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S Connolly

Publications and source records attributed to S Connolly.

At least 19 recordsLinked to original sources
PubMed2001

Lambert-Eaton myaesthenic syndrome: a possible association with Hodgkin's lymphoma.

Lambert-Eaton myasthenic syndrome is a presynaptic neuromuscular junction disorder typically associated with small cell lung carcinoma. The characterstic electrophysiological abnormality is a low amplitude compound muscle action potential that shows a marked increment after maximal voluntary contraction or brief tetanic nerve stimulation. We describe a patient who had LEMS in association with Hodgkin's disease. A 61 year old woman presented with proximal muscle weakness 6 years following successful treatment of Hodgkin's disease. Her symptoms responded well to treatment with diaminopyridine. 9 additional patients have been described with LEMS in association with lymphoproliferative diseases. A systemic malignancy is usually found within 2 years of LEMS diagnosis but may present later. LEMS should be considered in patients with Hodgkin's disease presenting with muscle weakness.

Female↗
PubMed2001

Amyotrophic lateral sclerosis associated with pregnancy.

Amyotrophic lateral sclerosis (ALS) is the most common, progressive motor neurone disease but is rare in the obstetric population. Only 4 cases have been described in the English literature since 1975. We describe a 29 year old woman who presented with ataxia, lower limb weakness and dysarthria 4 weeks after the birth of her first child. The symptoms had onset during the pregnancy but had not been considered remarkable. There were clinical features of upper and lower motor neurone involvement without any sensory loss. MRI of brain and spine was normal. CSF analysis was negative. EMG studies confirmed the presence of widespread anterior horn cell dysfunction compatible with ALS. The patient was commenced on Riluzole and has progressed clinically, at 12 months post diagnosis.

Adult↗
PubMed2000

Identification of patients most likely to benefit from implantable cardioverter-defibrillator therapy: the Canadian Implantable Defibrillator Study.

BACKGROUND: Patients with resuscitated ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation) benefit from implantable cardioverter-defibrillators (ICDs) compared with medical therapy. We hypothesized that the patients who benefit most from an ICD are those at greatest risk of death. METHODS AND RESULTS: In the Canadian Implantable Defibrillator Study (CIDS), 659 patients with resuscitated ventricular tachyarrhythmias were randomly assigned to receive an ICD or amiodarone and were then followed for a mean of 3 years. There were 98 and 83 deaths in the amiodarone and ICD groups, respectively. We used multivariate Cox analysis to assess the impact of baseline parameters on the mortality in the amiodarone group. Reduced left ventricular ejection fraction, advanced age, and poor NYHA status identified high-risk patients (P=0.0001 to 0.0009). Quartiles of risk were constructed, and the mortality reduction associated with ICD treatment in each quartile was assessed. There was a significant interaction between risk quartile and the ICD treatment effect (P=0.011). In the highest risk quartile, there was a 50% relative risk reduction (95% CI 21% to 68%) of death in the ICD group, whereas in the 3 lower quartiles, there was no benefit. Patients who are most likely to benefit from an ICD can be identified with a simple risk score (>/=2 of the following factors: age >/=70 years, left ventricular ejection fraction </=35%, and NYHA class III or IV). Thirteen of 15 deaths that were prevented by the ICD occurred in patients with >/=2 risk factors. CONCLUSIONS: In CIDS, patients at highest risk of death benefited most from ICD therapy. These can be identified easily on the basis of age, poor ventricular function, and poor functional status.

Aged↗
PubMed2000

Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators.

BACKGROUND: The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation, because the prevention of recurrences can improve cardiac function and relieve symptoms. Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence, but this agent has not been tested in a large, randomized trial. METHODS: We undertook a prospective, multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone. We randomly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone, given in an open-label fashion. The patients in the group assigned to sotalol or propafenone underwent a second randomization to determine whether they would receive sotalol or propafenone first; if the first drug was unsuccessful the second agent was prescribed. Loading doses of the drugs were administered and electrical cardioversion was performed (if necessary) within 21 days after randomization for all patients in both groups. The follow-up period began 21 days after randomization. The primary end point was the length of time to a first recurrence of atrial fibrillation. RESULTS: Of the 403 patients in the study, 201 were assigned to amiodarone and 202 to either sotalol (101 patients) or propafenone (101 patients). After a mean of 16 months of follow-up, 71 of the patients who were assigned to amiodarone (35 percent) and 127 of those who were assigned to sotalol or propafenone (63 percent) had a recurrence of atrial fibrillation (P<0.001). Adverse events requiring the discontinuation of drug therapy occurred in 18 percent of the patients receiving amiodarone, as compared with 11 percent of those treated with sotalol or propafenone (P=0.06). CONCLUSIONS: Amiodarone is more effective than sotalol or propafenone for the prevention of recurrences of atrial fibrillation.

Aged↗
PubMed2000

Amnesic syndrome with bilateral mesial temporal lobe involvement in Hashimoto's encephalopathy.

A 25-year-old woman presented with a subacute confusional state, headaches, unsteadiness, myoclonus, seizures, and an amnesic syndrome as a manifestation of Hashimoto's encephalopathy. Investigations showed biochemical hypothyroidism, raised thyroid microsomal antibodies, and weakly positive antineuronal antibodies. A T2-weighted MRI of the brain showed bilateral symmetric areas of increased signal in the mesial temporal lobes and hippocampi that had a low signal intensity on T1-weighted imaging. Despite clinical and radiologic improvement after steroid and thyroid hormone replacement therapy, a severe amnesic syndrome with associated localized MRI abnormalities persists.

Adult↗
PubMed2000

Increased intraocular pressure and visual field defects in high resistance wind instrument players.

OBJECTIVE: In this twofold study, part 1 aimed to determine whether the playing of high resistance wind instruments elevates intraocular pressure (IOP) and if so, to investigate the mechanism of IOP elevation and whether its magnitude differs while playing high resistance versus low resistance instruments. The purpose of part 2 was to evaluate whether high resistance players have a greater incidence of glaucomatous changes than other musicians. DESIGN: Three case reports and a cross-sectional study. PARTICIPANTS: Two players of high resistance instruments and one player of high and low resistance wind instruments participated in part 1 of the study. Nine high resistance wind players, 12 low resistance wind players, and 24 nonwind players were recruited among professional musicians in the Boston area to participate in part 2. INTERVENTION: In part 1, IOP and uveal thickness changes were measured by pneumatonometry and ultrasound biomicroscopy in two participants playing their high resistance wind instruments (trumpet and oboe) and in a third participant playing both high (trumpet) and low (clarinet and saxaphone) resistance instruments. Each musician in part 2 underwent medical and musical history, measurement of IOP, Humphrey visual field testing, slit-lamp examination, gonioscopy, and dilated examination. MAIN OUTCOME MEASURES: Intraocular pressure and uveal thickness changes, and visual field loss and optic nerve head appearance were the main parameters measured in part 1 and part 2, respectively. RESULTS: In part 1, pneumatonometry showed IOP elevation dependent on the force of blowing, and ultrasound biomicroscopy revealed uveal thickening associated with IOP elevation. The magnitude of IOP elevation was dependent on the amount of expiratory resistance provided by the particular instrument. Part 2 showed that life hours of high resistance wind instrument playing had a significant relationship to abnormal visual field (P = 0.03) and corrected pattern standard deviation (CPSD) scores (P = 0.007) in univariate logistic regression and univariate linear regression, respectively. A 0.011-unit increase in CPSD for each 1000 life hours of high resistance wind playing was found. CONCLUSIONS: High and low resistance wind musicians experience a transient rise in their IOP while playing their instruments as a result least in part of uveal engorgement. The magnitude of IOP increase is greater in high resistance wind players versus low resistance wind players. High resistance wind musicians had a small but significantly greater incidence of visual field loss (abnormal fields and increased CPSD scores) than other musicians, which was related to life hours of playing. The cumulative effects of long-term intermittent IOP elevation during high resistance wind instrument playing may result in glaucomatous damage, which could be misdiagnosed as normal-tension glaucoma.

Aged↗
PubMed1999

Can cardiovascular clinical characteristics be identified and outcome models be developed from an in-patient claims database?

The objective of this study was to assess whether administrative (claims) databases can be used to assess clinical variables and predict outcome. Although administrative databases are useful for assessing resource utilization, their utility for assessing clinical information is less certain. Prospectively gathered clinical databases, however, are expensive and not widely available. The UB92 formulation of the hospital bill was used as an administrative source of data and compared with the clinical cardiovascular database at Emory University. The claims database was compared with the clinical database for 11 variables. Outcome models were developed with multivariate methods. A total of 11,883 patients who underwent catheterization (5,255 underwent percutaneous transluminal coronary angioplasty [PTCA] and 3,794 underwent coronary artery bypass surgery [CABG]) between 1991 and 1995 were included. For some variables, the claims database correlated well (diabetes, sensitivity 87%, specificity 99%), whereas for others the claims database was less accurate (peripheral vascular disease, sensitivity 20%, specificity 99%). Uncertain coding in the claims database, which can result in the same code being used for co-morbid states and severity of disease, as well as complications, limited the ability of claims to predict outcome. Clinical databases may also be limited by lack of objectivity and missing data. The utility of claims databases to assess severity of disease and co-morbid states is limited, and outcome modeling and risk assessment from claims databases may be inappropriate and spurious. Developing better data standards and less expensive methods for acquisition of clinical data is necessary for improved outcome assessment.

Cardiovascular Diseases↗
PubMed1999

Accuracy of EEG dipole source localization using implanted sources in the human brain.

OBJECTIVES: The location of electrical sources in the brain can be estimated by calculating inverse solutions in which the location, amplitude and orientation of the electrical sources are fitted to the scalp EEG. To assess localization accuracy of the moving dipole inverse solution algorithm (ISA), we studied two patients who had depth electrodes implanted for presurgical planning of epilepsy surgery. METHODS: Artificial dipoles were created by connecting a single sine wave pulse generator to different pairs of electrodes in multiple orientations and depths. Surface EEG recordings of the resulting pulses were evaluated with the ISA using a 4-shell spherical head model and plotted on the subjects' MRI. Dipole localization errors were evaluated with respect to the number of averaged pulses, different electrode montages and different dipole locations and orientations. RESULTS: Dipoles located at 40-57 mm from the scalp surface had localization errors that were greater than those located at 62-85 mm. Localization accuracy improved with increasing numbers of pulses and recording electrodes. Results with a standard 10-20 array of 21 electrodes showed an average localization error of 17 mm, whereas 41 electrodes improved this to 13 mm. Mean angular errors were 31 and 30 degrees, respectively. CONCLUSIONS: The ISA was able to differentiate between tangential and radial dipoles. We conclude that our implementation of the ISA is a useful and sound method for localizing electrical activity in the brain.

Brain↗
PubMed1998

The outcome of tendon transfers for C6-spared quadriplegics.

The purpose of this study was to review retrospectively and evaluate a uniform group of C6-spared quadriplegics who had similar surgical procedures. Eight patients undergoing 12 procedures were reviewed at an average of 3.8 years follow-up. There were three bilateral procedures. All patients had extensor carpi radialis longus to flexor digitorum profundus and brachioradialis to flexor pollicis longus transfers to improve grip strength and key pinch. All patients reported subjective improvements in quality of life, activities of daily living and patient-centred goals. There were six excellent and two good results. Objective improvements included mild improvements in key pinch and grip strength.

Activities of Daily Living↗
PubMed1996

Mutagenic analysis of 2,3-diaminophenazine and 2-amino-3-hydroxyphenazine in Salmonella strains expressing different levels of O-acetyltransferase with and without plant and mammalian activation.

2,3-Diaminophenazine (DAP) and 2-amino-3-hydroxyphenazine (AHP) are products generated from oxidative-type phenylenediamine hair dyes and are also present in pesticide formulations as contaminants. Earlier studies demonstrated that DAP and AHP were mutagenic in Salmonella typhimurium strains after mammalian microsomal activation. Plant systems can activate structurally similar arylamines. S. typhimurium strains have been developed that express elevated levels of acetyl-CoA: N-hydroxyarylamine O-acetyltransferase (OAT). O-acetyltransferase expression is necessary for the generation of the ultimate arylamine promutagen after plant activation. A number of arylamines including 2-aminofluorene, benzidine and 4-aminobiphenyl were activated by plant cells into mutagens in the OAT over-expressing S. typhimurium strain, YG1024. The objectives of this research were to examine the mutagenicity of DAP and AHP with mammalian or plant activation in Salmonella strains with different acetyltransferase activities. The hypothesis tested was whether and to what degree a metabolite of DAP or AHP could serve as a substrate for bacterial O-acetyltransferase and induce mutation in Salmonella. DAP and AHP without activation induced both frameshift and base pair substitution mutations in S. typhimurium strains that exhibited elevated levels of O-acetyltransferase activity. The mutagenicity of DAP and AHP were greatly enhanced with mammalian hepatic microsomal activation resulting in a preferential induction of frameshift mutations. With the hisD3052 allele as the gene target, S9-activated DAP induced frameshift mutations in YG1024 and TA98 as well as the OAT deficient strain TA98/1,8-DNP6. S9-activated AHP induced mutation only in the OAT over-expressing strain, YG1024. With the hisG46 allele, O-acetyltransferase activity was necessary for the metabolism of DAP and AHP to products that induce base pair substitution mutations. An intriguing finding of this work was the antimutagenic capacity of TX1MX, a plant cell-free activation mixture. TX1MX repressed the mutagenic activity of DAP and AHP at frameshift and base pair substitution mutation targets.

Acetyltransferases↗
PubMed1996

How useful is thyroid function testing in patients with recent-onset atrial fibrillation? The Canadian Registry of Atrial Fibrillation Investigators.

BACKGROUND: Patients with recent-onset atrial fibrillation often undergo routine thyroid function screening to rule out thyroid disease as a cause of atrial fibrillation. METHODS: Patients with recent (< 3 months) onset of documented atrial fibrillation or flutter were enrolled in the Canadian Registry of Atrial Fibrillation from outpatient clinics, emergency departments, and hospital wards across Canada. Seven hundred twenty-six patients underwent baseline thyroid function screening and were assessed for presence of clinical thyroid disease. Serum thyrotropin level (TSH) was measured in 707 patients (97%), and thyroxine level (T4) in 407 patients (56%). RESULTS: A TSH level less than 0.1 mU/L was present in 5 patients (0.7%). A TSH level less than normal but more than 0.1 mU/L was present in 34 patients (4.7%). No patient had definite hypothyroidism (TSH > 20 mU/L), but 56 patients (7.7%) had an elevated TSH level that was less than 20 mU/L. During 1.7 years of follow-up, only 7 patients were found to have clinical hyperthyroidism, and 11 patients (1.5%) had hypothyroidism. Logistic regression analysis showed that palpitations (odds ratio, 4.9; 95% confidence interval, 1.7-14.0) and asymptomatic presentation (odds ratio, 5.5; 95% confidence interval, 1.9-16.2) were risk factors for low TSH level, and increasing age (odds ratio, 1.32 every 10 years; 95% confidence interval, 1.01-1.66) was a risk factor for high TSH level. The positive predictive value of palpitations and asymptomatic presentation for low TSH level were 9% and 8%, respectively. CONCLUSIONS: An abnormal TSH level is common in patients with recent-onset atrial fibrillation. However, clinical thyroid disease is uncommon. Routine TSH screening of patients who have atrial fibrillation has a low yield and may be better applied to those patients at higher risk of having undiagnosed clinical thyroid disease.

Atrial Fibrillation↗
PubMed1996

Ageing is associated with changes in glutamate release, protein tyrosine kinase and Ca2+/calmodulin-dependent protein kinase II in rat hippocampus.

We have used synaptosomes prepared from rat hippocampus to investigate the role of protein tyrosine kinase and Ca2+/calmodulin-dependent protein kinase II in modulating glutamate release in young animals and to investigate possible parallel age-related changes in release and kinase activity. We report that depolarization of synaptosomes with 40 mM KCl, which stimulated glutamate release, also significantly increased activity of both kinases, while the protein tyrosine kinase inhibitor, genistein and the Ca2+/calmodulin-dependent protein kinase II inhibitor, KN62 (1-(N,O-bis[5-isoquinolinesulfonyl]-N-methyl-tyrosyl)-4-phenylpiperax ine) decreased K(+)-stimulated, Ca2(+)-dependent release of glutamate. K(+)-stimulated release of glutamate was significantly decreased in hippocampal synaptosomes prepared from aged, compared to young, animals. In parallel with these changes in release, we report an age-related decrease in activities of both protein tyrosine kinase and Ca2+/calmodulin-dependent protein kinase II. We conclude that these kinases play a role in modulating release of glutamate in hippocampus and that the age-related decrease in glutamate release may be partly due to an age-related decrease in kinase activities.

Aging↗
PubMed1996

Follow-up of atrial fibrillation: The initial experience of the Canadian Registry of Atrial Fibrillation.

Previous reports of the follow-up of patients with atrial fibrillation have been confusing because of the variety of clinical presentations, heterogeneity of underlying pathology, and the initiation of follow-up at various stages of the patient's disease. The Canadian Registry of Atrial Fibrillation (CARAF) is a non-interventional, follow-up study of patients enrolled at the time of their initial diagnosis with atrial fibrillation at seven Canadian centres. At baseline, a comprehensive database recorded clinical, laboratory, and echocardiographic variables. No specific intervention was initiated and care was left to the attending physicians. Follow-up was performed at 3 months, 1 year, then annually. Echocardiograms were repeated every 2 years. Recurrence of atrial fibrillation, medical intervention, stroke, death, and other significant events have been specifically recorded. To date, 967 patients have been enrolled. Seven hundred and sixty-seven patients have been followed for 1 year, 468 for 2 years, and 217 for 3 years. Several studies have been undertaken on these patients. One study compared the variables of patients who were symptomatic with those who were asymptomatic. This study demonstrated that symptoms were more likely to occur if the patient were younger, had high blood pressure and high ventricular response during atrial fibrillation, and were female. These all achieve statistical significance and a formula was developed to predict the probability of symptoms in different subgroups of patients. Antiarrhythmic drug use was evaluated. Sotalol and propafenone were the most commonly used drugs and their use increased when atrial fibrillation was recurrent. Many patients initially received no antiarrhythmic drugs. Trends suggest that therapy is more aggressive with recurrence of the arrhythmia. The prevalence of thyroid abnormalities was investigated utilizing sensitive TSH measurements. This showed that overt hyperthyroidism is rare (1%) but laboratory abnormalities and history of thyroid dysfunction occurred more frequently, in 19% of patients. Another study evaluated antithrombotic therapy. Factors known to increase stroke risk, including congestive heart failure, previous stroke, and large left atrium all increased the use of anticoagulants. Anticoagulants were used more frequently in patients over the age of 65 and in patients with recurrent or chronic atrial fibrillation. There was concern that hypertension, shown to be a high predictor of stroke, did not result in a significant use of warfarin. Aspirin use was common in patients not placed on anticoagulants. Further studies are being undertaken with the ultimate goal to utilize baseline data to predict clinical outcomes.

Anti-Arrhythmia Agents↗
PubMed1996

Co-dominant inheritance of hyperekplexia and spastic paraparesis.

In four generations of a family with autosomal dominant hyperekplexia (startle disease), untreated affected adult members had pes cavus and extensor plantar responses, as well as hyper-reflexia. Electroencephalography during a startle, electromyography, nerve conduction velocities and somatosensory evoked potentials were normal. Genetic studies showed linkage to the CSF1R locus on chromosome 5q33-q35, which includes the glycine receptor. This either represents a variant of hyperekplexia with spasticity or suggests that genes for hyperekplexia and a form of hereditary spastic paraparesis may be closely linked.

Adult↗
PubMed1996

Double blind placebo controlled trial of short term transdermal scopolamine on heart rate variability in patients with chronic heart failure.

OBJECTIVE: To test the hypothesis that short term application of transdermal scopolamine increases heart rate variability (HRV) and restores sympathovagal balance in patients with stable congestive heart failure (CHF). DESIGN: A double blind placebo controlled crossover study. SETTING: Tertiary referral centre. PATIENTS: Twelve patients (mean age 66 (10)) with New York Heart Association class II-IV CHF. All patients had coronary artery disease (mean left ventricular ejection fraction 26.7 (8.9) %). INTERVENTION: Patients were randomly assigned to receive either a placebo skin patch or a transdermal scopolamine patch (Transderm, 0.05 mg/h). Patches remained in place for 48 hours with a 24 hour washout period before crossover. OUTCOME MEASURES: HRV was derived from (a) 24 hour time domain indices (mean RR interval, standard deviation of interbeat interval, and the baseline width of the frequency distribution of RR intervals) and (b) short data set (2.2 mm) power spectral measurements using autoregressive modelling. Autospectral measures were performed in both resting supine and standing (orthostatic) states. The 24 hour Holter record was obtained during the second day of patch application. RESULTS: There was a small but significant (P < 0.05) increase in all time domain HRV variables with scopolamine. There was a paradoxical fall in low frequency (LF) spectral power induced by orthostasis during baseline (-30%) and placebo (-34%) states. Conversely, scopolamine was associated with a 14% increase in LF power during orthostatic stress. Scopolamine thus significantly reduced the orthostatic fall in LF (P < 0.01) compared with either baseline or placebo values. No difference in circadian rhythm was seen between the scopolamine and placebo treatment periods. However, the abrupt fall in the high frequency (vagal) power during the early morning sleep-wake hours was reduced by scopolamine. Scopolamine was also associated with a significant rightward shift in the resting LF central frequency consistent with a vagomimetic effect. CONCLUSION: Patients with chronic stable CHF showed a paradoxical fall in the low frequency (sympathetic) power during orthostatic stress. Transdermal scopolamine applied over a 48 hour period partially restored the balance between sympathetic tone and vagal activity in CHF patients and maintained this balance during orthostatic stress.

Administration, Cutaneous↗