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Biomedical subjects

C E Fowler

Publications and source records attributed to C E Fowler.

4 recordsLinked to original sources

Coincident signalling between the Gi/Go-coupled delta-opioid receptor and the Gq-coupled m3 muscarinic receptor at the level of intracellular free calcium in SH-SY5Y cells.

In SH-SY5Y cells, activation of delta-opioid receptors with [D-Pen(2,5)]-enkephalin (DPDPE; 1 microM) did not alter the intracellular free Ca(2+) concentration [Ca(2+)](i). However, when DPDPE was applied during concomitant Gq-coupled m3 muscarinic receptor stimulation by carbachol or oxotremorine-M, it produced an elevation of [Ca(2+)](i). The DPDPE-evoked increase in [Ca(2+)](i) was abolished when the carbachol-sensitive intracellular Ca(2+) store was emptied. There was a marked difference between the concentration-response relationship for the elevation of [Ca(2+)](i) by carbachol (EC(50) 13 microM, Hill slope 1) and the concentration-response relationship for carbachol's permissive action in revealing the delta-opioid receptor-mediated elevation of [Ca(2+)] (EC(50) 0.7 mM; Hill slope 1.8). Sequestration of free G protein beta gamma dimers by transient transfection of cells with a beta gamma binding protein (residues 495-689 of the C terminal tail of G protein-coupled receptor kinase 2) reduced the ability of delta opioid receptor activation to elevate [Ca(2+)](i). However, DPDPE did not elevate either basal or oxotremorine-M-evoked inositol phosphate production indicating that delta-opioid receptor activation did not stimulate phospholipase C. Furthermore, delta-opioid receptor activation did not result in the reversal of muscarinic receptor desensitization, membrane hyperpolarization or stimulation of sphingosine kinase. There was no coincident signalling between the delta-opioid receptor and the lysophosphatidic acid receptor which couples to elevation of [Ca(2+)](i) in SH-SY5Y cells by a PLC-independent mechanism. In SH-SY5Y cells the coincident signalling between the endogenously expressed delta-opioid and m3 muscarinic receptors appears to occur in the receptor activation-Ca(2+) release signalling pathway at a step after the activation of phospholipase C.

Animals↗

Algorithm-based decision rules to safely reduce laboratory test ordering.

PURPOSE: Our study develops decision rules to define appropriate intervals at which repeat tests might be indicated for commonly ordered laboratory tests for hospitalized patients. METHODS: The final data set includes 5,632 adult patients admitted to the University of Virginia Hospital between July 1995 and December 1999. These patients had a hospital length of stay of five days or more and had results recorded for three routinely ordered laboratory tests for each of the first five days of their hospitalization. We use the serum potassium test to illustrate our algorithm-based decision rule methodology. RESULTS: Our decision rule begins with testing on the first two days of hospitalization and allows for repeat testing after observation of any non-normal values. The results show that the algorithm-based decision rule would lead to a 34% reduction for serum potassium tests for the first five days of hospitalization. Only one out of the 5,632 patients in our sample had a critical value that occurred only on a non-test day and, thus, was missed by the algorithm. CONCLUSIONS: The algorithm results are encouraging. We demonstrate that the number of tests can be reduced while missing critical values in only a small fraction of patients. Testing algorithms such as these can be used to reduce laboratory test ordering without compromising the quality of patient care.

Adult↗

MICs of rifampicin and chloramphenicol for mucoid Pseudomonas aeruginosa strains are lower when human lactoferrin is present.

MlCs of rifampicin and chloramphenicol for mucoid strains of Pseudomonas aeruginosa were lower in the presence of human lactoferrin (0.9 mg/mL, the concentration found in cystic fibrosis sputum) than in its absence. MICs for some strains were lowered to clinically achievable levels of the antibiotics, which is compatible with impressions of greater clinical efficacy in pseudomonas infections than would be predicted by standard sensitivity tests. The routine addition of lactoferrin to sensitivity media for testing of cystic fibrosis isolates may give more useful results than conventional tests as in-vivo conditions are more closely simulated.

Anti-Bacterial Agents↗