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Ascites increases the resting energy expenditure in liver cirrhosis.

The purpose of this study was to investigate the effect of ascites on the energy metabolism of patients with liver cirrhosis. The resting energy expenditure was determined in 10 patients with liver cirrhosis and ascites of moderate or large volume. The resting energy expenditure measurement was performed using indirect calorimetry and the resting energy expenditure predictive value was calculated with the Harris-Benedict equation, both before and after removal of ascitic fluid by paracentesis. Metabolic stress factors were absent in all cases. After an interval of 11.2 +/- 7.7 days between measurements, a weight loss of 16.6 +/- 10.3 kg was observed with paracentesis. The resting energy expenditure measured by indirect calorimetry showed a statistically significant decrease from 1682 +/- 291 to 1523 +/- 240 kcal/day (P less than 0.005) after removal of ascites. The repeatability of our indirect calorimetry method only allowed for the analysis of the results in 4 of 10 patients in whom ascites removal produced a consistent decrease in resting energy expenditure. There were no statistically significant differences between the measurements obtained by indirect calorimetry and those provided by the Harris-Benedict equation, but the latter had a moderate reliability in predicting the real resting energy expenditure of every patient. Our results suggest that, far from being an inert volume, ascites may be associated, at least in some patients, with an increased resting energy expenditure and therefore accelerate the appearance of protein energy malnutrition with corresponding complications.

Adult↗

Ventilation during rest and exercise in pregnancy and postpartum.

The expiratory minute volume (Ve), respiratory frequency (f), tidal volume (VT), carbon dioxide production (Vco2), and end-tidal carbon dioxide concentration (FETCO2) and pressure (PETCO2) were measured at monthly intervals in 12 normal women during pregnancy and two, six and 12 weeks, and six months postpartum. At eacy study, measurements were made sitting at rest and during steady-state exercise at 306 kpm/min on a bicycle ergometer. During pregnancy, a significant increase in VE occurred, both at rest and during exercise, due to a significantly greater VT. Although VCO2 was significantly increased at rest throughout pregnancy and with exercise in late pregnancy, the respiratory exchange ratio (R) was not significantly altered during pregnancy. The FETCO2 was lower during pregnancy than postpartum, both at rest and during exercise. The ventilatory equivalent for oxygen (VE/VO2) was greater at rest near term and during exercise throughout pregnancy. However, resting physiologic dead space increased during pregnancy. Alveolar ventilation (VA) was calculated on the basis of three alternative assumptions: (1) that PETCO2 during exercise accurately reflects mean alveolar PCO2; (2) that the physiological dead space does not change during exercise; and (3) that mean alveolar PCO2 does not change from rest to exercise. Exercise VA, calculated on the basis of any of these three assumptions, is greater during pregnancy than postpartum.

Carbon Dioxide↗

Influence of various growth factors and conditions on development of resting membrane potential and its electrogenic pump component of cultured rat skeletal myotubes.

The effects of different growth factors and growth conditions were studied on the development of resting membrane potential and its electrogenic--ouabain-sensitive--pump component in cultured rat myotubes. Resting potential and its electrogenic pump component were dependent on the initial plating density of the myotubes, both values increasing with increasing density. Medium from cells plated at high density, when used to replace the medium of low density cells, increased both the resting potential and its electrogenic pump component of low density myotubes. Treatment of myotubes with cytosine-arabinoside delayed the appearance of [3H]ouabain binding sites and electrogenic pump component of resting potential, but by 8 days in culture there was no difference between treated and control cells. Similarly, cells plated initially in 5% horse serum developed resting potential and its electrogenic pump component more slowly than those in 15% horse serum, but by 8-10 days in vitro, the differences were no longer apparent. Chick embryo extract was found to have little, if any, influence on development of resting potential and its electrogenic pump component. We conclude that the different growth conditions and factors to the extent that they influence membrane potential, do so by altering the time of appearance of Na-K ATPase, the activity of which contributes a considerable component to resting potential.

Animals↗

A constitutively active nonselective cation conductance underlies resting Ca2+ influx and secretion in bovine adrenal chromaffin cells.

We have combined fluorimetric measurements of the intracellular free Ca(2+) concentration ([Ca(2+)](i)) with the patch clamp technique, to investigate resting Ca(2+) entry in bovine adrenal chromaffin cells. Perfusion with nominally Ca(2+)-free medium resulted in a rapid, reversible decrease in [Ca(2+)](i), indicating a resting Ca(2+) permeability across the plasma membrane. Simultaneous whole-cell voltage-clamp showed a resting inward current that increased when extracellular Ca(2+) (Ca(2+)(o)) was lowered. This current had a reversal potential of around 0 mV and was carried by monovalent or divalent cations. In Na(+)-free extracellular medium there was a reduction in current amplitude upon removal of Ca(2+)(o), indicating the current can carry Ca(2+). The current was constitutively active and not enhanced by agents that promote Ca(2+)-store depletion such as thapsigargin. Extracellular La(3+) abolished the resting current, reduced resting [Ca(2+)](i) and inhibited basal secretion. Abolishment of resting Ca(2+) influx depleted the inositol 1,4,5-trisphosphate-sensitive Ca(2+) store without affecting the caffeine-sensitive Ca(2+) store. The results indicate the presence of a constitutively active nonselective cation conductance, permeable to both monovalent and divalent cations, that can regulate [Ca(2+)](i), the repletion state of the intracellular Ca(2+) store and the secretory response in resting cells.

Adrenal Medulla↗

Prognostic value of resting end-tidal carbon dioxide in patients with heart failure.

BACKGROUND: Cardiopulmonary exercise testing (CPET) variables provide valuable prognostic information in the heart failure (HF) population. The purpose of the present study is to assess the ability of resting end-tidal carbon dioxide partial pressure (PETCO2) to predict cardiac-related events in patients with HF. METHODS: 121 subjects diagnosed with compensated HF underwent CPET on an outpatient basis. Mean age and ejection fraction were 49.3 years (+/-14.7) and 28.4% (+/-13.4), respectively. Resting P(ET)CO2 was determined immediately prior to the exercise test in the seated position. Peak oxygen consumption (VO2) and the minute ventilation-carbon dioxide production (VE/VCO2) slope were also acquired during CPET. RESULTS: There were 41 cardiac-related hospitalizations and 9 cardiac-related deaths in the year following CPET. Mean resting P(ET)CO2, peak VO2 and VE/VCO2 slope were 34.1 mmHg (+/-4.6), 14.5 ml*kg(-1)*min(-1) (+/-5.1) and 35.9 (+/-8.7) respectively. Univariate Cox regression analysis revealed that resting P(ET)CO2 (Chi-square=28.4, p<0.001), peak VO2 (Chi-square=21.6, p<0.001) and VE/VCO2 slope (Chi-square=54.9, p<0.001) were all significant predictors of cardiac related events. Multivariate Cox regression analysis revealed resting P(ET)CO2 added to the prognostic value of VE/VCO2 slope in predicting cardiac related events (residual Chi-square=4.4, p=0.04). Peak VO2 did not add additional value and was removed (residual Chi-square=3.2, p=0.08). CONCLUSIONS: These results indicate a resting ventilatory expired gas variable possesses prognostic value independently and in combination with an established prognostic marker from the CPET. Resting P(ET)CO2 may therefore be a valuable objective measure to obtain during both non-exercise and exercise evaluations in patients with HF.

Adult↗

Interaction of the repressor element 1-silencing transcription factor (REST) with target genes.

The repressor element 1-silencing transcription factor (REST) has been proposed to restrict expression of repressor element 1 (RE1) bearing genes to differentiated neurons by silencing their expression in non-neural tissue. Here, we have examined the interaction of REST with the M(4) muscarinic acetylcholine receptor gene. We show that REST binds to the RE1 of the M(4) gene in those cell lines and brain regions where the M(4) gene is expressed but not in those where the M(4) is not expressed. Furthermore, in cells that express M(4), the presence of REST represses but is insufficient to silence transcription of M(4). In non-neural cells REST is absent from the RE1 of the silent M(4) gene and perturbation of REST function fails to induce M(4) expression. We propose that REST acts to regulate expression levels of some RE1-bearing genes in neural cells, thereby playing an important role in defining neuronal activity.

Base Sequence↗

Downregulated REST transcription factor is a switch enabling critical potassium channel expression and cell proliferation.

Induction of K(Ca)3.1 (IKCa) potassium channel plays an important role in vascular smooth muscle cell proliferation. Here, we report that the gene encoding K(Ca)3.1 (KCNN4) contains a functional repressor element 1-silencing transcription factor (REST or NRSF) binding site and is repressed by REST. Although not previously associated with vascular smooth muscle cells, REST is present and recruited to the KCNN4 gene in situ. Significantly, expression of REST declines when there is cellular proliferation, showing an inverse relationship with functional K(Ca)3.1. Downregulated REST and upregulated K(Ca)3.1 are also evident in smooth muscle cells of human neointimal hyperplasia grown in organ culture. Furthermore, inhibition of K(Ca)3.1 suppresses neointimal formation, and exogenous REST reduces the functional impact of K(Ca)3.1. Here, we show REST plays a previously unrecognized role as a switch regulating potassium channel expression and consequently the phenotype of vascular smooth muscle cells and human vascular disease.

Animals↗

Does the brain have a baseline? Why we should be resisting a rest.

In the last few years, the notion that the brain has a default or intrinsic mode of functioning has received increasing attention. The idea derives from observations that a consistent network of brain regions shows high levels of activity when no explicit task is performed and participants are asked simply to rest. The importance of this putative "default mode" is asserted on the basis of the substantial energy demand associated with such a resting state and of the suggestion that rest entails a finely tuned balance between metabolic demand and regionally regulated blood supply. These observations, together with the fact that the default network is more active at rest than it is in a range of explicit tasks, have led some to suggest that it reflects an absolute baseline, one that must be understood and used if we are to develop a comprehensive picture of brain functioning. Here, we examine the assumptions that are generally made in accepting the importance of the "default mode". We question the value, and indeed the interpretability, of the study of the resting state and suggest that observations made under resting conditions have no privileged status as a fundamental metric of brain functioning. In doing so, we challenge the utility of studies of the resting state in a number of important domains of research.

Journal Article↗

Resting energy expenditures measured by indirect calorimetry are higher in preadolescent children with cystic fibrosis than expenditures calculated from prediction equations.

OBJECTIVE: This study compared measured resting energy expenditures to resting energy expenditures calculated using Harris-Benedict equations (HBEs) and the Cystic Fibrosis Consensus Committee equations (CFCCEs). DESIGN: We studied 31 preadolescent boys and girls with cystic fibrosis who ranged in age from 3.25 to 12.75 years old. The patients were afebrile and not in pulmonary distress. Measured resting energy expenditures were determined using a portable metabolic measurement cart with fully automated calibration and data management. The measured resting energy expenditures obtained were compared with values obtained using HBEs and CFCCEs. RESULTS: For each patient, the measured resting energy expenditure value was above the predicted resting energy expenditure values derived from HBEs (P < or = .0001) and CFCCEs (P < or = .01). APPLICATIONS: The HBEs and the CFCCEs underestimated the energy expenditures of the study population by 13% and 8%, respectively. These findings support the usefulness of the measurement of energy expenditures in determining the energy needs of preadolescent patients with cystic fibrosis. In clinical practice, the resting energy expenditures would be multiplied by activity coefficients to determine the total daily energy expenditures of this population.

Basal Metabolism↗

Combined rest and exercise electrocardiographic repolarization findings in relation to structural and functional abnormalities in asymptomatic aortic regurgitation.

The relationship of combined rest and exercise electrocardiographic (ECG) repolarization abnormalities to left ventricular geometry and function was examined in 48 patients with asymptomatic chronic pure aortic regurgitation and no recent use of digitalis. Echocardiographic and radionuclide cineangiographic findings were compared in groups defined by the presence or absence of the "strain" pattern of repolarization abnormality on the resting ECG and also by the presence or absence of standard positive repolarization changes during upright treadmill exercise ( > 0.1 mV additional horizontal or downsloping ST depression). These hierarchic groups demonstrated trends toward progressively abnormal left ventricular dimensions, mass, wall stress, and change in ejection fraction with exercise. Although the presence of the strain pattern on the resting ECG alone was most strongly correlated with underlying functional and geometric abnormalities, an abnormal exercise test response was independently associated with abnormal left ventricular systolic dimension. The large group of patients with no symptoms and normal resting repolarization had only 0% to 4% prevalences of markedly increased systolic dimension (> 55 mm), reduced ejection fraction at rest (< 45%), or reduced ejection fraction during exercise (< 40%), whereas the small group of patients with abnormal resting repolarization and a positive exercise test response had 50% to 83% prevalences of these findings. These data suggest a possible role for rest and exercise ECG in the serial evaluation of patients with aortic regurgitation.

Adult↗

ST-segment elevation on Q leads at rest and during exercise: relation with myocardial viability and left ventricular remodeling within the first 6 months after infarction.

BACKGROUND: Resting ST-segment elevation on Q leads after an acute myocardial infarction has been related to a greater infarct size. Otherwise, the relation between exercise-induced ST-segment elevation and myocardial viability is controversial. We investigated the relation between ST-segment elevation on Q leads at rest and during exercise and regional dysfunction and its evolution, contractile reserve, left ventricular dilation, and coronary patency. METHODS AND RESULTS: Exercise testing and cardiac catheterization were performed at the first week after infarction in 51 patients. The study group was divided according to the existence (in 2 or more Q leads; n = 36) or not (n = 15) of resting ST-segment elevation and according to the existence (n = 28) or not (n = 23) of exercise-induced ST-segment elevation. Left ventricular end-diastolic and end-systolic volumes (mL/m2), regional wall motion (SD/chord), contractile reserve (wall motion percentage improvement with low-dose dobutamine), and coronary patency in the culprit artery were analyzed. Cardiac catheterization was repeated at the sixth month in 35 patients; systolic recovery (wall motion percentage improvement), left ventricular volumes, and coronary patency were again evaluated. Patients with resting ST-segment elevation showed poorer wall motion (2.1 +/- 0.8 SD/chord vs 1.2 +/- 1 SD/chord, P =.002), lesser contractile reserve (17% [0% to 39%] vs 41% [4% to 92%], P =.04), greater end-systolic volume (32 +/- 15 mL/m2 vs 23 +/- 11 mL/m2, P =.04), and higher percentage of occlusion (36% vs 7%, P =.04) than did patients without ST-segment elevation. Likewise, patients with exercise-induced ST-segment elevation showed lesser contractile reserve (8% [0% to 40%] vs 35% [12% to 86%], P =.03) than did patients without exercise-induced ST-segment elevation. The only independent predictors of contractile reserve were wall motion <2 SD/chord (odds ratio [OR] 7.1, confidence interval [CI] 6.3 to 7.9, P =.01) and the absence of exercise-induced ST-segment elevation (OR 5.7, CI 4.9 to 6.5, P =. 02). There were no significant differences between patients with and those without ST-segment elevation (at rest or during exercise) in systolic recovery or left ventricular volumes at the sixth month. CONCLUSIONS: ST-segment elevation on Q leads at rest is related to a poorer systolic function (more severe regional dysfunction, greater end-systolic volume, and less response to dobutamine). ST-segment elevation during exercise is independently related to a lesser contractile reserve. ST-segment elevation (at rest or during exercise) is not related to the evolution of volumes or regional dysfunction during the first 6 months after infarction.

Aged↗

Correlation of preoperative myocardial function, perfusion, and metabolism with postoperative function at rest and stress after bypass surgery in severe left ventricular dysfunction.

Previous studies of dobutamine echocardiography (DE) and positron emission tomography (PET) showed similar accuracy for predicting improvement in resting wall motion after revascularization, although limited direct comparative data are available. We sought to compare the relative accuracy of detecting contractile reserve, ischemia, perfusion, and myocardial metabolism for predicting functional recovery after coronary bypass surgery in 94 consecutive patients (aged 63+/-11 years) with chronic coronary disease and depressed left ventricular function (ejection fraction 28+/-5%). PET imaging comprised rest and dipyridamole stress myocardial perfusion images, with fluorodeoxyglucose to define metabolism-perfusion mismatch. A standard dobutamine-atropine stress was used, with evaluation of low- and peak-dose echocardiographic responses. Regional function was assessed after 13+/-16 weeks at rest in 68 patients who underwent isolated coronary bypass operation without evidence of perioperative infarction, and at rest and stress in a subgroup of 29 patients. Concordance between methods for evaluating abnormal segments (ischemic, viable, and scar) and accuracy of both tests for predicting improvement in regional function were identified. Concordance between PET and DE for identifying viable or nonviable myocardium was 63% using a 16-segment model. For predicting improved resting function after surgery, the sensitivity of PET (84%) was superior to DE (69%, p<0.001), but DE was more specific (78% vs. 37%, p<0.0001) and more accurate (75% vs. 53%, p<0.001) in predicting recovery at rest. Analysis of postoperative recovery of segmental function during stress also showed the specificity of DE to exceed that of PET (89% vs. 32%, p<0.001). The accuracy of DE was enhanced by evaluation of function during stress (86%, p<0.001), but this was not altered with PET (52%, p = NS). Thus, PET is more sensitive than DE in predicting functional recovery, but DE is more specific than PET. Evaluation of left ventricular functional recovery during stress may be preferable to assessment at rest.

Cardiotonic Agents↗

Microdissecting the genetic events in nephrogenic rests and Wilms' tumor development.

Nephrogenic rests are precursor lesions associated with about 40% of Wilms' tumors. This study identifies genetic steps occurring in the development of Wilms' tumor. Thirty-four Wilms' tumors with nephrogenic rests and/or areas of anaplasia were microdissected from paraffin sections to determine whether and at what stage loss of heterozygosity (LOH) occurred, using polymerase chain reaction-based polymorphic markers at 11p13, 11p15, and 16q. LOH at these loci have been identified in Wilms' tumors and are associated with identified or putative tumor suppressor genes. Three cystic nephromas/cystic partially differentiated nephroblastomas were also examined. LOH was detected in six cases at 11p13 and in six cases at 11p15, and two of these cases had LOH at both loci. All intralobar rests showing LOH also showed LOH in the tumor. A case with a small perilobar rest showed LOH of 11p13 only in the tumor. Five cases showing LOH at 16q were identified (this was identified only in the tumor, and not in the associated rest), and three of these had recurrence of the tumor. Two cases had a WT1 mutation (one germline and the other somatic), as well as LOH in both the intralobar rest and the tumor. A cystic partially differentiated nephroblastoma showed loss at 11p13 and 11p15, as well as at 16q. This study suggests that LOH at 11p13 and 11p15 and WT1 mutations are early events but that LOH at 16q occurs late in the pathogenesis of Wilms' tumor. Intralobar and perilobar nephrogenic rests are known to have different biological behaviors, and this study suggests that they are genetically different. A multistep model of Wilms' tumor pathogenesis is supported by these findings.

Adolescent↗

Gingerol, isoproterenol and ouabain normalize impaired post-rest behavior but not force-frequency relation in failing human myocardium.

OBJECTIVE: Rest- and stimulation frequency-dependent potentiation of contractile force is blunted in failing human myocardium. These alterations have been related to reduced sarcoplasmic reticulum (SR) Ca(2+)-reuptake and enhanced transsarcolemmal Ca(2+)-elimination by Na+/Ca(2+)-exchange. We investigated whether inotropic interventions that enhance SR Ca(2+)-uptake, or reduce Ca(2+)-elimination by Na+/Ca(2+)-exchange, normalize impaired post-rest and force-frequency behavior in left ventricular muscle strips from failing human hearts. METHODS: We tested the influence of [10]-gingerol which activates SR Ca(2+)-ATPase (10 mumol/l; n = 13), and isoproterenol which activates cAMP-dependent pathways (0.01, 0.1, 1 mumol/l; n = 40) on post-rest and force-frequency behavior. Ouabain which blocks Na+/K(+)-ATPase (0.03 mumol/l; n = 16) was used to test the effects of inhibiting Ca(2+)-elimination by Na+/Ca(2+)-exchange. For comparison, the effects of blocking SR Ca(2+)-uptake by thapsigargin (10 mumol/l; n = 14) were tested. In addition, Ca(2+)-uptake in myocardial homogenates was measured for gingerol (10 mumol/l; n = 6). RESULTS: Gingerol, isoproterenol (0.1, 1 mumol/l) and ouabain exerted significant positive inotropic effects under basal experimental conditions and normalized post-rest behavior. In contrast, force-frequency relation was only slightly improved by gingerol and isoproterenol (0.01 mumol/l). Ouabain and isoproterenol (1 mumol/l) further deteriorated force-frequency relation due to frequency-dependent significant increases in diastolic tension. Thapsigargin exerted negative inotropic effects and significantly deteriorated post-rest and force-frequency behavior. In addition, gingerol increased SR Ca(2+)-uptake significantly in myocardial homogenates. CONCLUSIONS: Inotropic interventions that stimulate SR Ca(2+)-ATPase or inhibit Na+/Ca(2+)-exchange normalize impaired post-rest behavior. Force-frequency behavior is only slightly improved by stimulation of SR Ca(2+)-ATPase but not by inhibition of Na+/Ca(2+)-exchange. This dissociation between post-rest and force-frequency behavior results from diastolic dysfunction at high stimulation rates.

Adult↗

The effects of blood pressure resting level and lability on cardiovascular reactions to laboratory stress.

Evidence that individuals with elevated resting blood pressures display excessive cardiovascular reactions to laboratory stress is regarded as implicating excessive reactivity in the pathogenesis of hypertension. However, it remains possible that this relationship is artifactual, in that resting blood pressure levels and cardiovascular reactions might both reflect intrinsic cardiovascular lability. To examine this possibility, blood pressure and heart rate were measured at rest and in response to an active laboratory stressor in 1259 men. Systolic blood pressure and heart rate reactions to the stressor were predicted by resting blood pressure. Although cardiovascular lability showed some association with both reactivity and resting blood pressure level, the resting blood pressure level-reactivity relationship survived statistical adjustment for such associations. Accordingly, the excessive cardiovascular reactions characteristic of individuals with elevated resting blood pressure would not appear to be explainable, to any substantial extent, by lability effects.

Adult↗

Resting energy expenditure and substrate utilisation rate in children with constitutional leanness or obesity.

BACKGROUND & AIM: The influence of energy expenditure on body weight regulation, in the absence of organic disease, has never been studied in a paediatric population covering a broad range of body weights. The aim of this study was to investigate resting energy metabolism in children with constitutional leanness, normal body weight, or common obesity. METHODS: Fourteen children with constitutional leanness, 16 children with obesity, and controls were studied. Resting energy expenditure and postabsorptive substrate utilisation rate were measured by indirect calorimetry and body composition was assessed from skinfold thicknesses. RESULTS: As compared to the predicted value calculated from the regression equation of resting energy expenditure on fat-free mass in the controls, resting energy expenditure was decreased in lean children (P=0.002), whereas no difference was found in obese children. In obese children and the overall population, fat mass was positively correlated with fat oxidation rate. In each group and in the overall population, fat oxidation rate was positively correlated to resting energy expenditure. CONCLUSIONS: Constitutionally lean children have a low resting metabolic rate, probably adaptive in nature. In obese children, resting energy expenditure is increased in proportion to the fat-free mass, and fat balance is the main determinant of energy balance. These data suggest a constitutional regulation of body weight.

Adipose Tissue↗

Differential induction of apoptosis in activated and resting T cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its repercussion on T cell responsiveness.

TCDD is well known for its immunotoxic effects on T cells, although the exact mechanism of toxicity remains unknown. In the current study, we investigated the effect of TCDD administration on resting and activated T cells within the same animal. To this end, C57BL/6 mice were injected intraperitoneally with either TCDD (50 microg/kg body weight) or the vehicle and were injected with anti-CD3 mAbs into the rear footpads to polyclonally activate T cells in the popliteal lymph nodes (LN). Axillary LN cells harvested from the same groups of mice served as a source of resting T cells. When the LN cells were tested for their proliferative responsiveness to stimulation with anti-CD3 mAbs in vitro, the activated popliteal LN, but not the resting axillary LN cells from TCDD-treated mice exhibited a significant decrease in responsiveness when compared to the vehicle controls. Inasmuch as TCDD has been shown to induce apoptosis in thymocytes, we addressed whether TCDD triggered apoptosis in LN cells, using the terminal deoxynucleotidyl transferase (TdT)-mediated FITC-dUTP nick end labeling (TUNEL) method. The axillary and popliteal LN cells from TCDD-treated mice failed to exhibit significant levels of apoptosis when freshly harvested. However, upon in vitro culture for 24 h with either tissue culture medium alone or with anti-CD3 mAbs, activated popliteal LN cells from TCDD-treated mice showed a significant increase in apoptosis when compared to similar cells from vehicle-treated mice. In contrast, resting axillary LN cells from TCDD-treated mice, similarly cultured in vitro, exhibited decreased levels of apoptosis when compared to the controls. Using a double-staining technique, the activated popliteal LN cells undergoing increased apoptosis in TCDD-treated animals were confirmed to be CD3+ T cells. Together, these data demonstrate that TCDD exerts differential effects on activated and resting T cells, even within the same animal, by inhibiting the proliferative responsiveness of activated, but not resting, T cells. Furthermore, this effect may be mediated by the ability of TCDD to induce increased apoptosis in activated, but not resting, T cells.

Animals↗

End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation: relation to rest-redistribution T1-201 tomography and dobutamine stress echocardiography.

OBJECTIVES: The study assessed whether end-diastolic wall thickness (EDWT), measured with echocardiography, is an important marker of myocardial viability in patients with suspected myocardial hibernation, and it compared this index to currently established diagnostic modalities of dobutamine stress echocardiography (DSE) and rest-redistribution thallium-201 (T1-201) scintigraphy. BACKGROUND: Because myocardial necrosis is associated with myocardial thinning, preserved EDWT may provide a simple index of myocardial viability that is readily available from the resting echocardiogram. METHODS: Accordingly, 45 patients with stable coronary artery disease and ventricular dysfunction underwent rest 2D echocardiograms, DSE and rest-redistribution T1-201 tomography before revascularization and a repeat resting echocardiogram > or =2 months later. RESULTS: Global wall motion score index decreased from 2.38 +/- 0.73 to 1.94 +/- 0.82 after revascularization (p < 0.001). Thirty-eight percent of severely dysfunctional segments recovered resting function. Compared to segments without recovery of resting function, those with recovery had greater EDWT (0.94 +/- 0.18 cm vs. 0.67 +/- 0.22 cm, p < or = 0.0001) and a higher T1-201 uptake (78 +/- 13% vs. 59 +/- 21%; p < 0.0001). An EDWT >0.6 cm had a sensitivity of 94% and specificity of 48% for recovery of function. Similarly, a T1-201 maximal uptake of > or =60% had a sensitivity of 91% and specificity of 50%. Receiver operating characteristic curves for prediction of recovery of regional and global function were similar for EDWT and maximum T1-201 uptake. Combination of EDWT and any contractile reserve during DSE for recovery of regional function improved the specificity to 77% without a significant loss in sensitivity (88%). CONCLUSIONS: End-diastolic wall thickness is an important marker of myocardial viability in patients with suspected hibernation, and it can predict recovery of function similar to T1-201 scintigraphy. Importantly, a simple measurement of EDWT < or =0.6 cm virtually excludes the potential for recovery of function and is a valuable adjunct to DSE in the assessment of myocardial viability.

Aged↗