Biomedical subjects
Publications and source records attributed to P Kilbridge.
Most early reports of implemented World-Wide Web (W3) medical record systems describe single institution architectures. We describe W3-EMRS, a multi-institutional architecture, and its implementation. Thorny problems in data sharing underlined by the W3-EMRS project are reviewed.
W3-EMRS is an architecture designed to access clinical data from remote heterogeneous electronic medical record system (EMRS) databases. We describe the technologies used in an experimental implementation of W3-EMRS that concurrently collects data from several sources and presents them in an integrated set of views. After describing some of the organizational constraints, the architectural decision, implementation methodology, and operation of the completed project are discussed.
From 1980-1986 intestinal mucosal lymphangiectasia was diagnosed histologically in eight patients (6 weeks to 16 years; four males/four females; seven white). The presenting features were diarrhea (six/eight), vomiting (four/eight), and growth deficit (seven/eight). Additional conditions in these patients included asthma, urinary tract infection, esophageal atresia, hydrops fetalis, inflammatory bowel disease, malabsorption syndrome, and thymic hypoplasia. Hypoalbuminemia and edema (four/eight) were more prominent in those patients under 5 years of age. Two had systemic lymphangiectasia and lymphopenia. The patients responded variably to hyperalimentation and dietary supplements, depending on the extent of their lymphangiectasia and the age at onset of symptoms. Dilated lymphatics were seen in the small intestinal mucosa under the surface epithelium. Lesions were often focal, requiring several biopsies or serial sections for detection. Other common findings were mild to moderate lymphoplasmacytic inflammation and mild to moderate villous injury with blunting and edema. Mild inflammation without lymphangiectasia was also present in esophageal, gastric, or colonic biopsies. Diagnosis should be made on the basis of endoscopic findings or in small-intestinal inflammatory conditions even in the absence of a classic clinical picture. Histologic confirmation may require more than one serially sectioned biopsy. This study confirms the diversity of disorders that may be associated with intestinal lymphangiectasia and shows that the disease in infants is more severe and generalized.
Genetic deficiency of the second component of complement (C2) is the most common complement-deficiency state among Western Europeans and is frequently associated with autoimmune diseases. To examine the molecular basis of this deficiency, we established cultures of blood monocytes from four families with C2-deficient members. Using a hemolytic-plaque assay, [35S]methionine metabolic labeling of proteins in tissue culture and immunoprecipitation, RNA extraction and Northern blot analysis, and DNA restriction-enzyme digestion and Southern blot analysis, we found that C2 deficiency is not due to a major gene deletion or rearrangement but is the result of a specific and selective pretranslational regulatory defect in C2 gene expression. This leads to a lack of detectable C2 mRNA and a lack of synthesis of C2 protein. The approach used in this study should prove useful in examination of other plasma protein deficiencies, especially those in which the deficient gene is normally expressed in peripheral-blood monocytes or tissue macrophages and in which ethical considerations preclude the use of liver or other tissue for study.
Expression of the alpha 1-proteinase inhibitor (alpha 1PI) gene was studied in human mononuclear cells. Using RNA blot and dot hybridization, alpha 1PI mRNA was detected in human peripheral blood monocytes, bronchoalveolar and breast milk macrophages, but not in B or T lymphocytes. Using incorporation of a radiolabeled amino acid precursor, synthesis and secretion of alpha 1PI were demonstrated in human monocytes and macrophages, but not in lymphocytes. In addition, alpha 1PI was secreted in functionally active form as shown by complexing with serine proteases. Biosynthesis of alpha 1PI by mononuclear phagocytes was greatest during the first 24 hr in culture and progressively decreased over the next 10 days. The reduction in alpha 1PI biosynthesis in vitro involved a mechanism acting at the pretranslational level as alpha 1PI mRNA content also progressively declined over 10 days in culture. The ease of sampling human monocytes and macrophages now permits examination of the biochemical defect in homozygous PiZ and PiS alpha 1PI deficiencies and study of the functional significance of locally produced alpha 1PI in normal tissues and sites of injury or inflammation.