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J M Smith

Publications and source records attributed to J M Smith.

At least 91 records · Page 5Linked to original sources
PubMed1999

Spectral analysis of periodic fluctuations in electrocardiographic repolarization.

Repolarization alternans (RPA) indicates alternate-beat fluctuations in the temporal or spatial characteristics of the echocardiogram (ECG) STU segment which may represent dispersion in repolarization. Spectral decomposition has revealed microvolt-level RPA which has been found to correlate with ventricular tachycardia (VT) and fibrillation, and is increasingly being used for clinical risk stratification. However, while interruptions in periodicity are known to affect spectral decomposition, their quantitative impact on RPA and its clinical utility have been poorly described. We therefore studied the effect of variable alignment, extrasystoles, dissimilar beats and beat exclusion on RPA magnitude in simulations and on the sensitivity and specificity of RPA for VT in a pilot clinical study. RPA magnitude was exquisitely sensitive to QRS alignment such that +/- 1 ms random beat misalignment reduced it by 68% in simulations. Correspondingly, suboptimal QRS alignment in clinical ECG's caused the sensitivity of RPA for inducible VT to fall from 93% to as low as 63%; while JT alignment was also less effective for RPA recovery. As an experiment in minimizing morphometric irregularities in clinical ECG's, we found that RPA magnitude actually fell when replacing either measurably dissimilar or ectopic beats with more representative beats. In addition, inserting or deleting beats also reduced RPA magnitude in clinical sequences and simulations. These statistical analyses suggest that the precision of beat alignment and interruptions to ECG periodicity, which may occur physiologically, may greatly reduce the clinical utility of RPA for VT. Dynamic alterations in RPA in response to sequence irregularities require further study before RPA may be optimally applied to screen for ventricular arrhythmias.

Chi-Square Distribution↗
PubMed1999

Differing rate dependence and temporal distribution of repolarization alternans in patients with and without ventricular tachycardia.

INTRODUCTION: Repolarization alternans (RPA) may reflect repolarization heterogeneities underlying VT, yet its temporal dynamics are poorly understood. We hypothesized that RPA occurring late, rather than early, within repolarization reflects a temporal variation in recovery that may predispose to wavefront fractionation and the initiation of reentrant VT, and that this temporal distribution may vary with heart rate. METHODS AND RESULTS: ECG leads I, aVF, and V1 were recorded in 40 patients during electrophysiologic study. RPA across the JT interval was computed spectrally for 64-beat sequences at paced cycle lengths (CLs) of 600, 500, and 400 msec, and expressed as the T wave alternans ratio (TWAR) on the vector ECG lead. Significant RPA (TWAR > or = 3) was reconstructed into the time domain, and its center of area used to represent its temporal distribution. Twenty-two patients were inducible into VT and 18 were not. RPA was of larger magnitude in inducible than noninducible patients (TWAR = 11.1 vs 4.42, P = 0.035; 38.3 vs 5.74, P = 0.004; and 88.8 vs 4.28, P = 0.001 in each, respectively), and was distributed later (P < 0.02; CL 600 msec). Applying TWAR > or = 3 to the distal half of the JT segment produced greater specificity for inducible VT (88.9%, 66.7%, and 69.2% at each CL, respectively) than did RPA of the entire JT segment (77.8%, 53.3%, and 69.2%). CONCLUSION: RPA is more specific for inducible VT when distributed late rather than elsewhere in repolarization, and this temporal distribution is heart rate sensitive. Further study is required to interpret these findings in the context of temporal dispersion of refractoriness.

Cardiac Pacing, Artificial↗
PubMed1998

Free recombination within Helicobacter pylori.

Sequences of three gene fragments (flaA, flaB, and vacA) from Helicobacter pylori strains isolated from patients in Germany, Canada, and South Africa were analyzed for diversity and for linkage equilibrium by using the Homoplasy Test and compatibility matrices. Horizontal genetic exchange in H. pylori is so frequent that different loci and polymorphisms within each locus are all at linkage equilibrium. These results indicate that H. pylori is panmictic. Comparisons with sequences from Escherichia coli, Neisseria meningitidis, and Drosophila melanogaster showed that recombination in H. pylori was much more frequent than in other species. In contrast, when multiple family members infected with H. pylori were investigated, some strains were indistinguishable at all three loci. Thus, H. pylori is clonal over short time periods after natural transmission.

Alleles↗
PubMed1998

Serotonergic modulation of eye blinks in cat and monkey.

Serotonergic modulation of spontaneous and reflexive blinking was studied in four cats and one monkey. In cats, facial nucleus injections of the type-2 serotonin receptor (5-HT2) antagonist ketanserin tended to increase the latency of the first (R1) and second (R2) components of the blink reflex to supraorbital nerve stimulation. Injections of serotonin tended to increase and of ketanserin, to decrease the duration and amplitude of R2. Serotonin also produced unilateral blepharospasm and hemifacial spasm. In the monkey, the 5-HT2 agonist 2,5-dimethoxy-4-iodoamphetamine increased spontaneous blink frequency while ketanserin decreased both peak blink velocity and spontaneous blink frequency. These findings in cat and monkey indicate that serotonergic innervation of the facial nucleus has a behaviorally important role in modulation of spontaneous and reflexive blinks and suggest that dysfunction of serotonergic systems could be important to the pathophysiology of some cases of blepharospasm.

Animals↗
PubMed1998

Estimating sample size for epidemiologic studies: the impact of ignoring exposure measurement uncertainty.

Sample size requirements for epidemiologic studies are usually determined on the basis of the desired level of statistical power. Suppose, however, that one is planning a study in which the participants' true exposure levels are unobservable. Instead, the analysis will be based on an imprecise surrogate measure that differs from true exposure by some non-negligible amount of measurement error. Sample size estimates for tests of association between the surrogate exposure measure and the outcome of interest may be misleading if they are based solely on the anticipated characteristics of the distribution of surrogate measures in the study population. We examine the accuracy of sample size estimates for cohort studies in which a continuous surrogate exposure measure is subject to either classical or Berkson measurement error. In particular, we evaluate the consequences of not adjusting the sample size estimation procedure for tests based on imprecise exposure measurements to account for anticipated differences between the distributions of the true exposure and the surrogate measure in the study population. As expected, failure to adjust for classical measurement error can lead to underestimation of the required sample size. Disregard of Berkson measurement error, however, can result in sample size estimates that exceed the actual number of participants required for tests of association between the outcome and the surrogate exposure measure. We illustrate this Berkson error effect by estimating sample size for a hypothetical cohort study that examines an association between childhood exposure to radioiodine and the development of thyroid neoplasms.

Adolescent↗
PubMed1998

Ulnar nerve injury associated with removal of Norplant implants.

Improperly placed Norplant implants pose a risk to neurovascular structures at the time of removal. Appropriate attention to insertion and removal should minimize the chance of injury. However, when injuries do occur, a logical and systematic approach to evaluation of the injury can help predict the outcome and establish a plan of care for the patient.

Adult↗
PubMed1998

Ketosis resistance in the male offspring of protein-malnourished rat dams.

Plasma beta-hydroxybutyrate concentrations were measured in the offspring of rats that were fed either a control (20% protein) diet or low-protein (8% protein) diet during pregnancy and lactation. Low-protein offspring had significantly lower plasma beta-hydroxybutyrate compared with controls in the fed state (P < .04) and after fasting for 24 hours (P < .001) and 48 hours (P < .04). There were no differences in blood glucose, acetoacetate, plasma glucagon, cholesterol, or glycerol between control and low-protein offspring. However, plasma nonesterified fatty acids (NEFAs) were significantly higher in low-protein offspring in the fed state (P < .05). In contrast, plasma triglycerides and insulin were significantly lower in low-protein offspring compared with controls when fed (P < .001) and after a 24-hour fast (P < .001). These results suggest that poor maternal and early postnatal nutrition can have long-term effects on ketone body metabolism in the offspring during adulthood. This apparent ketosis resistance is similar to that observed in some forms of human diabetes.

3-Hydroxybutyric Acid↗
PubMed1998

Asthma and allergic rhinitis in adoptees and their adoptive parents.

BACKGROUND: Since the highest risk for the development of atopic disease is in early life, environmental risk factors need to be separated from the genetic component in this high risk period. Adoptees removed at birth and placed in adoptive families present a way to separate environmental and genetic factors at this early susceptible age. METHOD: An opportunity for a pilot study of asthma and allergic rhinitis in adoptive families was presented when a psychiatrist (RC) was planning a behavioral study of young adult adoptees and their adoptive parents. A detailed questionnaire about allergic rhinitis and asthma was added after the psychiatrists' interview. Placement was not influenced by a history of allergy in adoptive or natural parents. The adoptee and at least one adoptive parent completed questionnaires in 367 families. The adoptees had been removed at birth and placed in the adoptive family within 3 months (83% within 1 month). RESULTS: Compared with adoptive families without asthma or allergic rhinitis, an adoptive mother with asthma or rhinitis, when the adoptive father was not affected, increased the risk for asthma in the adoptee (OR = 3.2, P < .0005). Asthma in the adoptive mother alone (OR = 3.2, P < .005) and allergic rhinitis alone (OR = 3.4, P < .005) increased the risk for asthma in the adoptee. Adoptive father asthma or allergic rhinitis showed a trend toward increased asthma in the adoptee (OR = 1.9, P < .1). CONCLUSION: This should be considered a pilot or feasibility study since subjects could not be examined or tested. Finding a risk for atopic respiratory disease or asthma associated with adoption by parents with asthma or allergic rhinitis suggests that further well planned adoptee studies should be made.

Adoption↗
PubMed1998

Is eye padding routinely necessary after uncomplicated phacoemulsification?

PURPOSE: To investigate the value of eye padding following uncomplicated phacoemulsification under peribulbar anaesthesia. METHODS: A prospective randomised controlled study was conducted to compare the effect of a conventional eye pad and shield with that of a clear eye shield applied without a pad in 83 patients undergoing routine phacoemulsification under peribulbar anaesthesia without lid block. The primary outcome measures were corneal fluorescein staining, discomfort, diplopia and mobility. RESULTS: Moderate or severe corneal fluorescein staining on the first post-operative day was significantly more common in the pad and shield group (39%) than in the clear shield group (19%) (p < 0.01). There was no significant difference in post-operative pain as measured either by visual analogue scale or by categorical pain scale. Forty per cent of the clear shield group reported transient post-operative diplopia during the immediate post-operative period compared with 7% of the pad and shield group (p < 0.001). There was no significant difference in reported mobility between the two groups. CONCLUSIONS: Following phacoemulsification under peribulbar anaesthesia, the use of a gauze eye pad is associated with greater corneal fluorescein staining than a clear plastic shield without pad and offers no reduction in discomfort. A clear shield protects the globe against direct trauma, is associated with reduced moderate to severe corneal staining and facilitates vision in the early post-operative period. Transient diplopia reported by some patients given a clear shield is not disabling and would not be expected to occur in patients with one seeing eye. The use of a clear shield alone is a safe alternative to eye padding and offers important advantages in patients with one seeing eye.

Aged↗
PubMed1998

Beat-to-beat repolarization lability identifies patients at risk for sudden cardiac death.

INTRODUCTION: Recent studies have implicated repolarization lability in the genesis of malignant ventricular arrhythmias. However, few data exist on assessment of temporal QT interval variability and its relation to arrhythmogenesis. We tested the ability of the QT variability index (QTVI), a measure of beat-to-beat QT interval fluctuations measured on a single ECG lead, to identify patients presenting with malignant ventricular arrhythmias and predict their subsequent occurrences. METHODS AND RESULTS: We measured the QTVI in 95 patients presenting for electrophysiologic study (EPS). The ability of the QTVI to identify patients with sudden cardiac death (SCD) or sustained monomorphic ventricular tachycardia (MVT) on presentation and during follow-up of 23.7+/-14.3 months was compared with spatial QT dispersion, T wave alternans ratio during atrial pacing, MVT inducibility at EPS, signal-averaged ECG, heart rate variability, and ejection fraction. The QTVI was higher in patients with heart disease than in controls (-0.7+/-0.7 vs -1.1+/-0.5, P < 0.05), and higher in patients presenting with SCD than in other patients with heart disease (0.0+/-0.6 vs -0.8+/-0.5, P < 0.05). The QTVI was the only clinical variable that identified patients who presented with SCD (P = 0.004, odds ratio = 12.5) on stepwise, logistic multiple regression. Fourteen patients had arrhythmic events during follow-up. In a Kaplan-Meier analysis of arrhythmic events, QTVI> or =0.1 was a discriminator for higher risk of arrhythmic events (P < 0.05). CONCLUSIONS: (1) This noninvasive measure of temporal repolarization lability identified patients with SCD and predicted arrhythmia-free survival. (2) Further studies are needed to determine the mechanisms that mediate beat-to-beat QT interval variability.

Death, Sudden, Cardiac↗
PubMed1998

Schistosome satellite DNA encodes active hammerhead ribozymes.

Using a computer program designed to search for RNA structural motifs in sequence databases, we have found a hammerhead ribozyme domain encoded in the Smalpha repetitive DNA of Schistosoma mansoni. Transcripts of these repeats are expressed as long multimeric precursor RNAs that cleave in vitro and in vivo into unit-length fragments. This RNA domain is able to engage in both cis and trans cleavage typical of the hammerhead ribozyme. Further computer analysis of S. mansoni DNA identified a potential trans cleavage site in the gene coding for a synaptobrevin-like protein, and RNA transcribed from this gene was efficiently cleaved by the Smalpha ribozyme in vitro. Similar families of repeats containing the hammerhead domain were found in the closely related Schistosoma haematobium and Schistosomatium douthitti species but were not present in Schistosoma japonicum or Heterobilharzia americana, suggesting that the hammerhead domain was not acquired from a common schistosome ancestor.

Animals↗
PubMed1998

The aetiology of developmental defects of enamel: a prevalence and family study in East London, U.K.

The aim of this study was to investigate genetic and environmental factors associated with hypoplastic defects of enamel in a detailed family study combined with an overall prevalence study. 68 percent of 1,518 children with a "complete" permanent dentition had enamel defects, 14.6 percent having hypoplasia. The Family Study consisted of 101 Index Cases from the Prevalence Study having 2 or more teeth with hypoplasia and their first degree relatives: they were compared with 101 matched controls and their relatives. The clinical examinations were supplemented with structured interviews to obtain social, medical and dental histories. Three Index Cases had amelogenesis imperfecta and 18 had "chronological hypoplasia". Bilateral hypoplasia of lower central incisors had a multifactorial aetiology (heritability 70 percent +/- 38 percent), while hypoplasia of pre-molars was associated with familial occurrence of defects. There was evidence suggesting a predisposition in some families to developmental defects of enamel.

Adolescent↗
PubMed1998

Pelvic fractures.

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Fractures, Bone↗
PubMed1997

Janus kinase-dependent activation of insulin receptor substrate 1 in response to interleukin-4, oncostatin M, and the interferons.

In addition to a role in response to insulin and insulin-like growth factors, insulin receptor substrate 1 (IRS-1) is phosphorylated in response to IL-4, the interferons (IFNs) and oncostatin M (OSM). Here mutant cell lines lacking JAK1, JAK2, or Tyk2 were used to determine the role(s) of the Janus kinase (JAK) family of protein-tyrosine kinases in IRS-1 phophorylation. 32D cells, which do not express IRS proteins, were analyzed for any requirement for these proteins in response to the IFNs. For the mutant human fibrosarcoma cell lines, phosphorylation of IRS-1 through the insulin-like growth factor receptor is independent of JAK1, JAK2, or Tyk2. In contrast, phosphorylation of IRS-1 mediated by the Type I IFNs, IL-4, and OSM is JAK-dependent. For the alphabeta-IFNs, activation of IRS-1 is dependent on JAK1 and Tyk2, consistent with the interdependence of these kinases in the IFN-alphabeta response. Neither IRS-1 nor IRS-2 was detectably activated by IFN-gamma. Consistent with this, activation of neither IRS proteins appears to be an absolute requirement for an antiproliferative or an antiviral response to the IFNs. For IL-4 and OSM phosphorylation of IRS-1 in the human fibrosarcoma cells is largely dependent on JAK1 but can also be mediated through Tyk2 or JAK2. Activation of phosphatidylinositol 3'-kinase in response to IL-4 and OSM, at least, was also JAK-dependent. The JAKs are, therefore, required not only for STAT activation but also for the activation, through a variety of different types of cytokine receptor, of an additional signaling pathway(s) through IRS-1 and phosphatidylinositol 3'-kinase.

Cell Division↗