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Biomedical subjects

M J Raymond

Publications and source records attributed to M J Raymond.

At least 19 recordsLinked to original sources

Cerebral blood flow velocity in term newborns following intrapartum fetal asphyxia.

Twenty-six term newborns with intrapartum fetal asphyxia, determined biochemically (umbilical artery base deficit > 12 mmol/l), were compared with 59 normal newborns to determine the effect of intrapartum fetal asphyxia on newborn blood pressure and cerebral blood flow velocity following delivery. Cerebral blood flow velocity observations with concurrent measures of blood pressure and heart rate were obtained during the 24 h after delivery and after 24 h. After delivery, diastolic blood pressure in the newborns of the asphyxia group was significantly greater than that of the newborns of the normal group and this difference persisted after 24 h. Cerebral blood flow velocity in the newborns of the asphyxia group was of the same order as that of the newborns of the normal group during the 24 h after delivery. However, there was a significant increase in both peak systolic and end-diastolic blood flow velocity after 24 h. The duration of metabolic acidosis may be a factor in the occurrence of this delayed cerebral blood flow velocity response. Observations of cerebral blood flow velocity should be continued for more than 24 h following delivery to determine the effect of intrapartum fetal asphyxia.

Asphyxia Neonatorum

Vasoactive intestinal peptide receptors on AR42J rat pancreatic acinar cells.

VIP receptors on AR42J rat pancreatic cells were analyzed by competition binding, affinity labeling and by N-glycanase digestion analyses. These studies revealed the presence of specific, high affinity (Kd approximately 1 nM) VIP receptors with a mass of 67 kDa or 59 kDa under reducing or non-reducing conditions, respectively. N-glycanase digestion of affinity labeled membranes generated a core receptor protein of approximately 44 kDa and evidence for at least two N-linked glycans on the mature receptor. The receptor lacked O-linked oligosaccharides but contained terminal sialic acid residues on its N-linked glycan(s) based on digestions with O-glycanase and neuraminidase. The similarity of the AR42J VIP receptor to the recently cloned cDNA for human VIP receptors makes this cell line an attractive model for further analysis of VIP receptor signal transduction events.

Animals

Multinucleated rat alveolar macrophages express functional receptors for calcitonin.

The fusion of mononuclear phagocytes occurs spontaneously in vivo and leads to the differentiation of either multinucleated giant cells or osteoclasts in chronic inflammatory sites or in bone, respectively. Although osteoclasts are responsible for resorbing bone, the functional role of giant cells in chronic inflammatory reactions and tumors remains poorly understood. We recently reported that the plasma membrane of multinucleated macrophages is, like that of osteoclasts, enriched in Na-K-adenosinetriphosphatases (ATPases). We also observed that the localization of their Na-K-ATPases is restricted to the nonadherent domain of the plasma membrane of cells both in vivo and in vitro, thus imposing a functional polarity on their organization. By following this observation, we wished to investigate whether these cells also expressed, like osteoclasts, functional receptors for calcitonin (CT). To this end, alveolar macrophages were fused in vitro, and both their structural and functional association with CT was analyzed and compared with those of mononucleated peritoneal and alveolar macrophages. Evidence is presented that multinucleated alveolar macrophages express a high copy number of functional receptors for CT. Our results also indicate that alveolar macrophages, much like peritoneal, express functional receptors for calcitonin gene-related peptide. It is suggested that multinucleated rat alveolar macrophages offer a novel model system to study CT receptors and that calcitonin may control local immune reactions where giant cells differentiate.

1-Methyl-3-isobutylxanthine

Neuropsychological sequelae of stroke as a function of handedness.

The preservation of visuospatial ability relative to verbal ability following right middle cerebral artery stroke was assessed in 19 left- and 19 right-handed male patients who were group-matched on the basis of age, education, and time elapsed since stroke. Analysis of covariance (covarying education) indicated that the left- and right-handed groups were significantly different with regard to the discrepancy between Verbal IQ and Performance IQ, with the left-handed patients showing a smaller difference than the right-handers. These results provide further evidence that sinistrality may be associated with less hemispheric specialization.

Brain Damage, Chronic

A differential scanning calorimetric study of the bovine lens crystallins.

Differential scanning calorimetry was performed on the five major lens crystallin fractions [HM-alpha, alpha, beta H, beta L, and (beta s + gamma)] of the bovine lens as well as on more purified forms of alpha- and gamma-crystallins. All were found to be relatively thermally stable although the alpha-crystallin were found to at least partially unfold at an approximately 10 degrees C lower temperature than the beta and gamma fractions. Increasing protein concentration had little effect on gamma-crystallin thermograms but had marked effects on those of the alpha- and beta-crystallins. Increases in the thermal stability with increasing protein concentration for the beta-crystallins can be explained most simply by the known beta L/beta H equilibrium, but, in the case of the alpha-crystallins, excluded volume effects may be an important factor. In both cases, the increased stability at high concentrations could be of physiological relevance. As well as the expected endothermic unfolding transitions, all of the lens crystallins revealed exothermic peaks that correlate with protein precipitation. Interestingly, this phenomenon occurs only after extensive structural alteration in the case of the alpha-crystallins but is present very early in the initial stages of structural perturbation of the beta- and gamma-crystallins.

Animals

Experimental evaluation of technetium-99m red blood cell radionuclide ventriculography for detecting pericardial bleeding.

Abnormal loculated or diffuse blood pools adjacent to the heart have been observed in patients with pericardial bleeding who have been imaged by gated equilibrium radionuclide ventriculography (RNV). To study the scintigraphic appearance of fresh pericardial blood, we performed equilibrium RNV in six dogs with measured volumes (10, 30, or 50 ml) of intrapericardial blood. Loculated and diffuse pericardial blood was simulated by injecting the blood either into an intrapericardial balloon, or freely into the pericardial space. Ability to detect pericardial blood was determined by blinded review, and blood volume analysis was attempted by measuring its scintigraphic thickness, brightness (relative to the left ventricle), extent, and background-subtracted count rate and a peak count index. Detection rates for 10, 30, and 50 ml were all 100% for loculated pericardial blood, and 67%, 100% and 100% for free pericardial blood, with the use of three scintigraphic views. Visually determined "extent" of the abnormal blood pool was the most reliable indicator of pericardial blood volume. When the volume was 30 ml or more, at least 40% of the heart was surrounded in 26 of 27 cases (96%); the specificity of this finding was 90%. We conclude from this animal study that RNV should be a sensitive method for detecting pericardial bleeding; visual appearance permits qualitative assessment of the volume of accumulated labeled blood.

Animals

Psycho-social aspects of youth unemployment: an interpretative theoretical model.

By utilizing representative samples of short-term (n = 33), long term (n = 14) unemployed adolescents and YTS trainees (n = 49) in North-East Scotland, the present study attempted to identify psycho-social variables involved in the individual adolescent's ability to cope with unemployment. The research was built around a series of semi-structured interviews with all subjects. Results suggested a variety of apparent contradictions--family support vs. parental pressure; informal community-based education as helpful vs. school education as irrelevant; high aspirations as reinforcing or frustrating; peer groups as supportive or socially constraining; time structure as welcome or monotonous and restrictive; self-esteem being sapped or maintained aggressively and defensively high. From the data a theoretical model is offered which attempts to resolve the paradoxes by interpreting the experience of unemployment for young people in terms of positive and negative "trade-offs".

Adolescent

Photoaffinity labeling of the gonadotropin receptor with native, asialo, and deglycosylated choriogonadotropin.

Human choriogonadotropin (hCG) is a heterodimeric hormone composed of an alpha and a beta subunit. hCG and its asialo (ashCG) and deglycosylated (dghCG) forms vary in their ability to stimulate hormone responsive adenylate cyclase. ashCG is a partial agonist, and dghCG is an antagonist. Photoactivatable moieties were coupled to hCG, ashCG, and dghCG, and the derivatives were radioiodinated. Competitive binding studies indicate that all of the derivatives had a similar affinity for the gonadotropin receptor on porcine granulosa cell membranes. Radiolabeled derivatives were used to photoaffinity label the gonadotropin receptor. Radiolabeled complexes were separated by NaDodSO4/PAGE. All of the derivatives produced similar autoradiographic patterns, except that dghCG produced an additional 48-kDa complex. To investigate the structure of the complexes further, peptide mapping of proteolytic digests was used. All, except for the 48-kDa complex, generated similar peptide maps indicating a relationship between those complexes in which the smaller components are part of the larger. The 48-kDa complex contained both subunits of 40-kDa dghCG. Therefore, this complex is expected to contain an additional component of 8 kDa. The complex was generated whether the hormone-receptor complex was photoaffinity labeled on cells, on isolated membranes, or after solubilizing in detergent. Formation was blocked by excess hCG and did not occur in the absence of UV irradiation. We conclude that the hCG derivatives are able to photoaffinity label the hCG receptor but that the dghCG derivative can photoaffinity label an additional component that was not observed when derivatives of hCG or ashCG were used to label the receptor.

Adenylyl Cyclases

Effects of intubation on coronary blood flow and myocardial oxygenation.

Effects on haemodynamics and myocardial oxygenation of endotracheal intubation were examined in 17 patients after halothane induction and 12 after 1 mg X kg-1 of IV morphine. Six patients having each anaesthetic were pretreated with IV propranolol (0.1 mg X kg-1) 45 minutes earlier. Arterial and intracardiac pressures, cardiac output and total coronary sinus blood flow (CSBF), both by thermodilution, were determined plus arterial-coronary differences of oxygen, haemoglobin and lactate. Blood pressure (BP), heart rate and CSBF were recorded continuously during intubation. The subjects were candidates for coronary bypass grafts, but had good ventricular function (mean ejection fraction 0.68 +/- 0.13 SD). From their reduced levels after induction, BP, cardiac index and systemic vascular resistance increased to awake levels following intubation. Mean CSBF in nonbetablocked patients increased to awake level along with BP. More myocardial oxygen was extracted and consumed after intubation, but lactate extraction continued: these data are evidence of adequate oxygen supply. Induction with either halothane or morphine effectively prevented the hypertensive response to intubation. Acute beta blockade led to less increase in heart rate from intubation.

Aged

Cardiac causes of shock early after open heart surgery: etiologic classification by radionuclide ventriculography.

Early after open heart surgery, cardiac shock due to tamponade is easily misdiagnosed as ventricular dysfunction. The distinction is critical to successful therapy. We assessed the utility of 99mTc-red blood cell, gated equilibrium radionuclide ventriculography in 50 patients with early postoperative cardiac shock after historical, clinical, and invasive hemodynamic evaluation failed to identify either tamponade or ventricular dysfunction as the specific cause of their shock. The cause was established by radionuclide ventriculography in 45 of 50 patients and led to a change in therapy in 21 patients. A single cause was found in 35 patients: 13 had severe global dysfunction of the left ventricle (three patients), right ventricle (seven patients), or both ventricles (three patients); three had severe segmental left ventricular dysfunction; and 19 had an exaggerated region of photon deficiency (nine patients) or an abnormal and accumulating blood pool (10 patients) surrounding small hyperdynamic ventricles. Sixteen of these 19 patients with scintigraphic evidence of tamponade underwent aspiration with a pericardial needle or reoperation early after radionuclide ventriculography, resulting in confirmation of scintigraphic findings and improved hemodynamics. Ten additional patients had combined ventricular dysfunction and a pericardial abnormality, and five of these underwent reoperation resulting in improved hemodynamics. Radionuclide ventriculography provided no explanation for the cause of cardiac shock in five patients. Thus, the various causes of cardiac shock early after open heart surgery can be distinguished by 99mTc-red blood cell, gated equilibrium radionuclide ventriculography, eliminating diagnostic uncertainty that can occur with traditional evaluation.

Adult

Detection of occult pericardial hemorrhage early after open-heart surgery using technetium-99m red blood cell radionuclide ventriculography.

Pericardial or mediastinal hemorrhage requiring reoperation occurs in 2% to 5% of patients, usually early (0 to 48 hours), after open-heart surgery. This hemorrhage may be occult, and resulting cardiac tamponade may easily be misinterpreted as ventricular dysfunction, common early postoperatively. In such cases, appropriate and timely intervention may not occur. Of 50 patients evaluated by technetium-99m red blood cell gated equilibrium radionuclide ventriculography (RNV) because of early postoperative cardiogenic shock of uncertain etiology, 17 had unique scintigraphic images suggestive of intrathoracic hemorrhage. Of these 17, 5 had a generalized "halo" of abnormal radioactivity surrounding small hyperdynamic right and left ventricles, 11 had localized regions of intense blood pool activity outside the cardiac chambers (two with compression of single chambers), and one demonstrated marked radionuclide activity in the right hemithorax (2000 ml of blood at reoperation). Twelve patients had exploratory reoperation for control of hemorrhage as a direct result of the scintigraphic findings, three were successfully treated with fresh frozen plasma and platelet infusions along with medical interventions to optimize cardiac performance, and two patients died in cardiogenic shock (presumed tamponade) without reoperation. In the 12 reoperated patients, all were confirmed to have active pericardial bleeding. Scintigraphic localization of abnormal blood pools within the pericardium corresponded to the sites at which active bleeding was witnessed at reoperation. The abnormal bleeding was etiologically related to the tamponade state, with marked improvement in hemodynamics after reoperation. Nine additional patients were reoperated for presumed tamponade after RNV revealed an exaggerated halo of photon deficiency surrounding the cardiac chambers.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Surgical Procedures

Diffuse slow washout of myocardial thallium-201: a new scintigraphic indicator of extensive coronary artery disease.

When coronary artery disease is extensive and of relatively uniform severity, regional myocardial hypoperfusion may be balanced during stress, precluding development of spatially relative perfusion defects. Assessment of the washout of thallium-201 from myocardial regions may provide diagnostic assistance in these cases because washout analysis is spatially nonrelative and hypoperfused myocardial regions manifest a slow thallium-201 washout rate. In 1,265 consecutive patients having quantitatively analyzed stress-redistribution scintigraphy, 46 had a diffuse slow washout pattern with no or a maximum of one regional perfusion defect. Thirty-two underwent clinically indicated coronary angiography, and 23 (72%) of these were found to have three vessel or left main disease. Of 30 similar patients without a diffuse slow washout pattern and with no or a maximum of one perfusion defect, only 5 (17%) had extensive coronary disease. An independent relation between diffuse slow washout and extensive coronary disease was demonstrated by a Mantel- Haentzel chi-square analysis of a wide variety of other indexes of extensive disease. A diffuse washout abnormality, even in the absence of other scintigraphic, clinical or electrocardiographic indicators, carries a high predictive value for three vessel or left main coronary artery disease. The predictive value is maintained when the exercise level achieved is submaximal. Although an infrequent occurrence (3.6% of tested patients), a diffuse slow washout pattern without other scintigraphic indications of extensive coronary disease should lead to further diagnostic testing.

Coronary Angiography

Nitrous oxide added to halothane reduces coronary flow and myocardial oxygen consumption in patients with coronary disease.

The haemodynamic and myocardial metabolic effects of adding 50 per cent nitrous oxide to 0.5 per cent halothane were studied in 13 patients, before the surgical incision for coronary artery vein grafts. Cardiac output and coronary sinus blood flow were determined by thermodilution, along with haemodynamic measurements. Measurements 15 minutes after addition of nitrous oxide revealed a significant decrease in heart rate, arterial pressure, cardiac index, coronary sinus blood flow and myocardial oxygen consumption. There was a significant increase in coronary sinus lactate content, and a significant decrease, from 27 to 11 per cent, in myocardial lactate extraction. We conclude that these circulatory changes were likely to be due to a depression of ventricular function by the nitrous oxide. The myocardia of these patients with severe coronary disease were becoming globally ischaemic while they were receiving 50 per cent oxygen, in the presence of hypotension. Nitrous oxide should be turned off when hypotension occurs in coronary patients.

Coronary Artery Bypass

Myocardial and systemic effects of nitroglycerin, given awake and during anaesthesia in coronary patients.

The haemodynamic and myocardial energy-metabolic effects of intravenous nitroglycerin (NTG) were investigated in seven male patients about to undergo coronary artery bypass grafting. Effects of one mg of NTG given at a rate of 100 micrograms . min-1 to sedated, awake hypertensive patients, were compared to effects of the same dose of NTG in the same patients, after sternotomy. Coronary sinus flow was measured by a thermodilution catheter and myocardial oxygen consumption (MVO2) was calculated using the arterio-coronary sinus difference of oxygen content. With the patients awake, cardiac index and stroke volume and work indices fell during NTG administration. There was only a small fall in arterial pressure as heart rate and systemic resistance increased. Pulmonary capillary wedge pressure decreased but not MVO2. With NTG administration during anaesthesia, arterial pressure fell significantly to normal, as systemic resistance decreased, without a change in heart rate or cardiac index. Calculated MVO2 decreased as the arterial-coronary venous difference of oxygen content increased. Both oxygen and lactate balance of the myocardium were maintained. NTG given during anaesthesia was more effective in reducing blood pressure and MVO2 than when given to awake patients.

Adjuvants, Anesthesia

Coronary artery stenoses. Relationship between angiographic severity and impact on mean diastolic pressure gradient.

Coronary angiography provides important anatomic information about coronary artery stenoses. However, it is unclear whether specific assumptions about hemodynamic impact can be made from the angiogram. We therefore studied the relationship between angiographic severity of coronary stenoses and the mean diastolic pressure gradient measured directly at coronary bypass operation. We studied 29 stenoses selected because they were the only lesions in a given vessel, they were well seen in two angiographic views, and there was no change in clinical status of the patient between angiographic and surgical procedures. Fourteen stenoses were in the left anterior descending artery, nine were in the right coronary artery, and six were in the left circumflex artery. Correlation between mean diastolic gradient and percent stenosis was good (r = 0.78, p = 0.001) and especially so for lesions in the left anterior descending artery (r = 0.84, p = 0.001). Lesions over 90% had a wide range of gradients, while lesions less than 90% tended to have more predictable gradients. Collaterals invariably identified vessels with stenoses causing major pressure gradients. History of myocardial infarction was associated with major gradients in supplying vessels. Length of stenosis was not an important influence on gradient over a stenosis. We conclude that in some defined instances, generalizations about hemodynamic (and presumed functional) impact of stenoses can be made from the angiographic assessment, but precise assumptions are not possible.

Adult

Arrhythmias and conduction disturbances following cardiac operation for the removal of left atrial myxomas.

Between September, 1971, and April, 1982, 11 patients (seven female) with left atrial myxomas underwent surgical resection at Cedars-Sinai Medical Center. The tumors ranged in size from 4 to 9 cm (mean 6.3 cm) and were attached to the interatrial septum (four superiorly, four inferiorly), the free atrial wall (one posteriorly, one at the dome), or both (one). Although all patients were symptomatic preoperatively, arrhythmias were uncommon; only one had chronic atrial fibrillation, and two others had had single episodes of paroxysmal atrial fibrillation in the immediate preoperative period. Early postoperatively, all but one patient had episodes of atrial fibrillation (eight patients), atrial flutter (four patients), junctional rhythm (six patients), sinus arrest (two patients), or complete heart block (three patients). Ten patients required antiarrhythmic therapy, and two required permanent pacemaker implantation. After a mean follow-up of 48 months (range 7 to 124), seven patients continue to have episodic or chronic supraventricular arrhythmias, with only three patients not using antiarrhythmic drugs regularly. The pathophysiological basis for these arrhythmias is unclear, but some patients appear to have sustained injury to the sinus node or atrioventricular node, while others have developed interatrial or intra-atrial conduction delays. Attention should be directed to the basis of these arrhythmias and conduction disturbances, as surgical technique may be the major determinant of this early and late postoperative complication.

Adult

Intravenous nitroglycerin and myocardial metabolism during anesthesia in patients undergoing myocardial revascularization.

Although intravenous nitroglycerin has been used to control the hypertensive response during sternotomy in patients undergoing myocardial revascularization, the effects of the drug on myocardial oxygen supply and demand have not been anesthetized for coronary artery bypass, were studied before and after administration of intravenous nitroglycerin (mean dose 12 microgram/kg in 6 minutes). Evaluation of myocardial metabolism showed an increase in coronary sinus oxygen content (p less than 0.05) and a reduction in myocardial oxygen consumption (p less than 0.05). Although mean myocardial lactate extraction and coronary sinus blood flow were not significantly altered in the group as a whole, variations in individual patient responses were observed and are discussed. These direct observations of global myocardial metabolism observed in this study group are similar to the conclusions reached by other investigators using indirect indices of myocardial oxygen supply and demand.

Anesthesia