Delayed onset of subendocardial diastolic thinning at rest identifies hypoperfused myocardium.

Background: Onset of myocardial relaxation is highly energy dependent. Perfusion and therefore energy substrate delivery are predominantly reduced in the subendocardial myocardium in the early stages of progressive ischemia. We hypothesized that delayed onset of subendocardial diastolic thinning will functionally identify regionally hypoperfused resting myocardium.

Acute gastrointestinal, genitourinary, and dermatological toxicity during dose-escalated 3D-conformal radiation therapy (3DCRT) using an intrarectal balloon for prostate gland localization and immobilization.

Purpose: We determined the acute gastrointestinal (GI), genitourinary (GU), and dermatologic (D) toxicity during dose-escalated three-dimensional conformal radiation therapy (3DCRT). A modified intrarectal balloon (Medrad) was used for prostate gland localization and immobilization.

Methods: Forty-six men with clinical category T1c to T3a, and at least one high-risk feature (PSA >10, Gleason > or =7, or MRI evidence of extracapsular extension or seminal vesical invasion) comprised the study cohort.

The impact of a delay in initiating radiation therapy on prostate-specific antigen outcome for patients with clinically localized prostate carcinoma.

Background: To determine whether a delay in initiating external beam radiation therapy (RT) following diagnosis could impact prostate-specific antigen (PSA) outcome for patients with localized prostate cancer, 460 patients, who received 3D conformal RT to a median dose of 70.4 Gy for clinically localized prostate cancer between 1992 and 2001, were studied.

Methods: The primary endpoint was PSA failure (American Society for Therapeutic Radiology and Oncology definition).

The language of loss when a baby dies prior to birth: cocreating human experience.

When a baby dies prior to birth, a woman and her family begin a life long journey of living and transforming with loss. The language used with families during times of devastating loss is important to reflect upon since, language has the potential to either intensify suffering or enhance the family's experience of grieving. Words that affirm the meaning the baby holds for the family can provide comfort as families engage with the reality of lost hopes and dreams.

Spectral normalization for ultrasonic contrast microbubble detection.

Ultrasonic contrast agents consisting of microbubbles are used to assess tissue perfusion. The microbubbles are highly reflective and nonlinear and thus produce harmonics that are stronger than those from tissues. However, the magnitude of harmonic signals resulting from a region with microbubbles also depends on the acoustic pressure of incident ultrasound and the attenuation of intervening tissues in the ultrasound path.

Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis.

Chronic progression of two T cell-mediated central nervous system (CNS) demyelinating models of multiple sclerosis, relapsing EAE (R-EAE) and Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is dependent on the activation of T cells to endogenous myelin epitopes (epitope spreading). Using transfer of carboxyfluorescein succinyl ester (CFSE)-labeled T-cell receptor (TCR)-transgenic T cells and mixed bone marrow chimeras, we show that activation of naive proteolipid protein (PLP)139-151-specific T cells in SJL mice undergoing PLP178-191-induced R-EAE or TMEV-IDD occurs directly in the CNS and not in the cervical lymph nodes or other peripheral lymphoid organs. Examination of the antigen-presentation capacity of antigen-presenting cell (APC) populations purified from the CNS of mice with PLP178-191-induced R-EAE shows that only F4/80-CD11c+CD45hi dendritic cells (DCs) efficiently present endogenous antigen to activate naive PLP139-151-specific T cells in vitro.

Completing the cycle of scholarship of practice: a model for dissemination and utilization of evidence-based interventions.

SUMMARY The scholarship of practice stresses that knowledge should arise out of a dialogue and collaboration between scholars and practitioners. Bringing evidence back to practice completes the scholarship of practice cycle. This article describes a strategic approach to the process of knowledge dissemination and utilization and how that approach was used to increase knowledge and utilization of the Matter of Balance fear of falling intervention among occupational therapy practitioners.

Impact on rectal dose from the use of a prostate immobilization and rectal localization device for patients receiving dose escalated 3D conformal radiation therapy.

Purpose: When >25% of the rectum is irradiated to > or = 70 Gy, the risk of developing Grade 2 or higher rectal complications is significantly increased. This study evaluates the impact on dose to the rectum from the use of an intrarectal (IR) balloon device, previously shown to immobilize the prostate gland and localize the rectum, in patients receiving dose escalated 3-dimentional (3D) conformal radiation therapy.

Materials And Methods: From July 2001 through February 2003, 28 consecutive patients with prostate cancer underwent computerized tomography-based simulation with and without the IR balloon in place.

Fate of donor hematopoietic cells in demyelinating mutant mouse, twitcher, following transplantation of GFP+ bone marrow cells.

The twitcher mouse is an authentic murine model of a genetic demyelinating disease globoid cell leukodystrophy. Allogeneic bone marrow transplantation (BMT) in twitcher mice resulted in the clinicopathological improvement. Thus, using green fluorescent protein (GFP) transgenic mice as the donor, we investigated the behavior and fate of the donor cells and the possibility of transdifferentiation of the donor cells into neuroglial cells in the chimeric twitcher mice.

Aldosterone target organ protection by eplerenone.

The classical mineralocorticoid effect of aldosterone on unidirectional transepithelial sodium transport in the kidney was long thought to be the predominant effect of this hormone. However, there is convincing evidence for additional extrarenal actions of aldosterone that are mediated via activation of mineralocorticoid receptors (MRs) in the heart, vasculature and brain. It is now postulated that many of the detrimental effects of aldosterone are mediated through MR activation in these nonclassical target organs.

The evolution of aldosterone antagonists.

Since the isolation and purification of aldosterone from adrenal extracts 50 years ago (Experientia 9 (1953) 33), scientists have learned a great deal about how and where aldosterone acts, the factors that control its release, what is its role in the pathophysiology of cardiovascular disease, how to make and study aldosterone antagonists, and for what medical purposes these agents are useful. In this paper, we will discuss the evolution of aldosterone antagonists from the relatively nonselective spironolactone (Aldactone), to the highly selective eplerenone (Inspra). Eplerenone represents a molecule with improved steroid receptor selectivity and pharmacokinetic properties in man compared to spironolactone.

The older homosexual: current concepts of lesbian, gay, bisexual, and transgender older Americans.

Lesbian, gay, bisexual, and transgender older adults require a comprehensive medical, behavioral, mental health, and social support evaluation as do all elders. Open communication and minimizing barriers in both the patient-provider relationship and throughout the continuum of care settings offer a safe environment for current and future care. Special attention should be given to ensure proper knowledge of social support systems including durable power of attorneys, housing and financial planning, and community services available.

Transgenic model of aldosterone-driven cardiac hypertrophy and heart failure.

Aldosterone classically promotes unidirectional transepithelial sodium transport, thereby regulating blood volume and blood pressure. Recently, both clinical and experimental studies have suggested additional, direct roles for aldosterone in the cardiovascular system. To evaluate aldosterone activation of cardiomyocyte mineralocorticoid receptors, transgenic mice overexpressing 11beta-hydroxysteroid dehydrogenase type 2 in cardiomyocytes were generated using the mouse alpha-myosin heavy chain promoter.

Effectiveness of an educational intervention in modifying parental attitudes about antibiotic usage in children.

Objective: To determine the effectiveness of educational materials in improving the attitudes of parents of young children about the judicious use of antibiotics.

Methods: We conducted a randomized controlled trial by recruiting parents of children who were younger than 24 months and being seen for any reason in primary care pediatric offices. At the time of enrollment, study parents indicated their level of agreement with 16 statements, including 9 statements about antibiotic usage and 7 about injury prevention.

Eplerenone, a new selective aldosterone blocker.

Activation of the renin-angiotensin-aldosterone system is associated with unsatisfactory outcomes in patients with hypertension and heart failure in that activation of this system is correlated strongly with both the incidence and extent of end-organ damage. Despite the availability of the angiotensin converting enzyme inhibitors (ACEi) and the angiotensin receptor blockers (ARB), unblocked aldosterone levels remain an important risk factor for cardiovascular disease progression. New preclinical data generated over the last few years strongly supports the hypothesis that aldosterone has important deleterious effects on the cardiovascular system independent of the classical action of this hormone on renal epithelial cells.

Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats.

Background: We evaluated the role of aldosterone as a mediator of renal inflammation and fibrosis in a rat model of aldosterone/salt hypertension using the selective aldosterone blocker, eplerenone.

Methods: Unnephrectomized, Sprague-Dawley rats were given 1% NaCl (salt) to drink and randomized to receive treatment for 28 days: vehicle infusion (control); 0.75 microg/hour aldosterone subcutaneous infusion; or aldosterone infusion + 100 mg/kg/day oral dose of eplerenone.

Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure.

Background: In heart failure (HF), aldosterone has been implicated in the formation of reactive interstitial fibrosis, a maladaptation that contributes to left ventricular (LV) remodeling. Eplerenone is a novel selective aldosterone blocker. The present study examined the effects of long-term monotherapy with eplerenone on the progression of LV dysfunction and remodeling in dogs with chronic HF.

Selective aldosterone blockade prevents angiotensin II/salt-induced vascular inflammation in the rat heart.

We studied the role of aldosterone (aldo) in myocardial injury in a model of angiotensin (Ang) II-hypertension. Wistar rats were given 1% NaCl (salt) to drink and randomized into one of the following groups (n = 10; treatment, 21 d): 1) vehicle control (VEH); 2) Ang II infusion (25 ng/min, sc); 3) Ang II infusion plus the selective aldo blocker, eplerenone (epl, 100 mg/kg.d, orally); 4) Ang II infusion in adrenalectomized (ADX) rats; and 5) Ang II infusion in ADX rats with aldo treatment (20 micro g/kg.

Aldosterone induces a vascular inflammatory phenotype in the rat heart.

Vascular inflammation was examined as a potential mechanism of aldosterone-mediated myocardial injury in uninephrectomized rats receiving 1% NaCl-0.3% KCl to drink for 1, 2, or 4 wk and 1) vehicle, 2) aldosterone infusion (0.75 microg/h), or 3) aldosterone infusion (0.

Structural, functional, and molecular characterization of the SHHF model of heart failure.

Heart failure is a complex multifactorial disease resulting in a myriad of progressive changes at the molecular, cellular, and physiological level. To better understand the mechanisms associated with the development of congestive heart failure, a comprehensive examination of the aging lean male spontaneously hypertensive, heart failure-prone rat (SHHF) was conducted. Myocardial function and structural integrity progressively diminished as evidenced by decreased ejection fraction and increased left ventricular volume measured using echocardiography.

Peripheral macrophage recruitment in cuprizone-induced CNS demyelination despite an intact blood-brain barrier.

The contribution of peripheral macrophage was assessed in cuprizone intoxication, a model of demyelination and remyelination in which the blood-brain barrier remains intact. Flow cytometry of brain cells isolated from cuprizone-treated mice revealed an increase in the percentage of Mac-1(+)/CD45(hi) peripheral macrophage. To confirm these results in situ, C57BL/6 mice were lethally irradiated, transplanted with bone marrow from GFP-transgenic mice, and exposed to cuprizone.

Recent studies with eplerenone, a novel selective aldosterone receptor antagonist.

Activation of the renin-angiotensin-aldosterone system is associated with unsatisfactory outcomes in patients with hypertension and congestive heart failure, in that activation of this system is correlated strongly with both the incidence and extent of end-organ damage. Despite the availability of the angiotensin-converting enzyme inhibitors and the AT1 receptor antagonists, unblocked aldosterone levels remain an important risk factor for cardiovascular disease progression. New preclinical data generated over the past few years strongly support the hypothesis that aldosterone has important deleterious effects on the cardiovascular system independent of the classical action of this hormone on renal epithelial cells.

Expression of immune-related molecules is downregulated in twitcher mice following bone marrow transplantation.

Twitcher (twi/twi) is a murine model of a human genetic demyelinating disease, globoid cell leukodystrophy (Krabbe disease). The affected mice usually die before reaching age 45 days, having demyelination associated with extensive glial activation. The twi/twi mice that receive wild-type bone marrow transplantation (BMT) survive up to 3 times longer with improved pathology.

Absence of macrophage-inflammatory protein-1alpha delays central nervous system demyelination in the presence of an intact blood-brain barrier.

Chemokines are small chemotactic cytokines that modulate leukocyte recruitment and activation during inflammation. Here, we describe the role of macrophage inflammatory protein-1alpha (MIP-1alpha) during cuprizone intoxication, a model where demyelination of the CNS features a large accumulation of microglia/macrophage without T cell involvement or blood-brain barrier disruption. RNase protection assays showed that mRNA for numerous chemokines were up-regulated during cuprizone treatment in wild-type, C57BL/6 mice.

Phagocytosis and clearance of apoptotic cells is mediated by MER.

Apoptosis is fundamental to the development and maintenance of animal tissues and the immune system. Rapid clearance of apoptotic cells by macrophages is important to inhibit inflammation and autoimmune responses against intracellular antigens. Here we report a new function for Mer, a member of the Axl/Mer/Tyro3 receptor tyrosine kinase family.