Decorin over-expression by decidual cells in preeclampsia: a potential blood biomarker.

BACKGROUND: Decorin, a leucine-rich proteoglycan that is produced by decidual cells, limits invasion and endovascular differentiation of extravillous trophoblast cells during early placentation by binding to multiple tyrosine kinase receptors, in particular, vascular endothelial growth factor receptor-2. OBJECTIVE: Because many studies have reported an association between poor trophoblast invasion and endovascular differentiation with preeclampsia, the studies reported here tested (1) whether decorin over-expression in the chorionic villi and/or basal decidua is associated with preeclampsia and, if so, (2) whether this association results in a hypoinvasive placenta, and (3) whether elevated plasma decorin concentration in the second trimester is a predictive biomarker for preeclampsia. STUDY DESIGN: Decorin messenger RNA expression was measured with quantitative polymerase chain reaction at the tissue level and with in situ hybridization at the cellular level using (35)S-labeled antisense complimentary RNA probe in placentas from healthy control subjects and subjects with preeclampsia (14 each, 23-40 weeks of gestation). Tissue sections of the same placentas were also immunostained for decorin protein. A decorin over-expressing human endometrial stromal cell line was tested for invasion-regulatory effects on an invasive first-trimester extravillous trophoblast cell line HTR-8/SVneo plated in cocultures that were separated by a semipermeable membrane. Furthermore, we conducted retrospective measurements of plasma decorin levels during the second trimester (15-18 weeks of gestation) in a cohort of 28 body mass index-matched pairs of control subjects and subjects with preeclampsia before the onset of clinical disease. RESULTS: First, decorin messenger RNA expression at the cellular level measured with in situ hybridization exhibited profoundly higher expression levels in basal plate decidual cells within the placentas from preeclamptic subjects than those from control subjects at all gestational ages, whereas no difference between the 2 subject groups was noted in villus mesenchymal cells. Similarly decorin messenger RNA expression at the tissue level in chorionic villi (primarily resulting from fetally derived mesenchymal cells) did not differ significantly between control and preeclampsia placentas. These findings were validated with immunostaining for decorin protein. Second, knocking down decorin gene in a decorin over-expressing endometrial cell line (used as an in vitro surrogate of decorin over-expressing decidual cells) in cocultures with extravillous trophoblast cells abrogated its invasion-restraining actions on trophoblast cells, which indicated paracrine contribution of decorin over-expressing decidua to the poor trophoblast invasiveness in situ. Finally, retrospective measurement of plasma decorin levels during the second trimester in 28 body mass index-matched pairs of control subjects and subjects with preeclampsia revealed elevated plasma decorin levels in all subjects with preeclampsia in all body mass index groups. A receiver operating characteristic curve analysis revealed strong diagnostic performance of plasma decorin in the prediction of preeclampsia status. Although there was no significant gestational age-related change in decorin levels during the second trimester in control or subjects with preeclampsia, we found that plasma decorin had a significant inverse relationship with body mass index or bodyweight. CONCLUSION: We conclude that decorin over-expression by basal decidual cells is associated with hypoinvasive phenotype and poor endovascular differentiation of trophoblast cells in preeclampsia and that elevated plasma decorin concentration is a potential predictive biomarker for preeclampsia before the onset of clinical signs.

Predictors of mortality in patients with lower extremity peripheral arterial disease: 5-year follow-up.

BACKGROUND: Peripheral arterial disease (PAD) is associated with increased mortality. Lower extremity (LE) revascularization improves symptoms, but less is known about long-term survival benefits of LE arterial revascularization. METHODS: Two hundred and eighty-three patients with an ankle brachial index (ABI) or=65 years (HR 2.42 [95% CI 1.52-3.85], P < 0.001), history of coronary artery disease (HR 1.67 [95% CI 1.13-2.46], P = 0.010), chronic kidney disease (HR 1.75 [95% CI 1.15-2.67], P = 0.010), and an ABI

Effects of an aqueous extract of Croton bonplandianum Baill in rats.

We have investigated the cytotoxic and biochemical effects of injecting aqueous phytoextract of Croton bonplandianum (Baill) leaves in male rats. Subchronic dosages of 3.25, 4.65 and 6.97mgphytoextractg(-1)b.wt.week(-1) were administered to rats. To test ameliorative effects, rats were injected with phytoextract mixed with 0.2mgg(-1)b.wt. of cyclophosphamide. Positive controls received only cyclophosphamide, while negative control groups were kept on normal diet and water. Our results demonstrate that phytoextract did not induce micronuclei formation in rats and shows insignificant amelioration (P<0.05). However, differences in serum LDH isoenzymes, ALP, SGOT, SGPT activities and bilirubin were remarkable and displayed dose as well as duration dependent variations. The most outstanding observation of this study was the release of cardiac TnI in sera of rats injected with 6.97mgg(-1)b.wt. of phytoextract for 21 days. Our findings suggest that at the highest concentrations used here phytoextract of C. bonplandianum is not clastogenic; instead it is cardio- and hepatotoxic.

Residents' practices and perceptions about do not resuscitate orders and pronouncing death: an opportunity for clinical training.

BACKGROUND: Although ''Do not resuscitate'' (DNR) orders are among the most commonly discussed patient preference treatment measures, few studies have assessed internal medicine residents' views on this complex topic. Our objective was to assess resident practices in establishing code status. We also examined resident training and experiences in pronouncing death. METHODS: An 18-question survey addressing DNR discussions and pronouncing death was emailed to internal medicine residents in the state of Illinois. Each question had multiple-choice options. RESULTS: A total of 175 residents completed the questionnaire (22% response rate). Seventy-eight percent of the residents had discussed DNR status with patients or their families at least 9 times. However, only one third of the residents felt very comfortable in such discussions. Only 26% of the residents had been observed by a faculty member during a code status discussion and fewer (16%) while pronouncing death. Do not resuscitate discussions rarely occurred in an outpatient clinic (27%). Most residents (90%) thought they would benefit from formal training in DNR discussion. CONCLUSION: Although most residents discuss DNR status with patients and families, only a quarter are observed in such discussions by attending physicians and only a third feel comfortable with this aspect of clinical care. Developing a structured residency program curriculum to address resident skills in end-of-life care would benefit residency training.