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Biomedical subjects

D M Gilligan

Publications and source records attributed to D M Gilligan.

At least 19 recordsLinked to original sources
PubMed2004

Prevention of immunization to D+ red blood cells with red blood cell exchange and intravenous Rh immune globulin.

BACKGROUND: Although young women who are D- occasionally receive unintentional transfusions with D+ red blood cells (RBCs), there are little data to assist with management of such an event. Two cases of D- girls transfused with D+ RBCs are reported. In an effort to prevent formation of anti-D, RBC exchange followed by administration of intravenous (IV) Rh immune globulin (RhIg) was used. CASE REPORTS: Patient 1, a 56-kg, 16-year-old D- girl, was involved in a motor vehicle crash. She received 4 units of Group O uncrossmatched D+ RBCs. Thirty-six hours after admission, she underwent RBC exchange with 10 units of D- RBCs, followed by a total of 2718 microg of IV RhIg over 32 hours. Six months later, her antibody screen was negative. Patient 2, a 39-kg, 10-year-old D- girl with aplastic anemia, received 1 unit of D+ RBCs. She underwent RBC exchange on the same day with 5 units of D- RBCs, followed by a total of 900 microg of IV RhIg over 8 hours. Six months later her antibody screen was negative. CONCLUSION: RBC exchange followed by a calculated dose of IV RhIg was successful in preventing allo-immunization to D. Several small studies suggest that both trauma and hematology patients may be less capable of becoming immunized with the transfusion of D+ blood components. Until these findings are more clearly defined, there will be times when prevention of immunization of any D- girl is desired. RBC exchange followed by RhIg appears to be one way to achieve this goal.

Adolescent↗
PubMed2001

Excimer laser for pacemaker and defibrillator lead extraction: techniques and clinical results.

Pacing and defibrillation leads may need to be removed for several reasons including infection, interference with others leads, lack of vascular access or redundancy. However, the removal of chronically implanted leads is a major technical challenge because of the extensive adhesions that develop along the course of the leads over time. The techniques to remove chronic leads have been greatly facilitated by the development of an excimer laser sheath. We undertook an analysis of our experience with laser extraction in the first 50 leads attempted. An excimer laser sheath system, developed by the Spectranetics Corporation, was used to extract 50 chronically implanted leads in 34 patients. The mean patient age was 64+/-12 years, all were male and the average duration that the leads had been implanted was 5.0+/-3.9 years. Two-thirds of the leads were pacemaker and one-third were defibrillator leads. There was a 100% clinical success rate and 48 of the 50 leads were completely removed. There were no major complications. There was one minor complication of subclavian vein thrombosis and two haemodynamically non-significant episodes of air embolism. The main limitation observed was failure of the excimer laser sheath to advance in 18% of cases, probably due to the presence of calcified adherences on leads. Two strategies were found useful to deal with this problem: under the clavicle stainless-steel sheaths were used to break up calcified adherences and within the venous system the laser sheath was upsized in order to advance over the calcification on the lead. It was concluded that excimer laser has greatly facilitated the removal of chronically implanted pacemaker and defibrillator leads. There is a high success rate and low complication rate in our experience. The main limitation of laser is the presence of calcified adherences.

Adult↗
PubMed2000

Frequency of anticoagulation for atrial fibrillation and reasons for its non-use at a Veterans Affairs medical center.

Randomized clinical trials have led to guidelines for anticoagulation in atrial fibrillation (AF). However, it is unclear how successfully these guidelines are being implemented in clinical practice and there is concern that anticoagulation is underused. Therefore, we examined the rate of anticoagulation in 998 patients with AF who attended a Veterans Affairs Medical Center over a 2-year period. Warfarin was prescribed for 504 patients (51%) and not prescribed for 494 patients (49%). Of these 494 patients, 446 had sufficient data for further assessment. Warfarin was judged not indicated in 200 because AF was transient or lone. Warfarin was indicated in 246 patients, 63% having > or =3 risk factors for thromboembolism. However, 184 of these patients also had at least 1 contraindication to anticoagulation. Thus, warfarin was prescribed to 67% of patients with AF in whom anticoagulation was indicated and to 89% of such patients in whom it was indicated and who had no contraindications. However, 25% of AF patients with strong indications for anticoagulation had concomitant contraindications, which precluded its use. We conclude that the use of warfarin for AF in this setting is higher than previously reported and approaching ideal levels. However, there remains a large, problematic subgroup of patients with AF in whom indications for and contra-indications to anticoagulation coexist.

Aged↗
PubMed2000

The mouse adducin gene family: alternative splicing and chromosomal localization.

Mouse cDNA sequences encoding alpha, beta, and gamma adducins were cloned from a mouse reticulocyte cDNA library. The purified clones contain alternatively spliced exons from all three adducin genes. In the case of alpha and beta, the inclusion of the alternatively spliced exons results in truncated polypeptide isoforms (called alpha-2 and beta-2). The mouse predicted amino acid sequences are compared with published rat and human sequences. For completion of this comparison, cDNA encoding the rat beta-1 carboxy terminus was cloned by PCR. The carboxy terminal region containing MARCKS homology, calmodulin-binding region-2, and spectrin-actin-binding site, is conserved among alpha-1, beta-1, and gamma-1 isoforms in mouse, rat, and humans. We also report here the localization of the gene encoding gamma adducin (Add3) to murine Chr 19, in a region that shows conserved synteny with human Chr 10.

Alternative Splicing↗
PubMed2000

Dual-chamber pacing in hypertrophic cardiomyopathy.

This review focuses on recent developments in the field of pacing in hypertrophic cardiomyopathy (HCM). Regarding mechanisms of action, recent data indicates that pacing acts by inducing dysynchronous left ventricular activation, thus reducing contractility and increasing end-systolic volume. Following several positive uncontrolled studies, three randomized crossover trials, with a total of approximately 140 patients, have now confirmed that gradients are on average halved with pacing but the reduction in symptoms has been modest and maximum exercise capacity has not been improved. These studies have identified a placebo effect from pacemaker implantation in HCM and have questioned the efficacy of pacing as a symptomatic therapy for HCM. There is probably a subgroup of patients with HCM who respond to permanent dual-chamber pacing but their precise identification is not yet clear. Permanent pacing should continue to be considered as one option in the management of the patient with drug refractory, symptomatic obstructive HCM.

Cardiac Pacing, Artificial↗
PubMed2000

Catheter ablation of ventricular tachycardia in patients with structural heart disease using cooled radiofrequency energy: results of a prospective multicenter study. Cooled RF Multi Center Investigators Group.

OBJECTIVES: The purpose of this multicenter study was to evaluate the safety and efficacy of a radiofrequency (RF) catheter ablation system with internal saline irrigation. BACKGROUND: Catheter ablation of ventricular tachycardia (VT) associated with structural heart disease is more difficult than ablation of idiopathic VT. The larger size of responsible reentrant circuits contributes to the difficulty in achieving an adequate ablation lesion with conventional techniques. Recently, cooling of the ablation electrode by saline irrigation has been shown to increase RF lesion size. METHODS: The patient population included 146 patients who participated in the Cooled RF Ablation System clinical trial and underwent an attempt at ablation of VT occurring in the presence of structural heart disease. The duration of follow-up was 243 +/- 153 days. RESULTS: Catheter ablation was acutely successful, as defined by elimination of all mappable VTs, in 106 patients (75%). In 59 patients (41%), no VT of any type was inducible after ablation. Twelve patients (8%) experienced a major complication. After catheter ablation, 66 patients (46%) developed one or more episodes of a sustained ventricular arrhythmia. CONCLUSIONS: The results of this study demonstrate that catheter ablation of all mappable forms of sustained VT can be performed with high initial success and a moderate incidence of major complications (8%).

Adult↗
PubMed2000

The acute effects of biatrial pacing on atrial depolarization and repolarization.

Permanent biatrial and/or multisite atrial pacing may prevent atrial fibrillation (AF), but the effects on atrial electrophysiology remain incompletely understood. Acute biatrial pacing was studied in 20 patients with and 28 without (controls) a history of atrial fibrillation and/or flutter. Twelve-lead electrocardiograms were recorded during pacing from the high right atrium (RA), from the distal coronary sinus (LA), and biatrial pacing. P wave duration was measured in each lead and the difference between maximum and minimum P duration was termed P wave dispersion. Effective refractory periods (ERPs) were measured during each pacing mode. The dispersion of P wave duration was 35 +/- 14 ms in controls and 40 +/- 29 ms in AF patients (P = 0.17). Compared to RA pacing, LA pacing shortened P duration in controls (127 +/- 18 to 107 +/- 16 ms, P < 0.05) and biatrial pacing markedly shortened P duration in controls (127 +/- 18 to 93 +/- 14 ms, P < 0.05) and AF patients (114 +/- 43 to 97 +/- 21 ms, P < 0.05). P wave dispersion was unaffected. In controls, the LA ERP was longer than the RA ERP. This phenomenon was not present in AF patients, whose LA ERP was shorter than that of controls. Biatrial pacing had no effect on atrial ERPs or the dispersion of atrial refractoriness. In conclusion, acute biatrial pacing does not affect atrial repolarization but it does cause a marked shortening of global biatrial depolarization. Distal coronary sinus pacing produces a shorter P wave than RA pacing. There is substantial dispersion in the surface P wave of the electrocardiogram, the significance of which awaits further study.

Atrial Fibrillation↗
PubMed1999

Diagnostic utility of mechanical, pharmacological and orthostatic stimulation of the carotid sinus in patients with unexplained syncope.

OBJECTIVES: The purpose of the present study was to systematically evaluate the diagnostic utility of mechanical, pharmacological and orthostatic stimulation of the carotid sinus in a consecutive series of patients with recurrent unexplained syncope. BACKGROUND: Carotid sinus hypersensitivity (CSH) is an infrequently recognized cause of recurrent unexplained syncope usually diagnosed by carotid sinus massage (CSM) in the supine position. The diagnostic utility of systematic assessment of mechanical, pharmacological and orthostatic stimulation of the carotid sinus has not been clearly established. METHODS: Eighty consecutive patients (63 +/- 12 years) with a history of recurrent unexplained syncope (mean episodes: 6 +/- 3); 30 age-matched controls (65 +/- 14 years) and 16 patients (59 +/- 12 years) with syncope not related to CSH were studied. Pharmacological stimulation of the carotid sinus was achieved by randomly administering bolus injections of nitroprusside and phenylephrine. Mechanical stimulation of the carotid sinus was performed by CSM applied for 5 s in the supine position and after 2 min at 60 degrees. A 60 degree low-dose isoproterenol head-up tilt test (HUTT) was also performed for a total duration of 30 min. RESULTS: Carotid sinus hypersensitivity was elicited by CSM in the supine position in seven (8.7%) patients, two (6.6%) controls and one (6.3%) patient with syncope unrelated to CSH, compared with 48 (60%) patients, two (6.6%) controls and one (6.3%) syncope unrelated to CSH patient after 60 degree HUTT, increasing the diagnostic yield by 51%. Baroreceptor gain was significantly reduced in the CSH group. Head-up tilt test was positive in 12 (25%) patients with CSH, two (6.6%) controls and two (12%) with documented syncope but not positive in any of the patients in which syncope remained unexplained. Diagnostic accuracy was enhanced by 38% (31% supine vs. 69% upright) when CSM was performed at 60 degrees. CONCLUSIONS: CSH was documented in 68% of patients, 8.7% in the supine position and 60% in the upright position. Sensitivity was increased by 51%, and diagnostic accuracy was enhanced by 38% by performing CSM in the upright position. Decreased baroreceptor gain was documented and may play a role in the pathophysiology of CSH.

Aged↗
PubMed1999

Targeted disruption of the beta adducin gene (Add2) causes red blood cell spherocytosis in mice.

Adducins are a family of cytoskeleton proteins encoded by three genes (alpha, beta, gamma). In a comprehensive assay of gene expression, we show the ubiquitous expression of alpha- and gamma-adducins in contrast to the restricted expression of beta-adducin. beta-adducin is expressed at high levels in brain and hematopoietic tissues (bone marrow in humans, spleen in mice). To elucidate adducin's role in vivo, we created beta-adducin null mice by gene targeting, deleting exons 9-13. A 55-kDa chimeric polypeptide is produced from the first eight exons of beta-adducin and part of the neo cassette in spleen but is not detected in peripheral RBCs or brain. beta-adducin null RBCs are osmotically fragile, spherocytic, and dehydrated compared with the wild type, resembling RBCs from patients with hereditary spherocytosis. The lack of beta-adducin in RBCs leads to decreased membrane incorporation of alpha-adducin (30% of normal) and unexpectedly promotes a 5-fold increase in gamma-adducin incorporation into the RBC membrane skeleton. This study demonstrates adducin's importance to RBC membrane stability in vivo.

Anemia↗
PubMed1999

Exclusion of the stomatin, alpha-adducin and beta-adducin loci in a large kindred with dehydrated hereditary stomatocytosis.

Defects in stomatin, alpha-adducin, and beta-adducin have been implicated in erythrocyte disorders of cation permeability. We performed linkage analysis of the genetic loci for these proteins in a large kindred with xerocytosis (dehydrated hereditary stomatocytosis). Using polymerase chain reaction-based genotyping techniques, all three loci are excluded as disease gene candidates.

Alleles↗
PubMed1999

Induction of ventricular fibrillation by T wave shocks: observations from monophasic action potential recordings.

INTRODUCTION: Shocks given during the vulnerable period of cardiac repolarization may induce ventricular fibrillation (VF). However, the relationship of the vulnerable period and the monophasic action potential (MAP) has not yet been reported in humans. The purpose of this study was, therefore, to determine how the monophasic action potential recorded from the right ventricle correlates with inducibility of VF using T wave shocks during ventricular pacing. METHODS: Eleven patients undergoing implantable cardioverter defibrillator (ICD) implantation had a MAP catheter positioned in the right ventricle (RV). The local monophasic action potential duration at 90% repolarization (MAP90) duration was measured during pacing at 400 ms. VF induction was attempted by pacing at 400 ms for 10 cycles and then giving a 1.0 joule monophasic T wave shock at varying coupling intervals (CI) to the last paced stimulus. The maximum and minimum CI that induced VF were determined and mapped in relation to the MAP90 recording. RESULTS: The average paced MAP duration was 275 +/- 20 ms. The minimum and maximum CI to induce VF were 255 +/- 24 ms and 325 +/- 36 ms respectively. This ranged from 93% to 118% of the MAP90 duration but because of delay in conduction time to the MAP catheter, shocks that induced ventricular fibrillation occurred between 74% and 99% of local repolarization time. CONCLUSION: VF is inducible with low energy T wave shocks falling during the last 25% of the right ventricular MAP90 recording. This corresponds with VF initiation during phase III repolarization.

Action Potentials↗
PubMed1999

Steroid eluting high impedance pacing leads decrease short and long-term current drain: results from a multicenter clinical trial. CapSure Z investigators.

Pacemaker lead technology has changed considerably over the past decades. The widespread use of low polarization highly porous electrodes and steroid elution electrodes has resulted in low chronic pacing thresholds, as well as a decrease in the incidence of exit block. Efforts to develop pacing leads with high impedance might theoretically lead to lower lead current drain, which is a component of battery capacity. Pulse generator longevity can be increased without sacrificing pacemaker capabilities if pacing current drain can be decreased. Decreasing the size of the stimulation electrode results in increased pacing impedance, and if pacing thresholds are unchanged, a decreased current drain is predicted by Ohm's law (I = V/R). There is limited data available on the pacing characteristics of large numbers of patients with high impedance leads, despite their recent general availability and increasing widespread use. This multicenter, controlled trial examined the differences in performance between standard steroid-eluting pacing leads in the atrium (Medtronic model 5524) and ventricle (Medtronic model 5024), and new high impedance steroid-eluting pacing leads in the atrium (Medtronic model 5534) and ventricle (Medtronic model 5034). Measurements of bipolar pacing thresholds at 2.5 V, pacing impedance, and sensing thresholds were determined within 24 hours of pacemaker implantation, and at 0.5, 1, 3, 6 and 12 months after pacemaker implantation in 609 patients. Pacing and sensing thresholds were similar for the control and high impedance leads at all times except for a slightly larger R wave with the high impedance leads at implantation and 12 months. The mean impedance of the high impedance pacing leads in the atrium and ventricle at 12 months was 992 +/- 175 and 1,080 +/- 220 omega, compared to 522 +/- 69 and 600 +/- 89 omega for the standard pacing leads in the atrium and ventricle (P < or = 0.001 for the high impedance leads compared to standard leads in each chamber). The mean atrial lead current (measured at 2.5 V) at 12 months was 2.6 +/- 0.5 mA with the high impedance lead, and 4.9 +/- 0.7 mA with the standard lead in the atrium (P < or = 0.001). In the ventricle, the mean lead current at 12 months was 2.4 +/- 0.4 mA with the high impedance pacing lead and 4.3 +/- 0.6 mA with the standard lead (P < or = 0.001). High impedance leads are associated with lower lead current drain than standard pacing leads in the atrium and ventricle for up to 1 year. No clinically important differences in sensing characteristics was noted with the high impedance leads in the atrium or ventricle compared to standard pacing leads. High impedance leads may result in increased pulse generator longevity.

Aged↗
PubMed1999

Optimal cardiac pacing after heart transplantation.

The transplanted heart is characterized physiologically by autonomic denervation, chronotropic incompetence, intermittent episodes of allograft rejection, and frequently by diastolic dysfunction. Sinus node dysfunction resulting in bradycardia is common in the early postoperative period following standard orthotopic cardiac transplantation. Bradycardia tends to remit spontaneously but there are no factors that accurately identify patients who will need long-term pacing. Patients in whom bradycardia persists beyond the second postoperative week despite treatment with theophylline require permanent pacemaker implantation. It has been observed that chronotropic incompetence and diastolic dysfunction are important determinants of exercise capacity following heart transplantation. Pacing that restores chronotropic competence improves exercise capacity, confirming the importance of impaired heart rate response. As in other settings, pacing that preserves atrioventricular (AV) synchrony results in increased cardiac output. For these reasons when pacing is necessary we recommend the DDDR mode (AAIR if intact AV nodal conduction is present) so that the 30%-50% of patients who remain pacemaker-dependent long-term obtain maximal benefit from their transplant.

Animals↗
PubMed1999

Symptomatic hypertrophic obstructive cardiomyopathy: the role of dual-chamber pacing.

BACKGROUND AND PURPOSE: The management of symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM) has traditionally consisted of beta blockers and calcium channel blockers. Surgical treatment has been employed for operable patients who became refractory to medical therapy. However, associated complications, mortality rate, and recurrence of functional limitations have shifted the focus toward alternative therapy modalities. Recently, permanent dual-chamber (DDD) pacemaker has been introduced as an alternative treatment option. PATIENTS AND METHODS: This study comprises clinical, angiographic, echocardiographic, and electrophysiologic data obtained at a single center on 10 symptomatic patients with HOCM who received a DDD pacemaker after medical therapy failed to relieve symptoms. Presenting symptoms were exertional dyspnea and chest pain (60%), syncope (20%), and presyncope (20%). These symptoms were documented for 8.9+/-7.1 years before pacemaker implantation. All patients were in New York Heart Association functional class III or IV before pacemaker therapy. RESULTS: Placement of a permanent DDD pacemaker decreased the left ventricular outflow tract gradient from 83+/-44 mm Hg (range: 35-180 mm Hg) to 47.1+/-25.3 mm Hg (range: 10-75 mm Hg) in these patients. Within 1 to 30 months, follow-up found that the functional status of eight out of the 10 patients had improved to New York Heart Association class 0 or I. CONCLUSION: In selected patients with symptomatic HOCM who fail to respond to medical therapy, DDD pacemaker may offer a nonsurgical alternative treatment option. Large-scale multicenter, prospective, randomized trials are needed to establish the role of this modality in the treatment of hypertrophic obstructive cardiomyopathy.

Activities of Daily Living↗
PubMed1998

Effect of atherosclerosis on endothelium-dependent inhibition of platelet activation in humans.

BACKGROUND: We investigated whether luminal release of nitric oxide (NO) contributes to inhibition of platelet activation and whether these effects are reduced in patients with atherosclerosis. METHODS AND RESULTS: Femoral blood flow velocity and ex vivo whole blood platelet aggregation by impedance aggregometry were measured in femoral venous blood during femoral arterial infusion of acetylcholine (ACh; 30 microg/min) in 30 patients, 19 of whom had angiographic atherosclerosis. Measurements were repeated with sodium nitroprusside (40 microg/min), L-arginine (160 micromol/min), and N(G)-monomethyl-L-arginine (L-NMMA; 16 micromol/min). There was significant inhibition of collagen-induced platelet aggregation with ACh (45+/-9.5% lower, P<0.001), and this inhibition was greater in patients without atherosclerosis (68.7+/-10.4% reduction) than in those with atherosclerosis (32.5+/-8.1%, P=0.04). The magnitude of inhibition correlated with vasodilation with ACh, indicating an association between the smooth muscle and antiplatelet effects of endothelium-dependent stimulation. Neither L-NMMA nor sodium nitroprusside altered platelet aggregation. L-Arginine inhibited platelet aggregation equally in vitro (34+/-8% reduction, P<0.01) and in vivo (37+/-13% reduction, P<0.01). CONCLUSIONS: Stimulation of NO release into the vascular lumen with ACh inhibits platelet aggregation, an effect that is attenuated in patients with atherosclerosis and endothelial dysfunction. Basal NO release does not appear to contribute to platelet passivation in vivo. L-Arginine inhibited platelet aggregation by its direct action on platelets. These findings provide a pathophysiological basis for the observed increase in thrombotic events in atherosclerosis. Use of L-arginine and other strategies to improve endothelial NO activity may impact favorably on thrombotic events in atherosclerosis.

Acetylcholine↗
PubMed1998

Utilization of an 86 bp exon generates a novel adducin isoform (beta 4) lacking the MARCKS homology domain.

A novel isoform of beta-adducin has been amplified and characterized from a human bone marrow cDNA library (GenBank #U43959). This isoform arises from the insertion of an 86 bp alternatively spliced and previously unrecognized exon (now termed exon 15) within codon 581 of the human red blood cell beta-adducin sequence. This results in an insertion of 28 novel amino acids. The remainder of the red cell beta-adducin mRNA is then translated in a different reading frame, adding an additional 35 novel amino acids prior to the stop codon. This new isoform, thus, replaces beta 1-adducin sequence after residue 580 with a total of 63 new amino acids. Sequences from genomic clones of the human beta-adducin gene show that this alternate exon is flanked by splice consensus sequences and is appropriately located in the genomic map between exons encoding up-stream and down-stream sequences, thus defining a new exon. The COOH-terminus of this new isoform, which we designate beta 4, lacks a 22 amino acid lysine-rich sequence common to both the human red cell alpha- and beta-adducin subunits and homologous to a highly conserved region in MARCKS, a filamentous actin-cross linking protein regulated by protein kinase C and calcium/calmodulin. beta 4-adducin preserves a previously identified calmodulin binding domain. PCR analysis indicates that this new beta-adducin isoform is expressed in fetal brain and liver, bone marrow, and NT-2 (neuroepithelial) cells, but is not detected in several other tissues. We anticipate that this new beta 4 isoform of beta-adducin will display unique and tissue-specific functional properties.

Alternative Splicing↗