人体液中喷布洛尔及其代谢物的GC/MS分析

用气相色谱一质谱联用(GC-MSD)系统分析方法检出了人尿中喷布洛尔的6个羟化代谢物,用Scp-Pak柱提取的方法检出了人血浆中的原型药物。并从分子结构上对此药物的代谢途径进行了研究。尿中提取和血中提取的回收率分别为90.83.%和85.88%,Gc-MSD的检测限为5pg。本方法适用于运动员兴奋剂的系统检查。     

Effects of finite angular steps and extent of profile data on the calculation of rotational x-ray dose distributions

Computer algorithms for rotational therapy beams, in most cases, perform dose calculations by summing stored fixed beam data at finite angular steps. Such an algorithm, based on the Bentley beam model, was evaluated by comparing calculations with measured data for an 18-MV x-ray beam. Measurements were made in a specially constructed cylindrical water phantom of 15-cm radius using a 0.1-cm3 ionization chamber for an arc of 180 degrees and for a field size of 7.2 X 7.2 cm2 at 100-cm source-axis distance. This study revealed that the Bentley beam model, with fixed beams summed every 10 degrees, predicts the dose in the treatment volume, centered about the isocenter, with an accuracy of approximately 2%. However, dose at depths between the phantom surface and the treatment volume could be underestimated by as much as 10% (3% of isocenter). This was shown to be partially due to the truncated tails of the off-axis profiles in the Bentley model, which extend only 8 mm outside the edge of the radiation field, and the large angular increment of integration (10 degrees). Using beam profiles extending to 4 cm outside the edge of the radiation field and angular steps of 5 degrees or less for summation of fixed beams reduced errors to less than 5%. Therefore, extended beam profiles and smaller angular steps for summing fixed beams are recommended for photon rotation calculation when increased accuracy is required.     

Electron bolus design for radiotherapy treatment planning: bolus design algorithms.

Computer algorithms to design bolus for electron beam radiotherapy treatment planning were investigated. Because of the significant electron multiple scatter, there is no unique solution to the problem of bolus design. However, using a sequence of operators, a bolus can be designed that attempts to meet three important criteria: adequate dose delivery to the target volume, avoidance of critical structures, and dose homogeneity within the target volume. Initial calculation of bolus shape was based upon creation operators forcing either the physical or the effective depths of the distal surface of the target volume to a specified value. Modification operators were then applied to the bolus to alter the shape to better meet the design criteria. Because the operators each address a single dosimetric issue, they can often adversely affect some other attribute of the dose distribution. In addition, an extension operator is used to design the bolus thickness outside the target volume. Application of these operators is therefore carried out in certain sequences and each may be used more than once in the design of a particular bolus. The effects of these operators on both the bolus and the resulting dose distribution are investigated for test geometries and patient geometries in the nose, parotid, and paraspinal region.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Presence of the AZF region in a female with an idic(Y)(q11)

In a child with some features of Turner's syndrome, gonosomal mosaicism with an isodicentric nonfluorescent (idic)Y chromosome was detected (mos 45,X/47,X,idic(Y)(q11),idic(Y)(11)/46,X,idic(Y)(q11)). Histopathological examination showed streak gonads with some evidence of ovarian stroma and no sign of gonadoblastoma. Polymerase chain reaction (PCR) analysis in blood lymphocytes and gonadal tissues using primers of seven loci along the Y chromosome, including the sex determined region (SRY), azoospermia factor region (AZF) and the deleted in azoospermia ( DAZ ) gene was positive for all loci tested, confirming the isodicentric character of the Y chromosome and indicating the presence of the AZF region. It is remarkable that the existence of spermatogenesis controlling genes does not play an important role in gonadal development and differentiation in a phenotypic female with some Turner stigmata. The data presented here are briefly discussed with previously-described patients.     

Dose properties of x-ray beams produced by laser-wakefield-accelerated electrons

Given that laser wakefield acceleration (LWFA) has been demonstrated experimentally to accelerate electron beams to energies beyond 25 MeV, it is reasonable to assess the ability of existing LWFA technology to compete with conventional radiofrequency linear accelerators in producing electron and x-ray beams for external-beam radiotherapy. We present calculations of the dose distributions (off-axis dose profiles and central-axis depth dose) and dose rates of x-ray beams that can be produced from electron beams that are generated using state-of-the-art LWFA. Subsets of an LWFA electron energy distribution were propagated through the treatment head elements (presuming an existing design for an x-ray production target and flattening filter) implemented within the EGSnrc Monte Carlo code. Three x-ray energy configurations (6 MV, 10 MV and 18 MV) were studied, and the energy width deltaE of the electron-beam subsets varied from 0.5 MeV to 12.5 MeV. As deltaE increased from 0.5 MeV to 4.5 MeV, we found that the off-axis and central-axis dose profiles for x-rays were minimally affected (to within about 3%), a result slightly different from prior calculations of electron beams broadened by scattering foils. For deltaE of the order of 12 MeV, the effect on the off-axis profile was of the order of 10%, but the central-axis depth dose was affected by less than 2% for depths in excess of about 5 cm beyond d(max). Although increasing deltaE beyond 6.5 MeV increased the dose rate at d(max) by more than 10 times, the absolute dose rates were about 3 orders of magnitude below those observed for LWFA-based electron beams at comparable energies. For a practical LWFA-based x-ray device, the beam current must be increased by about 4-5 orders of magnitude.     

RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection