Inhibin B levels in adolescents and young adults with type 1 diabetes

OBJECTIVE/METHODS: To assess exocrine and endocrine testicular function in subjects with diabetes, we evaluated serum inhibin B, gonadotrophins and testosterone levels in 33 male adolescent and young adult patients affected by type-1 diabetes (age 21.0 +/- 5 years; range 14.2-33.3), with a mean disease duration of 12.7 +/- 5.8 years (range 1.5-25.3) and various metabolic control (HbA1c 7.8 +/- 1.5%; range 5.5-13.2) and compared them with those of an age-matched group of 36 healthy control subjects (age 19.5 +/- 4.1 years; range 13.6-28.1). Both patients and controls had a testicular volume >or=15 ml. Inhibin B was measured by ELISA method. RESULTS/CONCLUSION: Diabetics and controls had comparable inhibin B (203 +/- 74 vs. 221 +/- 69 pg/ml, respectively) and follicle-stimulating hormone (FSH) levels, while luteinizing hormone (LH) and testosterone levels were significantly higher in the diabetic group. Inhibin B was negatively correlated both in patients and controls with FSH, while a negative correlation with LH was found only in the diabetic group. We conclude that our young diabetic males, after a mean disease duration of 12 years and various metabolic control, had inhibin B and FSH levels comparable to those of normal subjects. Therefore, they seem to have a regular testicular function and in particular a normal seminiferous tubule/Sertoli cell activity despite sustained hyperglycemia.     

Genetic disorders in children and young adults: a population study.

The data base of an ongoing population-based registry with multiple sources of ascertainment was used to estimate the present population load from genetic disease in more than 1 million consecutive live births. It was found that, before approximately age 25 years, greater than or equal to 53/1,000 live-born individuals can be expected to have diseases with an important genetic component. This total was composed of single-gene disorders (3.6/1,000), consisting of autosomal dominant (1.4/1,000), autosomal recessive (1.7/1,000), and X-linked recessive disorders (0.5/1,000). Chromosomal anomalies accounted for 1.8/1,000, multifactorial disorders (including those present at birth and those of onset before age 25 years) accounted for 46.4/1,000, and cases of genetic etiology in which the precise mechanism was not identified accounted for 1.2/1,000. Previous studies have usually considered all congenital anomalies (ICD 740-759) as part of the genetic load, but only those judged to fit into one of the above categories were included in the present study. Data for congenital anomalies are therefore also presented separately, to facilitate comparison with earlier studies. If all congenital anomalies are considered as part of the genetic load, then greater than or equal to 79/1,000 live-born individuals have been identified as having one or other genetic disorder before approximately age 25 years. These new data represent a better estimate of the genetic load in the population than do previous studies.     

Evaluation of a urinary multi-parameter biomarker set for oxidative stress in children, adolescents and young adults

The involvement of reactive oxygen species (ROS) and oxidative stress in pediatric diseases is an important concern, but oxidative stress status in healthy young subjects and appropriate methods for its measurement remain unclear. This study evaluated a comprehensive set of urinary biomarkers for oxidative stress in healthy children, adolescents and young adults. Results show that urinary excretion of acrolein-lysine, 8-hydroxy-2'-deoxyguanosine (8-OHdG), nitrite/nitrate and pentosidine were highest in the youngest subjects and decreased to constant levels by early adolescence. Urinary acrolein-lysine, 8-OHdG, nitrite/nitrate and pentosidine showed significant inverse correlations with age, but pyrraline did not change significantly with age. No significant differences in biomarkers were apparent between males and females. Younger subjects grow rapidly and sustain immune activation, and are probably exposed to high concentrations of ROS and nitric oxide. Consequently, they are more vulnerable to oxidation of lipids, proteins, DNA and carbohydrates. Normal reported values in this study are a basis for future studies of disease mechanisms involving oxidative stress and for future trials using antioxidant therapies for oxidative stress-related diseases in the pediatric field.     

Evaluation of a urinary multi-parameter biomarker set for oxidative stress in children,adolescents and young adults

The involvement of reactive oxygen species (ROS) and oxidative stress in pediatric diseases is an important concern, but oxidative stress status in healthy young subjects and appropriate methods for its measurement remain unclear. This study evaluated a comprehensive set of urinary biomarkers for oxidative stress in healthy children, adolescents and young adults. Results show that urinary excretion of acrolein–lysine, 8-hydroxy-2′-deoxyguanosine (8-OHdG), nitrite/nitrate and pentosidine were highest in the youngest subjects and decreased to constant levels by early adolescence. Urinary acrolein–lysine, 8-OHdG, nitrite/nitrate and pentosidine showed significant inverse correlations with age, but pyrraline did not change significantly with age. No significant differences in biomarkers were apparent between males and females. Younger subjects grow rapidly and sustain immune activation, and are probably exposed to high concentrations of ROS and nitric oxide. Consequently, they are more vulnerable to oxidation of lipids, proteins, DNA and carbohydrates. Normal reported values in this study are a basis for future studies of disease mechanisms involving oxidative stress and for future trials using antioxidant therapies for oxidative stress-related diseases in the pediatric field.     

Overweight and decreased baroreflex sensitivity as independent risk factors for hypertension in children, adolescents, and young adults

We studied the relationship between blood pressure (BP), body mass index (BMI, kg/m(2)) and baroreflex sensitivity (BRS, ms/mmHg) in adolescents. We examined 34 subjects aged 16.2+/-2.4 years who had repeatedly high causal BP (H) and 52 controls (C) aged 16.4+/-2.2 years. Forty-four C and 22 H were of normal weight (BMI between 19-23.9), and 8 C and 12 H were overweight (BMI between 24-30). Systolic BP was recorded beat-to-beat for 5 min (Finapres, controlled breathing 0.33 Hz). BRS was determined by the cross-spectral method. The predicting power of BMI and BRS for hypertension was evaluated by sensitivity, specificity, and receiver operating curve (ROC - plot of sensitivity versus specificity). H compared with C had lower BRS (p<0.01) and higher BMI (p<0.05). Multiple logistic regression analysis (p<0.001) revealed that a decreased BRS (p<0.05) and an increased BMI (p<0.01) were independently associated with an increased risk of hypertension. No correlation between BMI and BRS was found either in H or in C. Following optimal critical values by ROC, the sensitivity, specificity and area under ROC were determined for: BMI - 22.2 kg/m(2), 61.8 %, 69.2 %, 66.0 %; BRS - 7.1 ms/mmHg, 67.7 %, 69.2 %, 70.0 %; BMI and BRS - 0.439 a.u., 73.5 %, 82.7 %, and 77.3 %. Decreased BRS and overweight were found to be independent risk factors for hypertension.     

Population-based biochemistry, immunologic and hematological reference values for adolescents and young adults in a rural population in Western Kenya

Background

There is need for locally-derived age-specific clinical laboratory reference ranges of healthy Africans in sub-Saharan Africa. Reference values from North American and European populations are being used for African subjects despite previous studies showing significant differences. Our aim was to establish clinical laboratory reference values for African adolescents and young adults that can be used in clinical trials and for patient management.

Methods and Findings

A panel of 298, HIV-seronegative individuals aged 13–34 years was randomly selected from participants in two population-based cross-sectional surveys assessing HIV prevalence and other sexually transmitted infections in western Kenya. The adolescent (<18 years)-to-adults (≥18 years) ratio and the male-to-female ratio was 1∶1. Median and 95% reference ranges were calculated for immunohematological and biochemistry values. Compared with U.S-derived reference ranges, we detected lower hemoglobin (HB), hematocrit (HCT), red blood cells (RBC), mean corpuscular volume (MCV), neutrophil, glucose, and blood urea nitrogen values but elevated eosinophil and total bilirubin values. Significant gender variation was observed in hematological parameters in addition to T-bilirubin and creatinine indices in all age groups, AST in the younger and neutrophil, platelet and CD4 indices among the older age group. Age variation was also observed, mainly in hematological parameters among males. Applying U.S. NIH Division of AIDS (DAIDS) toxicity grading to our results, 40% of otherwise healthy study participants were classified as having an abnormal laboratory parameter (grade 1–4) which would exclude them from participating in clinical trials.

Conclusion

Hematological and biochemistry reference values from African population differ from those derived from a North American population, showing the need to develop region-specific reference values. Our data also show variations in hematological indices between adolescent and adult males which should be considered when developing reference ranges. This study provides the first locally-derived clinical laboratory reference ranges for adolescents and young adults in western Kenya.     

Parent-child correlation for various indices of adiposity in an endogamous Indian population

The study was conducted on 1,042 Punjabi adults and adolescent boys and girls (11-17 years) belonging to middle class families residing in Delhi, India. To study the relative influence of genetic and environmental factors on various fat measures, a set of 7 body measurements namely weight, stature and skinfold thickness at biceps, triceps, subscapular, suprailiac and medial calf measurements was taken on each subject. There was a redistribution of fat away from extremity towards the trunk, a rapid occurring process in males than in females. Increase in body mass index (BMI) with age was more pronounced in females than in males, both at adolescence and adult stage. There was an increase in grand mean thickness (GMT) calculated as mean of all five skinfold thicknesses, in adolescent girls where as in adolescent boys it fluctuated with age. The trunk/extremity ratios reflected a trend in favor of increase in trunk fat, more marked in boys than in girls. The correlations were of low magnitude, however, some skin folds displayed relatively higher value of correlation indicating that these could be determinant of adult obesity.     

Hemoglobin E distribution in ten endogamous population groups of Assam, India

Previous studies have reported a high incidence of hemoglobin E (HbE) in Northeast Indian populations. In the present study 10 endogamous populations of Assam belonging to two racial groups, Caucasoid and Mongoloid, were examined. The frequency of HbE gene (Hb beta E) in the Caucasoid caste populations is around 0.1, whereas the gene is highly prevalent in the Mongoloid populations, frequencies ranging between 0.2 and 0.6. Predominance of Hb beta E in the Tibeto-Burman speakers is contrary to observations made in Southeast Asia, where an association between Austro-Asiatic speakers and high prevalence of HbE exist. The highest occurrence of the gene in this area, which is on the far end of the proposed centre of distribution in Northern Kampuchea and Northeast Thailand, is also a deviation from the expected pattern of gene distribution. It is speculated that Hb beta E in the Tibeto-Burman populations of Assam arose by an independent mutation which contributed to the high frequencies of Hb beta E in the Northeast Indian populations.     

Human pancreatic polypeptide in children and young adults

Measurement of human pancreatic polypeptide may be useful for assessment of gastrointestinal function, integrity of the parasympathetic nervous system or screening for endocrine neoplasia. In adults hPP levels have been reported to increase with age. However hPP levels throughout childhood have not been well characterized in comparison with the adult range. We studied fasting human pancreatic polypeptide (hPP) from 45 pediatric patients, from infancy - 15 years, and 18 older adolescents and adults aged 16-45 years. The mean hPP level of children (233 +/- 147 pg/ml) was significantly higher than that (113 +/- 35 pg/ml) of adults (P less than .0001). There was no difference in mean hPP levels of children with normal growth hormone secretion compared to growth hormone deficient patients. There was no effect of gender or body mass index on hPP levels. We conclude that fasting hPP levels must be interpreted with respect to the age of the subject, children particularly, in that preteens may have higher fasting levels than older teenagers and adults.     

Skeletal manifestations of rickets in infants and young children in a historic population from England

Gross and radiographic changes characteristic of inadequate bone mineralization due to rickets are described in 21 immature skeletons from a 19th century urban population from Birmingham, England. The aims of the study are as follows: to evaluate and if possible augment existing dry-bone criteria for the recognition of rickets in immature skeletal remains; to investigate the value of radiography for the paleopathological diagnosis of rickets; and to compare and contrast the expression of rickets in this group with that previously documented for a rural agrarian population from Wharram Percy, England. Some gross skeletal signs of rickets which were not previously well-documented in paleopathological studies are noted. The worth of radiography for evaluating structural changes to both cortical and trabecular bone in the disease is demonstrated, and features useful for the interpretation of vitamin D deficiency are discussed. The pattern of skeletal elements affected and the severity of changes differs in the Birmingham group from that seen in the comparative rural population. It is emphasized that a variety of factors may influence the expression of rickets in paleopathological material, including rate of skeletal growth, age cohort affected, and intensity of vitamin D deficiency. Nevertheless, careful analysis, not only of the frequency of rickets but also of the degree of severity of lesions and the patterning with respect to skeletal elements affected, may enable more nuanced understanding of the biocultural context of the disease in earlier populations.     

P-wave body surface isointegral maps in children and in young adults

Only limited data are available on body surface potential distribution during atrial activation. The aim of this study was to establish the distributions and to analyze chosen quantitative parameters of atrial isointegral maps recorded using a limited 24-lead system in a young healthy population. A total of 166 subjects underwent a procedure of body surface potential mapping. Isointegral maps during the P wave were constructed and qualitatively and quantitatively evaluated. Three types of atrial activation in individual maps were found according to the different shape of the zero isointegral line and to mutual positions of extrema. The most frequently occurring type resembled the group mean maps and was in good agreement with published data obtained from full lead systems. The highest extrema were found in the young men group, while, surprisingly, the lowest values in the young women group. All minima and the majority of maxima were recorded outside the ranges of standard chest leads. The usefulness of the limited lead system to record isointegral P wave maps was shown and new data were presented that can be useful in noninvasive evaluation of atrial pathologies.     

Minimal sharing of Y-chromosome STR haplotypes among five endogamous population groups from western and southwestern India

We attempt to address the issue of genetic variation and the pattern of male gene flow among and between five Indian population groups of two different geographic and linguistic affiliations using Y-chromosome markers. We studied 221 males at three Y-chromosome biallelic loci and 184 males for the five Y-chromosome STRs. We observed 111 Y-chromosome STR haplotypes. An analysis of molecular variance (AMOVA) based on Y-chromosome STRs showed that the variation observed between the population groups belonging to two major regions (western and southwestern India) was 0.17%, which was significantly lower than the level of genetic variance among the five populations (0.59%) considered as a single group. Combined haplotype analysis of the five STRs and the biallelic locus 92R7 revealed minimal sharing of haplotypes among these five ethnic groups, irrespective of the similar origin of the linguistic and geographic affiliations; this minimal sharing indicates restricted male gene flow. As a consequence, most of the haplotypes were population specific. Network analysis showed that the haplotypes, which were shared between the populations, seem to have originated from different mutational pathways at different loci. Biallelic markers showed that all five ethnic groups have a similar ancestral origin despite their geographic and linguistic diversity.     

Finding from Asia, Australia, Europe, and North Amercia on secular change in mean height of children, youths, and young adults.

Studies conducted during the past century in Australia, Canada, Japan, Norway and the United States indicate that the magnitude of secular increase in mean height rose with advancing age from childhood to mid-adolescence. Comparisons for a period approximating two-thirds of a century yield average increases in mean height of 12.2 cm for female youths age 12 years, and 12.5 cm for male youths age 14 years; for the same calendar span, the amount of secular increase in mean height declines from mid-adolescence to early adulthood. Comparisons of Belgian females, spanning a period approximating 130 years, yield increases in mean height of 18.1 cm at age 12 years, 11.9 cm at age 16 years, and 3.7 cm in early adulthood. For a period of 90 years, increases obtained on United States White males are 14.8 cm at age 14 years, 8.8 cm at age 17 years, and 5.3 cm in early adulthood. These and other displayed findings show clearly that the search for causes of secular change should take particular account of a phenomenon widespread among human populations, i.e., the phenomenon of childhood and early adolescent growth in body height proceeding at a faster pace in recent decades than about a century ago.     

Genetic study of the Evens, an ancient human population of eastern Siberia

Three territorial subgroups of reindeer breeders, fishermen, and fur hunters living under conditions of partial isolation in remote parts of the Yakut ASSR, have been investigated with respect to polymorphic genetic systems. Analysis of covariance matrices containing allele frequencies in an array of 12 loci for a large sample of Evens, Nganasans, and reindeer Chukchi indicates that the genetic relationships support known phylogenetic, linguistic, and historical events.     

Modeling the blood lactate kinetics at maximal short-term exercise conditions in children, adolescents, and adults.

Whether age-related differences in blood lactate concentrations (BLC) reflect specific BLC kinetics was analyzed in 15 prepubescent boys (age 12.0 +/- 0.6 yr, height 1.54 +/- 0.06 m, body mass 40.0 +/- 5.2 kg), 12 adolescents (16.3 +/- 0.7 yr, 1.83 +/- 0.07 m, 68.2 +/- 7.5 kg), and 12 adults (27.2 +/- 4.5 yr, 1.83 +/- 0.06 m, 81.6 +/- 6.9 kg) by use of a biexponential four-parameter kinetics model under Wingate Anaerobic Test conditions. The model predicts the lactate generated in the extravasal compartment (A), invasion (k(1)), and evasion (k(2)) of lactate into and out of the blood compartment, the BLC maximum (BLC(max)), and corresponding time (TBLC(max)). BLC(max) and TBLC(max) were lower (P < 0.05) in boys (BLC(max) 10.2 +/- 1.3 mmol/l, TBLC(max) 4.1 +/- 0.4 min) than in adolescents (12.7 +/- 1.0 mmol/l, 5.5 +/- 0.7 min) and adults (13.7 +/- 1.4 mmol/l, 5.7 +/- 1.1 min). No differences were found in A related to the muscle mass (A(MM)) and k(1) between boys (A(MM): 22.8 +/- 2.7 mmol/l, k(1): 0.865 +/- 0.115 min(-1)), adolescents (22.7 +/- 1.3 mmol/l, 0.692 +/- 0.221 min(-1)), and adults (24.7 +/- 2.8 mmol/l, 0.687 +/- 0.287 min(-1)). The k(2) was higher (P < 0.01) in boys (2.87 10(-2) +/- 0.75 10(-2) min(-1)) than in adolescents (2.03 x 10(-2) +/- 0.89 x 10(-2) min(-1)) and adults (1.99 x 10(-2) +/- 0.93 x 10(-2) min(-1)). Age-related differences in the BLC kinetics are unlikely to reflect differences in muscular lactate or lactate invasion but partly faster elimination out of the blood compartment.