tbuckley/cabot-search huggingface dataset:
Use of Collagen Implant for Posterior Rectopexy in Complete Rectal Prolapse: Preliminary Communication
Authors: Amir V Kaisary, Richard J Luck, John E H Pendower
Journal: Journal of the Royal Society of Medicine (1984)

A variety of materials has been used for perirectal implantation in the treatment of complete rectal prolapse. A new material (Zenoderm) prepared from porcine corium has been used successfully in 4 patients. The material proved to be inert, biologically non-irritant, pliable, workable and strong.
Abstract 14004: Pharmacodynamic Profiles of Ticagrelor in Patients With ST-Elevation Myocardial Infarction: A Prospective Randomized Comparison of Escalating Loading Dose Regimens
Authors: Francesco Franchi, Fabiana Rollini, Jung Rae Cho, Mona Bhatti, Christopher DeGroat, Elisabetta Ferrante, Elizabeth C Dunn, Amit Nanavati, Edward Carraway, Siva Suryadevara, Martin M Zenni, Luis A Guzman, Theodore A Bass, Dominick J Angiolillo
Journal: Circulation (2014)

Background: Pharmacodynamic (PD) studies have shown that in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI), ticagrelor is associated with suboptimal platelet inhibition and elevated rates of high on-treatment platelet reactivity (HPR) in the early hours after loading dose (LD) administration. Impaired absorption affecting drug pharmacokinetics (PK) has been hypothesized as a contributing factor suggesting increasing LD regimens to improve PK/PD profiles. To date there are no randomized studies which have investigated the PK/PD effects of escalating ticagrelor LD regimens in patients undergoing PPCI. Methods: In this prospective, randomized study, STEMI patients undergoing PPCI (n=52) were randomized 1:1:1 to receive 180mg, 270mg or 360mg LD of ticagrelor. PK and PD analysis were performed before and at 6 time points after LD. PD assessments included P2Y 12 reaction units (PRU) measured by VerifyNow P2Y12 and platelet reactivity index (PRI) measured by VASP. PK assessments included plasma concentrations of ticagrelor and its metabolite AR-C124910XX. Results: At baseline there were no differences in platelet reactivity between groups. At 2 hrs (primary endpoint), there were no differences in PRU between groups (p=0.54). There were no differences in PRU between groups during the overall study time course (p=0.17; Figure). Accordingly, HPR (PRU&gt;208) at 2 hrs was observed in 30% of patients and was not reduced by escalating ticagrelor LD regimens. Consistent PD findings were observed with VASP-PRI. PK data tracked PD results, with a non-dose related delay in peak plasma concentrations of both ticagrelor and AR-C124910XX, particularly in HPR patients. Conclusions: In STEMI patients undergoing PPCI, increasing the LD regimen of ticagrelor did not translate into more prompt or potent P2Y 12 inhibition, which is attributed to impaired absorption in the early hours after drug administration.
For Debate: Reflex responses do not necessarily signify pain
Authors: A. R Lloyd-Thomas, M. Fitzgerald
Journal: BMJ (1996)

reduce subjective and objective aspects of pain to the common denominator?If we accept the first possibility-that there is a causal relation between physical and mental processes in the brain-then it is possible to have a perfect description of the neurophysiological mechanism of the fetus and yet not know what is it like to be a fetus."2If we choose the second option Reflex responses do not necessarily signify pain
Abstract 88: The Nkx3.1 homeobox gene maintains prostatic identity while its loss leads to prostate cancer initiation
Authors: Clémentine Le Magnen, Aditya Dutta, Cory Abate-Shen
Journal: Cancer Research (2015)

Abstract Background Maintenance of epithelial cell identity is tightly coordinated by tissue-specific gene expression programs, which are often deregulated during tumorigenesis. The homeodomain-containing transcription factor, Nkx3.1, is a key regulator of normal prostatic development and is frequently lost at early stages of prostate cancer initiation. In this study, we aim to elucidate detailed mechanisms governing Nkx3.1-driven maintenance of prostate identity and how deregulation of such can lead to prostate tumorigenesis. Models and Methods We evaluated the consequences of Nkx3.1 loss or gain of function in vivo using genetically-engineered mouse models and cell-recombination assays. RNA sequencing was performed to generate gene expression profiles, which were analyzed using Gene Set Enrichment analysis (GSEA), and validated by quantitative real-time PCR. In parallel, protein expression was assessed by immunofluorescence and western blot. Immunoprecipitation (IP) and chromatin-immunoprecipitation (ChIP) assays were performed using RWPE1 prostate epithelial cells. Results Here, we show that loss of function of Nkx3.1 leads to the progressive down-regulation of a prostate-specific gene expression program and to aberrant expression of genes that are not typically expressed in the prostate epithelium. Conversely, gain of function of Nkx3.1 in non-prostatic epithelium leads to the acquisition of a prostate-like morphology and expression of prostate-related genes. Our findings indicate that the underlying mechanism by which Nkx3.1 promotes prostatic identity is via epigenetic regulation of gene expression. In particular, we show that Nkx3.1 interacts with the histone methyl-transferase complex G9a/Glp. Finally, we demonstrate that this interaction is necessary for maintenance of prostate identity in vivo and that Nkx3.1 and G9a cooperate to control expression of genes that coordinate prostatic epithelial integrity. Conclusions Our results suggest that Nkx3.1 promotes prostatic identity by interacting with histone modifying enzymes to coordinate the expression of prostate-specific genes and that the loss of this function results in a failure to maintain prostate identity associated with early stages of prostate tumorigenesis. Citation Format: Clémentine Le Magnen, Aditya Dutta, Cory Abate-Shen. The Nkx3.1 homeobox gene maintains prostatic identity while its loss leads to prostate cancer initiation. [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 88. doi:10.1158/1538-7445.AM2015-88
Prognostic factors for treatment outcome in autotransplantation of intermediate-grade and high-grade non-Hodgkin's lymphoma with cyclophosphamide, carmustine, and etoposide.
Authors: C Wheeler, M Strawderman, L Ayash, W H Churchill, B E Bierer, A Elias, D G Gilliland, K Antman, E C Guinan, J P Eder
Journal: Journal of Clinical Oncology (1993)

PURPOSE We examined a consecutive series of 78 patients with non-Hodgkin's lymphoma treated on prospective protocols with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (CBV) plus autotransplantation to determine prognostic factors for time to treatment failure. PATIENTS AND METHODS Patients with relapsed, refractory, or poor-risk intermediate- and high-grade non-Hodgkin's lymphoma were treated with CBV with autologous marrow or peripheral-blood progenitor cell support. Patient characteristics before transplantation were examined in univariate analyses by the log-rank test and simultaneously in a Cox proportional hazards regression analysis. A best-predictive model was determined from those variables significant (P &lt; .10) in the univariate test. RESULTS In univariate analysis, intermediate-grade and immunoblastic lymphoma, responsiveness to pretransplant salvage chemotherapy, and transplantation after primary therapy (first complete response [CR] or partial response [PR]) were associated with prolonged time to treatment failure. In proportional hazards multiple regression analysis, intermediate-grade and immunoblastic histology, responsive disease, and autotransplantation in first CR or PR were positive prognostic factors, and these characteristics are the basis of the best-predictive model for prolonged time to failure. Actuarial 3-year failure-free survival of patients with stable or responding disease at autotransplant was 54%. CONCLUSION CBV is an effective conditioning regimen in intermediate-grade and immunoblastic non-Hodgkin's lymphoma. Patients with these histologies transplanted while responding to primary therapy, or those with stable disease or disease responding to salvage therapy at the time of autotransplant, are most likely to benefit. Patients with lymphoblastic lymphoma or diffuse undifferentiated lymphoma did poorly with CBV and should be offered alternative therapy.
The non-coding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers
Authors: Chunguang Guo, Frank Sah, Lydia Beard, James Willson, Kishore Guda, Sanford Markowitz
Journal: Clinical Cancer Research (2008)

B16   MicroRNAs (miRNA/miR) are a class of small non-coding RNAs implicated in the pathogenesis of various malignancies. In the current study, using micro(RNA)arrays, we found a ubiquitous loss of miR-126 expression in colon cancer lines when compared to normal human colon epithelia. Reconstitution of miR-126 in colon cancer cells resulted in a significant growth reduction as evidenced in clonogenic assays. A search for miR-126 gene targets revealed p85β, a regulatory subunit involved in stabilizing and propagating the PI3K signal, as one of the potential substrates. Restoration of miR-126 in cancer cells induced a ≥3-fold reduction in p85β protein levels, with no concomitant change in p85α, a gene that is functionally related to p85β but not a supposed target of miR-126. Additionally, using reporter constructs, we show that the p85β-39 UTR is directly targeted by miR-126. Furthermore, this miR-126 mediated reduction of p85β was accompanied by a substantial reduction in phosphorylated AKT levels in the cancer cells, suggesting an impairment in PI3K signaling. Finally, in a panel of matched normal colon and primary colon tumors, each of the tumors demonstrated miR-126 down-regulation together with an increase in the p85β protein level. Taken together, we propose that miR-126 regulates PI3K signaling partly by targeting p85β, and that the loss of miR-126 may provide a selective growth advantage during colon carcinogenesis.
Identifying needs of highly nicotine dependent COPD smokers using a stepped care model of psychological intervention
Authors: Su Yin Yap, Elizabeth Pang, Sarah Lunn, Carla Croft, Myra Stern
Journal: European Respiratory Journal (2014)

Smoking cessation is the most effective treatment for smokers with COPD. Quit rates are low, relapse rates high. We report a pilot study assessing benefits of adjunctive psychological intervention for smokers already on intensive treatment for stop smoking. Method: COPD Smokers attending a stop smoking service were offered up to 12 clinical psychology sessions. Initial assessment & formulation around factors maintaining smoking led to bespoke psychological interventions. Baseline data included demographics, smoking history & disease severity. Outcomes included attendance, quit rate & thematic analysis of barriers to cessation. Results: 57 patients (moderate COPD, high prevalence of complex physical & psychological comorbidities) were referred.  38% patients never engaged, 26% were lost to follow-up, 35% patients attended >2 sessions (mean=5, range 2-12). 7/20 had already quit (relapse prevention referrals), 13 were smokers. 86% of the relapse prevention group maintained their quit. No smoker quit although 4/13 reduced tobacco intake. Complex psychosocial barriers to quitting were identified. Conclusions: For COPD smokers with a heavy smoking history & multiple quit attempts, additional psychological interventions with quit smoking support may aid in preventing relapse but did not increase quit rates. Findings suggest that multi-skilled teams offering targeted psychological intervention may help this group.
Monitoring Mortality in Forced Migrants—Can Bayesian Methods Help Us to Do Better with the (Little) Data We Have?
Authors: Peter Heudtlass, Niko Speybroeck, Debarati Guha-Sapir
Journal: PLoS Medicine (2015)

In crisis situations, data are scarce-Peter Heudtlass and colleagues explore ways of best understanding the extra risk of death borne by forced migrants.
Cochrane reviews evidence on surgery for stress incontinence after controversy in Scotland:
Authors: Nigel Hawkes
Journal: BMJ (2015)

Surgery for urinary stress incontinence in women that involves mesh slings to support the muscles of the bladder is effective and has low rates of complications, an updated Cochrane review has found.1

A year after the operation more than 80% of women were cured, though the benefits declined slowly with time. At five years the cure rate fell to around 70%. Two common operations were used, differing in the way the sling was supported: either behind the pubic bone (the retropubic route) or side to side (the transobturator route). Both had similar success rates, the review found.

The operation became controversial after …
Medical thoracoscopy – A district general hospital experience
Authors: Nanu Acharya, Richard Budd, Muhammad Malik
Journal: European Respiratory Journal (2011)

The 2010 British Thoracic Society (BTS) guideline recommends the use of Medical Thoracoscopy (MT) in the management algorithm for malignant pleural effusion [1]. Despite this MT is not readily available outside of tertiary centres in the United Kingdom [1]. An internal audit in 2010 showed the burden of pleural effusion at Barnsley Hospital (BH) over an 18 month period led to 1195 medical admissions; 226 (18.9%) were malignant effusions.

The diagnostic process for exudative pleural effusions has altered recently in BH to include semi-rigid MT.

Method: A retrospective analysis of computed tomography (CT) reports, histology and length of stay (LOS) for all individuals who underwent diagnostic MT (dMT) was performed.

Results: 44 MTs have been done to date. 32 were diagnostic and 12 therapeutic. Diagnostic MT results are as follows:

Adenocarcinoma of Lung 10, Mesothelioma 2, Breast Carcinoma 3, Ovarian Carcinoma 1, Tuberculosis (TB) 2, Inflammatory Tissue 14.

CT reports prior to dMT revealed a low suspicion of malignancy in 18 and a high suspicion of malignancy in 14.

dMT histology confirmed malignancy in 14 patients within the high suspicion group. Within the low suspicion group dMT histology confirmed 2 cases of lung cancer, 2 cases of TB and no evidence of malignancy in 14.

Average LOS after all MT was 3.7 days (range 1-11). The average LOS prior to the introduction of MT was 7.3 days (range 1-59).

Conclusion: MT is cost-effective through reducing LOS and referral rates to tertiary centres. Additionally this study has highlighted a potential missed or delayed diagnosis in 12.5% of cases. Patient experience is improved by facilitating a timely patient journey within their local hospital.

Reference: 

*   1. BTS Pleural Disease Guidelines 2010
Plasma and platelet excitatory amino acids in psychiatric disorders
Authors: C A Altamura, M C Mauri, A Ferrara, A R Moro, G D'Andrea, F Zamberlan
Journal: American Journal of Psychiatry (1993)

Plasma and platelet levels of excitatory amino acids were measured in 38 psychiatric out-patients and in 19 comparison subjects; the patients had DSM-III-R diagnoses of organic mental disorders (N = 3), mood disorders (N = 15), schizophrenia (N = 13), and anxiety disorders (N = 7). The glutamate plasma levels were significantly higher in the patients with mood disorders than in the comparison group.
Feasibility and efficacy of weekly intraarterial cisplatin in locally advanced (stage III and IV) head and neck cancers.
Authors: J E Mortimer, M E Taylor, S Schulman, C Cummings, E Weymuller, G Laramore
Journal: Journal of Clinical Oncology (1988)

Thirty-five consecutive patients with primary unresectable head and neck cancers were considered eligible for protocol treatment with neoadjuvant intraarterial cisplatin. External carotid artery catheterizations were technically feasible in 29 patients (83%). Twenty-five patients with 28 primary tumors received intraarterial cisplatin, 100 mg/m2, every seven to 14 days for three cycles. The most common toxicity was nausea and vomiting. Ipsilateral hemialopecia, transient VII nerve palsy, and blurring of vision seem to be unique to this route of administration at this dose. A complete response was seen at the primary tumor site in nine of 28 (32%), with 14 of 28 partial responses (50%). In evaluating both primary tumor and nodal disease, five of 25 patients achieved a complete response and 15 of 25 a partial response. In previous reports, one complete response was observed in 74 patients with head and neck cancer treated with neoadjuvant intravenous (IV) cisplatin every 3 weeks. The overall response of 82% reported here is comparable to that reported with combination chemotherapy and suggests an advantage to the arterial administration of cisplatin when possible in the neoadjuvant setting.
Evaluation of the effect of sampling of spontaneous sputum over a prolonged period on the sensitivity for lung cancer
Authors: Jasmijn Hubers, Daniëlle Heideman, Judith Herder, Sjaak Burgers, Peter Sterk, Peter Kunst, Henk Smit, Pieter Postmus, Sylvia Duin, Peter Snijders, Gerrit Meijer, Egbert Smit, Erik Thunnissen
Journal: European Respiratory Journal (2011)

Introduction: Lung cancer is the most common fatal cancer worldwide with an average 5-year survival of 12%. To reduce lung cancer mortality, spiral CT screening is promising, although this is costly and has a high false-positivity rate. Therefore, a clear need exists for alternative screening assays, like sputum-based DNA methylation detection. This study was set out to determine whether the detection rate of RASSF1A hypermethylation is influenced by duration of sputum collection.

Methods: Sputum samples were prospectively collected from 51 lung cancer and 50 controls. Controls are patients with COPD. Spontaneous sputum was collected at home during nine consecutive days in three canisters. DNA was isolated and bisulphite treated. Subsequently, quantitative methylation-specific PCR (qMSP) was performed to assess methylation status of the RASSF1A gene promoter. All samples were tested in duplicate. Statistical analyses were conducted using chi-square tests.

Results: Analysis of each canister separately showed RASSF1A methylation in samples of day 1-3, 4-6, and 6-9 in 29%, 35%, and 33% of cases, respectively. These figures were significantly lower for control samples, i.e., 2%, 6%, and 2%, respectively (all P-values <0.001). Cumulative analysis of RASSF1A methylation, i.e., combining methylation positivity outcomes for day 1-6, and day 1-9, revealed RASSF1A methylation in 39% and 47% of cases, respectively, versus 8% and 8% of controls, respectively.

Conclusion: Our study suggests that sputum collected over multiple successive days results in a gain in sensitivity, at the expense of a small loss in specificity, for the detection of lung cancer.
One-pot synthesis of PEGylated plasmonic MoO3–x hollow nanospheres for photoacoustic imaging guided chemo-photothermal combinational therapy of cancer
Authors: Tao Bao, Wenyan Yin, Xiaopeng Zheng, Xiao Zhang, Jie Yu, Xinghua Dong, Yuan Yong, Fuping Gao, Liang Yan, Zhanjun Gu, Yuliang Zhao
Journal: Biomaterials (2015)
The National Health Service: doctors and society beyond 2000
Authors: K Stuart
Journal: Journal of the Royal Society of Medicine (1999)

The fiftieth anniversary of the National Health Service last year was greeted with a flurry of political and professional reviews, lectures and commentaries. Most of these were either implicitly or explicitly dismissive of the notion that the NHS has or should have a preventive or promotional health role. They focused on what the NHS has itself focused on-hospital services and costs, length and duration of waiting lists, management and administrative procedures. On 10 July 1998 the Prime Minister sustained the emphasis on hospital services and costs by making five commitments: the provision of more money; less waiting by patients; a higher quality of care; the cutting of red tape and putting more money into patient care; and modern treatment methods in new or updated hospitals. Sir Alexander Macara, as BMA Council Chairman, likewise focused on funding. He deplored the chronic under-funding of the NHS and expressed the hope that the forthcoming spending review would offer relief. Sir Alexander's hope and the Prime Minister's commitments were met when the Chancellor announced on 14 July that the NHS budget would increase by £21 billion during the next three years. Important as they clearly are, periodic additions to the funding of the NHS are not the whole answer. A continuing emphasis on personal services and costs has tended to obscure the need for revisions by the NHS of both its policies and its practices. However efficient its hospitals and however sophisticated its resources for the delivery of health care, an appropriate balance of emphasis has to be reached between the delivery of health care and the promotion of health.
Home treatment for chronic respiratory insufficiency: the situation in Europe in 1992. The European Working Group on Home Treatment for Chronic Respiratory Insufficiency
Authors: B Fauroux, P Howard, JF Muir
Journal: European Respiratory Journal (1994)

The search for improved quality of life and a reduction in health care costs is leading to the development of home treatment. The organization of home treatment for chronic respiratory patients in 13 European countries was evaluated at the end of 1992 by means of a questionnaire. Switzerland and the Association Nationale pour le Traitement A Domicile de l'Insuffisance Respiratoire Chronique (ANTADIR) in France maintain registers for patients on oxygen therapy, mechanical ventilation and sleep disorders. Sweden and Poland have a national register for patients receiving oxygen. In other countries, some information can be obtained from the National Health Service or the commercial provider. Oxygen concentrators are used preferentially in all countries except Italy, Denmark, Spain and The Netherlands. Home ventilator treatment is generally performed by volume-cycled ventilators. National prescription rules exist in some parts of Spain, Switzerland and Belgium. In other countries, such as Germany, prescriptions rely on recommendations elaborated by specialists or international guidelines. Service and equipment are provided by national organizations, health services, commercial companies or hospitals. Home supervision of the patient is performed by a nurse and/or a doctor and equipment maintenance by a technician. Important differences exist between countries in Europe in home treatment of chronic respiratory disease. Comparative analysis should help achieve uniform standards and provide a basis for future research.