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Biomedical subjects

C Young

Publications and source records attributed to C Young.

At least 145 records · Page 8Linked to original sources

Electrophysiologic significance of discrete slow potentials in dual atrioventricular node physiology: implications for selective radiofrequency ablation of slow pathway conduction.

Atrioventricular (AV) node reentrant tachycardia is now routinely cured by selective radiofrequency ablation of slow AV node pathway conduction. However, debate remains concerning the optimum method for localizing the site at which radiofrequency energy should be delivered to eliminate slow-pathway conduction. Some investigators have proposed simple anatomy-guided ablations posteriorly near the ostium of the coronary sinus, whereas others suggest an electrophysiology-guided ablation using either recorded "slow potentials" or mapping of the retrograde atrial exit site of slow AV note pathway conduction when possible. To examine these issues, we systematically studied slow potentials recorded in the AV junction of patients undergoing radiofrequency catheter ablation for medically refractory AV node reentrant tachycardia. In 67 patients with the slow-fast form of AV note reentrant tachycardia, we performed detailed atrial mapping along the tricuspid annulus within the triangle of Koch. Two types of slow potentials were identified. Low-amplitude, low-frequency potentials, found in 48% of patients, were localized to the mid to posterior portions of the triangle of Koch, whereas high-amplitude, high-frequency potentials, observed in 22% of patients, were located only posteriorly near the ostium of the coronary sinus. In response to a bolus infusion of adenosine or incremental atrial pacing-induced AV node Wenckebach periodicity, the low-amplitude, low-frequency potentials showed an increased duration and further reduction in amplitude and frequency and often totally disappeared. In contrast, in spite of these maneuvers, the high-amplitude and high-frequency potentials remained unchanged. Of the 25 (37%) of 67 patients in whom the earliest retrograde atrial activation during ventriculoatrial slow AV nodal pathway conduction could be recorded, no patient exhibited low-amplitude, low-frequency potentials, and only 7 (28%) of 25 of these patients showed high-amplitude, high-frequency potentials. High-amplitude, high-frequency potentials persisted after successful radiofrequency ablation of slow pathway conduction. Fewer applications of radiofrequency energy were required for successful elimination of slow pathway conduction in patients in whom the retrograde atrial exit site of slow-pathway conduction could be localized, compared with those patients who only exhibited retrograde fast AV nodal pathway conduction. We conclude that high-amplitude, high-frequency potentials are part of atrial activity, whereas the origin of low-amplitude, low-frequency potentials is unclear and may represent either true intranodal biophysical electrical activity or merely artifact or far-field potentials. Regardless, the recording of high-amplitude or low-amplitude potentials is not required for successful ablation of slow-pathway conduction, although the ability to localize the retrograde atrial exit of slow-pathway conduction may assist in the ablation procedure.

Adolescent↗

Who needs surveillance of the contralateral carotid artery?

BACKGROUND: Although the value of carotid endarterectomy has been proven, postoperative surveillance remains controversial. The purpose of this study was to determine the natural history of disease progression in the contralateral carotid artery by duplex surveillance, and to assess the cost of stroke prevention on this contralateral side. METHODS: Vascular laboratory records were reviewed to identify carotid endarterectomy patients who had two or more duplex studies between 1984 and 1995. Critical stenosis was defined as > or = 75% area reduction. RESULTS: In all, 324 patients were followed up with duplex scans for 1 month to 11 years (mean 30.3 months). The only factors that correlated with progression to critical stenosis were age and initial stenosis. Overall, 19.5% of patients progressed to critical stenosis within 5 years while the high-risk groups with age > 65 years or initial stenosis > or = 50% progressed to critical disease in 27% and 39%, respectively (P < or = 0.05). The cost per stroke prevented ranged from $143,500 to $418,200 when stratified by initial stenosis. CONCLUSION: Patients who have undergone a carotid endarterectomy demonstrate a propensity for progression of carotid stenosis in the unoperated (contralateral) artery. The cost/benefit ratio may be improved by varying the intensity of duplex surveillance of the contralateral carotid based on the patient's age and initial degree of stenosis.

Adult↗

Assessing myocardial perfusion with Albunex during coronary artery bypass surgery: technical considerations and safety of aortic root injections.

OBJECTIVE: To test the safety and report on limiting technical considerations, including optimal dosing of Albunex (Molecular Biosystems, Inc, Mallinckrodt Medical, St. Louis, MO) for myocardial opacification after intra-aortic root injections during cardiac surgery. DESIGN: This was a prospective randomized study with a control group who did not receive Albunex and a group who received intra-aortic root injections of Albunex. SETTING: Multicenter (two) independent university hospitals. PARTICIPANTS: 32 patients scheduled for elective coronary artery bypass surgery were evaluated after individual informed consent was obtained. INTERVENTIONS: 2 to 8 mL of Albunex were injected before and after coronary revascularization. MEASUREMENTS AND MAIN RESULTS: Quality of enhancement in each of four regions of the left ventricle was assessed from a short-axis mid-papillary ultrasound image by three experienced observers blinded to dose. Electrocardiogram (ECG), creatine phosphokinase (CPK) (MB fraction), and hemodynamics were evaluated at baseline and throughout the study period for up to 72 hours. No differences were noted between groups with respect to preoperative and postoperative CPK enzymes (CPK-MB fraction), ECG changes, hemodynamics, requirements for separation from CPB, need for postoperative inotropes, time to extubation, and time to discharge from the intensive care unit. The average total dose of Albunex injected was 19 mL +/- 4 (0.25 mL/kg). A single dose of 4.2 +/- 1.2 mL (0.05 mL/kg) appeared to offer optimal enhancement of contrast effect for myocardial perfusion assessment. CONCLUSION: Albunex is safe and easy to use for myocardial opacification when administered via an antegrade cardioplegia catheter into the aortic root during CPB.

Aged↗

Monoclonal B-cell population mimicking lymphoma in a patient with multiple sclerosis.

BACKGROUND: Diagnosis of intraparenchymal brain lesions has usually required invasive diagnostic procedures, because too few cells are shed into cerebrospinal fluid to permit cytologic diagnosis. Polymerase chain reaction technology makes it possible to identify cell populations that are present at a much lower frequency than traditional techniques. CASE REPORT: A young woman presented with multiple brain lesions raised the question of primary central nervous system lymphoma. Polymerase chain reaction analysis of cerebrospinal fluid showed evidence of a monoclonal B-cell population heightening suspicion of lymphoma. Brain biopsy showed acute demyelination most consistent with multiple sclerosis. CONCLUSION: Although T-cell restriction has been demonstrated in multiple sclerosis lesions, the finding of a monoclonal B-cell population was unexpected and to our knowledge has not been previously reported. This case emphasizes that monoclonality is not always indicative of a neoplastic process, particularly in the central nervous system.

Adult↗

Spatial relationships of utrophin, dystrophin, beta-dystroglycan and beta-spectrin to acetylcholine receptor clusters during postnatal maturation of the rat neuromuscular junction.

At the adult mammalian neuromuscular junction, acetylcholine receptors are concentrated at the tops of the postsynaptic folds and voltage-gated sodium channels are concentrated in their depths. It is likely that this arrangement involves linkage of the ion channels to components of the underlying membrane cytoskeleton. In rats, the mature distribution of acetylcholine receptors arises as part of the developmental remodelling of the junctional region during the first few weeks after birth. We have followed the changes during this period in the distribution of four proteins associated with the postsynaptic cytoskeleton at mature neuromuscular junctions (utrophin, dystrophin, beta-dystroglycan and beta-spectrin) to see if any of them co-localizes with acetylcholine receptors during the remodelling process, as would be required if it serves to link acetylcholine receptors to the cytoskeleton. Each protein was visualized with specific monoclonal antibodies and its distribution at various stages was compared with that of the acetylcholine receptors, labelled with alpha-bungarotoxin. We also related the changes in distribution of these postsynaptic proteins to the main stages in fold formation and, in the Discussion, to reported observations of the accumulation of voltage gated sodium channels during development. Our results show that utrophin labelling is closely co-localized with that of acetylcholine receptors throughout postnatal maturation. beta-dystroglycan labelling is present at most sites of high acetylcholine receptors density throughout maturation although it often extends beyond the region of highest acetylcholine receptors labelling density. By contrast, dystrophin and beta-spectrin labelling is not consistently concentrated at most neuromuscular junctions until after P7 and P14 respectively.

Age Factors↗

Cytochrome c oxidase deficiency in fibroblasts of a patient with mitochondrial encephalomyopathy.

Cytochrome c oxidase (CCO) deficiency is associated with various types of mitochondrial encephalomyopathy. The enzyme activities in different tissues and organs are varied. We report an 11-year-old girl with CCO deficiency, who presented with nystagmus, ptosis and optic atrophy. Her younger sister died of respiratory failure at 7 years of age and had the same initial clinical manifestations. Their parents were consanguineous. The girl had mild mental retardation and frequent premature ventricular contractions. Brain magnetic resonance imaging of the patient on admission revealed multiple lesions in both the gray and white matter. Except for arrhythmia and marked right axis deviation of the heart on electrocardiography, no other evidence of cardiac involvement was noted. Although a muscle biopsy was normal for both histochemical stains and electron microscopy, the enzyme assays in cultured skin fibroblasts revealed partial CCO deficiency, which may explain the clinical presentations.

Arrhythmias, Cardiac↗

Cardiac arrest-induced global cerebral ischemia studied in vitro.

The goal of the present study was to characterize the effects of chest compression-induced global cerebral ischemia on the hippocampal slice preparation. One of the characteristics of rats exposed to such cardiac arrest is a high susceptibility to sound-induced seizures. We tested audiogenic seizures as an in vivo indicator of ischemic cerebral damage and as a possible small animal model of epilepsy. The results of these tests were reported elsewhere. Long-Evans male rats (200-350 g) were subjected to 7 min of chest compression sufficient to stop the pumping action of the heart. The rats were then revived using cardiopulmonary resuscitation. Evaluation of cerebral damage following cardiac arrest and resuscitation was performed in vitro, by testing neuronal responses to electrical stimulation in hippocampal slices prepared from these animals. Sham control animals were used for comparisons. Twenty-one to 146 days after rats were chest-compressed, hippocampal slices were prepared. Sham control rats, anesthetized but not chest-compressed, were sacrificed one week later for preparation of slices. Rats in a second group exposed to 7-min chest compression, were sacrificed at different time intervals after their resuscitation (from 1 h to 7 days); hippocampal slices were prepared for electrophysiological analysis of neuronal damage. The results of these studies indicate that 3 weeks or longer after chest compression the evoked CA1 population spike amplitude in hippocampal slices was significantly attenuated; in 60% of these slices an epileptiform response was evoked. An increased proportion of slices prepared from rats 1 to 48 h after chest compression showed an augmentation in the amplitude of the evoked population spike; 72 h and up to 7 days after chest compression, an attenuation in the evoked CA1 population spike amplitude was observed, signaling delayed neuronal damage.

Animals↗

Early, but not late, antiepileptic treatment reduces relapse of sound-induced seizures in the post-ischemic rat.

Global ischemia was used to induce a sensitivity to sound-triggered generalized seizures in 24 male Long-Evans rats. All showed a generalized seizure when exposed to a 108 dB bell for 1 min. They were assigned randomly to 3 groups of 8, and received 30 additional sound exposures. The early treatment group was injected with valproate (200 mg/kg i.p) 1 h prior to each of the first 10 sound exposures. The late treatment group received the same treatment during the second set of 10 sound exposures after 10 sound exposures without treatment. The third group was untreated. Both early and late treated groups had a significant reduction in seizure incidence during the treatment period, i.e. both groups showed seizure control. However, in the late group seizures returned promptly when valproate treatment was discontinued, while the early group showed a sustained reduction in seizure susceptibility. Since this outcome corresponds to seizure remission, the findings of this study favor early treatment.

Acoustic Stimulation↗

Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6.

The Axl receptor tyrosine kinase was identified as a protein encoded by a transforming gene from primary human myeloid leukaemia cells by DNA-mediated transformation of NIH 3T3 cells. Axl is the founding member of a family of related receptors that includes Eyk, encoded by a chicken proto-oncogene originally described as a retroviral transforming gene, and c-Mer, encoded by a human proto-oncogene expressed in neoplastic B- and T-cell lines. The transforming activity of Axl demonstrates that the receptor can drive cellular proliferation. The function of Axl in non-transformed cells and tissues is unknown, but may involve the stimulation of cell proliferation in response to an appropriate signal, namely a ligand that activates the receptor. We report here the purification of an Axl stimulatory factor, and its identification as the product of growth-arrest-specific gene 6 (ref. 6). This is, to our knowledge, the first description of a ligand for the Axl family of receptors.

Amino Acid Sequence↗

Flumazenil may attenuate some subjective effects of nitrous oxide in humans: a preliminary report.

Two double-blind, randomized, crossover trials were conducted to study whether the benzodiazepine antagonist, flumazenil, would interact with the subjective and psychomotor effects of nitrous oxide in healthy volunteers. In both experiments, eight subjects inhaled 30% nitrous oxide in oxygen for 35 min and were challenged, 10 min into the inhalation, with flumazenil. Experiment 1 tested a range of flumazenil doses used clinically (0, 0.25, 0.5, and 1.0 mg/70 kg) whereas Experiment 2 tested a supraclinical flumazenil dose (0 and 5.0 mg/70 kg). Nitrous oxide increased mood ratings of "high," "drunk," and "tingling," and decreased psychomotor performance as assessed by the Digit Substitution Test. Flumazenil, at the supraclinical dose, significantly lowered the mood rating of "high." Decreases, though not significant (p < 0.10), were also obtained on the ratings "drunk," "elated," and "drug liking". Flumazenil, in both experiments, did not interact with the psychomotor effects of nitrous oxide. It appears that flumazenil, at a dose higher than that used clinically, may antagonize some of the subjective effects produced by nitrous oxide in humans.

Adult↗

Neurophysiologic studies and MRI in Pelizaeus-Merzbacher disease: comparison of classic and connatal forms.

Four patients with the classic form and 1 patient with the connatal form of Pelizaeus-Merzbacher disease were studied with magnetic resonance imaging, electroencephalography, and multimodal evoked potentials, including brainstem auditory evoked potentials, somatosensory evoked potentials, and visual evoked potentials. Comparisons between these findings were made. It was determined that the neurophysiologic studies, particularly brainstem auditory evoked potentials, are of value in early diagnosis of Pelizaeus-Merzbacher disease; brainstem auditory evoked potentials with only normal wave I may be a relatively reliable clue suggesting the classic form of Pelizaeus-Merzbacher disease in patients with nystagmus and chronic progressive encephalopathy. Magnetic resonance imaging allows an accurate assessment of the degree of hypomyelination; however, the clinical severity of various forms of Pelizaeus-Merzbacher disease seemed to be independent of the age of onset and the amount of residual myelin. The following may be distinguishing features between the connatal and classic forms of Pelizaeus-Merzbacher disease: hypoplasia of the cerebellum and brainstem, and diffuse brain atrophy on magnetic resonance imaging; optic atrophy with abnormal visual evoked potential; seizure disorder with abnormal electroencephalography, and/or auditory nerve impairment with abnormal wave I of brainstem auditory evoked potentials in the early stage of the disease.

Adult↗

Thenar hypoplasia in Klippel-Feil syndrome due to aberrant radial artery.

A 10-year-old boy with Klippel-Feil syndrome had progressive atrophy of the left thenar eminence and absence of left radial pulse. Neurophysiologic studies and angiography were normal. However, duplex sonography over the wrists revealed an aberrant left radial artery. We speculate that the thenar atrophy in this patient is congenital, which may be due to the anomaly of the left radial artery, and is further compromised by vascular compression in the thoracic outlet.

Child↗

CAG expansion affects the expression of mutant Huntingtin in the Huntington's disease brain.

A trinucleotide repeat (CAG) expansion in the huntingtin gene causes Huntington's disease (HD). In brain tissue from HD heterozygotes with adult onset and more clinically severe juvenile onset, where the largest expansions occur, a mutant protein of equivalent intensity to wild-type huntingtin was detected in cortical synaptosomes, indicating that a mutant species is synthesized and transported with the normal protein to nerve endings. The increased size of mutant huntingtin relative to the wild type was highly correlated with CAG repeat expansion, thereby linking an altered electrophoretic mobility of the mutant protein to its abnormal function. Mutant huntingtin appeared in gray and white matter with no difference in expression in affected regions. The mutant protein was broader than the wild type and in 6 of 11 juvenile cases resolved as a complex of bands, consistent with evidence at the DNA level for somatic mosaicism. Thus, HD pathogenesis results from a gain of function by an aberrant protein that is widely expressed in brain and is harmful only to some neurons.

Adult↗

Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons.

The gene defective in Huntington's disease encodes a protein, huntingtin, with unknown function. Antisera generated against three separate regions of huntingtin identified a single high molecular weight protein of approximately 320 kDa on immunoblots of human neuroblastoma extracts. The same protein species was detected in human and rat cortex synaptosomes and in sucrose density gradients of vesicle-enriched fractions, where huntingtin immunoreactivity overlapped with the distribution of vesicle membrane proteins (SV2, transferrin receptor, and synaptophysin). Immunohistochemistry in human and rat brain revealed widespread cytoplasmic labeling of huntingtin within neurons, particularly cell bodies and dendrites, rather than the more selective pattern of axon terminal labeling characteristic of many vesicle-associated proteins. At the ultrastructural level, immunoreactivity in cortical neurons was detected in the matrix of the cytoplasm and around the membranes of the vesicles. The ubiquitous cytoplasmic distribution of huntingtin in neurons and its association with vesicles suggest that huntingtin may have a role in vesicle trafficking.

Animals↗

Effects of ozone on the epithelial and inflammatory responses in the airways: role of tumor necrosis factor.

We have investigated the possibility that tumor necrosis factor alpha (TNF) plays a role in the increased airway permeability and an inflammatory response following an acute ozone (O3) exposure. Male Sprague-Dawley rats were injected, intraperitoneally, with either rabbit anti-mouse antibody to TNF (anti-TNF) or preimmune rabbit serum, 2 h before a 3-h exposure to O3 or purified air. Permeability, as determined by [99mTc] diethylenetriamine pentaacetate (DTPA) transport, total protein and albumin concentrations in the bronchoalveolar lavage (BAL), and the inflammatory cell response in the BAL were assessed 10 h after the exposure was completed. The O3-exposed group that was injected with anti-TNF showed a significant decrease in permeability to DTPA in comparison to the O3- exposed group injected with preimmune rabbit serum. There was no difference between the anti-TNF group and the purified air group. In contrast, the total protein and albumin levels in the BAL were significantly greater in both of the O3-exposed groups than in the purified air group. The concentrations of protein and albumin in the anti-TNF group did, however, show an attenuating trend when compared to the preimmune O3-exposed group. The polymorphonuclear leukocytes (PMNs) in BAL of the anti-TNF group also showed an attenuating trend when compared to the preimmune O3-exposed group, but both of these O3-exposed groups were significantly greater than the purified air group. Lung sections stained with naphthol AS-D chloroacetate esterase showed an increase in the number of stained PMNs in the anti-TNF group in comparison to the preimmune O3- and air-exposed groups. These data suggest that TNF plays a role in the increase in tracheal permeability as determined by DTPA transport, while the contributing role that TNF plays in bronchoalveolar permeability and the inflammatory response seen following an acute exposure to 0.8 ppm O3 is less evident.

Animals↗