tbuckley/cabot-search huggingface dataset:
Chancellor’s psychiatrist brother is struck off medical register
Authors: Clare Dyer
Journal: BMJ (2016)

Adam Osborne, the psychiatrist brother of the United Kingdom’s chancellor of the exchequer, George Osborne, has been struck off the UK medical register for “blatant disregard of the fundamental tenets of the medical profession.”

Osborne, 39, admitted having a two year sexual and emotional affair with a vulnerable patient he was treating for anxiety and depression at his private psychiatry practice in central London. The woman, referred to as Patient A, took an overdose and was rushed to hospital by ambulance on 9 February 2015, three days after the married psychiatrist ended the affair by email.

After Patient A’s stay in hospital she was admitted to an inpatient psychiatric facility because doctors were concerned about the high risk of self harm.

The Medical Practitioners Tribunal …
Phase II trial of preoperative cisplatin-irinotecan followed by concurrent cisplatin-irinotecan and radiotherapy: PET scan after induction therapy may identify early treatment failure
Authors: D. H. Ilson, M. Bains, N. Rizk, M. Shah, V. Rusch, M. Capanu, R. Flores, D. Kelsen, B. Park, S. Kepler, B. Minsky
Journal: Journal of Clinical Oncology (2006)

4023 Background: Response on PET scan during preoperative chemotherapy (chemo) for esophageal cancer (EC) has prognostic significance [JCO 19:3058;2001]. Induction chemo with weekly irinotecan(I)/cisplatin(C) relieves dysphagia, and weekly I/C administered with radiotherapy (RT) is well tolerated [ProcASCO 23:Abs 4017;2005]. We completed a Phase II trial of induction I/C followed by I/C/RT followed by surgery. Repeat PET scan was performed after induction chemo and prior to RT. Methods: Patients (pts) with resectable EC/GE junction carcinoma were staged with EUS, PET, and CT scan. Induction chemo consisted of I-65 mg/m 2 and C-30 mg/m 2 weeks 1,2,4,5, and weeks 7,8,10,11 with RT (180 cGy daily fractions to 5040 cGy). PET scan was repeated at week 6. Esophagectomy was planned 4–8 weeks after RT. Results: 60 pts were enrolled: 6 inevaluable, 54 evaluable, 3 await surgery; 49 male (91%), 5 female (9%), 41 adenocarcinoma (76%), 13 squamous (24%), median age 59, median PS 0, EUS T3N1 35 (65%), N1 40 (74%). Of 41 pts with dysphagia, 31 (76%) had resolution/improvement with induction chemo and 3/54 (6%) required a feeding tube. Of 51 pts, 3 clinical complete responders (CR) deferred surgery (1 refusal, 2 medically inoperable). Of 48 pts, 4 progressed during induction (8%), 9 progressed during RT (19%), and 35 underwent R0 resection (73%). 9/48 (19%) achieved pathologic CR. The median overall survival was 35.4 mos (median follow up 15 mos). In exploratory analysis in 54 pts, response after induction on the week 6 PET scan measured as a decline in SUV, correlated with time to tumor progression (TTP). The mean change in SUV was 43%. A set point of 22% or greater decline in SUV (PET responder) yielded the greatest distinction in TTP (PET responders TTP 18.5 mos, vs nonresponders 5.5 mos, p = 0.03). 4 pts with progression during induction crossed over to RT with paclitaxel: 3 (2 squamous, 1 adenocarcinoma) achieved durable disease control (one pathologic CR, one pathologic PR, one clinical CR). Conclusions: Response on PET scan during induction chemo for EC may identify early treatment failures, and may direct pts to successful salvage with alternative chemo during RT. Supported by a grant from Pfizer. [Table: see text]
Pros and Cons of Adding of Neoadjuvant Chemotherapy to Standard Concurrent Chemoradiotherapy in Cervical Cancer: a Regional Cancer Center Experience
Authors: S. Narayan, A. Kapoor, P.K. Bagri, M.K. Singhal, R. Sharma, R.K. Nirban, D. Singh, S. Maharia, G. Singh, P. Kumari, K. Harsh, N. Sharma, S.L. Jakhar, S. Beniwal, H.S. Kumar, A. Sharma, M. Bardia
Journal: Annals of Oncology (2014)
The influence of rest primary brain tumours on disease free and overall survival
Authors: D. D. Scepanovic, N. D. Bajic
Journal: Journal of Clinical Oncology (2006)

11529 Background: We analysed the influence of rest primary brain tumours on disease free survival (DFS) and overall survival (OS). Methods: From 1998 till 2004, 80 patients (pts) with primary brain tumours were treated with postoperative radiotherapy (RT). The male–female ratio was 44 versus (vs) 36 pts (55% vs 45%). The median age was 50 years (yrs) (min 17, max 79 yrs). Performance status was 90–100% in 30 pts, 80–90% in 39 pts and 70–80% in 11 pts. Low grade astrocytoma was reported in 13 pts, anaplastic astrocytoma and glioblastoma in 49 pts, low grade oligodendroglioma in 2 pts, meningeoma in 9 pts and others in 7 pts. The postoperative RT dose was 50 Gy in 20 pts while 60 pts was treated with dose above 50 Gy, 2 Gy per day, 5 fractions per week, linear accelerator X rays, 6 MeV energy. We analysed two groups of pts (50 pts had rest tumours after surgery and RT within 6 months (mo) of operation and 30 pts without rest tumours). We analysed the influence of age, pts ambulatory, corticosteroids therapy during RT, pathohystological diagnoses (PH), RT doses and chemotherapy (CT) application (carmustine, 80 mg/m2, i.v. 1–3 days after 6 weeks of RT completion) on DFS and OS. Results: The median follow up time was 16 mo (min 6, max 96 mo). Thirty pts (37.5%) is still alive while 50 pts (62.5%) died. Cox regression model gave us data of influence on DFS in this way: cortocosteroids therapy during RT, CT application, RT dose and furthermore on OS: age, pts ambulatory, PH report and RT dose. Logistic regression model gave us data for rest tumours group of pts (50 pts) to be the greatest influence on survival patients ambulatory and corticosteroids therapy during RT. Between two groups of pts there is statistically significant difference on DFS and OS (p &lt; 0.001). 1 yrs DFS was 30% and 2 yrs DFS was found in 26% of pts while 1 yrs OS was 44% and 2 yrs OS was 42% of pts. Conclusions: Pts with rest tumours especially anaplastic astrocytoma and glioblastoma have a shorter life span. However, RT dose does influence DFS and OS in pts with good performance status. No significant financial relationships to disclose.
Phase I/II Trial of Cyclophosphamide, Mitoxantrone, and Escalated Doses of Carboplatin Supported by Peripheral-Blood Stem Cells in Women With Metastatic Breast Cancer
Authors: Amita Patnaik, Janet MacKinnon, Paul Goss, Tracy Nagy, Keith Stewart, Armand Keating, Michael Crump
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To intensify a regimen of high-dose cyclophosphamide, mitoxantrone, and carboplatin that had previously produced high complete and overall response rates in metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-four patients with a median age of 43 years (range, 25 to 57 years) and previously untreated MBC who were responding to anthracycline-based or single-agent taxane chemotherapy received cyclophosphamide 1.5 g/m 2 /d and mitoxantrone 16 mg/m 2 /d combined with escalating doses of carboplatin 200 to 500 mg/m 2 /d, each given daily from days −6 to −3. Hematopoiesis was supported by mobilized peripheral-blood stem cells infused on day 0 and by use of granulocyte-macrophage colony-stimulating factor 300 μg/d subcutaneously starting on day 1. RESULTS: A total of six dose levels of carboplatin were examined. Grades 3 and 4 toxicity occurred in 10 patients and one patient, respectively, with grade 3 toxicity occurring in only five of 31 patients treated with ≤ 400 mg/m 2 of carboplatin. Major dose-limiting toxicities were cardiac, pulmonary, and renal. Four patients developed congestive heart failure: two had persistently low ejection fraction 11 and 36 months after peripheral-blood stem-cell transplantation (PBSCT), and two recovered. Hematologic recovery to an absolute neutrophil count of greater than 0.5 × 10 9 /L occurred at a median of 11 days (range, 8 to 25 days) and to a platelet count of greater than 20 × 10 9 /L at a median of 10.5 days (range, 6 to 60 days). There were two toxic deaths from sepsis: one on day 27 (level 5) and one from cardiac arrest on day 42 (level 6). CONCLUSION: The maximum-tolerated dose of carboplatin was 400 mg/m 2 /d in combination with mitoxantrone 16 mg/m 2 /d and cyclophosphamide 1,500 mg/m 2 , all drugs given over 4 days. This regimen is being tested in a phase III trial of high-dose chemotherapy and PBSCT versus standard treatment.
Abstract 14052: miR-223 Attenuates Cardiac Dysfunction in Polymicrobial Sepsis Through Inhibition of Sema3a Expression
Authors: Xiaohong Wang, Wei Huang, Yigang Wang, Chuanfu Li, Guo-Chang Fan
Journal: Circulation (2013)

Background: The occurrence of cardiovascular dysfunction in sepsis is associated with a significantly increased mortality rate of 70% to 90% compared with 20% in septic patients without cardiovascular impairment. Recent work has implicated microRNAs (miRs) in sepsis-associated inflammatory response, however, whether miRs are dys-regulated in septic hearts and their potential role remain elusive. Methods and Results: Male C57BL/6 mice (10-wk old) underwent cecal ligation and puncture (CLP) to induce sepsis. Six hours later, CLP-hearts and sham-operated mouse hearts were collected for isolation of total RNA to perform miR array analysis. Among 13 miRs dys-regulated in CLP-hearts, miR-223 was most significantly downregulated, which was further validated by stem-loop RT-PCR (n=6, p<0.001). To test whether a drop of miR-223 plays a role in sepsis-induced cardiac dysfunction, we first knocked down of miR-223 in cultured adult rat cardiomyocytes by adenoviral vector containing shRNA, followed by endotoxin (LPS, ...
A Pilot Study Of Bone Marrow and Adipose Tissue – Derived Mesenchymal Stem Cells In Chronic Myeloid Leukemia (CML); Mesenchymal Stem Cells Of The Bone Marrow Harbor The Bcr-Abl Fusion Gene In a CML Patient
Authors: Vasiliki Papadopoulou, Korina Peste, Dafni Koumpi, Vasiliki Stavropoulou, Panagiotis Theodorou Diamantopoulos, Dimitrios Dimitroulis, Konstantinos Zervakis, Fani Kalala, Nefeli Giannakopoulou, Niki Rougkala, Polyxeni Hatzinikolaou, Gerasimos Tsilimidos, Theodoros Iliakis, Eleni Variami, Nora-Athina Viniou
Journal: Blood (2013)
siRNA mediated silencing of Wilms tumor gene-1 (WT1) in leukemia cell lines
Authors: W. Glienke, I. Seil, N. Bauer, L. Bergmann
Journal: Journal of Clinical Oncology (2005)

3199 Background: The expression of WT1 is considered to have a proliferating and survival supporting effect in leukemia blast cells. The downregulation of WT1 by means of antisense-oligonucleotides and ribozymes revealed an inhibition of cell proliferation and induction of cell death. Generally, the repression of gene expression by small interfering RNA (siRNA) is highly effective and relatively free from unspecific effects. Here we describe the use of siRNA against WT1 in leukemic cell lines. Methods: We have used two different sequences designated siRNA-A corresponding to positions 129–147 of exon 2 within the WT1 open reading frame and siRNA-B corresponding to positions 83–103 of exon 4 within the WT1 open reading frame to downregulate WT1. RT-PCR and western blot analyses were used to examine WT1 gene expression in transfected leukemia cell lines. MTT-test was used to measure the cell viability and FACS analysis using annexin V-staining for apoptosis. Results: K562 and HL-60 cell lines transfected with siRNA-A targeted to WT1 had greatly decreased levels of WT1 mRNA and protein expression. SiRNA-B and control siRNA had almost no effect on WT1 mRNA and protein expression. SiRNA-A reduced WT1 mRNA in K562 and HL-60 cells by 24 hours after transfection. Cell proliferation was reduced by between 45% and 76% 48 hours after transfection, and apoptosis was increased from 6.6% in control cells to 12.2% 24 hours after transfection in transfected cells. 48 hours after transfection the amount of apoptotic cells increased up to 65% in transfected cells. Conclusion: WT1 mRNA and protein expression could effectively be downregulated by siRNA. Therefore, siRNAs targeted against human WT1 may be valuable tools as antiproliferative agents against leukemic cells. No significant financial relationships to disclose.
Combinatorial Genetic Modeling of<i>pfcrt</i>-Mediated Drug Resistance Evolution in<i>Plasmodium falciparum</i>
Authors: Stanislaw J. Gabryszewski, Charin Modchang, Lise Musset, Thanat Chookajorn, David A. Fidock
Journal: Molecular Biology and Evolution (2016)

The emergence of drug resistance continuously threatens global control of infectious diseases, including malaria caused by the protozoan parasite Plasmodium falciparum. A critical parasite determinant is the P. falciparum chloroquine resistance transporter (PfCRT), the primary mediator of chloroquine (CQ) resistance (CQR), and a pleiotropic modulator of susceptibility to several first-line artemisinin-based combination therapy partner drugs. Aside from the validated CQR molecular marker K76T, P. falciparum parasites have acquired at least three additional pfcrt mutations, whose contributions to resistance and fitness have been heretofore unclear. Focusing on the quadruple-mutant Ecuadorian PfCRT haplotype Ecu1110 (K76T/A220S/N326D/I356L), we genetically modified the pfcrt locus of isogenic, asexual blood stage P. falciparum parasites using zinc-finger nucleases, producing all possible combinations of intermediate pfcrt alleles. Our analysis included the related quintuple-mutant PfCRT haplotype 7G8 (Ecu1110 + C72S) that is widespread throughout South America and the Western Pacific. Drug susceptibilities and in vitro growth profiles of our combinatorial pfcrt-modified parasites were used to simulate the mutational trajectories accessible to parasites as they evolved CQR. Our results uncover unique contributions to parasite drug resistance and growth for mutations beyond K76T and predict critical roles for the CQ metabolite monodesethyl-CQ and the related quinoline-type drug amodiaquine in driving mutant pfcrt evolution. Modeling outputs further highlight the influence of parasite proliferation rates alongside gains in drug resistance in dictating successful trajectories. Our findings suggest that P. falciparum parasites have navigated constrained pfcrt adaptive landscapes by means of probabilistically rare mutational bursts that led to the infrequent emergence of pfcrt alleles in the field.
Candidate predictive biomarkers of cetuximab benefit in triple-negative breast cancer.
Authors: S. Khambata-Ford, J. O'Shaughnessy, D. Brickman, J. D. Jensen, L. Asmar, C. E. Horak
Journal: Journal of Clinical Oncology (2010)

1056 Background: A randomized phase II trial, USOR 04-070, investigated cetuximab (C) plus irinotecan/carboplatin (ICb) vs. ICb alone in metastatic breast cancer (mBC) patients (pts) without subtype restrictions. C improved overall response rate (ORR) only in triple negative (TN) pts (50.6% of total pts): 49% vs. 38% on ICb alone, without a difference in progression-free survival (PFS). To identify pts more likely to benefit from C, EGFR- related candidate biomarkers, including PTEN, EGFR, K-Ras, and PIK3CA, were retrospectively assessed in available specimens. Methods: Of 154 total pts, 124 had evaluable FFPE primary tumor tissue samples. K-Ras and PIK3CA mutations were analyzed by direct sequencing. EGFR and PTEN status was determined by immunohistochemistry (IHC) using the EGFR PharmDx kit and a monoclonal PTEN antibody. Gene/chromosomal copy number alterations are under evaluation globally by array comparative genomic hybridization (aCGH) with Agilent 4x180k arrays. Associations between BC subtype and biomarker status were assessed by chi-square tests. Relationships between biomarker status and PFS, overall survival (OS), and ORR were assessed by log-rank tests per study arm for treatment-specific effects across the total evaluable and the TN populations. Results: K-Ras (exon 2) mutation rate was 5% (n=119). PIK3CA mutations (exons 9 and 20) were present in 17% of samples overall (n=86), with similar rate in TN (17%) and ER+ pts (18%). Rates of EGFR and PTEN-positivity were 47% (n==08) and 48% (n=110), respectively. EGFR positive status was significantly associated with the TN BC subtype (p<0.0001). None of the candidate biomarkers was significantly associated with C benefit in the overall population including all BC subtypes. In TN pts, PTEN-positivity was associated with improved PFS on the C arm (HR=0.40; p=0.04). Conclusions: PTEN-positivity is associated with improved PFS on C in TN mBC. Our prior report (Carey et al, SABCS 2009) had shown that low gene expression levels of alpha-B crystalline (CRYAB) are associated with C benefit in these pts. These biomarkers may be useful for selecting patients that would benefit from C and should be evaluated further. Additional biomarkers may be identified by ongoing aCGH efforts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Authors’ reply to Amitai and Koren
Authors: Helen Dolk, Babak Khoshnood
Journal: BMJ (2016)

Amitai and Koren’s argument about the possible importance of postconceptional folic acid is interesting,1 2 but we would hesitate to call it “another solution” at this stage because this might distract from an effective multistranded preventive strategy.

The evidence that late folic acid (started postconceptionally) can prevent neural tube defects (NTDs) is not yet strong. The Chinese study cited needs to be independently confirmed in another study population because of the many differences between the women who took supplements before or after conception (those in the last group were more likely …
Clinical predictors and risk of optic pathway glioma (OPG) in Neurofibromatosis-1 (NF-1)
Authors: A. R. Mian, E. Schorry, R. Chakraborty, B. Chakraborty, J. P. Perentesis
Journal: Journal of Clinical Oncology (2006)

9016 Background: NF-1 is a progressive disease with wide spectrum of phenotype and unpredictability in clinical course. NF-1 patients are at significantly increased risk for development of a variety of neoplasms that cause morbidity and limited mortality, including OPG. There are limited data identifying risk factors predictive of subsequent OPG development. Objective: To identify key early clinical features which predict subsequent risk for development of OPG. Methods: Case-control study of NF-1 patients with and without OPG from Cincinnati Children’s Hospital NF-1 and Cancer Registries. Predictor variables were clinical risk factors (age at diagnosis of NF-1, race/ethnicity, gender, and history of familial NF-1, macrocephaly, plexiform neurofibroma, developmental delay, seizure disorder,), and the dependent variable was development of OPG by imaging. Patients received screening head MRI at the time of presentation with NF-1. Odds ratios (O.R.) were calculated with 75 cases (NF-1 and OPG) and 215 controls (NF-1 only) and statistically/clinically significant factors were further analyzed by logistic regression method. Results: Prevalence of OPG in NF-1 was 15.6%. Almost half had familial NF-1. Median age at diagnosis of NF-1 was 1.6 yrs (cases) and 2.4 yrs (controls). OPG was diagnosed at median age 4 yrs. Patients with T2 hyperintense lesions on imaging (UBOs) and age 4 years or less at diagnosis of NF-1 were at significantly increased risk of developing OPG (O.R=3.1, p=0.006 and O.R=3.1, p=0.002 respectively). In addition, presence of seizure disorder and developmental delay were borderline significant (O.R=2.8, p=0.07 and O.R=1.7, p=0.04 respectively). Race (Caucasian) appeared to have disease modifying effect on development and progression of OPG. Conclusions: Patients with T2 lesions on presentation MRI, developmental delay, seizures, and age 4 years or less at NF-1 diagnosis appear to be at an increased risk of developing OPG. Caucasian race appears to have a modifying effect on disease progression. Patients with these risk factors may be stratified as “high risk” and may benefit from close surveillance for early detection of OPG. The association of developmental delay and seizures may suggest a pathophysiologic relationship. No significant financial relationships to disclose.
SP0048 Overcoming Barriers to Health Literacy in Ethnic Populations using a Multi-Lingual Interactive Mind-Map
Authors: A. Adebajo
Journal: Annals of the Rheumatic Diseases (2015)

Health Literacy is becoming increasingly recognised as being very important in empowering patients to be active participants in their own healthcare. We have observed that rheumatology patients from ethnic minorities in the United Kingdom may have a number of problems in this regard. Firstly, many of them have low literacy skills. Secondly, they may have little or no understanding of the English Language. Thirdly, there may be cultural barriers to their being able to access health information and navigate healthcare systems. We have identified mindmaps as a way of overcoming these barriers and have been studying the effect of a multi-lingual interactive mindmap in South Asian populations within the United Kingdom. In particular, we have used this tool to provide layered information on osteomalacia for South Asian populations with poor literacy and poor English language skills. Our qualitative studies indicate that this tool is considered by the population to be highly effective and easy to use. Our semi quantitative analyses confirm significant benefit in terms of knowledge with the use of this intervention in the South Asian ethnic minority population studied. We also believe that the use of a multi-lingual interactive mindmap will lead to better concordance and better health outcomes in ethnic minority populations. We are currently evaluating this. In conclusion, we believe that health literacy is a very important contributor to health outcomes in the field of Rheumatology in particular, and health more generally. Preliminary findings from our research indicate that the use of interventions to improve health literacy such as a multi-lingual interactive mindmap is of benefit in patients from ethnic minorities. We also believe that this intervention may benefit to other such disadvantaged groups of people. <h3>Disclosure of Interest</h3> None declared