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Biomedical subjects

D Newman

Publications and source records attributed to D Newman.

At least 91 records · Page 5Linked to original sources
PubMed1996

Management of intracardiac device recalls: a consensus conference.

The incidence of cardiac device recalls seems to be increasing, due in part to increasing complexity, but also to greater public awareness and regulatory overview. Manufacturers are responsible for postmarket surveillance of their implanted products; evidence for poor performance is usually evaluated by a physician advisory committee, and unacceptable failure rates or modes prompt the issuance of a recall. A consensus conference was held March 6, 1995 in Toronto, Ontario to discuss the management of cardiac device recalls after the provincial Ministry of Health issued unique guidelines regarding a recent lead problem. Various stakeholders expressed their views and concerns: the federal regulatory body, the provincial Ministry of Health and hospital association, manufacturers, hospital legal counsel, patient and media advocates and physicians from the United Kingdom, the United States and Canada. Specific recommendations included the establishment of a national (or regional) pacemaker (device/lead) registry interposed between the manufacturer and the federal authority; the creation of a recall task force to deal with specific problems distinct from the manufacturers' physician advisory committee; emphasis on patient responsibility for obtaining regular follow-up and maintaining contact by a pacemaker passport system as exists in Europe; and the fair assignment of costs involved in a recall with specific emphasis on appropriate compensation for physicians and clinic personnel.

Algorithms↗
PubMed1996

Mesenchymal cell activation is the rate-limiting step of granulation tissue induction.

During wound repair a 3-day lag occurs between injury and granulation tissue development. When full-thickness, 8-mm-round, excisional wounds were made in the paravertebral skin of outbred Yorkshire pigs and harvested at various times, no granulation tissue was observed before day 4. Day 4 wounds were 3% filled with granulation tissue, day 5 wounds 48% filled, and day 7 wounds 88% filled. The prerequisites for granulation tissue induction are not known but hypothetically include fibrin matrix maturation or cell activation. To examine whether matrix maturation was necessary, wounds were allowed to heal for 5 or 7 days and then aggressively curetted, resulting in the formation of fresh fibrin clots in the newly formed wound spaces. In contrast to original wounds, no lag phase was observed; wounds curetted on day 5 were 23% filled with granulation tissue 1 day later and 99% filled 3 days later, whereas wounds curetted on day 7 were 47% filled 1 day later and completely filled within 2 days. Thus, granulation tissue formation resumed promptly and independently of fibrin clot matrix maturation. This observation suggested that mesenchymal cell activation might be the rate-limiting step in granulation tissue formation. To address this hypothesis more directly, cultured porcine or human fibroblasts, grown to 80% confluence in Dulbecco's minimal essential medium plus 10% fetal calf serum, were added to new wounds. These wounds were sealed with a freshly made exogenous fibrin clot. In some wounds, platelet releasate was added to the fibrin clot. Granulation tissue did not form in day 3 wounds, which had received either fibrin alone, fibrin and platelet releasate, or fibrin and fibroblasts. In contrast, granulation tissue was observed in wounds receiving fibrin, human fibroblasts, and platelet releasate. By day 4, wounds receiving cultured human fibroblasts, fibrin, and platelet releasate were 14% filled with granulation tissue compared with less than 4% granulation tissue in control wounds. Thus, fibroblast activation is a limiting step of granulation tissue formation, and continued cell stimulation is required for accelerated development.

Animals↗
PubMed1995

Characterization of the murine mu opioid receptor gene.

The analgesic and addictive properties of morphine and other opioid drugs are thought to result from their interaction with mu opioid receptors. Using a delta opioid receptor cDNA as a probe, we have isolated a murine mu opioid receptor cDNA clone (mMOR). Stable expression of mMOR in Chinese hamster ovary cells conferred high binding affinity for mu receptor ligands including morphine and [D-Ala2,N-methyl-Phe4,Gly5-ol]-enkephalin and low affinity for delta and kappa preferring ligands. Treatment of these cell lines with morphine and other mu agonists inhibited forskolin-induced cAMP accumulation, demonstrating a functional coupling of mMOR to the inhibition of adenylate cyclase. The predicted amino acid sequence of mMOR shares approximately 55% overall amino acid identity with the delta receptor and approximately 97% identity with the recently reported rat mu opioid receptor. Expression of the mu receptor in mouse brain as revealed by in situ hybridization parallels the reported pattern of distribution of mu-selective ligand binding sites. Chromosomal localization (to mouse chromosome 10) and Southern analysis are consistent with a single mu opioid receptor gene in the mouse genome, suggesting that the various pharmacologically distinct forms of the mu receptor arise from alternative splicing, post-translational events, or from a highly divergent gene(s).

Amino Acid Sequence↗
PubMed1995

Association between QT dispersion and autonomic dysfunction in patients with diabetes mellitus.

OBJECTIVES: We hypothesized that QT dispersion would be increased in patients with diabetes mellitus and autonomic dysfunction and that QT dispersion would be related to abnormal iodine-123 (I-123) metaiodobenzylguanidine (MIBG) uptake. BACKGROUND: Patients with diabetes mellitus and autonomic dysfunction have an increased incidence of sudden death. This event may be due to a sympathetic imbalance causing disturbances of repolarization. QT dispersion has recently been demonstrated to reflect dispersion of ventricular refractoriness and is a marker of arrhythmogenic potential. Uptake of I-123 MIBG is a reliable measure of whether the tissue examined receives sympathetic neuronal innervation. METHODS: Fifty-one diabetic patients and 11 normal subjects were studied. All patients had clinical evaluation for autonomic dysfunction (defined as at least two abnormal heart rate and blood pressure responses to five validated tests). Rest 12-lead electrocardiograms were recorded for measurement of QT dispersion, defined as the longest QT interval minus the shortest QT interval, and corrected for heart rate using Bazett's formula. Visual and quantitative measurements of I-123 MIBG uptake were performed using I-123 MIBG, and technetium-99m sestamibi uptake was used to assess perfusion. RESULTS: Thirty-five diabetic patients had autonomic dysfunction. Corrected QT dispersion was significantly greater in the patients than in the normal subjects (p = 0.02). The I-123 MIBG scores were also significantly greater in patients with than without autonomic dysfunction (p = 0.0004) and in normal subjects (p = 0.008). There was no correlation between QT dispersion and I-123 MIBG uptake score (r = 0.006, p = 0.97). CONCLUSIONS: Diabetic patients with autonomic dysfunction have increased QT dispersion and larger I-123 MIBG uptake defects. This finding suggests that such patients have a greater inhomogeneity of repolarization. The lack of correlation between QT dispersion and I-123 MIBG uptake suggests that these abnormalities are mediated by different mechanisms.

3-Iodobenzylguanidine↗
PubMed1995

Congenital genitourinary tract abnormalities following cocaine exposure in utero.

The purpose of this study was to review the clinical and ultrasound experience of renal tract abnormalities associated with cocaine exposure in utero. We undertook a 3-year chart review of all infants admitted to British Columbia's Children's Hospital neonatal intensive care unit and Sunny Hill Health Centre for Children in order to identify patients with the diagnostic code for maternal drug or substance use. There were 136 neonates with a positive history or urine drug screen. Renal ultrasound scans had been performed on 79 patients. Ultrasound abnormalities were found in 11 patients (14%) and included horseshoe kidney (2), unilateral abnormal small kidney (1), duplex kidney (1), and renal tract dilation (8). Clinical findings were glandular (2) and juxtaglandular (1) hypospadias with chordee. The patients with hypospadias did not have other abnormalities or abnormal renal ultrasound scans. In our population of infants exposed to cocaine in utero we detected an increased incidence of hypospadias and an increased incidence of renal tract abnormalities. We conclude that cocaine exposure in utero may well be a risk factor for renal tract anomalies. However, a larger, longer-term prospective study is necessary before definitive recommendations can be given for routine screening by ultrasound of all infants exposed to cocaine in utero.

Abnormalities, Drug-Induced↗
PubMed1994

Torsades de pointes ventricular tachycardia following right pneumonectomy: insights into the relation between right cardiac sympathetic nerve damage, QT intervals, and arrhythmias.

Polymorphic ventricular tachycardia in association with prolongation of the QT interval on the surface electrocardiogram (ECG) has long been recognized as an important cause of life threatening arrhythmias that can occur with congenital or acquired abnormalities of cardiac repolarization. One hypothesis of the origin of these arrhythmias states that overactivity of the left-sided sympathetic or under activity of the right-sided sympathetic neural input to the heart leads to prolonged repolarization and ventricular arrhythmias. This hypothesis has led to the application of left cervicothoracic sympathetectomy for control of arrhythmias in congenital long QT syndromes. Although animal models have shown QT prolongation following right stellate ganglionic section or left stellate stimulation, spontaneous ventricular arrhythmias following stellate stimulation or block in man have not been demonstrated. We report the case of a patient with life threatening ventricular arrhythmias following surgical damage to the right cardiothoracic sympathetic nerves.

Electrocardiography↗
PubMed1994

A report using a hybrid ICD system: the need for compatibility among implanted defibrillator components.

The successful implantation of an ICD system with hardware from three different manufacturers is described. This case exemplifies the need for compatibility of components among different manufacturers. This is most relevant at a time when rapidly changing technology and hardware availability may require a mixing, by informed practitioners, of ICD system components. The parallel to the development of the uniform IS-1 standard for bradycardia devices is made.

Defibrillators, Implantable↗
PubMed1994

Physiological and neuropsychological effects of theophylline in chronic obstructive pulmonary disease.

The effect of oral theophylline on clinical course, exercise, neuropsychological performance and bronchial reactivity was studied in chronic airflow obstruction. Twelve patients with chronic obstructive pulmonary disease (COPD) [mean age 62.4 +/- 1.6 years (SE), and forced expiratory volume in 1 sec of 1.15 +/- 0.1 l] were randomized to 4 weeks treatment with oral theophylline followed by 4 weeks of placebo, in a double-blind fashion. During each period, patients underwent clinical evaluation, incremental exercise, a battery of neuropsychological tests measuring a wide range of cognitive functions, and an inhaled methacholine provocation. On the active drug (levels 9.5 +/- 1 mg/l), vital capacity and maximal breathing capacity were 16 +/- 7% and 20 +/- 7% respectively, higher relative to placebo (P < 0.04). Exercise capacity, as reflected by peak O2 uptake and the anaerobic threshold, improved 14 +/- 5% and 18 +/- 5% (P < 0.04). In contrast, bronchial responsiveness to inhaled methacholine and the mean scores on the neuropsychological tests were not significantly altered by the drug. Clinical symptoms were unaltered, but mild side effects were more common on theophylline. We concluded that in moderate to severe COPD, theophylline treatment, at the low range of the therapeutic dose, improves lung function and exercise capacity. This improvement is achieved with no detectable alteration of bronchial reactivity to methacholine and with no deleterious effect on cognitive functions.

Aged↗
PubMed1994

Sotalol in patients with implanted automatic defibrillators: effects on defibrillation and comparison with amiodarone.

OBJECTIVES: Although many patients receiving implanted cardioverter defibrillators receive concomitant antiarrhythmic therapy, the risks and benefits of different agents for such patients are not well understood. It was hypothesized that sotalol, a drug with beta-blocking and class II antiarrhythmic properties would be useful in these patients. DESIGN: Nonrandomized prospective cohort study of the effects of sotalol versus other antiarrhythmic therapy on defibrillation energy requirements. SETTING: Tertiary care referral centre. PATIENTS: Patients referred for management of life threatening ventricular arrhythmia in whom an implanted cardioverter defibrillator was indicated on standard clinical grounds. INTERVENTIONS: Intraoperative testing of defibrillation energy requirements, exercise testing, electrophysiological testing. MAIN RESULTS: Fifteen patients were treated with oral sotalol (173.3 +/- 59.8 mg/day). Sotalol blunted maximal heart rate during treadmill exercise (120.9 +/- 29.9 beats/min). Mean right ventricular effective refractory period increased from 251.7 +/- 21.7 to 276.7 +/- 25.7 ms (P = 0.05). All patients received one large (28 cm2) and one small (14 cm2) epicardial electrode patch. The lowest energy to defibrillate successfully from induced ventricular fibrillation (VF) was 5.9 +/- 3.7 J (median 4.1 J), with all patients defibrillated at 15 J or less. In a concurrent comparison group of 16 similar patients not treated with sotalol (13 on amiodarone and three on beta-blockers), with identical or larger patch size, and identical placement, the lowest successful energy to defibrillate from induced VF was significantly higher (16 +/- 8.8 J) (P < 0.05). Mean cycle length of VF from intracardiac recordings was 232 +/- 37 ms, and was significantly inversely correlated with lowest successful energy (r = 0.61, P < 0.05). CONCLUSIONS: Oral sotalol may be useful in conjunction with an automatic defibrillator; it is associated with low defibrillation energy requirements in humans, and may alter VF.

Administration, Oral↗
PubMed1993

Evaluation of edrophonium as a provocative agent for vasovagal syncope during head-up tilt-table testing.

Vasovagal syncope after head-up tilting is thought to be secondary to a complex, neurally-mediated reflex with both vasodepressor and cardioinhibitory efferent components. The efficacy of edrophonium, an acetylcholinesterase inhibitor, as a provocative agent for triggering syncope during head-up tilt testing was evaluated. Forty-five consecutive patients (22 female and 23 male) with history of recurrent unexplained syncope received edrophonium (10 mg intravenous) after 30 minutes of 60 degrees head-up tilting alone. Twenty normal control subjects (9 female and 11 male) were tested with head-up tilt testing and edrophonium. Syncope was induced in 19 of 45 patients with the diagnosis of unexplained syncope. In 9 patients who developed syncope with head-up tilting alone, the predominant hemodynamic finding was marked vasodepression. In contrast, in 10 patients who developed syncope only after head-up tilting and edrophonium, the predominant hemodynamic findings were marked vasodepression and bradycardia. Syncope was induced in 1 of 20 normal subjects after head-up tilting and edrophonium. There was no long-term complication from using edrophonium. It is concluded that head-up tilt testing with edrophonium: (1) significantly increases the identification of patients with vasovagal syncope, (2) may be particularly useful when provocation with isoproterenol is undesirable, and (3) may be an effective method to help differentiate patients with a significant reflex cardioinhibitory component from those with a predominantly reflex vasodepressor component.

Adolescent↗
PubMed1993

Effect of sotalol on ventricular fibrillation and defibrillation in humans.

Antiarrhythmic drugs are frequently administered to patients receiving implanted cardioverter defibrillators. Some of these drugs may decrease the efficacy of defibrillation shocks from the defibrillator. Sotalol, a drug with beta-blocking and class III antiarrhythmic properties, lowers defibrillation energy requirements in experimental animals and may do so in humans. Oral sotalol 171 +/- 58 mg was administered before and after device implantation in 25 patients receiving implanted defibrillators. During sotalol therapy, the lowest energy required for successful defibrillation was 5.9 +/- 3.4 J (range 2-15J). In a concurrent nonrandomized comparison group of 23 patients, including 18 treated with amiodarone, the lowest successful energy was 16 +/- 10 J (p < 0.01). In 5 sotalol patients, ventricular fibrillation (VF) could not be induced at all (1 patient) or more than 2 or 3 times (4 patients) despite repeated 60 Hz stimulation. The induced VF had a pronounced tendency to terminate spontaneously, with the termination occurring at up to 23 seconds after the offset of 60 Hz stimulation. The cycle length of the VF was 236 +/- 34 msec, significantly greater than in patients not given drug therapy (191 +/- 21 msec, p < 0.01). In 10 patients, but none of the controls, intracardiac electrograms during surface electrocardiographic VF were regular, monoform, and without low-amplitude diastolic activity. In addition, monophasic action potentials during apparent VF showed maintenance of distinct and normal morphology. The ventricular effective refractory period increased after sotalol (249.4 +/- 19 to 278.4 +/- 24 msec; p < 0.03) and the maximum heart rate response to exercise was limited to 120 +/- 28 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗