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Biomedical subjects

J M Elliott

Publications and source records attributed to J M Elliott.

At least 19 recordsLinked to original sources
PubMed1998

Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: new neurohormonal predictors of left ventricular function and prognosis after myocardial infarction.

BACKGROUND: Newly discovered circulating peptides, N-terminal pro-brain natriuretic peptide (N-BNP) and adrenomedullin (ADM), were examined for prediction of cardiac function and prognosis and compared with previously reported markers in 121 patients with myocardial infarction. METHODS AND RESULTS: The association between radionuclide left ventricular ejection fraction (LVEF) and N-BNP at 2 to 4 days (r=-.63, P<.0001) and 3 to 5 months (r=-.58, P<.0001) after infarction was comparable to that for C-terminal BNP and far stronger than for ADM (r=-.26, P<.01), N-terminal atrial natriuretic peptide (N-ANP), C-terminal ANP, cGMP, or plasma catecholamine concentrations. For prediction of death over 24 months of follow-up, an early postinfarction N-BNP level > or = 160 pmol/L had sensitivity, specificity, positive predictive value, and negative predictive values of 91%, 72%, 39%, and 97%, respectively, and was superior to any other neurohormone measured and to LVEF. Only 1 of 21 deaths occurred in a patient with an N-BNP level below the group median (Kaplan-Meier survival analysis, P<.00001). For prediction of heart failure (left ventricular failure), plasma N-BNP > or = 145 pmol/L had sensitivity (85%) and negative predictive value (91%) comparable to the other cardiac peptides and was superior to ADM, plasma catecholamines, and LVEF. By multivariate analysis, N-BNP but not ADM provided predictive information for death and left ventricular failure independent of patient age, sex, LVEF, levels of other hormones, and previous history of heart failure, myocardial infarction, hypertension, or diabetes. CONCLUSIONS: Plasma N-BNP measured 2 to 4 days after myocardial infarction independently predicted left ventricular function and 2-year survival. Stratification of patients into low- and high-risk groups can be facilitated by plasma N-BNP or BNP measurements, and one of these could reasonably be included in the routine clinical workup of patients after myocardial infarction.

Adrenomedullin↗
PubMed1998

Investigation of the presynaptic effects of quinine and quinidine on the release and uptake of monoamines in rat brain tissue.

Quinine and quinidine are reported to potentiate the behavioural effects of serotonergic agents and monoamine uptake inhibitors. We have therefore investigated the presynaptic actions of quinine and quinidine on monoamine uptake and release in rat brain tissue in vitro. Quinidine evoked the release of [3H]5-HT, [3H]noradrenaline and [3H]dopamine from pre-loaded rat brain slices in a concentration dependent manner with EC50 values of 175, 486 and 150 microM, respectively. Quinine induced [3H]monoamine release with similar potencies. Both quinine and quinidine also inhibited the active uptake of [3H]5-HT, [3H]noradrenaline and [3H]dopamine into rat brain synaptosomes with IC50 values in the range 0.13-12.4 microM. The potency of each drug to inhibit [3H]5-HT uptake was significantly higher than that for [3H]noradrenaline or [3H]dopamine. The relative potency of quinidine compared to quinine was more marked in the case of [3H]5-HT (58-fold) than for [3H]noradrenaline (3-fold) or [3H]dopamine (4-fold). The inhibition of [3H]5-HT uptake by quinine and quinidine was competitive in nature and corresponded with the potencies of these drugs to inhibit [3H]paroxetine binding. No correlation was observed between the potencies of quinine and quinidine to induce the release of [3H]monoamines and to inhibit their uptake, suggesting that these effects are mediated by two distinct mechanisms. We conclude that the presynaptic actions of quinine and quinidine on monoamine uptake and release may be implicated in their potentiation of the effects of serotonergic agents and uptake blockers.

Animals↗
PubMed1997

Expression, genomic structure and high resolution mapping to 19p13.2 of the human smooth muscle cell calponin gene.

Smooth muscle cells (SMC) express a battery of cell-restricted differentiation genes, many of which are down-regulated during the course of vascular disease. Here, we present the mRNA expression, genomic structure and chromosomal mapping of the gene encoding human smooth muscle cell calponin (SMCC). Human SMCC transcripts are restricted to tissues and cells of SMC origin and, in the latter case, appear to be uniquely controlled in two distinct human SMC lines of uterine and aortic origin. Restriction mapping. Southern blot and PCR analysis of a 70-kb human bacterial artificial chromosome (BAC) revealed a genomic structure (seven exons spanning > 11 kb) very similar to that reported for the mouse SMCC gene. Using a variety of human-rodent somatic cell hybrid and radiation hybrid mapping panels, the human SMCC gene was mapped to a genomic interval of less than 1.32 Mb in 19p13.2. These results provide new information concerning the regulation of SMCC gene expression and demonstrate the utility of two human SMC lines for the further characterization of this gene's expression control. The identification of a BAC harboring the entire human SMCC locus represents an important reagent for future analysis of SMCC regulatory sequences. Finally, the localization of SMCC to a defined genomic interval will facilitate an analysis of its potential as a candidate gene for disease phenotypes mapping to 19p13.2.

Amino Acid Sequence↗
PubMed1997

Life and death on the waiting list for coronary bypass surgery.

AIM: To assess the baseline characteristics of patients referred for isolated coronary bypass surgery (CABG), waiting times for coronary bypass surgery and clinical events while waiting for coronary bypass surgery. To compare the New Zealand priority scoring system with a previously validated Ontario urgency score. METHODS: Outcomes in a consecutive case series of 88 patients referred from Christchurch Hospital for coronary bypass surgery between July 1 and December 31 1993 were compared with a previous Christchurch case series and a contemporary Canadian case series. Patients were stratified according to both Ontario and New Zealand priority scores. RESULTS: Of 88 patients, one patient died prior to surgery, 79 had undergone coronary bypass surgery (with three deaths), and eight were still waiting as at December 31 1995. Twenty five percent of patients had left main disease, another 60% had multivessel disease that included the proximal left anterior descending coronary artery and 64% had angina at rest or on minimal exertion. The median waiting time was 92 days (inter-quartile range 20-234), 8 (6-12) days in the 23 patients who underwent surgery as in-hospital cases, and 181 (83-295) in those who waited at home. Patients with left main disease waited a median of 41 (11-205) days. While waiting at home one patient died, one patient suffered a myocardial infarction, and 17 patients were readmitted with unstable angina. Readmissions were not predicted by New Zealand or Ontario priority scores, nor by clinical variables. CONCLUSIONS: Thresholds for referral are very similar, but waiting times for coronary bypass surgery are far longer in New Zealand than Canada. The long waiting times are a considerable cost to both patients and government. Priority scores facilitate comparison between countries but they may not predict readmission to hospital while on a long waiting list.

Aged↗
PubMed1997

Attitudes of the Singapore public to actions suggesting child abuse.

OBJECTIVE: The aim was to ascertain the views of the Singapore public on the acceptability of actions of an abusive nature. METHOD: In-depth interviews were carried out with 401 randomly sampled respondents in relation to a range of actions. Questions were asked concerning the acceptability of 18 actions, whether circumstances might justify eight of them, how respondents felt about reporting child abuse and whether they could recall any case they had come across. RESULTS: Respondents strongly disapproved of sexually motivated acts, and were more disapproving of physical abuse or neglect than of emotional abuse or neglect. Circumstances did affect how the less extreme actions were viewed. Respondents supported reporting child abuse, but were somewhat against mandatory reporting. They were able to recall details of a number of possible cases. CONCLUSION: We argue that definitions of child abuse should be general and not tied to specific actions, since the effects of actions may vary across cultures, and should be treated as an empirical matter. This allows a research agenda that focuses on the consequences of actions rather than issues of definition.

Adolescent↗
PubMed1997

Mianserin-induced down-regulation of human 5-hydroxytryptamine2A and 5-hydroxytryptamine2C receptors stably expressed in the human neuroblastoma cell line SH-SY5Y.

We have assessed the ability of the serotonergic antagonist mianserin to modulate the number and functional activity of human 5-hydroxytryptamine2A (5-HT2A) and 5-HT2C receptors stably expressed in the human neuroblastoma cell line SH-SY5Y. Incubation of cells expressing the 5-HT2A receptor with mianserin (100 nM) for 24 h caused a significant decrease (48%) in the binding capacity of [3H] ketanserin. This receptor down-regulation was associated with a corresponding decrease in the maximal production of inositol phosphates induced by 5-HT but not by carbachol. Exposure of cells expressing the 5-HT2C receptor to mianserin (100 nM) for 72 h but not for 24 h similarly resulted in a significant reduction (44%) in [3H]mesulergine binding. Corresponding analysis of inositol phosphate production by 5-HT at the 5-HT2C receptor after incubation with mianserin showed no change in maximal response after 24 h. No change in the binding capacity of either radioligand was seen after incubation with mianserin for 1 h. A decrease in the binding affinity of both radioligands was also observed after mianserin treatment, but this decrease was similar after 1 h of incubation to that seen after 24 or 72 h, and was probably due to the retention of mianserin within the tissue. We conclude that antagonist down-regulation is evident at human 5-HT2A and 5-HT2C receptors stably expressed in a human neuroblastoma cell line and is probably mediated by a direct action of mianserin at the receptor.

Cell Membrane↗
PubMed1996

Characterisation of human 5-hydroxytryptamine2A and 5-hydroxytryptamine2C receptors expressed in the human neuroblastoma cell line SH-SY5Y: comparative stimulation by hallucinogenic drugs.

Stable transfection of the human neuroblastoma cell line SH-SY5Y with the human 5-hydroxytryptamine2A (5-HT2A) or 5-HT2C receptor cDNA produced cell lines demonstrating ligand affinities that correlated closely with those for the corresponding endogenous receptors in human frontal cortex and choroid plexus, respectively. Stimulation of the recombinant receptors by 5-HT induced phosphoinositide hydrolysis with higher potency but lower efficacy at the 5-HT2C receptor (pEC50 = 7.80 +/- 0.06) compared with the 5-HT2A receptor (pEC50 = 7.30 +/- 0.08). Activation of the 5-HT2A receptor caused a transient fourfold increase in intracellular Ca2+ concentration. Whole-cell recordings of cells clamped at -50 mV demonstrated a small inward current (2 pA) in response to 10 microM 5-HT for both receptors. There were no differences in potency or efficacy of phosphoinositide hydrolysis among four hallucinogenic [d-lysergic acid diethylamide (LSD), 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI), 5-methoxy-N,N-dimethyltryptamine, and mescaline] and three nonhallucinogenic drugs (m-chlorophenylpiperazine, quipazine, and ergotamine). Comparison of equipotent doses producing 20% of the maximal response induced by 5-HT revealed selective activation of the 5-HT2A receptor by LSD and to a lesser degree by DOI, mescaline, and ergotamine. Quipazine and 5-methoxy-N,N-dimethyltryptamine were relatively nonselective, whereas m-chlorophenylpiperazine selectively activated the 5-HT2C receptor. It is unlikely therefore that hallucinosis is mediated primarily by activity at the 5-HT2C receptor, whereas activity at the 5-HT2A receptor may represent an important but not unique mechanism associated with hallucinogenic drug action.

Adrenergic alpha-Agonists↗
PubMed1995

One-year follow-up in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT I)

BACKGROUND: Directional atherectomy is a frequently used percutaneous revascularization strategy, but its long-term outcomes have not previously been compared with those of balloon angioplasty in a prospective trial. METHODS AND RESULTS: The 1012 patients enrolled in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT I) were followed for at least 1 year after randomization. Analyses of predetermined end points were performed, including a detailed analysis of the 14 patients who died. At 1 year, 11 patients had died in the atherectomy group compared with 3 in the angioplasty group (2.2% versus 0.6%, P = .035), with an excess of out-of-hospital deaths (2.2% versus 0.2%, P = .01) and late cardiac deaths (1.6% versus 0%, P = .01). Univariate predictors of death included age, abrupt closure, periprocedural enzyme elevation, and peripheral vascular complications. There was no evidence that the excess of deaths after atherectomy was linked to perforation, ectasia, or deep resection. Cumulative rates of myocardial infarction were higher in those who had been randomized to atherectomy than in those randomized to angioplasty (8.9% versus 4.4%, P = .005) with a trend toward excess Q-wave and non-Q-wave infarctions. By multivariate analysis, atherectomy was the only variable predictive of the combined end point of death or myocardial infarction. No clinical or angiographic characteristics added to this index. Rates of repeat percutaneous intervention at the target site (24.4% after atherectomy versus 25.9% after angioplasty), coronary artery bypass surgery (9.3% versus 9.1%), hospitalization (50% versus 47.1%), and stroke (1% in both groups) were not significantly different. CONCLUSIONS: Long-term follow-up of the 1012 patients randomized to atherectomy or angioplasty has revealed a statistically significant excess of deaths after directional atherectomy that was not evident at 6 months. This difference could be due to the chance occurrence of a low mortality rate in those randomized to angioplasty. The excess of myocardial infarctions after atherectomy remains statistically significant at 1 year. Further investigation is warranted to improve the safety of atherectomy.

Aged↗
PubMed1995

Characterization of the 5-hydroxytryptamine2A receptor-activated cascade in rat C6 glioma cells.

We have investigated the identity and intracellular cascade of responses resulting from activation of the endogenous 5-hydroxytryptamine receptor in the C6 rat glioma cell line. Sequence analysis of reverse transcription-polymerase chain reaction products derived from C6 glioma cell messenger RNA revealed complete homology with a portion of the rat 5-hydroxytryptamine2A receptor. The binding of [3H]ketanserin to cell membranes demonstrated a significant correlation with the 5-hydroxytryptamine2A receptor in rat frontal cortex. On intact cells, 5-hydroxytryptamine stimulated a concentration-dependent increase in phosphatidyl inositide turnover and intracellular [Ca2+] mediated by 5-hydroxytryptamine2A receptors. In whole-cell patch-clamp recordings, 5-hydroxytryptamine induced an outward current mediated predominantly by K+ ions (reversal potential = -80 mV). Using caged molecules containing Ca2+ or inositol 1,4,5-trisphosphate in the patch electrode solution, we found that rapid photolytic release of Ca2+ and particularly inositol 1,4,5-trisphosphate within the cytosol induced an outward current with characteristics similar to those seen after application of 5-hydroxytryptamine. Comparison between differentiated and undifferentiated cells revealed significantly higher receptor density and maximal phosphoinositide response to 5-hydroxytryptamine in undifferentiated cells but the associated rise in [Ca2+]i and activation of an outward current was observed more frequently in differentiated cells. Prolonged exposure of the cells to 5-hydroxytryptamine led to a decrease in all responses and to the down-regulation of receptor number. We conclude that the rat C6 glioma cell expresses a 5-hydroxytryptamine2A receptor identical to that found in rat brain and that stimulation of the receptor in C6 cells leads to the activation of Ca2+ activated K+ channels via phosphoinositide hydrolysis and subsequent rise in cytosolic Ca2+ ion concentration. However, the contrasting effects of differentiation on receptor number and phosphoinositide response to 5-hydroxytryptamine compared to Ca2+ release and conductance change indicate that a complex relationship exists between the component parts of the receptor-activated cascade.

Animals↗
PubMed1995

Recent developments in balloon valvuloplasty techniques.

The long-term outcome after mitral valvuloplasty is excellent and compares well with surgical treatment of mitral stenosis. Compared with the double balloon technique, the Inoue method is technically easier and may reduce acute complications without any adverse effect on long-term outcomes. Excellent long-term outcome is also seen after balloon valvuloplasty of aortic stenosis in the young and in pulmonary stenosis at all ages. Finally, although balloon aortic valvuloplasty in the elderly may not change the terrible prognosis of such patients, it does improve functional status and is a useful bridge to surgery in selected patients.

Adolescent↗
PubMed1995

Randomized trials of myocardial revascularization.

Over the past two decades there has been considerable refinement in randomized cardiovascular clinical trials. The common aim of randomized clinical trials of myocardial revascularization has been to understand the relative benefits of each technique on survival and nonfatal end points. The bypass surgery versus medicine trials that began in the 1970s provided evidence that the patients with advanced ischemic heart disease--three-vessel disease and/or substantially impaired LV function--have the most to gain from aggressive therapy (i.e., bypass surgery). In these cases, surgical revascularization provides survival benefit and has emerged as the reference standard for providing the most definitive revascularization. In long-term follow-up, however, surgery does not reduce the occurrence of myocardial infarction or angina compared with medical therapy. For patients with less extensive atherosclerosis and/or preserved ventricular function, trials comparing medical therapy, percutaneous coronary interventions, and bypass surgery have shown similar medium-term rates of death and infarction. In general, patients undergoing bypass surgery require the fewest subsequent antianginal medications, whereas patients undergoing PTCA require a moderate amount of antianginal medications, and patients treated solely with medical therapy require the most antianginal medications. Regardless, during long-term follow-up a similarly high number of patients are angina-free, although patients in the PTCA group require reintervention more often. Among patients treated percutaneously, techniques such as balloon angioplasty, directional atherectomy, stenting, rotablation, and laser may be considered. Compared with balloon angioplasty, greater acute gains in angiographic lumen have been obtained after directional atherectomy and stenting, but at the expense of increased periprocedural infarction after atherectomy, increased peripheral vascular complications after stenting, and increased late loss of lumen after both. Elective stenting has been associated with improved clinical outcome, whereas laser and rotational atherectomy have not, in comparison to balloon angioplasty. Restenosis remains the major limitation of all percutaneous approaches. Guidance for the individual patient is often less straightforward. Although general conclusions can be derived from patients cohorts in randomized trials, only a "gestalt" can be provided for the individual patient. For example, we have poor predictive capacity for restenosis, especially when this is recurrent despite repeated intervention. Only the demographic criteria of severe unstable angina and insulin-dependent diabetes mellitus are helpful in categorizing patients as "restenosis-prone." A substantial number of patients do not fit into the criteria adopted for entry into the revascularization trials--a point that is all too frequently forgotten.(ABSTRACT TRUNCATED AT 400 WORDS)

Coronary Disease↗
PubMed1994

The lymphoblast beta-adrenergic receptor in bipolar depressed patients: effect of chronic incubation with lithium chloride.

We have recently reported a study of beta-adrenergic receptor binding characteristics in lymphoblast cell lines derived from patients with bipolar disorder (BD) and healthy, matched control subjects. In the present study we have investigated the effects of incubating cells from the same subjects with lithium chloride (1 mM) for 7 days prior to assay. There was no difference in beta-adrenergic receptor number between control and BD cell lines and incubation with lithium had no effect on receptor number in either group. Exposure of the cells to isoprenaline (1 nM) for 24 h immediately prior to assay caused significantly less down-regulation in BD cells (15 +/- 5%) than control cells (39 +/- 4%), as described previously. Incubation with lithium significantly increased the down-regulation response to isoprenaline in BD cells (39 +/- 6%) but not in control cells (30 +/- 7%). After lithium, the agonist-induced decrease in beta-AR number in BD cells was no longer significantly different from that in control cells. We conclude that lithium selectively enhanced the agonist down-regulation of beta-adrenergic receptors in cells derived from patients with bipolar disorder. The functional significance of this result and the potential biochemical mechanisms responsible for this effect are discussed.

Adult↗