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Biomedical subjects

J M Morgan

Publications and source records attributed to J M Morgan.

At least 19 recordsLinked to original sources
PubMed2004

Evaluation of body weight as a predictive factor for transvenous ventricular defibrillation characteristics.

AIMS: To investigate the correlation between body weight and defibrillation threshold (DFT) for transvenous lead systems using a porcine model. METHODS AND RESULTS: Twenty-eight pigs were anaesthetised and DFTs assessed in single and dual coil configurations using a four-reversal binary search method. DFT was correlated with body weight in the RV --> Can and RV --> SVC + Can configurations. A Pearson correlation coefficient and a two-sided p-value were calculated. A positive correlation exists between body weight and DFT in RV --> Can (r=0.66, p<0.000) and RV --> SVC + Can (r=0.44, p=0.018). CONCLUSION: There is a significant correlation between body weight and DFT in swine. This tends to be greater in the two-electrode than in the three-electrode configuration. With these and previous human observations, one may predict a higher DFT in heavy individuals and make appropriate procedural adjustments.

Animals↗
PubMed2003

Comparison of coronary venous defibrillation with conventional transvenous internal defibrillation in man.

OBJECTIVE: Animal studies have shown that defibrillation in coronary veins is more effective than in the right ventricle. We aimed to assess the feasibility of placing defibrillation electrodes in the middle cardiac vein (MCV) in man and its impact on defibrillation requirements. METHODS: A prospective randomised study conducted in a tertiary referral centre. 10 patients (9 male) undergoing ICD implantation (65 (12) yrs) for NASPE/BPEG indications were studied. Defibrillation thresholds (DFT) were measured, using a binary search and an external defibrillator after 10 seconds of ventricular fibrillation, for the following configurations in each patient (order of testing randomised): RV + MCV --> Can and RV --> SVC + Can. INTERVENTIONS: A dual coil defibrillation electrode was placed transvenously in the right ventricle (RV) in the conventional manner. Using a guiding catheter a 3.2 Fr (67.5 mm length) electrode was placed transvenously in MCV. A test-can was placed subcutaneously in the left pectoral region. RESULTS: Lead placement was possible in 8/10 pts. Time to perform a middle cardiac venogram and place the electrode was 21 (23) mins. No adverse events were observed. Defibrillation current was less (6.7 (2.7) A) with RV + MCV --> Can compared to the conventional RV --> SVC + Can configuration (8.9 (3.4) A, p = 0.03). There was no significant difference in defibrillation voltage or energy. However, shock impedance was higher in the former configuration (57 (10) v. 43 (6) Omega, p = 0.001). CONCLUSIONS: In the majority of cases placement of a defibrillation lead in MCV is feasible. Defibrillation current requirements are 25% less when the shock is delivered using a MCV electrode.

Aged↗
PubMed2003

Radial intratumoral increase and correlation of microvessels and proliferation in solid breast carcinoma.

AIMS: To compare correlations between different morphometrically assessed measurements of tumour microvasculature and to identify those which show closest correlation with Ki67 and to examine radial intratumoral distribution of microvessels and proliferation. METHODS AND RESULTS: Immunohistochemically defined microvessels and Ki67+ cells were quantified in sequential fields of 0.12 mm2 (x600) in four transects in each of five tumours. The total number of vessels (TNV) correlated more closely with proliferative activity than the numbers of vessels with a discernible lumen (TLV) and TNV decreased towards the centre of the tumour whereas TLV did not. A higher proliferative index (PI) was found at the periphery of the tumours. Comparison between transects through subjectively identified microvessel hot-spots and non-hot-spot transects showed similar mean, median and peak vessel counts but showed a different distribution on chi2 analysis. CONCLUSIONS: TNV correlates most closely with PI in breast carcinomas. There is marked variation in microvessel density and PI between fields of 0.12 mm2 but there is a significant radial reduction in both from the edge towards the centre of tumours.

Antigens, CD34↗
PubMed2003

Effect of smoking and transdermal nicotine on colonic nicotinic acetylcholine receptors in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a disease largely of non-smokers, in which nicotine is of therapeutic value. The mode of action is unknown, but may involve nicotinic acetylcholine receptors (nAChRs) in the bowel wall. AIM: To investigate the presence of nAChRs in rectal mucosa, and the effect of smoking and nicotine on their expression. DESIGN: Prospective case-control study. METHODS: In situ hybridization (ISH) and immunocytochemistry (ICC) were used to show alpha3 nAChRs in colonic mucosa. Rectal mucosa was examined from controls (n=55) and patients with inactive UC (n=62), both smokers and non-smokers, by ICC, using two antibodies to show the density and distribution of receptors in the mucosa. Non-smokers with UC (n=43) were given transdermal nicotine or placebo patches for 6 months, and rectal biopsies, taken before and after treatment, were examined by ICC to show nAChRs. RESULTS: In normal colon, ISH and ICC showed alpha3 subunit in a wide variety of cells, including mucosal epithelium. In rectal biopsies, neither smoking nor nicotine influenced the expression of alpha3 immunoreactivity in epithelium, either in controls or UC. However, controls had a significantly greater density of immunodetectable mucosal epithelium alpha3 subunit, compared with UC patients. DISCUSSION: The presence of nAChRs in colonic epithelium may be pertinent to the beneficial effect of nicotine in UC, but since neither smoking nor nicotine treatment is associated with any change in the expression of epithelial alpha3 nAChRs, the effect may be due to functional changes in the receptor. The decreased number of alpha3 nAChRs in UC compared with controls may be related to an increased cell turnover in UC.

Administration, Cutaneous↗
PubMed2002

Complex and extensive infective endocarditis: a novel surgical approach.

Endocarditis involving the central fibrous body of the heart requires carefully planned surgical intervention. We present a novel approach in a 65-year-old male with extensive endocarditis involving the aortic root, ventricular septum, central fibrous body together with mitral, aortic and tricuspid valves.

Aged↗
PubMed2002

The effect of fixation and processing on the sensitivity of oestrogen receptor assay by immunohistochemistry in breast carcinoma.

AIMS: To investigate the effect of different fixation and processing regimens on the assessment of oestrogen receptor (ER) by immunohistochemistry (IHC). METHODS: The ER results for 420 patients from seven different hospitals in which antigen retrieval and IHC were performed centrally were compared. The intensity of ER positivity was assessed semiquantitatively using the Quick score (range 0-7). The scoring profiles of cases from each different source (hospital) were compared to detect differences in the proportion of cases that were negative (Quick score = 0), moderately positive (Quick score = 1-5), and strongly positive (Quick score = 6-7). RESULTS: There were no significant differences (p = 0.3; kappa(2) test) in the proportion of cases in each category. CONCLUSIONS: None of the fixation or processing regimens had a significant adverse effect on the sensitivity of the ER assessment performed by automated immunohistochemistry.

Biomarkers, Tumor↗
PubMed2002

Effect of margins of excision on recurrence after local excision of ductal carcinoma in situ of the breast.

AIMS: To determine important factors influencing recurrence after local excision of duct carcinoma in situ (DCIS) of the breast. MATERIALS AND METHODS: The extent (size) in millimetres, classification (by cytonuclear grade (NHSBSP system), by extent of necrosis, and by the Van Nuys system), and excision margins of 115 cases of screen detected DCIS treated by local excision were measured. A prognostic index was calculated by the addition of the Van Nuys classification (low grade, 1; moderate grade, 2; high grade, 3), margin score (> or = 10 mm, 1; 1-9 mm, 2; < 1 mm, 3), and size score (< or = 15 mm, 1; 16-40 mm, 2; and > or = 41 mm, 3), giving a total score of 3-9. RESULTS: Classification using cytonuclear grade, extent of necrosis, or the Van Nuys system did not correlate significantly with recurrence. The excision margin (in millimetres) was associated with recurrence (p = 0.027) and if excision margin status was simplified using the scoring system (> or = 10 mm, 1; 1-9 mm, 2; < 1 mm, 3), the margin score was significantly associated with recurrence (p = 0.03). A prognostic index based on the Van Nuys score, margin status, and size was significantly associated with recurrence (p = 0.003). CONCLUSION: The results support the hypothesis that the margin of excision is the most important factor predicting the recurrence of DCIS after local excision.

Aged↗
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↗