Search PubMed⌕ Search

Biomedical subjects

C J Mathias

Publications and source records attributed to C J Mathias.

At least 235 records · Page 13Linked to original sources
PubMed1986

The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure.

Day and night urine volume, morning and evening body weight, and supine and sitting blood pressure were measured in five patients with chronic autonomic failure who were not receiving treatment with drugs. All had nocturnal polyuria, overnight weight loss, and a pronounced postural fall in blood pressure, with lowest levels in the morning. Desmopressin (2-4 micrograms given intramuscularly at 8 pm) reduced nocturnal polyuria, diminished overnight weight loss, raised supine blood pressure, and reduced the postural fall, especially in the morning, when patients were often at their worst. Desmopressin may be a useful alternative to, or may supplement, other forms of treatment in some patients with autonomic failure.

Aged↗
PubMed1986

Detection and investigation of renal artery stenosis.

A retrospective analysis was done on 235 hypertensive patients undergoing renal arteriography. Of the 85 patients with renal artery stenosis 50 underwent 56 operations or angioplasties and have been followed up for at least a year. 41 (73%) of these procedures were curative or led to improved blood-pressure control. These results make it worthwhile identifying hypertensive patients with renal artery stenosis who may benefit from surgery or angioplasty. Vascular disease, epigastric bruit, and impaired renal function were commoner in the renal artery stenosis patients than in the 81 with normal arteriograms, but there were no features pathognomonic of stenosis. Intravenous urography had a sensitivity of 83% and a specificity of 69.5% in identifying renal artery stenosis; those for isotope renography were 90.5% and 38.5%, respectively. Divided renal vein renins did not predict the outcome of intervention. Arteriography should, if there are no contraindications to intervention, be the first and definitive investigation when renal artery stenosis is suspected--for instance, in hypertensive patients with accelerated or malignant hypertension, those whose blood pressure is poorly controlled by multiple therapy, and those who have had recent deterioration in blood-pressure control or renal function.

Adult↗
PubMed1986

Biodistribution of N-alkyl and N-fluoroalkyl derivatives of spiroperidol; radiopharmaceuticals for PET studies of dopamine receptors.

There is great interest in the application of positron labeled ligands to map the dopamine receptor in vivo. A series of fluorine-18-labeled N-alkyl and N-fluoroalkyl spiroperidol (SP) derivatives N-methyl[18F]SP; N-ethyl[18F]SP; N-(2-[18F]fluoroethyl)SP; N-propyl[18F]fluoropropyl) SP; N-(3-fluoropropyl) [18F]SP; N-(2-[18F]fluoropropyl)SP; N-(2-[18F]fluorobutyl)SP; N-(2-[18F]fluoropentyl)SP; and N-(2-[18F]fluorohexyl)SP were synthesized. The lipophilicity of these ligands (log octanol/water partition coefficient) varies from 2.67 to 5.56 and the initial brain uptake in rats, measured at 2 min, was greatest with the methyl, ethyl, propyl, fluoroethyl, and fluoropropyl derivatives. The highest striatum/cerebellum values 1 h after administration were obtained with the N-methyl, N-propyl, and N-3-fluoropropyl derivatives, while that of N-2-fluoroethyl showed the greatest uptake of total activity in the brain at this time. The uptake of all these ligands in the striatum could be blocked by cold SP showing the striatal uptake to be by the dopamine receptors.

Alkylation↗
PubMed1986

Pressor effect of arginine vasopressin in progressive autonomic failure.

The blood pressure (BP) and heart rate (HR) responses to 5 min incremental intravenous infusions of noradrenaline (NA) and arginine vasopressin (AVP) were investigated both in patients with progressive autonomic failure (PAF) and in normal volunteers. Stepwise infusion of NA at rates of 300-3000 pmol min-1 kg-1 produced a bradycardia and a dose related increase in BP in normal subjects. In subjects with PAF there was no significant HR response but the dose-BP response was shifted to the left with significant pressor responses at infusion rates of 60-300 pmol min-1 kg-1. Stepwise infusion of AVP at 0.2-5.0 pmol min-1 kg-1 caused transient bradycardia but no pressor response in seven normal volunteers. Further increases in AVP infusion in three other subjects achieved plasma AVP levels as high as 3000-4000 pmol/l, and still no significant pressor response was observed. Stepwise infusion of AVP at 0.05-2.0 pmol min-1 kg-1 in the eight subjects with PAF resulted in a pressor response without any change in HR. During this infusion plasma AVP increased from 0.8 +/- 0.2 (mean +/- SEM) to 30 +/- 2 pmol/l. A significant pressor response was already apparent at a plasma AVP level of 5.5 +/- 1.8 pmol/l.

Adult↗
PubMed1986

Atrial demand pacing to protect against vagal overactivity in sympathetic autonomic neuropathy.

The clinical features, investigation and management of a patient with a subacute autonomic neuropathy are described. A series of physiological and biochemical studies indicated severe but selective sympathetic cardiovascular dysfunction, associated with bradycardia. The bradycardia was enhanced by raising blood pressure but there was no other evidence either of cardiac vagal impairment or hyperreactivity. Oral atropine prevented the bradycardia but had to be withdrawn because of intolerable side effects. An atrial demand pacemaker was implanted to elevate basal heart rate and prevent bradycardia. The pacemaker alone did not improve postural hypotension but it enabled the blood pressure to be readily and safely controlled by a combination of drugs.

Autonomic Nervous System↗
PubMed1986

Platelet deposition on vascular grafts. The accuracy of in vivo quantitation and the significance of in vivo platelet reactivity.

An in vivo platelet imaging system utilizing indium-111-labeled platelets and technetium-99m-labeled red cells was used to serially study and compare platelet deposition on autologous external jugular vein grafts, autologous arterial grafts, polytetrafluoroethylene (Gore-tex) and two Dacron (Meadox and USCI) small diameter (4mm) vascular grafts implanted end-to-end in canine carotid and femoral arteries. This method of quantitating platelet deposition was validated by correlating deposition measured in vivo with deposition measured directly on explanted grafts (r = 0.94, p less than 0.01). Platelet accumulation on all grafts was greatest immediately after implantation and declined over time. None of the artery or vein grafts thrombosed, and they had the lowest level of platelet deposition at all times. Platelet deposition on Gore-tex grafts was significantly less than on USCI Dacron grafts from 24 hours to 1 month after implantation. There was no statistical difference in 1-month patency among the synthetic graft groups. Synthetic grafts that thrombosed during the first month accumulated significantly more platelets immediately after operation than did those grafts that remained patent. Patent Dacron grafts with low levels of platelet deposition had less thrombotic debris at explantation on the luminal surface than did those grafts with high levels of platelet deposition. Differences in initial platelet deposition appeared to be more a function of platelet reactivity within each dog rather than the material used in graft construction.

Animals↗
PubMed1986

Renal vascular responses to saralasin in conscious chemically denervated rabbits and patients with tetraplegia.

To determine the relative contributions of direct angiotensin-II-like myotropism and sympathetic nerve stimulation to the partial agonist effect of saralasin, the renal vascular responses to i.v. saralasin (5, 10, 20 micrograms/kg/min) were assessed in normal conscious rabbits before and after sympatholytic treatment with guanethidine (24 mg/kg/day for 9 days) and in 6 chronic tetraplegic patients (0.5, 1, 5 micrograms/kg/min) before and after alpha-adrenoreceptor blockade with i.v. thymoxamine (1 mg/kg/h). In rabbits saralasin reduced effective renal plasma flow (ERPF) and glomerular filtration rate (GFR), and increased renal vascular resistance (RVR) without affecting mean arterial blood pressure (BP). Responses were similar in both groups, but recovery following saralasin was more prolonged after treatment with guanethidine. When 0.1 microgram/kg/min (one fiftieth of the smallest i.v. dose) was infused just proximal to the renal arteries in 4 conscious rabbits (chronically cannulated), renal perfusion fell and RVR increased. In tetraplegics saralasin produced a transient rise in BP and variable increase in RVR; neither response being altered by thymoxamine. These results suggest that saralasin-induced renal vasoconstriction is independent of central and peripheral sympathetic activation, and is probably due to an intrinsic angiotensin-II-like myotropic action.

Adult↗
PubMed1985

Evaluation of PLED as a chelating ligand in the preparation of gallium and indium radiopharmaceuticals.

The 68Ga and 111In complexes of PLED (N,N'-dipyridoxylethylenediamine-N,N'-diacetic acid) were prepared and their biodistribution determined as a function of time following i.v. injection into rats. The 68Ga and 111In complexes behaved identically and were rapidly cleared from the blood via the kidneys into the urine. Similar rapid urinary excretion was observed in the gamma images obtained from a stump-tailed macaque injected with 111In-PLED. Paper electrophoresis at pH 7.35 showed a single radioactive peak for 111In-PLED which migrated towards the anode. PLED administered by i.p. injection was found to speed the blood pool clearance of previously administered 67Ga-citrate.

Animals↗
PubMed1985

Effect of haemodialysis on the control of the circulation in patients with chronic renal failure.

The mechanisms of hypotension during haemodialysis were investigated by studying cardiovascular reflexes, body fluid volumes, and osmolality in 11 patients with renal failure before and after haemodialysis and in 17 normal subjects before and after furosemide diuresis. Blood pressure and heart rate responses to tests of autonomic nervous function were unaffected in either group except that in the patients, head-up tilt after haemodialysis caused a fall in blood pressure. This was associated with a greater fall in cardiac output than before haemodialysis but with a similar rise in peripheral vascular resistance. Resting plasma noradrenaline levels were higher than normal, and the rise in plasma noradrenaline levels in response to tilt was unaffected by haemodialysis. Plasma renin activity rose in response to head-up tilt in normal subjects, but not in patients either before or after haemodialysis. Our studies indicate that changes in plasma potassium and osmolality or the possible peripheral circulatory effects of acetate do not impair the regulation of the circulation in response to haemodialysis. Haemodialysis does not reduce plasma noradrenaline levels. Impaired myocardial function in response to fluid depletion or unresponsiveness of the renin-angiotensin system may contribute to haemodialysis hypotension.

Adult↗
PubMed1985

Unmasking of the cardiovascular effects of carbohydrate in subjects with sympathetic denervation.

The cardiovascular, biochemical and hormonal effects of a standard meal and two differing carbohydrates have been studied in normal subjects and in patients with autonomic failure (AF) and impaired cardiovascular reflexes. In the normal subjects blood pressure (BP) was unchanged after a meal and oral glucose. In AF patients, however, there was a marked and prolonged fall in BP after the meal. A similar fall occurred after oral glucose with only a small fall after oral xylose. In normal subjects, the meal and glucose raised plasma noradrenaline levels, unlike in AF patients, in whom noradrenaline and adrenaline levels were unchanged. In normal subjects with intact autonomic reflexes there are minimal cardiovascular effects induced by a meal or glucose. In AF subjects neural mechanisms are impaired, which probably unmasks the primary effects of food ingestion. The ability of glucose, but not xylose, to induce a similar degree of hypotension suggests that insulin may play an important role in postcibal hypotension.

Aged↗
PubMed1985

Naloxone does not affect the cardiovascular, sedative or neurohormonal effects of clonidine in normal and hypertensive man.

The possibility that some of the cardiovascular, sedative or neurohormonal effects of clonidine are mediated by opiate receptors was investigated in normotensive and hypertensive subjects. In normal subjects intravenous (i.v.) clonidine lowered blood pressure, increased sedation and raised levels of plasma renin activity and growth hormone. Levels of other anterior pituitary hormones (prolactin, luteinizing hormone and follicle stimulating hormone) and of arginine vasopressin were unchanged. The effects of clonidine were similar after the administration of naloxone. In patients with essential hypertension clonidine lowered blood pressure, increased sedation and reduced plasma noradrenaline levels. There was an insignificant fall in levels of plasma renin activity. Prior administration of naloxone did not influence the effects of clonidine. It is concluded that the cardiovascular, sedative and neurohormonal effects of acutely administered clonidine are not dependent on opiate receptor activation in either normal or hypertensive man.

Adult↗
PubMed1985

Gallium-68 1,1,1-tris (5-methoxysalicylaldiminomethyl) ethane: a potential tracer for evaluation of regional myocardial blood flow.

Reaction of tris(acetylacetonato)gallium(III) with 1,1,1-tris(5-methoxysalicladiminomethyl)ethane, H3[(5-MeOsal)3 TAME], affords a neutral six-coordinate complex, Ga[5-MeOsal)3 TAME], for which the x-ray crystal structure is reported. The 67Ga and 68Ga complexes of H3[(5-MeOsal)3 TAME] and the bis(salicylaldimine) of triethylenetetramine were prepared and characterized by paper chromatography and electrophoresis. The biodistribution of lipophilic 68Ga[(5-MeOsal)3 TAME] was determined following intravenous injection in rats. Myocardial images obtained by positron emission tomography from three dogs injected with 68Ga[(5-MeOsal)3 TAME] show a correlation between 68Ga uptake and regional myocardial blood flow. Single-pass coronary extraction studies in open-chest dogs indicate that 68Ga[(5-MeOsal)3 TAME] behaves neither as a freely diffusible tracer nor as a microsphere analog.

Animals↗
PubMed1985

Cardiovascular and hormonal effects of clonidine in patients with essential hypertension and renal hypertension.

The putative role of the central nervous system in the maintenance of elevated blood pressure in patients with essential hypertension (EH) and renal hypertension [unilateral renal parenchymal disease (RPD) and unilateral renal artery stenosis (RAS)] was studied by investigating the cardiovascular and hormonal effects of the predominantly centrally acting sympatholytic agent, clonidine. Oral clonidine lowered blood pressure substantially in all three groups. Levels of plasma renin activity were unchanged in EH and RAS but progressively fell in RPD. Plasma noradrenaline levels fell in all three groups. Clonidine therefore reduced blood pressure to the same extent in three distinct groups of hypertensives, in two of which the initiating cause was undoubtedly renal. This indicates that, although the primary cause differed, a prominent factor sustaining hypertension may have been an increase or an inappropriate maintenance of central pressor mechanisms.

Adult↗
PubMed1984

Reduction of platelet deposition on vascular grafts using an antiplatelet graft coating technique.

The systemic use of platelet inhibitors has been shown to improve vascular graft function. In this study a biodegradable coating of polymeric polylactic acid (PLA) containing a microparticulate suspension of aspirin (ASA) 30% by weight, was applied to the lumenal surface of small diameter vascular prostheses to reduce platelet deposition on canine implanted arterial grafts. USCI 4-mm ID Dacron internal velour grafts were used. Coated and contralateral noncoated (control) prostheses were implanted in canine carotid and femoral arteries. Graft performance was assessed by determination of aspirin elution rates, in vivo red cell subtracted 111indium-labeled platelet scans, and post implant platelet aggregation studies. Eighty percent of the aspirin in the coated grafts was released during the first 24 hr of perfusion and approximately 20% of the aspirin remained in grafts after 1 month. In vivo platelet scans documented less platelet deposition on ASA-coated grafts when compared to controls 2 and 24 hr post implant (P less than 0.01, P less than 0.05, respectively). There was no significant difference in platelet deposition on ASA-coated and control grafts at 2 weeks or 1 month post implant. Post implant platelet aggregation studies indicated systemic platelet inhibition for 4-5 days. It was concluded that aspirin incorporation in a polylactic acid coating applied to 4-mm ID vascular prostheses reduced the platelet affinity of Dacron grafts and exerted a temporary local and systemic platelet inhibiting effect.

Animals↗
PubMed1984

Radiolabeling of platelets.

The radiolabeling of platelets has been studied for many years, both with megakaryocytes labeled in vivo and with direct platelet labels in vitro. The major aim of this work has been to evaluate platelet interactions in vivo. This has been made possible with indium-111-labeled platelets. The radionuclide is easily imaged and can be incorporated into platelets with ease. Unfortunately, the lipophilic complex used is not platelet-specific and must be exposed only to the isolated cell population for specific labeling. This requires isolation of platelets from whole blood followed by one of many variations of differential centrifugation, buffer washes, and resuspension techniques that have been reported. The major differences in these techniques are the resuspension media, the incubation time, and the ligand used. These variations are discussed with emphasis on known platelet characteristics and specific responses to these modifications.

Blood Platelets↗
PubMed1984

Scintigraphic detection of coronary artery thrombi in patients with acute myocardial infarction.

To determine whether coronary thrombi can be detected scintigraphically after acute myocardial infarction, 24 patients were studied with a new method employing indium-111-labeled platelets and technetium-99m-labeled red blood cells. Nine patients with suspected infarction were evaluated initially within 9 hours of the onset of symptoms and again 18 to 24 hours after onset. Eight patients with neurologic symptoms but without overt cardiac disease and seven patients with angina but without infarction served as unmatched control subjects. Foci of net indium accumulation were detected after image processing that incorporated subtraction of blood pool activity. Carotid and pulmonary artery reference regions, in which blood pool activity is high and active platelet deposition unlikely, were used to correct digitized cardiac scintigrams for indium-111 platelet activity in the blood pool. In patients with infarction, distinct foci of net indium accumulation were present in regions corresponding to the coronary artery supplying ischemic zones. This occurred in seven of eight patients at the time of the earliest evaluation (5.6 +/- 3.3 hours [mean +/- SD] after the onset of symptoms) and in eight of nine patients at the time of subsequent imaging (23.6 +/- 1.9 hours after onset). Only 1 of the 15 control patients exhibited a cardiac focus of net indium accumulation. The percent of indium excess (100 [total indium-111 activity-blood pool indium-111 activity]/blood pool indium-111 activity) within the cardiac region measured (+/- SD) 16.8 +/- 11.6% in all patients with myocardial infarction (19.1 +/- 11.2% in those with visually identified foci) compared with 0.4 +/- 4.3% in control patients (p less than 0.001). This method permits early detection and sequential assessment of coronary artery thrombi. It should permit improved characterization of the role of platelets in the pathogenesis of acute manifestations of coronary vascular disease and improved evaluation of interventions designed to prevent or lyse coronary thrombi.

Blood Platelets↗
PubMed1984

The immediate pressor response to saralasin in man: evidence against sympathetic activation and for intrinsic angiotensin II-like myotropism.

The cardiovascular and hormonal effects of intravenous saralasin (0.5, 1 and 5 micrograms min-1 kg-1) were assessed in nine tetraplegic patients (with complete cervical spinal cord transaction above the sympathetic outflow) and in six normal subjects. In the tetraplegic patients, saralasin caused an immediate transient pressor response which was not dose-dependent and substantially greater than the pressor response in normal subjects. The pressor response in the tetraplegic patients was not accompanied by a rise in levels of plasma noradrenaline. In the tetraplegic patients, after alpha-adrenoceptor blockade with thymoxamine (1 mg kg-1 h-1), twice the dose of intravenous noradrenaline was needed to induce the same pressor response. The pressor response to saralasin (5 micrograms kg-1 min-1), however, was unaffected by thymoxamine. Saralasin caused minimal changes in levels of plasma renin activity and plasma aldosterone in both groups. There was no relationship between basal plasma renin activity and the pressor response in either group. We therefore conclude that the immediate transient pressor response to saralasin in man is not due to central sympathetic stimulation, is unlikely to be due to peripheral sympathetic activation and is probably the result of intrinsic angiotensin II-like myotropism.

Adult↗