tbuckley/cabot-search huggingface dataset:
Random allocation or allocation at random? Patients' perspectives of participation in a randomised controlled trial
Authors: K. Featherstone, J. L Donovan
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objectives</b> To explore trial participants9 understandings of randomisation. <b>Design</b> In this exploratory study, which used qualitative research methods, in-depth, semistructured interviews were carried out with 20 participants from the CLasP randomised controlled trial. Interviews were recorded on audio tape and fully transcribed. Data were analysed by comparing transcripts and describing emergent themes, using a grounded theory approach. <b>Setting</b> The CLasP study comprises three linked multicentre, pragmatic randomised controlled trials evaluating the effectiveness and cost effectiveness of laser therapy, standard surgery, and conservative management for men with lower urinary tract symptoms or urinary retention, or both, related to benign prostatic disease. <b>Subjects</b> 20 participants in the CLasP study were interviewed. Sampling was purposeful: men were included from each of the treatment arms, the two major centres, and at different points in the trial. <b>Interventions and outcome measures</b> Interviews used a checklist of topics to encourage participants to describe their experiences. Narratives concerning randomisation were compared to identify common themes, retaining the context of the discussion to allow detailed interpretation. <b>Results</b> Most participants recalled and described aspects of randomisation, such as the involvement of chance, comparison, and concealed allocation. Many found the concept of randomisation difficult, however, and developed alternative lay explanations to make sense of their experiences. Inaccurate patient information and lay interpretations of common trial terms caused confusion. <b>Conclusions</b> The provision of clear and accurate patient information is important, but this alone will not ensure consistent interpretation of concepts such as randomisation. Patients may need to discuss the purposes of randomisation in order to understand them fully enough to give truly informed consent.
HYPERCALCEMIA OF MALIGNANCY: The Central Role of Parathyroid Hormone-Related Protein
Authors: John J. Wysolmerski, Arthur E. Broadus
Journal: Annual Review of Medicine (1994)

▪ Abstract Hypercalcemia is the most common metabolic complication of cancer. Malignancy-associated hypercalcemia (MAHC) can be divided into two syndromes, humoral hypercalcemia of malignancy (HHM) and local osteolytic hypercalcemia (LOH), based on whether a circulating hormone or local paracrine factors mediate accelerated bone resorption. Over the past decade, studies have shown that parathyroid hormone-related protein is the cause of the HHM syndrome, and recent data suggest that this protein may also play a paracrine role in some patients with local osteolytic hypercalcemia. Study of the regulation of parathyroid hormone-related protein gene expression is beginning to shed some light on the molecular mechanisms responsible for this common clinical problem.
Government says Public Health England should challenge it over health issues when necessary
Authors: A. O'Dowd
Journal: BMJ (2014)

The agency that heads up public health in England is right to challenge the government over issues that it believes are important, and no subjects are “out of bounds” for debate, the Department of Health has said.

This week the department published its official response1 to the parliamentary health select committee’s report2 on Public Health England, published in February. In that report, the committee said that the agency had so far …
Effect of Raloxifene on Prevention of Dementia and Cognitive Impairment in Older Women: The Multiple Outcomes of Raloxifene Evaluation (MORE) Randomized Trial
Authors: Kristine Yaffe, Kathryn Krueger, Steven R. Cummings, Terri Blackwell, Victor W. Henderson, Somnath Sarkar, Kristine Ensrud, Deborah Grady
Journal: American Journal of Psychiatry (2005)

This investigation examined whether raloxifene, a selective estrogen receptor modulator, affects the risk for Alzheimer's disease.The Multiple Outcomes of Raloxifene Evaluation was a randomized, placebo-controlled trial among postmenopausal women with osteoporosis. The effect of raloxifene (60 or 120 mg/day) on vertebral fractures was the primary outcome. Development of mild cognitive impairment and dementia was a secondary outcome. Women were given clinical and cognitive evaluations at baseline and annually. After 3 years, among the 5,386 women enrolled at participating sites, those who had clinical symptoms of dementia or scored in the lowest 10th percentile on cognitive screening were evaluated by a blinded dementia specialist and had brain scans and laboratory tests to evaluate dementia etiology. Dementia was diagnosed by a blinded adjudication committee.Of the 5,386 women, 5,153 (95.7%) were classified as cognitively normal, 181 (3.4%) had mild cognitive impairment, and 52 (1.0%) had dementia, 36 with Alzheimer's disease. Compared to those taking placebo, women receiving 120 mg/day of raloxifene had a 33% lower risk of mild cognitive impairment (relative risk, 0.67; 95% confidence interval [CI], 0.46-0.98) and somewhat lower risks of Alzheimer's disease (relative risk=0.52, 95% CI=0.22-1.21) and any cognitive impairment (relative risk=0.73, 95% CI=0.53-1.01). Risks of mild cognitive impairment, Alzheimer's disease, and any impairment were not significantly different in the group taking 60 mg/day of raloxifene.Raloxifene at a dose of 120 mg/day, but not 60 mg/day, resulted in reduced risk of cognitive impairment in postmenopausal women.
Sir Melville Arnott Douglas Arthur Longmore Ashworth Francis Henry Doyle Norman Peter Henry Gibbs Aaron Lask Albert Keith Pittman Elizabeth Ann Ryan Dudley James Toomey Norman Victor Wilkinson Enid Young
Authors: A. Geddes, I. Brown, M. Mynott, R. Steiner, P. Gibbs, B. Lask, S. Mitchell, D J D Perrins, D. Evans, A L G Smith, P Anderson
Journal: BMJ (1999)

He was one of the first full time clinical professors in English medical schools.In 1971 he resigned from the chair of medicine to take up the newly established British Heart Foundation chair of cardiology in Birmingham, where he remained until he retired in 1974.A member of the Territorial Army before the war he served in the Royal Army Medical Corps from 1939 to 1945 in South East Asia, north Africa (including the Siege of Tobruk), and northwest Europe.He was the last British officer to leave Shanghai and just escaped internment by the Japanese and was one of
Conservative Treatments of Intraocular Retinoblastoma
Authors: Livia Lumbroso-Le Rouic, Isabelle Aerts, Christine Lévy-Gabriel, Rémi Dendale, Xavier Sastre, Marc Esteve, Bernard Asselain, Danielle Bours, François Doz, Laurence Desjardins
Journal: Ophthalmology (2008)
In vitro bioassays for androgens and their diagnostic applications
Authors: P. Roy, M. Alevizaki, I. Huhtaniemi
Journal: Human Reproduction Update (2007)

Androgen levels are measured in today's clinical practice almost exclusively by immunoassays. The androgen that is most frequently determined is testosterone (T), but sometimes also the levels of other testicular, ovarian and adrenal androgens such as 5α-dihydrotestosterone, androstenedione, dehydroepiandrosterone and its sulphate may be determined. In many instances, especially when androgen levels are low (as in women and children), the quality of the immunomeasurements is insufficient and the correlation between hormone levels and clinical symptoms is poor. One alternative to improve the clinical relevance of androgen measurements is provided by the recently developed in vitro bioassays of total androgen bioactivity in serum. These assays are not yet ready for routine laboratory diagnostics, but they provide a useful tool for clinical research in disturbances of androgen production. Another application of these assays is the screening for androgenic and antiandrogenic activity in chemical compounds, environmental samples and when suspecting androgen abuse. The purpose of this article is to introduce the current problems of androgen measurement by immunoassays, to describe the novel in vitro bioassay techniques and to review the current information on their application in clinical research.
Sociopathy, evolution, and the brain
Authors: Ernest S. Barratt, Russell Gardner
Journal: Behavioral and Brain Sciences (1995)

Abstract We propose that Mealey's model is limited in its description of sociopathy because it does not provide an adequate role for the main organ mediating genes and behavior, namely, the brain. Further, on the basis of our research, we question the view of sociopaths as a homogeneous group.
Frequent <i>PVT1</i> Rearrangement and Novel Chimeric Genes <i>PVT1-NBEA</i> and <i>PVT1-WWOX</i> Occur in Multiple Myeloma with 8q24 Abnormality
Authors: Hisao Nagoshi, Tomohiko Taki, Ichiro Hanamura, Masakazu Nitta, Takemi Otsuki, Kazuhiro Nishida, Keiko Okuda, Natsumi Sakamoto, Satoru Kobayashi, Mio Yamamoto-Sugitani, Yasuhiko Tsutsumi, Tsutomu Kobayashi, Yosuke Matsumoto, Shigeo Horiike, Junya Kuroda, Masafumi Taniwaki
Journal: Cancer Research (2012)

Chromosome 8q24 rearrangements are occasionally found in multiple myeloma and are associated with tumor progression. The 8q24 rearrangements were detected by FISH in 12 of 54 patients with multiple myeloma (22.2%) and in 8 of 11 multiple myeloma cell lines (72.7%). The breakpoints of 8q24 in 10 patients with multiple myeloma and in all multiple myeloma cell lines were assigned to a 360 kb segment, which was divided into 4 regions: approximately 120 kb centromeric to MYC (5' side of MYC), the region centromerically adjacent to PVT1 (~ 170 kb region, including MYC, of 5' side of PVT1), the PVT1 region, and the telomeric region to PVT1. PVT1 rearrangements were most common and found in 7 of 12 patients (58.3%) and 5 of 8 cell lines (62.5%) with 8q24 abnormalities. A combination of spectral karyotyping (SKY), FISH, and oligonucleotide array identified several partner loci of PVT1 rearrangements, such as 4p16, 4q13, 13q13, 14q32, and 16q23-24. Two novel chimeric genes were identified: PVT1-NBEA in the AMU-MM1 cell line harboring t(8;13)(q24;q13) and PVT1-WWOX in RPMI8226 cell line harboring der(16)t(16;22)ins(16;8)(q23;q24). The PVT1-NBEA chimera in which PVT1 exon 1 was fused to NBEA exon 2 and the PVT1-WWOX in which PVT1 exon 1 was fused to WWOX exon 9 were associated with the expression of abnormal NBEA and WWOX lacking their N-terminus, respectively. These findings suggest that PVT1 rearrangements may represent a novel molecular paradigm underlying the pathology of 8q24 rearrangement-positive multiple myeloma.
The Stool Antigen Test for Detection of <i>Helicobacter pylori</i> after Eradication Therapy
Authors: Dino Vaira, Nimish Vakil, Marcello Menegatti, Ben van't Hoff, Chiara Ricci, Luigi Gatta, Giovanni Gasbarrini, Mario Quina, Jose M. Pajares Garcia, Arie van der Ende, Rene van der Hulst, Marcello Anti, Cristina Duarte, Javier P. Gisbert, Mario Miglioli, Guido Tytgat
Journal: Annals of Internal Medicine (2002)

Current noninvasive tests to confirm the eradication of Helicobacter pylori must be performed 4 weeks or more after eradication therapy is completed.To determine whether the stool antigen test, a relatively new noninvasive test for H. pylori, administered at various times after eradication therapy correctly identifies persons with persistent H. pylori infection.Prospective blinded study.Six clinical centers in the United States and Europe.84 H. pylori --infected patients undergoing endoscopy for upper abdominal symptoms.At baseline and on day 35 after the completion of triple eradication therapy, all patients underwent endoscopy with histologic examination, rapid urease test and culture, urea breath test, and a stool antigen test. The stool antigen test was also performed on days 3, 7, 15, 21, 28, and 35 after completion of therapy.Compared with the gold-standard endoscopic tests on day 35 after antimicrobial therapy, the urea breath test had a sensitivity of 94% (95% CI, 71% to 100%) and a specificity of 100% (CI, 94% to 100%). The stool antigen test had a sensitivity of 94% (CI, 71% to 100%) and a specificity of 97% (CI, 89% to 100%). On day 7 after treatment, the stool antigen test was predictive of eradication (positive predictive value, 100% [CI, 69% to 100%]; negative predictive value, 91% [CI, 82% to 97%]).A positive result on the stool antigen test 7 days after completion of therapy identifies patients in whom eradication of H. pylori was unsuccessful.
‘11 for Health’, a football-based health education programme for children: a two-cohort study in Mauritius and Zimbabwe
Authors: Colin W Fuller, Astrid Junge, Cadrivel Dorasami, Jeff DeCelles, Jiri Dvorak
Journal: British Journal of Sports Medicine (2011)

Objectives To implement and assess Fédération Internationale de Football Association Medical Assessment and Research Centre's ‘11 for Health’ football-based health education programme for children. Design Prospective, 2-cohort study. Setting In-school groups (Mauritius); out-of-school groups (Zimbabwe). Participants Mauritius: 389 children, aged 12–15 years; Zimbabwe: 395 children, aged 10–14 years. Intervention Eleven 90-min sessions, each divided into two 45-min halves of Play Football (focusing on one football skill) and Play Fair (focusing on one health issue). Main outcome measures 30-item questionnaire implemented pre and postintervention to assess children's health knowledge; six-item questionnaire implemented postintervention to assess children's views about the ‘11 for Health’ programme. Results Mean pre and postintervention health knowledge scores were greater in Mauritius (pre: 69.3%; post: 87.1%) than Zimbabwe (pre: 57.8%; post: 76.2%) but the mean gain in health knowledge was greater in Zimbabwe (18.4%) than Mauritius (17.8%). There were few significant differences in the outcomes for boys and girls in both countries. The ‘11 for Health’ programme was received positively by the children in both countries and there were no significant differences in the views of boys and girls in either country. Conclusions The study demonstrated that it was possible to achieve significant increases in children's knowledge for all health messages by implementing the ‘11 for Health’ programme in a school-based setting in collaboration with a national Football Association and in an out-of-school setting in collaboration with a non-government organisation. Based on these positive results, the authors recommend that the programme be widely implemented in Africa in co-operation with government and non-government organisations.
Andersen mutations of KCNJ2 suppress the native inward rectifier current in a dominant-negative fashion
Authors: P LANGE, F ER, N GASSANOV, U HOPPE
Journal: Cardiovascular Research (2003)

Objective: The Andersen's syndrome is a hereditary disease, which is characterized by cardiac arrhythmias, periodic paralysis and dysmorphic features. Recently, mutations of the KCNJ2 gene, which encodes the inward rectifying potassium channel subunit Kir2.1, have been identified in affected individuals. However, the functional effects of these mutations have not yet been fully elucidated. Methods and Results: To clarify this situation we generated known Andersen disease mutants of KCNJ2 which did not yield any measurable K+ currents in CHO cells indicating that the Andersen mutants failed to form functional homomultimeric complexes. EGFP-tagged KCNJ2 wild-type and mutant channels distributed in a similar homogeneous pattern in the cell membrane suggesting that protein trafficking was not altered by the Andersen mutations but rather implicating that the mutations rendered the KCNJ2 channel non-functional. In heterologous coexpression experiments the Andersen mutants exerted a dominant-negative effect on wild-type KCNJ2. However, the extent of suppression varied between the different KCNJ2 mutants. Given our results in CHO cells, we expressed the disease mutant KCNJ2-S136F in neonate rat cardiomyocytes using adenoviral gene transfer to test the effect of Andersen mutants on native IK1. IK1 density was indeed significantly reduced in KCNJ2-S136F-infected cells (n = 9) compared to control cells (n = 9) over a voltage range from −70 to −150 mV (P<0.05). Conclusion: These results support that Kir2.x channels are a critical component of native IK1 in neonate rat cardiomyocytes and that a dominant-negative suppression of IK1 in native cells is the pathophysiological correlate of the Andersen's syndrome.
CSF1R Signaling Blockade Stanches Tumor-Infiltrating Myeloid Cells and Improves the Efficacy of Radiotherapy in Prostate Cancer
Authors: Jingying Xu, Jemima Escamilla, Stephen Mok, John David, Saul Priceman, Brian West, Gideon Bollag, William McBride, Lily Wu
Journal: Cancer Research (2013)

Abstract Radiotherapy is used to treat many types of cancer, but many treated patients relapse with local tumor recurrence. Tumor-infiltrating myeloid cells (TIM), including CD11b (ITGAM)+F4/80 (EMR1)+ tumor-associated macrophages (TAM), and CD11b+Gr-1 (LY6G)+ myeloid-derived suppressor cells (MDSC), respond to cancer-related stresses and play critical roles in promoting tumor angiogenesis, tissue remodeling, and immunosuppression. In this report, we used a prostate cancer model to investigate the effects of irradiation on TAMs and MDSCs in tumor-bearing animals. Unexpectedly, when primary tumor sites were irradiated, we observed a systemic increase of MDSCs in spleen, lung, lymph nodes, and peripheral blood. Cytokine analysis showed that the macrophage colony-stimulating factor CSF1 increased by two-fold in irradiated tumors. Enhanced macrophage migration induced by conditioned media from irradiated tumor cells was completely blocked by a selective inhibitor of CSF1R. These findings were confirmed in patients with prostate cancer, where serum levels of CSF1 increased after radiotherapy. Mechanistic investigations revealed the recruitment of the DNA damage-induced kinase ABL1 into cell nuclei where it bound the CSF1 gene promoter and enhanced CSF1 gene transcription. When added to radiotherapy, a selective inhibitor of CSF1R suppressed tumor growth more effectively than irradiation alone. Our results highlight the importance of CSF1/CSF1R signaling in the recruitment of TIMs that can limit the efficacy of radiotherapy. Furthermore, they suggest that CSF1 inhibitors should be evaluated in clinical trials in combination with radiotherapy as a strategy to improve outcomes. Cancer Res; 73(9); 2782–94. ©2013 AACR.
Therapy for Recurrent High-Grade Gliomas: Does Continuous Dose-Intense Temozolomide Have a Role?
Authors: Patrick Y. Wen
Journal: Journal of Clinical Oncology (2010)

High-grade gliomas (HGG) are the most common malignant primary brain tumors, with an annual incidence in the United States of approximately 15,000 patients. 1 Currently, standard therapy for glioblastomas (WHO grade 4 gliomas) involves maximal safe surgical resection followed by radiotherapy with concomitant and adjuvant temozolomide. 2-4 Despite optimal therapy, these tumors inevitably recur with a median time-to-tumor progression of approximately 6.9 months, and median survival of only 15 months. 2 For anaplastic gliomas (WHO grade 3 gliomas) treatment with radiotherapy and chemotherapy results in a median time-to-tumor progression of approximately 1.2 to 2.6 years and a median survival of 2 to 7 years. 3,5,6 Treatment options for recurrent HGG are limited. Bevacizumab produces response rates of approximately 20% to 40% in glioblastomas and increases 6-month progression-free survival (PFS6) to approximately 30% to 50%. 7,8 Based on these results, bevacizumab recently received accelerated approval from the US Food and Drug Administration for treatment of recurrent glioblastomas. Similar results have been obtained with anaplastic gliomas. 9 The results of other therapies for recurrent HGG have been generally disappointing, with PFS6 of only 9% to 16%. 10,11 Nitrosoureas, such as lomustine and carmustine, increase PFS6 to approximately 21% to 24%, 12,13 but most other chemotherapeutic agents have
Admissions Integrity Preserved
Authors: Terrence S. Carden
Journal: JAMA (1978)

The recent threat to the integrity of the medical school admissions process posed by the US Congress has eased, temporarily at least, with the passage of a bill that all but rescinds an earlier legislative edict that attempted to force acceptance of transfer students from foreign medical schools. The original law, passed last year, had been contested vigorously by the medical schools, 14 of which were willing to forfeit substantial federal assistance rather than accept such transfer students. Other schools in more precarious financial straits were faced with the decision of compromising their integrity or being overwhelmed by their creditors.  In passing the original law, Congress was responding to numerous pressures, the most prominent coming from the parents and friends of American students studying in foreign medical schools with the hope of returning home to conclude their studies and enter practice. The proposal also seemed like an easy way to
Magnification chromoendoscopy for the detection of intestinal metaplasia and dysplasia in Barrett's oesophagus
Authors: P Sharma, A P Weston, M Topalovski, R Cherian, A Bhattacharyya, R E Sampliner
Journal: Gut (2002)

<b>Background:</b> The presence of intestinal metaplasia (IM) in the columnar lined distal oesophagus defines Barrett’s oesophagus with the risk of future malignant transformation. The distribution of both IM and dysplasia (low grade (LGD) and high grade (HGD)) within the columnar lined oesophagus is patchy and mosaic requiring random biopsies. Techniques that could help target areas of high yield within Barrett’s mucosa would be helpful. <b>Aim:</b> To study the utility of high magnification chromoendoscopy (MCE) in the detection of IM, LGD, and HGD in patients with Barrett’s oesophagus. <b>Methods:</b> Consecutive patients detected with columnar mucosa in the distal oesophagus were studied using an Olympus magnification endoscope (GIF-Q16OZ, 115×). The distal oesophagus was sprayed with indigo carmine solution and the oesophageal columnar mucosa patterns were noted under high magnification and targeted for biopsy. All biopsies were read by pathologists blinded to the endoscopic findings. <b>Results:</b> Eighty patients with suspected Barrett’s oesophagus (that is, columnar lined distal oesophagus) were studied: mean age 62.7 years (range 35–81). Mean length of columnar mucosa was 3.7 cm (range 0.5–17). Three types of mucosal patterns were noted within the columnar mucosa after spraying indigo carmine and using MCE: ridged/villous pattern, circular pattern, and irregular/distorted pattern. The yield of IM on target biopsies according to the patterns was: ridged/villous 57/62 (97%) and circular 2/12 (17%). Six patients had an irregular/distorted pattern and all had HGD on biopsy (6/6 (100%)). Eighteen patients had LGD on target biopsies; all had the ridged/villous pattern. All patients with long segment Barrett’s were identified using MCE whereas 23/28 patients (82%) with short segment Barrett’s had the ridged/villous pattern. <b>Conclusions:</b> MCE helps visually identify areas with IM and HGD having specific patterns but not patients with LGD (appear similar to IM). MCE may be a useful clinical tool for the increased detection of patients with IM as well as for surveillance of patients for the detection of HGD. If these preliminary results are validated, MCE would help identify high yield areas, potentially eliminating the need for random biopsies.