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Biomedical subjects

C J McDougall

Publications and source records attributed to C J McDougall.

8 recordsLinked to original sources
PubMed1997

Colon cancer prevention: intervening in a multistage process.

Colorectal cancer, one of the most common human malignancies, is also one of the best understood. The epidemiology of this disease, and its relationship to environmental influences, particularly diet, has been extensively studied. New insights into the molecular biology and genetics of colorectal cancer also provide clues to its etiology, and high-risk populations that are most likely to benefit from preventive measures can be identified. Using this information, promising strategies for prevention of colorectal cancer are under investigation. These strategies include dietary modification, screening and adenoma removal, and antitumor agents from both natural and synthetic sources.

Adenoma↗
PubMed1995

Rectal bleeding in patients less than 50 years of age.

The study group consisted of 102 patients that presented for evaluation of rectal bleeding. All patients were 50 years of age or less and were evaluated with a flexible endoscope and an anoscope. The findings from each examination were recorded independently. Sigmoidoscopy and anoscopy were performed in 56 patients less than age 40 (group I), and colonoscopy and anoscopy were performed on 46 patients between the ages of 40 but less than 50 years (group II). Anoscopy was superior to flexible endoscopy in detecting hemorrhoids in group I (P < 0.001 and group II (P < 0.004). The guaiac status of patients was not influenced by the presence of hemorrhoids. Three patients in group I and eight patients in group II had polyps. The likelihood of finding a polyp was not influenced by the guaiac status of the patients. Three patients in group I and one patient in group II had anal fissures that were missed with flexible endoscopy and detected with anoscopy. Five of 102 patients were noted to have diverticula; all of these were in group II. However, this was not felt to be the source of the bleed given the clinical history. Overall, six patients had colitis; all but one of these patients were less than 40 years of age. Flexible endoscopy and anoscopy provide complimentary information in middle-aged adults with rectal bleeding.

Adult↗
PubMed1995

Comparative effects of omeprazole on xenobiotic metabolizing enzymes in the rat and human.

Omeprazole induces CYP1A in the human liver and gut, which has led to concern about possible side effects. The purpose of this study was to compare the effects of omeprazole on phase 1 and phase 2 enzymes in the rat and human. Male rats were treated with intraperitoneal (40 or 80 mg/kg) or oral omeprazole (40 mg/kg) for 5 or 14 days, respectively. The activities and amounts of CYP1A, uridine diphosphate-glucuronosyltransferase, and glutathione transferase were determined in liver and gut. Enzyme activities were also determined in duodenal biopsy specimens from six healthy human volunteers before and after treatment with omeprazole (20 mg/day) for 10 days. Treatment with intraperitoneal omeprazole (40 mg/kg; 80 mg/kg) coinduced uridine diphosphate-glucuronosyltransferase (36%; 66%), glutathione transferase (22%; 50%), and CYP1A (26%; 50%) in rat liver. In rat small intestine, comparable levels of induction were observed for uridine diphosphate-glucuronosyltransferase and glutathione transferase; CYP1A was unaffected. Oral omeprazole had similar effects. Immunoblotting showed corresponding changes in the amounts of these enzymes. Omeprazole increased the activities of CYP1A (19% to 167%; p = 0.014) and uridine diphosphate-glucuronosyltransferase (11% to 68%; p = 0.04) in the duodenal biopsy specimens of all six human volunteers; glutathione transferase was unaffected. Thus, omeprazole coinduced multiple xenobiotic metabolizing enzymes in the rat and human. The pattern of induction differed in the rat and human, consistent with known differences in genetic regulatory elements in the two species.

Administration, Oral↗
PubMed1993

Colonic mucosal pH in humans.

Mucosal pH was measured at specific anatomic segments within the colon using a flexible pH probe in patients prepared for colonoscopy. The data revealed similar pH measurements along the length of the colon, irrespective of the presence or absence of colorectal neoplasia. Patients exhibited a relatively acidic right colon; a more alkaline transverse, left, and sigmoid colon; and a relatively acidic rectum. There were no apparent gender- or age-related effects on colonic mucosal pH.

Colon↗
PubMed1992

Loss of colonic HLA antigens in familial adenomatous polyposis.

The loss of HLA antigens by neoplastic cells is considered important for tumor growth and metastasis, since it may allow tumors to escape immune surveillance. We studied the expression of HLA class I and II antigens in the colons of 10 patients with familial adenomatous polyposis (FAP), a condition which leads inevitably to colorectal cancer. Expression of HLA class antigens was studied by immunohistochemistry in (a) adenomas from patients with FAP, (b) histologically normal mucosa distant from the adenomas, and (c) histologically normal colonic mucosa from normal subjects. The expression of HLA class I and II antigens was decreased in histologically normal mucosa from FAP patients compared to normal controls. Adenomas showed a similar but quantitatively more pronounced reduction (or loss) of HLA antigen expression. The reduction of HLA expression in adenomas was comparable to that observed in sporadic colon carcinomas. This generalized suppression of HLA gene expression in the colon of FAP patients, which precedes the onset of overt histological manifestations of neoplasia, may be an important early event in colon carcinogenesis.

Adenomatous Polyposis Coli↗
PubMed1990

Reduced expression of HLA class I and II antigens in colon cancer.

The expression of HLA class I and II antigens was studied by immunohistochemistry in (a) specimens of colon cancer from 25 patients, (b) normal colonic mucosa obtained 5-10 cm away from each tumor, and (c) colonic mucosa from 13 normal individuals. Thirteen of the tumor specimens had normal epithelium adjacent to the cancer, which thus served as an internal control. The expression of HLA class I antigens in colon cancer was dramatically reduced compared to control (P less than 0.0001): undetectable in 28%, diminished in 68%, normal in 4%. The expression of class II antigens was also reduced in cancer (P less than 0.0001 for all when compared to normal), being undetectable in most (HLA-DP 64%, HLA-DQ 72%, HLA-DR 68%). In 44% of the cancers all three HLA class II antigens were undetectable; in 92% at least one class II antigen was undetectable; and in 20% both class I and class II antigens were undetectable. No cancer specimen had a completely normal HLA phenotype. The expression of other surface antigens was preserved in cancer tissues and, therefore, loss of HLA antigens was not due to a nonspecific decline in surface molecules. When glands of normal mucosa immediately adjacent to cancer were compared to those of normal controls, significantly reduced expression of only HLA class I antigens (P = 0.0149) and HLA-DP (P = 0.034) was found. The expression of the HLA antigens in colonic mucosa remote from the cancer was no different from that of normal controls. Our data show extensive and significant reduction in the expression of HLA antigens in colon cancer; its potential relationship to immunosurveillance in cancer is discussed.

Colon↗
PubMed1990

The circadian rhythm of biliary colic.

We evaluated 50 consecutive patients with symptomatic gallstones for the clinical features of biliary pain with particular reference to the timing of their painful episodes. Thirty-eight of the 50 patients were able to provide the time of onset of biliary pain in the 24-h cycle. The time of onset of biliary pain displays significant circadian periodicity (p = 0.0032), with its peak at 00:25 h. Forty-five patients had more than 1 episode of pain. Of these 84% had either all or over half of their attacks of biliary pain at the same clock time. Twenty-two patients with renal colic (a close parallel to biliary pain) and 31 patients with episodic abdominal pain from miscellaneous causes showed no circadian or other periodicity in the time of onset of pain. In only 1 of these patients did the abdominal pain recur consistently at the same clock time. "Typical" biliary pain has its onset at night and tends to recur at the same clock time. It is steady and relatively mild, lasting 1-5 h, it is felt in the right upper quadrant or the epigastrium, may radiate to a variety of sites, is associated with some additional symptoms, and is not usually related to meals. The chronobiological and other features of biliary pain reported here should be useful in the diagnostic evaluation of abdominal pain.

Adolescent↗