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Biomedical subjects

Janine Janosky

Publications and source records attributed to Janine Janosky.

10 recordsLinked to original sources
PubMed2005

Influence of wet surfaces and fall height on pediatric injury risk in feet-first freefalls as predicted using a test dummy.

INTRODUCTION: Falls are a major cause of morbidity and mortality in children, but are also reported falsely in child abuse. Therefore, it is of interest to understand those factors which may lead to a higher likelihood of injury in a feet-first freefall. METHODS: We used laboratory freefall experiments and a 3-year-old Hybrid III anthropomorphic test dummy (ATD) to assess head and femur injury risk. Wet and dry linoleum impact surfaces were used from three fall heights: 22, 35 and 47 in. RESULTS: For a given fall height, dry surfaces were associated with higher head injury criteria (HIC) values than wet surfaces. Changes in fall height 22-47 in. did not significantly affect HIC values for falls onto either surface. Generally, compressive and bending femur loading increased significantly for wet as compared to dry linoleum. CONCLUSIONS: In simulated feet first freefall experiments up to 47 in. using a 3-year-old test dummy, a low risk of contact type head injury and femur fracture was found. However, both fall height and surface conditions influenced femur loading and head injury measures. Future efforts should explore the risk of head injury associated with angular acceleration in freefalls.

Acceleration↗
PubMed2005

Enhanced donor-specific alloreactivity occurs independently of immunosuppression in children with early liver rejection.

UNLABELLED: To determine whether early acute cellular rejection (ACR) is associated with sub-optimal immunosuppression in children with liver transplants (LTx). METHODS: Twenty-five children with primary LTx after pre-transplant rabbit anti-thymocyte globulin (rATG), and steroid-free tacrolimus (TAC) were evaluated. Mitogen-stimulated T- and B-cell responses and mixed lymphocyte response to donor and third-party antigens were performed at several time points between two consecutive TAC doses. TAC concentrations (C) associated with half-maximal effect (EC(50)) on lymphocytes was determined by pharmacodynamic equations. RESULTS: Mean age was 7.2 +/- 6.2 years, mean time to lymphocyte function studies was 25 +/- 19 days. Acute rejection occurred at a mean interval of 31 +/- 19 days after LTx. Rejectors (n = 16) demonstrated significantly higher EC(50) of TAC for the intra-cellular IFN-gamma in T cells (p = 0.005) and its CD8+ sub-population (p = 0.027) as well as the co-stimulatory/activation receptor CD54 on B cells (p = 0.0001). The response of recipient lymphocytes to donor antigen was significantly higher in rejectors, compared with non-rejectors (p = 0.015). The patient groups demonstrated no differences in third-party MLR, or in C of TAC. CONCLUSIONS: Independent of the amount of immunosuppressant, ACR of liver allografts in children is associated with enhanced donor-specific alloreactivity. This is accompanied by a cytotoxic T-cell sub-population with increased requirement for TAC.

Adolescent↗
PubMed2004

Multiparametric effect: concentration analyses.

Immunosuppressant drug toxicity currently competes with acute rejection, as the major cause of efficacy failure of potent new agents in clinical transplantation. The development of mechanistic drug targets as surrogate endpoints for use in the clinic has been facilitated by fluorescent imaging techniques which measure multiple cytokines and cell surface receptors on stimulated (peripheral blood) lymphocyte responses. However, the promise of delivering customized drug therapy to the transplant recipient remains unfulfilled. In this brief review, computational algorithms that can relate multiparametric effects to clinical drug concentrations of immunosuppressants are discussed. Based on Hill equations, these pharmacodynamic modeling techniques have been used to simulate single-agent effects, combination regimen effects, as well as the individual response to combination regimens. The potential implications of these models crystallize the clinical challenges confronting practitioners of clinical, post-transplant immunosuppression.

Algorithms↗
PubMed2004

Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents.

OBJECTIVES: To compare insulin sensitivity and pancreatic beta-cell function measured by the euglycemic and the hyperglycemic clamp, with simple estimates of insulin sensitivity and pancreatic beta-cell function in youth. Study design We measured insulin sensitivity with a euglycemic clamp and first- and second-phase insulin secretion with a hyperglycemic clamp in 156 AA and white youths. Estimates of insulin sensitivity (fasting insulin level [I(F)], the ratio of fasting glucose [G(F)] to I(F) [G(F)/I(F)], homeostasis model assessment estimate of insulin sensitivity [HOMA IS], and quantitative insulin sensitivity check index [QUICKI]) and estimates of pancreatic beta-cell function (I(F), the ratio of I(F) to G(F) [I(F)/G(F)], and homeostasis model assessment estimate of pancreatic beta-cell function [HOMA %B]) were derived from fasting measurements. RESULTS: In the total group, IS(Eu) correlated strongly with I(F) (r=-0.92), G(F)/I(F) (r=0.92), HOMA IS (r=0.91), and QUICKI (r=0.91) (P<.01). First-phase and second-phase insulin secretion correlated with I(F), I(F)/G(F), and HOMA %B (first-phase insulin secretion: r=0.76, 0.79, 0.82; second-phase insulin secretion: r=0.83, 0.86, 0.86, respectively; P<.01). CONCLUSIONS: Simple estimates of insulin sensitivity and pancreatic beta-cell function using fasting insulin and glucose levels serve as surrogate measures of insulin sensitivity and secretion in nondiabetic youths. The validity of these conclusions in children with impaired glucose tolerance and type 2 diabetes mellitus remains to be determined.

Adolescent↗
PubMed2003

Lymphocyte subsets may discern treatment effects in children and young adults with post-transplant lymphoproliferative disorder.

To identify potential alternatives to Epstein-Barr virus (EBV)-specific cytotoxic T-cell responses, peripheral lymphocyte subsets (PLS) (CD4+, CD8+, CD3+, CD19+, CD56+) were measured by flow cytometry in children with abdominal transplants (n = 22) and heart transplants (n = 2), with (n = 14) and without (n = 10, group C) post-transplant lymphoproliferative disorder (PTLD). PTLD resolved with reduced immunosuppression and antiviral therapy in eight children (group B). Recalcitrant PTLD was observed in six children (group A). Recalcitrant PTLD followed prior antilymphocyte therapy [monoclonal anti-CD3 antibody (OKT3) and thymoglobin (n = 3) and thymoglobin (n = 1)] for refractory rejection in four of these six children, and resolved after treatment with rituximab (anti-CD20 monoclonal antibody). Ten children without PTLD served as a control group (group C). Between group comparisons showed a numeric increase in CD8 + cells and significantly lower CD4:CD8 ratios in both PTLD groups (A and B) compared with group C. Group A children also demonstrated significant depletion of natural killer (NK) cells, and post-rituximab depletion of B-cells compared with group B (no rituximab treatment). We conclude that NK cell depletion with a reversed CD4:CD8 ratio may represent a persistent immunosuppressed state, which may result from prior antilymphocyte therapy and may predispose to recalcitrant EBV-PTLD. Clinical remission with rituximab is accompanied by B-cell depletion. Serial monitoring of PLS from the time of diagnosis of PTLD will be necessary to confirm these observations.

Adolescent↗
PubMed2003

Parent-reported language skills in relation to otitis media during the first 3 years of life.

As part of a larger study of the potential impact of early-life otitis media (OM) on speech, language, cognition, and behavior, we studied the degree of association between parent-reported language scores at ages 1, 2, and 3 years and the cumulative duration of middle-ear effusion (MEE) during the first 3 years of life in a demographically diverse sample of 621 children. We estimated the cumulative percentage of days with MEE from prospective monthly observations of middle-ear status and interpolations for periods between visits. For each child, parents completed the appropriate inventory of the MacArthur Communicative Development Inventories (CDI; L. Fenson et al., 1993) at ages 1, 2, and 3 years. We also evaluated the contribution of maternal education, as a proxy for socioeconomic status, to scores on the parent reports. Scores on the new CDI-III (B. Oliver et al., in press) varied positively with sociodemographic variables and were significantly correlated with scores from the CDI used when the children were younger. Unadjusted correlations between scores at ages 1 and 2 years and the percentages of days with MEE in the respective antecedent periods were statistically nonsignificant or of questionable clinical importance. The correlations between parent-reported scores at age 3 years and children's cumulative percentage of days with MEE in Years 1, 2, and 3 combined ranged from -.187 to -.248 (all p values < .001). The percentage of days with MEE and maternal education each contributed independently to scores at age 3 years. In the light of other findings from the larger study, we think it likely that the negative associations between language measures and MEE reflect confounding factors that contribute, on the one hand, to the duration of OM in young children and, on the other hand, to slow development of their language skills.

Audiometry↗
PubMed2003

Obesity, regional fat distribution, and syndrome X in obese black versus white adolescents: race differential in diabetogenic and atherogenic risk factors.

The incidence of type 2 diabetes mellitus in children is increasing with the increasing prevalence of obesity, particularly in African-American children. We hypothesized that African-American obese adolescents are more insulin resistant than their white peers, but have lower insulin secretion, thus increasing their risk of type 2 diabetes mellitus. The present study investigated insulin sensitivity and secretion, visceral adiposity (VAT), and cardiovascular disease (CVD) risk profile in black obese adolescents (BOA) vs. white obese adolescents (WOA). Twenty-four BOA and 26 WOA underwent a hyperinsulinemic-euglycemic clamp to assess insulin sensitivity, a hyperglycemic clamp to determine insulin secretion, dual energy x-ray absorptiometry for body composition and computed tomography scan at L4-L5 to measure VAT and sc abdominal adipose tissue. Fasting lipid and automated blood pressure measurements were obtained. The WOA and BOA groups were divided into low VAT and high VAT groups. BOA compared with WOA of similar body mass index and percent body fat had less visceral adiposity, lower hepatic glucose production, and lower lipid levels. Visceral adiposity was associated with lower insulin sensitivity in both groups [low vs. high VAT; BOA, 2.9 +/- 0.4 vs. 1.7 +/- 0.2 micromol/kg x min per pmol/liter (P = 0.016); WOA, 2.6 +/- 0.5 vs. 1.5 +/- 0.1 (P = 0.032)]. However, this was compensated by higher insulin secretion in whites (low VAT, 934.8 +/- 121.8; high VAT, 1590.6 +/- 232.8 pmol/liter; P = 0.037), but not in blacks (low VAT, 1398.9 +/- 214.0; high VAT, 1423.7 +/- 108.7 pmol/liter). Glucose disposition index (insulin sensitivity x first phase insulin) was lower in high VAT vs. low VAT BOA, but not in WOA. In each racial group, high VAT groups had elevation of systolic and diastolic blood pressure, but dyslipidemia was worse in WOA with high VAT. In conclusion, a given level of body mass index confers different metabolic risks for WOA vs. BOA. Although differences in fat patterning may help explain the more atherogenic risk profile in whites, the cause of the more diabetogenic insulin sensitivity/secretion profile in blacks remains unknown and needs to be investigated further.

Adipose Tissue↗
PubMed2002

Diminished antibody response to hepatitis B immunization in children with sickle cell disease.

Hepatitis B surface antibody titers were routinely measured in 150 children with sickle cell disease (SCD) after immunization, and the seroconversion rate was found to be lower than that in the general population (89% vs. 97%, P = 0.002). Most of the children who did not seroconvert after the series of 3 immunizations responded to booster injections (93%). Therefore, we recommend the measurement of hepatitis B surface antibody titers after immunization in those children with SCD at greatest risk for hepatitis B infection. An additional dose of hepatitis B vaccine should be administered to those without evidence of seroconversion.

Anemia, Sickle Cell↗
PubMed2002

Hyperinsulinemia in african-american children: decreased insulin clearance and increased insulin secretion and its relationship to insulin sensitivity.

African-American (AA) children are hyperinsulinemic and insulin resistant compared with American White (AW) children. This study investigated 1) whether AA/AW differences in insulinemia are associated with differences in insulin clearance; 2) whether dietary patterns, mainly carbohydrate and fat intake, play a role; and 3) whether the quantitative relationship between insulin sensitivity and secretion is similar between AA and AW children. Forty-four prepubertal children (22 AA and 22 AW) with comparable body composition and visceral adiposity were studied. All underwent a 3-h hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp to calculate insulin sensitivity and insulin clearance and a 2-h hyperglycemic clamp (12.5 mmol/l) to assess first- and second-phase insulin responses. Twenty-four-hour food recalls were analyzed for macronutrient intake. Insulin clearance (19.5 +/- 0.7 vs. 22.9 +/- 1.1 ml x min(-1) x kg(-1) fat-free mass [FFM]; P = 0.011) and insulin sensitivity were lower in AA versus AW children (14.8 +/- 1.0 vs. 18.9 +/- 1.4 micro mol x min(-1) x kg(-1) FFM; P = 0.021). Both insulin clearance and insulin sensitivity correlated inversely with dietary fat/carbohydrate ratio, which was higher in AA than in white children. Fasting C-peptide and insulin were higher in AA children with no difference in proinsulin levels. First- and second-phase insulin concentrations and glucose disposition index (insulin sensitivity x first-phase insulin) were higher in AA than in white children (12.8 +/- 2.1 vs. 7.2 +/- 0.6 micro mol. min(-1) x kg(-1) FFM; P = 0.019). In conclusion, the hyperinsulinemia observed in AA children is due to both lower insulin clearance and higher insulin secretion compared with their white peers. The quantitative relationship between insulin secretion and sensitivity is upregulated in AA children. This suggests that increased insulin secretion in AA children is not merely a compensatory response to lower insulin sensitivity. Dietary factors may have a role. Additional studies are needed to determine whether metabolic/nutritional factors, possibly mediated through free fatty acids, may play a role in the hyperinsulinism observed in AA children.

Basal Metabolism↗