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Biomedical subjects

R S Mitchell

Publications and source records attributed to R S Mitchell.

At least 55 records · Page 3Linked to original sources

Durability of the Hancock MO bioprosthesis compared with standard aortic valve bioprostheses.

To compare the durability of the Hancock modified orifice (Hancock MO, model 250 [H-MO]) valve with two other commonly used standard aortic valve bioprostheses, a cohort of 1,602 patients undergoing aortic valve replacement using porcine valves between 1971 and 1990 (excluding simultaneous mitral valve replacement) was analyzed retrospectively using Cox model multivariate techniques. Five hundred sixty-one patients received a composite H-MO valve, 652 received a standard Hancock model 242 (H) valve, and 389 received a Carpentier-Edwards model 2625 (C-E) valve. Mean age was 60 +/- 15 years (+/- 1 standard deviation) (71% male). Follow-up (10,247 patient-years) extended to 15 years and was 97% complete. The main focus of this study was bioprosthetic durability, using The American Association for Thoracic Surgery/The Society of Thoracic Surgeons guidelines to define structural valve deterioration (SVD). Multivariate analysis revealed that (younger) age (p < 10(-5), liver disease (p = 0.02), and 1981 to 1985 operative period (p = 0.012) were the only significant, independent predictors of SVD. In concordance with previous reports, the SVD freedom estimate was greater than 90% at 15 years for patients older than 70 years of age. Hepatic dysfunction had an adverse effect on SVD (estimated freedom from event at 10 years was 34 +/- 17% [standard error of mean] versus 78 +/- 2% for those without liver disease), but this affected only 3% of patients. Interestingly, one operative period (1981 to 1985) was associated with a slightly higher risk of SVD compared to the three other 5-year time windows. Valve type did not emerge as a significant risk factor for SVD.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Preliminary experience with the Endovascular Technologies bifurcated endovascular aortic prosthesis in a calf model.

PURPOSE: The purpose of this study was to develop a bifurcated endoluminal prosthesis for transfemoral placement in the aortoiliac position with a large-animal model that would simulate human implantation. METHODS: Fifteen calves (160 to 200 kg) underwent bilateral femoral artery exposure and transfemoral placement in the aortoiliac position of a bifurcated Dacron prosthesis, inserted through a 26F sheath with an over-the-bifurcation guide wire to retrieve the contralateral limb and secured proximally and distally with self-expanding attachment systems. The preferred location was determined before implantation and compared with final implant location by caliper measurements and angiography. Events during implantation, maneuvers used to accomplish accurate deployment, and final results, as judged by angiography and clinical evaluation, were recorded. Four animals survived and were used for chronic evaluation and healing by gross and microscopic studies. RESULTS: All grafts (n = 15) were patent at the end of the procedure. All (n = 7) noncrimped grafts had minor kinks in areas of curvature, whereas eight of eight crimped grafts (device modification) had none. Torque control of the body and individual limbs was necessary to correct twists before deployment in 10 of 15 grafts, with two greater than 30-degree twists remaining, which did not appear to affect flow. One implant was entirely deployed in the aorta because of parallax error, subsequently avoided by use of a marker board placed dorsally. Three premature deployments occurred, corrected by attachment system lock modification. The mean final implant position was within 2.9 +/- 1.4 mm (aortic), 1.6 +/- 1.1 mm, and 1.5 +/- 0.8 mm (contralateral and ipsilateral iliac limbs, respectively) of the intended position. Three of four animals intended for long-term evaluation were killed prematurely because of clinically evident spinal cord ischemia. Histologic sections at 2 weeks showed early wall repair without inflammatory cells and pannus ingrowth across the anastomosis. CONCLUSION: We conclude that implantation of a bifurcated endovascular prosthesis through the bilateral femoral approach is possible, provided the intended aortic implantation site (neck) is at least 12 mm in length (mean +/- 2 SD each direction). Torque control of each portion of the device will be needed in the majority of instances, with attention to parallax effect necessary for optimal placement. This animal model is not suitable for chronic graft evaluation because of its sensitivity for spinal cord ischemia. Healing data suggest graft incorporation similar to that of a surgically placed prosthesis.

Animals↗

Transluminal placement of endovascular stent-grafts for the treatment of descending thoracic aortic aneurysms.

BACKGROUND: The usual treatment for thoracic aortic aneurysms is surgical replacement with a prosthetic graft, but the associated morbidity and mortality are considerable. We studied the use of transluminally placed endovascular stent-graft devices as an alternative to surgical repair. METHODS: We evaluated the feasibility, safety, and effectiveness of transluminally placed stent-graft to treat descending thoracic aortic aneurysms in 13 patients over a 24-month period. Atherosclerotic, anastomotic, and post-traumatic true or false aneurysms and aortic dissections were treated. The mean diameter of the aneurysms was 6.1 cm (range, 5 to 8). The endovascular stent-grafts were custom-designed for each patient and were constructed of self-expanding stainless-steel stents covered with woven Dacron grafts. RESULTS: Endovascular placement of the stent-graft prosthesis was successful in all patients. There was complete thrombosis of the thoracic aortic aneurysm surrounding the stent-graft in 12 patients, and partial thrombosis in 1. Two patients initially had small, residual patent proximal tracts into the aneurysm sac, but both tracts thrombosed within two months after the procedure. In four patients, two prostheses were required to bridge the aneurysm adequately. There have been no deaths or instances of paraplegia, stroke, distal embolization, or infection during an average follow-up of 11.6 months. One patient with an extensive chronic aortic dissection required open surgical graft replacement four months later because of progressive dilatation of the arch. CONCLUSIONS: These preliminary results demonstrate that endovascular stent-graft repair is safe in highly selected patients with descending thoracic aortic aneurysms. This new method of treatment will, however, require careful long-term evaluation.

Adult↗

Surgical management of aortic dissection in patients with the Marfan syndrome.

BACKGROUND: Aortic dissection is one of the most lethal potential complications in patients with the Marfan syndrome. METHODS AND RESULTS: Among 360 patients undergoing operative treatment of aortic dissection between 1963 and 1992, 40 had the Marfan syndrome. There were 24 men and 16 women with a mean age of 35 +/- 9 years (+/- 1 SD; range, 15 to 54 years). These patients included 16 with acute type A, 2 with acute type B, 18 with chronic type A, and 4 with chronic type B aortic dissections. The aortic arch was involved in 29 cases. Preoperative complications included acute aortic valvular insufficiency in 13 patients, rupture into the pericardial space in 3, and loss of peripheral pulses in 9. The site of primary intimal tear was the ascending aorta in 25 patients, the aortic arch in 2, the descending aorta in 7, and not identified in 6. Operations included ascending aortic and aortic valvular replacement (with or without coronary artery reimplantation) in 22 patients, ascending aortic replacement alone in 5, and descending thoracic aortic replacement in 9. Four operative deaths (10 +/- 5% [+/- 70% confidence limits]) occurred in 3 acute patient-years and 1 chronic type A patient-years. Long-term follow-up (216 patient-years; range, 1 month to 22 years; mean, 5.4 years) revealed 15 late deaths, 7 from late aortic sequelae. The overall actuarial survival estimates were 71 +/- 8%, 54 +/- 10%, and 22 +/- 11% at 5, 10, and 15 years, respectively. Twenty late aortic operations were required in 14 patients. CONCLUSIONS: Despite satisfactory early results, the long-term survival of patients with the Marfan syndrome was suboptimal (albeit similar to those without the Marfan syndrome). Future progress will pivot on reducing the incidence of aortic dissection in these patients with medical therapy and/or earlier surgical intervention and enhanced postoperative serial imaging surveillance of the entire aorta.

Actuarial Analysis↗

Analysis of two distinct single-stranded DNA binding sites on the recA nucleoprotein filament.

The binding stoichiometry of Escherichia coli recA protein to single-stranded DNA (ssDNA) determined by two separate assays differs by a factor of 2.2-2.4. Using the fluorescence of etheno-DNA (epsilon DNA), a chemically modified ssDNA, the stoichiometry was found to be 7.0 +/- 0.6 bases/recA protein monomer in a nucleo-protein filament. Using a competition assay, a similar stoichiometry, 7.5 bases/recA, is found for unmodified poly(dT). Using the DNA-dependent ATPase of recA, which monitors bound protein rather than bound DNA, we find that each recA monomer needs to bind only 3.1 +/- 0.5 bases to fully activate the ATPase. The difference in site size determined by the two assays indicates that there are two DNA binding sites with differential effects on ATPase activation. When recA protein is mixed with ssDNA at a ratio of 7 bases/recA or greater, the complex that forms contains 7 bases/recA and acts as a kinetic trap for the ssDNA. Upon further addition of recA protein, no additional ATPase activity is observed. If, on the other hand, the ssDNA is initially mixed with excess recA (at a ratio of 3-3.5 bases/recA or less) the ATPase activity is twice as high. Analysis of the binding curves suggests that the first DNA strand binds recA to form a filament with a stoichiometry of 3-3.5 bases/protein monomer. The ATPase activity of recA is completely active in this complex. A second strand of DNA can then be bound to this filament yielding a final stoichiometry of approximately 7 bases/protein monomer. The presence of this second strand neither enhances nor inhibits ATP hydrolysis. This ternary complex may mimic the structures formed by recA in searching for homologous DNA sequences and/or in the strand exchange reaction.

Adenosine Triphosphatases↗

Intravascular stenting of acute experimental type B dissections.

To evaluate the efficacy of intravascular stenting for acute aortic dissection, 12 dogs underwent surgical creation of an acute type B dissection. Intravascular ultrasound evaluated luminal diameter, distal propagation, and branch involvement. Three animals underwent no further treatment (control). In 9 dogs, balloon-expandable intravascular stents (15-20 mm) were placed proximally to compress the intimal flap. One dog with a small dissection had complete obliteration of the false lumen after initial stent placement. Six dogs with extension below the diaphragm were initially stented proximally to restore flow; 3 were left with a residual distal false lumen, while 3 had additional stents placed to obliterate their entire false lumen. In the final 2 dogs, proximal stenting resulted only in partial compression of the false lumen. Two animals died within 24 hr due to prolonged hemodynamic instability and aortic rupture at the intimal flap, respectively. Six weeks later, radiologic and histologic evaluation was performed on the 10 surviving animals. All stented true lumens were patent without thrombus formation, and stents were covered by neointima. In dogs with stenting of the entire dissection, the aortic wall had healed and no false lumen was present. However, in all dogs with only proximal obliteration, 1/2 with partial compression, and 2/3 controls, a patent false channel was present indicative of a chronic dissection. Thus, we found that intravascular stents can restore true lumen flow and obliterate the false lumen in experimental dissections; however, stenting limited to the proximal dissection does not prevent formation of a chronic residual patent false lumen.

Acute Disease↗

Management of patients with intramural hematoma of the thoracic aorta.

BACKGROUND: Intramural hematoma of the thoracic aorta (IMH) is a diagnosis of exclusion and represents spontaneous, localized hemorrhage into the wall of the thoracic aorta in the absence of bona fide aortic dissection, intimal tear, or penetrating atherosclerotic ulcer. This process may arise from primary vasa vasorum hemorrhage within the aortic media or rupture of an atherosclerotic plaque. The clinical presentation of patients with IMH mimics that of acute aortic dissection; moreover, considerable diagnostic confusion exists despite the use of many different imaging modalities. The optimal mode of management of patients with IMH (medical versus medical plus surgical) remains problematic because of the paucity of information available. METHODS AND RESULTS: Thirteen patients with IMH were managed at two medical centers between 1983 and 1992. Patients with IMH caused by giant penetrating atherosclerotic ulcers were specifically excluded. There were 8 women and 5 men (mean age, 70 years [range, 54 to 82 years]). The admitting clinical diagnosis was acute aortic dissection, and all patients had a history of hypertension. There was no evidence of aortic dissection or intimal disruption as assessed by computed tomographic (CT) scan (n = 11), aortography (n = 10), magnetic resonance imaging (MRI) scan (n = 9), transesophageal echocardiography (TEE) (n = 6), or intravascular ultrasound (n = 1). The diagnosis of IMH was established by exclusion. The descending thoracic aorta was involved in 10 cases and the ascending/arch in 3. Conservative medical management was attempted initially. All 3 patients with IMH involving the ascending aorta ultimately required operative intervention, and 2 individuals died; 2 of 10 patients with descending aortic involvement eventually underwent surgery. Average hospital stay was 11 days; the mean follow-up interval for discharged patients was 29 months. CONCLUSIONS: IMH is a distinct pathological entity, should not be confused with aortic dissection, and probably will be identified more frequently in the future. All patients with IMH should be monitored carefully and treated with aggressive antihypertensive therapy. Frequent serial assessment is necessary using TEE or MRI/CT scans. Based on this small experience, patients with ascending/arch IMH, ongoing pain, or IMH expansion should probably undergo early graft replacement. Patients with IMH involving the descending thoracic aorta who have no evidence of progression and become pain free can probably be treated conservatively but require antihypertensive therapy and serial aortic imaging surveillance indefinitely.

Aged↗

Randomized, prospective assessment of bioprosthetic valve durability. Hancock versus Carpentier-Edwards valves.

BACKGROUND: Although the major limitation of porcine valves is their finite durability, no controlled clinical data exist regarding the relative durability of the two porcine bioprostheses implanted most commonly today, the Carpentier-Edwards (C-E) and Medtronic Hancock I (H) valves. METHODS AND RESULTS: To assess this question, 174 patients undergoing aortic (AVR) or mitral (MVR) valve replacement with a bioprosthesis between March 1980 and March 1982 were randomized to receive either a C-E or a H valve. There were 102 AVRs (54 C-E and 48 H) and 74 MVRs (39 C-E and 35 H). For both the AVR and MVR cohorts, the average patient age was 58 +/- 14 years (+/- SD). The male/female ratio was 2.2:1 for AVR and 0.57:1 for MVR. Clinical follow-up was undertaken periodically; the most recent follow-up closing interval was July through October 1992, and current follow-up was 96% complete. Cumulative follow-up totaled 1369 patient-years (mean, 7.7 +/- 3.6 years; median, 9.1 years; maximum, 12.0 years). The main focus of this analysis was bioprosthetic durability, using the AATS/STS guidelines defining "Structural Valve Deterioration" (SVD). Multivariate analysis revealed that (younger) age was the only significant (P = .024) independent predictor of SVD. Valve manufacturer (C-E versus H) and valve site (aortic versus mitral) did not emerge as significant independent risk factors for SVD. Actuarial rates (Cutler-Ederer) expressed as percent free of SVD (+/- SEM) at 10 years (n = number of patients remaining at risk) were 71 +/- 7% and 59 +/- 9% for the C-E (n = 26) and H (n = 17) groups, respectively, for the AVR cohort; for the MVR cohort, these estimates were 60 +/- 10% (n = 12) and 72 +/- 10% (n = 11), respectively, but these differences were not statistically significant (P = NS, Lee-Desu). CONCLUSIONS: After 10 years, there was no statistically significant difference in durability or other valve-related complications between the H and C-E aortic or mitral valves. Based on current information, the choice of a porcine bioprosthesis should be based on factors other than durability, including ease of implantation, hemodynamic performance, and cost.

Aortic Valve↗

The use of endovascular techniques for the treatment of complications of aortic dissection.

Intravascular ultrasonography, balloon angioplasty, stent placement, and endovascular septal fenestration have been used in the evaluation and treatment of vascular complications of acute and chronic aortic dissection in five patients. There were three men and two women with an average age of 52 years (range 39 to 64 years). There were three chronic type A dissections, one acute type B, and one subacute type B dissection. Intravascular ultrasonography was used in all five cases. The three patients with chronic type A dissections underwent unilateral renal artery angioplasty (RA PTA) and stent placement; one patient with an acute type B dissection and associated fibromuscular dysplasia underwent bilateral RA PTA without stent placement. These procedures were performed to ameliorate severe hypertension. The final patient, with a subacute type B dissection, underwent iliac artery stenting to correct severe lower extremity ischemia. During a second intervention, this patient, who also had bowel ischemia and nonresolving acute renal failure, underwent balloon dilatation of a preexisting septal fenestration to augment visceral blood supply and bilateral RA PTA and stent placement in an effort to improve renal function. This patient eventually died of gut ischemia. After RA PTA and stent placement, one patient had a major intrarenal hemorrhage that required coil embolization and transfusion. In the four survivors, RA PTA and stent placement resulted in immediate improvement in blood pressure control. This response has been sustained during follow-up intervals ranging from 8 to 18 months (average 10 months). Intravascular ultrasonography can clearly demonstrate the pathologic anatomy associated with aortic dissection (even when angiography is ambiguous) and is essential for guiding therapeutic endovascular interventions. Further exploration of the efficacy of these endovascular techniques is warranted in this high-risk group of patients with aortic dissection who have appropriate clinical indications.

Acute Disease↗

Early experience with cryopreserved saphenous vein allografts as a conduit for complex limb-salvage procedures.

PURPOSE: The lack of a suitable alternative to autogenous vein is often the limiting factor for complex lower extremity vascular reconstruction, especially when previously placed grafts have failed. Cryopreserved saphenous vein allografts have been used as an alternative conduit. This report reviews our early experience with this conduit in a series of complex redo revascularization procedures for limb salvage when no suitable autogenous vein was available. METHODS: Thirty-five patients underwent 39 lower extremity bypass grafts on 36 limbs. These patients had undergone a combined total of 72 prior revascularization procedures on the symptomatic limb, an average of two procedures per patient. Only five bypasses were performed as a primary procedure. There were 18 men and 17 women with a mean age of 71 years. Sixteen of the patients had diabetes. Thirty-four bypasses were performed for rest pain or ulceration, four for disabling claudication, and one for replacement of an aneurysmal vein graft. There were 35 femorotibial, three below-knee femoropopliteal, and one femoropedal reconstruction. Twenty-five grafts were constructed with cryopreserved vein only, whereas 14 were composite grafts; 10 were constructed with polytetrafluoroethylene, one with Dacron, and three with spliced native saphenous vein. The mean follow-up was 9 months (range 1 to 25 months). RESULTS: There was one early death (< 30 days) and two late deaths. Two patients died with a patent graft. There have been 12 early graft closures and an additional 17 late failures, resulting in primary cumulative graft patency rates of 67%, 56%, 43%, 28%, and 14% at 1, 3, 6, 12, and 18 months, respectively. Surgically correctable causes, including technical error and anastomotic stenosis, could be identified in 13 of the 29 graft failures. Salvage of failed grafts resulted in secondary cumulative graft patency rates of 87%, 77%, 61%, 46%, and 37% at these same intervals. There was no significant difference in primary or secondary graft patency rates related to diabetes, ABO graft compatibility, graft composition or orientation, indication for surgery, state of the outflow tract, or site of distal anastomosis. Limb salvage was attained in 24 (67%) of the 36 limbs. Two amputations were necessary despite patent grafts. CONCLUSIONS: Because of the poor overall graft patency rates, cryopreserved saphenous vein allografts should be used only as a last resort when no alternative autogenous conduit is available. Unless patency rates superior to those achievable with currently available prosthetic or biologic conduits can be attained by adjunctive measures such as routine anticoagulation or immunosuppressive therapy, the use of cryopreserved saphenous vein allografts for lower extremity revascularization should be deferred until improved preparation techniques provide a more durable conduit.

Adult↗

Three-dimensional spiral computed tomographic angiography: an alternative imaging modality for the abdominal aorta and its branches.

PURPOSE: We sought to apply a new technique of computed tomographic angiography (CTA) to the preoperative and postoperative assessment of the abdominal aorta and its branches. METHODS: After a peripheral intravenous contrast injection, the patient is continuously advanced through a spiral CT scanner, while maintaining a 30-second breath-hold. Thirty-five patients with abdominal aortic, renal, and visceral arterial disease have undergone CTA. RESULTS: Diagnostic three-dimensional images were obtained in patients with aortic aneurysms (n = 9), aortic dissections (n = 4), and mesenteric artery stenoses (n = 4). The technique has also been used to assess vessels after operative reconstruction or endovascular intervention in 18 patients. These preliminary studies have correlated well with conventional arteriographic findings. In aneurysmal disease both the lumen and mural thrombus and associated renal artery stenoses are visualized. The true and false channels of aortic dissections and the perfusion source of the visceral vessels are clearly shown; patency of visceral and renal reconstruction or stent placement are confirmed. CTA is relatively noninvasive and can be completed in less time than conventional angiography with less radiation exposure. CONCLUSIONS: This initial experience suggests that CTA may be a valuable alternative to conventional arteriography in the evaluation of the aorta and its branches.

Adult↗

Successful percutaneous balloon catheter treatment of renal artery occlusion and anuria.

Progressive renal failure may be due to renal artery stenosis and occlusion. Gradual occlusion of the renal arteries may allow the development of collateral arterial supply sufficient to avoid dialysis. Even when dialysis is required, significant viable renal parenchyma may still be present to allow escape from dialysis following revascularization of one or both kidneys. The chance of success in such cases is thought to be better if the patient still produces a significant amount of urine. We report here a patient who was completely anuric for five days and in whom excellent renal function returned after balloon angioplasty of one of two occluded renal arteries.

Acute Kidney Injury↗

Durability of porcine valves at fifteen years in a representative North American patient population.

Isolated aortic (n = 857) or mitral (n = 793) valve replacement with a porcine bioprosthesis was performed in 1650 patients between 1971 and 1980. Follow-up (total = 12,012 patient-years) extended to more than 15 years and was 96% complete. Patient age ranged from 16 to 87 years; mean age was 59 +/- 11 years (+/- 1 standard deviation) for the aortic valve replacement cohort and 56 +/- 12 years for the mitral valve replacement cohort. The operative mortality rates were 5% +/- 1% (+/- 70% confidence limits) and 8% +/- 1%, respectively, for the aortic and mitral subgroups. Estimated freedom from structural valve deterioration (+/- 1 standard error of the mean) after 10 and 15 years was significantly higher for the aortic than for the mitral valve replacement subgroup (85% +/- 0.4% and 63% +/- 3% versus 78% +/- 2% and 45% +/- 3%, respectively, p = 0.001). Reoperation-free actuarial estimates were also significantly greater for the aortic valve replacement cohort: 83% +/- 2% and 57% +/- 3% versus 78% +/- 2% and 43% +/- 3% for mitral valve replacement at 10 and 15 years, respectively. The mortality rate for reoperative aortic valve replacement was 11% +/- 1%; it was 8% +/- 1% for reoperative mitral valve replacement. Importantly, the estimates of freedom from valve-related death (including sudden, unexplained deaths) were relatively high at 10 and 15 years: 78% +/- 2% and 69% +/- 3% in the aortic cohort and 74% +/- 2% and 63% +/- 3% in the mitral cohort (p = not significant). Excluding sudden, unexplained deaths, these estimates were 81% +/- 3% (aortic) and 73% +/- 4% (mitral) at 15 years. Thromboembolism-free rates were 84% +/- 3% (aortic) and 78% +/- 6% (mitral) at 15 years, and freedom from anticoagulant-related hemorrhage was 96% +/- 1% and 89% +/- 2%, respectively. At the time of current follow-up, 13% of patients having aortic valve replacement and 50% of patients having mitral valve replacement were receiving warfarin sodium. The hazard functions for thromboembolism and prosthetic valve endocarditis were constant and remained less than 1%/pt-yr over the entire follow-up period.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗

Aortic dissection resulting from tear of transverse arch: is concomitant arch repair warranted?

Forty-seven patients with aortic dissection resulting from a primary tear located in the transverse aortic arch underwent surgical treatment. Twenty-six patients had acute type A, 7 had acute type B, 7 had chronic type A, and 7 had chronic type B aortic dissections. Of the 33 patients with acute dissections, 11 (7 acute type A and 4 acute type B) underwent concomitant arch repair with an operative (less than or equal to 30 days) mortality rate of 55% (35% to 73%, +/- 1 asymmetric 70% confidence limit) (2 of 7 acute type A and 4 of 4 acute type B). Concomitant arch repair was omitted in 22 patients with acute dissections (19 acute type A and 3 acute type B); the operative mortality rate was 41% (29% to 54%) (7 of 19 acute type A and 2 of 3 acute type B) (p = not significant versus arch repair). The overall survival rate for those with arch repair was 45% +/- 15% (+/- 1 standard error of the estimate) at 4 years, compared with 43% +/- 11% for patients without arch repair (p = not significant). Considering the type of dissection, the 4-year survival estimate for patients with acute type A dissections who underwent arch repair (5 hemiarch and 2 total arch) was 71% +/- 17% (versus 44% +/- 12% for acute type A patients without arch repair). There were no survivors among the 4 patients with acute type B dissections who had an arch repair (1 hemiarch and 3 total arch), whereas patients with acute type B dissections who did not undergo concomitant arch repair had a 4-year survival estimate of 33% +/- 27% (p = not significant versus arch repair). Four other patients with acute type B dissections resulting from an arch tear were managed medically and tended to have a slightly better prognosis (2-year survival estimate of 75% +/- 22% versus 14% +/- 13% for all surgically treated acute type B patients), but again this difference was not statistically significant. Multivariate analysis of the 47 surgical patients revealed that advanced age (p = 0.0008), preoperative dissection complications (p = 0.02), and other coexistent medical problems (p = 0.03) were the only significant, independent determinants of overall mortality. Initial arch repair was not a significant predictor. Nine percent (2/22) of patients with acute type A dissections who initially underwent isolated ascending aortic replacement required subsequent arch replacement; 1 died after reoperation.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗

recA protein filaments bind two molecules of single-stranded DNA with off rates regulated by nucleotide cofactor.

To probe the role of nucleotide cofactor in the binding of single-stranded DNA to recA protein, we have developed a sedimentation assay using 5'-labeled 32P-poly(dT).recA.poly(dT) complexes sediment quantitatively when centrifuged at 100,000 x g for 45 min, whereas free poly(dT) remains in the supernatant. In the presence of ATP, between 6 and 7 bases cosediment per recA monomer; but when ADP is present or in the absence of added nucleotide cofactor, only 3-3.5 bases/recA monomer cosediment. In competition experiments in which recA.32P-poly(dT) complexes are incubated with unlabeled poly(dT), we again find 3-3.5 bases of labeled poly(dT) cosedimenting per recA monomer when no nucleotide cofactor is present. However, when the same experiment is performed with ATP, only half of the expected 6-7 bases of labeled poly(dT) remain bound to the DNA, demonstrating that half of the poly(dT) in the complex exchanges rapidly with free poly(dT), whereas the other half equilibrates slowly, like poly(dT) in the absence of nucleotide. The rate of exchange of the second more tightly bound poly(dT) is accelerated when ADP is present. Our observations are rationalized by a model in which each recA protein helical filament binds two strands of poly(dT) with a stoichiometry of 3-3.5 bases/recA monomer/strand.

Adenosine Diphosphate↗