Effects of smoking and aging on oxidative DNA damage of human lymphocytes

The effects of H2O2-induced oxidative DNA damage in 80 healthy individuals with relation to age (20-25 and 55-60 years old) and smoking has been investigated with the comet assay technique. Both factors have shown a significant effect upon basal DNA damage with smoking appearing to have the most impact. A differentiation of the four groups response to induced oxidative damage was also observed. A distinctly separate behavior of the younger non-smokers group, when compared with the rest of the categories, was found. This is attributed to the lower degree of initial basal damage that occurs in their lymphocytes.      

Dietary carotenoids inhibit aflatoxin B1-induced liver preneoplastic foci and DNA damage in the rat: role of the modulation of aflatoxin B1 metabolism

To study the effects of carotenoids on the initiation of liver carcinogenesis by aflatoxin B1 (AFB1), male weanling rats were fed beta- carotene, beta-apo-8'-carotenal, canthaxanthin, astaxanthin or lycopene (300 mg/kg diet), or an excess of vitamin A (21000 RE/kg diet), or were injected i.p. with 3-methylcholanthrene (3-MC) (6 x 20 mg/kg body wt) before and during i.p. treatment with AFB1 (2 x 1 mg/kg body wt). The rats were later submitted to 2-acetylaminofluorene treatment and partial hepatectomy, and placental glutathione S-transferase-positive liver foci were detected and quantified. The in vivo effects of carotenoids or of 3-MC on AFB1-induced liver DNA damage were evaluated using different endpoints: liver DNA single-strand breaks (SSB) induced by AFB1, and in vivo binding of [3H]AFB1 to liver DNA and plasma albumin. Finally, the modulation of AFB1 metabolism by carotenoids or by 3-MC was investigated in vitro by incubating [14C]AFB1 with liver microsomes from rats that had been fed with carotenoids or treated by 3- MC, and the metabolites formed by HPLC were analyzed. In contrast to lycopene or to an excess of vitamin A, both of which had no effect, beta-carotene, beta-apo-8'carotenal, astaxanthin and canthaxanthin, as well as 3-MC, were very efficient in reducing the number and the size of liver preneoplastic foci. In a similar way as 3-MC, the P4501A- inducer carotenoids, beta-apo-8'-carotenal astaxanthin and canthaxanthin, decreased in vivo AFB1-induced DNA SSB and the binding of AFB1 to liver DNA and plasma albumin, and increased in vitro AFB1 metabolism to aflatoxin M1, a less genotoxic metabolite. It is concluded that these carotenoids exert their protective effect through the deviation of AFB1 metabolism towards detoxication pathways. In contrast, beta-carotene did not protect hepatic DNA from AFB1-induced alterations, and caused only minor changes of AFB1 metabolism: seemingly, its protective effect against the initiation of liver preneoplastic foci by AFB1 is mediated by other mechanisms.      

A prospective 10 year follow up study of patients with neurofibromatosis type 1

OBJECTIVE: To establish the prevalence and incidence of symptoms and complications in children with neurofibromatosis type 1 (NF1) and to assess possible risk factors for the development of complications. DESIGN: A 10 year prospective multidisciplinary follow up study. PATIENTS: One hundred and fifty children diagnosed with NF1 according to criteria set by the National Institutes of Health. RESULTS: In 62 of 150 children (41.3%) complications were present, including 42 (28.0%) children with one complication, 18 (12.0%) with two complications, and two (1.3%) with three complications (mean (SD) duration of follow up 4.9 (3.8) years). Ninety five of the 150 children presented without complications (follow up, 340.8 person-years). The incidence of complications was 2.4/100 person-years in this group. An association was found between behavioural problems and the presence of complications. CONCLUSION: This is the largest single centre case series of NF1 affected children followed until 18 years of age. Children with NF1, including those initially presenting without complications, should have regular clinical examinations.     

Healthy eating for infants–mothers'attitudes

Mothers'perceptions of desirable nutritional practices in infant feeding were examined using a questionnaire consisting of open and closed questions. A total of 1004 mother–infant pairs were recruited from a mixture of urban and rural areas in England. The sample represented a cross–section of socioeconomic groups and educational backgrounds. Mothers'attitudes to healthy eating for infants revealed some misconceptions; 83% felt that a high fibre intake was important or very important and 87% that a low fat intake was important or very important, while 20% considered that plenty of calories was not important. Other health guidelines were appropriately applied and most mothers considered a wide variety of foods, plenty to drink and a low sugar and salt intake to be important. These beliefs were representative of the sample population, irrespective of the socioeconomic group, location, age and education of the mother.     

Suffocation, choking, and strangulation in childhood in England and Wales: epidemiology and prevention

The causes, classification, and prevention of mechanical asphyxial death in children were examined. The Office of Population Censuses and Surveys (OPCS) identified children, under 15 years of age, who had died as a result of choking, suffocation, or strangulation in England and Wales during the years 1990 and 1991. Cases in the International Classification of Diseases (ICD) codes of E911-3, E953, E963, and E983 were selected and case details from HM coroners' records and the death certificates were extracted. The OPCS identified 136 children (99 boys, 37 girls) in the two year period, 65% were under 3 years of age. The children were classified as dying from choking (21 cases), aspirating gastric contents (39 cases), suffocation (29 cases), strangulation (11 cases), and hanging (36 cases). The strangulation cases could be further subdivided into a group of 12 younger children who were suspended from ligatures around the home and a group of 21 boys (8-14 years) who died of self initiated hanging. Overall, 11 children were deliberately killed and 31 children died in beds or cots. Children whose deaths are classified as being due to aspiration of vomit appear to be cases of the sudden infant death syndrome or background medical conditions. This study suggests the need for advice on maintaining a safe sleeping environment. Only one child choked on a toy and European Standards for Toy Safety appear to have been successful. The prevention of hanging in the group of older boys needs further exploration.     

Infantile osteopetrosis; bone marrow transplantation from a cousin donor

The successful correction of infantile osteopetrosis in an Asian child by bone marrow transplantation (BMT) from an HLA-A,B matched cousin donor is reported. Retrospective HLA molecular analysis revealed that patient and donor were incompatible for HLA-DPB1. Donor type cells detected in the patient after transplantation indicate successful engraftment. The patient is currently alive and well.     

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.     

Hypothyroidism secondary to topical iodine treatment in infants with spina bifida

Four infants with spina bifida, who had not undergone surgical closure of a lumbar myelomeningocele, were assessed and investigated for hypothyroidism. From birth, all were treated once daily with an iodine-containing ointment (Betadine) as a local antiseptic applied to the spina defect. All infants showed excess urinary iodine concentration. Two infants, without clinical evidence of hypothyroidism or goitre, showed low serum free thyroxine and high thyroid stimulating hormone concentrations at a mean age of four weeks and were started on thyroxine replacement treatment. Betadine ointment and thyroxine were stopped simultaneously at a mean age of nine months, following which all infants remained euthyroid. Thyroid function tests should be monitored routinely if iodine is applied as a topical antiseptic to infants.     

Variable outcome of a congenital cytomegalovirus infection in a quadruplet after primary infection of the mother during pregnancy

A congenital cytomegalovirus (CMV) infection in a quadruplet has not been reported previously in the literature. We describe a congenital CMV infection in a quadruplet after primary CMV infection of the mother during pregnancy. One infant died antenatally, while another had cholestatic jaundice at birth and died of liver failure at three months of age. Of the two surviving infants, one showed no signs or symptoms of congenital CMV infection at 18 months of age, whereas the other had hearing loss and delayed development. CMV cultures of urine were positive at six weeks of age in all three infants born alive. The diagnosis of congenital CMV infection after primary CMV infection of the mother during pregnancy was made retrospectively by detection of CMV-immediate early antigen in three placentas as well as by examination of serum obtained from the mother during pregnancy.     

The insulin-like growth factor I generation test in the investigation of short stature

Genotypic and phenotypic heterogeneity in patients with growth hormone (GH) insensitivity syndrome suggests that partial defects exist in the GH receptor. The insulin-like growth factor I (IGF-I) generation test was assessed as a means of identifying partial GH receptor defects in a heterogeneous group of 22 prepubertal children with short stature. In a subgroup of nine patients with peak GH levels of 63.7 ± 3.7 mU/l during a glucagon tolerance test, the response to the IGF-I generation test was no different from that for the group as a whole (peak GH, 43.3 ± 4.5 mU/l), despite the fact that this subgroup exhibited a negative relationship between height SDS and peak GH and a positive relationship between height SDS and IGF binding protein-3. This preliminary study therefore suggests that the IGF-I generation test in its present form will not be useful as a primary screening test for partial GH insensitivity. Despite this, the IGF-I generation test has been extremely useful in the confirmation of the diagnosis of GHIS and may therefore also prove useful in the confirmation of partial defects in the GH receptor. A subgroup of short children with peak GH levels above 40 mU/l had some characteristics of partial GH receptor deficiency. These children, to whom GH therapy would not normally be given, may respond better to recombinant human IGF-I.