PubMed HealthSearch

Biomedical subjects

G B Haycock

Publications and source records attributed to G B Haycock.

At least 19 recordsLinked to original sources

The syndrome of inappropriate secretion of antidiuretic hormone.

The physiology of the release of antidiuretic hormone (ADH) from the posterior pituitary is briefly reviewed. The importance of both osmolar and non-osmolar stimuli is emphasised. Osmolar and non-osmolar factors usually reinforce each other; for example, hydropenia leads to hyperosmolality and hypovolaemia, both promoting ADH release, while hydration has the opposite effect. In disease, osmolar and non-osmolar factors may become dissociated leading to baroreceptor-mediated ADH release in the presence of hyponatraemia and hypo-osmolality. Examples include heart failure, glucocorticoid or thyroxine deficiency, hepatic cirrhosis and nephrotic syndrome with or without the superimposed effect of diuretics, i.e. conditions in which circulatory, and in particular effective arterial, volume is reduced. It is dangerous to label such conditions as 'inappropriate' secretion of ADH since the maintenance of circulating volume is at least as important a physiological requirement as the defence of tonicity. The syndrome of inappropriate secretion of ADH (SIADH) is uncommon in childhood and should only be diagnosed when physiological release of ADH in response to non-osmolar as well as osmolar factors has been excluded. Criteria for the correct identification of SIADH are discussed; the presence of continuing urinary sodium excretion in the presence of hyponatraemia and hypo-osmolality is essential to the diagnosis. SIADH in children is usually due to intracranial disease or injury. The mainstay of treatment is water restriction which reverses all the physiological abnormalities of the condition. Hypertonic saline is rarely indicated for the short-term control of neurological manifestations such as seizures. Drugs have little or no place in the treatment of SIADH in children.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Insulin and growth in chronic renal failure.

We studied glucose metabolism using the hyperglycemic technique in a cross-section of 23 children (15 pubertal, 8 prepubertal) with stable chronic renal failure as a possible cause of their poor growth. Linear growth was expressed as growth velocity standard deviation score (GVSDS). GVSDS correlated with glucose disposal rate but not with insulin sensitivity index in the pubertal (r = 0.87, P < 0.001) and prepubertal (r = 0.86, P < 0.02) children with chronic renal failure. Thirteen children were followed longitudinally during medical suppression of hyperparathyroidism with dietary phosphate restriction and high-dose phosphate binders. Following significant suppression of serum parathyroid hormone (PTH) levels back to the normal range (932 +/- 240 ng/l to 199 +/- 50 ng/l), GVSDS, glucose disposal rate and insulin secretion all increased significantly (p < 0.01), with no change in insulin sensitivity index and renal function. The changes in GVSDS correlated with the changes in glucose disposal rate (r = 0.86, P < 0.02) and with the changes in insulin secretion (r = 0.80, P < 0.01). However, the changes in GVSDS did not correlate with the changes in PTH. The hypothesis that insulin may be more important than PTH in the pathogenesis of growth failure in chronic renal disease deserves further investigation.

Adolescent

Middle aortic syndrome: clinical and radiological findings.

Eight patients with the middle aortic syndrome are described. They were aged 2 months to 14 years at diagnosis; follow up was one to 11 years. Clinical presentations included asymptomatic hypertension (n = 5), severe headache, nose bleed, and chest pain (n = 1), and cardiac failure (n = 1). All had severe hypertension requiring multiple drug treatment. Diminished peripheral pulses were not helpful in the diagnosis, which is made on aortography. Associated clinical findings were Williams' syndrome (n = 3) and appreciable eosinophilia (n = 3). The differential diagnosis includes Takayasu's arteritis, fibromuscular dysplasia, and neurofibromatosis. Blood pressure was adequately controlled by medical treatment in six patients. Surgical angioplasty was performed in two. One patient remained normotensive without drug treatment 21 months after operation; the other died of sepsis and uncontrollable haemorrhage in the postoperative period. Medical treatment is satisfactory in most cases: surgery should be reserved for those in whom blood pressure cannot be controlled without unacceptable side effects of drug treatment. Although rare, the middle aortic syndrome should be considered in the differential diagnosis of hypertension when commoner causes have been excluded. Aortography is necessary for diagnosis.

Adolescent

Salt and the newborn kidney.

Renal function differs in term infants from that in adults, with lower glomerular filtration rate (GFR) and reduced proximal tubular reabsorption of sodium (Na) and water: nevertheless, it is adequate for their needs. This is not true of very preterm infants in whom hyponatraemia is common. Animal studies have shown that Na+, K(+)-ATPase and the Na+/K+ exchanger are poorly expressed at birth with rapid postnatal rises. Cell receptors for hormones that influence tubular Na transport are less numerous in the premature infant than later in life: intracellular second messenger systems may also be immature. The low GFR is due to vasoconstriction and may be necessary to prevent water and electrolyte wasting due to tubular overload. The hyponatraemia of prematurity could, in principle, be due either to Na loss or water excess and can be prevented either by giving additional Na or by restricting water intake. Na supplementation causes relative volume expansion (VE), water restriction volume contraction (VC); this is demonstrated by the effect of the two approaches on weight gain and on the levels of vasoactive hormones in the blood. We argue that moderate VE is more physiological than VC, both in attempting to simulate intrauterine conditions and in consideration of the infant's nutritional needs. The much less common complication of hypernatraemia is usually due to abnormal water loss and should be prevented by increasing water intake appropriately. The above applies to well, preterm babies: sick preterm infants are much more variable in their Na and water requirements than well infants of comparable gestation and weight and each needs an individually tailored regimen based on frequent clinical assessment and laboratory measurement.

Biological Transport

A practical approach to evaluating urinary tract infection in children.

All children with urinary tract infections should be investigated by either excretory urography or abdominal X-ray, ultrasonography and technetium 99m - dimercaptosuccinic acid scintigraphy. Patients in the following categories should also have micturating (voiding) cystourethrography to diagnose or exclude vesico-ureteral reflux: infants aged less than 1 year, children with recurrent (second or subsequent) infections, children with clinically diagnosed acute pyelonephritis and those with a family history of reflux or chronic pyelonephritis. Cystography can safely be omitted in children over 1 year of age with unscarred kidneys and none of the additional risk factors listed. They should be followed for 1-2 years following the first infection for evidence of recurrence.

Child

Effects of oral phosphocysteamine and rectal cysteamine in cystinosis.

Diurnal variation in leucocyte cystine and the effects of equimolar single doses of oral phosphocysteamine and rectal cysteamine were studied in eight patients with cystinosis, aged 1.8-16.5 years. No significant diurnal variation in leucocyte cystine was found. Absorption of cysteamine was reduced after rectal administration compared with the oral dose: mean (SD) peak concentration 17.2 (6.3) mumol/l v 36.4 (5.5) mumol/l at 40 min and mean (SD) area under the curve 22.3 (14.3) v 59.4 (33.1) mumol/h/l. Oral phosphocysteamine significantly reduced the mean (SD) leucocyte cystine from 8.09 (0.47) to 3.26 (1.48) nmol 1/2 cystine/mg protein at three hours. At 12 hours the mean leucocyte cystine was significantly lower than the pretreatment concentration. Rectal cysteamine did not significantly reduce the mean leucocyte cystine concentration. In conclusion, phosphocysteamine suspension may be administered every 12 hours. Rectal cysteamine administration is feasible but higher doses are required before efficacy can be judged.

Administration, Oral

Treatment of hyperkalaemia with intravenous salbutamol.

Thirteen children with hyperkalaemia were treated by intravenous infusions of salbutamol, 4 micrograms/kg over 20 minutes. Reductions in the mean (SD) plasma potassium concentrations, of 1.48 (0.5) and 1.64 (0.5) mmol/l were obtained at 40 and 120 minutes, respectively, after completion of the infusions. No side effects were noted.

Acute Kidney Injury

Recombinant human erythropoietin therapy in children maintained by haemodialysis.

Six children (aged 3 years 11 months to 15 years 9 months) with end-stage renal failure and anaemia (mean haemoglobin 7.1 g/dl, range 6.3-7.7 g/dl) on thrice-weekly haemodialysis were treated with recombinant human erythropoietin (rHuEPO), given as an intravenous bolus in an escalating dose regime after dialysis. All responded with an increase in reticulocyte count and haemoglobin concentration in a mean time of 11 weeks (range 9-13 weeks) and at a dose of 100 or 150 units/kg thrice weekly. The dose of rHuEPO was then adjusted to maintain the haemoglobin concentration within the lower half of the normal range for the child's age and sex. The mean haemoglobin after 12 weeks treatment was 10.9 g/dl (range 8.5-12.1 g/dl) and after 24 weeks, 10.5 g/dl (range 7.9-13.3 g/dl). Four children had no further need for blood transfusion and are thus no longer at risk of blood-borne infection, iron overload and sensitisation to HLA histocompatibility antigens. Serum ferritin fell in the three patients with evidence of iron overload; the three with low or normal iron stores at the onset of treatment maintained erythropoiesis with oral iron supplementation. HLA antibodies decreased in all patients. The only serious complication encountered was thrombosis of vascular access in one child. No child became seriously hypertensive or developed cerebral symptoms. The benefits of rHuEPO therapy for children with end-stage renal failure are potentially considerable and with careful monitoring, the risks low.

Adolescent

Oxandrolone for delayed puberty in boys taking long-term steroid therapy for renal disease.

Eleven boys, mean age 15.3 years (range 13.2-17.5), with pubertal delay in association with steroid therapy for steroid-sensitive nephrotic syndrome and following renal transplantation were treated with oxandrolone 2.5 mg daily for a mean of 0.50 years (range 0.34-0.61). Mean growth velocity increased from 3.9 cm/year (range 1.1-6.3) to 6.1 cm/year (range 2.0-14.4) and was maintained at 6.1 cm/year (range 0.4-10.2) (P less than 0.05). However, there was no significant difference in growth between the treated boys and age- and puberty-matched controls. Elevation of blood cyclosporin A and creatinine levels occurred in the transplant patients. Oxandrolone may initiate a pubertal growth spurt in patients taking steroid therapy for renal disease, but should be used with extreme caution because of potential side-effects.

Adolescent

Antidiuretic hormone following surgery in children.

We studied 13 children subjected to elective tonsillectomy, 6 of whom (study patients) received supplemental intravenous isotonic saline during and after operation, and 7 of whom (controls) did not. Clinical and biochemical evidence of hypovolaemia was present in the control but not in the study patients. Plasma antidiuretic hormone (ADH) and urine osmolality were higher in controls (p less than 0.005 and p less than 0.05 respectively). Plasma sodium concentration and osmolality were similar in the two groups. We conclude that hypovolaemia is the principal stimulus to ADH release following surgery and that, in addition to replacement of observed losses of blood and other fluids by fluids of appropriate composition, hypovolaemia should be prevented by the administration of maintenance quantities of isotonic fluid, rather than exacerbated by fluid restriction, in patients in whom oral fluid intake is interrupted for more than a brief period. Hypotonic and sodium free fluids should be avoided because of the risk of hyponatraemia.

Catecholamines

Prediction of acute renal failure after birth asphyxia.

Twenty-one babies of 34-41 weeks' gestational age with birth asphyxia (5 minute Apgar score less than or equal to 5 or umbilical artery pH less than or equal to 7.2) were studied during the first two days of life to find out whether the urinary excretion of tubular markers of renal function is of value in the early diagnosis of acute renal failure. Urinary retinol binding protein, myoglobin, and N-acetyl-beta-D-glucosaminidase (NAG), expressed as a ratio with urinary creatinine, were measured and excretion profiles repeated at 3-6 days in 15 infants and at 7-14 days in 11 infants. Plasma creatinine concentration, creatinine clearance, plasma myoglobin concentration, and fractional sodium excretion were measured where possible in asphyxiated infants. Control data were obtained from 50 healthy infants: 28 gave urine samples alone, 17 urine and blood, and five blood alone. Normal urinary values were derived from 17, 25, and three infants, respectively, for the three time periods. The number of control samples was limited for ethical reasons. Four asphyxiated infants had acute renal failure (group 1), four had tubular dysfunction without glomerular disturbance (group 2) and 13 had normal renal function (group 3). Group 1 were clearly identified by greatly increased urinary retinol binding protein (greater than 27,000 micrograms/mmol creatinine) and myoglobin (greater than 1500 micrograms/mmol creatinine) excretion measured in the first two days of life. In control infants the range of excretion of retinol binding protein within the same time period was 3 to 967 micrograms/mmol creatinine and urinary myoglobin was undetectable. Excretion of NAG failed to discriminate between groups 1 and 2. Acute renal failure occurred only in infants who had heavy myoglobinaemia. Tubular dysfunction in group 2 was transient and not accompanied by plasma electrolyte disturbances. We conclude that measurement of urinary excretion of retinol binding protein or myoglobin after birth is helpful in the early diagnosis of acute renal failure.

Acetylglucosaminidase

Quantitative microfocal radiography of children with renal osteodystrophy; comparison with laboratory and histological findings.

High definition microfocal radiography permitted the quantitative assessment of the radiographic features of renal osteodystrophy in the phalanges of 11 children in stable chronic renal failure, treated with phosphate binders for 1 year. The most consistent feature was subperiosteal cortical resorption, expressed as a ratio total length of resorbed subperiosteal bone/total length subperiosteal bone x 100. It was found that the extent of resorbed bone was significantly greater in the middle phalanx and on the ulnar surface of the phalanges. The radiological findings over the duration of the disease were compared with laboratory assessments and bone histomorphometry. The extent of the percentage of subperiosteal resorption at base line and its change during the study period correlated significantly with the level of serum parathyroid hormone levels and its change over the same period. No other significant correlations were found between radiographic features and laboratory assessments or with bone histomorphometry.

Adolescent

Renal function following acute renal failure in childhood: a long term follow-up study.

We measured glomerular and tubular function in 10 children, aged 7 to 19 years, 7 to 12 years after apparent recovery from their episodes of acute renal failure. Although glomerular filtration rate was normal in all, filtration fraction (inulin clearance/PAH clearance) was elevated in six of eight patients. Segmental tubular sodium transport was assessed using clearance techniques during hypotonic saline diuresis; both proximal and distal sodium reabsorption were normal when compared with age-appropriate normal standards. Tubular reabsorption of phosphate, glucose and amino acids were also normal, as were urinary concentrating and diluting capacity and distal tubular hydrogen ion secretion. We conclude that, despite normal glomerular filtration rate, glomerular function is abnormal in a significant number of children who have apparently recovered completely from ARF, probably due to destruction of a proportion of the total nephron population, predominantly those located in the superficial layers of the cortex.

Acute Kidney Injury

Safety and efficacy of calcium carbonate in children with chronic renal failure.

The safety and clinical efficacy of calcium carbonate therapy in children with chronic renal failure were assessed in 68 patients (average age 8.38 years) during a mean follow-up period of 19.9 months (range 1.2-49.4). Forty-seven episodes of hypercalcaemia occurred in 29 children (3.5 episodes per 100 patient-months). There were no significant differences in mean GFR or biochemical parameters between these patients at the start of calcium carbonate therapy and the group of children who never experienced hypercalcaemia. Good control of secondary hyperparathyroidism and a significant reduction in serum aluminum were achieved. Two of 23 hypercalcaemic patients showed nephrocalcinosis on ultrasonography. 99Tc pyrophosphate scanning failed to detect any other ectopic calcification. The incidence of hypercalcaemia increased significantly when the GFR was less than 15 ml/min per 1.73 m2 and was most frequent in children receiving dialysis (48 episodes per 100 patient-months). The decrease in GFR during therapy was significantly more in the hypercalcaemic group compared to the normocalcaemic group (P less than 0.01), despite no irreversible acute effects of hypercalcaemia being observed on the rate of decline of GFR. We believe that the reduced renal homeostatic reserve is a major factor predisposing to hypercalcaemia. Consequently calcium carbonate is safe to use in children with severe chronic renal failure with close biochemical monitoring; the benefits over aluminium phosphate binders far outweigh the risks of hypercalcaemia and ectopic calcification.

Adolescent