Search PubMed⌕ Search

Biomedical subjects

M R Lee

Publications and source records attributed to M R Lee.

At least 127 records · Page 7Linked to original sources
PubMed1985

gamma-L-Glutamyl-L-dopa is a dopamine pro-drug, relatively specific for the kidney in normal subjects.

gamma-L-Glutamyl-L-dopa was given by intravenous infusion to eight normal subjects at doses of 12.5 and 100 micrograms min-1 kg-1. Both doses of the dipeptide resulted in an increase in mean urinary sodium excretion. Mean effective renal plasma flow rose at both doses, but mean glomerular filtration rate increased only at the lower dose. There was a fall in mean plasma renin activity after the infusion of both 12.5 and 100 micrograms min-1 kg-1. Mean urine free dopamine excretion increased by 280- and 2500-fold at infusion rates of 12.5 and 100 micrograms min-1 kg-1 respectively. Mean plasma free dopamine rose at both doses but the increase at 12.5 micrograms min-1 kg-1 was not to a level previously associated with systemic effects of the catecholamine. On administration of the dipeptide at 12.5 micrograms min-1 kg-1 there were no changes in blood pressure or heart rate, but at the higher dose there was a fall in diastolic blood pressure. At a dose of 12.5 micrograms min-1 kg-1 in man, there is kidney specific conversion of gludopa to dopamine.

Adult↗
PubMed1985

The effect of oral fenoldopam (SKF 82526-J), a peripheral dopamine receptor agonist, on blood pressure and renal function in normal man.

The effect of a single oral dose of 100 mg of fenoldopam on renal function and blood pressure was investigated in seven healthy male subjects in a double-blind placebo controlled study. Mean diastolic blood pressure fell by 10 mm Hg, 45 min after oral dosing and then gradually returned to baseline values. There was an increase in pulse rate and a delayed rise in systolic blood pressure. Measured from 30 to 120 min after drug ingestion, mean effective renal plasma flow increased to 158% of the value observed after placebo; mean glomerular filtration rate rose to 109% of the placebo value. Measured from 120 to 210 min after administration of the drug, effective renal plasma flow and glomerular filtration rate had returned to baseline values. Fenoldopam produced a small increase in the mean sodium excretion rate which was not significantly different from the fall after placebo. No change was detected in urine flow or potassium excretion rate. Mean plasma renin activity increased three-fold 1 h after oral dosing. Plasma aldosterone did not show a parallel increase although the plasma concentration at 1 h was significantly higher than after placebo. The results show a pronounced renal vasodilator effect lasting about 2 h. The findings are consistent with marked DA1 receptor agonist activity.

Administration, Oral↗
PubMed1985

Patients with essential hypertension have an exaggerated natriuretic response to the dopamine pro-drug glutamyl-dopa.

The relatively kidney-specific dopamine pro-drug, gamma-L-glutamyl-L-dopa (gludopa) was administered to eight normal subjects and eight patients with essential hypertension, control studies being provided by the infusion of saline on a separate occasion. There was a more marked natriuresis in the hypertensives than in the normal subjects, even though, in contrast to the normals, the hypertensives showed no significant change in effective renal plasma flow (ERPF) or glomerular filtration rate (GFR). A significant fall in plasma renin activity (PRA) occurred in both groups. These observations suggest that a part of the dopamine-induced natriuresis is due to stimulation of tubular receptors, and that there is up-regulation of these receptors in essential hypertension.

Adult↗
PubMed1985

Failure of superoxide dismutase to alter equine arachidonic acid-induced platelet aggregation, in vitro or ex vivo.

Superoxide dismutase (SOD), a free radical scavenger with anti-inflammatory activity, was administered IM to horses. Ex vivo platelet aggregation in response to arachidonic acid was monitored to determine whether exogenous SOD altered equine platelet prostaglandin metabolism. Preparations of platelet-rich plasma obtained before SOD administration were incubated with different concentrations of SOD and were aggregated with arachidonic acid. Superoxide dismutase did not exert a demonstrable effect, either ex vivo or in vitro. Aspirin abolished arachidonic acid-induced platelet aggregation in vitro. This indicates that SOD (in the resting state) does not exert an effect on platelet-derived free radicals that could alter the arachidonic acid pathway of equine platelets, that equine platelets do not release free radicals, or that equine platelets are insensitive to the products formed from free radicals by SOD.

Animals↗
PubMed1984

A paradoxical fall in urine dopamine output when patients with essential hypertension are given added dietary salt.

The effect of dietary sodium on the urine dopamine excretion of eight hypertensive patients and six matched controls was studied under metabolic balance conditions over a 2 week period during which dietary sodium intake was increased from 20 to 220 mmol/day. The control group showed the expected increase in dopamine excretion in response to sodium but the hypertensive patients showed an initial fall followed by a return to baseline values. Neither group showed a rise in blood pressure but the hypertensive patients showed a greater weight gain on salt loading, although this change was not significant. The cumulative sodium balance was greater and more prolonged in the hypertensive patients, although this difference also did not attain statistical significance. This defect in dopamine mobilization may be important in relation to renal sodium handling by patients with essential hypertension.

Adult↗
PubMed1984

Lack of effect of ibopamine, a dopamine pro-drug, on renal function in normal subjects.

The effects of two single oral doses of ibopamine (150 and 600 mg) on heart rate, blood pressure, urine flow, sodium, potassium and creatinine excretion were studied in normal volunteers. No significant change was observed in urine flow, sodium, potassium or creatinine excretion at either dose. No significant change was observed in heart rate or blood pressure except that systolic blood pressure was transiently elevated after the 600 mg dose (P less than 0.05).

Adult↗
PubMed1984

Recurrence of asthma following removal of a noradrenaline-secreting phaeochromocytoma.

A patient with asthma and a phaeochromocytoma is described. At about the time she was first noted to be hypertensive her asthma resolved spontaneously but bronchospasm returned with some severity when the tumour was removed. The phaeochromocytoma was of the noradrenaline secreting variety. Possible mechanisms through which this catecholamine might have produced the observed alleviation of asthma are considered.

Adrenal Gland Neoplasms↗
PubMed1984

The spatial control of ganglionic neurite growth by the substrate-associated material from conditioned medium: an experimental model of haptotaxis.

Techniques are described for forming on the culture substrate a narrow pathway of material derived from medium conditioned by embryonic non-neuronal cells. There is a precise correlation between the known location of the pathway and the spatial distribution of neurites extended from whole ciliary ganglia or dissociated neurons grown on the patterned substrate. When individual growth cones moving on the pathway contact one of its edges, they turn sharply so as to remain on the pathway. This turning response is not simply due to a physical barrier to movement across the edge, since growth cones can cross onto the pathway when entering from the adjacent untreated substrate. The strong preference for neurites to maintain contact with the pathway also is not simply a result of their inability to survive or elongate outside of the pathway, since neurites from whole ganglia elongate readily on other regions of the substrate, although their growth is then undirected. Direct contact with the pathway is required for these directive effects, and there is no indication that the material bound to the substrate diffuses off and exerts its effects at a distance. The neurite-guiding activity is found in partially purified fractions of conditioned medium which also contain a substrate-bound inducer of neurite outgrowth. It is possible that both activities may be due to the same components of conditioned medium. These results suggest that ciliary ganglion growth cones are able to detect specific components of conditioned medium on the substrate and respond to their presence by changing their direction of movement so as to remain in contact with these components.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Evidence for a hypothalamic disturbance in cyclical oedema.

Fourteen women with cyclical oedema and six healthy female controls were investigated by use of a test in which thyrotrophin releasing hormone and luteinising hormone releasing hormone were given. Significant differences in the responses of prolactin, luteinising hormone, and follicle stimulating hormone were observed in the patients. These findings suggest that there may be a hitherto unrecognised hypothalamic defect in cyclical oedema that may account for some of the previously unexplained clinical features and lead to a more rational therapeutic approach in the management of the disorder.

Adult↗
PubMed1983

Failure of renal dopamine response to salt loading in chronic renal disease.

Eight patients with chronic glomerulonephritis and five age-matched normal volunteers were given additional sodium chloride by mouth under conditions of metabolic balance. Whereas in the normal volunteers plasma renin activity was suppressed and urinary excretion of free dopamine increased, in the patients dopamine was not mobilised and plasma renin activity was not completely suppressed. Abnormal retention of sodium and water in glomerulonephritis may be due partly to a failure to mobilise dopamine in the kidney. Specific renal dopamine agonists may be natriuretic and hypotensive in chronic glomerulonephritis.

Adult↗
PubMed1983

The protective effect of gamma-glutamyl L-dopa on the glycerol treated rat model of acute renal failure.

gamma-Glutamyl L-dopa, a renal pro-drug for dopamine, was administered to rats before and after injection of glycerol, and to a control group which received water in place of glycerol. A third group of rats was given glycerol but no gamma-glutamyl L-dopa. The plasma creatinine in rats given gamma-glutamyl L-dopa and glycerol was significantly lower than in rats receiving glycerol alone. The fall in urine creatinine excretion, and polyuria, after glycerol was reduced by gamma-glutamyl L-dopa and the natriuresis abolished. gamma-Glutamyl L-dopa given alone caused a 4000-fold increase in urine dopamine excretion, associated with a natriuresis. The administration of gamma-glutamyl L-dopa reduces the severity of renal failure produced by glycerol.

Acute Kidney Injury↗
PubMed1983

Urine dopamine during normotensive and hypertensive pregnancies and the puerperium.

Urinary excretion of dopamine, sodium and creatinine have been studied during pregnancy and the puerperium in three groups of women, normotensive, pre-eclamptic and those exhibiting gestational hypertension. Differences in the pattern of dopamine and salt excretion are evident in the two hypertensive groups and lend support to the concept that women who develop gestational hypertension have a defect in the mobilisation of dopamine similar to that observed in males with essential hypertension.

Adolescent↗
PubMed1983

Classification of human senile cataractous changes by the American Cooperative Cataract Research Group (CCRG) method. I. Instrumentation and technique.

The American Cooperative Cataract Research Group (CCRG) has adopted a system of classifying human cataractous changes that is based on separate and independent photographic documentation of opacification and nuclear color. This system has been extremely useful to the laboratory scientist who wishes to know the significance of associations between laboratory data and the extent or type of cataractous change. It has been applied to the analysis of nearly 2500 cataracts since 1976. This study presents the details of the instrumentation and technique of this new system and the results of classifying 2231 intracapsularly-extracted cataracts.

Aged↗
PubMed1983

Dopamine excretion during natriuresis of starvation.

Five obese subjects were studied when they were on a 3.35 MJ (800 kcal)-diet, 1.67 MJ (400 kcal) diet and during total starvation. Urine excretion of sodium and dopamine and plasma renin activity (PRA) and plasma aldosterone levels were measured. Urine sodium excretion increased from 88 +/- 9.8 mmol/d before starvation to 150 +/- 15.7 mmol/d on day 4 of starvation. Dopamine excretion increased from 0.92 +/- 0.23 mumol/d before starvation to 1.56 +/- 0.24 mumol/d on day 1 of starvation (P less than 0.01). These results suggest that dopamine excretion is increased in early starvation and may play a role in the natriuresis of starvation.

Adult↗
PubMed1982

Dopamine and the kidney.

It would seem established beyond peradventure that dopamine is formed in the kidney from circulating L-dopa. The likely site would appear to be the renal tubular cells but the contribution of the renal dopaminergic nerves needs further evaluation. Moreover it is probably that dopamine formed within the kidney acts there on specific receptors. This results in vasodilatation of renal blood vessels, by action on vascular receptors, and natriuresis, by an effect on tubular sodium transport mechanisms. Dopamine may form an integral part of the renal natriuretic cascade by, in its turn, evoking both the kallikrein-bradykinin system and the production of renal prostaglandins. Specific activation of the renal dopaminergic system by the administration of suitable agonists or renal prodrugs may prove possible in the future. Abnormalities in the renal production of dopamine may be important in several hypertensive and oedematous disorders. Further work will be required to establish a possible role for dopamine in these conditions and to determine whether they will benefit from treatment with suitable dopamine agonists. Dopamine, once regarded as of little importance outside the central nervous system, has certainly come to occupy a central place in renal salt handling. The ratio of dopamine production in the kidney to that for renin may be of pivotal importance in the control of systemic arterial pressure.

Animals↗
PubMed1982

Urine dopamine in normal and hypertensive pregnancies.

Dopamine output in urine was determined in two groups of women with hypertension in pregnancy. A highly significant elevation of urine dopamine was detected in those women with pre-eclampsia compared with that in matched control subjects. In contrast, no difference in urine dopamine output was detected between a group of multigravidae with hypertension in pregnancy and matched control subjects.

Adolescent↗