Opportunistic screening for bone disease using abdominal CT scans obtained for other reasons in newly diagnosed IBD patients.

Bone disease is prevalent among patients with inflammatory bowel disease (IBD), though bone density screening remains underutilized. We used CT scans performed for other indications in IBD patients to identify and monitor osteopenia using CT attenuation values at the lumbar spine. Significant rates of bone disease were detected which would have otherwise gone undiagnosed. INTRODUCTION: Osteoporosis affects about 14-42% of patients with IBD. Though screening is recommended in IBD patients with risk factors, it remains underutilized. In patients with newly diagnosed IBD, we used CT scans performed for other indications to identify and monitor progression of osteopenia. METHODS: Using the Ocean State Crohn's and Colitis Area Registry, we identified adult patients with one or more abdominal CT scans. Each patient had two age- and gender-matched controls. Radiologists measured attenuation through trabecular bone in the L1 vertebral body recorded in Hounsfield units (HU). Generalized estimating equations were used to measure how HU varied as a function of gender, type of IBD, and age. RESULTS: One hundred five IBD patients were included, and 72.4% were classified as "normal" bone mineral density (BMD) and 27.6% as potentially osteopenic: 8.6% with ulcerative colitis and 19.0% with Crohn's disease. We found a decrease in bone density over time (p < 0.001) and that BMD decreases more in Crohn's disease than in ulcerative colitis (p < 0.004). Sixty patients had two CT scans, and mean loss of 9.3 HU was noted. There was a non-significant decrease in BMD over time in patients exposed to > 31 days of steroids and BMD was stable with < 30 days of steroid exposure (p < 0.09). CONCLUSION: Using CT scans obtained for other indications, we found low rates of osteopenia and osteoporosis that may otherwise have gone undiagnosed. Refinement of opportunistic screening may have advantages in terms of cost-savings and earlier detection of bone loss.

Faecal calprotectin, lactoferrin, M2-pyruvate kinase and S100A12 in severe ulcerative colitis: a prospective multicentre comparison of predicting outcomes and monitoring response.

OBJECTIVE: To compare four faecal markers for their ability to predict steroid refractoriness in severe paediatric ulcerative colitis (UC). Construct validity and responsiveness to change were also assessed. METHODS: This was a prospective multicentre cohort study. Stool samples from 101 children (13.3 + or - 3.6 years; Pediatric UC Activity Index (PUCAI) at admission 72 + or - 12 points) were obtained at the third day of intravenous steroid therapy. Repeated samples at discharge were obtained from 24 children. Predictive validity was assessed using diagnostic utility statistics to predict steroid failure (ie, the need for salvage treatment). Concurrent validity was assessed using correlational analysis with the following constructs: PUCAI, Lindgren and Seo scores, physician's global assessment, albumin, erythrocyte sedimentation rate and C-reactive protein (CRP). Responsiveness was assessed using test utility and correlational strategies. RESULTS: Median values (IQR) were very high at baseline for all four markers (calprotectin 4215 microg/g (2297-8808); lactoferrin 212 microg/g (114-328); M2-pyruvate kinase (M2-PK) 363 U/g (119-3104); and S100A12 469 microg/g (193-1112)). M2-PK was numerically superior to the other three markers and CRP in predicting response to corticosteroid treatment (area under the receiver operating characteristic (ROC) curve 0.75 (95% CI 0.64 to 0.85; p<0.001) vs <0.65 for the others). However, it did not add to the predictive ability of the PUCAI (area under the ROC 0.81 (95% CI 0.73 to 0.89)). M2-PK also had the highest construct validity but with a modest mean correlation with all constructs (r=0.3; p<0.05). None of the markers was responsive to change (Spearman's rho correlation with change in the PUCAI <0.1; p>0.05, area under the ROC curve <0.65; p>0.05). CONCLUSIONS: The four markers were greatly elevated in severe paediatric UC. Only M2-PK had good construct and predictive validity, and none was responsive to change. The PUCAI, a simple clinical index, performed better than the faecal markers in predicting outcome following a course of intravenous corticosteroids in severe UC.

A regulatory element is characterized by purine-mediated and cell-type-specific gene transcription.

Purines and purine nucleotides were found to affect transcription of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene in whole nuclei isolated from intestinal mucosa of adult rats fed a purine- and purine nucleotide-free diet. Nuclear run-on transcription assays, performed on whole nuclei from different tissues and cell types, identified an intestine-specific decrease in the overall incorporation of [alpha-32P]UTP in HPRT transcripts from intestinal epithelial cell nuclei when exogenous purines or purine nucleotides were omitted from either the diet or culture medium. Using a 990-base-pair genomic fragment that contains the 5'-flanking region from the HPRT gene, we generated plasmid constructs with deletions, transfected the DNA into various cell types, and assayed for chloramphenicol acetyltransferase (CAT) reporter activity in vitro. We determined that an element upstream from the putative transcriptional start site is necessary to maintain the regulatory response to purine and nucleotide levels in cultured intestinal epithelial cells. These results were tissue and cell type specific and suggest that in the absence of exogenous purines, the presence of specific factors influences transcriptional initiation of HPRT. This information provides evidence for a mechanism by which the intestinal epithelium, which has been reported to lack constitutive levels of de novo purine nucleotide biosynthetic activity, could maintain and regulate the salvage of purines and nucleotides necessary for its high rate of cell and protein turnover during fluctuating nutritional and physiological conditions. Furthermore, this information may provide more insight into regulation of the broad class of genes recognized by their lack of TATA and CCAAT box consensus sequences within the region proximal to the promoter.

RNA synthesis by villus and crypt cell nuclei of rat intestinal mucosa.

Rat intestinal mucosa was separated by eversion and vibration to provide a sequence of fractions from predominantly villus cells to predominantly crypt cells. The proportions of these cell types in each fraction were computed from the concentrations of alkaline phosphatase (villus cells) and thymidine kinase (crypt cells) in each population. The isolated mucosal fractions varied from about 90% villus cells to 90% crypt cells. Following injection of the rats with [3H]thymidine, the nuclei were isolated from each mucosal cell fraction and the amount of radioactivity incorporated into DNA was measured as an index of crypt cell abundance. The isolated nuclei were also incubated with ribonucleoside triphosphates and the amount of RNA synthesized was measured. Nuclei labeled with [3H]thymidine were found only in fractions rich in crypt cells, whereas capacity for RNA synthesis remained very active in mucosal fractions consisting predominantly of villus cells. It is concluded that non-dividing villus cells continue to make RNA.

Resting energy expenditure in Gaucher's disease type 1: effect of Gaucher's cell burden on energy requirements.

The resting energy expenditure (REE; kcal/d) of 25 patients with Gaucher's disease type 1 was determined by indirect calorimetry. The average observed REE for the group was approximately 44% greater (P less than .01) than that predicted (predicted REE) for these patient's age, sex, height, and weight. The increased caloric requirements of these patients was manifested by a height-for-age less than or equal to the fifth percentile in seven of nine growing children and a muscle mass of less than the fifth percentile in 15 of 19 patients studied. The excess REE (observed REE--predicted REE) for individual Gaucher's disease type 1 patients was directly related to their liver volume as estimated from radionuclide scans and to the mass of the spleen as measured at splenectomy. The relationship between spleen mass and excess REE was demonstrated by an average 22.0% decrease in REE following splenectomy in five patients. Based on these data, the metabolic rate of the splenic tissue removed from the patients was calculated to be 96.8 kcal/d/kg, about twofold to threefold less than that of normal splenic tissue. These findings indicate that the elevated REE observed in these patients resulted from the large mass of Gaucher's cells, which although individually hypometabolic, were cumulatively an excessive metabolic burden. Furthermore, they suggest that indirect calorimetry may be a quantitative tool for measuring disease progression and the effect of therapeutic intervention in Gaucher's disease type 1.

Dietary purine nucleotides and the gastrointestinal tract.

There is a growing body of research that demonstrates a role for dietary nucleotides, the building blocks of RNA and DNA, during intestinal development, turnover, and repair. There is evidence that the effects of purine nucleotides may be mediated through intestinal gene transcription and, more specifically, through the action of transcription factors that, at least sometimes, are directly related to nutrition. Some of the suggested specific roles for dietary nucleotides include the enhancement of the normal host defense system, effects on neonatal lipid metabolism, and influence on iron bioavailability. This review focuses on the potential role of dietary (purine) nucleotides in the maintenance of intestinal integrity and reviews potential mechanisms for these effects.

Energy requirements in Alzheimer's disease patients.

Weight loss in Alzheimer's patients has been observed by many clinicians and reported in the international geriatric literature. It represents a puzzling challenge for clinicians and researchers, and it is an important issue for caregivers and nursing home staff concerned with state and federal requirements for nutrition and weight monitoring. Using indirect calorimetry, we studied the resting energy expenditure of 21 elderly patients; 12 were residing in a community setting, and 9 were institutionalized. Of the 12 community-living patients studied, 5 had early to moderate Alzheimer's disease, and 7 were nondemented control subjects. Of the 9 institutionalized patients, all were severely demented, bedridden, and fed exclusively by gastric tube in a closely monitored clinical environment with daily bedside weighing. Four had Alzheimer's disease, and 5 had multi-infarct dementia (MID). Among the outpatients, the Alzheimer's group showed increased energy requirements (p = 0.028) and a significantly different pattern of fat-free mass compared with control subjects (p = 0.031). These observations on community-residing elderly were consistent with, and extended by our findings on energy requirements of, the demented institutionalized patients. The calorie intake necessary for weight maintenance of the bedridden institutionalized patients was determined during their prolonged institutionalization. The presumed maintenance level of calorie intake was then verified during a 10 wk study. During the 10 wk, we documented no significant change in weight with constant energy intake. Compared with MID patients, Alzheimer's patients tended to weigh less (52.84 vs 56.4 kg; p = 0.20) but actually required more calories (1626 vs 1341 kcal, p < 0.011).(ABSTRACT TRUNCATED AT 250 WORDS)

Nutritional assessment of pediatric patients admitted to an acute-care pediatric service utilizing anthropometric measurements.

Two hundred consecutive pediatric patients were given a nutritional assessment at the time of their admission to the hospital. A weight-for-height below the 5th percentile was an indication of acute depletion and a height-for-age below the 5th percentile a sign of chronic depletion. Measurement of weight-for-height and/or height-for-age was below the 5th percentile in 32% of those assessed. Seventy-five percent of the acutely depleted children and 60% of the acute and chronically depleted children had midarm circumferences below the 5th percentile. Midarm muscle circumference below the 5th percentile was significantly more prevalent in all the depleted children. This paper reports the results of our study of the objective (quantitative) elements of our nutritional assessment. These measurements indicate that a significant number of patients are at nutritional risk at the time they are admitted to the hospital. An adequate nutritional assessment cannot be limited to objective considerations, however. A complete medical evaluation of the patient is required, including objective and subjective considerations.

Studies in the use of the intraperitoneal route for parenteral nutrition in the rat.

The effects of intraperitoneal administration of normal saline, dextrose, and amino acids were studied in a rat model for intraperitoneal alimentation. No adverse effects from the use of placement of an intraperitoneal catheter were found. Animals who received amino acids demonstrated a specific metabolic advantage over animals who received isocaloric amounts of carbohydrate. They lost less weight and maintained a higher serum albumin. The intraperitoneal route may provide a relatively simple and efficient method of studying parenteral nutrition in laboratory animals. Conceivably, it may also be of value for humans who are on chronic ambulatory peritoneal dialysis, or even as an alternative for central venous alimentation.

Pediatric gastroenterology at the Mount Sinai hospital.

The history of pediatric gastroenterology at Mount Sinai begins in 1960. Early publications by Drs. Korelitz and Gribetz on the management of inflammatory bowel disease in children served as the preface to forty years of progress in this important area. The history of pediatric gastroenterology includes important work by many individuals, including Horace Hodes, Lotte Strauss and Frederick Kopel. Early observations on the nature of inflammatory bowel disease (IBD), and its course, preceded work on nutritional therapies for IBD, mechanisms of gene-nutrient interactions, regulation of gene transcription, and molecular processes involved in bile transport in the liver and small intestine. Over the last twenty years, the division has grown in size and reputation. Today there are fourteen full-time faculty - 9 M.D.'s and 5 Ph.D.'s - who work in three funded research laboratories. There are also five advanced practice nurses (including three nurse practitioners), two social workers and two nutritionists, as well as several administrators and assistants. In addition to being recognized as a premier center for the treatment of children with general pediatric gastroenterological problems, especially inflammatory bowel disease, the division is also known as one of the nation's largest pediatric liver and liver transplant centers, and it is rapidly becoming one of the largest pediatric short gut syndrome and small bowel transplant centers.

Growth failure as the first expression of malnutrition in children with human immunodeficiency virus infection.

BACKGROUND: To define the onset, pattern, and earliest manifestations of malnutrition related to HIV infection. METHODS: A retrospective cross-sectional analysis of changes in weight and growth in a group of 54 children with perinatally acquired HIV infection was conducted. Eight children had asymptomatic HIV infection, 26 had symptomatic infection, and 20 had symptomatic infection and were referred for nutritional support. RESULTS: We found an early decline in the rate of linear growth with a relative preservation of the weight-for-age. Weight-for-height measurements were preserved until there was advanced HIV-related disease. CONCLUSIONS: This pattern can result in a false impression of adequate nutrition and emphasizes the importance of longitudinal growth data of the child with HIV infection. Evidence of linear growth failure before clinical wasting is apparent is an absolute indication for aggressive nutritional support.

The role of glutamine, short-chain fatty acids, and nucleotides in intestinal adaptation to gastrointestinal disease.

Important first steps have been taken towards establishing how some nutrients interact with genes and affect intestinal adaptation. These mechanisms may be typical of how other nutrients influence cell function and turnover and help to maintain intestinal integrity. The dietary effects of nucleotides on intestinal cell mucosa act at the gene transcription level. The dietary effects of nucleotides on immune suppression also may act through similar mechanisms. The effects of the other trophic agents may interact at this level or at other levels. Scientific interest in how the various tropic factors work to maintain and repair the gastrointestinal tract is manifested by a growing body of research that demonstrates potential mechanisms for nutrient-gene interaction and how much interactions affect intestinal development and turnover. It seems clear that intestinal gene transcription and the activity of transcription factors are at least sometimes directly related to nutrition. The techniques of molecular biology now permit the exploration and explanation of how dietary factors, such as glutamine, SCFAs, and nucleotides, affect normal and pathologic intestinal mucosal development, function, adaptation, and repair.

Restorative proctocolectomy in children with ulcerative colitis utilizing rectal mucosectomy with or without diverting ileostomy.

BACKGROUND: Controversies continue concerning the best way to perform restorative proctectomy (RP) for ulcerative colitis (UC). Can rectal mucosectomy and hand-sewn ileoanal anastomosis (IAA) withstand the challenge posed by extrarectal dissection with a double-stapled technique and no mucosectomy? Is a diverting ileostomy mandatory after RP? METHODS: The authors describe 30 consecutive children with UC who underwent RP with rectal mucosectomy and hand-sewn IAA. The authors assess the results and compare the first 14 patients (group 1) treated with temporary diverting ileostomies with the next 16 consecutive patients (group 2) without diverting ileostomies. RESULTS: The average age (13.8 years in group 1 v 10.4 in group 2), duration of illness before resection (3.2 years in group 1 v 1.5 in group 2), and gender breakdown (10 of 14 were girls in group 1, 10 of 16 were girls in group 2) were similar between the two groups. Outcome was not significantly different between the two groups. Average bowel movements per 24-hour period was 5.5 in group 1 and 4.2 in Group 2. Occasional nighttime staining occurred in two patients in group 1 and five in group 2. No one suffered daytime staining in group 1, and one patient had occasional daytime staining in group 2. Average quality of life (on a scale of 0 to 5) as assessed by the patients or parents was 4.4 in group 1 and 4.9 in group 2. There were 10 total complications in group 1. One child required a permanent stoma for ileoanal separation. Two patients required reoperations for complications caused by the diverting ileostomy. The single instance of peritonitis was in group 1 caused by anastomotic leak after ileostomy closure. There were five total complications in group 2, of which, two required temporary stomas for ileoanal separations. CONCLUSIONS: RP with rectal mucosectomy and hand-sewn IAA in children with UC provides good functional results. Peritonitis did not occur in the absence of diversion. Eliminating routine diverting ileostomy avoids the considerable complications and morbidity from the stoma and its closure.

Gene expression in the intestine: the effect of dietary nucleotides.

There is scientific concern regarding the role of dietary nucleotides in the maintenance and repair of the gastrointestinal tract. This concern is based on a growing body of research that demonstrates potential mechanisms for dietary nucleotides to affect intestinal development and turnover. It seems clear that intestinal gene transcription as well as the activity of transcription factors is at least sometimes directly related to nutrition. Implications of this work include the potential role of dietary nucleotides in infant nutrition and in intestinal repair. The techniques of molecular biology will now allow us to explore and explain how dietary factors such as nucleotides affect intestinal mucosal development, function, adaptation, and repair.

Fatigue is highly associated with poor health-related quality of life, disability and depression in newly-diagnosed patients with inflammatory bowel disease, independent of disease activity.

BACKGROUND: Fatigue is common in Crohn's disease (CD) and ulcerative colitis (UC). Data on fatigue in newly diagnosed patients are unavailable. AIM: To report prevalence of fatigue in newly diagnosed CD and UC patients and examine its association with health-related quality of life (HRQOL), depression and disability. METHODS: The Ocean State Crohn's and Colitis Area Registry (OSCCAR) is a statewide cohort of newly diagnosed inflammatory bowel disease patients in Rhode Island. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue Scale. Patients were administered instruments measuring HRQOL, overall disability and work impairment, and depression. RESULTS: Fatigue was prevalent in 26.4% of 220 subjects. Cohen's d effect sizes for fatigue were large: Short-Form 36 Health Survey mental health component (CD 1.5, UC 1.4) and physical health component (CD 1.4, UC 1.4), EuroQol-5D valuation of current health state (CD 1.2, UC 1.0), Inflammatory Bowel Disease Questionnaire (CD 1.9, UC 1.6) and Patient Health Questionnaire depression scale (CD 1.8, UC 1.7). Fatigued patients reported more work impairment (Score difference: CD 29.5%, UC 23.8%) and activity impairment (score difference: CD 32.3%, UC 25.7%) on the Work Productivity and Activity Impairment Questionnaire. Fatigue's association with all scores remained highly significant despite controlling for disease activity. CONCLUSIONS: Fatigue is strongly associated with poor HRQOL, disability and depression similarly in CD and UC even when controlling for disease activity. Fatigue's association with a wide range of patient-reported outcome measures suggests that monitoring fatigue is a simple way to screen for overall disruption in patient life.