Growth of long-term survivors of liver transplantation.

OBJECTIVE: To assess growth in survivors of liver transplantation. STUDY DESIGN: Growth was studied in 105 children up to seven years after liver transplantation. RESULTS: At transplantation, mean height standard deviation score (zH) was -1.22 but 19% of patients were severely growth retarded (height below 0.4th centile). Growth and pubertal retardation were seen in the first six months after liver transplantation. Significant catch up in growth and puberty continued for more than five years. At five years, mean zH was -0.95 and at seven years -0.84. The mean zH of patients at final height was -0.55. zH at six months was predicted by zH and bilirubin at the time of transplantation and prednisolone dose at six months. At four years, zH was predicted by zH at the time of transplantation and the cumulative prednisolone dose. There was no association between zH and age at transplantation, sex, or diagnosis, although those with biliary atresia and those undergoing transplantation under 2 years of age showed more initial growth delay and subsequent catch up. Average age at menarche was 14.2 years. CONCLUSIONS: The mean height of the group to have reached final height after liver transplantation was on the 27th centile. Those transplanted earlier in childhood are likely to achieve more normal final heights. High steroid dose, poor liver function, and retransplantation are associated with poorer height outcomes. Persisting severe short stature is largely confined to children with severely retarded growth at the time of transplantation. Transient delay in puberty and menarche occur early after transplantation, although appropriate pubertal progress is resumed after two to three years.

Income characteristics of rural older women and implications for health status.

This review examines the relationship between rural residence, income, and health status for older women in the U.S. little published research has focused on the interaction between financial status and the specific health-related needs of these rural women. Both descriptive data from the 1990 U.S. Census and empirical data from the health care literature are analyzed. Gender, rural residence, and poverty are identified as risk factors for reduced access to health care services, lower rates of health care service utilization, and poorer health outcomes.

A common and recurrent 13-bp deletion in the autoimmune regulator gene in British kindreds with autoimmune polyendocrinopathy type 1.

Autoimmune polyendocrinopathy type 1 (APS1) is an autosomal recessive disorder characterized by autoimmune hypoparathyroidism, autoimmune adrenocortical failure, and mucocutaneous candidiasis. Recently, an autoimmune regulator gene (AIRE-1), which is located on chromosome 21q22.3, has been identified, and mutations in European kindreds with APS1 have been described. We used SSCP analysis and direct DNA sequencing to screen the entire 1,635-bp coding region of AIRE-1 in 12 British families with APS1. A 13-bp deletion (964del13) was found to account for 17 of the 24 possible mutant AIRE-1 alleles, in our kindreds. This mutation was found to occur de novo in one affected subject. A common haplotype spanning the AIRE-1 locus was found in chromosomes that carried the 964del13 mutation, suggesting a founder effect in our population. One of 576 normal subjects was also a heterozygous carrier of the 964del13 mutation. Six other point mutations were found in AIRE-1, including two 1-bp deletions, three missense mutations (R15L, L28P, and Y90C), and a nonsense mutation (R257*). The high frequency of the 964del13 allele and the clustering of the other AIRE-1 mutations may allow rapid molecular screening for APS1 in British kindreds. Furthermore, the prevalence of the 964del13 AIRE-1 mutation may have implications in the pathogenesis of the more common autoimmune endocrinopathies in our population.

Effect of growth hormone on height, weight, and body composition in Prader-Willi syndrome.

AIMS: To evaluate the effect of the administration of growth hormone on stature, body weight, and body composition in children aged between 4 and 10 years with Prader-Willi syndrome. METHODS: Height, weight, and skinfold thickness were recorded in 25 children using standard anthropometric techniques at recruitment, and six months later, shortly before the start of daily subcutaneous injections of growth hormone. Body composition was assessed via a measurement of total body water using stable isotopes. Measurements were repeated at the end of the six months of growth hormone administration. Measurements of height, weight, and skinfold thickness were expressed as standard deviation scores (SDSs). RESULTS: There was a significant reduction in the percentage of body fat after growth hormone treatment; height velocity doubled during treatment; body weight did not change significantly when expressed as an SDS. Skinfold thickness at both the triceps and subscapular site decreased in absolute terms and when expressed as an SDS. CONCLUSIONS: These results indicate sufficient potential benefit to justify a more prolonged trial of growth hormone treatment and an exploration of different dosage regimens in children with Prader-Willi syndrome.

Radioiodine treatment of Graves' disease in young people.

In Europe young patients with Graves' disease are usually treated with antithyroid drugs initially, then if hyperthyroidism recurs after a prolonged course of such medication, they are offered definitive treatment by subtotal or total thyroidectomy. Neither of these forms of treatment is free from problems. Impressed with the simplicity and safety record of radioiodine therapy, we have treated 8 young patients with radioiodine. The patients all presented with typical Graves' disease and relapsed after 18-24 months of treatment with antithyroid drugs. They were then given the option of a further course of antithyroid medication or definitive treatment with radioiodine or surgery. Those who opted for radioiodine were treated with 131iodine in a dose of 300 MBq with the intention of ablating the thyroid. Antithyroid medication was resumed for 4-6 months and then withdrawn. Four patients became hypothyroid after a single dose of radioiodine but 4 needed a second dose. All became hypothyroid within 2 years. No adverse effects were observed, in particular no patient showed any deterioration in their eye disease. Radioiodine offers a simple, effective and inexpensive method of treatment for Graves' disease in young patients. There are no immediate adverse effects and, although some theoretical concerns remain, to date the long-term safety record of thyroid ablation is excellent and the potential risks seem to us to be outweighed by the advantages. Even when a moderately high initial dose of radioiodine is used, a second dose may be needed.

Initial evaluation of congenital hypothyroidism: a survey of general paediatricians in East Anglia.

The practice of general paediatricians in the initial evaluation of congenital hypothyroidism (CHT) was assessed. This was performed by a questionnaire survey of paediatricians in East Anglia of whom 84% responded. Nineteen of 25 clinicians based in seven district hospitals managed children with CHT. The median number of children in the care of each clinician was 4 (range 1-17) and the median number of children attending each hospital was 12 (range 5-23). All except one clinician arranged to confirm the diagnosis with a serum thyroid stimulating hormone concentration and free or total thyroxine. There was variation of opinion on the value of serum triiodothyronine and free triiodothyronine measurements, antibody screening, knee radiographs, and thyroid isotope scans. One clinician sought advice when notified of new children and two expressed the need for an investigation protocol. These findings indicate that most general paediatricians in East Anglia manage only a few children with CHT; the initial diagnosis is appropriately confirmed but they are uncertain about the value of other investigations.

Formal home care services: examining the long-term care needs of rural older women.

Little data or current research exists regarding the specific long-term care needs of rural older women. This article examines the variables that appear to influence the availability of formal home care services. Utilization is discussed within the context of the specific social, cultural, and demographic factors that are applicable to this group of individuals. A description of the unique health care considerations of older women is also presented, along with recommendations for future research efforts and programming initiatives.

Severe microcephaly with normal intellectual development: the Nijmegen breakage syndrome.

A brother and sister are described with severe microcephaly of prenatal onset, normal intellectual and motor development, chromosomal breakage and cellular immunodeficiency, which is characteristic of the autosomal recessive condition, Nijmegen breakage syndrome. The proband was a girl who presented at 15 months, with normal developmental milestones and an extremely small head circumference of 36 cm. Twenty per cent of her lymphocytes showed spontaneous translocations involving chromosome 7p13, 7q35, 14q11, and 14q32. The lymphocytes also showed excessive x ray induced chromosome damage. She had T cell lymphopenia, but normal immunoglobulins, and a normal alpha fetoprotein. A brother was born shortly after her diagnosis was made. He also had extreme microcephaly of 28 cm, with similar spontaneous and x ray induced chromosomal breakage, and T cell lymphopenia. Neither child has clinical evidence of immunodeficiency. To test the hypothesis that Nijmegen breakage syndrome and ataxia telangiectasia are allelic disorders, haplotype analysis was carried out in the family using DNA markers spanning the AT locus on chromosome 11q22. The affected boy had a different haplotype from his affected sister. Thus in this family, the Nijmegen breakage syndrome is not allelic to the ataxia telangiectasia locus on chromosome 11q, and the two conditions are genetically distinct. The normal intellect in these children raises questions about normal brain development in the presence of severe microcephaly.

Liver transplantation for homozygous familial hypercholesterolaemia.

Homozygous familial hypercholesterolaemia is a rare inherited condition with an incidence of approximately one in a million. It is associated with severe premature atherosclerosis and early death from cardiovascular complications. The results of liver transplantation reported to date have suggested only partially effective reduction of the hypercholesterolaemia. Three boys with familial hypercholesterolaemia, aged 10.0 to 15.1 years, received liver grafts at Addenbrooke's Hospital. Their untreated fasting lipid concentrations were grossly raised. All three had angiographic evidence of coronary atheroma and two had exertional angina. One child had such severe atheroma that coronary artery bypass surgery was considered necessary before liver transplantation. All three had straightforward operative and postoperative courses and their lipid concentrations returned rapidly to normal. One boy developed chronic rejection requiring retransplantation. Currently all three boys are well, on normal diets, and with normal liver function. It is concluded that (1) liver transplantation offers highly effective treatment for this lethal condition, (2) timing the operation is difficult but it should be undertaken before coronary artery disease has progressed too far (when combined liver and heart transplantation may be the only possibility), and (3) in well grown children with no previous abdominal surgery the immediate risks of liver transplantation are low but chronic rejection remains a danger.

Liver transplantation in patients with situs inversus.

Seven patients with situs inversus abdominis and one with situs inversus totalis underwent liver transplantation; all are alive at follow-up of between 7 months and 5 years. Two patients required retransplantation within the first 3 weeks (for primary non-function and thrombotic infarction). Seven had additional abnormalities associated with the polysplenia-biliary atresia syndrome. Liver transplantation in these patients involved selection of relatively small donor organs or use of reduced-size grafts. Delayed abdominal wall closure was necessary in two patients and all required a modification of the 'piggy-back' technique of suprahepatic vena caval anastomosis to overcome recipient venous anomalies. Biliary drainage by Roux-en-Y choledochojejunostomy was the preferred technique. Although technically challenging, situs inversus is not a contraindication to liver transplantation and patients should expect full recovery.

Hypercalcaemia in primary oxalosis: role of increased bone resorption and effects of treatment with pamidronate.

Primary oxalosis is a rare congenital disorder characterised by widespread deposition of calcium oxalate crystals throughout the body. In this paper, we describe the development and treatment of hypercalcaemia associated with oxalosis in a child who had undergone renal transplantation, combined liver and kidney transplantation, and two liver retransplant procedures in the past 5 years. Hypercalcaemia occurred on three separate occasions in association with liver dysfunction due to graft rejection; renal function was not grossly impaired and serum intact parathyroid hormone levels were normal. Intravenous pamidronate therapy led to rapid normalisation of the serum calcium concentration on all three occasions. Iliac crest biopsy revealed large numbers of oxalate crystals in the bone marrow, many of which were associated with macrophages, identified using the antibody MAC 387. Bone histomorphometry demonstrated an increase in the percentage eroded surface but no increase in osteoid surface. These observations indicate that hypercalcaemia associated with oxalosis can occur in the absence of renal dysfunction and may result from excessive bone resorption, induced either directly or indirectly by macrophages surrounding oxalate crystals in the bone marrow. Pamidronate therapy was effective in restoring serum calcium to normal.

Twenty-seven years of liver transplantation at Addenbrooke's Hospital, Cambridge.

Twenty-seven years ago, liver transplantation at Addenbrooke's Hospital was a very experimental procedure. It is now recognized as an accepted mode of treatment for end-stage liver failure. In the coming year, over 600 liver transplants will take place in the United Kingdom. All western European countries now have an active liver transplantation program and more than 17,000 liver transplants have already been performed. As results improve and the procedure becomes more readily and widely accepted, the donor shortage is likely to get worse, and will be only partially met by the introduction of split livers and living-related donors.