Neil Dalton

Presymptomatic detection of familial juvenile hyperuricaemic nephropathy in children

Abstract. 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 μmol/l), twice that of controls (154±41 μmol/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 ≤50 ml/min was still low (11.5±0.2%) compared with controls (18.4±5.1%). The 17 normouricaemic children (185±37 μmol/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.

Circulating concentrations of histamine, neutrophil chemotactic activity, and catecholamines during the refractory period in exercise-induced asthma

Circulating mediators and catecholamine concentrations have been measured in eight subjects with asthma who were subjected to two bouts of cycle ergometer exercise separated by 1 hour. The maximum falls in FEV1 were 21.9 +/- 2.3% (mean +/- SEM; n = 8) and 5.5 +/- 1.3% (mean +/- SEM; n = 8) after the first and second exercises, respectively. Serum neutrophil chemotactic activity (NCA) and plasma histamine and catecholamine levels in venous blood were measured with a microchemotaxis and two radioenzymatic techniques, respectively. There was a significant increase in NCA and plasma histamine concentrations after both exercise challenges, and there was no significant difference in the release of these mediators between the two exercise tests. Gel filtration chromatography demonstrated that the NCA detected after the first and second exercise tests had molecular sizes of approximately 600,000 daltons. There was no significant time-dependent increase in plasma norepinephrine and epinephrine concentrations after either exercise task, even though the patients were refractory to exercise-induced asthma after the second exercise. These results suggest that the refractory period in exercise-induced asthma is not caused by mediator depletion, as indicated by NCA and histamine measurements, or by protection of the airways through catecholamine release.

Hyponatraemia in Premature Babies and Following Surgery in Older Children

ABSTRACT. Hyponatraemia implies water retention in excess of sodium with or without increased loss of sodium from the body; extracellular fluid volume may be increased, normal or reduced. It has many causes which are briefly reviewed. Among these is the rare syndrome of inappropriate secretion of antidiuretic hormone (SIADH). It is suggested that SIADH is often diagnosed incorrectly because the raised ADH levels are appropriate for the volume status of the child. Precision in the diagnosis is important because whilst water restriction is necessary for the treatment of SIADH, other measures including the administration of extra fluid are often required if the raised ADH is appropriate. Hyponatraemia in the newborn may be caused by prerenal failure, renal failure or renal sodium wasting which is common in premature infants. Careful control of sodium intake as well as water intake is vital in this age group. Surgery is associated with water retention, but recent studies suggest that ADH levels are raised post‐operatively because of volume depletion and that present recommendations for fluid therapy during and following surgery are inadequate. The use of electrolyte‐free dextrose solutions should be abandoned and more liberal use of physiological saline or colloid is recommended.

Cardiovascular disease in renal allograft recipients is associated with elevated sialic acid or markers of inflammation

Abstract:  Background:  Cardiovascular disease (CVD) is more common in patients with renal failure, even after renal transplantation. We wished to examine the relationship between markers of inflammation and CVD in stable renal transplant patients.

Protective effect of circulating epinephrine within the physiologic range on the airway response to inhaled histamine in nonasthmatic subjects

The specific airway conductance response of six normal subjects to increasing doses of inhaled histamine was studied on two occasions. On each occasion either epinephrine (0.025 micrograms/kg/min) or saline was infused intravenously during the histamine challenge. This dose of epinephrine, when it was administered to seated normal subjects, produces plasma levels similar to those found at the end of strenuous exercise. Epinephrine caused a significant elevation in the concentration of histamine required to cause a 35% fall in specific airway conductance (PC35), although this was in part caused by a small airway dilator effect. The mean (+/-SD) PC35 rose from 21 mg/ml (+/-6) during saline infusion to 58 mg/ml (+/-27) during epinephrine infusion, p less than 0.05. Levels of circulating epinephrine, similar to those found during exercise in normal subjects, appear to be capable of protecting against bronchoconstrictor stimuli.

Phaeochromocytoma: report of three cases

The diagnosis and investigation of phaeochromocytoma was reviewed in three patients presenting to the paediatric renal centre with malignant hypertension. The initial diagnosis was made using urinary 4-hydroxy-3-methoxymandelic acid (VMA) and plasma adrenaline and non-adrenaline estimations. Our experience of the localization of phaeochromocytoma with ultrasound,131I-meta-iodobenzylguanidine (MIBG) and venous sampling was discussed and we have reappraised our approach to the localization of these tumours.

Amino Acid and Protein Metabolism in Chronic Renal Failure

Protein malnutrition is common in uraemia. Protein synthesis is probably reduced but protein breakdown is not increased at least under basal conditions. The reduction in protein synthesis may be due to a direct effect of an unidentified uraemic toxin(s) but, in addition, the adaptation to altered energy metabolism may reduce protein synthesis by increasing branch chain amino acid oxidation with a consequent reduction in the extracellular and intracellular pools of branch chain amino and keto acids. Lowering nitrogen toxicity by reducing nitrogen intake and supplementing with essential amino acids or keto acids may improve growth in some children.

Low dose dopexamine improves indices of hepato-splanchnic perfusion in children recovering from sepsis

ConclusionsBoth indices of hepato-splanchnic perfusion pHi and LPF/Cl (%) improved with the addition of dopexamine at 0.5 mcg/kg/min. In children, therefore, where there is a need for “gut protection” low dose dopexamine might be the drug of first choice.

Urinary proteins in vesicoureteric reflux: when the same thinking leads to different conclusions

On reading the paper by Tomlinson et al. [1] in the first 1994 issue of Pediatric Nephrology we were pleased with the conclusion that analysing tubular proteinuria in children with vesicoureteric reflux (VUR) may add something to the clinical picture of these patients. This has been the final conclusion of a previous paper by our group published in the same journal [2]. Despite this, there were some differences between the two studies. It should be stressed, however, that the two papers are in full agreement on many points and, in our view, the central message is the same. A major finding of our study was that 43 of 82 patients with VUR had augmented levels of retinol-binding protein (RBP) in urine; of this group 28 had a reduced glomerular filtration rate (GFR) and in these patients an effect of tubular overload on the urinary levels of the protein was hypothesised. The same finding was reported by Tomlinson et al. [1] in a larger population of children with VUR, but the proportion of patients with VUR without scarring and high urinary levels of RBP was lower than in our original report (3/40 compared with 4/23). In these patients, we found a twofold increase in urinary RBP or [32-microglobulin compared with the upper limits of a normal population of 91 school children [2]. Comparable normal limits were subsequently obtained in a larger population of 365 children [3] who had mean RBP urinary levels of 40 ~tg/g creatinine (range 1-150 gg/g), the maximal level corresponding to 18 on the scale utilised by Tomlinson et al. [1] (gg/mmol creatinine). Owing to the very large number of children studied, we believe our range effectively represents the normal limits for urinary RBP in an Italian paediatric population. Another difference between the two studies concerns the correlation found by Tomlinson et al. [1] between urinary RBP and renal scarring in patients with both normal and decreased GFR. We too observed a good correlation between urinary levels of RBP and degree of scarring when considering the whole population (i.e. normal and low GFR). However, we excluded patients with low GFR, since other mechanisms of tubular proteinuria may be operating in those patients. In summary, we think that the differences between the two studies are only artifactual, while the basic conclusions are the same, and indicate the usefulness of urinary RBP determination in patients with VUR. Long-term follow-up studies should more clearly indicate the real value of urinary RBP as a marker of incipient renal disease.