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Biomedical subjects

R N Pierson

Publications and source records attributed to R N Pierson.

At least 19 recordsLinked to original sources

A single-season prospective study of respiratory viral infections in lung transplant recipients.

The frequency and complications of respiratory viral infections (RVI) were studied in 50 ambulatory lung transplant patients during a single winter season, using viral antigens, viral cultures and PCR of nasal washes or bronchoalveolar lavages. Patients' survival, episodes of acute rejection and occurrence of bronchiolitis obliterans (BO) or BO syndrome (BOS) were monitored for 1 yr after the study. Overall, 32 (64%) patients had 49 symptomatic episodes. Documented infections included eight due to respiratory syncytial virus (RSV), one due to parainfluenza virus (PIV) and 10 due to influenza (FLU). Four of the FLU infections were serological rises without symptoms. Overall, 17 (34%) patients had documented viral infection; four patients had lower respiratory involvement and two (one RSV, one PIV) were hospitalised for aerosolised ribavirin treatment. After 1 yr there were three (6%) deaths unrelated to RVI. BO or BOS had occurred in one (6%) out of 17 patients with and three (12%) out of 33 without RVI. Respiratory viruses infected one-third of ambulatory lung transplant recipients in a single season. In conclusion, respiratory viral infection was not associated with subsequent graft dysfunction. Larger prospective studies are required to better define the acute and long-term morbidity of these infections.

Adult↗

Effect of age on outcomes after left ventricular assist device placement.

The influence of age on outcomes after left ventricular assist device (LVAD) implantation is not well studied. To address this question, we assessed 222 patients who underwent LVAD placement and were divided into quartiles based on age (years): group 1, or=60. Eighty-four patients died on LVAD support. Six- and 12-month survivals for the four groups of LVAD patients were 67.7, 73.7, 49.8, and 38.2, and 49.4, 57.3, 42.7, and 26.2, respectively (all P<.01). Older patients showed a higher risk of infections, embolic strokes, and respiratory complications. They were the least likely to undergo reoperations postimplantation (56%, 53%, 50%, 46%, P=.06). After adjusting for baseline differences between the groups, there was a trend toward increasing mortality with age, which did not reach significance (odds ratio 1.93; 95% confidence interval 0.95 to 3.92 for the oldest quartile as compared with the youngest). In conclusion, these results suggest in the absence of other high risk factors, age alone should not be used as an independent contraindication for LVAD implantation.

Adult↗

Relation of BMI to fat and fat-free mass among children and adolescents.

OBJECTIVE: Although the body mass index (BMI, kg/m2) is widely used as a surrogate measure of adiposity, it is a measure of excess weight, rather than excess body fat, relative to height. We examined the relation of BMI to levels of fat mass and fat-free mass among healthy 5- to 18-y-olds. METHODS AND PROCEDURES: Dual-energy X-ray absorptiometry was used to measure fat and fat-free mass among 1196 subjects. These measures were standardized for height by calculating the fat mass index (FMI, fat mass/ht2) and the fat-free mass index (FFMI, fat-free mass/ht2). RESULTS: The variability in FFMI was about 50% of that in FMI, and the accuracy of BMI as a measure of adiposity varied greatly according to the degree of fatness. Among children with a BMI-for-age > or =85th P, BMI levels were strongly associated with FMI (r=0.85-0.96 across sex-age categories). In contrast, among children with a BMI-for-age <50th P, levels of BMI were more strongly associated with FFMI (r=0.56-0.83) than with FMI (r=0.22-0.65). The relation of BMI to fat mass was markedly nonlinear, and substantial differences in fat mass were seen only at BMI levels > or =85th P. DISCUSSION: BMI levels among children should be interpreted with caution. Although a high BMI-for-age is a good indicator of excess fat mass, BMI differences among thinner children can be largely due to fat-free mass.

Absorptiometry, Photon↗

Pencil-beam versus fan-beam dual-energy X-ray absorptiometry comparisons across four systems: appendicular lean soft tissue.

Dual-energy X-ray absorptiometry (DXA) provides an important opportunity for estimating total body skeletal muscle (SM) mass from DXA-measured appendicular lean soft tissue (ALST). A DXA SM prediction model was developed with magnetic resonance imaging as the reference and ALST (i. e., sum of arm plus leg lean soft tissue) as a main predictor variable. In the present study we examined whether ALST estimates are comparable across systems (i. e., penciland fan-beam) and manufacturers. Pencil-beam systems (Lunar DPX and DPX-L) are usually considered more accurate but slower than fan-beam systems (Lunar Prodigy and Hologic Delphi A). In this study we compared ALST estimates in 35 healthy adults across these four systems. The methods gave similar group mean (+/-SD) values and were highly intercorrelated. There was no significant bias detected across the four systems. ALST estimates from the evaluated DXA systems are comparable and thus appear interchangeable as methods for quantifying total body SM in vivo.

Absorptiometry, Photon↗

A brief history of body composition-from F. D. Moore to the new Reference Man.

The history of applying body composition measurements to physiology is short, well less than a century. Progress has been phenomenal, on three different fronts: tracer dilution methods, neutron activation methods, and imaging methods. The latter have seen the most recent and exciting advances, and we have probably just "scratched the surface" for the futures of imaging, with spectroscopy showing great promise. However the physiological principles established in the 1950-1980 era are the reason we are here; measurements that lead to diagnosis, treatment, and understanding of disease mechanisms. The future is very bright.

Anthropometry↗

The relationship between body mass index and body cell mass in African-American, Asian, and Caucasian adults.

The objective of this study was to investigate the relationship between body mass index (BMI, kg/m(2)) and body cell mass (BCM) estimated from total body potassium (TBK) measured by whole body (40)K counting in healthy 284 African-Americans (AA), 269 Asians (A) and 536 Caucasians (C) aged 18-107 years and to study the effects of age, sex, and race on the relationship. Body fat and fat-free mass (FFM) were measured by dual-energy X-ray absorptiometry (DXA). There was a significant positive correlation between BCM and BMI. For a given BMI, A had lower BCM but decreased less per year of age than AA and C, and males had higher BCM than females in each ethnic group. The fraction, BCM/FFM decreased with BMI in all subgroups by race, sex, and age, and males decreased more per age and AA decrease more than A and C. Not only the BCM-BMI relationship but also BCM/FFM vs. BMI is important to health.

Absorptiometry, Photon↗

Is there an association between skeletal muscle mass and bone mineral density among African-American, Asian-American, and European-American women?

Skeletal muscle strength is a factor in the growth and maintenance of bone density and both skeletal muscle mass and bone mineral density are related to bone fracture risk. We studied the relationship between total body bone mineral density (TBBMD) and total appendicular skeletal muscle mass (TASM) estimated by dual-energy X-ray absorptiometry (DEXA) in African-American (AA), Asian-American (AsA), and European-American (EA) premenopausal (PRM) and postmenopausal (POM) women. The age- and weight-adjusted TBBMD-TASM association was positive in all PRM race groups and in POM EA, but was negative in POM AA and POM AsA. Body weight and age were positively and negatively associated with TBBMD, respectively, and the relationship was stronger in POM. In all race groups the variability in TBBMD was significantly greater in POM women.

Absorptiometry, Photon↗

Hyperacute lung rejection in the pig-to-human model. 2. Synergy between soluble and membrane complement inhibition.

BACKGROUND: The role of complement in hyperacute lung xenograft rejection has not been elucidated. The present study evaluates the effect of complement (C) C3/C5 convertase inhibition on hyperacute rejection of pig lung by human blood. METHODS: In an established ex-vivo model, lungs from pigs heterozygous for human decay accelerating factor (hDAF), non-transgenic littermate control pigs, or farm-bred pigs were perfused with fresh human blood that was either unmodified or treated with soluble complement receptor type 1 (sCR1: TP10, 100 microg/ml). RESULTS: Non-transgenic lungs from littermate controls had a median survival time of 35 min (range 5 to 210; P = 0.25 vs. farm-bred piglets: median 5 min, range 5 to 10). Lungs expressing hDAF survived for a median of 90 min (range 10 to 161; P = 0.5 and 0.01 vs. littermate and farm-bred controls, respectively), with sCR1, whereas hDAF (-) lungs failed by 35 min (range 6 to 307), hDAF (+) lungs survived for 330 min (range 39 to 577) [P = 0.002 vs. farm-bred; P = 0.08 vs. hDAF (-); P = 0.17 vs. sCR1/hDAF (-)]. The rise in pulmonary vascular resistance (PVR) at 5 min was blunted only by hDAF (+) with sCR1 (0.26 +/- 0.2 vs. 0.5 to 0.7 mmHg/ml/min for other groups). Plasma C3a and sC5b-9 and tissue deposition of C5b-9 were dramatically diminished using sCR1, and further decreased in association with hDAF. Histamine and thromboxane were produced rapidly in all groups. CONCLUSION: Complement plays an important role in lung HAR. However, even potent inhibition of C3/C5 convertase, both membrane bound in lung and by a soluble-phase inhibitor in the blood, does not prevent activation of inflammatory responses known to be particularly injurious to the lung. Our findings implicate a role for innate immune pathways resistant to efficient complement regulation. The role of anti-species antibody, coagulation pathway dysregulation, and additional environmental or genetic influences remain to be defined.

Acute Disease↗

Effects of whey protein and resistance exercise on body cell mass, muscle strength, and quality of life in women with HIV.

OBJECTIVE: To determine the effects of whey protein, resistance exercise, and combined protein and exercise treatment on body cell mass (BCM), muscle strength, and quality of life (QOL) in HIV-infected women with reduced BCM. DESIGN AND SETTING: Prospective, randomized, controlled trial at a university hospital in New York City. METHODS: A volunteer sample of 30 HIV-infected women were randomized to whey protein (PRO), progressive resistance exercise (PRE), or combined treatment (PRO-PRE) for 14 weeks after a 6-week control period. The main outcome measures were body weight, BCM, skeletal muscle, fat mass, muscle strength, and QOL. RESULTS: There were no significant changes in BCM, strength, or QOL during the control period. PRO patients gained 3.6 kg (P = 0.001), and 2.5 kg fat (P = 0.002) with no change in BCM (0.5 kg; P = 0.07) or skeletal muscle (0.6 kg; P = 0.12). The PRE group increased BCM (0.74 kg;P = 0.03) and skeletal muscle (1.2 kg; P < 0.001) and decreased fat (1.7 kg; P = 0.02). PRO-PRE increased BCM (0.61 kg; P = 0.01) without change in skeletal muscle (0.6 kg; P = 0.30). Strength increased for both exercise groups (range, 40.6-95.3%; P < 0.001). The QOL physical activity score improved for PRE (P = 0.02) and worsened for PRO (P = 0.01). CONCLUSIONS: Resistance exercise significantly increased BCM, muscle mass, muscle strength, and QOL in HIV-infected women with reduced BCM. Whey protein had little effect on BCM accrual. Combined protein and exercise did not increase BCM in excess of gains achieved by exercise alone.

Adult↗

Hemorrhagic colitis due to a novel Escherichia coli serotype (O121:H19) in a transplant patient.

Infection due to enterohemorrhagic Escherichia coli (EHEC) has not been described in immunosuppressed patients. We recently saw a case of EHEC infection caused by a novel Shiga toxin II-producing Escherichia coli serotype (O121:H19) that caused hemorrhagic colitis in a patient with renal and cardiac transplants. The patient's signs, symptoms, and colon pathology were similar to reports of EHEC infection in immunocompetent patients. This case suggests that the immunosuppressed state may not alter the clinical presentation or histopathologic findings of this disorder. Assays for EHEC are not routinely done at most hospitals. Therefore, clinicians caring for transplant patients should be aware of the typical clinical presentation of EHEC infection, so that they can initiate appropriate laboratory investigation in suspected cases.

Colitis↗

A multicenter, randomized, controlled trial of Celsior for flush and hypothermic storage of cardiac allografts.

BACKGROUND: A multicenter, randomized, controlled, open-label trial was conducted to evaluate the safety and efficacy of Celsior when used for flush and hypothermic storage of donor hearts before transplantation. METHODS: Heart transplant recipients were randomized to one of two treatment groups in which donor hearts were flushed and stored in either Celsior or conventional preservation solution(s) (control). Study subjects were followed for 30 days after transplantation. RESULTS: A total of 131 heart transplant recipients were enrolled (Celsior, n = 64; control, n = 67). The treatment groups were evenly distributed in donor and recipient base line characteristics. Graft loss rate was lower in the Celsior group on day 7 (3% versus 9%) and on day 30 (6% versus 13%), but the difference was not statistically significant based on 95% confidence interval analysis. No significant difference was measured between the Celsior and control groups in 7-day patient survival (97% versus 94%) and the proportion of patients with one or more adverse events (Celsior, 88%; control 87%) or serious adverse events (Celsior, 38%; control, 46%). Significantly fewer patients in the Celsior group developed at least one cardiac-related serious adverse event (13% versus 25%). CONCLUSIONS: Celsior was demonstrated to be as safe and effective as conventional solutions for flush and cold storage of cardiac allografts before transplantation.

Adult↗

Role of anti-Gal alpha13Gal and anti-platelet antibodies in hyperacute rejection of pig lung by human blood.

BACKGROUND: Previous work has shown that antibodies against porcine antigens are an important trigger of hyperacute lung rejection (HALR). The relative importance of Gal alpha1,3Gal epitopes and other antigens, such as those expressed on pig platelet membranes or lung itself, has not been defined. This study compares the efficiency of three anti-pig antibody depletion strategies, and their efficacy with regard to attenuation of HALR. METHODS: Plasma pooled from three human donors was adsorbed against Gal alpha1,3Gal disaccharide or porcine platelet extract (PPE), or passed through pig lung vasculature. Whole blood reconstituted using adsorbed plasma was then used to perfuse piglet lung, and results were compared with unmodified human blood. RESULTS: Depletion of lung-reactive anti-Gal alpha1-3Gal antibodies was most efficient with the alphaGal column (99% +/- 0.5% vs 87% to 93% +/- 11% for PPE and 92% to 95% +/- 8% for lung, p < 0.01 vs alphaGal column). PPE column tended to be more efficient (77% to 84% +/- 12%) in removing anti-PPE antibodies than pig lung (66% to 70% +/- 14%) or the alphaGal column (56% to 63% +/- 16%, p < 0.05). Lung survival and function with each antibody depletion strategy was improved relative to unmodified controls (mean survival > or = 146 minutes vs 8 minutes for controls). Although alphaGal and lung adsorption yielded more consistent lung protection (survival beyond 2 hours) than did PPE, no approach proved significantly superior. Complement C3a elaboration at 10 minutes was attenuated > 80% by each adsorption strategy, an effect that was most pronounced in the lung adsorption group (95%, p < 0.01). Histamine elaboration was blunted significantly by PPE adsorption but not in other groups (p < 0.05). Platelet but not leukocyte sequestration was decreased with antibody depletion compared with the nondepleted group (44% to 50% vs 82%, p < 0.01). CONCLUSIONS: Each antibody depletion strategy tested significantly prolongs lung xenograft survival and function compared with unmodified human blood, but none was sufficient to reliably prevent HALR. Depletion of antibodies against both alphaGal and additional cell membrane antigens, or control of antibody-independent pathogenic pathways, may be necessary to consistently prevent HALR.

Acute Disease↗

Total body water reference values and prediction equations for adults.

BACKGROUND: The clinical interpretation of total body water (TBW) necessitates the availability of timely comparative reference data. The prediction of TBW volume in renal disease is critical in order to prescribe and monitor the dose of dialysis in the determination of Kt/V. In clinical practice, urea distribution (V) is commonly predicted from anthropometric equations that are several decades old and for white patients only. This article presents new reference values and prediction equations for TBW from anthropometry for white and black adults. METHODS: The study sample included four data sets, two from Ohio and one each from New Mexico and New York, for a total of 604 white men, 128 black men, 772 white women, and 191 black women who were 18 to 90 years of age. The TBW concentration was measured by the deuterium or tritium oxide dilution method, and body composition was measured with a Lunar DXA machine. An all-possible-subsets of regression was used to predict TBW. The accuracy of the selected equations was confirmed by cross-validation. RESULTS: Blacks had larger TBW means than whites at all age groups. The 75th TBW percentile for whites approximated the TBW median for blacks at most ages. The white men and black men and women had the largest TBW means ever reported for healthy individuals. The race- and sex-specific TBW prediction equations included age, weight, and stature, with body mass index (BMI) substituted for weight in the white men. The root mean square errors (RMSEs) and standard errors for the individual (SEIs) ranged from approximately 3.8 to 5.0 L for the men and from 3.3 to 3.6 L for the women. In both men and women, high values of TBW were associated with high levels of total body fat (TBF) and fat-free mass (FFM). CONCLUSION: : TBW in these healthy adults is relatively stable through a large portion of adulthood. There are significant race and sex differences in TBW. These accurate and precise equations for TBW provide a useful tool for the clinical prediction of TBW in renal disease for white and black adults. These are the first TBW prediction equations that are specific for blacks.

Adult↗

Mediastinal fibrosis.

Mediastinal fibrosis is the least common, but the most severe, late complication of histoplasmosis. It should be differentiated from the many other less-severe mediastinal complications of histoplasmosis, and from other causes of mediastinal fibrosis. Posthistoplasmosis mediastinal fibrosis is characterized by invasive, calcified fibrosis centered on lymph nodes, which, by definition, occludes major vessels or airways.

Adult↗

Moderate energy restriction increases bone resorption in obese postmenopausal women.

BACKGROUND: Weight reduction reduces bone mineral density (BMD) and increases the risk of osteoporosis. OBJECTIVE: We investigated whether bone is mobilized in postmenopausal women during energy restriction and whether hormones regulate bone turnover and mass. DESIGN: Twenty-seven obese postmenopausal women with a mean (+/-SD) age of 55.9 +/- 7.9 y and body mass index (in kg/m(2)) of 33.0 +/- 3.8 completed the 6-mo study. Fourteen women followed a moderate energy-restricted diet (WL group) and 13 control subjects maintained their body weight (WM group). Body weight, bone turnover markers, serum parathyroid hormone (PTH), and dietary intake were measured throughout the study. Total-body BMD, sex hormone binding globulin, leptin, and estrone were measured at baseline and at week 25. RESULTS: In the WL group, body weight decreased by 10.2 +/- 5.5% (P < 0.001), body fat mass decreased by 18.7 +/- 11.3% (P < 0.001), and total-body BMD decreased by 1.2 +/- 1.2%; these changes were significantly different from those in the WM group (P < 0.05). Serial measurements showed chronically elevated rates of bone resorption and formation during energy restriction that were greater than in the WM group (P < 0.05). Serum sex hormone binding globulin increased and leptin decreased with weight loss (P < 0.05). Serum PTH tended to increase in the WL group but not in the WM group (P < 0.06). The reduction in fat mass with weight loss was directly associated with a decrease in serum estrone (P < 0.01, R(2) = 0.50). CONCLUSIONS: Moderate energy restriction increases bone turnover in obese postmenopausal women and may be regulated in part by alterations in serum PTH and estrone.

Absorptiometry, Photon↗

Magnitude and variation of ratio of total body potassium to fat-free mass: a cellular level modeling study.

Potassium is an essential element of living organisms that is found almost exclusively in the intracellular fluid compartment. The assumed constant ratio of total body potassium (TBK) to fat-free mass (FFM) is a cornerstone of the TBK method of estimating total body fat. Although the TBK-to-FFM (TBK/FFM) ratio has been assumed constant, a large range of individual and group values is recognized. The purpose of the present study was to undertake a comprehensive analysis of biological factors that cause variation in the TBK/FFM ratio. A theoretical TBK/FFM model was developed on the cellular body composition level. This physiological model includes six factors that combine to produce the observed TBK/FFM ratio. The ratio magnitude and range, as well as the differences in the TBK/FFM ratio between men and women and variation with growth, were examined with the proposed model. The ratio of extracellular water to intracellular water (E/I) is the major factor leading to between-individual variation in the TBK/FFM ratio. The present study provides a conceptual framework for examining the separate TBK/FFM determinants and suggests important limitations of the TBK/FFM method used in estimating total body fat in humans and other mammals.

Adipose Tissue↗

Thromboxane mediates pulmonary hypertension and lung inflammation during hyperacute lung rejection.

The role of thromboxane (Tx) in hyperacute rejection of pig lung by human blood was studied in an ex vivo model, wherein lungs from juvenile piglets were perfused with fresh heparinized human blood. In this model, hyperacute lung rejection was characterized by an abrupt rise in pulmonary vascular resistance (PVR; >1 cmH2O x ml(-1) x min) and prolific Tx elaboration (>15 ng/ml) within 5 min and loss of function within 10 min. Although papaverine significantly blunted the rise in PVR (<0.2 cmH2O x ml(-1) x min), Tx production was not inhibited (>20 ng/ml), and florid tracheal edema was usually evident within 20 min. In contrast, both inhibition of Tx synthesis (Tx < 3 ng/ml) with OKY-046 and blockade of the Tx receptor with SQ-30741 (Tx > 20 ng/ml) were not only associated with significantly lower peak PVRs (<0.2 cmH2O x ml(-1) x min) but also with attenuated increase in lung wet-to-dry ratio and airway edema. In concert, elaboration of histamine and tumor necrosis factor was blunted, and median survival increased >10-fold to 2 h (SQ-30741) and >4 h (OKY-046). Depletion of the pig lung macrophages with dichloromethyl bisphosphonate in liposomes, but not Pall filtration of the human blood or liposomes alone, significantly inhibited Tx elaboration (<0.2 vs. >8 ng/ml for Pall filtration or liposomes) and blunted PVR elevation (<0.3 cmH(2)O x ml(-1) x min) during initial perfusion. C3a and histamine elaboration were inhibited, and median survival was significantly prolonged (>4 h). These findings implicate Tx in the inflammation associated with hyperacute lung rejection and demonstrate that pulmonary intravascular macrophages are critical to its elaboration.

Acute Disease↗