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Biomedical subjects

C Beattie

Publications and source records attributed to C Beattie.

At least 55 records · Page 3Linked to original sources
PubMed1992

Depletion of O6-alkylguanine-DNA alkyltransferase by O6-benzylguanine in three-dimensional collagen cultures of normal human breast epithelial cells.

O6-Alkylguanine--DNA alkyltransferase (AGT) is a protein which removes the promutagenic O6-alkylguanine lesion induced in DNA by alkylating agents. Our results demonstrate that freshly isolated organoids from reduction mammoplasty specimens contain significant levels of AGT activity. AGT activity in breast epithelial cells shows interindividual variation. Constitutive levels of AGT activity remain unchanged during short-term serum-free culture of breast epithelial cells inside three-dimensional rat-tail collagen gel matrix. In the present study, we optimized conditions for depleting AGT activity in human breast epithelial cells cultured in three-dimensional collagen gel matrix using O6-methylguanine and O6-benzylguanine which are substrates for AGT. AGT activity was efficiently inactivated by exposure of cells to O6-methylguanine or O6-benzylguanine. Inactivation with O6-benzylguanine was more rapid, of greater magnitude and consistency and occurred at lower concentrations than with O6-methylguanine. Near-complete inactivation (> 99.5%) of AGT activity was reproducibly achieved with 50 microM O6-benzylguanine. In contrast, 500 microM O6-methylguanine was needed to obtain a maximal effect and this reduced AGT activity by only 53-93% of control. Within 30 min of adding the free base, 50 microM O6-benzylguanine depleted 95% of the levels of AGT compared to 30% inhibition with 500 microM O6-methylguanine. The profile for restoration of AGT activity was different following a 24 h incubation and subsequent removal of each of the guanine derivatives. AGT activity levels remained undetectable for at least 2 days after removal of 50 microM O6-benzylguanine from the medium and recovered to only 53% of control values after an additional 3 days. AGT activity levels remained undetectable for at least 2 days after removal of 50 microM O6-benzylguanine from the medium and recovered to only 53% of control values after an additional 3 days. In contrast, following removal of 500 microM O6-methylguanine, the activity was restored from its nadir of 16% of control values reaching pretreatment levels after 5 days. These results suggest that treatment with O6-benzylguanine may be used to modulate the incidence of transforming mutations in cultured human breast epithelial cells treated with chemical carcinogens which give rise to O6-alkylguanine adducts.

Animals↗
PubMed1992

Spinal cord stimulation evoked potentials during thoracoabdominal aortic aneurysm surgery.

Although monitoring of somatosensory evoked potentials elicited from stimulation of lower extremity peripheral nerves has been suggested as a method for assessing neural function during thoracoabdominal aortic aneurysm surgery, this technique has been reported to yield a large number of false positives. It was believed that direct stimulation of the spinal cord would eliminate some of the problems associated with peripheral evoked potentials. The present study compared in 18 patients the use of scalp recorded evoked potential following stimulation of either the posterior tibial nerve via percutaneous needles or the spinal cord via an epidural electrode previously placed fluoroscopically. In 10 patients in whom distal bypass or shunt was not used, peripheral evoked potentials totally disappeared within 5-30 min of aortic clamping. Spinal cord stimulation evoked potentials disappeared permanently in 2 patients shortly after aortic cross-clamping; 1 died shortly after the procedure, and the other awoke densely paraplegic and died the next day. When distal perfusion was maintained by shunt or bypass, the disappearance of both peripheral and spinal evoked potentials accurately predicted the neurologic outcome of 1 paralyzed patient. Loss of spinal cord stimulation evoked potentials was found to be correlated with adverse neurologic outcome. Over the period of aortic clamping a gradual decrease in mean amplitude (50% at 45 min [P less than 0.05]) and a 20% increase in mean latency time were observed. Maintenance of adequate distal perfusion may permit the use of peripheral evoked potentials in the assessment of spinal cord ischemia during aortic cross-clamping.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Epidural versus general anesthesia, ambient operating room temperature, and patient age as predictors of inadvertent hypothermia.

To elucidate the multifactorial nature of perioperative changes in body temperature, the influence of several clinical variables, including anesthetic technique, ambient operating room temperature, and age, were evaluated. Perioperative oral sublingual temperatures were measured in 97 patients undergoing lower extremity vascular surgery randomized to receive either general (GA) or epidural (EA) anesthesia. Surgery and anesthesia were performed in operating rooms (OR) with a relatively warm mean ambient temperature (24.5 +/- 0.4 degrees C) (GA, n = 30; EA, n = 33) or relatively cold mean ambient temperature (21.3 +/- 0.3 degrees C) (GA, n = 21; EA, n = 13). Patients were 35-94 yr old, with a mean age of 64.5 +/- 1.1 yr. A regression analysis was performed to determine the variables that correlated with intraoperative decrease in temperature and postoperative rewarming rate. The major correlates of greater intraoperative decrease in temperature were 1) GA (P = 0.003); 2) cold ambient OR temperature (P = 0.07); and 3) advancing patient age (P = 0.03). There was significant interaction between ambient OR temperature and type of anesthesia (P = 0.03): there was a greater intraoperative decrease in temperature with GA compared to EA in a cold OR but a similar decrease with GA and EA in a warm OR. The data also suggest an interaction between type of anesthesia and patient age (P = 0.06), showing a greater decrease in temperature with GA compared to EA in the younger patients, but a similar decrease between GA and EA in older patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Perioperative myocardial ischemia and infarction. Preface.

The chapters in this issue of International Anesthesiology Clinics deal with the detection, pathophysiology, and current treatment of myocardial ischemia and infarction. The editors and authors are concerned, in both their clinical and investigative activities, with the perioperative management of patients with cardiac disease. Some of them have previously written reviews in their particular areas of expertise, but the material presented herein is newly prepared and current. Several of the chapters are extensive expositions of subjects only briefly considered elsewhere. The editors hope this publication will inform clinicians and investigators and challenge them to further improve perioperative care in patients with cardiac disease.

Coronary Disease↗
PubMed1991

Angiographic localization of spinal cord blood supply and its relationship to postoperative paraplegia.

Forty-seven patients underwent selective catheterization of middle and lower thoracic intercostal and upper lumbar arteries to define the origin of the artery of Adamkiewicz. One patient had significant atheroembolism, and a second had transient lower extremity paresthesias. No other complications occurred. The origin was found in 26 (55%), and 21 patients underwent thoracoabdominal aneurysm repair with this knowledge. When the critical lumbar or intercostal artery could be included as part of a long proximal or distal anastomosis, all 12 patients could be included as part of a long proximal or distal anastomosis, all 12 patients survived, and one was paralyzed. However, if the aneurysm repair mandated a midgraft anastomosis to intercostal arteries critical to spinal cord perfusion, seven of nine patients either died or were paralyzed (p less than 0.05). In the group of 19 patients operated on in whom spinal cord blood supply was not identified three patients had a technically unsuccessful operation; two died, and one was paralyzed. Twelve of 16 patients who had an adequate, but unsuccessful attempt at localization were treated by intercostal "neglect" and survived. Late paresis developed in two patients, but they are walking now. One of the patients who died had multiple systems failure and awakened paraplegic. She had a patent, enlarged, thoracic radicular artery at T-5 which probably supplied to spinal cord and which was missed angiographically. Paralysis was associated with aneurysm extent (group 2 and III B, dissections vs group 1 & 3, p less than 0.05). Selective intercostal angiography requires further refinement, but it is safe and offers the promise of understanding the mechanisms and risks of spinal cord complications after repair of extensive thoracoabdominal aneurysms.

Adult↗
PubMed1991

Right- and left-arm blood pressure discrepancies in vascular surgery patients.

To identify a relationship between atherosclerotic vascular disease and differences in blood pressure between the right and left arms, blood pressure differences between arms were measured in patients with peripheral vascular disease (PVD, n = 58), in patients with coronary artery disease (CAD, n = 38), and in patients with no evidence of atherosclerotic disease, who served as a control group (n = 38). The incidence and magnitude of right and left arm pressure difference determined by the oscillometric technique were compared between the patient groups. The incidence of systolic pressure difference greater than or equal to 20 mmHg between arms in patients with PVD (21%) was greater than that in either those with CAD (3%) (P less than or equal to 0.05) or control subjects (0%) (P less than 0.01). The incidence of systolic pressure difference greater than or equal to 45 mmHg between arms in patients with PVD (10%) was greater than that in either those with CAD (0%) (P less than 0.05) or control subjects (0%) (P less than 0.05). Patients with PVD also had a greater incidence of right and left arm difference than did those with CAD or controls for mean and diastolic blood pressures. Of all patients with a systolic difference greater than 10 mmHg, neither the right nor the left arm blood pressure was consistently higher: 21 of 35 (60%) had a higher pressure in the right arm, and 14 of 35 (40%) had a higher pressure in the left arm (P = 0.33). Gender, diabetes, hypertension, smoking, and age were not associated with a difference in blood pressure between the right and left arms.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Monitoring of spinal cord stimulation evoked potentials during thoracoabdominal aneurysm surgery.

Repair of a thoracoabdominal aneurysm involves a significant risk of ischemic injury to the spinal cord. Standard monitoring of somatosensory evoked potentials, which relies upon peripheral nerve stimulation, becomes nonspecific and insensitive during this surgery when aortic cross-clamping produces lower extremity ischemia causing a peripheral conduction block. Techniques for the insertion of percutaneous epidural electrodes, developed originally for pain management, have been adapted to this setting to permit direct stimulation of the spinal cord for intraoperative monitoring of evoked potentials. The clinical outcome in patients monitored by this technique has been consistent with evoked potential findings.

Aorta, Abdominal↗
PubMed1991

Mechanisms of blood flow during pneumatic vest cardiopulmonary resuscitation.

Mechanisms of blood flow during cardiopulmonary resuscitation (CPR) were studied in a canine model with implanted mitral and aortic flow probes and by use of cineangiography. Intrathoracic pressure (ITP) fluctuations were induced by a circumferential pneumatic vest, with and without simultaneous ventilation, and by use of positive-pressure ventilation alone. Vascular volume and compression rate were altered with each CPR mode. Antegrade mitral flow was interpreted as left ventricular (LV) inflow, and antegrade aortic flow was interpreted as LV outflow. The pneumatic vest was expected to elevate ITP uniformly and thus produce simultaneous LV inflow and LV outflow throughout compression. This pattern, the passive conduit of "thoracic pump" physiology, was unequivocally demonstrated only during ITP elevation with positive-pressure ventilation alone at slow rates. During vest CPR, LV outflow started promptly with the onset of compression, whereas LV inflow was delayed. At compression rates of 50 times/min and normal vascular filling pressures, the delay was sufficiently long that all LV filling occurred with release of compression. This is the pattern that would be expected with direct LV compression or "cardiac pump" physiology. During the early part of the compression phase, catheter tip transducer LV and left atrial pressure measurements demonstrated gradients necessitating mitral valve closure, while cineangiography showed dye droplets moving from the large pulmonary veins retrograde to the small pulmonary veins. When the compression rate was reduced and/or when intravascular pressures were raised with volume infusion, LV inflow was observed at some point during the compressive phase. Thus, under these conditions, features of both thoracic pump and cardiac pump physiology occurred within the same compression. Our findings are not explained by the conventional conceptions of either thoracic pump or cardiac compression CPR mechanisms alone.

Animals↗
PubMed1991

Production of the mouse whey acidic protein in transgenic pigs during lactation.

The mouse whey acidic protein (WAP) gene was introduced into the genome of pigs and its expression was analyzed in the mammary gland. Mouse WAP was detected in milk of lactating females from five lines at levels between .5 and 1.5 g/liter, thereby representing as much as 2% of the total milk proteins. The corresponding mRNA was expressed in mammary tissue at levels similar to those of pig beta-lactoglobulin and beta-casein. The pattern of WAP secretion in three pigs over a period of 6 wk was quantitatively similar to that of pig beta-lactoglobulin. From the eight transgenic pigs analyzed, three successfully completed one lactational period, but five pigs stopped lactating a few days after parturition. Our results show that it is possible to produce large quantities of a foreign protein in milk of pigs over a full lactational period. However, expression of WAP can compromise the mammary gland and render it nonfunctional.

Animals↗
PubMed1990

Halothane alters the oxygen consumption-oxygen delivery relationship compared with conscious state.

The authors' objectives were as follows: 1) to characterize for the first time the relationship between whole body O2 delivery (DO2) and O2 consumption (VO2) in adult conscious dogs; and 2) to asses the effects of the inhalational anesthetic, halothane, on that relationship. DO2 was varied over a wide range in chronically instrumented dogs by gradual inflation and deflation of a hydraulic occluder implanted around the thoracic inferior vena cava to alter venous return and cardiac output. VO2 was measured at different values of DO2 in dogs in the fully conscious state and again during halothane anesthesia. A "binning" technique indicated that halothane decreased VO2 (P less than 0.01) at any given value of DO2 over a broad range of VO2. A two-line piecewise linear regression analysis technique indicated that halothane decreased (P less than 0.01) the critical O2 delivery (COD) from 20 +/- 3 to 10 +/- 1 ml.kg-1.min-1 and increased (P less than 0.01) O2 extraction at COD from 31 +/- 3 to 40 +/- 2%. However, the DO2-VO2 plots measured in both conscious and halothane-anesthetized dogs did not exhibit a discrete discontinuity but rather were closely fit (correlation coefficient = 0.98) by an exponential equation of the following form: O2 extraction = B1.(1 - exp (-DO2/B2))/DO2, where B1 is the delivery-independent estimate of VO2 and B2 is the "delivery constant," i.e., the DO2 associated with a VO2 equal to 63% of B1. Halothane decreased B1 (P less than 0.01) from 5.3 +/- 0.1 to 3.9 +/- 0.1 ml.kg-1.min-1 and decreased B2 (P less than 0.01) from 5.6 +/- 0.3 to 3.6 +/- 0.3 ml.kg-1.min-1 compared with that measured in conscious dogs. Thus, compared with the conscious state, halothane anesthesia alters the fundamental relationship between DO2 and VO2 and may have a beneficial effect on tissue oxygenation at low values of DO2.

Animals↗
PubMed1989

Aortic diameter and pressure-flow sequence identify mechanism of blood flow during external chest compression in dogs.

Aortic flow and pressure relations and aortic diameter were examined during sinus rhythm, internal cardiac massage, vest cardiopulmonary resuscitation, conventional manual cardiopulmonary resuscitation and high impulse manual cardiopulmonary resuscitation in 14 anesthetized large dogs. During sinus rhythm and during internal cardiac massage, ascending aortic flow and pressure increased simultaneously and the rise in ascending aorta pressure preceded the rise in descending aortic pressure by (mean +/- SEM) 28 +/- 4 and 30 +/- 1 ms, respectively. In contrast, during vest, conventional and high impulse cardiopulmonary resuscitation, ascending aortic flow lagged behind the initial rise in aortic pressure by 40 +/- 4 to 46 +/- 4 ms and ascending and descending aortic pressure increased simultaneously (p less than 0.001 for each external compression mode versus sinus rhythm and internal massage). The ratio of pulse pressure to stroke volume increased by an order of magnitude during all modes of external chest compression (p less than 0.001 versus sinus rhythm and internal massage) and aortic diameter decreased during vest and high impulse cardiopulmonary resuscitation (p less than 0.05 versus sinus rhythm and internal massage). The hemodynamics of external chest compression depart from the normal physiologic sequence of stroke volume-induced increase in aortic pressure and diameter. The rise in aortic pressure precedes flow into the aorta, stroke volume does not fully account for pulse pressure, and aortic diameter decreases during chest compression. These data support the hypothesis that blood flow is due to fluctuations in intrathoracic pressure for high impulse as well as vest and conventional cardiopulmonary resuscitation.

Animals↗
PubMed1989

Regional versus general anesthesia in high-risk surgical patients: the need for a clinical trial.

Regional anesthesia is often preferred over general anesthesia for patients with cardiovascular disease because of presumed decreased risk of perioperative myocardial ischemia. However, few studies have addressed this issue directly. To determine whether the type of anesthesia is independently associated with myocardial ischemia, records of 134 patients undergoing peripheral vascular grafting under general or regional anesthesia were examined. There were no significant differences preoperatively between groups in ASA class, age, sex, or prevalence of angina, diabetes, or hypertension. Twelve patients developed myocardial ischemia or infarction within 7 days of operation; 11 of these 12 patients had received regional anesthesia (p less than 0.015). The association between anesthetic approach and perioperative myocardial ischemia or infarction remained after adjustment for preoperative factors associated with ischemia or with type of anesthesia. General anesthesia does not appear to be associated with increased risk of myocardial ischemia, and stringent recommendations to avoid it in this population may be unfounded. A clinical trial is needed to define more clearly the risks and benefits of different types of anesthesia in high-risk patients.

Anesthesia, Conduction↗
PubMed1989

Con: regional anesthesia is not preferable to general anesthesia for the patient with heart disease.

The debate over regional anesthesia and general anesthesia with respect to relative risk in different classes of patients will probably be interminable until studies addressing the issue begin to specify the treatment protocols more carefully and to control as many variables as possible. Patients with cardiovascular disease who undergo major surgery are special cases in which either form of anesthesia may be acceptable or preferable. The benefits of lesser regional procedures do not necessarily extend to major conduction blockade in these individuals. Appropriate monitoring and goal-directed control of physiologic variables throughout the entire perioperative period may be more important than the type of anesthesia. General anesthesia that is carefully prepared, monitored, and conducted cannot be ruled out in the seriously ill.

Anesthesia, Conduction↗