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Biomedical subjects

M R Lee

Publications and source records attributed to M R Lee.

At least 109 records · Page 6Linked to original sources

The effect of carbidopa and indomethacin on the renal response to gamma-L-glutamyl-L-dopa in normal man.

1. The renal response to gamma-L-glutamyl-L-dopa (gludopa, 25 micrograms kg-1 min-1) was investigated in seven normal male volunteers. The effects of oral carbidopa (100 mg) and indomethacin (100 mg) on the response to gludopa were studied in the same group. 2. Gludopa at this dose level produced a 900-fold increase in urine dopamine excretion and caused a natriuresis and suppression of plasma renin activity with only minor effects on pulse rate and blood pressure. 3. Carbidopa inhibited the increase in dopamine excretion by 97% and abolished the renal actions of gludopa. 4. The increase in urine dopamine produced by gludopa was not altered by indomethacin and the urine sodium output was similar to that caused by gludopa alone. 5. Gludopa is an effective renal dopamine prodrug whose activity can be blocked by the dopa decarboxylase inhibitor carbidopa. The results with indomethacin suggest that dopamine and the prostaglandins form separate natriuretic systems in the kidney.

Adult↗

(+)-sulpiride antagonises the renal effects of gamma-L-glutamyl-L-dopa in man.

1. gamma-L-glutamyl-L-dopa (gludopa) was given by intravenous infusion to six healthy salt-replete men on two occasions, with and without pretreatment with (+)-sulpiride. 2. Gludopa increased sodium excretion, glomerular filtration rate and effective renal plasma flow whilst decreasing plasma renin activity. 3. (+)-sulpiride had no significant effect on baseline natriuresis, renal haemodynamics or plasma renin activity, but significantly attenuated the rise in sodium excretion, glomerular filtration rate and effective renal plasma flow produced by gludopa. 4. (+)-sulpiride abolished the acute fall in plasma renin activity seen with gludopa. 5. (+)-sulpiride raised serum prolactin concentration but did not affect the ris in urine dopamine excretion rate caused by gludopa. 6. Gludopa exerts its renal effects by stimulating specific dopamine receptors which are principally of the DA1 subtype.

Adult↗

The effect of lithium on the renal response to the dopamine prodrug gludopa in normal man.

1. The effect of oral lithium on the renal response to gamma-L-glutamyl-L-dopa (gludopa, 25 micrograms kg-1 min-1) was investigated in seven normal males. 2. Gludopa at this dose produced an 800-fold increase in urine dopamine excretion. It was natriuretic and suppressed plasma renin activity without altering blood pressure and pulse. 3. Lithium alone increased sodium excretion and stimulated plasma renin activity. However, it abolished the natriuresis produced by gludopa. 4. Gludopa did not significantly affect lithium clearance. 5. This study suggests that lithium interacts with dopamine at the proximal tubule and that the lithium clearance method is not suitable for investigating dopaminergic mechanisms in the kidney.

Adult↗

Effect of anaerobic digestion on oocysts of the protozoan Eimeria tenella.

The effect of anaerobic digestion of poultry waste on oocysts of the protozoan Eimeria tenella, a common enteric pathogen that causes coccidiosis in poultry, was investigated in this study. Thermophilic (50 degrees C) and mesophilic (35 degrees C) anaerobic digestors, with poultry manure as the substrate, were inoculated with the oocysts. The oocysts were damaged during anaerobic digestion, as determined by morphological change and loss of their ability to sporulate. The recovered oocysts were tested for their infectivity in young chicks, as measured by body weight gain, mortality, and cecal lesions. Oocysts lost all their infectivity during thermophilic digestion, while oocysts subjected to mesophilic digestion remained moderately infective in comparison with untreated oocysts, which produced severe coccidiosis, high mortality, and low body weight gain in chicks. Oocysts were inactivated at 50 degrees C when they were suspended in digestor fluid or saline. Inactivation at 35 degrees C was significantly stronger in the digestor fluid than in the saline, which implied that factors other than temperature were involved in the lethal effect of anaerobic digestion on protozoan oocysts. In this study we demonstrated that the treatment of animal waste by anaerobic digestion, especially at a thermophilic temperature, has the benefits of pathogen control and protection of human and animal health in a farm environment.

Anaerobiosis↗

Beware beta-adrenergic blockers in patients with severe urticaria!

The risks of beta-blockers in asthmatics are well known. However, there are increasing reports of severe, and often refractory, anaphylaxis in patients taking beta-blockers who experience other allergic phenomena. We describe the case of a 69-year-old lady with long-standing recurrent angio-oedema and giant urticaria who was placed on atenolol. Mechanisms whereby beta-blockers may precipitate or exacerbate anaphylaxis are outlined and the treatment of patients with anaphylaxis, taking beta-blockers, is discussed.

Aged↗

Functional interaction and partial homology between human immunodeficiency virus and neuroleukin.

Dementia is common in patients with AIDS, but the mechanism by which the human immunodeficiency virus type 1 (HIV-1) causes the neurological impairment is unknown. In this study the possibility that an antigen of HIV-1 suppresses neuronal responses to neurotrophic factors was examined. Both HIV-1 and a related retrovirus, simian immunodeficiency virus (SIV), inhibited the growth of sensory neurons from chick dorsal root ganglia in medium containing neuroleukin (NLK) but not in medium containing nerve growth factor. An unrelated type D retrovirus, simian acquired immunodeficiency syndrome virus, did not affect the growth of neurons in the presence of either neurotrophic factor. The inhibition by HIV-1 of neuron growth in the presence of NLK was found to be due to the gp120 envelope glycoprotein. Regions of sequence homology between gp120 and NLK may account for this inhibitory property of gp120 and functional interactions between gp120 and NLK may be important in the pathogenesis of the AIDS dementia complex.

Acquired Immunodeficiency Syndrome↗

The effect of intravenous frusemide on urine dopamine in normal volunteers: studies with indomethacin and carbidopa.

1. The urine dopamine response to intravenous frusemide (30 mg) was investigated in 15 salt replete male volunteers. The effects of oral indomethacin (100 mg) and oral carbidopa (100 mg) given before intravenous frusemide were studied in the same group of subjects. 2. Frusemide produced a significant increase in urine dopamine output within 15 min. 3. Indomethacin attenuated the natriuretic and renin responses to frusemide, but did not alter urine dopamine output. 4. Carbidopa lowered urine dopamine to undetectable levels, but did not significantly affect the natriuretic and renin responses to frusemide. 5. We conclude that urine dopamine excretion after frusemide is not directly related to increased sodium excretion or renin response and it is not mediated by the prostaglandins. In addition, dopamine does not contribute to the renal actions of frusemide under normal conditions.

Administration, Oral↗

Methaemoglobinaemia produced by phenazopyridine (Pyridium) in a man with chronic obstructive airways disease.

Life threatening methaemoglobinaemia developed after prolonged therapeutic use of phenazopyridine (Pyridium) in a patient with chronic obstructive airways disease. The combination of chronic obstructive airways disease and oxidant drugs (methaemoglobinaemia) may be lethal. The use of phenazopyridine should be abandoned. Certainly there is no indication to use it for more than a few days in any patient.

Aged↗

Dopamine, the kidney and essential hypertension studies with gludopa.

The formation and action of intrarenal dopamine is reviewed, as also is the evidence for the use of gamma-L-glutamyl-L-dopa as a relatively renally specific dopaminergic pro-drug. 'Salt sensitive' patients with essential hypertension may have a fault in the renal mobilisation of dopamine by sodium chloride. This failure of sodium to dopamine coupling may be particularly prevalent in the Negro race.

Dihydroxyphenylalanine↗

Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons.

A novel 56,000-dalton growth factor found in mouse salivary gland was purified, molecularly cloned, and expressed in monkey COS cells. The protein is a neurotrophic factor and also, surprisingly, a lymphokine product of lectin-stimulated T cells. The factor was therefore named neuroleukin. Neuroleukin promotes the survival in culture of a subpopulation of embryonic spinal neurons that probably includes skeletal motor neurons. Neuroleukin also supports the survival of cultured sensory neurons that are insensitive to nerve growth factor, but has no effect on sympathetic or parasympathetic neurons. The amino acid sequence of neuroleukin is partly homologous to a highly conserved region of the external envelope protein of HTLV-III/LAV, the retrovirus that causes acquired immune deficiency syndrome.

Amino Acid Sequence↗

Studies with fenoldopam, a dopamine receptor DA1 agonist, in essential hypertension.

A series of studies were undertaken to assess the effect of oral fenoldopam, a specific DA1 dopamine receptor agonist on blood pressure and renal function in patients with mild essential hypertension. Six patients with essential hypertension were entered into a dose-ranging study and received either placebo, 25, 50 or 100 mg fenoldopam. A significant, dose-related reduction in diastolic blood pressure, and increase in heart rate was demonstrated (both P less than 0.05), maximal at 45 min to 1 h. Fenoldopam increased plasma renin activity. In a double-blind study, seven patients received a single dose of fenoldopam 100 mg or placebo. Fenoldopam produced a significant fall in systolic (P less than 0.05) and diastolic (P less than 0.01) blood pressure and renal vascular resistance (P less than 0.01). Urine flow rate (P less than 0.05), sodium excretion (P less than 0.01), plasma renin activity (P less than 0.05) and plasma aldosterone (P less than 0.05) increased. Five patients underwent measurement of the above parameters following a single dose of fenoldopam 100 mg with a repeat of these measurements after they had taken fenoldopam 100 mg four times daily for 1 month. The acute response of blood pressure to the single dose appeared unchanged but tachyphylaxis was evident in the responses of heart rate, plasma renin activity and plasma aldosterone.

Adult↗

Domperidone treatment in man inhibits the fall in plasma renin activity induced by intravenous gamma-L-glutamyl-L-dopa.

The dopamine pro-drug gamma-L-glutamyl-L-dopa (gludopa) was administered intravenously to six normal subjects at a dose of 12.5 micrograms min-1 kg-1, either with or without the dopamine antagonist domperidone. A control was provided by the intravenous infusion of domperidone and saline on a separate occasion. Intravenous gludopa produced a significant natriuresis, whether administered alone or in combination with domperidone. After gludopa infusion, there was a significant fall in plasma renin activity, an effect which was attenuated significantly by concomitant treatment with domperidone. These observations suggest that blockade of renal DA2 dopamine receptors has little or no effect on gludopa-induced natriuresis, but that at least part of the dopaminergic inhibition of renin release is mediated by renal DA2 receptors.

Adult↗

Urine dopamine in starving obese subjects.

In seven obese female subjects undergoing a period of therapeutic starvation, the excretion of sodium, potassium and dopamine and plasma levels of renin and aldosterone were measured. Sodium excretion increased during starvation and was maximal on the 2nd day. The urinary excretion of dopamine was significantly higher on day 4 and it remained elevated till the end of the study. Plasma renin activity and plasma aldosterone levels were also higher on the 4th-6th days of starvation. These findings suggest that dopamine may not play a significant role in the natriuresis of starvation.

Adult↗

The acute effects of pergolide in cyclical oedema.

The acute effects of a single 10 micrograms dose of a new dopamine agonist, pergolide, were investigated in 6 healthy women and 6 women with cyclical oedema. There was a prompt and significant reduction in mean plasma prolactin concentrations with maximum suppression occurring at 4 hours in both groups. However, the prolactin suppression was significantly less in the women with cyclical oedema. This is further evidence for a prolactin disturbance in cyclical oedema, and consistent with the proposal that reduced dopaminergic tone may be an important abnormality in the disorder.

Adult↗