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Biomedical subjects

S R Hamilton

Publications and source records attributed to S R Hamilton.

At least 235 records · Page 13Linked to original sources

Adenocarcinoma in Barrett's esophagus after elimination of gastroesophageal reflux.

A 56-yr-old man with severe reflux esophagitis, Barrett's esophagus, and a peptic lower esophageal stricture underwent subtotal resection of the Barrett's esophagus with colonic interposition. After the interposition procedure, gastroesophageal reflux was eliminated, as evidenced by absence of clinical and radiographic findings and by the results of a later continuous pH probe recording. Despite the absence of reflux, 8 yr after the colonic interposition the patient was found to have adenocarcinoma in the remnant of the Barrett's esophagus. This case indicates that elimination of gastroesophageal reflux does not necessarily lead to regression of Barrett's mucosa, nor does it prevent development of adenocarcinoma. As a result, patients with Barrett's esophagus should remain under long-term surveillance for dysplasia and adenocarcinoma, even after successful antireflux therapy. If esophagectomy is performed, every attempt should be made to resect all of the esophagus lined by Barrett's mucosa.

Adenocarcinoma↗

[Studies on the prediction of intestinal recovery from ischemic injury by fluorescein fluorescence patterns].

Methods for the prediction of intestinal recovery from ischemic injury were evaluated in highly reproducible model of segmental intestinal strangulation in the rat. Systemic variables were minimized and survival was maximized by parenteral administration of antibiotics and nutrient solution, so that necrosis or recovery of the segment itself, not the rat, could be used as an endpoint of experiments. Recovery of ischemic intestine was assessed by two methods: Standard clinical criteria (color, peristalsis, pulsation.) Fluorescence after intravenous fluorescein injection. Findings were compared with ultimate viability assayed by histologic examination of each segment removed 48 hours after release of strangulation. Five distinctive patterns of fluorescein fluorescence were identified, two of which (normal pattern and fine granular pattern) reliably predicted survival of the segment, and two of which (perivascular pattern and no fluorescence) predicted subsequent necrosis. A fifth, coarse granular pattern usually, but not always, predicted non-recovery. Standard clinical criteria were relatively insensitive and could not be relied upon to detect nonviable segments. The fluorescein fluorescence method correctly identified all nonviable segments at the expense of an acceptably low overall false positive rate. This study suggests that the fluorescein methods is the method of choice for the prediction of small intestinal recovery following ischemic injury.

Animals↗

Multiclonal origin of polyps in Gardner syndrome.

Electrophoretic analysis of glucose-6-phosphate dehydrogenase was performed on polyp tissue from three black female patients with Gardner syndrome and who are heterozygous for the A and B forms of this enzyme. Polyp tissues from the three patients displayed the AB phenotype. This finding suggests a multiclonal origin of polyps in Gardner syndrome. Studies of tumors originating from such polyps may provide information about the sequence of cellular events leading to malignant transformation.

Clone Cells↗

Pathogenesis of polyps (adenomas).

The pathogenesis of adenomas in adenomatous polyposis of the gastrointestinal tract (familial polyposis coli, FPC) is not completely known. The morphologic features of the dysplastic epithelium and the morphogenesis of adenomas in FPC have been well described. Studies of the precursors to adenomatous epithelium have identified histopathologic, ultrastructural, and epithelial proliferative abnormalities in grossly normal colonic mucosa of FPC patients. The role of the intraluminal environment and the mechanisms of its interaction with the mucosa appear to be important areas for research directed at the pathogenesis of adenomas in FPC, due to the implications for therapy.

Adenoma↗

Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications.

Assessment of epithelial dysplasia in ulcerative colitis has been hindered by inconsistencies in and disagreements about nomenclature and interpretation. To resolve these issues, pathologists from ten institutions participated in three exchanges of multiple slides and, following each exchange, in discussions of the results. A classification system for the epithelial changes that occur in ulcerative colitis was developed, which should be applicable to other forms of inflammatory bowel disease as well. The classification makes use of standardized terminology, addresses specific problem areas, and offers practical solutions. The reproducibility of the system was studied by means of examinations of both inter- and intra-observer variations. The clinical implications of the findings were incorporated into suggestions for patient management. The basis of the classification is that the term "dysplasia" is reserved for epithelial changes that are unequivocally neoplastic and may therefore give rise directly to invasive carcinoma. Specimens are categorized as negative, indefinite, or positive for dysplasia. The negative category includes all inflammatory and regenerative lesions and indicates that only continued regular surveillance is required. The indefinite category is applied to epithelial changes that appear to exceed the limits of ordinary regeneration but are insufficient for an unequivocal diagnosis of dysplasia or are associated with other features that prevent such unequivocal diagnosis. Clinically, it indicates that early repeat biopsy is often required to assess the changes more accurately. The positive category is divided into two subcategories: 1) high-grade dysplasia, for which colectomy should be strongly considered after confirmation of the diagnosis, and 2) low-grade dysplasia, which also requires confirmation and early repeat biopsy or colectomy, depending on other findings.

Biopsy↗

Crohn's disease and ulcerative colitis in the same patient.

A well documented case of a patient with both Crohn's disease and ulcerative colitis is presented. A 29 year old woman underwent resection of her terminal ileum and ascending colon for typical Crohn's disease with ileocolitis. Eleven years later, an ileoproctocolectomy was performed for typical ulcerative colitis involving the left colon. The resection specimen also showed evidence of colonic Crohn's disease near the anastomotic site. This unusual case shows that Crohn's disease and ulcerative colitis can occur in the same patient. The rarity of such cases supports the concept that Crohn's disease and ulcerative colitis are separate entities, rather than different manifestations of the same disease process.

Adult↗

Pathologic features of Crohn's disease associated with recrudescence after resection.

The pathologic features of Crohn's disease which influence recrudescence after resection are not known precisely. The controversy regarding the relationship between recrudescence and histopathologic evidence of Crohn's disease in resection margins is of immediate interest to pathologists because of the surgical practice of requesting frozen section examination of margins. In our studies and those of others, histopathologic findings in margins were unrelated to outcome of the patient. Thus, it is our opinion that such frozen sections should not be done. We have also found that margin length from the transected ends of a specimen to areas of evident Crohn's disease were unrelated to outcome. We therefore recommend conservative resection to obtain grossly normal margins; such a strategy will prevent unnecessary sacrifice of functional bowel in an attempt to avoid recrudescence by "radical" resection. Documentation of the pathologic findings in a resection specimen, particularly the length of bowel with and site of active Crohn's disease, may prove to be important in relation to recrudescence. The influence of histopathologic features such as granulomas on recrudescence after resection is as yet uncertain.

Colectomy↗

Disseminated aspergillosis complicating hepatic failure.

Disseminated aspergillosis is not generally known as a complication of hepatic failure. Three patients with subacute hepatic necrosis died of clinically unrecognized disseminated aspergillosis. All of the patients had pulmonary aspergillosis and Aspergillus infections of the CNS. Focal neurologic deficits were clinically misconstrued as intracerebral hemorrhages caused by the coagulopathy of liver failure. Signs of invasive pulmonary aspergillosis were ascribed to refractory bacterial pneumonia. Each patient had a hospital course of longer than three weeks and each received treatment with corticosteroids and intravenous antibiotics. Invasive aspergillosis should be considered as a cause of refractory pneumonia and of new focal neurologic deficits in patients with hepatic failure.

Abscess↗

Dietary protein-induced colitis in breast-fed infants.

Six infants are reported who developed an inflammatory proctocolitis in the first month of life while being breast fed exclusively. All has been born at term and had normal perinatal courses. None had growth failure or constitutional symptoms other than bloody diarrhea. No toxic, bacterial, viral, or parasitic cause was established. Rectal inflammation was suggested by the presence of fecal leukocytes and was confirmed by sigmoidoscopic observation of focal ulcerations, edema, and increased friability. Rectal biopsies demonstrated a wide spectrum of acute and chronic inflammatory changes. All infants responded clinically to initiation of feeding with either a hydrolyzed casein or a soy protein-based formula. Breast-feeding was subsequently resumed in five of the six infants; all experienced immediate recurrence of symptoms. Elimination of cow milk protein from the maternal diet led to tolerance of breast-feeding in two infants but there was no change in the other three. We believe that dietary protein-induced enterocolitis, previously reported in formula-fed infants, occurs occasionally in the exclusively breast-fed infant as well.

Breast Feeding↗

En face histopathologic technic for examining colonic mucosa of resection specimens.

The en face histopathologic technic for examining colonic mucosa in the plane of the luminal surface is described and analyzed. Grossly normal colonic mucosa from 56 resection specimens was embedded en face and sectioned. The en face histopathologic slides showed sheets of mucosa with the crypts in cross section surrounded by lamina propria, an orientation to mucosal topography analogous to gross examination. A total of 1,931 cm2 of mucosa was embedded en face in 640 paraffin blocks, a mean of 3.0 +/- 0.8 (SD) cm2 per block. With routine processing of the same surface area, approximately 2,365 blocks (nearly four times as many as for the en face technic) would have been required. A total of 1,217 cm2 of mucosa appeared in the slides from the en face blocks, comprising 63 +/- 23% of the submitted tissue, compared with 0.3% in routine sections. Our analysis demonstrated that the en face technic is a useful tool in histopathologic studies of large areas of grossly normal colonic mucosa, particularly for quantitation and mapping of the findings.

Colon↗

Effects of parenteral keyhole limpet hemocyanin or cholera toxin on intestinal immune response to keyhole limpet hemocyanin.

This study evaluated whether subcutaneous priming with either keyhole limpet hemocyanin (KLH), a protein antigen lacking toxic properties, or cholera toxin (CT), whose toxic activity is known to modulate immune responses, would enhance or suppress the local intestinal IgA response to KLH. In rabbits given KLH into chronically isolated ileal loops, subcutaneous priming and boosting with the same antigen resulted in increased serum and loop fluid IgG anti-KLH, but loop fluid IgA anti-KLH was not statistically significantly different from controls. With subcutaneous administration of CT, loop fluid IgA anti-KLH and serum IgG anti-KLH showed a suggestion of an earlier rise than in controls, but were not significantly different. The failure of subcutaneous KLH or CT to enhance local intestinal IgA immune response to KLH indicated that the feasibility of parenteral priming must be determined individually for each antigen to which intestinal immunity is desired.

Animals↗

Ischemic injury in the cat small intestine: role of superoxide radicals.

Hemorrhagic lesions in the small intestinal mucosa have been demonstrated in humans and experimental animals following hemorrhagic shock and intestinal ischemia. In order to define the role of superoxide radicals and xanthine oxidase in the pathogenesis of the mucosal lesions, we compared the microscopic mucosal changes produced by 3 h of regional hypotension (intestinal arterial pressure = 30 mmHg) in untreated cats and cats pretreated with either superoxide dismutase or allopurinol. In the untreated animals the mucosa was characterized by massive epithelial lifting down the sides of the villi, completely denuded villi, and most frequently by disintegration of the lamina propria, hemorrhage, and ulceration. Pretreatment with either superoxide dismutase or allopurinol significantly attenuated the necrosis of villus and crypt epithelium produced by 3 h of ischemia. The results of this study suggest that superoxide radicals are involved in the pathogenesis of ischemic mucosal lesions and that the enzyme xanthine oxidase is the source of superoxide radicals in the ischemic small bowel.

Allopurinol↗

Intraoperative determination of small intestinal viability following ischemic injury: a prospective, controlled trial of two adjuvant methods (Doppler and fluorescein) compared with standard clinical judgment.

Two adjuvant techniques for the intraoperative assessment of small intestinal viability were compared with standard clinical judgment in a prospective, controlled study of 71 ischemic bowel segments in 28 consecutive patients operated on for acute intestinal ischemic disease. Each segment was independently assessed 15 minutes after surgical correction of the underlying lesion by: 1) standard clinical judgment; 2) Doppler-detected pulsatile mural blood flow; and 3) fluorescein ultraviolet fluorescence pattern. Viability endpoint for each segment was determined objectively by patient follow-up or "blinded" microscopic evaluation of histologically unequivocal resection specimens using criteria established by previous animal studies. Seventeen histologically equivocal specimens were excluded from the final results. Standard clinical judgment proved moderately accurate overall (89%) but would have led to a relatively high rate (46%) of unnecessary bowel resection. The Doppler technique did not increase accuracy in any category of evaluation. The fluorescein fluorescent pattern was correct in all 54 determinant bowel segments, and proved more sensitive specific, predictive, and significantly more accurate overall than either standard clinical judgment or the Doppler method. This controlled study suggests that the fluorescein technique is the method of choice for the prediction of small intestinal recovery following ischemic injury.

Adolescent↗

No impairment of local intestinal immune response to keyhole limpet haemocyanin in the absence of Peyer's patches.

The role of Peyer's patches in the local intestinal and serum antibody responses to keyhole limpet haemocyanin (KLH) was studied in rabbits with chronically isolated ileal loops. Four weekly doses of 400 microgram KLH were administered into loops prepared with and without Peyer's patches. Isotype-specific IgA and IgG anti-KLH in loop secretions collected twice each week and in sera collected weekly were assessed by enzyme-linked immunosorbent assay. Fluid IgA anti-KLH in loops without Peyer's patches first showed a statistically significant increase on day 25, 1 week later than control loops with Peyer's patches. However, some animals in the group without Peyer's patches showed a rise as early as day 7, and the differences from controls were not statistically significant at any time. No statistically significant rise in fluid or serum IgG anti-KLH occurred in either group. Thus, Peyer's patches were not essential for local intestinal antibody response to KLH, a soluble macromolecular antigen. The findings suggest that the innumerable small lymphoid nodules in the gastrointestinal tract, or other mechanisms of antigen processing, play an important role in local intestinal immune responses.

Animals↗

Comparison of nephelometry and immunofluorescence for immunoglobulin quantitation in pathologic sera.

Nephelometers from Beckman, Hyland and Technicon, and the immunofluorescent system from International Diagnostic Technology were evaluated for IgG, IgM, and IgA quantitation in pathologic sera. Within-run, between-run, and between-day imprecision of each instrument varied for each immunoglobulin and for different levels of the same immunoglobulin. Thus, no instrument showed clearly superior precision. However, for elevated immunoglobulin levels, Technicon had poorer between-day precision than the other instruments (p less than 0.05). Comparison of monoclonal immunoglobulin quantitation with monoclonal protein quantitation by serum protein electrophoresis in 13 patients showed best correlation for the Beckman instrument (r = 0.942). Quantitation of IgG, IgM, and IgA in 50 specimens required approximately 330, 390, 480, and 480 min to complete with Hyland, International Diagnostic Technology, Beckman, and Technicon, respectively. Our evaluation suggests that the proportion of abnormal specimens in the workload and the availability of reagents for desired assays should be considered in determining the suitability of one of these instruments for a particular laboratory.

Dysgammaglobulinemia↗

Surgical management of Crohn's disease. Influence of disease at margin of resection.

To determine the influence of microscopic disease at an anastomosis following intestinal resection for Crohn's disease, 97 patients undergoing 103 resections were reviewed. Most resections (85/103) involved both small and large bowel and were followed by an ileocolic anastomosis. All resection margins were available and were reviewed. In 52 instances there was no evidence of Crohn's disease at the margins. In 51 instances histologic evidence of Crohn's disease varying from chronic inflammation to tissue destruction was present in one or both margins. The incidence of immediate postoperative anastomotic complications (leak with fistula or abscess, or obstruction) was identical in patients with microscopically normal margins (3/52; 6%) and in patients with microscopic Crohn's disease at the margins (3/51; 6%). The patients were followed for a mean of 5.4 +/- 4.2 years. A clinical recurrence developed during the follow-up period in 50% (26/52) of those patients with normal margins, and in 61% (31/51) of those patients with involved margins. A suture line recurrence developed in 35% (18/52) and required reoperation in 17% (9/52) of those patients with microscopically normal margins. A suture line recurrence developed in 41% of the patients (21/51) and required reoperation in 24% (12/51) of those with microscopically involved margins. None of these differences are statistically significant. The presence or absence of microscopic disease at the anastomosis did not appear to influence immediate anastomotic wound healing or long-term recurrence rates. We therefore recommend conservative resections for Crohn's disease to achieve grossly uninvolved margins rather than the sacrifice of normal bowel to achieve histologically normal margins.

Adolescent↗