The purpose of this project is to define the morphologic basis of intestinal motor disorders and to correlate abnormalities of structure with abnormalities of function and the clinical behavior of each disorder. We plan to continue our studies of the smooth muscle and myenteric plexus of the gut in chronic idiopathic intestinal pseudo-obstruction, diabetic gastroparesis, diabetic diarrhea, idiopathic megacolon, cathartic colon, severe idiopathic constipation, esophageal motor disorders, and the extraintestinal nervous system in diabetic gastroenteropathy. We also plan to define the normal structure of the myenteric plexus and smooth muscles of premature infants, infants, and young children and to compare this with the findings in infants and young children who suffer from a variety of forms of intestinal pseudo-obstruction. Tissue made available via surgery or autopsy will be systematically studied by conventional light microscopy, silver staining of longitudinal sections of the myenteric plexus, and electron microscopy. Electron microscopy will especially be used to define differences between the various neural and muscle diseases encountered and to compare them with normals. In many cases, patients will have been clinically evaluated by the investigators and we will be able to correlate the radiographic and/or esophageal manometric findings with the pathologic findings. In other cases, tissue will be sent from outside institutions accompanied by appropriate records, x-rays, and the results of esophageal and gastroduodenal manometries.
Our aims are: 1) to define the nature and distribution of morphologic abnormalities (if present) in order to achieve a better understanding of pathogenesis; 2) establish diagnostic criteria by which pathologists will be able to diagnose some of these disorders; 3) correlate abnormalities of function with abnormalities of structure in order to increase diagnostic accuracy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
2R01AM028180-04A1
Application #
3151848
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1981-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Schuffler, M D; Pagon, R A; Schwartz, R et al. (1988) Visceral myopathy of the gastrointestinal and genitourinary tracts in infants. Gastroenterology 94:892-8
Krishnamurthy, S; Schuffler, M D (1987) Pathology of neuromuscular disorders of the small intestine and colon. Gastroenterology 93:610-39
Leon, S H; Krishnamurthy, S; Schuffler, M D (1987) Subtotal colectomy for severe idiopathic constipation. A follow-up study of 13 patients. Dig Dis Sci 32:1249-54
Achem, S R; Owyang, C; Schuffler, M D et al. (1987) Neuronal dysplasia and chronic intestinal pseudoobstruction: rectal biopsy as a possible aid to diagnosis. Gastroenterology 92:805-9
Perino, L E; Schuffler, M D; Mehta, S J et al. (1986) Radiation-induced intestinal pseudoobstruction. Gastroenterology 91:994-8
Krishnamurthy, S; Schuffler, M D; Belic, L et al. (1986) An inflammatory axonopathy of the myenteric plexus producing a rapidly progressive intestinal pseudoobstruction. Gastroenterology 90:754-8
Leon, S H; Schuffler, M D (1986) Visceral myopathy of the colon mimicking Hirschsprung's disease. Diagnosis by deep rectal biopsy. Dig Dis Sci 31:1381-6
McDonald, G B; Schuffler, M D; Kadin, M E et al. (1985) Intestinal pseudoobstruction caused by diffuse lymphoid infiltration of the small intestine. Gastroenterology 89:882-9
Schuffler, M D; Leon, S H; Krishnamurthy, S (1985) Intestinal pseudoobstruction caused by a new form of visceral neuropathy: palliation by radical small bowel resection. Gastroenterology 89:1152-6
Krishnamurthy, S; Schuffler, M D; Rohrmann, C A et al. (1985) Severe idiopathic constipation is associated with a distinctive abnormality of the colonic myenteric plexus. Gastroenterology 88:26-34