PubMed Health⌕ Search

Biomedical subjects

J Windle

Publications and source records attributed to J Windle.

At least 19 recordsLinked to original sources
PubMed2003

The maximum A posteriori approach to the inverse problem of electrocardiography.

In this paper we investigate the previously proposed maximum a posteriori (MAP) approach to the problem of determining epicardial potentials from measured body surface potentials, a form of the inverse problem of electrocardiography. The MAP inverse approach uses a priori knowledge of the covariances between epicardial electrograms in its estimate of epicardial potentials. However, in practice, this information is not generally available. In this paper we examined the effectiveness of this method when the covariances are estimated using one depolarization sequence and the MAP method is used with these covariances to estimate the epicardial potentials for a different depolarization sequence.

Algorithms↗
PubMed2000

Potential risk of vasovagal syncope for motor vehicle driving.

Vasovagal syncope is the most common cause of syncope, but its risk for driving remains uncertain. We analyzed the clinical characteristics of patients who had syncope during driving and subsequently underwent the head-up tilt test (HUTT). Of the 245 consecutive patients undergoing HUTT, 23 (9%) had > or =1 episode of syncope during driving. HUTT was positive in 19 (group A) and negative in 4 (group B) patients. No patient had structural heart disease. In group A, the driving incident occurred on the first syncope in 3 patients, and the other 16 patients had 1 to 4 episodes of prior syncope not associated with driving. In group B, the driving incident occurred on the first syncope in 1 patient, and the other 3 patients had prior syncope (3 episodes in each) not associated with driving. Seven group A and 1 group B patients had 2 syncope-related driving incidents, and the remaining patients had only 1 syncope-related driving incident. The syncope-related driving incidents caused personal injury in 7 group A and 2 group B patients. One incident in 1 group A patient caused the death of another driver. After HUTT, all but 1 patient in group A received medical treatment and only 1 patient in group B received empirical beta-blocker therapy. During the follow-up of 51+/-26 months, 1 patient died and another was lost to follow-up. Of the remaining patients, 4 patients had recurrence of syncope and 2 patients had presyncope in group A. One of these patients had another syncope-related driving incident. No group B patient had syncope recurrence. A second etiology of syncope was never found in any patient. We conclude that vasovagal syncope during driving is not uncommon in patients referred for syncope evaluation. Early medical attention to patients with vasovagal syncope may help reduce syncope-related driving incidents.

Adolescent↗
PubMed1998

Evaluation and management of atrial fibrillation in the emergency department.

AF is the most common sustained cardiac arrhythmia. Recognition and appropriate management of AF is important to optimize care of concurrent medical problems and prevent long-term consequences. DC cardioversion under sedation should be performed in patients with pulmonary edema, angina, or hypotension. Ventricular rate control is the first choice in stable patients with rapid ventricular rate. Anticoagulation should be considered in all patients with AF duration < 48 hours, except for those under 65 years old and having no other risk factors of stroke. Recent data imply that early attempts at cardioversion may increase success rates and decrease AF recurrence rates. Thus, transesophageal echocardiogram-guided early cardioversion may become more widely used.

Adrenergic beta-Antagonists↗
PubMed1998

The mean ventricular fibrillation cycle length: a potentially useful parameter for programming implantable cardioverter defibrillators.

In programming the implantable cardioverter defibrillator (ICD), the ventricular tachycardia (VT) detection cycle length (CL) is based on the CL of the documented tachycardia but the ventricular fibrillation (VF) detection CL is set arbitrarily. Appropriate programming of VF detection may not only reduce the incidence of inappropriate ICD shocks for non-VF rhythms but can also avoid the fatal underdetection of VF. The mean VFCL may provide a useful parameter for optimal ICD programming for VF detection if it is reproducible. This study examined the intrapatient reproducibility and interpatient variation of the mean VFCL in 30 ICD patients (25 men and 5 women, mean age 63 +/- 13 years). A total of 210 VF episodes (7 +/- 4 per patient, range 3-17) induced by T-wave shocks (166) or AC (44) at the ICD implant (30 patients) and the predischarge test (12 of 30 patients) were analyzed. The mean VFCL was calculated from the stored V-V intervals in the ICDs. Although the mean VFCL varied significantly from 171 +/- 6 to 263 +/- 11 ms (P < 0.01) among different patients, it was reproducible among different VF episodes in an individual patient (maximal variation 4-50 ms, P > 0.05). The mean VFCL was not significantly different between patients with and without antiarrhythmic drugs (210 +/- 32 vs 210 +/- 23 ms, P > 0.05) and was correlated with the ventricular effective refractory period (r = 0.5, P < 0.05). The mean VFCL varies greatly among different patients but remains reproducible in an individual patient, suggesting that the mean VFCL may serve as a reference for ICD programming of VF detection.

Adult↗
PubMed1996

Metazoan rDNA enhancer acts by making more genes transcriptionally active.

Enhancers could, in principle, function by increasing the rate of reinitiation on individual adjacent active promoters or by increasing the probability that an adjacent promoter is activated for transcription. We have addressed this issue for the repetitive metazoan rDNA enhancer by microinjecting Xenopus oocytes with enhancer-less and enhancer-bearing genes and determining by EM the frequency that each gene type forms active transcription units and their transcript density. We use conditions where transcription requires the normal rDNA promoter and is stimulated 30-50-fold by the enhancer. (In contrast, at saturating template conditions as used in previous EM studies, an aberrant mode of transcription is activated that is not affected by the rDNA enhancer or by the generally recognized rDNA promoter). The active transcription units on enhancer-less genes are found to be as densely packed with nascent transcripts and polymerases as those on enhancer-bearing genes and on the endogenous rRNA genes. Significantly, the enhancer-bearing genes are approximately 30-50-fold more likely to form such active transcription units than enhancer-less genes, consistent with their amounts of transcript. Complementary studies confirm that the enhancer does not affect elongation rate, the stability of the transcription complex, or transcript half-life. These data demonstrate that the repetitive metazoan rDNA enhancer causes more genes to be actively transcribed and does not alter the reinitiation rate on individual active genes.

Animals↗
PubMed1996

Trilateral tumors in four different lines of transgenic mice expressing SV40 T-antigen.

PURPOSE: A line of transgenic mice containing the simian virus (SV) 40 T-antigen (T-ag) gene driven by the beta-luteinizing hormone (BLH) promoter developed bilateral retinoblastoma and primitive neuroectodermal tumors (PNET) of the midbrain. Midbrain tumors arose from the subependymal layer of the cerebral aqueduct. Bilateral ocular and brain tumors ("trilateral") were found in three other SV40 T-ag transgenic murine lines containing different promoters (murine interphotoreceptor retinoid-binding protein (IRBP), human IRBP, and alpha A-crystallin). To gain insight into the regulatory mechanisms involved in central nervous system tumorigenesis, the authors examined brain tumors from four lines of SV40 T-ag mice with different promoters. METHODS: Formalin-fixed brain tumors were examined from four lines of transgenic mice containing different promoters linked to the protein coding region of the enhancerless SV40 T-ag oncogene. Transgenes contained the following promoters: BLH, mouse 1.8-kb IRBP, human 1.3-kb IRBP, and alpha A-crystallin. RESULTS: Mice with a 1.8-kb IRBP promoter develop retinal photoreceptor and pineal tumors. Intracranial tumors arising from the subependymal layer of the third ventricle also were observed. Mice with a 1.3-kb IRBP promoter exhibit bilateral retinal PNET and PNET originating from the subependymal layer of the third ventricle. Mice with the alpha A-crystallin promoter exhibit bilateral lens tumors and PNET of the midbrain. CONCLUSIONS: Ocular tumors in these mice may be ascribed to the promoter-driven, tissue-specific expression of SV40 T-ag. The common finding of PNET arising from the subependymal layer of the diencephalon is unlikely to be promoter related. These findings indicate that a regulatory region specific to the subependymal layer of the cerebral aqueduct and third ventricle resides in the structural region of the SV40 T-ag gene.

Animals↗
PubMed1996

Local carboplatin therapy in transgenic murine retinoblastoma.

PURPOSE: To determine the efficacy and toxicity associated with intraocular delivery of carboplatin in the treatment of murine transgenic hereditary retinoblastoma. METHODS: Forty-eight transgenic BLH-SV40 Tag retinoblastoma mice were administered five intravitreal injections of carboplatin in one eye. After 12 weeks, the eyes were examined histopathologically to evaluate tumor burden. Twelve rabbits were administered intravitreal injections of carboplatin in one eye, after which they underwent serial electroretinography. All experimental and control eyes were obtained for histopathology and electron microscopy. RESULTS: A dose-dependent inhibition of intraocular tumor growth by carboplatin was observed in transgenic retinoblastoma mice. Tumor development was inhibited in 50% of the mouse eyes at doses of 1.4 micrograms. In rabbits, retinal toxicity resulted when intravitreal injections of carboplatin were administered at doses of 10 micrograms or higher. CONCLUSIONS: Local delivery of carboplatin in serial doses effectively inhibits intraocular tumor growth in a dose-dependent manner in transgenic murine retinoblastoma.

Animals↗
PubMed1995

Importance of a non-dominant right coronary artery occlusion presenting as sudden cardiac death with prolonged right ventricular dysfunction and malignant arrhythmias.

We report a case of a patient who presented with sudden cardiac death secondary to a subtotal occlusion of a small non-dominant right coronary system. Catheterization several weeks following the initial episode revealed persistent severe right ventricular dysfunction with moderate hemodynamic compensation. Continued unstable arrhythmogenic potential at this point led to placement of an AICD device. The case highlights the potential hazard and often complacency involved in dealing with benign appearing lesions as this one.

Arrhythmias, Cardiac↗
PubMed1995

Erythromycin induced torsades de pointes.

Erythromycin is a widely used antibiotic in today's armamentarium of antibiotics. Although erythromycin induced ventricular tachyarrhythmia is rare, this potentially life-threatening reaction should be kept in mind. The relative rarity of 'torsades de pointes' arrhythmia suggests that other predisposing factors contribute to the acquired long QT syndrome. Since more and more macrolide products have been approved by the Food and Drug Administration for use in the United States, the potential problem with 'torsades de pointes' may exist with each of the macrolide antibiotic. Until the exact mechanisms of the arrhythmia are worked out, close monitoring of rhythms and QT intervals of high risk patients who require erythromycin is certainly advisable. Only a heightened awareness among the physicians and medical personnel can the adverse outcome be minimized.

Erythromycin↗
PubMed1992

Gonadotropin-releasing hormone neuronal cell lines.

Gonadotropin-releasing hormone (GnRH) cell lines were developed by genetically targeted tumorigenesis in transgenic mice. The cell lines designated GT1 cells have a neuronal phenotype, express neuronal but not glial markers and express the GnRH gene at high levels. The GnRH prohormone is processed in the cells to multiple molecular forms including biologically active GnRH and GnRH-associated peptide. Basal secretion of GnRH from the cells is regulated in part by fast Na+ channels necessary for propagated action potentials. In many instances, basal GnRH release is pulsatile with an interpulse frequency similar to that seen in castrated rodents, suggesting that GnRH neurons are the pulse generator and are capable of synchronizing their secretion in vitro. The secretion of GnRH is stimulated by depolarization and by the neurotransmitter norepinephrine. In related studies we have demonstrated that expression of Simian virus 40 T antigen in GnRH neurons of transgenic mice leads to hypothalamic hypogonadism due to the inability of GnRH nerve terminals to organize in the median eminence. These findings support the use of genetically-directed tumorigenesis to establish highly differentiated GnRH neuronal cell lines that are a valuable model to study the cell biology and regulation of the neurons.

Animals↗
PubMed1988

Signal-averaged electrocardiograms in patients with atrial fibrillation or flutter.

The signal-averaged QRS complex that is prolonged because of low amplitude late potentials predicts ventricular tachycardia. This study investigated if signal-averaged low amplitude atrial potentials predict atrial fibrillation or flutter (AFF). Low amplitude potentials were considered to be high-frequency, high amplitude P (HiFP) duration recorded between 50 and 250 Hz at 1.0 mm/microV amplitude minus unfiltered P (UnFP) duration at 0.1 mm/microV. In nine normals, HiFP averaged 115.6 msec +/- 9.8 SD. HiFP were wider in 26 control patients (133.5 msec +/- 15.7, p less than 0.005) but HiFP-UnFP (11.2 msec +/- 8.5) and signals less than 10 microV terminating HiFP inscription (21.7 msec +/- 23.4) were similar to normal values. Seventeen patients with paroxysmal or recently cardioverted AFF did not have significantly longer intervals than controls (HiFP averaged 138.8 msec +/- 23.0, HiFP-UnFP 13.2 msec +/- 9.3, and signals less than 10 microV 32.4 msec +/- 19.5). Therefore, signal-averaged P waves do not identify patients with AFF.

Adult↗