Haemolytic uraemic syndrome: prognostic factors.

Haemolytic uraemic syndrome (HUS) associated with Escherichia coli O157:H7 is the commonest cause of acute renal failure (ARF) in childhood. Production of verotoxin by the organism is pivotal in the pathogenesis of the disease. Verotoxin binds to a receptor on blood and endothelial cells, expressed as the P1 blood group antigen on red blood cells. A protective effect of the P1 phenotype has been proposed in this disease. This study investigates prognostic factors and the relationship between outcome and P1 phenotype in 27 cases of diarrhoea-associated HUS. A poor outcome as defined by the presence of chronic renal failure (CRF), hypertension or proteinuria on 6 month follow-up was associated with the age of the patient at presentation and with the following clinical markers: maximum WBC and duration of raised WBC, duration of anuria and duration of need for dialysis. None of these outcome measures or prognostic factors, and no extra-renal manifestations of the disease were associated with P1 phenotype.

An audit of medical paediatric out-patient appointments and letters.

All medical out-patient appointments of a firm of three consultants at the Royal Hospital for Sick Children were reviewed over a four week period. Of 758 appointments initially offered, 490 (64%) patients attended; 19% of patients cancelled and 17% did not attend without cancelling. Delay from referral to attendance ranged from 0 to 9 weeks. The characteristics of those patients experiencing prolonged registrar-only follow-up are described. The content of subsequent letters to family practitioners was usually adequate compared to accepted standards. Delays in dictation of letters were usually short in comparison to delays in typing. Such delays and the intervals between consultant review of out-patients may prove costly to providers. Potential improvement strategies are discussed.

Long-term follow up to determine the prognostic value of imaging after urinary tract infections. Part 1: Reflux.

In 3646 children with at least one confirmed urinary tract infection the prevalence of vesicoureteric reflux at presentation was correlated with progressive renal damage during follow up of not less than two and up to 16 years. Reflux was not demonstrated either at presentation or at any subsequent time in almost one half of the children who suffered progressive renal damage and was not a risk factor for progressive renal damage in boys under 1 year. It was an important risk factor in boys over 1 year and in girls of any age. The risk of progressive renal damage in children in whom micturating cystourethrography (MCU) did not reveal vesicoureteric reflux was substantially greater than in those who indirect isotope voiding study (IVS) did not show reflux. The risk of deterioration for those in whom reflux was demonstrated was similar for both techniques. This discrepancy indicates an appreciably higher false negative rate for the MCU than the IVS. Dilatation of the renal pelvis detected by ultrasound was associated with a significantly increased risk of progressive damage only when associated with reflux, but most children with progressive damage did not have a dilated collecting system at presentation.

Long-term follow up to determine the prognostic value of imaging after urinary tract infections. Part 2: Scarring.

Long term follow up of children with urinary tract infections, in whom imaging investigations were performed at presentation, has been used to identify features that distinguish those at greatest risk of progressive renal damage. No single investigation at presentation was able to predict subsequent deterioration but, by employing a combination of imaging investigations, it was possible to separate groups with high or low probability of progressive damage. In the low risk group the incidence of progressive damage was 0.2% (95% confidence interval (CI) 0 to 1.3%). The combination of both scarring and reflux at presentation, or one only of these but accompanied by subsequent documented urinary tract infection, was associated with a 17-fold (95% CI 2.5 to 118) increase in the relative risk of progressive renal damage compared with children without these features. The recommended combination of investigations at presentation for girls of any age and boys over 1 year is ultrasound and dimercaptosuccinic acid (DMSA) scintigraphy in all, to detect both scarring and significant structural abnormalities, renography in children with dilatation of any part of the urinary tract on ultrasound, to distinguish dilatation from obstruction, and an isotope voiding study in all who have acquired bladder control. This gives the best separation between those at high and those at low risk of progressive damage with least radiation dose and lowest rate of instrumentation. Micturating cystourethrography (MCU) should be restricted to girls who have not acquired bladder control, unless there is reason to suspect a significant structural abnormality such as urethral valves. A single non-febrile urinary tract infection that responds promptly to treatment is not a justification for performing MCU in boys under 1 year or in children of any age with bladder control. No case can be made for any abbreviated schedule of investigation. These risk factors should be taken into account when designing follow up protocols.

Omentectomy with peritoneal catheter placement in acute renal failure.

Catheter function was retrospectively analysed after surgical placement in 21 children requiring peritoneal dialysis for acute renal failure due to haemolytic uraemic syndrome. Substantial benefits were shown to have accrued from partial omentectomy which resulted in reliable access and trouble-free drainage in the 11 patients in whom it was carried out. Conversely 4 of 10 patients in whom partial omentectomy was not done experienced total catheter blockage whilst the other 6 experienced intermittent poor drainage. Partial omentectomy should be considered as integral to the surgical technique of peritoneal catheter placement for both short-term and long-term dialysis in children.

Intra-atrial calcium infusions, growth, and development in end organ resistance to vitamin D.

A five and a half year follow up of a girl with end organ resistant rickets is described. After failing to respond to high dose oral alfacalcidol (4 micrograms/kg/day) and calcium supplements, treatment for one year with domiciliary intra-atrial calcium infusions at 2 years of age induced a complete remission, which was maintained on subsequent high dose oral calcium supplement. Overnight infusions were well tolerated without adverse cardiovascular or renal sequelae or ectopic calcification. If the first three years of life are survived, the prognosis for a normal life on oral treatment is excellent.

Persisting vitamin D deficiency in the Asian adolescent.

A study of 221 children admitted to hospital in the course of a year allowed establishment of a reference range for plasma 25-hydroxyvitamin D. None of these children had evidence of biochemical rickets. Most Asian children, however, were vitamin D deficient in comparison, and this deficiency was most noticeable in girls aged 13 to 15 years: biochemical rickets occurred in six per cent of these adolescent Asians. If vitamin D requirements are not met during the physiological growth spurt, permanent pelvic deformity may result. Vitamin D deficiency persisting into pregnancy will adversely affect the infant, producing an increased risk of hypocalcaemic fits, dental enamel hypoplasia, infantile rickets, and reduced postnatal growth. Our data support the need for vitamin D supplementation, and we suggest that annual oral vitamin D supplements in the autumn would alleviate the problem.

Rigid spine syndrome and fatal cardiomyopathy.

A 7 1/2-year-old girl had the clinical features of the rigid spine syndrome of Dubowitz. Muscle biopsy showed a predominance of type 2 fibres with neither myopathic features nor an increase in connective tissue. In addition, she had a hypertrophic cardiomyopathy with which she presented in heart failure and from which she died suddenly one month later. The association of rigid spine syndrome with cardiomyopathy has not been reported previously.

The detection of pyelonephritic scarring in children by radioisotope imaging.

Radioisotope scintigraphy of the kidney and intravenous urography have been compared in 79 children with bacteriologically proven urinary tract infections, followed up over a period of between one and four years. Both techniques were in agreement as to the presence or absence of an abnormality, and the extent of any abnormality present, in 93.5% of the kidneys studied. There was a discrepancy in ten kidneys. Excretion urography has a sensitivity of 0.86 and a specificity of 0.92 in the detection of pyelonephritic scarring in children. Radioisotope scintigraphy has a sensitivity of 0.96 and a specificity of 0.98. It is therefore concluded that radioisotope scintigraphy is the preferred technique.

A comparison of two techniques of detecting vesico-ureteric reflux.

Indirect voiding radionuclide cystourethrography has been compared with micturating cystourethrography in 57 children with urinary tract infections. A quasi-quantitative technique utilizing a mini-computer to optimize the images from the gamma camera has been shown to be at least as sensitive as conventional radiological techniques but to give these results without catheterization, at a lower radiation dose and at lower cost.

Cyclic adenosine monophosphate excretion in urine of patients and carriers of congenital nephrogenic diabetes insipidus.

Urinary excretion of cyclic adenosine monophosphate (cAMP) is assessed in response to pitressin stimulation in three patients with nephrogenic diabetes insipidus, four carriers and seven controls. There is no significant difference in cAMP excretion between these groups when corrected for surface area, nor is there any significant increase in excretion after pitressin stimulation. There is very close correlation between urinary cAMP and both urinary concentration and urinary creatinine excretion. Urinary cAMP after pitressin stimulation does not discriminate between carriers of nephrogenic diabetes insipidus and control subjects.

The effect of transfer factor on neutrophil function in chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis with hypoparathyroidism in a 6-year-old-boy is described. In addition to defects of in vivo and in vitro correlates of delayed-type hypersensitivity to Candida albicans the child also had abnormalities of neutrophil function in terms of their capacity to respond by chemotaxis to a known attractant and to kill suspensions of C. albicans. Dialysable transfer factor was given on six occasions at intervals of between 26 and 45 days. Neutrophil chemotaxis (optimal conditions) was restored following each of the six injections, neutrophil chemotaxis (sub-optimal conditions) following five of the six injections and candidicidal capacity following four of the six injections. The effects of transfer factor were transient requiring repeated injections. The Candida delayed-type hypersensitivity skin test was restored to normal but lymphocyte transformation to Candida extract was not consistently positive following treatment. There was a slight clinical improvement following therapy. These abnormalities of neutrophil and lymphocyte function point to the complexity of chronic mucocutaneous candidiasis. The improvement in neutrophil chemotaxis and candidicidal capacity following treatment suggests that transfer factor may be a heterogeneous group of molecules, some of which affect granulocytes and restore defects in their function.

Fluid and electrolyte metabolism in the newborn infant.

This chapter has sought to gather together the background information on systems controlling homoeostasis of salt and water and their clinical derangement. The temptation to adopt an all-embracing approach to the management of these problems is strong but such an approach is difficult to achieve and indeed dangerous. The circumstances of each sick infant are unique and plans for treatment must be individually tailored and flexible, dependent upon clinical and biochemical progress. Future developments in this field are likely to involve further understanding of renal and hormonal control of fluid and electrolyte and it might be expected that as new methods of management emerge they will be accompanied by their own peculiar risks of inducing secondary homoeostatic disturbances. With regard to infant feeding each advance appears to underline the desirability of breast feeding and support current moves toward provision of low solute feeds for those who are artificially fed. Paediatricians should be vocal in their advocation of breast feeding and ensure that the major principles of salt and water handling are understood by all who work with small infants. An extra scoop of powdered milk can be more of a poison than a food.

Leucocyte function in a case of chronic benign neutropenia of infancy associated with circulating leucoagglutinins.

A case of chronic benign neutropenia is described in association with circulating leucoagglutinins. IgG and IgM leucoagglutinins demonstrated by Sephadex G-200 chromatography agglutinated neutrophils and monocyte enriched leucocyte preparations. Total IgG, IgA, IgM and IgE, total haemolytic complement, C3 and C4 complement components were all within normal limits. Lymphocyte populations and transformation were normal apart from a relative increase in the number of B lymphocytes. In vitro studies showed that the patient's monocytes responded in chemotaxis, phagocytosis and intracellular killing of S. aureus in a comparable fashion to that of control neutrophils. Although the patient's serum also agglutinated monocytes these findings do not exclude the possibility that leucoagglutinins may have aetiological significance in this disease. The study also emphasizes the versatility of the monocyte in benign neutropenia.

Haemangioma with coagulopathy: sustained response to prednisone.

Two cases of giant haemangioma with thrombocytopenia are described. A satisfactory and sustained response to prednisone was achieved in respect of both coagulation abnormalities and tumour size. It is proposed that prednisone is effective by enhancement of thrombosis and reduction of fibrinolysis within the tumour, thus promoting a natural form of resolution. It is suggested that prednisone therapy should be first-choice treatment of complicated haemangiomas.

Calcium balance in children treated with diphosphonates.

Serial mineral balances have been obtained in 3 children undergoing therapy with EHDP (ethane-1-hydroxy-1, 1-diphosphonate) for diseases involving ectopic calcification. Although clinical outcome was not uniformly satisfactory, all cases showed an overall reduction in calcium balance. This was due to increased faecal excretion of calcium and was most marked after a long duration of therapy. Although these results conflict with reported experience in adults, they are in agreement with published observations of the effects of EHDP on calcium absorption in experimental animals.