Sexual health of teenagers. Trends should be examined over longer period.
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Adolescent↗
Biomedical subjects
J Chalmers
Publications and source records attributed to J Chalmers.
The 1999 WHO-ISH Guidelines for the Management of Hypertension.
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Antihypertensive Agents↗
Substance P-immunoreactive boutons closely appose inspiratory protruder hypoglossal motoneurons in the cat.
In anesthetized cats, we recorded intracellularly from 26 hypoglossal motoneurons which were antidromically activated following electrical stimulation of either the medial or lateral branches of the hypoglossal nerve. Twenty-one of these neurons were protruder motoneurons 6 of which had inspiratory activity. Three of the protruder motoneurons with inspiratory activity were filled with Neurobiotin and found to be closely apposed to substance P-like immunoreactive nerve terminals.
Animals↗
Sex difference in the relationship of calcium and magnesium excretion to glycaemic control in type 1 diabetes mellitus.
In order to assess the variability and possible causes of calcium and magnesium losses in diabetes mellitus, urinary calcium and magnesium excretion were monitored six monthly over a 3-year period in 108 stable, type 1 diabetic patients who were having assessment of their clinical status and glycaemic control over the same period. In the patients studied the ranges of excretion of both calcium and magnesium were considerably wider than our non-diabetic reference ranges but the within subject variation in excretion was high. However, using mean values obtained over the study period, a direct relationship was observed between the excretion of both calcium and magnesium and HbA1 in female patients (P < 0.01) but not in males who had similar HbA1 values. The urinary excretion of calcium and magnesium did not relate to any of the other clinical or biochemical indices measured, including body mass index, daily insulin dose, retinal status or albumin excretion. It is suggested that, in poorly controlled patients, females may have a greater risk than males of developing the complications associated with chronic calcium and magnesium loss.
Adult↗
The use of free and fixed drug combinations to improve hypertension control in our populations.
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Antihypertensive Agents↗
Identification of posterior cricoarytenoid motoneurons in the rat.
The posterior cricoarytenoid (PCA) muscle is the sole abductor of the larynx and is controlled by motoneurons located in the nucleus ambiguus. These motoneurons receive inputs from a variety of interneurons, including those that impart respiratory modulation, and are responsible for the phasic inspiratory activity of the PCA muscle. Identification of PCA motoneurons is therefore an essential initial step in understanding the mechanisms responsible for coordinated vocal cord abduction. We identified PCA motoneurons in the rat model by retrograde labeling, and following antidromic activation. A total of 194 neurons were identified by retrograde labeling with cholera toxin B subunit (CTB). Labeling was exclusively ipsilateral where the contralateral vagus and superior laryngeal nerves had been divided. The neurons were multipolar, with dimensions of 33.2 +/- 6.4 microm (mean +/- standard deviation) in length and 22.4 +/- 3.4 microm in width. The neurons were located within a range of 0.6 to 2.4 mm caudal to the caudal pole of the facial nerve, 1.2 to 1.7 mm lateral to the midline, and 1.5 to 2.3 mm deep to the dorsal surface of the medulla. The PCA motoneurons were antidromically activated by focal stimulation of the PCA muscle. The extracellular field was recorded in 5 rats, and the PCA motoneurons were found within a range of 0.8 to 1.7 mm caudal to the caudal pole of the facial nerve, 1.5 to 2.0 mm lateral to the midline, and 1.9 to 2.4 mm deep to the dorsal surface of the medulla. The mean conduction velocity ranged from 37.0 +/- 5.8 to 68.6 +/- 5.0 m/s. An extracellular antidromic field potential, which corresponds to the distribution of the PCA motoneuron pool demonstrated by retrograde labeling with CTB, can be reliably obtained in a rat model following focal PCA muscle stimulation.
Animals↗
Intracellular recording from posterior cricoarytenoid motoneurons in the rat.
The ability to maintain coordinated vocal cord abduction and upper airway patency is dependent on the integrity of the posterior cricoarytenoid (PCA) motoneurons and their multiple neural connections. Study of the PCA motoneurons represents the initial step in understanding the complex mechanisms responsible for coordinated vocal cord abduction and may provide an insight into the possible pathological processes underlying the various clinical presentations of vocal cord dysfunction. Intracellular recordings were made from 11 PCA motoneurons in Sprague-Dawley rats, which all showed an inspiratory augmenting discharge pattern that is also characteristic of phrenic nerve activity. The resting membrane potential was -56+/-11 mV. Two PCA motoneurons were injected with Neurobiotin to demonstrate neuronal morphology, which was found to be similar to that obtained by retrograde labeling with cholera toxin B subunit. The technique described for intracellular recording of PCA motoneurons should allow more detailed morphological, electrophysiological, and immunohistochemical information to be obtained, to thereby identify some of the factors responsible for maintaining normal function of the PCA muscle.
Animals↗
Efficacy and safety of an oral fixed low-dose perindopril 2 MG/indapamide 0.625 MG combination: a randomized, double-blind, placebo-controlled study in elderly patients with mild to moderate hypertension.
The efficacy and safety of 12 weeks treatment with an oral fixed low-dose perindopril 2 mg + indapamide 0.625 mg (Per/Ind) combination in elderly and very elderly patients (65-85 years) with mild to moderate systolic and diastolic hypertension (SDH) or isolated systolic hypertension (ISH) were investigated vs placebo. This trial was a multinational randomized double-blind study with doubling of active drug dosage in nonresponders. Intention to treat analysis was performed in 383 patients (age 72.4 years; ISH 32%). 58.5% remained on their initial dosage. Per/Ind decreased supine diastolic and systolic blood pressure (sDBP/sSBP) by 13.2+/-8.0 mm Hg and 22.5+/-13.9 mm Hg (P <.0001) versus placebo -7.3+/-9.0 mm Hg and -12.3+/-15.2 mm Hg, respectively. In ISH (n = 123), Per/Ind decreased sSBP by 23.0+/-11.8 mm Hg (P <.0001). Overall response and normotension rates was 81.3% with Per/Ind (P <.0001). Adverse event rates (including hypokalemia) were similarly low in both groups. Analysis in the over-75 year subgroup showed similar safety and efficacy results. Fixed low-dose Per/Ind is a safe and effective treatment of hypertension including isolated systolic hypertension in the elderly.
Administration, Oral↗
Hypertension optimal treatment (HOT) study: a brilliant concept, but a qualified success.
BACKGROUND TO THE STUDY: The Hypertension Optimal Treatment (HOT) study was designed to answer two questions: whether low-dose aspirin (75 mg/day) is effective in the primary prevention of myocardial infarction, without an increase in cerebral haemorrhage in hypertensive patients whose blood pressure is well controlled, and whether there are additional benefits with a progressive reduction of diastolic blood pressure from 90 mmHg to below 80 mmHg. SUCCESSES: In a landmark outcome, low-dose aspirin was indeed shown to be effective in the primary prevention of myocardial infarction. Moreover, the study has shed light on many important issues for blood pressure lowering in the treatment of hypertension, providing an excellent demonstration that with aggressive combination therapy, the elevated blood pressure in hypertensive subjects can be lowered and maintained in the normotensive range in over 90% of cases. DISAPPOINTMENT: The biggest disappointment was that the intention to treat analysis failed to demonstrate a significant difference between the three randomized target blood pressure groups for the majority of cardiovascular events.
Antihypertensive Agents↗
Volhard Lecture. Brain, blood pressure and stroke.
BRAIN AND BLOOD PRESSURE IN EXPERIMENTAL ANIMALS: Our experiments in models of experimental hypertension in the rabbit in the early 1970s demonstrated that increased activity of bulbospinal pressor neurons containing noradrenaline or serotonin mediated the elevated arterial blood pressure. Other workers had demonstrated decreased activity of noradrenergic neurons in the medulla. Accordingly, I proposed the hypothesis that the hypertension in these models arose from 'disinhibition', due to unrestrained activity of descending pressor pathways, released from the inhibitory influences present in normal animals. Over the next 15-20 years, experiments from our group and from other laboratories demonstrated that there were two distinct bulbospinal pressor pathways descending from the rostral ventral medulla, one containing adrenaline, neuropeptide Y and glutamate, and the other containing serotonin, substance P and glutamate. It has also been established that the key depressor area is in the caudal ventrolateral medulla and that the main inhibitory input, restraining the activity of the bulbospinal pressor pathways, is a short gamma-aminobutyric acid (GABA) projection ascending from the caudal ventrolateral medulla to the rostral ventral medulla. More recent experiments in the spontaneously hypertensive rat (SHR) using the immediate-early gene c-fos as a marker of neuronal activity, have demonstrated that impaired activity of this short inhibitory GABA pathway in the SHR disinhibits the bulbospinal pressor pathway, thus contributing to the hypertension in this model. BLOOD PRESSURE AND STROKE IN HUMANS: The risks of primary stroke and of secondary or recurrent stroke are both directly related to the level of blood pressure and clinical trials have clearly demonstrated that lowering blood pressure markedly reduces the incidence of primary stroke. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was launched to test the hypothesis that lowering the blood pressure in subjects who have already had a stroke or a transient ischaemic attack will also reduce the risk of stroke. A major unresolved issue for practising clinicians is how to manage the raised blood pressure that is so common in the acute phase of stroke. Accordingly, the PROGRESS investigators are planning another major multinational trial to assess the benefits and risks of lowering blood pressure in the first 3 days after the onset of a stroke.
Animals↗
Advances in the diagnosis and treatment of arterial hypertension.
Hypertension is a major risk factor for the development of serious complications affecting the heart, brain, kidneys and the vascular system, leading to death and disability on a huge scale globally. This manuscript deals primarily with the clinical strategy for the control of hypertension and only refers in passing to the population strategy and primary prevention. It also concentrates on essential hypertension and does not deal with the diagnosis and management of secondary causes of hypertension. Rather, the paper describes the clinical evaluation, laboratory investigations and management of the patient with essential hypertension. The focus of management is on patients with mild and moderate hypertension, without any discussion of the treatment of more severe hypertension, malignant hypertension or hypertensive encephalopathy. Accordingly, the emphasis is on lifestyle factors important in both prevention and treatment of hypertension and on the drug treatment of patients with elevated blood pressures in routine clinical practice. The paper does not cover special populations or problems such as hypertension of pregnancy or hypertension in children.
Journal Article↗
Surveillance of sexually transmitted infections in Scotland.
Applications of the surveillance of sexually transmitted infections (STIs) include setting priorities for and planning preventive and treatment services, evaluating interventions, and shaping research hypotheses. In Scotland routine data on STIs, (other t
Journal Article↗
Bötzinger neurons project towards bulbospinal neurons in the rostral ventrolateral medulla of the rat.
Sympathetic nerve activity often fluctuates with the respiratory cycle, but the central neurons that impose this respiratory modulation have not been conclusively identified. In the present study, we used intracellular recording and dye-filling to identify expiratory neurons in the Bötzinger complex. Our aim was to see if Bötzinger neurons project towards putative cardiovascular neurons in the rostral ventrolateral medulla. In the first series of experiments, histochemistry and immunohistochemistry were used to reveal the labelled Bötzinger neurons and neurons immunoreactive for tyrosine hydroxylase. Two out of four Bötzinger neurons had axon varicosities that were closely apposed to tyrosine hydroxylase-immunoreactive neurons with cell bodies located within 0.6 mm caudal to the facial nucleus (three and five close appositions, respectively). In a second series of studies, rats were injected with cholera toxin B into the intermediolateral cell column of the spinal cord 4-7 days before the electrophysiological recording. Eight of the fourteen labelled Bötzinger neurons had a direct projection towards cholera toxin B-labelled neurons in the rostral ventrolateral medulla. Close appositions were found on both somata and proximal dendrites (5 +/- 2 close appositions/neuron, n = 8). The present study supports the idea that a direct projection from Bötzinger neurons to presympathetic neurons in the rostral medulla plays a role in the respiratory modulation of sympathetic nerve activity.
Animals↗
Operating theatres. Funders keepers.
Recruiting and retaining operating theatre staff is a constant problem for many trusts. One trust has introduced a pay supplement of 1,500 Pounds for all operating theatre staff, and is now planning to implement a single pay spine for all categories of operating theatre staff. The long-standing staffing difficulties suggest it is time to reconsider skill mix in operating theatres.
Employee Incentive Plans↗
Role of spinal GABA receptors in depressor responses to chemical stimulation of the A5 area in normal and hypertensive rats.
Chemical stimulation of neurons in the pontine A5 area by microinjection of L-glutamate lowers arterial blood pressure. The mechanism of this 'A5 depressor response' is not well-established. Here, we examine the involvement of spinal cord gamma-aminobutyric acid (GABA) receptors in this depressor response in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Experiments were conducted in male WKY and age-matched SHR anaesthetised with sodium pentobarbitone and chloral hydrate. An intrathecal catheter was implanted with the tip located between T9 and L2. Three days later, rats were re-anaesthetised and 10 nl of 40 mM L-glutamate was injected into the A5 area before, during and after, blockade of spinal cord GABA-A receptors by intrathecal injection of bicuculline methiodide (1 mM in 10 microliters phosphate-buffered saline). Injection of L-glutamate (10, 20, 40, 80 mM in 10 nl) produced depressor responses that were similar in WKY (n = 6) and SHR (n = 6). Intrathecal injection of bicuculline elicited a pressor response that was greater in SHR (n = 7, 28.5 +/- 7.6% increase in mean arterial pressure) than WKY (n = 11, 11.6 +/- 3.6%, p < 0.05). After bicuculline, the depressor response to injection of L-glutamate into the A5 area was eliminated in both WKY (n = 7) and SHR (n = 6). Intrathecal injection of vehicle had no effect on either resting arterial blood pressure or the depressor response to A5 stimulation. Basal blood pressure and control responses to A5 stimulation were fully restored by around 90 min after bicuculline injection in each animal. In separate groups of rats, intrathecal injection of muscimol elicited depressor responses that were greater in SHR (n = 6, -32.0 +/- 6.2%) than WKY (n = 6, -17.3 +/- 1.5%, p < 0.05). Our results suggest that the A5 depressor response is due to a projection from the A5 area to the spinal cord. This projection acts directly, or through a spinal interneuron and uses GABA as a neurotransmitter. Furthermore, our results indicate a hyper-responsiveness to GABA-A receptor stimulation in SHR since intrathecal bicuculline elicited much greater increases and intrathecal muscimol elicited much greater decreases, in blood pressure in SHR than in WKY. Finally, it seems likely that the A5-spinal depressor pathway is less effective in SHR than WKY under physiological conditions since chemical stimulation of the A5 area with L-glutamate produced a comparable depressor response in both strains.
Animals↗
Phosphate-activated glutaminase immunoreactivity in brainstem respiratory neurons.
The aim of this study was to determine if immunoreactivity for phosphate activated glutaminase (PAG), an enzyme involved in the biosynthesis of glutamate and a putative marker for neurons that use glutamate as a neurotransmitter, is present within respiratory neurons in the ventrolateral medulla oblongata. Intracellular recordings were obtained from neurons in the ventrolateral medulla of adult anaesthetised Sprague-Dawley rats. Neurons with a respiratory-related modulation of their membrane potential were filled with Neurobiotin (Vector, CA). After histochemical processing, sections of brainstem were examined by fluorescence and light microscopy. Some PAG immunoreactivity was found in all of the four types of respiratory neurons examined. PAG immunoreactivity was graded as strong or weak. (1) Of six inspiratory neurons in the rostral ventral respiratory group five were strongly PAG immunoreactive and one was weakly PAG immunoreactive. (2) Of six expiratory neurons in the caudal ventral respiratory group five were strongly PAG immunoreactive while one was weak. (3) Seven motoneurons in the nucleus ambiguous were all strongly PAG immunoreactive. (4) Five neurons in the Bötzinger area were examined. Four were weakly PAG immunoreactive while one contained strong PAG immunoreactivity. These data demonstrate a heterogeneity of PAG immunoreactivity amongst brainstem respiratory neurons.
Animals↗
Congenital anterior abdominal wall defects. Rate of abdominal wall defects is higher in Scotland than England and Wales.
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Abdominal Muscles↗
Design, construction and evaluation of systems to predict risk in obstetrics.
We present a systematic, practical approach to developing risk prediction systems, suitable for use with large databases of medical information. An important part of this approach is a novel feature selection algorithm which uses the area under the receiver operating characteristic (ROC) curve to measure the expected discriminative power of different sets of predictor variables. We describe this algorithm and use it to select variables to predict risk of a specific adverse pregnancy outcome: failure to progress in labour. Neural network, logistic regression and hierarchical Bayesian risk prediction models are constructed, all of which achieve close to the limit of performance attainable on this prediction task. We show that better prediction performance requires more discriminative clinical information rather than improved modelling techniques. It is also shown that better diagnostic criteria in clinical records would greatly assist the development of systems to predict risk in pregnancy.
Algorithms↗