The flow-dependent vasodilatation of peripheral conduit arteries is altered in HD patients and is associated with a slight but significant decrease in the vasodilating response to exogenous NO. These results suggest, in the absence of changes in basal radial vascular resistance and arterial diameter, more a decrease in endothelial NO bioavailability, than an increase in basal vascular tone.

Cisplatin is used widely in the treatment of a large number of carcinomas. The clinical use of cisplatin, however, can be complicated by myelotoxicity, ototoxicity and intestinal toxicity; we review briefly cisplatin nephrotoxicity. The principal route of its excretion is via the kidney, and accumulation of cisplatin in the renal cortex has been demonstrated. Three to five days following administration of cisplatin to rats, degenerative changes appear in the proximal tubule, including cytoplasmic vacuolization, tubular dilatation and pyknotic and hydropic degeneration. A decrease in renal plasma flow was observed very early on in patients receiving cisplatin at a dose of 20 mg/m2 over a period of 4 h, and an increase in urinary enzymes occurred rapidly. Hypomagnesaemia, hypocalcaemia and hypokalaemia were frequent. The mechanism of cisplatin nephrotoxicity remain unclear. Biotransformation of cisplatin could play an important role; a decrease in sulphydryl groups in the kidney may be a primary event, and reactive metabolites may be formed. The incidence of cisplatin nephrotoxicity has been observed to decrease when patients are prehydrated, and it was proposed recently that administration of a calcium blocker might reduce the nephrotoxic effects of cisplatin. The clinical recommendations are to avoid rapid cisplatin infusion rates (over 1 mg/kg per hour) and to induce hydration at least during and after cisplatin administration. New compounds with the same or better antitumour activity and less toxicity should be prepared. At present, carboplatin appears to be preferable to cisplatin because of the reduced incidence of untoward effects.

Six cases of chronic renal failure related to granulomatous renal sarcoidosis are reported and compared with data in the literature. The particular features of sarcoidosis granulomatous interstitial nephritis should be emphasised because presentation may be misleading. Renal failure usually presents with a rapidly progressive course, either isolated or associated with mild proteinuria and sterile leukocyturia, while extrarenal localisations may be absent. Diagnosis should be suspected on the basis of elevated or paradoxically normal serum calcium concentrations, due to increased plasma concentrations of calcitriol, while immunoreactive circulating parathormone concentrations are depressed. Calcitriol as well as angiotensin-converting enzyme could represent unregulated secretion products from granulomatous tissue and their plasma concentrations may roughly reflect activity of the disease. Early corticosteroid treatment dramatically improves renal function but long-term renal prognosis may be oblitered due to progressive chronic renal failure related to fibrosis scarring.

The pharmacokinetics of ofloxacin were investigated in 12 normal subjects and 21 uremic patients after the administration of a single oral 200-mg dose. An open three-compartment body model was used to calculate ofloxacin pharmacokinetic parameters. In healthy subjects, the peak plasma level averaged 2.24 0.90 pg/mI and was obtained at 0.83 ± 0.31 h. The absorption rate constant was 4.22 ± 1.64 h-'. The terminal half-life was 7.86 ± 1.81 h. The apparent volume of distribution was 2.53 ± 0.78 liters/kg. Total body and renal clearances were 241.4 ± 53.8 and 196.5 ± 42.9 ml/min per 1.73 m2, respectively. A total of 68.4 ± 11.9% of the dose was recovered unchanged in 24-h urine. In uremic patients, the terminal half-life increased in relation to the degree of renal failure: from 8 h in normal subjects to 37 h in severely uremic patients. Renal insufficiency did not significantly modify the peak plasma level, the apparent volume of distribution, the fractional clearance, or the nonrenal clearance of ofloxacin. However, the time to peak level was delayed in patients with creatinine clearance of <30 ml/min. Linear relationships were found between ofloxacin pharmacokinetic parameters and glomerular filtration rate data. Ofloxacin is only very slightly removed by hemodialysis. Dosage adjustments of ofloxacin in uremic patients are proposed.Ofloxacin is a new fluoroquinolone oral derivative characterized by a broad spectrum of activity against gramnegative and gram-positive bacteria, including obligate anaerobes. The activity of ofloxacin against Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria gonorrhoeae, and Clostridium perfringens was roughly comparable to that of norfloxacin and far exceeded that of pipemidic and nalidixic acids. Its activity against gram-positive aerobes was 4 to 16 times greater than that of norfloxacin (1, 6). Ofloxacin was well absorbed after oral administration and was excreted unchanged (70%) in urine.The purpose of this study was to determine the pharmacokinetic parameters of ofloxacin in normal subjects and in patients with various degrees of chronic renal impairment after the oral administration of a single 200-mg dose.