Changes in dietary fat intake preceding the diagnosis of cancer

We studied changes in dietary fat intake preceding the diagnosis of cancer in 96 men diagnosed with cancer during the Coronary Primary Prevention Trial and Post-trial Follow-up. Diet was assessed semiannually by 24-hour recall for the duration of the trial. Dietary fat intake was elevated in the interval 12-24 months before diagnosis compared with the interval 24-36 months before diagnosis [6.9 gm per day; 95% confidence interval (CI) = 0.04-13.7]. The percentage of calories as fat was also elevated (1.9%; 95% CI = 0.34-3.4). Fat consumption decreased in the 0- to 12-month prediagnostic interval. The basis for the elevation is unclear, but it may have been due to the metabolic effects of cancer before its diagnosis. Case-control studies of long-term diet may overestimate positive associations between dietary fat and cancer risk if the cases' recall includes the prediagnostic period, during which fat intake is elevated. In analyses of prospective studies of dietary fat and cancer, data from within the first 2-3 years of baseline should be examined separately to evaluate the potential for bias introduced by the inclusion of measurements representing transient elevations in dietary fat intake.     

Stages of change for reducing dietary fat intake over 18 months

OBJECTIVE: To describe the stages of change that take place over 18 months, using the criterion of fat intake < or = 30% of total energy to define effective action and to investigate the effect of a single dietary feedback report on dietary fat reduction. DESIGN: Subjects were randomly assigned to experimental or control conditions and assessed at 0, 6, 12, and 18 months for fat intake and stage of change. Subjects in the experiment group received 1 feedback report at baseline; all subjects received a report at 12 months. SUBJECTS: Potential subjects (n = 614) were recruited by mail from a random sample of nonsmoking adults (32% response rate). Subjects were excluded if consuming < or = 30% of energy from fat or if pregnant or lactating (n = 145). Although 83% of subjects (n = 389) completed the 18-month study, only 296 provided complete data for all time points. The study was restricted to these 296. INTERVENTION: Dietary feedback reports plus brief educational materials were provided following the experiment design. ANALYSES: Repeated measures analysis of variance with fat intake (percent of energy from fat) as the dependent variable and baseline stage and condition as independent variables. In addition, t tests were used to compare groups at specific time points. RESULTS: There was a main effect for time (F3,286 = 39, P < .0001) and baseline stage (F3,286 = 24, P < .0001), but no effect of feedback. There was a time-by-feedback interaction (F4,286 = 4.7, P < .01). There was a short-term effect of feedback over 6 months (t = 3.8, P < .001), but this effect was not significant at other time points. About 9% to 12% of subjects in the precontemplation or contemplation stages, 24% of subjects in the preparation stage, and 40% of unclassified subjects at baseline progressed to the action stage by 18 months. Between 12 and 18 months, subjects progressing at least 1 stage reduced their fat intake to a greater extent than subjects who failed to progress (t = 5.1, P < .0001). IMPLICATIONS: Interventions targeted to stage of change have the potential for accelerating the rate of change for dietary fat reduction, but reaching the goal of fat intake < or = 30% of total energy may require more intensive interventions than a single dietary feedback report.     

The influence of dietary fat on food intake and body weight

Excessive intake of dietary fat is associated with a number of nutrition-related disorders, including obesity, heart disease, and cancer. The over-consumption of fat may be related to its palatability, high energy density, or physiological effects. This article reviews possible reasons why fat intake is high, examines the relationship between diet composition and body weight, and explores potential fat reduction strategies. It is concluded that low-fat or fat-free products could be useful in reducing the percentage of calories derived from fat, although this assertion needs to be further tested in controlled laboratory experiments and validated on a population basis.     

Immune aspects of endometriosis: relevance of the uterine mucosal immune system

Endometriosis is classically defined as the growth of endometrial cells at sites outside the uterus. It is a common disease characterized by infertility, chronic pain and adhesion formation. Immune dysregulation, evidenced by decreased clearance of endometrial cells and aberrant production of cytokines by peritoneal fluid leukocytes, has been proposed as a mechanism which allows implantation and growth of ectopic endometrium. Cytokines are primary components of intercellular signaling between uterine epithelial and stromal cells, leukocytes, and the developing conceptus. Because their production is regulated by sex hormones, cytokines are well-placed to play a key role in the extensive tissue remodeling required to accommodate menstruation, implantation and pregnancy. Understanding this specialized hormonally-responsive mucosal immune system within the uterus will be critical to understanding the potential importance of the immune system in the pathogenesis of endometriosis. In this review, highlights of studies describing leukocyte populations, cytokines and cytokine receptors in uterine and ectopic endometrium and their proposed role in the regulation of immune processes and endometrial growth are presented, followed by a review of current data on immune aspects of endometriosis. Studies directed at investigating the hormonal regulation of cytokine secretion by uterine and peritoneal cell populations, and the effect of cytokines on endometrial proliferation, should provide a more complete understanding of their potential role in normal uterine growth and in the pathogenesis of endometriosis.     

The dilemma of Crohn's disease: ileosigmoidal fistula complicating Crohn's disease

Between 1965 and 1975, 27 patients underwent surgical treatment for ileosigmoidal fistulas complicating Crohn's disease at the Cleveland Clinic. There was no death and no anastomotic leak. The preferred procedure is resection of the ileocecal area involved by Crohn's disease with ileocolic anastomosis and a separate segmental resection of the sigmoid colon with colocolic anastomosis. A covering temporary loop ileostomy is used when there is associated pelvic sepsis or small-bowel obstruction.     

Positive association between dietary fat intake and risk of gastric stump carcinoma in rats

Effect of high- and low-fat diets on gastric stump carcinogenesis was experimentally investigated. A total of 130 Wistar male rats weighing 250-300 g received either sham operation or Billroth II partial gastrectomy, the resection of the distal two-thirds glandular stomach and reconstruction of gastro-jejunostomy. After surgery, each group of rats was switched from a standard diet (CRF-1) to a special diet containing either 15% soybean oil (high-fat) or 0.5% soybean (low-fat), fed ad libitum and tap water, and were killed 50 weeks after surgery. Gastric tumours were observed only in the animals that underwent gastrectomy while no tumours were detected in the animals following the sham operation. Tumours located invariably at the gastrojejunostoma, were carcinomas or adenomas in histology. Carcinomas developed in 12 of 29 gastrectomy animals (41%) fed the high-fat diet and 4 of 27 gastrectomy animals (15%) fed the low-fat diet. The difference was significant (P < 0.05). The incidence of adenoma was also significantly higher in the gastrectomy animals fed the high-fat diet (38%) than that in those fed the low-fat diet (15%) (P < 0.05). A daily faecal output of bile acids was significantly greater in the gastrectomy animals fed the high-fat diet (19.0 +/- 16.4 micromol/day) than that in those fed the low-fat diet (11.2 +/- 6.2 [micromol/day; P < 0.05). This study suggests that increased fat intake is associated with a high risk of gastric stump carcinoma.     

Effect of dietary corn starch intake on ruminal, small intestinal and large intestinal starch digestion in cattle

In Exp. 1, 24 yearling Holstein steers averaging 340 kg were fed either an alfalfa hay diet at a maintenance level of metabolizable energy (ME) intake or corn silage-corn diets at one, two or three times maintenance ME intake. After a 42-day adjustment period, steers were fed individually, and digestibilities of total alpha-glucosides, starch oligosaccharides and glucose were determined at 2-week intervals, with chromic oxide used as an indicator. Steers fed the alfalfa hay diet had higher (P less than .05) total tract digestibilities of total alpha-glucosides and starch than steers fed the corn diets. Fecal starch (percentage of dry matter) in steers fed the corn diets increased (P less than .05) from approximately 11 to 31% as level of ME intake increased from one to three times maintenance. Starch digestibilities for the corn diets fed at one, two and three times maintenance were 81.4, 76.4 and 76.0%, respectively. However, these trends toward reduced starch digestibilities were not significant. There appeared to be no apparent adaption of alpha-glucoside digestibility in the total digestive tract among steers fed different levels of corn over the intervals observed. In Exp. 2, four Holstein steers (350 KH) were each fitted with duodenal and ileal reentrant cannulas and fed either a low or a high level of corn. Alpha-glucoside intakes for animals given the low and high levels of cord averaged 1.7 and 3.2 kg, respectively. Steers fed the high level of corn digested more (p less than .05) alpha-glucoside in the total tract (2.9 vs 1.6 kg), reticulo-rumen (2.3 vs 1.2 kg) and large intestine level of corn. Steers fed the high level of corn also digested more corn in the small intestine (.415 vs .221 kg) than steers fed the lower level; however, differences were not significant. Although there were trends toward lower partial digestion coefficients (expressed as a percentage of alpha-glucoside presented to that segment) in the total tract, reticulo-rumen and small intestine for steers fed the high corn diet, the magnitude of the differences was not significant.     

Crohn's disease and intestinal carcinoma: presentation of 2 cases and review of the literature

We present the cases of two patients with Crohn's disease with consequent adenocarcinoma of the bowel. The first patient underwent an ileo-colic bypass 23 years before, a mucinous adenocarcinoma (Duke's stage C) was found on the anastomotic tract and on the excluded bowel, in areas within histologically recognizable Crohn's disease. In the second patient both the adenocarcinoma (Duke's stage C) of the transverse colon and the Crohn's disease (without any clinical evidence) in active phase has been found at the same time. We underline that such association seems to be not so rare as it seemed in the past. Accurate observation of patients, long time sufferers from the Crohn's disease, is advised to single out possible neoplastic complications at an early stage.     

Modulation of immune system function by measles virus infection: role of soluble factor and direct infection

Measles virus infection can result in a variety of immunologic defects. We have begun studies to determine the basis for the lack of immune responsiveness to antigen and mitogen following infection. Here we present data showing that Epstein-Barr virus-transformed B-cell lines infected with measles virus produce a soluble factor that can inhibit antigen-specific T-cell proliferation and inhibit the proliferation of uninfected B cells. The soluble factor was neither interleukin-10, transforming growth factor beta, nor alpha/beta interferon. B cells infected with measles virus or treated with the soluble factor were unable to present antigen to T cells in a manner that supported antigen-specific proliferation. This could represent one mechanism of how measles virus limits T-cell expansion. However, we found that once CD4(+) or CD8(+) T cells were activated, their cytolytic activity was intact whether infected with measles virus or treated with soluble factor. Thus, while slow to be generated these cytoxic cells could participate in viral clearance.     

Crohn's disease and ulcerative colitis mucosal T cells are stimulated by intestinal epithelial cells: implications for immunosuppressive therapy

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases, and their pathogenesis is attributed, in part, to alterations of the mucosal immune system. This study was designed to define the possible contribution of epithelial cells to the activation of lamina propria T lymphocytes (LPTs) in CD and UC. METHODS: LPTs isolated from CD, UC, and control surgical specimens were cocultured with freshly isolated allogeneic or autologous epithelial cells or epithelial cell lines. Resulting T-cell proliferation was evaluated by tritiated thymidine incorporation on day 5. RESULTS: When intestinal epithelial cells were used to stimulate mucosal T-cell proliferation, CD and UC LPTs were less responsive than control LPTs (p < 0.05 and p < 0.03, respectively). This difference between inflamed and control T cells was consistently observed by using a variety of different intestinal epithelial cell types. CONCLUSIONS: CD and UC mucosal T cells are hyporesponsive to activation by intestinal epithelial cells when compared with control LPTs. Elucidating the mechanism underlying the differential activation of CD and UC LPTs may help to better understand the immunopathogenesis of these conditions.     

Superantigens: structure and relevance to human disease

Superantigens are a class of immunostimulatory molecules produced by bacteria and viruses. Their potent immune effects are due to their unique ability to bind to the major histocompatibility complex (MHC) outside the antigen-binding cleft and to stimulate T cells in a T-cell receptor (TCR) Vbeta-specific manner. Structural studies have revealed the binding sites involved in the MHC/superantigen/TCR complex. The bacterial superantigens are responsible for a number of syndromes, including food poisoning and toxic shock syndrome, but their effects may be not only acute but also chronic and complex. Recent evidence suggests that superantigens may be relevant to the pathogenesis of autoimmune and immunodeficiency disorders. To illustrate the detrimental effects of superantigens on disease outcome, evidence demonstrating the modulation of experimental allergic encephalomyelitis, an animal model for multiple sclerosis, by superantigen, as well as the potential role of superantigens in HIV pathogenesis of AIDS, will be presented. The information presented may provide valuable insight into the role of superantigens in autoimmunity and HIV infection.     

Dietary fat intake and the risk of coronary heart disease in women

BACKGROUND: The relation between dietary intake of specific types of fat, particularly trans unsaturated fat and the risk of coronary disease remains unclear. We therefore studied this relation in women enrolled in the Nurses' Health Study. METHODS: We prospectively studied 80,082 women who were 34 to 59 years of age and had no known coronary disease, stroke, cancer, hypercholesterolemia, or diabetes in 1980. Information on diet was obtained at base line and updated during follow-up by means of validated questionnaires. During 14 years of follow-up, we documented 939 cases of nonfatal myocardial infarction or death from coronary heart disease. Mutivariate analyses included age, smoking status, total energy intake, dietary cholesterol intake, percentages of energy obtained from protein and specific types of fat, and other risk factors. RESULTS: Each increase of 5 percent of energy intake from saturated fat, as compared with equivalent energy intake from carbohydrates, was associated with a 17 percent increase in the risk of coronary disease (relative risk, 1.17; 95 percent confidence interval, 0.97 to 1.41; P=0.10). As compared with equivalent energy from carbohydrates, the relative risk for a 2 percent increment in energy intake from trans unsaturated fat was 1.93 (95 percent confidence interval, 1.43 to 2.61; P<0.001); that for a 5 percent increment in energy from monounsaturated fat was 0.81 (95 percent confidence interval, 0.65 to 1.00; P=0.05); and that for a 5 percent increment in energy from polyunsaturated fat was 0.62 (95 percent confidence interval, 0.46 to 0.85; P= 0.003). Total fat intake was not signficantly related to the risk of coronary disease (for a 5 percent increase in energy from fat, the relative risk was 1.02; 95 percent confidence interval, 0.97 to 1.07; P=0.55). We estimated that the replacement of 5 percent of energy from saturated fat with energy from unsaturated fats would reduce risk by 42 percent (95 percent confidence interval, 23 to 56; P<0.001) and that the replacement of 2 percent of energy from trans fat with energy from unhydrogenated, unsaturated fats would reduce risk by 53 percent (95 percent confidence interval, 34 to 67; P<.001). CONCLUSIONS: Our findings suggest that replacing saturated and trans unsaturated fats with unhydrogenated monounsaturated and polyunsaturated fats is more effective in preventing coronary heart disease in women than reducing overall fat intake.     

Influence of carbon chain length of dietary fat on intestinal alkaline phosphatase in chylous ascites

The long-term effects of chain length of dietary fat on intestinal lymphatic transport of alkaline phosphatase were investigated in two patients with chylous ascites due to leakage of intestinal lymph into the peritoneal cavity. Substitution of a medium-chain triglyceride diet for long-chain triglyceride resulted in a parallel fall in triglyceride and the intestinal isoenzyme of alkaline phosphatase in chylous ascites. The concentrations of lymph triglyceride were linearly related to lymph intestinal alkaline phosphatase levels, suggesting a positive relation between absorption of long-chain triglycerides and transport of mucosal alkaline phosphatase into lymph.     

Modulation by dietary salt of verapamil disposition in humans

BACKGROUND: The intestine is an increasingly well-recognized site of first-pass drug metabolism. In this study, we determined the influence of dietary salt on the steady-state disposition of verapamil, a drug that undergoes extensive first-pass metabolism. METHODS AND RESULTS: Eight normal volunteers received 120 mg of racemic verapamil orally twice a day for 21 days. The disposition kinetics of verapamil enantiomers were determined after coadministration of intravenous deuterated verapamil with the morning oral dose on days 7, 14, and 21. Each study day was preceded by 7 days on a fixed-salt diet: in 5 subjects, the initial study was conducted during a low-salt (10 mEq/d) diet, the second study during a high-salt (400 mEq/d) diet, and the third during a low-salt diet, whereas in the other 3 subjects, the sequence of diets was reversed. Plasma concentrations of both unlabeled enantiomers (ie, from oral therapy) were significantly (P<0.05) lower during the high-salt phase (eg, mean area under the time-concentration curve [0 to 12 hours] for S-verapamil: 7765+/-2591 ng. min. mL-1 [high salt] versus 12 514+/-3527 ng. min. mL-1 [low salt], P<0.05). Peak plasma concentrations were significantly lower and the extent of PR interval prolongation significantly blunted with the high-salt diet. In contrast, data with labeled drug (ie, reflecting the intravenous route) were nearly identical for the 2 diets. CONCLUSIONS: These data indicate that a clinically important component of presystemic drug disposition occurs at the prehepatic (presumably intestinal) level and is sensitive to dietary salt.     

Free radical theory of aging: effect of dietary fat on central nervous system function

Free radical reactions have been implicated in aging. A rise in the level of random free radical reactions in a biologic system might have a greater effect on the central nervous system (CNS) than elsewhere, partly because of the presence of glial cells and the unique connections between neurons. To evaluate this possibility, some animal experiments were conducted. The initial experiment involved old male Sprague-Dawley rats fed (since shortly after weaning) with semisynthetic diets characterized by fat differing in amount or degree of unsaturation. The number of errors made in a Hebb-Williams maze was determined and found to be higher as the amount or degree of unsaturation of the fat was increased. Likewise rats aged 6 and 9 months, fed semisynthetic diets containing 20 percent by weight of lard, oleinate, or safflower oil +alpha-tocopherol performed significantly better in a discrimination learning situation (Skinner box) than did rats fed a diet containing 20 percent by weight of safflower oil. The diets employed in these studies did not have a significant effect on the mortality rates. These results are compatible with the possibility that enhancing the level of lipid peroxidation has an adverse effect on the CNS, out of proportion to the effect on the body as a whole, as measured by the mortality rate.     

Effects of ethanol intake on the immune system of guinea pigs

Groups of guinea pigs were maintained with alcohol solutions not sufficient to result in liver dysfunction prior to and during investigations designed to determine whether ethanol would nonetheless impair cell-mediated or humoral immunity. No impairment of either was observed in any of the experimental groups.