Elevated C-reactive protein levels are associated with postoperative events in patients undergoing lower extremity vein bypass surgery

OBJECTIVES: Inflammatory markers such as high-sensitivity C-reactive protein (hsCRP) are associated with an increased risk of cardiovascular events and with the severity of peripheral arterial disease. The effects of inflammation on the development of vein graft disease remain speculative. We hypothesized that high levels of inflammatory markers would identify patients at increased risk for adverse events (graft failure, major cardiovascular events) after lower extremity bypass surgery. METHODS: Patients (n = 91) scheduled to undergo lower extremity bypass using autogenous vein were enrolled into a prospective study at two institutions. Exclusion criteria included the presence of major infection. A baseline plasma sample was obtained on the morning of lower extremity bypass. Biomarkers for inflammation included hsCRP, fibrinogen, and serum amyloid A (SAA). Values between patients with and without critical limb ischemia were compared. Proportions of events among dichotomized populations (upper limit of normal of each laboratory assay) were compared by log-rank test. RESULTS: Of the patients undergoing lower extremity bypass, 69% were men, 53% were diabetic, 81% were smokers, and their mean ankle-brachial index was 0.51 +/- 0.19. The indication for lower extremity bypass was critical limb ischemia in 55%. There were no perioperative deaths and two early graft occlusions. During a mean follow-up of 342 days (range, 36-694 days) there were four deaths, 27 graft-related events, and 10 other cardiovascular events. No relationships were found between events and demographics, comorbidities, baseline ankle-brachial index, or statin use. High-sensitivity CRP (P = .005), fibrinogen (P < .001), and SAA (P = .0001) levels were associated with critical limb ischemia at presentation. Among patients with an elevated hsCRP (>5 mg/L) immediately before surgery, major postoperative vascular events occurred in 60% (21/35), compared with a 32% (18/56) rate in those with a baseline CRP <5 mg/L (P = .004, log-rank test). On multivariable analysis, only elevated hsCRP correlated with adverse graft-related or cardiovascular events (P = .018). CONCLUSIONS: The inflammatory biomarkers of hsCRP, fibrinogen, and SAA correlate with peripheral arterial disease severity at presentation in patients undergoing lower extremity bypass. Patients with elevated hsCRP are at increased risk for postoperative vascular events, most of which are related to the vein graft. These findings suggest a potential relationship between inflammation and outcomes after lower extremity vein bypass surgery.     

A decade experience with infrainguinal revascularization in a dialysis-dependent patient population

OBJECTIVE: Although previous series have reported outcomes of lower extremity (LE) revascularization in patients with end-stage renal disease, the issue of LE bypass for limb salvage in this group has not been resolved. We herein present the largest series to date of a 10-year single-institution experience with LE bypass in patients with dialysis dependence. METHODS: With prospectively entered data from a university teaching hospital's vascular registry, we reviewed the records of all patients with dialysis dependence who underwent LE arterial bypass between January 1, 1990, and May 31, 1999. RESULTS: A total of 146 consecutive patients (177 limbs) underwent infrainguinal revascularization, of whom nearly all (92%) had diabetes and tissue loss (91%). The in-hospital mortality rate was 3% (five patients). The rates for perioperative congestive heart failure, myocardial infarction, arrhythmia, and wound infection were 2%, 3%, 5%, and 10%, respectively. The actuarial graft primary and secondary patency rates at 1 and 3 years were 84% and 85%, and 64% and 68%, respectively. The limb salvage rates were 80% and 80% at 1 and 3 years. The 1-year and 3-year cumulative survival rates were 60% and 18%, respectively. At 5 years, survival was poor with only 5% of the entire cohort of 146 patients still alive. Multivariate logistic regression analysis at 6 months identified age (odds ratio, 0.96, 0.91) and number of years on dialysis (odds ratio, 0.79, 0.74) as significant (P <.05) negative predictors of both limb salvage and survival, respectively. CONCLUSION: Infrainguinal arterial reconstruction can be performed on patients with dialysis dependence with acceptable rates of limb salvage given the high incidence rate of perioperative complications and poor longevity of this patient group. Advanced age and number of years on dialysis seem to correlate with poorer outcome.     

Early human thymocyte proliferation is regulated by an externally controlled autocrine transforming growth factor-beta 1 mechanism

Early thymocytes undergo extensive proliferation after their entry into the thymus, but cellular interactions and cytokines regulating this intrathymic step remain to be determined. We analyzed the effects of various T-cell growth factors and cellular interactions on in vitro proliferation of early CD2+CD3/TCR-CD4-CD8- (triple negative [TN]) human thymocytes. Freshly isolated TN cells were then assayed for their growth capacity after incubation with CD2I+III-monoclonal antibody (MoAb), recombinant human interleukin-2 (IL-2), IL-7, and/or IL-4. These cells displayed significant proliferative responses with IL-4, IL- 7, or CD2-MoAb+IL-2. The addition of recombinant transforming growth factor beta (TGF beta) or autologous irradiated CD3+CD8+CD4- cells to TN cell cultures dramatically decreased their growth responses to IL-2 and IL-7, whereas IL-4-induced proliferation was less sensitive to growth inhibition. We thus asked whether the CD8+ cell-derived inhibitory effect was due to TGF beta. The addition of neutralizing anti-TGF beta MoAb completely abolished CD8+ cell-derived inhibition of TN cell growth. Analysis of CD8+ cell-derived supernatants indicated that these cells had low TGF beta 1 production capacity, whereas TN cells secrete significantly high levels of TGF beta 1. Cell fixation studies showed that TN cells were the source of the TGF beta. TGF beta 1 released from TN cells was in the latent form that became the active inhibitory form through interaction of TN cells with CD8+ cells. Together, these data suggest a role for TGF beta 1 as an externally controlled, autocrine inhibitory factor for human early thymocytes, with a regulatory role in thymic T-cell output.     

A decade of experience with dorsalis pedis artery bypass: analysis of outcome in more than 1000 cases

OBJECTIVE: The purpose of this study was to review our experience over the last decade with the dorsalis pedis bypass for ischemic limb salvage in patients with diabetes mellitus. METHODS: The study was a retrospective analysis of a computerized vascular registry and chart review. From January 10, 1990 to January 11, 2000, 1032 bypasses to the dorsalis pedis artery were performed in 865 patients (27.6% of the 3731 lower extremity arterial bypass procedures performed in that time period). Five hundred ninety-seven patients (69%) were male, with a mean age of 66.8 years. Ninety-two percent had diabetes mellitus. All procedures were done for limb salvage. Conduits included 317 nonreversed saphenous vein (30.7%), 273 in situ (26.4%), 235 reversed vein (22.8%), 170 arm vein (16.5%), 35 other vein (3.4%), and two polytetrafluoroethylene (0.2%) grafts. The inflow arteries were as follows: 294 common femoral (28.5%), 550 popliteal (53.2%), 114 superficial femoral (11%), and 74 other (7.2%). RESULTS: The mortality rate within 1 month of surgery was 0.9%, and 42 grafts (4.2%) failed in the same interval, although 13 were successfully revised. In a follow-up period that ranged from 1 to 120 months (mean, 23.6 months), primary patency, secondary patency, limb salvage, and patient survival rates were 56.8%, 62.7%, 78.2%, and 48.6%, respectively at 5 years and 37.7%, 41.7%, 57.7%, and 23.8% at 10 years. Both polytetrafluoroethylene grafts failed in less than 1 year. Primary graft patency was worse in female patients (46.5% female versus 61.6% male at 5 years; P <.009) but better in patients with diabetes (65.9% diabetes mellitus versus 56.3% non-diabetes mellitus at 4 years; P <.04). Saphenous vein grafts performed better than all other conduits with a secondary patency rate of 67.6% versus 46.3% at 5 years (P <.0001). Multivariate analysis showed that length of stay greater than 10 days and dorsalis pedis bypass for the surgical indication of previous graft occlusion were independently predictive of worse graft patency at 1 year and use of saphenous vein as conduit was predictive of better patency. CONCLUSION: Dorsalis pedis bypass is durable with a high likelihood of ischemic foot salvage over many years. Saphenous vein is the preferred conduit when available. Short vein grafts from distal inflow sites are possible in more than 50% of cases. These results justify the routine use of pedal arterial reconstruction for patients with diabetes with ischemic foot complications.     

MR vascular imaging with a fast gradient refocusing pulse sequence and reformatted images from transaxial sections

The authors present a method for obtaining magnetic resonance (MR) images of intra- and extracranial vessels from thin contiguous transaxial sections. A section-selective gradient refocusing pulse sequence with a short repetition time caused flow-related enhancement from spins that flowed perpendicular to the transaxial sections. The signal was further enhanced by means of flow compensation gradients to rephase any phase shifts resulting from moving spins in the presence of the imaging gradients. Coronal and sagittal sections, reformatted from multiple transaxial sections, are shown to have excellent vessel contrast without the use of contrast material. These images were obtained in 12 minutes of acquisition time from as many as 60 sections of 3-mm thickness. Such a technique shows significant promise for MR angiography.     

Effect of intersection spacing on MR image contrast and study time

The effects of section separation on image contrast and calculated T1 relaxation times were investigated in healthy volunteers and a phantom using an early commercial version magnetic resonance imaging system. The effects are explained qualitatively on the basis of side lobes of excitation occurring outside the selected section resulting in reduction of the time permitted for T1 relaxation. The options for dealing with imperfect section selection, including separation of the sections (i.e., leaving gaps) and nonsequential excitation, are illustrated and the trade-offs involved in each explained.     

The extent and distribution of cancer in breasts with palpable primary tumors.

The term multicentricity has been employed to describe cancer cells beyond the borders of the primary tumor. However, it is not clear if there are multiple independent sites of origin or if the process simply represents spread of the cancer. The present study was designed to examine the distribution and extent of cancer in the breast and identify factors that bear on these events. All mastectomy specimens between 1980 and 1983 were systematically examined by means of multiple sections. One hundred seventy-nine of 657 patients (27%) were found to have separate foci. The most common histologic type (invasive ductal) was least likely to have multifocal disease (19%), while it was extremely common in the small group of patients with intraductal lesions (81%). Size was a factor in ductal but not in lobular lesions. Ninety per cent of the secondary foci were found in close proximity to the primary, suggesting spread rather than multicentricity. This implies a more limited and predictable distribution of cancer cells and opens the way to more rational selection and surgical preparation of patients for breast preservation.     

雪灵芝对二乙基亚硝胺诱导大鼠肝癌组织细胞的抑制作用

目的：验证雪灵芝是否具有抑制大鼠肝癌的功效。方法：实验于2003—09/2004—08在广西疾病预防控制中心SPF级动物实验室完成。选用健康成年SD大鼠160只。按体质量分层随机分为5组：空白对照组、模型组、雪灵芝高剂量组、雪灵芝中剂量组和雪灵芝低剂量组，每组32只。雪灵芝高、中、低剂量组大鼠分别灌胃2．500，1．250，0．625mL/kg雪灵芝溶液，阴性对照组和模型组灌胃等量蒸馏水，1次／d，连续60d。第61天开始雪灵芝高、中、低剂量组和模型组灌胃二乙基亚硝胺溶液，对照组灌胃等量的生理盐水。于停止灌胃90d后各组处死一半受试大鼠（雌雄各半），检测血常规及血清主要生化指标，观察各脏器大体形态改变、脏器的癌变程度。1周后给剩余大鼠灌胃雪灵芝溶液（不含二乙基亚硝胺）。7周后处死余下的一半雄性大鼠，进行相同操作。8周后处死余下的全部大鼠，操作及检测方法同前。结果：纳入的160只SD大鼠，145只进入结果分析，15只脱落。①病理切片检查结果：除阴性对照组，其他各组大鼠肝组织均发生癌变或癌前病变。雪灵芝高、中、低剂量组的癌前病变发生率与模型组相近（P〉0．05）；癌变的发生率均低于模型组，差异有显著性意义（P〈0．05，0．01）。②大体标本检查结果：阴性对照组大鼠肝脏的大体标本均无异常改变，其他各组大鼠的肝脏有些可见表面粗糙等病理改变。模型组大体标本病理改变的阳性率高于雪灵芝高、中、低剂量组，差异有显著性意义（P〈0．05）。肉眼观模型组癌变发生率高于其他各组。③其他脏器检查结果：模型组2只大鼠有肝癌肺转移。结论：以较大剂量的二乙基亚硝胺连续灌胃30d可以复制大鼠肝癌模型；雪灵芝对二乙基亚硝胺诱导的大鼠肝癌具有预防和抑制的作用。