Biomedical subjects

Peter Elliott

Publications and source records attributed to Peter Elliott.

21 records · Page 2Linked to original sources

PubMed2002

The MMPI-2 as a predictor of symptom change following treatment for posttraumatic stress disorder.

This study sought to examine the impact of personality factors on symptom change following treatment for 141 Vietnam veterans with chronic combat-related posttraumatic stress disorder (PTSD) using the Minnesota Multiphasic Personality Inventory-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). A series of partial correlation and linear multivariate regression analyses identified social alienation, associated with anger and substance use, as the most potent negative predictor of symptom change. Of the scales assessing personality disorder, Borderline Personality was identified as the strongest negative predictor of outcome. Regression analyses examining the most salient scales identified 5 items that contributed 14% of the variance in the prediction of change scores independently of the 21% accounted for by pretreatment PTSD severity.

Australia↗

PubMed2002

Effects of the proteasome inhibitor PS-341 on apoptosis and angiogenesis in orthotopic human pancreatic tumor xenografts.

Recent studies have shown that the transcription factor, nuclear factor kappaB (NF-kappaB), regulates critical survival pathways in a variety of different cell types, including human pancreatic cancer cells. The activation of NF-kappaB is controlled by proteasome-mediated degradation of its endogenous polypeptide inhibitor, inhibitor of nuclear factor kappaBalpha. We investigated the effects of PS-341, a peptide boronate inhibitor of the proteasome in human pancreatic cancer cells in vitro and in vivo. Comparison of PS-341's effects on the growth of eight different human pancreatic cancer cell lines revealed marked heterogeneity in drug responsiveness, ranging from highly resistant (IC50 > 10 microM; Panc-48, HS766T, and Mia-PaCa-2) to extremely sensitive (IC50 < 40 nM; L3.6pl, Hpaf2, and BxPC3). However, these effects did not correlate with differential inhibition of NF-kappaB activation. Direct quantification of apoptosis revealed that PS-341's effects on cell growth largely correlated with sensitivity to programmed cell death. Evaluation of PS-341's effects on established orthotopic tumor xenografts demonstrated that biweekly intravenous administration of the maximum-tolerated dose of the drug (1 mg/kg) led to significant reductions in the volumes of L3.6pl tumors but not Mia-PaCa-2 tumors. Laser scanning cytometer-mediated quantification of drug-induced apoptosis in the xenografts confirmed that PS-341 induced DNA fragmentation and activation of caspase-3 in L3.6pl tumors but not in Mia-PaCa-2 tumors. However, histological examination of drug-treated tumors revealed extensive central necrosis and reductions in microvessel density and VEGF expression in both tumor types. Taken together, our results demonstrate that PS-341 inhibits the growth of human pancreatic tumors via direct effects on tumor cells and indirect effects on the tumor vasculature.

Animals↗

PubMedDate not supplied

Methylprednisolone favourably alters plasma and urinary cytokine homeostasis and subclinical renal injury at cardiac surgery.

UNLABELLED: Whilst elevated urinary transforming growth factor beta-1 (TGFbeta) is associated with chronic renal dysfunction its role in acute peri-operative renal dysfunction is unknown. In contrast, peri-operative increases in urinary IL-1 receptor antagonist (IL-1ra) and TNF soluble receptor-2 (TNFsr-2) mirror pro-inflammatory activity in the nephron and correlate with renal complications. Steroids modulate some plasma cytokines (decreasing TNFalpha, IL-8, IL-6 and increasing IL-10), whereas ability to reduce plasma and urinary TNFsr-2 and IL-1ra and peri-operative renal injury is unknown. Patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB) were randomised to receive methylprednisolone (n = 18) or placebo (n = 17) before induction of anaesthesia. Plasma and urinary pro- and anti-inflammatory cytokine balance was determined along with subclinical proximal tubular injury and dysfunction, measured by urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine and alpha-1-microglobulin/creatinine ratios, respectively. In the control group compared with baseline, plasma IL-8, TNFalpha, IL-10, IL-1ra and TNFsr-2 were significantly elevated along with urinary IL-1ra, TNFsr-2 and TGFbeta1. Urinary NAG/creatinine and alpha-1-microglobulin/creatinine ratios rose from completion of revascularisation until 6 h with recovery at 24 h with a further rise in NAG/creatinine ratio at 48 h. Compared to placebo, the methylprednisolone group showed significantly reduced plasma IL-8, TNFalpha, IL-1ra and TNFsr-2 whereas plasma IL-10 increased. Compared to placebo, the methylprednisolone group demonstrated significantly reduced urinary NAG/creatinine ratio, TNFsr-2 and TGFbeta1 at 24 h whereas urinary alpha-1-microglobulin/creatinine ratios increased. CONCLUSIONS: Methylprednisolone administration during cardiac surgery significantly reduces plasma and urinary TNFsr-2 and IL-1ra, urinary TGFbeta1 and subclinical renal injury but not dysfunction.

Aged↗