The effects of selective beta-adrenoceptor antagonists and partial agonist activity on renal function during exercise in normal subjects and those with moderate renal impairment.

1. The effects of sustained moderate exercise in the sitting position on renal haemodynamics and glomerular filtration were measured in six normotensive patients with moderately impaired renal function and seven age-matched normal volunteers. 2. The changes in the effects of exercise on renal function induced by chronic cardioselective beta-adrenoceptor blockade by drugs with (epanolol) and without intrinsic sympathomimetic activity (atenolol) were examined. 3. Both beta-adrenoceptor blockers attenuated the heart rate increase with exercise, but only atenolol lowered blood pressure significantly. In resting volunteers on atenolol, associated with the fall in blood pressure there was a significant reduction in glomerular filtration rate. 4. Glomerular filtration fell significantly in all groups with exercise, and renal blood flow also fell in parallel. These changes were not influenced by drug treatment. 5. The exercise-induced rise in PRA was suppressed by atenolol but not by epanolol. 6. The renal function and haemodynamic responses to moderate exercise does not appear to be mediated by the systemic renin-angiotensin system or by beta 1-adrenoceptors.

Electrolyte and humoral responses of renal transplant patients to head-out water immersion.

Eighteen renal transplant recipients and sixteen volunteers were subjected to the physiological manoeuvre of head-out water immersion, in order to compare changes in electrolyte and humoral responses known to occur in healthy individuals with those arising as a result of renal denervation in the transplant recipients. Although the tubular sodium response to water immersion was normal, tubular potassium excretion was markedly different in the transplant patients. Plasma values of atrial natriuretic factor increased in both groups and showed a close temporal relationship to urinary excretion of cyclic GMP. The attenuation in transplant recipients of the well-documented suppression of plasma renin activity during water immersion was probably due to a combination of factors, namely lack of renal innervation and an increase in circulating ANF. The small but significant increase in the excretion of enzymically active urinary kallikrein observed only in the transplant recipients during immersion still requires explanation.

The pharmacokinetics of ofloxacin, desmethyl ofloxacin and ofloxacin N-oxide in haemodialysis patients with end-stage renal failure.

Six patients with end-stage chronic renal failure undergoing haemodialysis were given ofloxacin (600 mg) orally and blood samples were taken at intervals up to 32 h. In four patients samples were also taken before and after haemodialysis. Serum concentrations of ofloxacin, desmethyl ofloxacin and ofloxacin N-oxide were measured by HPLC. The drug was well tolerated. Mean pharmacokinetic parameters for ofloxacin were Cmax 5.5 h (S.D. 1.97 h), Tmax 3.9 h (S.D. 3.25 h), T1/2 28 h (S.D. 17.37 h), AUC0-24 83.1 mg/1 h (S.D. 32.69 mg/l h). The desmethyl metabolite was produced in all patients but only half produced N-oxide. Cmax values were 0.21 mg/l (desmethyl) and 0.37 mg/l (N-oxide). Ofloxacin and desmethyl ofloxacin were variably and only slightly removed by haemodialysis whilst ofloxacin N-oxide was not removed at all. These results confirm that dosage reduction of ofloxacin is required in haemodialysis patients. Therapeutic drug monitoring by HPLC is recommended because of the observed variability in absorption and plasma half life.

Effect of the partial beta-agonist prenalterol on plasma renin activity in patients with left ventricular failure.

Beta agonist therapy for heart failure has been disappointing, perhaps because of renin induced aldosteronism. To investigate this possibility we measured plasma renin activity (PRA) in 23 patients (17 male, 6 female, age 41-70) with New York Heart Association stage III heart failure due to ischaemic heart disease in a placebo controlled trial over one month. All patients received constant doses of digoxin and diuretics throughout the trial. Compliance was confirmed in all patients by digoxin and prenalterol assay. In a preliminary (dose titration) study of 9 patients there was a progressive, but non-significant rise of mean PRA from 14.8 to 17.6 and 27.7 ng/ml per h with doses of 20, 50 and 100 mg of prenalterol, respectively. After one month of treatment with prenalterol (n = 11), PRA was 12.8 +/- 2.4 (SEM) ng/ml per h which was not significantly different from the initial level of 14.4 +/- 2.3 ng/ml per h (n.s.). The placebo group (n = 12) results were 13.8 +/- 4.2 ng/ml per h at entry and 14.4 +/- 5.2 ng/ml per h at one month (n.s.). These results indicate that PRA is elevated by acute treatment with the partial beta agonist prenalterol but stimulation of renin secretion does not appear to occur with chronic therapy.

A preliminary report on the pharmacokinetics of ofloxacin, desmethyl ofloxacin and ofloxacin N-oxide in patients with chronic renal failure.

The in vitro activities of ofloxacin, desmethyl ofloxacin and ofloxacin N-oxide were determined and a specific high performance liquid chromatography (HPLC) assay for these 3 compounds was devised as part of a study of the pharmacokinetics of ofloxacin and its metabolites in patients with impaired renal function. Desmethyl ofloxacin had significant antimicrobial activity but less than that of the parent drug. In 2 patients with chronic renal failure, specific HPLC assay indicated an extended half-life for ofloxacin (approximately 13 hours) and the appearance in serum of low concentrations of both metabolites after 10 hours, persisting until the last blood sample was taken (32 hours). Further studies using specific assays are needed, particularly in patients undergoing haemodialysis and after administration of multiple doses.

The incidence of microaneurysms in polyarteritis nodosa.

Following reports of hemorrhage from renal microaneurysms caused by renal biopsy, renal arteriography has been used increasingly as a screening procedure prior to renal biopsy as well as for diagnostic investigation. The incidence of renal microaneurysms has been documented in a group of 40 cases of suspected polyarteritis nodosa, of whom 15 were confirmed, and only 2 had microaneurysms. Both subjects with microaneurysms had more florid clinical disease. In view of the low incidence of microaneurysms it is suggested that renal angiography should be used as a diagnostic investigation only in cases with florid clinical disease and not as a screening procedure prior to renal biopsy.

Intrinsic sympathomimetic activity of cardioselective beta-adrenoceptor blockers and effects on renal function.

The effects of a 21 infusion of isotonic sodium chloride on renal haemodynamics and sodium excretion were measured in nine normotensive volunteers. Changes in these responses to volume expansion induced by cardioselective beta-adrenoceptor blockade by drugs with (epanolol) and without intrinsic sympathomimetic activity (atenolol) were examined. Renal plasma flow was significantly lower before, during and after sodium chloride infusion whilst on treatment with atenolol compared with epanolol. Urinary sodium excretion was lower on atenolol than epanolol. Glomerular filtration rate was unchanged by either drug. Basal urinary kallikrein excretion was diminished by atenolol and both epanolol and atenolol inhibited the rise in urinary kallikrein excretion after sodium chloride infusion. Although some of these findings may be due to a more potent hypotensive effect of atenolol, intrinsic sympathomimetic activity may contribute to the apparent protective effects of epanolol on renal function.

Hypereosinophilic syndrome presenting as peripheral neuropathy.

An unusual case of hypereosinophilic syndrome is described which presented with peripheral neuropathy with no evidence of cardiac involvement. The response to steroid therapy is documented and the literature on peripheral neuropathy in hypereosinophilic syndrome is reviewed.

Haemodynamic and endocrine responses of the kidney to frusemide in mild essential hypertension.

Prostaglandin-dependent, frusemide-induced changes in renal plasma flow, glomerular filtration rate and plasma renin activity were measured in 14 patients with mild essential hypertension. The renal haemodynamic responses to frusemide were the same as in 10 normal subjects. Frusemide-induced changes in urinary PGE and kallikrein excretion were also the same as in normal subjects. Impaired renal release of vasodilator prostaglandins in essential hypertension is likely to be secondary to the hypertension rather than an underlying factor in its development.

Membranous nephropathy in a patient with nail-patella syndrome nephropathy.

Membranous nephropathy is described in a patient with nail-patella syndrome who also had the characteristic changes of nail-patella syndrome nephropathy on electron microscopy. This combination has not previously been reported. Nail-patella syndrome nephropathy is reviewed in relation to other glomerular lesions which have been reported.

Contribution of prostaglandins to the systemic and renal vascular response to frusemide in normal man.

In eight normotensive male volunteers indomethacin decreased both the peak urine flow rate and total sodium excreted within 1 h of an intravenous dose of frusemide. Resting effective renal plasma flow and glomerular filtration rate were unchanged by indomethacin, but the increase in both parameters after frusemide was inhibited. The early increase in plasma renin activity after frusemide was inhibited by indomethacin. Indomethacin decreased urinary excretion of PGE by 80% and the increase after frusemide was abolished. The urinary excretion of a metabolite of systemic PGI2 was unaltered in the 40-60 min period following frusemide. The early haemodynamic effects of frusemide are likely to be prostaglandin mediated, but there was no evidence of any change in systemic PGI2 synthesis after frusemide.

Immune status of subsided cases of tuberculoid (TT) and borderline tuberculoid (BT) leprosy.

A comparative study of lepromin reactions (early and late), M. leprae induced lymphocyte blastogenesis, per cent T Cell number in peripheral blood and immunoglobulin (IgG, IgA and IgM) levels have been made in TT-active, TT-subsided, BT-active and BT-subsided leprosy cases. No significant difference has been noted amongst these groups in the above mentioned investigations except in subsided BT cases where 9 out of 11 cases failed to evoke any late skin reaction to Dharmendra antigen. In addition, BT subsided cases also showed significantly raised levels of IgG. The significance of these findings with respect to their immunity and reinfection has been discussed.