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R S Sandler

Publications and source records attributed to R S Sandler.

At least 73 records · Page 4Linked to original sources
PubMed1995

High levels of inorganic sulfate cause diarrhea in neonatal piglets.

Artificially reared neonatal piglets were used to study the effect of inorganic sulfate on bowel function in human infants. Two experiments were conducted to evaluate the effect of high levels of inorganic sulfate on the growth, feed intake and feces consistency of artificially reared piglets, and to determine the dose at which at least 50% of piglets develop nonpathogenic diarrhea. The effect of sulfate level on kidney weight and concentration of inorganic sulfate in urine was also assessed. In each experiment, 40 pigs with an average initial age of 5 d were individually caged and reared with an automatic feeding device. Ten pigs per dietary treatment were fed one of four diets containing the following levels of added inorganic sulfate (mg/L of diet), as anhydrous sodium sulfate (USP): 0, 1200, 1600 and 2000 for Experiment 1 (18-d study), and 0, 1800, 2000 and 2200 for Experiment 2 (16-d study). The levels of added sulfate did not affect (P > 0.05) the growth of piglets, or their feed intake. Whereas 1200 mg added sulfate/L had essentially no effect on feces consistency, levels > 1800 mg/L of diet resulted in a persistent, nonpathogenic diarrhea in neonatal piglets. Added sulfate did not affect (P > 0.05) relative kidney weight. Inorganic sulfate in urine reached maximum concentration (P < 0.05) in pigs fed diets with 1600 and 1800 mg added sulfate/L in Experiments 1 and 2, respectively, but declined at higher levels. The results suggest that the level of added dietary inorganic sulfate at which 50% of piglets develop nonpathogenic diarrhea is between 1600 and 1800 mg/L.

Animals↗
PubMed1995

Physical activity and the risk of colorectal adenomas.

Physical activity has repeatedly been shown to protect against colorectal cancer. Since adenomas are precursors to most colorectal cancers, we examined the relation of physical activity to the risk for colorectal adenomas in a colonoscopy-based study of 200 adenoma cases and 384 adenoma-free controls. Physical activity was assessed by telephone using a modification of a validated questionnaire comprising 17 items concerning three activity dimensions: leisure, work, and sport. Dietary information was obtained with a validated semiquantitative food frequency questionnaire. We created indices for each dimension of physical activity, which we categorized by quartile. Using logistic regression analysis, we found that leisure activity protected women against colorectal adenomas. Women in the second through fourth quartiles were considerably less likely than those in the first quartile to develop adenomas [crude odds ratio = 0.48; 95% confidence interval (CI) = 0.28-0.81]. There was no protective effect of work activity among either men or women. Men who participated in no sport were at increased risk for adenomas (odds ratio = 1.68; 95% CI = 0.93-3.02). Physical activity appears to protect against both colorectal cancer and colorectal adenomas.

Adenoma↗
PubMed1995

Prostaglandin F2 alpha- and 12-O-tetradecanoylphorbol-13-acetate-induced alterations in the pathways of renal ammoniagenesis.

The mechanisms whereby prostaglandin F2 alpha (PGF2 alpha) and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibit ammoniagenesis and the reason why they behave differently at pH 7.4, were examined with (15N)glutamine to assess the metabolic pathways and 2'-7'-bis(2-carboxyethyl)-5-(and-6)-carboxylfluorescein, acetoxymethylester (BCECF-AM) to evaluate Na+/H+ antiporter activity. LLC-PK1 cultures were incubated for 1 h in a Krebs-Hensleit bicarbonate buffer of pH 7.4 and pH 6.8 supplemented either with 5-15N- or 2-15N-labeled glutamine, followed by the assessment of (15N)ammonia and (15N)amino acid formation. Exposure of cells to either PGF2 alpha or TPA completely inhibited the low pH-induced increases in (15N)ammonia formation from incubations with 5-15N, reflecting reduced flux through the mitochondrial phosphate-dependent glutaminase, and from (2-15N)glutamine, reflecting reduced flux through the mitochondrial glutamate dehydrogenase pathway. They also qualitatively reversed the acute acidosis-induced changes in (15N)alanine formation and (15N)glutamate accumulation in the media. By contrast only TPA, but not PGF2 alpha, modified glutamine metabolism at pH 7.4. Na+/H+ antiporter activity was assessed under both acidified and basal (pH 7.4) conditions by measuring changes in intracellular pH in cells loaded with BCECF. TPA and PGF2 alpha both stimulated Na+/H+ antiporter activity comparably under acidified conditions. When cells were studied at pH 7.4, TPA but not PGF2 alpha stimulated the Na+/H+ antiporter and increased steady-state intracellular pH.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1995

Rational approach to small polyps found on sigmoidoscopy.

Most colorectal cancers are thought to develop from benign adenomas. Because adenomas are found in a large proportion of asymptomatic individuals, most adenomas must remain benign. Current guidelines suggest that colonoscopy is not necessary when hyperplastic polyps are found at screening sigmoidoscopy. Existing data suggest that small adenomatous polyps may also not be associated with substantial risk of current or future malignancy. We suggest that small polyps seen on flexible sigmoidoscopy require neither biopsy nor subsequent colonoscopy. Such an approach requires further study, but could result in substantial cost savings, with modest risk to patients.

Adenomatous Polyps↗
PubMed1995

Evaluating risk: a primer for gastroenterologists.

OBJECTIVE: To review the various types of risk measures and to illustrate how interpretations may vary depending on how risk is presented. METHODS: We define different types of risk estimates and provide examples of their use from the recent gastroenterological literature. RESULTS: Calculations of absolute risk and the number of patients who must receive treatment to prevent one patient from experiencing a disease state (number needed to treat) provide useful information in assessing the utility of fecal occult blood testing for prevention of colorectal cancer and in estimating small bowel cancer rates for individuals with familial adenomatous polyposis. CONCLUSIONS: Measures such as relative risk and the odds ratio are best used in analyzing causality but may not be helpful in guiding clinical decisions. Absolute risk and attributable risk reveal the actual number of cases that can be explained by a given exposure and can thereby measure the impact of a clinical intervention for both the population and the patient. These measures should be the criteria for decision-making.

Adenomatous Polyposis Coli↗
PubMed1994

Childhood infections and the risk of inflammatory bowel disease.

Adults with inflammatory bowel disease from North Carolina were questioned during 1986 and 1987 to assess risk due to a variety of childhood infections and treatments with antibiotics. Responses were compared with those of neighbor controls. Persons with Crohn's disease were more likely to report an increased frequency of childhood infections in general (odds ratio 4.67, 95% CI 2.65-8.23) and pharyngitis specifically (odds ratio 2.14, 95% CI 1.30-3.51). This was validated by an increased frequency of tonsillectomy (odds ratio 1.53, 95% CI 1.07-2.20). Crohn's cases were more likely to report frequent treatment with antibiotics for both otitis (odds ratio 2.07, 95% CI 1.03-4.14) and pharyngitis (odds ratio 2.14, 95% CI 1.20-3.84). Although Crohn's cases were more likely to report frequent exposure to penicillin (odds ratio 1.81, 95% CI 0.98-3.31), there did not appear to be excess risk conferred by penicillin after controlling for frequency of infections. Persons with ulcerative colitis also reported an excess of infections generally (odds ratio 2.37, 95% CI 1.19-4.71), but not an excess of specific infections or treatments with antibiotics. Persons who reported an increased frequency of infections tended to have an earlier onset of Crohn's disease (P < 0.0001) and ulcerative colitis (P = 0.04). Finally, it was noted that urban living in childhood increased the risk for Crohn's disease. We conclude that childhood infections may be a risk factor for Crohn's disease and may presage the early onset of disease.

Adolescent↗
PubMed1994

The intensity of acidosis differentially alters the pathways of ammoniagenesis in LLC-PK1 cells.

Utilizing [5-15N] and [2-15N]-labeled glutamine and gas chromatography mass spectrometry methodology, we examined the pathways of ammoniagenesis under basal and acute acidotic conditions of pH 7.0 and pH 6.8, respectively. LLC-PK1 cultures were incubated for one hour with gentle rocking in a bicarbonate buffer of pH 7.4, pH 7.0, or pH 6.8 supplemented either with [5-15N] or [2-15N] glutamine at 37 degrees C in a 5% CO2/95% air incubator atmosphere. Incubation of cultures with [5-15N] glutamine at pH 7.4 resulted in a substantial amount of 15N ammonia formation which was not significantly altered by incubations at pH 7.0. By contrast, exposure to pH 6.8 significantly increased 15N ammonia formation in comparison with its production at pH 7.0 or 7.4. However, 15N ammonia production from [2-15N] glutamine was significantly stimulated at pH 7.0 and was further increased at pH 6.8. Incubation of the cells with [2-15N] glutamine resulted in a substantially lower amounts of 15N ammonia formation than produced with [5-15N] glutamine. Alanine formation from [2-15N] glutamine increased significantly at pH 7.0; but in contrast to 15N ammonia formation, pH 6.8 had no additional stimulatory effect on 15N alanine formation. Cells incubated with [2-15N] glutamine resulted in a significant decrement in 15N glutamate production at both pH 7.0 and 6.8 when compared with pH 7.4. 15N aspartate formation was unaltered by the changes in media pH.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1994

PGF2 alpha activation of Na/H antiporter and ammoniagenesis in parent/variant LLC-PK1 cells.

A novel variant of the LLC-PK1 cell line was used to examine directly the mechanism whereby PGF2 alpha and TPA inhibit renal ammoniagenesis. The variant cells, which exhibit a growth pattern and morphology similar to the parent cell line, were isolated by a self selection process utilizing long-term cultures of parent cells maintained under conditions of continuous gentle rocking of the media fluid. Incubation of both parent and variant LLC-PK1 cells for one hour in a glutamine supplemented Krebs-Hensleit media of low pH (pH 6.8) increased ammonia and alanine production in comparison to the basal rates at pH 7.4. The phorbol ester TPA and also PGF2 alpha inhibited the low pH-induced increases in ammonia and alanine formation in parent cells; however, neither TPA nor PGF2 alpha inhibited ammonia or alanine metabolism in variant cells. TPA and PGF2 alpha activated PKC similarly in the parent and variant cells as demonstrated by a significant increase in membrane bound enzyme activity. BCECF labeling of cells indicated that the parent and variant cells possess an amiloride sensitive Na+/H+ antiporter of comparable activity. Exposure of parent cells to PGF2 alpha or TPA resulted in the activation of Na+/H+ antiporter activity. By contrast, neither compound stimulated antiporter activity in variant cells. These studies strongly suggest that PKC mediated activation of the Na+/H+ antiporter accounts for the inhibition of ammonia production produced by both PGF2 alpha and TPA. In addition, this novel variant of LLC-PK1 cells should provide a valuable tool to investigate various normal and pathophysiological functions involving mediation by PKC and/or Na+/H+ antiporter activity.

Alanine↗
PubMed1994

Are women with breast cancer more likely to develop colorectal cancer? Critical review and meta-analysis.

Breast cancer has been reported to confer greater risk for colorectal cancer. In order to estimate the magnitude of this risk, we critically reviewed all studies evaluating the association of breast and colorectal cancer and performed a meta-analysis. The combined results from seven cohort studies demonstrated a weak association between breast cancer and the subsequent risk of colorectal cancer [pooled relative risk (RR) = 1.15; 95% confidence interval (CI) = 0.99-1.31]. Pooled results from five cohort studies showed that the risk of breast cancer after colorectal cancer was similar (pooled RR = 1.10; 95% CI = 1.03-1.17). The combined results from five cross-sectional/case-control studies revealed a positive association between breast cancer and colorectal adenomas (pooled RR = 1.74; 95% CI = 1.27-2.21). Population-based cohort studies, the strongest research design, show essentially no increase in risk of colorectal cancer in women with previous breast cancer. Based upon this evaluation, there appears little justification for special colorectal surveillance of women with previous breast cancer.

Adenoma↗
PubMed1994

Improving dietary behavior: the effectiveness of tailored messages in primary care settings.

OBJECTIVES: To achieve the Healthy People 2000 objectives, public health professionals must develop effective dietary interventions that address psychosocial and behavioral components of change. This study tested the effect of individually computer-tailored messages designed to decrease fat intake and increase fruit and vegetable intake. METHODS: Adult patients from four North Carolina family practices were surveyed at baseline and then randomly assigned to one of two interventions or to a control group. The first intervention consisted of individually computer-tailored nutrition messages; the second consisted of nontailored nutrition information based on the 1990 Dietary Guidelines for Americans. Patients were resurveyed 4 months postintervention. RESULTS: The tailored intervention produced significant decreases in total fat and saturated fat scores compared with those of the control group (P < .05). Total fat was decreased in the tailored group by 23%, in the nontailored group by 9%, and in the control group by 3%. Fruit and vegetable consumption did not increase in any study group. Seventy-three percent of the tailored intervention group recalled receiving a message, compared with 33% of the nontailored intervention group. CONCLUSIONS: Tailored nutrition messages are effective in promoting dietary fat reduction for disease prevention.

Adult↗
PubMed1993

Diet and risk of colorectal adenomas: macronutrients, cholesterol, and fiber.

BACKGROUND: Diet is thought to be important in the etiology of colorectal cancer. Studies suggest that a diet high in red meat and saturated fat and low in dietary fiber and vegetables may increase cancer risk. Diet may also be important in the development of colorectal adenomas that are precursors of most colorectal cancers, but this hypothesis has not been well studied. PURPOSE: This case-control study was designed to examine the effects of dietary consumption of cholesterol, fiber (vegetables, fruits, beans, and grains), and macronutrients (protein, carbohydrate, and fat) on risk for colorectal adenomas. METHODS: Analyses were based on data from 236 subjects (105 men and 131 women) with histologically confirmed adenomas (cases) and 409 adenoma-free control subjects (165 men and 244 women), all of whom had had colonoscopy. Case and control subjects were similar with respect to gender, body mass, race, marital status, education, and indications for colonoscopy. Using a validated quantitative food-frequency questionnaire, an experienced graduate nutritionist interviewed each subject by telephone. Sex-specific analyses were conducted because the ranges of nutrient intake were substantially different for men and women. Odds ratios (ORs) were calculated according to quintiles of nutrient intake. RESULTS: Carbohydrate intake was inversely related to adenoma risk in women (P for trend = .002). Compared with women in the lowest quintile of carbohydrate consumption, those in the highest quintile were 60% less likely to develop adenomas (OR = 0.39; 95% confidence interval [CI] = 0.19-0.80). Intake of fruit (P for trend = .028) and intake of fiber derived from vegetables and fruits (P for trend = .012) were also inversely related to adenomas in women. Total fat showed a positive association in women (P for trend = .004), with an OR of 2.69 for the highest versus the lowest quintile (95% CI = 1.31-5.50). Results were comparable for saturated fat (P for trend = .027). The risks in men were generally similar in direction and magnitude but were not statistically significant. CONCLUSIONS: These data support the hypothesis that a diet high in fat and low in carbohydrates, fruits, and fruit and vegetable fiber increases risk not only for colorectal cancer but also for precursor colorectal adenomas. IMPLICATIONS: These results, which are consistent with findings of other investigators, suggest that environmental factors, influencing risk for colorectal cancer, such as a high-risk diet, may lead to development of the precursor adenomas.

Adenoma↗
PubMed1993

Cigarette smoking, alcohol, and the risk of colorectal adenomas.

BACKGROUND: The present study was designed to further assess the reported association between cigarette smoking, alcohol, and colorectal adenomas. METHODS: A number of environmental and life-style risk factors were examined in 236 patients with histologically proven adenomas and 409 controls with no adenomas. RESULTS: Age, sex, race, and indication for procedure were similar in cases and controls. Those who had ever smoked were not at increased risk for adenomas compared with those who had never smoked. Years of smoking, cigarettes per day, and total pack-years showed no dose-response effect. Results for men and women were similar. Alcohol was a significant risk factor for men but not for women. Men in the highest quartile of daily caloric intake from alcohol were more than four times more likely than nondrinkers to develop adenomas, with a statistically significant trend in risk from the lowest to the highest quartile. These findings persisted after controlling for other potential risk factors for adenomas. The risk for colon and rectal polyps were similar. Men in the highest tertile of beer consumption were nearly six times more likely to develop adenomas than nondrinkers. CONCLUSIONS: Beer drinking is a risk factor for colorectal adenomas in this population.

Adenoma↗
PubMed1992

Childhood exposure to environmental tobacco smoke and the risk of ulcerative colitis.

Previous reports have suggested that there may be a protective effect of active cigarette smoking on the risk of ulcerative colitis. Because passive smoking may also have other health consequences, the authors examined the effect of exposure to environmental tobacco smoke during childhood on adult risk of ulcerative colitis in a case-control study of 172 cases drawn in 1986-1987 from the rosters of North Carolina chapters of the Crohn's & Colitis Foundation of America and 131 peer-nominated neighborhood controls. Active smokers were less likely to develop ulcerative colitis than were nonexposed nonsmokers (odds ratio = 0.53, 95% confidence interval 0.24-1.14). The risk was also decreased in passive smokers, i.e., those whose parents had smoked (odds ratio = 0.50, 95% confidence interval 0.25-1.00). Risk estimates were not related to sex, education, age at onset of symptoms, or year of onset of symptoms. Both active smoking in adulthood and passive childhood exposure to environmental tobacco smoke appear to decrease the risk of ulcerative colitis. The results indicate that childhood passive smoke exposures can influence adult susceptibility to ulcerative colitis.

Adult↗
PubMed1992

Rectal mucosal ornithine decarboxylase activity is not a useful marker of risk for colorectal neoplasia.

Rectal mucosal ornithine decarboxylase activity has been reported to distinguish patients with adenomas from normal controls. In order to further explore this association, we assayed biopsy samples from 119 unselected individuals undergoing routine colonoscopic examinations. The overall mean ODC activity was 127.4 (+/- 93.1 SD) pmol/mg protein/hr. There were no differences by age, sex, or race. Tissue handling and storage influenced ODC activity. Specimens collected and transported on Dry Ice had higher ODC activity than specimens initially frozen in a -20 degrees C freezer. After adjusting for storage and collection method, the activity was similar in subjects with adenomas (126.3 pmol/mg/hr) compared to those without adenomas (128.8 pmol/mg/hr). We conclude that variations in assay technique make comparisons between laboratories difficult. Patients with large-bowel adenomas do not necessarily have higher ODC activity in uninvolved rectal mucosa. Further study of the environmental and genetic factors that influence rectal mucosal proliferation may improve our understanding of carcinogenesis in the large bowel.

Adenoma↗