Re: Gamma-radiation sensitivity and risk of glioma.
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The purpose of this study was to compare the single-incision, "endoscopic" (ENDO) anterior cruciate ligament (ACL) reconstruction technique with the two-incision, "rear-entry" technique (RE). Sixty patients were entered into a prospective study. Thirty patients underwent ACL reconstruction by the RE technique, followed by 30 consecutive patients using the ENDO procedure. Postoperatively all patients followed a standardized rehabilitation protocol. Follow-up evaluation consisted of a detailed physical examination, range of motion, thigh girth, vertical leap, hop test, KT-1000 testing, and patient interview. They were scored according to the International Knee Documentation Committee (IKDC) protocol, which takes objective and subjective data into account. Patients were also assessed for level of sports activity including frequency and type. Finally, anteroposterior and lateral x-ray films were evaluated with a scoring system for tunnel location. Of the initial 60 patients entered into the study, 50 were available for a detailed clinical and functional review (83%). Demographic comparisons revealed 24 RE patients and 26 ENDO patients. There were 16 men and 8 women in the RE group. The ENDO group comprised 16 men and 10 women. There were 14 right knees and 10 left knees in the RE group. In the ENDO group there were 13 right knees and 13 left knees. The average age in the RE group was 24 years and 25 years in the ENDO group. The average follow-up was 35 months (range 31-40 months) in the RE group and 29 months (range 24-35 months) in the ENDO group. Complications included two patients with loss of motion in the RE group and three in the ENDO group. There were no significant differences between the two groups tested with respect to the overall IKDC rating scale. Anteroposterior and lateral x-ray films revealed no significant differences in femoral and tibial tunnel placement. In conclusion, no significant functional or radiographic differences at a minimum 2-year follow-up could be identified when comparing the two ACL reconstructive techniques.
The ligand substitution behavior of [ReBr3(CO)3](NEt4)2 (1) and [ReBr3(CO)2(NO)]NEt4 (2) in aqueous media was compared. Ligand exchange reactions were performed with multidentate chelating systems such as picolylaminediacetic acid (L1; N,N',O,O'), nitrilotriacetic acid (L2; N,O,O',O''), iminodiacetic acid (L3; N,O,O'), and bis(2-pyridyl)methane (L4; N,N'). The products of the substitution reactions were isolated and characterized by means of IR, NMR, MS, and X-ray structure analysis. NMR and crystallographic analyses confirmed the formation of single structural isomers in all cases with a ligand-to-metal ratio of 1:1. With ligands L1 and L2 and precursor 1 the tridentately coordinated complexes [Re(L1)(CO)3] (7) and [Re(L2)(CO)3]2- (8) were formed. With precursor 2 the same ligands unexpectedly coordinated tetradentately after displacing a CO ligand, yielding complexes [Re(L1)(CO)(NO)] (3) and [Re(L2)(CO)(NO)]- (4). In both complexes NO was found to be coordinated trans to the carboxylate group. Time-dependent IR spectra of the reaction of 2 with ligand L1 and L2 confirmed the loss of one CO during the reaction. The product of the reaction of 2 with L3 was identified as the neutral complex [Re(L3)(CO)2(NO)] (5), again, with the nitrosyl coordinated trans to the carboxylate. With 1, ligand L3 formed the anionic complex [Re(L3)(CO)3]- (9). Finally the reactions with L4 yielded the complexes [ReBr(L4)(CO)2(NO)]Br (6) and [ReBr(L4)(CO)3] (10), in which bromide was found to be coordinated trans to the NO and CO, respectively. The X-ray structures of 3, 5-7, and 10 are discussed: 3, monoclinic P2(1)/n, with a = 14.6071(6) A, b = 8.0573(3) A, c = 24.7210(11) A, beta = 107.117(5) degrees, and Z = 4; 5, triclinic P1, with a = 6.9091(5) A, b = 9.8828(7) A, c = 14.2834(10) A, alpha = 89.246(9) degrees, beta = 89.420(9) degrees, gamma = 86.196(9) degrees, and Z = 4; 6, triclinic P1, with a = 9.8236(8) A, b = 10.0949(8) A, c = 12.5346(10) A, alpha = 108.679(9) degrees, beta = 111.992(9) degrees, gamma = 95.426(10) degrees, and Z = 2; 10, monoclinic P2(1)/c, with a = 12.7491(12) A, b = 13.3015(13) A, c = 9.0112(9) A, beta = 107.195(2) degrees, and Z = 7.
A straightforward solvent wetting method was used to prepare felodipine solid dispersions in the presence of various carriers. Dichloromethane is not needed when HPMC solid dispersions were produced using the solvent wetting method. The amount of ethanol used to prepare solid dispersions did not have a significant effect on the dissolution rate of felodipine. The results of X-ray diffraction and thermal analysis indicated that the drug was in the amorphous state when PVP, HPMC, and poloxamer were used as carriers. The dissolution rates of felodipine in PVP, HPMC, or poloxamer solid dispersions were much faster than those for the corresponding physical mixtures. However, dissolution profiles were found to depend on the carrier used; the dissolution rate of felodipine increased slowly for solid dispersions prepared using HPMC, whereas rapid initial dissolution rates were observed for solid dispersions prepared using PVP or poloxamer. Increases in dissolution rates were partly dependent on the ratios of felodipine to carrier. No significant changes in crystal form were observed by X-ray diffraction or thermal analysis, and no significant changes in dissolution rate were observed when sorbitol and mannitol were used as carriers.
A new and high yielding method for the synthesis of [M(CO)(3)(eta(5)-2,3-C(2)B(9)H(11))](-) and the bifunctional metal complexes, rac-[M(CO)(3)(eta(5)-2-R-2,3-C(2)B(9)H(10))](-) (R = CH(2)CH(2)CO(2)H), from [M(CO)(3)Br(3)](2)(-) (M = Re, (99)Tc) was developed. The general approach entailed the addition of nido-[(C(2)B(9)H(12))(-)], or the acid substituted analogue, to [M(CO)(3)Br(3)](2)(-) (M = Re, (99)Tc) in the presence of TlOEt in THF. It was also possible to prepare the reported products in water using sodium carbonate in place of TlOEt. The reported approach led to the preparation, and X-ray crystallographic structure determination, of the first Tc-carborane complex reported to date (a = 13.606(17) A, b = 10.685(13) A, c = 15.534(16) A, alpha = gamma = 90 degrees, beta = 111.84(2) degrees). Because of the stabilities of the metal complexes, and the fact that the compounds can be prepared in water, the bifunctional derivatives can be considered as novel synthons for the preparation of organometallic (99m)Tc and (186/188)Re radiopharmaceuticals.
(R)-[1-(Dimethylamino)ethyl]benzene reacts with nBuLi in a 1:1 molar ratio in pentane to quantitatively yield a unique hetero-aggregate (2 a) containing the lithiated arene, unreacted nBuLi, and the complexed parent arene in a 1:1:1 ratio. As a model compound, [Li(4)(C(6)H(4)CH(Me)NMe(2)-2)(2)(nBu)(2)] (2 b) was prepared from the quantitative redistribution reaction of the parent lithiated arene Li(C(6)H(4)CH(Me)NMe(2)-2) with nBuLi in a 1:1 molar ratio. The mono-Et(2)O adduct [Li(4)(C(6)H(4)CH(Me)NMe(2)-2)(2)(nBu)(2)(OEt(2))] (2 c) and the bis-Et(2)O adduct [Li(4)(C(6)H(4)CH(Me)NMe(2)-2)(2)(nBu)(2)(OEt(2))(2)] (2 d) were obtained by re-crystallization of 2 b from pentane/Et(2)O and pure Et(2)O, respectively. The single-crystal X-ray structure determinations of 2 b-d show that the overall structural motifs of all three derivatives are closely related. They are all tetranuclear Li aggregates in which the four Li atoms are arranged in an almost regular tetrahedron. These structures can be described as consisting of two linked dimeric units: one Li(2)Ar(2) dimer and a hypothetical Li(2)nBu(2) dimer. The stereochemical aspects of the chiral Li(2)Ar(2) fragment are discussed. The structures as observed in the solid state are apparently retained in solution as revealed by a combination of cryoscopy and (1)H, (13)C, and (6)Li NMR spectroscopy.
The reaction of 2-(2'-pyridyl)benzothiazole, [NN], with the ReO(V)(3+) and TcO(V)(3+) cores in the presence of thiophenols, [S] (RC(6)H(4)SH, R = H, 4-CH(3), 4-OCH(3)), as coligands led to the isolation of hexacoordinated complexes of the MO[NN][S](3) type (M = Re, Tc). In all cases, two geometric mer isomers were formed, as evidenced by NMR spectroscopy and confirmed by X-ray crystallography. In both isomers, the coordination geometry about the metal ion is a distorted octahedral defined by the two nitrogen atoms of the bidentate ligand, the three sulfur atoms of the monodentate thiols, and the oxygen atom of the oxo group. The apical positions of the octahedron are occupied by the oxygen of the oxo group and, in one of the isomers, the nitrogen of the pyridyl moiety of 2-(2'-pyridyl)benzothiazole, while, in the second isomer, the imine nitrogen of 2-(2'-pyridyl)benzothiazole. The complexes are stable, neutral, and lipophilic. Complete (1)H and (13)C NMR assignments are reported for all complexes. The synthetic reaction was also successfully transferred at the technetium-99m tracer level by ligand exchange reaction using (99m)Tc-glucoheptonate as precursor in the presence of 2-(2'-pyridyl)benzothiazole and 4-CH(3)C(6)H(4)SH. The structure of the technetium-99m complex was established by high-performance liquid chromatographic comparison with the analogous oxotechnetium and oxorhenium complexes. The 2-(2'-pyridyl)benzothiazole ligand serves as a preliminary model for 2-(4-aminophenyl)benzothiazole, which possesses interesting properties for the development of technetium and rhenium radiopharmaceuticals for tumor imaging and/or radiotherapy as well as in vivo diagnosis of Alzheimer's disease.
The association of a supernova with GRB030329 strongly supports the 'collapsar' model of gamma-ray bursts, where a relativistic jet forms after the progenitor star collapses. Such jets cannot be spatially resolved because gamma-ray bursts lie at cosmological distances; their existence is instead inferred from 'breaks' in the light curves of the afterglows, and from the theoretical desire to reduce the estimated total energy of the burst by proposing that most of it comes out in narrow beams. Temporal evolution of the polarization of the afterglows may provide independent evidence for the jet structure of the relativistic outflow. Small-level polarization ( approximately 1-3 per cent) has been reported for a few bursts, but its temporal evolution has yet to be established. Here we report polarimetric observations of the afterglow of GRB030329. We establish the polarization light curve, detect sustained polarization at the per cent level, and find significant variability. The data imply that the afterglow magnetic field has a small coherence length and is mostly random, probably generated by turbulence, in contrast with the picture arising from the high polarization detected in the prompt gamma-rays from GRB021206 (ref. 18).
BACKGROUND: Sirolimus, a promising new immunosuppressive drug for organ transplantation, is currently associated with side effects, such as thrombocytopenia and hyperlipidemia. METHODS: Eight renal transplant recipients, who developed unexplained interstitial pneumonitis during sirolimus therapy, were extensively re-screened for all causes of pneumonitis. RESULTS: Interstitial pneumonitis was constantly characterized by bilateral interstitial infiltrates on chest x-rays and lung computed tomography scans, with marked general symptoms in all patients but one. Bronchoalveolar lavage (BAL) disclosed lymphocytic alveolitis (mainly of the CD4 type) in seven patients and alveolar hemorrhage in one. Transbronchial lung biopsies, performed in two patients, showed bronchiolitis obliterans with organizing pneumonia combined with lymphocytic interstitial pneumonitis. Pulmonary infections were ruled out by specific stainings and cultures of BAL, bronchial aspirates, and blood cultures. After the elimination of all possible causes, sirolimus-induced pneumonitis was considered probable. Discontinuation of sirolimus in seven cases and dose reduction in the remaining case dramatically improved clinical and radiological status within a few weeks and led to complete resolution within 3 months. CONCLUSIONS: Sirolimus is very probably responsible for interstitial pneumonitis on the following grounds: (a) occurrence of pneumonitis during sirolimus therapy; (b) absence of any other causes; and (c) resolution within 3 months of sirolimus discontinuation or dose reduction. Sirolimus should now be added to the list of possible causes of pulmonary complications after renal transplantation. Discontinuation or dose reduction of sirolimus led to complete and lasting resolution of symptoms.
Chorismate mutase catalyzes the first committed step in the biosynthesis of the aromatic amino acids phenylalanine and tyrosine in bacteria, fungi and higher plants. The recent re-annotation of the Mycobacterium tuberculosis genome has revealed the presence of a duplicate set of genes coding for chorismate mutase. The mycobacterial gene Rv1885c bears <20% sequence homology to other bacterial chorismate mutases, thus serving as a potential target for the development of inhibitors specific to the pathogen. The M. tuberculosis chorismate mutase was crystallized in space group C2 and the crystals diffracted to a resolution of 2.2 A. Matthews coefficient and self-rotation function calculations revealed the presence of two monomers in the asymmetric unit.
PURPOSE: To determine whether the oscillatory changes of radio-sensitivity which occur within fractions of a second to a few minutes following flash irradiation correlate with an altered incidence of apoptosis, DNA strand breaks or lipid-coupled signalling. MATERIALS AND METHODS: Human tumor cells (SQ-20B, LoVo) or Chinese hamster V79 fibroblasts were exposed to split-dose, pulse irradiation with 3.5 MeV electrons at high dose-rate (12 or 120 Gy x s(-1)) and the effects assessed by clonogenic assays, analysis of DNA cleavage and microscopic observation. RESULTS: The processes underlying oscillatory radiation response were saturable, but did not correlate with an increased incidence of DNA single- or double-strand breaks or apoptosis. N-acetylcysteine and inhibitors of lipid-derived signalling also failed to alter oscillatory response. However, this response did correlate with phenotypic alterations evoking mitotic or delayed cell death. Furthermore, high dose-rate irradiation provided a lower level of instability than protracted gamma-ray irradiation. CONCLUSIONS: It is proposed that the early steps of DNA damage recognition and repair following priming radiation exposure bring about rapid, synchronous remodeling of chromatin, evoking enhanced chromosome damage upon re-irradiation.
The site occupancies of the transition metals Cr, Fe, and Re dissolved in NiAl of stoichiometric composition have been determined by atomic layer resolved atom probe field-ion microscopy (APFIM). The investigations were supported by X-ray diffraction studies to evaluate the lattice parameters. These are influenced by atomic size effects and constitutional lattice defects like Ni antistructure atoms in the Al sublattice and vacancies in the Ni sublattice. The APFIM results were compared with ALCHEMI data and calculated site preference energies published in the literature. Chromium additions to stoichiometric NiAl with 0.8 at% in solid solution exhibit a strong preference for Al sites. The lattice parameter of NiAl(Cr) solid solution is decreased. Iron atoms dissolved in higher concentrations of 5 at % in NiAl are almost equally distributed within both sublattices. They are possessing a weak preference for Al sites, which causes a lattice expansion of NiAl(Fe) solid solution. ALCHEMI results and site preference energy data show a strong site preference of Cr atoms for the Al sublattice. In contrast, iron atoms exhibit a weak site preference for Ni sites depending upon the stoichiometry of the NiAl host lattice. Re solutes in low concentrations of about 0.2 at % in NiAl possess a strong site preference for the Ni sublattice. The increase of the lattice parameter of NiAl(Re) is due to the pronounced size effect of Re atoms. For these species no ALCHEMI and site preference energy data are available in the literature.
Flash-cooled crystals of the I222 form of concanavalin A undergo a sharp non-destructive non-reversible phase transition upon warming to between 160 and 165 K, characterized by an anomalous increase in unit-cell volume. The expansion is anisotropic and primarily affects the b and c axes. Three sets of 1.7 A X-ray diffraction data were collected from one crystal: immediately after flash-cooling (130 K), after slow warming to 170 K and after re-cooling to 130 K. Measurable changes in reflection width after the transition were apparent. Each data set was collected under very similar conditions (aside from temperature). Structures refined against each data set using a powerful phase-bias reduction algorithm indicate negligible rearrangement of the protein molecule and its first hydration shell. Further away from the protein surface, on the edge of the fully disordered solvent regions, a small number of more dramatic changes were apparent. Little is known about the behaviour of water confined within dimensionally restricted spaces, but solvent cavities and channels in protein crystals provide a rich source of reproducible nanoscale water assemblies. This paper presents information on the behaviour of water confined within protein cavities in relation to the physics of protein crystal annealing.
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