Iodine deficiency a persisting problem: assessment of iodine nutrition and evaluation of thyroid nodular pathology in Portugal.

BACKGROUND: The goal of eliminating iodine deficiency (ID) by the year 2000 has still not been achieved in several countries. More than 2 billion people worldwide (over 260 million school age children) remain ID. In Europe, there are still countries, such as Portugal, without national general population data on iodine nutrition (IN). This study aims at evaluating combined complementary data of the IN of the general population through urinary iodine concentration (UIC) and the thyroid histology profile from the inland region of Beira Interior (BI), in Portugal. METHODS: UIC from a population sample of 214 volunteers (131 females and 83 males), with ages ranging from 8 to 97 years (mean 51.5 years ± SD 20.74 years), from BI was determined; the thyroid histology pattern in BI (6-year period) was evaluated; and the iodine content of the largest surface water reservoir of BI, never previously reported, was measured. RESULTS: Median UIC of 62.6 µg/L was measured. Over 92 % of the population had UIC less than 100 µg/L. From 279 histology reports evaluated, the incidence of the different types of thyroid nodular pathology in BI was established. There were 60 histologic diagnoses of malignancy. The observed ratio of papillary to follicular carcinoma relatively close to 1 and the fairly high percentage of anaplastic carcinomas are characteristic of ID areas. CONCLUSIONS: The findings of this first general population study on IN from the inland region of BI, Portugal, document significant ID. This problem, with its serious public health implications, could be corrected by having affordable iodised salt widely and generally available and by promoting a proactive population attitude generated by ample public information and educational programs as to the negative consequences of ID.

Anorectal Crohn's disease.

Anorectal disease affects many patients with Crohn's disease. Clinical manifestations vary from asymptomatic skin tags to severe, debilitating perineal destruction and sepsis. Surgical management needs to be conservative and must focus on draining septic sites, preserving sphincter function, and palliating symptoms. Medical management has had some success in improving symptoms, but as yet, it has not been able to ameliorate most perianal complaints quickly and enduringly. Many new and exciting treatment modalities are being investigated with the hope that more effective approaches to these complex and difficult problems can be realized.

Nutrition.

The use of nutrition for the medical patient, in the inpatient setting and at home, will likely continue to increase in the future. Each patient should be evaluated in an individualized but systematic fashion. Each patient in whom malnourishment is suspected should undergo a thorough assessment for the presence and degree of malnutrition with an accurate calculation of nutritional requirements. It is important to choose the correct method of delivery of nutrition, to monitor and recognize any complications or problems that may arise, and to tailor the nutritional therapy to the unique diseases that are encountered in medicine. Although increasingly new advances and changes are occurring in the field of nutrition, nutritional support and therapy are best delivered and supplied to the patient with a network of health care workers, including the physician, the nurse, the dietitian, the social worker, and pharmacist.

Proposed association between ileoanal j-pouch perforation and rapid consumption of a high-calorie, high-fiber meal: report of two cases.

PURPOSE: We report two cases of ileoanal J-pouch rupture after rapid consumption of high-fiber, high-calorie meals. METHOD: We review the food intake, presentation, laboratory and radiographic data, and course of two patients who developed ileoanal J-pouch perforation after rapid consumption of meals rich in fiber or calories or both. The potential association between food consumption and rupture is explored. RESULTS: The authors propose that the rapid ingestion of a high-fiber, high-calorie meal may lead to an acute intraluminal pressure elevation or a closed-loop obstruction. These effects may be the basis for an association between food ingestion patterns and perforation at the distal transection site in an ileoanal J-pouch. CONCLUSION: The authors hypothesize that the rapid ingestion of a high-fiber, high-calorie meal may be associated with J-pouch perforation. Further investigative efforts are needed to confirm this association and to evaluate whether a causal relationship is present. If causality is established, physicians may develop a higher index of suspicion for pouch rupture in patients who present with abdominal disturbances after the rapid ingestion of a high-fiber, high-calorie meal.

Practical nutritional management in the trauma intensive care unit.

Critically injured patients offer an exceptional challenge to intensivists. Pre-existing disease states complicate horrendous disruptions in normal anatomy and physiology. The hypermetabolic, catabolic response brought on by trauma, shock, or sepsis serves to reprioritize the normal nutritional homeostasis of the body. Appropriate nutritional support not only minimizes the wasting effects of hypermetabolism but potentially offers additional benefits. Studies of feeding routes, substrates, and timing suggest that adequate support may decrease infectious complications and modulate the metabolic response. Injured patients are a heterogenous group, making the definition of adequate support and interpretation of experimental findings difficult. Ultimately, most severely injured patients need directed nutritional support because of their inability to ingest nourishment by conventional means. This article emphasizes a practical approach to these patients.

Nutrition in inflammatory bowel disease.

Clinical and basic research continues to expand our understanding of the complex pathogenesis of inflammatory bowel diseases. The potential roles played by fatty acid intake, serum leptin, and nitric oxide in the promotion of intestinal inflammation in Crohn's disease and ulcerative colitis will be reviewed. In addition, important advances in the areas of bone disease, vitamin deficiency, growth failure, and home parenteral nutrition will be discussed.

Wheat bran decreases aberrant crypt foci, preserves normal proliferation, and increases intraluminal butyrate levels in experimental colon cancer.

BACKGROUND: Dietary wheat bran protects against colon cancer, but the mechanism(s) of this effect is not known. Butyrate, produced by colonic bacterial fermentation of dietary polysaccharides, such as wheat bran, induces apoptosis and decreases proliferation in colon cancer cell lines. Whether similar effects occur in vivo is not well defined. We hypothesized that wheat bran's antineoplastic effects in vivo may be mediated in part by butyrate's modulation of apoptosis and proliferation. METHODS: Male F344 rats were fed wheat bran-supplemented or an isocaloric, isonitrogenous fiber-free diet. Rats were treated with one dose of the carcinogen azoxymethane or vehicle with sacrifice after 5 days (tumor initiation); or two doses (days O and 7) with sacrifice after 56 days (tumor promotion). Study variables included fecal butyrate levels and the intermediate biomarkers of colon carcinogenesis, aberrant crypt foci (ACF), and changes in crypt cell proliferation and apoptosis. RESULTS: During tumor initiation, wheat bran produced greater apoptosis (p = .01), a trend toward less proliferation, and preserved the normal zone of proliferation (p = .01). At tumor promotion, wheat bran decreased the number of ACF (proximal colon, p = .005; distal colon, p = .047) and maintained the normal proliferative zone. The fiber-free diet shifted the zone of proliferation into the premalignant pattern in both studies. Wheat bran produced significantly higher fecal butyrate (p = .01; .004, .00001) levels than the fiber-free diet throughout the tumor promotion study. CONCLUSIONS: Wheat bran increased apoptosis and controlled proliferation during tumor initiation and resulted in decreased ACF. Wheat bran's antineoplastic effects occurred early after carcinogen exposure, and were associated with increased fecal butyrate levels.

Cytokines and inflammatory bowel disease: a review.

The etiology and pathogenesis of inflammatory bowel disease (IBD) remains an area under intense investigation. Cytokine secretion, which is important in the regulation of normal gastrointestinal immune responses, appears to be dysregulated in IBD. In Crohn's disease, there appears to be an excessive T(H)1 T-cell response to an antigenic stimulus, leading to increased levels of proinflammatory cytokines, such as interferon-gamma (IFN-gamma), interleukin (IL)-12, IL-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha). In ulcerative colitis, a T(H)2 T-cell response appears to be the pathological process responsible for the inflammatory disease. New and innovative therapeutic strategies targeting cytokines, such as TNF-alpha, are producing some promising results in animal and human studies. As more is learned about the complex cytokine interactions in IBD, more effective treatments will undoubtedly ensue.

Nutrition and inflammatory bowel disease.

This article reviews the nutritional aspects of inflammatory bowel disease (IBD) including the mechanisms and manifestations of malnutrition and the efficacy of nutritional therapies. Nutrient deficiencies in patients with IBD occur via several mechanisms and may complicate the course of the disease. Nutritional status is assessed by clinical examination and the use of nutritional indices such as the Subjective Global Assessment of nutritional status. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted, especially in patients presumed to need parenteral nutrition.

Use of gastrostomy and combined gastrojejunostomy tubes for enteral feeding.

Recent economic changes in health care delivery have led to more frequent feeding by tube enterostomy. Over the last two decades percutaneous endoscopic gastrostomy (PEG) has been established as the standard method for long-term enteral access for nutrition, though operative gastrostomy remains indicated in a few conditions. Additionally, the combined gastrojejunostomy tube is indicated in selected patients in need of concomitant access to the jejunum and gastric decompression. This report reviews data regarding the safety and efficacy of the PEG tube and the indications for operative gastrostomy. Complications of feeding tubes and strategies to avoid or remedy them are also discussed. More recent techniques, including laparoscopic gastrostomy and jejunal access via the stomach, are reviewed as are some ethical concerns regarding the appropriateness of feeding enterostomies in certain patients.

Total proctocolectomy and ileoanal pouch: the role of contrast studies for evaluating postoperative leaks.

BACKGROUND: To assess the role of contrast enemas for the evaluation of leaks in symptomatic and asymptomatic patients after the first stage of restorative proctocolectomy. METHODS: We reviewed the findings of 59 contrast enemas in 40 patients who underwent total proctocolectomy with creation of an ileoanal pouch and a proximal diverting ileostomy. Thirty-seven patients initially underwent routine contrast studies of the ileoanal pouch, and three underwent contrast studies because of suspected fistulas or obstruction. Medical records were also reviewed to determine the clinical presentation and course of these patients. RESULTS: Of 37 patients who underwent routine postoperative contrast enemas, 33 (89%) had normal studies, three (8%) had clinically silent leaks (including two blind-ending tracks from the ileoanal anastomosis and one from the pouch), and one (3%) had pouchitis. In all three patients with unsuspected leaks, ileostomy closure was delayed. In two other patients with abdominal pain and fever, contrast enemas revealed leaks from the ileoanal pouch and distal ileum, respectively. The remaining patient had a contrast enema because of abdominal pain and distention; this patient had a distal ileal obstruction due to adhesions. CONCLUSIONS: Routine postoperative contrast studies revealed clinically silent leaks from the ileal J pouch or ileoanal anastomosis in three of 37 patients (8%) after the first stage of restorative proctocolectomy. Our findings suggest that routine contrast enema can detect clinically silent leaks after this surgery.

Nutrient pharmacotherapy for gut mucosal diseases.

The use of nutrients for pharmacotherapy is a recent advance in the treatment of gastrointestinal disorders or alterations of gut function and structure. Nutrients may have a direct effect on the gut, or may enhance the response to medications. Alternatively, pharmacologic agents may improve the absorption of nutrients. Potentially, pharmacotherapy may be an adjunct to the traditional approach used in the treatment of compromised patients.

Mechanisms of intestinal epithelial cell injury and colitis in interleukin 2 (IL2)-deficient mice.

Epithelial cell (EC) injury is a feature of all inflammatory bowel disorders (IBD). Although the mechanisms of EC injury are incompletely understood, it has been proposed that T-cell-mediated cytotoxicity and production of inflammatory cytokines are involved. This hypothesis was tested using the interleukin 2-deficient (IL2-/-) mouse model of IBD and cultures of primary colonic EC to determine if abnormal cytokine production or cytotoxicity by colonic T cells cause EC injury. Although capable of cell-mediated killing of allogeneic target cells, IL2-/- colonic T cells were unable to lyse syngeneic colonic EC. During disease progression, large numbers of IL4, TNF-alpha, and IFN-gamma-producing CD4+ and CD8+ cells accumulated within the intraepithelial spaces and lamina propria of the colon of IL2-/- mice. Although colonic EC expressed receptors for IFN-gamma and TNF-alpha, these cytokines did not adversely affect EC viability or growth in vitro consistent with these cytokines not being the primary mediators of EC injury in IBD. Our novel colonic EC culture system provides an in vitro accessible system in which to investigate further the nature of EC-lymphocyte interactions.

Intestinal adaptation after extensive small bowel resection: differential changes in growth and insulin-like growth factor system messenger ribonucleic acids in jejunum and ileum.

The distal small bowel exhibits greater adaptive growth than proximal segments after partial small intestine resection. To explore this process, we evaluated adaptive cellularity, intestinal insulin-like growth factor (IGF) system messenger RNA (mRNA) transcripts, and effects of recombinant IGF-I treatment in jejunum and ileum of adult rats. Gastrostomy-fed animals underwent 80% jejuno-ileal resection or intestinal transection and reanastomosis without resection, followed by infusion of human recombinant IGF-I (2.4 mg/kgXday) or vehicle. After 7 days, resected rats demonstrated modest adaptive growth in jejunum and marked cell proliferation in ileum. Resection increased IGF-I mRNA in both jejunum (183%) and ileum (249%) and up-regulated IGFBP-4 mRNA levels in both tissues. IGFBP-3 mRNA fell significantly in ileum after resection. IGF-I infusion modestly increased ileal cellularity after resection, but had no effect in jejunum. IGF-I markedly increased IGFBP-3 mRNA levels in jejunum after both transection and resection. These data confirm that bowel resection induces greater adaptive growth in ileum than jejunum. IGF-I administration modestly increases ileal, but not jejunal, growth after resection. Increased levels of intestinal IGF-I and IGFBP-4 mRNA suggest roles for IGF-I and IGFBP-4 in mediating small bowel adaptation. Higher levels of jejunal IGFBP-3 mRNA may be related to limited jejunal vs. ileal growth after extensive jejuno-ileal resection.

Advances in nutrition and gastroenterology: summary of the 1997 A.S.P.E.N. Research Workshop.

BACKGROUND: The 1997 A.S.P.E.N. Research Workshop was held at the annual meeting in San Francisco, on January 26, 1997. The workshop focused on advances in clinical and basic research involving the interface between nutrient and luminal gastroenterology. METHODS: Presentations on the genetic regulation of gastrointestinal development, the molecular biology of small intestinal adaptation, the effect of nutrition support on intestinal mucosal mass, the relationship between nutrition and gastrointestinal motility, nutrient absorption, and gastrointestinal tract substrate metabolism were made by the preeminent leaders in the field. RESULTS: The investigators presented an insightful analysis of each topic by reviewing data from their own laboratories and the published literature. CONCLUSIONS: This workshop underscored the important interactions between nutrition and luminal gastroenterology at the basic science, metabolic/physiologic, and clinical levels. The integration of presentations from the different disciplines provided a unique interaction of information and ideas to advance our understanding of nutrition and gastrointestinal tract.

Nutritional and metabolic advances in inflammatory bowel disease.

Crude measurements of nutritional status, such as body weight, are inadequate to assess the severity and consequence of malnutrition among inflammatory bowel disease patients. Functional deficiency resulting in osteopenia and muscle weakness have been demonstrated in these patients when compared to controls. Manipulating micronutrient and essential fatty acid intake may affect the degree of inflammation and functional status in these patients. Despite evidence that colonocyte oxidation of butyrate is impaired, pharmacologic doses of butyrate have been disappointing. Much of the general population fails to achieve the recommended daily allowance of lipid, micronutrients and fibre. Even in the absence of specific dietary manipulation, patient education regarding a prudent diet is sorely needed.

Butyrate inhibits deoxycholate-induced increase in colonic mucosal DNA and protein synthesis in vivo.

PURPOSE: Crypt surface hyperproliferation is an intermediate biomarker of colon cancer risk. In vitro studies indicate that the short-chain fatty acid and antineoplastic agent butyrate may reverse the crypt surface hyperproliferation induced by the secondary bile acid and tumor promoter, deoxycholate. We hypothesized that butyrate may reverse deoxycholate-induced crypt surface proliferation in vivo. METHODS: Thirty-one Sprague-Dawley rats (250-300 g) underwent surgical isolation of the colon and 24-hour luminal instillation of either sodium chloride, butyrate, deoxycholate, or butyrate plus deoxycholate (all solutions, 2 ml; pH 7; total sodium = 20 mM). Study variables included colon weight, mucosal DNA, mucosal protein, and proliferating cell nuclear antigen immunohistochemistry, labeling of which was determined in five crypt compartments from base to surface (12 crypts per rat). Labeling indexes were calculated as proliferating cell nuclear antigen immunohistochemistry-labeled cells divided by total counted cells in the whole colonic crypt and each of five crypt compartments. The phi(h) value (an index of premalignant risk) was calculated as the ratio of labeled cells in the two surface compartments divided by the total labeled cells. RESULTS: Deoxycholate significantly increased colon wet weight, mucosal protein, total crypt labeling indexes, crypt surface labeling indexes, and the phi(h) value and raised the mucosal DNA content. Butyrate alone slightly reduced total mucosal DNA and protein content. The combination of butyrate plus deoxycholate significantly decreased mucosal DNA and tended to reduce mucosal protein compared with deoxycholate alone. In contrast to prior in vitro findings, butyrate plus deoxycholate did not reverse the deoxycholate-induced surface hyperproliferative changes as measured by proliferating cell nuclear antigen labeling. CONCLUSIONS: Because co-treatment with butyrate plus deoxycholate inhibits deoxycholate-induced increases in total mucosal DNA and protein content, we conclude that butyrate may play a role in maintaining the proliferative balance of the colonic mucosa, in vivo. However, co-treatment with butyrate plus deoxycholate does not reverse the deoxycholate-induced increases in colon weight and proliferating cell nuclear antigen labeling indexes under the studied experimental conditions.

Increased expression of tissue cytokines in graft-versus-host disease after small bowel transplantation in the rat.

BACKGROUND: Graft-versus-host disease (GVHD) occurs in the recipient after small bowel transplantation (SBT). Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin 6 (IL-6), may be important mediators of GVHD. Increased expression of these cytokines might precede the clinical manifestations of GVHD induced by SBT. METHODS: Heterotopic SBT was performed using Lewis donors into Lewis x Brown Norway F1 (LBN-F1) recipients. The isograft control was performed from LBN-F1 into LBN-F1. Animals were killed on the 5th and 11th postoperative day (POD). mRNA was isolated from recipient native small bowel, colon, spleen, liver, and mesenteric lymph nodes and from nonsurgical controls as baseline. Semiquantitative reverse transcriptase polymerase chain reaction was performed to amplify mRNA transcripts for TNF-alpha, IFN-gamma, and IL-6 using alpha32P-dATP incorporation. Clinical signs, histologic assessment, and cytokine expression were correlated. RESULTS: On POD 5, there were neither clinical signs nor histologic features of GVHD, but mRNA expression of TNF-alpha and IL-6 in small bowel, IL-6 in spleen, and IFN-gamma in mesenteric lymph nodes were significantly increased in allograft animals when compared with normal and isograft tissues. On POD 11, both the clinical signs and histologic features of GVHD were seen, and TNF-alpha and IL-6 in native small bowel, TNF-alpha in colon, IFN-gamma in spleen, and IL-6 in mesenteric lymph nodes were significantly increased in allograft animals when compared with that in normal and isograft tissues. CONCLUSIONS: In conclusion, TNF-alpha, IFN-gamma, and IL-6 expression precede clinical onset and histologic evidence of GVHD in specific tissues. Therefore, increased expression of these cytokines is correlated with the development of GVHD in this model of SBT.

Deoxycholate inhibits in vivo butyrate-mediated BrDU labeling of the colonic crypt.

The short-chain fatty acid butyrate (NaBu) selectively increases colonic crypt base proliferation and inhibits "premalignant" crypt surface hyperproliferation while the secondary bile acid deoxycholate (DCA) induces surface hyperproliferation, in vitro. We hypothesized that NaBu and DCA have similar selective and antagonistic effects on the colonic crypt proliferative pattern, in vivo. Fifty-six adult SD rats underwent surgical isolation of the colon and 24-hr intraluminal instillation with physiological (10 mM) and pharmacological (25 mM) levels of butyrate alone or combined with a physiological DCA level (5 microM). Bromodeoxyuridine-labeling indices (LI) were determined as labeled cells divided by total cells, for the whole crypt and five crypt compartments from base to surface. Treatment with NaBu increased total LI when compared to NaCl. This effect was significant only at the crypt base. Both doses of NaBu resulted in similar LI with no further response at the higher concentration. In contrast to prior in vitro studies, DCA alone at this concentration did not affect LI, but when combined with NaBu, DCA inhibited the effects of NaBu at the crypt base and surface. The conclusions are: (1) the in vivo proliferative effects of NaBu are selective to the crypt base, (2) an in vivo low physiological DCA level does not promote crypt surface hyperproliferation but does inhibit butyrate's proliferative effect, and (3) NaBu and DCA interact in a complex and antagonistic manner to selectively modulate crypt base and surface proliferation, in the rat colon, in vivo. These findings may have clinical relevance since colonic levels of NaBu and DCA are affected by diet.