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Biomedical subjects

R S Mitchell

Publications and source records attributed to R S Mitchell.

At least 91 records · Page 5Linked to original sources

Biochemical (functional) adaptation of "arterialized" vein grafts.

Canine venous autografts and allografts were interposed in the femoral and carotid arterial positions in 29 dogs; grafts were harvested at three postoperative intervals (1-2 weeks, 4-6 weeks, and 8-10 weeks) for light and scanning electron (SEM) microscopy and lumenal surface prostacyclin (PGI2) production. Normal veins and arteries were used as controls. Radioimmunoassay for tritiated 6-k-PGF1 alpha, the stable metabolite of PGI2, was performed using a flow surface template incubation chamber during basal and arachidonic acid stimulated conditions. Using SEM, the autografts revealed normal endothelial cell (EC) surfaces at all time intervals; conversely, allografts exhibited extensive EC loss at 1-2 weeks with gradual reparation by 10-12 weeks (such that the EC surface was virtually indistinguishable from that of control veins or autografts). PGI2 production was significantly greater in control arteries than veins (p = 0.0001). At 1-2 weeks and 4-6 weeks, lumenal production of PGI2 in both the autografts and allografts was not significantly different from control vein; however, PGI2 production after 10-12 weeks was identical to normal arterial levels (and significantly [p less than 0.0044] higher than venous levels) in both basal and stimulated conditions. Although the mechanisms responsible for this functional (biochemical) "arterialization" process remain conjectural, increased biosynthesis and/or release of PGI2 by endothelial cells, acute phase inflammatory cells (allografts) mediated by interleukin-1 or myointimal cells seems most likely. Further elucidation of these sources of PGI2 is necessary, but these data demonstrate for the first time that venous grafts placed in the arterial circulation undergo complete functional adaptation (in addition to the well known morphological changes).

Adaptation, Physiological↗

Valvular-ventricular interaction: importance of the mitral apparatus in canine left ventricular systolic performance.

As the mitral valvular apparatus tenses during systole, forces transmitted along the chordae tendineae to the left ventricular chamber may influence left ventricular performance. To test this hypothesis, 10 dogs anesthetized with fentanyl were studied during cardiopulmonary bypass. The importance of the mitral apparatus in left ventricular systolic function was assessed independent of load by means of the slope of the contractile state-dependent left ventricular peak isovolumetric pressure-volume relationship (Emax), which was measured at constant heart rate and aortic pressure with a micromanometer inside a left ventricular intracavitary balloon before and immediately after all chordae tendineae were severed. Herniation of the balloon was prevented by a disk secured to the mitral anulus. Emax decreased from 11.97 +/- 3.35 (+/- SD) to 6.38 +/- 0.96 mm Hg/ml (p less than .001) with chordal severing. The volume intercept (Vo) was unchanged. Fluoroscopic studies of the balloon contour in eight additional dogs revealed dyskinesia in the area of the papillary muscle insertion and substantial alterations in chamber geometry during systole after the chordae were severed. Accordingly, we conclude that global left ventricular systolic performance is impaired when chordal attachments of the mitral valve are disrupted. Changes in left ventricular geometry or loss of inward force normally transmitted to the left ventricular wall as the valve tense may underlie these changes. These findings suggest that postoperative left ventricular dysfunction after mitral valve replacement may be attributable, in part, to excision of the native mitral apparatus at the time of surgery and support efforts to spare chordae during mitral valve surgery.

Animals↗

A prospective, randomized study of the effects of prostacyclin on platelets and blood loss during coronary bypass operations.

A randomized, double-blind study was designed to evaluate the therapeutic effect and safety of prostacyclin (epoprostenol) in patients undergoing cardiopulmonary bypass. One hundred patients having isolated coronary bypass grafting received 300 units/kg of heparin and then either prostacyclin (12.5 ng/kg/min from heparinization until cardiopulmonary bypass, 25 ng/kg/min during bypass) or buffer/diluent in a similar manner. Standardized anesthetic, perfusion, and surgical techniques were used. Drug and placebo groups were similar in demographic data and bypass times, and there were no deaths. Activated coagulation time and platelet count were significantly higher during cardiopulmonary bypass in patients receiving prostacyclin. Platelet count remained significantly higher 24 hours after bypass in the active drug group. Immediately after operation, there was significantly less prolongation of bleeding time (1.3 versus 2.9 minutes; p = 0.009) in the patients receiving prostacyclin. Blood loss was significantly reduced during the first 4 hours postoperatively in the prostacyclin group (261 +/- 159 versus 347 +/- 197 ml; p = 0.02). There was no significant difference between the groups when total blood loss was compared (710 +/- 351 versus 869 +/- 498 ml; p = 0.07). Patients receiving prostacyclin required an average of 257 ml less blood transfused in the intensive care unit (p = 0.02). We conclude that the clinical impact of prostacyclin in patients undergoing coronary artery operations was demonstrable, but small. Prostacyclin may provide clinical benefits in patients undergoing cardiopulmonary bypass when there are contraindications to or other difficulties with blood transfusion. With prostacyclin, reduced heparin dose is possible and therefore reduced protamine requirement would offer a potential benefit of less cardiovascular depression immediately after bypass. However, the advantages offered by prostacyclin are not sufficient to recommend its routine use during cardiopulmonary bypass.

Adult↗

Significant patient-related determinants of prosthetic valve performance.

With rare exception, the bulk of out knowledge concerning the performance of any particular valve substitute originates from one institution; thus, if valve-related complications are more a function of the patient substrate undergoing operation than the prosthesis per se, the usefulness of inter-institutional comparisons would be severely limited. To address this question, the outcome of 2,719 patients after mitral or aortic valve replacement over 12,955 patient-years of follow-up was analyzed by time-dependent multivariate statistical methods with respect to thromboembolic events, anticoagulant-related hemorrhage, valve failure, fatal valve failure, all valve-related morbidity and mortality, necessity for reoperation, and late survival. Many patient-related factors were significant predictors of the probability of certain patient groups for sustaining these valve-related complications. Hence, comparisons of results of valve performance from different institutions may be misleading unless patient populations are comparable.

Adolescent↗

Timing of abnormal interventricular septal motion after cardiopulmonary bypass operations. Lack of injury proved by preoperative, intraoperative, and postoperative echocardiography.

Abnormal interventricular septal motion after cardiopulmonary bypass is a widely known occurrence. The cause and exact timing of this phenomenon remain unclear. We have studied 21 patients prospectively with preoperative, intraoperative, and postoperative two-dimensional and M-mode echocardiograms. Intraoperative studies were obtained with the pericardium closed and open and after completion of procedures performed with cardiopulmonary bypass. Fourteen patients had coronary artery bypass graft operations alone. Six patients had valve replacement with or without coronary bypass, and one patient had removal of a left atrial myxoma. All patients had normal interventricular septal motion before the operation, and none had abnormal septal motion intraoperatively. Four to eight days postoperatively, the septum still thickened normally in all patients, with five patients having normal, nine patients abnormal, and seven patients paradoxical interventricular septal motion. Studies in 11 patients 1 to 4 months postoperatively showed no change from the early postoperative study. The pericardium was left open postoperatively in all patients. Six patients were studied a few hours after sternal closure and all had abnormal interventricular septal motion. We conclude that abnormal interventricular septal motion after cardiac operations is not due to injury of the septum, adhesion formation, or loss of pericardial constraint. Closure of the chest wall itself, with the pericardium left open, is associated with this abnormality.

Cardiomyopathies↗

Valve replacement in patients with native valve endocarditis: what really determines operative outcome?

The influence of 27 variables on operative mortality and late complications (defined as residual or recurrent endocarditis or late bland periprosthetic leak) was determined using discriminant analysis for 108 patients undergoing valve replacement for native valve endocarditis at Stanford University Medical Center from March, 1964, to January, 1983. Congestive heart failure was the indication for valve replacement in 86% of patients. Aortic valve replacement was required in 68% and mitral valve replacement, in 26%. Patients were arbitrarily defined as having active (58%) or healed (42%) endocarditis. Follow-up included 515 patient-years and extended to a maximum of 19 years. Operative mortality was 15 +/- 4%, and 17 patients had late complications (linearized rate, 3.3% per patient-year). Seven variables were significantly related to operative mortality in the univariate analysis, but only organism (Staphylococcus aureus versus all others, p = 0.0302) was a significant independent predictor of operative mortality. For late complications, only 2 of 7 significant univariate covariates proved to be significant independent determinants: organisms on valve culture or gram stain and the presence of annular abscess. Patients with S. aureus endocarditis not showing prompt response to antibiotic treatment must be considered for early operation. Similarly, timely operative intervention for patients with annular abscess will be essential in decreasing late valve infections and perivalvular leaks.

Actuarial Analysis↗

Percutaneous transluminal laser angioplasty for treatment of peripheral vascular disease. Clinical experience with 16 patients.

Percutaneous transluminal laser angioplasty of the peripheral arteries was performed in 16 patients with pain at rest, objective evidence of severe peripheral ischemia, conditions requiring amputation, and/or medical contraindications to surgery. In 14 patients the ipsilateral femoral artery was entered in an antegrade direction using the Seldinger technique, base-line angiograms taken, and laser angioplasty performed using argon ions transported to the target site by a 400-mu quartz fiber. Patency was established in 50% of cases and correlated directly with both total energy delivered and time and power per exposure: the lower the energy, the higher the patency rate. Complications included spasm, pain, and mechanical or laser perforation. The authors conclude that while percutaneous transluminal laser angioplasty of peripheral arteries using argon radiation is possible in man, its clinical value has not been established.

Adult↗

Evaluation for compensation of asbestos-exposed individuals. I. Detection and quantification of asbestos-related nonmalignant impairment.

An objective method for measuring nonmalignant respiratory impairment caused by inhaled asbestos has been devised. Three standard physiologic tests (the forced vital capacity [FVC], the forced expiratory volume in 1 s [FEV1], the single-breath diffusing capacity for carbon monoxide [DCO]) and the posteroanterior chest roentgenogram are utilized. The age-, height-, and sex-specific normal ranges of the FVC%, the DCO%, and the FEV1/FVC% have been used in the method. The theory and rationale are described. The resulting algorithm can be presented using a nomogram. Data on 586 asbestos-exposed subjects were analyzed by the proposed method. Empirical evaluation showed the sensitivity to be greater than 90% in definitive diagnosis of asbestosis without airflow obstruction, and the specificity to be greater than 80% for those cases judged eligible for nomographic evaluation. Exceptions were found in 15 cases diagnosed clinically as asbestosis, none of whom had any evidence of pulmonary fibrosis. In addition, 50 cases diagnosed as "no asbestosis" did have evidence of pulmonary fibrosis and would have qualified for some compensation by the proposed method. In summary, this approach has been shown to yield a reliable final asbestos-related lung impairment index that, when taken together with individual societal data, can provide a reliable basis for determining compensation.

Aged↗

Evaluation for compensation of asbestos-exposed individuals. II. Apportionment of risk for lung cancer and mesothelioma.

The incidence of lung cancer in the cigarette smoking population occupationally exposed to asbestos is inordinately high. A method for apportioning risk to these two agents has been developed. It utilizes degree of asbestos and smoking exposures; the time interval from onset and, where applicable, termination of both exposures; the time interval to diagnosis of lung cancer; and morphologic, physiologic, and radiological evidence of pulmonary fibrosis.

Adolescent↗

Detection and characterization of monoclonal antibodies specific to IgE receptors on human lymphocytes by flow cytometry.

BALB/c mice were immunized with human lymphoblastoid cells (RPMI 8866 cells) expressing surface receptors for IgE (Fc epsilon R). Spleen cells from animals displaying high titres of anti-Fc epsilon R antibodies were fused with HGPRT-deficient NSI myeloma cells. Anti-Fc epsilon R antibodies were identified by a flow cytometric assay based on their ability to block the binding of IgE-coated fluorescent latex particles to Fc epsilon R-positive cells. Fourteen monoclonal hybridoma cell lines secreting antibody of the required specificity were amplified in tissue culture and then grown in the peritoneal cavity of BALB/c mice in order to obtain ascitic fluids with high antibody titres. The specificity of each monoclonal antibody (Mab) to lymphocyte Fc epsilon R was shown by the following observations: (i) the intact monoclonal antibody molecule or, in some cases, its F(ab')2 fragments blocked the binding of IgE to several Fc epsilon R(+) cell lines different from that employed for the initial immunization; (ii) the Mab bound directly to all the Fc epsilon R(+) cell lines tested, but not to several Fc epsilon R(-) cells as determined by indirect immunofluorescence; (iii) the binding of Mab to Fc epsilon R(+) cells was selectively blocked by IgE, but not by the other classes of Ig; and (iv) Mab had no effect on the binding of IgG to Fc gamma R on normal human peripheral blood mononuclear cells (PBMC).

Animals↗

Effect of early postoperative volume loading on left ventricular systolic function (including left ventricular ejection fraction determined by myocardial marker) after myocardial revascularization.

The effects of early volume loading in terms of isovolumetric-phase and ejection-phase indexes of left ventricular systolic function were studied in 12 patients 5 hr after myocardial revascularization, with myocardial markers used to measure left ventricular volume directly and with simultaneous transmural left ventricular pressure measurements by micromanometers. Volume loading (increasing transmural left ventricular end-diastolic pressure from 11 +/- 4 to 15 +/- 5 mm Hg) induced a significant 14% increase in left ventricular end-diastolic volume index (LVEDVI), which was associated (as expected) with significant (p less than .005) augmentation of stroke work (+26%), left ventricular pressure-volume loop area (+35%), and stroke volume index (+22%) and with increments in left ventricular dP/dt and mean velocity of circumferential fiber shortening despite a simultaneous increase in left ventricular afterload. In contrast to previous radionuclide studies, however, left ventricular ejection fraction increased significantly (+9%) and the left ventricular end-systolic pressure-volume ratio did not fall. The relative change in ejection fraction was directly proportional to the increment in LVEDVI (r = .54, p = .03) and inversely related to the change in left ventricular end-systolic volume index (r = -.71, p = .0005). Patients who demonstrated a small or no increase in ejection fraction generally had a larger simultaneous increase in afterload, but one patient exhibited exhaustion of preload reserve. Ejection fraction, as an ejection-phase index of left ventricular performance, is highly dependent on afterload; therefore, interpretation of postoperative changes in ejection fraction must be undertaken only with strict caution.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗

Acute and chronic aortic dissections--determinants of long-term outcome for operative survivors.

A total of 135 survivors of surgical treatment of aortic dissection was followed for up to 15 years after surgery. Actuarial survival rates were 82 +/- 4% at 5 years and 64 +/- 6% at 10 years. There were no significant differences in long-term survival rates of patients in four subsets based on type and acuity of dissections. The incidence of late reoperation (dissection-related) was 13 +/- 4% at 5 years and 23 +/- 6% at 10 years; again, there was no significant difference among patients with different types or acuity of dissection. Multiple variables were investigated by multivariate discriminant analysis. Significant independent risk factors for late death included stroke, chronic renal dysfunction, remote myocardial infarction, and operation in the early years of this study. Younger age, site of intimal tear (arch), and cardiac tamponade portended a significantly higher likelihood of late reoperation. Except for stroke, no complication of the dissection or intraoperative factor significantly influenced late survival. Patients in whom the intimal tear was located in the aortic arch had the highest probability of late reoperation. Thus, dissection type, acuity, and distal extent, whether or not the tear was resected or concomitant aortic valve replacement performed, and a host of patient-related characteristics had no significant influence on the generally excellent long-term prognosis after surgical treatment. Indefinite surveillance of the remaining natural aorta is imperative (with reoperation when indicated) to attain such results.

Actuarial Analysis↗

Determinants of operative mortality for patients undergoing aortic valve replacement. Discriminant analysis of 1,479 operations.

The influence of 35 preoperative and intraoperative characteristics on operative mortality risk after 1,479 isolated aortic valve replacement procedures (1967 to 1981) was investigated utilizing univariate and multivariate logistic regression analyses. Mean age at operation was 58 +/- 13 years; 72% of patients were men. Physiology was classified as aortic stenosis (58%), regurgitation (30%), or both (9%). The overall operative mortality rate was 7% +/- 1%, but there were substantial differences in operative mortality rates among physiological subgroups (aortic regurgitation, 10% +/- 2%; aortic stenosis, 6% +/- 1%; stenosis/regurgitation, 5% +/- 2%). Independent determinants of operative mortality rate in the entire group were advanced New York Heart Association functional class, renal dysfunction, physiological subgroup, atrial fibrillation, and older age. In the aortic regurgitation subgroup, functional class, atrial fibrillation, and operative year were independent predictors. In the aortic stenosis subgroup, the significant determinants were functional class, renal dysfunction, age, prosthetic valve dysfunction, and absence of angina. Concomitant coronary bypass grafting, previous operation, endocarditis, and ascending aortic replacement had no independent predictive effect on operative mortality rate. Thus, the early results of aortic valve replacement can be related to several specific variables describing the functional and physiological status of the patient. Operative mortality rate is not independently related to previous operation or concomitant operative procedures. Specific differences in risk factors exist among the various physiological subgroups, probably reflecting the pathophysiology of the different hemodynamic lesions. This information should provide for a more rational approach to aortic valve replacement, at least in terms of early risk/benefit deliberations.

Adult↗

Operative risk of mitral valve replacement: discriminant analysis of 1329 procedures.

The influence of 34 variables on the operative mortality rate for isolated mitral valve replacement (MVR) was assessed by univariate and multivariate logistic regression analysis. The physiologic lesions were classified as stenosis (20%, operative mortality rate 8 +/- 1%), regurgitation (44%, operative mortality rate 13 +/- 2%), and mixed (34%, operative mortality rate 8 +/- 1%). Functional class (NYHA), previous myocardial infarction, and hepatic dysfunction were powerful independent clinical determinants of operative mortality (p less than .001), along with age at operation and emergency operation (p = .001, p = .04). Concomitant coronary artery bypass grafting or tricuspid annuloplasty, angina, ischemic etiology, and physiologic lesion were not significant independent determinants of operative risk. Interestingly, year of operation, prosthetic valve dysfunction, and previous cardiac surgery had no important effect on operative mortality. Early operative risk for MVR was related to preoperative cardiac and hepatic function. Prior myocardial infarction substantially increased the risk even if the mitral valve disease was not ischemic in origin. Increased operative mortality rate in the subgroup with mitral regurgitation was related to advanced left ventricular failure and myocardial infarction rather than the etiology of the mitral regurgitation. These clinical factors coupled with more refined measurements of left ventricular systolic pump function (independent of loading conditions) should permit more intelligent decision making regarding the optimal timing of MVR, at least in terms of early operative risk.

Adult↗

Lymphoma of the heart.

A case of malignant lymphoma involving the heart is reported. The patient presented with symptoms of cardiac decompensation. The echocardiographic findings of an echogenic mass arising from the pulmonary valve as well as demonstration of soft tissue density diffusely infiltrating the heart and mediastinum was confirmed by computer tomography and angiography. Although the findings on the noninvasive studies were highly indicative of tumor involvement, the temporal association of the symptoms to a motor vehicle accident lead to the erroneous diagnosis of intracardiac and mediastinal hematoma.

Diagnosis, Differential↗

Salvage of an ischemic limb by laser angioplasty: description of a new technique.

A 62-year-old male with severe claudication and rest pain of the left leg resulting from a totally occluded superficial femoral artery and a 95% stenosis of the deep femoral artery was treated with laser angioplasty after attempts at surgical revascularization were unsuccessful. A 200 mu silica fiber was inserted through a catheter and advanced into the lesion using 2 watts of delivered energy from an argon laser source. The fiber was then withdrawn from the lesion using 7 watts of energy to enlarge the lumen. No complications occurred, and posterior tibial blood flow was reestablished, as shown by Doppler flow measurements and resolution of clinical symptoms. We report a new technique of transcatheter fiberoptic-directed argon laser radiation (laser angioplasty) for the treatment of occlusive vascular disease.

Arterial Occlusive Diseases↗