Influence of muscle training on resting blood flow and forearm vessel diameter in patients with chronic renal failure.

BACKGROUND: Blood flow and vessel diameter are predictors of the success of vascular access procedures. This study investigated whether a simple exercise programme could influence these variables. METHODS: Twenty-three patients with chronic kidney disease were prescribed a simple exercise programme for one arm only; the investigators were blinded to the patients' choice. All underwent arterial and venous duplex imaging, handgrip strength and blood pressure measurements before and 1 month after the exercise programme. RESULTS: Twelve patients exercised their dominant and 11 their non-dominant arm. In the trained arm, the exercise programme resulted in a significant increase in handgrip strength, by a median (interquartile range) of 4 (0-8) kg (P < 0.001), and in the diameter of the brachial artery (0.2 (0.1-0.3) mm; P < 0.001), radial artery (0.3 (0.2-0.4) mm; P < 0.001), and cephalic vein (0.6 (0.4-1.2) mm in the forearm and 1.1 (0.4-1.2) mm above the elbow; P < 0.001). There was an increase in brachial artery mean velocity (3 (1-7) cm/s; P = 0.009) and peak systolic velocity (8 (1-15) cm/s; P = 0.020), despite a marginally lower systolic blood pressure (-8 (-16 to 0) mmHg; P = 0.007). There was no change in any of these parameters in the non-exercised arm. CONCLUSION: In patients with chronic kidney disease, forearm exercise increased blood flow and vessel diameters. This may be beneficial before vascular access formation.

Development and experience with an algorithm to evaluate suspected smallpox cases in the United States, 2002-2004.

Concerns that smallpox, an eradicated disease, might reappear because of a bioterror attack and limited experience with smallpox diagnosis in the United States prompted us to design a clinical algorithm. We used clinical features of classic smallpox to classify persons presenting with suspected smallpox rashes into 3 categories: those with high, those with moderate, and those with low risk of having smallpox. The classification guides subsequent diagnostic strategies, limiting smallpox laboratory testing to high-risk persons to minimize the number of false-positive test results. From January 2002 through June 2004, the Centers for Disease Control and Prevention (CDC) received 43 consultations regarding suspected smallpox cases. No patient was at high risk for having smallpox. One patient was tested for the presence of variola virus. Varicella was the diagnosis for 23 cases (53%). The algorithm worked well to guide clinical and public health responses to suspected smallpox cases. The poster is available from CDC, and an interactive version and laboratory protocol are available at http://www.bt.cdc.gov/agent/smallpox/diagnosis/riskalgorithm/index.asp. We recommend use of the algorithm in the United States and elsewhere.

The effect of precision of molecular orbital descriptors on toxicity modeling of selected pyridines.

The response-surface approach to QSARs attempts to model toxic potency of diverse groups of chemicals while avoiding problems associated with the identification of the mechanism of toxic action or specific chemical class often associated with other approaches. However, while hydrophobicity-dependent, simple regression QSARs derived for congeneric series of organic compounds typically have coefficients of determination greater than 0.90, more heterogeneous multiple regression QSARs exhibit typically 10-15% more unexplained variability. One difference between these approaches is the use of a quantum chemical (QC) descriptor, particularly molecular orbital (MO) energy values such as the energy of the lowest unoccupied molecular orbital (E(LUMO)). The reduced statistical fit exhibited by QSAR models, which include these QC-MO descriptors, could be a result of the variability inherent in the calculation of these descriptors. The present investigation with a structurally and mechanistically diverse set of pyridines revealed that variability is associated with the calculation of the MO descriptor E(LUMO) both between selected Hamiltonians and selected software packages. However, this variability in no way affects the statistical significance of QSARs for toxicity using these values. Specifically, the E(LUMO) values calculated with the PM3 and AM1 Hamiltonians in the two software packages were highly related. There was no relationship between molecular complexity or chemical reactivity and increased differences in individual ELUMO values as described by the standard errors of the mean. Although nine appeared to be the number of calculations, which best minimizes the standard error in energy values relative to computational costs; this minimization did not alter the statistics of the QSARs derived with single vs. mean E(LUMO) values. While the energy of the highest occupied molecular orbital (E(HOMO)) values were not used in the modeling of toxicity, a comparison of these values revealed greater variability between the Hamiltonians and software packages than observed for ELUMO values. Examination of the magnitudes of standard error of the E(HOMO) values in connection to structural features or reactivity likewise revealed no trends.

Intracardiac measurement of pre-ejection myocardial velocities estimates the transmural extent of viable myocardium early after reperfusion in acute myocardial infarction.

OBJECTIVES: We hypothesized that wall motion velocity during pre-ejection is proportional to the regional content of viable myocardium after reperfusion for acute myocardial infarction (AMI). BACKGROUND: Pre-ejection wall motion consists of short and fast inward and outward movement towards and away from the center of the left ventricle (LV) and is altered during regional ischemia. This short-lived event can be accurately quantified by Doppler myocardial imaging (DMI). METHODS: Fourteen open-chest pigs underwent 60 to 120 min of left anterior descending coronary artery occlusion followed by 30 min of reperfusion. The DMI data were collected using a phased-array intracardiac catheter (LV cavity) from ischemic and nonischemic myocardium encompassed within a plane passing through two epicardial bead markers. Peak tissue velocities during isovolumic contraction (IVC) (peak positive and peak negative), ejection (S) and early filling (E) were measured. The cardiac specimen was sliced through the epicardial markers in a plane approximating the ultrasound imaging plane. The transmural extent of necrosis (TEN) (%) was measured by triphenyltetrazolium chloride staining. RESULTS: During ischemia, positive IVC velocity was zero in ischemic walls with TEN >20%. At reperfusion, positive IVC velocity correlated better with TEN (r = -0.94, p < 0.0001) than it did S (r = -0.70, p < 0.01) and E (r = -0.81, p < 0.01). Differential IVC (the difference between peak positive and peak negative velocity) highly correlated with TEN, during ischemia (r = -0.78, p < 0.001) and during reperfusion (r = -0.93, p < 0.0001). CONCLUSIONS: Pre-ejection tissue velocity, as measured by intracardiac ultrasound, allows rapid estimation of the transmural extent of viable myocardium after reperfusion for AMI.

Thromboembolic complications after electrical cardioversion in patients with atrial flutter.

PURPOSE: To determine the incidence of thromboembolic complications after cardioversion in patients with atrial flutter. SUBJECTS AND METHODS: We reviewed 615 electrical cardioversions performed electively in 493 patients with atrial flutter. Embolic complications were evaluated during the 30 days after cardioversion. Follow-up data were obtained by follow-up visits and by contacting the treating physician. RESULTS: Anticoagulants had been administered in 415 cardioversions (67%). Cardioversion was successful in 570 procedures (93%). Three embolic events (in 3 patients) occurred in the 30 days after 550 successful cardioversions with completed follow-up (0.6% of successful procedures; 95% confidence interval, 0.1% to 1.6%). Two of the 3 patients had not been anticoagulated, whereas the third patient had subtherapeutic oral anticoagulation. No embolic event occurred in procedures performed with adequate anticoagulation. The incidence of embolism in patients regardless of subtherapeutic anticoagulation was 1% (3 of 303 successful cardioversions). CONCLUSIONS: We observed a low (0.6%) incidence of postcardioversion thromboembolic complications in patients with atrial flutter. Embolic events did not occur in patients with adequate anticoagulation.

Parametrization of electrophilicity for the prediction of the toxicity of aromatic compounds.

The aim of this study was to determine which descriptor best parametrized the electrophilicity of aromatic compounds with regard to their acute toxicity. To achieve this, toxicity data for 203 substituted aromatic compounds containing a nitro- or cyano group were evaluated in the 40-h Tetrahymena pyriformis population growth impairment assay. Quantitative structure-activity relationships (QSARs) were developed relating toxic potency [log(IGC(50)(-1))] with hydrophobicity quantified by the 1-octanol/water partition coefficient (log P) and electrophilic reactivity quantified by the molecular orbital parameters, either the energy of the lowest unoccupied molecular orbital (E(LUMO)) or maximum acceptor superdelocalizability (A(max)) was developed. For the full data set, E(LUMO) and A(max) were collinear (r = 0.87). A comparison of the QSARs [log(IGC(50)(-1)) = 0.40 log P - 0.94E(LUMO) - 1.27; n = 203, r(2) = 0.60, s = 0.49, F = 151] and [log(IGC(50)(-1)) = 0.37 log P + 13.1A(max) - 4.30; n = 203, r(2) = 0.70, s = 0.42, F = 237] reveals A(max) to be the better electrophilic parameter for modeling these data. Analysis of outliers indicates a preponderance of 4-subsituted nitrophenols and nitroanilines. Smaller datasets (51 and 102 compounds) selected in order to reduce the collinearity between A(max) and E(LUMO) were also evaluated. Results indicate A(max) to be the superior descriptor of electrophilicity for the purpose of toxicological QSARs for aromatic compounds. Development of QSARs using partial least-squares yielded similar results.

Analysis of systolic and diastolic time intervals during dobutamine-atropine stress echocardiography: diagnostic potential of the Doppler myocardial performance index.

Systolic and especially diastolic Doppler time intervals may be early markers of myocardial ischemia inducible by dobutamine-atropine stress echocardiography (DASE). We postulated that the Doppler myocardial performance index (MPI) may help differentiate ischemic from nonischemic responses. Hemodynamic and Doppler echocardiography variables were measured prospectively at every stress level of DASE in 32 patients (mean age 67 +/- 13 years). Adequate recordings were obtained in 27 patients; 13 had an ischemic response (group I) and 14 a nonischemic response (group II). Heart rate differed between groups at baseline. At equivalent peak stress, left ventricular wall motion score index was significantly greater and ejection fraction lower in group I patients. Of the Doppler variables, only the MPI consistently differed between groups, irrespective of the number of stress levels compared. The Doppler MPI may be a useful adjunct to wall motion analysis in the detection of myocardial ischemia during DASE.

Aortic valve sclerosis and aortic atherosclerosis: different manifestations of the same disease? Insights from a population-based study.

OBJECTIVES: The aim of this study was to examine the association between atherosclerosis risk factors, aortic atherosclerosis and aortic valve abnormalities in the general population. BACKGROUND: Clinical and experimental studies suggest that aortic valve sclerosis (AVS) is a manifestation of the atherosclerotic process. METHODS: Three hundred eighty-one subjects, a sample of the Olmsted County (Minnesota) population, were examined by transthoracic and transesophageal echocardiography. The presence of AVS (thickened valve leaflets), elevated transaortic flow velocities and aortic regurgitation (AR) was determined. The associations between atherosclerosis risk factors, aortic atherosclerosis (imaged by transesophageal echocardiography) and aortic valve abnormalities were examined. RESULTS: Age, male gender, body mass index (odds ratio [OR]: 1.07 per kg/m(2); 95% confidence interval [CI]: 1.02 to 1.12), antihypertensive treatment (OR: 1.93; CI: 1.12 to 3.32) and plasma homocysteine levels (OR: 1.89 per twofold increase; CI: 0.99 to 3.61) were independently associated with an increased risk of AVS. Age, body mass index and pulse pressure (OR: 1.21 per 10 mm Hg; CI: 1.00 to 1.46) were associated with elevated (upper quintile) transaortic velocities, whereas only age was independently associated with AR. Sinotubular junction sclerosis (p = 0.001) and atherosclerosis of the ascending aorta (p = 0.03) were independently associated with AVS and elevated transaortic velocities, respectively. CONCLUSIONS: Atherosclerosis risk factors and proximal aortic atherosclerosis are independently associated with aortic valve abnormalities in the general population. These observations suggest that AVS is an atherosclerosis-like process involving the aortic valve.

Pathophysiologic determinants of third heart sounds: a prospective clinical and Doppler echocardiographic study.

PURPOSE: We sought to determine the importance of a third heart sound (S(3)) and its relation to hemodynamic and valvular dysfunction. SUBJECTS AND METHODS: We prospectively enrolled 580 patients who had isolated valvular regurgitation (mitral, n = 299; aortic, n = 121) or primary left ventricular dysfunction with or without functional mitral regurgitation (n = 160). We analyzed the associations between the clinical finding of an audible S(3) (as noted in routine clinical practice by internal medicine physicians) and hemodynamic alterations measured by comprehensive quantitative Doppler echocardiography. RESULTS: S(3) was more prevalent in patients with primary left ventricular dysfunction (46%, n = 73) than in organic mitral (16%, n = 47) or aortic (12%, n = 14) regurgitation (P <0.001). Patients with an S(3) were more likely to have class III-IV symptoms (55% [74 of 137] vs. 18% [80 of 443] of those without an S(3), P <0.001) and had a higher mean [+/- SD] pulmonary pressure (55 +/- 15 vs. 41 +/- 11 mm Hg, P <0.001). An S(3) was also related to a higher early filling velocity due to a greater filling volume, restrictive filling, or both. An S(3) was a marker of severe regurgitation (regurgitant fraction > or =40%) in patients with primary left ventricular dysfunction (odds ratio [OR] = 2.4; 95% confidence interval [CI]: 1.1 to 5.5), mitral regurgitation (OR = 17; 95% CI: 5.8 to 52), and aortic regurgitation (OR = 7.1; 95% CI: 1.8-28). An S(3) was also associated with restrictive filling in primary left ventricular dysfunction (OR = 3.0; 95% CI, 1.6 to 5.9), marked dilatation in mitral regurgitation (OR = 20; 95% CI: 6.8 to 58), and an ejection fraction (<50%) in aortic regurgitation (OR = 19; 95% CI: 6.0 to 62). CONCLUSION: An audible S(3) is an important clinical finding, indicating severe hemodynamic alterations, and should lead to a comprehensive assessment and consideration of vigorous medical or surgical treatment.

Color M-mode and pulsed wave tissue Doppler echocardiography: powerful predictors of cardiac events after first myocardial infarction.

To assess the association between color M-mode flow propagation velocity and the early diastolic mitral annular velocity (E(m)) obtained with tissue Doppler echocardiography and to assess the prognostic implications of the indexes, echocardiography was performed on days 1 and 5, and 1 and 3 months after a first myocardial infarction in 67 consecutive patients. Flow propagation velocity correlated well with E(m) (r = 0.72, P <.0001). The ratio of peak E-wave velocity (E) to flow propagation velocity also correlated well with E/E(m) (r = 0.87, P <.0001). The positive predictive value of E/FPV > or =1.5 to identify patients with Killip class > or =II was 90%, and the negative predictive value 92%. The corresponding values for E/E(m) > or =10 were 70% and 90%. Cox proportional hazards analysis identified E/flow propagation velocity > or =1.5 (relative risk, 12.4 [95% confidence interval, 4.1-37.3]), E/E(m) > or =10 (relative risk, 11.5 [95% confidence interval, 3.8-34.7]), and Killip class > or =II (relative risk, 7.8 [95% confidence interval, 1.6-40.4]) to be predictors of the composite end point of cardiac death and readmission because of heart failure. Thus flow propagation velocity and E(m) are closely related after myocardial infarction and appear to have similar prognostic information.

Radiofrequency spectral analysis of attenuated ultrasound signals in experiments with echo contrast microbubbles.

Conventional gray-scale myocardial contrast echocardiography cannot distinguish perfused but attenuated from nonperfused myocardium because both may appear similar at low image intensity. We hypothesized that with radiofrequency spectral analysis of attenuated ultrasound signals, the harmonic-to-fundamental frequency ratio of the peak power spectrum (HFR(P)) could determine the presence of contrast microbubbles. We measured frequency responses of Optison microbubbles at defined degrees of ultrasound signal attenuation with different formulations of silicone (55D, 80A, and 3M); gray-scale intensities of Optison plus water compared with degassed water were analyzed at different attenuation settings (-25, -32, and -44 dB, respectively). HFR(P) values of Optison plus water were significantly higher than reference values of degassed water at each attenuation setting (55D, -14 +/- 2 dB versus -30 +/- 2 dB, P <.001; 80A, -19 +/- 2 dB versus -30 +/- 3 dB, P <.01; 3M, -22 +/- 2 dB versus -30 +/- 3 dB, P <.05), even though conventional videodensitometric analysis could not distinguish them. HFR(P) analysis objectively detects microbubbles in clinically relevant conditions of attenuation.

Annulus paradoxus: transmitral flow velocity to mitral annular velocity ratio is inversely proportional to pulmonary capillary wedge pressure in patients with constrictive pericarditis.

BACKGROUND: The early diastolic velocity of the mitral annulus (E') is reduced in patients with diastolic dysfunction and increased filling pressures. Because transmitral inflow early velocity (E) increases progressively with higher filling pressures, E/E' has been shown to have a strong positive relationship with pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure. However, previous studies have primarily involved patients without a pericardial abnormality. In constrictive pericarditis (CP), E' is not reduced, despite increased filling pressures. This study evaluated the relationship between E/E' and PCWP in patients with CP. METHODS AND RESULTS: We studied 10 patients (8 men; mean age, 64+/-7 years) with surgically confirmed CP. Doppler echocardiography was performed to measure early and late diastolic transmitral flow velocities. Tissue Doppler echocardiography was performed to measure E'. PCWP was measured with right heart catheterization. All patients were in sinus rhythm. Mean E and E' were 91+/-15 cm/s and 11+/-4 cm/s, respectively. Mean PCWP was 25+/-6 mm Hg. E' was positively correlated with PCWP (r=0.69, P=0.027). There was a significant inverse correlation between E/E' and PCWP (r=-0.74, P=0.014). Despite high left ventricular filling pressures, E/E' (mean, 9+/-4) was <15 in all but 1 patient. CONCLUSIONS: Paradoxical to the positive correlation between E/E' and PCWP in patients with myocardial disease, an inverse relationship was found in patients with CP.

Shape reconstruction of the left ventricle: accuracy of limited-plane three-dimensional echocardiography.

OBJECTIVE: To assess the accuracy of left ventricular cavity shape reproduction from 8 spatially related, apical two-dimensional ultrasonographic images. METHODS: We scanned 6 dog heart specimens. Left ventricular cavity casts were reconstructed from 48-tomogram (high-density), 8-tomogram (octaplane), and 2-tomogram (low-density biplane) apical data sets. The 48-plane left ventricular cast served as the reference. Spatial shape resolution of 3 mm in radial distance from the rotational axis to the interpolated endocardium was used as the criterion of shape accuracy. RESULTS: The adjusted limits of agreement for the octaplane and biplane left ventricular casts were +/-2.31 and +/-6.84 mm, respectively. CONCLUSIONS: The three-dimensional left ventricular cavity shape can be accurately reproduced by using a low-data density apical octaplane echocardiographic examination.

Varicella vaccine exposure during pregnancy: data from the first 5 years of the pregnancy registry.

OBJECTIVE: To assess the risks of congenital varicella syndrome and other birth defects in offspring of women who inadvertently received varicella vaccine during pregnancy or within 3 months of conception. METHODS: Pregnant women inadvertently exposed to varicella vaccine, reported voluntarily, were enrolled in the Pregnancy Registry for VARIVAX (Merck & Co., Inc., West Point, PA). The pregnancies were monitored and the outcomes ascertained from questionnaires completed voluntarily by the health care providers. The rates of congenital varicella syndrome and congenital anomalies were calculated for seronegative women prospectively reported to the registry. RESULTS: From March 17, 1995 through March 16, 2000, 362 pregnancy outcomes were identified from prospective reports. Ninety-two women were known to be seronegative to varicella, of whom 58 received their first dose of vaccine during the first or second trimester. No cases of congenital varicella syndrome were identified among 56 live births (rate 0%, 95% confidence interval [CI] 0, 15.6). Among all the prospective reports of live births, five congenital anomalies were reported. No specific pattern was identified in either the susceptible cohort or the sample population as a whole. CONCLUSION: No abnormal features have been reported that suggested the occurrence of congenital varicella syndrome or other birth defects related to vaccine exposure during pregnancy. Because of the small numbers, this study has limited precision, so continued surveillance is warranted. However, these results should provide some assurance to health care providers and women with inadvertent exposure before or during pregnancy.

Rapid three-dimensional echocardiography : clinically feasible alternative for precise and accurate measurement of left ventricular volumes.

BACKGROUND: Clinical applicability of conventional ultrasonographic systems using mechanical adapters for 3D echocardiographic imaging has been limited by long acquisition and processing times. We developed a rapid (6-s) acquisition technique that collects apical tomograms using a continuously internally rotating transthoracic transducer. This study was performed to examine the clinical feasibility of rapid-acquisition 3D echocardiography to estimate left ventricular end-diastolic and end-systolic volumes using electron-beam computed tomography as the reference standard. Methods and Results-We collected a series of 6 to 11 apical echocardiographic tomograms, depending on heart rate, in 11 patients. There was good correlation, low variability, and low bias between rapid 3D echocardiography and electron-beam computed tomography for measuring left ventricular end-diastolic volume (r=0.96; standard error of the estimate, 21.34 mL; bias, -4.93 mL) and left ventricular end-systolic volume (r=0.96; standard error of the estimate, 14.78 mL; bias, -6.97 mL). CONCLUSIONS: The rapid-acquisition 3D echocardiography extends the use of a multiplane, internally rotating handheld transducer so that it becomes a precise and clinically feasible tool for assessing left ventricular volumes and function. A rapid-image acquisition time of 6 s would allow repeated image collection during the course of a clinical echocardiographic examination. Additional work must address rapid and automated data processing.