Serum immunoglobulin A concentration in infancy, but not human milk immunoglobulin A, is associated with subsequent atopic manifestations in children and adolescents: a 20-year prospective follow-up study.

BACKGROUND: Serum and secretory IgA concentrations have been suggested to be inversely associated with allergic symptoms in children. Furthermore, low maternal milk IgA concentration has been suggested to be associated with the development of cow's milk allergy. OBJECTIVE: Our aim was to explore whether the serum IgA concentrations in infancy and the IgA concentration of maternal milk predict atopic manifestations in childhood and up to age 20 years. METHODS: A cohort of 200 unselected full-term newborns was prospectively followed up from birth to age 20 years with measurement of serum total IgA at ages 2 and 6 months. The mothers were encouraged to maintain exclusive breastfeeding for as long as possible. Total IgA concentration of maternal milk was measured at birth (colostrum, n=169) and at 2 (n=167) and 6 (n=119) months of lactation. The children were re-assessed at ages 5, 11 and 20 years for the occurrence of allergic symptoms, with skin prick testing and measurement of serum IgE. RESULTS: Children and adolescents with respiratory allergic symptoms and sensitization had a higher serum IgA concentration at age 2 months than the non-atopic subjects. Colostrum and breast milk IgA concentrations were not associated with the development of allergic symptoms in the recipient infant. However, maternal milk IgA concentration at 6 months of lactation was inversely associated with elevated serum total IgE and positive skin prick test to tree pollen in the offspring at age 20 years. CONCLUSIONS AND CLINICAL RELEVANCE: Increased serum IgA concentration at age 2 months is associated with the development of subsequent allergic symptoms and sensitization in childhood and adolescence. Maternal milk IgA concentrations are not associated with subsequent allergic symptoms in the recipient infant. The present study provides novel information on the role of IgA in the development of respiratory allergy and sensitization.

Serum cholesterol level in infancy is inversely associated with subsequent allergy in children and adolescents. A 20-year follow-up study.

BACKGROUND: Previous studies suggest an association between an altered lipoprotein profile and atopy. The association has been hypothesized to be due to alterations in the dietary fat intake, a factor possibly contributing to the increase of allergic diseases in industrialized countries. OBJECTIVE: We aimed at assessing whether there is an association between the serum lipid levels in infancy and subsequent development of allergic symptoms in childhood and adolescence. METHODS: A cohort of 200 unselected newborns was prospectively followed up from birth to age 20 years (from 1981 to 2002) with repeated measurements of total cholesterol from birth and throughout the first year of life. The subjects were re-examined at the ages of 5, 11 and 20 years, with assessment of the occurrence of allergic symptoms, skin prick testing (SPT) and measurement of total IgE and of the total, high- and low-density lipoprotein cholesterol. RESULTS: Children and adolescents with allergic symptoms, SPT positivity and an elevated IgE had lower total cholesterol levels in infancy and childhood than the non-atopic subjects. The difference was not detectable in cord blood, but became significant from age 2 months onward. CONCLUSION: The inverse association between the cholesterol level in infancy and subsequent manifestations of atopy seems not to be due to atopy-related dietary alterations, because it was already present in early infancy, when virtually all the infants were on a similar diet, i.e. on exclusive breastfeeding.

Retinol concentrations after birth are inversely associated with atopic manifestations in children and young adults.

BACKGROUND: Vitamin A has anti-inflammatory and immunomodulatory effects, and its deficiency results in impaired specific and innate immunity. Vitamin A is essential for inducing the gut-homing specificity on T cells. OBJECTIVE: As an impaired gut immune response in early infancy may contribute to the development of atopic sensitization, we looked for an association of plasma retinol concentrations and the subsequent development of allergic symptoms in healthy infants. METHODS: A cohort of 200 unselected, full-term newborns were followed up from birth to age 20 years. The plasma retinol concentration was determined in cord blood (n=97), at ages of 2, 4 and 12 months (n=95), and at ages 5 years (n=155) and 11 years (n=151). The subjects were re-examined at the ages of 5, 11 and 20 years with assessment of the occurrence of allergic symptoms during the preceding year, skin prick testing and measurement of serum total IgE. RESULTS: subjects with allergic symptoms or a positive skin prick test (SPT) in childhood or adolescence had lower retinol concentrations in infancy and childhood than symptom-free subjects. The difference was most pronounced at age 2 months. Retinol concentration at 2 months correlated inversely with positive SPT at ages of 5 and 20 years, and with allergic symptoms at age 20 years. CONCLUSION: Retinol concentration in young infants is inversely associated with the subsequent development of allergic symptoms. We propose that an inborn regulation of retinol may play a role in atopic sensitization, possibly through regulating the intestinal T cell responses.

Prolonged exclusive breastfeeding is associated with increased atopic dermatitis: a prospective follow-up study of unselected healthy newborns from birth to age 20 years.

BACKGROUND: Exclusive breastfeeding for the first 6 months is recommended by the World Health Organization and considered allergy preventive. However, it is not known whether prolonging exclusive breastfeeding for over 6 months provides further benefit in allergy prevention. OBJECTIVE: The aim of this prospective 20-year follow-up study was to find out whether the allergy protective effect can be enhanced by prolonging strictly exclusive breastfeeding for > or =9 months of age. A total of 200 unselected healthy newborns were enrolled in the study. Their mothers were encouraged to maintain exclusive breastfeeding for as long as possible. The number of infants on strictly exclusive breastfeeding was 167 at 2, 116 at 6, 36 at 9 and 7 at 12 months of age. Of the 200 infants, 42% had a family history of allergy. The children were re-assessed at ages 5 (n=163), 11 (n=150) and 20 years (n=164) with clinical examination, skin prick testing, and parental and personal structured interviews. RESULTS: Exclusive breastfeeding prolonged for > or =9 months was associated with atopic dermatitis (P=0.002) and symptoms of food hypersensitivity (P=0.02) at age 5 years, and with symptoms of food hypersensitivity at age 11 years (P=0.01), in children with a family history of allergy. CONCLUSION: Prolonging strictly exclusive breastfeeding for > or =9 months was not helpful in atopy prevention, instead, it was associated with increased atopic dermatitis and food hypersensitivity symptoms in childhood.

Long-term results in children with AML: NOPHO-AML Study Group--report of three consecutive trials.

In all, 447 children with acute myeloid leukaemia (AML) have been treated on three consecutive NOPHO studies from July 1984 to December 2001. NOPHO-AML 84 was of moderate intensity with an induction of three courses of cytarabine, 6-thioguanine and doxorubicin followed by four consolidation courses with high-dose cytarabine. The 5-year event-free survival (EFS), disease free survival (DFS) and overall survival (OS) were 29, 37 and 38%. NOPHO-AML 88 was of high intensity with the addition of etoposide and mitoxantrone in selected courses during induction and consolidation. The interval between the induction courses should be as short as possible, that is, time intensity was introduced. The 5-year EFS, DFS and OS were 41, 48 and 46%. In NOPHO-AML 93, the treatment was stratified according to response to first induction course. The protocol utilised the same induction blocks as NOPHO-AML 88, but after the first block, children with a hypoplastic, nonleukaemic bone marrow were allowed to recover before the second block. Consolidation was identical with NOPHO-AML 88. The 5-year EFS, DFS and OS in NOPHO-AML 93 were 48, 52 and 65%. The new NOPHO-AML protocol has been based on experiences from previous protocols with stratification of patients with regard to in vivo response and specific cytogenetic aberrations.

Long-term prognosis of children with Down's syndrome and leukaemia: a 34-year nation-wide experience.

BACKGROUND: Although the characteristics of leukaemia in patients with Down's syndrome (DS) have been well documented, little is known about the long-term results of treatment. METHOD: Retrospectively from 1968 to 1981 and prospectively from 1982 to 2002, the present authors collected data on every child with DS in Finland who had been diagnosed with leukaemia between 1968 and 1994. RESULTS: Forty-one children with DS had acute leukaemia: 28 had acute lymphoblastic leukaemia (ALL); and 13 had acute non-lymphoblastic leukaemia (ANLL). The median age of the subjects at diagnosis was 3.8 years (range = 0-15.9 years). Patients with ANLL were significantly younger (P = 0.001) and all patients under 2 years of age had ANLL. Out of the 28 patients with ALL, 23 (82%) entered primary remission, and of these 23 individuals, 10 remained alive and in continuous remission (CR) after a median of 11.6 years (range = 8.9-20.0 years). Out of the 13 patients with ANLL, five (38%) entered remission and four remained in CR after a median of 16.0 years (range = 9.1-19.2 years). Treatment -related toxicities were common: eight patients with ALL and two with ANLL died of septicaemia. Actuarial, event-free survival rates at 5 years were 53% and 43% for adequately treated subjects with ALL and ANLL, respectively. CONCLUSIONS: Standard leukaemia chemotherapy is effective in patients with DS. However, because toxicities are unacceptably frequent, specific anti-leukaemia regimens are needed for subjects with DS design.

Transferrin receptor in children and its correlation with iron status and types of milk consumption.

AIM: This study compared transferrin receptor (TfR) concentrations with iron parameters relative to a child's intake of cow's milk and follow-on formula. METHODS: TfR, beta-haemoglobin, serum ferritin and mean corpuscular volume (MCV) of red blood cells were analysed in a study population of 263 children aged 2.5 y. The amounts of cow's milk and follow-on formula consumed were recorded. RESULTS: There was a significant difference in concentrations of TfR/log ferritin between children whose milk intake was < 500 ml and those with a milk intake > or = 500 ml (p = 0.003). There were significantly higher values of TfR/log ferritin in children whose MCV of red blood cells was < or = 75 fl than in those with > 75 fl (p < 0.0001). The TfR concentrations were significantly lower after iron therapy than before treatment. CONCLUSION: Higher concentrations of TfR were correlated with lower concentrations of haemoglobin and MCV of red blood cells. Milk consumption increases the risk of a higher ratio of TfR/log ferritin. TfR concentrations were significantly lower after iron therapy.

Antibody status to HHV-6 in children with leukaemia.

Forty children with acute lymphoblastic (33) or myeloid leukaemia (seven) were studied for IgG and IgM antibodies and IgG avidity against human herpesvirus 6 (HHV-6) at the time of diagnosis, and compared with age-, sex- and season-matched children with various neurological diseases of suspected viral origin. Of the children with leukaemia, 97.5% had IgG antibodies and 40% IgM antibodies to HHV-6 compared with 92.3% and 7.7% of reference subjects (P = 0.005). A seronegative child with leukaemia seroconverted 3 weeks after the diagnosis. The avidity of IgG antibodies (based on the resistance to urea treatment) was high in all children with leukaemia. One reference child had HHV-6-specific IgG antibodies with low avidity, which together with his positive IgM indicated an acute infection. The presence of specific IgM antibodies in 40% of children with leukaemia and the high avidity of IgG suggest a reactivation or an inaproppriate primary response to HHV-6 infection. The results support the conclusion of the role of the HHV-6 infection at the onset of childhood leukaemia.

Iron-fortified and unfortified cow's milk: effects on iron intakes and iron status in young children.

UNLABELLED: Iron intakes and iron status were evaluated in 36 young Swedish children given either iron-fortified or unfortified cow's milk. All children had good iron status and had received breast milk or iron-fortified formulae during infancy. Twenty 1-y-old children were randomized to a diet with iron-fortified milk (7.0 or 14.9 mg Fe l(-1) and 16 to a diet with unfortified milk. The iron intakes in the unfortified group at 15 and 18 mo (mean +/- SD 5.19 +/- 2.29 and 5.84 +/- 1.62 mg d(-1)) were low in relation to Nordic Nutrition Recommendations, while the intakes in the iron-fortified group (10.20 +/- 2.60 and 10.87 +/- 2.79mg d(-1)) were normal in relation to recommendations. The gain (increase) from receiving fortified diet during the study period was at most [upper limit for 95% confidence interval (CI)] 2.6 g l(-1) in blood haemoglobin, 1.9 fl in mean corpuscular volume, 2.7 micromol in serum iron and 4.5% in transferrin iron saturation, and the gain (decrease) was at most (lower limit for 95% CI) 0.29g l(-1) in serum transferrin and 0.9mg l(-1) in serum transferrin receptor (TfR). None of these differences was statistically significant. There was an almost significantly higher increase in serum ferritin (1.4 times higher relation of values at the end compared with the beginning, p = 0.06) and a significantly higher (1.2; p = 0.047) decrease in TfR/ log10 ferritin ratio in the fortified group. CONCLUSION: One-year-old children starting out with good iron status given either iron-fortified or unfortified cow's milk from 12 to 18 mo maintain sufficient iron status during this period. However, children fed unfortified cow's milk have an iron intake which is low in relation to recommendations and the quantitative development of their reserve iron in iron stores seems to be weaker than that of the fortified group. The consequences of this require further study.

Impaired spermatogenesis: an unrecognized feature of cartilage-hair hypoplasia.

BACKGROUND: Cartilage-hair hypoplasia (CHH), an autosomal recessive chondrodysplasia, is characterized by severe growth failure, hypoplastic hair, impaired immunity, and deficient erythropoiesis. These features may result from a generalized defect in cell proliferation. AIM: In order to investigate whether an impairment of cell proliferation is present in spermatogenesis, we analysed fertility in a clinical and laboratory study of adult males with CHH. METHODS: Eleven adult males (median age 29 years, range 21-49 years) with CHH were included in the study. The patients were examined clinically for testicular volume and other clinical characteristics. Blood samples were collected to determine serum concentrations of sex hormones, sex hormone-binding globulin, inhibin B and gonadotrophins (basal and gonadotrophin-releasing hormone-stimulated). Semen samples were analysed for volume, sperm concentration, motility, morphology, and antibody status. RESULTS: The testicular size was subnormal in some patients, but the serum concentrations of testosterone, inhibin B and gonadotrophins were usually normal. The semen analyses were not within normal limits in any of the patients, as indicated by low sperm concentration, decreased motility and/or morphological changes. CONCLUSIONS: The defect in cell proliferation in men with CHH also involves the spermatogenic cells and is evident as an impairment of spermatogenesis.

Elevated serum transferrin receptor concentration in children with juvenile chronic arthritis as evidence of iron deficiency.

OBJECTIVES: Active juvenile chronic arthritis (JCA) is accompanied by anaemia of chronic disease, which may be indistinguishable from anaemia due to iron deficiency. We speculate that elevation of the serum transferrin receptor (sTfR) concentration, which should not be influenced by inflammation, would be useful for detecting the role of iron status in anaemic children with JCA. METHODS: sTfR concentrations were measured in 30 children with JCA. RESULTS: The median sTfR was elevated, 6.1 (range 3.4-13.0) mg/l. In 13 patients (43%) the concentrations exceeded the upper limit for healthy subjects. Haemoglobin (r = - 0.48, P = 0.008), mean corpuscular volume (r = - 0.47, P = 0.009) and mean corpuscular haemoglobin (r = - 0.65, P = 0.0001) correlated inversely with sTfR concentration. CONCLUSIONS: In 13 of the 30 patients with JCA, the sTfR concentration, which is an indicator of iron status and erythropoiesis, was elevated. The results raise the possibility that sTfR is able to distinguish iron-deficiency anaemia from anaemia of chronic disease. It should be further explored as a candidate.

Anemia in children with cartilage-hair hypoplasia is related to body growth and to the insulin-like growth factor system.

Cartilage-hair hypoplasia (CHH) is a metaphyseal chondrodysplasia characterized by severe short-limbed short stature, hypoplastic hair, and defective immunity. The patients also have anemia. As GH may regulate both body growth and erythropoiesis, we used CHH as a clinical model to study their interrelationships. Retrospective analysis of hematological data of 114 patients showed that the severity of the anemia and macrocytosis in CHH varies with age. The anemia was most severe in early childhood. A prospective study of 21 patients with CHH showed that height correlates with hemoglobin (P = 0.006) and mean corpuscular volume of red blood cells (P < 0.0001). The individual hemoglobin levels correlated with the GH parameters [P = 0.035 for insulin-like growth factor I (IGF-I) and P = 0.002 for IGF-binding protein-3], and the mean corpuscular volume of red blood cell values correlated with fetal hemoglobin. Bone marrow cultures obtained from six patients with CHH showed reduced or totally absent erythroid colony formation, which was not influenced by GH or IGF-I in vitro or by GH treatment in vivo. In patients with CHH, we observed an association between erythropoiesis and growth. We conclude that body growth and erythropoiesis share common regulators. One of these is the GH-IGF-I axis; other factors, as not yet identified, may also be important.

Military service of male survivors of childhood malignancies.

BACKGROUND: The objective of this study was to assess the eligibility for and the course of compulsory military service of childhood cancer survivors. METHODS: The medical, military recruitment, conscription, and military service data of male Finnish childhood cancer survivors were collected from manually filed records. Inclusion criteria were: survivors born 1977 or earlier, treated for a malignancy between birth and age 15 years, and followed by a pediatrician until at least age 18 years. The documents of 207 survivors from the Pediatric Clinics of Finnish University Hospitals were examined, and 130 of these survivors were considered eligible for military service. Demographic factors, the predictors of fitness for military service, factors associated with service interruption, the attained level of military training, and the health status of conscripts during service were evaluated. Comparisons were made with the Finnish male population of the same age and with conscripts serving at the corresponding time. RESULTS: Approximately 60% of studied survivors were enlisted. Positive predictors of fitness for service were year of birth of 1973 or later (odds ratio [OR], 3.2), height at call-up age of 170-174.9 cm (OR, 3.6), and the man's own positive opinion of his fitness for service (OR, 62.3). Negative predictors were age at diagnosis > or = 11 years (OR, 0.5), central nervous system radiotherapy (OR, 0.3), limb defects (OR, 0.02), and the group of sequelae concerning neurologic, cardiopulmonary, and gastrointestinal systems, or secondary malignancies (OR, 0.3). Survivors interrupted their service more often (20%) (P < 0.001). Leukemia survivors were less likely to interrupt their service (7%) compared with other survivors (P = 0.04). Factors associated with service interruption were: diagnosis (P = 0.04), the man's own opinion of his fitness for service (P = 0.013), surgery (P = 0.003), and height (P = 0.049), weight (P = 0.019), and body mass index (P = 0.035) at the beginning of military service. The attained level of military training was equal to that of controls. The survivors visited the garrison physician less frequently in total (mean, 5.9 times) (P < 0.001), visited because of infections as much as controls, and were off duty more (mean, 11.9 days) (P = 0.012) than controls. CONCLUSIONS: The current study found that childhood cancer survivors were less likely to meet the requirements set for military service in Finland. The causes of rejection usually were obvious, but approximately 30% were rejected merely on the basis of a former cancer diagnosis. However, enlisted survivors coped well with military service if their treatment sequelae were taken into consideration carefully at the time of enlistment. Vocational opportunities within the armed forces might be an appropriate career option even for survivors of childhood malignancies.

The serum transferrin receptor concentration in seven fetuses with hemolytic disease.

Six pregnant women who received intrauterine transfusions and their seven fetuses were followed during gestation. Hemoglobin concentration, hematocrit value, serum ferritin, and serum transferrin receptor (TfR) concentrations were measured. In the fetal samples, there was a tendency for the TfR concentration to decrease during gestation and after the intrauterine transfusions. Serum TfR values varied between 0.7 and 5.2 mg/L, which is near the postnatal level measured in premature infants. On the contrary, one would have expected to find highly elevated values due to the active fetal erythropoiesis. The fetal regulation of TfR production may differ from that described postnatally.

Higher concentrations of serum transferrin receptor in children than in adults.

BACKGROUND: The serum transferrin receptor (TfR) concentration in adults is suggested to provide a sensitive measure of iron depletion and together with the serum ferritin concentration to indicate the entire range of iron status, from iron deficiency to iron overload. However, little is known about TfR concentrations in children. OBJECTIVE: Our objective was to compare serum TfR and ferritin concentrations and their ratios in children and adults and look for correlations between TfR concentrations and other measures of iron status. DESIGN: Our study groups were healthy 1-y-old infants (n = 36), 11-12-y-old prepubertal boys (n = 35), and 20-39-y-old men (n = 40). RESULTS: TfR concentrations were higher in infants (x; 95% reference interval: 7.8 mg/L; 4.5, 11.1) than in prepubertal boys (7.0 mg/L; 4.7, 9.2) and higher in prepubertal boys than in men (5.8 mg/L; 3.1, 8.5). Geometric mean TfR-ferritin ratios were higher in infants (316; 95% reference interval: 94, 1059) than in prepubertal boys (219; 78, 614) and higher in prepubertal boys than in men (72; 23, 223). By multiple linear regression analysis, the best predictors of TfR concentration were serum iron (P = 0.004) and log serum ferritin (P < 0.0001), both being inverse correlations (R2 = 0.32). Mean corpuscular volume, blood hemoglobin, transferrin iron saturation, transferrin, and even age seemed to not have an influence on the TfR concentration and erythropoiesis was not a determinant of TfR concentration. CONCLUSIONS: Low serum ferritin and iron concentrations, even within the normal physiologic range, result in high TfR concentrations. The lower the iron stores, the stronger the influence of ferritin on TfR. A high TfR concentration in children, especially in infants, is a response to physiologically low iron stores. Age-specific reference concentrations for TfR are needed.

Oral iron is sufficient for erythropoietin treatment of very low birth-weight infants.

UNLABELLED: The aim of this study was to compare two different doses and means of administration of iron in recombinant human erythropoietin (rHuEPO)-treated very low birth-weight (VLBW) infants. VLBW infants (n = 41) were randomized to one of three groups. Fourteen infants were treated with rHuEPO (300 IU/kg three times a week s.c.) and oral iron (ferrofumarate, 6 mg of iron/kg per day). Another 14 infants received the same erythropoietin dose and intramuscular iron (ferroxypolymaltose, once 12 mg of iron/kg weekly). Thirteen infants were treated with the same dose of intramuscular iron but did not receive rHuEPO. After the 3-week study period, haemoglobin concentrations and reticulocyte counts were similar in the rHuEPO-treated groups and both were higher than in the group not receiving rHuEPO (P < 0.001). In both rHuEPO-treated groups the transferrin receptor concentration increased from 6.8-7.2 mg/l to 10.5-11.3 mg/l. CONCLUSION: In erythropoietin-treated very low birth weight infants the iron need for erythropoiesis can be met by oral administration of iron.

Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial.

CONTEXT: Heterozygous familial hypercholesterolemia (HeFH) is a common disorder associated with early coronary artery disease, especially in men. The age at which drug therapy should be started is still controversial, as is the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). OBJECTIVE: To assess the lipid-lowering efficacy, biochemical safety, and effect on growth and sexual development of lovastatin in adolescent boys with HeFH. DESIGN: One-year, double-blind, placebo-controlled, balanced, 2-period, 2-arm randomized trial. In the first period (24 weeks), lovastatin was increased at 8 and 16 weeks and the dosage remained stable during the second period (24 weeks). The study was conducted between 1990 and 1994. SETTING: Fourteen pediatric outpatient clinics in the United States and Finland. PATIENTS: Boys aged 10 to 17 years with HeFH. Of 132 randomized subjects (67 intervention, 65 placebo), 122 (63 intervention, 59 placebo) and 110 (61 intervention, 49 placebo) completed the first and second periods, respectively. INTERVENTION: Lovastatin, starting at 10 mg/d, with a forced titration at 8 and 16 weeks to 20 and 40 mg/d, respectively, or placebo. MAIN OUTCOME MEASURES: The primary efficacy outcome measure was low-density lipoprotein cholesterol (LDL-C). Primary safety measures were growth and sexual development. RESULTS: Compared with placebo, LDL-C levels of patients receiving lovastatin decreased significantly (P<.001) by 17%, 24%, and 27% receiving dosages of 10, 20, and 40 mg/d, respectively, and remained 25 % lower than baseline at 48 weeks. Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks (P = .85) and 48 weeks (P = .33); neither were serum hormone levels or biochemical parameters of nutrition. However, the study was underpowered to detect significant differences in safety parameters. Serum vitamin E levels were reduced with lovastatin treatment consistent with reductions in LDL-C, the major carrier of vitamin E in the circulation. CONCLUSIONS: This study in adolescent boys with HeFH confirmed the LDL-C-reducing effectiveness of lovastatin. Comprehensive clinical and biochemical data on growth, hormonal, and nutritional status indicated no significant differences between lovastatin and placebo over 48 weeks, although further study is required.

Biphasic increase in serum inhibin B during puberty: a longitudinal study of healthy Finnish boys.

We investigated the concentrations of serum inhibin B and the pro-alphaC-containing inhibins (pro-alphaC inhibin) and their relations to serum FSH levels in 38 healthy boys during their progression through puberty. Furthermore, we studied the effect of recombinant human FSH (rhFSH) on pro-alphaC inhibin production in three prepubertal gonadotropin-deficient boys. The serum inhibin B level increased between Tanner stages G1 and G2 (p < 0.02), simultaneously with the serum LH and testosterone concentrations. In advanced puberty, inhibin B changed less, and at stage G4, correlated negatively with serum FSH level (r = -0.57, p < 0.001, n = 37). The serum pro-alphaC inhibin level changed differently and increased also in advanced puberty. In prepubertal healthy subjects, the serum pro-alphaC inhibin and FSH levels correlated positively (r = 0.50, p = 0.051, n = 16), and during the rhFSH treatment of gonadotropin-deficient boys, serum pro-alphaC inhibin levels increased. These findings suggest that an increased production of inhibin B is an early event in puberty and that inhibin B can inhibit pituitary FSH secretion in the course of sexual maturation. Furthermore, they suggest that during puberty free inhibin (pro)-alpha-subunits, detected by the pro-alphaC inhibin assay, are present in large amounts and that FSH stimulates their production by prepubertal testes.

Young female survivors of childhood leukaemia do not have increased somatic concerns.

OBJECTIVE: This study examined whether experience of cancer in childhood leaves a hypersensitivity to various somatic symptoms. Further, are self-reported somatic symptoms explained by medical late-effects or a worry of recurrence of the cancer? METHODS: Of the total of 44 female survivors of leukaemia, 42 were compared with 69 age-matched healthy controls. We used a questionnaire to study self reported somatic symptoms and a face-to-face interview to explore worries about recurrence of the illness. Health status and medical late effects were evaluated by a paediatric haematologist. RESULTS: In contrast to our assumptions, young survivors of leukaemia reported fewer somatic symptoms than healthy age-matched comparison subjects (p < 0.001). Late physical sequelae were uncommon except in the survivors of allogeneic bone marrow transplantation. Of the survivors, 52% were afraid of recurrence of the illness. The presence of physical or visible impairment and worry of recurrence were unrelated to frequency of somatic symptoms. CONCLUSIONS: The results suggest that experience of childhood leukaemia and its treatment does not result in increased somatic concerns or hypochondriacal tendencies.

The apolipoprotein E phenotype has a strong influence on tracking of serum cholesterol and lipoprotein levels in children: a follow-up study from birth to the age of 11 years.

The extent to which an individual maintains his position relative to the rest of the population is called tracking. The objective of this study was to examine the effect of the apolipoprotein E (apoE) phenotype on the tracking of serum cholesterol and lipoproteins from birth to the age of 11 y. In a longitudinal follow-up study of healthy children, concentrations of total serum cholesterol and triglyceride were determined at birth (n = 193), and at the ages of 2 (n = 192), 4 (n = 192), 6 (n = 190), 9 (n = 188), and 12 mo (n = 196), and 5 (n = 162) and 11 y (n = 153). Concentrations of total HDL, HDL2, and HDL3, VLDL, and LDL cholesterol were determined at 2, 6, 9, and 12 mo (n = 36), and 5 (n = 162) and 11 y (n = 153). The apoE phenotype was determined in 151 children. The children had the following apoE phenotypes: 4 had type 4/4 and 40 type 3/4 (group apoE4), 94 had type 3/3 (group apoE3), and 11 had type 2/3 and 2 type 2/4 (group apoE2). The correlation coefficients for total cholesterol levels during childhood compared with the level at 11 y of age were: 0.03 at birth, 0.26 (p < 0.001) at 2 mo, 0.24 (p < 0.001) at 4 mo, 0.24 (p < 0.001) at 6 mo, 0.28 (p < 0.001) at 9 mo, 0.41 (p < 0.001) at 12 mo, and 0.60 (p < 0.001) at 5 y. When the children were divided into three groups according to their apoE phenotypes, these three groups had the following correlation coefficients at 4 mo, 12 mo, or 5 y of age compared with the level at the age of 11 y; group apoE2: r = 0.65 (p < 0.01), r = 0.59 (p < 0.01), and r = 0.72 (p < 0.01); group apoE3: r = 0.27 (p < 0.01), 0.43 (p < 0.001), and r = 0.64 (p < 0.001); and group apoE4: r = 0.14 (p = NS), r = 0.33 (p < 0.05), and 0.42 (p < 0.01). The apoE phenotype also strongly influenced the tracking of the LDL cholesterol levels; the correlation coefficients between 5 and 11 y of age were for group apoE2 r = 0.84 (p < 0.001), for group apoE3 r = 0.70 (p < 0.001), and for group apoE4 r = 0.37 (p < 0.05). Our results indicate that the apoE phenotype strongly influences the tracking of lipids. The children having apoE 2/3, 2/4, and 3/3 phenotypes maintained their relative cholesterol and lipoprotein levels better than the others throughout the first 11 y of age. Because the apoE phenotype strongly affects the tracking of serum cholesterol, the usefulness of cholesterol screening in predicting future cholesterol values should be analyzed, keeping the apoE phenotype in mind.