Study of 8-year-old children with a history of respiratory syncytial virus bronchiolitis in infancy.

Thirty-five children known to have had respiratory syncytial virus bronchiolitis in infancy were examined at the age of 8 and their respiratory function tested. The results were compared with those in 35 controls matched for age, sex, and social class. Although 18 of the children who had had bronchiolitis in infancy had experienced subsequent episodes of wheezing, these were neither severe nor frequent in most cases and had apparently ceased by the age of 8. Nevertheless, the mean exercise bronchial lability of the children who had had bronchiolitis was significantly higher than that of the control children and the mean peak expiratory flow rate at rest significantly lower. Atopy, assessed by family and personal history alone, did not seem to be related to either bronchiolitis or wheezing episodes after bronchiolitis. The parents of the children who had had bronchiolitis smoked significantly more cigarettes during the infant''s first year of life than those of the control children. The results suggest that bronchiolitis and childhood asthma are not closely related. Bronchial hyperreactivity might be inherited independently of atopy, but environmental factors seem the most likely link between severe respiratory infection in infancy and chronic or recurrent respiratory illness in adult life.     

GENETIC ENGINEERING TO AVOID GENETIC NEGLECT: FROM CHANCE TO RESPONSIBILITY

Currently our assessment of whether someone is a good parent depends on the environmental inputs (or lack of such inputs) they give their children. But new genetic intervention technologies, to which we may soon have access, mean that how good a parent is will depend also on the genetic inputs they give their children. Each new piece of available technology threatens to open up another way that we can neglect our children. Our obligations to our children and our susceptibilities to corresponding legal and moral sanctions may be about to explosively increase. In this paper I argue that we should treat conventional neglect and ‘genetic neglect’– failing to use genetic intervention technologies to prevent serious diseases and disabilities – morally consistently. I conclude that in a range of cases parents will have a moral obligation to use genetic treatments to prevent serious disabilities in their children. My particular focus is on prenatal interventions and their impact of the bodily integrity of expectant mothers. I conclude that although bodily integrity constrains moral obligations, it is outweighed in a range of cases.     

Biracial study of arterial pressures in the first and second decades of life.

The blood pressures of young Black and White American schoolchildren were measured and compared with those of Nigerian children of similar ages. Both diastolic and systolic pressures were consistently higher in the Nigerian children than in the Americans, both Black and White. The White children had the lowest pressures at each age. The mean weights and heights at each age were not significantly different in the three groups. Although the blood pressure of African children was higher than that of Black Americans, mean adult pressures are known to be similar in both groups. This suggests that the difference in childhood pressures must be due more to environmental factors than to genetic ones.     

GENETIC ANALYSIS OF MORNINGNESS AND EVENINGNESS

We studied the influence of genetic factors on individual differences in morningness-eveningness in a sample of Dutch twin families. Data were collected from adolescent twins (mean age 17.8 yr) and their parents (mean age of fathers 48.0 yr and of mothers 46.0 yr) and a sample of older twins (mean age 46.5 yr). Scores on morningness-eveningness were rated on a 5-point scale. Parents were more morning oriented than their children, and women were more morning oriented than men. With a twin-family study, separation of genetic and environmental influences on variation in morningness-eveningness is possible. Including parents and older twins in the study makes it possible to explore generation differences in these effects. The correlation between monozygotic twins was more than twice the correlation between dizygotic twins. This indicates that genetic effects may not operate in an additive manner. Therefore, a model that included genetic dominance was explored. Biometrical model fitting showed no sex differences for the magnitude of genetic and environmental factors. The total heritability—the sum of additive and nonadditive genetic influences—for morningness-eveningness was 44% for the younger generation and 47% for the older generation. However, the genetic correlation between the generations turned out to be lower than 0.5, suggesting that different genes for morningness-eveningness are expressed in both generations. (Chronobiology International, 18(5), 809-822, 2001)     

GENETIC ANALYSIS OF MORNINGNESS AND EVENINGNESS

We studied the influence of genetic factors on individual differences in morningness-eveningness in a sample of Dutch twin families. Data were collected from adolescent twins (mean age 17.8 yr) and their parents (mean age of fathers 48.0 yr and of mothers 46.0 yr) and a sample of older twins (mean age 46.5 yr). Scores on morningness-eveningness were rated on a 5-point scale. Parents were more morning oriented than their children, and women were more morning oriented than men. With a twin-family study, separation of genetic and environmental influences on variation in morningness-eveningness is possible. Including parents and older twins in the study makes it possible to explore generation differences in these effects. The correlation between monozygotic twins was more than twice the correlation between dizygotic twins. This indicates that genetic effects may not operate in an additive manner. Therefore, a model that included genetic dominance was explored. Biometrical model fitting showed no sex differences for the magnitude of genetic and environmental factors. The total heritability—the sum of additive and nonadditive genetic influences—for morningness-eveningness was 44% for the younger generation and 47% for the older generation. However, the genetic correlation between the generations turned out to be lower than 0.5, suggesting that different genes for morningness-eveningness are expressed in both generations. (Chronobiology International, 18(5), 809–822, 2001)     

Marfan disease

After reviewing the main features of the Marfan syndrome (musculoskeletal, ocular, cardiovascular, pulmonary abnormalities), its autosomal dominant inheritance with high penetrance but variable phenotype and presence of "soft" conditions preventing an easy diagnosis, the authors report their own data relevant to 73 probands: ratio of each clinical manifestation, state of 34% of familial cases and display of a paternal age effect in the sporadic cases. The pathogenic defect is unknown as like the location of the gene. The difficulties of the genetic counseling are then approached: unpredictability of the severity and of the prognosis in the unborn children of an affected patient, benefit of the echocardiography in the management of people at risk.     

Evaluation of the incidence of congenital rubella in GDR]

Annual number of congenital rubellas in GDR was evaluated by means of a mathematic model. Dates of inmunity rate of rubella in L. and P. districts obtained by means of haemagglutination inhibition reaction were taken into account. From these dates of a number of possible primary cases of rubella infection in wifes in the first 3 months of pregnancy as well as literary dates on mean number of monsters determined after the infection, i.e. 10--15--25% cases, were evaluated. There were obtained in relation with different mean numbers of monsters 37--56--93 cases of congenital rubellas for live born children from mothers at the age of 14 to 45 years. It results in total that the incidence of disease for live born children from mothers up to 45 years, is 0,2--0,5%, i.e. 2--5 children with congenital rubella on 10 000 live born children. Compared with literary data, it results a good correlation between proper evaluations and numbers of congenital rubella incidence quoted by other authors. In view of these evaluations, a conclusion to introduce protective rubella vaccination, is fully justified.     

Developmental evaluation of children born to mothers occupationally exposed to waste anesthetic gases

BACKGROUND: The etiology of developmental delay in children is frequently unknown. Increasing evidence supports the possibility that environmental and occupational factors might be part of the basis for such delays. This study focuses on the development of children born to mothers who were exposed during their pregnancy to waste anesthetic gases. METHODS: The study population included 40 children aged 5-13 years born to female anesthesiologists and nurses working in operating rooms (OpRs) exposed to waste anesthetic gases, and 40 unexposed children born to female nurses and physicians who worked in hospitals during their pregnancy but did not work in OpRs. The unexposed group was matched for children's age and gender and maternal occupation (nurses vs. doctors). By means of standardized developmental tests, the present study population was evaluated for their medical and neurodevelopmental state. Questionnaires were given for the detection of attention and activity levels as perceived by the parents. Additional questionnaires dealt with information concerning developmental milestones, maternal and fetal morbidity, and gynecological history. RESULTS: No differences were noted between the groups as newborns or in developmental milestones at the age of 5-13 years; however, the mean score of gross motor ability was significantly lower in the exposed versus the unexposed group. Additionally, the mean score of the DSM-III-R Parent-Teacher Questionnaire (PTQ) (i.e., measure of inattention/hyperactivity) was higher in the exposed group. The level of exposure, as measured by the number of weekly hours in the OpRs, was significantly and negatively correlated with fine motor ability and the score of IQ performance. CONCLUSIONS: Our study supports the hypothesis that occupational exposure to anesthetic gases might be a risk factor for minor neurological deficits of children born to mothers who work in OpRs and therefore indicates the need for more studies in this area and perhaps more caution among OpR pregnant women and employers.     

Attitudes to genetic testing in families with multiple cases of bipolar disorder

OBJECTIVES: This study assesses interest in genetic testing for gene variations associated with bipolar disorder and associated information needs. METHODS: Two hundred individuals (95 unaffected and 105 affected with either bipolar disorder, schizoaffective disorder--manic type, or recurrent major depression) from families with multiple cases of bipolar disorder were assessed, using mailed, self-administered questionnaires. RESULTS: The percentage of participants reporting interest in genetic testing was associated with the degree of certainty with which any test would indicate the development of bipolar disorder. Interest in genetic testing, given a 25% lifetime risk scenario, was lowest (with 77% of participants indicating interest), and highest for the 100% lifetime risk scenario (92%). Eighty percent of participants indicated interest in genetic testing of their own children; of these 30% reported wanting their children tested at birth, and 33% in early childhood. Forty-one percent of participants reported that they would be interested in preimplantation genetic diagnosis, and 54% in prenatal testing. LIMITATIONS: The possibility of ascertainment bias cannot be ruled out. Interest in hypothetical genetic testing for bipolar disorder may not necessarily translate into actual utilization. CONCLUSIONS: These results indicate that uptake of genetic testing for genotyping for low-risk alleles related to bipolar disorder is likely to be lower than for testing for high-penetrance gene mutations that follow Mendelian inheritance. The discrepancy between the desired age of testing children and the accepted current practice may be a source of distress and conflict for parents and health professionals alike.     

The Feet of Overweight and Obese Young Children: Are They Flat or Fat?

Objective: The purpose of this study was to determine whether the flat feet displayed by young obese and overweight children are attributable to the presence of a thicker midfoot plantar fat pad or a lowering of the longitudinal arch relative to that in non‐overweight children. Research Methods and Procedures: Foot anthropometry, an arch index derived from plantar footprints, and midfoot plantar fat pad thickness measured by ultrasound were obtained for 19 overweight/obese preschool children (mean age, 4.3 ± 0.9 years; mean height, 1.07 ± 0.1 m; mean BMI, 18.6 ± 1.2 kg/m²) and 19 non‐overweight children matched for age, height, and sex (mean age, 4.3 ± 0.7 years; mean height, 1.05 ± 0.1 m; mean BMI, 15.7 ± 0.7 kg/m²). Results: Independent t tests revealed no significant between‐subject group differences (p = 0.39) in the thickness of the midfoot plantar fat pad. However, the overweight/obese children had a significantly lower plantar arch height (0.9 ± 0.3 cm) than their non‐overweight counterparts (1.1 ± 0.2 cm; p = 0.04). Discussion: The lower plantar arch height found in the overweight/obese children suggests that the flatter feet characteristic of overweight/obese preschool children may be caused by structural changes in their foot anatomy. It is postulated that these structural changes, which may adversely affect the functional capacity of the medial longitudinal arch, might be exacerbated if excess weight bearing continues throughout childhood and into adulthood.     

Evidence for the late MMN as a neurophysiological endophenotype for dyslexia

Dyslexia affects 5-10% of school-aged children and is therefore one of the most common learning disorders. Research on auditory event related potentials (AERP), particularly the mismatch negativity (MMN) component, has revealed anomalies in individuals with dyslexia to speech stimuli. Furthermore, candidate genes for this disorder were found through molecular genetic studies. A current challenge for dyslexia research is to understand the interaction between molecular genetics and brain function, and to promote the identification of relevant endophenotypes for dyslexia. The present study examines MMN, a neurophysiological correlate of speech perception, and its potential as an endophenotype for dyslexia in three groups of children. The first group of children was clinically diagnosed with dyslexia, whereas the second group of children was comprised of their siblings who had average reading and spelling skills and were therefore "unaffected" despite having a genetic risk for dyslexia. The third group consisted of control children who were not related to the other groups and were also unaffected. In total, 225 children were included in the study. All children showed clear MMN activity to/da/-/ba/contrasts that could be separated into three distinct MMN components. Whilst the first two MMN components did not differentiate the groups, the late MMN component (300-700 ms) revealed significant group differences. The mean area of the late MMN was attenuated in both the dyslexic children and their unaffected siblings in comparison to the control children. This finding is indicative of analogous alterations of neurophysiological processes in children with dyslexia and those with a genetic risk for dyslexia, without a manifestation of the disorder. The present results therefore further suggest that the late MMN might be a potential endophenotype for dyslexia.     

Chromosomal abnormalities among offspring of childhood-cancer survivors in Denmark: a population-based study

Ionizing radiation and many cancer drugs have the potential to produce germ-cell mutations that might lead to genetic disease in the next generation. In a population-based study, we identified, from records in the Danish Cancer Registry, 4,676 children treated for cancer. Their 6,441 siblings provided a comparison cohort. The results of a search of the Central Population Register identified 2,630 live-born offspring of the survivors and 5,504 live-born offspring of their siblings. The occurrence of abnormal karyotypes diagnosed in these offspring and also in any pregnancies terminated following prenatal diagnosis of a chromosome abnormality was determined from the Danish Cytogenetic Registry. After exclusion of hereditary cases and inclusion of the prenatal cases, after correction for expected viability, the adjusted proportion of live-born children in survivor families with abnormal karyotypes (5.5/2,631.5 [0.21%]) was the same as that among the comparison sibling families (11.8/5,505.8 [0.21%]). There were no significant differences in the occurrence of Down syndrome (relative risk [RR]=1.07; 95% CI 0.16-5.47) or Turner syndrome (RR=1.32; 95% CI 0.17-7.96) among the children of cancer survivors, compared with the children of their siblings. These reassuring results are of importance to the survivors, to their families, and to genetic counselors.     

Huntington's disease. Contribution of clinical and epidemiological data to genetic counseling

From a regional survey (northwestern part of France 3,9 millions population) and from recent publications, the authors described clinical and epidemiologic aspects useful for genetic counselling. Besides the chronic chorea, the other clinical features justified the denomination "Huntington's disease". Misdiagnosis is frequent especially if the familial disorder is unknown. A prevalence of 50 X 10(-6) corresponds to 2750 choreics and 14.000 at risk descendants in France. Interfamilial heterogeneity is described from mean age of death which is 54.2 for the whole study: one third of families of late onset, around fifty (mean age of death: 64.6), one third of early onset, around thirty (mean age of death: 44.6). The 17 juvenile and infantile cases of the survey belong to this last group. The influence of gene-transmitters sex is more obvious if two generations are taken in account with a preponderance of fathers and grand-fathers in the early onset group and, to a lesser degree, of mothers and grand-mothers in the late onset group. The authors criticize the preclinical detection tests and, from attitudes of families, underline the ethical problems for the future predictive tests by genetic markers. The role of lay organisations is all the more important.     

EPIDEMIOLOGY OF ACCIDENTAL POISONING

In San Jose, California, studies of cases of accidental poisoning showed that the greatest hazard was to children 1 through 3 years of age. Drugs accounted for half the cases, household products for another third, and insecticides and rodenticides and others for the remainder. Most often poison material was within easy reach of the children. An analysis of families in which an accident occurred indicated that accidental poisoning might happen to any family. Since there was little after-effect of poisoning in cases in which treatment was obtained promptly, education directed toward getting prompt treatment seems most advisable. Community agencies interested in poison control need to focus their attention on parents of pre-school children.     

Impact of war on growth patterns in school children in Croatia

The objective of this paper is to present the growth patterns of school children in Osijek--the city which was exposed to severe attacks during the aggression on Croatia. The mean height and weight of Osijek schoolchildren aged 7 to 18 and the menarcheal age in girls in academic year 1995/96 were compared to the analogous data collected in 1980/81. The secular changes in height were heterogeneous. In older age groups from 12 in girls and 13 in boys, the mean height in 1995/96 increased markedly, whereas from 9 to 11 or 12, changes were undulating. In the youngest groups--at the age of 7 in both genders, and at 8 in boys, negative changes were observed. Markedly smaller height in this cohort was still pronounced in 1999/2000 when these children reached the age of 11. However, one year later (2000/01), at the age of 12, boys and girls caught up with their peers in the previous generations. These children during the war were approximately at the age of 2.5 to 4, a period when growth patterns are highly sensitive to adverse environmental influences. It might be possible that the emotional stress caused by a change of environment and separation from home, contributed to the deceleration of growth rate, i.e. the smaller height in a large part of childhood.     

The influence of gender and somatotype on single-leg upright standing postural stability in children

The purpose of this study was to investigate the influence of gender and somatotypes on single-leg upright standing postural stability in children. A total of 709 healthy children from different schools were recruited to measure the anthropometric somatotypes and the mean radius of center of pressure (COP) on a force platform with their eyes open and eyes closed. The results were that (a) girls revealed significantly smaller mean radius of COP distribution than boys, both in the eyes open and eyes closed conditions, and (b) the mesomorphic, muscular children had significantly smaller mean radius of COP distribution than the endomorphic, fatty children and the ectomorphic, linear children during the eyes closed condition. The explanation for gender differences might be due to the larger body weight in boys. The explanation for somatotype differences might be due to the significantly lower body height and higher portion of muscular profile in the mesomorphic children.     

The present prophylactic trends of rubella and measles

Starting from the epidemiological investigation on a sample of 22.560 subjects of different chronological age classes in the Latium region with the research of hemoagglutinoinhibiting antibodies of the Rubella virus, and of 9.800 subjects with the research of hemoagglutinoinhibiting antibodies of the Measles virus, the authors observe that the diffusion of the seroprotection presents on an average 82.5% for Rubella and 79.8% for Measles. On the strength of the results, referred also according to the established chronological age classes, any obligatory treatment against Rubella is excluded in prepuberal age. In order to prevent the risk of congenital malformation in cases of pregnant and not seroprotected subjects who, during the first three months of gestation might come into contact with sick affected by Rosolia or with healthy carriers, the authors suggest the vaccination three months before the conception. Evidently, this involves a screening of the adult female population before their marriage. On the contrary as concerns Measles, the vaccination within the second year of life is being hypothesized exactly on the basis of the consideration that this is a matter of a serious illness and not always free from grave complications. In these cases, after shortly referring on the results of the experiments of different authors, the mixed anti-Measles and anti-Rubella vaccination might be taken into consideration, though with all the precautions that are suggested.     

Genome-Wide Analysis of Human Metapneumovirus Evolution

Human metapneumovirus (HMPV) has been described as an important etiologic agent of upper and lower respiratory tract infections, especially in young children and the elderly. Most of school-aged children might be introduced to HMPVs, and exacerbation with other viral or bacterial super-infection is common. However, our understanding of the molecular evolution of HMPVs remains limited. To address the comprehensive evolutionary dynamics of HMPVs, we report a genome-wide analysis of the eight genes (N, P, M, F, M2, SH, G, and L) using 103 complete genome sequences. Phylogenetic reconstruction revealed that the eight genes from one HMPV strain grouped into the same genetic group among the five distinct lineages (A1, A2a, A2b, B1, and B2). A few exceptions of phylogenetic incongruence might suggest past recombination events, and we detected possible recombination breakpoints in the F, SH, and G coding regions. The five genetic lineages of HMPVs shared quite remote common ancestors ranging more than 220 to 470 years of age with the most recent origins for the A2b sublineage. Purifying selection was common, but most protein genes except the F and M2-2 coding regions also appeared to experience episodic diversifying selection. Taken together, these suggest that the five lineages of HMPVs maintain their individual evolutionary dynamics and that recombination and selection forces might work on shaping the genetic diversity of HMPVs.     

Fatal cases of influenza A(H3N2) in children: insights from whole genome sequence analysis

During the Northern Hemisphere winter of 2003-2004 the emergence of a novel influenza antigenic variant, A/Fujian/411/2002-like(H3N2), was associated with an unusually high number of fatalities in children. Seventeen fatal cases in the UK were laboratory confirmed for Fujian/411-like viruses. To look for phylogenetic patterns and genetic markers that might be associated with increased virulence, sequencing and phylogenetic analysis of the whole genomes of 63 viruses isolated from fatal cases and non fatal "control" cases was undertaken. The analysis revealed the circulation of two main genetic groups, I and II, both of which contained viruses from fatal cases. No associated amino acid substitutions could be linked with an exclusive or higher occurrence in fatal cases. The Fujian/411-like viruses in genetic groups I and II completely displaced other A(H3N2) viruses, but they disappeared after 2004. This study shows that two A(H3N2) virus genotypes circulated exclusively during the winter of 2003-2004 in the UK and caused an unusually high number of deaths in children. Host factors related to immune state and differences in genetic background between patients may also play important roles in determining the outcome of an influenza infection.     

Mating system parameters in species of genus Prosopis (Leguminosae)

The section Algarobia of genus Prosopis involves important natural resources in arid and semiarid regions of the world. Their rationale use requires a better knowledge of their biology, genetics and mating system. There are contradictory information about their mating system. Some authors claim they are protogynous and obligate outcrosser. However, some evidence have been shown indicating that they might not be protogynous and that they might be somewhat self-fertile. The current paper analyses genetic structure and mating system parameters in populations of seven species of this section from South and North America based on isozyme data. In all species a significant homozygote excess was found in the offspring population but not in mother plant genotypes. Multilocus and mean single locus outcrossing rates (tm, ts) indicated that about 15% selfing can occur in the studied populations. The heterogeneity between pollen and ovule allele frequencies was low suggesting population structuration, in agreement with the estimates of correlation of tm within progeny (rt) and correlation of outcrossed paternity (rp). The difference of FIS estimates between offspring and mother plants suggest some selection favouring heterozygotes between seedling and adult stages.