Placental IGF-I, IGFBP-1, zinc, and iron, and maternal and infant anthropometry at birth

Aim: To correlate placental protein levels of insulin‐like growth factor (IGF)‐I and insulin‐like growth factor binding protein (IGFBP)‐1, with previously determined levels of IGF‐I and IGF‐II mRNA expression, and the micronutrients zinc and iron, and maternal and newborn anthropometry. Methods: Placental samples were collected from rural field sites in Pakistan. Samples were divided into small and large for gestational age groups (SGA and LGA, respectively). IGFBP‐1 levels were assessed using Western immunoblotting. IGF‐I protein levels were assessed using ELISA techniques. IGF mRNA expression, zinc, and iron, were quantified as previously described and were used for comparative purposes only. Results: Thirty‐three subjects were included (SGA, n = 12; LGA n = 21). Higher levels of IGFBP‐1 were seen in the SGA group (p < 0.01). IGFBP‐1 correlated positively with maternal and infant triceps skin‐fold thickness in the LGA and SGA groups, respectively (p < 0.05). Significantly lower IGF‐I protein levels were seen in the SGA group. IGF‐I levels correlated significantly with maternal and newborn anthropometry. IGFBP‐1 correlated significantly with IGF‐II mRNA expression (p < 0.05). Conclusion: Placental protein levels of IGF‐I and IGFBP‐1 appear to be associated with maternal anthropometry. Maternal anthropometry may thus influence IGFBP‐1 and IGF‐I levels and may possibly be used for screening of pregnancies, with the potential for timely identification of these high‐risk pregnancies.     

Pertussis in infants, children, and adolescents: diagnosis, treatment, and prevention

Pertussis, or "whooping cough," caused by the gram-negative pleomorphic bacillus Bordetella pertussis, is a highly contagious, potentially life-threatening respiratory tract illness that has re-emerged worldwide as a cause of substantial morbidity and mortality in infants, children, and adolescents, despite high vaccination rates. Increased awareness and reporting, in addition to the availability of better diagnostic tests, partially explain the recent resurgence of pertussis. However, waning immunity after childhood immunization has resulted in a growing pool of susceptible adolescents and adults who are capable of transmitting pertussis to vulnerable unvaccinated or incompletely vaccinated infants. An acellular pertussis vaccine booster for adolescents has been recommended in the United States and other industrialized countries. Active immunization and early diagnosis are crucial in the management of pertussis.     

Lipids, lipoproteins and apolipoproteins AI, AII, B, CII, CIII and E in newborns.

In this study lipid and apolipoprotein patterns were investigated at birth and compared with those of adults. In cord sera, cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were 38.2, 46.2, 50.5, and 31.9%, respectively, of adult values. Apolipoprotein AII, B and CIII were 48.6, 30.6 and 44.5% of adult values, while apo AI, apo CII and apo E showed values approaching those of adults (63.4, 73.3 and 89.7%, respectively). Also cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios were lower in newborns. In cord sera, lipids were correlated with various apolipoproteins in a surprisingly different way from adult sera. HDL cholesterol was not inversely correlated with triglycerides, and showed a highly positive correlation with apo E, apo CII and apo CIII, which did not correlate with HDL cholesterol in adults. These data supported the presence of significant differences in plasma concentrations and composition of lipoproteins at birth. Therefore HDL, apo CII, and apo E seem to play a different and more important metabolic role in neonatal lipid metabolism.     

Stones, bones, and heredity

Genetic disorders of mineral metabolism cause urolithiasis, renal disease, and osteodystrophy. Most are rare, such that the full spectrum of clinical expression is difficult to appreciate. Diagnosis is further complicated by overlap of clinical features. Dent's disease and primary hyperoxaluria, inherited causes of calcium urolithiasis, are both associated with nephrocalcinosis and urolithiasis in early childhood and renal failure that can occur at any age but is seen more often in adulthood. Bone disease is an inconsistent feature of each. Dent's disease is caused by mutations of the CLCN-5 gene with impaired kidney-specific CLC-5 chloride channel expression in the proximal tubule, thick ascending limb of Henle, and the collecting ducts. Resulting hypercalciuria and proximal tubule dysfunction, including phosphate wasting, are primarily responsible for the clinical manifestations. Low-molecular-weight proteinuria is characteristic. Definitive diagnosis is made by DNA mutation analysis. Primary hyperoxaluria, type I, is due to mutations of the AGXT gene leading to deficient hepatic alanine–glyoxylate aminotransferase activity. Marked overproduction of oxalate by hepatic cells results in the hyperoxaluria responsible for clinical features. Definitive diagnosis is by liver biopsy with measurement of enzyme activity, with DNA mutation analysis used increasingly as mutations and their frequency are defined.

Conclusion

These disorders of calcium urolithiasis illustrate the value of molecular medicine for diagnosis and the promise it provides for innovative and more effective future treatments.     

Winning, losing, and violence

BACKGROUND: Although international sports events attract huge interest, and results can be a barometer of popular national standing, their impact on violent behaviour has not been investigated. METHODS: Associations between assault related emergency department (ED) attendances and international sporting events (home and away rugby and soccer matches) in a European capital city (Cardiff) served by one ED, between 1 May 1995 and 30 April 2002 were investigated. The frequency of assault related ED attendances were studied relative to whether the national team won or lost, controlling for potential covariates: match attendance, match location (home/away), results (win/lose), net scores, and day of match (weekend/weekday). Multiple linear regression was used to identify significant associations with ED assault related attendances. RESULTS: Matches which the Wales team won (p = 0.03), match attendance (p<0.001), and weekend matches (p<0.001) were positively associated with ED assault related injury attendances. Assault frequency measured in this way was no different for home and away matches. CONCLUSIONS: Assault injury resulting in ED treatment was more frequent when national teams won than when they lost. Sport type made no difference. Violence prevention efforts should be increased on international match days, when the national team is expected to win, when match attendance is large, and for away as well as home matches.     

Children, adolescents, and advertising

Advertising is a pervasive influence on children and adolescents. Young people view more than 40,000 ads per year on television alone and increasingly are being exposed to advertising on the Internet, in magazines, and in schools. This exposure may contribute significantly to childhood and adolescent obesity, poor nutrition, and cigarette and alcohol use. Media education has been shown to be effective in mitigating some of the negative effects of advertising on children and adolescents.     

Serum protein binding of diazepam, desmethyldiazepam, furosemide, indomethacin, warfarin, and phenobarbital in human fetus, mother, and newborn infant

The protein binding of diazepam, desmethyldiazepam, furosemide, indomethacin, warfarin, and phenobarbital in maternal and fetal cord serum at the time of birth, and in serum of neonates between 1 and 11 days of age was studied. The protein binding of diazepam and desmethyldiazepam was higher in the fetus than in the mother, thus explaining the fetal cumulation of these drugs in vivo. After birth, both drugs were partially displaced from neonatal binding sites. The decreased protein binding capacity in the mother and the neonate related to increased free fatty-acid levels. The pattern of protein binding of warfarin in the groups investigated was a mirror image of those of diazepam and its metabolite. The protein binding of indomethacin progressively decreased in the neonate during the first two postnatal weeks, while that of furosemide remained at lowered levels throughout this time interval. The protein binding of phenobarbital was similar in the groups investigated. Our results suggest that drugs such as diazepam, which can be displaced from binding sites by free fatty acids, may cumulate in the fetus and may exhibit much decreased protein binding and possibly unexpectedly strong effects in the neonate after birth.     

GH, IGF-I, and growth

Recent studies have confirmed the importance of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis as the major determinant of whole body growth in animals and humans and have highlighted the significance of IGF-I to human growth. Pharmacological studies in rodents and therapeutic studies in humans demonstrate that recombinant human (rh)IGF-I can induce a significant statural growth response. Mouse gene knockout studies have shown that IGF-I, rather than GH, is the major hormone controlling whole body growth. The relative importance of endocrine versus local IGF-I remains unresolved. In children who are GH- and IGF-I-deficient, treatment with GH stimulates a robust growth response. In children who are IGF-I-deficient but GH-sufficient, rhIGF-I might also be a useful treatment. Furthermore, pharmacological and genetic studies in animals show effects requiring the combined presence of GH and IGF-I, suggesting that rhGH and rhIGF-I together might be the optimal treatment for some children with short stature.     

Children, adolescents, and television

As we have indicated, children's television has either a documented or probable effect on a variety of health-related behaviors in children and adolescents in the United States. Studies of cognitive development indicate that television provides a stimulus for learning and that children learn from television. The adverse effects of television appear related to both the time spent watching television and the content of the programs that are viewed. The reviewed observations suggest that a variety of initiatives are warranted to alter the time children spend watching television, the content of programs, and the types of programs for children and adolescents that are produced and broadcast. These initiatives require the development of effective techniques and materials for counseling parents, as well as continued political and legislative activities at the local and national level. We must promote the conviction that time spent in activities other than television viewing will provide our children with the values necessary to understand and interact with an increasingly complex world. Effective governmental action on behalf of children to change television will require a reaffirmation and enforcement of the Public Interest Standard. For half a century, the broadcast media have been licensed to use the airwaves in the public interest. The diversity and magnitude of the adverse effects of television on the health of children strongly suggest that the use of television has not been in the public interest. Although cable television offers multiple alternatives, less than 60% of American households receive cable. Broadcast television still represents the only alternative for 40% of American children. Substantial regulatory change by the current administration is unlikely. Therefore, legislative activity to mandate broadcast practices responsive to the needs of children appears the most appropriate national approach.     

Bacterial infections,immune overload,and MMR vaccine. Measles,mumps, and rubella

Combined measles, mumps, and rubella (MMR) vaccine did not increase the risk of hospitalisation with invasive bacterial infection in the three months after vaccination; rather there was a protective effect. These results provide no support for the concept of "immunological overload" induced by multiple antigen vaccinations, nor calls for single antigen vaccines.     

Children, adolescents, obesity, and the media

Obesity has become a worldwide public health problem. Considerable research has shown that the media contribute to the development of child and adolescent obesity, although the exact mechanism remains unclear. Screen time may displace more active pursuits, advertising of junk food and fast food increases children's requests for those particular foods and products, snacking increases while watching TV or movies, and late-night screen time may interfere with getting adequate amounts of sleep, which is a known risk factor for obesity. Sufficient evidence exists to warrant a ban on junk-food or fast-food advertising in children's TV programming. Pediatricians need to ask 2 questions about media use at every well-child or well-adolescent visit: (1) How much screen time is being spent per day? and (2) Is there a TV set or Internet connection in the child's bedroom?     

Stones, bones, and heredity

Genetic disorders of mineral metabolism cause urolithiasis, renal disease, and osteodystrophy. Most are rare, such that the full spectrum of clinical expression is difficult to appreciate. Diagnosis is further complicated by overlap of clinical features. Dent's disease and primary hyperoxaluria, inherited causes of calcium urolithiasis, are both associated with nephrocalcinosis and urolithiasis in early childhood and renal failure that can occur at any age but is seen more often in adulthood. Bone disease is an inconsistent feature of each. Dent's disease is caused by mutations of the CLCN-5 gene with impaired kidney-specific CLC-5 chloride channel expression in the proximal tubule, thick ascending limb of Henle, and the collecting ducts. Resulting hypercalciuria and proximal tubule dysfunction, including phosphate wasting, are primarily responsible for the clinical manifestations. Low-molecular-weight proteinuria is characteristic. Definitive diagnosis is made by DNA mutation analysis. Primary hyperoxaluria, type I, is due to mutations of the AGXT gene leading to deficient hepatic alanine-glyoxylate aminotransferase activity. Marked overproduction of oxalate by hepatic cells results in the hyperoxaluria responsible for clinical features. Definitive diagnosis is by liver biopsy with measurement of enzyme activity, with DNA mutation analysis used increasingly as mutations and their frequency are defined.These disorders of calcium urolithiasis illustrate the value of molecular medicine for diagnosis and the promise it provides for innovative and more effective future treatments.     

Clicks,Whoops, and Honks

5 children are described with the midsystolic click—systolic murmur syndrome, sometimes accompanied by honks or whoops. The characteristic variation in auscultatory findings with posture is shown. The theory as to the mechanism of production of these findings is described, together with their aetiologies, prognosis, and treatment.     

Hyperdibasicaminoaciduria, hyperammonemia, and growth retardation: Treatment with arginine, lysine, and citrulline.

A 9-year-old girl with hereditary dibasicaminoaciduria has been studied for three years. Initially, clinical features were: growth failure; anorexia and aversion to protein, spontaneous daily protein intake averaging only 10 gm; fasting and postprandial venous hyperammonemia; subnormal plasma concentrations of lysine, arginine, ornithine, and citrulline, with generalized hypermonobasicaminoacidemia; abnormally high renal clearances of lysine, arginine, and ornithine; and intestinal malabsorption of lysine and arginine. Intestinal absorption of citrulline, a precursor of arginine and ornithine, was normal. The patient was observed during four sequential 6-month periods as follows: no treatment (Period I); dietary supplement of arginine and lysine (Period II); dietary supplement of citrulline and lysine (Period III); no treatment (Period IV). During Periods II and III growth rate increased 3- to 4-fold, spontaneous protein intake increased 2- to 3-fold, and abnormalities in blood NH3 and the plasma aminogram were partially corrected. In most respects the citrulline plus lysine supplement was more beneficial than that of arginine plus lysine.     

Media and children's aggression, fear, and altruism

Noting that the social and emotional experiences of American children today often heavily involve electronic media, Barbara Wilson takes a close look at how exposure to screen media affects children's well-being and development. She concludes that media influence on children depends more on the type of content that children find attractive than on the sheer amount of time they spend in front of the screen. Wilson begins by reviewing evidence on the link between media and children's emotions. She points out that children can learn about the nature and causes of different emotions from watching the emotional experiences of media characters and that they often experience empathy with those characters. Although research on the long-term effects of media exposure on children's emotional skill development is limited, a good deal of evidence shows that media exposure can contribute to children's fears and anxieties. Both fictional and news programming can cause lasting emotional upset, though the themes that upset children differ according to a child's age. Wilson also explores how media exposure affects children's social development. Strong evidence shows that violent television programming contributes to children's aggressive behavior. And a growing body of work indicates that playing violent video games can have the same harmful effect. Yet if children spend time with educational programs and situation comedies targeted to youth, media exposure can have more prosocial effects by increasing children's altruism, cooperation, and even tolerance for others. Wilson also shows that children's susceptibility to media influence can vary according to their gender, their age, how realistic they perceive the media to be, and how much they identify with characters and people on the screen. She concludes with guidelines to help parents enhance the positive effects of the media while minimizing the risks associated with certain types of content.     

Media and attention, cognition, and school achievement

Marie Evans Schmidt and Elizabeth Vandewater review research on links between various types of electronic media and the cognitive skills of school-aged children and adolescents. One central finding of studies to date, they say, is that the content delivered by electronic media is far more influential than the media themselves. Most studies, they point out, find a small negative link between the total hours a child spends viewing TV and that child's academic achievement. But when researchers take into account characteristics of the child, such as IQ or socioeconomic status, this link typically disappears. Content appears to be crucial. Viewing educational TV is linked positively with academic achievement; viewing entertainment TV is linked negatively with achievement. When it comes to particular cognitive skills, say the authors, researchers have found that electronic media, particularly video games, can enhance visual spatial skills, such as visual tracking, mental rotation, and target localization. Gaming may also improve problem-solving skills. Researchers have yet to understand fully the issue of transfer of learning from electronic media. Studies suggest that, under some circumstances, young people are able to transfer what they learn from electronic media to other applications, but analysts are uncertain how such transfer occurs. In response to growing public concern about possible links between electronic media use and attention problems in children and adolescents, say the authors, researchers have found evidence for small positive links between heavy electronic media use and mild attention problems among young people but have found only inconsistent evidence so far for a link between attention deficit hyperactivity disorder and media use. The authors point out that although video games, interactive websites, and multimedia software programs appear to offer a variety of possible benefits for learning, there is as yet little empirical evidence to suggest that such media are more effective than other forms of instruction.