Temperature increase of 21st century mitigation scenarios.

Estimates of 21st Century global-mean surface temperature increase have generally been based on scenarios that do not include climate policies. Newly developed multigas mitigation scenarios, based on a wide range of modeling approaches and socioeconomic assumptions, now allow the assessment of possible impacts of climate policies on projected warming ranges. This article assesses the atmospheric CO(2) concentrations, radiative forcing, and temperature increase for these new scenarios using two reduced-complexity climate models. These scenarios result in temperature increase of 0.5-4.4 degrees C over 1990 levels or 0.3-3.4 degrees C less than the no-policy cases. The range results from differences in the assumed stringency of climate policy and uncertainty in our understanding of the climate system. Notably, an average minimum warming of approximately 1.4 degrees C (with a full range of 0.5-2.8 degrees C) remains for even the most stringent stabilization scenarios analyzed here. This value is substantially above previously estimated committed warming based on climate system inertia alone. The results show that, although ambitious mitigation efforts can significantly reduce global warming, adaptation measures will be needed in addition to mitigation to reduce the impact of the residual warming.

SQUID-detected FMR: Resonance in single crystalline and polycrystalline yttrium iron garnet.

Here two new techniques for the detection of broadband (100 MHz-20 GHz) ferromagnetic resonance (FMR)/ferrimagnetic resonance in single and poly-crystalline materials, which rely on SQUID-based gradiometry detection of small changes in the magnetisation, are developed. In the first method, small changes in the along-the-applied-field projection of the coupled magnetic moment (Δmz) are detected as the material is driven into resonance. Absolute measurement of the longitudinal component of the magnetisation and the resonance induced lowering of this moment makes estimation of the precession cone angle accessible, which is typically difficult to extract using conventional cavity or stripline based detection methods. The second method invokes the change in Δmz with the resonance-induced thermal heating dmzdT. Magnetisation dynamics in bulk Y3Fe5O12 are observed over a broad range of experimental temperatures (4 K-400 K) and fields (10-500 mT). The inhomogeneous microwave excitation allows for the observation of higher magnetostatic modes and the convenient tracking of very broad resonances. The two SQUID-detection techniques when combined with conventional broadband vector network analyser-FMR, low-frequency magnetic susceptibility, and DC magnetometry, all easily realised, essentially concurrently, using the same module, greatly expand the amount of static and dynamic information accessible.

Prevalent myocarditis at necropsy in the acquired immunodeficiency syndrome.

The prevalence of myocarditis was retrospectively evaluated in 71 consecutive necropsy patients who died from acquired immunodeficiency syndrome (AIDS) between 1982 and 1986. Myocarditis was found in 37 cases (52%). Biventricular dilation at necropsy was present in seven cases (10%) and was accompanied by myocarditis in each case; fatal congestive heart failure occurred in four of these seven cases. Although viral, protozoan, bacterial, fungal and mycobacterial opportunistic pathogens were present in myocardial sections of 7 of 37 myocarditis cases, the etiology of myocarditis in the majority of these patients with AIDS remained idiopathic. Thus, myocarditis is a frequent finding at necropsy in patients with AIDS and may contribute to the development of biventricular dilation.

Synthesis, structure elucidation, and biochemical evaluation of 7 alpha- and 7 beta-arylaliphatic-substituted androst-4-ene-3,17-diones as inhibitors of aromatase.

The inhibition of aromatase, the cytochrome P450 enzyme complex responsible for the conversion of androgens to estrogens, may be useful for the endocrine treatment of breast cancer. Previously, several 7 alpha-thio-substituted androstenediones have been shown to be potent inhibitors of aromatase. Recent research has focused on producing a more metabolically stable aromatase inhibitor by replacing the carbon-sulfur bond at the 7 alpha-position with a carbon-carbon bond. The new inhibitors, 7 alpha-arylaliphatic-substituted androst-4-ene-3,17-diones (2-4), have alkyl chains of varying length between the steroid and the aryl ring at the 7 alpha-position. The desired targets were synthesized via a 1,6-conjugate addition of the appropriate cuprate to 17 beta-(tert-butyldimethylsiloxy)androsta-4,6-dien-3-one (7). The synthesis also resulted in the formation of the 7 beta-substituted diastereomers (10-11 and 13) as minor products. Initial assignments of the 7 alpha-phenethyl and 7 beta-phenethyl diastereomers were made using highfield 1-D and 2-D NMR studies. The assignment of the diastereomers was confirmed using X-ray crystallography. These compounds were all good inhibitors of aromatase in vitro when assayed using microsomes isolated from human placenta. The 7 alpha-substituted androst-4-ene-3,17-diones (2-4) were effective inhibitors with apparent Kis of 13-19 nM. The corresponding 17 beta-hydroxy analogs (8 and 14) and the 7 beta-substituted androstenediones (13 and 16) were less effective inhibitors with apparent Kis of 36-44 nM. Thus, a new series of 7 alpha-arylaliphatic-substituted androst-4-ene-3,17-diones has been synthesized, and the compounds are potent competitive inhibitors of aromatase.

Frequency of myocarditis, left ventricular dysfunction and ventricular tachycardia in the acquired immune deficiency syndrome.

To evaluate possible relations between clinical and histopathologic cardiac findings in patients with the acquired immune deficiency syndrome (AIDS), 58 consecutively autopsied AIDS patients were reviewed retrospectively. Twenty-six (45%) had histopathologic myocarditis. Fifteen of these 26 (58%) had greater than or equal to 1 clinical cardiac abnormalities: 6 had congestive heart failure or left ventricular (LV) dysfunction, or both, 4 had ventricular tachycardia (VT), 10 had electrocardiographic abnormalities and 4 had pericardial abnormalities. Of the 32 patients without myocarditis, 6 (19%) had pericardial or electrocardiographic abnormalities, or both, but none had congestive heart failure, LV dysfunction or VT. Overall, clinical cardiac abnormalities were found in 21 patients (36%). Patients with myocarditis had a significantly higher incidence of clinical cardiac abnormalities than patients without myocarditis (58 vs 19%, p less than 0.01). All patients with congestive heart failure, LV dysfunction or VT had myocarditis. Thus, serious clinical cardiac abnormalities were common in patients with AIDS and were associated with myocarditis.

Endotoxemia in human septic shock.

To evaluate the incidence, pattern and clinical importance of endotoxemia in septic shock, frequent, serial endotoxin determinations were made prospectively in patients with shock. Detectable endotoxin occurred in 43 of 100 patients with septic shock, but in only one of ten patients with shock due to nonseptic causes. During septic shock, endotoxemia frequently occurred in the absence of Gram-negative bacteremia. Using a logistic regression model, multiple organ failure occurred 10.3 times more frequently and depression of left ventricular ejection fraction (less than or equal to 45 percent) 4.8 times more frequently in endotoxemic patients. In patients with positive blood cultures, endotoxemia was associated with a high mortality. We conclude that endotoxemia occurs frequently in septic shock and is associated with severe manifestations of this syndrome, including cardiac depression and multiple organ failure. This study suggests that endotoxin is an important mediator of septic shock and supports efforts to develop anti-endotoxin therapies for treating patients with this disease.

A circulating myocardial depressant substance is associated with cardiac dysfunction and peripheral hypoperfusion (lactic acidemia) in patients with septic shock.

Using spontaneously beating rat myocardial cells as an in vitro model of myocardial depression, recent studies demonstrated that septic shock patients' sera frequently contain a myocardial depressant substance (MDS) that is associated with a reversible decrease in left ventricular ejection fraction (LVEF). To further characterize MDS, 50 consecutive patients with possible septic shock were studied serially from shock onset until recovery or death. Thirty-four patients had criteria diagnostic of septic shock, and 16 had a nonseptic critical illness. Of the 34, 14 met strict criteria for circulating MDS, with a mean inhibition of 35 percent (range 20 percent to 62 percent). Compared with those patients not exhibiting significant MDS activity, the 14 MDS-positive patients had a lower mean minimal EF (28 percent vs 39 percent, p less than 0.01), a greater mean decrease in EF (22.1 percent vs 8.8 percent, p = 0.002), a higher pulmonary artery wedge pressure (16.8 vs 11.9 mm Hg, p less than 0.01), greater LV dilatation (162 vs 118 ml/m2, p = 0.02), and a higher circulating mean peak lactic acid (6.9 vs 2.7 mmol/L, p less than 0.01). In the 14 MDS-positive patients, the in vitro myocardial cell depression had a negative correlation with the in vivo EF (r = -060, p less than 0.05). These findings suggest that a circulating MDS is a cause of the myocardial depression frequently accompanying human septic shock.

7alpha-Arylaliphatic androsta-1,4-diene-3,17-diones as enzyme-activated irreversible inhibitors of aromatase.

Inhibition of aromatase, the enzyme responsible for converting androgens to estrogens, may be therapeutically useful for the endocrine treatment of hormone-dependent breast cancer. Previous research on 7alpha-thiosubstituted androgens, especially 7alpha-(4'-aminophenylthio)-androsta-1,4-diene-3,17-di one, has shown that these compounds are potent enzyme-activated irreversible inhibitors of aromatase. Research on the synthesis of more metabolically stable inhibitors has focused on replacing the thioether linkage at the 7alpha position with a carbon-carbon linkage. Several 7alpha-arylaliphatic androst-4-ene-3,17-diones were previously shown to be potent competitive inhibitors of aromatase. The extension of the research on these 7alpha-arylaliphatic androgens includes the introduction of a C1-C2 double bond in the A-ring to provide enzyme-activated irreversible inhibitors. The desired 7alpha-arylaliphatic androsta-1,4-diene-3,17-diones were obtained from their corresponding 7alpha-arylaliphatic androst-4-ene-3,17-diones by oxidation using DDQ. A new improved synthesis of the 7alpha-arylaliphatic androst-4-ene-3,17-diones using an in situ preparation of the CuI-(n-Bu3)P complex was employed. The aryl ring of the 7alpha-phenethyl and 7alpha-phenpropyl derivatives were functionalized to their corresponding p-nitro and p-amino derivatives. These compounds were all potent inhibitors of aromatase with apparent K(i)s ranging between 7 and 19 nM. These inhibitors demonstrated enzyme-mediated inactivation of aromatase with apparent k(inact)s ranging from 4.4 x 10(-4) to 1.90 x 10(-3)/s. The best inactivator of the series was the 7alpha-phenpropylandrosta-1,4-diene-3,17-dione, which exhibited a T(1/2) of 6.08 min.

Aromatase inhibition in JAr choriocarcinoma cells by 7alpha-arylaliphatic androgens.

The JAr choriocarcinoma cell cultures have demonstrated high levels of aromatase activity and have been useful for assaying a wide variety of aromatase inhibitors for aromatase inhibition in intact cells. Recently, several 7alpha-arylaliphatic androgens have shown effective inhibition of human placental microsomal aromatase in vitro, with apparent Ki values ranging from 10 to 20 nM. A series of 7alpha-arylaliphatic androst-4-ene-3,17-dione compounds demonstrated potent competitive inhibition, and 7alpha-arylaliphatic androsta-1,4-diene-3,17-diones were enzyme-activated irreversible inhibitors. Both series of these potent inhibitors were investigated for the ability to inhibit aromatase activity in JAr cells by measuring the conversion of [1beta-3H]-androstenedione to 3H2O and unlabelled estrone. JAr cell cultures were incubated for 2 h at 37 degrees C with the aromatase inhibitors at concentrations of 10 pM to 10 microM, the percentage of enzyme inhibition was determined, and IC50 values for inhibitors were calculated. Both series of synthetic compounds demonstrated good to excellent aromatase inhibition, and the most effective inhibitors in both series were those compounds with a phenylpropyl substituent at the 7alpha-position of the steroid nucleus. The 7alpha-arylaliphatic androst-4-ene-3,17-diones exhibited inhibition of JAr aromatase activity with IC50 values from 300 to 434 nM. More potent aromatase inhibition was observed with the 7alpha-arylaliphatic androsta-1,4-diene-3,17-diones, which exhibited IC50 values from 64 to 232 nM. Enhanced efficacy of steroidal enzyme-activated irreversible inhibitors compared to competitive inhibitors was observed in these studies and is consistent with previous reports. These results suggest that JAr choriocarcinoma cells with high levels of aromatase activity may be useful in differentiating steroidal aromatase inhibitors exhibiting different mechanisms of enzyme inhibition. In summary, the 7alpha-phenylpropyl androsta-1,4-diene-3,17-dione analogs, which are enzyme-activated irreversible inhibitors, demonstrated the most effective inhibition of aromatase activity present in the JAr cell cultures among the various 7alpha-arylaliphatic androgens.

Biochemistry and pharmacology of 7alpha-substituted androstenediones as aromatase inhibitors.

The inhibition of aromatase, the enzyme responsible for converting androgens to estrogens, is therapeutically useful for the endocrine treatment of hormone-dependent breast cancer. Research by our laboratory has focused on developing competitive and irreversible steroidal aromatase inhibitors, with an emphasis on synthesis and biochemistry of 7alpha-substituted androstenediones. Numerous 7alpha-thiosubstituted androst-4-ene-3,17-diones are potent competitive inhibitors, and several 1,4-diene analogs, such as 7alpha-(4'-aminophenylthio)-androsta-1,4-diene-3,17-di one (7alpha-APTADD), have demonstrated effective enzyme-activated irreversible inhibition of aromatase in microsomal enzyme assays. One focus of current research is to examine the effectiveness and biochemical pharmacology of 7alpha-APTADD in vivo. In the hormone-dependent 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinoma model system, 7alpha-APTADD at a 50 mg/kg/day dose caused an initial decrease in mean tumor volume during the first week, and tumor volume remained unchanged throughout the remaining 5-week treatment period. This agent lowers serum estradiol levels and inhibits ovarian aromatase activity. A second research area has focused on the synthesis of more metabolically stable inhibitors by replacing the thioether linkage at the 7alpha position with a carbon-carbon linkage. Several 7alpha-arylaliphatic androst-4-ene-3,17-diones were synthesized by 1,6-conjugate additions of appropriate organocuprates to a protected androst-4,6-diene or by 1,4-conjugate additions to a seco-A-ring steroid intermediate. These compounds were all potent inhibitors of aromatase with apparent Kis ranging between 13 and 19 nM. Extension of the research on these 7alpha-arylaliphatic androgens includes the introduction of a C1-C2 double bond in the A-ring to provide enzyme-activated irreversible inhibitors. The desired 7alpha-arylaliphatic androsta-1,4-diene-3,17-diones were obtained from their corresponding 7alpha-arylaliphatic androst-4-ene-3,17-diones by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). These inhibitors demonstrated enzyme-mediated inactivation of aromatase with apparent k(inact)s ranging from 4.4 x 10(-4) to 1.90 x 10(-3) s(-1). The best inactivator of the series was 7alpha-phenpropylandrosta-1,4-diene-3,17-dione, which exhibited a T(1/2) of 6.08 min. Aromatase inhibition was also observed in MCF-7 human mammary carcinoma cell cultures and in JAr human choriocarcinoma cell cultures, exhibiting IC50 values of 64-328 nM. The 7alpha-arylaliphatic androgens thus demonstrate potent inhibition of aromatase in both microsomal incubations and in choriocarcinoma cell lines expressing aromatase enzymatic activity. Additionally, the results from these studies provide further evidence for the presence of a hydrophobic binding pocket existing near the 7alpha-position of the steroid in the active site of aromatase. The size of the 7alpha-substituent influences optimal binding of steroidal inhibitors to the active site and affects the extent of enzyme-mediated inactivation observed with androsta-1,4-diene-3,17-dione analogs.

Plasminogen activators in abdominal aortic aneurysmal disease.

Abdominal aortic aneurysms (AAA) are characterized by the destruction of the extracellular matrix (ECM) of the aortic wall, particularly its elastin elements. The fibrinolytic system is known to mediate proteolysis within the ECM. Plasmin, which is generated by plasminogen activators (PA), is capable of destroying the ECM directly and indirectly via the activation of latent matrix metalloproteases (MMP). In addition, plasmin also synergistically enhances the ability of macrophages to destroy ECM. In AAA tissue, elevated levels of both urokinase-type and tissue-type plasminogen activators (u-PA and t-PA) have been documented. u-PA and t-PA have been localized to macrophages within the inflammatory infiltrate which is characteristic of AAA. mRNA expression of both type PAs is elevated as well in comparison to both normal and atherosclerotic occlusive aorta. Supporting the role of PAs in AAA pathogenesis is the fact that plasmin is elevated in AAA tissue, as are MMP. As with PA, MMP expression has been localized to macrophages. These data all suggest that the aortic wall is being degraded in AAA by a synergistic combination of macrophages, PA, and MMP.

Differential expression of prostaglandin E2 and interleukin-6 in occlusive and aneurysmal aortic disease.

BACKGROUND: Both aortoiliac occlusive disease (AIOD) and abdominal aortic aneurysm disease (AAA) are traditionally considered degenerative conditions that are caused by atherosclerosis. Although it is becoming apparent that the pathophysiology of each condition has its own determinants, inflammation is thought to play a role in each. The purpose of this study was to analyze the inflammatory cytokines interleukin-6 (IL-6) and prostaglandin E2 (PGE2) in aortic disease and compare AAA with AIOD, as well as to compare both with normal aorta. METHODS: Aortic tissue was harvested at the time of aortic reconstructive surgery for AAA (n = 13) and AIOD (n = 14) or at time of organ harvest for normal (n = 16) aortic specimens. Whole organ cultures were immediately established, and the culture medium was collected after 72 hours. An enzyme-linked immunosorbent assay was used to assay for PGE2 and a lymphoproliferative assay was used to quantitate IL-6. Statistical analysis was performed using paired 2-tail t tests. RESULTS: Normal aorta expressed much less PGE2 (384 +/- 67 ng/mL) than either AAA (11,093 +/- 7,411 ng/mL) (P < .001) or AIOD (13, 719 +/- 3,355 ng/mL) (P < .002). However there was no statistically significant difference in PGE2 expression between the AAA and AIOD groups (P = . 44). The IL-6 assay also showed that normal aorta had very little expression (1,861 +/- 334 U/mL) compared with either AAA (14,329 +/- 4,159 U/mL) (P = . 02) or AIOD (39,805 +/- 8,426) (P < .001). Comparison between AAA and AIOD revealed significantly higher expression of IL-6 by the AIOD cultures (P = .03). CONCLUSIONS: AAA and AIOD are associated with increased expression of the proinflammatory cytokines PGE2 and IL-6. However, AIOD is associated with a much higher level of IL-6 expression than is AAA, although the level of PGE2 expression is the same. This differential expression of IL-6 may help explain the pathogenesis of these 2 distinct aortic diseases.

Insulin-like growth factor-I attenuates delayed graft function in a canine renal autotransplantation model.

BACKGROUND: Insulin-like growth factor-I (IGF-I) has been shown to accelerate recovery in animal models of ischemic or toxic acute renal injury. Ischemic renal injury is frequently encountered after cadaveric transplantation manifested as delayed graft function. This study was performed to determine whether perfusion of kidneys with preservation solution supplemented with IGF-I would improve the course of renal injury in a canine autotransplantation model of delayed graft function. METHODS: Dogs underwent unilateral nephrectomy with kidneys perfused and stored in Euro-Collins solution supplemented with vehicle (n = 11) or IGF-I (n = 8). After 24 hours of kidney preservation, a contralateral nephrectomy was performed and the stored kidney was autotransplanted. Renal function was examined for 5 days after the transplantation, and an inulin clearance was obtained at the time of death. RESULTS: Compared with dogs that received kidneys preserved in the vehicle, dogs receiving the IGF-I preserved kidneys had significantly lower daily serum creatinine and blood urea nitrogen levels during the course of 5 days after transplantation. Inulin clearance at death was nearly double in the IGF-I treated animals compared with the vehicle-treated controls (1.37 +/- 0.16 ml/min/kg versus 0.77 +/- 0.13 ml/min/kg; p < 0.05). CONCLUSIONS: Perfusion and storage of kidneys with preservation solution supplemented with IGF-I can attenuate the course of delayed graft function in a canine renal autotransplantation model. IGF-I may have potential for use in cadaveric human renal transplantation.

Long-term effectiveness of extraanatomic renal artery revascularization.

BACKGROUND: The efficacy of direct aortorenal bypass and renal artery endarterectomy are well established. The purpose of this study is to define better the results of extraanatomic renal revascularization procedures. METHODS: From April 1987 to March 1993, 124 patients underwent renal artery revascularization. Forty-eight (39%) of them (33 women, 15 men; average age, 65.9 years) underwent 49 extraanatomic renal artery bypasses. Preoperative risk factors included smoking in 30 patients (61%), history of myocardial infarction in 14 (29%), diabetes mellitus in 11 (22%), congestive heart failure in nine (18%), chronic obstructive pulmonary disease in 11 (22%), and stroke in six (12%). The average creatinine level was 2.3 mg/dl. The average number of antihypertensive medications was 2.4. Thirty iliorenal, 10 gastroduodenal-renal, seven hepatorenal, and two splenorenal bypasses were performed together with 10 contralateral nephrectomies. RESULTS: Six major postoperative complications occurred. There were no deaths. Forty-one (85%) of patients had improvement or cure of their hypertension. Seven (15%) of patients failed to respond to treatment, and three required subsequent nephrectomy. After operation the average creatinine level was 1.7 mg/dl and the average number of medications was 1.7. Mean follow-up period has been 23.2 months (range, 1 to 79 months). CONCLUSIONS: Extraanatomic bypass proved to be efficacious in treating hypertension and preserving renal function and has an acceptable rate of morbidity and mortality. We conclude that these procedures are an acceptable alternative to direct aortorenal artery revascularization.

Revascularization of the solitary kidney: a challenging problem in a high risk population.

BACKGROUND: Patients with significant atherosclerotic stenosis involving the artery to a solitary functioning kidney present a clinical challenge. METHODS: From August 1987 through August 1995, 35 of these patients (average age, 68.4 +/- 6.9 years) were treated. Comorbid conditions included previous myocardial infarction in 23% of the patients, congestive heart failure (CHF) in 34%, chronic obstructive pulmonary disease in 20%, and diabetes in 20%. The average creatinine level of the patients was 2.5 +/- 1.5 mg/dl. Indications for revascularization were hypertension in 86%, hypertensive crisis with CHF in 17%, and renal insufficiency in 69%. Procedures performed included 19 extra-anatomic bypasses, 8 concomitant with infrarenal aortic reconstruction and 2 concomitant with thoracoabdominal aortic aneurysm repair; 1 visceral segment endarterectomy; 1 renal artery endarterectomy with reimplantation; I superior mesenteric to renal artery bypass; 1 aortorenal bypass; and 2 percutaneous angioplasties with staged nephrectomies. RESULTS: At discharge, 91% of patients had stable or improved renal function with an average creatinine level of 1.7 +/- 0.8 mg/dl. Hypertension was cured or improved in 85%. Perioperative mortality was 6%, and major morbidity was 43%, including the need for permanent (9%) and temporary (9%) dialysis, respiratory insufficiency (18%), two early reoperations, six cardiac complications, one case of gastrointestinal bleeding, and one stroke. In the follow-up period (mean duration, 39.2 months), survival has been 73%, and no additional patients have required dialysis. CONCLUSIONS: Although significant perioperative morbidity exists in this high risk population, the long-term preservation of renal function and improvement in hypertension make solitary renal revascularization worthwhile.

Hydrocortisone rapidly induces aortic rupture in a genetically susceptible mouse.

The Blotchy mouse has an X-linked trait that leads to aortic aneurysms and subsequent fatal rupture in nearly all affected male mice. Heterozygous female mice occasionally develop aneurysms, but they rarely rupture. Ten heterozygous female mice received 0.45 mg/mL of hydrocortisone acetate in drinking water. Within 2 weeks, 9 of 10 mice were dead (6 with proved aortic rupture, 3 with presumed rupture). The 10th mouse was documented to have an aortic aneurysm. A dose-response curve was generated. Hydrocortisone's effect was shown to be dose-dependent. In another experiment, normal female mice received 0.10 mg/mL of hydrocortisone acetate for 14 days. Two mice developed aneurysms, and the others developed aortic ectasia. These experiments establish the role of hydrocortisone in the induction of aortic rupture in a mouse with genetic susceptibility and the induction of aneurysms and ectasia in normal mice.

Endovascular stent grafts for aneurysmal and occlusive vascular disease.

BACKGROUND: This report details our initial experience with two types of endovascular grafts- one for the treatment of infrarenal abdominal aortic aneurysms and the other for the treatment of iliac artery occlusive disease. METHODS: An abdominal aortic aneurysm was repaired in 34 patients using 3 different types of Ancure endografts (Menlo Park, California). Control patients (n = 9) had a standard aneurysm repair. Patients with chronic lower extremity ischemia (n = 7) secondary to iliac artery occlusive disease were treated with a Hemobahn endograft (W. L. Gore & Associates, Flagstaff, Arizona). RESULTS: Ancure graft deployment was achieved in 33 of 34 (97.1%) patients. Perioperative mortality for the Ancure and control group patients was 2.9% and 0%, respectively. Periprosthetic leaks were identified within 48 hours of deployment in 6 (18.2%) Ancure graft patients. All but 2 of the leaks resolved on serial follow-up. Additional endovascular procedures were required in 11 (32.4%) Ancure graft patients at the initial procedure or during follow-up to correct graft or arterial stenoses. Patients treated with an endovascular graft had significantly less blood loss and shorter hospital stays than control group patients. For Hemobahn patients, the technical success for graft deployment was 100%. There were no perioperative deaths. The ankle/brachial index increased from a mean of 0.52 preoperatively to 0.86 postoperatively (P = 0.004). One patient required a Wallstent in follow-up to correct a graft wrinkle. Angiography at 6 months demonstrated mild intimal hyperplasia in the stent graft in 5 of 6 patients. CONCLUSIONS: These early results support the potential for endovascular grafts in the treatment of aneurysmal and occlusive vascular disease. Further modifications in the devices and deployment techniques are necessary to reduce the incidence of periprosthetic leaks, graft limb stenoses, and intimal hyperplasia.

Limb salvage and patency after aortic reconstruction in younger patients.

PURPOSE: The purpose of this report was to compare patient characteristics, treatment, and outcome in younger and older patients with aortoiliac occlusive disease. METHODS: The medical records of 56 patients < or = 50 years of age (Group < or = 50) were retrospectively reviewed and compared to the records of 128 patients > or = 60 years of age (Group > or = 60). All patients were examined and treated between April 1987 and April 1994. Postoperatively, they were enrolled in a vascular laboratory surveillance program to serially monitor the status of the vascular reconstruction. Follow-up averaged more than 3 years in both groups and was available on greater than 90% of patients. RESULTS: Patients in Group < or = 50 had a higher incidence of smoking (68% versus 51%) and a lower incidence of hypertension (29% versus 50%) than patients in group > or = 60 (smoking P = 0.03, hypertension P = 0.007). No other significant differences were noted among cardiovascular risk factors. Preoperative indications for surgery were similar among patients in both groups. An aortoiliac endarterectomy was more commonly used to revascularize the lower extremities in younger patients than in their older counterparts (23% versus 7%, P = 0.002). Graft revisions were more frequently necessary after aortic reconstruction in Group < or = 50 than in Group > or = 60 (29% versus 8%, P = 0.0003); however patency rates computed by life table analysis were not significantly different. The primary patencies for Group < or = 50 and Group > or = 60 at 5 years were 64% and 67%, respectively; their secondary patency rates at 5 years were 84% and 89%, respectively. No significant difference was found in major limb amputation (8% in Group < or = 50 versus 5% in Group > or = 60, P = 0.46). We conclude that aortoiliac reconstruction for occlusive disease can be performed with similar secondary patency and amputation rates in young and old patients. However, close postoperative surveillance and frequent surgical revision are necessary to maintain patency and minimize amputation.

Incidence and etiology of abdominal aortic aneurysms.

Unlike coronary artery disease and cerebrovascular disease, the incidence of abdominal aortic aneurysms has increased dramatically over the past three decades. There appears to be a correlation between both hypertension and smoking and the development of aneurysms, and there is a substantial predominance of white men among the patients. Recent studies have also documented a strong genetic component to this disease. Several biochemical abnormalities have been noted in those with aortic aneurysms, including increased proteolysis (elastolysis and collagenolysis). At present, the precise etiology of aneurysmal disease remains unclear, but it will most likely turn out to be a heterogenous disease with several molecular forms.

Retroperitoneal aortoiliac reconstruction.

The retroperitoneal approach to the aorta and the iliac arteries provides excellent exposure for reconstruction of these vessels for aortoiliac occlusive disease. Furthermore, the weight of evidence in the literature indicates that this approach is associated with fewer complications, a shorter length of stay in the hospital, and lower costs. The major drawback to this approach at present appears to be a lack of familiarity with the technical aspects of this exposure. It is our hope that this article helps familiarize surgeons with this exposure and encourages them to use it more frequently for "routine" aortoiliac reconstruction.