tbuckley/cabot-search huggingface dataset:
Therapeutic effects of genetically engineered toxin (DAB486IL-2) in patient with chronic lymphocytic leukaemia
Authors: C.F. LeMaistre, C.M. Meneghetti, A.B. Deisseroth, M.G. Rosenblum, J.M. Reuben, D.R. Parkinson, K. Parker, J.P. Shaw, T. Woodworth
Journal: The Lancet (1991)
MOLECULAR PATHOLOGY OF MALIGNANT GLIOMAS
Authors: David N. Louis
Journal: Annual Review of Pathology Mechanisms of Disease (2006)

Malignant gliomas, the most common type of primary brain tumor, are a spectrum of tumors of varying differentiation and malignancy grades. These tumors may arise from neural stem cells and appear to contain tumor stem cells. Early genetic events differ between astrocytic and oligodendroglial tumors, but all tumors have an initially invasive phenotype, which complicates therapy. Progression-associated genetic alterations are common to different tumor types, targeting growth-promoting and cell cycle control pathways and resulting in focal hypoxia, necrosis, and angiogenesis. Knowledge of malignant glioma genetics has already impacted clinical management of these tumors, and researchers hope that further knowledge of the molecular pathology of malignant gliomas will result in novel therapies.
Noninvasive evaluation of cardiotoxicity of 5-fluorouracil and low doses of folinic acid: A one-year follow-up study
Authors: A.M. Grandi, G. Pinotti, E. Morandi, P. Zanzi, P. Bulgheroni, L. Guasti, A. Bertolini, A. Venco
Journal: Annals of Oncology (1997)
Mechanisms of syngeneic tumor rejection. Susceptibility of host-selected progressor variants to various immunological effector cells.
Authors: J L Urban, R C Burton, J M Holland, M L Kripke, H Schreiber
Journal: The Journal of Experimental Medicine (1982)

The ultraviolet radiation-induced fibrosarcoma 1591 generally is rejected by normal syngeneic mice and only rarely exhibits progressive growth. We isolated five of these rare progressor tumors from normal animals to determine the selective pressures that had been exerted upon the parental tumor by normal immunocompetent hosts. We found that the variant tumor cell lines could neither induce nor be killed by tumor-specific lymphocytes, suggesting that selection had been exerted against tumor cells expressing the tumor-specific antigen. In contrast, no selection against natural killer cell activity or against nonspecific T cell-mediated immunity seems to have occurred because progressor tumor cells were highly sensitive to these types of effector cells and in fact induced these effector cells more effectively than did the parental tumor. Nude mice were found to be as capable as normal mice in generating natural killer activity in response to a challenge with progressor tumor cells, but they were unable to mount a nonspecific T lymphocyte response. This may account for the fact that the progressor tumors grew at a significantly faster rate in nude animals than in normal mice. Thus, our study shows that in this tumor system nonspecific T cell-mediated immunity may play a role in retarding tumor growth, but the absolute resistance of normal animals to progressive tumor growth critically depends upon the presence of T cell-mediated tumor-specific immunity. Furthermore, neither NK cells nor nonspecific cytotoxic T lymphocytes appear to play a role in immunoselection against this tumor in normal immunocompetent hosts.
Acne, isotretinoin and suicide attempts: a critical appraisal
Authors: S.M. Langan, J.M. Batchelor
Journal: British Journal of Dermatology (2011)

Journal Article Acne, isotretinoin and suicide attempts: a critical appraisal Get access S.M. Langan, S.M. Langan Department of Non‐Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London and St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital NHS Foundation Trust, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.M. Batchelor J.M. Batchelor Department of Dermatology, Queen’s Medical Centre, Nottingham NG7 2UH, U.K. E‐mail: sinead.langan@lshtm.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 6, 1 June 2011, Pages 1183–1185, https://doi.org/10.1111/j.1365-2133.2011.10369.x Published: 01 June 2011
Diseases Caused by Defects in the Visual Cycle: Retinoids as Potential Therapeutic Agents
Authors: Gabriel H. Travis, Marcin Golczak, Alexander R. Moise, Krzysztof Palczewski
Journal: The Annual Review of Pharmacology and Toxicology (2006)

Absorption of a photon by an opsin pigment causes isomerization of the chromophore from 11-cis-retinaldehyde to all-trans-retinaldehyde. Regeneration of visual chromophore following light exposure is dependent on an enzyme pathway called the retinoid or visual cycle. Our understanding of this pathway has been greatly facilitated by the identification of disease-causing mutations in the genes coding for visual cycle enzymes. Defects in nearly every step of this pathway are responsible for human-inherited retinal dystrophies. These retinal dystrophies can be divided into two etiologic groups. One involves the impaired synthesis of visual chromophore. The second involves accumulation of cytotoxic products derived from all-trans-retinaldehyde. Gene therapy has been successfully used in animal models of these diseases to rescue the function of enzymes involved in chromophore regeneration, restoring vision. Dystrophies resulting from impaired chromophore synthesis can also be treated by supplementation with a chromophore analog. Dystrophies resulting from the accumulation of toxic pigments can be treated pharmacologically by inhibiting the visual cycle, or limiting the supply of vitamin A to the eyes. Recent progress in both areas provides hope that multiple inherited retinal diseases will soon be treated by pharmaceutical intervention.
The friends and family test: a qualitative study of concerns that influence the willingness of English National Health Service staff to recommend their organisation
Authors: Mary Dixon-Woods, Joel T Minion, Lorna McKee, Janet Willars, Graham Martin
Journal: Journal of the Royal Society of Medicine (2014)

Objectives The views of practitioners at the ‘sharp end’ of care provision are increasingly recognised as important indicators of quality of care. The National Health Service (NHS) Staff Survey in England has quantified employees' views on how far they would be happy with the standard of care provided by their organisation if a friend or family member needed treatment. We aimed to characterise the concerns that might affect the willingness of staff to recommend their own organisations. Design Qualitative study involving semi-structured interviews. Data analysis based on the constant comparative method. Participants Members of clinical and managerial staff in four NHS organisations ( n = 70), and senior stakeholders across the NHS including clinicians, managers and others with a strategic or senior-level perspective ( n = 98). Setting One hundred and sixty-eight interviews were conducted: 70 in four case study organisations and 98 across the wider English NHS. Main outcome measures Not applicable. Results Asking study participants the ‘if a friend…’ question offered insider views on the quality of care. Some staff had no concerns, but others, identified significant problems with consistency, reliability and behaviour of staff. Participants identified reasons for poor care that included inadequate organisational systems; structural problems of understaffing and under-resourcing; weaknesses in professional cultures and professional competence and failure to deal with problems such as unacceptable conduct. Participants emphasised that staff were not always able to deliver high-quality care because they worked in difficult conditions. Conclusions Asking staff to give accounts of their willingness to recommend their organisation to family and friends elicits important insights into quality and safety of care. Such accounts might be able to provide warning signs that could signal organisational decline and avert healthcare scandals, but use outside a research context requires further evaluation.
Cytology of bronchial biopsy rinse fluid to improve the diagnostic yield for lung cancer
Authors: A Rosell, E Monso, L Lores, X Vila, M Llatjos, J Ruiz, J Morera
Journal: European Respiratory Journal (1998)

Sampling techniques are combined during bronchoscopy to increase the diagnostic yield for endobronchial malignant tumours. Bronchial biopsy provides the definitive histological diagnosis in most cases, but accompanying cytological procedures such as washing, brushing, needle aspiration or imprint cytology can increase diagnostic yield. In this prospective study, a different cytological technique, that could enhance the diagnostic yield of bronchoscopy without increasing its time or cost, was tested. Flexible bronchoscopy was performed in 93 patients suspected of having pulmonary neoplasms. Bronchial biopsies were initially placed in a balanced salt solution. When bronchoscopy was finished, all visible tissue fragments were removed and placed in formalin to undergo histopathological examination and the rinse fluid was sent for cytological examination. Washing was performed routinely but no cytological brushing was employed. Eighty-two patients had final diagnoses of malignant neoplasm. In four (4.8%) of these patients, the only positive result came from the cytological examination of the bronchial biopsy rinse fluid. No false-positive results were found. The agreement with the histological results was 81.8%. The addition of bronchial biopsy rinse-fluid examination increased the sensitivity of bronchoscopy from 65.8% to 70.7% (McNemar's p=0.009). The cytological study of bronchial biopsy rinse fluid offers reliable positive results in an additional 4.8% of cases, thus enhancing bronchoscopic diagnostic yield for malignant endobronchial tumours while neither prolonging the procedure nor increasing costs.
Consistency in assessing the Disease Activity Score-28 in routine clinical practice
Authors: C A E Walsh, R H Mullan, P B Minnock, C Slattery, O FitzGerald, B Bresnihan
Journal: Annals of the Rheumatic Diseases (2007)

With the increasing availability of biological therapies for patients with rheumatoid arthritis (RA), the need to include reliable and reproducible clinical measures of disease activity in routine practice has been emphasised.1 Disease Activity Score-28 (DAS28) is validated for use in clinical trials;2–5 however, it is not known how it performs in a clinical setting.

The aim of this study was to evaluate consistency in the measurement of DAS28, and its individual components, by clinic staff in one centre with different levels of experience. Twelve patients with RA (six per exercise) were assessed for the inter-observer exercises. Five patients were assessed for the intra-observer exercise. Six members of the rheumatology team (two staff rheumatologists, two trainees in rheumatology, …
Prevalence of asymptomatic myocardial ischaemia in diabetic subjects.
Authors: M J Koistinen
Journal: BMJ (1990)

OBJECTIVE--To compare the prevalence of silent myocardial ischaemia associated with coronary artery disease in diabetic subjects with that in controls of similar age and sex. DESIGN--A controlled study in which subjects with positive findings on exercise electrocardiography, 24 hour electrocardiographic recording, or dynamic thallium scintigraphy (diabetics only) underwent coronary angiography. SETTING--Academic medical centre; referral based cardiology clinic. SUBJECTS--136 Diabetic subjects, of whom 72 (33 women, 39 men (mean age 46.0] were insulin dependent and 64 (19 women, 45 men (mean age 49.3] non-insulin dependent. 80 Controls matched for age and sex; all were clients of the Occupational Health Service of Oulu University Central Hospital or the State Occupational Health Service Station in Oulu in whom diabetes had been excluded by a glucose tolerance test. INTERVENTIONS--Any subject showing signs of myocardial ischaemia was referred for cardiac catheterization. MAIN OUTCOME MEASURES--Exercise electrocardiography and 24 hour electrocardiographic recording were regarded as positive if there were ST depressions of greater than or equal to 1 mm that were planar or downsloping and persisted for 0.08 seconds after the J point. Thallium tomographic imaging. With cardiac catheterisation, coronary artery lesions were classified as significant in half or more of the vessel lumen was narrowed, or insignificant if such narrowing was less than half. RESULTS--40 (29%) diabetes and four (5%) controls had positive results in one or more of the non-invasive tests. Coronary angiography was performed on 34 of the diabetics (six refused); 12 had significant coronary artery narrowing; seven had unimportant atherosclerosis; 15 had patent coronary arteries. Among the controls only one had unimportant atherosclerosis; the other three had patent arteries. CONCLUSIONS--These results confirm the high prevalence of asymptomatic myocardial ischaemia in diabetics. Non-invasive screening of diabetic subjects, however, does not seem justified because of the low preset probability of the presence of the disease and the inaccuracy of the available test methods.
AACR-FDA-NCI Cancer Biomarkers Collaborative Consensus Report: Advancing the Use of Biomarkers in Cancer Drug Development
Authors: Samir N. Khleif, James H. Doroshow, William N. Hait
Journal: Clinical Cancer Research (2010)

Recent discoveries in cancer biology have greatly increased our understanding of cancer at the molecular and cellular level, but translating this knowledge into safe and effective therapies for cancer patients has proved to be challenging. There is a growing imperative to modernize the drug development process by incorporating new techniques that can predict the safety and effectiveness of new drugs faster, with more certainty, and at lower cost. Biomarkers are central to accelerating the identification and adoption of new therapies, but currently, many barriers impede their use in drug development and clinical practice. In 2007, the AACR-FDA-NCI Cancer Biomarkers Collaborative stepped into the national effort to bring together disparate stakeholders to clearly delineate these barriers, to develop recommendations for integrating biomarkers into the cancer drug development enterprise, and to set in motion the necessary action plans and collaborations to see the promise of biomarkers come to fruition, efficiently delivering quality cancer care to patients.
Transtracheal air in the treatment of obstructive sleep apnoea hypopnoea syndrome
Authors: F Series
Journal: Thorax (2000)

A 49 year old woman with typical obstructive sleep apnoea hypopnoea syndrome underwent an unsuccessful trial with continuous positive airway pressure (CPAP) followed by uvulopalatopharyngoplasty with septorhinoplasty, treatment with protriptyline, and a second CPAP trial that was abandoned. Transtracheal air was then given and normalised sleep and breathing at a flow rate of 5 l/min. A sustained clinical improvement was observed at follow up visits. Transtracheal air could represent a simple and effective alternative to tracheotomy in patients with obstructive sleep apnoea hypopnoea syndrome in whom conventional treatments fail.
CLASSIFICATION AND REALLOCATION OF "EXHAUSTION" CASUALTIES IN A THEATRE OF WAR
Authors: C. H. GUNDRY
Journal: American Journal of Psychiatry (1946)

Almost all the psychiatric battle casualties could be retained in a theatre of war performing useful duties. The proportion returned to combatant duties after brief treatment in forward areas without being severed from their units was encouraging but return to combatant duty after treatment in neuropsychiatric units was possible in only a small proportion of cases. "Exhaustion" accounted for about 10 percent of battle casualties, exclusive of killed and missing. Relief of severe symptoms was comparatively easily obtained and men continued to be capable of performing duties in the rear without excessive sickness or crime rates but anxiety was stirred up by prospect of return to action—or briefly by incidental enemy air activity. There was little reason to expect that much improvement in rates of psychiatric battle casualties could have been brought about either by selection or treatment. It was obvious in case after case that childhood insecurity was the outstanding cause of predisposition and amelioration of much of this insecurity should have been possible. An editorial in the B. M. J. of March 7, 1942 concludes: "The last war emphasized the importance of mental conflict; this war has on the whole emphasized the importance of predisposition and especially of constitutional predisposition. One of the tasks of the future is to discover means of detecting this in a much higher proportion of cases than is possible now." However, it seems that by 1944 in the Canadian Army selection had been carried as far as it could be without being wasteful. Because of that observation and because of opinions developed after examination of a large number of individual soldiers my conclusion would be that the task of the future would be to reduce the amount of this constitutional predisposition. I think that current usage of the term constitution does not imply that it can be modified only by eugenics. I think that better socialization and better attention to individual mental hygiene provide the answer. A study of all possible experiences during the war could teach us a great deal about how individuals could be more adequately socialized. Ronald Fairbairn concluded one of the best articles I have seen about war neuroses (B. J. M., Feb. 13, 1943) with indications of his discouragement in efforts to deal with separation anxiety en masse, and the statement—"What these people really need is not a psychotherapist but an evangelist." Although in peace time more deliberate and individualized methods of bringing about the identification of persons with society should be more efficient than evangelism, its appeal implies useful clues.
Tackling Breast Cancers Resistant to Hormone Therapy
Authors: Tracy Hampton
Journal: JAMA (2015)

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Pharmacy Benefit Managers, Pharmacies, and Pharmacogenomic Testing: Prescription for Progress?
Authors: Eric J. Topol
Journal: Science Translational Medicine (2010)

Few would argue that the ability to match individual patients with the safest and most effective drugs and doses would be a major advance for clinical medicine. But while clinicians have been reluctant to routinely use pharmacogenomic analyses to guide their prescribing practices, pharmacy benefit managers and drugstores are proceeding with major pharmacogenetic initiatives.
Diverse functions of miR-125 family in different cell contexts
Authors: Yu-Meng Sun, Kang-Yu Lin, Yue-Qin Chen
Journal: Journal of Hematology & Oncology (2013)

Abstract MicroRNAs (miRNAs) are emerging as a novel class of non-coding RNA molecules that regulate gene expression at a post-transcriptional level. More than 1000 miRNAs have been identified in human cells to date, and they are reported to play important roles in normal cell homeostasis, cell metastasis and disease pathogensis and progression. MiR-125, which is a highly conserved miRNA throughout diverse species from nematode to humans, consists of three homologs hsa-miR-125a, hsa-miR-125b-1 and hsa-miR-125-2. Members of this family have been validated to be down-regulated, exhibiting its disease-suppressing properties in many different types of diseases, while they also have disease-promoting functions in certain contexts. MiR-125 targets a number of genes such as transcription factors, matrix-metalloprotease, members of Bcl-2 family and others, aberrance of which may lead to abnormal proliferation, metastasis and invasion of cells, even carcinomas. Furthermore, miR-125 plays a crucial role in immunological host defense, especially in response to bacterial or viral infections. In this review, we summarize the implication of miR-125 family in disease suppression and promotion, focusing on carcinoma and host immune responses. We also discussed the potential of this miRNA family as promising biomarkers and therapeutic targets for different diseases in future.
Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology
Authors: Charlotte I.S. Barker, Eva Germovsek, Rollo L. Hoare, Jodi M. Lestner, Joanna Lewis, Joseph F. Standing
Journal: Advanced Drug Delivery Reviews (2014)

Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose–concentration–effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future.
Idiosyncratic Liver Injury Induced by Vildagliptin With Successful Switch to Linagliptin in a Hemodialyzed Diabetic Patient
Authors: Noriaki Kurita, Takako Ito, Sayaka Shimizu, Takumi Hirata, Hirotsugu Uchihara
Journal: Diabetes Care (2014)

Recently, cases of liver injury associated with dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported (1,2). Some postulate the liver injury is mediated by class effect of DPP-4 inhibitors (1), as DPP-4 is identical to CD26 expressed in lymphocytes and macrophages and DPP-4 inhibitors suppress CD26-induced T-cell activation, thereby contributing to immunomodulation (3). However, no report presents whether liver injury associated with DPP-4 inhibitors is class effect or drug-specific. Here, we report a potential case of idiosyncratic liver injury associated with vildagliptin.

A 65-year-old woman receiving hemodialysis due to diabetic nephropathy presented with slowly progressive liver dysfunction. She was treated with insulin (4 units/day), acarbose (150 mg/day), and gliclazide (10 mg/day). With this regimen, her A1C was 7.6% (60 mmol/mol). After confirmation that …