In Vitro Assay for Phototoxic Chemicals

The photosensitizing potential of chemicals known to produce photosensitivity in humans was compared to chemicals not considered to be photosensitizers in an in vitro assay. The assay involved exposure of human lymphoid cells to UVA (320–400 nm), and in some cases UVB (280-320 nm) radiation, in the presence of the chemicals and the assessment of phototoxicity as measured by the incorporation of 3[H]-thymidine into nuclear DNA. All known photosensitizers tested were found to be phototoxic, while the nonphotosensitizing agents, with the exception of retinoic acid, were not phototoxic. Peripheral blood mononuclear cells were compared to a T lymphoblastoid cell line as target cells; the latter were superior in terms of convenience, cost and reproducibility of results. This test system has potential as a predictive assay for detecting additional phototoxic chemicals

Three-dimensional confinement of vapor in nanostructures for sub-Doppler optical resolution

International audienceWe confine a Cs thermal vapor in the interstitial regions of a glass opal. We perform linear reflection spectroscopy on a cell whose window is covered with a thin film (10 or 20 layers) of 1000 nm (or 400 nm) diameter glass spheres and observe sub-Doppler structures in the optical spectrum for a large range of oblique incidences. This original feature associated with the inner (3-dimensional) confinement of the vapor in the interstitial regions of the opal evokes a Dicke narrowing. We finally consider possible micron-size references for optical frequency clocks based on weak, hard to saturate, molecular line

Distribution of roots of random real generalized polynomials

The average density of zeros for monic generalized polynomials, $P_n(z)=\phi(z)+\sum_{k=1}^nc_kf_k(z)$, with real holomorphic $\phi ,f_k$ and real Gaussian coefficients is expressed in terms of correlation functions of the values of the polynomial and its derivative. We obtain compact expressions for both the regular component (generated by the complex roots) and the singular one (real roots) of the average density of roots. The density of the regular component goes to zero in the vicinity of the real axis like $|\hbox{\rm Im}\,z|$. We present the low and high disorder asymptotic behaviors. Then we particularize to the large $n$ limit of the average density of complex roots of monic algebraic polynomials of the form $P_n(z) = z^n +\sum_{k=1}^{n}c_kz^{n-k}$ with real independent, identically distributed Gaussian coefficients having zero mean and dispersion $\delta = \frac 1{\sqrt{n\lambda}}$. The average density tends to a simple, {\em universal} function of $\xi={2n}{\log |z|}$ and $\lambda$ in the domain $\xi\coth \frac{\xi}{2}\ll n|\sin \arg (z)|$ where nearly all the roots are located for large $n$.Comment: 17 pages, Revtex. To appear in J. Stat. Phys. Uuencoded gz-compresed tarfile (.66MB) containing 8 Postscript figures is available by e-mail from [email protected]

Iliac fixation inhibits migration of both suprarenal and infrarenal aortic endografts

ObjectiveTo evaluate the role of iliac fixation in preventing migration of suprarenal and infrarenal aortic endografts.MethodsQuantitative image analysis was performed in 92 patients with infrarenal aortic aneurysms (76 men and 16 women) treated with suprarenal (n = 36) or infrarenal (n = 56) aortic endografts from 2000 to 2004. The longitudinal centerline distance from the superior mesenteric artery to the top of the stent graft was measured on preoperative, postimplantation, and 1-year three-dimensional computed tomographic scans, with movement more than 5 mm considered to be significant. Aortic diameters were measured perpendicular to the centerline axis. Proximal and distal fixation lengths were defined as the lengths of stent-graft apposition to the aortic neck and the common iliac arteries, respectively.ResultsThere were no significant differences in age, comorbidities, or preoperative aneurysm size (suprarenal, 6.0 cm; infrarenal, 5.7 cm) between the suprarenal and infrarenal groups. However, the suprarenal group had less favorable aortic necks with a shorter length (13 vs 25 mm; P < .0001), a larger diameter (27 vs 24 mm; P < .0001), and greater angulation (19° vs 11°; P = .007) compared with the infrarenal group. The proximal aortic fixation length was greater in the suprarenal than in the infrarenal group (22 vs 16 mm; P < .0001), with the top of the device closer to the superior mesenteric artery (8 vs 21 mm; P < .0001) as a result of the 15-mm uncovered suprarenal stent. There was no difference in iliac fixation length between the suprarenal and infrarenal groups (26 vs 25 mm; P = .8). Longitudinal centerline stent graft movement at 1 year was similar in the suprarenal and infrarenal groups (4.3 ± 4.4 mm vs 4.8 ± 4.3 mm; P = .6). Patients with longitudinal centerline movement of more than 5 mm at 1 year or clinical evidence of migration at any time during the follow-up period comprised the respective migrator groups. Suprarenal migrators had a shorter iliac fixation length (17 vs 29 mm; P = .006) and a similar aortic fixation length (23 vs 22 mm; P > .999) compared with suprarenal nonmigrators. Infrarenal migrators had a shorter iliac fixation length (18 vs 30 mm; P < .0001) and a similar aortic fixation length (14 vs 17 mm; P = .1) compared with infrarenal nonmigrators. Nonmigrators had closer device proximity to the hypogastric arteries in both the suprarenal (7 vs 17 mm; P = .009) and infrarenal (8 vs 24 mm; P < .0001) groups. No migration occurred in either group in patients with good iliac fixation. Multivariate logistic regression analysis revealed that iliac fixation, as evidenced by iliac fixation length (P = .004) and the device to hypogastric artery distance (P = .002), was a significant independent predictor of migration, whereas suprarenal or infrarenal treatment was not a significant predictor of migration. During a clinical follow-up period of 45 ± 22 months (range, 12-70 months), there have been no aneurysm ruptures, abdominal aortic aneurysm–related deaths, or surgical conversions in either group.ConclusionsDistal iliac fixation is important in preventing migration of both suprarenal and infrarenal aortic endografts that have longitudinal columnar support. Secure iliac fixation minimizes the risk of migration despite suboptimal proximal aortic neck anatomy. Extension of both iliac limbs to cover the entire common iliac artery to the iliac bifurcation seems to prevent endograft migration

Explant analysis of AneuRx stent grafts: relationship between structural findings and clinical outcome

AbstractObjectiveWe reviewed the structural findings of explanted AneuRx stent grafts used to treat abdominal aortic aneurysms, and relate the findings to clinical outcome measures.MethodsWe reviewed data for all bifurcated AneuRx stent grafts explanted at surgery or autopsy and returned to the manufacturer from the US clinical trial and worldwide experience of more than 33,000 implants from 1996 to 2003. Devices implanted for more than 1 month with structural analysis are included in this article. Explant results were analyzed in relation to cause of explantation and pre-explant evidence of endoleak, enlargement, or device migration.ResultsOne hundred twenty explanted stent grafts, including 37 from the US clinical trial, were analyzed. Mean implant duration was 22 ± 13 months (range, 1-61 months). Structural abnormalities included stent fatigue fractures, fabric abrasion holes, and suture breaks. The mean number of nitinol stent strut fractures per explanted device was 3 ± 4, which represents less than 0.2% of the total number of stent struts in each device. The mean number of fabric holes per explanted device was 2 ± 3, with a median hole size of 0.5 mm2. Suture breaks were seen in most explanted devices, but composed less than 1.5% of the total number of sutures per device. “For cause” explants (n = 104) had a 10-month longer implant duration (P = .007) compared with “incidental” explants (n = 16). “For cause” explants had more fractures (3 ± 5; P = .005) and fabric holes (2 ± 3; P = .008) per device compared with “incidental” explants, but these differences were not significant (P = .3) when adjusted for duration of device implantation. Among clinical trial explants the number of fabric holes in grafts in patients with endoleak (2 ± 3 per device) was no different from those without endoleak (3 ± 4 per device; P = NS). The number of fatigue fractures or fabric holes was no different in grafts in clinical trial patients with pre-explant aneurysm enlargement compared with those without enlargement. Pre-explant stent-graft migration was associated with a greater number of stent strut fractures (5 ± 7 per device; P = .04) and fabric holes (3 ± 3 per bifurcation; P = .03) compared with explants without migration. Serial imaging studies revealed inadequate proximal, distal, or junctional device fixation as the probable cause of rupture or need for conversion to open surgery in 86% of “for cause” explants. Structural device abnormalities were usually remote from fixation sites, and no causal relationship between device findings and clinical outcome could be established.ConclusionsNitinol stent fatigue fractures, fabric holes, and suture breaks found in explanted AneuRx stent grafts do not appear to be related to clinical outcome measures. Longer term studies are needed to confirm these observations

Novel critical exponent of magnetization curves near the ferromagnetic quantum phase transitions of Sr1-xAxRuO3 (A = Ca, La0.5Na0.5, and La)

We report a novel critical exponent delta=3/2 of magnetization curves M=H^{1/delta} near the ferromagnetic quantum phase transitions of Sr1-xAxRuO3 (A = Ca, La0.5Na0.5, and La), which the mean field theory of the Ginzburg-Landau-Wilson type fails to reproduce. The effect of dirty ferromagnetic spin fluctuations might be a key.Comment: 4 pages, 5 figure

Implementation of cisternostomy as adjuvant to decompressive craniectomy for the management of severe brain trauma.

To evaluate the value of an adjuvant cisternostomy (AC) to decompressive craniectomy (DC) for the management of patients with severe traumatic brain injury (sTBI). A single-center retrospective quality control analysis of a consecutive series of sTBI patients surgically treated with AC or DC alone between 2013 and 2018. A subgroup analysis, "primary procedure" and "secondary procedure", was also performed. We examined the impact of AC vs. DC on clinical outcome, including long-term (6 months) extended Glasgow outcome scale (GOS-E), the duration of postoperative ventilation, and intensive care unit (ICU) stay, mortality, Glasgow coma scale at discharge, and time to cranioplasty. We also evaluated and analyzed the impact of AC vs. DC on post-procedural intracranial pressure (ICP) and brain tissue oxygen (PbO &lt;sub&gt;2&lt;/sub&gt; ) values as well as the need for additional osmotherapy and CSF drainage. Forty patients were examined, 22 patients in the DC group, and 18 in the AC group. Compared with DC alone, AC was associated with significant shorter duration of mechanical ventilation and ICU stay, as well as better Glasgow coma scale at discharge. Mortality rate was similar. At 6-month, the proportion of patients with favorable outcome (GOS-E ≥ 5) was higher in patients with AC vs. DC [10/18 patients (61%) vs. 7/20 (35%)]. The outcome difference was particularly relevant when AC was performed as primary procedure (61.5% vs. 18.2%; p = 0.04). Patients in the AC group also had significant lower average post-surgical ICP values, higher PbO &lt;sub&gt;2&lt;/sub&gt; values and required less osmotic treatments as compared with those treated with DC alone. Our preliminary single-center retrospective data indicate that AC may be beneficial for the management of severe TBI and is associated with better clinical outcome. These promising results need further confirmation by larger multicenter clinical studies. The potential benefits of cisternostomy should not encourage its universal implementation across trauma care centers by surgeons that do not have the expertise and instrumentation necessary for cisternal microsurgery. Training in skull base and vascular surgery techniques for trauma care surgeons would avoid the potential complications associated with this delicate procedure

DNA Damage Measured by the Comet Assay in Head and Neck Cancer Patients Treated with Tirapazamine

AbstractTirapazamine (TPZ) [3-amino -1,2,4-benzotriazine 1,4-dioxide, SR4233, WIN 59075, and Tirazone™] is a novel anticancer drug that is selectively activated by the low oxygen environment in solid tumors. By killing the radioresistant hypoxic cells, TPZ potentiates the antitumor efficacy of fractionated irradiation of transplanted tumors in mice. As this cell kill is closely correlated with TPZ-induced DNA damage, we investigated whether human head and neck cancers would show DNA damage similar to that seen in mouse tumors following TPZ administration. TPZ-induced DNA damage in both transplanted tumors in mice and in neck nodes of 13 patients with head and neck cancer was assessed using the alkaline comet assay on cells obtained from fine-needle aspirates. The oxygen levels of the patients' tumors were also measured using a polarographic oxygen electrode. Cells from the patients' tumors showed DNA damage immediately following TPZ administration that was comparable to, or greater than, that seen with transplanted mouse tumors. The heterogeneity of DNA damage in the patients' tumors was greater than that of individual mouse tumors and correlated with tumor hypoxia. The similarity of TPZinduced DNA damage in human and rodent tumors suggests that tirapazamine should be effective when added to radiotherapy or to cisplatin-based chemotherapy in head and neck cancers