Search PubMed⌕ Search

Biomedical subjects

S R Hamilton

Publications and source records attributed to S R Hamilton.

At least 217 records · Page 12Linked to original sources

Adenocarcinoma of the lower esophagus. A disease primarily of white men with Barrett's esophagus.

Sex and racial predilection, social history, and histology were analyzed in a biopsy-proven adenocarcinoma of the lower esophagus/esophagogastric junction collected over a 5-year period in two teaching institutions with different patient populations. Adenocarcinoma occurred in 11% of patients with biopsy-proven esophageal cancer. The disease occurred only in males at one center, and in a 7:1 ratio of males to females at the other center. Clear racial predilection was seen, since 12 of 13 patients with adenocarcinoma of the esophagus were white, whereas less than 20% of patients with squamous carcinoma of the esophagus were white. The finding of Barrett's epithelium in eight of the 13 cases strongly supports the theory that in white males, Barrett's epithelium is a precursor lesion of adenocarcinoma of the esophagus/esophagogastric junction.

Adenocarcinoma↗

Bacterial esophagitis in immunocompromised patients.

We studied the clinical and pathologic features of bacterial esophagitis in three index cases identified by endoscopic biopsy and in 20 autopsy cases. Fourteen of the 23 patients had malignant hematologic conditions, aplastic anemia, or solid tumors; ten were profoundly neutropenic (white blood cell count, less than 100/mm3 [less than 0.1 X 10(9)/L]). The organisms involved in bacterial esophagitis were gram-positive cocci in 14, gram-negative bacilli in three, mixed gram-negative bacilli and gram-positive cocci in five, and gram-positive bacilli in one. Four patients had bacteremic bacterial esophagitis; all were immunocompromised, three by profound neutropenia and one by gestational prematurity. Bacteria causing bacteremic bacterial esophagitis were all gram-positive: viridans-group streptococci. Staphylococcus aureus, Staphylococcus epidermis, and Bacillus species. Our study suggests that bacterial esophagitis is more common than has been recognized in the past and should be considered as a potential source of bacteremia in immunocompromised patients.

Adult↗

Kinetic changes in mucosal ornithine decarboxylase activity during azoxymethane-induced colonic carcinogenesis in the rat.

In the azoxymethane (AOM)-treated rat model of colonic carcinogenesis, serial injections of the carcinogen lead to the eventual development of colonic tumors. However, the precise nature of carcinogenesis events in this commonly used model is not well defined, and the occurrence of classic initiation and promotion phases after serial injections is uncertain. Since increases in ornithine decarboxylase (ODC) activity have been associated with promotion in other tumor models, we measured mucosal ODC during AOM carcinogenesis in the rat. We gave male Fischer 344 rats ten weekly injections of AOM at a dose of 3 mg/kg (Wk 1-10) and measured colonic mucosal ODC activity during the entire 25-wk course. Colonic tumor incidence at Wk 25 was 0% in controls and 48% in AOM animals (15 of 31). Mucosal ODC in AOM animals was significantly increased over controls. The time course of changes in mucosal ODC was similar throughout the entire colon and differed generally in magnitude only. Distinct and prolonged increases in ODC activity occurred within 4 h of a single injection of carcinogen and persisted for at least 14 days. With a second AOM injection on Day 7, there was another distinct and prolonged increase in ODC over the persistently elevated activity. Over the entire 25 wk, the increase in ODC was distinctly biphasic, higher at Wk 2, 11, and 13 than at Wk 6, 17, 21, and 25. The findings indicate that AOM induces an increase in mucosal ODC during colonic carcinogenesis, and they suggest that this carcinogenesis model, with ten weekly injections of carcinogen, has the properties of a multistep process. The early peak in ODC might be associated with the early carcinogenesis (initiation) phase(s), and a subsequent second increase in ODC might be associated with late carcinogenesis (post-initiation or promotion) phase (s). These results strengthen the utility of the rat AOM colonic carcinogenesis model for further studies of the role of ODC and polyamine metabolism in neoplastic transformation.

Animals↗

Pseudosarcomatous changes in inflammatory pseudopolyps of the colon.

The occurrence of pseudomalignant changes in biopsy specimens from two patients with ulcerative colitis and pseudopolyposis is described. One lesion was characterized by the proliferation of large ganglion cell-like cells, similar to those observed in proliferative fasciitis. Ultrastructural and immunohistochemical findings supported a fibroblastic origin. Biopsy specimens of an inflammatory pseudopolyp from the second patient showed proliferation of oval to spindle cells that were initially interpreted as a possible neoplasm. The site of origin and reactive nature of this lesion became apparent on a subsequent polypectomy specimen. Attention is called to the occurrence of pseudosarcomatous changes in inflammatory pseudopolyps of the gastrointestinal tract that may lead to an erroneous diagnosis of malignancy.

Adolescent↗

Purification of DNA from formaldehyde fixed and paraffin embedded human tissue.

The ability to isolate DNA from preserved human tissues would provide numerous experimental opportunities. In this report it is shown that DNA can be extracted from tissues prepared for routine histopathological examination (i.e., fixed with formaldehyde and embedded in paraffin). Although the extracted DNA is not intact, it is double stranded, cleavable with restriction endonucleases, and suitable for a variety of standard techniques used in molecular biology.

Carcinoma↗

Hypomethylation of DNA from benign and malignant human colon neoplasms.

The methylation state of DNA from human colon tissue displaying neoplastic growth was determined by means of restriction endonuclease analysis. When compared to DNA from adjacent normal tissue, DNA from both benign colon polyps and malignant carcinomas was substantially hypomethylated. With the use of probes for growth hormone, gamma-globin, alpha-chorionic gonadotropin, and gamma-crystallin, methylation changes were detected in all 23 neoplastic growths examined. Benign polyps were hypomethylated to a degree similar to that in malignant tissue. These results indicate that hypomethylation is a consistent biochemical characteristic of human colonic tumors and is an alteration in the DNA that precedes malignancy.

Chorionic Gonadotropin↗

Use of restriction fragment length polymorphisms to determine the clonal origin of human tumors.

A novel strategy to determine the clonal origin of human tumors has been devised. The strategy involves the use of a cloned polymorphic X-chromosomal gene and two restriction endonucleases. The first endonuclease distinguishes the paternal and maternal copies of the gene through a DNA polymorphism of restriction fragment length. The second endonuclease distinguishes active from inactive copies of this gene through changes in DNA methylation. As illustrations of this strategy, three human cancers were each shown to be monoclonal. The analysis described should have a wide variety of clinical and experimental applications.

Autoradiography↗

Colorectal carcinoma in patients with Crohn's disease.

Epidemiologic studies have shown a fourfold to 20-fold increased risk of colorectal carcinoma in patients with Crohn's disease as compared with the general population, but management for this risk is controversial. This paper presents a series of 10 patients with Crohn's disease and colorectal carcinoma from one institution and a review of the literature. Compared with 118 consecutive patients having colorectal carcinoma of the usual type at the same institution, the 10 patients were younger (mean age 55 vs. 65 yr, p less than 0.05) and had a higher prevalence of mucinous carcinoma (50% vs. 9%, p less than 0.01), providing evidence in addition to the previous epidemiologic results that Crohn's disease is a predisposing (premalignant) condition for colorectal carcinoma. Eight of the 10 patients had an antecedent history of Crohn's disease, ranging from 4 to 51 yr (mean 24 yr); 2 patients presented with colorectal carcinoma and were found to have Crohn's disease. Of particular note, 9 of the 10 patients had colitis or ileocolitis, and carcinoma occurred in bypassed rectum in 2 patients. One patient had two carcinomas. Three of the 11 carcinomas were not recognized preoperatively. The anatomic sites of the cancers were not significantly different from usual colorectal carcinoma, with 7 of the 11 tumors (64%) in the sigmoid colon and rectum. Dysplasia was identified in all 10 patients, and all of the 10 resected carcinomas were found to be contiguous with high-grade dysplasia. The findings in this study support the proposals based upon epidemiologic data that surveillance should be considered for patients with clinically evident colorectal involvement by Crohn's disease or a bypassed segment of colorectum.

Adenocarcinoma↗

Barrett's esophagus: its prevalence and association with adenocarcinoma in patients with symptoms of gastroesophageal reflux.

The pathologic reports of all 1,020 esophageal biopsy specimens obtained between 1975 and 1981 in patients with symptoms of gastroesophageal reflux were reviewed. Barrett's esophagus was identified in 84 patients (8 percent). The 362 patients seen between 1980 and 1981 were reviewed in detail. The symptoms in patients with Barrett's esophagus differed from those of the patients without Barrett's esophagus. Dysphagia was more often present in the former group (34 percent versus 16 percent, p less than 0.05) and epigastric distress was less frequent (11 percent versus 27 percent, p less than 0.05). Objective findings of hiatal hernia, esophageal stricture, and esophageal ulcers occurred more commonly in patients with Barrett's esophagus than in those without Barrett's esophagus (70 percent versus 48 percent, 31 percent versus 4 percent, and 14 percent versus 6 percent, respectively, p less than 0.05). Mid esophageal strictures were associated almost exclusively with Barrett's esophagus (five of six patients). At esophagoscopy, erythema was seen more commonly with Barrett's esophagus. The diagnosis was suspected by the endoscopist in only 34 percent of patients subsequently demonstrated histopathologically to have Barrett's esophagus. There was no significant difference in the prevalence of a positive Bernstein test result or gastroesophageal reflux on upper gastrointestinal series in patients with and without Barrett's esophagus. However, a hypotensive lower esophageal sphincter was found more commonly in patients with Barrett's esophagus (100 percent versus 53 percent, p less than 0.05). Thirteen of the 84 patients with Barrett's esophagus (15 percent) had a coexistent adenocarcinoma arising from Barrett's mucosa. These patients, when compared with the patients with Barrett's esophagus without carcinoma, were more often male (77 percent versus 51 percent, p = 0.1), more often had dysphagia (69 percent versus 34 percent, p less than 0.05), and more frequently had a comparatively short duration of symptoms (67 percent versus 36 percent, p less than 0.05). Our findings suggest that patients with Barrett's esophagus have a high risk of development of carcinoma. Because the entity is often not recognized at endoscopy, routine esophageal biopsy should be performed on all patients undergoing esophagoscopy for symptoms of gastroesophageal reflux. Patients with known Barrett's esophagus should be followed closely with repeated endoscopy and biopsy.

Adenocarcinoma↗

A muscle ablation sphincter to prevent diarrhea after total colectomy in puppies: a preliminary report.

Many adjunctive surgical techniques have been proposed to decrease diarrhea following total colectomy with an ileoanal anastomosis. A previously proposed method of longitudinal muscle ablation in canine small intestine to produce an "artificial sphincter" and increase transit time after massive small bowel resections has been applied to puppies who have had a total abdominal colectomy and ileoproctostomy. Total abdominal colectomy with ileoproctostomy at the level of the peritoneal reflection was performed in 6 mongrel puppies, aged 6-8 weeks. Two control puppies died within 2 weeks of the procedure with overwhelming diarrhea. Four experimental animals had "sphincters" (circumferential excision of a 1 cm length of longitudinal muscle) placed 5 cm proximal to the ileoproctostomy anastomosis. The puppies with colectomy plus sphincter were followed from 14 months to two years postoperatively and had intestinal transit times of 3-4 1/2 hours comparable to unoperated littermates. Intermittent postoperative barium enemas were performed and gross and histologic examination of the sphincters were carried out at necropsy. This muscle ablation technique when used in puppies with total abdominal colectomy and ileoproctostomy controls diarrhea, allows survival with normal growth and does not result in proximal small bowel enteritis.

Animals↗

Effects of carcinogen dosage on experimental colonic carcinogenesis by azoxymethane: an ultrastructural study of grossly normal colonic mucosa.

The transmission electron microscopic features of grossly normal colonic mucosa in the azoxymethane [(AOM) CAS: 25843-45-2]-treated rat model of colonic carcinogenesis were studied by the method of concomitant variation. Ten-week-old male F344 rats were given 10 weekly sc injections of AOM at doses of 3, 7, or 14 mg/kg body weight and were killed 1 week or 15 weeks after the last AOM dose. Grossly normal distal left colon was examined using transmission electron microscopy. Three transient dose-dependent features of colonic epithelial cells were identified: a) mitochondrial injury, b) nuclear pleomorphism and loss of polarity, and c) increased numbers of mitotic figures in the lower third of the crypts. Because these dose-dependent features were present only shortly after AOM administration, they appeared to be manifestations of carcinogen toxicity and associated reactive, regenerative epithelial changes. By contrast, four persistent dose-dependent features were identified: a) increased numbers of epithelial cells with enlarged nucleoli, b) increased numbers of mitotic figures in the middle third of crypts, c) reduced numbers of goblet cells, and d) reduced numbers of apical cytoplasmic vacuoles in the upper third of the crypts. Because these features persisted in a dose-dependent manner for many weeks after the last dose of AOM and were present after the latent period to tumor formation, they appear to be morphologic precursors to colonic carcinogenesis in the model.

Animals↗

The role of resection margin frozen section in the surgical management of Crohn's disease.

The use of frozen section examination of resection margins in selecting the site for an ileocolonic anastomosis was evaluated in patients with Crohn's disease. Seventy-nine patients with ileitis or ileocolitis who underwent first resection with removal of all apparent disease and primary ileocolonic anastomosis were studied. The patients with a resection margin examined by frozen section (FS group, n = 38) and those with margins chosen on the basis of visual inspection alone (NO-FS group, n = 41) were compared. Frozen section examination was found to be poor at detecting margin involvement: although 60 of 61 margins examined by frozen section were reported as negative at the time of operation, 20 of 61 were actually involved by Crohn's disease. Furthermore, despite the use of frozen section examination, the prevalence and severity of margin involvement in the FS and NO-FS groups were not statistically significantly different. Short term and long term clinical outcome were also not statistically different; the incidence of postoperative anastomotic leakage and obstruction was 13 per cent in the FS group and 5 per cent in the NO-FS groups (p NS). Clinical recrudescence rates by life table analysis in the FS and NO-FS groups were 37 +/- 9 per cent and 50 +/- 8 per cent, respectively, at five years, and 60 +/- 12 per cent and 66 +/- 9 per cent at ten years (p NS). Reoperation rates were 18 +/- 8 per cent at five years in both groups and 36 +/- 13 per cent in the FS group and 32 +/- 12 per cent in the NO-FS group at ten years. The findings support conservative resection to achieve grossly uninvolved margins rather than sacrifice of functional intestine in an attempt to achieve histopathologically uninvolved margins on frozen section.

Actuarial Analysis↗

Carcinoma arising in Barrett's esophagus.

Between 1951 and 1983, 32 patients who had adenocarcinoma develop in Barrett's esophagus were identified at our institution. Twenty-nine patients were male (91 per cent) and 29 were white. Amongst the 23 patients in whom the relevant data were available, 78 per cent admitted to regular alcohol intake and 78 per cent smoked. Only one of these patients did not smoke or drink alcohol. Surprisingly, only 61 per cent of the patients had symptoms suggestive of gastroesophageal reflux and reflux was demonstrated roentgenographically in only 41 per cent. Twenty-one of the patients underwent esophagogastrectomy. Life table analysis revealed a survival rate of 34 per cent at two years and 14.8 per cent at five years.

Adenocarcinoma↗

Endoscopic training in the academic GI program. Program Directors Workshop, March 29 and 30, 1984, Atlanta, Georgia. How the GI pathologist can interact best with the GI trainee.

Effective collaboration between endoscopists is essential if optimal results from gastrointestinal biopsy are to be achieved. Agreed upon ways to enhance communication should be established, such as special requisition forms and regular conferences to discuss biopsy findings. Endoscopists and pathologists should know about and feel free to discuss the other specialist's procedures and techniques. Furthermore, all procedures and techniques for obtaining, handling, and reaching diagnostic conclusions from biopsy specimens need to be carefully examined and optimized. Recommended approaches are presented.

Biopsy↗

The spectrum of carcinoma arising in Barrett's esophagus. A clinicopathologic study of 26 patients.

The clinical and pathologic features of carcinoma arising in Barrett's esophagus were studied in resection specimens from 26 patients. White males predominated (73%). A history of symptomatic gastroesophageal reflux was frequently absent, being elicited in only eight of 14 patients (57%) with a carefully obtained history at the time of presentation with carcinoma. Survival was relatively short with a median survival of 23 +/- 5 months, and only three patients had a disease-free survival longer than 2 years. A pathologic spectrum of carcinoma was found: differentiation ranged from well to poorly differentiated in the 20 patients with a single adenocarcinoma; two separate carcinomas were found in four patients; and a spectrum of differentiation in a single tumor was found in the other two cases, one an adenocarcinoid tumor and the other an adenosquamous carcinoma. The tumors were generally far advanced, with extension through the esophageal wall in 23 of 26 cases (88%) and metastases to lymph nodes in 17 of 24 cases (71%). Epithelial dysplasia, including carcinoma in situ in some cases, was found in Barrett's mucosa adjacent to the tumor in all 26 patients. Our findings suggest that a surveillance program for dysplasia in patients known to have Barrett's esophagus is warranted in an attempt to improve the outcome. However, the impact of surveillance on the incidence of Barrett's carcinoma may be lessened by its frequent occurrence in patients with asymptomatic gastroesophageal reflux.

Adenocarcinoma↗

"Bubbly" duodenal bulb in celiac disease: radiologic-pathologic correlation.

Small (1-4 mm) hexagonal filling defects were found on air-contrast studies of the duodenal bulb in three patients with unresponsive (atypical) celiac disease. Multiple biopsies confirmed both celiac disease and peptic duodenitis. Stimulated acid outputs determined in two patients were in the peptic ulcer range. Cimetidine therapy led to improved absorption in all three patients. Repeat upper gastrointestinal series and endoscopy in one patient showed no evidence of nodularity or peptic duodenitis, indicating that these changes may be reversible. Peptic disease may contribute to nodularity in the duodenal bulb and relative lack of response to a gluten-free diet of some patients with celiac disease. The finding of tiny nodules in the duodenal bulb in a patient with malabsorption should lead to consideration of celiac disease as a primary diagnosis with peptic duodenitis as an aggravating factor.

Adult↗

Esophageal Lewy bodies associated with ganglion cell loss in achalasia. Similarity to Parkinson's disease.

Achalasia and Parkinson's disease sometimes have similar clinical and neuropathologic features, including loss of esophageal peristalsis and neuronal loss within brainstem nuclei. We compared the neuropathologic features in autopsies of 8 achalasia patients, 22 Parkinson's disease patients (3 patients with dysphagia), and 50 age- and sex-matched controls. Degenerating ganglion cells in the esophageal myenteric plexus in 2 achalasia patients contained Lewy bodies, intracytoplasmic inclusions characteristically found in the brainstem in Parkinson's disease. Esophageal or colonic Lewy bodies were also found in 2 Parkinson's disease patients with dysphagia. No gastrointestinal tract Lewy bodies were identified in Parkinson's disease patients without dysphagia or in controls. One achalasia patient with esophageal Lewy bodies also had the inclusions and neuronal depigmentation in the vagal dorsal motor nucleus and substantia nigra, as seen in Parkinson's disease. Our findings indicate that a subset of achalasia and Parkinson's disease patients with dysphagia may have similar mechanisms of neuronal degeneration responsible for esophageal dysfunction.

Adult↗

Structure of the colon.

One's concept of the 'structure of the colon' is determined by the method used for examination: the radiologist, endoscopist, surgeon, pathologist, and electron microscopist have strikingly different perspectives. The gross and macroscopical anatomy, histology, and ultrastructure of the normal colorectum are reviewed. The structures primarily involved in secretion and motility, i.e. the mucosa and muscularis propria, are emphasised. Some important differences between human beings and experimental animals are described.

Animals↗