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Purpose: Human DNA topoisomerases I and II (topo-I and -II) are essential for vital cellular processes such as DNA replication, transcription, translation, recombination, and repair. In the present study, we correlate topo-I and -II expression and outcome after chemotherapy in primary and relapsed colorectal cancer.Patients and Methods: Patients with colorectal cancer that had recurred, following surgery and adjuvant chemotherapy and underwent a second operation were included in the present study. All had undergone surgical resection of the primary tumor and received post-operatively 5-FU-based (5FU + Leucovorin, Mayo Clinic regimen) adjuvant chemotherapy. Tumor tissue was collected at the initial operation from the primary tumor and at the time of recurrence (during the second operation following chemotherapy). All tissue samples were analyzed for levels of expression of both topo-I and topo-IIa using standard three-step immunohistochemistry on paraffin sections.Results: Forty patients were included. Levels of expression of topo-I and topo-II were higher in malignant cells from tumor recurrences compared to primary tumors (P = 0.0001 for both). There was a statistically significant positive relationship between patients age and levels of topo-I (P = 0.011) and topo-II (P = 0.011) expression.Conclusions: The study results reported here underscore the role of topoisomerase expression in colorectal cancer and suggest a potential role in tumor recurrence. [ABSTRACT FROM AUTHOR]

Fifty-two consecutive patients with advanced colorectal cancer who developed persistent diarrhea following chemotherapy with 5-fluorouracil despite dose reduction were treated with amifostine 800, 500 or 150 mg/m(2). The administered dose of 5-fluorouracil was significantly greater during amifostine treatment. Amifostine 800 mg/m(2) was associated with complete elimination of diarrhea, but 76.3% of patients developed infusion-related hypotension. At a dose of 500 mg/m(2), diarrhea was significantly reduced and milder compared with baseline and the incidence of hypotension was 54.2%. At the lowest dose of amifostine, 17.1% of patients developed Grade 1 diarrhea, a significant reduction over baseline, and hypotension occurred in 25.2% of patients. Treatment with amifostine also improved mucositis but had no effect on the relatively mild nausea and vomiting due to 5-fluorouracil. In this study, amifostine reduced the incidence and severity of diarrhea associated with 5-fluorouracil in patients with advanced colorectal cancer, with acceptable efficacy at a reduced dose that offered better tolerability. [ABSTRACT FROM AUTHOR]

A 37-yr-old man who had undergone renal transplantation for end-stage renal failure presented with a large right pelvic mass obstructing the transplanted kidney. Initially, this was diagnosed as an anaplastic tumor while he had been on immunosuppressive treatment for kidney allograft rejection after transplantation. Despite difficulties of classic histopathology to reveal the origin of his tumor, FISH analysis revealed the presence of chromosome 12p abnormalities, strongly indicative of a germ-cell tumor-more likely seminoma-with extragonadal presentation. Because of renal dysfunction, he was treated with carboplatin (dose adjusted according to renal clearance) and etoposide, and when he experienced a rather atypical progression with bone metastases, he was treated with single-agent paclitaxel, and died almost 13 mo after initial presentation. The case adds further to the existing small list of seminoma/GCTs developing in transplant recipients, points to the unusual presentation patterns and diagnostic histopathology challenges, and presents the difficulty in therapeutic options, as a result of frequent renal dysfunction and intercurrent immunosuppressive therapy. All of these issues together with an extensive literature review are discussed in detail. [ABSTRACT FROM AUTHOR]

Introduction European data on health-related quality of life (HRQoL) in adults with attention deficit/hyperactivity disorder (ADHD) in the general population is sparse. Aims and objectives To report HRQoL in UK adults with ADHD. Methods UK residents aged 18–55 years with a diagnosis of adult ADHD completed an online, cross-sectional survey including questions on disease history, the EuroQol Five Dimensions questionnaire with five-levels (EQ-5D-5L) and the Work productivity and activity impairment questionnaire: general health (WPAI:GH). ADHD symptom severity was assessed by telephone using ADHD rating scale version IV with adult prompts (ADHD-RS-IV). Results The survey was completed by 233 participants (65.2% women; 77.3% white British), mean age 32.6 years (standard deviation [SD] 9.5), mean ADHD-RS-IV total score 43.46 (SD 7.88). Their mean EQ-5D-5L utility score of 0.74 (SD 0.21) was lower than the UK population norm of 0.86 (SD 0.23). [1] WPAI:GH scores indicated that health problems resulted in impairments of 32.04% in work productivity and 45.79% in regular daily activities. Regression analyses adjusting for gender, age and co-morbidities demonstrated associations between EQ-5D-5L utility scores and gender (men had lower scores, P < 0.001), work impairment due to health problems (increasing impairment was associated with lower scores, P = 0.005) and age (for each additional year of age, scores decreased by 0.007, P = 0.010). Conclusions These results highlight the impact on health utility, work productivity and regular daily activities, and add to the description of the disease burden of adult ADHD in the UK. This study was funded by Shire Development LLC. [ABSTRACT FROM AUTHOR]

Purpose: Radiofrequency ablation (RFA) is a validated first-line treatment for osteoid osteoma (OO), but evaluation of long-term (LT) outcomes is more limited. Reported RFA technique including ablation time and temperature also vary greatly between and within reported studies. This study evaluates the immediate and LT efficacy and complication rate of a novel RFA technique in the treatment of OO at a single U.S. tertiary care center. Materials and Methods: We retrospectively reviewed the records of 21 patients treated with RFA for OO of the LE. Each RFA treatment included 2 consecutive 5-6 min 90°C ablations with inter-ablation cooling to 40°C and probe position adjustment depending on lesion size. Patients were also contacted for current data regarding pain following RFA, OO recurrence, and RFA-related complications. Demographic data, early and late-onset complications, and symptom-free interval (mean ± standard deviation) after RFA were evaluated. Results: LT follow-up was obtained for 19/21 patients (90%). Lesion sites included metatarsal (n=2), cuboid (n=1), navicular (n=1), talus (n=1), tibia (n=6), fibula (n=1), femur (n=6), and acetabulum (n=1). Mean time to follow-up was 60 months ± 44 months (range 12-152 months). Mean patient age at RFA was 16.1 years (range 2.2-37.4 years). No immediate RFA-related complications nor LT recurrences were reported. All (19/19) patients reported partial relief of pre-procedural pain within 1 day of RFA and total relief within 1 week of RFA. One patient (5%) with OO of the left cuboid developed multi-tarsal osseous stress injury 2 weeks after RFA coinciding with return to sports. Conclusion: Our study supports the LT safety and efficacy of a novel RFA technique employing sequential 5-6 minute RFAs as a first-line treatment of OO, including challenging treatment areas such as the foot and ankle. The 0 % recurrence rate and low complication rate compare favorably with prior reports. The single case of osseous stress injury in surrounding osseous structures 2 weeks post-RFA reiterates the importance of gradual return to activity after RFA of OOs, particularly OO of the foot. Study limitations include small sample size and recall bias of study participants. [Copyright &y& Elsevier]

In Mediterranean areas the dynamics of gully development act as an important indicator of desertification. However, little is known aboutthe influence of climate and land-use changes, and almost no field data exist to assess the sensitivity of a landscape to gully erosion. Two important components of gully erosion studies are the prediction of where gullies begin and where they end. To address some of these issues, topographical thresholds for gully initiation and sedimentation in six different Mediterranean study areas were established. Field measurements of local soil surface slope (S) and drainage-basin area (A) at the point of initiation of ephemeral gullies in intensively cultivated fields (five datasets) and permanent gullies in rangelands (three datasets) were carried out. A negative power relationship of the form S = aA-b was fitted through all datasets, and defined as the mean topographical threshold for gullying in the respectivearea. Topographically controlled slopes of sedimentation at the gully bottom were also measured. Compared to theoretical relationships for channel initiation by overland flow, relatively low values for b are obtained, suggesting a dominance of overland flow and an influence of subsurface flow. The influence of landsliding at steeper slopes appeared from the flattening of the overall negative trend in the higher slope range (S > 0.30) of the integrated dataset. Comparing the threshold lines of our datasets to the average trend lines through data found in literature revealed that vegetation type and cover could better explain differences in topographical thresholds level than climatic conditions. In cultivated fields, soil structure and moisture conditions, as determined by the rainfall distribution, are critical factors influencing topographical thresholds rather than daily rainfall amounts of the gully-initiating events. In rangelands, vegetation cover at the time of incision appears to be the most important factor diffe [ABSTRACT FROM AUTHOR]