Search PubMed⌕ Search

Biomedical subjects

C W Owens

Publications and source records attributed to C W Owens.

At least 19 recordsLinked to original sources
PubMed1997

Pharmacology and clinical use of moxonidine, a new centrally acting sympatholytic antihypertensive agent.

Moxonidine is a centrally acting antihypertensive. Its action is mediated by imidazoline I1 receptors located in the rostral ventro-lateral medulla (RVLM). Animal experiments show much smaller amounts are required to reduce blood pressure (BP) when it is given intracisternally, or injected directly into the RVLM, compared to intravenous dose. The antihypertensive action of microinjection of moxonidine into the RVLM in the spontaneously hypertensive rat (SHR) is abolished by pretreatment with imidazoline I1 blockade from efaroxan, but alpha(2) blockade from SKF 86466 has much less effect. Similarly the fall of BP in the SHR from intravenous moxonidine is reversed by the microinjection of efaroxan into the RVLM. Receptor binding studies demonstrate that moxonidine binds with an affinity for the imidazoline I1 receptor that is thirty-three times more effective than is alpha(2) receptor binding, while for clonidine the difference is only four times. Moxonidine reduces adrenaline, noradrenaline and renin levels in man, a finding consistent with central inhibition of sympathetic tone. Acute haemodynamic studies indicate that moxonidine results in a fall of BP due to a decline in systemic vascular resistance, while the heart rate, cardiac output, stroke volume and pulmonary artery pressures are not affected. Left ventricular end systolic and diastolic volumes are reduced. Left ventricular hypertrophy has been found to regress after 6 months treatment with moxonidine. After oral administration Tmax is about 1 h, bioavailability approaches 90%. Moxonidine is mostly excreted unchanged, biotransformation is unimportant. The T1/2 is 2.5 h, which is prolonged by renal insufficiency. However, suggesting possible retention in the central nervous system (CNS), the antihypertensive effect lasts longer than would be expected from the half-life, as moxonidine is suitable for once daily administration. Moxonidine is an effective antihypertensive agent. It has been compared with representatives from each important class of antihypertensive drugs, with clonidine, diuretics, both alpha- and beta-blocking drugs, calcium antagonists and ACE inhibitors. BP control has been similar with moxonidine and these other agents. The side effect profile of moxonidine is favourable, its lack of effect on central alpha(2) receptors is important in this regard.

Animals↗
PubMed1993

Malignant phaeochromocytoma and hypercalcaemia.

We describe a case of hypercalcaemia secondary to recurrent malignant phaeochromocytoma. Parathyroid-related protein (PTHrp 1-86) immunoreactivity was identified in plasma and PTHrp was identified by immunocytochemistry in tumour tissue.

Adrenal Gland Neoplasms↗
PubMed1992

Adverse reactions to diuretics.

Diuretics can result in various undesired biochemical changes, such as impotence, skin rashes, nausea, dizziness and lethargy as well as subjective side effects. The side effects are mostly predictable, their effects depending on both the circulatory blood volume and on the transport of water and solute in the renal tubules. Two of the commonest side effects are mild hypovolaemia, when any diuretic is used, and mild hypokalaemia when the non-potassium-sparing diuretics, such as thiazides and frusemide are used. Its occurrence is dose dependent and can be corrected by potassium supplements, but potassium-retaining diuretics, which also correct the often associated fall in serum magnesium, are preferable. Many reports link hypokalaemia with cardiac arrhythmias, but some dispute this association in the absence of the concomitant use of digoxin. Hyponatraemia rarely occurs, but can be life threatening. Calcium excretion is markedly reduced, but unlike other electrolyte disturbances from diuretics, this may be valuable: some suggest diuretics have an anti-osteoporotic action. Diuretics increase glucose and insulin resistance and should be used sparingly in diabetics. They rarely cause a non-ketotic hyperosmolar coma. Urate is raised, but clinical gout is not common. Cholesterol elevation has been reported in some studies, but long-term studies indicate that lipid changes are minor. Other rare side effects are not predictable from their pharmacological actions and these include the occurrence of skin rashes, thrombocytopenia, pancreatitis and interstitial nephritis; and ototoxicity from frusemide.

Blood Volume↗
PubMed1991

Heart and catecholamines.

Catecholamines mediate their effects in the heart through beta 1- and beta 2-receptors. Beta 1-receptors mediate the effects of sympathetic nerve stimulation. Alpha-receptors may have a role but, unlike the beta-receptor mediated responses, act without producing any increase in cyclic AMP. Prolonged receptor stimulation results in a reduction in beta-receptor sensitivity. In contrast blockade with a non-agonist agent is associated with an increase in catecholamine sensitivity which may be responsible for the withdrawal reactions that can occur when beta-blocking drugs are rapidly withdrawn in patients with ischaemic heart disease. Experimentally, prolonged noradrenaline infusions result in ventricular hypertrophy. Catecholamines have been implicated in several pathologies. High and rising catecholamine levels are associated with worsening of prognosis in patients with heart failure. These patients show a decreased beta-receptor number and cellular concentration of catecholamines. On the other hand cardiomyopathy is associated with an increased sensitivity to catecholamines. Catecholamines aggravate cardiac damage in ischaemia. Excessively high catecholamine loads cause myocardial damage in otherwise normal hearts, for example in patients with a phaeochromocytoma and those with various forms of cerebral damage such as subarachnoid haemorrhage, cerebrovascular accidents, and head injury.

Adrenergic beta-Antagonists↗
PubMed1990

Mode of action of beta-adrenergic blocking drugs in hypertension.

Although they have been in use for over 20 years, the antihypertensive mode of action of beta-blocking drugs remains a matter for debate. Blood pressure falls with beta-blockers that have beta 1-selectivity, intrinsic sympathomimetic activity and membrane activity, but not those with a high level of pure beta-stimulation. Several suggestions have been made to explain this effect; a direct action on the central nervous system, adrenergic neurone blocking, perhaps via pre-synaptic beta 2-receptors, anti-renin activity, an increase of vasodilator prostaglandins, effects secondary to reduced cardiac output, and resetting of baroreceptors secondary to reduced pressor peaks to various pressor stimuli from the reduction in cardiac activity consequent to beta-blockade. There are also beta-blocking drugs which additionally have direct action to reduce peripheral resistance, via beta 2-mediated vasodilation, an alpha-blocking action or a direct vasodilator activity. Most attention has been given to a possible correlation to the effect of beta-adrenoceptor blocking drugs on the blood pressure and renin levels. Several investigations have found patients with high renin levels respond best, normal renin patients respond less well and low renin patients relatively poorly. However, others have not found a clear relationship.

Adrenergic beta-Antagonists↗
PubMed1989

A log-dose-response study of xipamide and its effect on metabolic parameters.

An extended dose-response study with xipamide, using seven doublings of the dose, from 0.3125 to 40 mg/day at 4-week intervals, was carried out in 12 hypertensive patients. Blood pressure showed a progressive decline with doses from 5 to 20 mg, and 40 mg xipamide produced no greater fall. Some subjects showed a maximum fall in blood pressure with a single dose increase but most showed a declining blood pressure over two or more dose increases. Plasma urea increased with doses of 5-40 mg to a similar extent, but there was no fall in the mean potassium level except with the 40-mg dose. Urinary calcium was reduced (from 4.2 to 1.7 mmol/24 h) on the 40-mg dose and the corrected plasma calcium level rose from 2.28 to 2.32 mmol/l. Triglycerides, very-low-density lipoprotein cholesterol and plasma aldosterone increased at the maximum dose; the cholesterol ratio, however, was unchanged.

Blood Pressure↗
PubMed1987

Measurement of fingertip blood flow using thermal clearance reflects anastomotic rather than nutrient blood flow.

A thermal clearance probe was used to measure fingertip blood flow. When flow was occluded the baseline value was reproducible (coefficient of variation 2% between subjects), whereas basal and maximum flow were poorly reproducible even within subjects. Synchronous changes in thermal clearance were seen when two probes were used on fingers and toes of different limbs (r = 0.77 - 0.97), in keeping with a central control mechanism. Fingertip blood flow, as measured by thermal clearance, correlated with Po2 of venous blood draining from the dorsum of the hand (r = 0.72 - 0.92). Contralateral hand cooling caused a sharp reduction of fingertip thermal clearance by 44.2 +/- 3.7%. Thermal clearance traces were damped in fingers with heavy keratinization, and improved when keratin was removed. Comparisons with venous occlusion plethysmography (VOP) and photoelectric plethysmography (PPG) showed that thermal clearance correlates with both methods (r = 0.60 - 0.92 for VOP and 0.64 - 0.93 for PPG) but with much integration of the signal and a 10 s lag. It is concluded that the probes used measure predominantly anastomotic flow and not nutrient skin blood flow alone.

Arteriovenous Anastomosis↗
PubMed1982

The longer term efficacy of vasodilators in heart failure.

Studies among a total of about 300 patients with congestive heart failure treated over eight to ten months reveal a distinct and sustained benefit from vasodilator therapy. Increased longevity has not yet been established, but in most circumstances there has been noticeable symptomatic, radiological, and hemodynamic improvement. Unresolved problems continue to center around variability in response, difficulties in objective assessment (invasive and noninvasive) before and during therapy, and selection criteria for patients and drugs. Lesser problems include the construction of effective dosage schedules, deleterious effects after sudden withdrawal, development of tolerance, and side effects.

Arteries↗
PubMed1981

A severe 'stasis eczema', associated with low plasma zinc, treated successfully with oral zinc.

We describe a case of non-ulcerating severe stasis eczema in an elderly female associated with a low plasma zinc and which responded to treatment with oral supplements. The dermatological changes were not accompanied by oedema and were most marked over the lower legs and ankles, with patchy erythematous lesions extending to the inner thighs, over the dorsal surface of both hands and the forearms. There was some excoriation and a degree of lichenification. These lesions were intensely pruritic and resolved almost completely following treatment with oral zinc sulphate (220 mg daily) on two separate occasions.. Histological appearances of biopsy material included those of stasis eczema but there was also a marked degree of parakeratosis. The cause of the low plasma zinc was not identified.

Aged↗
PubMed1981

Obstructive sodium-losing nephropathy--a case report and review.

The third case in the literature of sodium-losing renal disease due to obstruction is presented. The experimental evidence and limited clinical experience is reviewed which suggests that the sodium loss is due to an inappropriate response in the adaptive processes that are initiated by the loss of functioning nephrons. The immediate treatment is by replacement of sodium but in the long term the condition may be reversed by very cautious reduction in sodium intake. Definitive treatment may be indicated where obstruction is the cause and consequently this should be sought in all cases of salt-losing renal disease.

Bicarbonates↗
PubMed1980

Agranulocytosis associated with carbamazepine, and a positive reaction with anti-lymphoid leukaemia antiserum during recovery.

Carbamazepine is a valuable drug in the treatment of trigeminal neuralgia and temporal lobe epilepsy. Rarely agranulocytosis has been described associated with its use but in this further non-fatal case a new finding of a positive reaction with anti-lymphoid leukaemia anti-serum was seen during the recovery phase. A brief review of 18 cases in the literature is provided and it is noted that 94% of reported cases are over the age of 45 years. The significance of the haematological finding is discussed.

Agranulocytosis↗
PubMed1980

Nitrogen estimation in biological samples by use of chemiluminescence.

We describe an apparatus modified for the chemiluminescent estimation of nitrogen in biological and clinical samples. Analytical characteristics have been assessed and results compared with those by the traditional Kjeldahl method. The chemiluminescence method, much faster and more sensitive than the traditional method, is at least as accurate, precise, and reproducible. Costs are low, and the method should find a place in laboratories needing, for example, rapid assessments of nitrogen balance in surgical patients and renal function in patients with renal failure, or estimations of small amounts of specific nitrogen-containing chemical substances in biological samples.

Animals↗