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Biomedical subjects

R F Jeffrey

Publications and source records attributed to R F Jeffrey.

26 records · Page 2Linked 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↗

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↗

Transient lupus anticoagulant and fansidar therapy.

A case of the Stevens-Johnson syndrome following Fansidar therapy is reported in which a marked feature was the presence of a circulating anticoagulant of the lupus inhibitor type. Treatment with steroids resulted in complete recovery and disappearance of the anticoagulant.

Adult↗

Renal disease associated with antineutrophil cytoplasmic antibody: 39 patients over a 5-year period.

We have reviewed 39 adult patients who presented over a 5-year period with biopsy confirmed renal disease in association with positive antineutrophil cytoplasmic antibody (18 with C-ANCA, 21 with P-ANCA). Twenty-three (59%) had primary systemic vasculitis, typically with aggressive renal histology including focal necrotising and crescentic glomerulonephritis. In the remaining patients a wide range of clinical syndromes and renal histological appearances were apparent: 30 had abnormal renal function (serum creatinine > 140 mumol/l), including 17 who were initially dialysis-dependent. Intensive immunosuppression was administered in 33 cases. When response was assessed at 3 months, renal function was stable or improved in 17 (52%), 5 of whom were able to discontinue dialysis. There was, however, an appreciable early mortality and, at latest follow-up (1-57 months), 12 patients had died and 8 were on the dialysis programme. On immunosuppression, ANCA became negative in the majority (median time 1.5 months) but recurred during clinical relapse in 11 cases. In asymptomatic patients (12 cases), the reappearance of ANCA positivity did not herald clinical relapse. The ANCA assay has increased awareness of systemic vasculitis but not removed the need for histological confirmation before instituting immunosuppression.

Adult↗