First- and second-trimester screening: detection of aneuploidies other than Down syndrome

OBJECTIVE: To evaluate the performance of first- and second-trimester screening methods for the detection of aneuploidies other than Down syndrome. METHODS: Patients with singleton pregnancies at 10 weeks 3 days through 13 weeks 6 days of gestation were recruited at 15 U.S. centers. All patients had a first-trimester nuchal translucency scan, and those without cystic hygroma had a combined test (nuchal translucency, pregnancy-associated plasma protein A, and free beta-hCG) and returned at 15-18 weeks for a second-trimester quadruple screen (serum alpha-fetoprotein, total hCG, unconjugated estriol, and inhibin-A). Risk cutoff levels of 1:300 for Down syndrome and 1:100 for trisomy 18 were selected. RESULTS: Thirty-six thousand one hundred seventy-one patients completed first-trimester screening, and 35,236 completed second-trimester screening. There were 77 cases of non-Down syndrome aneuploidies identified in this population; 41 were positive for a cystic hygroma in the first trimester, and a further 36 had a combined test, of whom 29 proceeded to quadruple screening. First-trimester screening, by cystic hygroma determination or combined screening had a 78% detection rate for all non-Down syndrome aneuploidies, with an overall false-positive rate of 6.0%. Sixty-nine percent of non-Down syndrome aneuploidies were identified as screen-positive by the second-trimester quadruple screen, at a false-positive rate of 8.9%. In the combined test, the use of trisomy 18 risks did not detect any additional non-Down syndrome aneuploidies compared with the Down syndrome risk alone. In second-trimester quadruple screening, a trisomy 18-specific algorithm detected an additional 41% non-Down syndrome aneuploidies not detected using the Down syndrome algorithm. CONCLUSION: First-trimester Down syndrome screening protocols can detect the majority of cases of non-Down aneuploidies. Addition of a trisomy 18-specific risk algorithm in the second trimester achieves high detection rates for aneuploidies other than Down syndrome. LEVEL OF EVIDENCE: II.     

New insight into artifactual phenomena during in vitro toxicity assessment of engineered nanoparticles: Study of TNF-α adsorption on alumina oxide nanoparticle

Biomolecules can be adsorbed on nanoparticles (NPs) and degraded during in vitro toxicity assays. These artifactual phenomena could lead to misinterpretation of biological activity, such as false-negative results. To avoid possible underestimation of cytokine release after contact between NP and cells, we propose a methodology to account for these artifactual phenomena and lead to accurate measurements. We focused on the pro-inflammatory cytokine tumor necrosis factor TNF-α. We studied well-characterized boehmite engineered NP [aluminum oxide hydroxide, AlO(OH)]. The rate of TNF-α degradation and its adsorption (on boehmite and on the walls of wells) were determined in cell-free conditions by adding a known TNF-α concentration (1500 pg/ml) under various experimental conditions. After a 24-h incubation, we quantified that 7 wt.% of the initial TNF-α was degraded over time, 6 wt.% adsorbed on the walls of 96-well plates, and 13 wt.% adsorbed on the boehmite surface. Finally, boehmite NP were incubated with murine macrophages (RAW 264.7 cell line). The release of TNF-α was assessed for boehmite NP and the experimental data were corrected considering the artifactual phenomena, which accounted for about 20–30% of the total.     

Comparison of computer-assisted instruction and seminar instruction to acquire psychomotor and cognitive knowledge of epistaxis management.

Epistaxis is a common problem faced by primary care physicians. Typically, first-hand experience with this problem is not obtained in medical school. A computer learning module was developed to address practical management of epistaxis. It was evaluated by use of third-year clerks and compared with an interactive seminar based on the same material. Fifty-eight students doing their required otolaryngology rotations were randomly separated into 3 groups: (1) doing a preinstruction test, (2) using the computer module, and (3) participating in a small-group seminar. All participants were tested with a short written test and a practical test that involved performing anterior nasal pack placement in a model patient. Percentage scores for the 2 groups were compared by use of t tests, and there was no significant difference between the written, practical, or combined scores at a level where P = 0.05. This study shows that basic patient management and a simple procedure can be taught as effectively with a computer module as with a small-group interactive seminar.     

Evaluation of educational preparation for cancer and palliative care nursing for children and adolescents in England.

This paper reports the findings of a study which was carried out to evaluate the educational preparation of cancer and palliative care nurses in England. The study was carried out in three stages and covered the following areas; documentary analysis of curriculae, assessment of practice, patients and professionals views of threshold and expert practice. The findings suggested that although there was widespread compliance with a national standard for cancer nursing, this was not the case for palliative care nursing. There was uncertainty about what should be assessed in practice and ambiguity about what was actually assessed. Partnership with children and their parents, clinical skills, multi-disciplinary working, and personal attributes were the main foci for expectations of threshold practice but an expert panel had difficulty in describing the attributes of higher level practice. The paper also describes how some of recommendations from the study are being taken forward in current policy and practice.     

Fetal hemoglobin gene activation in a phase II study of 5,6-dihydro-5-azacytidine for bronchogenic carcinoma

5-Azacytidine and several of its analogues are known to inhibit DNA methylation, alter gene expression, and inhibit cell growth. We report a Phase II study in which we investigated the antineoplastic activity of 5,6-dihydro-5-azacytidine and its induction of fetal hemoglobin synthesis when given by a 5-day continuous i.v. infusion of 1650 mg/m2/day that was repeated every 21 days. Fetal hemoglobin was measured in all patients; increased synthesis was found in 13 of the 17, in the absence of clinically significant anemia. Of the four patients who did not develop increased fetal hemoglobin, three had only one cycle of therapy. Fourteen patients with bronchogenic carcinoma were treated, and ten were evaluable for disease response. Five patients had disease stability of 2 or more mo, and five progressed on treatment. Three additional patients with mesothelioma were treated, and the two who were evaluable for disease response had stabilization of their disease. Fifteen of the 17 patients who received 5,6-dihydro-5-azacytidine developed a pleuritic-type chest pain, 12 had abnormal electrocardiograms, and four developed positive anti-nuclear antibodies. No significant hemopoietic, hepatic, or renal toxicities were observed. This study demonstrates that 5,6-dihydro-5-azacytidine in the dose and schedule used has no significant therapeutic activity in the treatment of lung cancer but does possess an unusual spectrum of clinical toxicities as well as the property of inducing fetal hemoglobin synthesis.