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Biomedical subjects

L R Smith

Publications and source records attributed to L R Smith.

At least 91 records · Page 5Linked to original sources
PubMed1991

Complexity and sequence identification of 24 rat V beta genes.

Twenty-four TCR V beta genes were cloned by anchored PCR from the Lewis rat strain and identified by nucleotide and amino acid sequence comparisons to known mouse V beta genes. Rat V beta genes exist in 17 single-member and 3 multimember subfamilies and exhibit 86 to 94 and 72 to 92% nucleotide and amino acid sequence similarities, respectively, to their mouse counterparts. A single rat gene, designated V beta 20, having no previously known mouse counterpart was identified; a closely related gene was subsequently isolated from the C57BL/6 mouse strain. Characterization of the rV beta genes provides the basis for addressing rat T cell tolerance mechanisms and V beta gene usage in immunologically mediated rat disease models.

Amino Acid Sequence↗
PubMed1991

Management and long-term outcome of aortic dissection.

All 163 patients admitted to one institution between 1975 and 1988 with aortic dissection were reviewed. Type I and type II patients received grafting of the ascending aorta, with an intraoperative mortality rate of 11%. For type III dissection, management was medical in 53 patients, while 19 required surgery for aortic rupture or expansion, with an intraoperative mortality rate of 11%. The 9- or 10-year survival rates were 29%, 46%, and 29% for types I, II, and III respectively. Of 135 patients with primary aortic dissection, 17 (13%) required subsequent aortic surgery. Cause of late death was other cardiovascular disease in 38%, rupture of another aortic segment in 18%, sudden death in 24%, and other medical conditions in 21%. Although operative therapy for types I and II dissections and reserving operation for selected type III dissections provides acceptable long-term survival, careful follow-up is necessary due to concurrent cardiovascular disease and residual aortic disease.

Academic Medical Centers↗
PubMed1991

Cerebral blood flow autoregulation is preserved during cardiopulmonary bypass in isoflurane-anesthetized patients.

In 21 patients undergoing elective coronary artery bypass surgery, cerebral blood flow (CBF) was measured during hypothermic nonpulsatile cardiopulmonary bypass to test the hypothesis that isoflurane abolished the mean arterial pressure-CBF relation (pressure-flow autoregulation). Cerebral blood flow was determined by 133Xe clearance. The patients were randomly divided into three groups according to anesthesia during cardiopulmonary bypass: group 1 received midazolam and fentanyl; group 2 received, in addition to midazolam and fentanyl, 0.6% isoflurane; and group 3 received, in addition to midazolam and fentanyl, 1.2% isoflurane. The groups were maintained at a constant temperature, PaO2, PaCO2, and pump flow during CBF measurements. Mean arterial pressure was increased by phenylephrine greater than or equal to 25% after the first CBF determination. Isoflurane decreased mean arterial pressure significantly (P less than 0.05) and was associated with lower CBF. Increasing the mean arterial pressure 29% in group 1, 25% in group 2, and 34% in group 3 had no effect on CBF. We conclude that, within the range studied, pressure-flow CBF autoregulation is preserved during isoflurane anesthesia administered for cardiopulmonary bypass.

Adult↗
PubMed1991

Effects of cardiopulmonary bypass and cardioplegia on regional and global cardiac actions of halothane in dogs.

Cardiopulmonary bypass (CPB) with aortic cross-clamping represents a controlled period of global cardiac ischemia. We hypothesized that CPB (asanguineous prime), with aortic cross-clamping and repeated cardioplegia, alters myocardial function, which would be manifested as an exaggerated myocardial depression caused by halothane after CPB. In nine dogs anesthetized with fentanyl and midazolam, halothane dose-response curves (0.0%-2.0%) were compared before and after CPB. A reduced mean arterial blood pressure (46.4 +/- 3.7 vs 85.8 +/- 5.9 mm Hg), associated with a marked hemodilution (hematocrit, 19% +/- 1% vs 41% +/- 2%), was observed after CPB. Cardiac output and systolic shortening were not significantly different after versus before CPB during fentanyl-midazolam anesthesia. Normalized to fentanyl-midazolam hemodynamics, halothane dose-response curves before and after CPB were identical for all variables except cardiac output, where halothane caused a slight but statistically significantly more pronounced decrease after CPB compared with before CPB. The effect of halothane on left ventricular function, therefore, is relatively unaffected by CPB with cardioplegia.

Animals↗
PubMed1991

Comparison of bicycle and treadmill radionuclide angiocardiography.

The purpose of this study was to test motion-correction algorithms for initial-transit radionuclide angiocardiograms acquired at rest and during bicycle and treadmill exercise. Treadmill data was spatially reoriented by computer software designed to eliminate motion of a 125I point source simultaneously recorded at a lower energy window. A second algorithm based on left ventricular centroid counts further corrected for motion on all studies. Exercise left ventricular ejection fraction was higher on the treadmill (0.68 +/- 0.07) compared to the bicycle (0.64 +/- 0.08) (p less than 0.0001, r = 0.88). Treadmill exercise also resulted in larger end-diastolic volumes (180 +/- 30 versus 157 +/- 36, p less than 0.0001), stroke volumes (124 +/- 28 versus 101 +/- 29, p less than 0.0001) and cardiac outputs (19.9 +/- 4.6 versus 15.9 +/- 5.0, p less than 0.0001). Similar variances for these hemodynamic measurements suggest that the mean differences observed were physiologic and that error from body motion was effectively corrected by this approach. We conclude that the measurement of left ventricular function during treadmill exercise, when combined with these techniques for correcting motion, is a reasonable alternative to conventional bicycle exercise.

Adult↗
PubMed1991

Determinants of early versus late cardiac death in patients undergoing coronary artery bypass graft surgery.

Most analyses of risk factors affecting survival after coronary artery bypass graft surgery have not differentiated among factors that influence early and late survival. For this reason, a multiphase model was applied to survival data from 2,967 patients undergoing a first coronary artery bypass graft at the Duke University Medical Center between 1969 and 1984. There were 709 deaths during follow-up to 19.6 years. The data were analyzed using a multivariable survival model that separates the underlying hazard function into as much as three different phases, each incorporating separate risk factors. Two distinct phases were detected. One phase dominated early survival (0-1 year), and the second phase dominated late survival (greater than 1 year). Surgery performed earlier in our experience was associated with elevated risk of dying in both phases but with different magnitudes, whereas lower ejection fraction, greater extent of coronary disease, older age, conduction abnormality, and history of hypertension were associated with elevated risk of dying similarly in both phases (p less than 0.05). Severity of angina symptoms and lower weight were associated with an elevated risk of dying only in the early phase (p less than 0.05; because few of the patients were obese, estimates of the relative risk of morbid obesity could not be estimated), whereas vascular disease, diabetes, and extent of myocardial damage were associated with an elevated risk of dying only in the late phase (p less than 0.05). These data illustrate both the differential influence of risk factors over time and the importance of multiphase models.

Cohort Studies↗
PubMed1991

Influence of diabetes and mammary artery grafting on survival after coronary bypass.

The effect of diabetes on survival after coronary bypass surgery is uncertain. Also, although the overall clinical benefits of internal mammary artery (IMA) grafting are well established, the survival benefit attributable to IMA grafting in diabetics is not well characterized. To determine the influence of diabetes and IMA grafting on survival after bypass surgery in the current surgical era, characteristics related to subsequent outcome were analyzed in 5,654 consecutive patients undergoing surgery in the decade of the 1980s. The 1,132 diabetic patients (20%) had more extensive coronary disease, had more left ventricular dysfunction, were older, were more frequently female, received a greater number of grafts (mean, 3.5 versus 3.1), and received more IMA grafts (67% versus 58%) than the 4,522 nondiabetic patients (all p less than 0.001). Overall 5-year survival probability was 0.91 in nondiabetic and 0.80 in diabetic patients (p less than 0.0001). Nondiabetic survival exceeded diabetic survival even in high-risk subgroups such as ejection fraction less than or equal to 0.40 (0.80 versus 0.66, p less than 0.02), age greater than or equal to 65 years (0.85 versus 0.73, p less than 0.0003), and, urgent surgery (0.89 versus 0.76, p less than 0.0001). By multivariate analysis, impairment of left ventricular function, advanced age, failure to use an IMA graft, diabetes, female sex, urgent surgery, number of diseased vessels, and mitral insufficiency were incremental risk factors for cardiac mortality (all p less than 0.006). Failure to use an IMA graft and diabetes were equally strong predictors of outcome. Use of an IMA graft conveyed an independent survival benefit to both nondiabetic (p less than 0.0001) and diabetic (p less than 0.02) patients. The magnitude of the survival benefit attributable to IMA grafting in the two groups did not differ (p = 0.4). Diabetes is an important risk factor for late cardiac mortality after bypass surgery and should be included in analyses of the efficacy of therapies for coronary artery disease. IMA grafting conveys a similar benefit to diabetic and nondiabetic patients but does not negate the adverse effect of diabetes on survival.

Age Factors↗
PubMed1991

The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants, and children.

Cardiopulmonary bypass management in neonates, infants, and children often requires the use of deep hypothermia at 18 degrees C with occasional periods of circulatory arrest and represents marked physiologic extremes of temperature and perfusion. The safety of these techniques is largely dependent on the reduction of metabolism, particularly cerebral metabolism. We studied the effect of hypothermia on cerebral metabolism during cardiac surgery and quantified the changes. Cerebral metabolism was measured before, during, and after hypothermic cardiopulmonary bypass in 46 pediatric patients, aged 1 day to 14 years. Patients were grouped on the basis of the different bypass techniques commonly used in children: group A--moderate hypothermic bypass at 28 degrees C; group B--deep hypothermic bypass at 18 degrees to 20 degrees C with maintenance of continuous flow; and group C--deep hypothermic circulatory arrest at 18 degrees C. Cerebral metabolism significantly decreased under hypothermic conditions in all groups compared with control levels at normothermia, the data demonstrating an exponential relationship between temperature and cerebral metabolism and an average temperature coefficient of 3.65. There was no significant difference in the rate of metabolism reduction (temperature coefficient) in patients cooled to 28 degrees and 18 degrees C. From these data we were able to derive an equation that numerically expresses a hypothermic metabolic index, which quantitates duration of brain protection provided by reduction of cerebral metabolism owing to hypothermic bypass over any temperature range. Based on this index, patients cooled to 28 degrees C have a predicted ischemic tolerance of 11 to 19 minutes. The predicted duration that the brain can tolerate ischemia ("safe" period of deep hypothermic circulatory arrest) in patients cooled to 18 degrees C, based on our metabolic index, is 39 to 65 minutes, similar to the safe period of deep hypothermic circulatory arrest known to be tolerated clinically. In groups A and B (no circulatory arrest), cerebral metabolism returned to control in the rewarming phase of bypass and after bypass. In group C (circulatory arrest), cerebral metabolism and oxygen extraction remained significantly reduced during rewarming and after bypass, suggesting disordered cerebral metabolism and oxygen utilization after deep hypothermic circulatory arrest. The results of this study suggest that cerebral metabolism is exponentially related to temperature during hypothermic bypass with a temperature coefficient of 3.65 in neonates infants and children. Deep hypothermic circulatory arrest changes cerebral metabolism and blood flow after the arrest period despite adequate hypothermic suppression of metabolism.

Adolescent↗
PubMed1990

Heparin and infarct coronary artery patency after streptokinase in acute myocardial infarction.

Anticoagulant therapy is frequently used after thrombolytic agents in the treatment of acute myocardial infarction (AMI) although it is unclear that such therapy will prevent subsequent infarct vessel reocclusion. The role of duration of heparin therapy in maintaining infarct artery patency was studied retrospectively in 53 consecutive AMI patients who received streptokinase therapy and underwent coronary angiography acutely and at 14 +/- 1 days. Of the 39 patients with initial infarct vessel patency, patency at follow-up angiography was observed in 100% (22 of 22) of those who received greater than or equal to 4 days of intravenous heparin but in only 59% (10 of 17) of those patients who received less than 4 days of heparin (p less than 0.05). Of the 14 patients not initially recanalized after streptokinase, patent infarct-related arteries at follow-up angiography were found in 3 of 8 (38%) treated with greater than or equal to 4 days of heparin therapy but in none of the 6 patients treated for less than 4 days (difference not significant). No significant difference in hemorrhagic complications was noted between the short- and long-term heparin treatment groups. Thus, greater than or equal to 4 days of intravenous heparin therapy after successful streptokinase therapy in AMI is more effective in maintaining short-term infarct vessel patency than a shorter duration of therapy and it may maintain the short-term patency of the infarct vessel in those patients who later spontaneously recanalize.

Angiography↗
PubMed1990

Coding sequence polymorphisms among V beta T cell receptor genes.

The four V beta gene segments, V beta 1, 3.1, 6, and 10, which previously have been shown by RFLP analyses to differ between TCR V beta a and V beta b haplotypes, were cloned and sequenced from V beta a SWR mice and compared with V beta b strains to define coding sequence polymorphisms distinguishing these haplotypes. V beta 3.1 and 6 alleles differed between strains by a single amino acid, whereas V beta 1 and 10 alleles differed by 4 and 6 amino acids, respectively. The overall interhaplotypic V beta polymorphisms appeared to be limited when based upon compilation of this information and previously published V beta sequences. One application of these data was to attempt to elucidate the molecular basis underlying the recently reported allele-specific autoimmune disease, collagen-induced arthritis. Based on the present structural data and the additional evidence, contrary to what was suggested, the V beta 6 gene does not appear to be the sole participant in anticollagen responses.

Amino Acid Sequence↗
PubMed1990

Sequence of I-E genes from autoimmune New Zealand white mice.

Autoimmune New Zealand white (NZW) mice contribute to (New Zealand black x New Zealand white)F1 mice 1 or more major histocompatibility complex-linked genes that strongly correlate with susceptibility to murine lupus. The NZW class II major histocompatibility complex genes, I-E alpha and I-E beta, were cloned and sequenced and found to differ from normal B10.PL (H-2u) mice by 3 amino acids in the first domain of the I-E beta subunit. Of these differences, the arginine at position 72 of NZW mice could be an important disease determinant since it lies in a predicted antigen-binding cleft.

Amino Acid Sequence↗
PubMed1990

Pharmacokinetic model-driven infusion of fentanyl: assessment of accuracy.

Computer-assisted continuous infusion (CACI) is a pharmacokinetic model-driven infusion device that enables physicians to administer intravenous (iv) drugs in a quantitative fashion, specifying a theoretical blood or plasma concentration. This study evaluated the accuracy of CACI administration of fentanyl using a newly developed CACI device programmed with a well-known set of pharmacokinetic parameters for fentanyl. Patients received diazepam 1 or 2 h before surgery. Anesthesia was induced by a combination of 70% N2O and fentanyl administered by CACI to a predicted concentration of 15-25 ng.ml-1. After neuromuscular blockade and tracheal intubation, the desired plasma fentanyl concentration (setpoint) entered into CACI was 3-6 ng.ml-1, and then the setpoint fentanyl concentration was titrated according to strict criteria of adequate or inadequate anesthesia. Plasma samples for subsequent assay of fentanyl concentration then were taken: at predefined stimuli, when inadequate anesthesia occurred, or 5 min before an anticipated decrease in the fentanyl setpoint. The predictive accuracy of CACI was assessed by calculating for each patient the tenth, 50th, and 90th percentile of the performance error and absolute performance error from each measured and predicted plasma sample pair. Cumulative probability functions for each of these were then plotted. Precision was defined as the dispersion of the tenth to 90th percentile of the median percent performance error for the population and was found to be -31-26%. The median population performance error was -4%, and the median population absolute performance error was 21%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The aerodynamic characteristics of speech produced by normal speakers and cleft palate speakers with adequate velopharyngeal function.

Pressure-flow data were obtained on 20 noncleft adults with normal speech and 26 adults with repaired cleft palate. All subjects had adequate velopharyngeal function as determined by preliminary aerodynamic assessment. Subjects were considered to have adequate closure if they had velopharyngeal areas no greater than 0.049 cm2 during production of /p/ in the word "hamper." Although the subjects in both groups demonstrated velopharyngeal adequacy, the subjects with cleft palate produced speech with significantly less nasal airflow. In addition, their intra-oral pressure curve was shifted forward in time. These differences suggest that speakers with cleft palate and adequate velopharyngeal function make certain compensatory adjustments that may be necessary because of differences in velopharyngeal movement capabilities. The potential significance of this for treatment planning is discussed.

Adolescent↗
PubMed1990

Esmolol for treatment of intraoperative tachycardia and/or hypertension in patients having cardiac operations. Bolus loading technique.

Esmolol, administered as a bolus followed by continuous infusion, was used to treat the occurrence of transient tachycardia and hypertension or tachycardia alone before cardiopulmonary bypass in 45 patients. The study was conducted in two phases. Phase I (15 patients) was a dose-finding study and phase II (30 patients) was a randomized, double-blind, placebo-controlled efficacy study. All patients received the last dose of their usual beta-adrenergic blocker the night before the operation and were anesthetized with midazolam, vecuronium, and enflurane in oxygen. Treatment criteria were either a systolic blood pressure greater than 140 mm Hg and a heart rate greater than 70 or a heart rate greater than 80 beats/min. In phase I, graduated doses of esmolol were given to successive patients. A dose of 80 mg followed by a 12 mg/min infusion was declared effective. Phase II patients were randomized to receive esmolol (n = 16) or placebo (n = 14). Hemodynamic data were collected at baseline and 1, 3, 5, and 10 minutes after the administration of esmolol. Plasma norepinephrine was measured at baseline, 1, and 10 minutes. Esmolol significantly (p less than 0.05) reduced heart rate at 1, 3, 5, and 10 minutes but did not change blood pressure, pulmonary artery diastolic pressure, right atrial pressure, cardiac output, or systemic vascular resistance. Our results show that a bolus loading dose of esmolol is safe and effective in the treatment of tachycardia in patients with ischemic heart disease and that esmolol rapidly blocks the beta-adrenergic effects of norepinephrine associated with surgical stress.

Adrenergic beta-Antagonists↗
PubMed1990

Comparison of medical and surgical therapy for uncomplicated descending aortic dissection.

To guide the choice of medical versus surgical therapy for patients with descending (type B) aortic dissection (tear in the descending aorta without involvement of the ascending aorta), multivariate survival analysis was applied to 136 patients admitted to two medical centers between 1975 and 1988 with acute (n = 89) or chronic (n = 47) descending dissection: group 1, all 136 patients; group 2, 106 patients without rupture, pulse loss, or visceral organ compromise; and group 3, 56 patients from group 2 without major cardiac or renal disease (23 surgical and 33 medical). Group 3 medical and surgical subgroups were well matched for baseline characteristics and were potential candidates for either mode of therapy. By Cox model analysis, significant predictors of mortality were pleural rupture, other dissection complications, increasing age, and cardiac disease (all p less than 0.01). Surgical versus medical therapy was not an independent determinant of survival in any of the three groups for acute or chronic dissection. Survival probabilities for all group 3 patients at 1, 5, and 10 years were 0.94, 0.87, and 0.32 (medical) and 0.90, 0.80, and 0.50 (surgical). Despite the limitations of this retrospective study (including the possibility of undefined treatment selection biases), these data suggest that medical or early surgical therapy is associated with equivalent outcome in selected patients with uncomplicated acute or chronic descending aortic dissection.

Adrenergic beta-Antagonists↗
PubMed1990

Clinical evaluation of single versus multiple mammary artery bypass.

The superior patency and clinical advantages of internal mammary artery (IMA) grafting are well established. However, the relative benefits of routine multiple IMA grafting remain uncertain. To determine whether routine multiple compared with single IMA utilization improved survival of patients undergoing coronary bypass procedures, 1,063 patients were prospectively allocated, beginning in 1984, to divergent management strategies of single (group 1, n = 420) versus multiple IMA grafting (group 2, n = 643). Subsequent analysis of anatomical extent of disease and preoperative baseline risk factors showed no differences (p = NS) between the two groups. All variables reflecting operative technique were similar (p = NS) for the two groups, except 74% of group 1 patients with multivessel disease received a single IMA graft, whereas 71% of group 2 patients with multivessel disease received multiple IMAs (p less than 0.05). By multivariate analysis, impairment of left ventricular ejection fraction, acute evolving myocardial infarction, advanced age, and unstable angina were incremental risk factors for mortality (all p less than 0.03), but group assignment (p = 0.4) and ultimate therapy were not (p = 0.6). Survival probabilities (expressed as 30-day group 1/group 2; 4-year group 1/group 2) were overall (0.97/0.98; 0.93/0.90), elective (0.98/0.99; 0.97/0.92), acute (0.95/0.97; 0.89/0.88), age of less than 65 years (0.98/0.99; 0.97/0.93), age of 65 years or older (0.93/0.97; 0.84/0.89), ejection fraction of 0.40 or more (0.97/0.99; 0.95/0.94), ejection fraction of less than 0.40 (0.95/0.96; 0.87/0.82), nondiabetic (0.98/0.98; 0.94/0.91), and diabetic (0.92/0.97; 0.88/0.87). No differences in survival were significant (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗