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Biomedical subjects

M J Farthing

Publications and source records attributed to M J Farthing.

At least 91 records · Page 5Linked to original sources
PubMed1997

Review and analysis of the effects of olestra, a dietary fat substitute, on gastrointestinal function and symptoms.

Olestra, a dietary fat substitute, was recently made available to consumers in savory snacks in three cities. Early reports of gastrointestinal complaints attributed to olestra attracted media coverage and fostered confusion among physicians and consumers about the nature of olestra and its effects on the digestive system. We reviewed all published studies of olestra's gastrointestinal effects and all relevant unpublished studies submitted to the Food and Drug Administration. Each study was analyzed by a group of expert gastroenterologists and epidemiologists. The symptoms reported with olestra ingestion are similar to those reported with ingestion of fiber and sorbitol, although the mechanisms involved in changing stool characteristics differ among these food additives. Olestra's effects on stool habit and characteristics are due to its presence in the stool. Large amounts are more likely to induce gastrointestinal symptoms than small amounts. There is no evidence that olestra induces pathological change in bowel function: there is no increased fluid or electrolyte nor is there altered gastrointestinal motility or microflora. Olestra and triglyceride ingestion resulted in a similar frequency of symptoms in normal adults and children and in people with chronic inflammatory bowel disease in remission. Olestra traverses the digestive tract intact to become a stool additive. Some subjects develop a change in bowel habit and stool characteristics due to the presence of more olestra in the stool. These changes resemble those associated with ingestion of sorbitol and fiber.

Controlled Clinical Trials as Topic↗
PubMed1997

Regional proliferative patterns in the colon of patients at risk for hereditary nonpolyposis colorectal cancer.

UNLABELLED: Patients from a hereditary nonpolyposis colorectal cancer (HNPCC) kindred (Lynch Type 1 and Type 2) have an increased risk of developing large-bowel cancer. Tumors occur at a young age and are characteristically right-sided. Colonic mucosal proliferation is known to be increased in several groups of patients at risk of colorectal cancer. PURPOSE: This study was performed to assess the pattern of mucosal proliferation at different sites in the colon of patients at risk of HNPCC and to determine whether this pattern differs from normal patients. METHODS: Mucosal biopsies were obtained at colonoscopy from 21 patients at risk for HNPCC (16 females; mean age, 42 years) and from 7 normal patients (4 females; mean age, 38 years), and mucosal proliferation was quantified using the whole crypt mitotic count (WCMC) technique. RESULTS: In patients from HNPCC families, WCMC and crypt area were significantly greater in the cecum than in the transverse colon and left colon (P < 0.001). Compared with normal patients, WCMC in HNPCC patients was significantly greater in the cecum only (P < 0.05). A significant right-to-left shift was also observed in normal patients, but the percentage increase from right to left was two-fold greater in HNPCC patients. CONCLUSIONS: These results confirm a proximal-to-distal proliferative gradient in the human colon and suggest that this may be exaggerated in HNPCC. This increased proximal proliferative rate may be a factor in the development of right-sided cancer in these patients.

Adult↗
PubMed1997

K-ras mutations are found in DNA extracted from the plasma of patients with colorectal cancer.

BACKGROUND & AIMS: Circulating DNA can be isolated from the plasma of healthy subjects and from patients with cancer. The aim of this study was to detect K-ras mutations in DNA extracted from the plasma of patients with colorectal cancer. METHODS: Tumor and plasma DNA were extracted from 14 patients with colorectal cancer (stages A-D), and K-ras alterations were detected using a polymerase chain reaction assay that uses sequence-specific primers to amplify mutant DNA. These results were confirmed with another polymerase chain reaction assay that creates an enzyme restriction site in the absence of a K-ras mutation followed by direct sequencing and additional cloning techniques. RESULTS: Seven patients (50%) had a codon 12 K-ras mutation within their primary tumor, and identical mutations were found in the plasma DNA of 6 patients (86%). Mutant DNA was not detected in the plasma specimens of 7 patients whose tumors tested negative for K-ras alterations or in healthy control subjects. Similar results were obtained using all three molecular biological techniques. CONCLUSIONS: K-ras abnormalities can be detected in circulating DNA extracted from the plasma specimens of patients with colorectal cancer. If these results are confirmed in larger studies, genetic analysis of plasma DNA may have clinical applications in the future.

Adult↗
PubMed1997

Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival.

BACKGROUND & AIMS: The E-cadherin-catenin complex plays a critical role in the maintenance of normal tissue architecture. Mutation of any of its components is believed to result in loss of cell-cell adhesion and contribute to neoplasia. The aim of this study was to examine the expression of E-cadherin and alpha-, beta-, and gamma-catenin in gastric carcinoma and dysplasia and determine any relationship with tumor characteristics and survival. METHODS: Immunoperoxidase staining of E-cadherin and alpha-, beta-, and gamma-catenin was performed using 89 gastric carcinomas, lymph node metastases, and gastric biopsy specimens from 14 patients with dysplasia and 10 healthy controls. RESULTS: Membranous staining was observed in control biopsy specimens for all components of the complex. Up to 57% of gastric dysplasia and 90% of tumors stained abnormally for one or more components of the cadherin-catenin complex. Abnormal E-cadherin and gamma-catenin staining occurred more frequently in diffuse than intestinal tumors (P < 0.0005 and < 0.05, respectively). No association with tumor grade or stage was found. A survival advantage was noted in intestinal and diffuse tumors retaining membranous expression of beta-catenin, independent of tumor type, grade, or stage (P < 0.005). CONCLUSIONS: Abnormal expression of the E-cadherin-catenin complex occurs frequently in gastric carcinoma. The close correlation with poor survival suggests that abnormal beta-catenin may be a useful prognostic marker.

Adult↗
PubMed1997

In vivo effects of the 5-HT3 antagonist alosetron on basal and cholera toxin-induced secretion in the human jejunum: a segmental perfusion study.

BACKGROUND: 5-hydroxytryptamine type 3 receptor antagonists have been shown to reduce fluid and electrolyte secretion or promote absorption in experimental models of small intestinal secretion. The aim of this study was to compare the effects of a single dose (4 mg) of the 5-hydroxytryptamine type 3 receptor antagonist alosetron and placebo on jejunal fluid and electrolyte movement in humans under basal conditions (n = 7) and following cholera toxin-induced secretion (n = 5) in a randomized, double-blind, crossover design over two separate study periods. METHODS: One hour after oral alosetron or placebo, jejunal intubation was performed. A 30 cm segment of jejunum, isolated by two occluding balloons, was exposed to 15 microg of purified cholera toxin for 2 h prior to triple lumen perfusion with a plasma electrolyte solution containing [14C]-polyethylene glycol as a nonabsorbable volume marker. In the basal study, intestinal perfusion was performed without exposure to cholera toxin. Collection and analysis of the effluent from the jejunal segment allowed fluid and electrolyte movement to be calculated. RESULTS: Alosetron treatment increased basal jejunal fluid absorption (median 5.1 mL/cm/h [interquartile range 4.2 to 7.1] compared with placebo (3.8 [3.6 to 4.3] P = 0.028, two sided Wilcoxon matched pairs signed rank test)). However, following establishment of a secretory state by cholera toxin, alosetron failed to significantly promote absorption or reduce secretion (0.3 [-1.2 to 1.2] compared to placebo (-4.3 [-7.7 to -1.3] P = 0.14)). Adverse events during the study, which included anorexia, nausea, dizziness and loose bowel movements, were not considered to be clinically important. There were no clinically significant changes in laboratory parameters. CONCLUSION: The 5-hydroxytyptamine type 3 receptor antagonist, alosetron, increased basal fluid absorption in normal human small intestine but failed to have a beneficial effect in cholera toxin-induced secretion.

Adult↗
PubMed1997

Cryptosporidiosis in adults in Lusaka, Zambia, and its relationship to oocyst contamination of drinking water.

In Lusaka, where human immunodeficiency virus seroprevalence in young adults is approximately 25%, four townships were studied to establish the prevalence of persistent diarrhea in adults and the etiologic importance of cryptosporidiosis in adults with persistent diarrhea. Cryptosporidium parvum oocyst contamination of urban water supplies was measured and the results used to categorize these populations into high or low exposure. In total, 506 adults were reported as having had diarrhea in the 2 weeks prior to the survey; 101 of these episodes were persistent. Adults with persistent diarrhea in the high-exposure areas were more likely to have cryptosporidiosis (odds ratio, 5.14; 95% confidence interval, 1.57-17.2; risk ratio, 1.83; 95% confidence interval, 1.04-3.21; P = .003) although overall prevalence of persistent diarrhea was not greater in these areas. This association was not confounded by animal exposure, travel, or boiling water. Within these urban populations, water contamination with C. parvum was a major influence on the prevalence of infection.

Adult↗
PubMed1997

Research misconduct.

Explore the source record for details and available documents.

Duplicate Publications as Topic↗
PubMed1997

Enteropathy in Zambians with HIV related diarrhoea: regression modelling of potential determinants of mucosal damage.

BACKGROUND: AIDS is characterised by small intestinal mucosal damage, but its aetiopathogenesis is poorly understood. Enteric infections in Africa differ from those in northern countries, where protozoan infections have been associated with severe enteropathy in AIDS patients. AIMS: To characterise enteropathy in Zambian AIDS patients compared with local controls, and to assess relative contributions of enteric infection, nutritional impairment, and immune dysfunction. METHODS: Computer aided mucosal morphometry of small intestinal biopsy specimens from 56 HIV infected Zambians with persistent diarrhoea and 26 diarrhoea free controls, followed by regression modelling. RESULTS: Patients with HIV related diarrhoea had reduced villous height and increased crypt depth compared with controls. There was no difference between HIV positive and negative controls. In regression models applied to AIDS mucosal measurements, villous height and crypt depth were related to nutritional parameters and to serum soluble tumour necrosis factor receptor p55 concentration. Crypt depth was also related to lamina propria plasma cell count. Intestinal infection was found in 79%, which consisted predominantly of microsporidia in 34%, Isospora belli in 24%, and Cryptosporidium parvum in 21%, but detection of these enteropathogens was not related to severity of enteropathy. CONCLUSIONS: Nutritional and immune disturbances were associated with enteropathy, accounting for over one third of the variation in mucosal morphometric parameters.

Adolescent↗
PubMed1997

Highlights of the year in gastroenterology.

The past 12 months have been a period of steady progress in the field of gastroenterology. Helicobacter pylori continues to dominate many areas of clinical research and the indications for eradication are increasing. A potent, topically-acting corticosteroid for Crohn's disease, and new hope and potential treatments for IBS sufferers are other developments.

Administration, Topical↗