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R S Mitchell

Publications and source records attributed to R S Mitchell.

At least 19 recordsLinked to original sources
PubMed2001

Role of the non-homologous DNA end joining pathway in the early steps of retroviral infection.

Early after infection, the retroviral RNA genome is reverse transcribed to generate a linear cDNA copy, then that copy is integrated into a chromosome of the host cell. We report that unintegrated viral cDNA is a substrate for the host cell non-homologous DNA end joining (NHEJ) pathway, which normally repairs cellular double-strand breaks by end ligation. NHEJ activity was found to be required for an end-ligation reaction that circularizes a portion of the unintegrated viral cDNA in infected cells. Consistent with this, the NHEJ proteins Ku70 and Ku80 were found to be bound to purified retroviral replication intermediates. Cells defective in NHEJ are known to undergo apoptosis in response to retroviral infection, a response that we show requires reverse transcription to form the cDNA genome but not subsequent integration. We propose that the double-strand ends present in unintegrated cDNA promote apoptosis, as is known to be the case for chromosomal double-strand breaks, and cDNA circularization removes the pro-apoptotic signal.

3T3 Cells↗
PubMed2001

Treatment of endocarditis with valve replacement: the question of tissue versus mechanical prosthesis.

BACKGROUND: It remains unknown whether there is any important clinical advantage to the use of either a bioprosthetic or mechanical valve for patients with native or prosthetic valve endocarditis. METHODS: Between 1964 and 1995, 306 patients underwent valve replacement for left-sided native (209 patients) or prosthetic (97 patients) valve endocarditis. Mechanical valves were implanted in 65 patients, bioprostheses in 221 patients, and homografts in 20 patients. RESULTS: Operative mortality was 18+/-2% and was independent of replacement valve type (p > 0.74). Long-term survival was superior for patients with native valve endocarditis (44+/-5% at 20 years) compared with those with prosthetic valve endocarditis (16+/-7% at 20 years) (p < 0.003). Survival was independent of valve type (p > 0.27). The long-term freedom from reoperation for patients who received a biologic valve who were younger than 60 years of age was low (51+/-5% at 10 years, 19+/-6% at 15 years). For patients older than 60 years, however, freedom from reoperation with a biological valve (84+/-7% at 15 years) was similar to that for all patients with mechanical valves (74+/-9% at 15 years) (p > 0.64). CONCLUSIONS: Mechanical valves are most suitable for younger patients with native valve endocarditis; however, tissue valves are acceptable for patients greater than 60 years of age with native or prosthetic valve infections and for selected younger patients with prosthetic valve infections because of their limited life expectancy.

Adult↗
PubMed2000

Institutional peer review can reduce the risk and cost of carotid endarterectomy.

HYPOTHESIS: Surgeon-directed institutional peer review, associated with positive physician feedback, can decrease the morbidity and mortality rates associated with carotid endarterectomy. DESIGN: Case series. SETTING: Tertiary care university teaching hospital. PATIENTS/INTERVENTIONS: All patients undergoing carotid endarterectomy at our institution during a 5-year period ending August 1998. RESULTS: Stroke rate decreased from 3.8% (1993-1994) to 0% (1997-1998). The mortality rate decreased from 2.8% (1993-1994) to 0% (1997-1998). Length of stay decreased from 4.7 days (1993-1994) to 2.6 days (1997-1998). The total cost decreased from $13,344 (1993-1994) to $9548 (1997-1998). CONCLUSIONS: An objective, confidential peer review process that provides ongoing feedback of performance to surgeons and documents that performance in relationship with that of peers seems to be effective in reducing the morbidity and mortality rate associated with carotid endarterectomy. In addition, the review process lowered the hospital cost of performing carotid endarterectomy.

Aged↗
PubMed2000

PCR analysis of the immunoglobulin heavy chain gene in polyclonal processes can yield pseudoclonal bands as an artifact of low B cell number.

Polymerase chain reaction (PCR)-based analysis for detecting immunoglobulin heavy chain gene (IgH) rearrangements in lymphoproliferative disorders is well established. The presence of one or two discrete bands is interpreted as a monoclonal proliferation, whereas a smear pattern represents a polyclonal population. Prompted by our observation of discrete bands in histologically reactive processes with a relative paucity of B cells, we sought to determine whether low numbers of B cells in biopsy specimens could artifactually produce pseudomonoclonal bands. We performed IgH PCR analysis on serially diluted DNA samples from 5 B cell non-Hodgkin's lymphomas (B-NHLs), 5 reactive lymph nodes, 5 reactive tonsils and 10 microdissected germinal centers from a lymph node with follicular hyperplasia. We also assessed multiple aliquots of DNA samples from small biopsy specimens of reactive lymphocytic processes from the stomach (5 cases). PCR products were evaluated using high resolution agarose or polyacrylamide gels, and DNA sequencing was performed on IgH PCR products from two reactive germinal centers, which yielded monoclonal bands of identical size. All 5 B-NHLs harboring monoclonal B cell populations yielded single discrete bands, which were maintained in all dilutions. By contrast, all of the reactive lesions with polyclonal patterns at 50 ng/microl starting template concentration showed strong pseudomonoclonal bands at dilutions of 1:1,000 to 1:1,500 in placental DNA. Two of the microdissected reactive germinal centers that showed bands of identical size on duplicate reactions were proven to have different IgH sequences by sequencing. We conclude that specimens containing low numbers of polyclonal B cells may produce pseudomonoclonal bands on IgH PCR analysis. IgH PCR analysis should be performed on multiple aliquots of each DNA sample, and only samples that yield reproducible bands of identical size can be reliably interpreted as monoclonal.

B-Lymphocytes↗
PubMed2000

Endovascular repair of abdominal aortic aneurysms: eligibility rate and impact on the rate of open repair.

OBJECTIVE: The purpose of this study was to determine the rate of eligibility among patients with abdominal aortic aneurysms (AAAs) considered for endovascular repair and to examine the effect of an endovascular program on the institutional pattern of AAA repair. METHODS: All patients evaluated for endovascular AAA repair since the inception of an endovascular program were reviewed for determination of eligibility rates and eventual treatment. Open AAA repairs were categorized as simple (uncomplicated infrarenal), complex (juxtarenal, suprarenal, thoracoabdominal, infected), or ruptured, and their rates before and after initiation of an endovascular program were compared. RESULTS: Over 3 years, 324 patients were considered for endovascular AAA repair; 176 (54%) were candidates, 138 (43%) were not candidates, and 10 (3%) did not complete the evaluation. The rate of eligibility increased significantly from 45% (66/148 patients) during the first half of this period to 63% (110/176 patients) during the second half (P <. 001). Candidates were significantly younger (74.4 +/- 7.6 years) than noncandidates (78.3 +/- 6.7 years) (P <.01), and their aneurysm diameter tended to be smaller (57.6 +/- 9.2 mm compared with 60.8 +/- 12.3 mm; P =.06). The most common reason for ineligibility was an inadequate proximal aortic neck. Of 176 candidates, 78% underwent endovascular repair, and 6% underwent open repair. Of 138 noncandidates, 56% underwent surgical repair. Over a period of 6 years, 542 patients with AAAs (429 simple, 86 complex, 27 ruptured) underwent open repair. The total number and ratio of simple to complex open repairs for nonruptured aneurysms during the 3 years before the initiation of the endovascular program (213 simple, 44 complex) were not significantly different from the repairs over the subsequent 3-year period (216 simple, 42 complex). Similarly, no difference in the total number and the ratio of simple to complex open repairs was found between the first and the second 18-month periods since the initiation of the endovascular program. CONCLUSIONS: The rate of eligibility of patients with AAA for endovascular repair appears to be higher than previously reported. The presence of an active endovascular program has not decreased the number or shifted the distribution of open AAA repair.

Aged↗
PubMed2000

Neurosurgical and neuroendovascular management of Takayasu's arteritis.

OBJECTIVE: The roles of surgical and endovascular treatments for patients with Takayasu's arteritis are not clear. We report our experience in the neurosurgical and/or neuroendovascular treatment of patients with Takayasu's arteritis who exhibited ischemic neurological symptoms. METHODS: Between 1994 and 1998, seven patients with Takayasu's arteritis and neurological symptoms were treated at the Stanford University Medical Center. All patients were angiographically evaluated and received maximal medical therapy. Cerebral blood flow studies were performed for six patients. Three patients underwent surgical revascularization procedures alone, two underwent combinations of surgical and endovascular procedures, and two underwent endovascular treatment alone. RESULTS: The most common neurological symptoms were dysequilibrium, syncope, and visual disturbances. The characteristic angiographic features of Takayasu's arteritis were identified for all patients. The subclavian arteries and proximal carotid and vertebral arteries were involved in all patients. Two patients exhibited improvement of their symptoms after endovascular treatment alone. There were two deaths after surgery, involving patients with severe global cerebral hypoperfusion. All other surgically treated patients exhibited improvement of their symptoms, with patent grafts, up to 4 years after surgery. Cerebral blood flow improved after treatment. CONCLUSION: Improvement of symptoms can be achieved with surgical revascularization and/or endovascular treatment. Staged revascularization might be better than one-stage bilateral high-flow grafting for patients with severe global hypoperfusion.

Adolescent↗
PubMed2000

Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons.

PURPOSE: To compare the number of retinal ganglion cells (RGCs) topographically mapped with specific visual field threshold test data in the same eyes among glaucoma patients. METHODS: Seventeen eyes of 13 persons with well-documented glaucoma histories and Humphrey threshold visual field tests (San Leandro, CA) were obtained from eye banks. RGC number was estimated by histologic counts of retinal sections and by counts of remaining axons in the optic nerves. The locations of the retinal samples corresponded to specific test points in the visual field. The data for glaucoma patients were compared with 17 eyes of 17 persons who were group matched for age, had no ocular history, and had normal eyes by histologic examination. RESULTS: The mean RGC loss for the entire retina averaged 10.2%, indicating that many eyes had early glaucoma damage. RGC body loss averaged 35.7% in eyes with corrected pattern SD probability less than 0.5%. When upper to lower retina RGC counts were compared with their corresponding visual field data within each eye, a 5-dB loss in sensitivity was associated with 25% RGC loss. For individual points that were abnormal at a probability less than 0.5%, the mean RGC loss was 29%. In control eyes, the loss of RGCs with age was estimated as 7205 cells per year in persons between 55 and 95 years of age. In optic nerves from glaucoma subjects, smaller axons were significantly more likely to be present than larger axons (R2 = 0.78, P<0.001). CONCLUSIONS: At least 25% to 35% RGC loss is associated with statistical abnormalities in automated visual field testing. In addition, these data corroborate previous findings that RGCs with larger diameter axons preferentially die in glaucoma.

Aged↗
PubMed2000

Retrograde axonal transport of BDNF in retinal ganglion cells is blocked by acute IOP elevation in rats.

PURPOSE: To determine whether acute experimental glaucoma in rats obstructs retrograde transport of brain-derived neurotrophic factor (BDNF) to retinal ganglion cells (RGCs). METHODS: Forty rats had unilateral injection of either (125)I-BDNF (20 animals) or a mixture of (125)I-BDNF and 100-fold excess nonradiolabeled BDNF (20 animals). In each group of 20 animals, eyes contralateral to injection had either normal intraocular pressure (IOP; 10 animals) or IOP elevated to 25 mm Hg below the systolic blood pressure of the eye (10 animals). In each group of 20 rats, ipsilateral eyes had IOP set at systolic blood pressure (4 eyes), had optic nerve transection (10 eyes), or had normal IOP (6 eyes). Six hours after injection, animals were killed and tissues were fixed, embedded, and sectioned for autoradiography. Grain counts were performed over retina and optic nerve using automated image analysis. RESULTS: IOP elevation to 25 mm Hg below systolic blood pressure (perfusion pressure [PP] 25) decreased median retinal nerve fiber layer (NFL) grains by 38% compared with controls (P: < 0.001). Competition by cold BDNF reduced NFL grains by 28% (P: = 0.013). Considering only the radioactivity representing specific retrograde transport of BDNF, IOP elevation to PP25 reduced transport by 74%, whereas elevation to PP0 (equaling systolic blood pressure) reduced specific transport by 83%. CONCLUSIONS: BDNF is transported retrogradely from the superior colliculus in adult rats, and this transport is substantially inhibited by acute IOP elevation. Deprivation of BDNF among RGCs may contribute to neuron loss in glaucoma.

Acute Disease↗
PubMed2000

Endovascular treatment of aortic dissections and thoracic aortic aneurysms.

Diseases of the thoracic aorta pose a significant challenge to the surgeon because of the complexity of the disease and the characteristics of the patient population. Frequent comorbidities and increasing age account for mortality rates between 5% and 20% for surgical repair of descending thoracic aortic aneurysms and in excess of 50% for Stanford type B aortic dissections, when complicated by preoperative end-organ ischemia. Endovascular techniques of fenestration, stenting, and stent-grafting have emerged as viable alternatives to conventional surgery in these patients. The authors review their experience using endovascular stent-grafts in the treatment of 103 patients with descending thoracic aortic aneurysms and 19 patients with acute aortic dissections. Fenestration and stenting are also addressed as adjuvant therapies in the treatment of complicated aortic dissections. Actuarial survival for aneurysms was 81% +/- 5% at 1 year and 73% +/- 5% at 2 years. Stent-grafting for acute aortic dissections achieved instant relief of symptoms in 71% of cases with an early procedural mortality of 16%, and endovascular revascularization of ischemic beds was achieved in 93% +/- 4% of cases of peripheral or visceral ischemia. The authors' experience supports the use of endovascular techniques in the treatment of thoracic aortic pathologic conditions. Longer follow-up and results of ongoing trials that use newer devices will help define the indications for their future use.

Aged↗
PubMed1999

Differential requirements for tumor necrosis factor receptor-associated factor family proteins in CD40-mediated induction of NF-kappaB and Jun N-terminal kinase activation.

CD40 is a member of the tumor necrosis factor receptor family that mediates a number of important signaling events in B-lymphocytes and some other types of cells through interaction of its cytoplasmic (ct) domain with tumor necrosis factor receptor-associated factor (TRAF) proteins. Alanine substitution and truncation mutants of the human CD40ct domain were generated, revealing residues critical for binding TRAF2, TRAF3, or both of these proteins. In contrast to TRAF2 and TRAF3, direct binding of TRAF1, TRAF4, TRAF5, or TRAF6 to CD40 was not detected. However, TRAF5 could be recruited to wild-type CD40 in a TRAF3-dependent manner but not to a CD40 mutant (Q263A) that selectively fails to bind TRAF3. CD40 mutants with impaired binding to TRAF2, TRAF3, or both of these proteins completely retained the ability to activate NF-kappaB and Jun N-terminal kinase (JNK), implying that CD40 can stimulate TRAF2- and TRAF3-independent pathways for NF-kappaB and JNK activation. A carboxyl-truncation mutant of CD40 lacking the last 32 amino acids required for TRAF2 and TRAF3 binding, CD40(Delta32), mediated NF-kappaB induction through a mechanism that was suppressible by co-expression of TRAF6(DeltaN), a dominant-negative version of TRAF6, but not by TRAF2(DeltaN), implying that while TRAF6 does not directly bind CD40, it can participate in CD40 signaling. In contrast, TRAF6(DeltaN) did not impair JNK activation by CD40(Delta32). Taken together, these findings reveal redundancy in the involvement of TRAF family proteins in CD40-mediated NF-kappaB induction and suggest that the membrane-proximal region of CD40 may stimulate the JNK pathway through a TRAF-independent mechanism.

Amino Acid Sequence↗
PubMed1999

Endovascular stent-graft placement for the treatment of acute aortic dissection.

BACKGROUND: The standard treatment for acute aortic dissection is either surgical or medical therapy, depending on the morphologic features of the lesion and any associated complications. Irrespective of the form of treatment, the associated mortality and morbidity are considerable. METHODS: We studied the placement of endovascular stent-grafts across the primary entry tear for the management of acute aortic dissection originating in the descending thoracic aorta. We evaluated the feasibility, safety, and effectiveness of transluminal stent-graft placement over the entry tear in 4 patients with acute type A aortic dissections (which involve the ascending aorta) and 15 patients with acute type B aortic dissections (which are confined to the descending aorta). Dissections involved aortic branches in 14 of the 19 patients (74 percent), and symptomatic compromise of multiple branch vessels was observed in 7 patients (37 percent). The stent-grafts were made of self-expanding stainless-steel covered with woven polyester or polytetrafluoroethylene material. RESULTS: Placement of endovascular stent-grafts across the primary entry tears was technically successful in all 19 patients. Complete thrombosis of the thoracic aortic false lumen was achieved in 15 patients (79 percent), and partial thrombosis was achieved in 4 (21 percent). Revascularization of ischemic branch vessels, with subsequent relief of corresponding symptoms, occurred in 76 percent of the obstructed branches. Three of the 19 patients died within 30 days, for an early mortality rate of 16 percent (95 percent confidence interval, 0 to 32 percent). There were no deaths and no instances of aneurysm or aortic rupture during the subsequent average follow-up period of 13 months. CONCLUSIONS: These initial results suggest that stent-graft coverage of the primary entry tear may be a promising new treatment for selected patients with acute aortic dissection. This technique requires further evaluation, however, to assess its therapeutic potential fully.

Acute Disease↗
PubMed1999

Thoracic aortic aneurysm repair with an endovascular stent graft: the "first generation".

OBJECTIVE: The feasibility and efficacy trial of an endovascular stent-grafting system for the treatment of aneurysms of the descending thoracic aorta was investigated. METHODS: After Institutional Review Board approval, 103 patients (mean age 69 years) underwent stent graft repair of a descending thoracic aortic aneurysm between July 1992 and November 1997. The stent graft was fabricated using self-expanding "Z" stents covered by a woven Dacron tube graft. Follow-up, which averaged 22 months, was 100% complete. Simultaneous open abdominal aortic aneurysm repair was performed in 19 patients. RESULTS: Complete aneurysm thrombosis was achieved in 86 patients (83%). Early mortality, defined as a death during the same hospitalization or in less than 30 days, was 9 +/- 3%, and was significantly associated with preoperative cerebrovascular accident (CVA) or myocardial infarction. Major perioperative morbidity occurred in 31 patients, and included paraplegia in 3, CVA in 7, and respiratory insufficiency in 12 patients each. Actuarial survival was 81 +/- 4% at 1 year, and 73 +/- 5% at 2 years. Treatment failure (including all late, sudden, unexplained deaths) occurred in 38 patients, and only 53 +/- 10% of patients were free of treatment failure at 3.7 years. Five patients required late operative therapy for endoleaks associated with aneurysm enlargement. CONCLUSIONS: Satisfactory results were achieved using this "first-generation" homemade stent graft device. Mortality and morbidity occurred frequently, but may have been associated with the high-risk character of this patient population. Medium-term results were acceptable, but continued aortic enlargement, with the late development of endoleaks, is a significant concern. Second-generation devices with commercial development, coupled with this initial experience, should allow improved clinical results in the future. Longer term follow-up is still necessary to fully define the efficacy of this endovascular approach.

Adult↗
PubMed1999

Percutaneous balloon fenestration and stenting for life-threatening ischemic complications in patients with acute aortic dissection.

OBJECTIVES: Acute aortic dissection frequently causes life-threatening ischemia of end-organs, historically associated with mortality exceeding 60%. Reperfusion with the use of interventional radiologic methods has evolved as a promising treatment. We report results of our initial 6 years of experience with percutaneous balloon fenestration of the intimal flap and endovascular stenting. METHODS: Forty patients (32 male and 8 female) with a median age of 53 years (range 16-86 years) underwent percutaneous treatment for peripheral ischemic complications of 10 type A and 30 type B acute aortic dissections since 1991. Twenty patients had ischemia of multiple organ systems. Thirty patients had renal, 22 had leg, 18 had mesenteric, and 1 had arm ischemia. RESULTS: Fourteen patients were treated with stenting of either the true or false lumen combined with balloon fenestration of the intimal flap, 24 with stenting alone, and 2 with fenestration alone. Successful revascularization was achieved in 93% +/- 4% (+/-70% confidence levels) of patients (37/40). Nine patients had procedure-related complications. The 30-day mortality rate was 25% +/- 7% (10/40), often related to irreversible ischemia of intra-abdominal organs that was present before the procedure. Of the remaining 30 patients, 5 have died and the remaining 25 continue to have relief of ischemic symptoms at a mean follow-up of 29 months. CONCLUSION: Percutaneous balloon fenestration of the intimal flap and endovascular stenting is an effective treatment for life-threatening ischemic complications of acute aortic dissection.

Acute Disease↗
PubMed1999

Endovascular solutions for diseases of the thoracic aorta.

Technology is proceeding at a very brisk pace. Harnessing that technology for clinical use is both a challenge and an opportunity. This combination of surgical and interventional methods has allowed for improved clinical outcomes in certain complex aortic problems. This article explores and discusses new techniques used in detection and treatment of diseases of the thoracic aorta.

Aged↗
PubMed1998

Characterization of interactions between the anti-apoptotic protein BAG-1 and Hsc70 molecular chaperones.

The anti-cell death protein BAG-1 binds to 70-kDa heat shock proteins (Hsp70/Hsc70) and modulates their chaperone activity. Among other facilitory roles, BAG-1 may serve as a nucleotide exchange factor for Hsp70/Hsc70 family proteins and thus represents the first example of a eukaryotic homologue of the bacterial co-chaperone GrpE. In this study, the interactions between BAG-1 and Hsc70 are characterized and compared with the analogous GrpE-DnaK bacterial system. In contrast to GrpE, which binds DnaK as a dimer, BAG-1 binds to Hsc70 as a monomer with a 1:1 stoichiometry. Dynamic light scattering, sedimentation equilibrium, and circular dichroism measurements provided evidence that BAG-1 exists as an elongated, highly helical monomer in solution. Isothermal titration microcalorimetry was used to determine the complex stoichiometry and an equilibrium dissociation constant, KD, of 100 nM. Kinetic analysis using surface plasmon resonance yielded a KD consistent with the calorimetrically determined value. Molecular modeling permitted a comparison of structural features between the functionally homologous BAG-1 and GrpE proteins. These data were used to propose a mechanism for BAG-1 in the regulation of Hsp70/Hsc70 chaperone activity.

Amino Acid Sequence↗
PubMed1998

The "first generation" of endovascular stent-grafts for patients with aneurysms of the descending thoracic aorta.

OBJECTIVE: Our goal was to determine whether endovascular stent-grafting is feasible and effective for patients with aneurysms of the descending thoracic aorta. METHODS: Starting in July 1992, we conducted a prospective, uncontrolled clinical trial in 103 patients (mean age 69 years [range 34-89 years]) who underwent endovascular treatment of aneurysms of the descending thoracic aorta using a custom-fabricated, self-expanding stent-graft device. Follow-up was 100% complete and averaged 22 months. Sixty-two patients (60%) were judged not to be reasonable candidates for a conventional "open" surgical procedure. RESULTS: Complete thrombosis of the aneurysm was ultimately achieved in 86 (83%) patients. The early mortality rate was 9% +/- 3% (+/- 70% CL). Multivariable analysis revealed that myocardial infarction or stroke was linked with a higher likelihood of early death (P = .001). Early serious complications included paraplegia in 3% +/- 2% and stroke in 7% +/- 3%. Actuarial survival estimates at 1 year and 2 years were 81% +/- 4% and 73% +/- 5% (+/- 1 SE), respectively; being judged not to be a surgical candidate portended a higher probability of death (P = .003). According to the intent-to-treat principle, "treatment failure" (including all late sudden unexplained deaths) occurred in 38 patients; 53% +/- 10% of patients were free from treatment failure at 3.7 years. Stent-graft related complications occurred commonly and were linked with several anatomic, technical, and patient-related risk factors. CONCLUSIONS: This 5-year clinical trial involving use of a "first generation" device indicates that endovascular stent-grafting of descending thoracic aortic aneurysms is feasible with acceptable medium-term results. More refined, commercially developed devices available today offer less traumatic and more precise stent-graft deployment; these major technical advantages, coupled with important lessons we have learned over time and better patient selection, should be associated with more salutary clinical results in the future.

Adult↗
PubMed1997

Composite valve graft versus separate aortic valve and ascending aortic replacement: is there still a role for the separate procedure?

BACKGROUND: To ascertain if operative technique has any bearing on outcome, the surgical results after aortic root replacement using either a composite valve graft (CVG) or a separate graft and valve (GV) were analyzed. METHODS AND RESULTS: Three hundred and ninety consecutive, nonrandomized patients treated for aortic valve disease and ascending aortic aneurysm (n=278) or type A dissection (n=112 [45 acute]) between 1965 and 1995 were analyzed retrospectively. One hundred and thirty-five patients received a CVG, and 255 had separate GV replacement. Mean age was 52+/-16 years (+/-1 SD). Eighty-two patients (44% of the CVG group) had the Marfan syndrome (MFS). Follow-up (96% complete) totaled 2247 patient-years and extended to 27 years. The operative mortality rate was 10+/-3% (+/-70% confidence limits) for patients receiving a CVG and 15+/-2% for GV replacement (P=NS). The 15-year actuarial survival estimate was higher for the CVG group (53+/-14% [+/-SEM] versus 36+/-4%, P=.037). Seven patients in the CVG group required reoperation on the aortic valve or ascending aorta, as did 49 in the GV group. The probabilities of freedom from reoperation on the aortic rootwere 82+/-9% and 75+/-4% at 10 years for the CVG and GV group (P=NS). Thirty variables were analyzed in a multivariate model: pulmonary disease, higher New York Heart Association functional class, and longer cardiopulmonary bypass time were linked with higher operative mortality risk; older age, emergency operation, coronary artery disease, and liver dysfunction were independent determinants of late death. Younger age and use of a bioprosthesis were predictors of late reoperation. Type of procedure (GV versus CVG) was not a significant predictor of any outcome variable. CONCLUSIONS: The long-term results after CVG or GV were similar, which reflects proper patient selection. Use of a composite valve graft theoretically confers more protection against recurrent aortic root aneurysm, and, unless one opts for a valve-sparing aortic root replacement procedure, is most appropriate for younger patients, those with the MFS (including acute dissections), and others with marked pathological involvement of the sinuses. On the other hand, use of a separate GV should not be abandoned; in carefully selected patients (and if properly performed, eg, excision of the sinuses), GV also provides satisfactory results.

Adult↗