PubMed Health⌕ Search

Biomedical subjects

R W Burt

Publications and source records attributed to R W Burt.

At least 19 recordsLinked to original sources
PubMed1992

Population genetics of colonic cancer.

BACKGROUND: There are several well known but rare syndromes of inherited colonic cancer. Genetic epidemiologic studies also have demonstrated that relatives of individuals with colonic cancer in general exhibit an excess risk for this malignancy. METHODS: This report reviews the literature pertinent to genetic and familial risk for colonic cancer with emphasis on the recent work that suggests that inherited susceptibility to colonic neoplasms is common. RESULTS: The adenomatous polyposis syndromes are rare inherited colonic cancer conditions caused by a mutant gene which recently has been characterized. Hereditary nonpolyposis colorectal cancer is likewise inherited and may account for up to 5% of cases. The molecular genetics of this disease remain to be clarified. The majority of colonic cancer cases are considered sporadic but are known to often cluster in families. Recent work suggests that inherited susceptibility may be the basis of this familial occurrence. Screening strategies based on inherited and familial risk are suggested. CONCLUSIONS: Knowledge of the familial and inherited risk for colonic cancer is leading to a better understanding of this disease and is suggesting more directed preventive strategies.

Adenomatous Polyposis Coli↗
PubMed1992

Hereditary aspects of colorectal adenomas.

BACKGROUND: Inheritance is important to the development of colonic adenomatous polyps and colon cancer. Current knowledge of inherited susceptibility to colonic neoplasms suggests that colon cancer screening strategies should consider familial and genetic risk. METHODS: This report reviews the literature pertinent to adenomatous polyp and colon cancer inheritance and suggests polyp-cancer screening procedures based on inherited or familial risk. RESULTS: Colorectal adenomas and cancer occur in several rare inherited syndromes and more commonly as sporadic cases. Intensive screening protocols have been suggested for the inherited syndromes because of the high associated cancer risk. Recent evidence suggests that inherited susceptibility also may be important in a large fraction of the so-called sporadic cases. Preliminary screening guidelines are suggested for this category based on the number of first-degree relatives affected with colon cancer. CONCLUSIONS: Inherited susceptibility appears to be more important to the pathogenesis of colorectal adenomas and cancer than previously recognized. Screening strategies which consider inherited risk may increase the effectiveness of cancer detection and prevention.

Adenoma↗
PubMed1992

Carotid artery disease: evaluation with acetazolamide-enhanced Tc-99m HMPAO SPECT.

Sixty patients were studied for carotid artery disease and were further evaluated with hexamethyl-propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) both at baseline (with the patient resting) and after administration of acetazolamide (ACZ). Of these 60 patients, 58 (97%) had symptoms and 49 (82%) had stenoses greater than 70% in at least one internal carotid vessel. Nine patients (15%) had symmetric findings on baseline examinations and at SPECT with ACZ. Thirty-two patients (53%) had asymmetric findings on baseline, but in 24 of these patients (75%) additional lesions were observed after ACZ administration. Nineteen patients (32%) had asymmetric findings only after ACZ was administered. HMPAO SPECT with ACZ allows detection of diminished cerebral perfusion reserve that is not found when HMPAO SPECT is performed with the patient at rest. This procedure helps provide an objective evaluation of the hemodynamic effects of carotid stenosis.

Acetazolamide↗
PubMed1992

Acetazolamide enhanced single photon emission computed tomography (SPECT) evaluation of cerebral perfusion before and after carotid endarterectomy.

Twenty-five patients were tested before and after carotid endarterectomy with resting and acetazolamide enhanced single photon emission computed tomography (SPECT) scans with hexamethyl propyleneamine oxine (HMPAO) or iofetamine hydrochloride I123 (123I labeled IMP), both widely available radiopharmaceuticals. Twenty preoperative SPECT studies were asymmetric, revealing focal or diffuse decreased perfusion reserve, and 13 also demonstrated infarcts. Five patients had symmetric (normal) studies. After carotid endarterectomy, 22 cases had changed flow distribution patterns. Usually improvement of reactivity ipsilateral occurred to the area operated on. In four, contralateral improvement was also found. Three of the patients who had preoperative symmetrical scans had increased ipsilateral reactivity after surgery indicating previous global loss of reactivity. Acetazolamide SPECT scans demonstrate a decreased perfusion reserve in 20 patients with carotid artery stenosis, indicating reduced perfusion and poor collateral circulation. Postoperative studies confirm improvement by demonstrating recovery of vascular reactivity in 84% of the patients. Acetazolamide enhanced SPECT scans may be helpful in providing objective evidence for selection of patients for carotid endarterectomy, especially in those who have an 80% carotid artery stenosis, but are asymptomatic.

Acetazolamide↗
PubMed1991

Increased brain retention of Tc-99m HMPAO following acetazolamide administration.

Sixty-five patients referred for Tc-99m HMPAO SPECT brain perfusion studies had measurements of global Tc-99m HMPAO retention after injection at rest and after acetazolamide pretreatment. Acetazolamide produced relative changes in Tc-99m HMPAO retention similar to those previously reported with Xe-133 regional cerebral blood flow (rCBF) measurements. This addition to imaging protocols allows another objective evaluation of the cerebral vascular reserve.

Acetazolamide↗
PubMed1990

Abnormalities of lectin histochemistry in familial polyposis coli and hereditary nonpolyposis colorectal cancer.

A transformation in the composition of colonic glycoconjugates has been described in adenomas, carcinomas, and certain premalignant conditions. These changes have been detected histochemically by the labeling patterns of fluorescein-conjugated lectins, which bind specific carbohydrate structures on fixed tissue sections. This study was performed to determine whether abnormal lectin binding patterns are present in tissues from patients genetically predisposed to colonic neoplasms and whether these patterns could be used as phenotypic markers for inheritance of the genotype. Lectin staining patterns of 22 colectomy specimens from patients with familial polyposis coli (FPC) and rectal biopsy specimens from 47 patients at risk for hereditary nonpolyposis colorectal cancer (HNPCC) (also known as Lynch syndromes I and II) were compared with rectal biopsy specimens from 27 sex-matched controls. The fluorescein-conjugated lectins included the agglutinins derived from peanut, Dolichos biflorus, Ulex europeus, and wheat germ (including the succinylated derivative). Using a technique for quantitating lectin binding on the tissue sections that provided a score from 0 to 400, labeling with certain lectins was found to vary slightly as a function of age and sex. Histologically normal mucosa from patients with FPC bound significantly less wheat germ agglutinin but significantly more U. europeus and succinylated wheat germ agglutinins than controls. Adenomas and dysplastic flat mucosa from the colectomy specimens of patients with FPC showed significantly less binding with D. biflorus, succinylated wheat germ, and wheat germ agglutinins than controls. Rectal tissues from patients at risk for HNPCC were found to bind significantly less peanut agglutinin and D. biflorus agglutinin than controls. Of interest, staining of the tissues by peanut and wheat germ lectins increased as a function of patient age; the control subjects were older than the patients with familial colon cancer, which could possibly account for the observations made with these two lectins. These results provide evidence that the premalignant colonic epithelium in familial polyposis and the hereditary nonpolyposis colon cancer syndromes may be biologically different and indicate that glycoconjugate modifications are early events in the evolution of the neoplastic phenotype.

Age Factors↗
PubMed1990

Congenital hypertrophy of the retinal pigment epithelium predicts colorectal polyposis in Gardner's syndrome.

We studied prospectively the utility of congenital hypertrophy of the retinal pigment epithelium as a predictor of colonic polyposis in offspring of patients with familial adenomatous polyposis with extracolonic manifestations (Gardner's syndrome). After they underwent initial indirect ophthalmoscopy, we followed up 34 individuals at 50% genetic risk for familial adenomatous polyposis with extracolonic manifestations due to an affected parent. All 34 obtained their first colorectal endoscopic examination during a follow-up period of up to 4 years. The 16 individuals who did not have congenital hypertrophy of the retinal pigment epithelium (aged 13 to 40 years; mean, 25 years) remained polyp free, while 14 of 18 individuals with congenital hypertrophy of the retinal pigment epithelium (aged 9 to 30 years; mean, 18 years) were found to have colorectal adenomatous polyposis. Our findings indicate that the presence of multiple patches of congenital hypertrophy of the retinal pigment epithelium in children and young adults at risk for familial adenomatous polyposis with extracolonic manifestations is a clinically useful predictor of colorectal polyposis.

Adenomatous Polyposis Coli↗
PubMed1990

Risk and surveillance of individuals with heritable factors for colorectal cancer. WHO Collaborating Centre for the Prevention of Colorectal Cancer.

Heritable and genetic factors pertinent to colon cancer can be divided into three categories: inherited syndromes, genetic epidemiology, and molecular genetics. Familial adenomatous polyposis (FAP) and Gardner syndrome (GS) are rare dominantly inherited syndromes characterized by hundreds to thousands of colonic adenomatous polyps. Colon cancer occurs at a young age in both diseases unless the colon is removed. Peutz-Jeghers syndrome and familial juvenile polyposis are inherited hamartomatous polyposis conditions with a less dramatic, but definite, increased risk for colon cancer. These four polyposis syndromes together account for less than 1% of cases of colon malignancy. Hereditary nonpolyposis colorectal cancer is a dominantly inherited form of colon cancer characterized by an early age of onset and a predilection for proximal colonic tumours. Multiple primary malignancies are frequently observed and one or several adenomatous polyps are often present in affected individuals; 4-6% of colon cancer cases occur in relationship to this syndrome. Genetic epidemiological studies have consistently shown that first-degree relatives of persons with colon cancer have a twofold to threefold increased risk of having colon malignancy. More recent studies have found a similar risk among relatives of those with adenomatous polyps. Studies of colon cancer and adenomatous polyps in pedigrees have further demonstrated that this familial clustering probably occurs on the basis of partially penetrant inherited susceptibilities. These inherited susceptibilities probably interact with environmental factors to give rise to polyp growth and finally colon cancer. Molecular studies have begun to elucidate the genetic mechanisms of colon cancer at the DNA level. The germinal mutation of FAP and GS has been localized to the long arm of chromosome 5. Tissue samples from "random" adenomatous polyps and colon cancers have shown frequent and specific acquired DNA sequence deletions on chromosomes 5, 17, and 18. Mutations and over-expression of the ras oncogene likewise have been observed in such tissues. The chromosome 5 defect in polyp and cancer tissues is probably at the same locus as the germinal mutation of FAP. There is evidence that this locus normally regulates expression of the c-myc oncogene, which in turn probably has a regulatory function in DNA replication. The chromosome 17 deletion is a mutation of the gene for the transformation-associated protein, p53. Appropriate screening starting at a relatively young age is necessary to prevent cancer in the inherited syndromes. Screening is also indicated in close relatives of those with nonsyndromic or common colon cancer in view of the moderately increased risk for colon cancer in this group.(ABSTRACT TRUNCATED AT 400 WORDS)

Colorectal Neoplasms↗
PubMed1989

Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine.

Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine-123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction. Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a finding is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake. This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.

3-Iodobenzylguanidine↗
PubMed1989

Inherited susceptibility to colorectal cancer.

Colorectal cancer and its potential precursor, adenomatous polyps, tend to aggregate in families, but it is not clear why. Heritability is established for only rare colorectal cancers, some prominently involving polyposis. Preliminary studies suggest, however, that susceptibility to the common colorectal cancer precursors, "sporadic" adenomatous polyps, is also inherited.

Adenoma↗
PubMed1989

Characteristics of familial colon cancer in a large population data base.

Early age onset and proximal colonic location are two specific characteristics of colon cancer which have been used clinically to assess the risk that an individual case is of familial rather than sporadic origin. This practice derives from the observation that these characteristics are typical of the rare, nonpolyposis inherited colorectal cancer syndromes. This study examines these two characteristics in cases of common colon cancer to determine whether they actually distinguish individuals at increased risk for familial colorectal cancer. Familial clusters of colon cancer in the Utah Population Data Base were examined. Common colon cancers were found to cluster excessively in families; however, the measure of familial clustering for distal colonic cases was increased to the same degree as proximal colonic cases. Early age onset was likewise not a distinguishing factor of familial cases. These results suggest that factors other than those that predispose to the rare syndromes are important in determining familial risk for common colon cancers, and that the absence of these two clinical features should not suggest the absence of familial risk of colorectal cancer.

Adult↗
PubMed1989

High prevalence of adenomatous polyps of the duodenal papilla in familial adenomatous polyposis.

Eighteen consecutive asymptomatic patients with familial adenomatous polyposis (both familial polyposis coli and Gardener's syndrome) were studied over a 12-month period; side-viewing upper endoscopy and biopsy were used to assess the frequency of adenomatous polyps of the duodenal papilla. Nine of the 18 patients demonstrated adenomatous polyps of the papilla, varying in size and appearance from microadenomas in normal-appearing duodenal papillae (two) to a sessile polyp 3 cm in diameter. Two were tubulovillous adenomas (0.5 cm and 2 cm in diameter) and the remainder were tubular adenomas. Severe atypia and malignancy were not encountered. These findings reveal that adenomas of the duodenal papilla are common in individuals with familial adenomatous polyposis. Because of these findings and because of the known risk of periampullary adenocarcinomas and nonmalignant complications of polyps of the duodenal papilla in patients with familial adenomatous polyposis, upper gastrointestinal screening of such patients should include examination of the duodenal papilla with a side-viewing endoscope.

Adenomatous Polyposis Coli↗
PubMed1988

Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers.

We studied 670 persons in 34 kindreds by flexible proctosigmoidoscopic examination (60 cm) to determine how frequently colorectal adenomas and cancers result from an inherited susceptibility. Kindreds were selected through either a single person with an adenomatous polyp or a cluster of relatives with colonic cancer. The kindreds all had common colorectal cancers, not the rare inherited conditions familial polyposis coli and nonpolyposis inherited colorectal cancer. Likelihood analysis strongly supported the dominant inheritance of a susceptibility to colorectal adenomas and cancers, with a gene frequency of 19 percent. According to the most likely genetic model, adenomatous polyps and colorectal cancers occur only in genetically susceptible persons; however, the 95 percent confidence interval for this proportion was 53 to 100 percent. These results suggest that an inherited susceptibility to colonic adenomatous polyps and colorectal cancer is common and that it is responsible for the majority of colonic neoplasms observed clinically. The results also reinforce suggestions that first-degree relatives of patients with colorectal cancer should be screened for colonic tumors. This evidence of an inherited susceptibility to a cancer with well-recognized environmental risk factors supports the hypothesis that genetic and environmental factors interact in the formation and transformation of polyps.

Adenomatous Polyposis Coli↗
PubMed1988

Duodenal polyposis and malignancy in a case of familial polyposis coli.

Familial polyposis coli is characterized by progressive adenomatosis with ultimate progression to colon cancer. It is becoming clear that these patients also have a high incidence of upper gastrointestinal adenomatous polyps, with some developing periampullary malignancies similar to those seen in Gardner's syndrome. This has led to recommendations for periodic endoscopic screening of asymptomatic polyposis patients. We report a patient with familial polyposis coli who developed an adenocarcinoma in the distal duodenum. This case points out the importance of screening the upper gastrointestinal tract in patients at risk.

Adenocarcinoma↗
PubMed1988

The adenomatous polyp and the hereditary polyposis syndromes.

Adenomatous polyps are the benign precursors of colorectal adenocarcinoma. Colonic adenomas occur commonly in adults in Western countries. There is recent evidence that inheritance may play an important role in the etiology of these adenomatous polyps. Colonic adenomatous polyposis (numerous colonic adenomas) is the central feature of several rare inherited syndromes that give rise to colorectal cancer. There also appears to be a risk of gastrointestinal and other malignancies in the rare inherited syndromes of hamartomatous polyposis.

Adenomatous Polyposis Coli↗