Time to symptomatic vascular stenosis at different locations in patients with arteriovenous grafts.

Most arteriovenous grafts fail due to irreversible thrombosis, superimposed on hemodynamically significant vascular stenosis. Previous studies observed the highest frequency of stenosis at the venous anastomosis, without addressing the timing of stenosis. The present study quantified time to symptomatic stenosis at different vascular locations, and related it to permanent graft failure. A prospective computerized vascular access database was queried retrospectively to identify 309 hemodialysis patients receiving new upper extremity grafts during a 4-year period at a large dialysis center. For each vascular site we calculated the time to symptomatic stenosis using survival techniques. The cumulative likelihood of symptomatic stenosis at 2 years was 67% for venous anastomotic stenosis, 19% for intra-graft stenosis, 16% for venous outlet stenosis, 13% for central vein stenosis, and 5% for arterial anastomotic stenosis. The cumulative risk of graft failure at 2 years was 40%. Stenosis at the venous anastomosis was twice as likely as cumulative graft failure (hazard ratio [HR] 1.95; 95% confidence interval [CI], 1.65-2.52, p < 0.001). In contrast, intra-graft stenosis was half as likely as cumulative graft failure (HR 0.45; 95% CI, 0.36-0.61, p < 0.001). Central vein stenosis was more likely in patients with a previous ipsilateral catheter compared with those without one (HR 2.40; 95% CI, 1.39-5.58, p = 0.004). Symptomatic stenosis occurs much earlier at the venous anastomosis compared with other vascular sites. Moreover, preexisting ipsilateral internal jugular dialysis catheters more than double the risk of central vein stenosis.

Clonogenic analysis reveals reserve stem cells in postnatal mammals. II. Pluripotent epiblastic-like stem cells.

Undifferentiated cells have been identified in the prenatal blastocyst, inner cell mass, and gonadal ridges of rodents and primates, including humans. After isolation these cells express molecular and immunological markers for embryonic cells, capabilities for extended self-renewal, and telomerase activity. When allowed to differentiate, embryonic stem cells express phenotypic markers for tissues of ectodermal, mesodermal, and endodermal origin. When implanted in vivo, undifferentiated noninduced embryonic stem cells formed teratomas. In this report we describe a cell clone isolated from postnatal rat skeletal muscle and derived by repetitive single-cell clonogenic analysis. In the undifferentiated state it consists of very small cells having a high ratio of nucleus to cytoplasm. The clone expresses molecular and immunological markers for embryonic stem cells. It exhibits telomerase activity, which is consistent with its extended capability for self-renewal. When induced to differentiate, it expressed phenotypic markers for tissues of ectodermal, mesodermal, and endodermal origin. The clone was designated as a postnatal pluripotent epiblastic-like stem cell (PPELSC). The undifferentiated clone was transfected with a genomic marker and assayed for alterations in stem cell characteristics. No alterations were noted. The labeled clone, when implanted into heart after injury, incorporated into myocardial tissues undergoing repair. The labeled clone was subjected to directed lineage induction in vitro, resulting in the formation of islet-like structures (ILSs) that secreted insulin in response to a glucose challenge. This study suggests that embryonic-like stem cells are retained within postnatal mammals and have the potential for use in gene therapy and tissue engineering.