Biomedical subjects

P O'Leary

Publications and source records attributed to P O'Leary.

At least 19 recordsLinked to original sources

PubMed2006

Economic evaluation of the familial cancer programme in Western Australia: predictive genetic testing for familial adenomatous polyposis and hereditary non-polyposis colorectal carcinoma.

AIM: To evaluate costs and outcomes of genetic testing for familial colorectal cancer through services provided by Genetic Services of Western Australia (GSWA). METHODS: Costs and outcomes of predictive DNA-based testing for inherited colorectal cancers (CRC) were assessed, specifically for familial adenomatous polyposis (FAP) and hereditary non-polyposis CRC (HNPCC) using a decision-analysis model. Costs were assigned according to standards of care in Western Australia (WA). Cancer risks and the efficacy of surveillance on long-term outcomes were derived from the published literature. RESULTS: The cost-effectiveness of genetic testing was compared in first-degree relatives of known mutation carriers who have a 50% risk of carrying the mutated gene (intervention group) to individuals with the same risk but who do not undergo a genetic test (control subjects). Compared with control subjects undergoing the same high-level surveillance and surgery, the FAP and HNPCC intervention groups provided total savings of 13,390 US dollars and 14,783-15,460 per person (males-females), respectively. HPNCC mutation carriers also gained 1 CRC-free year. Compared to control subjects having only population surveillance, individuals in the FAP intervention group delayed the onset of CRC by 40 years for a net cost of 9,042 US dollars. Individuals in the HNPCC intervention group delayed the onset of CRC by 8 years at a net cost of 12,141 US dollars for males and 12,596 US dollars for females. CONCLUSIONS: Genetic testing for familial CRC in WA allows targeted surveillance for mutation carriers, which ensures the efficient use of resources and reduces cancer-related morbidity, if clinical recommendations for intervention are adopted.

Adenomatous Polyposis Coli↗

PubMed2003

Subcutaneous glucose sensor values closely parallel blood glucose during insulin-induced hypoglycaemia.

AIMS: To assess the accuracy of the Minimed continuous glucose monitoring system (CGMS) in estimating blood glucose concentration during a controlled reduction in blood glucose. RESEARCH DESIGN AND METHODS: We studied nine adolescent diabetics (age 14 +/- 1.5 years) wearing the CGMS during hyperinsulinaemic hypoglycaemic clamp studies. The glucose values obtained by the CGMS were compared with the venous blood samples taken during the studies and measured at the bedside using a glucose oxidase technique. RESULTS: Blood glucose was lowered from euglycaemia to a mean of 2.8 mmol/l over 120 min and maintained at that level for a further 40 min. A total of 429 paired glucose measurements were available for analysis. Analysis using weighted Deming regression and t-tests revealed small differences between the methods, with blood glucose levels slightly higher than interstitial fluid levels. The mean difference across all values was 0.13 mmol/l. The observed difference was greatest at blood glucose values < 3.3 mmol/l. CONCLUSIONS: This study suggests that during a fall in systemic glucose the subcutaneous glucose sensor provides an accurate reflection of blood glucose. However, a small difference is apparent at blood glucose values < 3.3 mmol/l.

Adolescent↗

PubMed2002

Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur.

Although skeletal pain plays a major role in reducing the quality of life in patients suffering from osteoarthritis, Paget's disease, sickle cell anemia and bone cancer, little is known about the mechanisms that generate and maintain this pain. To define the peripheral fibers involved in transmitting and modulating skeletal pain, we used immunohistochemistry with antigen retrieval, confocal microscopy and three-dimensional image reconstruction of the bone to examine the sensory and sympathetic innervation of mineralized bone, bone marrow and periosteum of the normal mouse femur. Thinly myelinated and unmyelinated peptidergic sensory fibers were labeled with antibodies raised against calcitonin gene-related peptide (CGRP) and the unmyelinated, non-peptidergic sensory fibers were labeled with the isolectin B4 (Bandeira simplicifolia). Myelinated sensory fibers were labeled with an antibody raised against 200-kDa neurofilament H (clone RT-97). Sympathetic fibers were labeled with an antibody raised against tyrosine hydroxylase. CGRP, RT-97, and tyrosine hydroxylase immunoreactive fibers, but not isolectin B4 positive fibers, were present throughout the bone marrow, mineralized bone and the periosteum. While the periosteum is the most densely innervated tissue, when the total volume of each tissue is considered, the bone marrow receives the greatest total number of sensory and sympathetic fibers followed by mineralized bone and then periosteum. Understanding the sensory and sympathetic innervation of bone should provide a better understanding of the mechanisms that drive bone pain and aid in developing therapeutic strategies for treating skeletal pain.

Afferent Pathways↗

PubMed2001

Dynamic equilibria in the products of intramolecular Buchner additions of diazoketones to aryl rings bearing methoxy substituents.

Rhodium carboxylate catalyzed aromatic addition reactions of a range of diazoketones bearing methoxy-substituted aryl rings have been explored. While the existence of norcaradiene-cycloheptatriene equilibria in related compounds is well established, the aromatic addition products in this study display more complex dynamic equilibria due to conjugation with the methoxy group; the experimental evidence for this is discussed in detail. In the azulenone products 21-26 derived from p-methoxy-substituted diazoketones 14-16, the diastereomers interconvert via a spiro intermediate 39. A related mechanistic process in the azulenones 43-46 derived from the o-methoxy-substituted diazoketones 17, 18 interconverts regioisomers, explaining the conflicting reports for the regioselectivity of the cyclization of diazoketone 1. With the m-methoxy-substituted diazoketone 19, involvement of the methoxy group through a different pathway results in fragmentation of the azulenone to form the tetralone 47. With the azulenones 21-26 exclusive trapping of the norcaradiene associated with the less thermodynamically stable diastereomers in a cycloadduct with N-phenylmaleimide is observed. Due to the presence of the activating methoxy substituent on the aromatic ring, the aromatic addition reactions of the diazoketones studied were not very sensitive to the nature of the rhodium catalyst.

Journal Article↗

PubMed2000

Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone cream to pre-and postmenopausal women.

OBJECTIVE: The use of topically applied micronised ('natural') progesterone as a substitute for synthetic oestrogens and progestogen preparations is controversial. The aim of this study was to examine the changes in blood and salivary concentrations of progesterone following a single topical application of a progesterone cream. PATIENTS AND MEASUREMENTS: We investigated six premenopausal women in the luteal phase and six postmenopausal women to determine the short-term changes in serum, urinary and salivary progesterone concentrations following a single 64 mg topical application of micronised progesterone. RESULTS: Serum progesterone concentrations did not increase during the first 3 hours after application of progesterone cream, however, salivary values rose significantly in both premenopausal and postmenopausal women, consistent with the view that progesterone is absorbed and transported through the body. Salivary progesterone concentrations were significantly elevated above basal levels by 30-60 minutes and reached peak levels at 1-4 h, with mean levels approximately fivefold higher in premenopausal, than in menopausal women. CONCLUSIONS: Salivary progesterone measurements confirm that topically applied progesterone is absorbed, despite the lack of change in serum progesterone concentrations. However, at the dose administered, serum progesterone levels do not reach those observed after oral or vaginally delivered progesterone preparations. Higher doses may be required to induce biological responses within the endometrium.

Absorption↗

PubMed1999

T-independent type 2 antigens induce B cell proliferation in multiple splenic sites, but exponential growth is confined to extrafollicular foci.

During the primary splenic response to the T-independent type 2 (TI-2) antigen (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll, small numbers of antigen-specific B cells have entered S phase of the cell cycle 24 h after intraperitoneal immunization. These are distributed in all splenic compartments (T zones, marginal zones, follicles, and red pulp), indicating early proliferation induced by NP-Ficoll does not require accessory signals delivered in a particular splenic microenvironment. Subsequently B blasts accumulate selectively in the outer T zone areas, but exponential growth leading to plasma cell production occurs only in extrafollicular foci. This growth peaks after 5 days, but 20% of peak numbers of antibody-containing cells are still present 3 months after immunization and 9% of these cells are proliferating. It is unclear if these late plasmablasts are sustained by self-renewal or continued recruitment of virgin cells into the response. Unlike TD and TI-1 responses NP-specific memory cells do not accumulate in the splenic marginal zones. The level of Cgamma3 switch transcripts increases during the first 24 h of the response, but does not increase further during exponential plasmablast growth.

Animals↗

PubMed1999

Dendritic cells associated with plasmablast survival.

A subset of myeloid dendritic cells is described which is associated with the ability of splenic and lymph node plasmablasts to survive and differentiate into plasma cells. Plasmablast-associated dendritic cells (PDC) are CD11c(high), DEC-205(-) and unlike conventional dendritic cells do not associate with T cells. The following findings suggest a requirement for PDC if plasmablasts are to differentiate to plasma cells. First, when large numbers of B cells are recruited into antibody responses and plasmablasts outgrow the PDC stroma, only those associated with PDC survive and differentiate into plasma cells. Conversely, if the number of PDC is increased by ligating their CD40, more plasmablasts survive on the expanded PDC stroma and differentiate into plasma cells. Finally, in T cell-deficient mice, the plasma cells that develop atypically in the T zones in response to thymus-independent antigens are associated with ectopic PDC.

Animals↗

PubMed1999

A partnership for community-based nursing experience: Head Start/Harper College.

In an effort to provide a meaningful community-based nursing experience for the students of William Rainey Harper College, a project was developed with the Community Economic Development Association of Cook County, Illinois to link second-year nursing students and clients in a Head Start program. The goals were designed to meet the needs of both the students and the Head Start clients. The students provided a portion of the health service plan for the Head Start families, and at the same time they received a comprehensive community/family learning experience. Throughout the second year of the nursing program the students followed their assigned family utilizing a unique integration of pediatric and psychiatric nursing concepts. The article will outline the project from development to completion of the first year of student involvement. It will address successes, failures, and changes made in the second year of the program.

Child, Preschool↗

PubMed1999

What is the future for nurse executives?

This article describes the future role of nurse executives as designers of health care rather than respondents to internal and external environmental forces. The successful executives will be proactive, dedicated, and politically astute. These individuals will engineer vertical organizations that are empowered, fluid, and flexible. These new organizational skills will be developed through innovative executive educational programs designed at the master's and doctoral levels. Well-established executives from business, education, public health, medicine, administration, health systems, and education will become the faculty preparing these individuals. These programs will integrate other health care disciplines through an integrated and flexible approach to learning. The development of these roles will influence policy and decision making at all levels within health care.

Education, Nursing, Graduate↗

PubMed1998

Decreased epinephrine responses to hypoglycemia during sleep.

BACKGROUND: In patients with type I diabetes mellitus, hypoglycemia occurs commonly during sleep and is frequently asymptomatic. This raises the question of whether sleep is associated with reduced counterregulatory-hormone responses to hypoglycemia. METHODS: We studied the counterregulatory-hormone responses to insulin-induced hypoglycemia in eight adolescent patients with type I diabetes and six age-matched normal subjects when they were awake during the day, asleep at night, and awake at night. In each study, the plasma glucose concentration was stabilized for 60 minutes at approximately 100 mg per deciliter (5.6 mmol per liter) and then reduced to 50 mg per deciliter (2.8 mmol per liter) and maintained at that concentration for 40 minutes. Plasma free insulin, epinephrine, norepinephrine, cortisol, and growth hormone were measured frequently during each study. Sleep was monitored by polysomnography. RESULTS: The plasma glucose and free insulin concentrations were similar in both groups during all studies. During the studies when the subjects were asleep, no one was awakened during the hypoglycemic phase, but during the final 30 minutes of the studies when the subjects were awake both the patients with diabetes and the normal subjects had symptoms of hypoglycemia. In the patients with diabetes, plasma epinephrine responses to hypoglycemia were blunted when they were asleep (mean [+/-SE] peak plasma epinephrine concentration, 70+/-14 pg per milliliter [382+/-76 pmol per liter]; P=0.3 for the comparison with base line), as compared with when they were awake during the day or night (238+/-39 pg per milliliter [1299+/-213 pmol per liter] P=0.004 for the comparison with base line, and 296+/-60 pg per milliliter [1616+/-327 pmol per liter], P=0.004, respectively). The patients' plasma norepinephrine responses were also reduced during sleep, whereas their plasma cortisol concentrations did not increase and their plasma growth hormone concentrations increased slightly. The patterns of counterregulatory-hormone responses in the normal subjects were similar. CONCLUSIONS: Sleep impairs counterregulatory-hormone responses to hypoglycemia in patients with diabetes and normal subjects.

Adolescent↗

PubMed1998

Sleep, respiratory rate, and growth hormone in chronic neonatal lung disease.

This study assessed whether respiratory rates (RRs) correlate with urinary growth hormone (U-GH) excretion and sleep architecture in infants with chronic neonatal lung disease (CNLD) in early (1 month), middle (6 months), and late (10 months) infancy. Twenty-three preterm infants (CNLD=16, controls=7) were studied on 51 occasions. CNLD infants were stratified according to mean non-REM sleep respiratory rate (NREM RR) in early infancy into "High RR CNLD" infants (mean NREM RR >2 SD higher than controls) and "Normal RR CNLD" infants (mean NREM RR within 2 SD of controls' mean). "High RR CNLD" infants (RR >45) had a lower mean birthweight (P=0.015), current weight (P=0.042), current length (P=0.02), and growth velocity in early infancy (grams/week gained: P=0.042) than "Normal RR CNLD" and control infants. Mean (95% CI) U-GH excretion (ng U-GH/g urinary creatinine) was higher in "High RR CNLD" infants in air or their usual O2 (1,932 [459, 3,406]) than "Normal RR CNLD" (394 [147, 642]) and controls (320 [147, 492]) (P=0.024). With resolution of tachypnea by mid-infancy, hemoglobin oxygen saturation (SaO2) >93%, mean growth parameters and U-GH excretion for the "High RR CNLD" group were not significantly different from "Normal RR CNLD" and control groups. CNLD infants demonstrated increased sleep efficiency (P=0.016), whereas controls had similar sleep efficiency between early and middle infancy (P=0.452). Mean percent time in REM sleep (REM%) and slow wave sleep (SWS%) were not significantly different between early and middle infancy and did not vary in relation to respiratory rate. We conclude that tachypneic infants with CNLD have slower growth and elevated U-GH excretion in early infancy. With resolution of tachypnea, growth improved, U-GH excretion decreased, and sleep consolidation occurred. An elevated U-GH in tachypneic CNLD infants may reflect stress, compromised nutrition (GH resistance), or a feedback loop involving a direct effect of GH on lung growth and repair.

Bronchopulmonary Dysplasia↗

PubMed1998

Optical oxygen sensor instrumentation based on the detection of luminescence lifetime.

Optical oxygen sensors are mainly based on the principle of luminescence quenching. In contrast to arready existing intensity-based systems, the measurement of the luminescence lifetime provides certain advantages, such as insensitivity to photobleaching or leaching of the dye, or changes in the intensity of excitation light. This facilitates the use of simple optical systems or optical fibres. A new family of oxygen-sensitive dyes, the porphyrin-ketones, has been introduced, which exhibits favorable spectral properties and decay times in the order of tens and hundreds of microseconds. This allows the use of simple optoelectronic circuitry and low-cost processing electronics. An optical oxygen sensor module has been developed with the dimensions of only 120 x 60 x 30 mm. The prototype is based on the measurement of the decay time of the luminophore by measuring the phase shift between the square-wave excitation and the detected square-wave of the emission coming from the sensor. The instrument is based on semiconductor devices (light-emitting diodes, photodiodes) and may be used for the detection of oxygen in gaseous or liquid samples. The measurement range of the device is from 0 to 200 hPa oxygen partial pressure with a resolution of < 1 hPa over the whole measurement range. The overall measurement accuracy of < +/- 1 hPa has been obtained for periods of 24 h of continuous measurement in a thermostatted environment. The sensor response times t90 are typically < 1 s for gases and 0.5 to 5 min for liquid samples.

Biosensing Techniques↗

PubMed1998

What makes a coronary myocardial bridge symptomatic?

The clinical significance of coronary myocardial bridging has been debated and different interventional strategies proposed. We discuss the case of a patient who presented with the recent onset of symptoms of exertional chest pain, diaphoresis, and electrocardiographic signs of acute anterior myocardial wall ischemia. Cardiac catheterization demonstrated a segmental high-grade narrowing of the mid left anterior descending coronary artery during systole consistent with bridging. Intravenous fluid resuscitation and calcium channel blockade resulted in normalization of his electrocardiogram and complete resolution of his anginal symptoms and coronary angiographic systolic narrowing.

Administration, Oral↗

PubMed1997

Thyroid function in a population of children with attention deficit hyperactivity disorder.

OBJECTIVE: To determine the prevalence of thyroid hormone abnormalities and generalized resistance to thyroid hormone in a population of children with attention deficit hyperactivity disorder (ADHD) as compared to reference ranges determined from a control population and hence to determine if routine thyroid hormone screening in children with non-familial ADHD is indicated. METHOD: Children attending the State Child Development Centre in Perth, Western Australia with ADHD, as defined by the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) provided the study population. The control population consisted of 353 normal children with a history of allergy in whom radioallergosorbent (RAST) testing was being performed. RESULTS: The prevalence of thyroid hormone abnormalities in the study population was 2.3% (95% CI 0.6%, 5.7%). There were no cases of generalized resistance to thyroid hormone. The prevalence of thyroid hormone abnormalities in the general population of children and adolescents has been reported to vary between 1 and 3.7%. CONCLUSION: Routine thyroid hormone screening is not indicated in children with non-familial ADHD.

Adolescent↗

PubMed1996

New instrumentation for optical measuring of oxygen in gas or dissolved in liquids.

The optical oxygen sensor is a novel device for the determination of oxygen in gases or dissolved in liquids. It is based on the measurement principle of fluorescence quenching, which is completely different from that of polarographic oxygen sensors (today the most widespread devices of oxygen detection). The new instrument offers features and advantages, which render it not only a realistic alternative, but, for specific applications, make it superior to existing electrochemical methods. The system is based on low-cost semiconductor devices (light-emitting diodes, photodiodes, low-cost analogue and digital components) and new LED-compatible oxygen-sensitive membranes. The flow cell of the instrument may be thermostatted and the sensor can be calibrated by a simple two-point calibration procedure. The optical oxygen sensor is particularly suitable for measuring dissolved oxygen in respirometry, since no oxygen is consumed by the device and the signal is independent of sample flowrate or stirring speed. Typical fields of application are monitoring of oxygen in ground and drinking water, in process control in bioreactors and in breath gas and blood gas analysis.

Biosensing Techniques↗

PubMed1996

The impact of antenatal screening for Down syndrome in Western Australia: 1980-1994.

Since the early 1970s, women in Western Australia have been screened for fetal Down syndrome risk on the basis of maternal age. Women 35 years of age or more at delivery, were offered fetal karyotyping with genetic diagnostic testing via amniocentesis or chorionic villus sampling. An increase in the prevalence of Down syndrome of 3.9% per year (95% confidence interval: 1.8-6.0%) was observed between 1980 and 1994, almost all of which was accounted for by increased maternal age. In 1991, a maternal serum screening (MSS) programme for Down syndrome was first implemented in Western Australia and has since evolved in 6 separate laboratories providing Down risk assessment in 1994. The gradual introduction of MSS programmes had little discernible impact until 1994, when 38% of Down syndrome fetuses were ascertained as a result of increased-risk MSS tests and the birth prevalence of Down syndrome decreased significantly. In this report, we review antenatal screening programmes and their impact on the birth prevalence of Down syndrome in Western Australia.

Adult↗

PubMed1996

Serum progesterone and human chorionic gonadotrophin measurements in the evaluation of ectopic pregnancy.

We evaluated the clinical usefulness of measuring the serum concentrations of human chorionic gonadotrophin (HCG) and progesterone to distinguish between early viable and nonviable pregnancies. We investigated 110 women with clinical symptoms of abnormal pregnancy. A single HCG measurement did not clearly distinguish between ectopic and failing intrauterine pregnancies; an HCG value below 3,000 IU/L, together with a serum progesterone below 40 nmol/L, predicted abnormal pregnancy outcome in 97% of women (positive predictive value: 91%; negative predictive value: 95%). Serum HCG value above 3,000 IU/L or progesterones above 40 nmol/L, discriminated between an ongoing pregnancy and an abnormal pregnancy in 87% women (positive predictive value: 95%; negative predictive value: 91%) and provided reassurance of an ongoing pregnancy. Our results suggest that a combination of serum progesterone and HCG measurements provide clinically useful biochemical information which enhances the prediction of pregnancy outcome.

Chorionic Gonadotropin↗

PubMed1994

Optical triple sensor for measuring pH, oxygen and carbon dioxide.

A triple sensor unit consisting of opto-chemical sensors for measurement of pH, oxygen and carbon dioxide in bioreactors is presented. The pH and the CO2 sensor are based on the color change of a pH-sensitive dye immobilized on a polymeric support. The resulting changes in absorption are monitored through optical fibers. The oxygen sensor is based on the quenching of the fluorescence of a metal-organic dye. All three sensors are fully LED compatible. The sensitive membranes consist of plastic films and can be stored and replaced conveniently. The sensors are sterilizable with hydrogen peroxide and ethanol. In addition, the pH sensor is steam sterilizable. Accuracy, resolution and reproducibility fulfill the requirements for use in biotechnological applications. Calibration procedures for each sensor are presented. The working principle and the performance of all three sensors are described, with particular emphasis given to their application in bioreactors.

Carbon Dioxide↗