Biomedical subjects

S A Thomas

Publications and source records attributed to S A Thomas.

At least 37 records · Page 2Linked to original sources

PubMed2001

Community values and preferences in transplantation organ allocation decisions.

This paper is concerned with community values and preferences in organ transplantation allocation decisions. With recent trends in organ shortages, transplant teams face difficult allocation decisions amongst increasing numbers of "worthy" potential recipients. It is argued that the debate about these decisions ought to be informed in part by a systematic knowledge of prevailing community standards. A community sample of 238 adults (140 women and 98 men, with a mean age of 47.0 years) completed a questionnaire concerning which factors ought to affect recipient priority for transplantation. Longer waiting time, better prognosis, younger age and being a parent were the most frequently selected criteria for organ allocation decisions. The participants also rank ordered 16 potential recipients presented in the form of case scenarios in terms of priority for transplantation. The 16 case scenarios were constructed from a factorial combination of four variables: age of recipient (young vs old); the time the recipient had been on a waiting list (long vs short); recipient prognosis (excellent vs fair); and parental status (children vs no children). It was found that one case scenario involving a young parent with an excellent prognosis and long waiting time was ranked first by 75.2% of all participants. Analysis revealed that transplant recipient age and prognosis were the most influential factors in determining the priority rankings for organ allocation. The study has demonstrated that judgement and decision analysis procedures can be used to elicit community values and preferences about complex resource allocation decisions.

Adult↗

PubMed2001

Important role of endogenous norepinephrine and epinephrine in the development of in vivo pressure-overload cardiac hypertrophy.

OBJECTIVES: We sought to define the role of norepinephrine and epinephrine in the development of cardiac hypertrophy and to determine whether the absence of circulating catecholamines alters the activation of downstream myocardial signaling pathways. BACKGROUND: Cardiac hypertrophy is associated with elevated plasma catecholamine levels and an increase in cardiac morbidity and mortality. Although considerable evidence suggests that G-protein-coupled receptors are involved in the hypertrophic response, it remains controversial whether catecholamines are required for the development of in vivo cardiac hypertrophy. METHODS: We performed transverse aortic constriction (TAC) in dopamine beta-hydroxylase knockout mice (Dbh(-/-), genetically altered mice that are completely devoid of endogenous norepinephrine and epinephrine) and littermate control mice. After induction of cardiac hypertrophy, the mitogen-activated protein kinase (MAPK) signaling pathways were measured in pressure-overloaded/wild-type and Dbh(-/-) hearts. RESULTS: Compared with the control animals, cardiac hypertrophy was significantly blunted in Dbh(-/-) mice, which was not associated with altered cardiac function, as assessed by transthoracic echocardiography in conscious mice. The extracellularly regulated kinase (ERK 1/2), c-jun-NH(2)-terminal kinase (JNK) and p38 MAPK pathways were all activated by two- to threefold after TAC in the control animals. In contrast, induction of the three pathways (ERK 1/2, JNK and p38) was completely abolished in Dbh(-/-) mice. CONCLUSIONS: These data demonstrate a nearly complete requirement of endogenous norepinephrine and epinephrine for the induction of in vivo pressure-overload cardiac hypertrophy and for the activation of hypertrophic signaling pathways.

Animals↗

PubMed2001

Complications of fluoroscopically guided caudal epidural injections.

OBJECTIVES: To assess the incidence of complications of fluoroscopically guided caudal epidural injections. DESIGN: A retrospective cohort design study in which chart review was performed on patients, who presented with radiculopathy and received fluoroscopically guided caudal epidural steroid injections. All injections were performed consecutively over a 12-mo period. An independent observer reviewed medical charts, which included a 24-hr post procedure telephone call by an ambulatory surgery center nurse, who asked a standardized questionnaire about complications after the injections. Physician follow-up office notes 1 to 3 wk after injection along with epidurograms were reviewed. RESULTS: The charts of 139 patients, who received 257 injections, were reviewed. Complications per injection included 12 episodes of insomnia the night of the injection (4.7%), 9 transient nonpositional headaches that resolved within 24 hr (3.5%), 8 increased back pain (3.1%), 6 facial flushing (2.3%), 2 vasovagal reactions (0.8%), 2 episodes of nausea (0.8%), and 1 increased leg pain (0.4%). No dural punctures occurred. CONCLUSIONS: No major complications occurred. The incidence of minor complications was 15.6% per injection. All reactions resolved without morbidity and no patient required hospitalization.

Adult↗

PubMed2001

Living with an implantable cardioverter-defibrillator: a review of the current literature related to psychosocial factors.

Sudden cardiac death (SCD) is responsible for 300,000 deaths annually. Lethal ventricular dysrhythmias account for the majority of SCDs. Implantable cardioverter-defibrillators (ICDs) are the emerging treatment for lethal dysrhythmias. Although reductions in SCD mortality with ICDs are clear, the psychologic and social consequences of these devices reveal a mixed success. Patients with ICDs have high levels of anxiety and depressive symptoms. Conversely, most studies of quality of life in patients with ICDs report that the device is well accepted despite fears of being shocked. The ICD shocks are a unique aspect of treatment and have the potential to cause psychologic distress. Nursing needs to provide care from a holistic perspective. Support groups provide reassurance and allow patients to discuss expectations and fears related to the ICD. Research needs to be conducted to explore the impact of these devices on the lives of patients and their families.

Anxiety↗

PubMed2001

Use of dopamine-beta-hydroxylase-deficient mice to determine the role of norepinephrine in the mechanism of action of antidepressant drugs.

Norepinephrine (NE) is thought to play an important role in the pathophysiology of depression, and in the mechanism of action of antidepressant compounds. Previously, we created mice that are unable to synthesize NE and epinephrine due to targeted disruption of the dopamine-beta-hydroxylase gene (Dbh). To specifically test the role of NE in mediating behavioral changes elicited by antidepressants, these mice were examined in the forced swim test. There was no difference in baseline immobility scores in the forced swim test between Dbh(+/-) mice, which have normal levels of NE, and Dbh(-/-) mice. However, the Dbh(-/-) mice failed to demonstrate antidepressant-like behavioral effects following the administration of several classes of antidepressants. These included the NE reuptake inhibitors desipramine and reboxetine, the monoamine oxidase inhibitor pargyline, and the atypical antidepressant bupropion. In addition, desipramine significantly reduced immobility in the Dbh(-/-) mice following pretreatment with the synthetic NE precursor L-threo-3,4-dihydroxyphenylserine, but not saline. Biochemical studies showed that there was no significant difference in the regional brain levels of NE transporter immunoreactivity or monoamine oxidase activity, the primary targets for most of the compounds examined. Taken together, these data show that the use of mice that lack endogenous NE may be an important strategy for unraveling the role of NE in tests sensitive to the effects of various psychotherapeutic agents.

Animals↗

PubMed2001

Transport characteristics of the anti-human immunodeficiency virus nucleoside analog, abacavir, into brain and cerebrospinal fluid.

The role of the blood-brain and blood-cerebrospinal fluid (CSF) barriers in the distribution of anti-human immunodeficiency virus (HIV) drugs is integral to the design of effective treatment regimens for HIV infection within the brain. Abacavir (formerly 1592U89) is a nucleoside analog reverse transcriptase inhibitor, which has activity against HIV. The ability of this drug to reach the brain at therapeutic concentrations has been explored by means of an established bilateral in situ brain perfusion model in combination with high-performance liquid chromatography analysis in the anesthetized guinea pig. The influence of other drugs on the entry of abacavir into the brain was also investigated and is of special significance with the use of three of more anti-HIV drugs as the recommended treatment for HIV infection. The results of this study indicate that intact [(14)C]abacavir can cross the blood-brain and blood-CSF barriers and enter the brain and cisternal CSF. Further studies, at a perfusion time of 10 min, revealed that the uptake (R(cerebrum)) of this (14)C-labeled drug (10.1 +/- 0.6%) was not affected by the presence of 0.86 to 200 microM unlabeled abacavir (6.8 microM; 11.0 +/- 1.4%), the nucleoside transport inhibitor [10 microM 6-(4-nitrobenzyl)thio-9-beta-D-ribofuranosylpurine; 9.7 +/- 3.3%], or a substrate for the nucleobase transporter (100 microM adenine; 12.7 +/- 3.0%). This would suggest that the entry of abacavir into the brain would not be affected by the presence of other anti-HIV drugs. The results of this animal study indicate that abacavir would be a useful addition to a treatment regimen against HIV-infection within the brain.

Algorithms↗

PubMed2000

Synthetic strands of neonatal mouse cardiac myocytes: structural and electrophysiological properties.

The aim of the present study was to morphologically and electrically characterize synthetic strands of mouse ventricular myocytes. Linear strands of mouse ventricular myocytes with widths of 34.7+/-4.4 microm (W(1)), 57.9+/-2.5 microm (W(2)), and 86.4+/-3. 6 microm (W(3)) and a length of 10 mm were produced on glass coverslips with a photolithographic technique. Action potentials (APs) were measured from individual cells within the strands with cell-attached microelectrodes. Impulse propagation and AP upstrokes were measured with multisite optical mapping (RH237). Immunostaining was performed to assess cell-cell connections and myofibril arrangement with polyclonal antisera against connexin43 and N-cadherins and monoclonal antibodies against cardiac myosin. Light microscopy and myosin staining showed dense growth of well-developed elongated myocytes with lengths of 34.2+/-4.2 microm (W(1)), 36. 9+/-5.8 microm (W(2)), and 43.7+/-6.9 microm (W(3)), and length/width ratios of 3.9+/-0.2. Gap junctions were distributed around the cell borders (3 to 4 junctions/microm(2) cell area). Each cell was connected by gap junctions to 6.5+/-1.1 neighboring cells. AP duration shortened with time in culture (action potential duration at 50% repolarization: day 4, 103+/-34 ms; day 8, 16+/-3 ms; P:<0.01). Minimum diastolic potential and AP amplitude were 71+/-5 and 97.2+/-7.6 mV, respectively. Conduction velocity and the maximum dV/dt of the AP upstroke were 43.9+/-13.6 cm/s and 196+/-67 V/s, respectively. Thus, neonatal ventricular mouse myocytes can be grown in continuous synthetic strands. Gap junction distribution is similar to the neonatal pattern observed in the hearts of larger mammals. Conduction velocity is in the range observed in adult mice and in the higher range for mammalian species probably due to the higher dV/dt(max). This technique will permit the study of propagation, AP, and structure-function relations at cellular resolution in genetically modified mice.

Action Potentials↗

PubMed2000

Synthesis of 1,3-diynes via palladium-catalyzed reaction of 1, 1-dibromo-1-alkenes.

[reaction: see text] Both symmetric and unsymmetric 1,3-diynes were prepared from the palladium-catalyzed reaction of 1,1-dibromo-1-alkenes. The formation of symmetric 1,3-diynes 2 (homocoupling) was catalyzed by a weak ligand, tris(2-furyl)phosphine (TFP), and the addition of catalytic amount of CuI accelerated the reaction. The synthesis of unsymmetric 1,3-diynes 4 (the Sonogashira reaction) required a highly electron rich tris(4-methoxyphenyl)phosphine as the ligand, and CuI promotes the formation of byproduct 1,1-diynyl-1-alkenes 5.

Journal Article↗

PubMed2000

Total synthesis and antifungal evaluation of cyclic aminohexapeptides.

The need for new therapies to treat systemic fungal infections continues to rise. Naturally occurring hexapeptide echinocandin B (1) has shown potent antifungal activity via its inhibition of the synthesis of beta-1,3 glucan, a key fungal cell wall component. Although this series of agents has been limited thus far based on their physicochemical characteristics, we have found that the synthesis of analogues bearing an aminoproline residue in the 'northwest' position imparts greatly improved water solubility (> 5 mg/mL). The synthesis and structure-activity relationships (SAR) based on whole cell and upon in vivo activity of the series of compounds are reported.

Acute Disease↗

PubMed2000

Perceptions of registered nurses working with assistive personnel in the United Kingdom and the United States.

This study examines registered nurse perceptions of their role in acute care hospitals that use nursing care assistants (NCA) and unlicensed assistive personnel (UAP). Also studied was registered nurse (RN) satisfaction with nursing care assistants and unlicensed assistive personnel in the United Kingdom (UK) and the United States of America (USA). The purpose of this study is to assist RNs and managers in the re-design of health-care delivery systems by investigating: 1. The differences and similarities of registered nurses in the UK and the USA in the perceptions of changes in the RN role when working with nursing care assistants or unlicensed assistive personnel. 2. The differences between and similarities of registered nurses in the UK and the USA in perceptions of NCA and UAP abilities to perform delegated duties, to communicate pertinent clinical information and to provide more time for professional nursing activities. Registered nurse perceptions in the UK were compared with the findings of a previous study of RN role changes and satisfaction in the USA. Registered nurses in the UK did not perceive a profound change in their role when working with UAP and were more satisfied with their use than were RNs in the USA.

Adult↗

PubMed2000

State and territorial boards of nursing approaches to the use of unlicensed assistive personnel.

This study examined U.S. state and territorial boards of nursing approaches to the regulation of the use of: unlicensed assistive personnel (UAP) in acute care hospitals; state and jurisdictional authority, oversight and disciplinary action related to registered nurse (RN) delegation, supervision and assignment; educational preparation requirements for UAP; and future projections for their use. A survey was administered to 53 state and territorial boards of nursing officials in 1998. A majority of the states reported that they had regulations/guidelines for RN's who supervised UAP and regulations that protected the use of the RN title. Few states used the American Nurses Association or National Council of State Boards of Nursing definitions for delegation, supervision, or assignment. The majority have formulated their own definitions. The majority of states reported no standardized curriculum in place for UAP employed in acute care hospitals. More than half of the states reported that no plans existed for developing a curriculum.

Acute Disease↗

PubMed2000

Smoking patterns, health behaviors, and health-risk behaviors of college women.

In 1993, 22% of college women smoked; in 1997, the rate increased to 29%. College-age women (<24 years) showed the greatest increase in smoking. The purpose of this study is to describe smoking behaviors of college women. The sample included 21 college-age female smokers. Each woman was interviewed about smoking habits and completed a health survey, the Fagerstrom Test for Nicotine Dependence, a Self-Efficacy Scale for predicting smoking relapse, a Decisional Balance Scale for smoking, a readiness for change tool, and the Derogatis Stress Profile. The majority of the students began smoking at the age of 14 years or younger and smoked fewer than 10 cigarettes per day. The biggest obstacles to quitting were being around other smokers and social activities involving alcohol. These students did not smoke when ill and were interested in quitting smoking. Smoking frequency correlated significantly with dependency and stage of change. Advanced practice nurses have a unique opportunity to identify these young smokers, educate them about smoking-cessation options, and offer specific strategies to help these women stop smoking.

Adolescent↗

PubMed1999

Absence of troponin I degradation or altered sarcoplasmic reticulum uptake protein expression after reversible ischemia in swine.

The findings of troponin I (TnI) proteolysis (in isolated rat hearts) and induction of selected sarcoplasmic reticulum (SR) calcium-regulatory genes (after repetitive total coronary occlusions in swine) have given rise to the hypothesis that the time course of functional recovery of stunned myocardium reflects the resynthesis of reversibly damaged proteins. Although stunning occurs after brief total occlusions and prolonged partial occlusions (ie, short-term hibernation), the time course of functional recovery varies from a few hours to several days, suggesting that the severity of protein damage or mechanisms responsible for the dysfunction may differ. To study this, we examined SR gene expression and TnI degradation in stunned myocardium produced by 10-minute total left anterior descending coronary artery (LAD) occlusions (n=4) or 1-hour partial LAD occlusions, in which flow was reduced to approximately 50% of control values for 60 minutes (n=6) in swine. One hour after reperfusion, LAD wall thickening was severely depressed in both models despite normal perfusion and no triphenyltetrazolium chloride evidence of necrosis. Normal myocardium exhibited TnI immunoreactivity at 31 kDa and a weak secondary band at 27 kDa. Irreversible injury or calpain activation in vitro produced a marked increase in the intensity of the 27-kDa band, consistent with TnI degradation. Stunned myocardium demonstrated no change in the 31- or the 27-kDa band, and the percentage of the 27- to 31-kDa band remained constant after 10-minute total occlusions (LAD, 5.9+/-0.9%; normal, 4.9+/-1.6%) and 1-hour partial occlusions (LAD, 8.5+/-1.9%; normal, 7.3+/-1.4%) and in sham controls (LAD, 10.9+/-1.5%; normal, 9.8+/-1.4%). Northern analysis showed no alterations in TnI or SR gene expression, but the stress protein HSP-70 was variably induced. Thus, stunned myocardium occurs without TnI degradation or altered SR gene expression, indicating that additional mechanisms are responsible for the reversible dysfunction after single episodes of regional ischemia in swine.

Animals↗

PubMed1999

Enhanced contractility and decreased beta-adrenergic receptor kinase-1 in mice lacking endogenous norepinephrine and epinephrine.

BACKGROUND: Elevated circulating norepinephrine (NE) has been implicated in causing the profound beta-adrenergic receptor (betaAR) downregulation and receptor uncoupling that are characteristic of end-stage human dilated cardiomyopathy, a process mediated in part by increased levels of beta-adrenergic receptor kinase (betaARK1). To explore whether chronic sustained NE stimulation is a primary stimulus that promotes deterioration in cardiac signaling, we characterized a gene-targeted mouse in which activation of the sympathetic nervous system cannot lead to an elevation in plasma NE and epinephrine. METHODS AND RESULTS: Gene-targeted mice that lack dopamine beta-hydroxylase (dbh-/-), the enzyme needed to convert dopamine to NE, were created by homologous recombination. In vivo contractile response to the beta1AR agonist dobutamine, measured by a high-fidelity left ventricular micromanometer, was enhanced in mice lacking the dbh gene. In unloaded adult myocytes isolated from dbh-/- mice, basal contractility was significantly increased compared with control cells. Furthermore, the increase in betaAR responsiveness and enhanced cellular contractility were associated with a significant reduction in activity and protein level of betaARK1 and increased high-affinity agonist binding without changes in betaAR density or G-protein levels. CONCLUSIONS: Mice that lack the ability to generate NE or epinephrine show increased contractility associated primarily with a decrease in the level of betaARK1 protein and kinase activity. This animal model will be valuable in testing whether NE is required for the pathogenesis of heart failure through mating strategies that cross the dbh-/- mouse into genetically engineered models of heart failure.

Adrenergic beta-Agonists↗

PubMed1999

Dopamine beta-hydroxylase deficiency impairs cellular immunity.

Norepinephrine, released from sympathetic neurons, and epinephrine, released from the adrenal medulla, participate in a number of physiological processes including those that facilitate adaptation to stressful conditions. The thymus, spleen, and lymph nodes are richly innervated by the sympathetic nervous system, and catecholamines are thought to modulate the immune response. However, the importance of this modulatory role in vivo remains uncertain. We addressed this question genetically by using mice that lack dopamine beta-hydroxylase (dbh-/- mice). dbh-/- mice cannot produce norepinephrine or epinephrine, but produce dopamine instead. When housed in specific pathogen-free conditions, dbh-/- mice had normal numbers of blood leukocytes, and normal T and B cell development and in vitro function. However, when challenged in vivo by infection with the intracellular pathogens Listeria monocytogenes or Mycobacterium tuberculosis, dbh-/- mice were more susceptible to infection, exhibited extreme thymic involution, and had impaired T cell function, including Th1 cytokine production. When immunized with trinitrophenyl-keyhole limpet hemocyanin, dbh-/- mice produced less Th1 cytokine-dependent-IgG2a antitrinitrophenyl antibody. These results indicate that physiological catecholamine production is not required for normal development of the immune system, but plays an important role in the modulation of T cell-mediated immunity to infection and immunization.

Animals↗

PubMed1999

The provision of preventive care by general practitioners measured by patient completed questionnaires.

The objective of this study was, by means of patient self-report, to measure the provision of preventive care to patients of a sample of Australian general practitioners. Patient-completed questionnaires from a consecutive sample of Australian general practitioners enrolled in the Quality Assurance and Continuing Medical Education Program of the Royal Australian College of General Practitioners were used. Patients were attendees at Australian general practices. The main outcome measures included the following: the provision of tetanus immunization within the last 10 years; blood pressure measurement within the last 12 months; cholesterol screening within the past 5 years; provision of adequate information to enable patients to stop smoking if they desired; discussion about the benefits of diet and exercise to enhance life, and about alcohol intake; provision of cervical smears in the past 2 years; provision of adequate instruction in breast self-examination and overall satisfaction with service provision. A total of 12,605 questionnaires from 133 general practices were completed. There was wide variability between practices in the reported provision of preventive care items including an average of 86% (range 36-100) of patients reporting the provision of blood pressure checking in the past 12 months, 62% (range 25-97%) reporting the provision of tetanus immunization in the past 10 years, and 63% (range 10-91%) reporting having had a cervical smear in the past 2 years. Patients who were very satisfied were more likely to have reported that they had received blood pressure measurement in the past 12 months, participated in discussions about the benefits of diet and exercise in enhancing life, and participated in discussions about alcohol intake and provision of adequate instruction in the technique of breast self-examination. Patient self-reporting identified variability between practitioners in the provision of preventive care conforming to accepted guidelines. Patients who reported that they were very satisfied or who regularly attend only one general practice reported the provision of more preventive care than those who were not very satisfied or who regularly visited two or more general practitioners.

Adolescent↗

PubMed1999

Mental health care: a collaborative, holistic approach.

Managed care has dramatically transformed mental health care. The solo physician practice, once the dominant mode of delivery of care, has almost disappeared. Multidisciplinary, collaborative practices have emerged as flexible, cost-effective alternatives. The article describes a holistic, collaborative model of mental health care. A holistic model includes the professionals, administrative staff, patients, and families in the treatment plan and maximizes collaboration. Cooperation and trust among all the individuals involved are essential to ensure a comprehensive plan to restore health.

Cooperative Behavior↗

PubMed1999

Norepinephrine is required for leptin effects on gene expression in brown and white adipose tissue.

Exogenous leptin enhances energy utilization in ob/ob mice by binding its hypothalamic receptor and selectively increasing peripheral fat oxidation. Leptin also increases uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT), but the neurotransmitter that mediates this effect has not been established. The present experiments sought to determine whether leptin regulates UCP1 expression in BAT and its own expression in white adipose tissue (WAT) through the long or short forms of leptin receptor and modulation of norepinephrine release. Mice lacking dopamine beta-hydroxylase (Dbh-/-), the enzyme responsible for synthesizing norepinephrine and epinephrine from dopamine, were treated with leptin (20 microg/g body weight/day) for 3 days before they were euthanized. UCP1 messenger RNA (mRNA) and protein expression were 5-fold higher in BAT from control (Dbh+/-) compared with Dbh-/- mice. Leptin produced a 4-fold increase in UCP1 mRNA levels in Dbh+/- mice but had no effect on UCP1 expression in Dbh-/-. The beta3-adrenergic agonist, CL-316,243 increased UCP1 expression and established that BAT from both groups of mice was capable of responding to beta-adrenergic stimulation. Similarly, exogenous leptin reduced leptin mRNA in WAT from Dbh+/- but not Dbh-/- mice. In separate experiments, leptin produced comparable reductions in food intake in both Dbh+/- and Dbh-/- mice, illustrating that norepinephrine is not required for leptin's effect on food intake. Lastly, db/db mice lacking the long form of the leptin receptor failed to increase UCP1 mRNA in response to exogenous leptin but increased UCP1 mRNA in response to CL-316,243. These studies establish that norepinephrine is required for leptin to regulate its own expression in WAT and UCP1 expression in BAT and indicate that these effects are likely mediated through the centrally expressed long form of the leptin receptor.

Adipose Tissue↗