Familial steroid-responsive nephrotic syndrome and HLA antigens in Bengali children.

We investigated the major histocompatibility complex class I and II loci in three Bengali families with nine children affected with steroid-sensitive nephrotic syndrome (SSNS). A sequence-specific primer (SSP) of DNA typing method was used to detect human leukocyte antigens (HLA). The unaffected siblings and their parents were also studied. Similar to previous reports, there was a high frequency of HLA-DR7.1 (DRB1*0701), DR53 (DR B4*01011-0104) and DQ2 (DQB2*0201-3) antigens in the affected children. However, there was a similar finding in the unaffected children and their parents. HLA-DR7.1 probably was not a causative factor, since it had no predictive value for the occurrence or the severity of SSNS in the affected families. Siblings with identical HLA typing behaved differently (they either had or did not have SSNS). In these families there was no correlation between predisposition to the nephrotic syndrome and the genetic determinant responsible for HLA.

Changes in the choline content of human breast milk in the first 3 weeks after birth.

UNLABELLED: Choline is an essential constituent of membrane phospholipids in great demand in the developing brain and liver. We have previously demonstrated that human neonates excrete large amounts of betaine, a product of choline oxidation, in their urine. Estimates of perinatal choline intake using previously published data compared with our measurements of betaine excretion indicated that choline insufficiency might occur at certain periods after birth. In this study we measured the choline content of expressed human breast milk in colostrum (2-6 days after birth), mature milk (7-22 days after birth) and several infant formula foods, using proton nuclear magnetic resonance spectroscopy. In colostrum choline was present in both the aqueous (free choline, phosphocholine and glycerophosphocholine) and lipid fractions (phosphatidylcholine and sphingomyelin). After 6-7 days there was a mean increase of 114% in the total choline content; 82% of the rise was accounted for by increases in phosphocholine and glycerophosphocholine, and 14% by (free) choline. The choline content of most formula feeds was comparable with the level in colostrum but below that of mature milk. Both the total choline content and ester composition of mature milk were comparable with more recent measurements using high-performance liquid chromatography. CONCLUSION: The choline content of human breast milk doubles 6-7 days after birth and, unlike that of many formula feeds, appears to be sufficient to account for betaine excretion in healthy full-term neonates. However, for premature babies who usually receive much lower quantities of milk, yet have a higher demand for choline, the intake may be inadequate.

Does the rapid response to cisplatin-based chemotherapy justify its use as primary treatment for intracranial germ-cell tumours?

We reviewed presentation, diagnostic problems and outcome of eight cases of primary intracranial germ-cell tumour (4 germinoma, 4 teratoma) treated with Cisplatin-based chemotherapy at our centre over the last ten years. Three patients received primary chemotherapy with Cisplatin-based regimens followed by radiotherapy for subsequent relapse, two were treated with a combination of chemotherapy and external radiotherapy, and three received chemotherapy for relapse after radiotherapy. The response to Cisplatin-based chemotherapy was rapid, with some patents exhibiting symptomatic improvement within 24 h. Four patients achieved complete remission within 21 days, and three of these have remained progression-free. Four patients in total have survived for 32 to 128+ months. Six of seven patients tested pre-treatment had central diabetes insipidus and five had partial anterior pituitary failure. The endocrine deficit progressed in two, with no recovery in any patient. It is arguable that chemotherapy should be the primary therapy in all such cases diagnosed on the basis of tumour markers and imaging, with surgery and/or radiotherapy as later options. As these tumours are rare, such questions can only be answered by collaboration studies.

Ganciclovir treatment of congenital cytomegalovirus infection: a report of two cases.

Ganciclovir has been shown to be effective against cytomegalovirus (CMV) in vitro, but its role in the treatment of congenital cytomegalovirus infection is unknown. We describe its use in the management of two cases of congenital CMV infections. The drug was well tolerated and virus shedding in the urine was eliminated, though hepatosplenomegaly and neurodevelopmental delay persisted in both cases.

The calcitonin-CGRP gene in the infantile hypercalcaemia/Williams-Beuren syndrome.

We have investigated 13 families, each of which have one member with infantile hypercalcaemia/Williams-Beuren syndrome (IHWBS), for either a germ cell mutation of, or an association with, the calcitonin-CGRP gene. Restriction fragment mapping studies of the calcitonin-CGRP gene using five restriction enzymes (TaqI, Bg/II, PvuII, PstI, and SacI) and region specific probes failed to show any abnormalities of this gene complex. NO association of IHWBS with polymorphism of the calcitonin-CGRP/parathormone locus was found. Therefore, although the aetiology of IHWBS may be caused by a new dominant mutation, there is no evidence to implicate major rearrangements of the calcitonin-CGRP and parathormone genes.

Vitamin D metabolites in idiopathic infantile hypercalcaemia.

Metabolites of vitamin D were measured in plasma from 83 patients with idiopathic infantile hypercalcaemia syndrome who were mentally handicapped but had normal calcium values at the time of the study. No significant difference was detected in the mean plasma concentrations of 25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D3, or 25,26-dihydroxyvitamin D3 between patients and age matched controls. The mean plasma concentration of 25-hydroxyvitamin D3 was significantly lower in patients than controls but this may be a secondary phenomenon related to less sunlight exposure. In addition, two hypercalcaemic patients with this syndrome were studied during the first year of life, and were found to have normal concentrations of vitamin D metabolites. These findings do not support a role for abnormal vitamin D metabolism in the pathogenesis of this syndrome.

Idiopathic infantile hypercalcaemia--a continuing enigma.

Seventy six children with documented Fanconi-type idiopathic infantile hypercalcaemia were studied and compared with 41 with the Williams-Beuren syndrome. Clinical comparison showed, as expected, very close similarities but also considerable differences, particularly in the severity of feeding problems and the degree of failure to thrive. The estimated incidence of idiopathic infantile hypercalcaemia alone has remained constant for the past 20 years, at approximately 18 cases per year in the United Kingdom (1 per 47 000 total live births). Long term morbidity in these children is mainly due to mental handicap and arteriopathy, but hypertension (29%), kyphoscoliosis (19%), hyperacusis (75%), and obesity (50%) may be added complications. In one child, hypercalcaemia recurred during adolescence but this seems to be excessively rare. More detailed investigation before treatment is required to discover the aetiology of hypercalcaemia in this condition.

Glutaric aciduria type I presenting with hypoglycaemia.

We present a child with glutaryl CoA-dehydrogenase deficiency (type I glutaric aciduria) who presented with bilateral subdural hydromas, and progressive choreoathetosis and dysarthria. The diagnosis was made when she was investigated for hypoglycaemia at the age of 3.5 years. Temporary adrenocortical insufficiency was also noted. Three years after diagnosis the adrenal insufficiency and hypoglycaemia have resolved and treatment with riboflavin and 'lioresal', a GABA analogue, has prevented any further neurological deterioration.

Cystic fibrosis mimicking Bartter's syndrome.

A four-month-old female presented with dehydration and an unexplained hypoelectrolytaemia and metabolic alkalosis in association with hyperreninaemia and hyperaldosteronism. These findings suggested Bartter's syndrome. Sweat sodium concentrations were within normal limits. Total skin water loss was estimated and found to be sufficient for the sodium loss in the sweat to exceed the dietary intake. Reinvestigation at three years revealed normal plasma electrolytes, plasma renin activity and aldosterone values but sweat sodium concentrations were in excess of 80 mmol/l, indicating a diagnosis of cystic fibrosis.

Neonatal rickets. Histopathology and quantitative bone changes.

Ribs from 3 preterm infants, who had died after prolonged intravenous feeding and artificial ventilation, were examined histologically and assessed for the degree of osteomalacia and osteoporosis in cancellous bone of the shaft. A grid counting technique was used. Osteomalacia was noted in all 3 cases but to a lesser degree than in classical vitamin D-deficient controls. Osteoporosis was pronounced in the cases of neonatal rickets, but this was not a feature of the vitamin D-deficient controls. Histological features were similar to those reported in experimental phosphate-deficient rickets and vitamin D-resistant rickets.

Experience with human growth hormone in Great Britain: the report of the MRC Working Party.

The Working Party on human growth hormone (hGH) has during the past decade developed a system for the evaluation and treatment of patients suffering from hGH lack. Today there are nineteen measurement centres in the United Kingdom at which patients are assessed and where the effects of therapy are monitored. The current supply of hGH, which is prepared from pituitary glands collected by pathologists in the National Health Service, is just enough to meet demand, but research conducted on behalf of the Working Party suggests that hGH deficiency is more common than has been thought and that the prevalence may be as high as one in 10 000. If, as is hoped, patients are diagnosed younger and more patients with partial deficiency are recognized, demand may soon outstrip supply. Work is in progress to define better methods of hGH production and optimal dose regimens, both of which will help to minimize the problem of supply and demand. A few children have anti-hGH antibodies, which block growth as a result of treatment. Improved hGH production techniques may result in a less antigenic product and the resolution of this problem. Many of the Working Party's activities began as research and have evolved into service. Because of this shift in emphasis, and although much research is still to be done, responsibility for provision of treatment with hGH transferred from the Medical Research Council to the Department of Health and Social Security in July 1977.

Relation between changes in plasma calcium in first week of life and renal function.

(1) Of 71 infants fed on reconstituted dried or evaporated cow's milk, 31 showed a fall in plasma calcium between the 1st and 6th days of life, whereas in 35 breast-fed infants this occurred in only 5. (2) Those artificially-fed infants who had shown a rise in plasma calcium over this period had significantly lower plasma creatinine values and significantly higher excretion of creatinine than those infants who showed a fall in calcium levels. (3) Artificially-fed infants who had shown a rise in calcium had significantly lower plasma osmolality and significantly higher osmolar excretion in the urine than those infants who showed a fall in plasma calcium. (4) It is suggested that a delay in the normal increase in glomerular filtration rate during the first week of life in some infants leads to phosphate retention. This, together with a higher dietary intake of phosphate, leads to a decrease of the plasma calcium to hypocalcaemic levels.