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Biomedical subjects

S T Anderson

Publications and source records attributed to S T Anderson.

At least 19 recordsLinked to original sources
PubMed2001

Standards for the function of an academic 12-lead electrocardiographic core laboratory.

An academic 12-lead electrocardiogram (ECG) core laboratory aims to provide the highest possible quality ECG recording, measurement, and storage to aid clinicians in research into important cardiovascular outcomes and to maximize the credibility of scientific results based solely, or in part, on ECG data. This position paper presents a guide for the structure and function of an academic ECG core laboratory. The key functional aspects are: 1) Data collection, 2) Staff composition, 3) Diagnostic measurement and definition standards, 4) Data management, 5) Academic considerations, 6) Economic consideration, and 7) Accreditation. An ECG Core Laboratory has the responsibility for rapid and accurate analysis and responsible management of the electrocardiographic data in multicenter clinical trials. Academic Laboratories, in addition, provide leadership in research protocol generation and production of research manuscripts for submission to the appropriate peer-review journals.

Accreditation↗
PubMed2001

Dopaminergic input to the ventromedial hypothalamus facilitates the oestrogen-induced luteinizing hormone surge in ewes.

In this study we examined the release of dopamine and noradrenaline in the ventromedial hypothalamus (VMH) of ovariectomized ewes during the oestrogen-induced luteinizing hormone (LH) surge by measuring their respective metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and methoxyhydroxyphenylglycol (MHPG) using microdialysis. Further we investigated whether inhibition of catecholamine synthesis in the VMH by bilateral reverse dialysis of alpha-methyl-p-tyrosine (alpha-MPT) would block the oestrogen-induced LH and/or prolactin surges. Oestradiol treatment (50 microg oestradiol benzoate) of ovariectomized ewes resulted in a biphasic LH response, significantly (p < 0.05) decreasing LH concentrations from 2.5 to 10.5 h after injection, followed by an LH surge beginning at 16 h. Prolactin concentrations were also significantly (p < 0.05) increased in oestradiol-treated ewes from 13 h. VMH DOPAC concentrations in oil-vehicle-treated animals were at the level of detection (0.02 ng/ml) in most samples over the 24-hour sampling period. In oestradiol-treated ewes, VMH DOPAC levels were initially low before and up to 8 h after oestradiol injection but then increased significantly (p < 0.05) at 10-12 h and remained elevated up to 20 h after injection. In contrast, oestradiol injection had no effect on MHPG concentrations in the VMH. Bilateral reverse microdialysis of alpha-MPT into the VMH significantly (p < 0.05) delayed the time from oestradiol injection to the onset of the LH surge, the time to peak LH concentration and attenuated the LH surge compared with reverse dialysis of Ringer solution alone. In contrast, alpha-MPT treatment had no effect upon the oestradiol-induced increase in prolactin concentrations. This study provides evidence that the VMH is an important hypothalamic site in the neuro-endocrine control of the LH surge in ewes. The results suggest that dopaminergic neurons with terminals in the VMH are part of a neuronal pathway mediating the positive feedback effects of oestradiol on gonadotropin-releasing hormone secretion and the LH surge.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Adrenoceptor subtype involvement in suppression of prolactin secretion by noradrenaline.

In sheep, injection of noradrenaline suppresses prolactin secretion by a direct effect at the pituitary gland. The aims of this study were to use primary cultures of ovine pituitary cells to examine the receptor subtypes that mediate the inhibitory effect of noradrenaline on prolactin secretion and, by using receptor antagonists in vivo, determine whether noradrenaline acts as a prolactin release-inhibiting factor (PIF). Noradrenaline and dopamine suppressed prolactin secretion from ovine pituitary cells with ED50s of 60.9+/-46.6 and 1.5+/-1.0x10-9 mol/l, respectively (P<0.05). The in-vitro prolactin release-inhibiting effect of noradrenaline (10-7 mol/l) was not blocked by the dopamine antagonists pimozide (D2) or SCH23390 (D1) but was blocked by each of the adrenoceptor antagonists (alpha1-adrenoceptor antagonists prazosin and WB4101, the alpha2-adrenoceptor antagonist yohimbine and the beta-adrenoceptor antagonist propranolol). The response to adrenoceptor agonists was also tested in vitro. The alpha1-adrenoceptor agonists phenylephrine and cirazoline significantly suppressed prolactin. Of the alpha2-agonists, clonidine had no effect whereas oxymetazoline and p-aminoclonidine both suppressed prolactin. The beta-adrenoceptor agonist isoproterenol also suppressed prolactin while the specific beta3-antagonist BRL37344 had no effect. When the adrenoceptor antagonists were tested in vivo in ewes manipulated to be in the luteal phase, only WB4101 significantly (P<0.05) increased plasma prolactin concentrations but this response was small and only observed in one of two experiments. In summary, these experiments suggest that adrenoceptors and not dopamine receptors are responsible for the inhibitory effect of noradrenaline on prolactin secretion in vitro but do not implicate a particular adrenoceptor subtype. The in-vivo experiments do not provide convincing evidence for a role for noradrenaline as a physiologically important PIF.

Adrenergic Agonists↗
PubMed1999

Combined historical and electrocardiographic timing of acute anterior and inferior myocardial infarcts for prediction of reperfusion achievable size limitation.

The historical time of acute symptom onset is not always an accurate indication of the timing of onset of an acute myocardial infarction (AMI). Consideration of electrocardiographic (ECG) timing parameters could supplement historical timing alone as a clinical guide for decisions regarding the use of reperfusion therapy. Three hundred ninety-five patients from 4 trials of thrombolytic therapy conducted in the northwestern United States and western Canada are included in the present study. A total of 316 patients received either streptokinase or tissue plasminogen activator, and 79 received no reperfusion therapy. Historical time of symptom onset was acquired by emergency or cardiology department personnel and recorded on patient report forms. An ECG method for estimating the timing of the AMI, the Anderson-Wilkins (AW) acuteness score, was calculated from the initial standard 12-lead recording by investigators blinded to the knowledge of symptom duration or any other study variables. Tomographic thallium-201 imaging 7 weeks after hospital admission was used to measure final AMI size. The ECG timing method achieved a relation with final AMI size similar to that previously reported for historical timing. The AW acuteness score proved most useful for anterior AMI location when there was a > or = 2 hour delay following symptom onset, but was most useful for the inferior AMI location when there was a < 2 hour delay. Despite a longer delay, patients with high AW acuteness scores had 50% lower final anterior AMI size than those with low scores; and despite a shorter delay, those with low ECG acuteness scores had 50% greater final inferior AMI size than those with high scores. The AW acuteness score combined with the historical estimation of symptom duration should provide a more accurate basis for predicting the potential for limitation of final AMI size than either method alone. These results could potentially provide the basis for developing a new method for noninvasive guidance of clinical decisions regarding administration of reperfusion therapy in the initial evaluation of patients with AMI.

Electrocardiography↗
PubMed1998

PACAP stimulates dopamine neuronal activity in the medial basal hypothalamus and inhibits prolactin.

In sheep intracerebroventricular injection of PACAP (10 nmol) significantly (P<0.01) stimulated the levels of the dopamine metabolite DOPAC within the medial basal hypothalamus (as measured by in vivo microdialysis) and this effect was temporally correlated with a significant (P<0.05) suppression in peripheral prolactin concentrations. This result is in accord with the hypothesis that PACAP suppresses prolactin secretion from the anterior pituitary gland by stimulating dopamine release from tuberoinfundibular dopaminergic neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Hypothalamic dopamine D1 receptors are involved in the stimulation of prolactin secretion by high environmental temperature in the female sheep.

Recent evidence suggests that dopamine, acting via its D1 receptors, may function as a neurotransmitter in intrahypothalamic pathways involved in the stimulation of prolactin secretion. Functional dopamine D1 receptors are present in the ventromedial hypothalamic nucleus (VMH) and we hypothesized that they might be part of a prolactin-stimulatory pathway activated by stress. We tested this hypothesis in a series of experiments on sheep involving two different forms of stressors, audiovisual (barking dog) and high environmental temperature. We attempted to block the stimulation of prolactin secretion by infusion into the VMH of an antagonist specific for the D1 receptor. Ovariectomised, oestradiol-implanted merino ewes were surgically implanted with bilateral guide tubes directed at the VMH. After a 180 min pretreatment period, the ewes either were or were not exposed to a stressor (30 min of barking dog or 120 min at 35 degrees C, 65% relative humidity). D1 receptor antagonist, SCH23390 or vehicle (0.9% saline) was infused into the VMH (1.7 microliters/h, 120 nmol/h) for 60 min prior to and during the stressor period. Blood was sampled every 15 min via jugular cannulae and the plasma was assayed for prolactin, cortisol and growth hormone (GH). Both stressors significantly increased prolactin concentrations over control levels. SCH23390 infusion significantly attenuated the prolactin response to high environmental temperature, but had no effect on the prolactin response to audiovisual stress. Cortisol concentrations were significantly increased by audiovisual stress only and were not affected by SCH23390. GH concentrations were not changed by either stressor or infusion. Drug infusion alone did not affect the concentration of the hormones. The data suggest that the VMH D1 receptors are involved in a prolactin stimulatory pathway in response to high environmental temperature. The inability of the D1 antagonist to affect the response to the barking dog indicates that this pathway is stress-specific, implying that there is more than one mechanism or pathway involved in the prolactin response to different stressors.

Acoustic Stimulation↗
PubMed1998

Skin cancer prevention counseling by pharmacists: specific outcomes of an intervention trial.

The purpose of this study was to evaluate the effects of an intervention on pharmacists' behaviors, knowledge, and attitudes related to skin cancer prevention counseling. Fifty-four pharmacy sites (N = 178 pharmacists) were randomly assigned to the intervention or control condition. Intervention consisted of video-based training, prompts installed in the pharmacy to promote pharmacist-patient discussions on the topic, and group-based feedback on previous week's counseling rates. Outcomes were measured using a mailed survey. The proportion of patients counseled at post-test was significantly higher among intervention subjects, adjusting for pretest values. Similar results were found for pharmacists' skin cancer knowledge and self-rated expertise, but not for counseling-related attitudes. The intervention was successful. If implemented on a wide scale, large segments of the U.S. population would be exposed to skin cancer prevention advice.

Adult↗
PubMed1998

Increased ovulation rate in Merino ewes immunized against small synthetic peptide fragments of the inhibin alpha subunit.

Four experiments were carried out in Merino ewes during a period of 4 years to determine the long-term effects of immunization against different synthetic peptides mimicking the amine terminal of the alpha subunit of porcine inhibin. Peptides were conjugated to human serum albumin and 100-200 micrograms emulsified in Freund's complete adjuvant for the primary immunization. Usually two booster injections were given at monthly intervals with 50-100 micrograms conjugated peptide using either incomplete Freund's adjuvant or Montanide:Marcol. In some experiments a further immunization was carried in the next year. Blood samples were taken 10 days after each immunization, during the luteal phase, for estimation of gonadotrophin concentrations and determination of inhibin antibody titres. One day after blood sampling cloprostenol was used to induce luteolysis and laparoscopy was performed in the subsequent oestrous cycle. Immunization of ewes with synthetic peptides 1-32, 1-26, 7-26 and 8-30 resulted in large increases in the ovulation rate (OR). An approximately two-fold increase in OR was observed following the first booster immunization with these peptides and a three- to five-fold increase after the second booster immunization. Immunization with these large peptides resulted in a sustained increase in OR for a period of at least 1 year after the second booster immunization. Of the shorter peptides, peptides 10-26 and 13-26 gave a reasonable ovulatory response, although it was more difficult to obtain a response with peptides 1-16, 8-22, 13-25, 8-19 and 10-19; peptides 7-13 and 1-6 gave no response (but were examined for one breeding season only). The smaller peptides led to lower inhibin antibody titres that were not necessarily associated with increased follicle-stimulating hormone (FSH) or OR. More intensive blood sampling in one experiment showed that following primary immunization against peptide 1-32 there was a transient increase in plasma FSH, which did not lead to an increased OR. Moreover, a prolonged period of raised FSH after the first booster was significantly correlated with increased OR. In these animals antibody titres were only slightly increased after primary immunization, but after the first booster immunization higher titres were observed that were significantly correlated with trough FSH values and the subsequent OR. These results are interpreted as showing that (1) to obtain an increase in OR peptides 1-32, 1-26 and 7-26 are suitable as immunogens; (2) smaller peptides are less reliable, often require multiple injections, and the response may be delayed; and (3) an extended period of raised plasma FSH is needed to give a large ovulatory response.

Animals↗
PubMed1998

How healthcare organizations can achieve true integration.

Of the many organizations that have attempted to become integrated delivery systems (IDSs), only a few have actually achieved this goal. Achieving true integration requires commitment to an ongoing process that consists of a series of increasingly challenging phases: development of the organization's unifying concept and culture, specification of the organizational and administrative structure, integration of funds and other assets, development of synergistic operations, and ongoing commitment to ensuring organizational responsiveness to market forces. In addition, including physicians in the integration process is essential for achieving true integration. To effectively integrate physician practices into the larger organization, IDSs need to overcome physician resistance to losing perceived autonomy and control. Physicians are most likely to accept integration into an IDS if they recognize the advantages they gain from allowing the IDS to assume administrative control of their practices.

Delivery of Health Care, Integrated↗
PubMed1997

Gonadotrophin and prolactin secretion in castrated male sheep following subcutaneous or intracranial treatment with testicular hormones.

Interactions between testosterone, estradiol, and inhibin in the control of gonadotrophin secretion in males are poorly understood. Castrated rams were treated with steroid-free bovine follicular fluid (bFF), testosterone, or estradiol and for 7 d (2 x 2 x 2 factorial design). Given independently, none of the exogenous hormones affected follicle-stimulating hormone (FSH) concentrations, but the combination of one or both steroids with bFF reduced FSH secretion. Testosterone and estradiol reduced luteinizing hormone (LH) pulse frequency (there was no synergism), and bFF had no effect. Plasma prolactin concentrations were not affected by any treatment. To locate the central sites of steroid action, castrated rams were bilaterally implanted in the preoptic area (POA), ventromedial nucleus (VMH), or arcuate nucleus (ARC). These implants did not affect FSH or prolactin concentrations, or LH pulse amplitude. The frequency of the LH pulses was not affected by testosterone in any site. Estradiol located in the ARC, but not the POA or VMH, decreased LH pulse frequency. In summary, FSH secretion is controlled by synergistic interactions between inhibin and estradiol or testosterone, whereas GnRH/LH pulse frequency is controlled by testicular steroids. Estradiol acts partly, at least, in the ARC, but the central site of action, testosterone remains unknown.

Animals↗
PubMed1997

Admission prediction of expected final myocardial infarct size using weighted ST-segment, Q wave, and T wave measurements.

Formulas for predicting final acute myocardial infarction (MI) size from ST-segment deviation on an initial electrocardiogram were proposed by Aldrich et al. for anterior and inferior infarct locations. This study of 529 patients who did not receive thrombolytic therapy was performed to determine the effectiveness of the Aldrich formulas for predicting final QRS MI size; to propose new formulas for predicting final MI size using ST-segment deviation, Q wave, and T wave information in a development population of 322 patients; and to evaluate the new formulas in a randomly selected population of 207 patients. The Aldrich formulas achieved correlations with final infarct size of r = .40 for anterior and r = .43 for inferior MI locations in the present population which are weaker than those previously reported. Formulas that consider electrocardiographic parameters in addition to ST-segment deviation were proposed for both anterior and inferior final MI size. In the test set of 207 patients, these models explained 16.9% and 15.2% of the variation in final MI size for anterior and inferior locations respectively. They may prove useful in assessing the extent of myocardial salvage where interventions are to be tested.

Electrocardiography↗
PubMed1997

A method for drug infusion into the lateral median eminence and arcuate nucleus of sheep.

The role of catecholamines in the control of the GnRH pulse generator is unclear as studies have relied on the use of peripheral or intracerebroventricular injections, which lack specificity in relation to the anatomical site of action. Direct brain site infusions have been used, however, these are limited by the ability to accurately target small brain regions. One such area of interest in the control of GnRH is the median eminence and arcuate nucleus within the medial basal hypothalamus. Here we describe a method of stereotaxically targeting this area in a large animal (sheep) and an infusion system to deliver drugs into unrestrained conscious animals. To test our technique we infused the dopamine agonist, quinpirole or vehicle into the medial basal hypothalamus of ovariectomised ewes. Quinpirole significantly suppressed LH pulsatility only in animals with injectors located close to the lateral median eminence. This in vivo result supports the hypothesis that dopamine inhibits GnRH secretion by presynaptic inhibition in the lateral median eminence. Also infusion of quinpirole into the medial basal hypothalamus suppressed prolactin secretion providing in vivo evidence that is consistent with the hypothesis that there are stimulatory autoreceptors on tubero-infundibular dopamine neurons.

Animals↗
PubMed1997

Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) on hormone secretion from sheep pituitary cells in vitro.

Although vasoactive intestinal polypeptide (VIP) is thought to be a prolactin releasing factor, in vivo studies on sheep suggest that it is inactive in this species. Recent studies, based primarily on the rat, suggest that the related pituitary adenylate cyclase-activating polypeptide (PACAP) is also a hypophysiotrophic factor but again in sheep, this peptide has no in vivo effects on hormone secretion despite being a potent activator of adenylate cyclase in vitro. This lack of response to either peptide in vivo in sheep could be due to the low concentration of peptide that reaches the pituitary gland following peripheral injection. In the present study we therefore adopted an alternative approach of evaluating in vitro effects of these peptides on GH, FSH, LH or prolactin secretion from dispersed sheep pituitary cells. In a time-course study, PACAP (1 mumol/l) increased GH concentrations in the culture medium between 1 and 4 h and again at 12 h but had no effect in the 6 and 24 h incubations. Prolactin, LH and FSH were not affected by PACAP. The response to various concentrations of PACAP (1 nmol/l-1 mumol/l) were then evaluated using a 3 h incubation. Again prolactin and LH were not affected by PACAP and there was a small increase in GH concentrations but only at high concentrations of PACAP (0.1 and 1 mumol/l; P < 0.05). PACAP also stimulated FSH secretion in cells from some animals although this effect was small. The GH response to PACAP was inhibited by PACAP(6-38), a putative PACAP antagonist, but not by (N-Ac-Tyr1, D-Arg2)-GHRH(1-29)-NH2, a GH-releasing hormone (GHRH) antagonist. The cAMP antagonist Rp-cAMPS was unable to block the GH response to PACAP suggesting that cAMP does not mediate the secretory response to this peptide. At incubation times from 1-24 h, VIP (1 mumol/l) had no effects on prolactin, LH or GH secretion and, in a further experiment based on a 3 h incubation, concentrations of VIP from 1 nmol/l-1 mumol/l were again without effect on prolactin concentrations. Interactions between PACAP and gonadotrophin releasing hormone (GnRH), GHRH and dopamine were also investigated. PACAP (1 nmol/l-1 mumol/l) did not affect the gonadotrophin or prolactin responses to GnRH or dopamine respectively. However, at a high concentration (1 mumol/l), PACAP inhibited the GH response to GHRH. In summary, these results show that PACAP causes a modest increase in FSH and GH secretion from sheep pituitary cells but only at concentrations of PACAP that are unlikely to be in the physiological range. The present study confirms that VIP is not a prolactin releasing factor in sheep.

Animals↗
PubMed1996

Mortality in rheumatoid arthritis: do age and gender make a difference?

Rheumatoid arthritis (RA) is a significant cause of morbidity and mortality in both sexes. The extent to which age and gender are risk factors for increased mortality in RA, however, is still not clear. A review of existing literature on the effect of gender and age on mortality was performed. Twenty-five articles were identified from the world literature over the past decade. Ten articles representative of the existing literature in this field were analyzed in detail. Articles chosen as representative were characterized by peer-reviewed publication, large sample size, and geographic diversity of patient populations. One detailed analysis of prior literature also was included. The results failed to show a clear association between gender, age, and mortality in RA. Retrospective analyses of death certificates suggest an increased mortality among elderly women with RA. Longitudinal studies, however, suggest that both increasing age and male sex portend a worse prognosis in RA. A better understanding of mortality risk factors in RA, particularly with respect to age and gender, would require large randomized prospective trials conducted over long periods.

Age Factors↗
PubMed1996

Pituitary adenylate cyclase-activating polypeptide acts within the medial basal hypothalamus to inhibit prolactin and luteinizing hormone secretion.

In this study, we investigated the hypothalamic regulatory role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the control of LH and PRL secretion. Overiectomized ewes were surgically prepared with bilateral guide tubes directed at the preoptic area (POA) or medial basal hypothalamus (MBH). After recovery from surgery, PACAP38 (0.1 nmol in 2.5 microliters over 1 h) or vehicle was bilaterally infused into each site in separate trials. Infusion of PACAP38 into the POA had no effect on either LH or PRL secretion. However, infusion of the peptide into the MBH suppressed PRL secretion during the 3-h postinfusion period; the responding animals (n = 9) had injectors located in the arcuate nucleus. In the three nonresponding animals, both injectors were outside the arcuate nucleus. Mean LH concentration, LH pulse frequency, and pulse amplitude were also significantly suppressed, with LH pulsatility declining in seven of eight animals during infusion of the peptide in the MBH. These results suggest that PACAP acts in the arcuate nucleus region of the MBH, and not the rostral POA, to inhibit both LH and PRL secretion.

Animals↗
PubMed1995

T wave amplitudes in normal populations. Variation with ECG lead, sex, and age.

Consideration of increased T wave amplitude (tall T waves), either alone or in association with other electrocardiographic (ECG) parameters, may be beneficial for the early detection of acute transmural ischemia, and quantification of the increase might be used in quantifying the ischemic area. The primary purpose of this study was to quantify normal T wave amplitude limits according to ECG lead, sex, and age. One thousand nine hundred thirty-five subjects in two normal populations were analyzed, and the 98th percentile of the positive T wave amplitude for each ECG lead (including -aVR) was considered the upper limit of normal. Normal T wave amplitude was two times greater in the precordial than in the limb leads, and it was approximately 25% greater in men than in women in all leads. There was approximately a 10% decrease in normal T wave amplitude between 18-39- and 40-59-year-old patients and a 15% decrease between 40-59- and 60-79-year-old patients. The upper limit of normal T wave amplitudes identified in this study confirm those developed by Lepeschkin for use as means for each lead when age and sex are not considered. These limits might be incorporated into both normograms and automated ECG analysis systems to determine the presence or absence of tall T waves in patients presenting with symptoms of acute transmural ischemia.

Adolescent↗
PubMed1994

Panoramic display of the orderly sequenced 12-lead ECG.

The standard 12-lead electrocardiogram (ECG) has been developed over many years. The ECG has had a long and successful history of providing diagnostic information in clinical medicine. Cardiac arrhythmias have been elucidated by deductive reasoning from continuous ECG recordings with confirmation from electrophysiologic studies. Recently, there has been renewed interest in the morphology of the QRS complex, ST-segment, and T wave, which raises the important question of considering whether the usual method of display provides maximal diagnostic capabilities. The conventional display provides a logical visualization of precordial lead recordings representing the horizontal plane, but does not provide a logical visualization of the limb lead recordings representing the frontal plane. Many clinical problems require the consideration of serial ECGs necessitating the comparison of separate pages. An alternate format presenting serial recordings on a single page would be advantageous. Some automated ECG analysis systems already include the capability for multiple display formats, but these have not yet been widely used in clinical practice. This point of view paper introduces a new display format for the standard 12-lead ECG that includes: (1) a presentation of an orderly sequence of leads to facilitate scanning through different points in space and (2) a presentation of recordings of 12-lead sequences to facilitate scanning through different points in time. This display format could either replace or supplement the conventional ECG format.

Arrhythmias, Cardiac↗