Cytogenetic findings in pediatric renal cell carcinoma

Adenocarcinomas of the kidney are rare childhood tumors. Only 30 cases with chromosomal abnormalities have been reported, and neither their karyotypic characteristics nor the molecular mechanisms behind their pathogenesis are clear, except for a special group of papillary tumors characterized by X-chromosome abnormalities. We have cytogenetically analyzed short-term cultured cells from two pediatric renal carcinomas, one papillary, and one chromophobe renal cell carcinoma, revealing the following karyotypes: 58-60,XX,-X,-1,+7,-8,-9,-11,-14,-15,+17,-18,-19,-21,-22 and 36,X,-X,-1,-2,-5,-6,-9,-10,-13,-17,-21/37,idem,+r/36,idem,-14,+1-2r, respectively. The findings indicate that subsets of pediatric renal cell carcinoma show karyotypes that are similar to their adult counterparts.     

Exhaustion and endocrine functioning in clinical burnout: an in-depth study using the experience sampling method

The current study investigates the relationship between HPA-axis functioning and burnout symptoms by employing an electronic symptom diary. This diary method circumvents the retrospection bias induced by symptom questionnaires and allows to study relationships within-in addition to between-subjects. Forty two clinically burned-out participants completed the exhaustion subscale of the Maslach burnout inventory and kept an electronic diary for 2 weeks to assess momentary exhaustion and daily recovery through sleep. On 3 consecutive weekdays within the diary period, saliva was sampled to determine the cortisol awakening response (CAR), levels of dehydroepiandrosterone-sulphate (DHEAS) on the first 2 weekdays, and to conduct the dexamethasone suppression test (DST) on the third weekday. We found significant relationships between endocrine values and general momentary symptom severity as assessed with the diary, but not with the retrospective questionnaire-assessed burnout symptoms. Simultaneous assessments of endocrine values and burnout symptoms assessed with the diary after awakening rendered significant associations between persons, and a trend within persons. More severe burnout symptoms were consistently associated with a lower level and smaller increase of CAR, higher DHEAS levels, smaller cortisol/DHEAS ratios and a stronger suppression after DST. Burnout symptoms were significantly related to endocrine functioning in clinical burnout under the best possible conditions of symptom measurement. This adds support to the view that severity of burnout symptoms is associated with HPA-axis functioning.     

IL-13 genetic polymorphism identifies children with late wheezing after respiratory syncytial virus infection

BACKGROUND: The nature of wheezing after respiratory syncytial virus lower respiratory tract infection (RSV LRTI) is usually transient. However, some children will develop persistent or late wheezing. OBJECTIVE: We hypothesized that early and late postbronchiolitis wheezing are determined by distinct clinical, immunologic, and genetic variables. METHODS: A cohort of 101 children hospitalized for RSV LRTI was prospectively followed for 6 years. During RSV LRTI, cytokine studies were performed and genetic polymorphisms were determined. Parents performed daily log registration of respiratory symptoms during the first 3 years of follow-up and again at age 6 years during the winter season. RESULTS: Distinctive associations for early and late postbronchiolitis wheezing were found. We previously showed that airflow limitation during RSV LRTI as well as convalescent monocyte IL-10 production are associated with early wheezing. These variables were not associated with late wheezing. On the other hand, atopic family history was not associated with early wheezing, but it was associated with late wheezing. Most importantly, the IL-13 Gln allele was associated with late wheezing (odds ratio 3.27, 95% confidence interval 1.32-8.06), but it was not associated with early wheezing. CONCLUSION: This study revealed distinct clinical, immunologic, and genetic determinants of early and late wheezing after RSV LRTI, indicating distinct pathophysiological mechanisms. We conclude that late wheezing at age 6 years, but not early postbronchiolitis wheezing, is an asthmatic phenomenon and genetically related to a functional IL-13 polymorphism. CLINICAL IMPLICATIONS: After RSV LRTI, wheezing at age 6 years is not related to early postbronchiolitis wheezing and represents a distinct disease entity.     

Excessive body weight is associated with additional loss of quality of life in children with asthma

BACKGROUND: Asthma and excessive body weight frequently coexist, whereas the exact relationship between the 2 diseases is unknown. OBJECTIVE: To study whether asthma combined with excessive body weight has a greater effect on quality of life in children than the separate effects of asthma or excessive body weight alone. METHODS: In a cross-sectional design, 1758 school children (age 7-10 years) participated: 4 study groups were composed of children with asthma and with/without excessive body weight, and healthy controls with/without excessive body weight. Diagnosis of asthma was defined by either a doctor's diagnosis or by core questions of the International Study of Asthma and Allergies in Childhood questionnaire in combination with either reversible airway obstruction or bronchial hyperresponsiveness. Excessive body weight was defined by using international cutoff points for body mass index. Quality of life was evaluated by the Pediatric Asthma Quality of Life Questionnaire. RESULTS: For all domains of quality of life, children with both asthma and excessive body weight had lower scores than children with either asthma alone or excessive body weight alone. Compared with healthy controls, the score was 25% lower in children with asthma and excessive body weight, 14% lower in children with asthma and normal weight, and only 1% lower in overweight controls. CONCLUSION: Excessive body weight is associated with an additional decrease in quality of life in children with asthma. CLINICAL IMPLICATIONS: Clinicians should be aware of the interaction between asthma and excessive body weight and the effect on quality of life and should give extra attention to children with both conditions.     

Demonstration of scan path optimization in proton therapy

A three-dimensional (3D) intensity modulated proton therapy treatment plan to be delivered by magnetic scanning may comprise thousands of discrete beam positions. This research presents the minimization of the total scan path length by application of a fast simulated annealing (FSA) optimization algorithm. Treatment plans for clinical prostate and head and neck cases were sequenced for continuous raster scanning in two ways, and the resulting scan path lengths were compared: (1) A simple back-and-forth, top-to-bottom (zigzag) succession, and (2) an optimized path produced as a solution of the FSA algorithm. Using a first approximation of the scanning dynamics, the delivery times for the scan sequences before and after path optimization were calculated for comparison. In these clinical examples, the FSA optimization shortened the total scan path length for the 3D target volumes by approximately 13%-56%. The number of extraneous spilled particles was correspondingly reduced by about 13%-54% due to the more efficient scanning maps that eliminated multiple crossings through regions of zero fluence. The relative decrease in delivery time due to path length minimization was estimated to be less than 1%, due to both a high scanning speed and time requirements that could not be altered by optimization (e.g., time required to change the beam energy). In a preliminary consideration of application to rescanning techniques, the decrease in delivery time was estimated to be 4%-20%.     

Absorption spectroscopy of EBT model GAFCHROMIC film

The introduction of radiochromic films has solved some of the problems associated with conventional 2D radiation detectors. Their high spatial resolution, low energy dependence, and near-tissue equivalence make them ideal for measurement of dose distributions in radiation fields with high dose gradients. Precise knowledge of the absorption spectra of these detectors can help to develop more suitable optical densitometers and potentially extend the use of these films to other areas such as the measurement of the radiation beam spectral information. The goal of this study is to present results of absorption spectra measurements for the new GAFCHROMIC film, EBT type, exposed to 6 MV photon beam in the dose range from 0 to 6 Gy. Spectroscopic analysis reveals that in addition to the two main absorption peaks, centered at around 583 and 635 nm, the absorption spectrum in the spectral range from 350 to 800 nm contains six more absorption bands. Comparison of the absorption spectra reveals that previous HD-810, MD-55, as well as HS GAFCHROMIC film models, have nearly the same sensitive layer base material, whereas the new EBT model, GAFCHROMIC film has a different composition of its sensitive layer. We have found that the two most prominent absorption bands in EBT model radiochromic film do not change their central wavelength position with change in a dose deposited to the film samples.     

A device guidance method for organ motion compensation in MRI-guided therapy

Organ motion compensation in image-guided therapy is an active area of research. However, there has been little research on motion tracking and compensation in magnetic resonance imaging (MRI)-guided therapy. In this paper, we present a method to track a moving organ in MRI and control an active mechanical device for motion compensation. The method proposed is based on MRI navigator echo tracking enhanced by Kalman filtering for noise robustness. We also developed an extrapolation scheme to resolve any discrepancies between tracking and device control sampling rates. The algorithm was tested in a simulation study using a phantom and an active mechanical tool holder. We found that the method is feasible to use in a clinical MRI scanner with sufficient accuracy (0.36 mm to 1.51 mm depending on the range of phantom motion) and is robust to noise. The method proposed may be useful in MRI-guided targeted therapy, such as focused ultrasound therapy for a moving organ.     

Soluble mannosylated myelin peptide inhibits the encephalitogenicity of autoreactive T cells during experimental autoimmune encephalomyelitis

We have previously shown that immunization with a mannosylated myelin peptide in complete adjuvant induces tolerance instead of disease in experimental autoimmune encephalomyelitis (EAE), a rodent model for multiple sclerosis. In this report we demonstrate that treatment with a soluble mannosylated epitope of proteolipid protein (M-PLP(139-151)) significantly inhibits disease mediated by autoreactive myelin-specific T cells during EAE. Treatment with M-PLP(139-151), applied in different EAE models, significantly reduced the incidence of disease and the severity of clinical symptoms. Delayed-type hypersensitivity responses were abolished after peptide treatment, emphasizing the impact on peripheral T-cell reactivity. Histological analysis of spinal cord tissue from mice treated with M-PLP(139-151) revealed the presence of only few macrophages and T cells. Moreover, little expression of interferon-gamma, interleukin-23, or major histocompatibility complex class II antigen was detected. Immune modulation by M-PLP(139-151) was primarily antigen-specific because an irrelevant mannosylated peptide showed no significant effect on delayed-type hypersensitivity responses or on the course of EAE. Therefore, mannosylated antigens may represent a novel therapeutic approach for antigen-specific modulation of autoreactive T cells in vivo.     

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in prostatic adenocarcinoma

We studied endoglin and vascular endothelial growth factor (VEGF) expression as prognostic markers in prostatic adenocarcinoma in 50 radical prostatectomy specimens. Cases were further categorized by Gleason score as follows: 8 to 10, 9 cases; 7(4 + 3), 9 cases; 7 (3 + 4), 14 cases; 6, 13 cases; and 4 or 5, 5 cases. All cases were immunostained for endoglin, CD31, and VEGF. Positively stained microvessels were counted in densely vascular foci in a x 400 field. VEGF staining intensity was scored on a 2-tiered scale. Results were correlated with survival and other parameters. Endoglin demonstrated significantly more microvessels than did CD31 (mean +/- SD, 37 +/- 15 vs 22 +/- 17; P < .001). VEGF expression was low in 21 cases (42%) and high in 29 (58%). Endoglin correlated positively with Gleason score, lymph node metastases, tumor stage, and preoperative prostate-specific antigen level (P < .05) but not with CD31. VEGF correlated significantly with angiolymphatic invasion and Gleason score (P < .05). A high endoglin microvessel count and VEGF expression correlated with shorter survival. Endoglin is a more specific and sensitive marker for tumor angiogenesis than CD31 and may serve as a prognostic marker for prostatic adenocarcinoma.