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Biomedical subjects

John M Morgan

Publications and source records attributed to John M Morgan.

29 records · Page 2Linked to original sources
PubMed2003

Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels.

Patients with combined hyperlipidemia and low high-density lipoprotein (HDL) cholesterol levels may benefit from combination therapy with a statin and niacin; therefore, we assessed the efficacy and safety of rosuvastatin and extended-release (ER) niacin alone and in combination in 270 patients with this atherogenic dyslipidemia. Men and women > or =18 years with fasting total cholesterol levels > or =200 mg/dl, triglycerides 200 to 800 mg/dl, apolipoprotein B > or cf=110 mg/dl, and HDL cholesterol <45 mg/dl were randomized to 1 of 4 treatments in this 24-week, open-label, multicenter trial: rosuvastatin 10 to 40 mg; ER niacin 0.5 to 2 g; rosuvastatin 40 mg/ER niacin 0.5 to 1 g; or rosuvastatin 10 mg/ER niacin 0.5 to 2 g. Percent changes from baseline in low-density lipoprotein (LDL) cholesterol, non-HDL cholesterol, and other lipid measurements at week 24 were determined by analysis of variance, with statistical testing performed separately between the rosuvastatin monotherapy group and each remaining treatment group. Daily doses of rosuvastatin 40 mg reduced LDL and non-HDL cholesterol significantly more than either ER niacin 2 g or rosuvastatin 10 mg/ER niacin 2 g (-48% vs -0.1% and -36% for LDL cholesterol and -49% vs -11% and -38% for non-HDL cholesterol, respectively; p <0.01 for all comparisons); no additional reduction in LDL or non-HDL cholesterol was observed with the combination of rosuvastatin 40 mg/ER niacin 1.0 g (-42% and -47%; p = NS). Triglyceride reductions ranged from -21% (ER niacin monotherapy) to -39% (rosuvastatin 40 mg/ER niacin 1 g), but no observed differences were statistically significant. Compared with rosuvastatin alone, rosuvastatin 10 mg/ER niacin 2 g produced significantly greater increases in HDL cholesterol (11% vs 24%, p <0.001) and apolipoprotein A-I (5% vs 11%, p <0.017). Similar increases in HDL cholesterol and apolipoprotein A-I were noted between the monotherapy groups. Over 24 weeks, rosuvastatin alone was better tolerated than either ER niacin alone or the combinations of rosuvastatin and ER niacin.

Adolescent↗
PubMed2003

New device indications: practice and cost implications in Europe.

The potential clinical value of implantable devices, for both diagnostic and therapeutic uses in cardiology practice, has increased greatly with technical innovation. This coupled with an increased recipient population size (as the population ages) and increased referral rates (as that population and its healthcarers are educated), has increased the demand for such devices and the associated economic burden is impacting on healthcare resources. Although there is a commonality of approach to clinical practice in Europe, aided by the publication of European guidelines, the implementation of these is hindered by the need to overcome national obstacles, particularly for new indications for established therapies and for innovative therapies. Cost efficacy assessments and evidence-based medicine are blurred and used as rationing tools. National inequalities and disparate healthcare systems will become divisive in a European theatre that is otherwise seeing greater political and economic integration. There needs to be a mature and honest debate on how to bring the benefits of implantable device medical technology to the patient population which will benefit.

Arrhythmias, Cardiac↗
PubMed2003

High density endocardial mapping of shifts in the site of earliest depolarization during sinus rhythm and sinus tachycardia.

Previous mapping studies of sinus rhythm suggest faster rates arise from more cranial sites within the lateral right atrium. In the intact, beating heart, mapping has been limited to epicardial plaques or single endocardial catheters. The present study was designed to examine shifts in the site of the earliest endocardial depolarization during sinus rhythm and sinus tachycardia using high density activation mapping. Noncontact mapping of the right atrium during sinus rhythm was performed on ten anesthetized swine. Recordings were made during sinus rhythm, phenylephrine infusion, and isoproterenol infusion. The hearts were then excised and the histological sinus node identified. The mean minimum and maximum cycle lengths recorded were 355 +/- 43 and 717 +/- 108 ms. A median of three (range two to five) sites of earliest endocardial depolarization were documented in each animal. With increasing heart rate the site of earliest endocardial depolarization remained stationary until a sudden shift in a cranial or caudal direction, often to sites beyond the histological sinoatrial node. The endocardial shift was unpredictable with considerable variation between animals; however, faster rates arose from more cranial sites (r = 0.46, P = 0.023). There was no difference in the mean cycle length of sinus rhythm originating from specific positions on the terminal crest (r = 0.44, P = 0.17). Cranial sites displayed a more diffuse pattern of early depolarization than caudal sites. In the porcine heart the relationship between heart rate and site of earliest endocardial depolarization shows considerable variation between individual animals. These findings may have implications for clinical mapping and ablation procedures.

Animals↗
PubMed2003

"Double" potentials define linear lesion conduction block using a novel mapping/linear lesion ablation catheter.

INTRODUCTION: A novel mapping/ablation catheter using a coaxially ablation electrode (E) that is moveable between distal and proximal ring electrodes along its shaft was used to create a linear lesion over the cavotricuspid isthmus (CTI) and bidirectional block in 32 patients (21 men; age 38-79 years) undergoing ablation for counterclockwise atrial flutter. METHODS AND RESULTS: Two bipolar electrograms (E1 and E2) were recorded: between E and the distal ring electrode and between E and the proximal ring electrode. Interpole distance varied for both as the E traversed the slide shaft. Given the catheter's concept, these bipoles are orientated exactly along the line of lesion creation. Prior to ablation, unitary bipolar electrograms were recorded along the catheter slide shaft position. As the CTI lesion was created (E moved along the catheter slide shaft in 2-mm steps with radiofrequency energy delivered to achieve 65 degrees C for 60 sec at each), double potentials (DP) were observed. Interpotential distance became maximal with completion of the linear lesion and bidirectional block. DPs were noted in all these procedures. With pacing from the low septal right atrium at bidirectional block creation, interpotential timing was 140.9 +/- 15 msec and from the low right atrial free wall was 145.13 +/- 18 msec. In sinus rhythm, DP interpotential timing was less (35.13 +/- 9 msec) as activation fronts arrived from both septal and anterior atrial aspects. CONCLUSION: Bipolar recordings from the coaxially moveable electrode catheter provide unique electrogram data. DPs recorded during and after linear lesion creation can define conduction block across that lesion without the need for additional mapping catheters or complex mapping technology.

Adult↗
PubMed2003

Hypercholesterolemia. The NCEP Adult Treatment Panel III Guidelines.

Coronary heart disease (CHD) is a significant cause of morbidity and mortality in older patients. Therefore, its treatment and prevention is vital to improving the length and quality of life for the geriatric population at large. Clinical trial data have demonstrated that patients age 65 and older derive the same benefit from blood cholesterol reduction as younger adults. As a result, the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) recommends appropriate therapeutic lifestyle changes and drug therapy for older individuals with established CHD or for those at high risk for CHD. Drug therapy in this population, while safe, requires careful monitoring and dose adjustment due to potentially altered drug metabolism and concomitant medications. These factors lead to use of lower starting doses of lipid-lowering medications in older patients. Prudent individualized evaluation and customized therapy provide optimal cardiovascular outcomes.

Drug Therapy, Combination↗
PubMed2002

Effects of walnut consumption as part of a low-fat, low-cholesterol diet on serum cardiovascular risk factors.

Serum components, such as lipoproteins, coagulation factors (factor VII, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), fibrinogen), and homocysteine have been associated with cardiovascular disease. Dietary intervention with a low-fat, low-cholesterol diet has favorably influenced cardiovascular disease and certain food, specifically the consumption of nuts, has been associated with reduced cardiovascular risks. The effects of walnuts, as part of a low-fat, low-cholesterol diet, on serum cardiovascular risk factors were determined. Sixty-seven (67) outpatients with borderline high total cholesterol following a low-fat, low-cholesterol diet for six weeks before being randomly assigned to continue the diet or have 64 grams/day of walnuts in conjunction with the diet. After six weeks, the patients' diets were switched. Therefore, all patients consumed 64 grams/day of walnuts for six weeks during part of the trial as part of a low-fat, low cholesterol diet. Serum lipids demonstrated a significant reduction in triacyglycerols and favorable trend with decreases in total cholesterol, low-density lipoprotein (LDL) cholesterol, and a slight increase in high-density lipoprotein (HDL) cholesterol. No statistical effects on homocysteine or the coagulation factors were observed. However, there was a slight favorable trend for tPA and PAI-1. This study demonstrated that walnuts, when consumed as part of a low fat, low-cholesterol diet, have a beneficial effect on serum cardiovascular risk factors. However, these changes may not explain all of the beneficial effects that walnut consumption has on cardiovascular disease.

Analysis of Variance↗
PubMed2002

Characteristics of right atrial activation during coronary sinus pacing.

INTRODUCTION: Anatomic and electrical connections between the left atrium and right atrium (RA) have been described. The relationship between coronary sinus (CS) pacing site and RA activation has not been examined. METHODS AND RESULTS: Fifteen anesthetized swine underwent high-density noncontact mapping of the RA during pacing from up to five different sites within the CS. Isopotential mapping identified the site of earliest RA depolarization and the pattern of subsequent activation. Hearts were excised and endocardial dissection performed. Earliest RA activation occurred at the CS os with proximal CS pacing sites and at Bachmann's bundle at distal pacing sites. The mean depth at which a shift in earliest RA activation site occurred was 46 +/- 13 mm (range 21 to 63 mm). RA activation times following earliest activation at the CS and Bachmann's bundle were 40 +/- 4 msec and 51 +/- 6 msec (P < 0.002). Conduction delay or block was recorded at the lateral cavotricuspid isthmus, terminal crest, and tendon of Todaro. Latest RA activation always occurred in the high anterolateral atrium after ascending the anterolateral wall. The lateral RA was activated by the wavefront that traversed the posterior wall rather than by the wavefront crossing the cavotricuspid isthmus, even with earliest RA activation at the CS os. CONCLUSION: The site of earliest RA activation during CS pacing is dependent upon the pacing depth within the CS. In the porcine heart, areas of conduction delay influence RA activation patterns and timings. These findings may have implications for patients undergoing assessment of radiofrequency ablation of atrial flutter.

Animals↗
PubMed2002

Three-dimensional mapping of right atrial activation during sinus rhythm and its relationship to endocardial architecture.

INTRODUCTION: Previous mapping studies of right atrial (RA) activation during sinus rhythm have been limited by the use of epicardial electrode plaques in open chest subjects or microelectrodes in the excised heart. This study describes global RA endocardial activation patterns using high-density mapping and compares the results with underlying endocardial architecture. METHODS AND RESULTS: Noncontact mapping of the RA was performed in 21 anesthetized swine. Isopotential and isochronal maps were superimposed upon three-dimensional reconstructions of RA geometry. Hearts were excised and endocardial dissection performed. Two patterns of RA activation were recorded. The site of earliest endocardial activation occurred either laterally at a position consistent with the terminal crest or superiorly at the junction between the superior caval vein and RA appendage. The subsequent spread of depolarization followed the longitudinal orientation of muscle fibers. Areas of conduction delay and block were seen at the junction between the terminal crest and posterior wall, the cavotricuspid isthmus, and around the margins of the triangle of Koch. Endocardial dissection at these sites demonstrated complex fiber orientation. A lateral site of earliest activation demonstrated a more prominent display of conduction delay or block. CONCLUSION: The spread of the sinus impulse follows endocardial myofiber orientation and is dictated by the site of earliest activation. Even during sinus rhythm, anisotropic conduction results in areas of conduction block or delay. These findings have implications in the development of reentrant arrhythmias and may influence surgical or electrophysiologic procedures.

Animals↗
PubMed2002

Cost-effectiveness of implantable cardioverter defibrillator therapy.

Cost-efficacy assessment of implantable cardioverter defibrillator (ICD) therapy has proved contentious and may have limited uptake of ICD therapy, particularly in Europe. Published modeling assessments are too inaccurate to determine clinical practice, and assessments based on clinical studies are incomplete (from the cost-efficacy viewpoint). Although ICD therapy seems certain to be most cost-effective in patients who are likely to have good longevity if their risk of sudden cardiac death is countered, the benefit of ICD therapy is not necessarily limited to such groups. Physicians and health economists need to develop a better understanding of how to assess high-technology therapy costs so that uptake of such therapy is appropriately expedited with due regard to ethical and cost constraints.

Cost-Benefit Analysis↗
PubMed2002

A formalin-fixed, paraffin-processed cell line standard for quality control of immunohistochemical assay of HER-2/neu expression in breast cancer.

To ensure the accuracy and reproducibility of immunohistochemical assays for determining HER-2/neu status of patients with breast cancer, a reliable standard for monitoring assay sensitivity is necessary. We optimally fixed and paraffin processed human ovarian and breast carcinoma cell lines SKOV-3, MDA-MB-453, BT-20, and MCF-7 in quantities sufficient to meet the needs of a laboratory for the foreseeable future. The material was tested, alongside HercepTest kit cell lines (DAKO, Carpinteria, CA), by 7 breast cancer centers in the United Kingdom and France with different immunohistochemical assays and markers. The cell lines also were analyzed by fluorescence in situ hybridization (FISH) by 2 centers using HER-2/neu kits. FISH produced 100% agreement between the 2 centers: SKOV-3 and MDA-MB-453 showed HER-2/neu amplification and BT-20 and MCF-7 did not. Immunohistochemical analysis and a common evaluation method produced 100% agreement that SKOV-3 and MCF-7 showed 3+ and zero HER-2/neu overexpression, respectively. For MDA-MB-453, there was 71% (5/7) concordance of 2+ immunohistochemical staining and 86% (6/7) concordance of zero or 1 + staining for BT-20. The cell lines provide a valuable standard for gauging HER-2/neu assay sensitivity irrespective of the antibody, antigen retrieval system, detection system, or method of evaluation used.

Breast Neoplasms↗