The DDNC is committed to work that will uncover the causes of diseases, find treatments for diseases and study the effect of medications on diseases. The goal of this endeavor is to learn new knowledge that will improve the lives of children with gastrointestinal, liver, pancreatic disease or nutritional problems.

The DDNC has several clinical studies that are funded from research agencies.

Gastroesophageal reflux in infants and children

Extent of the problem and its complications is funded by the Centers for Disease Control and attempts to understand the natural history of infant reflux by retrospectively reviewing charts of children with the diagnosis of reflux and prospectively by enrolling 2500 consecutively born infants into a monitoring program.

Nonalcoholic Steatohepatitis (NASH)

Nonalcoholic steatohepatitis is funded by the Peter and Tommy Fund. Nonalcoholic steatohepatitis (NASH) is a disease of the liver that is associated with obesity and adult onset, or type II, diabetes. NASH is not a benign disease. Many people with NASH have a shortened life expectancy than those who no not have NASH. NASH is associated with cirrhosis and is the third most common reason for liver transplantation in adults. No one knows what causes NASH, but it is know that in obese people there is increased fat in the liver. In addition to fat, cells that cause inflammation are found in the liver in patients with NASH. It is thought that these inflammatory cells may cause liver damage that results in fibrosis, cirrhosis and ultimately liver failure. The purpose of this research is to understand the relationship among obesity and the molecular factors that control inflammation so the interaction of the two can be better understood and treatments developed.

Frequency and Types of Mucosal Glucoamylase Enzyme Deficiencies (Collaborative work with Baylor Children's Hospital and the USDA Nutrition Research Center in Houston, TX)

Starch digestion links energy stored by photosynthesis in plants to energy needs of man. Starch granules from grains and tubers contribute ~66% of all human food energy needs. Maltase-glucoamylase is the final step in complex digestion of starch from insoluble glucose polymer to soluble glucose. Amylase produces glucose oligomers by internal starch cleavage and maltase-glucoamylase releases terminal glucose. The phenotype of maltase-glucoamylase deficiency is poorly understood. Because the malabsorbed substrate has greater mass, the symptoms are not as striking as those of lactose or sucrose malabsorption. We found that 28% of children with chronic dyspepsia have maltase-glucoamylase deficiency. This is in contrast to a general frequency of 12%. Isolated maltase-glucoamylase deficiency makes up only 11% of deficient individuals. The remaining 88% have pandisaccharidase and pan-a-glucosidase deficiencies. This study tests genotype and phenotype of dyspeptic individuals with isolated maltase-glucoamylase deficiencies for coding mutations and searches for trans-acting genes that are altered in maltase-glucoamylase/ pandisaccharidase and pan-a-glucosidase deficient individuals. The objectives are: 1 Mutations in the coding region will be sought in patients with isolated glucoamylase deficiencies. All mutations detected in the human coding region will be expressed in COS-1 cell lines to determine the functional significance of each mutation. 2. Altered regulatory genes will be sought in patients with multiple disaccharidase deficiencies. The clinical phenotypes and genetic inheritance will be investigated with noninvasive breath tests and through gene mapping in kindred using 13C-starch and 13C-sucrose breath tests and quantitative trait loci analysis from blood DNA. The function of the regulatory genes will be explored by co-expression studies in the COS-1 cell line.

Genetics of lactase (Collaborative work with Boston Children's Hospital)

Lactase deficiency is common problem in many populations, yet the genetic control of the enzyme is unknown. This study will assess the genetic control of the function of the lactase enzyme in the small intestinal lining.

Anemia of Chronic disease and Inflammatory Bowel Disease

This is an investigator-initiated research, sponsored by the Pharmaceutical Industry. Pediatric patients with Inflammatory Bowel Disease (IBD) often develop microcytic hypochromic anemia, secondary to poor oral intake of iron, malabsorption of nutrients and/or gastrointestinal losses. Although the exact number of IBD patients with anemia is unknown, prevalence reports suggest anemia may be very common among patients with IBD. In many cases the anemia is responsive to the standard treatment with iron given either orally or parentally. Due to the potential serious adverse events of iron dextran and iron gluconate, iron sucrose is the preferred course of treatment. In other cases, the anemia is refractory to the standard treatment. Postulated theory implicates the anemia of chronic disease, which is linked with the proliferation and maturation of erythroid cells. Proinflammatory cytokines are produced in increased amounts in IBD. Such cytokines can induce a relative deficiency of erythropoietin, as well as a resistance to the target receptor. A lack of erythropoietin may be an important factor in the pathophysiology of anemia associated with chronic disease. Microcytic hypochromic anemia in pediatric patients with IBD could be multifactorial in origin, and may require different approaches to treatments. This proposal is designed to develop a therapeutic algorithm to treat microcytic hypochromic anemia of chronic disease in pediatric patients with IBD.

Bacterial overgrowth in Irritable Bowel Syndrome

This is an investigator-initiated research, sponsored by the Pharmaceutical Industry. Small Bowel bacterial overgrowth (SBBOG) can cause gastrointestinal symptoms including bloating, gassiness, diarrhea, and constipation. Several lines of evidence indicate that SBBO could play a role in the pathogenesis of Irritable bowel syndrome (IBS). IBS is considered a functional disorder. The etiology of this syndrome is poorly understood. The Rome criteria help to diagnose the disorder. We hypothesize that in those patients who fulfill the Rome's criteria for IBS and who have a positive lactulose breath test (LBHT), when treated appropriately for SBBO with antibiotics will respond by clearing the small bowel of bacteria and improving IBS symptoms. Most antibiotics used for the treatment of intestinal diseases are aminoglycosides. These antibiotics are effective against gram-positive and some gram-negative bacteria. They are especially effective against aerobes. However, they do not cover the entire range of microorganisms responsible for intestinal infections. These antibiotics systemically absorbed which can lead to serious side effects. In this context ciprofloxacin and metronidazole are the two most widely used antibiotics; both have known side effects attributed to systemic absorption. Rifaximin is a rifamycin analogue with a broad spectrum of activity similar to that of rifampin; however, because gastrointestinal absorption is poor, its development focused on specific use for intestinal infections and diseases. We will monitor intestinal pH, and intestinal pressure pre and post treatment with antibiotics with the "SmartPill pH.p Capsule". We speculate that patients with IBS and SBBO have alteration in the intestinal pH, as well as the intestinal pressure, that will be modified after the antibiotic treatment. We also speculate to find differences in the intestinal pressures in the different types of IBS, diarrhea predominant, constipation predominant, or alternation of symptoms.

Bacterial overgrowth in Inflammatory Bowel Disease

This is an investigator-initiated research, sponsored by the Pharmaceutical Industry. The etiology of inflammatory disease (IBD) is unknown, but a body of evidence from clinical and experimental observation indicates a role for intestinal microflora in the pathogenesis of this disease. An increasing number of both clinical and laboratory-derived observations support the importance of luminal components in driving the inflammatory response in Crohn's disease. A growing amount of evidence indicates that the intestinal flora plays a pathogenic role in IBD: hence, the use of anti-bacterial agents as ancillary treatment in patients with ulcerative colitis, or Crohn's disease. The rationale of antibiotic therapy in the treatment of IBD is to decrease the bacterial load that act as an antigen that triggers an immune response. Numerous antibiotics have been used for several years in the treatment of intestinal diseases, most are members of the class of aminoglycosides. These are effective against gram-positive and some gram-negative bacteria, above all aerobes, and do not therefore cover the entire range of microorganisms responsible for intestinal infections. With these antibiotics, moreover, it is not possible to exclude intestinal absorption, which can lead to serious side effects. Ciprofloxacin and metronidazole are the two most widely studied antibiotics proved effective therapy for patients with active ileo-colonic and colonic Crohn's disease, but with known side effects attributed to systemic absorption. Rifaximin is a rifamycin analogue with a broad spectrum of activity similar to that of rifampin; however, because it is poorly absorbed through the gastrointestinal tract, it's development was focused for intestinal infections and diseases. The primary objective of this study is to evaluate the subject's disease activity response as measured by the pediatric Crohn's disease activity index (PCDAI) that includes a questionnaire, physical exam and blood work with the treatment of oral rifaximin for 21 days in mild to moderate Crohn's disease flare-up in pediatric patients, 12 to 18 years of age, inclusive. The secondary objective of the study is to evaluate the amount of time the subject's disease activity response remains improved post 21 days of treatment of rifaximin. We hypothesize that oral rifaximin treatment for 21 days will be an effective treatment modality for patients with confirmed Crohn's disease presenting with mild to moderate disease flare up.

Toll-like Receptors and IBD

Members of the Toll-like receptor family are key regulators of both innate and adaptive immune responses. These receptors bind molecular structures that are expressed by microbes but are not expressed by the human host. Activation of these receptors initiates an inflammatory cascade that attempts to clear the offending pathogen and set in motion a specific adaptive immune response. Defects in sensing of pathogens or mediation of the inflammatory cascade may contribute to the pathophysiology of disease and injure the host by activating a deleterious immune response, such as in inflammatory bowel disease. The focus of this research is to identify specific toll-like receptor mutations that may be associated with the development of inflammatory bowel disease.

Eosinophilic Esophagitis

Eosinophilic esophagitis (EOE) is a disease of children and adults characterized by poor feeding, vomiting, dysphagia, and food impaction. The diagnosis is made based on infiltration of eosinophils in the esophagus. Although definitive epidemiological data has yet to be established, many authors have observed an apparent rise in the incidence of EOE in recent years. This study assesses the incidence and outcome of EOE that was diagnosed in the 1980's

PEDS-CORI (Pediatric Endoscopy Database System for the Clinical Outcomes Research Initiative)

The PEDS-CORI is a computerized national database of endoscopic procedures. The CORI database, begun in 1995, provides a qualitative and quantitative overview of adult endoscopy. Recently a pediatric database, PEDS-CORI has become available.

The Digestive Diseases and Nutritional Center at Children's Hospital of Buffalo is one of the first five pediatric sites to participate. This database will allow us to learn about the characteristics of pediatric endoscopy, to explore the natural history of the disease processes from childhood to adult, to examine the cost effectiveness of endoscopy diagnosis, and to compare our practices with other regions.

The benefits of participating, which have just been outlined, help us to continually improve our services locally as well as improving the state of pediatric endoscopy nationwide.

Industry Sponsored Research

The DDNC works with many manufactures to test medications for safety and efficacy in children as mandated by the Food and Drug Administration (FDA). These trials are often beneficial for families in that all care and medications are supplied free of charge. There are many ongoing trials and new trials are added to our practice periodically. If you are interested you can contact our research nurse for information.