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Canfield MC; Tamarappoo BK; Moses AM; Verkman AS; Holtzman EJ 《Human molecular genetics》1997,6(11):1865-1871
Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused
most often by mutations in the vasopressin V2 receptor (AVPR2). We studied
a family which included a female patient with NDI with symptoms dating from
infancy. The patient responded to large doses of desmopressin (dDAVP) which
decreased urine volume from 10 to 4 I/day. Neither the parents nor the
three sisters were polyuric. The patient was found to be a compound
heterozygote for two novel recessive point mutations in the aquaporin-2
(AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is
the site for inhibition of water permeation by mercurial compounds and is
located near to the NPA motif conserved in all aquaporins. Osmotic water
permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2
was not increased over water control, while expression of L22V cRNA
increased the Pf to approximately 60% of that for wild-type AQP2.
Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the
function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO
cells showed that the C181W mutant had an endoplasmic reticulum-like
intracellular distribution, whereas L22V and wild-type AQP2 showed endosome
and plasma membrane staining. Water permeability assays showed a high Pf in
cells expressing wild-type and L22V AQP2. This study indicates that AQP2
mutations can confer partially responsive NDI.
相似文献
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Sengupta PP Krishnamoorthy VK Abhayaratna WP Korinek J Belohlavek M Sundt TM Chandrasekaran K Seward JB Tajik AJ Khandheria BK 《The American journal of cardiology》2008,102(3):357-362
Brain (B-type) natriuretic peptide (BNP) and tissue Doppler imaging may distinguish restrictive cardiomyopathy (RCMP) from idiopathic constrictive pericardial disease (CP). However, their comparative efficacy is unknown for patients with CP from secondary causes (e.g., surgery or radiotherapy). We compared the efficacy of tissue Doppler imaging and BNP for differentiation of RCMP (n = 15) and CP (n = 16) were compared. BNP was higher in patients with RCMP than CP (p = 0.008), but the groups overlapped, particularly for BNP <400 pg/ml. BNP was lower with idiopathic CP than secondary CP (139 +/- 50 vs 293 +/- 69 pg/ml; p <0.001) or RCMP (139 +/- 50 vs 595 +/- 499 pg/ml; p <0.001), but not significantly different between those with secondary CP and RCMP (293 +/- 69 vs 595 +/- 499 pg/ml; p = 0.1). Patients with CP and RCMP had less overlap in early diastolic and isovolumic contraction tissue Doppler imaging velocities compared with BNP, with clear separation of groups evident with mean early diastolic annular velocities (averaged from 4 walls). Early diastolic tissue Doppler imaging velocity was superior to BNP for differentiation of CP and RCMP (area under the curve 0.97 vs 0.76, respectively; p = 0.01). In conclusion, mean early diastolic mitral annular velocity correctly distinguished CP from RCMP even when there was a large overlap of BNP between the 2 groups. 相似文献
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Elhendy A Modesto KM Mahoney DW Khandheria BK Seward JB Pellikka PA 《Journal of the American College of Cardiology》2003,41(1):129-135
OBJECTIVES: This study evaluated the clinical, exercise stress test, and echocardiographic predictors of mortality and cardiac events in patients with left ventricular hypertrophy (LVH). BACKGROUND: Left ventricular hypertrophy is associated with an increased risk of cardiovascular morbidity and mortality. METHODS: Symptom-limited treadmill exercise echocardiography was performed for evaluation of coronary artery disease in 483 patients (age, 66 +/- 11 years; 281 men) with LVH. End points during follow-up were all-cause mortality and hard cardiac events (cardiac death and nonfatal myocardial infarction [MI]). RESULTS: Forty-six patients died and 14 had nonfatal MI. The cumulative mortality rate was higher in patients with abnormal exercise echocardiography (3% vs. 0.4% at one year, 11.7% vs. 3.7% at three years, and 18.3% vs. 9.5% at five years, p < 0.001). In a sequential multivariate analysis model of clinical, exercise test, and rest and exercise echocardiographic data, incremental predictors of mortality were workload (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3 to 0.9), rate pressure product (HR, 0.7; 95% CI, 0.5 to 0.9), left ventricular (LV) mass index (HR, 1.4; 95% CI, 1.1 to 1.8), and failure to increase ejection fraction (EF) with exercise (HR, 2.1; 95% CI, 1.1 to 3.8). Predictors of cardiac events were history of coronary artery bypass grafting (HR, 2.6; 95% CI, 1.2 to 5.4), lower exercise rate-pressure product (HR, 0.6; 95% CI, 0.5 to 0.8), resting wall motion score index (HR, 1.4; 95% CI, 1.1 to 1.8), and failure to increase EF with exercise (HR, 3.3; 95% CI, 1.6 to 6.9). CONCLUSIONS: In patients with LVH, LV mass index and EF response to exercise are independent predictors of mortality, incremental to clinical and exercise test data and resting LV function. A normal exercise echocardiogram predicts a relatively low mortality rate during the following three years. 相似文献
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B K Khandheria C Shub A J Tajik C L Taylor D J Hagler J B Seward 《International journal of cardiology》1989,23(1):91-98
Color flow imaging provides visualization of intracardiac blood flow. The usefulness of this technique was evaluated in 93 patients with atrial septal defect. Color flow imaging improves the sensitivity of two-dimensional Doppler echocardiography in the diagnosis of atrial septal defect. In addition, it enhances communication between the cardiologist and the cardiovascular surgeon. 相似文献
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Patent foramen ovale in cryptogenic stroke: current understanding and management options 总被引:1,自引:0,他引:1
Wu LA Malouf JF Dearani JA Hagler DJ Reeder GS Petty GW Khandheria BK 《Archives of internal medicine》2004,164(9):950-956
There is increasing interest in the association between patent foramen ovale (PFO) and documented stroke of unknown cause, commonly referred to as cryptogenic stroke. We reviewed the literature and, on the basis of the available data, designed a diagnostic and treatment algorithm for patients with PFO and cryptogenic stroke. Patent foramen ovale is relatively common in the general population, but its prevalence is higher in patients with cryptogenic stroke. Importantly, paradoxical embolism through a PFO should be strongly considered in young patients with cryptogenic stroke. There is no consensus on the optimal management strategy, but treatment options include antiplatelet agents, warfarin sodium, percutaneous device closure, and surgical closure. High-risk features in the patient's history (ie, temporal association between Valsalva-inducing maneuvers and stroke, coexisting hypercoagulable state, recurrent strokes, and PFO with large opening, large right-to-left shunt, or right-to-left shunting at rest, and a coexisting atrial septal aneurysm) should prompt PFO closure. 相似文献
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Panupong Jiamsripong Tadaaki Honda Christina S Reuss R Todd Hurst Hari P Chaliki Diane E Grill Stephen L Schneck Rochelle Tyler Bijoy K Khandheria Steven J Lester 《European journal of echocardiography》2008,9(3):351-355
AIM: To compare and contrast 3 different echocardiographic methods used to measure left atrial (LA) volume: biplane area length (AL), biplane modified Simpson (SIMP), and prolate ellipse (PE) methods. METHODS AND RESULTS: A review of consecutive patients who presented to our outpatient echocardiography laboratory for a resting transthoracic study between April 2006 and May 2006 was performed. Echocardiograms were reexamined and LA volume measured using the AL, SIMP, and PE methods. Of 102 consecutive patients evaluated, 97 had a measure of LA volume using all 3 methods. A significant difference in the measurement of mean +/- SD LA volume was noted among the 3 different methods: 37 +/- 16 mL/m(2) for AL, 34 +/- 14 mL/m(2) for SIMP, and 27 +/- 12 mL/m(2) for PE. The PE method yielded routinely smaller values compared with either the AL or SIMP method (P < 0.001). Differences increased with increased LA volume. The SIMP method derived consistently smaller (<5 mL/m(2)) values than those of the AL method, consistent across the full range of LA volumes. CONCLUSION: Significant differences exist among these 3 commonly used methods for measuring LA volume. Standardization of the measurement of LA volume is recommended. 相似文献