The clinical quandary of left and right ventricular diastolic dysfunction and diastolic heart failure.

Diastolic heart failure is a common clinical entity that is indistinguishable from systolic heart failure without direct evaluation of left ventricular function. Diastolic heart failure is a clinical diagnosis in patients with signs and symptoms of heart failure but with preserved left ventricular function and normal ejection fraction, and is often seen in patients with a long-standing history of hypertension or infiltrative cardiac diseases. In contrast, diastolic dysfunction represents a mechanical malfunction of the relaxation of the left ventricular chamber that is primarily diagnosed by two-dimensional transthoracic echocardiography and usually does not present clinically as heart failure.

Suitability of the Arden Syntax for representation of quality indicators.

Background: The lack of computable clinical quality indicators in standard format makes use of the measures in electronic health records (EHR) difficult.

Objective: Assess Arden Syntax as a formalism for quality indicators.

Method: Thirty-nine measures were encoded as medical logic modules and shortfalls identified.

Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial.

In this 3-yr, randomized, double-blind, placebo- and active-controlled study, healthy postmenopausal women with osteoporosis (55-85 yr of age) were treated with bazedoxifene 20 or 40 mg/d, raloxifene 60 mg/d, or placebo. The primary endpoint was incidence of new vertebral fractures after 36 mo; secondary endpoints included nonvertebral fractures, BMD, and bone turnover markers. Among 6847 subjects in the intent-to-treat population, the incidence of new vertebral fractures was significantly lower (p < 0.

Selecting patients for osteoporosis therapy.

Our goal globally is to better identify individuals at risk for osteoporotic fracture so that those at high risk can be treated and unnecessary treatment for those at low risk can be avoided. Bone mineral density (BMD) information is not sufficient to identify all patients at high risk. Approximately half of patients in the community with fractures do not have osteoporosis by the 1994 World Health Organization BMD criteria.

The prevalence and clinical relevance of sexual dysfunction in women and men with chronic heart failure.

Sexual dysfunction is a common problem of increasing incidence that is associated with multiple co-morbid conditions and chronic diseases. In heart failure, however, exact numbers are unknown, in part secondary to under-reporting and under-interrogating by health care providers. A gender-specific questionnaire was modified from established sexual dysfunction questionnaires to correspond to a non-randomized outpatient heart failure population, to assess the prevalence and demographic distribution of sexual dysfunction and potential treatments expectations.

Intermittent outpatient nesiritide infusion reduces hospital admissions in patients with advanced heart failure.

Recombinant B-type natriuretic peptide (BNP) is a therapeutic modality in patients with decompensated congestive heart failure. Retrospectively tested are the effects of intermittent outpatient nesiritide infusion on symptoms, hospital readmission rates, endogenous BNP, and renal function in patients with advanced heart failure. Twenty-four patients in heart failure in New York Heart Association (NYHA) classes III-IV received a 6- to 8-hour intermittent nesiritide outpatient infusion (0.

Evidence that human thyroid cells express uncleaved, single-chain thyrotropin receptors on their surface.

The prevailing concept is that, in human thyroid tissue in vivo, all cell-surface TSH receptors (TSHR) cleave into disulfide linked A and B subunits. Because this viewpoint is based on studies using homogenized thyroid tissue and because of TSHR fragility, we studied TSHR subunit structure in intact thyroid cells, primary human thyrocyte cultures, FRTL-5 rat thyroid cells, and WRO (follicular) and NPA (papillary) thyroid cancer cell lines. To overcome the handicap of very low TSHR expression in thyroid cells, we generated a TSHR-expressing adenovirus (TSHR-Ad-RGD) with an integrin-binding RGD motif enabling efficient entry into cells lacking the coxsackie-adenovirus receptor.

The effectiveness of atypical antipsychotic medications in depressive disorders.

Clinical evidence supporting the use of atypical antipsychotic medication (broad-spectrum psychotropic agents) in the treatment of depressive disorders is increasing rapidly. Animal models suggest that when atypical antipsychotic medications are used in combination with a selective serotonin reuptake inhibitor there is additional activation of frontal dopaminergic and noradrenergic neurotransmitter systems. This stimulated the initiation of several clinical trials that showed the efficacy of atypical antipsychotic medication augmentation of selective serotonin reuptake inhibitors for patients with treatment-resistant depression.

Percutaneous dilatational tracheostomy for emergent airway access.

The study objective of this article was to evaluate percutaneous dilatational tracheostomy (PDT) for emergent airway access. This is a case series of 9 patients who presented over a 58-month period. All patients were in severe respiratory difficulty where intubation by conventional means was unsuccessful.

Genetic determinants of osteoporosis susceptibility in a female Ashkenazi Jewish population.

Purpose: To determine the heritability of low bone mineral density (BMD) at the hip in Ashkenazi Jewish families.

Methods: BMD at hip was accessed by dual x-ray absorptiometry (DEXA) in 166 female subjects from 61 families. Variance component analysis was used to estimate genetic contributions.

Etiological classification of CNS malformations: integration of molecular genetic and morphological criteria.

Classification is a creative activity that helps us understand relationships. The traditional classifications of central nervous system malformations was based exclusively upon descriptive morphology, but these criteria must now be integrated with molecular genetic data to enable an etiological classification that also remains useful to the clinician, radiologist and pathologist, who rely upon imaging and tissue examination for diagnosis. Many cerebral malformations previously thought to be a single disorder are now known to be common end-results of several independent genetic mutations.

Improved survival in women with BRCA-associated ovarian carcinoma.

Background: The objective of this study was to determine the clinical characteristics, treatment response, and frequency of p53 overexpression in Ashkenazi Jewish women with hereditary ovarian carcinoma.

Methods: Seventy-one Jewish women with epithelial ovarian carcinoma (EOC) were tested for the three BRCA founder mutations using single-strand conformation polymorphism analysis, heteroduplex analysis, and protein truncation testing. Clinical and histopathologic data were reviewed retrospectively.

Diagnosis of coronary pseudoaneurysm by Optison.

Intravenous contrast agents that traverse the pulmonary circulation have been used for endocardial border definition, myocardial perfusion, diagnosis of intracardiac thrombi, and in cardiovascular emergencies such as myocardial rupture. We report a patient who presented with a new inferior myocardial infarction and an extracardiac mass compressing the right atrium, in whom diagnosis of right coronary pseudoaneurysm was made on the basis of delayed appearance of Optison contrast into the pseudoaneurysm and was subsequently confirmed by angiography and surgery. Thus, we extend the diagnostic indication of myocardial contrast agents to patients with extracardiac masses.

Molecular genetic and morphologic integration in malformations of the nervous system for etiologic classification.

Molecular genetics has brought new insight into the etiology and pathogenesis of nervous system malformations, and provided a means of precise genetic diagnosis including the prenatal detection of many cerebral dysgeneses. Many cerebral malformations previously thought to be a single disorder are now known to be common end results of many independent genetic mutations. Examples are holoprosencephaly and lissencephaly.

Chronic Hepatitis C.

Infection with hepatitis C virus (HCV) accounts for 40% of cases of chronic liver disease in the United States and is now the most common indication for liver transplantation. Estimates suggest that 4 million people (1.8%) of the American population are or have been infected with HCV.

Optical mapping of ventricular defibrillation in isolated swine right ventricles: demonstration of a postshock isoelectric window after near-threshold defibrillation shocks.

Background: Investigators who studied ventricular defibrillation by use of optical mapping techniques failed to observe an initial defibrillation event (isoelectric window or quiescent period) shown by electrode mapping studies. This discrepancy has important implications for the mechanisms of defibrillation. The purpose of the present study was to demonstrate an optical equivalent of an isoelectric window after a near-threshold defibrillation shock.

Portal-Systemic shunts reduce asialoglycoprotein receptor density in rats.

Unlabelled: The clinical usefulness of quantitative functional imaging techniques that use asialoglycoprotein receptor (ASGP-R) binding is based on the correlation between ASGP-R density and hepatic functional reserve. Portal-systemic shunting (PSS) is common in patients with cirrhosis and portal hypertension-the same group that is most frequently considered for such imaging. PSS occurs spontaneously through collateral vessels and from the creation of surgical shunts or placement of transjugular intrahepatic portal-systemic shunts (TIPS).

Comparing cardiac action potentials recorded with metal and glass microelectrodes.

Machine-pulled high-impedance glass capillary microelectrode is standard for transmembrane potential (TMP) recordings. However, it is fragile and difficult to impale, especially in beating myocardial tissues. We hypothesize that a high-impedance pure iridium metal electrode can be used as an alternative to the glass microelectrode for TMP recording.

VI. Genome structure and cognitive map of Williams syndrome.

Williams syndrome (WMS) is a most compelling model of human cognition, of human genome organization, and of evolution. Due to a deletion in chromosome band 7q11.23, subjects have cardiovascular, connective tissue, and neurodevelopmental deficits.

Smoking increases tissue factor expression in atherosclerotic plaques: implications for plaque thrombogenicity.

Background: Smoking increases the risk of atherothrombotic events. To determine whether smoking influences plaque thrombogenicity, we examined the effect of cigarette smoking and aspirin use on tissue factor (TF) expression in atherosclerotic plaques.

Methods And Results: A total of 23 apoE-/- mice were exposed to cigarette smoke with (n=9) or without (n=14) aspirin treatment.

Microdialysis update: optimizing the advantages.

Microdialysis was introduced in the early 1970s as a method to measure dynamic release of substances in the brain (see Tossman & Ungerstedt, 1986). The technique has been refined over the past three decades due to the development of new materials for dialysis membranes and commercial availability of smaller, more consistently fabricated probes. A typical microdialysis probe consists of rigid metal concentric tubing with a semipermeable region at the tip (Fig.

Characteristics of wave fronts during ventricular fibrillation in human hearts with dilated cardiomyopathy: role of increased fibrosis in the generation of reentry.

Objectives: We sought to evaluate the characteristics of wave fronts during ventricular fibrillation (VF) in human hearts with dilated cardiomyopathy (DCM) and to determine the role of increased fibrosis in the generation of reentry during VF.

Background: The role of increased fibrosis in reentry formation during human VF is unclear.

Methods: Five hearts from transplant recipients with DCM were supported by Langendorff perfusion and were mapped during VF.

Evidence for complex nuclear inheritance in a pedigree with nonsyndromic deafness due to a homoplasmic mitochondrial mutation.

The relationship between mitochondrial genotype and clinical phenotype is complicated in most instances by the heteroplasmic nature of pathogenic mitochondrial mutations. We have previously shown that maternally inherited hearing loss in a large Arab-Israeli kindred is due to the homoplasmic A1555G mutation in the mitochondrial 12S ribosomal RNA gene [Prezant et al., 1993: Nat Genet 4:289-294].

Effects of procainamide on wave-front dynamics during ventricular fibrillation in open-chest dogs.

Background: There is increasing evidence that both functional reentrant wave fronts and multiple wavelets are present during ventricular fibrillation (VF). However, the effects of procainamide on the characteristics of activation waves during VF are poorly understood.

Methods And Results: Seven dogs were studied; six underwent subendocardial chemical ablation procedures.

Induction of meandering functional reentrant wave front in isolated human atrial tissues.

Background: The purpose of this study was to test the hypothesis that a single meandering functional reentrant wave front can result in rapid and irregular electrogram activity in human atrial tissues.

Methods And Results: The study used the explanted hearts of five human cardiac transplant recipients. Three right and two left atrial tissue samples, 3.