Arteriovenous fistula outcomes in the era of the elderly dialysis population

BACKGROUND: The growth of patients > or =65 years on hemodialysis is increasing. Guidelines recommend arteriovenous fistula (AVF) access but their outcomes in elderly patients are controversial. This study compared the outcomes of AVF in patients <65 years old (65- group) versus those > or =65 years old (65+ group). METHODS: This retrospective analysis of prospectively collected data included 444 incident, first-time AVF created in a large dialysis center between January 1, 1995 and July 1, 2003. The primary outcome of AVF cumulative patency was evaluated using Kaplan-Meier survival analysis with log-rank test comparison. A Cox model determined factors associated with AVF loss. RESULTS: One hundred ninety-six patients (44%) were in the 65+ group. In total, there were 230 (52.2%) radiocephalic, 186 (42.2%) brachiocephalic, and 25 (5.6%) basilic vein transposed AVF. The one-year AVF cumulative survival was 75.1% (65+ group) and 79.7% (65- group); the five-year survival was 64.7% (65+ group) and 71.4% (65- group). The overall total procedure, angioplasty, thrombolysis, and revision rates per access-year were 0.83, 0.30, 0.66, and 0.16, respectively. The 65+ group had a relative risk of 1.7 of their AVF failing to mature compared with the 65- group. Multivariate analysis yielded these variables significant for AVF loss: male sex HR 0.63 (95% CI 0.44-0.91), coronary artery disease HR 2.1 (95% CI 1.5-3.0), and Caucasian ethnicity HR 0.63 (95% CI 0.44-0.91). CONCLUSION: Age should not be a limiting factor when determining candidacy for AVF creation due to equivalent survival and procedural rates. Failure of fistula maturation is a primary concern to patients of all ages and demands further study.     

Neonatal-perinatal risk factors for the development of persistent pulmonary hypertension of the newborn in preterm newborns

There is a long-held belief that preterm newborns lack sufficient arteriolar musculature to maintain a prolonged elevated pulmonary vascular resistance (PVR) after birth. Net ductal flow is thought to be minimal, with the developing pulmonary circulation incapable of significant vasoconstriction. We identified retrospectively 15 premature newborns over a 10-year period weighing < or = 1500 g and with a gestational age of < or = 30 weeks with documented persistent pulmonary hypertension of the newborn (PPHN) in the first 24 hours after birth. We matched 36 newborns of similar weight and gestation with no clinical evidence of shunting. The control group weaned to an FiO2 < or = 0.50 by 12 hours after birth. Despite similar gestational ages, the PPHN group (n = 15) had significantly higher birth weights than the control group (n = 36). The duration of ruptured membranes, maternal tobacco use, and use of antenatal steroids were significantly higher in the PPHN group. We speculate that these three factors might act in a synergistic relationship with which to accelerate pulmonary vascular smooth muscle development in premature newborns.     

Adoptive immunotherapy of tumor in mice in combination with cyclophosphamide

Cyclophosphamide causes temporary regression of Dalton's lymphoma when injected at palpable stage. Dose-dependent response to cyclophosphamide was analyzed. Low dose was found to be most effective as compared to the high dose. Adoptive transfer of immunized splenocytes after cyclophosphamide therapy protects the animals from the danger of reappearance of tumor. Such combination therapy is proved to be effective in causing complete and permanent regression of tumor in majority of the treated animals.     

Antitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal growth factor receptor targeting in head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is characterized by epidermal growth factor receptor (EGFR) overexpression, where EGFR levels correlate with survival. To date, EGFR targeting has shown limited antitumor effects in head and neck cancer when administrated as monotherapy. We previously identified a gastrin-releasing peptide/gastrin-releasing peptide receptor (GRP/GRPR) aurocrine regulatory pathway in HNSCC, where GRP stimulates Src-dependent cleavage of EGFR proligands with subsequent EGFR phosphorylation and mitogen-activated protein kinase (MAPK) activation. To determine whether GRPR targeting can enhance the antitumor efficacy of EGFR inhibition, we investigated the effects of a GRPR antagonist (PD176252) in conjunction with an EGFR tyrosine kinase inhibitor (erlotinib). Combined blockade of GRPR and EGFR pathways significantly inhibited HNSCC, but not immortalized mucosal epithelial cell, proliferation, invasion, and colony formation. In addition, the percentage of apoptotic cells increased upon combined inhibition. The enhanced antitumor efficacy was accompanied by increased expression of cleaved poly(ADP-ribose) polymerase (PARP) and decreased phospho-EGFR, phospho-MAPK, and proliferating cell nuclear antigen (PCNA). Using reverse-phase protein microarray (RPPA), we further detected decreased expression of phospho-c-Jun, phospho-p70S6K, and phospho-p38 with combined targeting. Cumulatively, these results suggest that GRPR targeting can enhance the antitumor effects of EGFR inhibitors in head and neck cancer.