Operation for gastro-oesophageal reflux associated with severe mental retardation

One hundred and seventy six children with severe mental retardation underwent a fundoplication for considerable gastro-oesophageal reflux. There were six 'early' (3%) deaths and five 'late' deaths. Major complications developed in 17 (10%) children whereas 86 (49%) had 'minor' complications. A revision operation was required in 27 patients. Overall 142 (81%) children achieved a good result. In spite of the high complication rate and the need for a secondary operation in 15% of the patients, the quality of life for these children and their parents and carers is greatly improved by antireflux surgery.     

Isolated vitamin E deficiency and progressive ataxia

A case of progressive spinocerebellar syndrome due to isolated vitamin E deficiency is reported. Measurement of the vitamin E concentration in serum should be included when investigating all children with unexplained, progressive ataxia, even in the absence of malabsorption. Replacement treatment in patients with a vitamin E deficiency can arrest or improve the associated neurological disorder.     

Aetiology of idiopathic growth hormone deficiency in England and Wales

Information on height, sex, age, and condition of mothers' pregnancy and labour was obtained on all first- and second-degree relatives of 140 cases of idiopathic growth hormone deficiency (GHD). Less detailed information was available for 68 further cases, the two samples together constituting all cases from England and Wales treated under the Medical Research Council Clinical Trial of Human Growth Hormone up till 1974. Compared with the Perinatal Mortality survey of 1958, idiopathic GHD cases showed a significantly greater incidence of breech births (13-7%), of forceps deliveries especially in multiparae (5-6%), and of reported early vaginal bleeding (7-1%). The incidences of breech and forceps were both higher in cases with multiple pituitary hormone deficiency than in cases of 'isolated' GHD. The frequency of either breech or forceps was 43% in multiple and 20% in 'isolated' GHD. Heights of fathers and sibs of affected cases averaged the 50th centile; those of mothers the 35th centile. The ratio of boys to girls affected was 3-8. There were 4 families with more than one member affected; 4-5% of the brothers of probands were themselves affected, 2% of fathers and 1-5% of both sisters and mothers. In the world literature the sex ratio averages about 2-9 with little difference between series; the frequency of breech delivery averages 21% with large differences (2% to 50%) between series. A table of relative risks is given from which a screening procedure may be constructed; following 1% of selected births would give 10% of cases, and 20% of births 50% of cases. We propose a multifactorial aetiology for GHD which brings it into line with malformations such as anencephaly, cleft lip and palate, and pyloric stenosis. An underlying liability to the disease is postulated, continuously distributed in the population and depending on both polygenic and environmental factors among which sex and birth trauma are important. The disease becomes manifest when the liability value reaches a fixed threshold. On this assumption, heritability of idopathic GHD is approximately the same as that of coeliac disease, pyloric stenosis, and patent ductus.     

Lack of p53 and ras mutations in Helicobacter hepaticus-induced liver tumors in A/JCr mice

Helicobacter hepaticus is a recently discovered bacterium that invades mouse liver causing chronic active hepatitis followed by development of preneoplastic hepatocellular foci, hepatocellular adenomas and carcinomas. This establishes a unique animal model for study of the mechanisms of cancer development due to a chronic bacterial infection. A possible mechanism of bacteria-associated tumorigenesis is mutation of oncogenes or tumor suppressor genes. Since mutations in ras oncogenes have been widely detected in a variety of chemically induced and spontaneous mouse liver tumors and specific mutations in the p53 tumor suppressor gene have been associated with human bladder cancers attributed to chronic schistosomal infection, we studied exons 1 and 2 of the N-, K- and H-ras genes and exons 5-8 of the p53 gene for the presence of point mutations in 25 liver tumors from 10 naturally infected A/JCr mice, ranging in age from 16 to 24 months. The 20 adenomas and five carcinomas varied in size from 0.1 to 2.3 cm and arose in livers characterized by a wide assortment of pathological profiles, including hepatitis, inflammation, hyperplasia, hypertrophy, leukocyte infiltration, necrosis and focal phenotypic alteration. DNA samples extracted from formalin-fixed paraffin-embedded tissues were screened by PCR/SSCP analysis and showed no mutations in the analyzed genes. Complete absence of mutations in ras genes in 25 mouse liver tumors is unusual. Other genes may be targeted or H. hepaticus infection causes liver cancer through other pathways than direct damage to DNA.      

Measurement of 2,6-diamino-4-hydroxy-5-formamidopyrimidine and 8-oxo- 7,8-dihydroguanine in isolated DNA exposed to gamma radiation in aqueous solution

Hydroxyl radical-mediated modifications of nucleobases are among the main deleterious processes induced in DNA by ionizing radiation. Determination of the underlying mechanisms in both isolated and cellular DNA requires the development of accurate assays for the detection of modified bases. High-performance liquid chromatography associated with electrochemical detection (HPLC-EC) and gas chromatography coupled to mass spectrometry (GC-MS) are the two main methods used for this purpose. In the present work, HPLC-EC was applied to the measurement of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) following enzymatic digestion of DNA. Evidence was provided for the quantitative aspect of the latter step. Moreover, a GC-MS assay was designed for the detection of 2,6-diamino-4-hydroxy-5- formamidopyrimidine (FapyGua). It was first shown that the widely used hot formic acid hydrolysis of DNA induced a complete decomposition of the lesion. A similar observation was also made for 4,6-diamino-5- formamidopyrimidine (FapyAde). A milder DNA hydrolyzing agent, HF in pyridine, was substituted to HCOOH for the quantitative release of FapyGua from DNA. The radiation-induced formation of 8-oxodGuo and FapyGua in aqueous solution of DNA was compared. Insights in the mechanistic aspects were inferred from the results of gamma-irradiation studies carried out under different gas saturating conditions. It was clearly shown that the formation of both lesions is mediated by HO.. In addition, the presence of oxygen favors the formation of 8-oxodGuo at the expense of FapyGua.      

Urinary excretion of 3-methyladenine after consumption of fish containing high levels of dimethylamine

The urinary excretion of the DNA alkylation product, 3-methyladenine (3- MeAde), was measured in human volunteers who were on controlled diets and consumed fresh fish, or frozen-stored fish that contained 50-fold higher levels of dimethylamine (DMA), with or without ingested nitrate. DMA potentially could react with nitrosating agents in the diet or within the body, and produce the potent carcinogen N- nitrosodimethylamine (NDMA), which can then react with DNA to form several adducts including 3-MeAde. Our findings show that there was no increase in urinary levels of 3-MeAde after consumption of fish preserved by frozen storage relative to levels after consumption of fresh fish. Furthermore, consumption of 225 mg sodium nitrate (equal to the nitrate content in a large glass of beet juice) at 1 h prior to consumption of the frozen-stored fish did not increase urinary 3-MeAde levels as would be expected if nitrate enhanced endogenous nitrosation of DMA. In contrast, urinary excretion of 3-MeAde from a volunteer who was a moderate cigarette smoker (11 cigarettes per day) was approximately 3- to 8-fold higher than dietary 3-MeAde intake. These findings indicate that consumption of high levels of DMA in fish does not result in detectable levels of NDMA formation and genetic damage as measured by the urinary biomarker 3-MeAde.      

Trends in growth in England and Scotland, 1972 to 1994

AIM: To monitor the growth of 5 to 11 year old English and Scottish children from 1972 to 1994. No similar data are available from any other study. DESIGN: Mixed longitudinal. SUBJECTS: In England 7000 children were sampled in the first year, falling to 5000. In Scotland the original sample was 2000 but this was enlarged later to 3500. MAIN OUTCOME MEASUREMENTS: Height, weight, weight for height index, and triceps skinfold thickness. RESULTS: Height of English children in most age groups increased by more than 1 cm and by more than 2 cm in Scotland during the period 1972 to 1994. Triceps skinfold measurement increased by almost 8% in 7 year old English boys and by 7% in 7 year old girls. In Scotland triceps skinfold measurement increased by nearly 10% in 7 year old boys and by 11% in 7 year old girls. Weight for height index followed a similar pattern. CONCLUSION: Children in England and Scotland are becoming taller for a given age. The increases in fatness indicate an urgent need for realistic interventions for reductions in obesity in the whole population. As weight for height index is less sensitive than skinfold thickness we recommend triceps and subscapular skinfold thickness measurements for monitoring obesity in children.