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Biomedical subjects

R F Gilmour

Publications and source records attributed to R F Gilmour.

At least 55 records · Page 3Linked to original sources

Intraoperative anaphylaxis: an association with latex sensitivity.

Latex products have recently been identified as the cause of severe intraoperative anaphylactic reactions. We have identified a group of pediatric patients who appear to be at increased risk for such reactions. Fifteen patients with either spina bifida or congenital urologic abnormalities experienced 19 intraoperative anaphylactic reactions. All patients had frequent previous exposures to rubber materials since infancy as part of their management and/or investigative procedures. Seven of 15 patients had a previous history of local skin reactions to rubber. Only four patients were atopic. All patients had undergone multiple (two of 26) operative procedures before their reactions, the onset of which ranged from 40 to 290 minutes after induction of anesthesia. The reactions varied in intensity from urticaria to severe cardiorespiratory collapse. All these patients subsequently had positive allergy skin tests and positive RAST to latex antigen. We conclude that this group is at risk when they are exposed to latex intraoperatively as a result of frequent past exposure to these materials. Allergic evaluation for latex allergy may assist in the preoperative evaluation of similar patients. In sensitized patients, appropriate prophylactic measures, particularly the avoidance of latex, is required.

Adolescent↗

Low dimensional chaos in cardiac tissue.

Chaos is a term used to characterize aperiodic activity arising in a dynamical system, or in a set of equations describing the system's temporal evolution as a result of a deterministic mechanism that has sensitive dependence on initial conditions. Chaos, in that sense, has been proposed to make an important contribution to normal and abnormal cardiac rhythms. To date, however, descriptions of chaos in heart tissue have been limited primarily to periodically forced cardiac pacemakers. Because many cardiac rhythm disturbances, particularly those initiated or perpetuated by re-entrant excitation, originate from within non-pacemaker cardiac tissues, demonstrations of chaos in non-pacemaker tissue might provide a deterministic explanation for a wide variety of complex dysrhythmias. Here we report experimental evidence for chaotic patterns of activation and action potential characteristics in externally driven, non-spontaneously active Purkinje fibres and ventricular muscle. The results indicate that there is an apparent link between the mechanism of low dimensional chaos and the occurrence of reflected responses which could lead to more spatially disorganized phenomena. A detailed mechanism for the low dimensional chaos observed experimentally is pursued using a difference equation model. Critical features of the model include a non-monotonic relationship between recovery time during rhythmic stimulation and the state of membrane properties, and a steeply sloped recovery of membrane properties over certain ranges of recovery times. Besides explaining our results, the analytical model may pertain to irregular dynamics in other excitable systems, particularly the intact dysrhythmic heart.

Animals↗

Intraoperative anaphylaxis to latex.

This case report describes intraoperative anaphylaxis occurring in a fourteen-year-old female with spina bifida in which latex surgical gloves were incriminated as the aetiologic agent. The patient was non-atopic but since eight years of age she had developed localized angioedema and urticarial skin reactions on exposure to rubber. She had previously undergone several uneventful surgical procedures. Forty-five minutes following induction of anaesthesia and during laparotomy for elective cholecystectomy she experienced sudden onset of increased airway pressure, oxygen desaturation, tachycardia, profound hypotension and erythema consistent with an anaphylactic reaction. Resuscitation with manual ventilation and oxygen, intravenous fluids and an epinephrine infusion was successful. Subsequent investigations for allergies demonstrated a strongly positive skin prick test and RAST to latex antigen, with negative results to anaesthetic agents, antibiotics and inhalant allergens. During two later operations prophylaxis consisting of diphenhydramine, ranitidine and hydrocortisone appeared to prevent further reactions. Latex should be considered as a cause of life-threatening intraoperative allergic reactions in patients with a history of rubber allergy or frequent exposure to latex products.

Adolescent↗

High grade vesicoureteral reflux: analysis of observational therapy.

Between 1981 and 1987, 300 patients with high grade (III, IV and V international classification) vesicoureteral reflux were treated at a single pediatric hospital. Only patients with primary vesicoureteral reflux were included in the study. The guiding principle during this period was that all patients with high grade vesicoureteral reflux would be observed on prophylactic antibiotics (observational therapy) and surgical correction would be reserved for specific indications. Of the 300 patients 132 received observational therapy alone and 168 required surgical correction for specific indications after varying periods of observation. In both groups the duration of persistent reflux was analyzed using a life-table method. In patients with grade V reflux we observed resolution in 3 patients whereas 23 required surgical correction. Of those patients in the observation group with grade IV reflux 83% had persistent reflux at 2 years and 70% still had reflux at 5 years. For those with grade III reflux the persistence rate was 83% and 50%, respectively. Neither age, sex nor side of reflux had a correlation with the rate of resolution. When tested grade of reflux correlated loosely (p = 0.07). During the period of observational therapy new renal scars developed in 23 patients (8%). We conclude that high grade vesicoureteral reflux can resolve in a minority of patients over a protracted interval. On the basis of this analysis, we advocate consideration of surgical correction in these patients after a 4-year period of observational therapy and for specific indications.

Adolescent↗

Recent studies on the biological actions of vitamin D on intestinal transport and the electrophysiology of peripheral nerve and cardiac muscle.

Vitamin D, with parathyroid hormone and calcitonin, is an essential factor in the homeostatic regulation of systemic calcium in most vertebrate species. Targets for this aspect of vitamin D action, through its biologically active metabolites, are primarily the intestine, kidney and bone. Each of these tissues or organs are stimulated by 1,25(OH)2D3 to increase the transport calcium into the extracellular fluid compartment when plasma calcium levels are below normal and/or when there is a greater need for calcium to meet the requirements of physiological processes, such as growth, gestation and lactation. During such periods, the efficiency of the absorption of calcium from the intestine increases, the resorption of calcium salts from bone is stimulated, and the efficiency of the reabsorption of filtered calcium by the renal tubule is increased. In addition to the homeostatic function of vitamin D, there is an increasing amount of evidence that vitamin D has important effects on tissues and organs other than those concerned with calcium homeostasis. With regard to the intestinal epithelial system, the genomic effect of 1,25(OH)2D3 was shown several years ago when the de novo synthesis of a specific vitamin D-induced calcium-binding protein (CaBP, calbindin-D) was demonstrated. In our view, this appears to be an essential factor in the well-documented enhancement of calcium absorption by vitamin D. The function of calbindin-D, a high affinity calcium-binding protein, in the absorptive process is not precisely known but currently considered to act as an intracellular facilitator of the diffusion of calcium from the microvillar pole of the enterocyte to the basal-lateral membrane. There is evidence that vitamin D influences another step in the absorptive process. This step appears to be associated with the entrance of luminal calcium into the enterocyte, the first step in the transepithelial transport process. This response appears to occur relatively early (1 h or less) after 1,25(OH)2D3 is given to vitamin D-deficient animals, whereas the de novo synthesis of transport proteins has a much longer lag time (about 4 h). The in vitro absorption studies of Nemere et al (1984) and the in vivo experiments of our group (Wasserman et al, 1982) accentuate this point. However, the more rapid reaction, i.e., the possible modification of the permeability properties of the brush border membrane, does not result in a substantive increase in overall calcium absorption unless the enterocyte had been "primed" by previous exposure to vitamin D. The "priming" reaction might represent the synthesis of CaBP or some other intracellular component.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Depressant effect of magnesium on early afterdepolarizations and triggered activity induced by cesium, quinidine, and 4-aminopyridine in canine cardiac Purkinje fibers.

Magnesium chloride has been shown to terminate torsades de pointes in some patients with the acquired long QT syndrome. The mechanism for this effect is unknown. Recently early afterdepolarizations (EADs) and triggered activity (TA) have been proposed as causes of torsades de pointes. The purpose of the present study was to examine whether magnesium suppressed EADs that were initiated in vitro by different agents and if so its mechanism of action. TA arising from EADs was induced by quinidine (1 to 4 mumol/L, n = 5) at high temperature (38.5 to 40 degrees C), cesium chloride (5 to 12 mmol/L, n = 6), and 4-aminopyridine (1.5 to 5 mmol/L, n = 7) in canine cardiac Purkinje fibers superfused with modified Tyrode's solution (KCI = 2.7 mmol/L). MgCl2 (2 to 7 mmol/L) reversibly abolished TA and suppressed EADs. Tetrodotoxin (TTX; 1 to 5 mumol/L) also abolished TA elicited by 4-aminopyridine (n = 6). We then examined the effects of MgCl2, TTX, and verapamil on depolarization-induced automaticity by means of a single sucrose gap technique to gain insight into the mechanism of action of magnesium. MgCl2 (5 mmol/L) abolished automaticity arising from membrane potentials more negative than -70 mV and prolonged the spontaneous cycle length at less negative membrane potentials. The effects of TTX (1 to 5 mumol/L) resembled those of MgCl2. Verapamil (1 mumol/L) prolonged the cycle length of the initial automatic response at high levels of membrane potential and progressively reduced the amplitude of the subsequent automatic potentials. It abolished automaticity arising from less negative membrane potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗

OPC-88117 suppresses early and delayed afterdepolarizations and arrhythmias induced by cesium, 4-aminopyridine and digitalis in canine Purkinje fibers and in the canine heart in situ.

The effects of OPC-88117, a new investigational antiarrhythmic drug, on early and delayed afterdepolarizations (EAD and DAD, respectively) were assessed in vitro in canine Purkinje fibers and in vivo in the canine right ventricle. OPC-88117 had similar electrophysiologic properties to class I antiarrhythmic agents in that it decreased Vmax. OPC-88117 decreased the amplitude and prolonged the coupling interval of DAD induced by acetylstrophanthidin. Likewise, OPC-88117 suppressed EAD induced in vitro by 4-aminopyridine. In vivo, cesium-induced EAD, ventricular arrhythmia, and atrioventricular block were suppressed by OPC-88117. In summary, OPC-88117 suppressed DAD and EAD in vitro and inhibited EAD and triggered activity in the in situ canine heart.

4-Aminopyridine↗

Oscillations of diastolic interval and refractory period following premature and postmature stimuli in canine cardiac Purkinje fibers.

The effective refractory period (ERP) of His Purkinje tissue is known to oscillate following sudden changes in stimulus frequency. It has been proposed that the oscillation of ERP is caused by oscillation of the diastolic interval. This hypothesis was tested in vitro in canine cardiac Purkinje fibers superfused with normal and hyperkalemic (10 mM KCl) Tyrode's solution. The ERP of responses to premature stimuli, responses to postextrastimuli, and responses to postmature stimuli were measured. ERP of premature responses and postextrasystolic responses oscillated in normal Tyrode's solution. Oscillations of ERP of premature responses and postextrasystolic responses were damped in hyperkalemic Tyrode's solution. Determinations of the restitution of ERP as a function of diastolic interval revealed that oscillation of ERP of premature and postextrasystolic responses was for the most part predictable from the diastolic interval during superfusion with normal Tyrode's solution. In contrast, both hyperkalemic Tyrode's solution and postmature stimuli shifted the restitution curves, resulting in ERPs that were markedly longer than those predicted from the diastolic interval alone. Shifts in the restitution curves completely accounted for damping of the oscillation of ERP in hyperkalemic Tyrode's solution and with postmature stimuli. These data may relate to alterations of refractoriness during sudden changes in ventricular rate, such as occur during atrial fibrillation or ventricular tachycardia.

Animals↗

The enema continence catheter in spina bifida: successful bowel management.

Patients with spina bifida who have fecal incontinence are managed by means of a large-volume saline enema. To facilitate administration of the enema, a special catheter has been devised that prevents leakage of the enema fluid. Continence has been achieved in 112 children and youths with spina bifida who were managed in this fashion.

Adolescent↗

The anal sphincter force in health and disease.

The measurement of the strength of the anal sphincters has heretofore involved voluntary cooperation by the patient. In some children one cannot count on the maximum squeeze pressure being generated and in others the child is too young to understand what is required. We have devised an objective method of measuring the anal sphincter force (ASF) and have collected data derived from over 256 children over the course of 24 months. These include patients with Hirschsprung's disease, constipation, postoperative incontinence, spina bifida, and normal children both conscious and anesthetized. The results are presented and the value of the test and its applications are discussed.

Adolescent↗

Biological response of bladders rendered continent by insertion of artificial sphincter.

Artificial sphincters were inserted in 44 children for intractable urinary incontinence. Of the patients 70 per cent achieved satisfactory continence (minimum followup 18 months) with no revisions, and 10 per cent were rendered continent with 1 revision and 10 per cent with multiple revisions. The procedure failed in 10 per cent of the patients primarily because of infection. Extensive urodynamic studies were performed at reoperation and postoperatively. Long-term urodynamic followup was available in 36 continent children. Hydronephrosis occurred in 2 per cent of the upper tracts assessed and 18 per cent of the patients had significant residual urine. Mean bladder capacity tended to increase progressively postoperatively. Mean bladder compliance also was well maintained.

Child↗

Urodynamics.

Urologic problems constitute a very significant percentage of all clinical problems in pediatrics. Incorporation of urodynamic evaluation and followup is important in achieving optimal results in a significant number of these entities. In terms of cost effectiveness, it is particularly efficient in this age of extremely high-priced technology.

Adolescent↗

Overdrive suppression of conduction at the canine Purkinje-muscle junction.

We have shown previously that overdrive suppression of conduction in depolarized His-Purkinje tissue requires conduction asymmetry. In this study we examined whether overdrive suppression of conduction can occur at the Purkinje-muscle junction, where natural asymmetry of conduction exists. Canine Purkinje-muscle preparations were superfused with hyperkalemic Tyrode's solution (KCl 8 to 12 mM), and action potentials were recorded from Purkinje, junctional, and muscle cells. Initially, the Purkinje fiber was paced at the shortest cycle length at which 1:1 anterograde Purkinje-muscle conduction occurred. The papillary muscle then was paced for 10 to 50 beats at shorter cycle lengths during which, because of conduction asymmetry at the Purkinje-muscle junction, 1:1 retrograde muscle-Purkinje conduction also occurred. After overdrive papillary muscle pacing, Purkinje fiber pacing at the same cycle length that previously resulted in 1:1 conduction now produced transient Purkinje-muscle conduction block (overdrive suppression of conduction). The degree and duration of overdrive suppression of conduction were proportional to the rate and duration of overdrive pacing. After overdrive pacing, Purkinje cell action potential amplitude and Vmax recovered within 300 msec, yet conduction block persisted for up to 7 sec. In contrast, excitability in papillary muscle cells near the Purkinje-muscle junction increased continuously after overdrive pacing. These data suggest that rapid activation of Purkinje cells during overdrive pacing was not required for overdrive suppression of conduction and that restoration of conduction after overdrive pacing was determined primarily by recovery of excitability in papillary muscle cells. Transient Purkinje-muscle conduction block after periods of rapid ventricular rates might account for overdrive-induced conduction disturbances normally attributed to bundle branch block.

Action Potentials↗

Effects of 4-aminopyridine on rate-related depression of cardiac action potentials.

Canine cardiac Purkinje fibers and atrial trabeculae and rat and cat papillary muscles superfused with a hyperkalemic, hypoxic, and acidotic Tyrode solution were depolarized to membrane potentials (-70 to -60 mV) at which action potential amplitude declined as the coupling intervals of pacing stimuli were prolonged from 500 to 4,500 ms. The rate-related decline of action potential amplitude appeared to be due to time-dependent recovery of the early outward current rather than to a decrease in inward calcium current, since it was prevented by 4-aminopyridine (1.0 mM), but not by isoproterenol (1.0 microM), caffeine (5.0 mM), or CsCl (5-20 mM) and it was accompanied by an exponential increase of developed tension. Experiments using Purkinje fibers mounted in a single sucrose gap chamber demonstrated that the rate-related decline of action potential amplitude was maximal at membrane potentials between -70 and -40 mV and was negligible at less negative or more negative membrane potentials. These results may pertain to the mechanism for deceleration-dependent bundle branch block.

4-Aminopyridine↗

Effects of sympathetic tone on vagally induced phasic changes in heart rate and atrioventricular node conduction in the anesthetized dog.

We examined the effects of stellate ganglia stimulation on the phase-dependent chronotropic and dromotropic responses to brief vagal bursts in open-chest anesthetized dogs. Stellate stimulation affected the phasic vagal effects on heart rate by shortening the latent period, shifting the phase at which maximum decrease in heart rate occurred to earlier phases, and reducing the maximum decrease in heart rate. These effects were due primarily to an increase in the basic heart rate. No significant sympathetic-parasympathetic interaction occurred for heart rate, indicating that accentuated antagonism did not occur with brief vagal bursts. Stellate stimulation primarily decreased the amplitude of the phasic vagal effects on atrioventricular nodal conduction, regardless of the underlying heart rate, and a significant sympathetic-parasympathetic interaction was associated with this effect. The peak of the phase-dependent vagal effects on heart rate and atrioventricular nodal conduction were phase-shifted with one another. From these findings, we postulate the small changes in sympathetic tone might shift the predominant phase-dependent vagal effect from one on heart rate to one on atrioventricular nodal conduction. Furthermore, our results suggest that dynamic vagal control of heart rate and atrioventricular node conduction involves both phase-dependent and phase-independent factors. Sympathetic activity appears to affect only the phase-independent factor(s) in the control of heart rate, whereas it affects both phase-dependent and phase-independent factors in the control of atrioventricular node conduction.

Animals↗

Anaphylactoid and systemic reactions following saline enema administration. Six case reports.

This report describes six children with spina bifida who have experienced a total of 13 episodes of generalized hives, angioedema and in two cases, anaphylactoid reactions immediately following saline enema infusions. The enemas were administered using a kit comprised of a plastic bag, tubing, and rectal end-piece. The reactions always occurred with the first use of new kits. A third child developed a systemic reaction with only the rectal end-piece in situ and without infusion of fluid. An in-hospital challenge using a new end-piece in one patient, who was clinically the most sensitive, produced an acute anaphylactoid reaction implicating the end-piece as the most likely source of the problem. The definitive mechanism(s) of the reactions and the agent(s) responsible for them presently remain unknown.

Anaphylaxis↗