Modifying effects of amlodipine on cyclosporin A-induced changes in renal function in patients with psoriasis.

OBJECTIVE: To assess the benefit of amlodipine, a calcium channel blocker, on renal function and vasoactive hormones in individuals with normal kidneys and blood pressure and who were being treated with cyclosporin A for refractory psoriasis. DESIGN: An open-label, two-stage, longitudinal study was employed. METHODS: Patients were divided into two groups: Group I received cyclosporin A, 5 mg/kg per day for 6 months titrated down to 2.5-3.5 mg/kg per day for 6 months, then concomitant amlodipine 5 mg/day for 6 months; and Group II received concomitant cyclosporin A, 5 mg/kg per day, and amlodipine, 5 mg/day, for 6 months. Blood pressure, serum creatinine, glomerular filtration rate, urinary magnesium, plasma renin activity and urinary kallikrein excretion were measured before and after treatment. RESULTS: Eighteen patients were enrolled, and 12 completed the study. In Group I (n = 7), 12 months of cyclosporin A therapy significantly increased systolic blood pressure and significantly decreased glomerular filtration rate, plasma renin activity and active urinary kallikrein. Amlodipine reversed these changes. In Group II (n = 5), 6 months of concomitant cyclosporin A and amlodipine significantly reduced active urinary kallikrein levels. No significant changes occurred in the other measured parameters in either group. CONCLUSIONS: Cyclosporin A produces a sustained and significant fall in glomerular filtration rate and urinary kallikrein excretion, even in patients with normal kidneys and blood pressure. Amlodipine is potentially capable of reversing these nephrotoxic effects.

Presymptomatic detection of familial juvenile hyperuricaemic nephropathy in children.

We studied 34 apparently healthy children and 2 propositi from kindreds with familial juvenile hyperuricaemic nephropathy (FJHN) - a disorder characterised by early onset, hyperuricaemia, gout, familial renal disease and a similarly low urate clearance relative to glomerular filtration rate (GFR) [fractional excretion of uric acid (FEur) 5.1+/-1.6%] in young men and women. In addition to the propositi, 17 asymptomatic children were hyperuricaemic -- mean plasma urate (368+/-30 micromol/l), twice that of controls (154+/-41 micromol/l). Eight of them had a normal GFR ( > 80 ml/min per 1.73 m2), and 11 renal dysfunction, which was severe in 5. The FEur in the 14 hyperuricaemic children with a GFR > 50 ml/min was 5.0+/-0.5% and in the 5 with a GFR < or =50 ml/min was still low (11.5+/-0.2%) compared with controls (18.4+/-5.1%). The 17 normouricaemic children (185+/-37 micromol/l) had a normal GFR (>80 ml/min) and FEur (14.0+/-5.3%). The results highlight the dominant inheritance, absence of the usual child/adult difference in FEur in FJHN and presence of hyperuricaemia without renal disease in 42% of affected children, but not vice versa. Since early allopurinol treatment may retard progression to end-stage renal failure, screening of all relatives in FJHN kindreds is essential.

A collaborative audit of the management of hypertension in general practice.

We carried out an audit of the management of essential hypertension in general practice, against standards based on current guidelines. We examined the records of 882 hypertensive subjects (on medication) in whom hypertension had been diagnosed between January 1989 and December 1993, from 14 general practices in the Portsmouth and South East Hampshire Health Authority. The overall prevalence of hypertension was 3.5%. Pretreatment blood pressure had been measured on three or more occasions in 87% of patients. Pretreatment blood pressure was equal to or greater than 150/95 mmHg in 96% and 160/100 mmHg in 86.5% of patients. A thiazide diuretic was the initial drug of choice in 30% of patients, with beta-blockers being the most popular initial treatment. Ninety per cent of patients had had their blood pressure measured at least once during the preceding year. In 82.5% of patients, current blood pressure was less than 150/95 mmHg, while 44% achieved a current blood pressure less than 140/90 mmHg. We conclude that the prevalence of hypertension in this population was lower than expected, suggesting the need for improved screening. We also propose that the initial treatment choice should be a thiazide in the majority, which would result in significant cost saving. The blood pressure control was suboptimal compared to current guidelines.

Is blood pressure related to kidney size and shape?

OBJECTIVE: To examine the relationship between blood pressure and the size and shape of the kidneys in healthy volunteers from the community. DESIGN: A cross-sectional community-based study of normal volunteers in Portsmouth City, Hampshire, UK. SUBJECTS: Subjects numbered 185 (99 female), aged 19-66 years. RESULTS: Blood pressure was higher in men, and in those with higher body mass index. Both systolic and diastolic blood pressure were correlated with the derived kidney volume. However, when corrected for age, sex and BMI the relationship was not statistically significant. Blood pressure correlated inversely with the width : length ratio of the left kidney. CONCLUSIONS: Blood pressure was not correlated with kidney size in this group of adults.

Biological assay for tissue kallikrein: comparison with the synthetic substrate S2266.

A highly sensitive biological assay for tissue kallikrein is described, using human kininogen as substrate; and quantitation, by radioimmunoassay, of generated kinins. Using purified human urinary kallikrein as a reference standard we have correlated the kininogenase activity of kallikrein with amidase activity as measured by cleavage of the synthetic substrate S2266.

Association of myocarditis and acute renal failure complicating meningococcal septicaemia.

We report a case of meningococcal septicaemia complicated by myocarditis, cardiogenic shock and acute renal failure. Following protracted haemodynamic support and haemodialysis, there was complete recovery of cardiac and renal function.

Meningococcal septicaemia presenting as erythema multiforme.

A 48-year-old woman presented with a three-week history of recurrent, generalised rash, flitting joint pains, frontal headache and shivering attacks. On admission she was pyrexial and exhibited a symmetrical generalised maculopapular rash with a few target lesions. The rash faded within the first 24 hours, but over the following week it recurred at intervals of 48 hours and was accompanied by fever and headache. She was started on a short course of steroids, which did not alter her symptoms or signs. Eight days after admission, the patient underwent a lumbar puncture, despite the absence of definite signs of meningeal irritation. The cerebrospinal fluid (CSF) was turbid and diagnostic of bacterial meningitis. Cultures of blood and CSF taken on the day of admission both grew Neisseria meningitidis. The patient was successfully treated; symptoms were completely resolved.

Hyperammonaemic coma in ureterosigmoid urinary diversion.

We report on a patient with ureterosigmoid anastomosis, who presented with recurrent episodes of confusion, agitation and aggressive behaviour, culminating in coma. Investigations revealed profound hyperammonaemia, which responded to treatment with sodium benzoate and sodium phenylacetate. No definite cause was found for the abnormality, apart from possible urinary tract infection. The patient remains well on a protein restricted diet with mildly elevated levels of plasma ammonia.

Pharmacokinetics of cyclosporin in man following a single oral dose: relationship to body fat content.

We have investigated the pharmacokinetics of the immunosuppressive drug cyclosporin in 11 patients receiving regular dialysis therapy. After a single oral dose of cyclosporin, whole blood concentrations were measured at regular intervals for 24 h. Body fat content was estimated in each subject from the measurement of skin-fold thickness and mid-arm circumference. In ten of the 11 patients there was a relatively uniform response in the increase of cyclosporin blood concentration to a peak within the first 6 h. Calculated area under the blood concentration curve did not correlate with total bodyweight, but correlated strongly with body fat content as well as fat-free mass. This study suggests that more predictable blood concentrations of cyclosporin might be achieved if the initial dose were calculated on the basis of fat-free mass rather than total bodyweight.

Rabies presenting with myocarditis and encephalitis.

We report a case of rabies acquired in Zambia by a 45-year-old woman who presented with a history of an influenza-like illness, abnormal behaviour and signs of myocarditis. A provisional diagnosis of systemic viral infection was made. Within 12 h of admission the patient developed features of rabies that included hydrophobia. She was artificially paralysed and ventilated electively. Empirical antibiotic therapy was given also. Signs of myocarditis and fever disappeared within 48 h. Her clinical condition remained stable but she required heavy sedation. On the ninth day after admission the patient developed features of inappropriate secretion of antidiuretic hormone and gradually became water-logged. Intake of fluid was therefore restricted. Her level of consciousness deteriorated progressively to the point where sedation was no longer required. Brain death was diagnosed 14 days after admission.

A simplified method for monitoring blood concentration of cyclosporin by a finger-stab technique.

We have developed a simple method of sample collection which allows the measurement of cyclosporin (CsA) to be made from blood obtained from a finger stab and collected onto filter paper. CsA concentrations estimated from blood spots and venous samples obtained at the same time showed good correlation. This method has various practical applications: peak and trough blood CsA concentrations (as well as profiles) may be routinely measured from samples collected by patients at home; it may be of particular value in children and other patients with poor venous access.

Phaeochromocytoma presenting with cardiogenic shock and acute renal failure.

A patient with a 12 hour history of headache, breathlessness and hypotension developed acute renal failure necessitating haemodialysis for 12 days. During recovery she developed hypertension, tachycardia and facial flushing. Investigations revealed a right adrenal phaeochromocytoma. Whilst postural hypotension is common in phaeochromocytoma, profound shock with acute renal failure is rare. This may have been precipitated by concomitant drug therapy, myocardial necrosis or by necrosis within the tumour.

Lactase insufficiency in Chinese children detected by oral milk and lactose challenge.

A study to determine the incidence of late-onset lactose intolerance was undertaken in 68 normal Chinese children in Singapore using measurements of breath hydrogen concentrations, following a lactose or milk challenge, as indicator of lactose malabsorption. Evidence of lactose malabsorption was detected in 26% of children given a lactose challenge, and in 21% of those given a milk challenge. It is concluded that late-onset lactase insufficiency is common in Chinese children in Singapore.