tbuckley/cabot-search huggingface dataset:
Doctor who hid private practice earnings from taxman is fined £200 000
Authors: Clare Dyer
Journal: BMJ (2015)

A leading specialist in cardiovascular radiology who hid his private practice earnings from the UK taxman has been ordered to pay a £200 000 (€270 000; $305 000) fine within 28 days or go to prison for two and a half years.

Raad Mohiaddin, a consultant radiologist at the Royal Brompton Hospital and professor of cardiovascular imaging at the National Heart and Lung Institute, Imperial College London, failed to declare self employed earnings outside his NHS employment between 2003 and 2011. He avoided paying almost £409 611 in income tax and national insurance.

He pleaded guilty to one charge …
Immunological evaluation of personalized peptide vaccination for patients with malignant glioma: The results of a clinical phase I trial
Authors: R. Yamanaka, N. Yajima, T. Mine, A. Yamada, M. Shigemor, K. Ito
Journal: Journal of Clinical Oncology (2006)

1524 Purpose: To investigate the safety and immunological responses of personalized peptide vaccination in patients with malignant glioma. Patients and Methods: Twenty-six patients with recurrent malignant glioma entered in the phase I clinical study of personalized peptide vaccination. Peripheral blood mononuclear cells (PBMCs) and plasma prior to vaccination were provided for cellular and humoral responses in vitro to each of 31 or 36 peptides in cases of HLA-A24+ or HLA-A2+ patients, respectively, and then only the reactive peptides (maximum: 4) were allowed to in vivo administration. Post-vaccination PBMCs and plasma, and also pre-and post-vaccination cerebrospinal fluid, were provided for their reactivity to the vaccinated peptides. Expression of class 1 molecule on glioma cell was evaluated using EMR 8–5 antibody by immunohistochemical analysis. Results: The protocol was generally well tolerated, although the majority of patients developed grade 1 or 2 local redness and swelling at the injection site. Increase in cellular and humoral responses specific to at least one of the vaccinated peptides was observed in the post vaccination (6th)-PBMCs and -plasma from 62%, 73% respectively. More importantly, peptide-specific IgG were found in the post-vaccination cerebrospinal fluid of tumor sites. Clinical responses were 4 partial response, 8 stable disease, and 8 progressive disease. The clinical response was correlated to the expression of MHC class 1 on the glioma cell. The median overall survival for patients with recurrent glioblastoma multiforme in this study was 622 days. Conclusion: Personalized peptide vaccination is well tolerated and has ability to induce immune responses to the majority of malignant glioma patients along with several cases of major tumor regression. These results would encourage the phase II clinical study of personalized peptide vaccination to patients with recurrent malignant glioma. No significant financial relationships to disclose.
Determinants of participation in the Study of Tamoxifen and Raloxifene (STAR): Experience of a minority-based community oncology program
Authors: C. Holmberg, L. Adams-Campbell, J. P. Costantino, J. Pearson, W. Mccaskill-Stevens
Journal: Journal of Clinical Oncology (2005)

1011 Background: To increase minority participation in STAR, outreach efforts were implemented at Howard University Cancer Center (HUCC). A large number of women completed risk assessment forms (RAF) to determine risk eligibility for the trial. To learn about the decision-making of trial participation, we compared STAR participants (SP) and STAR decliners (SD). Methods: This pilot study is a prospective, observational study of women who are risk-eligible for STAR. 25 women were contacted for an information session; 7 participated. Four previously enrolled SP were included in the study (N = 11). Subjects completed a survey to assess: education; reasons for interest in STAR; influence of social environment on the decision; expectations regarding STAR; and understanding of STAR. To enhance questionnaire data, in-depth, open-ended interviews were conducted. Results: The sample consisted of 7/11 African-American (AA), 2/11 white, 1/11 Brazilian, and 1/11 Japanese. The range of education was similar in all groups as were answers to reasons for interest in STAR, influence of social environment, expectations regarding STAR, and understanding of STAR. 5/11 were SP (all AA); 4/11 were SD and 2/11 wanted to enroll but were ineligible (SI) from comorbidity and menopausal status. 3/4 SD had previously participated in research. 2/4 SD had a sister with breast cancer; 0/4 had a mother with breast cancer. In contrast 2/2 SI and 3/5 SP had a mother with breast cancer; one also had a sister with breast cancer. 1/5 SP only had a sister with breast cancer. The 4 SPs wanted to honor their relative and forego the suffering they witnessed. 1/5 SP had strong community values and participated to enhance treatment opportunities for AA women. Advancing treatment and prevention options for AA women was important to all SP. HUCC was a very important factor for SP as they consider it a premier institution focusing on bettering AA lives. Conclusion: The participants’ experiences at the institution offering the trial, their perception of the importance of trial results for others, and personal disease experience were important factors in the decision-making for participation in the STAR chemoprevention trial. No significant financial relationships to disclose.
The Year Book of Family Practice—1983.
Journal: Annals of Internal Medicine (1983)

REVIEWSdiscussed in two separate chapters.Neither of the two complete summaries of the US Dietary Goals is listed in the index.There is no listing for aging or geriatrics even though special issues pertaining to the nutritional status of the elderly are addressed in the chapter on drug-diet interactions and in the one on food assistance programs.These omissions prevent the use of this volume as a reference text.
Phase II study of intravenous (IV) bevacizumab and paclitaxel, and intraperitoneal (IP) cisplatin, followed by bevacizumab consolidation for advanced ovarian (O) or peritoneal (P) cancers
Authors: D. D. McMeekin, G. Lanneau, J. Curiel, K. Moore, J. Walker, R. Mannel
Journal: Journal of Clinical Oncology (2009)

5540 Background: Excessive toxicity and difficulty in completing prescribed cycles are cited as factors behind the lack of routine acceptance of IP therapy in O/P cancer. In an effort to increase the probability of completing 6 cycles of IP therapy, we evaluated a modified IP regimen with the addition of bevacizumab to determine the proportion of patients able to receive 6 cycles successfully. Methods: An open label phase II study was conducted in patients (pts) with stage II-III O/P cancers with residual disease &lt; 1 cm. The primary outcome measure the feasibility of delivering 6 cycles of IP therapy with a completion rate of &gt; 80% being clinically relevant. Pts received paclitaxel 135 mg/m 2 IV on day 1 followed by cisplatin 75 mg/m 2 IP day 2. Bevacizumab 15 mg/kg day 1 IV was started with the second cycle. Cycles were administered every 21 days for a total of 6 cycles. Following completion of primary therapy, bevacizumab @ 15mg/kg IV was given in consolidation every 21 days for 12 cycles. Pts were assessed for toxicity and disease status. This preliminary analysis reports data from experience with 6 cycles of IP therapy. Results: 22 patients have been enrolled (21-O, 1-P) with a median age of 58 yrs. Two pts discontinued therapy due to IP port problems (following cycle 1 and 4) and per protocol, were replaced. Two pts are on active treatment (completed cycle 5). Of 20 evaluable pts, 2 pts discontinued prematurely (1 after cycle 1 due to elevated liver function tests, 1 after cycle 4 due to grade 3 neuropathy), and 1 pt received cycle 6 by IV route secondary to abdominal pain with IP infusion. The proportion of patients successfully completing 5 cycles of IP therapy was 18/20 (90%), and to date 15/18 (83%) pts have completed 6 cycles. One patient developed a DVT, one had an intra-abdominal fistula requiring surgical intervention after cycle 6. Conclusions: The addition of bevacizumab to an IP regimen for O/P cancers did not add to enhanced acute toxicity. The present regimen using 75 mg/m2 CDDP IP and no day 8 paclitaxel appears to be tolerable, with &gt;80% of pts able to receive 6 cycles of therapy. [Table: see text]
EUCAST technical note on isavuconazole breakpoints for Aspergillus, itraconazole breakpoints for Candida and updates for the antifungal susceptibility testing method documents
Authors: M.C. Arendrup, J. Meletiadis, J.W. Mouton, J. Guinea, M. Cuenca-Estrella, K. Lagrou, S.J. Howard, M.C. Arendrup, J. Meletiadis, S.J. Howard, J. Mouton, J. Guinea, K. Lagrou, S. Arikan-Akdagli, F. Barchiesi, P. Hamal, H. Järv, C. Lass-Flörl, M. Mares, T. Matos, K. Muehlethaler, T.R. Rogers, C. Torp Andersen, P. Verweij
Journal: Clinical Microbiology and Infection (2016)
Genetic Deficiency of Glutathione <i>S</i> -Transferase P Increases Myocardial Sensitivity to Ischemia–Reperfusion Injury
Authors: Daniel J. Conklin, Yiru Guo, Ganapathy Jagatheesan, Peter J. Kilfoil, Petra Haberzettl, Bradford G. Hill, Shahid P. Baba, Luping Guo, Karin Wetzelberger, Detlef Obal, D. Gregg Rokosh, Russell A. Prough, Sumanth D. Prabhu, Murugesan Velayutham, Jay L. Zweier, J. David Hoetker, Daniel W. Riggs, Sanjay Srivastava, Roberto Bolli, Aruni Bhatnagar
Journal: Circulation Research (2015)

Myocardial ischemia-reperfusion (I/R) results in the generation of oxygen-derived free radicals and the accumulation of lipid peroxidation-derived unsaturated aldehydes. However, the contribution of aldehydes to myocardial I/R injury has not been assessed.We tested the hypothesis that removal of aldehydes by glutathione S-transferase P (GSTP) diminishes I/R injury.In adult male C57BL/6 mouse hearts, Gstp1/2 was the most abundant GST transcript followed by Gsta4 and Gstm4.1, and GSTP activity was a significant fraction of the total GST activity. mGstp1/2 deletion reduced total GST activity, but no compensatory increase in GSTA and GSTM or major antioxidant enzymes was observed. Genetic deficiency of GSTP did not alter cardiac function, but in comparison with hearts from wild-type mice, the hearts isolated from GSTP-null mice were more sensitive to I/R injury. Disruption of the GSTP gene also increased infarct size after coronary occlusion in situ. Ischemia significantly increased acrolein in hearts, and GSTP deficiency induced significant deficits in the metabolism of the unsaturated aldehyde, acrolein, but not in the metabolism of 4-hydroxy-trans-2-nonenal or trans-2-hexanal; on ischemia, the GSTP-null hearts accumulated more acrolein-modified proteins than wild-type hearts. GSTP deficiency did not affect I/R-induced free radical generation, c-Jun N-terminal kinase activation, or depletion of reduced glutathione. Acrolein exposure induced a hyperpolarizing shift in INa, and acrolein-induced cell death was delayed by SN-6, a Na(+)/Ca(++) exchange inhibitor. Cardiomyocytes isolated from GSTP-null hearts were more sensitive than wild-type myocytes to acrolein-induced protein crosslinking and cell death.GSTP protects the heart from I/R injury by facilitating the detoxification of cytotoxic aldehydes, such as acrolein.
The effect of alemtuzumab maintenance therapy on B and T lymphocytes in chronic lymphocytic leukemia
Authors: M. S. Kaufman, N. Driscoll, C. Johnson, A. Caramanica, D. Janson, Y. Lebowicz, T. Wasil, K. Rai
Journal: Journal of Clinical Oncology (2007)

7092 Background: We are conducting a pilot, exploratory study of the potential value of alemtuzumab(alem) in maintenance therapy of previously treated chronic lymphocytic leukemia (CLL) patients(pts) after they have achieved stable disease or partial remission with chemo or chemo-immunotherapy. We present the results of serially monitored CD19+ (B)lymphocytes and CD4+ (T) lymphocytes on eight evaluable patients. Methods: 30mg doses of alem were administered SC to all patients at the following schedule: wkly for 8 doses (8 wks), followed by q2 wks for 8 doses(16 wks), followed by q3 wks for 8 doses (24 wks). This schedule provides a total of 48 wks of maintenance treatment with alem. Patients received standard prophylaxis with sulfamethoxizole and acyclovir with regular CMV monitoring by quantitative PCR. Results: In the table we present data on the pattern of decrease in blood CD19+(B) cells and CD4+ (T) cells on eight evaluable pts at different time points after starting alem maintenance. Because flow cytometry was not done on all pts at each time point, the number of pts contributing to the calculation of mean counts at each given time point is variable. CD19+(B) cells were markedly reduced to 37% of baseline consistently, from 8 wks onward. CD4+(T) cells, on the other hand, were consistently higher than 50% of the baseline after 8 wks. No opportunistic infections were seen in any pt and treatment was well tolerated. Conclusion: These results from a single institution based pilot study demonstrate that alem used in maintenance schedule is effective in keeping the blood levels of CD19+(B) cells extremely low without concordant suppression of CD4+(T) lymphocytes. No significant financial relationships to disclose. [Table: see text]
A phase II trial of Tetrathiomolybdate [TM] after cytoreductive surgery for malignant pleural mesothelioma (MPM)
Authors: H. I. Pass, G. Brewer, T. Stevens, S. Sharma, D. Smith, A. Wali, S. Merajver
Journal: Journal of Clinical Oncology (2004)

7051 Background: Resection and adjuvant therapy for MPM results in a 2-year survival of 60% for Stages I/II, and 25% for Stage III (Rusch et al; Proc ASCO 2000). Median time to progression is 7–12 months after resection. Angiogenesis is a predictor of poor prognosis in MPM; TM is an oral copper (Cu)-depleting agent that inhibits angiogenesis and decreases levels of VEGF when ceruloplasmin (Cp) is reduced to 5–15 mg/dl. We hypothesize that cytoreduction of MPM followed by continuous TM can increase survival and delay progression by keeping residual disease in a dormant state. Methods: 34 cytoreduced MPM patients were registered for postoperative TM beginning 4–6 weeks after surgery at 180 mg/day with the dose adjusted to maintain Cp between 5–15 mg/dl. TM was continued until progression; chest/abdominal CTs were performed every 4 months. Results: 4 patients progressed prior to reaching target Cp. The remaining 25 men and 5 women, median age 67 (range 49–81yrs.) remained on TM a median of 10 months (range 4 to>36 mos.). The most common Grade (Gr) 3 toxicity was anemia: 27 episodes (15 patients), requiring transfusion in 7, or TM dose reduction alone (8). One patient had asymptomatic Gr 3 SGPT/SGOT rise which reversed with TM dose modification. All patients reached target Cp levels within 34±2 days (95% CI 30–39 days), and VEGF levels at baseline Cp (Cp=45.2±2 mg/dl) decreased from 2086±390 pg/ml to 1250±712 pg/ml (p<0.002) at target Cp [13±2 mg/dl (p<0.0001 from baseline)]. Survival /progression data are seen shown below. Conclusions: TM has antiangiogenic effects in postoperative MPM patients and the VEGF serum level is a robust biomarker in this therapy. TM has minimal toxicity and is at least comparable in efficacy to previous multimodality trials of cytotoxic agents for MPM. TM should be evaluated for use with standard MPM regimens, as well as for postsurgical maintenance monotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Mensanna Lilly Pharmaceuticals Attenuon lawyers
Hormone Dependence of 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene-Induced Mammary Tumor Growth: Correlation With Prostaglandin E&lt;sub&gt;2&lt;/sub&gt; Content&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: M K Foecking, W E Kibbey, H Abou-Issa, R H Matthews, J P Minton
Journal: JNCI Journal of the National Cancer Institute (1982)

Prostaglandin content in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors was correlated with growth responses to alterations in endogenous estrogen and prolactin. Prostaglandin E2 (PGE2) content varied inversely with tumor latency. Ovariectomy of tumor-bearing Sprague-Dawley rats resulted in regression of tumors in 90% of the castrated rats. PGE2 content in tumors from ovariectomized rats was elevated twofold (P less than 0.05) compared to PGE2 content in tumors from intact controls. Haloperidol treatment promoted tumor growth even after ovariectomy and returned tumor PGE2 values to control levels. Tumors grouped by growth status irrespective of hormone status showed an inverse relationship between PGE2 content and growth response.
Cardiometabolic Risks and Severity of Obesity in Children and Young Adults
Authors: Asheley C. Skinner, Eliana M. Perrin, Leslie A. Moss, Joseph A. Skelton
Journal: New England Journal of Medicine (2015)

The prevalence of severe obesity among children and young adults has increased over the past decade. Although the prevalence of cardiometabolic risk factors is relatively low among children and young adults who are overweight or obese, those with more severe forms of obesity may be at greater risk.We performed a cross-sectional analysis of data from overweight or obese children and young adults 3 to 19 years of age who were included in the National Health and Nutrition Examination Survey from 1999 through 2012 to assess the prevalence of multiple cardiometabolic risk factors according to the severity of obesity. Weight status was classified on the basis of measured height and weight. We used standard definitions of abnormal values for total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, triglycerides, blood pressure, glycated hemoglobin, and fasting glucose and report the prevalence of abnormal values in children and young adults according to weight status.Among 8579 children and young adults with a body-mass index at the 85th percentile or higher (according to the Centers for Disease Control and Prevention growth charts), 46.9% were overweight, 36.4% had class I obesity, 11.9% had class II obesity, and 4.8% had class III obesity. Mean values for some, but not all, cardiometabolic variables were higher with greater severity of obesity in both male and female participants, and the values were higher in male participants than in female participants; for HDL cholesterol, the mean values were lower with greater severity of obesity. Multivariable models that controlled for age, race or ethnic group, and sex showed that the greater the severity of obesity, the higher the risks of a low HDL cholesterol level, high systolic and diastolic blood pressures, and high triglyceride and glycated hemoglobin levels.Severe obesity in children and young adults was associated with an increased prevalence of cardiometabolic risk factors, particularly among boys and young men.
Benefits of a reservoir nasal cannula (oxymizer) versus a conventional nasal cannula during exercise in hypoxemic COPD patients
Authors: Rainer Gloeckl, Maximilian Matthaei, Inga Heinzelmann, Stella Seeberg, Thomas Damisch, Bernd Sczepanski, Sandra Winterkamp, Andreas Jerrentrup, Claus Vogelmeier, Klaus Kenn
Journal: European Respiratory Journal (2014)

Background:

The Oxymizer® device is a special oxygen nasal cannula that provides a higher luminal diameter in combination with an incorporated oxygen reservoir. Thus it is assumed that a higher oxygen content can be delivered in order to increase oxygenation.

Methods:

Aim of this prospective cross-over study was to investigate the effects of the Oxymizer® in comparison to a conventional nasal cannula (CNC). N=43 patients with severe COPD (age: 60±9y, FEV1: 37±16% pred.) and indication for long-term oxygen therapy were recruited during pulmonary rehabilitation. After an initial incremental cycle test patients performed 4 constant cycling work rate tests (CWRT) at 70% of their peak work rate (twice with Oxymizer® and twice with CNC in random order).

Results:

Endurance time was significantly higher when patients cycled using Oxymizer® in comparison to CNC (858±754 sec. vs 766±652 sec.; p<0.01). Beside of a longer cycling duration, PaO2 values at the end of CWRT were also significantly higher with Oxymizer® (65±11 mmHg versus 62±10 mmHg; p<0.001). However, in a subgroup analysis we found that patients with an oxygen supplementation of ≥4 liters/min obtained an markedly higher increase in exercise capacity by using the Oxymizer® than patients with lower oxygen flow rates (increase in endurance time 161±225 sec. versus 20±123 sec.; p<0.05).

Conclusion:

This study showed that oxygen delivery via Oxymizer® is superior to CNC with regards to endurance capacity and a better oxygenation during exercise in patients with severe COPD. It seems that especially patients with high oxygen flow rates of ≥4 liters/min benefit most from the use of an Oxymizer®.
Adjuvant chemotherapy in soft tissue sarcoma (STS): A meta-analysis of published data
Authors: J. M. O’Connor, M. Chacón, F. E. Petracci, R. D. Chacón
Journal: Journal of Clinical Oncology (2008)

10526 Background: The beneficial use of adjuvant chemotherapy to reduce risk of recurrence and mortality in soft tissue sarcoma STS is still controversial. Data from one meta-analysis (doxorubicin based) showed improved relapse free survival (RFS), but not overall survival (OS). We performed a non individual meta-analysis from the published studies to evaluate if adjuvant doxorubicin − / + ifosfamide improves 5- 10 years DFS and OS in STS. Methods: We performed a review of the available literature identified from multiple databases. The key words used were "soft tissue sarcoma", "adjuvant chemotherapy" and "randomized trial". Data were pooled for Meta-analysis using the Peto's Odds Ratio (OR). Event-based relative odds ratios (OR) with 95% confidence intervals (CI) were derived. A heterogeneity test was applied. A subgroup analysis according to ifosfamide or non ifosfamide regimen was also performed. Results: We included one meta-analysis (SMAC 1997), and four published or presented randomized controlled phase III trials (EORTC 62931, 2 Italian studies and one Austrian study) were selected including a total of 2170 patients. Endpoints of interest for this meta-analysis were: Disease-Free Survival (DFS), Recurrence Free-Survival (RFS) and Overall Survival (OS) at 5 and 10 years. Results are summarized in the table below. Conclusion: This meta-analysis supports previous data stating that adjuvant doxorubicin +/ - ifosfamide regimens are significantly beneficial in terms of DFS and OS at 5 years. We observed a tendency to improved survival at 10 years in the adjuvant arm. The addition of modern regimens with ifosfamide did not improve the data of the previous meta-analysis with doxorubicin based-chemotherapy. End point OR (Odds Ratio) 95% CI P value DFS 5 years 0.71 0.54 - 0.85 0.000 RFS 5 years 0.75 0.61 - 0.92 0.007 OS 5 years 0.79 0.66 - 0.94 *0.005 RFS 10 years 0.71 0.58 - 0.85 0.000 OS 10 years 0.87 0.72 - 1.04 0.12 * Heterogeneity p=0.005. Other comparisons NS for heterogeneity. No significant financial relationships to disclose.
All overweight adults should be screened for abnormal blood sugar, says US task force
Authors: Jacqui Wise
Journal: BMJ (2015)

All overweight and obese adults aged 40 to 70 should be screened for abnormal blood sugar levels, says new guidance from the US Preventive Services Task Force.

The recommendation, published in the Annals of Internal Medicine , said that patients with high blood sugar levels should be referred to intensive behavioural counselling to promote a healthy diet and regular exercise.1

Estimates from 2012 show that 12% …