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Biomedical subjects

F E Silverstein

Publications and source records attributed to F E Silverstein.

At least 19 recordsLinked to original sources

Improving the gastrointestinal safety of NSAIDs: the development of misoprostol--from hypothesis to clinical practice.

Arthritis is a major source of disability for the American population. It results in significant morbidity for the millions of patients affected and costs billions of dollars yearly for diagnosis and management. Nonsteroidal antiinflammatory drugs (NSAIDs) are the principal therapy for the majority of arthritis patients. It has been estimated that more than 15 million people with arthritis take these drugs daily. This use is predicted to increase greatly not only as a result of an aging population, with the consequent increase in the prevalence of arthritis, but also because NSAIDs may prove to have a role in decreasing colonic neoplasia and in reducing the likelihood of conditions such as Alzheimer's disease. It is therefore increasingly important to understand the nature of the side effects associated with these agents as well as ways of decreasing or preventing their occurrence. NSAIDs inhibit the enzymes cyclooxygenase-1 and cyclooxygenase-2. This reduces the synthesis of prostaglandins and therefore decreases joint inflammation, but it may also lead to the development of gastric and duodenal ulcers. For this reason, exogenous prostaglandins have been studied for their potential role in preventing NSAID-associated ulcers and ulcer complications. This paper reviews the development of the prostaglandin E1 analog misoprostol, the theory behind its use as a mucosal protective agent, and the results of studies in animals as well as in normal volunteers and patients with arthritis. Ultimately, a study was performed to evaluate whether misoprostol reduces the incidence of serious ulcer complications in patients taking NSAIDs. It is an interesting story, which promises to be of increasing importance as NSAID use expands to new indications while concern remains about their associated complications, especially those related to the gastrointestinal tract.

Anti-Inflammatory Agents, Non-Steroidal

[High frequency ultrasonography of the gastrointestinal wall].

If an ultrasound probe comes close to the area of interest, high ultrasound frequencies can be applied. Endoscopic ultrasonography is performed by means of echoendoscopes or miniature probes using ultrasound frequencies between 7 and 30 MHz. A high frequency ultrasound image of the normal gastrointestinal wall usually shows five layers corresponding closely to the histological layers of the wall. Corrections have to be made, however, for interface echoes between layers with different acoustic impedances. We describe studies performed with the aim of correlating ultrasound images of the normal and diseased gastrointestinal wall with the histology. Ultrasound images of the normal gastrointestinal wall and pathological changes like ischemia, ulcers, tumours and inflammation are presented.

Gastric Mucosa

Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate whether concurrent administration of misoprostol reduces the occurrence of serious upper gastrointestinal complications, such as perforation, gastric outlet obstruction, or bleeding, in patients with rheumatoid arthritis who are receiving nonsteroidal anti-inflammatory drugs (NSAIDs). DESIGN: 6-month randomized, double-blind, placebo-controlled trial. SETTING: 664 clinical practices of family medicine, internal medicine, or rheumatology in the United States and Canada. PATIENTS: 8843 men and women (mean age, 68 years) receiving continuous therapy with any of 10 specified NSAIDs for control of symptoms of rheumatoid arthritis. Patients were enrolled between July 1991 and August 1993. INTERVENTION: Patients were randomly assigned to receive 200 micrograms of misoprostol or placebo four times a day. MEASUREMENTS: Development of serious upper gastrointestinal complications detected by clinical symptoms or findings (not by scheduled endoscopy). RESULTS: Serious upper gastrointestinal complications were reduced by 40% (odds ratio, 0.598 [95% CI, 0.364 to 0.982; P = 0.049]) among patients receiving misoprostol (25 of 4404 patients) compared with those receiving placebo (42 of 4439 patients). During the first month, more patients receiving misoprostol (20%) than placebo (15%) withdrew from the study, primarily because of diarrhea and related problems (P < 0.001). Risk factors for serious upper gastrointestinal complications were increasing age, history of peptic ulcer or bleeding, and cardiovascular disease. Patients with all four risk factors would have a 9% risk for a major complication in 6 months. CONCLUSIONS: In older patients with rheumatoid arthritis, misoprostol reduced serious NSAID-induced upper gastrointestinal complications by 40% compared with placebo.

Aged

Future developments in endoscopic imaging.

Endoscopic imaging capabilities have significantly improved over the past 10 years. Improvements in fibreoptic technology have made possible the development of very thin endoscopes that can directly visualize the biliary and pancreatic ducts. The application of the CCD to endoscopy has made electronic endoscopy possible, and holds promise for stereoendoscopy. The ability to digitize endoscopic images can be developed to store, transmit, magnify, enhance and otherwise manipulate data obtained during endoscopy, and will probably be utilized routinely in the future. Laser and ultrasound technology are likely to enhance significantly our ability to examine ultrastructural aspects of gastrointestinal organs and surrounding tissues, and may play an important role in cancer surveillance programs. Vital staining techniques are likely to find widespread use in early cancer detection programmes, and may be useful to follow prospectively lesions observed or treated during endoscopy. Finally, the new developments in 'virtual imaging' may find applications in the field of gastrointestinal endoscopy and other 'minimally invasive' surgical procedures.

Diagnostic Imaging

Simultaneous M-mode echoesophagram and manometry in the sheep esophagus.

We report the simultaneous measurement of esophageal wall layer thickness and intraluminal pressure in the sheep esophagus using a miniature suction device incorporating a high-frequency ultrasound transducer and a manometry system. Transnasal placement of the device into the distal esophagus of a conscious sheep allowed observation of 133 swallowing events during three trials, each lasting from 45 to 60 minutes. In a fourth trial, 11 sequential dry and 23 sequential wet swallows were compared. Maximum manometric pressure, esophageal wall layer thickness, and duration of contraction were measured. All swallowing events produced simultaneous increases in intraluminal pressure and esophageal wall thickness. Mean maximal pressures were lower for dry swallows (18 +/- 2.1 mm Hg) than wet swallows (22 +/- 3.0 mm Hg) (p < .01). Thickness of the inner (circular) muscle layer increased above baseline by 124% for dry swallows and 161% for wet swallows (p < .01). We conclude that thickening of the esophageal inner (circular) muscle layer may be important in the generation of intraluminal esophageal pressure in the sheep esophagus.

Animals

Measurement of the ultrasonic attenuation of fat at high frequency.

RATIONALE AND OBJECTIVES: High-frequency ultrasound devices are often limited by a decreased depth of acoustic imaging caused by the increased attenuation of tissue at high frequencies. We investigated the role of adipose tissue in this phenomenon. METHODS: A substitution technique was used to calculate the ultrasonic attenuation (decibels per centimeter) of fresh samples of sheep rumen, omental fat, and back fat and swine back fat and various concentrations of bovine milk fat at 22 degrees C and 37 degrees C for frequencies of 15 and 20 MHz. RESULTS: The attenuation was significantly higher for sheep adipose tissue than for the intestinal wall, in descending order, omental fat, back fat, and rumen wall (P < 0.01). A correlation was found between bovine milk fat concentrations and attenuation at both frequencies (R2 > 0.9). The attenuation of adipose tissues decreased significantly with an increase in temperature (P < 0.01), whereas the attenuation of sheep rumen showed no significant change (P > 0.1). CONCLUSIONS: The ultrasonic attenuation of fat may contribute to limitations on the use of high-frequency ultrasound in clinical situations in which adipose tissue is present.

Adipose Tissue

Chemical- and radiation-induced esophageal injury.

The esophageal wall can only respond to injury in a limited fashion. This article explores some of the protective mechanisms involved as well as current approaches to diagnosis and management of chemical- and radiation-induced esophageal injury.

Burns, Chemical

Transmission of infection by gastrointestinal endoscopy and bronchoscopy.

OBJECTIVE: To review reports on the transmission of infections by flexible gastrointestinal endoscopy and bronchoscopy in order to determine common infecting microorganisms, circumstances of transmission, and methods of risk reduction. DATA SOURCES: Relevant English-language articles were identified through prominent review articles and a MEDLINE search (1966 to July 1992); additional references were selected from the bibliographies of identified articles. STUDY SELECTION: All selected articles related to transmission of infection by gastrointestinal endoscopy or bronchoscopy; 265 articles were reviewed in detail. DATA SYNTHESIS: Two hundred and eighty-one infections were transmitted by gastrointestinal endoscopy, and 96 were transmitted by gastrointestinal endoscopy, spectrum of these infections ranged from asymptomatic colonization to death. Salmonella species and Pseudomonas aeruginosa were repeatedly identified as the causative agents of infections transmitted by gastrointestinal endoscopy, and Mycobacterium tuberculosis, atypical mycobacteria, and P. aeruginosa were the most common causes of infections transmitted by bronchoscopy. One case of hepatitis B virus transmission via gastrointestinal endoscopy was documented. Major reasons for transmission were improper cleaning and disinfection procedures; the contamination of endoscopes by automatic washers; and an inability to decontaminate endoscopes, despite the use of standard disinfection techniques, because of their complex channel and valve systems. CONCLUSIONS: The most common agents of infection transmitted by endoscopy are Salmonella, Pseudomonas, and Mycobacterium species. To prevent endoscopic transmission of infections, recommended disinfection guidelines must be followed, the effectiveness of automatic washers must be carefully monitored, and improvements in endoscope design are needed to facilitate effective cleaning and disinfection.

Bronchoscopes

Experimental use of high-frequency ultrasound to image bowel wall after porcine intestinal transplantation.

A means to monitor intestinal allografts will be crucial for the future success of small bowel transplantation. We have previously demonstrated the ability of high-frequency ultrasound (US) to diagnose porcine intestinal ischemia in vitro. The aim of this study was to compare the histologic appearance of normal porcine small bowel versus bowel undergoing acute rejection, using 8.5-MHz US images. We allowed porcine heterotopic small bowel allograft transplants to reject and then removed, at scheduled intervals from postoperative day 0 to 12, specimens of both the transplanted bowel and the native bowel. We examined the tissues in vitro with an 8.5-MHz linear array US system then studied them histologically. Histologically, the earliest changes of rejection occurred at days 4 to 5, with mild submucosal edema, endotheliitis, and vasculitis affecting the small vessels; the mucosa remained normal. By days 7 to 8, the submucosal endotheliitis became more prominent, with focal thrombosed small vessels; the mucosa now appeared abnormal with flattened villi, erosions, and necrosis. By days 10 to 12, marked submucosal edema, vasculitis, endotheliitis, and necrotic mucosa were present. Ultrasonically, normal intestinal wall has five wall layers, corresponding to mucosa, submucosa, muscularis propria, and subserosal fat. The US criteria for abnormality were loss of folds, decreased numbers of echo layers, discontinuity of layers, and a homogeneous appearance. Using these US criteria, blinded observers differentiated normal from abnormal bowel wall after transplantation with a sensitivity of 84% and a specificity of 81%. Most of the errors occurred with the day 4 and 5 specimens, which appeared nearly normal on US.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Use of ultrasound to detect intestinal wall ischemia in piglets.

To evaluate the use of ultrasound (US) to detect intestinal wall ischemia, we isolated segments of jejunum on single vascular pedicles in five piglets. We sequentially clamped these segments in intervals of 0 to 6 h, reperfused them for 24 h, and then examined them in vitro histologically and with an 8.5 MHz US scan. All segments were grossly viable except those with 6 h of ischemia. Histologically, mild submucosal edema developed after 1 to 2 h of ischemia; after 3 to 4 h, mucosal necrosis, loss of folds, worsening submucosal edema, and prominent neutrophilic infiltration occurred; after 5 to 6 h, severe mucosal necrosis with hemorrhage and submucosal edema was present. Ultrasonically, we saw five wall layers in the control group corresponding to mucosa, submucosa, muscularis propria, and subserosal fat. After mild (1 to 2 h) ischemia, all layers were present except for a discontinuity in layer 3. After moderate (3 to 4 h) ischemia, the five layers persisted but with a markedly thickened submucosal layer, reduced echogenicity, and flattened mucosal folds. With severe (5 to 6 h) ischemia, we observed a loss of all normal layers with no discernible architecture. Using these US criteria, blinded observers were able to differentiate normal/mild from moderate/severe ischemia with a sensitivity and specificity of 100%. These data suggest that US can differentiate, in vitro, normal from moderate and severe degrees of intestinal wall ischemia that correlates well with the histological appearance. Endoscopic US or surgically implantable US probes can potentially help diagnose clinical intestinal wall ischemia.

Animals

Clinical application of linear ultrasound probes.

The linear ultrasound probe should be viewed as an adjunct to conventional endoscopic ultrasonography with combined ultrasound endoscopes. It certainly does not replace these instruments for staging neoplasms and imaging extraintestinal organs such as the pancreas. It can be a simpler alternative to these instruments when applied at the time of endoscopy to obtain more information about wall thickness and the cause of an intramural mass. It can add information when used to image within impassable malignant strictures. Further development of the linear probes with the addition of a balloon over the transducer and the advent of new probes that utilize other scanning mechanisms is anticipated and should make this imaging system even more useful.

Endoscopy

Evaluation of a 20-MHz ultrasound transducer used in diagnosing porcine small bowl ischemia.

The authors have previously demonstrated the ability of an 8.5-MHz linear array to detect moderate or severe intestinal ischemia in a porcine model. This study compares the ability of the 8.5-MHz linear array with a prototype miniature 20-MHz ultrasound (US) imaging probe in detecting small bowel ischemia. Five piglets were studied in which vascular clamps were applied to isolated jejunal pedicles, then released sequentially at hourly intervals to induce ischemia from 0 to 6 hours. After 24 hours of reperfusion, the tissue was removed and examined with both the 8.5-MHz linear array and the 20-MHz probe. A histologic examination also was done. The acoustical criteria used for interpretation were presence or absence of folds, number of echo layers, relative thickness of layers and homogeneity and continuity of layers. The 8.5-MHz system predicted the duration of ischemia with a kappa value of 0.66 +/- 0.03, whereas the 20-MHz system had a kappa value of 0.49 +/- 0.03. Both systems were able to distinguish normal or mild ischemia from moderate or severe ischemia with sensitivity and specificity rates of at least 94%. Both 8.5- and 20-MHz US systems detected intestinal ischemia in vitro. Further studies are indicated to determine the ideal frequency and design for a US system that can be used clinically.

Animals

Diagnosis of inflammatory bowel disease with ultrasound. An in vitro study.

Transabdominal ultrasound is frequently used to detect complications of inflammatory bowel disease. It has been proposed that ultrasound can distinguish between ulcerative colitis and Crohn's disease based on the degree of thickening and changes in the layered structure of the intestine. The authors evaluated the ability of ultrasound to distinguish between ulcerative colitis, Crohn's colitis, and normal colon by blindly comparing images made of resected colon specimens. The histologic interpretation of precisely the same area of tissue that was imaged was compared with the blinded image interpretation. Images from all 18 colitis specimens were correctly interpreted as being abnormal because of increased submucosal and overall wall thickness. Published ultrasound criteria for distinguishing between Crohn's disease and ulcerative colitis based on overall wall thickness and indistinctness of layers were inaccurate in 4 of 15 specimens and indeterminate in 3 cases. Ultrasound appears to be accurate in distinguishing normal from inflamed colon, but ultrasound findings alone should not be used to determine the cause of bowel inflammation.

Colitis, Ulcerative

Histologic correlates of gastrointestinal ultrasound images.

Endoscopic ultrasound imaging has potential for improving the diagnosis of gastrointestinal disease. However, the anatomic correlates of gastrointestinal ultrasound images have not been precisely defined. We have compared ultrasound images with the corresponding histologic sections of 81 specimens of resected and postmortem, normal and diseased gastrointestinal tissue. The five layers seen on ultrasound images of the normal gastrointestinal tract correspond to (1) superficial mucosa, (2) deep mucosa, (3) submucosa plus the acoustical interface between the submucosa and muscularis propria, (4) muscularis propria minus the acoustical interface between the submucosa and muscularis propria, and (5) serosa and subserosal fat. This interpretation takes into consideration the echoes produced by the tissue layers and the echoes produced by the interfaces between layers. Abnormal findings on ultrasound images of neoplastic and inflammatory diseases correspond to histologic tissue structure. When properly interpreted, ultrasound images of the gastrointestinal wall can provide potentially useful diagnostic information.

Digestive System

Experimental evaluation of an endoscopic ultrasound probe: in vitro and in vivo canine studies.

We developed an endoscopic echo probe that can be passed via the biopsy channel of a flexible fiberoptic or video endoscope with a 3.5-mm channel. The probe moves along the gastrointestinal wall under direct endoscopic vision. The translational scanning action is sensed by a position potentiometer and combines with the ultrasonic B-mode echoes to produce a cross-sectional image of the wall. The system uses an ultrasound frequency of 20 MHz to produce high-resolution images. The device was used to image canine gastrointestinal tissue in vitro and in vivo during endoscopy. Ultrasound images of the gut wall correlate with histologic structure. This probe overcomes some of the problems associated with the combined ultrasound endoscopes now in use. Use of the probe with video endoscopy allows the endoscopic and ultrasound images to be displayed side by side, simplifying coordination of application of the two techniques.

Animals

A 20-MHz ultrasound system for imaging the intestinal wall.

An ultrasound system has been developed which uses high-frequency (20 MHz) ultrasound to provide high-resolution images of tissue. The system provides 0.21-mm range and 0.65-mm lateral resolution. The transducer aperture size is 1.8 mm maximum. Miniature probes have been developed which can image via the biopsy channels of standard fiberoptic endoscopes as well as probes for imaging in vitro. A commercially available video "frame grabber" is used in conjunction with a standard microcomputer for image acquisition. This allows images to be displayed and recorded on standard television equipment and be stored and manipulated digitally. The features of the system allow in vivo imaging, in vitro imaging after resection, and histological images of the same tissue region to be acquired and compared. This method is particularly useful in learning how to correctly interpret ultrasonic images of the intestinal wall. The use of 20 MHz is advantageous in achieving excellent resolution and small size probes. The system provides a unique approach to imaging the intestinal wall.

Analog-Digital Conversion