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Biomedical subjects

D Boyle

Publications and source records attributed to D Boyle.

At least 37 records · Page 2Linked to original sources
PubMed2000

Steady-state pharmacokinetics of carvedilol and its enantiomers in patients with congestive heart failure.

Carvedilol is a relatively new drug with beta- and alpha 1-receptor blocking activity and antioxidant effects recently approved for the treatment of congestive heart failure (CHF). An ascending, multiple-dose study was completed in 20 male patients with stable New York Heart Association (NYHA) Class III or IV CHF. The pharmacokinetics of carvedilol, S(-)-carvedilol, R(+)-carvedilol, and the active metabolites of carvedilol was assessed at steady state after twice-daily oral administration of carvedilol for 7 days at 6.25, 12.5, 25, and 50 mg doses. Carvedilol exhibited stereoselective pharmacokinetics in CHF patients with dose-proportional increases in steady-state plasma concentrations of carvedilol and its enantiomers. Mean AUC and Cmax values for carvedilol were up to twofold higher in patients with Class IV CHF as compared to those with Class III CHF. Steady-state plasma concentrations of the active metabolites also increased in a dose-proportional manner and were typically 10% or less of that observed for carvedilol. In general, carvedilol was adequately tolerated by adult male CHF patients at the dose levels (6.25-50 mg) evaluated in this study as adverse events were consistent with those frequently observed in patients with CHF.

Adult↗
PubMed2000

International Guidelines for Neonatal Resuscitation: An excerpt from the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science. Contributors and Reviewers for the Neonatal Resuscitation Guidelines.

The International Guidelines 2000 Conference on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiac Care (ECC) formulated new evidenced-based recommendations for neonatal resuscitation. These guidelines comprehensively update the last recommendations, published in 1992 after the Fifth National Conference on CPR and ECC. As a result of the evidence evaluation process, significant changes occurred in the recommended management routines for: * Meconium-stained amniotic fluid: If the newly born infant has absent or depressed respirations, heart rate <100 beats per minute (bpm), or poor muscle tone, direct tracheal suctioning should be performed to remove meconium from the airway. * Preventing heat loss: Hyperthermia should be avoided. * Oxygenation and ventilation: 100% oxygen is recommended for assisted ventilation; however, if supplemental oxygen is unavailable, positive-pressure ventilation should be initiated with room air. The laryngeal mask airway may serve as an effective alternative for establishing an airway if bag-mask ventilation is ineffective or attempts at intubation have failed. Exhaled CO(2) detection can be useful in the secondary confirmation of endotracheal intubation. * Chest compressions: Compressions should be administered if the heart rate is absent or remains <60 bpm despite adequate assisted ventilation for 30 seconds. The 2-thumb, encircling-hands method of chest compression is preferred, with a depth of compression one third the anterior-posterior diameter of the chest and sufficient to generate a palpable pulse. * Medications, volume expansion, and vascular access: Epinephrine in a dose of 0.01-0.03 mg/kg (0.1-0.3 mL/kg of 1:10,000 solution) should be administered if the heart rate remains <60 bpm after a minimum of 30 seconds of adequate ventilation and chest compressions. Emergency volume expansion may be accomplished with an isotonic crystalloid solution or O-negative red blood cells; albumin-containing solutions are no longer the fluid of choice for initial volume expansion. Intraosseous access can serve as an alternative route for medications/volume expansion if umbilical or other direct venous access is not readily available. * Noninitiation and discontinuation of resuscitation: There are circumstances (relating to gestational age, birth weight, known underlying condition, lack of response to interventions) in which noninitiation or discontinuation of resuscitation in the delivery room may be appropriate.

Blood Volume↗
PubMed2000

Suppression of TNF-alpha production in human mononuclear cells by an adenosine kinase inhibitor.

Adenosine exerts potent anti-inflammatory activities through inhibition of cytokine synthesis by activated monocytes. Adenosine is rapidly phosphorylated intracellularly by adenosine kinase. GP515, an adenosine kinase inhibitor, prevents the phosphorylation of adenosine to AMP and thereby locally enhances the adenosine concentration. GP515 has exhibited significant anti-inflammatory effects in several murine models of inflammation. In this study we investigated the effect of GP515 alone and in combination with exogenous adenosine or with rolipram, a phosphodiesterase inhibitor, on tumor necrosis factor alpha (TNF-alpha) synthesis in human peripheral blood mononuclear cells (PBMC) or whole blood. Lipopolysaccharide (LPS; 10 ng/mL)-stimulated PBMC were incubated in the absence or presence of these substances. GP515 alone showed a dose-dependent suppression of TNF-alpha production with an IC50 of 80 microM. The TNF-alpha-inhibiting effects of adenosine and GP515 were reversed in the presence of the cAMP antagonist (Rp)-cAMPS, supporting the hypothesis of a cAMP-mediated pathway. Combinations of GP515 with either adenosine or rolipram led to an additive inhibition of TNF-alpha synthesis. These experiments are the first to demonstrate efficacy of an adenosine kinase inhibitor in TNF-alpha suppression in cells of human origin. The findings form a basis to investigate these strategies in animal models of TNF-alpha-mediated chronic inflammatory diseases.

Adenosine↗
PubMed1999

Deamidation of alpha-A crystallin from nuclei of cataractous and normal human lenses.

PURPOSE: To quantitate the extent of deamidation of asparagine-101, glutamine-50, and glutamine-6 of alpha-A crystallin in the nucleus from human cataractous and normal lenses. METHODS: Reverse phase chromatography was used to prepare alpha-A crystallin from total proteins of the nucleus from cataractous and age-matched normal human lenses. Synthetic peptides were made corresponding to the expected amidated and deamidated tryptic fragments containing asparagine-101, glutamine-50, and glutamine-6. The peptides were used to identify and quantitate amidated and deamidated forms of tryptic fragments from alpha-A crystallin eluting from a reverse phase column. RESULTS: Significant amounts of deamidation of asparagine-101 and glutamine-50, but not glutamine-6, were present in alpha-A crystallin from nuclear sections of both cataractous and age-matched normal lenses. Quantitative analysis of tryptic peptides containing these residues indicated no statistical difference in deamidation in cataractous versus normal lenses. CONCLUSIONS: There was no significant difference in the extent of deamidation of asparagine-101, glutamine-50, and glutamine-6 for alpha-A crystallin, purified from the nucleus of cataractous versus age-matched normal lenses. These results strongly suggest that deamidation of these residues does not play a role in the biogenesis of human nuclear cataract.

Aged↗
PubMed1999

Beyond correspondence, video conferencing, and voice mail: Internet-based master's degree courses in nursing.

The changing health care system and increasing demands for primary care providers have prompted an increase in nurse practitioner programs in the United States. Nurses in rural areas that are underserved by primary care practitioners often are faced with time and distance barriers to returning to school for advanced education. This article describes Internet-based courses as a unique distance learning platform for preparing primary care nurse practitioners at the University of Kansas (KU) School of Nursing. Discussion includes course development process, matching methods to course content, and other information on promoting interaction between students and faculty.

Curriculum↗
PubMed1998

Deamidation of specific glutamine residues from alpha-A crystallin during aging of the human lens.

Although it has been hypothesized that age-dependent deamidation of glutamine and/or asparagine residues may play an important role in the turnover of proteins in vivo, surprisingly little is known concerning the extents of deamidation of biologically important proteins with very long half-lives. Alpha-A crystallin is the most abundant protein of the adult human lens, which contains long-lived proteins in the central fetal-embryonic region that were synthesized before birth of the individual. Peptides, corresponding to tryptic fragments of alpha-A crystallin, were synthesized with either the expected glutamine-6, glutamine-50, and glutamine-147 residues, or deamidated glutamic acid residues at the same positions. These synthetic peptides were used to identify and quantitate the amidated versus deamidated forms of each tryptic fragment of alpha-A crystallin from the fetal-embryonic region of lenses from donors of increasing age up to 64 years old. The results demonstrate that all three glutamine residues are very stable, with glutamine-50 undergoing a maximum of approximately 30% deamidation after 64 years postsynthesis, while glutamine-6 and glutamine-147 undergo no detectable deamidation during the same period of time. Together, these results are consistent with the hypothesis that resistance to age-dependent, nonenzymatic deamidation may be an important prerequisite for the stability of proteins in vivo.

Adult↗
PubMed1998

Pharmacokinetics of intravenously and orally administered eprosartan in healthy males: absolute bioavailability and effect of food.

Eighteen healthy males received a single 300 mg oral dose of eprosartan as the commercial wet granulation formulation under fasting conditions and following a high-fat breakfast and a single 20 mg intravenous (i.v.) dose. The pharmacokinetics of i.v. eprosartan (mean +/- S.D.) were characterized by a low systemic plasma clearance (131.8 +/- 36.2 mL min(-1)) and a small steady-state volume of distribution (12.6 +/- 2.6 L). Oral bioavailability averaged 13.1%, due to incomplete absorption. In vitro dynamic flow cell dissolution data showed that pH-dependent aqueous solubility of eprosartan is one factor which limits absorption. Eprosartan terminal half-life was shorter after i.v. (approximately 2 h) versus oral (approximately 5-7 h) administration, which may be due to detection of an additional elimination phase or absorption rate-limited elimination following oral administration. Oral administration of eprosartan following a high-fat meal compared with fasting conditions resulted in a similar extent of absorption (based on AUC), but a decreased absorption rate. Cmax was approximately 25% lower, and a median delay of 1.25 h in time to Cmax was observed when eprosartan was administered with food. These minor changes in exposure are unlikely to be of clinical consequence; therefore, eprosartan may be administered without regard to meal times.

Acrylates↗
PubMed1998

The effectiveness of low dose tranexamic acid in primary cardiac surgery.

PURPOSE: This randomized controlled clinical trial compared three doses of tranexamic acid (TA) in primary cardiac surgery in terms of blood loss and transfusion requirements. METHODS: Patients presenting for primary coronary artery bypass grafting (CABG) and/or valve replacement were randomly assigned to one of three TA regimens: 20 mg.kg-1 (LD), 50 mg.kg-1 (MD), and 100 mg.kg-1 (HD). All participants and staff were blinded to the allocation. Haemoglobin (Hgb), haematocrit and platelet count were determined preoperatively, after bypass, at CCA arrival, and 12 and 24 hr after surgery. Coagulation parameters were measured before and after surgery. Blood loss was measured intraoperatively and for 24 hr postoperatively following a standardized protocol. Blood products were administered in a standardized fashion. RESULTS: Two hundred twenty patients completed the trial over 10 months: 74 in LD, 75 in MD and 72 in HD dose groups. All patients groups were comparable; similar procedures were performed in each group. No differences were identified for blood loss intra-operatively (490 +/- 232 ml, 523 +/- 413 ml, 488 +/- 357 ml, respectively), 24 hr post-operatively (543 +/- 223 ml, 544 +/- 231, 458 +/- 210 ml, respectively), and overall (1032 +/- 358 ml, 1067 +/- 502 ml, 946 +/- 459 ml, respectively). Blood product administration was similar in the three groups. No differences in postoperative complications were found. CONCLUSIONS: This study demonstrates the equivalency of the three doses of TA in primary cardiac surgical procedures. The use of low dose (20 mg.kg-1) TA results in comparable outcomes, without additional complications.

Analysis of Variance↗
PubMed1997

Differential utilization of hospice services in nursing homes.

During the completion of an interpretive evaluation project, differences in rates of dying patients using hospice services between nursing homes were examined. Rates were found to vary from 2% to 39% in 23 nursing homes owned by one company. Twenty of the 23 administrators responded to a survey regarding attitudes toward hospice care in the nursing home. Nursing homes with administrators most sympathetic to hospice care had rates three times higher than nursing homes with administrators least sympathetic. Specific concerns were discussed in interviews with four of the least sympathetic administrators. The findings are congruent with program implementation theory which describes the discretionary power of local administrators to limit access to new programs that they find problematic.

Attitude of Health Personnel↗
PubMed1997

Injury from dairy cattle activities.

Animals have been implicated as an important source of injury for farm household members. Little is known, however, about the specific activities associated with the animal/livestock operations that place a person at increased or decreased risk for injuries. The primary aim of this case-control study was to identify which dairy cattle operation activities (that is, milking, feeding, cleaning barns, trimming and treating feet, dehorning, assisting with difficult calvings, and doing treatments) were associated with an increased or decreased risk of injury. We found milking to have the greatest increase in risk for injury. The ratios for increasing hours per week spent at milking (0, 1-10, 11-20, 21-30, 31-63) were 1.0, 2.3, 5.5, 10.9, and 20.6, respectively. We also found an increased rate ratio associated with trimming or treating hooves (rate ratio = 4.2).

Adolescent↗
PubMed1997

Semantic priming impairment in HIV.

HIV+ subjects have shown impairment on tests of executive function including automatic attention and verbal tasks. Impairment of semantic priming in HIV patients would suggest a disruption of automatic semantic activation. We examined semantic priming in HIV+ individuals and HIV- control participants with no history of substance abuse, neurologic or psychiatric disorder unrelated to HIV. HIV+ participants were divided into cognitively normal and cognitively impaired subgroups on the basis of a neuropsychological battery of 15 tests. Participants were presented with English words and nonword letter strings and indicated if the stimulus was a word or nonword. The nonwords were orthographically and phonologically correct and were created by rearranging the letter sequence of words ("ulpit"). All words had an obvious antonym ("deep"); two-thirds were presented as sequential antonym pairs ("enter"-"exit"). There were no group differences in speed of response to nonwords, indicating no generalized reaction time deficit. While control and cognitively normal HIV+ participants showed an effect of priming on reaction time to correctly detected words, cognitively impaired HIV+ participants did not. The lack of semantic priming demonstrated by cognitively impaired HIV+ participants suggests that they have lessened activation of automatic semantic networks.

Adult↗
PubMed1997

Five years of work-related injuries and fatalities in Minnesota. Agriculture: a high-risk industry.

This report describes the Minnesota Fatality Assessment and Control Evaluation Study (MN FACE), a federally funded initiative to study fatal injuries in the workplace. The purpose of the program is to investigate various types of occupational fatalities and to identify risk factors that contribute to work-related fatalities. Initially, the MN FACE program only investigated fatalities related to falls, confined spaces, and electrocutions. In 1994, MN FACE also began investigating fatalities associated with agricultural work. Agriculture continues to be one of the nation's most hazardous industries, ranking fourth among industries in the United States at high risk for work-related fatalities. MN FACE investigated 46 agriculture-related fatalities during 1994-95. Forty-one percent of the fatalities involved tractors, and 66% of these accidents were tractor rollovers. Other leading causes of agricultural fatalities included grain bin and manure pit asphyxiations.

Accidents, Occupational↗
PubMed1997

Psychometric evaluation of the Organizational Job Satisfaction Scale.

Findings are reported from a replicated evaluation of the psychometric properties of the Organizational Job Satisfaction Scale. Data lend strong support for the scale which assesses four dimensions of organizational job satisfaction. Principal component factor analysis of data from two independent samples of urban staff registered nurses (RNs) (n = 496; n = 532) confirmed four dimensions of pay, interaction, administration, and status. Cronbach's alpha for subscales ranged from .76 to .88. Pearson correlation coefficients for the interrelationships among subscales and an estimate of theta verified internal consistency. The Organizational Job Satisfaction Scale scores correlated significantly with a criterion measure of job enjoyment. Hypothesis testing of theoretically predictable relationships supported construct validity. Scores on the organizational job satisfaction subscales correlated significantly with automony, stress, and commitment. Item revisions and recommendations for future use of the instrument are discussed.

Adult↗
PubMed1997

Detection of virus infection-associated antigen and 3D antibodies in cattle vaccinated against foot and mouth disease.

The analysis of sera obtained from animals vaccinated or revaccinated with inactivated vaccines against foot and mouth disease (FMD) virus showed that these vaccines induced antibodies against the virus infection-associated (VIA) antigen, detectable by agar gel immunodiffusion (AGID). The present study evaluates the antibody response to protein 3D and the VIA antigen (VIAA) of FMD virus induced by different vaccines in a group of 51 calves. This response was detected using AGID and a liquid-phase blocking sandwich enzyme-linked immunosorbent assay (ELISA) for anti-3D antibodies (ELISA-3D). No anti-VIAA or anti-3D antibodies were detected after the initial vaccination. Following revaccination, animals giving positive results were detected by both methods. This immune response disappeared 60-120 days post-revaccination (dprv) according to the AGID method, and 90-180 dprv when ELISA-3D was used. Samples of oesophageal-pharyngeal fluid obtained from animals that remained positive for anti-VIAA antibodies at 90-120 dprv gave negative results for viral isolation, indicating that the transitional antibody response induced by the vaccine was due to the presence of non-structural antigens in the vaccine and not to viral infection. These results indicate that the ELISA-3D method could be used as a complementary method for sero-epidemiological studies as an indirect indicator of viral activity, as long as the age and vaccination status of the animals being sampled are taken into consideration.

Animals↗
PubMed1996

Quantitative analysis of interleukin-1-alpha gene expression in middle ear cholesteatoma.

Regardless of its origin, cholesteatoma is characterized by the presence of a keratinizing epithelium with an hyperproliferative behavior leading to a very important bone resorption. Previous studies have demonstrated overexpression of interleukin-1 (IL-1 protein in middle ear cholesteatoma by immunohistochemistry and enzyme-linked immunosorbent assay, suggesting a significant role for IL-1-alpha. In this study, the presence of IL-1-alpha messenger ribonucleic acid (mRNA) was quantified by in situ hybridization on frozen sections (n = 10) and by computer-assisted image analysis. Human skin obtained from the external ear canal (n = 10) was used as the control. A higher percentage of cells hybridized for the antisense probes IL-1-alpha mRNA was found in cholesteatoma epithelium. Furthermore, keratinocytes of the suprabasal cell layers were also found to contain specific hybridizations. Some cells in cholesteatoma stroma also contained IL-1-alpha mRNA transcripts. The results of this study confirm the central role of IL-1-alpha in the epithelium hyperproliferation and bone resorption observed in middle ear cholesteatoma.

Cholesteatoma, Middle Ear↗