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Biomedical subjects

S A Thomas

Publications and source records attributed to S A Thomas.

At least 73 records · Page 4Linked to original sources
PubMed1997

Registered nurse role changes and satisfaction with unlicensed assistive personnel.

This study examines registered nurse perceptions of changes in the role of the registered nurse and registered nurse satisfaction with the use of unlicensed assistive personnel in acute hospital care delivery systems. Six major functional areas were examined: leadership, communication patterns, health teaching, evaluation activities, care management responsibilities, and unit tasks. Moderate to profound changes were reported in areas relating to the team leader role. Registered nurses reported dissatisfaction with unlicensed assistive personnel's ability to perform delegated nursing tasks, communicate pertinent information, and provide more time for professional nursing activities.

Adult↗
PubMed1997

Quantification of efflux into the blood and brain of intraventricularly perfused [3H]thymidine in the anaesthetized rabbit.

Studies using choroid plexuses incubated in vitro have led to the conclusion that pyrimidine deoxyribonucleosides, such as thymidine, enter the brain predominantly through the blood-cerebrospinal fluid (CSF) barrier across the choroid plexuses. In order to examine this hypothesis, ventriculocisternal perfusions were carried out to determine the magnitude of the passage of [3H]thymidine from the CSF into the brain and blood. These experiments demonstrated that approximately 50% of the [3H]thymidine was eliminated from the CSF perfusate, some 41.6 +/- 5.6% passing into the blood and only 7.6 +/- 0.6% to the brain. Efflux into both the blood and brain was saturable, with a Km of 17.8 microM and a Vmax of 0.46 nM min-1, and partially nitrobenzylthioinosine (NBMPR) sensitive. However, a non-saturable component did exist (Kd, 13.8 microliters min-1). Overall, the rapid removal of [3H]thymidine from the CSF and its low uptake from the CSF into the brain suggests that the choroid plexuses would be an inefficient pathway for the entry of this pyrimidine deoxyribonucleoside into the brain.

Affinity Labels↗
PubMed1997

Blood-brain barrier permeability and bioavailability of a highly potent and mu-selective opioid receptor antagonist, CTAP: comparison with morphine.

D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) is a cyclic, penicillamine-containing octapeptide that is structurally similar to somatostatin and displays greater antagonist potency and selectivity for mu-opioid receptors, compared with the classical mu-selective antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2. The aim of this study was to determine whether CTAP can enter the central nervous system (CNS) by crossing either the blood-brain barrier or the blood-cerebrospinal fluid barrier (CSF) and to characterize the mechanism of CNS entry. CNS entry of [3H]CTAP was compared with that of the vascular space marker [14C]inulin and the mu-agonist [3H]morphine. By using an in situ brain perfusion technique coupled to high-performance liquid chromatographic analysis, greater amounts of radioactivity were detected in the brain or CSF at most time points for [3H]CTAP, compared with [14C]inulin. [3H]CTAP was found to remain predominantly intact in the brain after a 20-min rat brain perfusion (62.8%). CTAP was also stable in the blood and serum of rats (T1/2 > 500 min), showing that the structure of this peptide offers enzymatic resistance. Additionally, [3H]CTAP was found to be extensively protein-bound to albumin in the perfusion medium (68.2%) and to proteins in rat serum (84.2%). Entry into the brain and CSF was not inhibited by the addition of unlabeled CTAP to the perfusion medium, suggesting that passage into the CNS is most likely through diffusion across the membranes that comprise the blood-brain barrier, rather than by saturable transport. Also, greater amounts of [3H]morphine entered both the brain and CSF after a 20-min brain perfusion, compared with [3H]CTAP. The increased CNS penetration observed for [3H]morphine, compared with [3H]CTAP, is likely due to the increased lipophilicity of morphine, as shown by its higher octanol/saline partition coefficient. Based on the pharmacokinetic profile, CTAP may be a promising mu-selective antagonist that can be used as a treatment for opiate overdose or addiction and also as a pharmacological tool to further understand opioid neurobiology.

Animals↗
PubMed1997

The entry of [D-penicillamine2,5]enkephalin into the central nervous system: saturation kinetics and specificity.

The delta opioid receptor-selective, enzymatically stable peptide [D-Penicillamine2,5]enkephalin (DPDPE) has recently acquired special significance with the identification of a saturable uptake system for this analgesic into the CNS. The aim of the present study was to characterize further the entry of [3H]DPDPE into the brain and CSF by means of a bilateral in situ brain perfusion method. Initial experiments revealed a saturable [3H]DPDPE uptake into the brain that followed Michaelis-Menten type kinetics with a K(m) value of 45.5 +/- 27.6 microM, a V(max) value of 51.1 +/- 13.2 pmol x min(-1) x g(-1) and a K(d) value of 0.6 +/- 0.3 microl x min(-1) x g(-1). Uptake of [3H]DPDPE into the CSF could not be inhibited (K(d) = 0.9 +/- 0.1 microl x min(-1) x g(-1)). Entry of [3H]DPDPE into the CNS was not inhibited in the presence of 10 mM 2-aminobicyclo-[2,2,1]-heptane-2-carboxylic acid (BCH) or 50 microM ICI 174,864, which suggests that the saturable mechanism does not involve the large neutral amino acid transporter or binding to opioid receptors. It would also appear that [3H]DPDPE is not in competition with either poly-L-lysine or insulin to enter the CNS. However, both of these substances significantly increased the CNS entry of [3H]DPDPE but not that of the vascular space marker [14C]sucrose, and this may have valuable clinical implications. It is not known at present which saturable uptake mechanism is responsible for the CNS entry of [3H]DPDPE, but overall the results suggest a carrier-mediated transport system.

Animals↗
PubMed1997

Structure-activity relationships of a series of [D-Ala2]deltorphin I and II analogues; in vitro blood-brain barrier permeability and stability.

[D-Ala2]deltorphins are enzymatically stable, amphibian heptapeptides that have a higher affinity and selectivity for delta-opioid receptors than any endogenous mammalian compound known. This study investigated the in vitro blood-brain barrier permeability, using primary bovine brain microvessel endothelium culture, and the resistance to enzymatic degradation, in mouse 15% brain membrane homogenates and 100% plasma, of [D-Ala2]deltorphin I, [D-Ala2]deltorphin II and several analogues. Derivatives were designed with the addition of N-terminal neutral and basic amino acids or with alterations of the amino acids present within the deltorphin sequences. The results indicated that the N-terminal sequence and the amino acids in position 4 and 5 are critical to deltorphin analogue BBB permeability and biological stability, i.e., t 1/2 brain; 4.8 hr- [D-Ala2]deltorphin I; > 15 hr- [D-Ala2, Ser4, D-Ala5]deltorphin. Although, no analogue was found to increase the BBB permeability coefficient (PC; x10(-4) cm/min) of the parent compounds ([D-Ala2]deltorphin II, PC = 23.49 +/- 2.42) analogues were identified: [Arg0, D-Ala2]deltorphin II, PC = 19.06 +/- 3.73 and [Pro-1, Pro0, D-Ala2]deltorphin II, PC = 22.22 +/- 5.93; which had similar permeability coefficients, even though they had larger molecular weights and, in the case of the cationic prodrug, a significantly lower lipophilicity. These analogues provide directions in the development of future pro-drugs for the treatment of pain and this study further clarifies the structure-activity relationship of the deltorphins.

Analgesics, Opioid↗
PubMed1997

Psychological factors and survival in the cardiac arrhythmia suppression trial (CAST): a reexamination.

BACKGROUND: Evaluating the independent effects of psychosocial and physiological factors on survival of cardiac patients is difficult because it requires obtaining extensive physiological and psychosocial data and long-term follow-up of high-risk patients. OBJECTIVES: To examine the independent contributions of psychosocial and physiological status to survival of patients who had had myocardial infarction. METHODS: The sample consisted of 348 patients in the Cardiac Arrhythmia Suppression Trial who had asymptomatic ventricular arrhythmias after myocardial infarction. Psychosocial status was assessed with the Social Support Questionnaire-6, Social Readjustment Rating Scale, State-Trait Anxiety Inventory, Self-Rating Depression Scale, Jenkins Activity Survey, and Expression of Anger Scale. Physiological data included measurement of left ventricular ejection fraction; history of previous myocardial infarction, congestive heart failure, and diabetes; and results of Holter monitoring. RESULTS: At the first follow-up, after the effect of the physiological predictors was controlled for, psychosocial factors were significant independent predictors of survival. Among men in the nonactive medication group (n = 263), higher state anxiety, lower anger outward, more past life events, and lower expectations of future life events were predictors of mortality. Data suggested that the relationship of anger to mortality might differ for men and women. Increases in past life events and depression from baseline to first follow-up were greater among those who died than among those who lived. CONCLUSION: Among patients who had asymptomatic ventricular arrhythmias after myocardial infarction, psychological status during the period after infarction contributed to mortality beyond the effect of physiological status. The results reaffirm the critical interrelationship between mind and body for cardiovascular health.

Adult↗
PubMed1997

The passage of azidodeoxythymidine into and within the central nervous system: does it follow the parent compound, thymidine?

The transport of azidodeoxythymidine (AZT) into and within the central nervous system (CNS) has special clinical significance due to the ability of AZT to alleviate certain neurological symptoms associated with the acquired immunodeficiency syndrome (AIDS). AZT was thought to be similar to its parent compound, thymidine, in that it entered the CNS via the choroid plexuses (blood-CSF barrier) and could not cross the blood-brain barrier (BBB). However, a saturable transport system for thymidine at the BBB has recently been identified. The aim of this study was to test the hypothesis that AZT follows its physiological counterpart in its mode of entry into and movement within the CNS. Initial experiments using the in situ brain perfusion technique indicated that the blood-to-CNS transfer constants for [3H]AZT (blood-to-cerebrum; 0.95 +/- 0.12 microl/min/g) were significantly lower than those determined for [3H]thymidine. Also, [3H]AZT entered the CNS purely by a diffusive process. The movement of [3H]AZT within the CNS was further investigated by a ventriculocisternal perfusion technique and indicated that the majority of intraventricularly perfused [3H]AZT remained within the ventricles (79.9%), with little escaping to blood (14.1 +/- 3.1%) or brain (6.0 +/- 1.3%). Overall, these results suggest that the choroid plexus/CSF pathway was unlikely to be solely responsible for the levels of [3H]AZT observed in brain and that the BBB plays a significant role in the brain entry of this analog. However, in contrast to thymidine, AZT enters the CNS purely by a diffusional process.

Animals↗
PubMed1996

Adherence and arrhythmic mortality in the cardiac arrhythmia suppression trial (CAST).

Patient adherence to therapy is essential to assess treatment efficacy, particularly in clinical trials. Active treatment usually is expected to benefit patients. The healthy adherer effect, the association or greater adherence to all health-promoting behaviors, including medication and overall concern for health, explains the improved survival of more adherent patients in both active and placebo medication groups of several clinical trials. The Cardiac Arrhythmia Suppression Trial (CAST), a placebo-controlled double-blind clinical trial of post-myocardial infarction (MI) patients with asymptomatic ventricular arrhythmias, in which active medication (encainide or flecainide) led to increased mortality, provided an opportunity to examine the relationship of adherence to survival from a different perspective. We consider whether adherence to active treatment was related to arrhythmic mortality and whether a healthy adherer effect might counteract the effect of treatment on mortality among patients taking active medication. Adherence (average pill count) at the first follow-up visit did not differ in the active treatment (92.2%, standard deviation (SD) = 11.97, n = 574) and placebo (90.8%, SD = 13.66, n = 579) groups. In a Cox proportional hazard regression model, medication adherence predicted arrhythmic mortality among the active (P < 0.0062) but not the placebo medication group. The effect of adherence on arrhythmic mortality was significant beyond the effects of ejection fraction, race, spouse, smoking status, diuretic medication, and history of MI. A 10% increase in adherence led to more than a threefold increase of risk of arrhythmic death. The design of the CAST, which included a titration phase, may have tended to select relatively adherent patients since only those whose arrhythmias were suppressed with active medication were randomized into the trial. The data do not support a strong healthy adherer effect in the CAST. There was no evidence in this study that a healthy adherer effect counterbalanced the effect of the active medication.

Anti-Arrhythmia Agents↗
PubMed1996

Detection and distribution of heat shock proteins 27 and 90 in human benign and malignant prostatic tissue.

OBJECTIVE: To determine whether it is possible to predict the behaviour of prostate tumours by identifying cellular characteristics, specifically specific heat shock proteins (HSPs). MATERIALS AND METHODS: An immunohistochemical study staining for HSP 27 and 90 was undertaken on 15 benign and 13 malignant samples of freshly frozen prostatic tissue obtained from patients with a similar age range in each group (benign, mean age 71.6 years, range 61-86; malignant, mean age 72.7 years, range 58-87). Gleason scores for the tumours ranged from 2 to 8. RESULTS: Consistent patterns of cytoplasmic staining were seen in all sections of tissue from benign prostatic hyperplasia (BPH). The stroma stained strongly positive for HSP 27, but negatively for HSP 90 and glandular epithelium showed positive apical staining for both HSPs. Stromal patterns in prostatic carcinoma tissue were similar to that of BPH tissue for both HSP 27 and 90. Areas of prostatic intra-epithelial neoplasia stained as strongly as did adjacent areas of BPH. For HSP 27, there was varied staining of individual epithelial cells, suggesting cellular heterogeneity, with an apparent reduction in staining with increasing Gleason score and invasiveness. For HSP 90, this pattern was less marked, with a predominance for positive staining throughout all grades of carcinoma. CONCLUSIONS: The distribution of HSPs, primarily HSP 27, may aid in identifying different cell populations within prostatic carcinomas and thus help forecast biological behaviour.

Aged↗
PubMed1996

Blood pressure.

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Blood Pressure↗
PubMed1995

Pet ownership, social support, and one-year survival after acute myocardial infarction in the Cardiac Arrhythmia Suppression Trial (CAST).

Social support and pet ownership, a nonhuman form of social support, have both been associated with increased coronary artery disease survival. The independent effects of pet ownership, social support, disease severity, and other psychosocial factors on 1-year survival after acute myocardial infarction are examined prospectively. The Cardiac Arrhythmia Suppression Trial provided physiologic data on a group of post-myocardial infarction patients with asymptomatic ventricular arrhythmias. An ancillary study provided psychosocial data, including pet ownership, social support, recent life events, future life events, anxiety, depression, coronary prone behavior, and expression of anger. Subjects (n = 424) were randomly selected from patients attending participating Cardiac Arrhythmia Suppression Trial sites and completed baseline psychosocial questionnaires. One year survival data were obtained from 369 patients (87%), of whom 112 (30.4%) owned pets and 20 (5.4%) died. Logistic regression indicates that high social support (p < 0.068) and owning a pet (p = 0.085) tend to predict survival independent of physiologic severity and demographic and other psychosocial factors. Dog owners (n = 87, 1 died) are significantly less likely to die within 1 year than those who did not own dogs (n = 282, 19 died; p < 0.05); amount of social support is also an independent predictor of survival (p = 0.065). Both pet ownership and social support are significant predictors of survival, independent of the effects of the other psychosocial factors and physiologic status. These data confirm and extend previous findings relating pet ownership and social support to survival among patients with coronary artery disease.

Adult↗
PubMed1995

Antitumor activity of 9(R)-dihydrotaxane analogs.

A novel reduced taxane, 13-acetyl-9(R)-dihydrobaccatin III (1) has been isolated from Taxus canadensis. The selective C-13 deacetylation of this isolate has allowed for the preparation of a wide variety of 9(R)-dihydrotaxane analogs. In general, this series has shown greater stability and water solubility than the 9-carbonyl series while retaining antimicrotubule and tumor cell cytotoxicity activities relative to taxol. Placement of polar functionalities at the C-7 position results in loss of activity whereas alkylation or acylation of either C-7 or C-9 hydroxyl groups ameliorate the activity.

Animals↗
PubMed1995

Noradrenaline is essential for mouse fetal development.

Catecholamines such as noradrenaline and adrenaline have been implicated in numerous physiological processes but, although catecholamine synthesis begins at mid-gestation, previous studies have provided little evidence for any role in early development. Furthermore, there are several case reports of humans with noradrenaline deficiency. To investigate this, we use gene targeting to produce mice lacking dopamine beta-hydroxylase and therefore unable to synthesize noradrenaline or adrenaline. We report here that in heterozygous mothers, most homozygous embryos died in utero, and only about 5% reached adulthood. Survival probably depends on catecholamine transfer across the placenta because, in homozygous mothers, all embryos die in utero. Mortality was due to lack of noradrenaline in utero because it could be prevented by treatment with dihydroxyphenylserine, a precursor that can be converted to noradrenaline in the absence of dopamine beta-hydroxylase. Mutant embryos had a histological phenotype similar to that of embryos deficient in tyrosine hydroxylase, suggesting that death might be due to cardiovascular failure.

Animals↗
PubMed1995

Altered behavior and long-term potentiation in type I adenylyl cyclase mutant mice.

The murine Ca(2+)-stimulated adenylyl cyclase (type I) (EC 4.6.1.1), which is expressed predominantly in brain, was inactivated by targeted mutagenesis. Ca(2+)-stimulated adenylyl cyclase activity was reduced 40-60% in the hippocampus, neocortex, and cerebellum. Long-term potentiation in the CA1 region of the hippocampus from mutants was perturbed relative to controls. Both the initial slope and maximum extent of changes in synaptic response were reduced. Although mutant mice learned to find a hidden platform in the Morris water task normally, they did not display a preference for the region where the platform had been when it was removed. These results indicate that disruption of the gene for the type I adenylyl cyclase produces changes in behavior and that the cAMP signal transduction pathway may play an important role in synaptic plasticity.

Adenylyl Cyclases↗
PubMed1995

Rehabilitation teams decisions on discharge housing for stroke patients.

For older people who have had a stroke, appropriate housing can promote independence and well being. However, suboptimal team accommodation recommendations may result in placement of an individual where their needs are not met, and their skills are not maximized. Although clinical judgments regarding patient discharge are routinely made by rehabilitation teams, this area has received limited research attention. This study examines how rehabilitation teams determine the most appropriate housing to recommend to stroke patients after their discharge from hospitals. A Social Judgment Theory approach was used to document and analyze the accommodation recommendations and policies of 13 rehabilitation teams (clinician n = 74). Teams were asked to consider 50 hypothetical stroke patients, and determine the most appropriate discharge housing to recommend to these patients. Each stroke patient was described in terms of 8 attributes: mobility status, ability to manage their own affairs, patient's choice of housing, personal activity of daily living (ADL) skills, domestic and community ADL skills, general health status, social situation, and premorbid living arrangements. Clinicians were provided with a response scale on which to record their recommendations. The results showed considerable yet reliable differences among teams concerning recommendations made, and judgment policies adopted. Although the highly structured and hypothetical nature of this research limits the external validity of findings, the results suggest that teams may also face difficulties with housing recommendations in the more complex clinical environment. Further studies to assess actual clinical team decision making are needed. Such studies could lead to the development of a standardized research-based protocol to help teams formalize and optimize their housing recommendations.

Aged↗
PubMed1995

Cardiovascular reactivity during verbal communication: an emerging risk factor.

Cardiovascular reactivity (CR), the abrupt increase in blood pressure and heart rate that occurs during stress, is emerging as a potential risk factor for hypertension and coronary heart disease. This article reviews the research on CR to verbal communication, an everyday stressor. A case study is presented to illustrate the usefulness of this research to clinical practice. Strategies to decrease CR during talking are presented.

Adult↗
PubMed1995

Changes related to care delivery patterns.

Nurse administrators, faced with a need to increase productivity and reduce costs in response to lower inpatient volumes and increased competition, are restructuring systems of care delivery. A survey of acute care hospitals was conducted to determine the extent of changes in nursing care delivery models, skill mix, assignment of non-nursing personnel to the nursing department, use of unlicensed assistive personnel, and registered nurse role changes in healthcare delivery systems employing unlicensed personnel.

California↗