morphine and Pancreatic-Diseases

The article reviews advances in gastrointestinal aspects of cystic fibrosis (CF) published in the literature over the past year, and highlights new and interesting research.. Animal models can be used to understand the pathophysiology of gastrointestinal complications in CF. The CF mouse is useful for studying distal intestinal obstruction, dysmotility and dysbiosis, and the CF pig model has helped us better understand meconium ileus and pancreatic and hepatobiliary secretory problems. Studies in humans help elucidate the evolution of pancreatic insufficiency, how reflux may lead to lung disease, problems with intestinal dysmotility, mechanisms leading to pancreatitis and the increased prevalence of gastrointestinal cancer. Biomarkers are shedding light on CF-related liver disease. Rectal biopsies can help in diagnosis and in studying new drugs for CF.. Gastrointestinal complications of CF are likely to be seen with increasing frequency as patients with CF lead longer lives. CF animal models and modern research techniques are providing new insights into extrapulmonary complications. CF clinicians should be familiar with diagnosis and management of common gastrointestinal complications and should build bridges with specialists so that referrals can be made when needed.

Topics: Animals; Cystic Fibrosis; Digestive System Diseases; Disease Models, Animal; Dysbiosis; Gastrointestinal Diseases; Humans; Ileus; Intestinal Obstruction; Liver Diseases; Meconium; Mice; Pancreatic Diseases; Prognosis; Rectum; Swine

Topics: Animals; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Intestinal Obstruction; Meconium; Mice; Mutation; Pancreatic Diseases

Lung disease causes most of the morbidity and mortality in cystic fibrosis (CF). Understanding the pathogenesis of this disease has been hindered, however, by the lack of an animal model with characteristic features of CF. To overcome this problem, we recently generated pigs with mutated CFTR genes. We now report that, within months of birth, CF pigs spontaneously developed hallmark features of CF lung disease, including airway inflammation, remodeling, mucus accumulation, and infection. Their lungs contained multiple bacterial species, suggesting that the lungs of CF pigs have a host defense defect against a wide spectrum of bacteria. In humans, the temporal and causal relations between inflammation and infection have remained uncertain. To investigate these processes, we studied newborn pigs. Their lungs showed no inflammation but were less often sterile than controls. Moreover, after introduction of bacteria into their lungs, pigs with CF failed to eradicate bacteria as effectively as wild-type pigs. These results suggest that impaired bacterial elimination is the pathogenic event that initiates a cascade of inflammation and pathology in CF lungs. Our finding that pigs with CF have a host defense defect against bacteria within hours of birth provides an opportunity to further investigate CF pathogenesis and to test therapeutic and preventive strategies that could be deployed before secondary consequences develop.

Topics: Animals; Animals, Newborn; Cystic Fibrosis; Disease Models, Animal; Ileus; Inflammation; Lung; Meconium; Mucus; Pancreatic Diseases; Radiography, Thoracic; Survival Analysis; Swine; Time Factors

Cystic Fibrosis (CF) is a common autosomal recessive disease that affects multiple organs. The lack of an animal model with manifestations like those typically found in humans has slowed understanding of its pathogenesis. Therefore, because of the similarities between human and swine anatomy, biochemistry, physiology, size, and genetics, we chose to develop a porcine model of CF. We used homologous recombination in primary cultures of porcine fibroblasts to disrupt the CFTR gene and then used those cells as nuclear donors for somatic cell nuclear transfer. After crossing heterozygous pigs, we produced CFTR-/- pigs. The newborn CFTR null piglets manifested meconium ileus, pancreatic destruction, early focal biliary cirrhosis, and gall bladder abnormalities that were very similar to those observed in humans with CF. At birth, there were no abnormalities in the airway epithelium or submucosal glands and no evidence of inflammation, consistent with findings in the newborn human. We hope that this porcine model will help elucidate the pathogenesis of CF and thereby lead to the development of new mechanism-based therapies.

Topics: Animals; Animals, Genetically Modified; Animals, Newborn; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Disease Models, Animal; Gallbladder Diseases; Gene Targeting; Humans; Ileus; Infant, Newborn; Liver Diseases; Meconium; Models, Biological; Mutation; Pancreatic Diseases; Phenotype; Respiratory System; Species Specificity; Swine

Cystic fibrosis (CF), the most common lethal autosomal recessive disease in white populations, is characterized by dysfunctional chloride ion transport across epithelial surfaces. Although recurrent pulmonary infections and pulmonary insufficiency are the principal causes of morbidity and death, gastrointestinal symptoms commonly precede the pulmonary findings and may suggest the diagnosis in infants and young children. The protean gastrointestinal manifestations of CF result primarily from abnormally viscous luminal secretions within hollow viscera and the ducts of solid organs. Bowel obstruction may be present at birth due to meconium ileus or meconium plug syndrome. Complications of meconium ileus include volvulus, small bowel atresia, perforation, and meconium peritonitis with abdominal calcifications. Older children with CF may present with bowel obstruction due to distal intestinal obstruction syndrome or colonic stricture, and tenacious intestinal residue may serve as a lead point for intussusception or cause recurrent rectal prolapse. Radiologic studies often demonstrate thickened intestinal mucosal folds in older children and uncommonly show colonic pneumatosis, peptic esophageal stricture due to gastroesophageal reflux, and duodenal ulcer. Appendicitis due to inspissated secretions is uncommon. Obstruction of ducts and ductules produces exocrine pancreatic insufficiency, pancreatitis, cholestasis, cholelithiasis, and cirrhosis with portal hypertension. On imaging studies, the pancreas is commonly small and largely replaced by fat, sometimes displays calcifications, and is rarely replaced by macrocysts. Radiologic features of hepatobiliary disease include an enlarged radiolucent liver from steatosis, gallstones, a shrunken nodular liver, splenomegaly, and portosystemic collateral vessels. With the improved survival of CF patients, an increased risk for developing gastrointestinal carcinomas has been established, many occurring as early as the 3rd decade.

Topics: Adult; Biliary Tract Diseases; Child; Cystic Fibrosis; Digestive System Diseases; Gastrointestinal Diseases; Humans; Infant, Newborn; Intestinal Obstruction; Liver Diseases; Meconium; Pancreatic Diseases; Tomography, X-Ray Computed; Ultrasonography

An autopsy case of bilateral renal dysplasia with other congenital malformations is reported. Malformations included severe pancreatic fibrosis with meconium ileus, situs inversus totalis, cardiovascular anomalies, and others. The only syndrome of multiple congenital malformations involving renal dysplasia which is similar to the present case is Ivemark's syndrome, though the present case lacked hepatic lesions. Apart from the pancreatic lesion, there were no abnormalities compatible with cystic fibrosis (mucoviscidosis). It was considered that meconium ileus in the present case was caused by pancreatic achylia secondary to severe pancreatic fibrosis, unrelated to cystic fibrosis, but closely allied to renal dysplasia.

Topics: Abnormalities, Multiple; Cystic Fibrosis; Diagnosis, Differential; Female; Humans; Infant, Newborn; Intestinal Obstruction; Kidney; Meconium; Pancreatic Diseases; Situs Inversus

Topics: Adolescent; Adult; Child; Child, Preschool; Cystic Fibrosis; Female; Growth Disorders; Humans; Infant; Infant, Newborn; Intestinal Obstruction; Male; Meconium; Pancreatic Diseases; Respiratory Tract Infections; Sweating

Topics: Cystic Fibrosis; Humans; Infant, Newborn; Intestinal Obstruction; Meconium; Pancreatic Diseases; Syndrome

Topics: Abnormalities, Multiple; Cystic Fibrosis; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Obstruction; Male; Meconium; Pancreas; Pancreatic Diseases

Topics: Adult; Female; Fetal Diseases; Humans; Infant, Newborn; Intestinal Obstruction; Meconium; Pancreatic Diseases; Peritonitis; Pregnancy

Topics: Chymotrypsin; Feces; Humans; Infant, Newborn; Intestinal Obstruction; Meconium; Pancreas; Pancreatic Diseases; Trypsin

Surgeons whose practice involves many infants and children should be acquainted with all abnormalities of pancreatic malformation and function. Conditions amenable to surgical treatment are few, but serious. Trauma to the pancreas in childhood is most commonly diagnosed by fever, leukocytosis, rectus spasm and elevated serum amylase. Drainage of the lesser sac and debridement of devitalized tissue may prevent the sequelae of pseudocyst formation which seems to follow the untreated injury. True congenital cysts are characterized by an epithelial lining.Mucoviscidosis complicated by meconium ileus remains a challenging disease of the newborn that requires early operation. Ten per cent of infants with cystic fibrosis may be threatened by intestinal obstruction from this cause. Some children surviving the newborn period go on to develop obstruction later. Annular malformation of pancreas may produce upper intestinal (duodenal) obstructive symptoms immediately after birth. Surgical correction by duodenojejunostomy should be postponed only long enough to correct severe fluid or electrolyte imbalances. Idiopathic spontaneous hypoglycemia has the most serious prognosis if convulsions are allowed to recur. Increased metabolic rates in infants increase the need for control of blood sugar levels by either administration of cortisone or pancreatic resection. If adenoma is the cause, a conservative resection of the tumor suffices. If serial frozen section fails to reveal either tumor or hypertophy of insulin-producing cells, blind pancreatectomy may be indicated, for irreversible brain damage develops early in uncontrolled hypoglycemia.

Topics: Child; Congenital Abnormalities; Cystic Fibrosis; Drainage; Female; Humans; Hypoglycemia; Infant; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Intestinal Obstruction; Meconium; Neoplasm Recurrence, Local; Pancreas; Pancreatectomy; Pancreatic Cyst; Pancreatic Diseases; Surgical Procedures, Operative

Topics: Child; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Meconium; Pancreas; Pancreatic Diseases; Peritonitis

Topics: Child; Disease; Humans; Infant; Infant, Newborn, Diseases; Meconium; Pancreas; Pancreatic Diseases; Peritonitis

Any newborn who continues to vomit in the first few days of life, particularly if the vomitus contains bile and if the abdomen is distended, should have immediate investigation because intestinal obstruction in the newborn is a fatal condition unless promptly recognized and surgically corrected. The most common cause of obstruction at this age is atresia and the simplest possible surgical procedure which adequately corrects this deformity should be done. It is also possible to successfully correct the obstruction caused by other congenital deformities such as annular pancreas and meconium ileus. Although prematurity is a definite factor in the outcome, intestinal obstruction in the newborn can be corrected with a surprisingly low mortality. Occasionally unusual methods are needed to tide these infants over the critical period of postoperative care.

Topics: Child; Cystic Fibrosis; Humans; Ileus; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Intestinal Obstruction; Meconium; Pancreas; Pancreatic Diseases

Topics: Child; Cystic Fibrosis; Disease; Humans; Ileus; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Obstruction; Intestine, Small; Meconium; Pancreas; Pancreatic Diseases; Survivors

Topics: Child; Cystic Fibrosis; Disease; Humans; Ileus; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Diseases; Intestinal Obstruction; Intestines; Meconium; Pancreas; Pancreatic Diseases

Topics: Child; Cystic Fibrosis; Disease; Humans; Ileum; Ileus; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Obstruction; Intestinal Volvulus; Meconium; Pancreas; Pancreatic Diseases; Peritonitis

Topics: Child; Disease; Humans; Hydrogen Peroxide; Ileus; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Obstruction; Meconium; Pancreas; Pancreatic Diseases

Topics: Child; Disease; Humans; Ileus; Infant; Infant, Newborn, Diseases; Intestinal Obstruction; Meconium; Pancreas; Pancreatic Diseases; Twins

Topics: Child; Colon; Disease; Exocrine Pancreatic Insufficiency; Humans; Ileus; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Obstruction; Meconium; Pancreas; Pancreatic Diseases

Topics: Disease; Enzymes; Humans; Infant, Newborn; Intestinal Atresia; Intestinal Mucosa; Meconium; Pancreas; Pancreatic Diseases

Topics: Child; Cystic Fibrosis; Cysts; Disease; Humans; Ileus; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Obstruction; Meconium; Pancreas; Pancreatic Diseases

Topics: Child; Cystic Fibrosis; Disease; Humans; Ileus; Infant; Infant, Newborn, Diseases; Intestinal Obstruction; Meconium; Pancreas; Pancreatic Diseases

Topics: Cystic Fibrosis; Disease; Fetal Diseases; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Meconium; Pancreas; Pancreatic Diseases; Peritonitis