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Biomedical subjects

Richard N Pierson

Publications and source records attributed to Richard N Pierson.

At least 55 records · Page 3Linked to original sources
PubMed2004

Optimal timing of cardiac transplantation after ventricular assist device implantation.

OBJECTIVE: We sought to determine the influence of the interval from ventricular assist device implantation to cardiac transplantation on end-organ function and posttransplantation survival. METHODS: United Network for Organ Sharing data on 2692 heart transplantations performed in adult patients in the United States between October 1999 and March 2001 were reviewed. RESULTS: Seventeen percent (466) of adult heart transplant recipients were bridged to transplantation with a ventricular assist device. Almost half of patients with ventricular assist devices undergoing transplantation were upgraded to status 1A as a result of ventricular assist device-related complications occurring more than 30 days after ventricular assist device implantation. Creatinine and total bilirubin levels were less in patients undergoing transplantation after 2 to 4 weeks of mechanical support. One-year survival was higher in the nonventricular assist device than in the ventricular assist device group (85.7% vs 79.7%, P =.0004). Within the ventricular assist device group, survival was lower for patients undergoing transplantation within 2 weeks of ventricular assist device implantation compared with those undergoing transplantation later (74.2% vs 84.2 %, P =.03). One-year survival among patients supported with a ventricular assist device for more than 30 days without complications was 91.4%. Multivariate analysis demonstrated a significant independent effect of the time interval from ventricular assist device implantation to transplantation on posttransplantation mortality and suggested that a period of lowest risk might exist between 1 and 3 months after implantation. CONCLUSIONS: Survival after cardiac transplantation is influenced by the time interval from ventricular assist device insertion to transplantation. Survival is significantly lower when performed within 2 to 4 weeks of ventricular assist device implantation.

Adult↗
PubMed2004

Height and adiposity among children.

OBJECTIVE: Although BMI (kilograms per meter squared) is widely used as a surrogate measure of adiposity, it is moderately associated (r approximately 0.3) with height among children. We examined whether the resulting preferential classification of taller children as overweight, based on a BMI > or = 95th percentile, is appropriate. RESEARCH METHODS AND PROCEDURES: We assessed the cross-sectional relation of height among 5- to 18-year-old subjects (n = 1180) to levels of BMI, the sum of 10 skinfold thicknesses, and percentage body fat as determined by DXA. RESULTS: The prevalence of a BMI level > or = 95th percentile was substantially higher among 5- to 11-year-old subjects who were relatively tall for their age than among shorter children. Among 5- to 8-year-old boys, for example, each SD increase in height-for-age was associated with a 4.6-fold increase in the prevalence of overweight (p < 0.001). Height not only was associated with BMI but also showed similar correlations with the skinfold sum and with percentage body fat; furthermore, the magnitudes of these associations decreased with age. We also found that the association between percentage body fat and BMI (r = 0.85 to 0.90) was close to the maximum correlation that can be achieved by any weight-height index. DISCUSSION: The use of BMI, which preferentially classifies taller young children as overweight, is appropriate because height and adiposity are correlated before the age of 12 years.

Absorptiometry, Photon↗
PubMed2004

Sex-specific fat distribution is not linear across pubertal groups in a multiethnic study.

OBJECTIVE: To investigate sexual dimorphism and race differences in fat distribution (android/gynoid) before and during puberty. RESEARCH METHODS AND PROCEDURES: Fat distribution was measured by skinfold thickness and DXA in healthy African-American, Asian, and white subjects (n = 920), divided into pre-, early, and late pubertal groups. RESULTS: Gynoid fat masses adjusted for covariates were lower in late pubertal compared with prepubertal boys, but were not consistently greater in late pubertal compared with prepubertal girls. Progression of sex-specific fat distribution with increasing maturation was present in Asians only. Among African-American and white subjects, early pubertal boys had greater gynoid fat mass compared with the prepubertal group, whereas early pubertal girls had less gynoid fat mass compared with the prepubertal group. Sexual dimorphism in fat distribution was present in all pubertal groups, except among whites at early puberty. Among girls, Asians had lower gynoid fat than whites and African Americans in all pubertal groups. Among boys, Asians had less gynoid fat by DXA in early puberty and late puberty. DISCUSSION: Comparison among races demonstrated differences in sexual dimorphism and sex-specific fat distribution with progression in pubertal group. However, in all race groups, the fat distribution of late pubertal boys was more "male" or "android" than prepubertal boys, but late pubertal girls did not differ consistently from prepubertal girls. These findings suggested that the greater sexual dimorphism of fat distribution in late puberty compared with prepuberty may be attributable to larger changes in boys with smaller changes in girls.

Adipose Tissue↗
PubMed2004

Dual-energy x-ray absorptiometry-measured lean soft tissue mass: differing relation to body cell mass across the adult life span.

Lean soft tissue (LST) measured by dual-energy X-ray absorptiometry (DEXA) is used as a metabolic measure in aging research despite evidence of extracellular fluid expansion and a corresponding reduction in body cell mass (BCM) in older participants. We investigated the hypothesis that the fraction of LST as BCM is smaller with greater age. Men and women (n = 2043) had DEXA and 40K-counting for body potassium and BCM measured on the same day. Both BCM and LST were lower with greater age but the relative lowering was larger for BCM. A multiple linear regression model was fitted with BCM/LST as the dependent variable, and age, sex, and interaction terms as independent variables. Men had a mean BCM/LST greater (p < .001) than women; quadratic and cubic age terms were also significant or approached significance. Thus, the fraction of LST as BCM is smaller in older adults, a finding that has implications for the interpretation of DEXA results.

Absorptiometry, Photon↗
PubMed2004

Thoracic organ transplantation.

This article presents an overview of factors associated with thoracic transplantation outcomes over the past decade and provides valuable information regarding the heart, lung, and heart-lung waiting lists and thoracic organ transplant recipients. Waiting list and post-transplant information is used to assess the importance of patient demographics, risk factors, and primary cardiopulmonary disease on outcomes. The time that the typical listed patient has been waiting for a heart, lung, or heart-lung transplant has markedly increased over the past decade, while the number of transplants performed has declined slightly and survival after transplant has plateaued. Waiting list mortality, however, appears to be declining for each organ and for most diseases and high-severity subgroups, perhaps in response to recent changes in organ allocation algorithms. Based on perceived inequity in organ access and in response to a mandate from Health Resources and Services Administration, the lung transplant community is developing a lung allocation system designed to minimize deaths on the waiting list while maximizing the benefit of transplant by incorporating post-transplant survival and quality of life into the algorithm. Areas where improved data collection could inform evolving organ allocation and candidate selection policies are emphasized.

Algorithms↗
PubMed2004

Pencil-beam vs fan-beam dual-energy X-ray absorptiometry comparisons across four systems: body composition and bone mineral.

We compared bone mineral density (BMD) and body fat percentage (%fat) between two pencil-beam (Lunar DPX and DPX-L) and two fan-beam (Lunar Prodigy, Hologic Delphi A) dual-energy X-ray absorptiometry (DXA) systems. We examined these values in the total-body, spine, femur, and forearm scans in 78 healthy adults across these four DXA systems. BMD and %fat values were highly correlated among the four instruments. DPX-L gave the lowest mean %fat and Prodigy gave the highest mean %fat for both sexes. The means were system dependent for %fat estimates across the four DXA machines. There was a significant difference detected in BMD estimates across manufacturers, with the Delphi A providing systematically lower values than the Lunar systems in the whole body, spine, and femur sites but higher values than the Lunar systems in the forearm. The present study results show that both %fat and bone mineral estimates between pencil-beam and fan-beam systems are highly correlated, but vary by system. Significant differences exist between the instruments, especially between different manufacturers, and most of the comparisons are sex dependent. We conclude that longitudinal studies should always be evaluated on the same system when possible, and translation models should be used to assess cross-instrument differences.

Absorptiometry, Photon↗
PubMed2004

Measurement of percentage of body fat in 411 children and adolescents: a comparison of dual-energy X-ray absorptiometry with a four-compartment model.

OBJECTIVE: Pediatricians are encountering body composition information more frequently, with percentage of body fat (%BF) measurement receiving particular attention as a result of the obesity epidemic. One confounding issue is that different methods may yield different %BF results in the same person. The objective of this study was to compare dual-energy X-ray absorptiometry (DXA) with the criterion 4-compartment model (4-CM) for measurement of %BF in a large pediatric cohort and to assist pediatricians in appropriate interpretation of body composition information by recognizing differences between techniques. METHODS: Height, weight, anthropometrics, body density by underwater weighing, total body water by deuterium dilution, and bone mineral content and %BF by DXA (Lunar DPX/DPX-L) were measured in 411 healthy subjects, aged 6 to 18 years. Values for %BF by 4-CM and DXA were compared using regression analysis. RESULTS: The mean +/- standard deviation values for %BF by DXA (22.73% +/- 11.23%) and by 4-CM (21.72% +/- 9.42%) were different, but there was a strong relationship between the 2 methods (R2 = 0.85). DXA underestimated %BF in subjects with lower %BF and overestimated it in those with higher %BF. The relationship between the 2 methods was not affected by gender, age, ethnicity, pubertal stage, height, weight, or body mass index. The standard error of the estimate was 3.66%. CONCLUSION: This analysis demonstrates a predictable relationship between DXA and 4-CM for %BF measurement. Because of its ease of use, consistent relationship with 4-CM, and availability, we propose that DXA has the capacity for clinical application including prediction of metabolic abnormalities associated with excess %BF in pediatrics.

Absorptiometry, Photon↗
PubMed2004

Prediction models for evaluation of total-body bone mass with dual-energy X-ray absorptiometry among children and adolescents.

OBJECTIVE: The performance of dual-energy x-ray absorptiometry (DXA) in identifying children with decreased bone mass is increasing, but there is no consensus regarding how to interpret the results. The World Health Organization diagnostic categories for normal, osteopenia, and osteoporosis, based on T scores, are not applicable to children and adolescents who have not yet reached peak bone mass. The pediatric reference standards provided by DXA manufacturers have been questioned. Bone mineral density determined with DXA is "areal" density (a 2-dimensional measurement of a 3-dimensional structure), and its misleading nature among growing and maturing children is well recognized. Few published pediatric reference values for bone mineral density measured with DXA include factors that are known to affect the results besides age and gender. Our objective was to develop an algorithm for the evaluation of bone mass among children that included known determinants of bone mass and of its measurement with DXA. METHODS: Height, weight, pubertal status, and total-body bone mineral content, total-body bone area, and total-body bone mineral density measured with DXA were recorded for an ethnically diverse group of healthy pediatric subjects (n = 1218; age: 6-18 years). Prediction models for bone measurements were developed and validated with healthy pediatric subjects and then applied to children with medical disorders. RESULTS: There was a significant gender effect, as well as an interaction between gender and ethnicity. Separate models were developed for log total-body bone mineral content, log total-body bone area, and 1/total-body bone mineral density for girls and boys. The variability explained for each measurement increased from level 1, including age and ethnicity (76-86%), to level 2, including age, ethnicity, height, and weight (84-97%), and to level 3, including age, ethnicity, height, weight, and bone area (89-99%). Pubertal stage was an additional significant predictor of bone measurements but increased the explained variability by only 0.1% with height and weight in the models. The values predicted with each model were not different from measured values for the validation group but were different for patients with medical disorders, with different patterns according to the diagnoses. CONCLUSIONS: These models, including known determinants of bone mass and of bone measurements with DXA, provide an evaluation of pediatric bone mass that proceeds in steps from level 1 to level 3. The outcomes were different for patients at risk for compromised bone mass, compared with healthy children, with specific patterns for each medical disorder. We propose an algorithm for evaluation of bone measurements that follows levels 1 to 3. Our findings suggest that application of this algorithm to well-characterized groups of pediatric patients could identify disease-specific features of DXA results. We recommend this approach as a basis for consensus regarding the clinical evaluation of pediatric bone mass, and we suggest that it could lead to meaningful classification of pediatric bone disorders, investigation of pathophysiologic processes, and development of appropriate interventions.

Absorptiometry, Photon↗
PubMed2003

Body cell mass: model development and validation at the cellular level of body composition.

Existing models to estimate the metabolically active body cell mass (BCM) component in vivo remain incompletely developed. The classic Moore model is based on an assumed BCM potassium content of 120 mmol/kg. Our objectives were to develop an improved total body potassium (TBK)-independent BCM prediction model on the basis of an earlier model (Cohn SH, Vaswani AN, Yasumura S, Yuen K, and Ellis KJ. J Lab Clin Med 105: 305-311, 1985), to apply this improved model in subjects to explore the sex and age dependence of the TBK/BCM ratio, to develop a new TBK/BCM model on the basis of physiological associations between TBK and total body water (TBW) at the cellular level of body composition, and to fit this new model with available reference data. Subjects were 112 healthy adults who had the following components measured: TBW by 2H2O or 3H2O, extracellular water by NaBr, total body nitrogen by in vivo neutron activation, bone mineral by dual-energy X-ray absorptiometry, and TBK by whole body counting. Human reference data were collected from earlier published reports. The improved Cohn model-derived TBK/BCM ratio was (mean +/- SD) 109.0 +/- 10.9 mmol/kg and was not significantly related to sex and age. A simplified version of the new TBK-TBW model provided a TBK/BCM ratio almost identical (109.1 mmol/kg) to that derived by the improved Cohn model. The TBK-BCM prediction formula derived from the improved and new models [BCM (kg) = 1/109 x TBK (mmol); or BCM = 0.0092 x TBK] gives BCM estimates approximately 11% higher than the classic Moore model (BCM = 0.0083 x TBK) formulated on rough tissue composition estimates. The present analyses provide a physiologically based, improved, and validated TBK-BCM prediction formula that should prove useful in body composition and metabolism research.

Adult↗
PubMed2003

Hyperacute rejection of mouse lung by human blood: characterization of the model and the role of complement.

BACKGROUND: The pathophysiology of hyperacute lung rejection (HALR) is not fully understood. A mouse model of HALR by human blood would be valuable to efficiently dissect the molecular mechanisms underlying this complex process, but it has not been described. METHODS: We developed a xenogenic mouse lung-perfusion model. Perfusion with heparinized autologous blood (n=3) was compared with human blood unmodified (n=7) or pretreated with C1 inhibitor (n=5) or soluble complement receptor type 1 (n=6) at unchanged flow conditions. RESULTS: Perfusion with autologous blood was associated with stable physiologic parameters and no overt evidence of lung injury for up to 2 hr. Pulmonary artery perfusion pressure increased rapidly after introduction of unmodified human blood, plasma anti-Gal(alpha)1,3Gal antibodies declined (90% immunoglobulin [Ig]M, 80% IgG), and lungs reliably met survival endpoints within 11 min (median 10 min, confidence interval [CI]: 9-11). Human Ig and neutrophils were rapidly sequestered in the lung. Survival was significantly prolonged in the soluble complement receptor type 1 group (36 min, CI: 26-46) (P<0.01) and in the C1 inhibitor group (23 min, CI: 21-25) (P<0.05), and pulmonary vascular resistance elevation and complement activation were significantly attenuated but not prevented. CONCLUSIONS: Hyperacute rejection of mouse lung by human blood occurs with kinetics, physiology, and histology closely analogous to the pig-to-human model. In addition, as in that model, neither of two potent soluble-phase complement inhibitors prevented complement activation or HALR. We conclude that the mouse lung model is relevant to dissect the cellular and molecular mechanisms governing HALR.

Acute Disease↗
PubMed2003

Factors influencing body composition in persons with spinal cord injury: a cross-sectional study.

To determine the body composition differences across age, 133 men with chronic spinal cord injury (SCI) (66 with tetraplegia, 67 with paraplegia) were compared with an age-, height-, and ethnicity-matched able-bodied male reference population (n = 100) using two different dual-energy X-ray absorptiometry densitometers. The effects of duration of injury, level, and completeness of lesion were analyzed in the SCI population. Independent of age, total body and regional lean mass were lower and fat mass was higher in persons with SCI compared with controls. The SCI group was 13 +/- 1% (means +/- SE) fatter per unit of body mass index (kg/m2) compared with the control group (P < 0.0001). Advancing age was strongly associated with less lean mass and greater adiposity in those with SCI, whereas it was mildly related in the controls. Total body and regional arm and trunk, but not leg, lean tissues were lower in subjects with SCI, across all ages, than in the controls. In summary, persons with SCI were fatter for any body mass index and demonstrated significantly less lean and more adipose tissues for any given age compared with controls.

Adipose Tissue↗
PubMed2003

Hyperacute lung rejection in the pig-to-human model. III. Platelet receptor inhibitors synergistically modulate complement activation and lung injury.

BACKGROUND: The influence of platelet von Willebrand factor (vWF)-glycoprotein (GP)Ib-V-IX and GPIIb-IIIa receptor interactions in the context of hyperacute rejection (HAR) of pulmonary xenografts has not previously been explored. METHODS: Aurintricarboxylic acid (ATA, an inhibitor of platelet-GPIb interactions with vWF), SC52012A (SC, a synthetic GPIIb/IIIa inhibiting peptide), or both were added to heparinized whole human blood before perfusion of isolated piglet lungs. Results were compared with unmodified blood ("unmodified"). RESULTS: Perfusion of porcine lungs with unmodified human blood resulted in an immediate rise in pulmonary vascular resistance (PVR), fluid and platelet sequestration in the lung, and, without exception, cessation of function within 15 minutes with a mean survival of 8 minutes. Addition of ATA or SC before lung perfusion significantly decreased the rise in PVR, diminished histamine release, and prolonged survival to 31+/-11 and 31+/-22 minutes, respectively. When the therapies were combined, mean survival was 156+/-77 minutes (P<0.05 vs. either monotherapy). Complement activation was synergistically attenuated only when the drugs were used together. CONCLUSIONS: Platelet protein receptor adhesive interactions play an important role in amplification of complement activation during hyperacute lung rejection. Inhibiting recruitment of platelets at the site of initial immunologic injury to endothelial cells may protect porcine organs against thrombosis and inflammation during the initial exposure to human blood.

Acute Disease↗
PubMed2003

A modified bronchial anastomosis technique for lung transplantation.

BACKGROUND: Low rates of major complications have been reported for the intussuscepting bronchial anastomotic technique but stenosis, malacia, and granulation tissue at the anastomosis may cause clinically important morbidity. We hypothesized that a modification of the telescoping technique that improves bronchial wall apposition might be associated with improved bronchial healing and clinical outcomes. METHODS: The telescoping horizontal mattress "U-stitch" suture technique was modified to incorporate figure-of-eight sutures placed in the cartilaginous wall between each of three intussuscepting U stitches. Serial videotape records of 152 individual anastomoses (99 modified, 53 telescoped) in 118 consecutive operative survivors were retrospectively reviewed by examiners blinded with respect to technique used. Stenosis, airway instability, mucosa quality, and devascularized luminal tissue were graded at 4 to 14 days (initial), 4 to 12 weeks (early), and 6 to 12 months (late) after transplantation. RESULTS: The incidence of anastomotic stenosis was significantly lower using the modified technique at the initial (p = 0.025) and late (p = 0.015) observations. In the initial phase airway instability (p = 0.015) and devascularization grades (p = 0.001) were also significant lower in the modified group. There were no significant differences in mucosal condition between techniques. The modified telescoping technique was associated with significant survival advantage (mean 17.7%; p = 0.029) by multivariate analysis. The incidence of major airway complications (dehiscences and stenoses required stents) tended to be lower (3% versus 6%) in the modified group. CONCLUSIONS: The modified telescoping bronchial anastomosis technique is associated with improved early and late bronchial healing and higher 5-year survival without increased major airway complications.

Anastomosis, Surgical↗
PubMed2003

Modeling the effects of functional performance and post-transplant comorbidities on health-related quality of life after heart transplantation.

BACKGROUND: Health-related quality of life and functional performance are important outcome measures following heart transplantation. This study investigates the impact of pre-transplant functional performance and post-transplant rejection episodes, obesity and osteopenia on post-transplant health-related quality of life and functional performance. METHODS: Functional performance and health-related quality of life were measured in 70 adult heart transplant recipients. A composite health-related quality of life outcome measure was computed via principal component analysis. Iterative, multiple regression-based path analysis was used to develop an integrated model of variables that affect post-transplant functional performance and health-related quality of life. RESULTS: Functional performance, as measured by the Karnofsky scale, improved markedly during the first 6 months post-transplant and was then sustained for up to 3 years. Rejection Grade > or =2 was negatively associated with health-related quality of life, measured by Short Form-36 and reversed Psychosocial Adjustment to Illness Scale scores. Patients with osteopenia had lower Short Form-36 physical scores and obese patients had lower functional performance. Path analysis demonstrated a negative direct effect of obesity (beta = - 0.28, p < 0.05) on post-transplant functional performance. Post-transplant functional performance had a positive direct effect on the health-related quality of life composite score (beta = 0.48, p < 0.001), and prior rejection episodes grade > or =2 had a negative direct effect on this measure (beta = -0.29, p < 0.05). Either directly or through effects mediated by functional performance, moderate-to-severe rejection, obesity and osteopenia negatively impact health-related quality of life. These findings indicate that efforts should be made to devise immunosuppressive regimens that reduce the incidence of acute rejection, weight gain and osteopenia after heart transplantation.

Bone Diseases, Metabolic↗
PubMed2003

Effect of complement fragment 1 esterase inhibition on survival of human decay-accelerating factor pig lungs perfused with human blood.

BACKGROUND: The role of complement in hyperacute lung xenograft rejection has not been fully elucidated. The present study evaluates the effect of complement (C) 1 esterase inhibition on hyperacute rejection of human decay-accelerating factor (hDAF)-positive pig lung by human blood. METHODS: Using a modification of an established ex vivo model, right and left lungs from individual animals were surgically isolated and separately perfused. Pigs homozygous for hDAF were perfused with fresh human blood that was either untreated or treated with complement 1 esterase inhibitor (C1-Inh) at doses of 1 U/ml (n = 5), 5 U/ml (n = 3) or 10 U/ml plasma (n = 5). RESULTS: Only C1-Inh at 10 U/ml prolonged survival time (230 +/- 48.3 minutes) as compared with controls (65.6 +/- 26.5 minutes, p < 0.05) and diminished complement activation (C3a and C5a, p < 0.05). Interestingly, a low concentration of C1-Inh increased the pulmonary vascular resistance (PVR; 1 U/ml: 0.54 +/- 0.3; 10 U/ml: 0.19 +/- 0.08). Sequestration of neutrophils (92 +/- 3%) and platelets (64 +/- 13%) was not prevented by any concentration of C1-Inh. Tissue deposition of C3b and C5b-9 were diminished by hDAF expression, and further blunted by treatment, with 10 U/ml C1-Inh. CONCLUSIONS: Complement plays a critical role in early events of lung hyperacute rejection (HAR). However, even potent inhibition of C1 esterase and C3/C5 convertase, using serum C1-Inh in pig lungs homozygous for hDAF expression, does not prevent rapid lung injury. Our findings implicate innate immune pathways resistant to efficient complement regulation, and suggest a role for neutrophils and platelets in the lung's particular vulnerability.

Animals↗
PubMed2003

CD154 regulates primate humoral immunity to influenza.

Current methods of immunosuppression for the purposes of allowing solid organ transplantation in humans are broadly inhibitory and thus are associated with an increased risk of opportunistic infections and neoplasia. We have shown previously that a selective blockade of CD40-CD154 interactions during heart transplantation in cynomolgus macaques significantly delays immune-mediated graft injury. Here, we determined the effect of anti-CD154 mAb therapy on primate serologic responses to immunization with influenza virus hemagglutinin (HA), a T-cell-dependent Ag. We found that CD154 blockade attenuated primary and secondary serum Ab responses of IgM and IgG isotypes to influenza, even when anti-CD154 treatment was discontinued prior to reimmunization. These findings show that in primates CD40-CD154 interactions are necessary for both primary and secondary Ab responses to viral Ags. Furthermore, the data suggest that viral Ag stimulation of primates in the absence of CD154 stimulation may have a tolerizing effect on that Ag.

Animals↗