Search PubMedSearch

Biomedical subjects

M Wallace

Publications and source records attributed to M Wallace.

At least 19 recordsLinked to original sources

Treatment planning for adenocarcinoma of the rectum and sigmoid: a patterns of care study. PCS Committee.

PURPOSE: To conduct a study of the process of treatment planning and treatment of adenocarcinoma of the rectum and sigmoid in the United States, and to compare survey results to consensus guidelines. METHODS AND MATERIALS: A consensus committee developed guidelines for the radiotherapeutic management of adenocarcinoma of the rectum and sigmoid, and also developed a survey form that was used to gather data to evaluate the practice patterns for patients treated in 1989 and 1990 against the consensus guidelines. Seventy-three facilities were randomly selected for site visits from the 1321 radiation therapy facilities in the US: 21 academic, 26 hospital based, and 26 free standing. During the site visits, the radiotherapy records were examined by the surveyor physicist and radiation oncologist to extract and record the required data. Data collected included items related to treatment specific parameters, including treatment planning considerations. Analyses included stratification as to the types of institutions, academic, hospital based, or free standing. RESULTS: For many treatment parameters there are discrepancies between the patterns of practice determined by the surveys and the consensus guidelines for radiotherapy treatment of adenocarcinoma of the rectum and sigmoid. Significant differences in practice among the stratified institution types were found in only a few parameters.

Adenocarcinoma

Treatment planning for primary breast cancer: a patterns of care study.

PURPOSE: The 1989 Patterns of Care Study included treatment planning for early breast cancer. A Consensus Committee of radiation physicists and oncologists determined current guidelines and developed questionnaires to determine treatment planning and delivery processes used by the participating institutions (e.g., use of portal films). This article presents and analyzes the results of that survey. METHODS AND MATERIALS: The survey included 449 respondents, distributed as follows: 136 (30%) from Strata I (academic facilities); 169 (38%) from Strata II (hospital based facilities); and 144 (32%) from Strata III (freestanding facilities). The treatment planning procedures surveyed included: whether individualized tissue compensators are used, whether inhomogeneity corrections are used in dose calculations, the use of computerized tomography, whether isodose distributions for external beam tangents and interstitial implants are generated, the use of lymphoscintigraphy, immobilization devices, simulations, portal films, etc. RESULTS: The survey results demonstrated that out of 305 patients from Strata I and II institutions, 237 (78%) had simulated tangential fields. Consistent with this finding is that 76% of patients from Strata I and II institutions were immobilized, while only 51% of Strata III patients were. Moreover, only 18 out of the 449 (4%) of cases did not have any type of external beam dose distribution calculated--presumably, in these cases missing tissue compensation would be unlikely. On the other hand, 41% of the Strata II, 27% of Strata III, but only 19% of Strata I (p < 0.0002) cases received CT. Surprisingly, 19% of the Strata I, 35% of the Strata II, and 25% of the Strata III (p = 0.0011) patients received lymphoscintigraphy, perhaps reflecting the use of wide tangents to encompass the internal mammary nodes in these patients. In terms of optimizing treatments, 74% of Strata I, 70% of Strata II, and 78% of Strata III patients had wedges used on both tangential fields, although in 5, 12, and 14%, respectively, no beam modification of any sort was used. Furthermore, it should be noted that in 7% of the Strata I, 23% of Strata II, and 37% of Strata III cases there was no attempt to reduce the divergence of the tangential fields into the lung. On the other hand, if one considers the 135 (of 449) patients where matching of the tangential and supraclavicular fields was applicable, 41% of Strata I, 22% of Strata II and 46% of Strata III patients had those fields matched in a vertical plane, which would involve sophisticated alignment procedures. Quality control of treatment delivery was high: 97% of all surveyed received portal films at least once. The use of thermoluminescent dosimetry (TLD) to measure the dose to the contralateral breast was of little interest: only 4 of the 305 Strata I and II patients received in vivo measurements. CONCLUSIONS: This national survey has established the patterns of treatment planning for early breast cancer. It shows a generally consistent approach-although a number of statistically significant variations have been identified.

Breast Neoplasms

A conditional lethal mutant in the fission yeast 26 S protease subunit mts3+ is defective in metaphase to anaphase transition.

We have isolated a conditional lethal mutant mts3 in the fission yeast Schizosaccharomyces pombe which at the permissive temperature is resistant to the mitotic poison MBC and at the restrictive temperature is defective in metaphase to anaphase transition. The predicted amino acid sequence of mts3+ is 36% identical with the budding yeast gene NIN1. NIN1 cloned into a fission yeast expression vector can rescue both mts3 temperature-sensitive and null alleles demonstrating that NIN1 is the budding yeast homologue of the fission yeast mts3+ gene. The phenotype of the mts3 null is identical with the mts3 ts mutant demonstrating that the phenotype of the mts3 ts mutant is due to loss of mts3+ function. The deduced amino acid sequences of both mts3+ and NIN1 show homology to peptide sequences obtained from subunit 14 of the 26 S protease purified from bovine or human cells.

Amino Acid Sequence

The genetic basis of a new partial D antigen: DDBT.

The Rh system, the most polymorphic system on red cells, is genetically controlled by two different but highly homologous genes on chromosome 1. The RHCE gene encodes different RhCcEe polypeptides and the RHD gene encodes D antigens. It is well established that in D negative individuals the RHD gene is either absent or grossly deleted. The D antigen comprises at least nine serologically defined D epitopes. The D antigen can be divided into different partial D categories, reflecting a different pattern of specific D epitopes. In this study a newly defined partial D antigen, DDBT, was studied. D epitope mapping revealed the presence of D epitopes 6/7 and 8 and the absence of the other D epitopes. The molecular basis of this phenotype was studied by Southern blotting, by RHD typing using the polymerase chain reaction (RHD-PCR) and by sequence analysis of Rh transcripts. The DBT phenotype appeared to be encoded by a hybrid RHD gene, in which exons 5, 6 and 7 (and possibly the identical exon 8) were replaced by the corresponding exons of the RHCE gene. From this study it may be concluded that D epitopes 1, 2, 3, 4, 5 and 9 are dependent on the presence of RHD exons 5, 6, and 7.

Base Sequence

Denaturing gradient gel electrophoresis: a novel method for determining Rh phenotype from genomic DNA.

Denaturing gradient gel electrophoresis (DGGE) was carried out on PCR products amplified from exons 2 and 5 of RHD and RHCE. Exon 2 of RHD and exon 2 of the C allele of RHCE have an identical sequence, which differs from that of the c allele of RHCE. One band representing D and/or C, and another representing c, could be distinguished by DGGE of exon 2 amplifications of genomic DNA from individuals with the appropriate Rh phenotype. C and c could only be distinguished in D-negative samples. Exon 5 of RHD and exon 5 of the E and e alleles of RHCE all have different nucleotide sequences. Bands representing D, E and e could be distinguished following DGGE of the products of exon 5 amplification of genomic DNA from individuals with red cells of the appropriate Rh phenotype. In samples from individuals with VS+ red cells (V+ or V-) there was a shift of the band representing e. Sequencing demonstrated that VS is associated with a RHCE e sequence with a single base change predicting a Leu245 --> Val substitution in the Rh polypeptide. This substitution may be responsible for the VS and e5 antigens.

Base Sequence

Gamma delta T lymphocyte responses to HIV.

Natural immunity may be involved in controlling viral spread in hosts infected with HIV. A panel of gamma delta T cell receptor-positive lymphocyte clones was isolated from the peripheral blood of healthy HIV- donors and tested for anti-HIV cytotoxic responses. Twelve of 30 (40%) V gamma 9+/V delta 2+ T cell clones, but none of seven V delta 1+ T cell clones, displayed lytic activity against HIV-infected cells. The V gamma 9+/V delta 2+ clones cytotoxic for HIV-infected cells also lysed Daudi cells. However, not all V gamma 9+/V delta 2+ clones which lysed Daudi targets had the capacity to lyse HIV-infected cells. Some of the gamma delta T cell clones were also investigated for potential proliferative responses to HIV-infected cells. One V gamma 9+/V delta 2+ T cell clone (ME8-7) and one V delta 1+ T cell clone (ME18-2) demonstrated proliferative responses towards HIV-infected cells. Another V gamma 9+/V delta 2+ clone (VM39) proliferated in response to cell-free HIV. Taken together, these results provide direct evidence of anti-HIV gamma delta T cell responses in healthy, HIV- persons.

Clone Cells

The Rh antigen D: partial D antigens and associated low incidence antigens.

The expression of the Rh antigen D varies quantitatively and qualitatively (partial D); published information and 15 years' work studying D variants are discussed in this review. D epitopes correspond to the reaction patterns of monoclonal anti-D with partial D antigens. Partial D antigens can be reported in terms of their D epitopes but the epitope profile of cells with a quantitative variant of D (weak D) is difficult to determine reliably by haemagglutination tests. Nine partial D antigens, categories II-VII, DFR and two not previously reported, are identified by their epitope profiles and by association with low incidence antigens. Monoclonal anti-D recognize 16 D epitopes and more epitopes are anticipated. The specificities of polyclonal anti-D made by people with partial D antigens are considered in terms of possible D epitope specificities: recognized epitope specificities, or combination thereof, were not able to account for all observed reaction patterns of anti-D made by immunized individuals with partial D phenotypes. An attempt is made to understand partial D antigens and their associated low incidence antigens in terms of the molecular genetic information available.

Antibodies, Monoclonal

The D antigen characteristic of RoHar is a partial D antigen.

The results of testing RoHarr cells with panels of monoclonal anti-D suggest that the D antigen (referred to as DHar) encoded by the haplotype (D)c(e) Rh33 is a partial D antigen. IgM monoclonal anti-D are more efficient than IgG monoclonal anti-D in detecting DHar.DHar expresses some but not all of both epD5 and epD6/7 and appears to lack epD1-epD4, epD8 and epD9.

Epitopes

Expression of LAR-PTP2 in rat lung is confined to proliferating epithelia lining the airways and air sacs.

The LAR family tyrosine phosphatase LAR-PTP2B (RPTP sigma) was previously shown to be expressed in the central and peripheral nervous system. Here we show that LAR-PTP2, the larger alternatively spliced form of the gene, is expressed in proliferating undifferentiated lung epithelia in a developmentally regulated manner: Using in situ hybridization and parallel immunostaining with proliferating cell nuclear antigen to detect proliferating cells, we demonstrate that LAR-PTP2 is expressed exclusively in the undifferentiated epithelial cell layer lining the bronchi, bronchioles, and air sacs in late fetal development and in the neonatal lung. These cells correspond to Clara and fetal alveolar type II cells, as determined by parallel immunostaining with antibodies to surfactant proteins A and B. LAR-PTP2 expression declined progressively with postnatal development, and by adult stage there was no detectable expression in the airways or in the distal (type I and II) mature nonproliferating alveolar epithelial cells. These results suggest that LAR-PTP2 may be involved in the regulation of epithelial cell proliferation/differentiation during lung development.

Aging

Patterns of care survey results: treatment planning for carcinoma of the prostate.

PURPOSE: Treatment planning has been defined differently at various institutions to encompass tasks ranging from the initial evaluation of the patient to the delivery of the treatment as well as a more narrow view, focused primarily on isodose computation. To evaluate the impact of much of the new treatment-planning technology that has become available, it is necessary to define and develop recommended guidelines for the treatment-planning process. METHODS AND MATERIALS: The 1989 Patterns of Care Study (PCS) included questionnaires to access treatment planning practices currently in use for the entire census of oncology facilities in the United States. These questionnaires were developed by a consensus committee consisting of both physicists and radiation oncologists whose charge was to formulate a description of current treatment-planning practices. The description was based on the committee's experience and knowledge of the treatment-planning process considered to be widely available and in general use, as well as a review of the literature. From the description of the treatment-planning process, a set of guidelines for treatment planning was developed for prostate as well as each of the other disease sites included in the PCS. Data from the study defined the general structure, methodology, process, and tools used by each institution involved in the Patterns of Care Survey Study. National averages for all of the variables were calculated with weighted averages, with the weights reflecting the sample design and number of patients in the different types of facilities. The data were stratified according to academic, hospital, or free-standing facility and were compared with the Consensus Guidelines for Treatment Planning of the Prostate. DISCUSSION: Based on the consensus statement, the treatment-planning process was separated into the following categories: (a) Treatment-Planning Workup, (b) Treatment Plan Implementation, (c) Treatment Delivery, (d) Treatment Verification, and (e) Quality Assurance. The results from the survey were summarized for each category and compared with the consensus statement. CONCLUSIONS: Although there is an increasing trend toward using computed tomography (CT) information to acquire individualized patient data, volume definition and localization are often completed in the simulator without the direct use of CT information (47%). As more sophisticated beam arrangements and blocking are used, one needs to look at the full three-dimensional (3D) volume to ensure that there are no marginal misses due to blocking and beam arrangement. Improved and more widespread use of immobilization devices is also required with conformal treatments and reduced margins. The results of the survey helped to identify and establish the standard of practice for treatment planning of the prostate as well as to provide documentation for better defining a complete description of the treatment planning process. Well-documented guidelines will provide more consistent treatment of patients, which should have an impact on outcome.

Clinical Protocols

Treatment planning for Hodgkin's disease: a patterns of care study.

PURPOSE: To conduct a survey of the process of treatment planning for the radiation treatment of Hodgkin's Disease in the United States, and to compare survey results with consensus guidelines as determined by recognized experts. METHODS AND MATERIALS: A consensus committee developed guidelines for the radiotherapeutic management of Hodgkin's Disease. A series of survey forms were designed to evaluate the standards of practice and compare these with the consensus guidelines. A total of 61 facilities divided evenly into the strata of academic, hospital based, and free standing had eligible Hodgkin's Disease cases. There were 275 eligible cases of Hodgkin's Disease evaluated. Data collected from the radiation oncology records included treatment-specific parameters such as energy, dose, blocking, and calculations, as well as treatment planning practices. Statistical analysis was performed on each data element and for all institution strata. RESULTS: For a number of treatment parameters, there were some discrepancies note between the current United States practice and the consensus guidelines. Some significant differences were found in practice between the stratified institution types. A representative sample of results are: the majority of Hodgkin's Disease patients are treated with x-ray energies in the recommended range, between 4 and 10 MV. Standard mantle (for upper extended field treatment) and modified spade (for lower extended field treatments) are the fields of choice for all types of facilities. The consensus guidelines recommended that dose calculations at multiple points be obtained; however, 15% of patients in the survey received only a single point calculation. Current irregular field dosimetry calculation software does not take account of inhomogeneities. Thirty percent of Hodgkin's Disease patients do not receive a gap calculation for the abutment of upper and lower extended fields. In 70% of treatment fields, no compensation is used. Very few patients receive any kind of in vivo dosimetry check. CONCLUSION: The survey served to verify that, in general, Hodgkin's Disease treatment planning at all strata of institution has kept pace with recommended practice as delineated in current literature and texts. Small pockets of practice still need improvement in technique and equipment. Changes in practice were identified that can contribute to improved dose uniformity and accuracy.

Consensus Statements as Topic

Treatment planning structure and process in the United States: a "Patterns of Care" study.

PURPOSE: To conduct a study of the structure and process of treatment planning in the United States. METHODS AND MATERIALS: A Patterns of Care treatment planning consensus committee developed a survey form that was used to gather data for 106 items relating to the structure and process of treatment planning. These questions were general in nature and not specific to any particular disease site. Seventy-three facilities were randomly selected for site visits from the 1321 radiation therapy facilities in the United States: 21 academic, 26 hospital, and 26 free-standing. During the site visit the facility physicist, assisted by the site-visit physicist, completed the form. RESULTS: Twenty-nine percent of facilities have cobalt-60 machines; 25% have 4 MV linacs; 75% have photon energies in the range of 5-8 MV; and less than 10% have energies greater than 20 MV. Academic facilities led hospital and free-standing facilities by about 30 percentage points in the availability of all electron energies (88 vs. 58%, approximately, in the range 4-13 MeV and scaling downward to about 60 vs. 30% at the highest energies). The national averages for the availability of Cs-137, Ir-192, and I-125 were 87, 73, and 44%, respectively. Computerized tomography (CT) scanning is not available or not used in 15% of hospital and free-standing facilities. Ninety-six percent of facilities have treatment planning computers; at 10% of facilities physicians do not participate in treatment planning. The estimated national averages of facilities having formal quality assurance (QA) programs for treatment planning systems, simulators, film processors, and blocking systems are 44, 79, 62, and 55%, respectively. Sixty-three percent of facilities obtain independent machine calibrations. CONCLUSION: This is the first patterns of treatment planning study carried out in the United States and the results reported here will establish a baseline for future studies. The present study has identified some elements that were unexpected, such as the percentage of facilities lacking formal QA programs for treatment planning systems; however, it has not established any impact of such findings. It is recommended that future studies include the availability of new technologies such as multileaf collimation, dynamic wedges, digital portal imaging, and CT simulation. With the increasing nationwide concern with the cost of health care, we must continue to monitor the implementation, use, and impact on treatment outcome of new and expensive technologies.

Brachytherapy

Gamma/delta T lymphocytes in viral infections.

T lymphocyte progenitors differentiate into two distinct T cell lineages. Although the alpha beta and gamma delta T cell lineages resemble each other phenotypically and functionally, there are some striking differences. Some gamma delta T cells recognize, similarly to alpha beta T cells, peptides presented by major histocompatibility complex (MHC) proteins or MHC-like molecules. However, there are gamma delta T cells that recognize MHC molecules in a fundamentally different manner in comparison with alpha beta T cells. Also in contrast recognizing nonpeptide antigens. Most responses of gamma delta T cells appear to be directed against microbial pathogenic agents including bacteria, parasites, and viruses. In particular, the potent cytotoxic responses of gamma delta T cells against cells infected with, for example, herpesviruses or lentiviruses may be essential for the overall antiviral defense of vertebrates. The analysis of antiviral immunosurveillance by gamma delta T cells is crucial for understanding the unique biological role of this lymphocyte subset.

Animals

Scattered radiation in a neonatal surgical unit.

We studied the doses of "scattered" received by neonates in a Neonatal Surgical Unit by placing thermoluminescent dosemeters in various positions expect the direct beam. Doses of "scattered" radiation received by neonates as a results of exposure of their neighbours to X-ray examinations were found to be negligible. Sick neonates need not be moved from their neighbours undergoing exposure to X-rays.

Humans

Touch-evoked agitation produced by spinally administered phospholipid emulsion and liposomes in rats. Structure-activity relation.

BACKGROUND: Phospholipid-based liposomes can alter the kinetics of spinally administered agents. We have observed that spinal delivery of these preparations results in an unexpected touch-evoked agitation, a state in which light touch evokes vocalization by the rat. In the current study we characterized this agitated state induced by various liposome preparations. METHODS: Rats prepared with lumbar intrathecal catheters received a variety of phospholipids delivered spinally as emulsions or as liposomes. Before and after injection, the animal's hot-plate latency (52.5 degrees C surface), spontaneous mobility, and spontaneous and evoked pain behavior were assessed. RESULTS: Spinal delivery of L-alpha-phosphatidylcholine of egg yolk (L-EPC) and the phospholipase hydrolysis product (lyso-L-alpha-phosphatidylcholine [lyso-L-EPC]) produced dose-dependent touch-evoked agitation; the order of potency and rapidity of onset was lyso-L-EPC > L-EPC, with no difference in activity whether administered as an emulsion or as a liposome preparation. Examination of the activity of a series of pure phospholipids revealed the ordering of touch-evoked agitation potency (where PC = phosphatidylcholine) to be L-monopalmitoyl-PC (lyso product of L-dipalmitoyl-PC) > L-dipalmitoyl-PC > L-distearoyl-PC, L-dioleoyl-PC >> L-dilauroyl-PC > L-dimyristoyl-PC; D-dipalmitoyl-PC = 0. The effect of unsaturation on touch-evoked agitation cannot be predicted because dioleoyl-PC and dioleoyl phosphatidylglycerol produced touch-evoked agitation but dipalmitoleoyl-PC did not. Substitution of glycerol for choline as the head group had no influence on touch-evoked agitation. Spinal treatment with an inhibitor of phospholipase (mepacrine) or a cyclooxygenase (ketorolac) blocked the touch-evoked agitation of L-EPC but not that of lyso-L-EPC. CONCLUSIONS: These results emphasize that certain L-isomeric phospholipids with their gel-transition temperatures near body temperature can produce prominent touch-evoked agitation after spinal delivery, an effect likely mediated by a phospholipase hydrolysis product. This touch-evoked agitation, which is consistent with neurotoxicity reported in the early literature on lysophospholipids, suggests that the choice of lipids for the formulation of liposomes intended for spinal drug delivery should be carefully considered.

Animals