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Biomedical subjects

C Young

Publications and source records attributed to C Young.

At least 127 records · Page 7Linked to original sources

Cingulate cortex synaptic terminal proteins and neural cell adhesion molecule in schizophrenia.

The neuronal organization and patterns of afferent innervation are abnormal in the cingulate cortex in schizophrenia, and associated changes in synaptic terminals could be present. A panel of monoclonal antibodies was defined with biochemical and fusion protein studies as detecting syntaxin (antibody SP6), synaptophysin (antibody SP4) and synaptosomal-associated protein-25 (antibody SP12). These antibodies and a polyclonal antibody reactive with neural cell adhesion molecule were used to investigate the cingulate cortex in schizophrenia. Immunocytochemistry indicated that syntaxin immunoreactivity had a considerably wider distribution than synaptophysin. Overall, multivariate analysis indicated increased synaptic terminal protein immunoreactivity in schizophrenia compared to controls (P=0.004). Controlled for age and post mortem interval, syntaxin immunoreactivity was significantly elevated in schizophrenia (P=0.004), and neural cell adhesion molecule immunoreactivity was also elevated (P=0.05). The neural cell adhesion molecule to synaptophysin ratio was increased (P=0.005), possibly indicating the presence of less mature synapses in schizophrenia. Elevated syntaxin immunoreactivity is consistent with increased glutamatergic afferents to the cingulate cortex in schizophrenia, and combined with the neural cell adhesion molecule to synaptophysin ratio results suggests that synaptic function in this region in schizophrenia may be abnormal.

Antigens↗

Radiosurgery for arteriovenous malformations: the University of Toronto experience.

BACKGROUND: From July 1989 to February 1996, 130 patients underwent stereotactic radiosurgery. We report the results of the first 50 patients eligible for a minimum of three years of follow-up. METHODS: Twenty women and 30 men, (mean age: 37.5 years) were treated by dynamic rotation on a 6 MV linear accelerator. Prior treatment was embolization in seventeen, surgery in three and embolization and surgery in six. All had DSA and enhanced CT scanning, while some had MRI. Forty-seven treatments used a single isodose. Restricting eloquent normal tissue to 15 Gy, margin doses (at 50-90% isodose) were 12 Gy (one patient); 15 Gy (sixteen patients); 20 Gy (31 patients); 25 Gy (two patients). Maximum diameters were: < 1.5 cm (12 patients); < 2.0 cm (nine patients); < 2.5 cm (twelve patients); < 3.0 cm (thirteen patients; 3.0 cm (four patients). RESULTS: Forty-five patients were evaluable at three years, with thirty-nine having angiography. Twenty-five had angiographically confirmed obliterations; two had parenchymal AVMs obliterated but with residual dural components; four had MRI evidence of obliteration (refused angiography). One patient acutely had a seizure; one patient (with hemorrhages, resection, and embolizations preceding two applications of radiosurgery, separated by 3.5 years) had worsening of memory. CONCLUSIONS: Our uncorrected (five patients unevaluable at three years) and corrected angiographically confirmed obliteration rates are 54% and 60% respectively. Our follow-up (98% accounting of cohort; 78% angiographic rate) and explicit derivation of denominators help delineate the efficacy of radiosurgery at these doses.

Adult↗

Prediction of obliteration of arteriovenous malformations after radiosurgery: the obliteration prediction index.

OBJECTIVE: To describe the response to single dose photon stereotactic radiosurgery of arteriovenous malformations (AVMs) so that the probability of success or failure of treatment may be predicted for the individual patient. METHOD: The obliteration prediction index (OPI) was calculated for AVMs by dividing the marginal dose of radiation in Gray (Gy) by the lesion diameter in centimetres in cohorts of 42 patients treated with the modified linear accelerator at Toronto-Sunnybrook Regional Cancer Centre and 394 patients treated with the gamma unit at the Royal Hallamshire Hospital, Sheffield, United Kingdom. Patients were grouped into ranges by OPI and the proportion of success and failure was calculated for each group. An exponential function [P = 1-A.e(-B.OPI)] was fitted to the data by the least squares method. RESULTS: Despite systematic differences in radiation treatment, that is, marginal doses of 15 and 20 Gy in Toronto and most Sheffield patients with a marginal dose of 25 Gy, the resultant data points exhibited similar behaviour. CONCLUSION: The function [P = 1-A.e(-B.OPI)] partly describes the biological effect of radiation and is independent of the radiation device used. Radiosurgery centres can use this model to facilitate predictions of successful treatment for individual patients.

Follow-Up Studies↗

Predictors of psychological adjustment to genetic testing for Huntington's disease.

In the present study the authors assessed predictors of adjustment to genetic testing for Huntington's disease. Fifty-two genetically positive and 108 genetically negative persons were studied for 1 year following testing. Adjustment, defined by hopelessness and depressive symptoms, was measured at 3, 6, 9, and 12 months after disclosure and was within normal limits for both groups. Those less well adjusted had tested positive, were married, had no children, or were closer to their estimated ages of onset. The study delineated risk factors for psychological distress that should be considered by people contemplating testing for Huntington's disease.

Adaptation, Psychological↗

Utrophin abundance is reduced at neuromuscular junctions of patients with both inherited and acquired acetylcholine receptor deficiencies.

Congenital myasthenic syndromes are a heterogeneous group of conditions in which muscle weakness resulting from impaired neuromuscular transmission is often present from infancy. One form of congenital myasthenic syndrome is due to a reduction of the number of acetylcholine receptors (AChRs) at the neuromuscular junction. We describe four new cases of AChR deficiency, characterized by a reduction in both miniature endplate potential amplitude and AChR abundance accompanied by elongation of the neuromuscular junction and some decrease in postsynaptic folding. A number of cytoplasmic proteins are normally associated with the postsynaptic membrane and may contribute to the clustering of AChRs at the neuromuscular junction. We therefore investigated the expression of several of these proteins in these AChR-deficiency patients. In each patient, immunolabelling of the neuromuscular junction for rapsyn, dystrophin, beta-dystroglycan and a form of beta-spectrin was strong but that for utrophin was markedly reduced or absent. This suggested that a defect in utrophin expression might underlie the congenital AChR deficiency. However, a reduction in utrophin labelling was also seen in three patients with adult acquired autoimmune myasthenia gravis in whom AChR loss results directly from the extracellular binding of autoantibodies. We conclude that the loss of AChRs in AChR deficiency does not result from the absence of rapsyn or beta-dystroglycan and that reduction of utrophin is probably secondary to the loss of AChRs. The possible role of AChRs and/or utrophin in determining the extent of postsynaptic folding is discussed.

Action Potentials↗

Fatty acid compositions of colostrum, cord blood, maternal blood and major infant formulas in Japan.

Lipid profiles in colostrum, cord blood, maternal blood and major infant formulas in Japan were analyzed. In the first part of the study, colostrum obtained from 36 normal delivery women and six kinds of infant formulas provided by three major milk companies were analyzed for their fatty acid composition using capillary gas-lipid chromatography. Although enriched with docosahexaenoic acid (DHA), the percent composition of DHA in the six infant formulas (0.15-0.21%) was significantly lower than that in the colostrum (1.1 +/- 0.54). Arachidonic acid (AA) and eicosapentaenoic acid (EPA) were present in the colostrum but not detectable in the infant formulas. It is recommended that although the exact amount of specific fatty acids needed in the infant diet was not completely known, to be as close as possible to natural breast milk, the level of DHA, EPA and AA should be raised in the infant formulas. In the second part of the study, 19 pairs of maternal and cord blood were analyzed for their lipid profile. All samples were from normal vaginal delivery. The measurement of cholesterol, triglycerides, phospholipids and free fatty acids was performed with commercially available enzymatic methods on an automated discrete random access analyzer. Total fatty acid was determined as described in the first part of the study. The results were analyzed with Spearman's rank correlation coefficient. No correlation could be found between maternal and fetal concentrations of cholesterol, triglycerides, phospholipids or total fatty acids. Correlation could be found in non-esterified fatty acids, in palmitic acids, and oleic acid levels. It was concluded that the lipid transport and metabolism in the fetal-placenta unit is complex and further delicate investigation is required.

Adult↗

An update on Australia's future population growth and its population problems.

"Population projections need to be continually updated as new information becomes available.... With an assumption of a total fertility rate of 1.865 children per woman and annual net migration of 50,000, ABS [Australian Bureau of Statistics] projections published in 1996 and additional projections in 1997 suggest a population of 24.5 million in 2051 and an ultimate population of more than 25 million. The analysis in this article...puts Australia's various population problems into a proper perspective and tries to direct attention away from the unnecessary preoccupation with population decline."

Australia↗

A Philadelphia chromosome positive CML patient with a unique translocation studied via GTG-banding and fluorescence in situ hybridization.

The Philadelphia (Ph) chromosome was the first consistently occurring chromosome abnormality associated with a single cancer type, chronic myelogenous leukemia (CML). This translocation has since been reported with other chromosome abnormalities. The present report describes a case of Ph chromosome positive CML with a unique complex translocation identified using molecular cytogenetics in addition to routine techniques. GTG-banding revealed abnormalities in at least chromosomes 9, 13, 17, and 22. Fluorescence in situ hybridization (FISH) studies were performed as an adjunct to conventional cytogenetic analyses. Using FISH with the Oncor bcr/abl probe, the Ph translocation previously hypothesized was confirmed. Applying FISH with paired painting probes in various combinations, a complex translocation involving chromosomes 9, 13, 15, 17, and 22 was observed. The results of the GTG-banding and FISH studies were compared with each other and correlated with those of the hematological findings. In an extensive search of the medical literature database (Medline, Health, Cancerlit, Ovid, and CINAHL) spanning nearly three decades (1965-1994), we found no previous report of this specific translocation. Therefore, to the best of our knowledge, this is a unique translocation associated with Ph chromosome positive CML.

Aged↗

Correlation of P-wave polarity with underlying electrophysiologic mechanisms of long RP' tachycardia.

Analysis of surface electrocardiograms from patients with long RP' tachycardia due to either atypical atrioventricular node reentrant tachycardia, permanent junctional reciprocating tachycardia, or low atrial tachycardia was performed. Although a negative P wave in the inferior leads is common to all 3 mechanisms, the results suggest that a positive or isoelectric P wave in electrocardiographic lead I strongly supports a diagnosis of atypical atrioventricular node reentrant tachycardia, whereas a negative or biphasic P wave in lead I argues against this mechanism.

Adult↗

Spectrum of electrophysiologic and electropharmacologic characteristics of verapamil-sensitive ventricular tachycardia in patients without structural heart disease.

Verapamil-sensitive ventricular tachycardia (VT) is a well-recognized clinical entity that some authorities believe may result from triggered activity. Despite its uniform response to verapamil, however, there is evidence that this uncommon form of VT may not be as homogeneous as first believed. Standard intracardiac electrophysiologic techniques were used to study verapamil-sensitive VT in 32 patients (aged 38 years +/- 20 years) without evidence of structural heart disease. More than half of these patients (69%) exhibited VT with a right bundle branch block-type QRS pattern, with the remainder (31%) displaying VT with a left bundle branch block pattern. In 31% of the patients the VT could be induced by fixed-cycle length atrial pacing, whereas in 59% of patients fixed-cycle length ventricular pacing was necessary. A critical range of cycle lengths for VT induction was required in 66% of the patients. Ventricular tachycardia was initiated with single atrial premature extrastimuli in 16% of patients, single ventricular extrastimuli in 50% of patients, and double ventricular premature extrastimuli in 9% of patients. Ventricular tachycardia displaying cycle-length alternans was observed in 28% of patients. In only 19% of patients was it possible to entrain VT during pacing from the right ventricular apex. Isoproterenol infusion was required for tachycardia induction in 50% of patients, 44% of whom had VT with a left bundle branch block QRS pattern, with the remaining 56% exhibiting VT with a right bundle branch block pattern. Beta-adrenergic blockers suppressed 53% of verapamil-sensitive VT in patients tested, whereas adenosine terminated VT in 50% of patients, with 81% of these patients exhibiting either a left bundle branch block QRS pattern or isoproterenol dependence. Ventricular tachycardia exhibiting a left bundle branch block pattern was more likely to be isoproterenol dependent (p <0.05) and adenosine sensitive (p <0.001). However, verapamil-sensitive, catecholamine-dependent VT was no more likely to be adenosine sensitive than the catecholamine-independent form of the arrhythmia (p >0.5). Verapamil-sensitive VT exhibits properties expected of both a reentrant and triggered arrhythmia, and it is inconsistently dependent on both exogenous catecholamines for induction and intravenous adenosine for termination. Verapamil-sensitive VT encompasses a heterogeneous group of tachycardias that may result from multiple cellular electrophysiologic mechanisms.

Adenosine↗

Are young people leaving home earlier or later?

"Although the popular view is that young people are leaving home later, a closer investigation of [Australian] data from 1979 to 1995 shows that this is not entirely true. Decreases are observed in the proportion of 15-19 year old men and women living at home at least since the mid-1980s, the increase for 20-24 year old men ceased in 1990, and only 20-24 year old women show a sustained increase. If only unattached young adults are considered instead of the conventional measure, any increases are even more subdued. The overall trend seems to be that while late leavers may be leaving home later, early leavers are leaving earlier or at the same time."

Adolescent↗

Audiogenic seizures following global ischemia induced by chest compression in Long-Evans rats.

Transient global ischemia was used to produce a rat model of generalized tonic-clonic epilepsy. Controlled chest compression in ketamine-anesthesized Long-Evans rats produced transient global ischemia by mechanically preventing the heart from pumping blood. Circulation was restored by standard cardiopulmonary resuscitation techniques. With a temporal muscle (skull) temperature of 35 +/- 0.4 degrees C, 75% (76/102) of the rats survived 7 min of chest compression. Generalized seizures could be evoked in 78% (59/76) of the surviving rats by a 60 s exposure to a loud sound (bell, 110 dB) beginning 24 h after the ischemic episode. The seizure patterns seen resembled those described by Maresceaux (1987) for genetically seizure-prone Wistar rats. Susceptibility to sound-induced seizures declined with time, with wide variations in recovery rate between individuals; one rat showed a daily sound-induced seizure for over 5 months. Seizures were attenuated or blocked by treatment with carbamazepine or sodium valproate. This model is similar to the great vessel occlusion model used by Kawai et al. (1995), but is less invasive. We believe it will be useful in the evaluation of therapies for acquired generalized (grand mal) seizures.

Acoustic Stimulation↗

Ventricular pacing threshold and refractoriness after defibrillation shocks in patients with implantable cardioverter-defibrillators.

The aim of this study was to examine the effect of ventricular fibrillation and a subsequent defibrillation shock on ventricular excitability and refractoriness in human beings. We studied 16 consecutive patients with implantable cardioverter-defibrillators undergoing follow-up studies. The pre- and post-shock pacing threshold, ventricular effective refractory period, monophasic action potential duration, and serum catecholamine levels were measured. Compared with the baseline state, immediately after ventricular fibrillation, and a successful defibrillation shock: (1) the ventricular effective refractory period decreased from 251 +/- 24 ms to 222 +/- 30 ms (p < 0.01), (2) the monophasic action potential duration decreased from 210 +/- 16 ms to 179 +/- 23 ms (P < 0.01) at 50% repolarization and from 274 +/- 24 ms to 240 +/- 26 ms (P< 0.01) at 90% repolarization, (3) the pacing threshold was not significantly altered and, (4) serum levels of epinephrine and norepinephrine were elevated. These results show that although ventricular fibrillation and subsequent defibrillation had no effect on the ventricular pacing threshold in human beings, it was associated with a decrease in post-shock monophasic action potential duration and ventricular effective refractory period, contrary to some previously reported findings.

Action Potentials↗

Localization of the origin of the atrioventricular junctional rhythm induced during selective ablation of slow-pathway conduction in patients with atrioventricular node reentrant tachycardia.

During radiofrequency catheter ablation of slow atrioventricular node pathway conduction in patients with atrioventricular node reentrant tachycardia, an atrioventricular junction rhythm is frequently observed. The origin and relation to ablation success of this junctional rhythm was examined in this study. By using standard intracardiac electrophysiology techniques, we studied the radiofrequency energy-induced atrioventricular junctional rhythm in 43 consecutive patients with atrioventricular node reentrant tachycardia undergoing selective ablation of slow-pathway conduction. The frequency of atrioventricular junctional activity was correlated with successful and unsuccessful attempts at ablation of slow-pathway conduction. Also, we compared the sequence of retrograde atrial activation of radiofrequency energy-induced atrioventricular junctional beats in a subgroup of 22 patients with the retrograde activation sequence observed during pacing from the right ventricular apex and the site of successful ablation of slow-pathway conduction. A total of 201 radiofrequency-energy applications was delivered in 43 patients with > or = 5 atrioventricular junctional beat(s) induced during 110 (55%) of 201 ablation attempts. Atrioventricular junctional activity was noted during 98% of successful ablations but only 43% of the unsuccessful attempts (sensitivity, 98%; specificity, 57%; negative predictive value, 99%). The mean time to appearance of atrioventricular junctional beats was 8.8 +/- 4.1 sec (mean +/- SD) after the onset of radiofrequency-energy application. In 22 (100%) of 22 patients in whom detailed atrial mapping was performed, the retrograde atrial activation sequence of the radiofrequency-induced atrioventricular junctional beats was earliest in the anterior atrial septum, identical to that seen during pacing from the right ventricular apex. Earliest retrograde atrial activation was at the posterior septum in all patients during pacing from the successful ablation site, a markedly different activation pattern compared with that seen during either radiofrequency ablation or ventricular pacing. Whereas the occurrence of atrioventricular junctional activity during radiofrequency ablation does not necessarily herald a successful ablation of slow atrioventricular node pathway conduction, its absence strongly suggests that the energy is being applied in an unsuccessful fashion. Furthermore, it appears that radiofrequency energy-induced atrioventricular junctional beats originate not from the endocardium in contact with the ablating catheter tip but instead appear to exit remotely from the anterior atrial septal region. This finding supports the existence of specialized tissues in the atrioventricular junction that preferentially transmit the effects of radiofrequency energy to an anterior exit site, possibly identical to the atrial exit site of the retrograde fast atrioventricular node conduction pathway.

Atrioventricular Node↗