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Biomedical subjects

P Bedard

Publications and source records attributed to P Bedard.

At least 19 recordsLinked to original sources
PubMed1991

Inhibitory and stimulatory effects of fluoride on the calcium pump of cardiac sarcoplasmic reticulum.

While studying the effects of membrane phosphorylation on active Ca2+ transport in cardiac sarcoplasmic reticulum (SR) we used NaF (a conventional phosphatase inhibitor) in the Ca2+ transport assay medium to suppress protein dephosphorylation by endogenous phosphatases. Unexpectedly, depending on the experimental conditions employed, NaF was found to cause a strong inhibitory or stimulatory effect on ATP-dependent, oxalate-facilitated Ca2+ uptake (Ca2+ pump) activity of SR. Investigation of this phenomenon using canine cardiac SR revealed the following. Exposure of SR to NaF in the absence of Ca2+ or ATP in the Ca2+ transport assay medium (prior to initiating Ca2+ transport by the addition of Ca2+ or ATP) promoted a striking concentration-dependent inhibitory effect of NaF (50% and 90% inhibition with approx. 4 and 10 mM NaF, respectively) on Ca2+ uptake by SR; the magnitude of inhibition did not differ appreciably with varying oxalate concentrations. In contrast, exposure of SR to NaF in the presence of both Ca2+ and ATP resulted in a concentration-dependent stimulatory effect of NaF (half-maximal stimulation at approx. 2.5 mM NaF with 2.5 mM oxalate in assay) on Ca2+ uptake; the magnitude of stimulation decreased with increasing oxalate concentration (greater than 2-fold at 1 mM oxalate, 10% at 5 mM oxalate). The inhibitory effect prevailed when SR was exposed to NaF in the presence of Ca2+ alone (without ATP) or ATP alone (without Ca2+). Both the inhibitory and stimulatory effects of NaF were specific to fluoride ion, as NaCl (1-10 mM) showed no effect on Ca2+ uptake by SR under identical assay conditions. A persistently less active state of the Ca2+ pump (evidenced by decreased Ca2+ transport rates) resulted upon pretreatment of SR with NaF in the absence of Ca2+ or ATP; presence of Ca2+ and ATP during pretreatment prevented this transition. The inhibitory action of NaF on the Ca2+ pump was accompanied by a two-fold increase in K0.5 for Ca2+ and decrements in Hill coefficient (nH) and Ca(2+)-stimulated ATP hydrolysis, as well as steady-state level of Ca(2+)-induced phosphoenzyme. The stimulatory effect of NaF, on the other hand, was associated with an increase in the ratio of Ca2+ transported/ATP hydrolysed with only minor changes, if any, in the above parameters. These findings imply that the divergent effects of fluoride are dependent on specific conformational states of the Ca(2+)-ATPase which evolve during the catalytic and ion transport cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1991

Comparison of accuracy of transesophageal versus transthoracic echocardiography for the detection of mitral valve prolapse with ruptured chordae tendineae (flail mitral leaflet).

The accuracy of transesophageal echocardiography was compared with that of transthoracic echocardiography in the detection of ruptured chordae tendineae (flail mitral leaflet) in 27 patients with mitral valve prolapse (MVP) who underwent valve repair or replacement for mitral regurgitation. Confirmation of the presence of ruptured chordae resulting in a flail leaflet was available at surgery in all cases. The echocardiographic studies were read blindly by 2 independent observers with any differences resolved by a third. Mean (+/- standard deviation) age was 63 +/- 13 years. Men (n = 20) outnumbered women (n = 7) (p less than 0.02), and tended to be younger (p = 0.06). Flail leaflets were identified in 20 of 27 patients. In 1 patient, both leaflets were involved and in the remaining 19 patients posterior leaflets (15 patients) were more frequently affected than anterior leaflets (4 patients). Transesophageal echocardiography correctly identified all 20 patients with flail leaflets, but 1 false positive study occurred among the 7 patients without a flail leaflet. In contrast, transthoracic echocardiography identified only 12 of 20 patients with flail leaflets, with no false positive studies. Transesophageal echocardiography was more accurate, correctly classifying 26 of 27 (96%) cases versus 19 of 27 (70%) by the transthoracic approach (p less than 0.01). This study suggests a higher incidence of chordal rupture to the posterior leaflet in patients with MVP and demonstrates improved accuracy of transesophageal over transthoracic echocardiography in the detection of flail leaflets.

Aged↗
PubMed1990

Severe mitral insufficiency post-balloon valvuloplasty: the late changes found in a disrupted mitral valve.

The case of a 45-yr-old woman who had balloon valvuloplasty for rheumatic mitral stenosis is presented. An anterior mitral leaflet tear occurred as a complication of the procedure. Both partial healing of the anterior mitral leaflet and gradual dilatation of the left atrium occurred which allowed the damaged valve to remain in situ for several months. Some of the late changes which occur after such a complicated valvuloplasty are illustrated here, as this patient eventually required surgery and valve excision for definitive repair.

Catheterization↗
PubMed1990

[Anatomo-physiologic substratum of akinesia in primates].

Severe akinesia can be observed in macaques following MPTP injections destroying dopaminergic nigrostriatal neurons. Akinesia also results from inhalation of toxic substances inducing bilateral lesions of the two pallidal nuclei and of the pars reticulata of the substantia nigra, and not of the pars compacta. Most of the recent studies of the anatomo-physiological substratum of akinesia used MPTP injections. Deoxyglucose studies have shown a clear increase in the neuronal activity of the medial nucleus of the pallidum and of its thalamic projection territory. Electrophysiological studies have shown a major modification of the spontaneous activity of medial pallidal neurons which is influenced in an excessive and non selective manner by sensorimotor inputs. Analysis of the relative three dimensional geometry of nervous arborizations have shown that the striato-pallido-nigral system is extremely convergent. Akinesia consecutive to nigrostriate lesions could be linked to an excessive and anarchic activation of this system. The contradiction which exists between akinesia with an abnormal activity of the medial pallidum and akinesia with bilateral pallidal lesions could only be apparent if akinesia was linked to the ineffective emission or to the interruption of messages to the thalamus.

Animals↗
PubMed1989

Regulation of the ATP-dependent calcium uptake activity of heart sarcolemmal vesicles by endogenous cytosolic proteins.

In a previous study we described the inhibitory action of a cytosolic protein fraction from heart muscle on ATP-dependent Ca2+ uptake by sarcoplasmic reticulum; further, this inhibition was shown to be blocked by an inhibitor antagonist, also derived from the cytosol (Narayanan et al. Biochim Biophys Acta 735: 53-66, 1983). The present study examined the effects of the endogenous cytosolic Ca2+ transport inhibitor and its antagonist on ATP-dependent Ca2+ uptake by sarcolemmal vesicles isolated from rat and canine heart. The cytosolic inhibitor caused strong inhibition (up to 97%) of Ca2+ uptake by sarcolemma (SL); this inhibition could be reversed by the cytosolic inhibitor antagonist. Studies on the characteristics of inhibition revealed the following: a) Inhibition was dependent on the concentration of the inhibitor (50% inhibition with approximately 80 micrograms inhibitor protein). b) The inhibitor reduced the velocity of Ca2+ uptake without appreciably influencing the apparent affinity of the transport system for Ca2+ but caused greater than 2-fold decrease in its apparent affinity for ATP. c) The rates of unidirectional passive Ca2+ release from actively Ca2+ loaded SL vesicles were not altered by low concentrations of the inhibitor (less than 100 micrograms/ml) which were effective in producing marked inhibition of Ca2+ uptake; at higher concentrations (greater than 100 micrograms/ml), the inhibitor caused increase in the rates of passive Ca2+ release. These findings demonstrate that the activity of the ATP-driven Ca2+ pump of cardiac SL can be regulated in vitro by endogenous cytosolic proteins.

Animals↗
PubMed1989

Effects of endogenous calcium transport inhibitor from heart muscle on the active calcium uptake and passive calcium release properties of sarcoplasmic reticulum.

In the present study, the effects of the cytosolic Ca2+ transport inhibitor on ATP-dependent Ca2+ uptake by, and unidirectional passive Ca2+ release from, sarcoplasmic reticulum enriched membrane vesicles were examined in parallel experiments to determine whether inhibitor-mediated enhancement in Ca2+ efflux contributes to inhibition of net Ca2+ uptake. When assays were performed at pH 6.8 in the presence of oxalate, low concentrations (less than 100 micrograms/mL) of the inhibitor caused substantial inhibition of Ca2+ uptake by SR (28-50%). At this pH, low concentrations of the inhibitor did not cause enhancement of passive Ca2+ release from actively Ca2+-loaded sarcoplasmic reticulum. Under these conditions, high concentrations (greater than 100 micrograms/mL) of the inhibitor caused stimulation of passive Ca2+ release but to a much lesser extent when compared with the extent of inhibition of active Ca2+ uptake (i.e., twofold greater inhibition of Ca2+ uptake than stimulation of Ca2+ release). When Ca2+ uptake and release assays were carried out at pH 7.4, the Ca2+ release promoting action of the inhibitor became more pronounced, such that the magnitude of enhancement in Ca2+ release at varying concentrations of the inhibitor (20-200 micrograms/mL) was not markedly different from the magnitude of inhibition of Ca2+ uptake. In the absence of oxalate in the assay medium, inhibition of Ca2+ uptake was observed at alkaline but not acidic pH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1977

Nomifensine in Parkinson's disease.

1. Eight patients who failed or ceased to respond to levodopa, or who had developed the "on-off" phenomenon were treated additionally with nomifensine. 2. The dosage of nomifensine started at 50 mg, was increased to 150 mg daily, and other medication was continued unchanged. The duration of treatment was from 2-5 months. Assessments were carried out at 2-week intervals using a validated rating scale. 4. Loss of dopaminergic nigrostriatal neurones characterizes Parkinson's disease, and it is probably for this reason that indirect dopamine (DA) agonists, whose actions depend on intact presynaptic mechanisms, are less active. 3. Nomifensine was not shown to be of antiparkinsonian value in these patients but may be of value as an antidepressant in patients with Parkinson's disease.

Adult↗
PubMed1976

Shuddering attacks in children: an early clinical manifestation of essential tremor.

Six infants and children presenting with shuddering attacks had evidence and a family history of essential tremor. Although this association had not been recognized, the shuddering spells caused considerable concern and led to a wide range of diagnoses. The attacks start in infancy or early childhood, are brief, often associated with some posturing, and may be very frequent. They are benign and tend to become less frequent or to remit during the latter part of the first decade. The recognition of this syndrome should avoid unnecessary investigation and concern. The pathophysiology of shuddering attacks seems to represent an expression of the mechanism of essential tremor in the immature brain. The ultimate nature of these attacks will undoubtedly be clarified when a neurochemical basis for essential tremor is found.

Adult↗
PubMed1976

Triple-vessel coronary artery disease: Effect of revascularization on late survival.

Of the first 600 patients to receive aortocoronary bypass grafts 383 had three diseased vessels, and of them 36 (9%) have died: 20 (5%) in hospital and 16 (4%) late. In 10 of those who died, ventricular function was normal, class I or class II and in the other 26 function was class III or class IV. For all ventricular classes except class IV, improvement in myocardial blood flow with operation was considerably lower than average in those who died. The leading cause of late death was congestive heart failure followed by myocardial infarction, and then by other cardiac complications. Of patients with good (normal, classes I or II) ventricular function, 3.5% died during a mean follow-up period of 27 months; and since, according to published reports, 1% of patients with triple-vessel disease without surgical intervention die each month, the data from this study suggest that survival in this group is improved by 23.5%. This study also shows that in patients with triple-vessel disease and good ventricular function, adequate coronary artery bypass operations (i.e., placement of three grafts or more) improves survival.

Coronary Artery Bypass↗
PubMed1975

Emergency hospitalization of young children: some neglected psychological considerations.

In spite of the fact that emergency admission is the most common form of hospitalization for young children, as well as containing the greatest potential for trauma, almost no reference has been made to it in the psychological literature on pediatric hospitalization. To explore the theoretical and practical feasibility of research in this area, a pilot study was designed to investigate the reactions of a sample of children, parents, and staff to the first six hours of emergency hospitalization, compared with those of a similar sample to elective admission. Sixteen children (eight in each group) aged 11 to 48 months were selected on a time-sample basis from the patient population of a large, metropolitan, pediatric hospital and were followed by trained observors using a specially designed observation schedule. The results indicated that, as expected, emergency does constitute an even greater stress for children, parents, and staff that the already stressful situation of elective admission. In both conditions however, the results were more complex and more disturbing than anticipated. The implications of these findings, as well as suggestions for further research, are discussed.

Acute Disease↗
PubMed1975

Surgery for coronary artery disease and congestive heart failure.

A group of 41 patients presenting primarily with symptoms of congestive heart failure was investigated by coronary arteriography and myocardial revascularization. Of these patients 20 underwent resection of left ventricular aneurysm or left ventricular plication as well as revascularization. Revascularization plus resection of left ventricular aneurysm gives gratifying results, but revascularization in the presence of severe generalized hypokinesis is less satisfactory; however, the improvement in clinical condition in a sufficient number of patients is such that this approach to their management is justified. Accordingly, every patient with coronary artery disease and congestive heart failure should be investigated by angiography. Numerous factors influence the results of revascularization for the relief of congestive heart failure; the most useful as a criterion to aid patient selection is left ventriculography. In this group of 41 patients 66% were helped by myocardial revascularization.

Adult↗