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Biomedical subjects

M Wheeler

Publications and source records attributed to M Wheeler.

At least 19 recordsLinked to original sources
PubMed2000

The Fort McMurray Demonstration Project in Social Marketing: theory, design, and evaluation.

CONTEXT: The Fort McMurray Demonstration Project in Social Marketing is a multifaceted program that applies the techniques of social marketing to health and safety. This paper describes the origins of the project and the principles on which it was based. VENUE: Fort McMurray, in the province of Alberta, Canada, was selected because the community had several community initiatives already underway and the project had the opportunity to demonstrate "value added." CONCEPT: The project is distinguished from others by a model that attempts to achieve mutually reinforcing effects from social marketing in the community as a whole and from workplace safety promotion in particular. DESIGN: Specific interventions sponsored by the project include a media campaign on cable television, public activities in local schools, a community safety audit, and media appearance by a mascot that provides visual identity to the project, a dinosaur named "Safetysaurus." The project integrated its activities with other community initiatives. MAIN OUTCOME MEASURES: The evaluation component emphasizes outcome measures. A final evaluation based on injury rates and attitudinal surveys is underway. RESULTS: Baseline data from the first round of surveys have been compiled and published. In 1995, Fort McMurray became the first city in North America to be given membership in the World Health Organization's Safe Community Network.

Adult↗
PubMed2000

Glycine-gated chloride channels in neutrophils attenuate calcium influx and superoxide production.

Recently, it was demonstrated that liver injury and TNF-alpha production as a result of endotoxin (lipopolysaccharide, LPS) were attenuated by feeding animals a diet enriched with glycine. This phenomenon was shown to be a result of, at least in part, activation of a chloride channel in Kupffer cells by glycine, which hyperpolarizes the cell membrane and blunts increases in intracellular calcium concentrations ([Ca(2+)](i)) similar to its action in the neuron. It is well known that hepatotoxicity due to LPS has a neutrophil-mediated component and that activation of neutrophils is dependent on increases in [Ca(2+)](i). Therefore, the purpose of this study was to determine if glycine affected agonist-induced increases in [Ca(2+)](i) in rat neutrophils. The effect of glycine on increases in [Ca(2+)](i) elicited either by the bacterial-derived peptide formyl-methionine-leucine-phenylalanine (FMLP) or LPS was studied in individual neutrophils using Fura-2 and fluorescence microscopy. Both FMLP and LPS caused dose-dependent increases in [Ca(2+)](i), which were maximal at 1 microM FMLP and 100 microgram/ml LPS, respectively. LPS increased intracellular calcium in the presence and absence of extracellular calcium. Glycine blunted increases in [Ca(2+)](i) in a dose-dependent manner with an IC(50) of approximately 0.3 mM, values only slightly higher than plasma levels. Glycine was unable to prevent agonist-induced increases in [Ca(2+)](i) in chloride-free buffer. Moreover, strychnine (1 microM), an antagonist of the glycine-gated chloride channel in the central nervous system, reversed the effects of glycine (1 mM) on FMLP- or LPS-stimulated increases in [Ca(2+)](i). To provide hard evidence for a glycine-gated chloride channel in the neutrophil, the effect of glycine on radioactive chloride uptake was determined. Glycine caused a dose-dependent increase in chloride uptake into neutrophils with an ED(50) of approximately 0.4 mM, an effect also prevented by 1 microM strychnine. Glycine also significantly reduced the production of superoxide anion from FMLP-stimulated neutrophils. Taken together, these data provide clear evidence that neutrophils contain a glycine-gated chloride channel that can attenuate increases in [Ca(2+)](i) and diminish oxidant production by this important leukocyte.

Animals↗
PubMed2000

Biosynthesis and functions of melanin in Sporothrix schenckii.

Sporothrix schenckii is a human pathogen that causes sporotrichosis, an important cutaneous mycosis with a worldwide distribution. It produces dark-brown conidia, which infect the host. We found that S. schenckii synthesizes melanin via the 1,8-dihydroxynaphthalene pentaketide pathway. Melanin biosynthesis in the wild type was inhibited by tricyclazole, and colonies of the fungus were reddish brown instead of black on tricyclazole-amended medium. Two melanin-deficient mutant strains were analyzed in this study: an albino that produced normal-appearing melanin on scytalone-amended medium and a reddish brown mutant that accumulated and extruded melanin metabolites into its medium. Scytalone and flaviolin obtained from cultures of the reddish brown mutant were identified by thin-layer chromatography, high-performance liquid chromatography, and UV spectra. Transmission electron microscopy showed an electron-dense granular material believed to be melanin in wild-type conidial cell walls, and this was absent in conidial walls of the albino mutant unless the albino was grown on a scytalone-amended medium. Melanized cells of wild-type S. schenckii and the albino grown on scytalone-amended medium were less susceptible to killing by chemically generated oxygen- and nitrogen-derived radicals and by UV light than were conidia of the mutant strains. Melanized conidia of the wild type and the scytalone-treated albino were also more resistant to phagocytosis and killing by human monocytes and murine macrophages than were unmelanized conidia of the two mutants. These results demonstrate that melanin protects S. schenckii against certain oxidative antimicrobial compounds and against attack by macrophages.

Adult↗
PubMed1999

Preoperative pregnancy testing in a tertiary care children's hospital: a medico-legal conundrum.

STUDY OBJECTIVES: To track physician and nursing practice regarding preoperative pregnancy screening and testing in a setting where testing is the established policy. DESIGN: Prospective study. SETTING: University-affiliated, urban, tertiary care pediatric hospital. PATIENTS: 261 menarcheal patients, aged 10 to 34 years, presenting for ambulatory surgery in a 15-month period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 235 routine pregnancy tests performed, three were positive (1.3%). All patients denied the possibility of pregnancy; all reported last menstrual period less than 3 weeks prior to their scheduled surgery. Two of the three patients whose pregnancy tests were positive were adults. Only two study patients were unsure about the possibility of pregnancy; both patients tested negative. No patient younger than 15 years tested positive (0 of 107). History was an unreliable marker for pregnancy. CONCLUSIONS: Medical history alone may be an unreliable marker for ruling out pregnancy in patients presenting for outpatient surgery in an urban pediatric hospital. The policy for preoperative pregnancy screening adopted by a hospital or health care facility should be predicated on the principle of "best interest of the patient." Considerations must include local law, ethical responsibility, and the balance between cost and risk based on the best and most current scientific information.

Adolescent↗
PubMed1999

A grouping interpretation of the modality effect in immediate probed recognition.

In a series of experiments on immediate probed recognition for eight 3-digit numbers, it was shown that if the target modality involved auditory components and the effect of the similarity of the modality of the probe to that of the targets was controlled, unequivocal evidence was obtained for an auditory superiority effect (modality effect) for hit rates for the final items of the list. Moreover, false-alarm rates were significantly lower following targets with an auditory component than they were following silently seen targets. It is argued that this pattern of hits and false alarms is consistent with the idea that targets that have an auditory component yield memory representations that are better grouped as units than are those for targets that are only silently seen; in particular, if a new probe has a first digit that accidentally matches the first digit of a target item, it is more likely that the subject will mistakenly identify this new probe as old (give a false alarm) if the target has only been partially encoded because it was only silently seen.

Auditory Perception↗
PubMed1999

Home and laboratory pregnancy-testing kits.

Home pregnancy test kits are more sensitive than many pregnancy kits used in laboratories or health centres. Nurses should know the sensitivity of the kit used in their centre or laboratory. A positive home pregnancy test should always be treated as the correct result until sufficient tests have been carried out to prove otherwise.

Female↗
PubMed1998

Insulin-like growth factor-I and bone mineral density.

To assess the relationship between insulin-like growth factor-I (IGF-I) and bone mineral density (BMD) 201 healthy postmenopausal women (age 41-68 years) within 10 years of menopause were studied. In all subjects, BMD at the lumbar spine and left hip were measured using dual-energy X-ray absorptiometry and blood samples were obtained. In all subjects, serum IGF-I and parathyroid hormone (PTH) were measured. In a subgroup of these subjects serum concentrations of IGF-binding protein-3 (IGFBP-3), osteocalcin (OC), bone-specific alkaline phosphatase (BALP), tartrate-resistant acid phosphatase (TRAP), and carboxyterminal propeptide of type I procollagen (PICP) were also measured. Serum IGF-I correlated significantly with age (r = -0.159, p = 0.0241), serum OC (r = 0.226, p = 0.0131), BALP (r = 0.259, p < 0.0001), and TRAP (r = 0.261, p < 0.0015), but not with PICP, PTH, or BMD at any site. Although there was a strong correlation between IGF-I and IGFBP-3 (r = 0.559, p < 0.0001), there was no correlation between IGFBP-3 and any of the markers of bone turnover (OC, BALP, TRAP, or PICP) nor with PTH or BMD at any site. We conclude that IGF-I and markers of bone turnover are related, but there is no relationship between IGF-I and BMD.

Absorptiometry, Photon↗
PubMed1998

Premedication of pediatric tonsillectomy patients with oral transmucosal fentanyl citrate.

UNLABELLED: We assessed the safety and efficacy of oral transmucosal fentanyl citrate (Fentanyl Oralet; Abbott Laboratories, Abbott Park, IL), administered preoperatively to provide both preoperative sedation and postoperative analgesia, in a randomized, double-blind, placebo-controlled study in 40 children, 2-10 yr of age, scheduled for tonsillectomy. In the preoperative holding area, one group (Group O) received Fentanyl Oralet (fentanyl 10-15 micrograms/kg), and the other (Group IV) received only the candy matrix. Patients in Group O received an i.v. injection of saline, and those in Group IV received an i.v. injection of fentanyl (2 micrograms/kg) after removal of the first tonsil. Except for the opioid, patients received a standard anesthetic. Preoperative sedation and cooperation were assessed. Postoperative pain was evaluated using an objective pain scale. Patients in Group O were more sedated but no more cooperative at the induction of anesthesia compared with those in Group IV. No patient vomited preoperatively or experienced preoperative or postoperative desaturation. Time to postanesthesia care unit (PACU) discharge was not different between groups. There was no significant difference in the number of patients requiring morphine in the PACU (6 of 21 in Group O versus 10 of 19 in Group IV). Plasma fentanyl concentrations were not a reliable indicator of the need for postoperative morphine. Among the patients who required morphine postoperatively, there was an 11-fold variation in plasma fentanyl concentrations at the time of morphine administration. Derived pharmacokinetic parameters were similar to those previously reported in children; bioavailability of the fentanyl in Fentanyl Oralet was 0.33. We conclude that premedication with Fentanyl Oralet did not differ with i.v. fentanyl in regard to the induction of anesthesia and postoperative analgesia. IMPLICATIONS: In this double-blind, randomized study, we studied the efficacy of Fentanyl Oralet (10-15 micrograms/kg) preoperatively for providing postoperative analgesia in children undergoing tonsillectomy. We found no incidence of preoperative desaturation or vomiting in any patient. This is in contrast to other studies, in which there was a longer time interval between Fentanyl Oralet completion and induction of anesthesia. The bio-availability of the fentanyl in Fentanyl Oralet was estimated to be 33%, which is less than that reported in adults (approximately 50%). There was no difference in postoperative opioid requirements between patients who received 2 micrograms/kg of fentanyl i.v. and those who received Fentanyl Oralet.

Administration, Oral↗
PubMed1998

A bronchoscopic, computer-assisted examination of the changes in dimension of the infant tracheal lumen with changes in head position: implications for emergency airway management.

BACKGROUND: Resuscitation guidelines caution against extreme extension or flexion of an infant's head because tracheal obstruction may occur. No data support this recommendation. The authors therefore examined the dimensions of the tracheal lumen in neutral, extended, and flexed head positions in infants undergoing general endotracheal anesthesia for elective surgery. METHODS: Eighteen healthy full-term infants were studied. A flexible fiberoptic bronchoscope was passed through a previously inserted endotracheal tube and positioned above the cricoid cartilage. Video recordings were taken in each of three head positions. Recordings were analyzed by an investigator blinded to head position. A computer-digitized technique was used to measure anterior-posterior and lateral dimensions and cross-sectional area. Data were analyzed using paired t tests and sign tests. RESULTS: No significant differences in mean tracheal dimensions with changes in head position were found. No infant had complete tracheal obstruction. Infants were equally as likely to have a small increase as they were to have a small decrease in tracheal dimension with changes in head position. CONCLUSIONS: Despite the belief that infants and neonates have obstruction at the level of the trachea with extreme positions of the head, the authors were unable to demonstrate this phenomenon.

Airway Obstruction↗
PubMed1998

Alleles of the cholesterol 7 alpha-hydroxylase (CYP7) gene in pigs selected for high or low plasma total cholesterol.

Crossbred pigs were selected for high (HTC) or low (LTC) plasma total cholesterol (TC). Pigs from the seventh (n = 51) and eighth (n = 92) generations were used to determine restriction fragment length polymorphisms (RFLP). Using TaqI restriction enzyme digestion, the frequencies of two alleles (2.8- or 5.0-kb fragments) of the cholesterol 7 alpha-hydroxylase (CYP7) gene were determined in the two populations as a potential indicator of TC concentration at 8 weeks of age. Only the 2.8-kb fragment allele was present in the 26 HTC pigs tested in Generation 7. In the LTC pigs both the 2.8- and 5.0-kb alleles were present in 12 pigs, and only the 5.0-kb allele was present in 13 pigs. The allele frequencies of the 2.8 and 5.0 fragments, respectively, were .26 and .74 in LTC pigs and 1.00 and 0 in HTC pigs. There was an association (P < .001) between the 5.0- and 2.8-kb CYP7 alleles, respectively, and low and high TC concentrations. In Generation 8, all HTC pigs were homozygous for the 2.8-kb allele. The 5.0 kb allele was present in all LTC pigs tested and was homozygous in 57% of LTC pigs. Mean plasma TC was 105.0 mg/dl in 30 pigs homozygous for the 2.8-kb allele in Generation 8; means for LTC pigs were 53.5 and 60.4 mg/dl in 35 pigs homozygous for the 5.0-kb allele and in 27 heterozygous pigs, respectively. High TC was associated with the presence of the 2.8-kb allele, and low TC was associated with the presence of the 5.0-kb allele in both Generations 7 and 8. We conclude that TaqI RFLP analysis of the CYP7 gene is a reliable indicator for TC in these swine.

Alleles↗
PubMed1997

Carboxyfullerenes as neuroprotective agents.

Two regioisomers with C3 or D3 symmetry of water-soluble carboxylic acid C60 derivatives, containing three malonic acid groups per molecule, were synthesized and found to be equipotent free radical scavengers in solution as assessed by EPR analysis. Both compounds also inhibited the excitotoxic death of cultured cortical neurons induced by exposure to N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or oxygen-glucose deprivation, but the C3 regioisomer was more effective than the D3 regioisomer, possibly reflecting its polar nature and attendant greater ability to enter lipid membranes. At 100 microM, the C3 derivative fully blocked even rapidly triggered, NMDA receptor-mediated toxicity, a form of toxicity with limited sensitivity to all other classes of free radical scavengers we have tested. The C3 derivative also reduced apoptotic neuronal death induced by either serum deprivation or exposure to Abeta1-42 protein. Furthermore, continuous infusion of the C3 derivative in a transgenic mouse carrying the human mutant (G93A) superoxide dismutase gene responsible for a form of familial amyotrophic lateral sclerosis, delayed both death and functional deterioration. These data suggest that polar carboxylic acid C60 derivatives may have attractive therapeutic properties in several acute or chronic neurodegenerative diseases.

Animals↗
PubMed1997

Muscarinic receptor subtypes and receptor-coupled phosphatidylinositol hydrolysis in rat bladder smooth muscle.

BACKGROUND: The purpose of this study was to evaluate the muscarinic receptor subtypes expressed in rat bladder smooth muscle and characterize the muscarinic receptor-coupled phosphatidylinositol (PI) hydrolysis in order to clarify the first step of bladder smooth muscle contraction. METHODS: Expressions of mRNAs of muscarinic receptor subtypes were examined by Northern blot analysis. Changes in the mass of inositol 1,4,5-trisphosphate (IP3) and the inhibitory effects of muscarinic subtype specific antagonists on PI hydrolysis were determined after carbachol stimulation. RESULTS: mRNAs of m2 and m3 genes, encoding M2 and M3 receptors, were expressed in rat bladder smooth muscle. Carbachol produced a rapid increase of IP3, which returned to the basal level within 30 seconds. 4-Diphenylacetoxyl-N-methylpiperidine methiodide (4-DAMP; M1 and M3 antagonist) strongly inhibited the PI hydrolysis, but methoctramine (M2 antagonist) partially inhibited it at 10(-4) mol/L. The IC50 value for atropine was 9.5 x 10(-9) mol/L, for pirenzepine 6.4 x 10(-6) mol/L, and for 4-DAMP 1.5 x 10(-7) mol/L. CONCLUSION: M2 and M3 receptors are expressed in rat urinary bladder. Only M3 receptor was involved in the production of IP3, which might induce the initial phase of contractile response in rat bladder smooth muscle after carbachol stimulation.

Animals↗
PubMed1997

Studies of melatonin effects on epithelia using the human embryonic kidney-293 (HEK-293) cell line.

The expression of melatonin receptors (MR) of the Mel1a subtype in basolateral membrane of guinea pig kidney proximal tubule suggests that melatonin plays a role in regulating epithelial functions. To investigate the cellular basis of melatonin action on epithelia, we sought to establish an appropriate in vitro culture model. Epithelial cell lines originating from kidneys of dog (MDCK), pig (LLC-PK1), opossum (OK), and human embryo (HEK-293) were each tested for the presence of MR using 2-[125I]iodomelatonin (125I-MEL) as a radioligand. The HEK-293 cell line exhibited the highest specific 125I-MEL binding. By intermediate filament characterization, the HEK-293 cells were determined to be of epithelial origin. Binding of 125I-MEL in HEK-293 cells demonstrated saturability, reversibility, and high specificity with an equilibrium dissociation constant (Kd) value of 23.8 +/- 0.5 pM and a maximum number of binding sites (Bmax) value of 1.17 +/- 0.11 fmol/mg protein (n = 5), which are comparable with the reported Kd and Bmax values in human kidney cortex. Coincubation with GTPgammaS (10 microM) and pertussis toxin (100 ng/ml) provoked a marked decrease in binding affinity (Kd was increased by a factor of 1.5-2.0), with no significant difference in Bmax. Melatonin (1 microM) decreased the forskolin (10 microM) stimulated cAMP level by 50%. HEK-293 cells do not express dopamine D1A receptor. Following transient transfection of HEK-293 cells with human dopamine D1A receptor (hD1A-R), exposure of the cells to dopamine stimulated an increase in the level of cAMP. Similarly, transient transfection of HEK-293 cells with rat glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and PTH type 1 receptors, each resulted in an hormone inducible increase in cAMP levels. Surprisingly, only the stimulatory effect of dopamine could be inhibited by exposure to melatonin. The inhibitory effect of melatonin on dopamine D1-induced increase in cAMP was completely inhibited by pertussis toxin (100 ng/ml, 18 h). Immunoblot and immunocytochemical studies were carried out using two polyclonal antibodies raised against the extra and cytoplasmic domains of Mel1a receptor. Immunoblot studies using antibody against the cytoplasmic domain of Mel1a receptor confirmed the presence of a peptide blockable 37 kDa band in HEK-293 cells. Indirect immunofluorescent studies with both antibodies revealed staining predominantly at the cell surface, but staining with the antibody directed against the cytoplasmic domain required prior cell permeabilization. By RT-PCR, HEK-293 cells express both Mel1a and Mel1b messenger RNAs, but the messenger RNA level for Mel1b is several orders of magnitude lower than for Mel1a. We conclude that HEK-293 cells express MR predominantly of the Mel1a subtype. Our evidence suggests that one of the ways that melatonin exerts its biological function is through modulation of cellular dopaminergic responses.

Animals↗