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Biomedical subjects

R L Smith

Publications and source records attributed to R L Smith.

At least 253 records · Page 14Linked to original sources

Establishing intravenous access: a study of local anesthetic efficacy.

We performed a double-blind, randomized, prospective study to determine the local anesthetic that provided the best analgesia for insertion of an 18-gauge intravenous (i.v.) catheter and to determine whether alkalinization of lidocaine decreases the pain of intradermal injection. There were 280 healthy adult patients assigned randomly to seven different groups: benzyl alcohol 0.9% in normal saline, 2-chloroprocaine 3%, lidocaine 1%, lidocaine 1% with preservative, alkalinized lidocaine 1% with preservative, normal saline, and a control group that received i.v. catheter placement without previous drug injection. A 10-cm visual analog pain scale (VAPS) was used to obtain pain scores after pre-i.v. drug injection and after iv catheter insertion. Benzyl alcohol in normal saline (0.61 +/- 0.11) and alkalinized lidocaine (0.69 +/- 0.10) had the lowest mean pain scores for drug injection and these were significantly different from other drugs (P < 0.05). Alkalinized lidocaine (0.7 +/- 0.18) had the lowest mean pain score for i.v. catheter insertion with nothing (no previous drug injected) (3.47 +/- 0.38) and normal saline (3.97 +/- 0.18) had the highest mean pain scores (P < 0.05). We conclude that alkalinized lidocaine decreased the pain associated with its injection. Alkalinized lidocaine was the best local anesthetic for i.v. catheter placement. Benzyl alcohol in normal saline was also effective.

Adult↗

Fibroblast response to metallic debris in vitro. Enzyme induction cell proliferation, and toxicity.

Bovine synovial fibroblasts in primary monolayer culture were exposed to particulate metallic debris. The effects of the metallic particles on the synthesis and secretion of proteolytic enzymes and on cell proliferation and viability were examined. Uniform suspensions of titanium, titanium-aluminum, cobalt, and chromium particles, ranging in size from approximately 0.1 to ten micrometers (average, one to three micrometers), were prepared; the particle concentrations (the volume of particles divided by the total volume of the suspension) ranged from 0.0005 to 5 per cent. Aliquots of the particle suspensions were added to the synovial fibroblast cultures. The final particle concentrations in the media ranged from 0.0000083 to 0.83 per cent. After seventy-two hours of exposure, each medium was harvested and was assayed for proteolytic and collagenolytic activity and for hexosaminidase levels. Neutral metalloproteases, quantified by collagenolytic and caseinolytic (proteolytic) activity, represent enzymes, secreted by cells, that are capable of degrading extracellular matrix. Hexosaminidase is a marker for lysosomal enzyme activity that can include more than thirty enzymes, such as proteases, lipases, nucleases, and phosphatases. Cell proliferation was quantified by uptake of 3H-thymidine. Cell morphology was examined by scanning electron microscopy. Titanium, titanium-aluminum, and chromium significantly stimulated 3H-thymidine uptake at low particle concentrations (p < 0.01, p < 0.002, and p < 0.002, respectively). Exposure to cobalt, even at the lowest particle concentration, resulted in a significant decrease in thymidine uptake (p = 0.027). At the highest particle concentrations, all particles were toxic, as evidenced by the absence of thymidine uptake. At high particle concentrations, all of the metals caused a decrease in caseinolytic (proteolytic) and collagenolytic activity in the culture media. Titanium elevated the lysosomal enzyme marker, hexosaminidase, except at high concentrations. Chromium and titanium-aluminum had no significant effect on hexosaminidase at any particle concentration, while cobalt decreased all enzyme markers at mid-particle to high-particle concentrations. Scanning electron microscopy demonstrated that the morphological response of fibroblasts to titanium included membrane-ruffling and extension of filopodia, typical of active fibroblasts. In contrast, exposure to cobalt at the same concentration resulted in cell crenation, indicative of cell death.

Alloys↗

Collaboration and integration can protect sub-acute services. Interview by Donald E.L. Johnson.

An integrated system, from the perspective of Ronald L. Smith, president of Harris Methodist Health System in Fort Worth, Texas, is a system that combines financing, management, primary care, ambulatory care, pharmaceutic services, and home health care in all areas. In his interview by Donald E.L. Johnson, editor and publisher of Health Care Strategic Management, Smith believes that as hospital bottom lines get thinner and more difficult to obtain, there will need to be mergers and/or collaborations to minimize over-capacity in an area.

Attitude of Health Personnel↗

Pulmonary cryptococcosis mimicking methotrexate pneumonitis.

An 81-year-old man being treated with weekly low dose methotrexate (MTX) for psoriasis was admitted with a 2-month history of cough, shortness of breath and 7% eosinophilia in the peripheral blood. Chest roentgenogram revealed bilateral alveolar and interstitial infiltrates. Although the clinical presentation suggested MTX pneumonitis, a transbronchial lung biopsy established a diagnosis of pulmonary cryptococcosis. Pulmonary cryptococcosis should be included in the list of infectious processes that can mimic MTX pneumonitis.

Aged↗

Pulmonary function changes after large volume paracentesis.

Large volume paracentesis (LVP) is a safe, rapid, and effective treatment of ascites in cirrhotic patients. We investigated the effects of a 5-L aspiration of ascites on pulmonary function parameters in eight hemodynamically stable patients with cirrhosis and tense ascites. None had known lung disease or abnormal chest roentgenograms. At baseline, mean lung volumes, diffusing capacity, and arterial pO2 were all reduced from normal predicted values. Airflow, however, when related to lung volume, was normal. Post-LVP, lung volumes increased significantly; the mean expiratory reserve volume showed the greatest percent increase (105%) and correlated with the increases in the vital capacity, functional residual capacity, and total lung capacity. Airflow, the mean diffusing capacity, and arterial oxygenation were not significantly changed after LVP. We conclude that LVP significantly increases indices of lung volume but does not significantly alter parameters of airflow or gas exchange.

Ascites↗

Glycosaminoglycans inhibit Candida albicans adherence to extracellular matrix proteins.

The ability of Candida albicans to adhere to subendothelial extracellular matrix (ECM) may be important in the pathogenesis of disseminated candidiasis. ECM proteins, such as fibronectin, laminin, and types I and IV collagen bind C. albicans avidly. These proteins all possess heparin-binding domains. The influence of the glycosaminoglycans (GAGS) including heparin, heparan sulfate and dextran sulfate on C. albicans adherence to subendothelial ECM and ECM proteins was studied. It was demonstrated that the GAGS inhibited C. albicans adherence to ECM and ECM proteins. This possibly occurred by the GAGS binding to the ECM proteins and, in so doing, masking a preferred ligand for C. albicans adherence.

Binding Sites↗

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 9. The synthesis and biological evaluation of novel simvastatin analogs.

Substitution of hydroxy and hydroxyalkyl functionality at C-7 of the hexahydronaphthalene nucleus of simvastatin has provided novel analogs. The synthetic strategy employed epoxidation or Lewis acid-catalyzed aldol reaction of the 8-keto silyl enol ether as a key reactive intermediate. These analogs were evaluated as potential hypocholesterolemic agents via initial determination of their ability to inhibit HMG-CoA reductase in vitro. Oral activity of these compounds was determined in an acute rat model and a three-week study in cholestyramine-primed dogs. Compounds were identified that possessed in vitro and in vivo activity comparable to that of simvastatin.

Administration, Oral↗

4-substituted thiophene- and furan-2-sulfonamides as topical carbonic anhydrase inhibitors.

A series of 4-substituted thiophene- and furan-2-sulfonamides was prepared and was found to possess nanomolar-level potency for inhibition of human carbonic anhydrase II in vitro. Selected examples from this group were further evaluated for their potential to act as topically effective ocular hypotensive agents in the ocular normotensive albino rabbit and the ocular alpha-chymotrypsinized rabbit. Solubility studies in water and pH 7.4 buffer were carried out to estimate the ability of compounds to be formulated in solution. The sensitization potential of key representative structures was determined by in vitro glutathione reactivity studies and guinea pig maximization testing.

Animals↗

Cloning, primary sequence and chromosomal localization of human FMO2, a new member of the flavin-containing mono-oxygenase family.

We have previously reported the cloning of cDNAs for a flavin-containing mono-oxygenase (FMO) of man, designated FMO1 [Dolphin, Shephard, Povey, Palmer, Ziegler, Ayesh, Smith & Phillips (1991) J. Biol. Chem. 266, 12379-12385], that is the orthologue of pig and rabbit hepatic FMOs. We now describe the isolation and characterization of cDNA clones for a second human FMO, which we have designated FMO2. The polypeptide encoded by the cDNAs is 558 amino acid residues long, has a calculated M(r) of 63337, and contains putative FAD- and NADP-binding sites that align exactly with those described in other mammalian FMOs. Human FMO2 has 51-53% primary sequence identity with human FMO1, rabbit pulmonary FMO and rabbit liver FMO form 2, and thus represents a fourth, distinct, member of the mammalian FMO family. The corresponding mRNA is present in low abundance in adult human liver. Southern blot hybridization with single-exon probes demonstrated that human FMO2 and FMO1 are the products of single genes. The gene encoding FMO2 (designated FMO2) was mapped, by the polymerase chain reaction, to human chromosome 1, the same chromosome on which FMO1 is located.

Amino Acid Sequence↗

Thieno[2,3-b]furan-2-sulfonamides as topical carbonic anhydrase inhibitors.

Novel 5-[(alkylamino)methyl]thieno[2,3-b]furan-2-sulfonamides were prepared and evaluated in vitro for inhibition of human carbonic anhydrase II (CA II) and ex vivo for their ability to inhibit Ca II in the albino rabbit eye after topical administration. Compound 11a was found to lower intraocular pressure (IOP) in both the alpha-CT ocular hypertensive albino rabbit and the normal albino rabbit, but was ineffective at lowering IOP in a hypertensive, pigmented monkey model. Since 11a was highly bound to ocular pigment, a series of less basic analogs was prepared. Examples in this series were both less extensively bound to ocular pigment and more active at reducing IOP in pigmented rabbits after topical dosing. Key examples displayed moderate reactivity toward glutathione.

Administration, Topical↗

Necrotizing pneumonitis caused by 5-fluorouracil infusion. A complication of a Hickman catheter.

The authors report the case of a patient with a Hickman catheter that migrated into the lung parenchyma. The resultant inadvertent infusion of 5-fluorouracil caused necrotizing chemical pneumonitis. Possible mechanisms of catheter migration include the lateral orientation of the catheter tip and the partial thrombosis of the innominate vein and superior vena cava. The patient recovered but had residual contraction fibrosis of the right upper lobe of the lung.

Aged↗

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International System of Units↗

Rabbit knee immobilization: bone remodeling precedes cartilage degradation.

This study analyzed processes underlying osteoporosis and osteoarthrosis after short-term immobilization of the right hind limb of postadolescent (2.8 kg) and mature (4.0 kg) rabbits. After 3 weeks, the lateral posterior aspect of the lateral tibial plateau and the lateral femoral condyle of the immobilized limb exhibited prominent subchondral vascular eruptions. Femoral metaphyseal bone density decreased 27 and 18% in the immobilized limbs of postadolescent and mature rabbits, respectively. Calcein green fluorescence increased 1.9-fold (p less than 0.001) in the metaphyseal trabeculae of immobilized femurs. With immobilization, sulfate incorporation into femoral cartilage glycosaminoglycan increased, although total cartilage glycosaminoglycan and hydroxyproline levels were unchanged. Thymidine incorporation into DNA increased four- to fivefold in tibial and femoral cartilage of the immobilized limb. In this study, bone loss and remodeling preceded erosive cartilage degradation.

Animals↗