Revisiting the bis(dimethylamido) metallocene complexes of thorium and uranium: improved syntheses, structure, spectroscopy, and redox energetics of (C5Me5)2An(NMe2)2 (An = Th, U).

The reaction of (C5Me5)2AnCl2 (An = Th, U) with 2.8 or 4 equivalents of LiNMe2, respectively, affords (C5Me5)2An(NMe2)2 in high yields. In addition to improved syntheses, the solid-state structures, voltammetric data, and UV-visible-NIR spectra for these classic actinide bis(dimethylamido) complexes are presented for the first time.

An automated quasi-continuous capillary refill timing device.

Capillary refill time (CRT) is a simple means of cardiovascular assessment which is widely used in clinical care. Currently, CRT is measured through manual assessment of the time taken for skin tone to return to normal colour following blanching of the skin surface. There is evidence to suggest that manually assessed CRT is subject to bias from ambient light conditions, a lack of standardisation of both blanching time and manually applied pressure, subjectiveness of return to normal colour, and variability in the manual assessment of time. We present a novel automated system for CRT measurement, incorporating three components: a non-invasive adhesive sensor incorporating a pneumatic actuator, a diffuse multi-wavelength reflectance measurement device, and a temperature sensor; a battery operated datalogger unit containing a self contained pneumatic supply; and PC based data analysis software for the extraction of refill time, patient skin surface temperature, and sensor signal quality. Through standardisation of the test, it is hoped that some of the shortcomings of manual CRT can be overcome. In addition, an automated system will facilitate easier integration of CRT into electronic record keeping and clinical monitoring or scoring systems, as well as reducing demands on clinicians. Summary analysis of volunteer (n = 30) automated CRT datasets are presented, from 15 healthy adults and 15 healthy children (aged from 5 to 15 years), as their arms were cooled from ambient temperature to 5°C. A more detailed analysis of two typical datasets is also presented, demonstrating that the response of automated CRT to cooling matches that of previously published studies.

Uranyl sorption by smectites: spectroscopic assessment of thermodynamic modeling.

Batch sorption experiments and thermodynamic modeling of the interaction of UO2(2+) and its hydrolysis products with two smectitic clay minerals, the reference material SWy-1 [McKinley et al., Clays Clay Miner. 43 (1995) 586] and the soil isolate LK-1 [Turner et al., Geochim. Cosmochim. Acta 30 (1996) 3399], have established a conceptual framework for uranyl/smectite surface complexation based on general reactions between aqueous uranyl species and the reactive sites on the mineral surfaces. In this report, we have formulated and spectroscopically tested a set of hypotheses based on this conceptual framework using samples prepared under similar or identical conditions to evaluate the agreement between surface complexation/speciation as enumerated by spectroscopic characterization and that elaborated by the surface complexation model. Both steady-state and time-resolved optical emission spectral data are presented for uranyl on both smectite minerals as well as on the analogue phases SiO2 and Al(OH)3 spanning the pH range from approximately 4 to 8 and the background electrolyte concentrations from approximately 0.001 to 0.1 M. The spectral data enable the explicit identification of an outer-sphere exchange-site population of the hydrated cation [UO2(OH2)5(2+) ] in SWy-1. Spectral data also clearly establish the existence of inner-sphere surface complexes on the analogue phases and on the amphoteric clay crystallite edge sites [aluminol (>Al-OH) and silanol (>Si-OH)]. Based on the spectral characteristics of these uranyl edge-site populations, it is possible to readily infer for the SiO2, Al(OH)3, and SWy-1 samples the evolution in surface speciation with increasing pH to more hydrolyzed uranyl-surface complexes consistent with the conceptual model. The spectral domain characteristics of the edge-site populations on LK-1 with increasing pH suggest that there is no change in the hydrolysis of the uranyl-surface species. However, emission lifetime data are interpreted as indicating a shift in the surface speciation of the same uranyl-surface species from aluminol sites to silanol sites with pH increase. This observation is also consistent with the conceptual framework of the model. Data are also reported for Eu3+/smectite samples to provide additional insight into the exchange site populations. The emission spectra for Eu3+ in the basal-plane exchange sites differs significantly between SWy-1 and LK-1 samples reflecting a difference in the basal plane spacing between these two minerals, but the emission lifetime data suggest that the Eu3+ cation remains fully hydrated in both systems. The overall general description of surface speciation of uranyl on these mineral phases as enumerated by spectroscopy is in good accord with that derived from the conceptual thermodynamic model, lending added confidence to our understanding and descriptions of surface complexation behavior in this complex geochemical system.

Uterine serous carcinoma: a comparison of therapy for advanced-stage disease.

Management of advanced-stage uterine serous carcinoma (USC) is uncertain, and postsurgical therapeutic options swing between radiation and chemotherapy. The aim of this study is to evaluate the utility of radiotherapy compared to platinum-based chemotherapy in women with advanced-stage USC. We retrospectively identified cases of USC at our institution. Survival distributions were calculated by the Kaplan-Meier method. Two-tailed t-tests were used to compare time to progression and time to death. We identified 24 women diagnosed with either stage III or IV USC. Time to progression for women receiving radiotherapy was 5.3 months as compared with 12.4 months for women receiving chemotherapy (P = 0.01). Mean time to death for the radiotherapy group was 8 months compared to 18 months in the chemotherapy group (P = 0.04). Kaplan-Meier survival curves were significantly different between the two groups (P = 0.01). While radiotherapy appears to control USC recurrences in the pelvis, the disease often recurs distantly. When compared to radiotherapy, platinum-based chemotherapy appears to increase disease-free survival and time to death in women with advanced-stage USC.

Reaction of the uranyl(VI) ion (UO(2)(2+)) with a triamidoamine ligand: preparation and structural characterization of a mixed-valent uranium(V/VI) oxo-imido dimer.

The synthesis and structural characterization of a mixed-valent uranium(V/VI) oxo-imido complex are reported. Reaction of the uranyl chloride complex [K(18-crown-6)](2)[UO(2)Cl(4)] (1) with the triamidoamine ligand Li(3)[N(CH(2)CH(2)NSiBu(t)Me(2))(3)] yields oxo-imido [K(18-crown-6)(Et(2)O)][UO(mu(2)-NuCH(2)CH(2)N(CH(2)CH(2)NSiBu(t)Me(2))(2))](2) (2) as the major isolated uranium product in moderate yield. The reaction that forms 2 involves activation of both the triamidoamine ligand and the uranyl dioxo unit of 1. An X-ray crystal structure determination of 2 reveals a dimeric complex in which the coordination geometry at each uranium center is that of a capped trigonal bipyramid. The multidentate triamidoamine ligand coordinates to uranium through the capping amine and two of the three pendant amido ligands, while the third pendant amido donor has been activated to generate a bridging imido ligand by loss of the silyl substituent. One of the uranyl oxo groups is retained as a terminal ligand to complete the coordination sphere for each uranium center. The oxo and imido nitrogen may be regarded as the axial ligands of the trigonal bipyramid, while the two amido ligands and the other imido donor occupy equatorial coordination sites. The central amine of the tripodal set serves as the capping ligand. Distortion of the axial O-U-N angle from 180 degrees emanates from the proximity of the capping amine and the bridging interaction to the other uranium center. The structure and bonding in 2 are assessed in the context of metal-ligand multiple bonding in high-valent actinide complexes. The possibility of valence averaging [5.5/5.5 vs 5.0/6.0] via delocalization or rapid intramolecular electron-transfer dynamics of the unpaired electron is also discussed in the context of crystallographic, spectroscopic (NMR, IR, Raman, and EPR), and electrochemical data. Crystal data for 2: triclinic space group P1 macro, a = 12.1144(6) A, b = 12.6084(6) A, c = 14.5072(7) A, alpha = 101.374(1) degrees, beta = 103.757(1) degrees, gamma = 109.340(1) degrees, z = 1, R1 = 0.0523, wR2 = 0.1359.

Three-dimensional conformal radiation treatment planning and delivery for low- and intermediate-grade gliomas.

Three-Dimensional conformal radiation treatment (3D-CRT) planning and delivery is an external beam radiation therapy modality that has the general goal of conforming the shape of a prescribed dose volume to the shape of a 3-dimensional target volume, simultaneously limiting dose to critical normal structures. 3-Dimensional conformal therapy should include at least one volumetric imaging study of the patient. This image should be obtained in the treatment position for visualizing the target and normal anatomic structures that are potentially within the irradiated volume. Most often, computed tomography (CT) and/or magnetic resonance imaging (MRI) are used; however, recently, other imaging modalities such as functional MRI, MR spectroscopy, and positron emission tomography (PET) scans have been used to visualize the clinically relevant volumes. This article will address the clinically relevant issues with regard to low- and intermediate-grade gliomas and the role of 3D-CRT planning. Specific issues that will be addressed will include normal tissue tolerance, target definition, treatment field design in regard to isodose curves and dose-volume histograms, and immobilization.

Drug-induced methemoglobinemia during thoracoscopic lung biopsy.

Acquired methemoglobinemia occurs rarely in clinical practice. We present a case of a 57-year-old man who developed severe drug-induced methemoglobinemia after exposure to benzocaine spray and lidocaine jelly during intubation for an elective thoracoscopic lung biopsy. Information regarding the classifications, pathophysiology, diagnosis, and treatment of this entity is reviewed.

Brain metastases.

Metastatic tumors to the brain are an increasing cause of morbidity and mortality in patients with systemic cancers. Many new therapies used to treat systemic cancers do not penetrate the central nervous system (CNS) and do not protect patients from the development of brain metastases. Surgery, radiosurgery, and radiation therapy are all used to treat brain metastases. It is in our opinion a mistake to use only one or two of these modalities to the exclusion of other(s). The role of systemic chemotherapy is still limited, due to both the issues of drug delivery caused by the blood brain barrier and to the relative resistance of many of these tumors to chemotherapy. Traditionally, brain metastases have been grouped together regardless of the origin of the tumor and have been treated with a single algorithm. As we encounter more patients for whom treatment of the brain metastases is an important determinant of survival, we must tailor our treatment strategies to individual tumor types. Also, we must recognize differences in each tumor's sensitivity to chemotherapy and radiotherapy and differences in their biology.

Clinical experience with retreatment for palliation.

Every radiation oncologist is faced occasionally with the need to consider reirradiation for palliation. Because reirradiation has the potential to exceed normal tissue tolerances, there is a need to have information on the efficacy and toxicity of retreatment. This article reviews the reirradiation literature and provides guidance to clinicians with regard to the risks, benefits, and side effects of retreatment.

Basicity of uranyl oxo ligands upon coordination of alkoxides.

Uranium(VI) alkoxide complexes are prepared via metathesis reactions of [UO2Cl2(THF)2]2 with potassium alkoxides in nonaqueous media. The dark red compound U[OCH2C(CH3)3]6, 1, results from redistributive exchange of oxo and neopentoxide ligands between more than one uranium species. Single-crystal X-ray diffraction analysis of 1 reveals a monomer in which the uranium is coordinated in a pseudooctahedral fashion by six neopentoxide ligands. Imposition of steric congestion at the metal center prevents oxo-alkoxide ligand exchange in the reactions using more sterically demanding alkoxides. Simple metathesis between uranyl chloride and alkoxide ligands occurs in the synthesis of golden yellow-orange UO2(OCHPh2)2(THF)2, 2, and yellow UO2[OCH(tBu)Ph]2(THF)2, 3. Single-crystal X-ray diffraction analysis of 2 reveals a monomer in which the uranium is coordinated in a pseudooctahedral fashion by two apical oxo ligands, two diphenylmethoxide ligands occupying trans positions, and two tetrahydrofuran ligands. Coordination of diisopropylmethoxide allows for synthesis of a more complex binary alkoxide system. Single-crystal X-ray diffraction analysis of watermelon red [UO2(OCH(iPr)2)2]4, 4, reveals a tetramer in which each uranium is coordinated in a pseudooctahedral fashion by two apical oxo ligands, one terminal alkoxide, two bridging alkoxide ligands, and one bridging oxo ligand from a neighboring uranyl group. These compounds are characterized by elemental analysis, 1H NMR, infrared spectroscopy, and, for 1, 2, and 4, single-crystal X-ray diffraction analysis. Luminescence spectroscopy is employed to evaluate the extent of aggregation of compounds 2-4 in various solvents. Vibrational spectroscopic measurements of 2-4 imply that, in contrast to the case of uranyl complexes prepared in aqueous environments, coordination of relatively strongly donating alkoxide ligands allows for enhancement of electron density on the uranyl groups such that the uranyl U=O bonds are weakened. Crystal data are as follows. 1: monoclinic space group C2/m, a = 10.6192(8) A, b = 18.36(1) A, c = 10.6151(8) A, beta = 109.637(1) degrees, V = 1949.1(3) A3, Z = 2, dcalc = 1.297 g cm-3. Refinement of 2065 reflections gave R1 = 0.045. 2: monoclinic space group P2(1)/c, a = 6.1796(4) A, b = 15.669(1) A, c = 16.169(1) A, beta = 95.380(1) degrees, V = 1558.7(2) A3, Z = 2, dcalc = 1.664 g cm-3. Refinement of 3048 reflections gave R1 = 0.036. 4: tetragonal space group I4, a = 17.8570(6) A, b = 17.8570(6) A, c = 11.4489(6) A, V = 3650.7(3) A3, Z = 2, dcalc = 1.821 g cm-3. Refinement of 1981 reflections gave R1 = 0.020.

Acute and chronic animal models for excessive dermal scarring: quantitative studies.

Excessive scarring in the form of keloids and hypertrophic scars continues to be a clinical problem for some patients. The lack of an animal model for such scarring has been an obstacle to studying the cellular and molecular biology of these entities. Previous observations made by the authors that some surgical scars in the rabbit ear remain raised for months after wounding prompted us to investigate whether the rabbit ear might provide a model by which to study excessive dermal scarring. After establishing the model in preliminary study, 40 excisional wounds, 6 mm in diameter, were created over the ventral surface of rabbit ears. Elevated scars were treated with either intralesional triamcinolone acetonide or saline at day 16 postwounding. On day 22, 25 scar wounds were used for thorough histomorphometric analysis, 15 wounds were eliminated prior to analysis because of invagination of epithelial tissue, which made analysis difficult. Total area of scar and Hypertrophic Index, a ratio comparing scar prominence with the thickness of adjacent unwounded tissue, were measured for 25 (62 percent) of the resulting scars. Both total area of scar and Hypertrophic Index were found to be significantly decreased in the steroid-treated group (p < 0.02 and < 0.03, respectively). In a chronic form of this model, in which larger excisions were taken, an excessive accumulation of both new collagen and cartilage over 9 months was observed. An animal model for excessive dermal scarring that allows quantitation of scar formation and, at an early stage, can be modulated in a predictable way with intralesional corticosteroid treatment is presented. This model may parallel hypertrophic scarring in humans and thus might provide a tool by which to study its pathophysiology and objectively evaluate therapeutic modalities.

Transforming growth factor beta 3 (TGF beta 3) accelerates wound healing without alteration of scar prominence. Histologic and competitive reverse-transcription-polymerase chain reaction studies.

BACKGROUND: Transforming growth factor (TGF) beta 3 is a new isoform of the TGF beta superfamily and is presumed to play an important role in wound repair and scarring. OBJECTIVE: To examine the effects of TGF beta 3 on wound healing and on reducing scarring. DESIGN AND INTERVENTIONS: Dermal ulcers were created on the ears of 75 anesthetized young female rabbits. Either TGF beta 3 or vehicle was applied topically to the wounds. Wounds were bisected and analyzed histologically at postwounding day 7. A second group of wounds was treated with topical TGF beta 3 and TGF beta 2 or vehicle at days 0 and 3 and harvested at days 21 through 42 as an excessive scarring model. The third group of wounds was treated with TGF beta 1, TGF beta 2, and TGF beta 3 and vehicle. The granulation tissue was harvested at day 7, and cellular RNA was extracted for performing competitive reverse-transcription polymerase chain reaction. MAIN OUTCOME MEASUREMENT: The amount of new epithelium and granulation tissue was measured in TGF beta 3- and vehicle-treated wounds. The hypertrophic index was calculated for scarring wounds treated with TGF beta 2 and TGF beta 3 or vehicle. Levels of TGF beta 1 messenger RNA were measured in those wounds that were treated with TGF beta 1, TGF beta 2, and TGF beta 3 and in their controls. RESULTS: The use of TGF beta 3 (0.3-0.75 microgram per wound) increased granulation tissue formation by more than 100% (P < .005). Epithelialization showed a biphase, either increasing 30% (P < .04) or decreasing 25% (P < .001) dependent on dose. No significant difference in the hypertrophic index was noted in TGF beta 3-treated wounds compared with controls. Levels of TGF beta 1 messenger RNA increased (7.1- to 14.9-fold) in those wounds treated with TGF beta s compared with controls at day 7. CONCLUSIONS: Exogenous TGF beta 3 displays substantial vulnerary properties in wound healing and may be useful in treating nonhealing wounds. However, the observation that TGF beta 3 can reduce scarring was not confirmed in this study, and the messenger RNA level in response to TGF beta 3 suggests that it behaves similarly to TGF beta 1.

Superconductivity at 45 k in rb/tl codoped c60 and c60/c70 mixtures.

The appearance of superconductivity at relatively high temperatures in alkali metal-doped C(60) fullerene provides the challenge to both understand the nature and origin of the superconductivity and to determine the upper limit of the superconducting transition temperature (T(c)). Towards the latter goal, it is shown that doping with potassium-thallium and rubidium-thallium alloys in the 400 to 430 degrees C temperature range increases the T(c) of C(60)/C(70) mixtures to 25.6 K and above 45 K, respectively. Similar increases in T(c) were also observed upon analogous doping of pure C(60). Partial substitution of potassium with thallium in interstitial sites between C(60) molecules is suggested by larger observed unit cell parameters than for the K(3)C(60) and K(4)C(60) phases. Contrary to previous results for C(60) doped with different alkali metals, such expansion does not alone account for the changes in critical temperature.

Earthworm mucus stimulates oviposition in a predatory fly (Diptera: Anthomyiidae).

Coenosia tigrina larvae feed on earthworms. We hypothesized that earthworm mucus contains a kairomone that stimulates oviposition behavior in adultC. tigrina females, thus minimizing the search area in the soil required for newly eclosed larvae to find earthworms. In bioassays, adult females responded with extension of the ovipositor 25-43% of the time to earthworm-mucus-soaked filter paper disks compared to 6-7% in response to water-soaked disks. Ovipositor extension on mucus-soaked disks was followed by egg-laying 29% of the time and 0% of the time on water-soaked disks. Egg-laying byC. tigrina followed a diurnal periodicity, with most eggs laid in the latter half of the photophase even in the absence of earthworm mucus. More eggs were deposited from 1600 to 1800 hr by females given access to earthworm mucus during that period than were deposited by females not given access. There was no difference in the number of eggs deposited from 0600 to 0800 hr, by females given access to earthworm mucus or not. This is a time of day when few eggs are normally laid. This paper is the first report of an earthworm-produced kairomone in an insect-earthworm interaction. The kairomone may have potential for enhancing biological control of the onion maggot,Delia antiqua, which is a prey of adultC. tigrina.

Winning strategies for academic centers.

Academic medical centers must expand market share, develop high-volume product lines in targeted disease groupings and create large-scale programs to stand out in a crowded marketplace and build competitive advantages. The author outlines key strategies that will help administrators differentiate their institutions from their competitors.

Positioning academic medical centers and teaching hospitals to thrive in the next decade.

Market share for academic medical centers and teaching hospitals will decline over the next five years necessitating new strategies to ensure growth and profitability. These types of institutions are, however, in a strong position to compete and gain market share locally by building a defensible competitive advantage. This article offers three avenues for increasing market share: networking, brand name product differentiation, and business diversification.