A technique for computing dose volume histograms for structure combinations

Graphical displays of three-dimensional dose distribution data are often too complex to be easily assimilated and interpreted for the evaluation of radiation treatment plans. Histograms showing dose versus volume are convenient and useful tools for summarizing dose distribution information throughout the entire volume of a given anatomic structure. They can quickly highlight characteristics such as dose uniformity and hot and cold spots, and can be used to produce statistics including tumor control and normal tissue complication probabilities. To obtain a dose volume histogram for a given structure, it may be necessary to examine its spatial relationships with neighboring structures. They may overlap, be completely disjoint, or one may be contained within another. To resolve potential ambiguities, a procedure has been developed that assigns hierarchies to anatomical structures for the purpose of histogram calculation. The hierarchy assigned to each structure is used to determine the structure within which a given dose matrix point is considered to lie. In this manner, regions of structure intersection are assigned to one object or another, and dose volume histograms can be calculated for each structure separately. From this framework, addition and subtraction of histograms can also be performed. Details of the algorithm are presented along with an example using patient data.     

Anti-subnucleosome reactivities in systemic lupus erythematosus (SLE) patients and their first-degree relatives

Antibodies specific for dsDNA appear to have different genetic origins and pathogenic consequences, compared with histone/dsDNA-specific antibodies, in a recently described murine model. The purpose of this study was to examine if this is also true in human lupus. Sera from 40 SLE families (comprising 40 probands and 153 first-degree relatives), and 45 normal adult controls were assayed for the levels of anti-dsDNA, anti-H1/dsDNA, anti-H2A/H2B/dsDNA, and anti-H3/H4/dsDNA autoantibodies by ELISA. Both the probands and the first-degree relatives exhibited significantly increased levels of antinuclear antibodies (ANA) targeting the different subnucleosomal epitopes. Importantly, probands with anti-dsDNA antibodies had a significantly higher incidence of renal disease compared with those with just anti-H2A/H2B/dsDNA antibodies, in resonance with murine studies. The frequency of anti-dsDNA and anti-H2A/H2B/DNA ANA among the first-degree relatives was 11.8% and 18.3%, respectively. Surprisingly, whereas probands with anti-dsDNA ANA had families with several seropositive members, first-degree relatives of patients with anti-H2A/H2B/DNA ANA (but not anti-dsDNA ANA) were uniformly ANA-free. These findings suggest that anti-dsDNA ANA in lupus may not only have worse disease associations, they may also have very different genetic origins, compared with anti-H2A/H2B/DNA (or anti-nucleosome) ANA.     

Microdissection genotyping of archival fixative treated tissue for Gaucher disease

The genetic diagnosis of Gaucher disease by molecular methods is complicated by the existence of a highly homologous transcribed pseudogene (96% identity) that is found in close proximity to the true gene on chromosome 1q21. In addition, the pseudogene sequence can mimic disease-causing mutations in the true gene. Selective polymerase chain reaction (PCR) amplification of the true gene can be accomplished in extracted DNA from fresh-frozen samples by designing oligonucleotide primers to hybridize to defined regions that are not present in the pseudogene. This standard molecular approach, which entails amplification of relatively long segments of intact DNA, is not feasible in archival, paraffin-embedded, solid-tissue specimens in which the negative effects of chemical fixation result in DNA strand scission and breakdown of nucleic acid. A novel approach, specifically created for use with archival, fixative-treated tissue specimens, was developed for detection and characterization of common mutations of Gaucher disease. Three separate robust PCR reactions were formulated, 2 for selective amplification of portions of only the true gene exons 2 and 9, with a third reaction targeting exon 10, wherein both the true and pseudogene were coamplified. In the latter, DNA sequencing was used to determine the presence of true and pseudogene allele content in addition to identification of base sequence alterations. This method, requiring a single, 4-microm-thick histologic section, was successfully applied to archival paraffin block tissue specimens that had been in storage for up to 75 years. It was capable of accurately genotyping common Gaucher disease mutations as well as discovering a novel mutation and genetic polymorphism. We recommend our approach when only fixative-treated tis sue is available for molecular genotyping.     

Comparison of EGS4 and MCNP4b Monte Carlo codes for generation of photon phase space distributions for a Varian 2100C

Monte Carlo based dose calculation algorithms require input data or distributions describing the phase space of the photons and secondary electrons prior to the patient-dependent part of the beam-line geometry. The accuracy of the treatment plan itself is dependent upon the accuracy of this distribution. The purpose of this work is to compare phase space distributions (PSDs) generated with the MCNP4b and EGS4 Monte Carlo codes for the 6 and 18 MV photon modes of the Varian 2100C and determine if differences relevant to Monte Carlo based patient dose calculations exist. Calculations are performed with the same energy transport cut-off values. At 6 MV, target bremsstrahlung production for MCNP4b is approximately 10% less than for EGS4, while at 18 MV the difference is about 5%. These differences are due to the different bremsstrahlung cross sections used in the codes. Although the absolute bremsstrahlung production differs between MCNP4b and EGS4, normalized PSDs agree at the end of the patient-independent geometry (prior to the jaws), resulting in similar dose distributions in a homogeneous phantom. EGS4 and MCNP4b are equally suitable for the generation of PSDs for Monte Carlo based dose computations.     

Recurrent diffuse lipomatosis of the neck--a case report

Diffuse lipomatosis is a rare disorder of adipose tissue occurring in young people . It has a predilection for trunk and proximal extremities where it presents as poorly circumscribed overgrowth of fatty tissue. Definite diagnosis is established by histological examination of tumor. Though it attains extensive size and has a high tendency to recur, the clinical course is benign.     

Damaged chromatin does not prevent the exit from metaphase I in fused mouse oocytes

The presence of checkpoint mechanisms which are able to recognize damaged chromatin and thereafter to prevent exit from metaphase I has been investigated in giant mouse oocytes produced by fusion of a normal metaphase I oocyte with an equivalent oocyte with damaged chromatin. The presence of damaged chromatin did not prevent the onset of anaphase I in both sets of chromatin in the fused cells. Interestingly, fused or unfused cells containing only damaged chromatin failed to enter anaphase and persisted instead in a metaphase-like state. These results demonstrate the fragility of checkpoint controls in mammalian female germ cells.