Search PubMed⌕ Search

Biomedical subjects

K M Olsen

Publications and source records attributed to K M Olsen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Evidence on the origin of cassava: phylogeography of Manihot esculenta.

Cassava (Manihot esculenta subsp. esculenta) is a staple crop with great economic importance worldwide, yet its evolutionary and geographical origins have remained unresolved and controversial. We have investigated this crop's domestication in a phylogeographic study based on the single-copy nuclear gene glyceraldehyde 3-phosphate dehydrogenase (G3pdh). The G3pdh locus provides high levels of noncoding sequence variation in cassava and its wild relatives, with 28 haplotypes identified among 212 individuals (424 alleles) examined. These data represent one of the first uses of a single-copy nuclear gene in a plant phylogeographic study and yield several important insights into cassava's evolutionary origin: (i) cassava was likely domesticated from wild M. esculenta populations along the southern border of the Amazon basin; (ii) the crop does not seem to be derived from several progenitor species, as previously proposed; and (iii) cassava does not share haplotypes with Manihot pruinosa, a closely related, potentially hybridizing species. These findings provide the clearest picture to date on cassava's origin. When considered in a genealogical context, relationships among the G3pdh haplotypes are incongruent with taxonomic boundaries, both within M. esculenta and at the interspecific level; this incongruence is probably a result of lineage sorting among these recently diverged taxa. Although phylogeographic studies in animals have provided many new evolutionary insights, application of phylogeography in plants has been hampered by difficulty in obtaining phylogenetically informative intraspecific variation. This study demonstrates that single-copy nuclear genes can provide a useful source of informative variation in plants.

Biological Evolution↗
PubMed1999

Effect of omeprazole, lansoprazole, and ranitidine on the DNA synthesis of mononuclear cells.

OBJECTIVE: To examine and compare the effects of omeprazole, lansoprazole, and ranitidine on the DNA synthesis of peripheral blood mononuclear cells. DESIGN: Ex vivo laboratory study. SETTING: Clinical research laboratory of an academic medical center. SUBJECTS: Healthy volunteers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Venous blood was collected from normal subjects and peripheral blood mononuclear cells (PBMCs) were isolated using centrifugation techniques over a Ficoll-Hypaque density gradient. PBMCs were added to 12-well culture plates in four groups of media: a) control; b) control plus lansoprazole (25 microg/mL); c) control plus omeprazole (0.35 microg/mL); and d) control plus ranitidine (50 microg/mL). PBMCs were exposed to the drug for 96 hrs, with addition of phytohemagglutinin (2.5 microg/ mL) for the last 48 hrs, and 3H-thymidine (1 microCi) during the final 6 hrs. PBMCs were filtered onto glass-fiber filter paper and the radioactivity was determined by scintillation counting. Since radioactivity is measured only in those cells undergoing DNA synthesis or cell division, results are expressed as quantification of 3H-thymidine uptake. Median disintegrations per min (DPM)/number of PBMCs per well+/-SEM are reported: control 68.3+/-37.8; ranitidine 38.4 +/-94.2; lansoprazole 14.6+/-84.4; and omeprazole 15.1+/-48.9. There was a significant difference between lansoprazole vs. ranitidine (p< .01), and omeprazole vs. ranitidine (p< .05), and no significant difference between lansoprazole and omeprazole. CONCLUSIONS: This is the first study to compare the potential immunomodulating effects of these commonly used agents. Ranitidine caused increased DNA synthesis in PBMCs when compared with lansoprazole and omeprazole. This phenomenon may be an important, often disregarded, effect of histamine-2-receptor antagonists when used in postsurgical or trauma patients who have T-lymphocyte-mediated immune suppression.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Antimicrobial activities and postantibiotic effects of clarithromycin, 14-hydroxy-clarithromycin, and azithromycin in epithelial cell lining fluid against clinical isolates of haemophilus influenzae and Streptococcus pneumoniae.

The antimicrobial activity of concentrations of selected macrolides found in epithelial cell lining fluid was investigated. Clarithromycin demonstrated greater potency and a significantly longer postantibiotic effect (PAE) than azithromycin against Streptococcus pneumoniae. Azithromycin displayed greater potency, faster killing, and a longer PAE than clarithromycin against Haemophilus influenzae. Drug concentrations in epithelial cell lining fluid similar to those found in tissue did not improve the synergistic potential of 14-hydroxy-clarithromycin and indicate that a maximal PAE may exist despite increasing concentrations of drug.

Anti-Bacterial Agents↗
PubMed1999

Ethanol feeding does not affect the efficacy or pharmacokinetics of azithromycin, trovafloxacin, or ceftriaxone in a rat model of pneumococcal pneumonia.

A rat model of ethanol feeding was used to study the effects of ethanol on antibiotic therapy of pneumococcal pneumonia. Male Sprague-Dawley rats (150 g) received a liquid diet containing 36% of total calories as ethanol. Controls were pair-fed a liquid diet without ethanol or received rat chow. Diets began 7 days pre- and continued postinfection. Rats were infected transtracheally with type 3 Streptococcus pneumoniae and then treated with azithromycin (50 mg/kg), trovafloxacin (50 mg/kg), or ceftriaxone (100 mg/kg) injected subcutaneously twice daily for 5 days. Antibiotic levels in serum, lung cells, and lavage fluid were measured by HPLC. Ethanol- and pair-fed rats had depressed baseline peripheral neutrophil counts but were able to generate adequate numbers of peripheral and pulmonary polymorphonuclear leukocytes early in the course of their infection. Ethanol feeding did not alter the pharmacokinetics of azithromycin, trovafloxacin, or ceftriaxone. All three antibiotics were equally effective in curing experimental pneumococcal pneumonia, and survival rates were similar in treated ethanol-fed and control rats.

Animals↗
PubMed1996

Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses.

The intrapulmonary pharmacokinetics of oral azithromycin were studied in 25 healthy volunteers, each of whom received an initial dose of 500 mg and then 250 mg once daily for four additional doses. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed 4, 28, 76, 124, 172, 244, 340, and 508 h after the first dose was administered. Azithromycin concentrations in epithelial lining fluid (ELF), alveolar macrophages, peripheral blood monocytes, and serum were measured by high-performance liquid chromatography. Azithromycin was extensively concentrated in cells and ELF. Drug concentrations in AMs (peak mean +/- standard deviation, 464 +/- 65 micrograms/ml) exceeded 80 micrograms/ml up to 508 h (21 days) following the first dose, while concentrations in PBMs (peak, 124 +/- 28 micrograms/ml) exceeded 20 micrograms/ml up to 340 h (14 days). Azithromycin concentrations in ELF peaked at 124 h (3.12 +/- 0.93 micrograms/ml) and were detectable up to 172 h (7 days), when they were 20 times the concurrent serum concentrations. Although the clinical significance of antibiotic concentrations in these compartments is nuclear, the sustained lung tissue penetration and extensive phagocytic accumulation demonstrated in this study support the proven efficacy of azithromycin administered on a 5-day dosage schedule in the treatment of extracellular or intracellular pulmonary infections.

Adult↗
PubMed1995

Glyburide protein binding and the effect of albumin glycation in children, young adults, and older adults with diabetes.

Because glyburide is a weak acid that is more than 98% bound to albumin, the authors evaluated the binding in vitro and the influence of albumin glycation in children, young adults, and older adults with diabetes mellitus. Glyburide binding to non-glycated albumin was greater than 98%, and remained constant over a total concentration range of 50 to 1000 ng/mL. Increasing the albumin concentration from 0.5 to 5.0 g/dL was logarithmically related to the free fraction of glyburide. After the in vitro glycation of albumin (range, 5.7-15.6%), mean (+/- SD) glyburide binding was 99.05 +/- 0.082%, a value in agreement with that obtained from control serum. Serum samples from 57 subjects with type I and 16 patients with type II diabetes were incubated with 300 ng/mL of unlabeled glyburide and 200 ng/mL of 14C-glyburide. The extent of albumin glycation varied from 5 to 22% for the type I subjects and 5 to 14% for the type II subjects. The free fraction from these groups ranged from 1.07 to 1.75% and 0.66 to 0.88% for the type I and type II subjects, respectively. Although these values did not differ significantly from those of the control samples, the glyburide free fraction in patients with type I diabetes (1.39 +/- 0.85%) was significantly greater than that found for the 16 elderly patients with type II diabetes (0.78 +/- 0.05%). A significant linear relationship was not found between glyburide free fraction and the degree of albumin glycation for either group. Glyburide protein binding did not appear to be influenced by the extent of albumin glycation.

Adolescent↗
PubMed1995

Comparison of fluid volumes with whole bowel irrigation in a simulated overdose of ibuprofen.

OBJECTIVE: To determine the effect of 2 different fluid volumes of polyethylene glycol whole bowel irrigation (WBI) solution on absorption of an ingested toxin in a simulated overdose model. DESIGN: Prospective, randomized, crossover trial. SETTING: Clinical research unit. PARTICIPANTS: Nine adult men. INTERVENTIONS: On 2 separate days, volunteers ingested approximately 75 mg/kg of ibuprofen. In treatment 1, 30 minutes after ingestion of ibuprofen, a 3-L WBI at 2 L/h was begun. This procedure was repeated in treatment 2 with an 8-L. WBI administered at 2 L/h. Fourteen timed serum samples were collected prior to and after drug ingestion for a 24-hour period and analyzed for ibuprofen concentration. The peak serum concentration, time to peak concentration, total area under the serum concentration-time curve (AUC), clearance, and volume of distribution were compared. RESULTS: The mean +/- SD AUCs did not differ between the 3-L (1185.3 +/- 216.9 mg.h/L) and 8-L (1153.5 +/- 251.5 mg.h/L) treatments (p = 0.710). Time to peak serum concentration, peak serum concentration, clearance, and volume of distribution were comparable for the 2 treatments (p > 0.05). CONCLUSIONS: These data indicated that a total WBI volume of 3 L would be expected to perform as well as 8 L administered at the same rate. We recommend that further research define the optimal dose of WBI in acute ingestion of toxins.

Adult↗
PubMed1995

Measurement of serum isopropanol and the acetone metabolite by proton nuclear magnetic resonance: application to pharmacokinetic evaluation in a simulated overdose model.

The purpose of this investigation was to 1) compare the performance of proton nuclear magnetic resonance spectroscopy to gas chromatography head-space analysis in the measurement of serum isopropanol and its metabolite, acetone, obtained during a simulated overdose, and 2) compare pharmacokinetic parameters obtained using the two analytical techniques. Three healthy volunteers ingested 0.6 mL/kg of 70% isopropanol and blood samples were obtained at baseline, 0.16, 0.33, 0.66, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, and 24.0 hours post-ingestion. Resulting sera were analyzed by gas chromatography head-space analysis and proton nuclear magnetic resonance spectroscopy for determination of isopropanol and acetone concentrations. A correlation between concentrations quantitated by gas chromatography head-space analysis versus proton nuclear magnetic resonance spectroscopy was determined using linear regression. Pharmacokinetic disposition parameters were determined from serum concentration-time data and compared using analysis of variance. For isopropanol, the linear regression equation which describes the relationship between gas chromatography head-space analysis and proton nuclear magnetic resonance spectroscopy was y = 1.041x - 2.180 (r2 = 0.995, p < 0.0001); for acetone, y = 1.022x - 0.946 (r2 = 0.984, p < 0.0001). Pharmacokinetic disposition parameters derived from the two analytical methods were comparable. Proton nuclear magnetic resonance spectroscopy can be used to rapidly quantitate serum isopropanol and acetone concentrations in the same sample when gas chromatography head-space analysis is unavailable. Also, proton nuclear magnetic resonance spectroscopy can be used to follow serial serum concentrations during an ingestion for the purpose of pharmacokinetic analysis.

1-Propanol↗
PubMed1994

Safe administration of iron dextran to a patient who reacted to the test dose.

Parenteral iron therapy is infrequently required but generally well tolerated. We present a case in which intravenous iron dextran was successfully given to a patient who had an anaphylactoid reaction to the test dose. After pretreatment with methylprednisolone, diphenhydramine, ephedrine, and dextran 1, 2 g of iron dextran were safely given over several days; pretreatment was administered only on day 1. In the rare cases in which an anaphylactic agent must be given to a patient with a history of a life-threatening reaction to the agent, pretreatment along with slow escalation of dose may allow safe administration of the offending drug.

Aged↗
PubMed1994

Phenytoin and plasmapheresis: importance of sampling times and impact of obesity.

The effect of plasmapheresis (PP) on total and free phenytoin clearance is reported. An obese patient with the diagnosis of thrombotic thrombocytopenic purpura (TTP) was treated with PP. Twelve episodes of PP, having exchange volumes of 1.5-2.25 times the plasma volume with a mean +/- SD 7.7 +/- 0.8 L of plasma removed, were studied. A significant (p < 0.05) difference was observed with a mean change in plasma phenytoin concentrations from pre- to end-PP of 7.32 +/- 2.5 mg/L compared to 1.98 +/- 0.7 mg/L observed pre-PP to 1 h post-PP. These values corresponded to 48.4 +/- 11.6 and 15.0 +/- 6.7% decreases in phenytoin concentrations at the two aforementioned time periods. To prevent misinterpretation of plasma phenytoin concentrations, samples should not be obtained for at least 2 h after PP.

Blood Specimen Collection↗
PubMed1993

Comparison of the in vivo and in vitro nuclear magnetic resonance detection of trifluoromethyl penicillin V in rats.

Fluorine nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging were examined as noninvasive methods for characterizing antibiotic disposition and pharmacokinetics in vivo. For determination of their utility, a 19F surface coil was constructed and an m-(trifluoromethyl)-containing penicillin V analogue (LY242072; 1) was synthesized. Various concentrations of 1 were injected intravenously into anesthetized rats whose urethras were occluded. The animals were placed on the surface coil, which was tuned to 19F, and then into a 4.7-T, 33-cm bore instrument, in which in vivo measurements of 1 were made on urine excreted into the bladder. At sacrifice, the urine was collected, and antibiotic levels were determined in vitro by both HPLC and high-resolution NMR. The limit of detection of 1 by NMR was 0.7 mg/mL of urine. When compared with standard in vitro quantitative methods using current technology, quantitation by in vivo surface coil NMR is not precise. Magnetic resonance imaging was used to image the bladder at a 35-mm3 voxel resolution with datum collection times of approximately 1 h. The 19F surface coil was used successfully to spectroscopically locate xenobiotic fluorine in the rat thorax. 19F NMR may offer an opportunity for the noninvasive in vivo detection of the distribution of various classes of therapeutic compounds.

Animals↗
PubMed1993

Effect of culture conditions on mast cell eicosanoid synthesis.

When mast cells are grown in culture from mouse bone marrow cells, some cells are in suspension and some attach. The cells in suspension released leukotrienes and thromboxane when stimulated. Removal from the attached cells increased eicosanoid formation in the suspended cells two- to six-fold. The upregulation of arachidonic acid metabolism seemed to be due to an increase in phospholipase activity. The attached cells resembled macrophages in morphology, but stained positively for mast cells and produced PGD2 an arachidonic acid metabolite which is characteristic for mast cells. The attached cells did not synthesize eicosanoids when stimulated with IgE/antigen or A23187. Addition of arachidonic acid caused cyclooxygenase product formation but not leukotrienes. No 5-lipoxygenase was detected by immunoblot analysis. Lack of eicosanoid synthesis was, therefore, due to the loss of 5-lipoxygenase and phospholipase activity, while the cyclooxygenase was preserved. These experiments demonstrate that attachment of mast cells to plastic can significantly alter their eicosanoid metabolism.

Animals↗
PubMed1993

Potential drug interactions with H2-receptor antagonists in intensive care unit patients.

This study's objectives were to identify the incidence of potential histamine-2 receptor antagonist drug interactions in a population of critically ill patients and to identify those at greatest risk for drug interactions. A literature review was completed to identify medications documented to interact when administered concomitantly with histamine-2 receptor antagonists. Data were prospectively collected on 277 consecutive patients admitted into the cardiac care units, medical intensive care units, and surgical intensive care units of two teaching hospitals. The mean age was 55 +/- 16.4 years and one or more organ insufficiency was identified in 52.7% of patients. At least one potential drug interaction was found in 81.6%, with an average of 1.57 potential interactions occurring per patient. Cardiac care unit and medical intensive care unit patients had significantly more potential interactions with drugs having narrow therapeutic indices (P < 0.03). Also, cardiac care unit patients received significantly more medications documented to interact with ranitidine alone or both cimetidine and ranitidine (P < 0.003). Patients admitted to an intensive care unit and receiving a histamine-2 receptor antagonist may require more frequent monitoring because of the potential for drug interactions.

Age Factors↗
PubMed1993

Stability of flumazenil with selected drugs in 5% dextrose injection.

The compatibility and stability of flumazenil mixed with aminophylline, dobutamine hydrochloride, dopamine hydrochloride, cimetidine hydrochloride, famotidine, ranitidine hydrochloride, heparin sodium, lidocaine hydrochloride, or procainamide hydrochloride were studied. Flumazenil (1.0 mg) was mixed with each of the other drugs in polyvinyl chloride minibags containing 50 mL of 5% dextrose injection to achieve concentrations commonly used when the drugs are administered by continuous i.v. infusion. All admixtures were analyzed for color change, pH, and particulate matter. Flumazenil concentrations were measured by a stability-indicating high-performance liquid chromatographic assay at baseline and 2, 4, 8, 12, and 24 hours after mixing. No detectable changes in color, pH, or particulate matter were observed. In the presence of each drug except dopamine hydrochloride, at least 95% of initial flumazenil concentration was present 24 hours after mixing. Flumazenil in the presence of dopamine hydrochloride was stable for 12 hours. Flumazenil was visually compatible and chemically stable when admixed with 5% dextrose injection and selected drugs.

Chemistry, Pharmaceutical↗
PubMed1992

Nicotine absorption after pulmonary instillation.

Levels of nicotine in plasma were determined by gas chromatography in eight mongrel dogs after instillation of 0.5 mg of nicotine in 100 microL of normal saline at three levels of the tracheobronchial tree: the trachea, a subsegmental bronchus of the right middle lobe, and a subpleural location of the right middle lobe ("distal"). An equivalent dose was given intravenously (iv). Peak of nicotine concentrations in plasma were significantly lower after instillation at the trachea (11.5 +/- 4.4 ng/mL) and the subsegmental bronchus (18.2 +/- 5.0 ng/mL) than after an iv dose (30.3 +/- 10.7 ng/mL); p < 0.05 for each comparison. In addition, the peak concentration after instillation at the trachea was significantly lower than that after instillation at the distal site (22.1 +/- 6.2 ng/mL, p < 0.05). Time to peak concentration was significantly longer after tracheal instillation (5.3 +/- 3.0 min) than after subsegmental instillation (2.0 +/- 0.0 min) or iv infusion (2.0 +/- 0.0 min); p < 0.05 for each comparison. Total drug absorbed, half-life, and clearance were equivalent from all four sites. This study demonstrated that quantitative absorption of nicotine from the described lung sites is equivalent to that after an iv dose, with slower absorption and lower peak concentrations from the tracheal site.

Absorption↗