Assessment of mitral regurgitation severity by Doppler color flow mapping of the vena contracta

BACKGROUND: Although Doppler color flow mapping is widely used to assess the severity of mitral regurgitation (MR), a simple, accurate, and quantitative marker of MR by color flow mapping remains elusive. We hypothesized that vena contracta width by color flow mapping would accurately predict the severity of MR. METHODS AND RESULTS: We studied 80 patients with MR. Vena contracta width was measured in multiple views with zoom mode and nonstandard angulation to optimize its visualization. Flow volumes across the left ventricular outflow tract and mitral annulus were calculated by pulsed-Doppler technique to determine regurgitant volume. Effective regurgitant orifice area was calculated by dividing the regurgitant volume by the continuous-wave Doppler velocity-time integral of the MR jet. The cause of MR was ischemia in 24, dilated cardiomyopathy in 34 mitral valve prolapse in 12, endocarditis in 2, rheumatic disease in 2, mitral annular calcification in 1, and uncertain in 5. Regurgitant volumes ranged from 2 to 191 mL. Regurgitant orifice area ranged from 0.01 to 1.47 cm2. Single-plane vena contracta width from the parasternal long-axis view correlated well with regurgitant volume (r = .85, SEE = 20 mL) and regurgitant orifice area (r = .86, SEE = 0.15 cm2). Biplane vena contracta width from apical views correlated well with regurgitant volume (r = .85, SEE = 19 mL) and regurgitant orifice area (r = .88, SEE = 0.14 cm2). A biplane vena contracta width > or = 0.5 cm was always associated with a regurgitant volume > 60 mL and a regurgitant orifice area > 0.4 cm2. A biplane vena contracta width < or = 0.3 cm predicted a regurgitant volume < 60 mL and a regurgitant orifice area < 0.4 cm2 in 24 of 29 patients. No other parameter, including jet area, left atrial size, pulmonary flow reversal, or semiquantitative MR grade, correlated significantly with regurgitant volume or regurgitant orifice area in a multivariate analysis. CONCLUSIONS: Our results demonstrate that careful color flow mapping of the vena contracta of the MR jet provides a simple quantitative assessment of MR that correlates well with quantitative Doppler techniques.     

Powerlessness and HIV prevention among people who trade sex for drugs (''strawberries'')

Agonistic analogs of GnRH have emerged as effective drugs in the treatment of pelvic pain associated with endometriosis. Iatrogenic hypoestrogenism is the fundamental mechanism through which GnRH agonists induce regression of the exquisitely estrogen-dependent endometriotic lesions. The decrease in bone mass consistently observed in women on long-term GnRH agonist treatment has prompted regulatory agencies such as the FDA to approve the use of these drugs for a maximum of six months in the treatment of endometriosis. The very high recurrence rate of pelvic symptomatology after the interruption of medical therapy underlines the importance of strategies aiming at improving the safety of effective long-term treatments. Data has recently become available suggesting the existence of an ideal range of circulating estradiol levels which would maintain a normal bone metabolism and still cause atrophy of endometriotic lesions. Add-back regimens including estrogen preparations have been therefore studied with variable results. In strict analogy, as oral progestins have been shown to improve bone mass in postmenopausal women, regimens employing progestin add-back have been proposed. Our review describes most of the currently published studies employing these and other substances in association with the commonly used GnRH agonists in patients with symptomatic endometriosis.     

Doppler spectrum analysis versus direct femoral artery pressure measurement for rapid assessment of aortoiliac obstruction

Adequate patient selection is required to limit the clinical workload and improve the cost-effectiveness of noninvasive hemodynamic evaluation of the aortoiliac system. In a prospective blinded fashion the traditional invasive technique of direct femoral artery pressure measurements and the computerized Doppler spectrum analysis of blood flow velocities in the common femoral artery were studied. Both tests for rapid assessment of aortoiliac obstruction were compared with duplex ultrasonographic imaging, using a peak systolic velocity ratio of 2.5 to demonstrate stenoses of 50% or more. In a series of 17 consecutive patients (34 aortoiliac segments) with suspected aortoiliac obstructive disease, a good level of agreement (kappa = 0.6) was found for both methods when compared with duplex scanning. Analysis of deviations from the duplex registrations indicated an overestimation of the pathologic cases using femoral artery pressure measurements and an underestimation using Doppler spectrum analysis of blood flow velocities in the common femoral artery. Both methods were well tolerated, but femoral artery pressure measurements had a higher technical failure rate. Because of its noninvasive character and its feasibility the Doppler technique is preferred for the selection of patients for more extensive duplex sonographic investigation.     

Separation of inhibition and activation of the allosteric yeast chorismate mutase

Yeast chorismate mutase (EC 5.4.99.5) shows homotropic activation by the substrate, allosteric activation by tryptophan, and allosteric inhibition by tyrosine. In this study mutants of chorismate mutase have been found that remain sensitive to one allosteric effector (tryptophan) but insensitive to the other (tyrosine). These mutations are located in the catalytic domain: loop 220s (212-226) and helix 12 (227-251). The first example starts with the Thr-266 --> Ile mutant that had previously been shown to be locked in the activated R state. The additional mutation Ile-225 --> Thr unlocks the R state and restores the activation by tryptophan but not the inhibition by tyrosine. The second example refers to a molecular trigger for the switch between the T and R state: a hydrogen-bonded system, which stabilizes only the T state, from Tyr-234 to Glu-23 to Arg-157. Various mutants of Tyr-234, especially Tyr-234 --> Phe, are unresponsive to tyrosine but are activated by tryptophan. This separation of activation from inhibition may indicate a pathway for activation that is independent of the allosteric transition and may also be consistent with an intermediate structure between T and R states.     

Ca-ATPase and bone cell mineralization

The plasma membrane Ca-ATPases play an important role in the regulation of intracellular Ca2+ ion concentration by pumping Ca2+ out of the cell into the extracellular fluid at the expense of ATP. These pumps potentially play an important role in the delivery of Ca2+ during mineralization of hard tissues such as bone. The properties of the plasma membrane Ca2+ pump are compared with those of the sarco(endo)plasmic reticulum and the factors regulating pump function are presented. The different gene products for the plasma membrane Ca-ATPases are described as well as their known functional significance. Particular attention is paid on the plasma membrane Ca2+ pumps present in mineralizing tissues and evidence supporting a role for these pumps in the transcellular delivery of Ca2+ during the process of mineralization is also presented.     

Noninvasive hemodynamic assessment of the internal mammary artery in myocardial revascularization

Using transthoracic B-mode imaging and Doppler spectrum analysis it was found that the luminal diameter of the internal mammary artery and its hemodynamics were not significantly different among 15 preoperative patients (64 +/- 10 years) who underwent myocardial revascularization using the left internal mammary artery and young and older control groups (25 +/- 3 years and 61 +/- 9 years, respectively). These data indicate that older age does not significantly adversely influence the degree of intimal thickening and compliance in the internal mammary artery. Doppler spectrum analysis of the internal mammary artery in the patients who were operated on revealed conversion from a triphasic systolic waveform preoperatively to a unidirectional combined systolic/diastolic waveform at 1 week and 2 and 6 months postoperatively, characterized by a significant increase in the diastolic blood flow velocity and a significant decrease in the systolic blood flow velocity and the pulsatility and resistance indices. This study indicates that transthoracic B-mode imaging and Doppler spectrum analysis are promising noninvasive techniques in the preoperative assessment of internal mammary artery morphology and physiology. In addition, Doppler spectrum analysis can also be used in the long-term serial assessment of the internal mammary artery conduit after myocardial revascularization.     

Stoichiometry and arrangement of heteromeric olfactory cyclic nucleotide-gated ion channels

Native cylic nucleotide-gated (CNG) channels are composed of alpha and beta subunits. Olfactory CNG channels were expressed from rat cDNA clones in Xenopus oocytes and studied in inside-out patches. Using tandem dimers composed of linked subunits, we investigated the stoichiometry and arrangement of the alpha and beta subunits. Dimers contained three subunit types: alphawt, betawt, and alpham. The alpham subunit lacks an amino-terminal domain that greatly influences gating, decreasing the apparent affinity of the channel for ligand by 9-fold, making it a reporter for inclusion in the tetramer. Homomeric channels from injection of alphawtalphawt dimers and from alphawt monomers were indistinguishable. Channels from injection of alphawtalpham dimers had apparent affinities 3-fold lower than alphawt homomultimers, suggesting a channel with two alphawt and two alpham subunits. Channels from coinjection of alphawtalphawt and betabeta dimers were indistinguishable from those composed of alpha and beta monomers and shared all of the characteristics of the alpha+beta phenotype of heteromeric channels. Coinjection of alphawtalpham and beta beta dimers yielded channels also of the alpha+beta phenotype but with an apparent affinity 3-fold lower, indicating the presence of alpham in the tetramer and that alpha+beta channels have adjacent alpha-subunits. To distinguish between an alpha-alpha-alpha-beta and an alpha-alpha-beta-beta arrangement, we compared apparent affinities for channels from coinjection of alphawtalphawt and betaalphawt or alphawtalphawt and betaalpham dimers. These channels were indistinguishable. To further argue against an alpha-alpha-alpha-beta arrangement, we quantitatively compared dose-response data for channels from coinjection of alphawtalpham and beta beta dimers to those from alpha and beta monomers. Taken together, our results are most consistent with an alpha-alpha-beta-beta arrangement for the heteromeric olfactory CNG channel.