Partial PFO Closure for Persistent Hypoxemia in a Patient with Ebstein Anomaly.

Ebstein anomaly is characterized by deformities of the anterior leaflet of the tricuspid valve and atrialization of the right ventricle. Patients with severe tricuspid regurgitation are recommended to have tricuspid valve surgery with concomitant atrial septal defect closure. A 73-year-old female with Ebstein anomaly presented with severe hypoxemia. Transthoracic echocardiography revealed severe tricuspid regurgitation and a patent foramen ovale with right-to-left shunting. Complete percutaneous patent foramen ovale closure led to acute decompensation; however, partial closure led to hemodynamic stability and improved oxygenation. In conclusion, similar patients with "patent foramen ovale dependency" from longstanding shunts may benefit from partial patent foramen ovale closure.

Transthoracic echocardiography: impact on diagnosis and management in tertiary care intensive care units.

The purpose of this study was to evaluate the utility of transthoracic echocardiography (TTE) in an intensive care unit by determining its impact on diagnosis and management. Over a six-month time period, we performed a prospective observational study on all patients admitted to either the medical or the surgical intensive care unit. Structured interviews were conducted with referring physicians before and after the TTE to determine the referring physicians' pre-TTE diagnosis, reasons for requesting the TTE, and whether the TTE resulted in a change in diagnosis and/or management. A total of 135 TTE examinations were done in 126 patients. The referring physicians deemed that clinical information was inadequate to make a definitive diagnosis and management plan in 36/135 (27%) of the requests. In 99/135 (73%) studies, physicians indicated that there was probably sufficient clinical information to formulate a diagnosis and management plan, but ordered a TTE to corroborate their clinical findings. Overall, a change in diagnosis occurred in 39/135 (29%) of studies, and a change in management in 55/135 (41%) of studies. Diagnosis was changed in 19/99 (19%) studies with adequate clinical data, and in 20/36 (56%) studies with inadequate clinical data (P<0.001). Management was changed in 34/99 (34%) of studies with adequate clinical data and in 21/36 (58%) of studies with inadequate clinical data (P=0.017). Of the 62 management changes, 57/62 (92%) changes were minor, and 5/62 (8%) were major. In conclusion we have found that TTE frequently resulted in a change in the diagnosis and management.

Effects of Matrine on proliferation and differentiation in K-562 cells.

We investigated the effects of Matrine on proliferation by trypan blue exclusion and differentiation by benzidine staining positive cells in K-562 cells, assayed the telomerase activity using PCR-ELISA assay, analyzed cell cycle by fluorescence-activated cell sorter analysis of the DNA content, and also determined the gene expression level of c-myc, N-ras and p53 by northern blot and dot blot analysis. The results showed that with the addition of 0.1 mg/ml Matrine, cell growth was inhibited significantly by 4 days, benizidine-positive cells rose from 1% to 2% in control cells to 15% in treated cells on day 5; treatment of K-562 cells with 0.1 mg/ml Matrine for 5 days resulted in a marked inhibition in telomerase activity, in a manner that correlated with the extent of differentiation; after exposure to Matrine for 72 h, 64.6% cells were arrested in the G1-phase of the cell cycle, the fraction of cells in S-phase had decreased from 56.9% in control cells to 24.4% in differentiated cells, and the levels of N-ras and p53 mRNA were remarkably increased for 24 and 48 h, respectively, c-myc mRNA expression level declined for 24 h and was inhibited significantly for 48 h. Our study confirmed that Matrine plays a significant effect on the inhibition of proliferation cells and inducing differentiation in K-562 cells.

Prospective multicenter study of pregnancy outcomes in women with heart disease.

BACKGROUND: The maternal and neonatal risks associated with pregnancy in women with heart disease receiving comprehensive prenatal care have not been well defined. METHODS AND RESULTS: We prospectively enrolled 562 consecutive pregnant women with heart disease and determined the outcomes of 599 pregnancies not ending in miscarriage. Pulmonary edema, arrhythmia, stroke, or cardiac death complicated 13% of pregnancies. Prior cardiac events or arrhythmia, poor functional class or cyanosis, left heart obstruction, and left ventricular systolic dysfunction independently predicted maternal cardiac complications; the cardiac event rate can be predicted using a risk index incorporating these predictors. Neonatal complications (20% of pregnancies) were associated with poor functional class or cyanosis, left heart obstruction, anticoagulation, smoking, and multiple gestations. CONCLUSIONS: Pregnancy in women with heart disease is associated with significant cardiac and neonatal complications, despite state-of-the-art obstetric and cardiac care. Maternal cardiac risk can be predicted with the use of a risk index.

Tissue Doppler imaging consistently detects myocardial abnormalities in patients with hypertrophic cardiomyopathy and provides a novel means for an early diagnosis before and independently of hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH), the clinical hallmark of familial hypertrophic cardiomyopathy (FHCM), is absent in a significant number of subjects with causal mutations. In transgenic rabbits that fully recapitulate the FHCM phenotype, reduced myocardial tissue Doppler (TD) velocities accurately identified the mutant rabbits, even in the absence of LVH. We tested whether humans with FHCM also consistently showed reduced myocardial TD velocities, irrespective of LVH. METHODS AND RESULTS: We performed 2D and Doppler echocardiography and TD imaging in 30 subjects with FHCM, 13 subjects who were positive for various mutations but did not have LVH, and 30 age- and sex-matched controls (all adults; 77% women). LV wall thickness and mass were significantly greater in FHCM subjects (P<0.01 versus those without LVH and controls). There were no significant differences in 2D echocardiographic, mitral, and pulmonary venous flow indices between mutation-positives without LVH and controls. In contrast, systolic and early diastolic TD velocities were significantly lower in both mutation-positives without LVH and in FHCM patients than in controls (P<0.001). Reduced TD velocities had a sensitivity of 100% and a specificity of 93% for identifying mutation-positives without LVH. CONCLUSIONS: Myocardial contraction and relaxation velocities, detected by TD imaging, are reduced in FHCM, including in those without LVH. Before and independently of LVH, TD imaging is an accurate and sensitive method for identifying subjects who are positive for FHCM mutations.

[Antigen analysis of Trichomonas vaginalis trophozoite by SDS-PAGE and two-dimensional gel electrophoresis].

OBJECTIVE: To analyze soluble antigens of Trichomonas vaginalis. METHODS: Soluble antigens of the parasite from a patient suffering from trichomonad vaginitis were analyzed by SDS-PAGE, immunoblotting and two-dimensional gel electrophoresis. RESULTS: A total of 26 distinct protein bands were demonstrated by using 10% resolution gel. Nine of them were main bands, eight with MWs 15-62 kDa, one with MW 97 kDa. By immunoblotting the specific anti-T. vaginalis antibodies raised in rabbit recognized 24 protein bands with 8 main bands in them. Two-dimensional gel electrophoresis revealed up to 43 individual trichomonad polypeptide spots, among which, 9 were main ones. The pI and MWs of these spots were 3.65-5.84 and 27-->100 kDa respectively. CONCLUSION: Eight protein bands out of 26 soluble antigen bands of the parasite showed high immunogenicity. There were 9 main polypeptide spots in 43 polypeptide spots of the parasite.

Aortic valve area discrepancy by Gorlin equation and Doppler echocardiography continuity equation: relationship to flow in patients with valvular aortic stenosis.

BACKGROUND: In vitro studies have shown a discrepancy between aortic valve area (AVA) measurements derived invasively by Gorlin equation (Gorlin AVA) and noninvasively by Doppler echocardiography (Doppler-echo) continuity equation (Doppler AVA) during low flow states. OBJECTIVE: To assess whether a flow-related discrepancy between Gorlin AVA and Doppler AVA occurs in the clinical setting in patients with isolated valvular aortic stenosis. PATIENTS AND METHODS: Seventy-five consecutive patients with isolated valvular aortic stenosis, who had AVA determined both invasively by Gorlin equation and noninvasively by Doppler-echo continuity equation, were retrospectively reviewed. RESULTS: Gorlin AVA and Doppler AVA correlated (r=0.68) over the narrow AVA range (Gorlin AVA 0.30 to 1.22 cm2); however, Doppler AVA was systematically larger than Gorlin AVA (0.80+/-0.21 versus 0.70+/-0.23 cm2, AVA difference = 0.10+/-0.17 cm2, P<0.0001). The AVA difference was inversely related to invasive cardiac index (r=-0.51) and was significantly greater at low flow states (cardiac index less than 2.5 L/min/m2) than at normal flow states (cardiac index 2.5 L/min/m2 or more) (0.16+/-0.15 versus -0.03+/-0.15 cm2, P<0.0001). Independent predictors of the AVA difference were the difference between Doppler-echo and invasive cardiac output (P<0.0001); the difference between Doppler-echo and invasive mean transvalvular pressure gradient (P=0.0002); and the average cardiac output (Doppler-echo plus invasive cardiac output/2, P=0.001) at the time of the hemodynamic assessments. The AVA difference was not related to average pressure gradient, average AVA or patient characteristics. CONCLUSIONS: A flow-related discrepancy between Gorlin AVA and Doppler AVA occurs in the clinical setting of patients with isolated valvular aortic stenosis. This discrepancy should be considered when assessing aortic stenosis severity during low flow states, where Gorlin AVA may be significantly smaller than Doppler AVA.

A prospective transesophageal echocardiographic study to assess a new type of left atrial spontaneous contrast at rest and during respiratory manoeuvres.

BACKGROUND: Recent observations suggest that a spontaneous echocardiographic contrast with fast motion (FEC) mimicking intravenous contrast can be seen in the left atrium in the absence of intravenous contrast injection. OBJECTIVE: To assess the incidence of FEC and to evaluate the differentiating features between FEC and injected saline contrast. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral centre. PATIENTS AND METHODS: Transesophageal echocardiography was performed in 91 consecutive patients with a mean age of 58+/-15 years. Patients with mechanical valves and congenital heart disease were excluded. Images of the right atrium, left atrium and pulmonary veins were obtained in the absence of an intravenous catheter during quiet respiration, cough and the Valsalva manoeuvre. The same procedure was repeated during injection with agitated saline after venous cannulation. RESULTS: In the absence of intravenous cannulation, FEC was detected in eight patients (9%) during quiet respiration, 36 patients (40%) during cough and 55 patients (60%) during the Valsalva manoeuvre. During the Valsalva manoeuvre, FEC was detected in the right atrium in 41 patients (45%) and in the left atrium in 33 patients (36%) (P=0.15). FEC was not related to a history of embolic event, left atrial smoke or patent foramen ovale. Intra- and interobserver agreements in the detection of FEC were 96% and 90%, respectively. CONCLUSIONS: FEC can be observed frequently in the left atrium during cough or the Valsalva manoeuvre, and awareness of FEC is important to avoid the erroneous diagnosis of patent foramen ovale.

Accelerated wound healing in mice with a disruption of the thrombospondin 2 gene.

Mice that lack the extracellular matrix protein thrombospondin 2 have, among several abnormalities, an increase in vascular density, abnormal collagen fibrils, and dermal fibroblasts that are defective in adhesion. These findings suggested that responses involving these processes, such as wound healing, might be altered. To investigate the healing process, excisional wounds were made with the aid of a biopsy punch. Such wounds, observed over a 14 d period, appeared to heal at an accelerated rate and with less scarring in thrombospondin 2-null mice. Histologic analysis of thrombospondin 2-null wound sites revealed the presence of an irregularly organized and highly vascularized granulation tissue. In addition, thrombospondin 2-null wounds retained a higher total cellular content, than control wounds. No differences in wound re-epithelization rates were observed, but thrombospondin 2-null epithelia formed rete pegs and were thicker than control epithelia. By immunohistochemistry, we detected elevated levels and an irregular deposition pattern for fibronectin in thrombospondin 2-null wounds, observations that correlated with the abnormal collagen organization in the granulation tissue. Immunostaining for thrombospondin 2 in control wounds showed that the protein is present in both early and late wounds, in a scattered cell-associated pattern or widely distributed cell- and matrix-associated pattern, respectively. Our results suggest that thrombospondin 2 plays a crucial part in the organization and vascularization of the granulation tissue during healing, possibly by modulating fibroblast-matrix interactions in early wounds and regulating the extent of angiogenesis in late wounds.

What is the real clinical utility of echocardiography? A prospective observational study.

This was a prospective, structured interview to evaluate physician expectations of echocardiography and the subsequent impact on patient care. The setting involved requests for echocardiograms in patients admitted to a tertiary care teaching hospital. Measurements included assessment of the diagnostic and therapeutic implications of echocardiography perceived by the physicians and subsequently reported and confirmed by blinded chart review. From January to May 1997, 542 echocardiograms were performed on 500 inpatients (age 62 +/- 17 years; 56% men). Referring physicians were mainly house staff (83%) and from medical services. The main indications were evaluation of left ventricular function (54%) or valve function (16%). At the time of the request, 89% of physicians believed that echocardiography was needed to guide future investigations or treatment, although in 24% of cases, physicians could not provide details of such. A reported change in treatment occurred in 57% and was validated by chart review in 38%. Changes occurred more frequently in patients in the intensive care unit versus those not in the intensive care unit (54% vs 37%, P =.02) but were similar between attending physicians and house staff (frequency of change 41% vs 39%, P = not significant) and between those with and those without previous echocardiograms (38% vs 39%, P = not significant). The utility of the echocardiogram to influence treatment decisions in hospitalized patients is high, especially in critically ill patients. However, this impact is less than is anticipated at the time of the initial request. Further studies involving more select populations of patients are required.

Long-term benzodiazepine users--characteristics, views and effectiveness of benzodiazepine reduction information leaflet.

OBJECTIVE: The authors looked at the clinical characteristics of long-term benzodiazepine users and how they viewed their use of benzodiazepine. We also examined the effectiveness of a self-help leaflet on reducing benzodiazepine use. METHOD: One hundred and nine long-term benzodiazepine users (daily use for more than 1 year) were assessed. Their perceived beneficial and undesirable effects of benzodiazepine and intention to reduce benzodiazepine use were studied and their history of benzodiazepine use was obtained. Psychiatric diagnosis and medical history were reviewed. A self-help leaflet was provided to 56 users whose anxiety symptoms were assessed to have been under control. We re-examined these 56 users 3 months later on their use of benzodiazepine and anxiety levels. RESULTS: The 109 long-term benzodiazepine users used a therapeutic dose of benzodiazepine (median: 10 mg diazepam equivalent) regularly for a median of 9 years (range: 1-40). Most of the users found benzodiazepine helpful and only 11% of them reported undesirable side effects. Half of the 109 subjects refused to reduce the dosage. Most of the subjects still experienced significant anxiety despite the use of benzodiazepine. Fourteen of the 56 subjects provided with a self-help leaflet were able to reduce a median of 2.5 mg of diazepam equivalent when re-examined after 3 months. CONCLUSION: The results are compared with previous studies in Western societies and are discussed in the light of clinical management of patients with anxiety disorders.

Low dose dobutamine echocardiography in the assessment of contractile reserve to predict the outcome of valve replacement for chronic aortic regurgitation.

BACKGROUND: When to perform surgery for aortic regurgitation is a difficult clinical decision. Occult left ventricular (LV) dysfunction may be present in patients with minimal or no symptoms, and in some patients LV dysfunction may persist after valvular replacement. OBJECTIVES: To examine the role of preoperative low dose dobutamine echocardiography (LDDE) in predicting postoperative outcome in patients who had aortic valve replacement for aortic regurgitation. PATIENTS AND METHODS: The study group comprised 16 patients (15 men, aged 48 +/- 15 years) undergoing elective surgery for aortic regurgitation. Preoperative echocardiograms were obtained in the resting state and during dobutamine infusion at 7.5 micrograms/kg/min. Complete recovery was defined by normalization of LV size and function, and the absence of symptoms at the six-month follow-up visit. Patients with complete recovery (group 1) and without complete recovery (group 2) were compared in relation to their echocardiographic parameters at rest and during LDDE. RESULTS: Of 16 patients in the study, nine were in group 1 and seven were in group 2. Age, functional class and LV end-diastolic dimensions were similar between the two groups. Group 1 patients had a smaller preoperative LV end-systolic dimension index (22.4 +/- 3.3 versus 29.9 +/- 5.9 mm/m2, P < 0.05) and a higher preoperative ejection fraction (53 +/- 8% versus 37 +/- 13%, P < 0.01). Dobutamine infusion augmented the difference in ventricular size and function between patients in group 1 and those in group 2 (LV end-systolic dimension index 18.9 +/- 3.9 mm/m2 versus 28.8 +/- 7.1 mm/m2, P < 0.01; ejection fraction 61 +/- 7% versus 41 +/- 12%, P < 0.01). CONCLUSIONS: Dobutamine accentuates differences in ventricular size and function between those with and without subsequent complete recovery following valve surgery. Because preoperative ejection fraction during LDDE is highly predictive of postoperative ejection fraction, LDDE may have a role in predicting the clinical outcome of patients following aortic valve replacement for aortic regurgitation.

Management of patients with mild aortic stenosis undergoing coronary artery bypass grafting.

BACKGROUND: The management of mild aortic stenosis during coronary artery bypass grafting remains controversial. METHODS: We reviewed the medical records of consecutive patients between January 1, 1977, and December 31, 1994, to identify 51 patients with mild aortic stenosis who underwent isolated coronary artery bypass grafting (group A), and 19 patients with mild aortic stenosis who underwent combined coronary artery bypass grafting and aortic valve replacement (group B). Patients with more than moderate aortic regurgitation were excluded. Preoperative angiograms were reviewed to assess the severity of calcification and restricted mobility of the aortic cusps. RESULTS: In group A there were 11 deaths and 8 subsequent aortic valve replacements; in group B there were 5 deaths and 3 prosthetic valve-related complications. There was no difference in event-free survival between the two groups after adjusting for the difference in age. Among group A patients, the initial transvalvular gradient (p = 0.0005) and aortic valvular calcification (p = 0.06) identified patients who demonstrated progression to severe aortic stenosis during follow-up. CONCLUSIONS: Our data suggest that routine aortic valve replacement during coronary artery bypass grafting in patients with mild aortic stenosis is not indicated, but concomitant aortic valve replacement may be appropriate in patients with higher transvalvular gradients and calcified valves.

Feasibility and complications of single-plane and biplane versus multiplane transesophageal imaging: a review of 2947 consecutive studies.

OBJECTIVE: To analyze and compare the incidence of procedural complications and failure of intubation with various sizes of probes used in transesophageal echocardiography. DESIGN: Retrospective chart review. SETTING: A Canadian, tertiary care hospital. PATIENTS: A total of 2947 consecutive transesophageal echocardiographic patient examinations between January 1992 and March 1996 at the University of Ottawa Heart Institute, Ottawa, Ontario. RESULTS: The multiplane probe (MP) was used in 1274 studies, biplane (BP) in 1642 and single plane (SP) in 31. Data for BP and SP were combined because of their similar size. Complications or failed intubation occurred in 86 studies (2.9%). There were 53 complications (1.8%) and 40 failed intubations (1.4%). Seven patients (0.3%) had both. Complications were death in one, tracheal intubation or bronchospasm in nine, bleeding in nine, angina in two, pulmonary edema in two, superficial thrombophlebitis in two, supraventricular tachycardia in one and minor adverse events in 27. Complications were unrelated to the choice of probe (MP 2%, BP and SP 1.7%, not significant). Failure of intubation (40 cases) was more common with MP than with BP and SP (2.3% versus 0.7%, P = 0.0003, OR 3.5, 95% CI 1.7 to 7.5). The main reasons for failure were cervical spondylosis in 16 patients and hypersensitive pharynx despite topical anesthesia and sedation in 13 patients. Of 21 cases of failed MP intubation, 16 (76%) were subsequently successful with BP. CONCLUSIONS: Serious complications with transesophageal echocardiography, although infrequent, do occur. The MP carries a 3.5-fold increased risk of failed intubation. In the majority of failures, successful intubation can be achieved with a smaller probe.

Genomic organization and characterization of a three-gene rat adult beta-globin haplotype.

The isolation and detailed characterization of a three-beta-globin gene (GloB) haplotype in the Sprague-Dawley (S-D) rat is described. An enriched library, lambda SDHelib, was screened with a human GloB probe, humbg44, and from which a beta minor gene, Rathbbz, was isolated, sequenced and characterized. A S-D rat GloB-specific probe, Ratbgze12, derived from the Rathbbz gene, was then used to screen a S-D rat genomic library, lambda SDglib. The clone T1510 was isolated and identified to include the entire Rathbbz gene and part of another GloB gene, Rathbby, which was 5' upstream from Rathbbz. Chromosomal walking upstream using the riboprobe, rnaT71, led to the isolation of an overlapping clone, Ta49, which was shown to include two full-length GloB genes; the most 5' was Rathbbx followed by Rathbby. Sequence data suggests that Rathbbx is a beta major gene, whereas Rathbby is a hybrid gene of Rathbbx and Rathbbz. Genomic hybridization confirmed this particular three-gene haplotype in the S-D rat. This haplotype, a1, may be the prototype of the GloB cluster in rat.