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Biomedical subjects

M Tierney

Publications and source records attributed to M Tierney.

At least 19 recordsLinked to original sources
PubMed2002

A DNA-based method for identification of krill species and its application to analysing the diet of marine vertebrate predators.

Accurate identification of species that are consumed by vertebrate predators is necessary for understanding marine food webs. Morphological methods for identifying prey components after consumption often fail to make accurate identifications of invertebrates because prey morphology becomes damaged during capture, ingestion and digestion. Another disadvantage of morphological methods for prey identification is that they often involve sampling procedures that are disruptive for the predator, such as stomach flushing or lethal collection. We have developed a DNA-based method for identifying species of krill (Crustacea: Malacostraca), an enormously abundant group of invertebrates that are directly consumed by many groups of marine vertebrates. The DNA-based approach allows identification of krill species present in samples of vertebrate stomach contents, vomit, and, more importantly, faeces. Utilizing samples of faeces from vertebrate predators minimizes the impact of dietary studies on the subject animals. We demonstrate our method first on samples of Adelie penguin (Pygoscelis adeliae) stomach contents, where DNA-based species identification can be confirmed by prey morphology. We then apply the method to faeces of Adelie penguins and to faeces of the endangered pygmy blue whale (Balaenoptera musculus brevicauda). In each of these cases, krill species consumed by the predators could be identified from their DNA present in faeces or stomach contents.

Animals↗
PubMed2000

Glial intranuclear inclusion bodies in a patient with Alzheimer's disease.

We report a case of dementia in an elderly woman with the pathological findings of Alzheimer's disease and numerous intranuclear inclusions in astrocytes and occasionally in neurons. These inclusions were seen in the cerebral cortex, limbic areas, basal ganglia, thalamus, brain stem and cerebellum. They expressed ubiquitin and were ultrastructurally composed of haphazardly arranged straight filaments. The presence of similar intranuclear inclusions in previous cases of adult-onset dementia without other neuropathological changes suggests an important link between these kind of inclusions and dementia. To our knowledge, this type of intranuclear inclusions has not been previously described in association with Alzheimer pathology.

Aged↗
PubMed1999

An AU-rich sequence in the 3'-UTR of plasminogen activator inhibitor type 2 (PAI-2) mRNA promotes PAI-2 mRNA decay and provides a binding site for nuclear HuR.

The plasminogen activator inhibitor type 2 (PAI-2) gene is regulated by transcriptional and post-transcriptional processes. We have previously shown that insertion of the 3'-untranslated region (3'-UTR) of PAI-2 mRNA into the 3'-UTR of a beta-globin reporter mRNA reduces constitutive beta-globin mRNA expression and that this requires, at least in part, an AU-rich motif. Here we have directly assessed the role of this motif in PAI-2 mRNA stability using both chimeric and non-chimeric reporter systems. We first show that the full-length PAI-2 mRNA is indeed unstable with a half-life of 1 h. Using the c-fos promoter-driven human growth hormone (HGH) mRNA as a reporter, we demonstrate that the 580 nt 3'-UTR of PAI-2 accelerates chimeric HGH mRNA decay in a process which is dependent on the intact AU-rich sequence. Furthermore, disruption of this motif within a constitutively expressed PAI-2 cDNA produces a 2.5- and 2. 7-fold increase in PAI-2 mRNA and protein levels in HT-1080 cells, respectively. RNA electrophoretic mobility shift and supershift assays indicate that this motif provides a specific binding site for cellular proteins that include nuclear HuR. Taken together, these data show that a correlation exists between the binding of HuR to the AU-rich motif in vitro and the destabilizing properties conferred by this sequence in vivo.

3' Untranslated Regions↗
PubMed1998

Effect of an intravenous iron dextran regimen on iron stores, hemoglobin, and erythropoietin requirements in hemodialysis patients.

Iron deficiency is a common cause of delayed or diminished response to erythropoietin (EPO) in hemodialysis patients. Although oral iron is often prescribed to replete iron stores, this approach to iron supplementation may not be adequate with chronic EPO therapy. Intravenous (IV) iron dextran may be an effective alternative approach to replete iron stores and may facilitate more cost-effective use of EPO. The purpose of this study was to evaluate an IV iron dextran regimen that consisted of a loading dose phase followed by monthly maintenance doses of iron dextran. The effect of this regimen on iron stores, hemoglobin, and EPO doses was evaluated. This was an open prospective study in adult hemodialysis patients who were iron deficient as defined by a serum ferritin less than 100 ng/mL or transferrin saturation (TSAT) of less than 20%. Patients were loaded with 1 g iron dextran in five divided doses and then received monthly maintenance doses of 100 mg for the 4-month study period. Values of serum ferritin, TSAT, hemoglobin, and EPO dose were followed for the 4-month study period. Thirty hemodialysis patients receiving EPO were identified as being iron deficient and were enrolled in the study. The mean serum ferritin increased significantly from 49 ng/mL at baseline to 225 ng/mL at the end of the study period (P < 0.0001). Mean TSAT also increased significantly from 27% to 33% (P = 0.002). Values for hemoglobin did not change significantly during the study period; however, there was a significant reduction in EPO dose from a mean baseline dose of 112 U/kg/wk to 88 U/kg/wk at the end of the study period (P = 0.009). Seventeen patients experienced an increase in hemoglobin or a decrease in EPO dose. Economic analysis showed that approximately $580 (Cdn) per patient per year could be saved by use of IV iron dextran. The administration of the IV iron dextran regimen in the iron-deficient hemodialysis population was effective at repleting and maintaining iron stores and reducing EPO use.

Adult↗
PubMed1997

The presence of angiotensin II receptors in elasmobranchs.

The presence of specific Ang II receptors in membrane fractions was investigated using 125I-labeled homologous Ang II ([Asn1, Pro3, Ile5]Ang II; df Ang II) in Triakis scyllia. Specific binding sites occurred in a variety of tissues, with highest binding in interrenal tissue (17.11 +/- 2.45 fmol Ang II/mg protein) and gill (6.26 +/- 0. 69 fmol Ang II/mg protein) and possible Ang II receptors in rectal gland and other tissues. 125I-[Asn1, Pro3, Ile5]Ang II (10(-10)M) binding to branchial cell membrane fraction (25 microg protein) in 5 mM MgCl2, 125 mM NaCl, 50 mM Tris-HCl, 0.2% bovine serum albumin at 28 degrees (1) is rapid and saturable; (2) increases as a function of membrane concentration and time; and (3) optimally fits to a two-site (high-and low-affinity) model. The equilibrium dissociation constant (0.11 +/- 0.01 nM) and binding site concentration (35.00 +/- 1.16 fmol/mg protein) are similar to those of mammalian and avian vascular Ang II receptors. Bound labeled ligand was not competitively displaced by dogfish Ang I, dogfish C-type natriuretic peptide, bradykinin, or the AT1 receptor antagonist, CV 11974. The AT2 receptor antagonist, CGP 42112, was much less potent at displacing the labeled ligand compared to the unlabeled ligand.

Angiotensin II↗
PubMed1995

The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100). The AIDS Clinical Trials Group (ACTG) of the National Institute of Allergy and Infectious Diseases.

Twenty-nine patients were enrolled in a phase I dose-escalating tolerance trial of N-butyl-deoxynojirimycin, an alpha-glucosidase I inhibitor that inhibits human immunodeficiency virus (HIV)-1 replication by altering glycosylation of gp120. Dosing was begun at 8 mg/kg/day and subsequent doses were 16, 32, 48, and 64 mg/kg/day. The maximum tolerated dose was not achieved because of slow accrual and because the study was stopped after the finding of cataracts in initial long-range rat toxicology studies. These cataracts were later shown to be transient and not found in other animals. The most common side effects were gastrointestinal, with diarrhea and flatulence occurring in most subjects, which seemed to partially improve on a modified diet that excluded complex carbohydrates. Grade III elevations in liver function tests were seen in two patients. Grade III leukopenia and neutropenia were seen in seven patients, but were only severe enough in two to require discontinuation. No significant trends in CD4 cell counts or HIV-1 p24 levels were noted.

1-Deoxynojirimycin↗
PubMed1994

Evaluation of cost minimization strategies of anaesthetic drugs in a tertiary care hospital.

A survey was undertaken to compare anaesthetic drug expenditures over a three-year period, to evaluate the impact of strategies offered to curtain continuously rising drug costs. Suggestions to control rising expenditures were based primarily on education of staff and residents regarding drug costs, emphasizing rational use of the more expensive drugs, and minimizing drug wastage. To assess the impact of these measures, a review of annual hospital budgets, global pharmacy expenditures, and anaesthetic drug expenditures was conducted for the period 1991 to 1993. Both absolute and proportional costs of anaesthetic drugs were compared, by year, according to six major classes: opioid analgesics (OA), muscle relaxants (MR), inhalational anaesthetic drugs (INH), intravenous anaesthetic drugs (i.v.), local anaesthetic drugs (LA) and a category labelled other drugs (OTH). In addition, the utilization patterns and unit price changes were compared for each drug for the periods 1991-92, and 1992-93. Total hospital drug costs increased from $7.1 M to $8.5M over the three years. During the same period, the cost of anaesthetic drugs decreased from $379K to $361K, despite an augmentation in annual case load from 12,507 to 13,076 surgical procedures. For the entire survey period, the mean cumulative anaesthetic drug cost was 4.6% of the pharmacy budget, or 0.24% of the hospital budget. Analysis by drug class revealed a $51K decrease in expenditures on OA. due to decreased utilization of fentanyl and alfentanil, and a decrease in the price of fentanyl. The increased expenditure on INH drugs was primarily due to an increase in acquisition costs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Neuropathologic diagnosis of Alzheimer disease: interrater reliability in the assessment of senile plaques and neurofibrillary tangles.

A diagnosis of definite Alzheimer disease (AD) is made when there is a history of progressive dementia combined with the pathologic findings of numerous senile plaques and neurofibrillary tangles in neocortex. Recent studies have shown, however, that there may be significant interrater variability in the quantitation of these histopathologic lesions. In the present two-center study, interrater reliability and test-retest reliability for plaque and tangle counts were examined when histologic staining and sampling were controlled. We report similar levels of reliability for plaque and tangle counts in 35 cases of AD, nine normal elderly controls and six non-AD dementias: Pearson correlations for interrater reliability ranged from 0.68 to 0.88, and from 0.97 to 0.99 for test-retest reliability. Using quantitative cut-points, concordance between laboratories for experimental diagnoses of AD versus non-AD made on the basis of these lesion counts ranged from 84 to 92% (kappa scores: 0.69-0.84). The agreement between these experimental diagnoses and the clinicopathologic diagnoses of record ranged from 74 to 86% (kappa scores: 0.50-0.71). Thus, under optimal conditions, a moderate to substantial degree of interrater reliability can be attained in the pathologic diagnosis of AD.

Aged↗
PubMed1991

Adult children as caregivers: egocentric biases in judgments of sibling contributions.

This study examined filial caregivers' views of their own and their siblings' costs and contributions to the care of their parents. The respondents viewed their siblings' responses to the parents' needs as remarkably similar to their own, in spite of there being no actual similarity. Despite these perceived similarities, however, respondents perceived their siblings as contributing less than themselves, gaining less satisfaction, feeling freer to alter their caregiving, and being resistant to increasing their relative contributions. In order of importance, the extent of contact between the siblings, their feelings of closeness, the extent of parents' needs, their gender, the extent of resources spent, and personal regard for their siblings were significant predictors of these egocentrically biased perceptions. As expected, these egocentrically biased perceptions were important predictors of personal regard for their siblings.

Bias↗
PubMed1991

Measuring body fat: calibrating the rulers. Intermethod comparisons in 389 normal Caucasian subjects.

A systematic study of 389 normal Caucasians stratified for sex and age compared all of the traditional methods for measuring fat: body water, underwater weighing, body potassium, and anthropometrics and the newer methods of dual-photon absorptiometry, bioimpedance analysis, and total body electrical conductivity. Measurements by all methods are highly intercorrelated, but methods differences show the population means for fat percent to range from 26 to 35% of body weight across eight methods. All methods show increasing fat (as % body weight) with age in both sexes but vary in secular slope. The goal of this report is to provide direct translations between each of the eight methods. Intermethod comparison equations are given as simple linear regressions by using each method both as dependent and independent variable for each sex, permitting translation for results by any method to any other.

Adipose Tissue↗
PubMed1991

A peer review quality assurance program in drug information.

The development and implementation of a peer review quality assurance program for a drug information service is described. Eight drug information centres across Canada initially agreed to participate as peer reviewers. Critera were developed to select drug information requests that would qualify for the program. Peer review responses were compared to the centre's response by a panel of four drug information pharmacists. Thirteen of 14 requests sent to peer reviewers were returned and there was agreement between the conclusions and recommendations provided in the responses by our drug information centre and the peer review pharmacist in 11 cases. Peer reviewer pharmacists tended to prepare more in depth responses. This represents the first report of a peer review quality assurance program for a drug information service.

Canada↗
PubMed1991

Impact of toxicology screens in the diagnosis of a suspected overdose: salicylates, tricyclic antidepressants, and benzodiazepines.

A retrospective review of 150 cases determined the contribution of salicylate assays, tricyclic antidepressant (TCA) screens, and benzodiazepine screens to the diagnosis of overdose patients. Seventy percent of salicylate assays and 42% of TCA screens were ordered when there was no history of ingestion of clinical indication of overdose with these agents. In 12% of the cases benzodiazepine screens did not provide useful information. A positive history of salicylate ingestion, tinnitus and hyperventilation were the best predictive indicators of salicylate ingestion. The best predictors of TCA toxicity were a positive history of ingestion, a decreased level of consciousness, and a prolonged QRS interval. The combination of a positive history of ingestion and a decreased level of consciousness was a sensitive indicator of benzodiazepine toxicity. The annual cost of screens/assays which did not contribute to diagnosis was estimated to be $4649. Based on this study, a thorough history and clinical assessment of the overdose patient takes precedence over analytical screens in determining the drug(s) involved.

Adolescent↗
PubMed1990

Effects of short-term endotracheal intubation on vocal function.

Transient voice change associated with endotracheal intubation has generally been attributed to vocal fold trauma. To assess the role of altered vocal fold function in transient voice change, a study was designed to evaluate the audioacoustic, endoscopic, and laryngostroboscopic characteristics of the postintubation voice. Vocal function of 10 patients undergoing short-term outpatient surgical procedures using general anesthesia and endotracheal intubation were studied preoperatively and postoperatively. A second group of 10 patients that did not have surgery or general anesthesia was used as an age-matched control. Fundamental frequency, frequency perturbation, electroglottography, endoscopy (including laryngeal stroboscopy), and subjective speech analysis by experienced listeners were used to assess vocal function. No consistent differences in fundamental frequency were observed, although patient-to-patient variation was marked. Statistically significant increases in cycle-to-cycle fundamental frequency variation (jitter) were found postoperatively in the majority of the postintubation patients (P less than 0.05). Electroglottography, laryngeal endoscopy, and stroboscopic laryngoscopy did not demonstrate consistent changes in glottic mucosal function. Listener judgments characterized the postintubation voice change by decreased intensity, increased roughness, and lowered affect without consistent changes in pitch. The perception of decreased affect in the voices (characterized by reduction in pitch variation, vocal stress, and increases in pause times) was a strong perceptual marker for change in the post-intubation voice. Objective measures of laryngeal function suggest that the glottic contribution to postintubation voice change is minimal and that this dysphonia is probably multifactorial.

Adolescent↗