Inverse Planning – a Comparative Intersystem and Interpatient Constraint Study

PURPOSE: To compare commercial treatment-planning systems (TPS) for inverse planning (IP) and to assess constraint variations for specific IMRT indications. MATERIAL AND METHODS: For IP, OTP, XiO and BrainSCAN were used and step-and-shoot intensity-modulated radiotherapy (IMRT) delivery was assumed. Based on identical constraints, IP was performed for a prostate, head and neck, brain, and gynecologic case. IMRT plans were compared in terms of conformity/homogeneity, dose-volume histograms (DVHs), and delivery efficiency. For ten patients each of a class of indications, constraint variations were evaluated. RESULTS: IMRT plans were comparable concerning minimum target dose, homogeneity, conformity, and maximum doses to organs at risk. Larger differences were seen in dose gradients outside the target, monitor units, and segment number. Using help structures proved efficient to shape isodoses and to reduce segmentation workload. For IMRT class solutions, IP constraint variations depended on anatomic site. CONCLUSION: IP systems requiring doses as input and having objective functions based on physical parameters had a very similar performance. Constraint templates can be established for a class of IMRT indications.     

The role of medical comorbidity in outcome of major depression in primary care: the PROSPECT study.

OBJECTIVE: The authors described the influence of specific medical conditions on clinical remission and response of major depression (MDD) in a clinical trial evaluating a care-management intervention among older primary-care patients. METHODS: Adults age 60 years and older were randomly selected and screened for depression. Participants were randomly assigned to Usual Care or to an Intervention with a depression care-manager offering algorithm-based care for MDD. In all, 324 adults meeting criteria for MDD were included in these analyses. Remission and response was defined by a score on the Hamilton Rating Scale for Depression <10 and by a decrease from baseline of > or =50%, respectively. Medical comorbidity was ascertained through self-report. Cognitive impairment was defined by a score <24 on the Mini-Mental State Exam (MMSE). RESULTS: In Usual Care, rates of remission were faster in persons who reported atrial fibrillation (AF) than in persons who did not report AF and slower in persons who reported chronic pulmonary disease than in persons who did not report chronic pulmonary disease; rates of response were less stable in persons with MMSE <24 than in those with MMSE > or =24. In the Intervention condition, none of the specific chronic medical conditions were significantly associated with outcomes for MDD. CONCLUSIONS: Because disease-specific findings were observed in persons who received Usual Care but not in persons who received more intensive treatment in the Intervention condition, our results suggest that the association of medical comorbidity and treatment outcomes for MDD may be determined by the intensity of treatment for depression.     

Verifikation und Anwendungen des voxelbasierten Monte-Carlo-(VMC++-)Elektronen-Dosismoduls von Oncentra™ MasterPlan

PURPOSE, MATERIAL AND METHODS: The dose calculation accuracy of the voxel-based Monte Carlo (VMC++) electron dose module of Oncentra MasterPlan (Nucletron B.V., Veenendaal, The Netherlands) was verified by measurements in homogeneous water phantoms. RESULTS: Measured and calculated dose maxima on the central beam axis (calculations with 10,000-20,000 incident electron histories per cm(2)) agree well using standard applicator configurations as well as individually shaped inserts. Profile scans with higher electron energies (>/= 15 MeV) reveal differences up to 5% especially in the penumbra region. Depth dose curves agree best in the vicinity of maximum depths. In the buildup region energy-dependent differences up to 5% in both directions could be observed. In the decay region of depth dose curves calculated doses were up to 10% higher than measured values. CONCLUSION: Good VMC++ accuracy combined with moderate computing times of 1-15 min per beam satisfy all clinical needs. VMC++ allows, for the first time, accurate routine dose evaluations of radiation therapy with electrons. Adequate positioning of the dose reference point is essential. Even small displacements may significantly influence the calculation of monitor units.     

Promoting clinically effective practice: general practitioners' awareness of sources of research evidence

BACKGROUND: Practitioners are being encouraged to base their clinical practice on research evidence. In order to do this, they must be aware of and use the sources of evidence. METHODS: A questionnaire survey was undertaken to establish GPs' awareness of research evidence in their clinical practice and, in fundholding practices, its influence on purchasing plans. Questionnaires were sent to 360 lead fundholders in North Thames Region and 440 of a random sample of the remaining general practitioners in the region for comparison. RESULTS: Questionnaires were returned by 62% of lead fundholders and 63% of GPs in the random sample. There was limited use of the electronic sources of clinical effectiveness. There was greater reported awareness of published sources of research evidence and fundholding GPs were significantly more likely to have referred to publications summarizing research evidence. CONCLUSIONS: GPs seem to make more use of published clinical effectiveness sources than the electronic databases. Consequently, they need educational and technical support if they are to make full use of the available sources of research evidence available in other media.      

Liver-infiltrating T helper cells in autoimmune chronic active hepatitis stimulate the production of autoantibodies against the human asialoglycoprotein receptor in vitro.

Autoantibodies against the human asialoglycoprotein receptor (ASGPR) occur in the sera of patients with autoimmune liver disorders. Liver-infiltrating T cell clones that specifically recognize the ASGPR have been described in patients with autoimmune chronic active hepatitis (AI-CAH) and primary biliary cirrhosis (PBC). Recently, we have shown that peripheral blood mononuclear cells (PBMC) from patients with AI-CAH or PBC but not chronic viral hepatitis secreted anti-ASGPR antibodies in vitro. In this study we characterized the influence of liver-infiltrating T cells on the secretion of ASGPR-specific autoantibodies by autologous B cells in cell culture supernatants. T cell clones from liver biopsies of three patients with chronic autoimmune liver disorders (one with AI-CAH, two with PBC) were isolated and investigated for their proliferative response to soluble ASGPR and their helper function provided to autoantibody-secreting B lymphocytes. PBMC from these patients secreted autoantibodies spontaneously in their cell culture supernatants and showed a proliferative response to ASGPR. T cell-depleted PBMC, however, lacked spontaneous antibody secretion. Four CD4+CD8- liver-infiltrating T cell clones showed a proliferative response to ASGPR and also induced spontaneous anti-ASGPR antibody production in cell culture supernatants when added to autologous T cell depleted PBMC. Activated supernatants of these T cell clones failed to induce antibody production. None of seven CD4+CD8- and two CD4-CD8+ T cell clones non-responding to ASGPR provided this help for antibody secretion. Anti-ASGPR secretion in vitro could not be inhibited by the addition of MoAbs raised against monomorphic determinants on HLA class II molecules. The addition of purified ASGPR or polyclonal-activating pokeweed mitogen showed no influence on the production of autoantibodies in these cultures. These data show that B lymphocytes require T cell help for the production of ASGPR-specific antibodies. This help can be provided by ASGPR-responsive T helper cells via cellular interactions.     

Class II (DR) antigen expression on CD8+ lymphocyte subsets in acquired immune deficiency syndrome (AIDS)

In a selected group of human immunodeficiency virus (HIV)-infected patients we confirm the expansion of a CD8⁺ T-lymphocyte subset, i.e., the CD8⁺/Leu7⁺ cells, which account for 30% of the lymphocytes, compared to 3% in the control donors. In addition, a CD8⁺ T-lymphocyte subset that coexpresses class II (DR) antigens, i.e., CD8⁺/DR⁺ cells, is also increased from 1.5% in controls to 27% in the HIV-infected patients. Using three-color immunofluorescence and flow cytometry we can demonstrate that the CD8⁺/Leu7⁺ and the CD8⁺/class II⁺ cells are not distinct but overlapping subsets. In the HIV-infected patients 42% of the CD8⁺/Leu7⁺ cells were strongly positive for class II and these CD8⁺/Leu7⁺/class II⁺ cells accounted for 13% of all lymphocytes. These findings indicate that the expanded CD8⁺/Leu7⁺ cells are activated and hence might be actively involved in immune defense in acquired immune deficiency syndrome (AIDS).     

Kaposi's sarcoma-associated herpesvirus serology in Europe and Uganda: multicentre study with multiple and novel assays

A multicentre study was undertaken to define novel assays with increased inter-assay concordance, sensitivity, specificity and predictive value for serological diagnosis of human herpesvirus type 8 (HHV-8) infection. A total of 562 sera from European and Ugandan human immunodeficiency virus (HIV)-infected or uninfected individuals with or without Kaposi's sarcoma (KS) and blood donors were examined under code by 18 different assays in seven European laboratories. Sera from KS patients and all non-KS sera found positive by at least 70%, 80%, or 90% of the assays were considered "true positive." The validity of the assays was then evaluated by univariate logistic regression analysis. Two immunofluorescence assays (IFA) for detection of antibodies against HHV-8 lytic (Rlyt) or latent (LLANA) antigens and two enzyme-linked-immunosorbent assays (ELISA) (M2, EK8.1) for detection of antibodies against HHV-8 structural proteins were found to be highly concordant, specific, and sensitive, with odds ratios that indicated a high predictive value. When used together, the two IFA (Rlyt-LLANA) showed the best combination of sensitivity (89.1%) and specificity (94.9%). The performance of these assays indicate that they may be used for the clinical management of individuals at risk of developing HHV-8 associated tumours such as allograft recipients.