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Biomedical subjects

J R Hansen

Publications and source records attributed to J R Hansen.

At least 19 recordsLinked to original sources

Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group.

OBJECTIVE: To determine the efficacy, safety and immunogenicity of the heptavalent CRM197 pneumococcal conjugate vaccine against invasive disease caused by vaccine serotypes and to determine the effectiveness of this vaccine against clinical episodes of otitis media. METHODS: The Wyeth Lederle Heptavalent CRM197 (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a double blind trial; 37,868 children were randomly assigned 1:1 to receive either the pneumococcal conjugate vaccine or meningococcus type C CRM197 conjugate. The primary study outcome was invasive disease caused by vaccine serotype. Other outcomes included overall impact on invasive disease regardless of serotype, effectiveness against clinical otitis media visits and episodes, impact against frequent and severe otitis media and ventilatory tube placement. In addition the serotype-specific efficacy against otitis media was estimated in an analysis of spontaneously draining ears. RESULTS: In the interim analysis in August, 1998, 17 of the 17 cases of invasive disease caused by vaccine serotype in fully vaccinated children and 5 of 5 of partially vaccinated cases occurred in the control group for a vaccine efficacy of 100%. Blinded case ascertainment was continued until April, 1999. As of that time 40 fully vaccinated cases of invasive disease caused by vaccine serotype had been identified, all but 1 in controls for an efficacy of 97.4% (95% confidence interval, 82.7 to 99.9%), and 52 cases, all but 3 in controls in the intent-to-treat analysis for an efficacy of 93.9% (95% confidence interval, 79.6 to 98.5%). There was no evidence of any increase of disease caused by nonvaccine serotypes. Efficacy for otitis media against visits, episodes, frequent otitis and ventilatory tube placement was 8.9, 7.0, 9.3 and 20.1% with P < 0.04 for all. In the analysis of spontaneously draining ears, serotype-specific effectiveness was 66.7%. CONCLUSION: This heptavalent pneumococcal conjugate appears to be highly effective in preventing invasive disease in young children and to have a significant impact on otitis media.

Bacterial Vaccines↗

Cross-validation of bioelectrical impedance analysis of body composition in children and adolescents.

BACKGROUND AND PURPOSE: The reliability and validity of measurements obtained with two bioelectrical impedance analyzers (BIAs), an RJL Systems model BIA-103 and a Berkeley Medical Research BMR-2000, were investigated using the manufacturers' prediction equations for the assessment of fat-free mass (FFM) (in kilograms) in children and adolescents. SUBJECTS: Forty-seven healthy children and adolescents (23 male, 24 female), ranging in age from 8 to 20 years (mean = 12.1, SD = 2.3), participated. METHODS: In the context of a repeated-measures design, the data were analyzed according to gender and maturation (Tanner staging). Hydrostatic weighing (HYDRO) and Lohman's Siri age-adjusted body density prediction equation served as the criteria for validating the BIA-obtained measurements. RESULTS: High intraclass correlation coefficients (ICC > or = .987) demonstrated good test-retest (between-week) measurement reliability for HYDRO and both BIA methods. Between-method (HYDRO versus BIA) correlation coefficients were high for both boys and girls (r > or = .97). The standard errors of estimate (SEEs) for FFM were slightly larger for boys than for girls and were consistently smaller for the RJL system than for the BMR system (RJL SEE = 1.8 kg for boys, 1.3 kg for girls; BMR SEE = 2.4 kg for boys, 1.9 kg for girls). The coefficients of determination were high for both BIA methods (r2 > or = .929). Total prediction errors (TEs) for FFM showed similar between-method trends (RJL TE = 2.1 kg for boys, 1.5 kg for girls; BMR TE = 4.4 kg for boys, 1.9 kg for girls). DISCUSSION AND CONCLUSION: This study demonstrated that the RJL BIA with the manufacturer's prediction equations can be used to reliably and accurately assess FFM in 8- to 20-year-old children and adolescents. The prediction of FFM by the BMR system was acceptable for girls, but significant overprediction of FFM for boys was noted.

Adolescent↗

Effects of maturational stage on insulin sensitivity during puberty.

During puberty, plasma insulin levels increase, and insulin sensitivity decreases along with multiple other physical and hormonal changes. To determine 1) the time course of the decrease in insulin sensitivity in relationship to Tanner stage of genital development, and 2) how this change relates to changes in GH secretion, insulin-like growth factor-I (IGF-I), IGF-binding protein-3, and gonadal steroid secretion, we studied 58 healthy children and adolescents (34 males and 24 females; age 7-15 yr) using overnight GH sampling and frequently sampled iv glucose tolerance tests. The insulin sensitivity index (ISI) was calculated using the program MINMOD. ISI differed significantly by Tanner stage (P < 0.05, by analysis of variance) with a decrease from Tanner stage 1 to 2 (P < 0.05). IGF-I and IGF-binding protein-3 followed opposite patterns to ISI, with lower levels in Tanner stage 1 than in stages 2-5 (P < 0.05). Mean GH levels did not increase until Tanner stage 4 (P < 0.05) and then fell during Tanner stage 5. Multiple linear regression analysis revealed negative relationships among ISI, IGF-I, and body mass index. No relationship was found with GH. We conclude that the pubertal change in ISI is not necessarily associated with increased GH secretion, but is associated with increased GH peripheral effect, as indicated by the relationship between ISI and IGF-I.

Adolescent↗

Validity of near infrared body composition analysis in children and adolescents.

The purpose of this study was to evaluate the validity and reliability of the Futrex 5000A near infrared (NIR) spectrophotometer for the assessment of body composition in children and adolescents. Forty-eight subjects (24 boys and 24 girls) with a mean age of 12.7 +/- 2.7 yr underwent three methods of body composition testing: NIR, densitometry by hydrostatic weighing (HYDRO), and skinfold anthropometry (SKF). Percent body fat (%BF) and fat free mass (FFM) derived from the Lohman's age-adjusted Siri equation served as the criterion. Within session test-retest reliability was determined for the NIR device for all subjects and between-week reliability was evaluated for all test methods in 14 subjects. Based on the excellent within- and between-session reliability (ICC ranged from 0.907-0.999), the system offers the potential of obtaining longitudinal data in growth and development studies. However, the significant mean differences, moderate correlations with the criterion (r = 0.62-0.71) and inflated standard errors of estimate (SEE = 4.9-5.5% BF, 2.2-2.9 kg FFM) and total prediction errors (TE = 5.5-8.0% BF, 2.7-3.7 kg FFM) indicate that refinement of prediction equations is needed to establish the measurement validity. Continued research with expanded populations is needed to further demonstrate and evaluate the utility of this device.

Adipose Tissue↗

Cross-validation of the Slaughter skinfold equations for children and adolescents.

Prior to sexual maturation, children and adolescents have more water and less bone mineral content than adults, resulting in less dense fat-free body mass (FFM). This suggests that previously established adult skinfold/density equations are inappropriate for use with children and adolescents for the prediction of body fatness (%BF) and FFM. To overcome this problem, Slaughter and colleagues have introduced new skinfold (SKF) equations that take into account the changing density of FFM in children and adolescents as they mature. The purpose of our study was to cross-validate a select set of the Slaughter SKF equations by comparing them with a criterion measurement (Lohman's Siri age-adjusted body density equation) in 122 subjects ranging in sexual maturation from pre- to post-pubescent and ranging in age from 8-17. Our cross-validation found very high intraclass (reliability) correlations (ICCs = 0.98-0.99) and high validity correlations (rs = 0.79-0.99). The standard errors of the estimate for %BF ranged from 3.5-4.6% and total errors for %BF ranged from 3.6-4.6%. The Slaughter equation using tricep and calf SKF for females was significantly different (P < 0.05) from the criterion measure in its prediction of %BF. In males, there was an interaction between the SKF equation and subject maturation level. The data indicate that the Slaughter SKF equations hold promise for estimating body composition in children and adolescents but are still in need of refinement.

Adipose Tissue↗

MR imaging of the pituitary gland in central precocious puberty.

Cranial magnetic resonance imaging was performed in 17 children with central precocious puberty (CPP) and 19 aged-matched controls to compare the appearance of the pituitary gland. Gland size was measured on T1-weighted sagittal and coronal images. The gland was graded according to the concavity or convexity of the upper surface, and the signal intensity of the gland was assessed visually. The mean pituitary volume in 13 CPP children without hypothalamic tumor (292.6 mm3) was significantly greater than that in normal controls (181.35 mm3). The mean volume for the four CPP children with hypothalamic tumor was smaller (145.0 mm3). Compared to controls, the upper pituitary surface in CPP patients appeared convex in a higher proportion. The anterior pituitary was isointense to pons in all patients and controls. Although the posterior pituitary bright spot was present in 14 controls and 11 CPP patients, none with hypothalamic tumor showed it.

Astrocytoma↗

Assessment of depot leuprolide acetate dose-adequacy for central precocious puberty.

The development of GnRH analogs (GnRHa) has made it possible to treat children with central precocious puberty (CPP). This treatment may prevent adult short stature due to premature epiphyseal fusion. Achievement of this goal, however, is dependent upon adequate suppression of gonadal steroid production as a result of GnRHa-induced pituitary desensitization and decreased gonadotropin release. A depot formulation of a GnRHa [leuprolide acetate (dLA)] is being used by many clinicians for the treatment of CPP, but studies to establish the optimal dose of dLA have not been performed. In this study we evaluated the effectiveness of dLA (7.5 mg, im, every 4 weeks). Six children (7-10 yr old) with CPP treated with dLA were assessed clinically and divided into two groups: A (incompletely suppressed) and B (well suppressed). Each group had overnight blood sampling and a GnRH stimulation test the following morning. LH pulses were analyzed and compared to 11 normal prepubertal children. Mean LH concentration, LH curve area, LH pulse frequency, and mean LH pulse amplitude were significantly greater (P less than 0.03) in group A than in group B or the normal prepubertal children. There was no significant difference among the three groups in GnRH-stimulated peak LH release. These results indicate that dLA (7.5 mg, im, every 4 weeks) does not produce complete desensitization in all children with CPP and suggest that overnight monitoring of LH release is more sensitive than GnRH stimulation testing for the assessment of dLA dose adequacy.

Child↗

Sebaceous gland activity and serum dehydroepiandrosterone sulfate levels in boys and girls.

BACKGROUND AND DESIGN: Increases in sebaceous gland activity are often the earliest sign of the approach of puberty in children. These increases have been attributed to increases in the secretion of adrenal androgens, but the supporting data are sparse and are based on measurements of urinary, rather than serum, androgen concentrations. In this study, we examined sebum composition, serum levels of dehydroepiandrosterone sulfate, and pubertal stage in 111 boys and girls, aged 2 to 15 years. Sebum composition was evaluated by measuring the ratio of wax esters/(cholesterol + cholesterol esters), a ratio known to increase with increasing sebaceous gland activity. RESULTS: Both wax esters/(cholesterol + cholesterol esters) ratios and serum dehydroepiandrosterone sulfate levels began to increase in children 7 to 10 years old. These changes occurred in many children before the appearance of any physical signs of puberty. Wax esters/(cholesterol + cholesterol esters) ratios were correlated with dehydroepiandrosterone sulfate levels in both boys and girls. In prepubertal children, the regression lines passed through the origin. In subjects who were in early or late puberty, the y intercepts of the regression lines had positive values. CONCLUSION: Adrenal androgens appear to be the major determinants of sebaceous gland activity during the prepubertal period and to be additive to another hormone or hormones during puberty.

Adolescent↗

Heart rate monitoring of physical activity in children and adolescents: the Muscatine Study.

To assess the usefulness of whole-day heart rate monitoring as a quantitative measure of physical activity in children, the activity of 76 children and adolescents (ages 6 to 17 years), randomly selected from a school population, was measured during a typical summer day using a light-weight, nonrestrictive heart rate telemetry unit. A 12-hour recall and a simple self-rating of usual activity questionnaire were also administered on the same day. An additional 12-hour recall questionnaire was administered on another day. Within 1 month of the heart rate monitoring, the skinfold measures, peak aerobic capacity, and sexual maturation were assessed. Data analysis indicated that activity as measured by telemetry was related to questionnaire recall on the monitored day (r = .50), nonmonitored day (r = .32), and self-rating (r = .35); level of activity as measured by telemetry was related to peak aerobic capacity in girls (r = .36) but not in boys (r = -.06); body fat was related inversely to activity (r = -.32); and prepubescent children were more active than post- and pubescent children (P less than .003). No difference was found in activity level between boys and girls (P greater than .05). This study suggests that for children whole-day heart rate monitoring is an objective, nonobtrusive method for measuring physical activity; and maturation, but not gender, is an influential mediating factor for activity.

Adolescent↗

Clinical management issues in males with sex chromosomal mosaicism and discordant phenotype/sex chromosomal patterns.

The recent availability of Y DNA probes has made it possible to identify two forms of 46,XX male syndrome: Y DNA positive and Y DNA negative. The Y DNA positive male results from a X;Y translocation with a low recurrence risk; the Y DNA negative males are due to a mutation with a high recurrence risk. 46,XX males and mosaic forms are phenotypically indistinguishable. A review of the case histories for 11 individuals indicates that affected males have highly variable genital and nongenital phenotypes. Physical findings may be clearly apparent or nonexistent. With the exception of external genitalia, the basis for this variability is unknown. It may be related to differences in Y chromatin expression as the result of variable inactivation of the X chromosomes, or to the existence of minor deletions or point mutations secondary to an exchange of genetic material. Common and uncommon clinical problems in these individuals require evaluation and follow-up care that is provided through a cooperative, interdisciplinary approach.

Adolescent↗

Gonadotropin-releasing hormone modulation of protein kinase-C activity in perifused anterior pituitary cell cultures.

The ability of GnRH to modulate protein kinase-C (PKC) activity was examined in perifused rat pituitary cell cultures. Under these conditions, LH release and GnRH receptor number remained unchanged after repeated pulses of 1 nM GnRM, whereas PKC (measured both enzymatically and by radioligand assay) showed an initial increase in kinase activity after the first pulse of GnRH (approximately 2-fold), followed by down-regulation of PKC activity with subsequent pulses of the releasing hormone. It was also observed that the GnRH-stimulated down-regulation of PKC was dependent on the presence of extracellular calcium, which was not the case for the initial up-regulation of PKC. These findings are consistent with a modulating role of the GnRH receptor on PKC activity through a Ca2(+)-dependent process. This study also provides further evidence that GnRH-stimulated LH release and PKC activity can be uncoupled.

Animals↗

Human collagen genes encoding basement membrane alpha 1 (IV) and alpha 2 (IV) chains map to the distal long arm of chromosome 13.

At least 20 genes encode the structurally related collagen chains that comprise greater than 10 homo- or heterotrimeric types. Six members of this multigene family have been assigned to five chromosomes in the human genome. The two type I genes, alpha 1 and alpha 2, are located on chromosomes 17 and 7, respectively, and the alpha 1 (II) gene is located on chromosome 12. Our recent mapping of the alpha 1 (III) and alpha 2 (V) genes to the q24.3----q31 region of chromosome 2 provided the only evidence that the collagen genes are not entirely dispersed. To further determine their organization, we and others localized the alpha 1 (IV) gene to chromosome 13 and in our experiments sublocalized the gene to band q34 by in situ hybridization. Here we show the presence of the alpha 2 type IV locus also on the distal long arm of chromosome 13 by hybridizing a human alpha 2 (IV) cDNA clone to rodent-human hybrids and to metaphase chromosomes. To our knowledge, these studies represent the only demonstration of linkage between genes encoding both polypeptide chains of the same collagen type.

Amino Acid Sequence↗

Relative roles of calcium derived from intra- and extracellular sources in dynamic luteinizing hormone release from perifused pituitary cells.

GnRH releases LH from pituitary gonadotropes by a calcium-dependent mechanism. Previous studies in static cell cultures have not revealed a role for intracellular-derived calcium during GnRH-stimulated LH release. In the present study we have reexamined this possibility using a perifusion system, which permits a more dynamic assessment of early cellular events. Chelation of extracellular calcium by EGTA and calcium channel blockade by methoxyverapamil prevented sustained LH release. A component of early LH release occurred independently of extracellular calcium mobilization. This previously unrecognized aspect of LH release was shown to be dependent upon intracellular calcium. The molecular mechanism by which this calcium-dependent signal is translated into a cellular response does not appear to be mediated by calmodulin or protein kinase C, whereas sustained LH release appears mediated by calmodulin. While calcium derived from extracellular sources is still viewed as the major messenger for sustained LH release, these experiments provide evidence for the involvement of intracellular-derived calcium during early GnRH-stimulated LH release.

Animals↗

Reye syndrome associated with aspirin therapy for systemic lupus erythematosus.

A 14-year-old girl in whom Reye syndrome developed during aspirin therapy for an inflammatory disorder proven to be systemic lupus erythematosus is reported. This case and similar cases of Reye syndrome in patients with juvenile rheumatoid arthritis suggest that an etiologic relationship exists between salicylate therapy and Reye syndrome in children with collagen vascular disorders.

Adolescent↗