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Biomedical subjects

R Chen

Publications and source records attributed to R Chen.

641 records · Page 36Linked to original sources
PubMedDate not supplied

GEM: a proposal for a more comprehensive guideline document model using XML.

OBJECTIVE: To develop a guideline document model that includes a sufficiently broad set of concepts to be useful throughout the guideline life cycle. DESIGN: Current guideline document models are limited in that they reflect the specific orientation of the stakeholder who created them; thus, developers and disseminators often provide few constructs for conceptualizing recommendations, while implementers de-emphasize concepts related to establishing guideline validity. The authors developed the Guideline Elements Model (GEM) using XML to better represent the heterogeneous knowledge contained in practice guidelines. Core constructs were derived from the Institute of Medicine's Guideline Appraisal Instrument, the National Guideline Clearinghouse, and the augmented decision table guideline representation. These were supplemented by additional concepts from a literature review. RESULTS: The GEM hierarchy includes more than 100 elements. Major concepts relate to a guideline's identity, developer, purpose, intended audience, method of development, target population, knowledge components, testing, and review plan. Knowledge components in guideline documents include recommendations (which in turn comprise conditionals and imperatives), definitions, and algorithms. CONCLUSION: GEM is more comprehensive than existing models and is expressively adequate to represent the heterogeneous information contained in guidelines. Use of XML contributes to a flexible, comprehensible, shareable, and reusable knowledge representation that is both readable by human beings and processible by computers.

Algorithms↗
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UMLS concept indexing for production databases: a feasibility study.

OBJECTIVES: To explore the feasibility of using the National Library of Medicine's Unified Medical Language System (UMLS) Metathesaurus as the basis for a computational strategy to identify concepts in medical narrative text preparatory to indexing. To quantitatively evaluate this strategy in terms of true positives, false positives (spuriously identified concepts) and false negatives (concepts missed by the identification process). METHODS: Using the 1999 UMLS Metathesaurus, the authors processed a training set of 100 documents (50 discharge summaries, 50 surgical notes) with a concept-identification program, whose output was manually analyzed. They flagged concepts that were erroneously identified and added new concepts that were not identified by the program, recording the reason for failure in such cases. After several refinements to both their algorithm and the UMLS subset on which it operated, they deployed the program on a test set of 24 documents (12 of each kind). RESULTS: Of 8,745 matches in the training set, 7,227 (82.6 percent ) were true positives, whereas of 1,701 matches in the test set, 1, 298 (76.3 percent) were true positives. Matches other than true positive indicated potential problems in production-mode concept indexing. Examples of causes of problems were redundant concepts in the UMLS, homonyms, acronyms, abbreviations and elisions, concepts that were missing from the UMLS, proper names, and spelling errors. CONCLUSIONS: The error rate was too high for concept indexing to be the only production-mode means of preprocessing medical narrative. Considerable curation needs to be performed to define a UMLS subset that is suitable for concept matching.

Abstracting and Indexing↗
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Kidney is the only source of human plasma renin in 45-kb human renin transgenic mice.

Prorenin is expressed in certain extrarenal tissues, but normally only the kidneys process prorenin to renin and secrete renin into the circulation. Although transgenic animal lines containing the human renin (hREN) structural gene with either 0.9-kb or 3-kb 5'-flanking DNA express the transgene appropriately in renal juxtaglomerular cells and secrete hREN into the circulation, the source of the circulating renin is not known. In the present study, we observed that 13-kb hREN transgenic mice that contain the structural gene and 0.9-kb 5'-flanking DNA express hREN mRNA in many unusual tissues. We also observed that circulating hREN levels in 13-kb hREN mice increased after bilateral nephrectomy. These results suggested that the hREN gene is expressed at inappropriate locations where prorenin might be processed to renin. To determine if more distal sequences flanking the hREN gene might contribute to cell and tissue specificity, we used a 45-kb hREN genomic fragment that contained the structural gene and about 25-kb 5'- and 8-kb 3'-flanking DNA sequences to generate 3 separate transgenic lines that contained the intact transgene sequences. Ribonuclease protection assays revealed a much narrower tissue distribution of hREN expression than in the 13-kb hREN transgenic mice. In each 45-kb hREN line, hREN mRNA was present only in the kidney, adrenal, lung, eye, ovary, and brain. Moreover, 24 hours after nephrectomy, human plasma renin fell to very low levels, indistinguishable from those of nontransgenic littermates, indicating that their circulating hREN is of renal origin. These studies suggest that sequences flanking the structural gene, missing from previous hREN transgenic lines, suppress renin gene expression at inappropriate extrarenal sites where cellular proteases, to which prorenin is not normally exposed, could convert prorenin to renin, resulting in abnormal secretion of renin into the plasma.

Animals↗
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Pregnancy outcome in patients with insulin dependent diabetes mellitus and diabetic nephropathy treated with ACE inhibitors before pregnancy.

The preconception and intrapregnancy parameters that are relevant to outcome in women with insulin dependent diabetes mellitus (IDDM) and diabetic nephropathy remain controversial. We analyzed the types and frequencies of maternal and neonatal complications in 24 IDDM patients with diabetic nephropathy (24 pregnancies), all with preserved to mildly impaired renal function. All patients received treatment with captopril for at least six months prior to planned pregnancy and were maintained under strict glycemic control from at least three months before pregnancy to delivery. A successful pregnancy outcome (live, healthy infant without severe handicaps two years after delivery) was observed in 87.5% of the patients. Preexisting hypertension was the only parameter found to be significantly predictive of an unsuccessful outcome (p = 0.0004). We conclude that in patients with IDDM complicated by diabetic nephropathy, pre-pregnancy captopril treatment combined with strict glycemic control offers a prolonged protective effect against possible renal deterioration and probably improves pregnancy outcome.

Adult↗
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Mometasone furoate nasal spray is rapidly effective in the treatment of seasonal allergic rhinitis in an outdoor (park), acute exposure setting.

The objective of this study was to determine the time to onset of symptom relief following a single dose of mometasone furoate nasal spray (MFNS) in symptomatic patients with seasonal allergic rhinitis (SAR). This was a single-center, placebo-controlled, double-blind, randomized, parallel-group study with a 7-day run-in period followed by a single-dose administration of medication or placebo in an outdoor park setting. The park site provided an acute exposure to seasonal (tree and grass) pollens. Patients remained in the park of approximately 12 hours after dosing, during which time hourly assessments of SAR symptoms were recorded on a diary card. Two hundred thirty-nine patients with symptoms of SAR entered the study. Patients receiving any concurrent medication for treatment of their symptoms were excluded. Patients were randomized in a 1:1 ratio to receive treatment with either a single dose of MFNS (200 micrograms/or matching placebo nasal spray. Outcome measures included an assessment of overall therapeutic response and change from baseline in total nasal plus non-nasal sign/symptom severity score, total nasal sign/symptom severity score, and total non-nasal sign/symptom severity score. Improvement in total nasal symptom scores, total non-nasal symptom scores, and total nasal plus non-nasal symptom scores were greater and more sustained in patients receiving MFNS than in patients receiving placebo. The mean decrease from baseline in total nasal plus non-nasal symptom scores was significantly greater in MFNS-dosed patients than in placebo-dosed patients at 5 hours after dosing (p < 0.01). The mean decrease from baseline in total nasal symptom scores was significantly greater in MFNS-dosed patients than in placebo-dosed patients at 7 hours after dosing (p < 0.01). The between-treatment differences in total nasal plus non-nasal symptom scores and total nasal symptom scores remained significant for all subsequent hourly assessments through 12 hours post-dose. Patient assessments of overall response to therapy at end point were significantly different between treatment groups (p < 0.01) with 60.5% of MFNS-treated patients reporting complete, marked, or moderate relief compared with 46.5% of placebo-treated patients. Mometasone furoate nasal spray produces a statistically significant improvement in nasal symptom scores in patients with SAR by 7 hours after administration of a single 200 micrograms dose (100 micrograms in each nostril).

Administration, Topical↗
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Regulation of gadd153 mRNA expression by hypoxia in pulmonary artery smooth muscle cells.

Hypoxia causes pulmonary hypertension and induces oxygen radicals in pulmonary artery smooth muscle cells (PASMCs). Since oxidative stress regulates gaddl53 expression, we examined gaddl53 mRNA in PASMCs cultured in a hypoxic environment. Gadd153 mRNA content was increased in PASMCs cultured for 24 hours in 1% oxygen. This increase was not abrogated by inhibition of protein synthesis. To explore the signaling pathways mediating hypoxic regulation of gaddl53 mRNA, the impact of calcium channel blockade by verapamil, G protein inhibition by pertussis toxin, and protein kinase C (PKC) down-regulation, was examined. Although none of these interventions reduced basal expression of gaddl53 mRNA in PASMCs, all of them suppressed the induction by hypoxia. In contrast, antioxidants had no effect. These observations indicate hypoxia induces gaddl53 expression in PASMCs through common signaling pathways.

Animals↗
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Pharmacokinetic procedures for the estimation of organ clearances for the formation of short-lived metabolites. Acetaminophen-induced glutathione depletion in hamster liver.

Several approaches have been developed to estimate in vivo the intrinsic clearances of enzymes that catalyze the formation of chemically reactive metabolites that do not escape the organs in which they are formed. Two basic models are considered. Model 1 is a general model in which the chemically reactive metabolite is inactivated by a combination of a pseudo-first order reaction, such as a reaction with large pools of protein, and a second order reaction with a depletable endogenous substance, such as glutathione or an enzyme. Model 2 is a special case, in which at low doses of the parent compound the reactive metabolite preferentially reacts with a depletable endogenous substance, such as glutathione. In developing both models we have assumed that the rate of formation of reactive metabolite follows first order kinetics and that the concentration of reactive metabolite in liver reaches a steady state almost instantaneously. In developing Model 2 we also have assumed that the depletion of hepatic reduced glutathione is due solely to the formation of glutathione conjugates. The uses of the approaches based on Model 2 were illustrated by studying the effects of a marginally toxic dose of acetaminophen on the depletion and subsequent repletion of hepatic glutathione in hamsters. From the calculated rate of synthesis of glutathione in liver, the fraction of the dose of acetaminophen converted to the glutathione conjugate in liver, and the clearance for the formation of glutathione conjugate in vivo was estimated and was found to be similar to that obtained with hepatic 9,000 g supernatant preparations. Other uses of the models are described.

Acetaminophen↗
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Inflammatory pseudotumor of the liver. Report of the fine needle aspiration cytologic findings in a case initially misdiagnosed as malignant.

The fine needle aspiration (FNA) cytologic features are described in a case of inflammatory pseudotumor of the liver (xanthogranuloma), a disease generally regarded as of unknown etiology. The initial FNA findings were those of an acute exudative process, with atypical biliary duct epithelium and hepatocytes. These were interpreted as verifying the radiologic impression of a malignancy. Histologic study of subsequently resected nodules revealed the true nature of the case. As the lesion evolved, granulomatous inflammation supervened, characterized by numerous foamy histiocytes and lesser populations of plasma cells and lymphocytes. Numerous gram-positive cocci were readily demonstrated, suggesting that the lesion was an unusual tissue response to an intrahepatic bacterial infection. The lesion eventually resolved with prolonged antibiotic therapy.

Biopsy, Needle↗
PubMedDate not supplied

Analysis of tear fluid by CE/LIF: a noninvasive approach for glucose monitoring.

Nanoliter volumes of human tear fluid were collected by means of a capillary tube without inducing tearing and were analyzed for glucose content. The tear fluid was subjected to two enzymatic reactions to generate a fluorescent compound that is proportional to the concentration of glucose in the sample. CE with laser-induced fluorescence (LIF) detection was used to monitor the fluorescent species generated, hence glucose in the tear samples. The reproducibility of the method for six different preparations was < 9% relative standard deviation (RSD). The procedure was compared with the glucose dehydrogenase method for the determination of glucose in blood before using it to determine glucose in tear fluid. Blood and tear samples were collected from six healthy human subjects. The results showed that the higher glucose content in tear samples is consistent with the higher glucose content in blood samples. The glucose concentration of the tear samples analyzed ranged from 128 to 166 microM, and that of blood ranged from 3.3 to 4.3 mM.

Blood Glucose↗