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.

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.

Recombinant human growth hormone enhances the metabolic efficacy of parenteral nutrition: a double-blind, randomized controlled study.

This multicenter, randomized, double-blind study was performed to investigate whether recombinant GH improves the efficacy of total parenteral nutrition (TPN). Fifteen stable patients requiring parenteral feeding due to gastrointestinal/pancreatic disease were studied. Constant maintenance TPN providing approximately 30 kcal/kg day and approximately 1.6 g protein/kg.day was administered during an initial 7-day baseline period. After randomization, daily sc injections of saline (control, n = 9) or GH (10 mg/day, n = 6) were administered a 14-day treatment period as nutrient intake remained constant. Elemental balances for nitrogen (N), potassium (K), phosphorus (P), and sodium (Na) were determined daily and serial blood indices, vital signs, and other clinical parameters were monitored. Nutrient balances approached equilibrium during the baseline week in both groups. With GH administration, a significant increase in N, K, and P balance occurred; in contrast, nutrient balances did not change significantly from baseline values in control patients. The cumulative change (delta) in nutrient balances from the baseline week was also significantly greater in the GH-treated patients (delta N: control+2 +/- 7 g vs. GH+36 +/- 6. g, P less than 0.005; delta K:+57 +/- 45 mmol vs.+199 +/- 19 mmol, P less than 0.03; delta P: -27 +/- 30 mmol vs. +91 +/- 69 mmol, P less than 0.02). Plasma insulin-like growth factor-I concentrations rose 5-fold and serum cholesterol rose slightly with GH; no other significant change in group mean blood values occurred. One patient receiving GH and chronic prednisone therapy developed moderate hyperglycemia and mild peripheral edema; no other deleterious effects attributable to GH were observed. GH was well tolerated and significantly enhanced nutrient retention compared to standard parenteral feeding alone. GH improves the efficacy of parenteral nutrient utilization in patients requiring TPN.

Small bowel disaccharidase activity in the rat as affected by intestinal resection and pectin feeding.

This study investigated the effects of small bowel resection (SBR) and a pectin-supplemented elemental diet (ED) on intestinal disaccharidase activity. Rats underwent placement of feeding gastrostomy and swivel apparatus. Control animals were returned to their cages while resected animals underwent an 80% SBR. Postoperatively, animals received either a pectin-free ED or the ED supplemented with 2% pectin. After 2 wk jejunal and ileal mucosal sucrase, maltase, and lactase activities and protein content were determined. Feeding the ED after SBR resulted in significant increases in all three ileal segmental disaccharidase activities but only maltase activity was significantly increased in the jejunum. The pectin-supplemented ED, however, significantly enhanced the adaptation of jejunal and ileal segmental sucrase, maltase, and lactase activity to SBR with the increase in all three jejunal disaccharidase activities being significantly greater than that of the resected animals fed the ED alone.

Parenteral nutrition supplemented with short-chain fatty acids: effect on the small-bowel mucosa in normal rats.

When enteral nutrition is excluded from animals maintained solely with total parenteral nutrition (TPN), atrophy of the intestinal mucosa is observed. Short-chain fatty acids (SCFAs) are produced in the colon by the fermentation of dietary carbohydrates and fiber polysaccharides and have been shown to stimulate mucosal-cell mitotic activity in the intestine. This study compared the effects of an intravenous and an intracecal infusion of SCFAs on the small-bowel mucosa. Rats received standard TPN, TPN with SCFAs (sodium acetate, propionate, and butyrate), TPN with an intracecal infusion of SCFAs, or rat food. After 7 d jejunal and ileal mucosal weights, DNA, RNA, and protein were determined. Standard TPN produced significant atrophy of the jejunal and ileal mucosa. Both the intracecal and intravenous infusion of SCFAs significantly reduced the mucosal atrophy associated with TPN. The intravenous and intracolonic infusion of SCFAs were equally effective in inhibiting small-bowel mucosal atrophy.

Comparison of parenteral nutrition and enteral feeding with pectin in experimental colitis in the rat.

The effect of a pectin-supplemented enteral diet on experimental colitis was compared with parenteral nutrition and with a pectin-free enteral diet. Forty-five rats had feeding catheters placed into either the stomach (IG, n = 31) or the superior vena cava (IV, n = 14) and then received acetic acid (colitis) or saline (control) enemas. After the enema, all rats received the same diet, either IG or IV, for 6 d except for 15 rats (IGP, 9 colitis and 6 controls), which had 1% pectin added to the diet. At the end of the feeding period the IGP group had significantly less colonic inflammation and/or necrosis than either IV (p less than 0.03) or IG (p less than 0.04) groups. Nitrogen balance, serum albumin, total iron-binding capacity and body weight did not differ significantly among dietary regimens. Thus, the degree of bowel injury in experimental colitis was decreased when animals were fed a pectin-supplemented enteral diet and this effect was independent of nutritional status.

Experimental short-bowel syndrome: effect of an elemental diet supplemented with short-chain triglycerides.

To determine whether short-chain triglycerides (SCTs, 1:1 triacetin:tributyrin, wt:wt) enhance intestinal adaptation in short-bowel syndrome (SBS), male Sprague-Dawley rats underwent 60% distal small-bowel resection with cecectomy and received either a chemically defined diet (CD) or a CD containing 40% of nonprotein energy as either medium-chain triglycerides (MCTs) or SCTs. After 12 d the SCT group had significantly increased jejunal mucosal weight compared with the MCT and CD groups and had significantly increased segment weight and mucosal protein compared with the CD group. In the colon the SCT group had significantly increased segment and mucosal weights and mucosal protein and DNA compared with both the MCT and CD groups. Body-weight change and measurements of serum ketones, albumin, glucose, and triglycerides revealed no significant differences among groups. SCTs improved jejunal and colonic adaptive growth and maintained comparable nutritional status in SBS when compared with CD alone or CD with MCTs.

Improvement of structure and function in orthotopic small bowel transplantation in the rat by glutamine.

Significant atrophy and impaired absorption occur in the heterotopically transplanted small intestinal isograft, and these deficits are corrected when the preferred fuel of the enterocyte, glutamine (Gln), is supplemented to total parenteral nutrition (TPN). In the orthotopic small bowel isograft, this study determined whether Gln-enriched TPN enhanced mucosal structure and function, and decreased bacterial translocation to mesenteric lymph nodes (MLN). Seventeen adult Lewis rats received orthotopic jejunal isografts and central venous catheters for TPN. Rats received either TPN with 2% Gln or the same TPN with isonitrogenous balanced nonessential amino acids for 10 days. Eight normal, chow-fed rats served as baseline controls. Mucosal villous height, surface area, crypt depth, weight, protein and DNA contents, brush border enzymes, 14C glucose absorption, and bacterial translocation to MLN were evaluated in both the graft and host jejunum and the control animals. Gln-enriched TPN significantly increased mucosal villous height (P < 0.01), surface area (P < 0.01), and glucose absorption (P < 0.01), and it reduced bacterial translocation (P < 0.05) when compared with the non-Gln TPN group. For most study variables, there were no significant differences between Gln-enriched TPN or baseline and between the graft and host jejunum for Gln- and non-Gln-supplemented animals. There were no significant differences in DNA content and brush border enzymes among groups. These results indicate that Gln-enriched TPN improves mucosal structure and glucose absorption and reduces bacterial translocation to MLN in the orthotopic small bowel isograft.

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.

Insulin-like growth factor-I improves mucosal structure and function in transplanted rat small intestine.

The transplanted small intestine develops significant mucosal atrophy, impaired nutrient and water absorption, and increased bacterial translocation to mesenteric lymph nodes in rats maintained on elemental diets or total parenteral nutrition. This study determined the effects of administration of an peptide growth factor (insulin-like growth factor-I[IGF-I]) on the mucosal structure and barrier function of rat small bowel isografts. Thirty-six adult Lewis rats underwent either resection of the distal 60% of the small bowel and proximal colon followed by a 40-cm orthotopic jejunal isograft or proximal small bowel transection and distal small bowel resection to leave an analogous length of small intestine in control animals. All rats received an isocaloric, isonitrogenous, polymeric diet (200 kcal/kg/day, 2 gN/kg/day) by gastrostomy and were infused with either IGF-I (2.4 mg/kg/day) or vehicle by osmotic pumps subcutaneously. After 10 days of treatment, jejunal crypt cell production, mucosal morphometric indices, glucose and water absorption, body weight, and bacterial translocation to mesenteric lymph nodes (MLN) were measured. Jejunal mRNA content for IGF-I, IGF-I receptor, and IGF-binding proteins 3 and 4 (IGFBP-3,4) were determined by Northern blotting. Crypt cell production, villus height, crypt depth, and villus surface area were significantly increased in control and transplanted jejunum of rats infused with IGF-I when compared to animals given vehicle alone. Additionally, jejunal glucose absorption and water absorption were significantly improved in both IGF-I groups when compared with their respective vehicle controls. IGF-I infusion increased body weight in transplanted and control animals and markedly reduced bacterial translocation to MLN after small bowel transplantation. Jejunal levels of IGF-I mRNA were significantly increased in transplanted animals when compared to transected controls. IGF-I treatment significantly increased IGFBP-3 tissue mRNA levels in both transected and transplanted animals. These results demonstrate that IGF-I administration, after small bowel transplantation, improves mucosal structure and absorptive function and reduces bacterial translocation to MLN. IGF-I may have important effects in transplanted small bowel both as an endogenous and administered growth factor.

Increased expression of interleukin-8 mRNA in ulcerative colitis and Crohn's disease mucosa and epithelial cells.

: Interleukin-8 (IL-8) is a chemotactic cytokine (chemokine), which both attracts and activates granulocytes. IL-8 could have a central function in the initiation and perpetuation of the inflammatory bowel diseases (IBD), due to its relative resistance to inactivation and long half-life in vivo. Using a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay, we have observed elevated levels of IL-8 mRNA in colonic mucosal sections obtained from surgically resected specimens from ulcerative colitis (UC) and Crohn's disease (CD) patients with actively inflamed mucosa. The level of IL-8 mRNA expression in the intestinal mucosal biopsies from UC and CD patients was much greater in involved as opposed to noninvolved mucosal sections. The highest expression of IL-8 mRNA detected by RT-PCR was in UC mucosa and in isolated intestinal epithelial cells from UC patients. Increased IL-8 production by cells in IBD intestinal mucosa as well as IBD epithelial cells may be involved in the continuous attraction and activation of granulocytes in the inflamed intestine in both UC and CD patients. Chemokines, such as IL-8, are potent chemoattractant molecules and may have a central role in the augmentation and perpetuation of inflammation in IBD.

Summary of round table conference: gut dysfunction in critical illness.

There is recent evidence that intestinal function is an important determinant in the outcome of critically ill patients. The barrier function is an important characteristic of the gut. Its workings are complex and it consists of epithelial, molecular, and immune components. The pathogenesis of gut dysfunction among critically ill patients is multifactorial, consisting of the quality and quantity of microorganisms, the permeability of the epithelium, and the extent of the vascular perfusion. A practical bedside measure of gut dysfunction is intolerance to enteral feedings. Potential therapies for gut dysfunction include the use of vasoactive drugs to enhance perfusion, selective decontamination to decrease bacteria and endotoxin, and the early and frequent administration of enteral nutrients.

Butyrate inhibits seeding and growth of colorectal metastases to the liver in mice.

BACKGROUND: The short-chain fatty acid butyrate inhibits growth of colorectal carcinoma cells in vitro. Mevalonate, a short-chain fatty acid structurally and metabolically related to butyrate, is important in signal transduction and is essential for cell growth. We investigated butyrate's effects on seeding and growth of colorectal tumor cells metastatic to the liver in vivo and hypothesized that butyrate's antiproliferative effects are associated with inhibition of mevalonate-mediated cell growth. METHODS: Hepatic metastases were induced by injecting 1 x 10(5) MC-26 (N-methyl-N-nitrosourea-induced murine colorectal carcinoma) cells into the spleen of BALB/c mice. Mice were treated with a continuous intravenous infusion of butyrate (2 gm/kg/day) for 7 days starting 24 hours before tumor cells were injected. Study variables included liver weight and number of hepatic surface metastases. Proliferation studies on MC-26 cells were performed in vitro to examine the effects of butyrate alone or combined with mevalonate or mevastatin (an inhibitor of mevalonate synthesis). RESULTS: Butyrate reduced seeding and growth of colorectal tumor cells in vivo. Mevalonate diminished butyrate's antiproliferative action in vitro, whereas mevastatin potentiated this effect. CONCLUSIONS: These studies (1) show that butyrate inhibits seeding and growth of hepatic colorectal metastases in vivo, (2) associate butyrate's antiproliferative effects with inhibition of mevalonate-mediated cell growth, and (3) indicate that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may have synergistic antiproliferative effects when combined with butyrate.

The effect of enteral feedings supplemented with pectin on the healing of colonic anastomoses in the rat.

The effect of the addition of pectin to an elemental diet on the healing of experimental colonic anastomoses was investigated. Transection and anastomosis of the ascending colon and feeding gastrostomy were performed in 24 Sprague-Dawley rats. All rats then received an elemental diet, and 12 of them had 1% (w/v) citrus pectin added to their diet. On the seventh postoperative day, animals that received pectin-supplemented diets had significantly greater bursting pressures at the anastomoses (266 versus 234 mm Hg, p less than 0.04) and significantly lower colonic mucosal pH (6.2 versus 6.8, p less than 0.001) than animals that received the elemental diet only. The colons from animals fed pectin also had significantly higher hydroxyproline content at the anastomosis than those of the control animals (46.6 versus 40.7 micrograms hydroxyproline nitrogen/mg tissue nitrogen, p less than 0.05). The decreased intracolonic pH is consistent with the hypothesis that improved healing is a local effect mediated by the presence of short-chain fatty acids resulting from the fermentation of pectin.

Effects of intraluminal infusion of short-chain fatty acids on the healing of colonic anastomosis in the rat.

The effects of an intracolonic infusion of short-chain fatty acids (SCFA) on the healing of colonic anastomosis in the rat were investigated. Thirty-three Sprague-Dawley rats underwent transection and anastomosis of the descending colon and transection and diversion of the ascending colon. The proximal limb of the ascending colon was exteriorized as an end colostomy, and the distal (defunctionalized) limb was cannulated for continuous infusion. Rats received either no infusion (N = 11) or an infusion of either electrolytes (N = 11) or SCFA (acetate, propionate, and butyrate; N = 11) into the defunctionalized colonic segment. On the sixth postoperative day bursting pressure (BP) and bowel wall tension (BWT) were determined. The occurrence of spontaneous anastomotic dehiscence was significantly less for the SCFA group (0/11) compared with the no infusion group (5/11, p less than 0.01). The anastomotic suture line burst in significantly fewer colons from the SCFA group (1/11) than either the electrolyte infusion (8/11, p less than 0.003) or the no infusion (6/6, p less than 0.001) groups. BP and BWT were significantly higher for the SCFA group (BP: 147 +/- 10 mm Hg; BWT: 59 +/- 1.0 dyne 10(3)/cm) than for either the electrolyte (BP: 99 +/- 30 mm Hg, p less than 0.002; BWT: 45 +/- 19, p less than 0.03) or no infusion (BP: 111 +/- 42, p less than 0.02; BWT 36 +/- 15, p less than 0.007) groups. The results of this study indicate that intracolonic infusion of SCFA resulted in significantly stronger colonic anastomosis in the rat.

Experience with a new gastrostomy-jejunal feeding tube.

Many patients in need of long-term feeding by tube enterostomy have neurologic or mechanical deficits that increase their risk for aspiration. To reduce this risk, a combined gastrostomy-jejunal tube has been developed. This tube permits gastric decompression while the formula is being delivered into the jejunum. The use of this tube has been evaluated in 45 patients. There were three (7%) major complications and two (4%) postoperative deaths. The deaths did not appear to be directly related to the insertion of the tube. There was no clinical evidence of aspiration. This tube can be used to deliver postoperative and long-term enteral nutrition with minimal rates of morbidity and mortality.

Intestinal malrotation during pregnancy.

BACKGROUND: Malrotation of the intestine is an uncommon anomaly most often seen in infants, but occasionally in adults. Rarely, symptoms from malrotation may occur during pregnancy. CASE: A 30-year-old woman, with a long history of abdominal pain and constipation, developed more frequent and severe symptoms in the second trimester of pregnancy. She was monitored closely and treated conservatively and went on to deliver a full-term, healthy infant. In the postpartum period, barium radiographs demonstrated a midgut malrotation. During exploratory laparotomy, obstructive peritoneal bands were noted and were transected. The mobile cecum and ascending colon were fixated to the abdominal wall. CONCLUSION: Symptoms from a malrotation may develop during pregnancy and may be nonspecific and vague. Although complications from malrotation can be life-threatening, a conservative approach with surgical intervention in the postpartum period may be appropriate in the proper clinical setting.

Left-sided colectomy with retroileal colorectal anastomosis.

Following resection of the sigmoid and descending colon for cancer or extensive diverticular disease, it may be impossible to make a colorectal anastomosis due to inadequate length of the residual transverse colon. To correct this problem, the remaining transverse colon may be pulled into the pelvis by making a "window" in the terminal part of the ileal mesentery. From January 1966 to January 1975, 302 resections of the descending colon with colorectal anastomoses were performed by one of the authors (R.B.T.) for upper sigmoid cancer and extensive diverticulitis at the Cleveland Clinic. Eleven patients (4%) had retroileal colorectal anastomoses. The retroileal apprach is a technical aid when performing an extensive left-sided colectomy and/or when there is insufficient length of residual transverse colon to make a tension-free colorectal anastomosis.

Malnutrition in veterans administration surgical patients. Updated standards.

A prospective nutritional assessment of 106 hospitalized Veterans Administration surgical patients was performed; 60 healthy, age-matched outpatient veterans were studied for controls. Standard biochemical and anthropometric indices were measured. Malnutrition was defined for each index as a value more than 2 SD below the mean established from the VA control population, the values from which were also compared with conventionally accepted published standards of malnutrition. Striking discrepancies in the incidence of abnormal nutritional indices in our patients were observed, depending on which standard was used. The frequencies of abnormal in our surgical patients using VA control values or published norms, respectively, were: albumin level, 43% vs 19%; hematocrit value, 38% vs 27%; total iron-binding capacity, 30% vs 37%; arm muscle circumference, 11% vs 0%; and triceps skin fold, 19% vs 35%. Future studies of nutritional assessment in hospitalized patients should use control subjects closely related to the target population in age and other demographic variables.

Energy expenditure in patients with inflammatory bowel disease.

The basal energy expenditure (BEE) calculated from the Harris-Benedict equation was compared with the resting energy expenditure (REE) measured by indirect calorimetry in 12 consecutive hospitalized patients with inflammatory bowel disease. The BEE proved to be equivalent to the REE in the prediction of daily caloric requirements. Patients weighing less than 90% of their ideal body weight had significantly increased energy requirements on a per-kilogram-weight basis as compared with those weighing more than 90% of their ideal body weight. Daily caloric requirements based on 1.75 X BEE would provide 45 kcal/kg/24 hr, which is consistent with reported values necessary for anabolism.