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Biomedical subjects

R S Mitchell

Publications and source records attributed to R S Mitchell.

At least 73 records · Page 4Linked to original sources
PubMed1990

Treatment of patients with aortic dissection presenting with peripheral vascular complications.

The incidence of peripheral vascular complications in 272 patients with aortic dissection during a 25-year span was determined, as was outcome after a uniform, aggressive surgical approach directed at repair of the thoracic aorta. One hundred twenty-eight patients (47%) presented with acute type A dissection, 70 (26%) with chronic type A, 40 (15%) with acute type B, and 34 (12%) with chronic type B dissections. Eighty-five patients (31%) sustained one or more peripheral vascular complications: Seven (3%) had a stroke, nine (3%) had paraplegia, 66 (24%) sustained loss of a peripheral pulse, 22 (8%) had impaired renal perfusion, and 14 patients (5%) had compromised visceral perfusion. Following repair of the thoracic aorta, local peripheral vascular procedures were unnecessary in 92% of patients who presented with absence of a peripheral pulse. The operative mortality rate for all patients was 25% +/- 3% (68 of 272 patients). For the subsets of individuals with paraplegia, loss of renal perfusion, and compromised visceral perfusion, the operative mortality rates (+/- 70% confidence limits) were high: 44% +/- 17% (4 of 9 patients), 50% +/- 11% (11 of 22 patients), and 43% +/- 14% (6 of 14 patients), respectively. The mortality rates were lower for patients presenting with stroke (14% +/- 14% [1 of 7 patients]) or loss of peripheral pulse (27% +/- 6% [18 of 66 patients]). Multivariate analysis revealed that impaired renal perfusion was the only peripheral vascular complication that was a significant independent predictor of increased operative mortality risk (p = 0.024); earlier surgical referral (replacement of the appropriate section of the thoracic aorta) or more expeditious diagnosis followed by surgical renal artery revascularization after a thoracic procedure may represent the only way to improve outcome in this high-risk patient subset. Early, aggressive thoracic aortic repair (followed by aortic fenestration and/or abdominal exploration with or without direct visceral or renal vascular reconstruction when necessary) can save some patients with compromised visceral perfusion; however, once visceral infarction develops the prognosis is also poor. Increased awareness of these devastating complications of aortic dissection and the availability of better diagnostic tools today may improve the survival rate for these patients in the future. The initial surgical procedure should include repair of the thoracic aorta in most patients.

Adolescent↗
PubMed1990

Differences in Hancock and Carpentier-Edwards porcine xenograft aortic valve hemodynamics. Effect of valve size.

We prospectively compared the hemodynamic performance of Hancock and Carpentier-Edwards bioprosthetic aortic valves in a randomized study of 100 patients. A total of 47 patients received the Hancock valve, and 53 received the Carpentier-Edwards valve. Mean pressure gradients were measured using micromanometer catheters and cardiac outputs by thermodilution. Multiple measurements were made in each patient with atrial pacing, volume infusion, and inotropic drugs for a total of 319 observations. The pressure gradients and Gorlin valve areas showed significant scatter caused by both flow-dependent and patient-dependent variability. Mean transvalvular pressure gradients were therefore compared after adjustment for flow rate and for random interpatient differences using analysis of variance and covariance. Pressure gradients were lower and Gorlin valve areas larger for the Hancock valve than for the Carpentier-Edwards valve, but the differences were significant only for the smaller valve sizes. Compared with the Carpentier-Edwards valve, the mean pressure gradients were significantly lower for the Hancock 19-mm modified orifice (MO) valves (16.9 versus 31.7 mm Hg, p = 0.04), for the 21-mm valves (15.2 versus 22.4 mm Hg, p = 0.003), and for the 23-mm MO valve (9.2 versus 13.8 mm Hg, p = 0.04). The Gorlin areas were also significantly larger for the Hancock 19-mm MO valve (0.85 versus 0.77 cm2, p = 0.004) and the 21-mm MO valve (1.11 versus 0.89 cm2, p = 0.0009) but not for the 23-mm MO valve (1.59 versus 1.14, p = 0.08). Mean gradients and valve areas were not different for any of the larger valve sizes.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1990

Hemodynamic comparison of Hancock and Carpentier-Edwards mitral bioprosthetic valves.

Although it is known that pressure gradients and calculated valve areas in bioprosthetic valves are highly flow dependent, no studies have compared bioprosthetic valve performances while adjusting for differences in flow rate. We therefore studied 75 patients undergoing mitral valve replacement who were randomized to receive either Hancock (n = 35) or Carpentier-Edwards (n = 40) bioprosthetic valves. Pressure gradients were measured using transducer-tipped catheters to record left ventricular and left atrial pressures and cardiac outputs by thermodilution. Repeated measurements were made in each patient after either pacing, fluid infusion, or pharmacological intervention to vary flow rates for a total of 239 measurements (mean, 3.2 measurements per patient). Using analyses of variance and covariance, mean valve gradients and the calculated Gorlin area were adjusted for flow rate, valve size, valve type, and interpatient differences to compare hemodynamics. Without flow and interpatient adjustment, the univariate analysis suggested higher mean gradients in the Carpentier-Edwards 29-mm valves (p = 0.038), with a trend toward higher gradients and smaller areas in the Hancock 33-mm valves (p = 0.057 and 0.059, respectively). After adjustment for flow rate and interpatient differences, however, there was no difference at any valve size in the mean pressure gradients (p = 0.13-0.89) or Gorlin valve areas (p = 0.34-0.96). Although measurements within a given patient were consistent, marked interpatient variabilities in gradients and areas were observed for identical valve types and sizes, which were as significant as flow-dependent or size-dependent changes. We conclude that comparisons of valve performance should adjust for variations in flow rate and for interpatient differences with the use of repeated-measures designs.(ABSTRACT TRUNCATED AT 250 WORDS)

Bioprosthesis↗
PubMed1989

Comparison of the Directigen 1-2-3 Group A Strep Test with culture for detection of group A beta-hemolytic streptococci.

The Directigen 1-2-3 Group A Strep Test (DGAST; BBL Microbiology Systems, Cockeysville, Md.) was compared with conventional culture procedures on Trypticase soy agar with 5% sheep blood (BBL) and Selective Streptococcal Agar (ssA; BBL) for detection of group A beta-hemolytic streptococci (GABHS) for 1,006 patients complaining of sore throat. The DGAST was performed at five acute-care clinics according to the instructions of the manufacturer; interpretation of the cultures was done at the central microbiology laboratory. Of 924 patients with complete data, 243 (26.3%) were positive for GABHS on culture when both sheep blood agar and ssA were used. Of the patients with positive cultures, 159 were detected by the DGAST, yielding a sensitivity of 65.4%, a specificity of 84.7%, a positive predictive value of 60.5%, and a negative predictive value of 87.3%. The greater the number of colonies on culture, the greater the sensitivity of the DGAST, and the more intense the positive reaction on the DGAST, the higher the positive predictive value of the test. For the identification of GABHS, sheep blood agar was superior to ssA by 12.9% at 24 h and by 3.4% at 48 h of incubation.

Acute Disease↗
PubMed1989

Inhibition of accelerated cardiac allograft arteriosclerosis by fish oil.

Accelerated coronary arteriosclerosis remains the most important factor limiting long-term survival of heart transplant recipients, and dietary fish oil supplementation with omega-3 polyunsaturated fatty acids has been suggested to have a protective effect against coronary disease in epidemiologic studies and to inhibit arteriosclerosis in animal experiments. Therefore we tested the hypothesis that fish oil administration inhibits the development of allograft coronary arteriosclerosis by using a heterotopic heart transplant model. Three groups of Lewis rats (n = 10 each) received heterotopic heart transplants from Brown-Norway donors and were treated with cyclosporine intraperitoneally on a tapering schedule. Group 1 received fish oil daily by gavage (2 ml/kg/day; Emulsified Super MaxEpa, Twin Labs, Ronkonkona, N.Y.). Group 2 received an equal amount of safflower oil, as well as aspirin (1 mg/kg/day) and dipyridamole (3 mg/kg/day). Group 3 received safflower oil only. All rats were put to death 110 days later, at which time there was no statistically significant difference in graft function as assessed by palpation (scale 0 to 4, mean = 3.7 +/- 0.5 [+/- standard deviation]; analysis of variance: p = 0.72) or in microscopic grade of rejection (scale, 0 = none to 3 = severe, mean 2.1 +/- 0.6; analysis of variance: p = 0.68) between any of the groups. The coronary arteries were histologically scored for the degree of arteriosclerosis (scale, 0 = normal to 3 = occluded), and a mean grade of coronary disease was calculated for each heart. The fish oil-treated group had significantly less severe allograft coronary arteriosclerosis (analysis of variance: p = 0.005) than did groups 2 and 3 (mean grade 0.23 +/- 0.22 versus 1.04 +/- 0.75 and 0.96 +/- 0.55 (p less than 0.05, Scheffe F test), whereas groups 2 and 3 had similar degrees of coronary disease (p = no significant difference). These data demonstrate that fish oil supplementation inhibited accelerated coronary arteriosclerosis in this cyclosporine-treated heart allograft rat model, whereas antiplatelet agents in these doses were ineffective. Although the mechanism of this protective effect remains incompletely understood, it does not appear to involve enhanced immunosuppression. Fish oil and specific omega-3 polyunsaturated fatty acids should be further investigated as potentially useful agents to ameliorate accelerated allograft coronary arteriosclerosis in other animal species and perhaps eventually in man.

Animals↗
PubMed1989

Surgical management of acute aortic dissection complicated by stroke.

Although patients with acute type A aortic dissection are best managed by emergency surgical intervention, preoperative stroke is known to be an independent predictor of late mortality and is considered by some to be a contraindication to operation because of the risk of precipitating hemorrhagic cerebral infarction and poor long-term outcome. In a series of 272 consecutive, unselected patients with aortic dissection undergoing surgical treatment during a 25-year span (1963-1987), 128 (47 +/- 3% [+/- 70% confidence level (CL)]) had an acute type A dissection. A total of seven patients with acute type A dissection (2.6 +/- 1% of all patients, 5.5 +/- 2% of the acute type A cohort) developed a new stroke preoperatively. Thirteen (4.8 +/- 1%) patients had a diminished or absent carotid pulse, only four (31 +/- 13%) of whom sustained a stroke. One patient died in the immediate postoperative period due to severe brain injury, yielding an operative mortality rate of 14 +/- 14%. Two patients had persistent neurological deficits and died within 4 months of operation; the actuarial survival estimate at 1 year was 57 +/- 19% (mean +/- SEM). One patient recovered function of one upper extremity (preoperative left hemiparesis compounded by paraplegia) but died 6 years later. The remaining three long-term survivors (43 +/- 19%) had major resolution of their neurological deficits and are clinically well 2-8 years postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1988

Effects of aspirin, dipyridamole, and cod liver oil on accelerated myointimal proliferation in canine veno-arterial allografts.

The effects of the administration of aspirin (ASA), dipyridamole (DPM), and cod liver oil (CLO) on graft patency rate and degree of intimal hyperplasia were investigated in a canine, hypercholesterolemic veno-arterial allograft model in an attempt to modify this immunologically mediated vascular injury. The drug regimens were ASA 1 mg/kg/day, DPM 10 mg/kg/day, combined ASA and DPM (ASA + DPM), and CLO (1.8 g/day eicosapentanoic acid [EPA] and 1.2 g/day docosahexanoic acid [DHA]), and control. The early angiographic patency rate (1-3 weeks) was 81% +/- 10% (+/- 70% confidence limits); the 90-day overall patency rate was 60% +/- 4% (87/144), with no statistically significant differences among the groups (range 46 +/- 10-71 +/- 9%). Qualitatively, there was no difference in luminal thrombus, intimal hemorrhage, or lesion eccentricity. Considering the relatively short time of graft implantation, an extensive amount of microscopic disease was observed; quantitatively, the mean intimal thickness was 515 +/- 17 microgram overall but was not statistically different between the groups. The fraction of potential lumenal area occupied by intimal thickening was 0.37 +/- 0.01 but again did not differ significantly between the groups. These doses of ASA, DPM, ASA + DPM, and CLO did not alter graft occlusion or retard the marked degree of subintimal myointimal cell hyperplasia that was generated in this hypercholesterolemic canine veno-arterial allograft preparation. Possible explanations for these negative findings include inadequate dosage or form of omega-3 fatty acids and the antiplatelet drugs administered, excessive variability in graft response due to uncharacterized immunologic histocompatibility, and the possible influence of non-platelet-mediated mechanisms. Nevertheless, this preparation is attractive as a reproducible model of accelerated (immunologically mediated) experimental arteriosclerosis.

Animals↗
PubMed1988

Inhibition of vein graft intimal thickening by eicosapentanoic acid: reduced thromboxane production without change in lipoprotein levels or low-density lipoprotein receptor density.

Marine lipids containing omega-3 fatty acids (chiefly, eicosapentanoic acid [EPA] and docosahexanoic acid [DHA]) may inhibit the development of atherosclerotic vascular disease, but the mechanisms responsible for this putative beneficial effect are unknown. We investigated the effects of EPA and DHA in a canine model of accelerated vein graft arteriosclerosis during a 3-month period. Twenty-five dogs were divided into three dietary groups: group I (control), group II (2.5% cholesterol), and group III (2.5% cholesterol plus 2 gm EPA/day [as MaxEPA]). The effects of EPA on vein graft intimal thickening, platelet and vascular prostaglandin metabolism, lipid and lipoprotein receptor metabolism, and hematologic parameters were assessed. Cholesterol feeding caused a significant 54% increase in graft intimal thickness compared with control animals (124.9 +/- 50.4 vs 81.2 +/- 32.4 micron; p = 0.013), which was prevented by supplementation with EPA in group III (56.9 +/- 30.0 micron; p = 0.001 vs group II). Intimal thickness in group III was not significantly different from that of control. EPA supplementation was also associated with a 38% decline in serum thromboxane levels from 457.0 +/- 129.3 pg/0.1 ml in group II to 283.5 +/- 96.9 pg/0.1 ml in group III (p = 0.007). The alterations in lipoprotein metabolism associated with cholesterol feeding were not affected by EPA: in both groups II and III, serum cholesterol and high-density lipoproteins and liver cholesterol content were elevated and hepatic low-density lipoproteins (LDL) receptor content was reduced. There were no differences between the three groups in terms of vein graft or native vessel prostacyclin production, hematocrit, platelet count, or coagulation parameters. In this canine model, dietary supplementation with marine omega-3 fatty acids reduced the extent and magnitude of accelerated vein graft intimal thickening induced by hypercholesterolemia; moreover, this beneficial effect was associated with lower serum thromboxane production and appeared to be independent of alterations in lipoprotein metabolism or LDL receptor density.

Animals↗
PubMed1987

recA protein-promoted ATP hydrolysis occurs throughout recA nucleoprotein filaments.

When recA protein binds cooperatively to single-stranded DNA to form filamentous nucleoprotein complexes, it becomes competent to hydrolyze ATP. No correlation exists between the ends of such complexes and the rate of ATP hydrolysis. ATP hydrolysis is not, therefore, restricted to the terminal subunits on cooperatively bound recA oligomers, but occurs throughout the complex. Similarly, during recA protein-promoted branch migration (during DNA strand exchange), ATP hydrolysis is not restricted to recA protein monomers at the branch point. DNA cofactors of lengths varying from 16 bases to over 12,000 bases support ATP hydrolysis. The maximum value of kcat at infinite DNA concentration is about 29/min independent of the length of the DNA cofactor. The apparent dissociation constant, however, is a strong function of DNA length, providing evidence for a minimum site size of 30-50 bases for efficient binding of recA protein.

Adenosine Triphosphatases↗
PubMed1987

When should Doppler-determined valve area be better than the Gorlin formula?: Variation in hydraulic constants in low flow states.

In low flow states, underestimation errors occur when the Gorlin formula is used to calculate valve area. A model of valvular stenosis designed to examine changes in the hydraulic discharge coefficient (Cd) and coefficient of orifice contraction (Cc) may explain these errors. Unsteady flow was examined in a pulsatile pump model and in a dog model. Valve areas were calculated from pressure and flow data using: a modified form of the Gorlin formula (assuming constant values for Cd and Cc) and a corrected formula (with values of Cd and Cc obtained from steady state data). Valve area was also calculated using the continuity equation with velocity and flow data (constant Cc). Flow velocities were measured using a newly designed ultrasound Doppler catheter capable of resolving flow velocities of up to 5.5 m/s. Both the corrected formula and continuity equation were highly predictive of actual valve area (r = 0.99, slope or M = 0.96 and r = 0.99, M = 1.06, respectively). The modified Gorlin equation was less accurate and tended to underestimate valve areas (r = 0.87, M = 0.83). This underestimation was most notable at low rates of flow (Gorlin: r = 0.94, M = 0.53; continuity: r = 0.93, M = 0.81 and r = 0.94, M = 0.89, respectively) more accurately than the modified Gorlin formula (r = 0.69, M = 0.49). In patients with low cardiac output, hemodynamic formulas, such as the Gorlin formula, which assume a constant value for the hydraulic discharge coefficient (Cd), may be less accurate than formulas using either a corrected value of Cd or Doppler-determined flow velocity and mean systolic flow.

Animals↗
PubMed1987

A prospective, randomized study of the effects of prostacyclin on neuropsychologic dysfunction after coronary artery operation.

This randomized, double-blind study was designed to evaluate the effect of prostacyclin (epoprostenol) on the incidence and severity of postoperative neuropsychologic dysfunction in patients undergoing coronary artery operation. Four days before operation and 1 week after operation, 100 patients having coronary artery bypass grafting underwent detailed neurologic and psychologic examinations and computed tomographic scans of the brain. The psychologic examination was repeated 2 months after operation. During cardiopulmonary bypass, all patients received 300 U/kg of heparin and then either buffer-diluent or prostacyclin (12.5 ng/kg/min from the time of heparinization until onset of cardiopulmonary bypass and 25 ng/kg/min during cardiopulmonary bypass). No deaths or major neurologic complications occurred in this series. Ninety-six patients completed the psychologic and neurologic evaluations 1 week after operation; 74 of these patients were evaluated psychologically 2 months after operation. Psychologic testing demonstrated similar declines in postoperative performance in both the prostacyclin-treated and the control groups; these changes were no longer present in either group 2 months after operation. Results of neurologic examinations and computed tomographic scans of the brain were unchanged. We conclude that the administration of prostacyclin during cardiopulmonary bypass in patients undergoing routine coronary artery operation has no effect on perioperative cognitive changes.

Adult↗
PubMed1987

Primary cardiac neoplasms. Early and late results of surgical treatment in 42 patients.

Forty-two patients underwent resection of primary cardiac neoplasms at Stanford University Medical Center and the Palo Alto Veterans Administration Medical Center between 1961 and 1986. A total of 27 atrial myxomas, seven benign nonmyxomatous tumors, and eight malignant tumors were resected. The mean age was 47 years (range 8 to 79) in 27 female and 15 male patients. The clinical presentations included congestive heart failure in 24 patients, palpitations in nine, neurologic symptoms in six, recurrent cardiac tamponade in three, vasculitis in two, and chest pain in two. Thirty-one of 34 benign lesions were completely resected, although one patient required cardiac transplantation to resect completely an "inoperable" benign tumor. All gross tumor was resected in four of eight patients with malignant lesions. All patients survived operation, but three with malignant disease died within 30 days. Late outcome was known for 41 of 42 (98%) patients. Total follow-up for the series was 200.1 patient-years, for an average of 4.7 years (range 1 month to 18 years). Excellent early and late results were obtained in patients with benign lesions, as there was no known tumor recurrence even if resection was incomplete. Effective palliation and local control of disease is possible with extensive resection of malignant primary tumors, but more effective adjuvant therapy will be necessary to improve long-term prognosis.

Adolescent↗
PubMed1986

A reconsideration of cerebral perfusion in aortic arch replacement.

Ten patients underwent aortic arch replacement for aneurysmal disease from 1970 to 1985 using a simplified cardiopulmonary bypass (CPB) technique with partial brachiocephalic perfusion, low CPB flow (30 to 50 ml/kg/min), moderate systemic cooling (26 degrees to 28 degrees C), and topical hypothermic myocardial protection. The arterial line from a single pump head has a Y shape to perfuse the femoral artery (20F cannula) and either the innominate or left carotid artery (14F). Of the 10 patients (mean age, 58 years) with arch aneurysm (6 atherosclerotic, 2 dissections, and 2 degenerative), 3 had previously undergone major cardiovascular operations. Concomitant procedures included aortic valve replacement in 4 and coronary artery bypass grafting in 3. Eight patients survived the procedure, and 1 died three weeks after operation of a ruptured abdominal aneurysm. Among the survivors, CPB time was 119 +/- 36 minutes (+/- standard deviation), myocardial ischemia time was 79 +/- 32 minutes, and intraoperative blood requirement was 5.9 +/- 3.4 units. There were no postoperative strokes. Neurological complications were only minor and included an asymptomatic miosis and ulnar nerve paresthesias in 1 patient and transient vocal cord palsy in another. Applicable in most patients undergoing elective resection of degenerative and atherosclerotic arch aneurysms and in selected patients with arch dissections, this simplified technique of brachiocephalic perfusion without circulatory arrest provides an attractive and safe alternative; the potential advantages are technical simplicity, reduced CPB and operating times, and satisfactory cerebral protection.

Adult↗
PubMed1986

Pharmacological, hematological, and physiological effects of a new thromboxane synthetase inhibitor (CGS-13080) during cardiopulmonary bypass in dogs.

The hematological and pharmacological effects of a new thromboxane synthetase inhibitor, CGS-13080 (imidazo[1,5-alpha]pyridine-5-hexanoic acid), were investigated during cardiopulmonary bypass in a blinded, randomized manner in dogs. Compared with placebo, CGS-13080 suppressed thrombin-stimulated platelet thromboxane B2 production by 90% during cardiopulmonary bypass (p less than .001), an effect that persisted for two hours after stopping the infusion. In the CGS-13080-treated group, plasma 6-keto-prostaglandin F1 alpha levels significantly increased over time (p less than .03) and were somewhat higher when compared with those in the placebo-treated group. This observation suggests that an "endoperoxide shunt" may have occurred. In the control group, an inverse correlation between platelet count and level of thromboxane B2 per platelet following in vitro thrombin stimulation (r = .5, p less than .001) was apparent, but there was no correlation between these two variables (r = .18, p less than .10) in the CGS-13080-treated group. No adverse hemodynamic or other effects attributable to CGS-13080 occurred during or immediately following cardiopulmonary bypass. These results suggest that CGS-13080 is an effective inhibitor of thromboxane B2 production during cardiopulmonary bypass in dogs and has no adverse physiological effects.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Prosthetic graft infection: limitations of indium white blood cell scanning.

The lack of a rapid, noninvasive, and accurate method to confirm or rule out prosthetic graft infection continues to constitute a compelling and vexing clinical problem. A host of adjunctive diagnostic techniques has been used in the past, but early promising results subsequently have usually not yielded acceptable sensitivity (reflecting false negatives) and specificity (reflecting false positive) data. White blood cell (WBC) indium 111 scanning has recently been added to this list. The utility and accuracy of 111In WBC scans were assessed by retrospective review of WBC scan results in 70 patients undergoing evaluation for possible prosthetic graft infection over a 7-year period. Operative and autopsy data (mean follow-up, 18 months for survivors with negative scans) were used to confirm the 22 positive, 45 negative, and three equivocal WBC scans. The false positive rate (+/- 70% confidence limits) was 36% +/- 6% (n = 8) among the 22 patients with positive scans (44% +/- 6% [11 of 25] if the three equivocal scans are included as false positive), yielding a specificity of 85% +/- 5% and an overall accuracy rate of 88% +/- 4% (80% +/- 5% and 84% +/- 5%, respectively, if the three equivocal cases are considered as false positive). All three patients with equivocal scans ultimately were judged not to have prosthetic graft infection. As implied by the high accuracy rate, the sensitivity of the test was absolute (100% [14 of 14]); there were no false negative results. (ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗