Relation between socioeconomic deprivation and death from a first myocardial infarction in Scotland: population based analysis.
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Age Factors↗
Biomedical subjects
J Chalmers
Publications and source records attributed to J Chalmers.
Differential expression of catecholamine biosynthetic enzymes in the rat ventrolateral medulla.
Adrenergic (C1) neurons located in the rostral ventrolateral medulla are considered a key component in the control of arterial blood pressure. Classically, C1 cells have been identified by their immunoreactivity for the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH) and/or phenylethanolamine N-methyltransferase (PNMT). However, no studies have simultaneously demonstrated the expression of aromatic L-amino acid decarboxylase (AADC) and dopamine beta-hydroxylase (DBH) in these neurons. We examined the expression and colocalization of all four enzymes in the rat ventrolateral medulla using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Retrograde tracer injected into thoracic spinal segments T2-T4 was used to identify bulbospinal neurons. Using fluorescence and confocal microscopy, most cells of the C1 group were shown to be double or triple labeled with TH, DBH, and PNMT, whereas only 65-78% were immunoreactive for AADC. Cells that lacked detectable immunoreactivity for AADC were located in the rostral C1 region, and approximately 50% were spinally projecting. Some cells in this area lacked DBH immunoreactivity (6.5-8.3%) but were positive for TH and/or PNMT. Small numbers of cells were immunoreactive for only one of the four enzymes. Numerous fibres that were immunoreactive for DBH but not for TH or PNMT were noted in the rostral C1 region. Single-cell RT-PCR analysis conducted on spinally projecting C1 neurons indicated that only 76.5% of cells that contained mRNA for TH, DBH, and PNMT contained detectable message for AADC. These experiments suggest that a proportion of C1 cells may not express all of the enzymes necessary for adrenaline synthesis.
Animals↗
A half-century of Australian health and medical research.
In 1951, the Journal published an overview of medical research in Australia since Federation. This concluded that, with a few notable exceptions, discoveries were few and research funding was paltry. In contrast, in 2001, Australia has become a significant contributor to international medical research. Three Australians have been awarded Nobel Prizes for research performed in Australia, and others have received international awards. Research growth has been driven by the development of the tertiary education sector and independent medical research institutes. Nevertheless, there is no room for complacency.
Australia↗
The risk of neonatal death in relation to birth weight and maternal hypertensive disease in infants born at 24-32 weeks.
OBJECTIVE: To determine the risk of neonatal death (NND) in relation to birth weight for gestational age and the presence or absence of maternal hypertensive disease in preterm neonates. DESIGN: Record linkage of maternity data and neonatal mortality data. SETTING: Scotland, UK. POPULATION: A group of 6946 live singleton preterm neonates without lethal congenital abnormalities born at 24-32 weeks between 1986 and 1992 inclusive. This group included 1448 cases of maternal hypertensive disease and 850 neonatal deaths. MAIN OUTCOME MEASURE: Neonatal death. RESULTS: The median birth weight for each gestational week was estimated from a fitted curve and each birth weight was recalculated as a multiple of the relevant median. The frequency of NND was much higher at lower gestations (73% at 24 weeks down to 2% at 32 weeks). Though the overall frequency of NND was lower in cases with hypertensive disease (8.6% versus 13.2%) this can be attributed to the fact that there were relatively fewer hypertensive cases in the high risk group at 24-27 weeks. In the 5498 cases not associated with maternal hypertensive disease, there were 726 NNDs. The mean MoM of birthweight for these NNDs was 0.982 (95% CI 0.967-0.996); this was only marginally different from the population mean (0.998; 95% CI 0.993-1.004). In the 1448 cases with maternal hypertensive disease, there were 124 NNDs. The overall birthweight for gestational age in the hypertensive group was substantially less than that of the whole population (mean MoM 0.84; 95% CI 0.83-0.85) and that of the 124 NNDs was still lower (mean MoM 0.75; 95% CI 0.724-0.782). For both hypertensive and non-hypertensive cases, inspection of the data categorised into deciles showed that there was a continuous increase in the frequency of NND throughout the weight range, being lowest for the heaviest babies and highest for those in the lower centiles. CONCLUSION: (1) There is a relationship between birthweight for gestational age and risk of NND in infants born at 24-32 weeks; (2) this relationship is a continuum throughout the whole range of birthweight, not focused exclusively on a group defined as SGA; (3) provided appropriate birthweight standards are used, there is no extra effect on mortality from maternal hypertensive disease.
Birth Weight↗
Blood pressure lowering in diabetes: a brief review of the current evidence and description of a new trial.
1. Diabetes is a major global public health problem. The prevalence of this disease is predicted to increase sharply in the coming decades, particularly in less-developed regions of the world. 2. Most premature morbidity and mortality associated with diabetes relates to markedly increased risks of major cardiovascular diseases, such as myocardial infarction and stroke (macrovascular events), as well as microvascular complications, such as nephropathy and retinopathy. 3. Hypertension is a prevalent and important risk factor for vascular events in these patients. However, observational data demonstrate a continuous relationship between blood pressure and risk of vascular events, suggesting that even those individuals considered normotensive may benefit from blood pressure lowering. 4. Trials of blood pressure lowering among mostly hypertensive individuals with diabetes have demonstrated benefit of intervention on macrovascular and microvascular outcomes. Recent data may suggest additional effects of angiotensin- converting enzyme inhibitors independent of blood pressure lowering. 5. Issues where data are lacking with respect to blood pressure lowering in diabetes include the effects of blood pressure lowering among non-hypertensive individuals and the effects of blood pressure lowering regimens based on different classes of drug. 6. Data expected to address some of these issues are being collected. These include a prospective meta-analysis of blood pressure-lowering trials with large numbers of patients with diabetes. A new large-scale randomised trial, ADVANCE (Action in Diabetes and Vascular Disease), is also described.
Antihypertensive Agents↗
Progress in reducing the burden of stroke.
1. The burden of stroke worldwide is growing rapidly, driven by an ageing population and by the rapid rate of urbanization and industrialization in the developing world. There are approximately 5 million fatal and 15 million non-fatal strokes each year and over 50 million survivors of stroke alive, worldwide, today. 2. The most important determinant of stroke risk is blood pressure, with a strong, continuous relationship between the level of the systolic and diastolic pressures and the risk of initial and recurrent stroke, in both Western and Asian populations. 3. Randomized clinical trials have clearly demonstrated that blood pressure lowering reduces the risk of initial stroke by 35-40% in hypertensive patients; but, until recently, there was no conclusive evidence that blood pressure lowering was effective in the secondary prevention of stroke. 4. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) has provided definitive evidence that blood pressure lowering in patients with previous stroke or transient ischaemic attack (TIA) reduces the incidence of secondary stroke by 28%, of major vascular events by 26% and of major coronary events by 26%. These reductions were all magnified by approximately 50% in a subgroup of patients in whom the angiotensin-converting enzyme inhibitor perindopril was routinely combined with the diuretic indapamide. 5. Successful global implementation of a treatment with perindopril and indapamide in patients with a history of stroke or TIA would markedly reduce the burden of stroke and could avert between 0.5 and one million strokes each year, worldwide.
Angiotensin-Converting Enzyme Inhibitors↗
Challenges for the prevention of primary and secondary stroke: the importance of lowering blood pressure and total cardiovascular risk.
It is well established that blood pressure lowering is effective for the primary prevention of stroke and other cardiovascular disorders in subjects with blood pressures as low as 140/90 mmHg, and up to 80 years of age. Despite this knowledge, blood pressure levels are controlled in less than 25% of the hypertensive population worldwide. It has taken longer to prove that blood pressure lowering is equally effective for the prevention of recurrent stroke. The results of PROGRESS (Perindopril Protection Against Recurrent Stroke Study) have confirmed that a perindopril-based regimen in subjects with cerebrovascular disease substantially reduces the incidence of secondary stroke and primary myocardial infarction. It is daunting to recall that it has taken almost two decades for beta-blockers to be widely used for the secondary prevention of myocardial infarction, since widespread use of the PROGRESS regimen would prevent more than half a million strokes worldwide each year. The real challenge now is to implement novel and effective strategies for the control of blood pressure and other cardiovascular risk factors worldwide. Strategies should include lifestyle measures, such as stopping smoking, exercise and reducing overweight. There is a real need to identify hypertensive subjects and treat them with blood pressure lowering drugs for primary prevention. In subjects with established cardiovascular disease, consideration should be given to a range of proven interventions for secondary prevention, such as blood pressure lowering, irrespective of current blood pressure, anti-platelet drugs, statins for lowering cholesterol and glycaemic control in diabetics. Among new strategies to lower overall cardiovascular risk, consideration should be given to the development of single-pill combinations of drugs of known efficacy, including various combinations of ACE inhibitors, diuretics, beta-blockers, aspirin and statins, among others.
Antihypertensive Agents↗
Pneumococcal vaccination: opinion of general practitioners and hospital doctors in Scotland, 1999-2000.
A cross sectional survey by postal questionnaire was carried out to examine general practitioners' (GPs) and hospital doctors' (HDs) knowledge, attitudes and practice (KAP) with regard to pneumococcal vaccination in primary and hospital care in Scotland. Most GPs and HDs considered patients with chronic medical conditions, as recommended by the Department of Health (DoH), to be candidates for pneumococcal vaccination. Although the DoH does not currently recommend the vaccine for all the elderly, 47% of GPs and 46% of HDs reported that the vaccine should be given to this group. GPs (61-85%) and HDs (48-55%) indicated that they considered the vaccine to be safe and effective. The acceptance of pneumococcal vaccine was much lower than for influenza vaccine however, and 79% of HDs and 17% of GPs had never used the vaccine. Documented policies (with or without set targets) for pneumococcal vaccine existed in only 14% of general practice and 3% of hospital settings. Over 70% of respondents indicated that GPs should take responsibility for pneumococcal vaccination. The main sources of knowledge about pneumococcal vaccines were stated to be discussion with colleagues, review of medical literature, past experience, and the DoH recommendations. A clear immunisation policy and financial support for vaccination were identified as important strategies to improve pneumococcal vaccine coverage. Strategies directed toward these factors could enhance vaccine delivery and coverage of vaccine in high-risk individuals.
Cross-Sectional Studies↗
Calbindin-immunoreactive neurons in the reticular formation of the rat brainstem: catecholamine content and spinal projections.
Calbindin-D28k (calbindin) is a calcium-binding protein that is distributed widely in the rat brain. The localisation of calbindin immunoreactivity in the medulla oblongata and its colocalisation with adrenaline-synthesising neurons [phenylethanolamine-N-methyltransferase-immunoreactive (PNMT-IR)] was examined (Granata and Chang [1994] Brain Res. 645:265-277). However, detailed information about the distribution of calbindin-IR neurons in the reticular formation of the medulla oblongata in particular is lacking. In this report, the authors address this issue with an emphasis on the quantitation of calbindin-IR neurons, catecholamine neurons [tyrosine hydroxylase (TH)-IR, or PNMT-IR], and spinally projecting neurons in the ventral brainstem. Rats received injections of the retrograde tracing agent cholera toxin B (CTB) into the thoracic spinal cord or into the superior cervical ganglion. Immunocytochemistry was used to reveal calbindin, TH, PNMT, and CTB immunoreactivity. Ten calbindin-IR cell groups were identified within the pontomedullary reticular formation. Seven previously undescribed but distinct clusters of calbindin-IR neurons were found. Within the ventral pons, a population of calbindin-IR neurons occurred dorsal but adjacent to the A5 cell group. These calbindin-IR neurons did not contain either TH or PNMT immunoreactivity, and few if any of these neurons projected to the spinal cord. A distinct group of calbindin-IR neurons was present in the ventral medulla. Seventy-five percent of these calbindin-IR neurons contained TH immunoreactivity, 45% contained PNMT immunoreactivity, and 21% were spinally projecting neurons. Spinally projecting, calbindin-IR neurons were a subpopulation of PNMT-IR cells. In the caudal ventral medulla, no TH-IR or PNMT-IR cells were calbindin-IR. In the intermediolateral cell column, close appositions of calbindin-IR terminals on identified sympathetic preganglionic neurons as well as calbindin-IR synapses indicated that these neurons may affect directly the sympathetic outflow. The results demonstrate for the first time the existence of a new subpopulation of spinally projecting, PNMT-IR neurons in the rostral ventrolateral medulla.
Animals↗
Delta opioid receptor immunoreactive boutons appose bulbospinal CI neurons in the rat.
Bulbospinal sympathoexcitatory neurons in the rostral ventrolateral medulla are inhibited by activation of delta opioid receptors. However, it is not known whether this opioidergic effect is pre- or post- synaptic. Here, using retrograde tracing and immunocytochemistry in adult rats, we provide evidence that the delta opioid receptor is located on boutons that are presynaptic to both catecholaminergic and non-catecholaminergic neurons that project to the spinal cord. We suggest that the sympathoinhibitory action of delta opioid receptor activation in the rostral ventrolateral medulla is mediated presynaptically, resulting in a reduction of excitatory neurotransmitter release from boutons that oppose sympathoexcitatory bulbospinal neurons.
Adrenergic Fibers↗
"I don't like Mondays"-day of the week of coronary heart disease deaths in Scotland: study of routinely collected data.
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Adult↗
Long-term efficacy of a new, fixed, very-low-dose angiotensin-converting enzyme-inhibitor/diuretic combination as first-line therapy in elderly hypertensive patients.
OBJECTIVE: To determine the long-term efficacy and safety of a fixed, very-low-dose tablet combining one-half the standard dose of perindopril with one-quarter the standard dose of indapamide as first-line treatment in elderly patients. DESIGN: Double-blind, randomized, placebo-controlled study in an outpatient setting. PATIENTS AND INTERVENTIONS: Following a single-blind, placebo run-in period of 4 weeks, patients [65-85 years, with mild-to-moderate essential hypertension or isolated systolic hypertension (ISH)] were randomized to receive one tablet of perindopril 2 mg/indapamide 0.625 mg (Per/ Ind) (n=193) or placebo (n=190), daily for 12 weeks. After this first 12-week period, all patients on Per/Ind (n=138) and patients responding to placebo (n=61) were maintained on their previous regimen for a further 48 weeks. Patients in the placebo group whose blood pressure was not normalized, were switched to Per/Ind (n=60). MAIN OUTCOME MEASURE: The primary endpoint was the proportion of patients with blood pressure that normalized between weeks 0 and 60. RESULTS: After 1 year of treatment (intention-to-treat) supine systolic and diastolic blood pressure decreased by 23.0 +/- 15.3 mmHg and 13.3 +/- 94 mmHg with Per/Ind (n=253: 193 from randomized Per/Ind group and 60 from the placebo group switched at week 12). The mean decreases in systolic blood pressure were similar in essential hypertension and ISH (systolic blood pressure 23.2 versus 22.7 mmHg, respectively). Per/Ind treatment (n=253) achieved an initial normalization of blood pressure in 96.2% [95% confidence interval (CI) 93.6-98.9%; Kaplan-Meier estimate] of Per/Ind-treated patients; 79.8% (95% CI 74.1-85.5%) of these maintained a normalized blood pressure throughout the 1 -year follow-up. The incidence of adverse events was similarly low in the placebo and active therapy groups. Efficacy and safety results for the over 75 years subgroup were similar to those for the younger elderly subjects CONCLUSIONS: The fixed, very low-dose combination of perindopril 2 mg/indapamide 0.625 mg results in sustained blood pressure control when used as first line treatment of elderly hypertensive patients over 1-year, and is well-tolerated.
Aged↗
Prevention of cardiovascular diseases in developing countries: agenda for action (statement from a WHO-ISH Meeting in Beijing, October 1999).
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Cardiovascular Diseases↗
Measuring the costs and benefits of heart disease monitoring.
OBJECTIVE: To evaluate the costs and benefits of alternative systems of coronary heart disease monitoring in Scotland. DESIGN: An option appraisal was conducted to evaluate the costs and benefits of implementing a coronary heart disease monitoring system. This involved a review of existing Scottish datasets and relevant reports, specification of options, definition and weighting of benefit criteria by key stakeholders, assessment of options by experts, and costing of options. The options were assessed by 33 stakeholders (grouped as cardiologists, patient representatives, general practitioners, public health physicians, and policy makers), plus 13 topic experts. SETTING: Scotland (population 5.1 million). RESULTS: Between group mean benefit weights were: mortality rates and case fatality (10.6), quality of life (9.8), patient function (8.8), hospital activity (7.8), primary care activity (9.25), prescribing (5.72), socioeconomic impact (4.0), risk factors (7.4), prevalence (5.0), incidence (6.0), case registration (6.82), international comparability (4.2), breadth of coverage (8.8), and frequency (5.8). Differences between group weights were significant for prevalence (p = 0.048) and international comparability (p = 0.032). Four monitoring options were identified: a community epidemiology model, based on MONICA (monitoring trends and determinants in cardiovascular disease) study methodology applied to a series of eight representative communities, had the highest benefits, at an average annual discounted cost of approximately pound 360,000; models based on the Australian cardiovascular disease monitoring scheme and on enhanced routine data offered fewer benefits at discounted average annual costs ranging from pound 165,000 to pound 195,000; finally, a coronary heart disease registry modelled on the Scottish Cancer Registry scheme would have had fewer benefits and substantially higher costs than the other options. CONCLUSIONS: The most beneficial coronary heart disease monitoring system is the community epidemiology model, based on MONICA methodology. Option appraisal potentially offers an explicit and transparent methodology for evidence based policy development.
Coronary Disease↗
Spinal GABA(A) receptors do not mediate the sympathetic baroreceptor reflex in the rat.
Activation of baroreceptors causes efferent sympathetic nerve activity (SNA) to fall. Two mechanisms could account for this sympathoinhibition: disfacilitation of sympathetic preganglionic neurons (SPN) and/or direct inhibition of SPN. The roles that spinal GABA and glycine receptors play in the baroreceptor reflex were examined in anesthetized, paralyzed, and artificially ventilated rats. Spinal GABA(A) receptors were blocked by an intrathecal injection of bicuculline methiodide, whereas glycine receptors were blocked with strychnine. Baroreceptors were activated by stimulation of the aortic depressor nerve (ADN), and a somatosympathetic reflex was used as control. After an intrathecal injection of vehicle, there was no effect on any measured variable or evoked reflex. In contrast, bicuculline caused a dose-dependent increase in arterial pressure, SNA, phrenic nerve discharge, and it significantly facilitated the somatosympathetic reflex. However, bicuculline did not attenuate either the depressor response or sympathoinhibition evoked after ADN stimulation. Similarly, strychnine did not affect the baroreceptor-induced depressor response. Thus GABA(A) and glycine receptors in the spinal cord have no significant role in baroreceptor-mediated sympathoinhibition.
Adrenergic Fibers↗
The World Heart Federation's white book: impending global pandemic of cardiovascular diseases: challenges and opportunities for the prevention and control of cardiovascular diseases in developing countries and economies in transition.
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Cardiovascular Diseases↗
Blood pressure burden: vascular changes and cerebrovascular complications.
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Angiotensin-Converting Enzyme Inhibitors↗
PROGRESS (Perindopril Protection Against Recurrent Stroke Study): regional characteristics of the study population at baseline. PROGRESS Management Committee.
OBJECTIVE: To determine the effects of an angiotensin-converting enzyme (ACE) inhibitor-based blood pressure lowering regimen on the risk of stroke among patients with a history of cerebrovascular disease. Secondary aims include investigation of the effects of treatment on other cardiovascular events, dementia, and disability. DESIGN AND METHODS: PROGRESS (Perindopril Protection Against Recurrent Stroke Study) is a double-blind, placebo-controlled, randomized trial being conducted in 172 centres in 10 countries (Australia, Belgium, China, France, Italy, Ireland, Japan, New Zealand, Sweden, and the United Kingdom). Patients were randomly assigned to treatment with the ACE inhibitor perindopril (and the diuretic indapamide for those with no definite indication for or contraindication to treatment with a diuretic) or matching placebo(s). Both hypertensive and normotensive patients were eligible for inclusion. Follow-up is scheduled for completion in 2001. RESULTS: Of 6105 patients randomly allocated to study groups on completion of recruitment in November 1997, 1110 were recruited from Australia and New Zealand, 1520 from China, 713 from France and Belgium, 557 from Italy, 815 from Japan, 675 from Sweden, and 715 from the UK and Ireland. Regional differences in the baseline characteristics included a greater rate of diabetes, lacunar infarction, and cerebral haemorrhage in patients from China and Japan, and a more frequent history of myocardial infarction in Australia and New Zealand. Previous treatment with calcium antagonists was very frequent in Japan and China, whereas diuretic treatment was most often documented in the UK and Ireland. CONCLUSIONS: Analysis of baseline characteristics of patients recruited from seven distinct geographic regions revealed some interesting differences, but more striking was the consistency of characteristics of patients recruited from many different countries across the world.
Aged↗