Mucosal healing and a fall in mucosal pro-inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn's disease.

BACKGROUND: Although enteral nutrition is a recognized form of treatment for intestinal Crohn's disease, there are persisting problems with feed palatability and only limited data as to its mode of action. AIM: To assess the effects of a specific oral polymeric diet (CT3211; Nestle, Vevey, Switzerland), which is rich in transforming growth factor beta2, on the mucosal inflammatory process. METHODS: Twenty-nine consecutive children with active intestinal Crohn's disease were treated with CT3211 as the sole source of nutrition for 8 weeks. Patients were assessed clinically, and endoscopically, whilst cytokine mRNA was measured in mucosal biopsies before and after treatment by quantitative reverse transcriptase polymerase chain reaction. RESULTS: After 8 weeks 79% of children were in complete clinical remission. Macroscopic and histological healing in the terminal ileum and colon was associated with a decline in ileal and colonic interleukin-1beta mRNA (pre-treatment to post-treatment ratio 0.008 and 0.06: P < 0.001, P = 0.006). In the ileum there was also a fall in interferon gamma mRNA (ratio 0.15, P < 0.001) with a rise in transforming growth factor beta1 mRNA (ratio 10, P = 0.04), whilst in the colon interleukin-8 mRNA fell with treatment (ratio 0.06, P < 0.05). CONCLUSIONS: The clinical response to oral polymeric diet CT3211 is associated with mucosal healing and a down regulation of mucosal pro-inflammatory cytokine mRNA in both the terminal ileum and colon. In the ileum there was also an increase in transforming growth factor beta1 mRNA.

Improvement in quality of life of children with acute Crohn's disease does not parallel mucosal healing after treatment with exclusive enteral nutrition.

BACKGROUND: Crohn's disease is a chronic debilitating disorder affecting a child's physical and emotional well-being. Recent emphasis on 'quality of life' (QOL) has led to re-evaluation of available medical treatments. AIM: To assess prospectively change in QOL, clinical disease activity and intestinal mucosal inflammation in active paediatric Crohn's disease after treatment with exclusive enteral nutrition. In addition, we evaluated whether change in QOL could predict changes in paediatric Crohn's disease activity index (PCDAI) and mucosal inflammation (endoscopic and histologic). METHODS: The IMPACT II questionnaire was used prospectively and longitudinally in 26 consecutively recruited children [16 males (67%), median 14 years, s.d. = 1.7 years] with active Crohn's disease (PCDAI > 20). They were treated with a new polymeric enteral feed (ACD004, Nestle) for a period of 8 weeks. All had PCDAI, QOL and endoscopic assessment at the time of diagnosis and after 8 weeks of treatment. RESULTS: Twenty-three of 26 children achieved a clinical remission at 8 weeks, with improvement in the QOL scores (P < 0.05). The change in QOL score after treatment was predictive of achieving a clinical remission, but not of histological improvement. CONCLUSIONS: Although children may find dietary restrictions difficult, this study confirms a clear improvement in QOL after treatment with exclusive enteral nutrition. However, improvement in QOL scores is not reflected by improvement in mucosal inflammation. Whilst improving QOL remains a core principal in patient management, the long-term consequences of ongoing mucosal inflammation must be better understood before relying only on short-term QOL measures to dictate treatment choices.

Separation of pure toxic peptides from a beta-gliadin subfraction using high-performance liquid chromatography.

The beta v subfraction was isolated from peptic-tryptic digests of beta-gliadin by chromatography on Biogel P-10 and applied to a Lichrosorb RP-18 or a mu-Bondapak C-18 column. Fractionation was achieved using reverse-phase high-performance liquid chromatography with a linear gradient of acetonitrile in ammonium acetate. A better resolution was obtained with the mu-Bondapak column. The first-eluted peptides a, b and c1 appeared to be well purified and apparently uncontaminated. Analysis of peptides a and b showed that they contained 40 to 42% glutamine/glutamic acid, 20 to 23% proline, 14 to 16% valine and 8 to 10% leucine. They had valine as the N-terminal amino acid and their molecular mass was estimated as 5500 using sodium dodecylsulfate electrophoresis after dansylation. Peptide c1 differed from peptides a and b in containing less valine and leucine and additional amino acids such as threonine, phenylalanine and tyrosine. In addition, it had a lower molecular mass (approximately 5000) and serine as the N-terminal amino acid. Peptide b exhibited an obvious cytotoxicity for cultured coeliac jejunal mucosa at a very low concentration (0.01 g/l) and was the most toxic peptide.

Use of oral supplements in malnourished elderly patients living in the community: a pharmaco-economic study.

BACKGROUND & AIMS: Inadequate nutritional support in elderly patients is likely to be responsible for increased morbidity and increased associated costs. Conversely prescribing oral supplements to ensure sufficient protein and energy intake should be beneficial. Even though this claim makes sense there is a lack of objective data to support the evidence. The objective of the present study was to assess the cost of malnutrition and related comorbidities among elderly patients living in the community and to determine the impact of nutritional support practice on these outcomes. METHODS: Observational, prospective, longitudinal, cohort study with a 12 months follow-up conducted with 90 general practitioners in France. Two groups of physicians were selected based on historical prescribing practice: group 1 with rare and group 2 with frequent prescription of oral nutrition supplements. The resulting study population was 378 elderly malnourished patients aged over 70, living in the community, either at home or in institutions. Nutritional status at baseline was determined using the Mini Nutritional Assessment (MNA) scale. Main outcome measures were nutritional status, malnutrition-related comorbidities and medical care consumption. RESULTS: Populations in the two groups of patients were balanced for age, gender, weight and body mass index but differed significantly in terms of housing status (P < 0.005) and nutritional status (P < 0.001). After adjustment for baseline characteristics, MNA improved within both groups over time but improvement was significantly higher in group 2 than in group 1 (P < 0.01). The adjusted cost per patient of hospital care (EUR -551), nursing care (EUR -145) and other medical care was significantly reduced in group 2 as compared to group 1, with cost savings of EUR -723 per patient (90% CI: EUR -1.444 to EUR -43). Including the costs related to nutritional products, the total cost savings per patient attributable to nutrition support were EUR -195 (90% CI: EUR -929 to EUR +478). CONCLUSION: Appropriate nutrition support can address the problem of malnutrition among elderly individuals living in the community and may contribute to reduce the costs of health care.

Preoperative nutritional evaluation of elderly patients: the Mini Nutritional Assessment as a practical tool.

BACKGROUND AND GOAL: Age and malnutrition are each surgical risk factors. Because the Mini Nutritional Assessment (MNA) has been specifically designed for assessing the nutritional status of elderly patients, it can be used for preoperative nutritional evaluation. Therefore, the MNA was included in the preoperative clinical evaluation of patients over 60 years of age to describe their nutritional status. METHODS: Every patient over 60 years of age, scheduled for elective surgery, was seen in anaesthesiology consultation and was submitted to the MNA. The MNA is a clinical score consisting of four additive items: 'Anthropometric assessment' based on BMI, mid-arm and calf circumferences, weight loss; global evaluation; dietetic assessment, and subjective assessment - these last three items being obtained through a specific questionnaire. It requires no biological marker. Awarding to the obtained score, the MNA stratifies patients in the following categories: well-nourished (24

Is a 24-h cyclic closed enteral feeding system microbiologically safe in geriatric patients?

BACKGROUND AND AIMS: The microbiological quality of a 1-l closed enteral feeding system (CS) was prospectively monitored under clinical conditions simulating cyclic feeding over a 24-h period in geriatric patients. METHOD: The set was connected after diet sampling (T0). After 5-h feeding, the set was disconnected and a sample taken (T5). Diet was sampled after 12 h before (T12A) and after a 10 ml diet-flush of the set (T12B), after 24-h (T24) and in the pouch (P24). Concentrations of micro-organisms were considered significant when above 10(4) colony-forming units per millilitre. RESULTS: Twenty-one CS were examined. T0 samples were all sterile; 10 out of 21 T5 were contaminated. The microbiological content of the diet was lower in T12B, compared to T12A (P=0.002). None of the P24 samples was contaminated; 19 were sterile and two contained low levels of micro-organisms that had been previously found in the sets. CONCLUSION: The CS was sterile before connecting to the patient. Retrograde contamination of the set was observed without contamination of the pouch after 24-h hanging time. Performing a diet-flush decreased the rate of diet contamination at the distal extremity of the set. Thus, cyclic enteral nutrition using the same pouch during a 24-h period seems to be safe in geriatric patients.

Epidemiological study of malnutrition in elderly patients in acute, sub-acute and long-term care using the MNA.

MNA is a simple and accurate way to assess the nutritional status in routine practice, and is suitable for systematic use and large epidemiologic studies. The purpose of this study was to evaluate the difference in the nutritional status of elderly patients hospitalized in different types of care in the same hospital, and to evaluate its relationship with risk factors. Nutritional status was evaluated in 918 elderly patients hospitalized in acute care (AC) (n=299), sub-acute care (SAC) (n=196) or long-term care (LTC) (n=423), using the MNA (Mini-Nutritional Assessment), a nutritional assessment tool including 18 items grouped in 4 domains, within the first 48 h after admission (all subjects) and at the end of hospitalization (AC, SAC). More patients were rated in the "malnourished" class in SAC (32.5%) than in AC (24.5%) and LTC (24. 7%). Retrospective analysis showed that the initial nutritional status was linked to the type of care and the nature of underlying pathology. The nutritional status on arrival was worse in patients in SAC, and better in those in LTC (p = 0.005). This is probably due to a difference in the kind of patients hospitalized. The nutritional status was worse in patients suffering from infectious disease, stroke, dementia and traumatic injuries, and, conversely, better in patients suffering from cardiopathy, metabolic and gastro-intestinal (except cancerous) diseases (p < 0.0001). Prospective analysis showed that duration of hospitalization was the only variable found to be linked to an improvement of nutritional status. The MNA is a rapid, effective and cheap tool for the assessment of nutritional status and moreover for evaluation of the mortality risk of patients admitted into AC and SAC.

Remission induced by a new specific oral polymeric diet in children with Crohn's disease.

We have been able to show that CT3211 is an effective oral treatment in children with active Crohn's disease. It was well tolerated, and there were minimal side effects. At the mucosal site of disease there was macroscopic and histological improvement, together with evidence of downregulation of the pro-inflammatory cytokines IL-1 beta, IL-8, and IFN-gamma.

[Etiopathogenesis of celiac disease: the attraction and flimsiness of hypotheses]. / Etiopathogénie de la maladie coeliaque: attrait et fragilité des hypothèses.

The pathogenetic mechanisms which induce the intestinal lesions observed in coeliac disease are still unknown. The hypothesis of a primary intestinal peptidase deficiency has not been confirmed. The immunological theory is supported by a large number of findings, but it cannot explain all of the facts. The concept of a surface cell membrane abnormality aims at making up for the previous shortcomings, but it is based on very few unconfirmed data. Although the new pathogenetic theories for auto-immune diseases, and especially coeliac disease, are of considerable interest, experimental confirmation is eagerly awaited. Recently isolated pure toxic gliadin peptides may be of great value to test these new concepts in future research work.

[Cryptosporidiosis, isosporiasis, lambliasis in immunologic deficiencies]. / Cryptosporidiose, isosporose, lambliase au cours des déficits immunitaires.

Digestive disorders are very frequent in the course of immune deficiencies. Parasitic infestations are often their cause, Giardia lamblia was the first known agent and is chiefly found in deficiencies of humoral immunity. Recent studies allowed a better evaluation of the relationships between the host's immune system and parasite, such as production of anti-Giardia antibodies, presence of non specific anti-Giardia factors in blood and maternal milk and the part played by cellular immunity. Another protozoan of the cryptosporidium species was recently considered as responsible for severe diarrhea in cases with immune deficiencies, especially AIDS and some congenital immune deficiencies (5 cases in children with immune deficiencies and diarrhea during the past 3 years). Children without immune deficiencies may also be contaminated, as shown by several epidemiological studies. Finally, a third type of protozoan, Isospora belli and Isospora hominis was also involved in the occurrence of severe digestive disorders. All these parasitic infestations in children with immune deficiencies were characterized by their difficult treatment, their chronicity and frequent relapse and, overall by the usual association with other bacterial and viral agents.

Immunologic characteristics of intestinal lymphoid cells of the guinea pig.

Populations of lymphoid cells from the gastrointestinal tract of guinea pigs were compared with splenic cells for both morphologic and functional characteristics. Gastrointestinal lymphoid cells were isolated from mesenteric lymph nodes, Peyer's patches, and also for the epithelium and lamina propria of the small intestinal mucosa. Isolated intraepithelial and lamina propria lymphocyte populations contained (a) T cells, B cells, and macrophages; (b) T cells that proliferated to phytohemagglutinin and concanavalin A; and (c) B cells that proliferated to bacterial lipopolysaccharide. Using inbred guinea pigs, the intraepithelial and lamina propria lymphocytes were shown to contain T cells capable of proliferating to alloantigens in mixed leukocyte culture, and also cells capable of stimulating alloreactive T cells. These studies demonstrate the presence of immunologically reactive T cells and B cells in isolated small intestinal mucosal lymphoid cells from guinea pigs.

[Cryptosporidiosis. Prospective epidemiologic survey in hospitalized children with diarrhea]. / Cryptosporidiose. Enquête épidémiologique, prospective, chez des enfants hospitalisés atteints de diarrhée.

The pathogenic role of Cryptosporidium in diarrhea is well known in animals and now admitted in humans. Organism is common both to animals and humans. Diarrhea is particularly severe in immunocompromised patients. In order to determine occurrence of cryptosporidiosis in the pediatric population and therefore the contamination risk of the immunocompromised patients in the hospital, stool examinations were carried out in a prospective way in 190 hospitalized children with diarrhea on a 12 month-period. Cryptosporidium was detected 5 times in 4 children, among 57 positive stool examinations. No chronic carrier was found. In all the cases recovery was observed within one month. No child was immunodeficient. No outbreak was observed. The results confirm that immunologically competent children can be infected by cryptosporidium and have diarrhea, recovery and clearing of the stools always occurring spontaneously.

[Constant flow alimentation in Crohn's disease of children]. / L'alimentation à débit constant au cours de la maladie de Crohn de l'enfant.

Enteral nutrition in children with Crohn's disease is a preferred treatment of acute attacks. When maintained for three months, it effectively acts on digestive symptoms, makes possible the resumption of growth and onset of a delayed puberty. In contrast, it does not appear to modify the long-term course of the disease: 7 out of 10 patients had relapses 3 to 6 months after interruption of enteral nutrition.

[Does the hydrolysis of proteins change the acceptability and the digestive tolerance of milk for infants? The results of a comparative and randomized prospective study]. / L'hydrolyse des protéines modifie-t-elle l'acceptabilité et la tolérance digestive d'un lait pour nourrissons? Résultats d'une étude prospective comparative et randomisée.

A prospective randomized study of growth and digestive tolerance in a cohort of 60 healthy infants with no history for allergic disease is reported. A milk-based formula and a formula of identical composition whose proteins had undergone hydrolysis were fed successively to the study infants according to a crossover design, for eight weeks. Intake, weight gain and length gain were comparable and satisfactory with both diets. With the hydrolyzed protein formula, stools were greener in color and significantly more numerous, although both parameters remained within normal limits. The most noteworthy result was the significantly greater rate of regurgitations in the group given the hydrolyzed protein formula, i.e., 26% versus 8% in the group fed a conventional modified milk formula. These results show that use of partial protein hydrolysate formulas is associated with minor digestive adverse effects.

Intestinal malignant lymphoma in a child with familial celiac disease.

A case of intestinal malignant lymphoma occurring in a 10-year-old North African girl with celiac disease is reported. Celiac disease was diagnosed at age 4. A gluten-free diet was started and was maintained for the next 6 years. Seven months after the patient returned to a normal diet, clinical symptoms and subtotal villous atrophy relapsed. Within the next month an abdominal malignant lymphoma was diagnosed. After chemotherapy the tumor disappeared but recurred 6 months later, involving the colon and the liver. Death occurred shortly thereafter. A brother, two years older, also with proven celiac disease, is presently on a strict gluten-free diet. Both children shared the same histocompatibility antigens (HLA A2-B17/A29-B12, identity at the D locus). Whether or not relapse of celiac disease played a role in the appearance of the tumor remains highly speculative; however, the case of our patient suggests that familial involvement and, in some instances, ethnic origin may constitute risk factors predisposing to malignancy.