Comparison of Doppler ultrasonography and the hepatic venous pressure gradient in assessing portal hypertension in liver cirrhosis

BACKGROUND AND AIM: This prospective study aimed to determine whether Doppler ultrasonography can represent the hepatic venous pressure gradient (HVPG) as an assessment of the severity of portal hypertension and the response to terlipressin, which reduces the portal pressure in liver cirrhosis. METHODS: The HVPG and the Doppler ultrasonographic parameters, such as the portal venous velocity and the splenic venous velocity, the pulsatility and the resistive index of the hepatic, splenic and renal arteries were measured in 138 patients with liver cirrhosis. The changes in the HVPG and the portal venous velocity after administering terlipressin were evaluated in 43 of the 138 patients. The patients who showed a reduction in the HVPG of more than 20% of the baseline were defined as responders to terlipressin. RESULTS: None of the Doppler ultrasonographic parameters correlated with the HVPG. Both the HVPG (28.0 +/- 19.8%) and the portal venous velocity (29.7 +/- 13.2%) showed a significant reduction after terlipressin administration. However, the portal venous velocity decreased significantly, not only in the responders (31.0 +/- 12.0%) but also in the non-responders (25.2 +/- 16.4%). CONCLUSIONS: Doppler ultrasonography does not represent the HVPG, and is therefore not suitable for replacing HVPG as a means of assessing the severity of portal hypertension and the response to drugs which reduce the portal pressure in liver cirrhosis.     

Assessment of the Systolic Left Ventricular Myocardial Velocity Profile and Gradient Using Tissue Doppler Imaging in Patients with Hypertrophic Cardiomyopathy

To determine the systolic characteristics of the hypertrophied myocardium in patients with hypertrophic cardiomyopathy (HCM), we evaluated the left ventricular [left ventricle (LV)] myocardial velocity profile (MVP) and gradient obtained from tissue Doppler imaging (TDI). Transmural wall-motion velocities in the ventricular septum and LV posterior wall were recorded in 12 patients with asymmetric septal hypertrophy and 12 healthy volunteers, and their profiles and gradients were determined. The maximum systolic myocardial velocity gradient in the ventricular septum was significantly lower in the HCM group than in the control group (0.88 ± 0.35 versus 2.24 ± 0.41; P < 0.001), whereas the gradient in the LV posterior wall was only slightly lower in the HCM group than in the control group (2.69 ± 0.82 versus 3.45 ± 0.96). In the control group, the MVPs in the ventricular septum and LV posterior wall were closely linear, suggesting that the transmural velocity is uniform during systole. MVPs in the ventricular septum and LV posterior wall in the HCM group also were closely linear, whereas the distribution of velocities in the ventricular septum was fairly dispersed compared with the control group. The myocardial velocity gradient on the right ventricular side of the ventricular septum decreased or disappeared in the patients with HCM, suggesting a nonuniform distribution of velocities. In conclusion, the MVP and gradient obtained from TDI may represent new indices for evaluating regional LV contractile abnormality in patients with HCM.     

Vascular access for hemodialysis: arteriovenous fistula

The long-term survival and quality of life of patients on hemodialysis (HD) is dependant on the adequacy of dialysis via an appropriately placed vascular access. The optimal vascular access is unquestionably the autologous arteriovenous fistula (AVF), with the most common method being the conventional radio-cephalic fistula at the wrist. Recent clinical practice guidelines recommend the creation of native fistula or synthetic graft before the start of chronic HD therapy to prevent the need for complication-prone dialysis catheters. This could also have a beneficial effect on the rapidity of worsening kidney failure. A multidisciplinary approach (nephrologists, surgeons, radiologists and nurses) should improve the HD outcome by promoting the use of AVF. An important additional component of this program is the Doppler ultrasound for preoperative vascular mapping. Such an approach may be realized without unsuccessful surgical explorations, with a minimal early failure rate and a high maturation, even in patients with diabetes mellitus.     

Are inotropic agents contraindicated in congestive heart failure?

Summary The myocardium in the patient with congestive heart failure is abnormal and probably unable to generate sufficient chemical energy to meet the heart's mechanical needs. Such a condition of energy starvation would have several important implications; among these is that inotropic stimulation, by increasing energy utilization, could accelerate the progressive death of myocardial cells that characterizes end-stage heart failure. An important goal of therapy in these patients, therefore, is to reduce cardiac energy expenditure. This can be accomplished by unloading the failing heart, which has already been shown to prolong survival in patients with severe congestive heart failure. Slowing the progressive death of myocardial cells may also be accomplished by the administration of negative, rather than positive, inotropic drugs.Supported in part by NHLBI Program Project HL-33026.     

The modular architecture of protein-protein binding interfaces

Protein-protein interactions are essential for life. Yet, our understanding of the general principles governing binding is not complete. In the present study, we show that the interface between proteins is built in a modular fashion; each module is comprised of a number of closely interacting residues, with few interactions between the modules. The boundaries between modules are defined by clustering the contact map of the interface. We show that mutations in one module do not affect residues located in a neighboring module. As a result, the structural and energetic consequences of the deletion of entire modules are surprisingly small. To the contrary, within their module, mutations cause complex energetic and structural consequences. Experimentally, this phenomenon is shown on the interaction between TEM1-beta-lactamase and beta-lactamase inhibitor protein (BLIP) by using multiple-mutant analysis and x-ray crystallography. Replacing an entire module of five interface residues with Ala created a large cavity in the interface, with no effect on the detailed structure of the remaining interface. The modular architecture of binding sites, which resembles human engineering design, greatly simplifies the design of new protein interactions and provides a feasible view of how these interactions evolved.     

Tissue Doppler imaging (TDI) for on-line detection of regional early diastolic ventricular asynchrony in patients with coronary artery disease

Diastolic filling of the left ventricle is often impaired in patients with coronary artery disease (CAD) in the absence of systolic wall motion abnormalities or previous myocardial infarction. The current study was designed to assess the ability of tissue Doppler imaging (TDI) for on-line detection of regional diastolic wall motion abnormalities to identify CAD in patients with preserved systolic function. 20 normal subjects (age 51 ± 13years) and 17 CAD patients with normal systolic function and 70% luminal narrowing of the LAD (age 56 ± 11years) were included. Coronary anatomy was unknown to the echocardiographer. In the parasternal short axis and the apical 4-chamber-view, peak tissue velocities of the anterior/inferior and the midseptal/midlateral LV segments during rapid ejection (RE), isovolumic relaxation (IR), rapid filling (RF) and atrial contraction (AC) were analyzed by color-M-Mode-TDI. In the apical view, in 13 of 35 (37%) patients with adequate recordings, myocardial asynchrony was detected during IR: while the septum was moving inwards (red color-coding), the lateral wall was moving outwards (blue/green coding). In the remaining 22 patients (63%) a slow, synchronous outward motion of septum and lateral wall with homogeneous color-coding (blue/green) was seen. Unblinding of the coronary status revealed a critical LAD stenosis in all 13 patients (100%) with myocardial asynchrony. Analysis of midseptal peak velocities during IR revealed positive velocities (1.22 ± 1.64cm/s) in CAD patients and negative velocities (–1.39 ± 0.81cm/s) in normal subjects. Thus, TD1 allowed for the on-line detection of early diastolic asynchrony in 13 of 16 (82%) patients with critical LAD-narrowing. Due to the rapid assessment of regional wall motion abnormalities, TDI might help to identify CAD in patients with normal systolic function.     

Relationship of Leffler (Bronsted) alpha values and protein folding Phi values to position of transition-state structures on reaction coordinates

The positions of transition states along reaction coordinates (r++) for simple chemical reactions are often estimated from Leffler alpha values, the slope of plots of DeltaG++ (activation energy) versus DeltaG(0) (equilibrium free energy) for a series of structural variants. Protein folding is more complex than simple chemical reactions and has a multitude of reaction coordinates. Phi-Value analysis measures degree of structure formation at individual residues in folding transition states from the ratio DeltaDeltaG++/DeltaDeltaG(0) for mutations. alpha values are now being used to analyze protein folding by lumping series of Phi values into single plots. But, there are discrepancies in the values of alpha for folding with more classical measures of the extent of structure formation, which I rationalize here. I show for chemical reactions with just a single reaction coordinate that alpha = r++ only for limiting cases, such as for reactants and products being in parabolic energy wells of identical curvature. Otherwise, alpha can differ radically from r++, with alpha being determined just by the angles of intersection of reactant and product energy surfaces. Phi is an index of the progress of a local, energy-based reaction coordinate at the global transition state: Phi <0.5 corresponds to <50% progress of the local coordinate at the global transition state and Phi >0.5 means >50%. Protein Leffler plots can force different local indexes to a single fit and give skewed underestimates of the extent of global structure formation in transition states that differ from other measures of structure formation.     

An experimentally determined protein folding energy landscape

Energy landscapes have been used to conceptually describe and model protein folding but have been difficult to measure experimentally, in large part because of the myriad of partly folded protein conformations that cannot be isolated and thermodynamically characterized. Here we experimentally determine a detailed energy landscape for protein folding. We generated a series of overlapping constructs containing subsets of the seven ankyrin repeats of the Drosophila Notch receptor, a protein domain whose linear arrangement of modular structural units can be fragmented without disrupting structure. To a good approximation, stabilities of each construct can be described as a sum of energy terms associated with each repeat. The magnitude of each energy term indicates that each repeat is intrinsically unstable but is strongly stabilized by interactions with its nearest neighbors. These linear energy terms define an equilibrium free energy landscape, which shows an early free energy barrier and suggests preferred low-energy routes for folding.     

Comparison of transthoracic echocardiography using second harmonic imaging, transcranial Doppler and transesophageal echocardiography for the detection of patent foramen ovale in stroke patients.

AIMS: The comparison of three imaging methods to determine which is the most accurate and reliable for the detection of right-to-left shunt. METHODS AND RESULTS: One hundred and seven patients who were hospitalized for stroke underwent: a transthoracic echocardiography (TTE) using second harmonic, a transcranial Doppler (TCD) and a transesophageal echocardiography (TEE) from August 2003 to April 2004. All studies were recorded on a videotape and were studied by a physician blinded to the study. With TTE and TEE, we found 44 (41%) patent foramen ovales. All contrast tests were positive with TCD for these 44 patients. For two patients, the contrast test was positive only with TTE and TCD. We found four false negative contrast tests with TTE. Among the 63 patients who had a negative contrast test with TEE and TTE, the results were the same with TCD for 59 of them; we were not able to determine a cause for the four positive tests. CONCLUSION: This study confirms that transesophageal echocardiography has limitations in the diagnosis of patent foramen ovale. In this study, the negative predictive value of transcranial Doppler was excellent. Therefore, this examination is able to exclude a patent foramen ovale with a high level of confidence.     

多普勒超声心肌作功指数评价氯沙坦钾对老年高血压患者左室功能的作用

目的 :应用多普勒超声指标心肌作功指数 (MPI)评价氯沙坦钾对老年原发性高血压 (EH)患者左室功能的作用。方法 :38例老年EH患者 ,按照超声心动图左室肥厚 (LVH)的诊断标准分成无LVH(2 8例 )和LVH(10例 )两组 ,给予氯沙坦钾 5 0mg每日 1次口服 ,疗程 2 4周。治疗前后多普勒超声心动图测定左室室壁厚度和收缩、舒张功能 ,根据等容舒张期时间 (IRT)和等容收缩期时间 (ICT)之和与射血时间 (ET)的比值计算MPI。结果 :LVH组患者经氯沙坦钾治疗后左室重量指数 (LVMI)降低 ,但差异无统计学意义。两组患者射血分数 (EF)治疗前后均在正常范围 ,经氯沙坦钾治疗后IRT均显著缩短 [(12 0 .4 6± 2 3.84 )ms∶(96 .4 6± 2 3.19)ms;(12 5 .4 0± 2 5 .81)ms∶(92 .5 6± 2 9.98)ms,P <0 .0 1],MPI降低 [(0 .6 1± 0 .14 )∶(0 .4 4± 0 .12 ) ,P <0 .0 1;(0 .6 0± 0 .14 )∶(0 .4 7± 0 .13) ,P <0 .0 5 ]。MPI与IRT呈正相关 (r =0 .80 ,P <0 .0 1) ,与LVMI不相关 (r =- 0 .0 95 ,P >0 .0 5 )。结论 :氯沙坦钾能提高老年EH患者的左室功能。MPI综合反映心脏的收缩和舒张功能 ,其不受左室构型的影响 ,在高血压患者收缩功能正常的情况下是反映早期左心功能不全的指标。