and at a continuous rate throughout the follow-up. The price for this success that was found in approximately 90% of patients is a complication rate of 38%; 85% of these patients, almost one third of all patients, must undergo some type of revision surgery. However, once the complications are resolved, these patients achieve the same level of weight loss and improvement in quality of life as patients with an uncomplicated postoperative course.
Adult↗
Duodenoesophageal reflux induces esophageal adenocarcinoma without exogenous carcinogen.
In the rat model, esophageal adenocarcinoma reproducibly develops following surgically induced duodenal reflux into the esophagus and administration of nitrosamine. In addition, decreasing gastric acid via partial or total gastrectomy increases the prevalence of adenocarcinoma in this model. We questioned whether carcinogen was necessary for cancer development in the gastrectomized model and whether esophageal acidification could reverse the effect of gastrectomy. Three groups of 26 rats each were randomized to a surgical procedure to produce one of the following reflux models: gastroduodenal reflux by esophagojejunostomy, duodenal reflux by total gastrectomy and esophagojejunostomy, or no reflux by Roux-en-Y reconstruction. In a second experiment, 42 rats were operated on to induce duodenal reflux. One week following surgery, they were randomized to receive acidified water (pH 1.8) or tap water. The animals were killed at 24 weeks of age, and the esophagus was evaluated histologically. All animals with reflux had severe esophagitis and 87% developed columnar lining of the distal esophagus. Nearly half (48%) developed adenocarcinoma at the anastomotic site 16 weeks postoperatively and without carcinogen administration. Cancer prevalence did not differ between animals with gastroduodenal or duodenal reflux but tended to be lower in animals receiving acidified water. Duodenoesophageal reflux is carcinogenic in the rat model. Exogenous carcinogen is not necessary for cancer development in gastrectomized rats.
Adenocarcinoma↗