tbuckley/cabot-search huggingface dataset:
Soundings: Ancient resentments
Authors: Kevin Barraclough
Journal: BMJ (2002)

The comment arched obliquely across the discussion and slightly winded me with its weight of unspoken assumptions: “Of course, nurses are not doctors' handmaidens, you know.” I blinked and spluttered a little as the nursing manager eyed me with a certainty born of our four minute acquaintance. She clearly regarded the comment as justified, not on the basis of any knowledge of my views, but because I was a doctor and therefore likely to oppress nurses. My protestations of innocence were incoherent and defensive, and merely hardened her steely gaze.

I remember the first time I heard this “handmaiden” phrase. I was a newly qualified house officer and had been deputised by my colleagues to approach a rather fearsome nursing manager about the knotty question of nurses giving intravenous drugs. The nursing manager had declared a few weeks before that giving intravenous drugs was not part of the nursing role, which was a bit of a blow for those of us working a one in two rota. She was rather a frightening lady who believed in speaking her mind—particularly if it was unpleasant. As is often the case, her stated aim of calling a spade a spade was actually a euphemism for being rude. My argument that the nurses were working a 40 hour week to our 120 hour week was dismissed with a tirade which I presumed was born of centuries of injustice. I asked the advice of a senior colleague. Don't meddle in the affairs of dragons, he said, because you are small and crunchy and taste good with ketchup.

Certainly, 20 years ago I could see where the manacles of such resentments were forged. In my first weeks of walking the wards of a London teaching hospital there were several consultants vying to outdo each other in unconscious parodies of Sir Lancelot Spratt. But already then they were a dying breed. I remember a decade later the sad resignation of a gentle cardiologist nearing retirement. He had given up trying to persuade the ward sister to allow a nurse to accompany him on his ward round.

I had thought that these perceived resentments had faded into history, but it is surprising how persistent they seem to be in the career nurse manager. I'm sure that doctors are largely responsible for this, but am equally sure it remains a significant unacknowledged obstacle to getting this mess we call the NHS sorted out.
OC-101 Lymph node positivity in patients with anal cancer treated in the modern era: prognostic impact and patterns of locoregional relapse (L‐nuance)
Authors: H Sekhar, R Kochhar, L Malcomson, MP Saunders, B Chakrabarty, PE Fulford, MS Wilson, ST O’Dwyer, AG Renehan
Journal: Gut (2015)

<h3>Introduction</h3> Chemo-radiotherapy (CRT) is the first line treatment in patients with anal squamous cell carcinoma (ASCC). Clinical lymph node positivity (LN+) is considered an adverse prognosticator. Accurate lymph node staging impacts on treatment, such that in LN+ patients, lymphatic fields are treated with prophylactic phase I wide volume radiotherapy. Modern imaging modalities, namely magnetic resonance imaging (MRI) and PET-CT scanning increase sensitivity to detect LN+, but It is unclear whether enhanced pre-treatment staging impacts upon oncological outcome. <h3>Method</h3> From 1990 to 2014 we characterised the pattern of changes in the detection rates of LN+ in patients with ASCC through a dedicated anal cancer MDT serving a population of 3 million. We divided time periods as: (i) pre-MRI era; (ii) MRI era; and (iii) MRI + PET-CT era. In patients receiving curative CRT, we determined actuarial rates for loco-regional and inguinal relapses, and cancer-specific survival (CSS), using Kaplan-Meier curves. Imaging modalities were compared using log-rank tests, and Cox multivariate models that also conditioned for period and cohort effects. <h3>Results</h3> From 971 patients with new ASSC, 550 were treated with CRT [M, F: 207:343, median age (range): 61 (29–89)]. In the pre-MRI era (pre-2004), LN+ was identified in 18% (36/200); with the use of MRI the detection rate increased to 34% (62/185); and further increased to 48% (58/120) with the use of MRI and PET-CT in combination (post-2011) (p &lt; 0.001). In multivariate models, T stage was the only other independent determinant of LN+ (T1 2% (1/55) vs T4 55% (55/100), p &lt; 0.001). The secular trends were associated with an altered prognostic profile. For the pre-MRI era the 5 year survival of LN+ and LN- was 51% and 78%; for the post-MRI era the 5 year survival was 75% and 85% for LN+ and LN- respectively. Additionally, there was loss of discrimination between the two prognostic categories with the significant difference in survival between the groups during the pre-MRI era being lost in the MRI-era (p = 0.0014 and 0.089 respectively) – a Will Roger phenomenon. There were minor improvements in 3-year loco-regional relapse rates over the time periods. The overall rate of inguinal nodal relapse was low (3%). <h3>Conclusion</h3> MRI and PET scans improve pre-treatment staging in anal cancer although precise characterisation of the specific lymphatic fields involved needs further evaluation. Demonstration of the Will Roger’s effect challenges the prognostic value of pre-treatment nodal status in anal cancer and current treatment algorithms. This study was generously supported by the BDRF. <h3>Disclosure of interest</h3> None Declared.
Abstract 235: SNORD76, a box C/D snoRNA, acts as a tumor suppressor in glioblastoma
Authors: Luyue chen, Lei Han, kailiang zhang, jianwei wei, peiyu pu, jianning zhang, chunsheng kang
Journal: Cancer Research (2015)

Abstract Background Gliomblastoma (GBM) is associated with disproportionately high morbidity and mortality, reflecting the need to develop new diagnostic and therapeutic targets for this disease. Recently, accumulating evidence has suggested that small nucleolar RNAs (snoRNAs) are gaining prominence and are more actively involved in tumorigenesis than previously thought. However, no report concerning the implication of snoRNAs in glioma has been published to date. Methods The expression of SNORD76 and its host gene, GAS5, in glioma patients were evaluated by quantitative PCR. Flow cytometry was used to analyze to cell cycle distribution after SNORD76 over-expression. After SNORD76 over-expression in GBM cell lines, cell growth and anti-tumor effect were investigated in vitro and in vivo. Results SNORD76 expression was selectively decreased in glioblastoma (WHO grade IV) compared with low grades glioma (WHO grade II and III). Forcibly expressed SNORD76 inhibited proliferation and anchorage-independent growth of glioma cells. Flow cytometry demonstrated that enforced SNORD76 expression arrested the cells at S phase of the cell cycle. Western blot Cell cycle-associated proteins cyclin A1, cyclin B1 and p107 were down-regulated after SNORD76 over-expression, while the expression of Rb and pRb increased. The growth of orthotopic tumors was significantly inhibited by forced expression of SNORD76. Conclusion In summary, engineered restoration of SNORD76 caused marked repression of glioma growth in vitro and in vivo. The tumor suppression could be achieved at least partially through inducing S phase arrest in an Rb-associated manner. Thus, SNORD76 may act as a potential tumor suppressive gene in the development and progression of glioblastoma and may be a potential specific glioblastoma biomarker. Citation Format: Luyue chen, Lei Han, kailiang zhang, jianwei wei, peiyu pu, jianning zhang, chunsheng kang. SNORD76, a box C/D snoRNA, acts as a tumor suppressor in glioblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 235. doi:10.1158/1538-7445.AM2015-235
Depression of the Tuberculin Reaction by Viral Vaccines
Authors: Jacob A. Brody, Theresa Overfield, Laurel M. Hammes
Journal: New England Journal of Medicine (1964)

TEMPORARY depression of the tuberculin reaction was reported first by Pirquet1 in 1908 in a child with measles. Since that time depressions of the tuberculin reaction have been noted to follow many infectious diseases, including pertussis,2 typhus,3 scarlet fever,4 influenza5 and rubella.6 This phenomenon also occurs during terminal tuberculosis,7 after radiation8 and with high doses of steroids.9 Recently, through direct suggestion under hypnosis, depression of tuberculin sensitivity was elicited.10 Because measles causes a depression of tuberculin reaction, and possibly a worsening of clinical tuberculosis,11 12 13 several investigators have studied the effects of measles vaccines on tuberculin sensitivity. Mellman and Wetton14 showed . . .
Making sense of the noise?
Authors: Stephen Aspinall
Journal: British Journal of Sports Medicine (2016)

We are bombarded with information on a daily basis and clinicians subscribe to multiple information sources; some are more opinion-based and author-biased and others more rooted in hard to understand academia with sometimes unfathomable practical applications. The multiple professions and variety of researchers that form the BJSM community offer a refreshing platform for making some sense of the vast amounts of information on offer.

The multichannel BJSM content helps us focus on what is important and even if it does not always give us the answers we want, it gives us direction and helps us to understand the questions we need to ask. Systematic review hacks for the sports and exercise clinician ( see page 447 ) by Dr Clare Ardern is a ‘go to’ piece for many practitioners, especially those working alone or in …
Widow's fight for husband's sperm
Authors: R. Winston
Journal: BMJ (1996)

Widow's fight for husband's sperm Intervention by BMA's ethics committee was ill judged EDrTOR,-The involvement of the BMA's ethics committee in the recent decision by the Human Fertilisation and Embryology Authority to refuse to allow Mrs Diane Blood to be inseminated with sperm obtained from her husband after his death was ill judged.'In a letter to the authority Dr Stuart Horner, the chairman of the ethics committee, said, "ethically, whether the consent is in writing or given orally is irrelevant.The essential issue is the quality of that consent."No reasonable person would be likely to disagree with that sensible statement.However, he went on to say, "From the information portrayed in the media there is no evidence that Mr Blood had clearly thought through the issue."Many people are extremely concerned that the ethics committee made representations to the authority on the basis of evidence purely derived from the media.As it happens, there is ample evidence that both Mr and Mrs Blood had con- sidered this issue extremely seriously before Mr Blood's sudden death.
Management of Cancer of the Prostate
Authors: Alastair J.J. Wood, William J. Catalona
Journal: New England Journal of Medicine (1994)

Prostate cancer is the second leading cause of death from cancer among men; 25 percent of men with prostate cancer die of the disease1. Moreover, many patients who do not die of prostate cancer require treatment to ameliorate symptoms such as pain, bleeding, and urinary obstruction. Thus, prostate cancer is also a major cause of suffering and of health care expenditures.The high rate of mortality from prostate cancer may be due to late detection. In recent studies, screening for prostate cancer has combined the measurement of serum prostate-specific antigen (PSA) -- the most accurate single test for the . . .
Problems with orders for medication as needed
Authors: F J Ayd
Journal: American Journal of Psychiatry (1985)

The safety of an order for medication as needed depends on assumptions and knowledge that may or may not accompany that order. Physicians should consider carefully the need for prescribing potent medications on an as-needed basis for newly admitted patients, particularly if these patients have not been examined, their histories are unknown, and no diagnosis has been established. In addition, the language of such orders should leave as little as possible to chance. Interpretation of orders should not be left to the discretion of staff members who may be inexperienced in the administration of medications that require frequent monitoring and astute interpretation of side effects.
IgE Casein/IgE Î2-Lactoglobulin in Gastrointestinal Phenotype of Cow's Milk Allergy
Authors: Victor Matheu, Paloma Poza-Guedes, Inmaculada Sanchez-Machin, Yvelise Barrios, Andres Franco, Ruperto Gonzalez
Journal: Journal of Allergy and Clinical Immunology (2016)
Pericarditis in Infection Due to Coxsackie Virus Group B, Type 3
Authors: J. Frederick Bell, Armon Meis
Journal: New England Journal of Medicine (1959)

WEINSTEIN1 has reported a case of acute benign pericarditis associated with infection due to Coxsackie virus Group B, Type 5. Evidence for the etiology was based upon a marked drop in titer of complement-fixing antibodies in serum specimens obtained consecutively after infection. Movitt et al.2 have described a case of benign pericarditis caused by Coxsackie virus Group B, Type 3. Virus was isolated from the stool in this case, and earlier samples of serum permitted the demonstration of a rise in antibody titer. A case of pleurodynia with associated pericarditis caused by this type is described below.Case ReportA . . .
Chromosome Aberrations in 2159 Consecutive Newborn Babies
Authors: F. Sergovich, G. H. Valentine, A. T. L. Chen, R. A. H. Kinch, M. S. Smout
Journal: New England Journal of Medicine (1969)

Preliminary results of chromosome studies on cultured umbilical-cord-blood leukocytes from a consecutive series of 2159 infants born during a year indicated that gross chromosome abnormalities were present in 0.48 per cent (cultures were successful in 1066 males and 1015 females, representing 96.3 per cent ascertainment). These included four infants with XYY, one with XXY and one with D/D translocation trisomy (all male), as well as two with regular trisomy 21, one with D/D balanced translocation and one with cri du chat (all female). These results suggest that D/D translocation heterozygosis will be found in random human populations with a rate of at least 1 in 1000 and probably represents the most frequent type of chromosomal rearrangement. The XYY condition appears in the order of 1 in 250 males. This may represent the most common form of aneuploidy in human beings.
Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes
Authors: Glen I. Spielmans, Margit I. Berman, Eftihia Linardatos, Nicholas Z. Rosenlicht, Angela Perry, Alexander C. Tsai
Journal: PLoS Medicine (2013)

In a systematic review and meta-analysis, Glen Spielmans and colleagues find that adjunctive atypical antipsychotic medications are associated with small-to-moderate improvements in depressive symptoms in patients with depression, but there is little evidence for improvement on measures of quality of life, and these medications are linked to adverse events such as weight gain.
Case 21-2011
Authors: Alice T. Shaw, David G. Forcione, Subba R. Digumarthy, A. John Iafrate
Journal: New England Journal of Medicine (2011)

A 31-year-old man was seen at this hospital because of dysphagia and a mediastinal mass compressing the esophagus. CT images showed gastrohepatic and subcarinal lymphadenopathy and multiple lung nodules. A diagnostic procedure was performed, and management decisions were made.
Parainfluenza Virus Respiratory Infection after Bone Marrow Transplantation
Authors: Christine H. Wendt, Daniel J. Weisdorf, M. Colin Jordan, Henry H. Balfour, Marshall I. Hertz
Journal: New England Journal of Medicine (1992)

Pneumonia complicates about half of all bone marrow transplantations, and in about a third of the cases no specific cause is identified. Although parainfluenza virus is a common cause of respiratory infection in normal children, its role in transplant recipients is unknown.We describe the incidence and clinical course of parainfluenza infection among the 1253 recipients of bone marrow transplants at our center from 1974 through 1990. We performed viral cultures on all such recipients who had manifestations of a viral infection or fever without apparent cause.Among the 1253 patients, we found 27 (2.2 percent) who had parainfluenza virus infection as demonstrated by culture (12 of 580 adults and 15 of 673 children). Eight of these patients had only upper respiratory tract involvement, all of whom had positive nasopharyngeal cultures. Of the remaining 19, 8 had symptoms of both upper and lower respiratory tract involvement, and 11 had only lower respiratory involvement, of whom only 6 had positive nasopharyngeal cultures. Four required bronchoalveolar lavage for diagnosis. A median of nine days elapsed from the onset of symptoms until the culture became positive, and overall only 33 of 118 cultures obtained were positive. Respiratory failure developed in 6 of the 19 patients with lower respiratory tract involvement, and all died.Parainfluenza virus is a cause of serious lower respiratory tract involvement in both adults and children who undergo bone marrow transplantation. Given the insensitivity of current culturing techniques, it may be underdiagnosed.
Extended Therapy with Intravenous Arginine Butyrate in Patients with β-Hemoglobinopathies
Authors: Graham D. Sher, Gordon D. Ginder, Jane Little, Suya Yang, George J. Dover, Nancy F. Olivieri
Journal: New England Journal of Medicine (1995)

Enhanced production of fetal hemoglobin lessens the severity of β-thalassemia and sickle cell disease. Intravenous infusion of arginine butyrate can increase the number of reticulocytes containing fetal hemoglobin in patients with these disorders, and it has induced a substantial increase in hemoglobin in one patient with thalassemia. We therefore tested the efficacy of this agent in patients with β-hemoglobinopathies.
Abstract B42: Hope for a future: Conditional survival estimates for childhood cancer in Australia, 2002-2011
Authors: Danny Youlden, Peter Baade, Andrew Hallahan, Patricia Valery, Adele Green, Joanne Aitken
Journal: Cancer Research (2016)

Abstract Purpose: Conditional survival rates provide a more realistic assessment of long-term prognosis than survival rates calculated from the date of diagnosis because they take into account the time that a patient has already remained alive following diagnosis. However, estimates of conditional survival are scarce for childhood cancer. Here we provide results from a national population-based childhood cancer registry by diagnostic group, age at diagnosis and stage of cancer. Methods: De-identified population-based data were obtained from the Australian Paediatric Cancer Registry for children aged 0-14 years diagnosed with cancer between 1983 and 2010. Mortality status was followed up to the end of 2011. The hybrid period method was used to calculate relative survival estimates for those who were at risk during the period 2002 to 2011. Conditional survival was then obtained from the ratio of the relative survival estimates at different time points. Results: A total of 13,537 children were eligible for inclusion in the study. Five-year survival for all childhood cancers combined improved from 82% at diagnosis (95% confidence interval = 81%-83%) to 89% (88%-90%), 95% (94%-96%) and 97% (97%-98%) conditional on surviving 1, 3 and 5 years after diagnosis, respectively. Conditional survival reached 95% within five years of diagnosis for nearly all types of cancer, regardless of age or stage at diagnosis. Conclusions: Most children diagnosed with cancer who are alive five years after diagnosis can anticipate a similar chance of survival to children in the general population. For childhood cancer patients and their families, this information provides a more accurate and optimistic picture of long-term prognosis than has been available until now. Citation Format: Danny Youlden, Peter Baade, Andrew Hallahan, Patricia Valery, Adele Green, Joanne Aitken. Hope for a future: Conditional survival estimates for childhood cancer in Australia, 2002-2011. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B42.
180P: Immunotherapy as an effective therapy approach for advanced non-small cell lung cancer (NSCLC): A single institution experience in the context of clinical trials and expanded access use
Authors: J. Martínez Pérez, A. Falcón González, I. Sánchez Simón, A. Cervera, M. Alonso García, M.J. Flor Oncala, I. Gallego Jiménez, P. Maíquez, L. Jiménez González-Serna, J. Corral
Journal: Journal of Thoracic Oncology (2016)
Discovery of TH-302: An achiral hypoxia-activated cytotoxic prodrug
Authors: C. P. Hart, S. Ammons, J. X. Duan, D. Jung, J. Wang, H. Jiao, F. Meng, L. Lan, J. W. Evans, M. Matteucci
Journal: Journal of Clinical Oncology (2007)

3515 Background: Selective targeting of the hypoxic compartment of the tumor microenvironment is both a challenge and an opportunity for discovering and developing new cancer therapeutics. Chronic and transient hypoxia underlie resistance to chemotherapeutics and radiation. We have taken a modular design approach to synthesize hypoxia-activated prodrugs. Different nitro-containing heterocyclic triggers were linked to bis alkylating phosphorous mustard toxins and profiled in in vitro and in vivo assays predictive of compound efficacy and pharmacokinetics (PK). Methods: Drug candidates were synthesized and characterized using standard synthetic methods. In vitro efficacy was assessed with cancer cell line cytotoxicity and clonogenic assays. In vivo efficacy was assessed with xenograft models in monotherapy and combination therapy modes. Results: Screening trigger-toxin combinations in H460 lung cancer cell proliferation assays under anoxic, hypoxic, and aerobic conditions yielded structure-activity relationships (SAR) and identified TH- 302, a 2-nitroimidazole triggered bromo analog of ifosfamide, as a potent and selective molecule. TH-302 exhibits in vitro proliferation IC 50 values of 0.2, 5, and 90μM and clonogenic IC 90 values of 0.1, 5, and 30μM under conditions of 0%, 0.6%, and 21% O 2 , respectively. In vitro profiling showed sufficient solubility, plasma and microsomal stability, resistance to drug efflux mechanisms, and PK. In vivo efficacy was assessed with the H460 ectopic xenograft model. TH-302 administered alone (100mpk, ip, Q3Dx5) or in combination with cisplatin (6mpk, iv, Q7Dx2) showed mean tumor volume growth delays to 500mm 3 (TGD 500 ) of 10 days for TH-302 alone, 4 days for cisplatin alone, and 20 days for the combination. These results have been confirmed and extended using different tumor models, dosing regimens, and combinations which included Taxol and 5-FU. TH-302 demonstrates dose-proportional PK in multiple species. Conclusions: TH-302, a novel hypoxia-activated cytotoxic prodrug, has promising preclinical in vitro and in vivo efficacy and selectivity and has entered IND-enabling studies. Acute and subchronic toxicology is underway in rats and dogs. We expect to file an IND for clinical studies of TH-302 this year. No significant financial relationships to disclose.