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1.
Allergy ; 71(6): 803-10, 2016 06.
Article in English | MEDLINE | ID: mdl-26797802

ABSTRACT

BACKGROUND: With the exception of the presence of the FIP1L1-PDGFRA fusion gene, little is known about predictors of imatinib response in clinically-defined hypereosinophilic syndrome (HES). METHODS: Subjects with FIP1L1-PDGFRA-myeloid neoplasm (FP; nĀ =12), PDGFRA-negative HES with ≥4 criteria suggestive of a myeloid neoplasm (MHES; nĀ =10), or steroid-refractory PDGFRA-negative HES with <4 myeloid criteria (SR; nĀ =Ā 5) were enrolled in a prospective study of imatinib therapy (NCT00044304: registered at clinicaltrials.gov). The primary outcome was an eosinophil count <1.5 Ɨ 109/L at one month and improvement of clinical symptoms. Clinical, molecular, and bone marrow responses to imatinib were assessed. A retrospective cohort of 18 subjects with clinically-defined HES who received imatinib (300-400 mg daily ≥ 1 month) were classified according to the criteria used in the prospective study. RESULTS: Overall, imatinib response rates were 100% in the FP group (nĀ = 16), 54% in the MHES group (n = 13) and 0% in the SR group (nĀ = 16). The presence of ≥ 4 myeloid features was the sole predictor of response. After ≥ 18 months in complete remission, imatinib was tapered and discontinued in 8 FP and 1 MHES subjects. Seven subjects (6 FP, 1 MHES) remain in remission off therapy for a median of 29 months (range 14-36). CONCLUSIONS: Clinical features of MHES predict imatinib response in PDGFRA-negative HES.


Subject(s)
Hypereosinophilic Syndrome/diagnosis , Hypereosinophilic Syndrome/drug therapy , Imatinib Mesylate/therapeutic use , Phenotype , Protein Kinase Inhibitors/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers , Bone Marrow/pathology , Eosinophils , Female , Follow-Up Studies , Humans , Hypereosinophilic Syndrome/genetics , Leukocyte Count , Male , Middle Aged , Prognosis , Receptor, Platelet-Derived Growth Factor alpha/genetics , Treatment Outcome , Young Adult , mRNA Cleavage and Polyadenylation Factors/genetics
2.
Analyst ; 141(12): 3562-72, 2016 Jun 21.
Article in English | MEDLINE | ID: mdl-27067797

ABSTRACT

Both photons and electrons may be used to excite surface plasmon polaritons, the collective charge density fluctuations at the surface of metal nanostructures. By virtue of their nanoscopic and dissipative nature, a detailed characterization of surface plasmon (SP) eigenmodes in real space-time ultimately requires joint nanometer spatial and femtosecond temporal resolution. The latter realization has driven significant developments in the past few years, aimed at interrogating both localized and propagating SP modes. In this mini-review, we briefly highlight different techniques employed by our own groups to visualize the enhanced electric fields associated with SPs. Specifically, we discuss recent hyperspectral optical microscopy, tip-enhanced Raman nano-spectroscopy, nonlinear photoemission electron microscopy, as well as correlated scanning transmission electron microscopy-electron energy loss spectroscopy measurements targeting prototypical plasmonic nanostructures and constructs. Through selected practical examples from our own laboratories, we examine the information content in multidimensional images recorded by taking advantage of each of the aforementioned techniques. In effect, we illustrate how SPs can be visualized at the ultimate limits of space and time.

4.
Nanotechnology ; 24(9): 095707, 2013 Mar 08.
Article in English | MEDLINE | ID: mdl-23403363

ABSTRACT

Metal nanoparticles exhibit a localized surface plasmon resonance (LSPR) which is very sensitive to the size and shape of the nanoparticle and the surrounding dielectric medium. The coupling between the electromagnetic radiation and the localized surface plasmon in metallic nanoparticles results in a sizable enhancement of the incident fields, making them possible candidates for plasmonic applications. In particular, partially exposed metallic nanoparticles distributed in a dielectric matrix can provide prime locations for LSPR spectroscopy and sensing. We report the synthesis and characterization of a plasmonic substrate consisting of Ag nanoparticles partially buried in MgO. Ag nanoparticles of different shapes and size distributions were synthesized below the surface of MgO by implanting 200 keV Ag(+) ions followed by annealing at 1000 Ā°C for 10 and 30 h. A detailed optical and structural characterization was carried out to understand the evolution of the Ag nanoparticle and size distribution inside the MgO matrix. Micro x-ray diffraction (Micro-XRD) was employed to investigate the structural properties and estimate the crystallite size. The nanoparticles evolved from a spherical to a faceted morphology with annealing time, assuming an octahedral shape truncated at the (001) planes, as visualized from aberration-corrected transmission electron microscopy (TEM) images. The nanoparticles embedded in MgO were shown to be pure metallic Ag using atom probe tomography (APT). The nanoparticles were partially exposed to the surface by employing plasma etch techniques to remove the overlaying MgO. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were employed to study the surface morphology and obtain a height distribution for the partially exposed nanoparticles.

5.
J Chem Phys ; 138(12): 124501, 2013 Mar 28.
Article in English | MEDLINE | ID: mdl-23556730

ABSTRACT

Ultrafast deep-ultraviolet through near infrared (210-950 nm) transient absorption spectroscopy complemented by ab initio multiconfigurational calculations offers a global description of the photochemical reaction pathways of bromoform following 255-nm excitation in methylcyclohexane and acetonitrile solutions. Photoexcitation of CHBr3 leads to the ground-state iso-CHBr3 product in a large quantum yield (Ć¢ĀˆĀ¼35%), formed through two different mechanisms: concerted excited-state isomerization and cage-induced isomerization through the recombination of the nascent radical pair. These two processes take place on different time scales of tens of femtoseconds and several picoseconds, respectively. The novel ultrafast direct isomerization pathway proposed herein is consistent with the occurrence of a conical intersection between the first excited singlet state of CHBr3 and the ground electronic state of iso-CHBr3. Complete active space self-consistent field calculations characterize this singularity in the vicinity of a second order saddle point on the ground state which connects the two isomer forms. For cage-induced isomerization, both the formation of the nascent radical pair and its subsequent collapse into ground-state iso-CHBr3 are directly monitored through the deep-ultraviolet absorption signatures of the radical species. In both mechanisms, the optically active (i.e., those with largest Franck-Condon factors) C-Br-Br bending and Br-Br stretching modes of ground-state iso-CHBr3 have the largest projection on the reaction coordinate, enabling us to trace the structural changes accompanying vibrational relaxation of the non-equilibrated isomers through transient absorption dynamics. The iso-CHBr3 photoproduct is stable in methylcyclohexane, but undergoes either facile thermal isomerization to the parent CHBr3 structure through a cyclic transition state stabilized by the polar acetonitrile medium (Ć¢ĀˆĀ¼300-ps lifetime), and hydrolysis in the presence of water.


Subject(s)
Quantum Theory , Ultraviolet Rays , Photochemical Processes , Spectroscopy, Near-Infrared , Trihalomethanes/chemistry
6.
Spinal Cord ; 51(4): 289-94, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23184022

ABSTRACT

STUDY DESIGN: Cohort. OBJECTIVES: To examine patterns of pain intensity and variability during acute spinal cord injury (SCI) rehabilitation. SETTING: Large medical university in the Midwestern United States. METHODS: Data were collected from the medical records of consecutively admitted patients with new (< or =2 months after onset), traumatic (that is, injury resulting from external forces) or non-traumatic (that is, injury resulting from disease processes) SCI. A total of 11,001 hourly pain ratings on 1709 inpatient days were collected from 56 inpatients. Multi-leveling modeling was used to test models of pain intensity, pain variability, diurnal variability and pain medication administration. RESULTS: Pain intensity and variability decreased during the inpatient stay. Compared with those with non-traumatic injuries, those with traumatic injuries had significantly higher pain; those with American Spinal Injury Association Impairment Score (AIS) A scores had a slower decline of pain, while those with AIS D scores had a sharper decline. Pain increased from morning to evening during the latter days of the inpatient stay whereas pain was relatively stable during the early days in the inpatient stay. Those not using a ventilator at admission were significantly less likely to receive a pain medication than those who were, despite no significant differences in pain levels. CONCLUSION: Pain changes during acute rehabilitation, however, the moderating effect of time suggests that change is not consistent across all injury characteristics. Findings suggest that not only should pain management be individualized but it should also reflect a greater understanding of change over time.


Subject(s)
Circadian Rhythm , Pain/complications , Pain/diagnosis , Spinal Cord Injuries , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Inpatients , Male , Middle Aged , Models, Statistical , Pain/drug therapy , Pain Measurement , Spinal Cord Injuries/complications , Spinal Cord Injuries/psychology , Spinal Cord Injuries/rehabilitation , Time Factors , United States , Young Adult
7.
Diabetologia ; 55(3): 625-31, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22193511

ABSTRACT

AIMS/HYPOTHESIS: Increased arterial stiffness is a risk factor for adverse cardiovascular events in adults with obesity-related insulin resistance (IR) or type 2 diabetes mellitus. Adolescents with type 2 diabetes have stiffer vessels. Whether stiffness is increased in obesity/IR in youth is not known. We sought to determine if IR was a determinant of arterial stiffness in youth, independent of obesity and cardiovascular risk factors. METHODS: We measured cardiovascular risk factors, IR, adipocytokines and arterial stiffness (brachial artery distensibility [BrachD], pulse wave velocity [PWV]) and wave reflection (augmentation index [AIx]) in 343 adolescents and young adults without type 2 diabetes (15-28 years old, 47% male, 48% non-white). Individuals <85th percentile of BMI were classified as lean (n = 232). Obese individuals were grouped by HOMA index as not insulin resistant (n = 46) or insulin resistant (n = 65) by the 90th percentile for HOMA for lean. Mean differences were evaluated by ANOVA. Multivariate models evaluated whether HOMA was an independent determinant of arterial stiffness. RESULTS: Risk factors deteriorated from lean to obese to obese/insulin resistant (all p ≤ 0.017). Higher AIx, lower BrachD and higher PWV indicated increased arterial stiffness in obese and obese/insulin-resistant participants. HOMA was not an independent determinant. Age, sex, BMI and BP were the most consistent determinants, with HDL-cholesterol playing a role for BrachD and leptin for PWV (AIx RĀ²= 0.34; BrachD RĀ² = 0.37; PWV RĀ² = 0.40; all p ≤ 0.02). CONCLUSIONS/INTERPRETATION: Although IR is associated with increased arterial stiffness, traditional cardiovascular risk factors, especially obesity and BP, are the major determinants of arterial stiffness in healthy young people.


Subject(s)
Adolescent Development , Brachial Artery/growth & development , Insulin Resistance , Vascular Stiffness , Adiposity , Adolescent , Adult , Blood Pressure , Body Mass Index , Brachial Artery/pathology , Cardiovascular Diseases/epidemiology , Cholesterol, HDL/blood , Cohort Studies , Cross-Sectional Studies , Female , Humans , Leptin/blood , Longitudinal Studies , Male , Obesity/blood , Obesity/metabolism , Obesity/pathology , Ohio/epidemiology , Risk Factors , Young Adult
8.
Allergy ; 67(9): 1149-56, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22775568

ABSTRACT

RATIONALE: Churg-Strauss syndrome (CSS) and hypereosinophilic syndrome (HES) overlap considerably in clinical presentation. A reliable means of distinguishing between these groups of patients is needed, especially in the setting of glucocorticoid therapy. METHODS: A retrospective chart review of 276 adult subjects referred for evaluation of eosinophilia > 1500/Āµl was performed, and subjects with a documented secondary cause of eosinophilia or a PDGFR -positive myeloproliferative neoplasm were excluded. The remaining subjects were assessed for the presence of American College of Rheumatology (ACR) criteria. Laboratory and clinical parameters were compared between subjects with biopsy-proven vasculitis (CSS; n = 8), ≥4 ACR criteria (probable CSS; n = 21), HES with asthma and/or sinusitis without other CSS-defining criteria (HESwAS; n = 20), HES without asthma or sinusitis (HES; n = 18), and normal controls (n = 8). Serum biomarkers reported to be associated with CSS were measured using standard techniques. RESULTS: There were no differences between the subjects with definite or probable CSS or HES with respect to age, gender, or maintenance steroid dose. Serum CCL17, IL-8, and eotaxin levels were significantly increased in eosinophilic subjects as compared to normal controls, but were similar between the eosinophilic groups. Serum CCL17 correlated with eosinophil count (P < 0.0001, r = 0.73), but not with prednisone dose. CONCLUSIONS: In patients with a history of asthma and sinusitis, distinguishing between ANCA-negative CSS and PDGFR-negative HES is difficult because of significant overlap in clinical presentation and biomarker profiles.


Subject(s)
Biomarkers/blood , Chemokine CCL11/blood , Chemokine CCL17/blood , Churg-Strauss Syndrome/blood , Hypereosinophilic Syndrome/blood , Interleukin-8/blood , Adult , Aged , Aged, 80 and over , Churg-Strauss Syndrome/metabolism , Churg-Strauss Syndrome/pathology , Female , Humans , Hypereosinophilic Syndrome/metabolism , Hypereosinophilic Syndrome/pathology , Male , Middle Aged , Retrospective Studies , Young Adult
9.
Diabetologia ; 54(4): 722-30, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21085926

ABSTRACT

AIMS/HYPOTHESIS: We sought to evaluate the effects of obesity and obesity-related type 2 diabetes mellitus on cardiac geometry (remodelling) and systolic and diastolic function in adolescents and young adults. METHODS: Cardiac structure and function were compared by echocardiography in participants who were lean, obese or obese with type 2 diabetes (obese diabetic), in a cross sectional study. Group differences were assessed using ANOVA. Independent determinants of cardiac outcome measures were evaluated with general linear models. RESULTS: Adolescents with obesity and obesity-related type 2 diabetes were found to have abnormal cardiac geometry compared with lean controls (16% and 20% vs <1%, p < 0.05). These two groups also had increased systolic function. Diastolic function decreased from the lean to obese to obese diabetic groups with the lowest diastolic function observed in the obese diabetic group (p < 0.05). Regression analysis showed that group, BMI z score (BMIz), group Ɨ BMIz interaction and systolic BP z score (BPz) were significant determinants of cardiac structure, while group, BMIz, systolic BPz, age and fasting glucose were significant determinants of the diastolic function (all p < 0.05). CONCLUSIONS/INTERPRETATION: Adolescents with obesity and obesity-related type 2 diabetes demonstrate changes in cardiac geometry consistent with cardiac remodelling. These two groups also demonstrate decreased diastolic function compared with lean controls, with the greatest decrease observed in those with type 2 diabetes. Adults with diastolic dysfunction are known to be at increased risk of progressing to heart failure. Therefore, our findings suggest that adolescents with obesity-related type 2 diabetes may be at increased risk of progressing to early heart failure compared with their obese and lean counterparts.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Obesity/physiopathology , Adolescent , Adult , Blood Pressure/physiology , Body Mass Index , Child , Cross-Sectional Studies , Diastole/physiology , Echocardiography , Female , Humans , Male , Systole/physiology , Waist Circumference/physiology , Young Adult
10.
J Phys Chem A ; 114(36): 9919-26, 2010 Sep 16.
Article in English | MEDLINE | ID: mdl-20568790

ABSTRACT

We report experimental and computational studies of the photolysis of atmospherically important 1,2-dibromoethanes (1,2-C(2)X(4)Br(2); X = H, F) in Ar matrixes at 5 K. Using the pulsed deposition method, we find that significant conformational relaxation occurs for 1,2-C(2)H(4)Br(2) (EDB; observed anti/gauche ratio =30:1) but not for 1,2-C(2)F(4)Br(2) (TFEDB; anti/gauche = 3:1), which is traced to a larger barrier to rotation about the C-C bond in the latter. Laser photolysis of matrix-isolated EDB at 220 nm reveals the growth of infrared bands assigned to the gauche conformer and C(2)H(4)-Br(2) charge transfer complex (both as major products), and the C(2)H(4)Br radical and C(2)H(3)Br-HBr complex as minor (trace) products. The presence of the C(2)H(4)-Br(2) complex is confirmed in the UV/visible spectrum, which shows an intense charge transfer band at 237 nm that grows in intensity upon annealing. In contrast to previous reports, our experimental and computational results do not support a bridged structure for the C(2)H(4)Br radical in either the gas phase or matrix environments. We also report on the laser photolysis of matrix-isolated TFEDB at 220 nm. Here, the dominant photoproducts are the anti and gauche conformers of the C(2)F(4)Br radical, the vibrational and electronic spectra of which are characterized here for the first time. The increase in yield of radical for TFEDB vs EDB is consistent with the stronger C-Br bond in the fluoro-substituted radical species. The photochemistry of the C(2)F(4)Br radical following excitation at 266 nm was investigated and found to lead C-Br bond cleavage and formation of C(2)F(4). The implications of this work for the atmospheric and condensed phase photochemistry of the alkyl halides is emphasized.

11.
Int J Obes (Lond) ; 33(10): 1118-25, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19704412

ABSTRACT

BACKGROUND: Obesity-related cardiovascular diseases (CVDs) are a major cause of cardiovascular (CV) mortality. Obesity-related reduction in vascular protective adipose-derived proteins, such as adiponectin (APN), has an important role. METHODS: We compared brachial artery distensibility (BrachD) with APN, the level of adiposity and other CV risk factors (CVRFs) in 431 post-pubertal subjects (mean 17.9 years). Gender differences in average values were examined by t-tests. Correlations among BrachD, obesity and other CVRFs were examined. Regression analysis was performed to determine whether APN provided an independent contribution to BrachD, while controlling for obesity and other CVRFs. RESULTS: Male subjects had lower BrachD (5.72+/-1.37 vs 6.45+/-1.60% change per mm Hg, P<0.0001) and lower APN (10.50+/-4.65 vs 13.20+/-6.53; all P<0.04) than female subjects. BrachD correlated with APN (r=0.25, P< 0.0001). Both BrachD and APN correlated with measures of body size, including height, weight and body mass index (BMI). Both correlated with higher systolic blood pressure, glucose, insulin and lower high-density lipoprotein cholesterol (all P<0.01). In multivariate analysis, APN, gender, APN*gender and BMI z-score predicted BrachD (r(2)=0.305). On the basis of gender difference, only BMI z-score was significant for male subjects (r(2)=0.080), whereas APN and BMI z-score contributed for female subjects (r(2)=0.242, all P<0.0001). CONCLUSIONS: BrachD is independently influenced by obesity in both male and female subjects. In female subjects, APN exerts an additional independent effect even after adjusting for blood pressure (BP), lipid levels and insulin. Differences in the effect of the APN-adiposity relationship on obesity-related vascular disease may be one reason for gender differences in the development and progression of atherosclerosis.


Subject(s)
Adiponectin/blood , Adiposity/physiology , Atherosclerosis , Blood Pressure/physiology , Brachial Artery/physiopathology , Obesity , Adolescent , Atherosclerosis/blood , Atherosclerosis/physiopathology , Body Composition , Body Mass Index , Brachial Artery/metabolism , Female , Humans , Male , Obesity/blood , Obesity/complications , Obesity/physiopathology , Risk Factors , Sex Factors , Young Adult
12.
Pediatr Transplant ; 12(6): 666-71, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18331544

ABSTRACT

ACKD has been observed in children on dialysis and with chronic renal insufficiency. In one report, ACKD was observed in 30% of pediatric liver transplant recipients after 10 yr. We retrospectively reviewed all renal imaging and measurements of GFR of 235 childhood liver transplant recipients with no known risk for renal cyst formation, no evidence of renal cyst(s) at the time of transplantation and renal imaging at least one yr post-transplant. Twenty-six patients (11%) developed one or more cyst(s). Mean GFR was significantly lower in patients with renal cyst(s). Two (1.4%) of the 146 patients treated with tacrolimus and 24 (27%) of the 89 patients treated with CsA acquired renal cyst(s) (p < 0.001). CsA-treated patients had significantly lower GFR. Multivariate analysis identified CsA as the only independent variable associated with ACKD. These results confirm that ACKD can be a late complication of pediatric liver transplantation. Those at most risk are at least 10-yr post-liver transplantation, have been treated with CsA and have impaired renal function. We speculate that ACKD in these patients is the result of calcineurin inhibitor nephrotoxicity. Whether patients with ACKD will be prone to develop solid renal tumors is unknown.


Subject(s)
Cyclosporine/adverse effects , Kidney Diseases, Cystic/etiology , Kidney Diseases/drug therapy , Liver Transplantation/adverse effects , Child , Child, Preschool , Female , Glomerular Filtration Rate , Humans , Immunosuppressive Agents/adverse effects , Infant , Kidney Diseases, Cystic/pathology , Male , Retrospective Studies , Risk , Time Factors
13.
Chem Commun (Camb) ; 53(53): 7310-7313, 2017 Jun 29.
Article in English | MEDLINE | ID: mdl-28480910

ABSTRACT

Tip-enhanced Raman scattering (TERS) can be used to image plasmon-enhanced local electric field variations with extremely high spatial resolution under ambient conditions. This is illustrated through TERS images recorded using a silver atomic force microscope tip coated with strategically selected molecular reporters and used to image a sputtered silver film.

15.
Circulation ; 100(22): 2244-7, 1999 Nov 30.
Article in English | MEDLINE | ID: mdl-10577998

ABSTRACT

BACKGROUND: Traditional risk factors account for only half of the morbidity and mortality from coronary heart disease (CHD). There is substantial evidence that oxidative injury plays a major role in the atherosclerotic process. Thus, antioxidants may protect against development of atherosclerosis. Glutathione, an intracellular tripeptide with antioxidant properties, may be protective. METHODS AND RESULTS: This case-control study compared total serum glutathione (tGSH) in 81 adolescent male offspring of parents with premature CHD (ie, before 56 years of age) and 78 control male offspring of parents without known or suspected CHD. Case offspring had significantly lower tGSH than control offspring. In multiple logistic regression with parental CHD status as the dependent variable, age entered as a covariate, and other CHD risk factors competing to enter the model as significant independent predictor variables, LDL cholesterol (odds ratio [OR], 2.15 [units=1.5 SD]; 95% CI, 1.21 to 3.82), tGSH (OR, 0.40; 95% CI, 0.22 to 0.71), HDL cholesterol (OR, 0.42; 95% CI, 0.22 to 0.78), and total serum homocysteine (OR, 2.6; 95% CI, 1.35 to 5.02) entered the model as significant predictors of parental CHD status. CONCLUSIONS: Low tGSH in adolescent boys is a significant independent predictor of parental CHD, in addition to elevated LDL cholesterol, low HDL cholesterol, and elevated total serum homocysteine concentrations.


Subject(s)
Coronary Disease/epidemiology , Glutathione/blood , Adolescent , Aged , Anthropometry , Blood Pressure , Case-Control Studies , Cohort Studies , Coronary Artery Disease/blood , Coronary Artery Disease/epidemiology , Coronary Artery Disease/genetics , Coronary Disease/blood , Coronary Disease/genetics , Glutathione/deficiency , Homocysteine/blood , Humans , Lipids/blood , Logistic Models , Male , Middle Aged , Ohio/epidemiology , Oxidation-Reduction , Oxidative Stress , Parents , Sulfhydryl Compounds/blood
16.
J Am Coll Cardiol ; 21(4): 997-1001, 1993 Mar 15.
Article in English | MEDLINE | ID: mdl-8450171

ABSTRACT

OBJECTIVES: The aim of this study was to determine if left ventricular preload, afterload or contractility is a correlate of left ventricular mass index in hypertensive pediatric patients. BACKGROUND: It is believed that decreased contractility and increased preload are associated with left ventricular hypertrophy in adult hypertensive patients. METHODS: Ninety pediatric hypertensive patients underwent echocardiography to assess left ventricular mass, preload (diastolic dimension and volume) and afterload (end-systolic wall stress, vascular resistance and blood pressure). Contractility was assessed by 1) the end-systolic stress/volume ratio, and 2) the difference between measured and predicted velocity of circumferential fiber shortening. Univariate and multivariate analyses were performed. RESULTS: Univariate analysis showed significant correlations between left ventricular mass and 1) body mass (r = 0.33, p < 0.001), 2) black race (r = 0.37, p < 0.0003), 3) diastolic dimension (r = 0.26, p < 0.01), 4) diastolic volume (r = 0.20, p < 0.05), and 5) stress/volume ratio (r = -0.53, p < 0.0001) but not the difference between measured and predicted velocity of circumferential fiber shortening. A multivariate model included body mass, age at diagnosis, diastolic dimension, wall stress and vascular resistance but not the difference between measured and predicted velocity of circumferential fiber shortening. CONCLUSIONS: Contractility is not significantly related to left ventricular mass. The positive correlation between mass and stress/volume may be due to the dependence of the latter variable on loading conditions. We speculate that both elevated preload and systemic vascular resistance may have a role in the development of hypertrophy in hypertensive pediatric patients.


Subject(s)
Heart Ventricles/pathology , Hypertension/physiopathology , Myocardial Contraction/physiology , Ventricular Function, Left , Adolescent , Child , Echocardiography , Female , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Hemodynamics , Humans , Hypertension/pathology , Male
17.
J Am Coll Cardiol ; 27(1): 193-7, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8522694

ABSTRACT

OBJECTIVES: The purpose of this study was to determine in preterm newborn infants the effects of ductal ligation on ventricular performance and its determinants: preload, afterload and contractility. BACKGROUND: Neonatal ventricular performance is highly sensitive to afterload. Therefore, the increase in systemic vascular resistance associated with ligation of a patent ductus arteriosus might worsen ventricular performance in the preterm infant. METHODS: All 14 premature infants undergoing patent ductus arteriosus ligation in a 1-year period at our institution underwent echocardiography at three times: before, immediately after and 24 h after ligation. Indexes studied included ventricular performance (fractional area change), preload (left ventricular end-diastolic dimension), afterload (end-systolic wall stress) and contractility (the difference between the measured and predicted velocity of circumferential fiber shortening). Blood pressure was measured; systemic resistance was calculated. These data were compared with those of 14 preterm infants without patent ductus arteriosus. RESULTS: The infants with patent ductus arteriosus had higher values for ventricular performance (mean +/- SD fractional area change 60 +/- 9% vs. 52 +/- 11%, p < 0.05) and lower values for wall stress (22 +/- 6 vs. 44 +/- 17 g/cm2, p < 0.05) before ligation than did the control group. At 24 h after ligation, ventricular performance was not significantly changed (fractional area change 60 +/- 9% to 57 +/- 12%). There were significant increases in blood pressure and systemic vascular resistance but no changes in wall stress or contractility. CONCLUSIONS: Ventricular performance is higher in premature infants with than in those without patent ductus arteriosus because afterload is lower in the former group. Although ductal ligation increases blood pressure and systemic resistance, wall stress and ventricular performance are maintained. Our results suggest that the premature newborn maintains ventricular performance during stress, at least in part, by manipulating afterload.


Subject(s)
Ductus Arteriosus, Patent/surgery , Infant, Premature, Diseases/surgery , Infant, Premature/physiology , Ventricular Function, Left/physiology , Blood Pressure/physiology , Chi-Square Distribution , Ductus Arteriosus, Patent/diagnosis , Ductus Arteriosus, Patent/physiopathology , Echocardiography , Humans , Infant, Newborn , Infant, Premature, Diseases/diagnosis , Infant, Premature, Diseases/physiopathology , Ligation , Myocardial Contraction/physiology , Stress, Mechanical , Vascular Resistance/physiology
18.
J Am Coll Cardiol ; 24(1): 194-200, 1994 Jul.
Article in English | MEDLINE | ID: mdl-8006265

ABSTRACT

OBJECTIVES: The purposes of this study were to evaluate left ventricular performance and contractility at rest and during exercise to determine mechanisms and correlates for alterations in performance and blood pressure in pediatric patients after successful repair of coarctation of the aorta. BACKGROUND: Blood pressure and left ventricular function are elevated in children despite successful repair. The mechanisms for these changes are not understood. METHODS: Thirty asymptomatic pediatric patients with successful coarctation repair (mean age [+/- SD] 12.5 +/- 4 years) underwent echocardiographic determination of left ventricular mass, performance (shortening fraction), preload (indexed diastolic dimension), afterload (end-systolic wall stress), contractility (velocity of circumferential fiber shortening/wall stress relation) and Doppler gradient at rest and during exercise. Data were compared with those of 24 control subjects (mean age 21.0 +- 4 years). Because of the age discrepancy between groups, age-dependent echocardiographic data were indexed by body surface area. RESULTS: The mean age at operation was 5 +/- 4 years, and the average follow-up period was 7.5 +/- 3 years. The average blood pressure gradient between upper and lower limbs was 4 mm Hg. Left ventricular mass was higher in the postoperative group than in the control group (1.58 vs. 1.31 g/ht2.7, p = 0.04), as were values at rest for performance (44% vs. 31%, p = 0.0001), preload (3.9 vs. 3.7 cm/body surface area0.5), indexes systolic blood pressure (1.05 vs. 0.91, p = 0.0001) and contractility (0.23 vs. -0.05 circumferences/s, p= 0.001). Afterload was lower at rest (36 vs. 52 g/cm2, p = 0.0004). These differences between groups persisted during and after exercise. Contractility underwent an exaggerated increase after exercise in the postoperative group. CONCLUSIONS: Left ventricular performance in children after coarctation repair is higher at rest and during exercise than in control subjects as a result of higher preload and contractility and lower afterload. These changes may be due to associated hypertrophy. Persistent postoperative hypertension may be due to a hyperdynamic, hypercontractile state caused by residual gradients manifested only during exertion.


Subject(s)
Aortic Coarctation/physiopathology , Cardiovascular System/physiopathology , Adolescent , Adult , Aortic Coarctation/diagnosis , Aortic Coarctation/surgery , Child , Echocardiography/methods , Echocardiography/statistics & numerical data , Exercise/physiology , Exercise Test/methods , Exercise Test/statistics & numerical data , Female , Hemodynamics , Humans , Hypertension/diagnosis , Hypertension/physiopathology , Male , Postoperative Complications/diagnosis , Postoperative Complications/physiopathology , Rest/physiology , Systole , Ventricular Function, Left
19.
J Am Coll Cardiol ; 32(3): 766-72, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9741525

ABSTRACT

OBJECTIVES: This study sought to evaluate the effects of veno-venous ultrafiltration on myocardial contractility in children undergoing cardiopulmonary bypass (CPB) for repair of congenital heart defects. BACKGROUND: Ultrafiltration (UF) is currently used to diminish postoperative fluid accumulation following CPB in children. Previous reports indicate improvement in hemodynamics immediately after UF, but the mechanism of its action is unknown. METHODS: Twenty-three patients (ages 2 months to 9.1 years; 13 males, 10 females) underwent UF for 10 min after CPB. Twelve patients underwent UF immediately after CPB (Group A). They were studied: (1) before and (2) after CPB, (3) after UF, and (4) 10 min after UF. Eleven patients underwent UF 10 min after CPB (Group B). They were studied: (1) before and (2) after CPB, (3) after a 10-min delay before UF, and (4) after UF. Contractility was determined by the difference in the observed and predicted velocity of circumferential fiber shortening for the measured wall stress, using transesophageal echocardiography. Left ventricular wall thickness was also measured. RESULTS: There was significant improvement in contractility after UF in both groups (mean+/-SD, Group A: -0.28+/-0.13 to -0.01+/-0.21 circ/s, p < 0.05; Group B: -0.26+/-0.16 to -0.11+/-0.17 circ/s, p < 0.05). Myocardial thickness to cavity dimension decreased in both groups following UF (Group A: 0.19+/-0.04 to 0.14+/-0.03, p < 0.05; Group B: 0.18+/-0.04 to 0.14+/-0.03, p < 0.05). CONCLUSIONS: UF improves hemodynamics by improving contractility and possibly by reducing myocardial edema in children following cardiac surgery. Enhanced patient outcome after ultrafiltration may in part be due to these changes.


Subject(s)
Heart Defects, Congenital/surgery , Hemofiltration , Postoperative Care , Cardiopulmonary Bypass , Child , Child, Preschool , Echocardiography, Transesophageal , Female , Heart Defects, Congenital/physiopathology , Hemodynamics/physiology , Humans , Infant , Male , Myocardial Contraction/physiology , Postoperative Complications/physiopathology , Prospective Studies
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