Leveraging non-binding instruments for global health governance: reflections from the Global AIDS Reporting Mechanism for WHO reform.

As countries contend with an increasingly complex global environment with direct implications for population health, the international community is seeking novel mechanisms to incentivize coordinated national and international action towards shared health goals. Binding legal instruments have garnered increasing attention since the World Health Organization adopted its first convention in 2003. This paper seeks to expand the discourse on future global health lawmaking by exploring the potential value of non-binding instruments in global health governance, drawing on the case of the 2001 United Nations General Assembly Special Session Declaration of Commitment on HIV/AIDS. In other realms of international concern ranging from the environment to human rights to arms control, non-binding instruments are increasingly used as effective instruments of international cooperation. The experience of the Global AIDS Reporting Mechanism, established pursuant to the Declaration, evidences that, at times, non-binding legal instruments can offer benefits over slower, more rigid binding legal approaches to governance. The global AIDS response has demonstrated that the use of a non-binding instrument can be remarkably effective in galvanizing increasingly deep commitments, action, reporting compliance and ultimately accountability for results. Based on this case, the authors argued that non-binding instruments deserve serious consideration by the international community for the future of global health governance, including in the context of WHO reform.

The role of the humoral immune response to Clostridium difficile toxins A and B in susceptibility to C. difficile infection: a case-control study.

Antibody levels to Clostridium difficile toxin A (TcdA), but not toxin B (TcdB), have been found to determine risk of C. difficile infection (CDI). Historically, TcdA was thought to be the key virulence factor; however the importance of TcdB in disease is now established. We re-evaluated the role of antibodies to TcdA and TcdB in determining patient susceptibility to CDI in two separate patient cohorts. In contrast to earlier studies, we find that CDI patients have lower pre-existing IgA titres to TcdB, but not TcdA, when compared to control patients. Our findings suggest that mucosal immunity to TcdB may be important in the early stages of infection and identifies a possible target for preventing CDI progression.

In the shadow of the dam - Hydrology of the Little Conemaugh river and its South Fork, with insights about past and future flooding.

The Little Conemaugh River watershed and its South Fork sub-basin figure prominently in historical flooding of Johnstown, Pennsylvania and nearby communities with catastrophic flooding in 1889, 1936, and 1977 (reviewed herein). Historical stream gage data and data from a new gage on the South Fork (established via a novel, portable cableway system) are used with Nexrad rainfall data to assess watershed response and provide novel analysis of flood hydrology in the Little Conemaugh basin and the sub-basin. Using unit hydrograph estimates for longer duration storms (>8 h) and different baseflow conditions, we probe possible effects of several design storms, including those stemming from a hurricane remnant scenario (Agnes in 1972) and 50-, 100-, and 500-year 12-hour precipitation depths. The unit hydrographs provided peak discharge (Qpeak) estimates for 1977 (the only flood event with available hourly rainfall data) that are in good agreement with empirical peak discharges. Significant channel improvements completed in 1943 were designed to carry the largest known natural flow on record at that time (1936 Qpeak). Preliminary results from design storm scenarios indicate the need for a careful evaluation of extreme discharges and their return periods (including snowmelt-related contributions), as future flood levels in Johnstown may occur more frequently than originally thought. The 1977 flood, which triggered 7 dam failures and eclipsed 1936 Qpeak, resulted from less than 40% the estimated probable maximum precipitation (PMP) for a 12-hour storm. Peak discharges of similar magnitude would have ensued in 1972 had remnants of Hurricane Agnes tracked slightly westward. Flooding and infrastructure problems could be compounded for storms of 24-hour or longer durations, similar to record flooding seen in central Pennsylvania and New York in 1972. Flood recurrence, emergency procedures, and dam safety (particularly, spillway capacity in the Little Conemaugh basin and surrounding region) should likely be reassessed and protective early-warning measures (ineffective in 1977) implemented for the people of Johnstown.

A role for syndecan-1 in coupling fascin spike formation by thrombospondin-1.

An important role of cell matrix adhesion receptors is to mediate transmembrane coupling between extracellular matrix attachment, actin reorganization, and cell spreading. Thrombospondin (TSP)-1 is a modulatory component of matrix expressed during development, immune response, or wound repair. Cell adhesion to TSP-1 involves formation of biochemically distinct matrix contacts based on stable fascin spikes. The cell surface adhesion receptors required have not been identified. We report here that antibody clustering of syndecan-1 proteoglycan specifically transduces organization of cortical actin and fascin bundles in several cell types. Transfection of COS-7 cells with syndecan-1 is sufficient to stimulate cell spreading, fascin spike assembly, and extensive protrusive lateral ruffling on TSP-1 or on syndecan-1 antibody. The underlying molecular mechanism depends on glycosaminoglycan (GAG) modification of the syndecan-1 core protein at residues S45 or S47 for cell membrane spreading and on the VC2 region of the cytoplasmic domain for spreading and fascin spike formation. Expression of the VC2 deletion mutant or GAG-negative syndecan-1 showed that syndecan-1 is necessary in spreading and fascin spike formation by C2C12 cells on TSP-1. These results establish a novel role for syndecan-1 protein in coupling a physiological matrix ligand to formation of a specific matrix contact structure.

High yield expression of biologically active recombinant full length human tuftelin protein in baculovirus-infected insect cells.

Tuftelin is an acidic protein expressed at very early stages of mouse odontogenesis. It was suggested to play a role during epithelial-mesenchymal interactions, and later, when enamel formation commences, to be involved in enamel mineralization. Tuftelin was also detected in several normal soft tissues of different origins and some of their corresponding cancerous tissues. Tuftelin is expressed in low quantities, and undergoes degradation in the enamel extracellular matrix. To investigate the structure and function of tuftelin, the full length recombinant human tuftelin protein was produced. The full length human tuftelin cDNA was cloned using Gateway recombination into the Bac-to-Bac system compatible transfer vector pDest10. This vector adds a hexahistidine tag to the N-terminus of the expressed protein, enabling one-step affinity purification on nickel column. The recombinant human tuftelin protein was transposed into the bacmid and expressed in Spodoptera frugiperda (Sf9) insect cells. The yield of the purified, his-tagged recombinant full length human Tuftelin (rHTuft+) was 5-8 mg/L culture. rHTuft+ was characterized by SDS-PAGE, Western blot, ESI-TOF spectrometry, restriction mapping and MS/MS sequencing. The availability of the purified, full length recombinant human tuftelin protein opened up the possibility to investigate novel functions of tuftelin. Application of rHTuft+ agarose beads onto embryonic mouse mandibular explants caused changes in the surrounding epithelial cells, including morphology, orientation and spatial organization. Further studies using DiI labeling, revealed that rHTuft+, placed on the tooth germ region, brought about recruitment of adjacent embryonic mesenchymal cells. These findings support the hypothesis that tuftelin plays an important role during embryogenesis.

Tumour necrosis factor inhibitors in ankylosing spondylitis.

Ankylosing spondylitis (AS) is the most common form of spondyloarthropathy. Non-steroidal anti-inflammatory medications and exercise are used to manage the chronic inflammatory spinal pain and stiffness. Up to 20% of patients have a peripheral inflammatory arthritis, which is treated with standard disease-modifying anti-rheumatic drugs especially sulfasalazine and methotrexate. Patients may also have extra-articular manifestations, such as anterior uveitis, psoriasiform skin lesions and inflammatory bowel disease. Anti-tumour necrosis (TNF) therapy has been used with great success in rheumatoid arthritis. There are now good data of the efficacy of anti-TNF therapies in the short and medium terms in AS. Etanercept, infliximab and adalimumab have been shown in randomized placebo-controlled trials of short duration to significantly reduce disease activity, including pain and stiffness as well as improving function, spinal movement and quality of life. It is hoped that long-term therapy will prevent radiologic progression and ankylosis and studies of long-term efficacy are awaited. Anti-TNF therapies are generally well tolerated in AS. It is important to screen for latent tuberculosis before the commencement of anti-TNF therapy. The side-effect profile of anti-TNF therapies in AS does not appear different from that in rheumatoid arthritis. Currently, treatment with anti-TNF therapy in AS is indicated in established disease with radiographic damage. There is evidence that response to therapy is greater in patients with earlier disease and less damage. Future developments may see this therapy extended to patients with pre-radiographic AS.

Metabolic clearance and production rates of human growth hormone.

The metabolic clearance rate (MCR) of human growth hormone (HGH) was determined by the constant infusion to equilibrium technique utilizing HGH-(125)I. 22 control subjects had a MCR of 229 +/-52 ml/min (mean +/-SD). No difference was evident between sexes, or between various age groups. Patients with acromegaly demonstrated normal MCR's. Moreover, acute elevations of plasma growth hormone concentrations in normal subjects did not alter the MCR of HGH. The MCR was relatively constant from day to day and within the day when subjects were evaluated in the supine position. In contrast, the assumption of the upright position was associated with a mean 24% decrease in the MCR. These results were contrasted with the MCR of HGH observed in a small number of patients with altered thyroid function or diabetes mellitus. In six patients with hypothyroidism the MCR (131 +/-36 ml/min) was significantly decreased (P < 0.001); whereas the MCR in eight patients with hyperthyroidism (240 +/-57 ml/min) did not differ from control subjects. The MCR in eight patients with insulin-independent diabetes mellitus (IID) (185 +/-41 ml/min) and in eight patients with insulin-dependent diabetes mellitus (IDD) (136 +/-31 ml/min) were significantly different from control subjects (P = < 0.05 and P = < 0.001, respectively). These data were interpreted to indicate that the plasma HGH-removing mechanism(s) is not saturated at physiologic plasma HGH levels, that plasma HGH levels alone may not permit distinction between variations in pituitary release of the hormone and its rate of clearance from the plasma, and that the estimation of the MCR of HGH may help clarify the mechanism of abnormal plasma HGH responses to various stimuli. Production rates of HGH (PR) in control subjects (347 +/-173 mmug/min) were contrasted with hyperthyroid patients (529 +/-242 mmug/min, P < 0.05), hypothyroid patients (160 +/-69 mmug/min, P < 0.02), IID (245 +/-100 mmug/min, NS), and IDD (363 +/-153 mmug/min, NS). Considerable variability in the determination of the concentrations of immunoprecipitable HGH-(125)I and endogenous plasma HGH concentrations was encountered at apparent equilibrium conditions. Since both factors are necessary for the PR calculations, the wide 95% confidence limits of the PR's did not permit a clear interpretation of the significance of these observations.

Epithelial P2X purinergic receptor channel expression and function.

P2X purinergic receptor (P2XR) channels bind ATP and mediate Ca(2+) influx--2 signals that stimulate secretory Cl(-) transport across epithelia. We tested the hypotheses that P2XR channels are expressed by epithelia and that P2XRs transduce extracellular ATP signals into stimulation of Cl(-) transport across epithelia. Electrophysiological data and mRNA analysis of human and mouse pulmonary epithelia and other epithelial cells indicate that multiple P2XRs are broadly expressed in these tissues and that they are active on both apical and basolateral surfaces. Because P2X-selective agonists bind multiple P2XR subtypes, and because P2X agonists stimulate Cl(-) transport across nasal mucosa of cystic fibrosis (CF) patients as well as across non-CF nasal mucosa, P2XRs may provide novel targets for extracellular nucleotide therapy of CF.

Intracardiac thrombus causing peritoneovenous shunt failure: detection by two-dimensional echocardiography.

Peritoneovenous shunts have become an accepted mode of therapy for ascites refractory to medical treatment. However, their use is known to be associated with significant morbidity and mortality. Reported is the case of a patient with a Denver shunt who developed massive intracardiac thrombosis and subsequent shunt malfunction, despite preserved shunt patency.

Day to day variability of Doppler color flow jets in mitral regurgitation.

Doppler color flow mapping offers the potential to assess serial changes in mitral regurgitation associated with therapeutic interventions such as surgical valve repair or after-load reduction. However, the day to day variability of color flow jets in mitral regurgitation must be established to distinguish therapeutic responses from random variation. Therefore, 14 patients with mitral regurgitation were each studied on 5 sequential days by color flow velocity mapping. Instrument settings were kept constant for each patient, and no patient had a significant change in heart rate, blood pressure, left ventricular end-diastolic dimension or circumferential wall stress between studies. To assess day to day variability, the area of the Doppler color flow map was carefully measured in multiple views by an experienced echocardiographer. Mitral regurgitant jet area by color flow mapping tended to be greater from apical rather than parasternal views (5.6 +/- 4.0 versus 2.9 +/- 2.1 cm2, respectively, p less than 0.03). The maximal jet area in any view ranged from 0.4 to 15.0 cm2 in individual subjects. Variability of maximal jet area within subjects was not statistically significant by repeated measures analysis of variance (F = 1.88, p = 0.13); however, the coefficient of variation was approximately 15%. Thus, a reduction in jet area of greater than or equal to 30% would be needed to predict a therapeutic response at the 95% confidence level. These data have important implications regarding the use of color flow mapping to assess the efficacy of therapeutic interventions in mitral regurgitation.

Artifactual regional gray level variability in contrast-enhanced two-dimensional echocardiographic images: effect on measurement of the coronary perfusion bed.

The purpose of this study was to determine the extent of regional variability of image echocardiographic amplitude (expressed as gray level variability) in contrast-enhanced two-dimensional echocardiographic images, and to assess the effect of such baseline gray level variability on quantitation of the coronary perfusion bed. In 10 anesthetized closed chest dogs, short-axis papillary muscle echocardiographic images were obtained during control preinjection conditions and during injection of three contrast agents into the left main coronary artery with and without circumflex artery occlusion. Regional echocardiographic amplitude variation was measured by computer-based videodensitometric analysis of mean gray levels in four myocardial regions after cavity (background) gray level subtraction. To determine the effect of regional gray level variability on quantitation of the coronary perfusion bed, the contrast-enhanced left anterior descending artery perfusion bed was measured by two methods. The circumferential method ignored myocardial contrast inhomogeneity by measuring the circumferential extent of contrast enhancement, whether or not the enhancement by contrast medium extended transmurally. The exact method measured only the area of myocardium actually enhanced by contrast medium, which often did not extend transmurally. The perfusion beds determined by the two echocardiographic methods were compared with the anatomic perfusion bed determined by postmortem barium-gelatin coronary arteriography. Regional gray levels varied qualitatively and quantitatively in the control state (before contrast injection), with lateral regions being less bright than axial regions. After injection of contrast medium, brightness increased in all regions, the axial regions brightening most.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic valve morphology: an important in vitro determinant of proximal regurgitant jet width by Doppler color flow mapping.

In vitro and in vivo studies suggest that proximal aortic regurgitant jet width on Doppler color flow mapping predicts severity of aortic regurgitation. The influence of aortic valve morphology on proximal regurgitant jet width has not been studied. Despite equal cross-sectional area, differences in aortic valve morphology may influence regurgitant jet width and thus estimates of severity of aortic regurgitation. Aortic valve simulations representing degenerative, rheumatic and bicuspid valves as well as a circle in two cross-sectional areas (0.2 cm2 and 0.7 cm2) were placed in a flow model using two gradients (50 and 100 mm Hg) to produce simulated aortic regurgitant jets. Flow maps were obtained from parasternal and apical positions with color gain, frames per second, low velocity reject and depth held constant. The mean of three regurgitant jet widths for each shape, size and gradient were compared by three factor analysis of variance. Aortic valve morphology significantly affected regurgitant jet width in both parasternal and apical views (p = 0.0001 by analysis of variance) with bicuspid shapes producing regurgitant jet widths significantly different from all other shapes. Valve area also consistently significantly influenced proximal regurgitant jet width (p = 0.0001) in both views. Initial pressure gradient was less important. It is concluded that in an in vitro flow model aortic valve morphology introduces significant variability in the measurement of proximal regurgitant jet widths independent of orifice cross-sectional area. Estimates of severity of aortic regurgitation may therefore be influenced considerably by aortic valve morphology.

Differential enhancement of postischemic segmental systolic thickening by diltiazem.

Prolonged depression of segmental systolic thickening after brief coronary artery occlusion may result principally from events during reperfusion rather than during the ischemic interval. Thus, cellular calcium overload at reperfusion may be a mediator of contractile dysfunction after brief ischemia, and reduction of calcium entry by diltiazem, a calcium channel antagonist, may enhance recovery of systolic thickening after brief periods of ischemia. Thirteen awake unsedated dogs instrumented with hemodynamic catheters, left anterior descending coronary artery occluders and five to six pairs of intramyocardial sonomicrometers underwent two 15 min coronary artery occlusions with 24 h reperfusion. The order of infusion of diltiazem (15 micrograms/kg per min) or saline solution was alternated. Systolic thickening, hemodynamic variables and regional myocardial blood flow were measured serially over 24 h. Despite equally severe ischemic dysfunction during coronary occlusion, diltiazem-treated segments with systolic thinning during ischemia recovered control segmental thickening significantly earlier than saline solution-treated segments (at 30 versus 180 min of reperfusion). Blood pressure was mildly decreased during diltiazem treatment; therefore, a second group of 10 dogs underwent a similar occlusion and reflow period during infusion of nitroprusside to lower mean arterial pressure equivalently. Decreases in blood pressure in this group resulted in some improvement in segmental systolic function; however, this did not reach statistical significance at any time. Regional myocardial blood flows were similar in the saline solution- and diltiazem-treated groups during ischemia and reflow. Thus, it is concluded that 1) diltiazem infusion significantly enhanced recovery of segmental systolic thickening after 15 min of ischemia and 24 h of reperfusion; 2) the enhancement in segmental systolic function could not entirely be attributed to decreased mean arterial pressure; 3) improvement in postischemic segmental ventricular function was seen only in those segments with systolic thinning during ischemia; thus, segments with the most severe ischemic dysfunction benefited most; and 4) there were no important differences in regional myocardial blood flow during ischemia and reperfusion between saline- and diltiazem-treated animals.

Segmental systolic responses to brief ischemia and reperfusion in the hypertrophied canine left ventricle.

OBJECTIVES AND BACKGROUND: Left ventricular hypertrophy is associated with increased mortality, increased myocardial infarct size and an increased incidence of sudden death. Although reperfusion after ischemia has been shown to result in decreased infarct size and recovery of systolic thickening, it is unknown how left ventricular hypertrophy might influence recovery of regional systolic thickening after ischemia and reperfusion. We hypothesized that left ventricular hypertrophy might attenuate or abolish the functional response to reperfusion. METHODS: Three groups of chronically instrumented, conscious dogs (dogs with left ventricular hypertrophy and hypertension; dogs with left ventricular hypertrophy and reduced blood pressure and a control group without hypertrophy and with normal blood pressure) underwent 15 min of ischemia and 24 h of reperfusion. Segmental systolic thickening was measured by sonomicrometers and myocardial segments were grouped by percent of control segmental systolic thickening retained at 15 min of ischemia (class 1 greater than or equal to 67%, class 2 from 0% to 66%, class 3 less than 0% control systolic thickening). The recovery of each class of segment was measured serially during reperfusion. Hemodynamic variables and regional myocardial blood flow were also measured. RESULTS: There were no differences among groups in recovery of segmental systolic thickening for class 1 segments. Systolic thickening in class 2 (hypokinetic) segments was significantly depressed (p less than 0.05 compared with control value) in the group with left ventricular hypertrophy and reduced blood pressure (but not in the group with hypertrophy and hypertension) during early reperfusion; systolic thickening in class 3 (dyskinetic) segments showed a similar trend in the group with hypertrophy and reduced pressure. CONCLUSIONS: Although left ventricular hypertrophy with hypertension did not attenuate the contractile response to reperfusion, hypertrophy with reduced blood pressure was associated with significantly greater depression of segmental systolic thickening early during reperfusion.

Race and the decision to refer for coronary revascularization: the effect of physician awareness of patient ethnicity.

OBJECTIVES: We sought to assess whether there were differences, relative to racial ethnicity, in coronary revascularization recommendations made by a panel that had no knowledge of the patients' ethnicity. BACKGROUND: Coronary revascularization is employed less frequently in African American than in white patients. It is unclear whether this utilization pattern is driven by clinical differences between the two populations or by nonclinical factors. METHODS: Data were reviewed from 938 (26.5% African American, 73.5% white) consecutive cardiac catheterizations done between 1993 and 1995. Revascularization recommendations were made by cardiologists and cardiothoracic surgeons provided with the patients' clinical and angiographic data, but without knowledge of their ethnicity. Revascularization recommendations were compared between African American and white patients and correlated with clinical characteristics. RESULTS: No difference was noted in the percentage of African American and white patients recommended for revascularization, without reference to whether the recommendation was for percutaneous transluminal coronary angioplasty (PTCA) or for coronary artery bypass graft surgery (CABG) 40 vs. 46%, p = NS). African Americans were recommended more frequently for PTCA (22 vs. 18%, p = NS), whereas CABG was recommended for more white patients (28 vs. 18%, p = 0.002). Significantly fewer African Americans had disease in the left main or left anterior descending coronary artery or in multiple arteries. After adjusting for age, co-morbidity, left ventricular dysfunction and the extent of coronary disease, African Americans were more likely to have a recommendation for PTCA (odds ratio [OR] 1.42, 95% confidence interval [CI] 0.96 to 2.11, p = 0.08) and less likely to have a recommendation for CABG (OR 0.59, 95% CI 0.37 to 0.94, p = 0.02). CONCLUSIONS: This study suggests that when only clinical factors are considered, the rates of recommendations for revascularization will be similar for white and African American patients; but the type of revascularization procedure may differ by ethnicity and may depend, in part, on clinical factors.

Extreme bradycardia during sleep apnea caused by myxedema.

A 52-year-old man with myxedema was evaluated for anterior chest pain that was considered to be compatible with myocardial ischemia. The night after admission he developed extreme bradycardia, hypotension, and apneic episodes lasting up to 25 s. Continuous positive airway pressure and administration of medroxyprogesterone acetate prevented further episodes and relieved much of the somnolence and lethargy that had contributed to the evidence for myxedema. Alveolar hypoventilation caused by decreased sensitivity to carbon dioxide, inadequate central neural drive, peripheral muscle force, and obesity all may have contributed to the apnea. Chest pain has not recurred, and results of electrocardiography have remained normal following full thyroid hormone replacement. The early recognition of myxedema causing sleep apnea will allow specific treatment to avoid the cardiovascular risks related to prolonged apnea and will help avoid confusion with other etiologies of cardiovascular abnormalities.

Can beta-hydroxybutyrate be detected at the bedside by in vitro oxidation with hydrogen peroxide.

The diagnosis of ketoacidosis with an inordinately high plasma and urinary concentration ratio of beta-hydroxybutyrate (beta-OHB) to acetoacetate (AcAc) is difficult, because only AcAc and acetone react with the diagnostic reagents used clinically to detect ketones. The purpose of this study was to assess the validity of the claim that beta-OHB can be identified with a simple modification of the usual bedside test for ketones, using hydrogen peroxide (H2O2) and Ketostix (Ames Division, Miles Laboratories, Inc., Elkhart, Indiana). Unfortunately, the lowest detectable concentration of urinary beta-OHB was 50 mmol/L, and serum beta-OHB could not be detected at levels less than 100 mmol/L, a clinically irrelevant level. The relative insensitivity, the inapplicability to serum, and the potential hazard of the routine use of 30% H2O2 by practicing physicians or houseofficers render the method of limited value.

Aortic valve morphology influences regurgitant volume in aortic regurgitation: in vitro evaluation.

STUDY OBJECTIVE: According to the Gorlin hydraulic orifice equation, aortic regurgitation volume can be determined by the regurgitant orifice cross sectional area, diastolic filling period, mean pressure gradient between the aorta and left ventricle, and a constant relating the coefficients of contraction (Cc) and velocity (Cv). This study was performed to determine whether variation in aortic valve morphology affects regurgitant flow volume, Cc and Cv. DESIGN: Four aortic valve templates, modelled after circular, rheumatic, degenerative, and bicuspid lesions, were constructed with equal orifice cross sectional areas in two sizes, 0.2 and 0.7 cm2. These valves were studied in vitro in a flow model of aortic regurgitation, wherein aortic pressure was regulated by varying the height of a column of fluid. Flow, pressure, and velocity were measured, and the coefficient Cc and Cv were calculated from standard equations. MEASUREMENTS AND MAIN RESULTS: Regurgitant volume was assessed at diastolic filling periods of 0.5 and 1.0 s and averaged 15% greater for bicuspid and degenerative as compared to circular or rheumatic valve shapes (p = 0.0001). This difference was accentuated at the shorter diastolic filling time and higher pressure gradient, such that bicuspid lesions allowed 29% more regurgitant flow across the 0.2 cm2 orifice at fluid height of 120 cm over 0.5 s. This difference in regurgitant volume between valve shapes was due to an increased Cc for the bicuspid and degenerative valve shapes, suggesting that they are more efficient orifices than rheumatic or circular valve shapes. CONCLUSIONS: Aortic valve morphology influences regurgitant volume in aortic regurgitation. Specifically, degenerative and bicuspid orifice shapes have a higher contraction coefficient and allow more regurgitant flow than rheumatic or circular orifices at a given driving pressure and diastolic filling time.

Interventricular septal rupture complicating acute myocardial infarction: from pathophysiologic features to the role of invasive and noninvasive diagnostic modalities in current management.

Rupture of the interventricular septum is a serious complication of acute myocardial infarction, accounting for 5% of deaths due to acute infarction. The septal perforation most frequently occurs during the first week after the infarction. The majority of these patients present with at least two-vessel coronary artery disease, and most cases have a total occlusion of the infarct-related artery. The degree of associated right ventricular damage is clinically important. Unpredictable hemodynamic deterioration can rapidly develop in 80% of the patients, and mortality with medical therapy alone exceeds 90%. Because the preoperative hemodynamic status of these patients appears to be a major determinant for survival, accurate diagnosis, urgent management, and early operative correction are necessary to avoid a catastrophic clinical outcome. Traditionally, diagnostic procedures included first, the insertion of a pulmonary artery catheter for recording of pressures, sequential oximetry, and calculation of the shunt's magnitude and the cardiac output followed by left ventriculography and coronary arteriography for angiographic demonstration of the shunt and the coronary anatomy. Currently, optimal utilization of color flow Doppler and two-dimensional and transesophageal echocardiography offers a significant clinical advantage and can be used to shorten the time spent on diagnosis, evaluation, and management prior to the urgent surgical repair. The elimination of time-consuming diagnostic tests can contribute to further improvement in the survival rate.

Left ventricular dysfunction due to chronic right ventricular pressure overload. Resolution following percutaneous balloon valvuloplasty for pulmonic stenosis.

Left ventricular dysfunction due to chronic right ventricular pressure overload is well documented in experimental animals, but is controversial in humans. Whether left ventricular dysfunction resolves following the relief of chronic right ventricular pressure overload has not been studied. In this report, rapid improvement in both right and left ventricular function following successful percutaneous balloon valvuloplasty is described in a patient with severe isolated valvular pulmonic stenosis and biventricular dysfunction. It appears that: (1) geometric distortion played a major role in his reversible left ventricular dysfunction, and (2) severe biventricular dysfunction should not be a contraindication to valvuloplasty for valvular pulmonic stenosis.