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Biomedical subjects

J M Morgan

Publications and source records attributed to J M Morgan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Single capacitive discharge utilizing an auxiliary shock in the coronary venous system reduces the defibrillation threshold.

UNLABELLED: Auxiliary shocks (AS) from electrodes sutured to the left ventricle (LV) prior to primary biphasic shocks (PS) have been shown to reduce defibrillation thresholds (DFT). Two capacitors are required to generate these waveforms. We investigate delivery of AS from one capacitor using a novel waveform. The epicardial surface of the LV is accessed transvenously via the middle cardiac vein (MCV) avoiding a thoracotomy. METHODS: A defibrillation electrode was placed in the right ventricle (RV) and superior vena cava (SVC) in 12 pigs (37+/-2 kg). A 50x1.8 mm electrode was inserted in the MCV through a guide catheter. A can was placed in the left pectoral region. A monophasic AS (100 microF, 1.5 J) was delivered along one pathway before switching to deliver a biphasic waveform (40% tilt, 2 ms phase 2) along another. DFTs (PS+AS) were assessed using a binary search. Two configurations not incorporating AS acted as controls. DFTs were compared using repeated measures analysis of variance. RESULTS: DFTs of the four novel configurations (AS/PS) were: RV-->Can/MCV-->Can=14.9+/-3.7 J, MCV-->Can/RV-->Can=17.2+/-5.7 J, RV-->SVC+Can/MCV-->SVC+Can=13.4+/-4.6 J, MCV-->SVC+Can/RV-->SVC+Can=17.1+/-5.9 J. Delivering AS in the RV followed by PS in the MCV reduced the DFT (RV-->Can (19.9+/-7.3 J, P<0.01) and RV-->SVC+Can (19.2+/-6.0 J, P<0.05)). CONCLUSIONS: Delivering AS prior to PS in the MCV reduces the DFT by up to a third compared to conventional configurations of RV-->Can and RV-->SVC+Can. This is possible using only a single capacitor and an entirely transvenous approach to the LV.

Animals↗
PubMed2001

Inappropriate shock therapy in a heart failure defibrillator.

A 63-year-old male with dilated cardiomyopathy underwent implantation of a "heart failure" defibrillator capable of biventricular pacing. He received an inappropriate shock 5 hours after the procedure. Stored electrograms revealed that during each sinus beat the ventricular channel recorded up to three separate events. These resulted from far-field atrial sensing by the coronary venous lead, appropriate right ventricular sensing, then delayed left ventricular sensing (the result of left bundle branch block). As a consequence of far-field left atrial sensing the two subsequent ventricular electrograms fell within the VF zone. Following an atrial premature beat, VF detection criteria were satisfied and shock therapy delivered. Although coronary venous lead repositioning eliminated far-field atrial sensing, double counting of the widely split right and left ventricular electrograms still occurred during sinus rhythm. Shortening the programmed AV delay resulted in constant biventricular pacing with a single electrogram.

Algorithms↗
PubMed2001

Feasibility of a left atrial electrical disconnection procedure for atrial fibrillation using transcatheter radiofrequency ablation.

INTRODUCTION: An effective, catheter-based treatment for persistent atrial fibrillation (AF) remains elusive. This study assessed the feasibility of transcatheter left atrial (LA) electrical disconnection and its effect on AF inducibility. METHOD AND RESULTS: Thirteen anesthetized swine underwent noncontact mapping of the right atrium (RA) during coronary sinus (CS) pacing. Sites of earliest RA activation were identified using isopotential maps. An ablation catheter was navigated to these sites and a cluster of radiofrequency (RF) lesions applied until earliest activation shifted to a new site. The procedure was repeated until the atria were electrically disconnected. AF induction was attempted before and after ablation. Earliest RA activation was the CS os during proximal CS pacing and Bachmann's bundle during distal CS pacing. These two sites were successfully ablated in all 13 animals. Earliest activation then shifted to the fossa ovalis. RF energy was applied at a median of 2.5 sites (range 1 to 5) around the fossa, then at sites in the triangle of Koch, septum, cavotricuspid isthmus, and posterior wall. Atrial electrical disconnection was achieved in 10 of 13 animals (5 LA electrical disconnection, 3 RA electrical disconnection, 2 biatrial electrical disconnection with complete heart block). After atrial electrical disconnection, the LA became electrically silent. Before ablation, AF was inducible in every animal. After atrial electrical disconnection, AF was inducible in 3 of 10 animals. CONCLUSION: Atrial electrical disconnection is feasible using noncontact mapping and RF ablation. Successful electrical disconnection of the atria reduces AF inducibility. This approach is worthy of further evaluation as a management strategy for persistent AF, combined with device therapies.

Animals↗
PubMed2001

Megacystis-microcolon-intestinal hypoperistalsis syndrome and the absence of the alpha3 nicotinic acetylcholine receptor subunit.

BACKGROUND & AIMS: The megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare disease of childhood that presents early with intestinal hypoperistalsis, hydronephrosis, and hydroureters. Transgenic mice that lack the alpha3 subunit containing nicotinic acetylcholine (nAChR) have a phenotype similar to that of MMIHS. METHODS: We examined the expression of this subunit in control and MMIHS tissue derived from patients using in situ hybridization (ISH) and immunocytochemistry (ICC). RESULTS: In controls, both techniques showed a wide distribution of alpha3 nAChRs present in ganglion cells, muscle, and epithelium. By contrast, most MMIHS tissue gave negative staining with ISH and variable results with ICC. CONCLUSIONS: These observations are consistent with a lack of alpha3 nAChRs contributing to the pathogenesis of MMIHS.

Abnormalities, Multiple↗
PubMed2001

Thyroid transcription factor-2 gene expression in benign and malignant thyroid lesions.

Thyroid transcription factor-2 (TTF-2) is a recently cloned thyroid-specific gene and is central to the development and differentiation of the thyroid follicular cell. Information regarding transcript levels in normal and diseased adult human thyroids is lacking. We have investigated TTF-2 gene expression in various thyroid pathologies and assessed its potential in preoperative diagnosis of thyroid nodular disease, which is a common clinical problem. We have used reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) and detected TTF-2 transcripts in 60% of 125 samples of adult human thyroids tested by RT-PCR (64% of 35) or ISH (59% of 90). In normal thyroid tissues TTF-2 transcript levels are low, 18 of 36 were weakly positive and 18 of 36 negative when tested by ISH. In the benign lesions, TTF-2 transcripts were detected either by RT-PCR or ISH in 8 of 8 Graves disease; 3 of 7 Hashimoto's; 2 of 2 follicular hyperplasia; 15 of 21 follicular adenoma; 11 of 13 multinodular goiters and 0 of 1 hyalinizing trabecular adenoma. In the malignant thyroid lesions, TTF-2 transcripts were detected in 8 of 18 follicular cancers; 0 of 2 anaplastic carcinoma, and 11 of 17 papillary cancers. Compared with normal thyroids, transcripts were more abundant in 24% of thyroid lesions tested by ISH. In conclusion, we report for the first time on TTF-2 gene expression in normal and diseased adult human thyroids.

Adult↗
PubMed2001

Safety profile of thalidomide after 53 weeks of oral administration in beagle dogs.

Fifty-six adult beagle dogs (28 male, 28 female) were orally administered thalidomide at 43, 200, or 1000 mg/kg/day for 53 weeks. Sixteen (2/sex/dose group) and 32 (4/sex/dose group) dogs were euthanized and necropsied after 26 and 53 weeks of dosing, respectively. The remaining 8 animals (2/sex/group; high-dose and control groups) were dosed for 53 weeks, euthanized, and necropsied at 58 weeks after a 5-week recovery period. There were no deaths during the study. The only observed clinical signs attributable to thalidomide administration were green-colored urine, white-colored fecal residue presumed to be unchanged thalidomide, enlarged and/or blue coloration of female mammary tissue, and prolonged estrus. There were no thalidomide-related changes in body weights, food consumption, electrocardiography, ophthalmoscopy, neurological function, and endocrine function. The mostly slight and/or transient variations observed in some hematology and blood chemistry values of dosed dogs were considered to be toxicologically insignificant and were supported by the lack of histopathologic correlates. The only gross finding attributable to thalidomide was a yellow-green discoloration of the femur, rib, and/or calvarium that was observed at each euthanization interval including recovery. There was no microscopic correlate for this finding. No thalidomide-related microscopic changes were seen in any of the organs and tissues at 26 weeks. Mammary duct dilatation and/or glandular hyperplasia observed in females at 53 and 58 weeks and hepatic bile pigment exhibited by high-dose males at 53 weeks were microscopic changes considered to be thalidomide-related. There was no gross and histopathologic evidence of any tumors. In summary, thalidomide at up to 1000 mg/kg/day for 53 weeks did not induce any major systemic toxicity or tumors in dogs. The NOAEL was 200 mg/kg/day.

Animals↗
PubMed2001

Comparison of core oestrogen receptor (ER) assay with excised tumour: intratumoral distribution of ER in breast carcinoma.

AIMS: The use of the H score (involving the assessment of intensity and distribution of positivity) on sections stained for the oestrogen receptor (ER) by immunocytochemistry (ICC) allows different samples to be compared and detailed correlations to be made between hormone receptor expression and morphology. This study assessed the reliability of core biopsy in predicting ER expression in the same tumour excised later at treatment. The distribution of ER within excised tumours was investigated. METHODS: The distribution of ER positivity was investigated in 51 diagnostic core biopsies and across the diameter of 51 subsequently excised tumours in a field by field (magnification, x40; field diameter, 0.4 mm) assessment using the semiquantitive H scoring system. RESULTS: The ER H score in diagnostic core biopsy was significantly higher (p = 0.05, paired rank test; overall mean, 130; n = 51) than the mean in the corresponding excised tumour (mean, 110; n = 51). There was a significant downward trend in ER positivity from the periphery of tumours towards the centre (p = 0.001). The reduction of ER positivity was 6 H score units (2%)/mm. If core biopsies were orientated with the tumour edge at one end no change in ER positivity with field number along the length of the core could be demonstrated. CONCLUSIONS: ER estimation in core biopsies correlated well with expression in tumours but ER expression was higher in the core biopsies than in the excised tumours. ER expression was higher at the periphery of tumours than at the centre. The higher ER expression in cores may reflect the higher chance of sampling the peripheral part of a tumour using a needle core.

Biopsy, Needle↗
PubMed2001

Pericardial mesothelioma following mantle field radiotherapy.

A 49-year-old female was referred with recurrent pericardial effusion following mantle field radiotherapy for Hodgkin s lymphoma. She underwent video-assisted thoracoscopy and resection of a pericardial window. Intraoperatively she suffered a cardiac arrest and subsequently died in the early postoperative period despite maximal therapy. Pathological examination revealed extensive myocardial fibrosis and multiple nodules of pericardial mesothelioma. The latter has hitherto not been recognised following mediastinal radiation. The cardiac complications of mantle field radiotherapy are discussed.

Fatal Outcome↗
PubMed2000

Electrophysiological mapping and ablation of intra-atrial reentry tachycardia after Fontan surgery with the use of a noncontact mapping system.

BACKGROUND: Atrial tachyarrhythmias are a complication of Fontan surgery. Conventional electrophysiological mapping and ablation techniques are limited by the complex anatomic and surgical substrate and a high arrhythmia recurrence rate. This study investigates the use of noncontact mapping to identify arrhythmia circuits and guide ablation in Fontan patients. METHODS AND RESULTS: Eleven arrhythmias were recorded in 6 patients. Noncontact mapping improved recognition of the anatomic and surgical substrate and identified exit sites from zones of slow conduction in all clinical arrhythmias. Radiofrequency linear lesions were targeted across these critical zones in 5 patients. One patient underwent surgical cryotherapy. Although immediate success was achieved in 3 of 5 patients with radiofrequency ablation, 2 patients had a recurrence after a mean of 6.4 months of follow-up. The patient who underwent cryoablation remains free of arrhythmias. CONCLUSIONS: Noncontact mapping can identify arrhythmia circuits in the Fontan atrium and guide placement of ablation lesions. Arrhythmia recurrence is high, possibly because of inadequate lesion creation rather than inaccurate mapping and lesion targeting.

Adolescent↗
PubMed2000

Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy.

This study compares the effect of plant stanol ester spread with a placebo spread on cholesterol in patients taking statin therapy, but who still had elevated low-density lipoprotein (LDL) cholesterol. This was a randomized, double-blind, placebo-controlled clinical trial, with 67 women and 100 men with LDL cholesterol >/=130 mg/dl and triglycerides </=350 mg/dl who had been taking a stable dose of a statin drug for at least 90 days before the start of the study. For 8 weeks, participants consumed 3 servings/day of the plant stanol ester spread that provided 5.1 g/day of plant stanol ester or a placebo. The addition of plant stanol ester spread significantly reduced total cholesterol and LDL cholesterol at 2, 4, and 8 weeks when compared with placebo spread. Plant stanol ester spread reduced total cholesterol at 8 weeks by 12% compared with a placebo reduction of 5% (-7% difference; p <0.0001). Plant stanol ester spread reduced LDL cholesterol at 8 weeks by 17% compared with a 7% reduction in the placebo group (-10% difference, p <0.0001). The absolute reduction in LDL cholesterol at 8 weeks was 24 and 10 mg/dl in the stanol ester and placebo groups, respectively. The plant stanol ester spread group also had greater reductions in both serum total cholesterol and LDL cholesterol than the placebo group at 2 and 4 weeks (p <0.001 for all comparisons). Both spreads were well tolerated by study participants, and no significant adverse events were noted. Consumption of spread that provided 5.1 g/day of plant stanol esters effectively reduced elevated total and LDL cholesterol levels in participants on a stable regimen of a statin.

Administration, Oral↗
PubMed2000

Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia.

This multicenter trial evaluated the safety and efficacy of escalating doses of Niaspan (niacin extended-release tablets) and placebo (administered once-a-day at bedtime) in patients with primary hyperlipidemia on the percent change from baseline in levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. Extended-release niacin was initiated at a dose of 375 mg/day, raised to 500 mg/day, and further increased in 500-mg increments at 4-week intervals to a maximum of 3,000 mg/day. A total of 131 patients (n = 87, extended-release niacin; n = 44, placebo) were treated for 25 weeks with study medication after a 6-week diet lead-in/drug washout phase and 2-week baseline LDL cholesterol stability phase. Significant decreases from baseline in levels of LDL cholesterol and apolipoprotein B became apparent with the 500-mg/day dose and were consistent at all subsequent doses (p < or =0. 05), reaching 21% and 20%, respectively, at the 3,000-mg/day dose. Significant increases from baseline in levels of high-density lipoprotein cholesterol became apparent with the 500-mg/day dose and were consistent at all subsequent doses (p < or = 0.05), reaching 30% at the 3,000-mg dose. Significant decreases from baseline in triglycerides and lipoprotein(a) occurred at the 1,000-mg dose and were apparent at all subsequent doses (p < or =0.05), reaching 44% and 26%, respectively, at the 3,000-mg dose. The most common adverse events were flushing and gastrointestinal disturbance. Transaminase increases were relatively small, and the proportion of patients who developed liver function abnormalities on extended-release niacin was not significantly different from placebo. Thus, extended-release niacin was generally well tolerated and demonstrated a dose-related ability to alter favorably most elements of the lipid profile.

Adult↗
PubMed2000

Niacin dosing: relationship to benefits and adverse effects.

Because of the original observation by Altschul et al., that nicotinic acid (niacin), not nicotinamide, in pharmacologic doses lowered human serum cholesterol levels, an avalanche of reports have been published over the past 45 years on the plasma lipid-regulating properties of this drug and its beneficial cardiovascular effects. A myriad of studies that have examined efficacy, safety, adverse effects, and pharmacologic properties of niacin rendered convincing evidence that niacin, used alone or combined with other agents, has favorable effects on serum lipoprotein regulation and on containment of atherothrombotic cardiovascular diseases. However, because of the unusual side effect profile of niacin and the availability of various formulations of this drug, niacin must be used prudently and with careful instruction and monitoring of patients. This review summarizes the pertinent and recent literature on niacin that impacts its therapeutic use. We also discuss some controversial issues and personal clinical experience and opinions on this topic.

Anticholesteremic Agents↗
PubMed2000

Increased defibrillation threshold with right-sided active pectoral can.

UNLABELLED: The aim of this study was to identify the optimal position on the chest wall to place an implant able cardioverter defibrillator in a two-electrode system, consisting of a right ventricular electrode and active can. METHODS AND RESULTS: Defibrillation thresholds (DFT) were measured in 10 anaesthetised pigs (weight 33-45 kg). An Angeflextrade mark lead was introduced transvenously to the right ventricular apex. The test-can (43 cc) was implanted submuscularly in each of four locations: left pectoral (LP), right pectoral (RP), left lateral (LL) and apex (A). The sequence in which the four locations were tested was randomized. Ventricular fibrillation (VF) was induced using 60 Hz alternating current. Rectangular biphasic shocks were delivered 10 seconds after VF induction. The DFT was measured using a modified four-reversal binary search. The results of the four configurations were: LP, 14.6+/- 4.0 J; RP, 18.8+/- 4.2 J; LL, 14.7+/- 4.1 J; A, 14.9+/- 3.1 J. Repeated measures analysis of variance showed that the DFT of RP was significantly higher than LP, LL and A (p < 0.05). CONCLUSIONS: Implanting an active can in the RP position increases the DFT by 29% compared to LP, LL and A sites. The can position on the left thorax does not appear to have a significant influence on DFT.

Animals↗
PubMed2000

Reduction in defibrillation threshold using an auxiliary shock delivered in the middle cardiac vein.

Defibrillation in the middle cardiac vein (MCV) has been shown to reduce ventricular defibrillation thresholds (DFTs). Low amplitude auxiliary shock (AS) from an electrode sutured to the left ventricle at thoracotomy have also been shown to reduce DFT if delivered immediately prior to a biphasic shock (between the ventricular RV and superior vena caval (SVC) electrodes). This study investigates the impact on DFT of an AS shock from a transvenously placed MCV lead system. A standard defibrillation electrode was positioned in the RV in eight anesthetized pigs (35-43 kg). A 50 x 1.8-mm electrode was inserted in the MCV through an 8 Fr angioplasty guide catheter. A 150-V (leading edge) monophasic AS was delivered (95 microF capacitor) from the MCV-->Can with three different pulse widths (3, 5, 7 ms). A primary biphasic shock (PS) (95 microF capacitor, phase 1: 44% tilt, 1.6-ms extension and phase 2: 2.5-ms fixed duration) was delivered from the RV-->Can +/- AS. The four configurations were randomized and DFTs (PS + AS) assessed using a modified binary search. Ventricular fibrillation (VF) was induced with 60 Hz AC followed 10 seconds later by the test shock. The DFTs were compared using repeated measures analysis of variance (ANOVA). All configurations incorporating AS produced significant (P < 0.05) reduction in the DFT compared to no AS (13.8 +/- 7.4 J). There was no difference in the efficacy of differing pulse widths (P > 0.05); 3 ms (11.0 +/- 5.4 J), 5 ms (11.5 +/- 6.0), and 7 ms (10.6 +/- 5.3 J). In conclusion, delivering an AS from a transvenous lead system deployed in the MCV reduces the DFT by 23% compared to a conventional RV-->Can shock alone.

Analysis of Variance↗
PubMed2000

Radiofrequency ablation of idiopathic left ventricular tachycardia at the site of earliest activation as determined by noncontact mapping.

INTRODUCTION: The most effective method for guiding radiofrequency (RF) ablation of idiopathic left ventricular tachycardia (ILVT) has yet to be determined. We investigated the use of noncontact mapping in five patients with this condition. METHODS AND RESULTS: The multielectrode array was positioned in the left ventricular apex via the retrograde approach. Isopotential color maps of ILVT were examined to determine the site of earliest endocardial activation. The ablation catheter was steered to the target site using the locator signal. Pace mapping was performed and contact electrograms examined for diastolic potentials. RF energy was applied to the target site. Sustained ventricular tachycardia was induced in 2 patients and nonsustained ventricular tachycardia in 3. The site of earliest activation was at the apical septum in 3, the inferior apex in 1, and the base of the inferior wall in 1. Mean timing was 21 +/- 10 msec before onset of the surface QRS. Diastolic activity was visualized with noncontact mapping at the base of the septum in 1 patient. A Purkinje potential was seen at the ablation site in only 1 patient. No diastolic activity was seen in the remaining 3 patients. Tachycardia was successfully terminated in all 5 patients with a median of four RF applications. No patient suffered a recurrence after 9.6 +/- 4.7 months of follow-up. CONCLUSION: By identifying the precise site of earliest activation during ILVT, noncontact mapping has been shown to be an effective and safe method for guiding RF ablation.

Adult↗