Inflammatory myopathy with cytochrome oxidase negative muscle fibers: methotrexate treatment.

Inflammatory myopathy with cytochrome oxidase negative muscle fibers (IM/COX-) is characterized by slowly progressive weakness, most prominent in the quadriceps, muscle fibers with reduced COX staining and mitochondrial DNA mutations, and a poor response to corticosteroid treatment. We reviewed records of quantitative measurements of muscle strength in 7 IM/COX- patients to evaluate the outcomes after treatment with oral, once weekly, methotrexate for an average of 15 months. We compared the results to 6 patients with IM/COX- who received no long-term immunosuppression, and to 4 with inclusion body myositis (IBM) who received methotrexate during the same period.

Effects of high-dose lisinopril-isosorbide dinitrate on severe mitral regurgitation and heart failure remodeling.

In long-term, 1-year follow-up, uptitration of angiotensin-converting enzyme inhibitor and nitrate therapy over established doses can further improve severe functional mitral regurgitation in patients with dilated cardiomyopathy due to a reversal of heart failure-related left ventricular remodeling. With marked left ventricular enlargement, >6.8 cm end-diastolic diameter, heart failure remodeling may be irreversible and resistant to further medical intervention.

Undetected cardiogenic shock in patients with congestive heart failure presenting to the emergency department.

The purpose of this study was to examine the use of lactic acid levels and continuous central venous oxygen saturation (central venous oximetry) to stratify and treat patients with acutely decompensated end-stage chronic congestive heart failure (CHF) presenting to the emergency department. This prospective, convenience, non-outcome study was performed at an urban tertiary care hospital. Patients with end-stage CHF with an ejection fraction <30% presenting in decompensated CHF were eligible for the study.

Paradoxical hypertension after reversal of heart failure in patients treated with intensive vasodilator therapy.

Hypertension is a major cause of heart failure, evolving from left ventricular hypertrophy to systolic and diastolic dysfunction. Although effective heart failure therapy has been associated with a lowering or no change in systemic arterial blood pressure in long-term follow-up, this study describes the symptomatic, clinical, and left ventricular functional response of a subgroup of heart failure patients with a prior history of hypertension who demonstrated a paradoxical hypertensive response despite high-dose vasodilator therapy. We prospectively identified 45 patients with a past history of hypertension who had become normotensive with symptomatic heart failure.

The pleckstrin homology domain of oxysterol-binding protein recognises a determinant specific to Golgi membranes.

Background: Peripheral membrane proteins are targeted to the cytoplasmic face of specific intracellular membranes. The organelle-specific ligands recognised by peripheral proteins include other proteins and lipids. Oxysterol-binding protein (OSBP) translocates from the cytoplasm to the Golgi apparatus on binding oxygenated derivatives of cholesterol.

A role for giantin in docking COPI vesicles to Golgi membranes.

We have previously shown that p115, a vesicle docking protein, binds to two proteins (p130 and p400) in detergent extracts of Golgi membranes. p130 was identified as GM130, a Golgi matrix protein, and was shown to act as a membrane receptor for p115. p400 has now been identified as giantin, a Golgi membrane protein with most of its mass projecting into the cytoplasm.

Ancient schwannoma masquerading as parotid pleomorphic adenoma.

Pleomorphic adenoma of the parotid gland is common. We report a typical case of a parotid gland swelling which clinically, radiologically and cytologically represented a pleomorphic adenoma. Only following surgical excision and histological examination however, was the true diagnosis of ancient schwannoma made.

The incremental risk of female sex in heart transplantation: a multiinstitutional study of peripartum cardiomyopathy and pregnancy. Cardiac Transplant Research Database Group.

Background: Controversy remains regarding the reason females seem to be at increased risk for rejection after heart transplantation. Therefore this study was performed to define the effect of a pretransplantation diagnosis of peripartum cardiomyopathy and the effect of previous pregnancy on the outcome (incidence of rejection and death) of females after heart transplantation.

Methods: In this multiinstitutional study of 3244 adult (greater than 13 years of age) heart transplant recipients, (a) the outcome of 40 females who underwent transplantation for peripartum cardiomyopathy was compared with that of 200 females of childbearing age (13 to 45 years) who underwent transplantation for other indications and (b) the posttransplantation outcome of 543 females with a history of pregnancy was compared with that of 101 nulliparous adult females and 2562 adult males.

Reverse remodeling in heart failure with intensification of vasodilator therapy.

Background: Heart failure therapy with beta-receptor blockade has been shown to effect a partial reversal of left ventricular (LV) remodeling in heart failure.

Hypothesis: We tested the hypothesis that, in the absence of beta blockade, uptitration of angiotensin-converting enzyme (ACE) inhibitor and nitrate therapy over conventional dosages would improve symptoms as well as LV function in patients with severe heart failure.

Methods: For patients with nonischemic or ischemic cardiomyopathy, intensive high-dose angiotensin-converting enzyme inhibitor and nitrate therapy was uptitrated.

Response of symptomatic myocardial ischemia in ischemic cardiomyopathy to intensive vasodilator therapy.

To determine the cardiovascular protective effects of angiotensin-converting enzyme inhibitors, we examined the response to intensive vasodilator therapy in patients with ischemic cardiomyopathy and ongoing angina pectoris. We found that for patients with ischemic cardiomyopathy and ongoing active angina, intensive vasodilator therapy with angiotensin-converting enzyme inhibition and nitrates improved not only heart failure-related symptoms, but also resulted in a significant improvement in symptomatic ischemia and ischemia-related morbid events.

p47 is a cofactor for p97-mediated membrane fusion.

At least two distinct ATPases, NSF and p97, are known to be involved in the heterotypic fusion of transport vesicles with their target membranes and the homotypic fusion of membrane compartments. The NSF-mediated fusion pathway is the best characterized, many of the components having been identified and their functions analysed. In contrast, none of the accessory proteins for the p97-mediated fusion pathway has been identified.

The relationship of histology to genotype in chronic HCV infection.

The histological description of chronic hepatitis is undergoing considerable change at present. It has become important to define chronic hepatitis aetiologically and then define levels of necro-inflammatory change (grade) and fibrosis (stage). The aim of this study was to compare the ability of different histological scoring systems to detect differences in the pathological changes associated with infection with the different HCV genotypes that are known to have different natural histories.

The vesicle docking protein p115 binds GM130, a cis-Golgi matrix protein, in a mitotically regulated manner.

The docking of transport vesicles with their target membrane is thought to be mediated by p115. We show here that GM130, a cis-Golgi matrix protein, interacts specifically with p115 and so could provide a membrane docking site. Deletion analysis showed that the N-terminus binds to p115, whereas the C-terminus binds to Golgi membranes.

Effects of cardiac sympathetic innervation on coronary blood flow.

Background: The role of cardiac sympathetic nerves in regulating coronary blood flow is controversial. We sought to determine the degree to which cardiac efferent sympathetic signals modulate coronary blood flow. The heterogeneous sympathetic reinnervation in transplanted hearts provides a model for studying the vasomotor responses to adrenergic stimulation in reinnervated and denervated coronary territories of the same heart.

The design of the Mortality Assessment in Congestive Heart Failure Trial (MACH-1, mibefradil).

Background: Despite the advances in therapy for heart failure with the use of angiotensin-converting enzyme inhibitors, heart failure remains a major medical problem, impacting on well-being and survival.

Hypothesis: Mibefradil is a member of new class of agents that, due to its unique mechanism of action and pharmacologic and physiologic profile, may offer a significant advance in the treatment of heart failure. Mibefradil is a nonvoltage-regulated T-channel calcium blocker that differs from all the other currently available L-channel calcium blockers.

Acute reversibility of pulmonary hypertension predicts neither long-term hemodynamic response nor outcome in patients awaiting heart transplantation.

For transplant wait-list patients with end-stage congestive heart failure, reversibility of pulmonary hypertension tested with acute administration of vasodilators is a prerequisite to listing for transplantation. We have shown that the magnitude of the initial pulmonary vasodilatory response to nitroprusside predicts neither the extent of the long-term hemodynamic response nor the subsequent need for transplantation versus clinical improvement and removal from transplant consideration.

Clinical status of patients removed from a transplant waiting list rivals that of transplant recipients at significant cost savings.

We retrospectively contrasted the medical outcome of patients removed from the heart transplant consideration list because of clinical improvement with that of transplant recipients. Of 60 patients awaiting transplantation, 18 were removed from the list (group A), and 42 required transplant or died (group B). Group A significantly improved regarding exercise oxygen uptake, ejection fraction, and hemodynamics.

Responses to arm exercise in patients with compensated heart failure.

Purpose: This study compares the responses of 20 male patients (mean age 51 +/- 11 years) with stable heart failure during peak and submaximal arm and leg exercise.

Methods: On day 1, subjects completed two symptom-limited graded exercise tests, one with their arms and one with their legs. On day 2, subjects performed arm only and leg only exercise at a matched power output of 30 Watts (W).

Biliary sludge: can ultrasound reliably detect the presence of crystals in bile?

Objective: To determine the accuracy of routine gallbladder ultrasound in the detection of crystals in bile.

Methods: Preoperative ultrasonography was performed in 40 patients undergoing elective cholecystectomy. Bile was aspirated at operation and examined microscopically for the presence and quantity of crystals.

Impact of medical therapy on pulmonary hypertension in patients with congestive heart failure awaiting cardiac transplantation.

Pulmonary artery (PA) hypertension in transplant recipients increases mortality from right heart failure following heart transplantation. We examined the impact of long-term medical therapy on the severity of PA hypertension in patients with end-stage congestive heart failure on a transplant waiting list. The initial and final, quarterly right heart catheterization data on 60 patients (50 men, aged 50 +/- 9 years, New York Heart Association class III to IV) awaiting heart transplantation were analyzed and the patients divided into 2 groups: group A, those with persistent elevated systolic PA pressures throughout the 10-month follow-up (n = 31 of 60), and group B, those who had any decrease in systolic PA pressure during that period (n = 29 of 60).

Binding of the vesicle docking protein p115 to Golgi membranes is inhibited under mitotic conditions.

The vesicle docking protein p115 showed saturable, high affinity binding to interphase Golgi membranes. The affinity of binding was up to 20-fold lower using membranes preincubated with mitotic cytosol. In contrast, binding was not affected by mitotic pretreatment of p115.

Exercise training in patients with heart failure. A randomized, controlled trial.

Objective: To assess the benefit of exercise training in patients with heart failure caused by left ventricular systolic dysfunction and to further describe the physiologic changes associated with exercise training in these patients.

Design: Randomized, controlled trial.

Setting: Urban outpatient clinic.