Biomedical subjects

S R Hamilton

Publications and source records attributed to S R Hamilton.

At least 199 records · Page 11Linked to original sources

PubMed1987

Prevalence and importance of pigmented ocular fundus lesions in Gardner's syndrome.

We examined 134 members of 16 families with Gardner's syndrome for pigmented ocular fundus lesions. Of 41 patients with documented Gardner's syndrome, 37 (90.2 percent) had such lesions. The lesions were bilateral in 32 of the patients (78.1 percent) and in 2 of 42 controls (4.8 percent). Twenty (46.5 percent) of 43 first-degree relatives at 50 percent risk for Gardner's syndrome had bilateral pigmented fundus lesions, indicating that they had probably inherited the abnormal gene. The presence of bilateral lesions, multiple lesions (more than four), or both appeared to be a specific (specificity, 0.952) and sensitive (sensitivity, 0.780) clinical marker for Gardner's syndrome. The lesions are probably congenital; they were observed in a three-month-old baby at risk. The multiplicity of the pigmented fundus lesions and their association with diffuse disturbances of the retinal pigment epithelium in the same eye suggest a widespread expression of the abnormal gene in the retinal pigment epithelial cells.

Female↗

PubMed1987

The differential diagnosis of idiopathic inflammatory disease by colorectal biopsy.

The differential diagnosis of idiopathic inflammatory bowel disease by colorectal biopsy poses a challenge to the endoscopist as well as the pathologist. Distinguishing non-idiopathic colitis from idiopathic colitis is the fundamental first step. No single histopathologic feature distinguishes between non-idiopathic and idiopathic inflammatory bowel disease or between the two forms of idiopathic inflammatory bowel disease (ulcerative colitis and Crohn's disease involving the colon). Interaction between the endoscopist and pathologist is essential in optimizing the contribution of colorectal biopsy to management of patients with inflammatory bowel disease.

Biopsy↗

PubMed1987

Granular small bowel mucosa: a reflection of villous abnormality.

Diffuse mucosal granularity was reported recently in small bowel Crohn's disease. The radiographic appearance corresponded on histopathologic examination to villous hypertrophy, fusion, or epithelial bridge formation. We have observed similar granularity in Crohn's disease but also in several other conditions, including radiation enteritis, pancreatic glucagonoma, protein-losing enteropathy, and small bowel ischemia. Histopathologic examination demonstrated various alterations in villous morphology, such as edema, hyperplasia, clubbing, or fusion. In Crohn's disease, this appearance was sometimes an indication of early inflammatory disease but was also seen following extensive small bowel resection, possibly due to villous enlargement resulting from intestinal adaptation. These findings suggest that granular mucosa in the small bowel is a nonspecific finding reflecting an alteration in villous structure.

Adult↗

PubMed1987

Protection of the small intestine from nonocclusive mesenteric ischemic injury due to cardiogenic shock.

In a pericardial tamponade model of cardiogenic shock in pigs, we had previously shown that acute reductions in cardiac output produce severe mesenteric ischemia due to disproportionate splanchnic vasoconstriction. In this study, we extended the period of cardiogenic shock in order to investigate the pathogenesis of ischemic injury to the small intestinal wall. Four hours of tamponade produced sustained changes in splanchnic hemodynamics, similar to those observed in the prior short-term experiments. The resultant mesenteric ischemia caused necrotic lesions of the small intestine which were characteristic of those seen in nonocclusive mesenteric ischemia in human subjects. Prior alpha-adrenergic blockade failed to prevent either sustained mesenteric vasospasm or ischemic injury. In contrast, prior blockade of the renin-angiotensin axis, whether by nephrectomy or angiotensin-converting enzyme inhibition, blocked the splanchnic vasoconstriction, and thereby protected the small intestine from ischemic injury. The primary hemodynamic and pathologic features of this model of nonocclusive mesenteric ischemia appear to be mediated by the renin-angiotensin axis.

Animals↗

PubMed1987

Occult radiopaque jaw lesions in familial adenomatous polyposis coli and hereditary nonpolyposis colorectal cancer.

The purposes of this study were to determine the association, in 10 pedigrees, between adenomatous polyposis coli, hereditary nonpolyposis colorectal cancer, and occult radiopaque jaw lesions, and to assess whether these radiodensities are predictors for adenomatous polyposis. In seven kindreds with adenomatous polyposis, all patients with polyps had jaw lesions; in one kindred, no jaw lesions were found. In one of two kindreds with hereditary nonpolyposis colorectal cancer, no affected individuals had jaw lesions. In the other, the 1 affected patient with dental radiographs had generalized jaw lesions. Twelve children less than 16 yr old at risk for adenomatous polyposis were observed. Seven children with jaw lesions developed polyps after a mean interval of 4 yr. Five children without jaw lesions were polyp-free during a 5-10-yr follow-up. Thus, occult jaw lesions are consistently found only in some families with adenomatous polyposis coli, providing support for heterogeneity in polyposis syndromes. Jaw lesions are good predictors for polyp development in kindreds with adenomatous polyposis coli and jaw lesions. Their role as markers in hereditary nonpolyposis colorectal cancer needs exploration.

Adenomatous Polyposis Coli↗

PubMed1987

Chronic colitis with thickening of the subepithelial collagen layer (collagenous colitis): histopathologic findings in 15 patients.

The histopathologic features of collagenous colitis were studied in 14 women and one man. All but one patient presented with chronic watery diarrhea: 10 had a history of thyroid disease or unspecified arthritis. All 15 patients showed characteristic thickening of the subepithelial collagen layer (SCL) in colorectal biopsy specimens, but in the distal colorectum the thickening was sometimes absent or borderline. Patchy or diffuse injury to the surface epithelium was seen in all cases and was independent of SCL thickening. The injured surface epithelium was infiltrated by lymphocytes and variably by eosinophils and neutrophils, causing it to resemble the surface epithelial injury seen in the small intestine in celiac disease. Crypts were commonly infiltrated by lymphocytes but without associated epithelial injury. The lamina propria in all patients was expanded by lymphocytes, plasma cells, and eosinophils. Neutrophilic cryptitis was seen in seven patients but was usually sparse. Watery diarrhea abated in eight patients treated with corticosteroids or sulfasalazine and was often paralleled by restoration of surface epithelium, reduction in surface epithelial lymphocytes, diminished SCL thickening, and reduced lamina propria eosinophils. Therapy did not consistently alter other inflammatory changes. The possible role of autoimmunity in collagenous colitis should be investigated because of the following circumstantial evidence: the overwhelming female predominance; the frequent presence of possible immunologically mediated disorders such as thyroid and joint disease; the resemblance of surface epithelial changes to those in celiac disease; and the response to corticosteroids.

Adult↗

PubMed1987

Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification.

Primary malignant gliomas from 63 patients were analyzed to determine the relationship between amplification of the gene encoding the epidermal growth factor receptor (EGFR) and expression of the corresponding mRNA. Twenty-four tumors were found to have amplified the EGFR gene and amplification of other genes occurred in three additional tumors. Hybridization with synthetic RNA probes was used to quantitate mRNA levels in situ. All 24 tumors with amplification of the EGFR gene had high levels of expression of this gene, while none of the 39 tumors without amplification had increased levels. This shows that, in human gliomas, large increases in the expression of the EGFR gene are invariably associated with alterations in gene structure.

ErbB Receptors↗

PubMed1987

The relationship between columnar epithelial dysplasia and invasive adenocarcinoma arising in Barrett's esophagus.

The authors assessed the relationship between dysplasia in Barrett's esophagus and invasive adenocarcinoma in a study of both endoscopic biopsy specimens and esophagectomy specimens. They reviewed the pathologic findings and clinical follow-up of 14 patients with dysplasia in Barrett's mucosa in endoscopic biopsy specimens. They also studied systematically the histopathologic features of the Barrett's mucosa in 43 esophagectomy specimens resected for Barrett's carcinoma. In the biopsy specimens, dysplasia occurred in distinctive-type Barrett's mucosa of 13 patients (93%) but in cardiac-type mucosa of only 3 (21%). Six patients had high-grade dysplasia; five underwent esophagectomy and three of these were found to have superficially invasive adenocarcinoma. The other patient with high-grade dysplasia as well as eight patients with intermediate- or low-grade dysplasia are not known to have carcinoma on available follow-up. In the study of resection specimens, high-grade dysplasia was strongly associated with adjoining invasive adenocarcinoma, because 84% of areas with invasion had high-grade dysplasia and 92% of areas with high-grade dysplasia showed invasion. The authors' findings suggest that the dysplasia-carcinoma sequence most commonly occurs in Barrett's mucosa of the distinctive type; high-grade dysplasia in Barrett's mucosa is a marker indicating high probability of invasive carcinoma; the presence of high-grade dysplasia in biopsy specimens of Barrett's mucosa is an indication for esophagectomy in suitable surgical candidates.

Adenocarcinoma↗

PubMed1987

The fundamental hemodynamic mechanism underlying gastric "stress ulceration" in cardiogenic shock.

Acute hemorrhagic ulceration of the gastric mucosa is seen frequently in patients with hypovolemic or cardiogenic shock. Although such lesions clearly are related to regional gastric ischemia, little attention has been directed at the underlying mechanism(s) mediating the ischemia itself. To this end, anesthetized pigs were subjected to sustained cardiogenic shock (mild hemorrhage and pericardial tamponade) such that cardiac output was reduced to 38 +/- 1% of the baseline level for 4 hours, followed by release of the tamponade, reinfusion of the shed blood, and resuscitation for 2 hours. During the period of shock, there was profound regional gastric ischemia, resulting from severe and disproportionate gastric vasoconstriction. "Blinded" gross and microscopic evaluation of the stomachs removed after the experiment revealed severe mucosal ischemic necrosis, hemorrhage, and ulceration, whereas sham-operated pigs showed no lesions. The characteristics of this model therefore mimic the essential features of the gastric "stress ulceration" syndrome. Prior confirmed total alpha-adrenergic blockade with phenoxybenzamine failed to alter these features significantly. In contrast, prior ablation of the renin-angiotensin axis, whether by angiotensin-converting enzyme inhibition with teprotide or by bilateral nephrectomy, significantly and substantially ameliorated the ischemia, vasospasm, and mucosal injury. In this model of cardiogenic shock, acute gastric mucosal "stress ulceration" is caused by a disproportionately severe regional gastric ischemia resulting from selective splanchnic vasospasm that is unaffected by sympathetic blockade but abolished by prior ablation of the renin-angiotensin axis. Like nonocclusive small bowel ischemia, ischemic colitis, and the "shock liver" syndrome, gastric "stress ulceration" is yet another component of the multiple splanchnic organ failure syndrome that appears to be mediated primarily by the remarkable sensitivity of the splanchnic vascular bed to the renin-angiotensin axis.

Animals↗

PubMed1987

Intestinal ischemic injury following mild hypothermic stress in the neonatal piglet.

The core body temperature of unanesthetized neonatal piglets was lowered 4 +/- 1 degrees C for 4.5 h. Although systolic blood pressure, arterial blood gases, and pH were similar in hypothermic and control animals, grossly evident small intestinal injury occurred in 94% of hypothermic piglets but in none of the controls (p less than 0.01). The histopathology of the intestinal lesions in the experimental animals was characteristic of ischemic injury and ranged from superficial mucosal necrosis to transmural infarct. The lesions were more frequent in the mid- and distal small bowel and involved the muscularis propria only in the distal small bowel. The location and histopathologic characteristics of the bowel lesions in these animals support the concept that mild hypothermia could be a pathogenetic factor in the ischemic bowel lesions of human neonatal necrotizing enterocolitis.

Animals↗

PubMed1987

Collagenous colitis: physiologic and histopathologic studies in seven patients.

Collagenous colitis is a clinicopathologic syndrome with chronic watery diarrhea, diffuse colitis with surface epithelial injury, and a distinctive collagen band beneath the surface epithelium especially in the proximal colon. The cases of seven patients (including six middle-aged women) with chronic, watery, noninfectious diarrhea were studied. Roentgenographic and endoscopic findings were not diagnostic. Two patients had rectal mucosal inflammation but sparing of the distal colon from subepithelial collagen. Other findings included thyroid disease (four patients), urethral fibrosis (three), elevated erythrocyte sedimentation rate (six), and eosinophilia (three). The colon was thought to be the main source of diarrheal fluid, but bile salt malabsorption, steatorrhea, and net small-bowel secretion were additive factors in some patients. With antiinflammatory treatment the diarrhea abated, the surface epithelial injury decreased, and the subepithelial collagen resolved (two patients), but lamina propria inflammation persisted. Collagenous colitis seems to be a chronic systemic, and perhaps autoimmune, disorder.

Adult↗

PubMed1987

Surgical prophylaxis against large bowel tumors in an animal model.

Subtotal removal of high-risk organs is of uncertain value as cancer prophylaxis. This study examined to what extent partial colectomy prevented carcinogen-induced large bowel tumors. Male Fischer 344 rats (N = 98) were given five weekly subcutaneous injections of azoxymethane 7 mg/kg, then treated as follows: group I (controls), the ileocecal junction was divided and reanastomosed without resection; group II, a proximal 1/3 colon resection was performed; and group III, a proximal 2/3 colon resection was performed. After 7 months the rats were sacrificed and colorectal tumors confirmed histologically. Sixty-nine animals survived for analysis. Tumor incidence and average number of tumors per rat were not significantly changed by resection. Surgical prophylaxis was compromised by a high frequency of multiple tumors and by a higher than expected frequency of tumors in the remaining bowel.

Animals↗

PubMed1987

Intestinal necrosis due to sodium polystyrene (Kayexalate) in sorbitol enemas: clinical and experimental support for the hypothesis.

Five patients who suffered catastrophic colonic necrosis are presented. All patients were uremic and received sodium polystyrene (Kayexalate) in sorbitol enemas for the treatment of hyperkalemia shortly before the development of signs and symptoms of colonic necrosis. In all specimens extensive ischemic necrosis was present, and Kayexalate crystals were noted in the intestinal lumen. Four of the five patients eventually died. To further investigate the occurrence of colonic necrosis after the administration of Kayexalate in sorbitol enemas, a series of experiments were performed in rats. Two groups of Sprague-Dawley rats were studied. One group was made uremic by performance of bilateral nephrectomy. The other group underwent sham operation. Enemas of saline, Kayexalate alone, sorbitol alone, or Kayexalate in sorbitol were administered. In nonuremic rats, transmural necrosis was noted in seven of 10 rats receiving sorbitol enemas and in six of 10 rats receiving Kayexalate in sorbitol enemas. No significant pathologic changes were noted in the rats receiving other enemas. In uremic rats, extensive transmural necrosis was noted in all rats receiving enemas of sorbitol or Kayexalate in sorbitol. All of these 19 rats died within the period of observation compared with no deaths in 18 rats that received enemas without sorbitol (p less than 0.001).

Adolescent↗

PubMed1986

Gene amplification of c-myc and N-myc in small cell carcinoma of the lung.

The relationship of the copy numbers of the c-myc and N-myc oncogenes to tumor formation and progression was studied in small cell carcinoma of the lung. When 96 neoplastic lesions from 45 patients were examined, these lesions could be grouped into three categories: high copy (tumors with greater than 3 copies of the N-myc or c-myc gene per haploid genome), middle copy (1.5 to 3 copies per genome), and normal copy. Fourteen of the patients had middle copy tumors, but this was almost always a result of chromosome duplication rather than the amplification of a small genetic locus. In contrast, five patients had high copy tumors, with the increased copy number in each case due to gene amplification. The amplification did not occur in a heterogeneous fashion within individual patients, since all metastatic lesions from patients with high copy lung tumors were also high copy, while none of 41 metastatic lesions from the other patients were high copy. These data suggest that gene amplification is an important step in neoplastic growth in a subset of patients with small cell carcinoma of the lung and that this genetic event occurs relatively early (before metastasis) in this subset.

Carcinoma, Small Cell↗

PubMed1986

Androgen receptors in experimentally induced colon carcinogenesis.

Sex hormones may play a role in colonic carcinogenesis, as evidenced by epidemiologic and experimental data showing different tumor rates in males and females. We investigated the effects of hormonal manipulation on tumor development and on androgen receptor binding in both colonic wall and experimentally induced tumors in male rats. Five of six groups, each with 40 animals, were given 10 weekly s.c. injections of azoxymethane (AOM), 7.5 mg/kg body weight. Group-I served as normal controls. Group-II received AOM only. Group-III was castrated 2 weeks prior to carcinogen treatment. Group-IV was castrated similarly and then hormone substituted with testosterone propionate. Group-V was chemically castrated with the anti androgen cyproterone acetate. Group-VI was castrated and given hormone vehicle. Scatchard analysis for androgen receptors in cytosol from normal colonic wall and tumor was performed with 3H-methyltrienolone as the ligand. Androgens were found to have an inhibitory effect on carcinogenesis: chemical castration increased colonic tumor development (P less than 0.05 for multiplicity), and testosterone administration produced a borderline statistically significant reduction in tumor incidence in surgically castrated rats (P less than 0.053), particularly in the right colon. Specific binding sites for androgen with high affinity and low capacity were found in the colonic wall of all groups. Receptor density was not altered by AOM administration, but increased after surgical castration. Receptor density was markedly lower in tumors than in normal colonic wall. Receptor binding sites in tumors were not altered by the various hormonal manipulations. Our study demonstrated that although cytoplasmic androgen receptors are present in colonic wall and in experimental tumors, AOM-induced colonic carcinogenesis appears to be only mildly affected by manipulation of androgens.

Animals↗

PubMed1986

Growth characteristics of autochthonous experimental colonic tumors as assessed by serial colonoscopic measurement in rats.

We report the growth characteristics of autochthonous experimental colonic tumors as assessed by serial measurements at colonoscopy. Male Fischer 344 rats were given 10 weekly subcutaneous injections of the bowel carcinogen azoxymethane, 10 mg/kg (weeks 1-10). Beginning in week 15, colonoscopy to the splenic flexure was performed weekly with a pediatric fiberoptic bronchoscope. Width of identified tumors was measured in photographs that included a scale passed through the biopsy channel, and tumor volume was calculated using computerized image analysis. Sensitivity, specificity, predictive values, and efficiency of colonoscopy for identification of tumors were 85%-100%. Cumulative tumor incidence in the descending colon increased in a relatively linear fashion from 3% at week 15 to 68% at week 30. Tumor width by colonoscopy correlated well with width at necropsy (r = 0.951). Growth curves of individual tumors were highly variable; however, tumor width showed stable mean weekly growth rates. By contrast, mean calculated tumor volume rose exponentially, with deviation from the fitted curve in the sixth week. All tumors greater than 3 mm in width or greater than 10 mm3 in volume showed invasion. Final tumor width and volume, and growth of tumor volume during the initial week but not the later weeks of observation, correlated with depth of invasion. Our findings suggest that colonoscopic measurement was useful to study the growth characteristics of autochthonous experimental colonic tumors; azoxymethane administration produced persistently altered colonic epithelium that had variable latent periods until development of visible tumors in individual rats; the growth curves of individual colonic tumors were exponential, although variable, during the initial weeks; invasion was found in small tumors and depth of invasion correlated with growth rate during the initial week but not the later weeks. This aggressive behavior of the tumors early in their course contrasts with colorectal adenomas in humans and argues against the routine occurrence of an adenoma-carcinoma sequence in the model we used.

Animals↗

PubMed1986

Computed tomography findings in gastrointestinal involvement by opportunistic organisms in acquired immune deficiency syndrome.

The computed tomography findings in two cases of gastrointestinal superinfection by opportunistic organisms in acquired immune deficiency syndrome are presented. Findings included thickening of the mucosal folds and the bowel wall in the small intestine and colon associated with cytomegalovirus and cryptosporidiosis. These cases indicate that it is important to look carefully at the gastrointestinal tract when performing computed tomography in this group of patients. Unsuspected bowel pathology may be demonstrated, or disease may be confirmed in clinically suspected cases.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Pathogenesis of nonocclusive ischemic colitis.

The nonocclusive component of ischemic colitis in anesthetized pigs was mimicked using cardiogenic shock produced by pericardial tamponade. Increases in pericardial pressure produced decreases in arterial pressure (PA) and cardiac output (CO), with corresponding rises in total peripheral resistance (i.e., cardiogenic shock). This was associated with marked reductions in blood flow through the inferior mesenteric artery (IMA), due primarily to disproportionate increases in IMA vascular resistance. Levels of plasma renin activity correlated closely with these changes in mesenteric hemodynamics. Confirmed, total alpha adrenergic blockade with phenoxybenzamine failed to block this selective mesenteric vasoconstriction, while ablation of the renin-angiotensin axis with captopril completely abolished it, thereby ameliorating the colonic ischemia. Central intravenous infusions of pathophysiologic levels of angiotensin II, without tamponade, mimicked the response to shock seen with tamponade alone. In an additional group of pigs, 4 hours of sustained shock (tamponade) followed by 2 hours of normotension (release of tamponade and resuscitation) produced lesions characteristic of ischemic colitis, including full-thickness mucosal ulceration. Such lesions were ameliorated significantly in pigs in which the renin-angiotensin system had been ablated by bilateral nephrectomy. Nonocclusive ischemic colitis appears to be mediated primarily by a remarkable sensitivity of the colonic vasculature to the renin-angiotensin axis.

Animals↗