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Biomedical subjects

F Macrae

Publications and source records attributed to F Macrae.

15 recordsLinked to original sources
PubMed1998

Characteristics of small bowel carcinoma in hereditary nonpolyposis colorectal carcinoma. International Collaborative Group on HNPCC.

BACKGROUND: Small bowel carcinoma is uncommon. However, hereditary nonpolyposis colorectal carcinoma (HNPCC) patients are at increased risk of small bowel carcinoma. The purpose of this study was to characterize small bowel tumors in HNPCC patients. METHODS: A questionnaire was mailed to the members of International Collaborative Group on HNPCC (ICG-HNPCC) requesting clinicopathologic data in their registries on HNPCC patients with small bowel carcinoma. Survival was estimated utilizing the Kaplan-Meier method. RESULTS: Forty-two individuals from 40 HNPCC families developed 42 primary and 7 metachronous small bowel tumors. There were 46 adenocarcinomas and 3 carcinoid tumors. The median age at diagnosis of the index small bowel tumor was 49 years. Mismatch repair gene mutations were present in 15 of 42 patients (36%). There were nine hMLH1 and six hMSH2 mutations. The small bowel was the first site of carcinoma in 24 patients (57%). The median survival for the 42 patients was 47 months (range, 0-447 months). The overall 5- and 10-year survival rates were 44% and 33%, respectively. CONCLUSIONS: Small bowel tumors can be the presenting neoplasms in HNPCC patients. Similar to colorectal carcinoma in HNPCC, small bowel adenocarcinomas in HNPCC patients occur at an earlier age and appear to have a better prognosis than those occurring in the general population.

Adenocarcinoma↗
PubMed1997

Use of prototype automated blood culture system and gas-liquid chromatography for the analysis of continuous ambulatory peritoneal dialysis associated infection.

AIMS: (1) To compare the recovery of organisms from continuous ambulatory peritoneal dialysis (CAPD) effluent fluid obtained from patients with clinical evidence of peritonitis, with an automated system (AS) and the Septichek blood culture system; (2) to evaluate the times to detection of organisms with the two systems; (3) to identify anaerobes from CAPD samples by extended anaerobic culture and gas-liquid chromatography (GLC). METHODS: 168 CAPD effluent fluid samples were studied, representing 157 episodes of peritonitis in 97 patients. CAPD samples were inoculated into two AS bottles-one anaerobic, one aerobic-and a Septichek bottle; samples were also examined for cell count, Gram stain, and direct culture. Culture bottles were then subcultured onto various media, and any organisms isolated were identified. After routine culture, GLC was performed on culture fluid in the anaerobic AS and Septichek bottles. When volatile fatty acids were detected, the broths were cultured anaerobically on specialised medium for a further five days. RESULTS: 147 organisms were isolated from the 168 samples: 96 (57%) yielded growth of significant organisms by direct culture, as compared to 129 (76.8%) by both AS and Septichek. There was no significant difference in isolation rates between AS and Septichek, but time to detection was more rapid with the AS system (p < 0.002). GLC showed volatile fatty acid in 15 specimens; of these, 14 subsequently grew anaerobic organisms. CONCLUSIONS: AS was comparable to Septichek for numbers of isolations. Speed to detection was faster with the AS, which may be an advantage in management of patients with CAPD peritonitis. GLC showed anaerobes in several cases which would not have been detected without prolonged anaerobic culture; thus anaerobic cultures are recommended for patients who are unresponsive to antimicrobials or who have evidence of bowel perforation.

Bacteria↗
PubMed1996

RNA-based mutation screening in hereditary nonpolyposis colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is a cancer syndrome inherited in an autosomal dominant fashion. Four susceptibility genes are known, which code for DNA mismatch repair enzymes. The purpose of this study was to identify the HNPCC gene defects in a cohort of Australian HNPCC families and to evaluate the use of RNA-based screening methods. Six mutations were identified, four in the hMLH1 gene and two in hMSH2, by using a combination of DNA-based and RNA-based methods. One of the hMLH1 defects was a missense mutation, and the other five mutations would be expected to result in a shortened protein. These included a rare type of mRNA splicing mutation in hMLH1 exon 17. By use of reverse-transcriptase (RT) PCR, defective transcripts were detectable for three of the hMLH1 mutations but not for the fourth one, which was predicted to cause skipping of exon 15. Furthermore, many more alternative transcripts for the hMLH1 gene were found than previously described, and these were more abundant in the RNA samples prepared from whole blood than from lymphoblastoid cell lines. This confounded RNA-based screening for HNPCC mutations, because it was difficult to determine which aberrant RT-PCR fragment was the real hereditary defect. One of the splice-site mutations reported here causes skipping of exons 9 and 10, which also occurs as an alternative transcript. When the protein-truncation test was used, the results were indistinguishable between the patients in this family and controls. Other aberrant transcripts were also observed that varied in size between individuals but were unrelated to the hereditary defects. This study has important implications for the design of reliable diagnostic tests for HNPCC gene defects.

Cell Line↗
PubMed1995

Randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas.

BACKGROUND: Epidemiologic evidence of associations between the high intake of fat and low intake of dietary fiber, beta carotene, and other dietary constituents and the risk of colorectal neoplasia has been inconsistent and has not provided a sufficient basis for recommendations concerning the dietary prevention of large-bowel cancer in humans. PURPOSE: We conducted a clinical trial to assess the effects on the incidence of adenomas of reducing dietary fat to 25% of total calories and supplementing the diet with 25 g of wheat bran daily and a capsule of beta carotene (20 mg daily). METHODS: We performed a randomized, partially double-blinded, placebo-controlled factorial trial in which half the patients were assigned to each intervention, resulting in seven intervention groups and one control group. Eligibility criteria included histologic confirmation of at least one colorectal adenoma and confidence expressed by the colonoscopist that all polyps had been removed. Dietary changes were individually initiated and monitored by dietitians and research nurses. At surveillance colonoscopy, the size and location of all polyps were recorded, and their histology was later centrally reviewed. Among 424 patients who were randomly assigned in the trial, 13 were found to be ineligible upon histologic review. Among the remaining 411, complete outcome data were collected from 390 at 24 months and from 306 at 48 months. All P values are from two-sided tests of statistical significance. RESULTS: There was no statistically significant prevention of total new adenomas with any of the interventions. We found a statistically non-significant reduced risk of large adenomas (> or = 10 mm) with the low-fat intervention: At 24 months, the odds ratio (OR) adjusted for potential confounders = 0.4 and 95% confidence interval (CI) = 0.1-1.1; at 48 months, OR = 0.3 and 95% CI = 0.1-1.0. Less and statistically nonsignificant reductions in the risk of large adenomas were found with wheat bran: At 24 months, OR = 0.8 and 95% CI = 0.3-2.2; at 48 months, OR = 0.8 and 95% CI = 0.3-2.5. Patients on the combined intervention of low fat and added wheat bran had zero large adenomas at both 24 and 48 months, a statistically significant finding (P = .03). CONCLUSIONS: Because only small numbers of patients were studied, our finding that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large adenomas in this randomized, controlled trial must be treated with caution. The results do suggest, however, that these interventions may reduce the transition from smaller to larger adenomas, a step that may critically define those adenomas most likely to progress to malignancy.

Adenoma↗
PubMed1991

Epidemiology and early detection of colorectal cancer.

Further information consolidating the roles of dietary fat and fiber and physical inactivity in colorectal carcinogenesis has been published in the year under review. A large cohort study identified animal fat as the most important dietary risk factor, and a meta-analysis of fiber supported the role particularly of vegetable fiber in protection. An important population-based study in Scandinavia identified age at onset of ulcerative colitis as a factor independent of length of follow-up; risk at 35 years after onset was 40% for those with early-stage onset. An update at the St. Mark's Hospital, London, surveillance experience offers measured support for endoscopic screening for dysplasia and curable cancer. A unique paper from Japan defines a relative risk of cancer after polypectomy of 2.3. A case-control study of occult blood screening showed that the sensitivity of guaiac testing for fecal occult blood (Hemoccult, Smith Kline Diagnostics, CA) for asymptomatic colorectal cancer is just under 50%. Cost-benefit modeling suggests that annual occult blood testing and 3- to 5-yearly flexible sigmoidoscopy are optimal.

Colorectal Neoplasms↗
PubMed1987

Hemoccult tests.

Explore the source record for details and available documents.

False Positive Reactions↗
PubMed1985

Surveillance and early diagnosis of colorectal cancer.

Colorectal cancer is a major health problem in western countries such as the United States. The annual incidence of more than 130,000 new cases, and the annual mortality of more than 60,000 people justifies a consideration of efforts for its control. New concepts of risk, better understanding of the adenoma-adenocarcinoma natural history, and new screening and diagnostic technology have provided a basis for possible preventive approaches. Trials are in progress evaluating the fecal occult blood test and sigmoidoscopy screening tests, and colonoscopy as a diagnostic and surveillance test. Evaluation of data from the trials requires many considerations regarding bias and validity. Although the data from screening trials appear to be promising, they are still preliminary. In the interim, guidelines have been proposed for screening strategies related to average risk and high risk groups. Considerably more work will be required in order to provide the scientific basis for the control of large bowel cancer. In addition, efforts will have to be directed toward the effective communication of new concepts, data and techniques to the majority of physicians who interact with the at-risk population. Efforts will also have to be directed to the public at large to enhance their compliance with the approaches to increase their awareness of colorectal cancer as an important disease and to eliminate their misconceptions. Finally the cost effectiveness of various screening strategies will have to be examined once data indicates a benefit of such approaches.

Clinical Trials as Topic↗