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Biomedical subjects

S Connolly

Publications and source records attributed to S Connolly.

At least 19 recordsLinked to original sources
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↗
PubMed1996

Skin lesion with a fatal neurologic outcome (Degos' disease)

Degos' disease, a rare multisystem vasculopathy of unknown etiology, only occasionally involves the nervous system. We report the Mayo Clinic experience of the neurologic features of Degos' disease in a series of 15 patients. All 15 patients had the typical skin lesions of Degos' disease, confirmed by skin biopsy. Ten patients developed neurologic manifestations including fatal hemorrhagic or ischemic strokes (n=5), disabling polyradiculoneuropathy (n=1), and nonspecific neurologic symptoms without objective findings (n=4). Results of laboratory tests varied but none were pathognomonic of the disease. Long-term follow-up revealed death in six patients; nine patients were nearly asymptomatic. Immunosuppressive and antiplatelet agents were not of benefit. CNS infarcts and hemorrhages with intravascular thrombi, but without evidence of vasculitis, were characterized features at autopsy.

Adolescent↗
PubMed1995

Neuromuscular effects of Papuan Taipan snake venom.

Snakebite is a cause of significant morbidity in Central Province, Papua New Guinea. Three adult patients with clinical evidence of neurotoxicity following envenomation by the Papuan taipan had serial neurophysiological examinations over the course of their subsequent hospitalization. All required artificial ventilation for 2.5 to 5 days. The compound muscle action potential (CMAP) amplitudes declined over the first 2 to 4 days after envenoming and then gradually increased in parallel with clinical recovery. Repetitive stimulation studies revealed a distinctive pattern of abnormality. Activation resulted in brief potentiation of the CMAP followed by significantly greater decrement than observed at rest. This effect lasted up to 30 minutes and was not altered after intravenous edrophonium. Single-fiber electromyographic recordings during the recovery phase of the illness were abnormal with marked blocking and increased jitter. All patients were able to return home.

Adult↗
PubMed1995

Neurophysiological assessment of peripheral nerve and spinal cord function in asymptomatic HIV-1 infection: results from the UCMSM/Medical Research Council neurology cohort.

As part of the Medical Research Council prospective study of the neurological complications of HIV infection, neurophysiological tests of spinal cord and peripheral nerve function were recorded in a cohort of homosexual or bisexual men. The studies included motor and sensory nerve conduction studies, vibration perception thresholds, somatosensory evoked potentials and motor evoked potentials elicited by magnetic stimulation. The results were compared with markers of immune function. The findings from 114 volunteers were analysed in a cross-sectional study. Fifty-nine were HIV-seropositive but asymptomatic, 26 had progressed to the symptomatic stages of HIV disease and 29 were persistently HIV-seronegative. There was some evidence of a mild sensory axonopathy in the symptomatic HIV-seropositive group. No differences were detected between the asymptomatic HIV-seropositive group and the HIV-seronegative comparison group. There were no consistently significant correlations between the neurophysiological measurements and CD4 counts and beta 2-microglobulin levels. On repeated testing, there was no evidence of a trend towards deterioration over a mean period of approximately 3 years in 36 HIV-seropositive subjects who remained asymptomatic compared with 22 HIV-seronegatives. These findings have failed to demonstrate neurophysiological evidence of spinal cord or peripheral nerve dysfunction in the asymptomatic stages of HIV infection.

Adult↗