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Biomedical subjects

C J Mathias

Publications and source records attributed to C J Mathias.

At least 217 records · Page 12Linked to original sources
PubMed1988

Haemodynamic actions of clonidine in tetraplegia--effects at rest and during urinary bladder stimulation.

We studied the haemodynamic effects of clonidine (2 micrograms/kg/iv) in 7 tetraplegics and 7 normal subjects. Measurements of blood pressure, stroke volume, cardiac output and digital (finger) skin blood flow were made before and after clonidine for 60 minutes. Blood pressure, stroke volume and cardiac output did not fall in tetraplegics, unlike normals. Resting digital skin blood flow was higher in tetraplegics and fell after clonidine. In normal subjects however, an increase in digital skin blood flow occurred after clonidine. The pressor and digital vasoconstrictor responses to bladder stimulation were attenuated after clonidine. The inability of clonidine to induce a fall in blood pressure, stroke volume, cardiac output and cause peripheral vasodilation in tetraplegics is consistent with its central sympatholytic effects. Attenuation of the responses to bladder stimulation suggest an effect on spinal sympathetic neurones.

Adolescent↗
PubMed1988

Haemodynamic, hormonal and urinary responses to postural change in tetraplegic and paraplegic man.

We have studied the haemodynamic, hormonal and urinary effects of postural change in 6 tetraplegic patients, 6 paraplegic patients and 6 normal subjects. Measurements of blood pressure and heart rate, plasma renin activity, plasma aldosterone, urine volume and electrolyte excretion were made for 60 minutes while sitting and 60 minutes while recumbent. In tetraplegics the blood pressure was lower when sitting and rose during recumbency, unlike paraplegics and normal subjects. Plasma renin activity and aldosterone were higher in tetraplegics when sitting compared to normal subjects and did not fall during recumbency. Urine output increased significantly after recumbency in tetraplegics, but not in paraplegics or normal subjects. Both urinary sodium and potassium excretion were lower in tetraplegics and higher in paraplegics compared to normal subjects when sitting. In paraplegics the fall in both sodium and potassium excretion did not appear to be related to change in posture. Our observations indicate that recumbency induces a diuresis in tetraplegics but not in paraplegics or in normal subjects. The diuresis in tetraplegics may be related to the accompanying haemodynamic and hormonal changes induced by recumbency.

Aldosterone↗
PubMed1988

Intravenous morphine causes hypertension, hyperglycaemia and increases sympatho-adrenal outflow in conscious rabbits.

1. In conscious rabbits, intravenous morphine (3 mg/kg) caused hypertension, bradycardia, hyperglycaemia and sedation. These changes were accompanied by large increases in plasma adrenaline and smaller increases in plasma noradrenaline. 2. These effects of morphine were prevented by intravenous naloxone, demonstrating their dependence on stimulation of opiate receptors. 3. Pretreatment with the antihistamines cimetidine and chlorpheniramine enhanced the morphine-induced rise in blood pressure, excluding a role for histamine release in the hypertensive action of morphine. 4. The centrally acting alpha 2-adrenergic agonist clonidine prevented the morphine-induced hypertension and rise in plasma catecholamines, suggesting that these effects are exerted via central pathways. Clonidine alone reduced blood pressure and heart rate and produced hyperglycaemia. 5. alpha-Adrenergic blockade with phenoxybenzamine reduced the increase in blood pressure after morphine, although the increase in plasma catecholamines was augmented. 6. Pentobarbitone anaesthesia prevented the morphine-induced cardiovascular changes, the increase in plasma catecholamines and the hyperglycaemia. 7. These findings indicate, that in conscious rabbits, morphine induces hypertension by stimulation of opiate receptors leading to increased sympatho-adrenal activity. The hyperglycaemia appears to be in response to secretion of adrenaline. These effects probably result from a central action of morphine.

Animals↗
PubMed1988

Cardiovascular and neurohormonal changes following central sympathetic blockade with clonidine in human unilateral renal artery stenosis.

The role of central pressor mechanisms in the maintenance of blood pressure in six hypertensive patients with angiographically proven unilateral renal artery stenosis was investigated by studying the haemodynamic and hormonal responses before and after central sympathetic blockade with clonidine. To assess the dependency of blood pressure on the direct effects of angiotensin II, the same patients were studied on a separate occasion after administration of the angiotensin converting enzyme (ACE) inhibitor, captopril. There was a substantial fall in blood pressure after administration of clonidine with a smaller fall after captopril. Clonidine-induced hypotension was accompanied by a fall in cardiac output, through a reduction in the stroke volume and heart rate. Forearm vascular resistance was unchanged. There was a selective decrease in digital skin vascular resistance and plasma noradrenaline, indicating reduced sympathetic activity. Plasma renin activity and aldosterone levels did not fall. After administration of captopril, there was a fall in cardiac output due to a fall in the stroke volume but not in the heart rate. Forearm vascular resistance, digital skin vascular resistance and plasma noradrenaline were unchanged. Plasma renin activity rose and plasma aldosterone fell. We conclude that in our hypertensive patients with renal artery stenosis, clonidine lowered blood pressure by a reduction in central sympathetic activity independently of renin suppression. In these patients captopril had minimal hypotensive effects, indicating a smaller role for the direct vascular effects of angiotensin II.

Adult↗
PubMed1988

Breast cancer: PET imaging of estrogen receptors.

Thirteen patients with primary breast masses were studied with positron emission tomography (PET) and 16 alpha-[fluorine-18]-fluoroestradiol-17 beta. PET images demonstrated uptake of the labeled estrogen analog at sites of primary carcinomas and in several foci of axillary lymph node metastases, as well as in one distant metastatic site. There was excellent correlation between uptake within the primary tumor measured on the PET images and the tumor estrogen-receptor concentration measured in vitro after excision (r = .96). This technique may provide an in vivo method of assessing estrogen receptors in primary and metastatic breast cancers and thus guide management of this disease with antiestrogen chemotherapy.

Adenocarcinoma↗
PubMed1988

Vascular effects of clonidine in patients with tetraplegia and unilateral brachial plexus injury.

Evidence from studies in both animals and in tetraplegics with complete cervical spinal cord transection and preganglionic lesion, indicates that clonidine lowers blood pressure predominantly by a centrally mediated action. We have investigated the haemodynamic basis of this action and performed additional studies in patients with unilateral brachial plexus injury and postganglionic lesions, to further determine the site and mechanism of its action. Blood pressure fell after clonidine in normal subjects but not in tetraplegics. In normal subjects, the fall in blood pressure was associated with a fall in cardiac output, due to a fall in both heart rate and stroke volume. Digital skin vasodilatation occurred after clonidine in normal subjects and only in the innervated limb in patients with unilateral brachial plexus injury. In tetraplegics and in the denervated limb in unilateral brachial plexus injury, there was no vasodilatation; instead a vasoconstrictor response occurred, due to the peripheral adrenoceptor action of clonidine. We conclude that the fall in blood pressure and cardiac output in normal subjects after clonidine were due to its central sympatholytic action. Digital skin vasodilatation after clonidine in normal subjects and the innervated limb in unilateral brachial plexus injury was due to the withdrawal of vasoconstrictor tone and requires intact descending sympathetic pathways.

Adult↗
PubMed1987

Intravenous dihydroergotamine to relieve pelvic congestion with pain in young women.

The selective venoconstrictor dihydroergotamine (DHE) was given intravenously to 12 women with evidence of pelvic congestion. In 6 the effect of the drug on pelvic veins was observed by pelvic venography. After DHE there was a mean reduction of 35% in the diameter of the pelvic veins measured and the contrast medium cleared rapidly, with a visible reduction in pelvic congestion. In the other 6 women DHE was given during an acute attack of pelvic pain. The effect of the drug on pain relief was assessed by a single-blind crossover trial with intravenous saline as the placebo and by a visual analogue scale to assess the intensity of pain. Pain was significantly lower post-DHE 4 and 8 h and 2 and 4 days after treatment than after placebo. The results confirm a close association between demonstrable pelvic congestion and pelvic pain.

Acute Disease↗
PubMed1987

Hypotensive and sedative effects of insulin in autonomic failure.

The haemodynamic responses to intravenous insulin (0.15 units/kg) were measured in five patients with chronic autonomic failure who were not receiving drug treatment. After the administration of insulin supine blood pressure fell steadily, with a substantial reduction even before the onset of hypoglycaemia. None of the patients showed the usual range of neuroglycopenic symptoms, but they all became drowsy, with increasing sedation as the blood glucose concentration fell. In four other patients with autonomic dysfunction intravenous injection of 25-50 ml of 50% glucose alone caused a striking, although transient, fall in blood pressure. Hypoglycaemia was reversed by a 10 minute intravenous infusion of 100 ml of 25% glucose; this did not lower blood pressure further and rapidly restored previous levels of alertness. Consideration must be given to the hypotensive potential of insulin in patients with autonomic failure during an insulin stress test. The inability of these patients to show the usual manifestations of hypoglycaemia, plus the short lived, though pronounced, reduction in blood pressure after intravenous administration of 50% glucose, may further increase the risks of this procedure.

Aged↗
PubMed1987

Radiolabeled hypoxic cell sensitizers: tracers for assessment of ischemia.

Hypoxic, non-functional, but viable, tissue may exist in heart and brain following an arterial occlusion. Identification of such tissue in vivo is crucial to the development of effective treatment strategies. It has been suggested that certain compounds capable of sensitizing hypoxic tumor cells to killing by x-rays (i.e., misonidazole) might serve as in vivo markers of hypoxic tissue in ischemic myocardium or brain if properly radiolabeled. To this end we have radiolabeled two fluorinated analogs of nitroimidazole based hypoxic cell sensitizers with the 110 minute half-lived positron-emitting fluorine-18. The ability of these tracers to quantitate the presence of hypoxic tissue has been studied in a gerbil stroke model. The in vivo uptake of one of these tracers [F-18]-fluoronormethyoxymisonidazole is dependent on the extent of tissue hypoxia, and thus, appears to have potential as a diagnostic indicator of non-functional but viable tissue when the tracer is used in conjunction with positron emission tomography.

Animals↗
PubMed1987

Characterization of the uptake of 16 alpha-([18F]fluoro)-17 beta-estradiol in DMBA-induced mammary tumors.

In order to investigate possible correlations between the uptake of 16 alpha-([18F]fluoro)-17 beta-estradiol (18F-ES) by 7,12-dimethylbenz(a) anthracene (DMBA)-induced tumors in rats and the estrogen receptor (ER) content of these tumors, a comprehensive study was performed in which the tissue distribution of 18F-ES was measured in tumor-bearing rats, together with simultaneous measurements of blood volume (by technetium-labeled red blood cells) and blood flow (by iodoantipyrine infusion). In addition, the time course of 18F-ES metabolism and the tissue distribution of the metabolites was studied. Metabolism of 18F-ES is very rapid, and after 2 h, most of the activity in blood and nontarget tissues is due to metabolites; target tissue activity, however, is due mainly to unmetabolized compound. Most of the circulating activity, both 18F-ES and its metabolites, is strongly associated with macromolecules or cells, and while the metabolites are not taken up selectively by target tissues, they do enter nontarget tissues. Tumor blood volume and blood flow vary widely, but not in a way that appears related to tumor necrosis. The uptake of 18F-ES by the uterus and DMBA-induced mammary tumors of adult rats reaches maximum levels (ca 0.35 and 0.10% I.D./g X kg, respectively) at early times (0-1 h), and drops slowly thereafter. The uterus to nontarget or tumour to nontarget tissue ratios, however, start low and continue to increase, reaching maximum levels (ca 20 and 15, respectively) at 2-3 h. There does not, however, appear to be a simple relationship between tumor uptake (either as % I.D./g X kg or tumor to nontarget ratio) measured at a single 3 h time point and tumor ER content, even considering differences in tumor blood flow. This suggests that an estimation of tumor ER content will require the application of more complex pharmacodynamic models that involve the measurement of the complete profile of receptor lignad uptake, retention, and washout from target to nontarget areas. The application of such models will be assisted by the development of estrogen receptor binding ligands that are not converted to circulating metabolites.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Increased sensitivity of the denervated transplanted human heart to isoprenaline both before and after beta-adrenergic blockade.

It is not known whether surgical denervation leads to increased beta-receptor sensitivity after human cardiac transplantation. We assessed cardiac beta-receptor sensitivity by studying the heart rate response to isoprenaline of the denervated donor heart as compared with the innervated recipient heart in eight patients who underwent heterotopic cardiac transplantation and in six patients with orthotopic transplantation. Changes in the donor and recipient hearts seen in these 14 patients were further compared with those seen in 10 normal volunteers. Incremental intravenous infusion of isoprenaline (5, 10, and 15 ng/kg/min) raised heart rate to a greater extent in the donor compared with the recipient hearts in the eight patients who had heterotopic grafts (slopes [beats/min/ng/kg]: donor = +2.26, recipient = +1.59; p less than .01). In addition, the donor hearts of the transplant patients were more sensitive than hearts of the normal volunteers (slopes: donor = +2.26, normal = +0.94; p less than .01). The changes in the two groups of donor hearts were similar (slopes: orthotopic = +2.24, heterotopic = +2.27; NS). The recipient hearts in the patients with heterotopic transplants were more sensitive than the hearts of the normal volunteers (p less than .05), suggesting that the observed differences in isoprenaline sensitivity in the patients with heterotopic grafts were not caused by a decreased sensitivity of the recipient heart. After beta-blockade, the heart rate responses to isoprenaline were attenuated to the same extent in denervated and innervated hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1987

Neurogenic components of hypertension in human renal artery stenosis.

In renal artery stenosis activation of the renin-angiotensin system elevates blood pressure by direct peripheral effects and probably through stimulation of sympathetic activity, which can be induced by angiotensin-II either centrally or peripherally. In animals specific brain lesions and afferent renal denervation can either attenuate or prevent renovascular hypertension. We investigated the neurogenic mechanisms responsible for hypertension in 21 patients with unilateral renal artery stenosis off drug therapy, by studying the cardiovascular and hormonal effects of Clonidine. The responses to Captopril served as an indicator of the peripheral effects of angiotensin-II. Both oral and intravenous Clonidine lowered blood pressure substantially and for a prolonged period even in patients who had been refractory to multiple antihypertensive drug therapy. Levels of plasma renin activity were unchanged after Clonidine. Plasma noradrenaline levels fell. Pressor responses to infused angiotensin-II were not reduced. These data suggest that Clonidine lowers blood pressure independently of hormonal and peripheral vascular interactions and is consistent with its predominantly central sympatholytic effects. Oral Captopril, unlike Clonidine, had variable hypotensive effects directly related to the basal level of plasma renin activity. The largest reductions were observed in those with the highest level of renin. Our studies indicate that neurogenic mechanisms, probably centrally mediated, have an important and often major role in maintaining hypertension in human renal artery stenosis. These may result from the central effects of angiotensin-II, and/or from increased afferent renal nerve activity, as demonstrated experimentally. The neurogenic components maintaining hypertension in renal artery stenosis are largely dependent on renal ischaemia as revascularisation (by surgery or angioplasty) or nephrectomy, either ameliorates or cures the hypertension in the majority of our patients.

Aortography↗
PubMed1987

Role of the central nervous system in human secondary hypertension.

The central nervous system may initiate or maintain hypertension in humans by a variety of mechanisms. Increased cerebral pressor activity can cause hypertension in some patients with the Guillain-Barré syndrome, where disinhibition of cerebral centres may result from an afferent baroreflex lesion. The brain itself initiates hypertension in patients with cerebral tumours, cerebrovascular accidents, and subarachnoid haemorrhage. The use of drugs (including alcohol), or at times their withdrawal, results in hypertension through neurogenic mechanisms. Impaired cerebral activity also contributes, as in tetraplegic patients in whom paroxysmal hypertension is a consequence of increased spinal sympathetic reflex activity, which is not restrained or appropriately counteracted by the brain because of the cervical spinal cord transection. Neurogenic factors also play a role in the maintenance of hypertension in patients in whom the initiating cause is clearly humoral. In renal artery stenosis for instance, cerebral actions of angiotensin II may later gain ascendance over its peripheral effects, especially as circulating levels fall, as has been demonstrated with the centrally acting sympatholytic agent, clonidine. This is an example of humoroneural coupling that contributes to the hypertension. Increased afferent renal nerve activity may be an additional factor, especially in patients with renal parenchymal disease, where renin appears to play a minor role. The role of the nervous system in other causes of primary hypertension is presently less clear. In phaeochromocytoma noncatecholamine tumour products may have neurogenic effects that could account for the ability of clonidine to lower blood pressure in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1987

Autonomic dysfunction.

The autonomic nervous system is closely involved in the majority of bodily functions. Different disease processes and a variety of drugs can result in autonomic dysfunction, some with minor but others with major consequences. This review considers factors which relate to the recognition, investigation and principles of management of such disorders.

Autonomic Nervous System Diseases↗
PubMed1987

Fluorine-18 labeling of proteins.

Two fluorine-18-labeled reagents, methyl 3-[18F]fluoro-5-nitrobenzimidate and 4-[18F]fluorophenacyl bromide, have been prepared for covalent attachment of fluorine-18 to proteins. Both reagents can be prepared in moderate yields (30-50%, EOB) in synthesis times of 50-70 min. Reaction of these reagents with proteins (human serum albumin, human fibrinogen, and human immunoglobulin A) is pH independent, protein concentration dependent, and takes 5-60 min at mild pH (8.0) and temperature (25-37 degrees C), in yields up to 95% (corrected). The 18F-labeled proteins are purified by size exclusion chromatography.

Fibrinogen↗
PubMed1987

Measurements of pulmonary vascular permeability with PET and gallium-68 transferrin.

We quantified pulmonary vascular permeability with positron emission tomography (PET) and gallium-68-(68Ga) labeled transferrin. Six dogs with oleic acid-induced lung injury confined to the left lower lobe, two normal human volunteers, and two patients with the adult respiratory distress syndrome (ARDS) were evaluated. Lung tissue-activity measurements were obtained from sequential 1-5 min PET scans collected over 60 min, after in vivo labeling of transferrin through intravenous administration of [68Ga]citrate. Blood-activity measurements were measured from simultaneously obtained peripheral blood samples. A forward rate constant describing the movement of transferrin from pulmonary vascular to extravascular compartments, the pulmonary transcapillary escape rate (PTCER), was then calculated from these data using a two-compartment model. In dogs, PTCER was 49 +/- 18 in normal lung tissue and 485 +/- 114 10(-4) min-1 in injured lung. A repeat study in these dogs 4 hr later showed no significant change. Values in the human subjects showed similarly marked differences between normal and abnormal lung tissue. We conclude that PET will be a useful method of evaluating vascular permeability changes after acute lung injury.

Animals↗