tbuckley/cabot-search huggingface dataset:
Predicting the onset of knee pain: results from a 2-year prospective study of new workers
Authors: G. T Jones, E. F Harkness, E. S Nahit, J. McBeth, A. J Silman, G. J Macfarlane
Journal: Annals of the Rheumatic Diseases (2006)

To determine the relative contribution of work-related mechanical (injury) factors and psychosocial factors to the onset of a new episode of knee pain, in a cohort of newly employed workers.A prospective cohort study of newly employed workers from 12 diverse occupational settings in England (The New Workers Study). 859 newly employed workers, free of knee pain, were identified. Information about occupational mechanical factors (manual handling and postural activities), the occupational physical environment, and psychological and psychosocial factors was collected by self-completion questionnaires. Participants were followed up after 12 and 24 months to identify cases of knee pain onset. Generalised estimating equations were used to estimate the risk of new-onset knee pain, with respect to the exposures previously measured.In total, over the 2-year follow-up period, 108 cases of new-onset knee pain were observed. Mechanical load, postural factors, psychological distress and work-place psychosocial factors all influenced the risk of new-onset knee pain over the 2-year follow-up period. On multivariate analysis, two factors remained independently predictive of knee pain onset: lifting or carrying heavy weights in one hand, and the level of general psychological distress.In addition to mechanical (injury) factors, psychological factors are important risk factors for knee pain onset as shown in a population of young newly employed workers.
Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study
Authors: H Fidder, F Schnitzler, M Ferrante, M Noman, K Katsanos, S Segaert, L Henckaerts, G Van Assche, S Vermeire, P Rutgeerts
Journal: Gut (2008)

<h3>Background and aims:</h3> This study evaluates the long-term safety of infliximab in patients with inflammatory bowel disease (IBD) treated with the drug over a 14-year period. <h3>Methods:</h3> The medical records of 734 patients with IBD treated with infliximab and 666 control patients not treated with infliximab were reviewed for adverse events. The time of onset and outcome, severity and concomitant medication were recorded. <h3>Results:</h3> Patients and controls were followed up for serious adverse events for a median time of 58 months (IQR 33–88) and 144 months (IQR 83–163), respectively. 112 severe adverse events occurred in 93 patients (13%) treated with infliximab and 157 occurred in 126 (19%) control patients (OR 1.33 (95% CI 0.56 to 3.00, p = 0.45). There was no difference between the two groups in mortality, malignancies and infection rate. Tuberculosis was diagnosed in two patients receiving infliximab who had negative skin tests at baseline whereas none of 16 patients with positive skin tests who received prophylaxis developed tuberculosis. Concomitant treatment with steroids was the only independent risk factor for infections in patients treated with infliximab (OR 2.69 (95% CI 1.18 to 6.12), p = 0.018). The most commonly observed systemic side effects were skin eruptions including psoriasiform eruptions in 150 patients (20%). <h3>Conclusions:</h3> Long-term infliximab treatment had a good overall safety profile in the patient cohort studied.
Fighting obesity: Clarification from World Health Organization
Authors: Catherine Le Gales-Camus, Amalia Waxman
Journal: BMJ (2004)

EDITOR—Jain's editorial calling for increased research into effective interventions against obesity contained some inaccuracies about the World Health Organization's role in this important global health issue.1

The WHO global strategy on diet, physical activity, and health never “implicated” the marketing of junk foods, called for an immediate ban on the advertising of unhealthy foods to children, or was stalled. A …
Telomere Dysfunction Causes Sustained Inflammation in Chronic Obstructive Pulmonary Disease
Authors: Valerie Amsellem, Guillaume Gary-Bobo, Elisabeth Marcos, Bernard Maitre, Vicky Chaar, Pierre Validire, Jean-Baptiste Stern, Hiba Noureddine, Elise Sapin, Dominique Rideau, Sophie Hue, Philippe Le Corvoisier, Sabine Le Gouvello, Jean-Luc Dubois-Randé, Jorge Boczkowski, Serge Adnot
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation of unknown pathogenesis.Objectives: To investigate whether telomere dysfunction and senescence of pulmonary vascular endothelial cells (P-ECs) induce inflammation in COPD.Methods: Prospective comparison of patients with COPD and age- and sex-matched control smokers. Investigation of mice null for telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes.Measurements and Main Results: In situ lung specimen studies showed a higher percentage of senescent P-ECs stained for p16 and p21 in patients with COPD than in control subjects. Cultured P-ECs from patients with COPD exhibited early replicative senescence, with decreased cell-population doublings, a higher percentage of β-galactosidase–positive cells, reduced telomerase activity, shorter telomeres, and higher p16 and p21 mRNA levels at an early cell passage compared with control subjects. Senescent P-ECs released cytokines and mediators: the levels of IL-6, IL-8, monocyte chemotactic protein (MCP)-1, Hu-GRO, and soluble intercellular adhesion molecule (sICAM)-1 were elevated in the media of P-ECs from patients compared with control subjects at an early cell passage, in proportion to the senescent P-EC increase and telomere shortening. Up-regulation of MCP-1 and sICAM-1 led to increased monocyte adherence and migration. The elevated MCP-1, IL-8, Hu-GROα, and ICAM-1 levels measured in lungs from patients compared with control subjects correlated with P-EC senescence criteria and telomere length. In Tert−/− and/or Terc−/− mouse lungs, levels of the corresponding cytokines (MCP-1, IL-8, Hu-GROα, and ICAM-1) were also altered, despite the absence of external stimuli and in proportion to telomere dysfunction.Conclusions: Telomere dysfunction and premature P-EC senescence are major processes perpetuating lung inflammation in COPD.
Complete remission after rituximab therapy in an HIV-positive patient with pemphigus vulgaris
Authors: M. Polansky, N. Patel, R. Feldman
Journal: British Journal of Dermatology (2015)

Journal Article Complete remission after rituximab therapy in an HIV‐positive patient with pemphigus vulgaris Get access M. Polansky, M. Polansky Department of Dermatology University of Texas Health Science Center at Houston Houston TX U.S.A E‐mail: maxpolansky@gmail.com Search for other works by this author on: Oxford Academic Google Scholar N. Patel, N. Patel Vanderbilt Medical School Nashville TN U.S.A Search for other works by this author on: Oxford Academic Google Scholar R. Feldman R. Feldman Department of Dermatology Emory Medical School Atlanta GA U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 6, 1 December 2015, Pages 1557–1559, https://doi.org/10.1111/bjd.13990 Published: 01 December 2015
THE VALUE OF RADIOLOGY (DIAGNOSIS AND TREATMENT) AS AN AID TO THE GENERAL PRACTITIONER
Authors: J. H. D. Webster
Journal: BMJ (1934)

MTHBYBRSITionThe influence of the stage of the canmer on the risk of urinary infection is shown by the fact that among women 77 per cent. of the late cases became infected and only 59 per cent. of the early cases.Similarly, among men infections occurred in 42 per cent. of the late cases and in only 32 per cent. of the early cases (Fig. 4).The average age in each group was approximately the same, and it seems justifiable to attribute the increased incidence of uriinary infection in the more advanced cases of cancer to a decline in general health.70 60.40 20 KARLY LATEY LATE 10 ASES 59 % 77 % 32 % 42 % Women Men FIG.4.-Influence of the patient's general condition as shown by the frequency of post-operative urinary infections in early and late cases of cancer of the rectum.
Amphiphysin IIm Is Required for Survival of Chlamydia pneumoniae in Macrophages
Authors: Elizabeth S. Gold, Randi M. Simmons, Timothy W. Petersen, Lee Ann Campbell, Cho-Chou Kuo, Alan Aderem
Journal: The Journal of Experimental Medicine (2004)

Macrophages play a critical role in both innate and acquired immunity because of their unique ability to internalize, kill, and degrade bacterial pathogens through the process of phagocytosis. The adaptor protein, amphiphysin IIm, participates in phagocytosis and is transiently associated with early phagosomes. Certain pathogens, including Chlamydia pneumoniae, have evolved mechanisms to subvert macrophage phagosome maturation and, thus, are able to survive within these cells. We report here that, although amphiphysin IIm is usually only transiently associated with the phagosome, it is indefinitely retained on vacuoles containing C. pneumoniae. Under these wild-type conditions, C. pneumoniae do not elicit significant nitric oxide (NO) production and are not killed. Abrogation of amphiphysin IIm function results in C. pneumoniae–induced NO production and in the sterilization of the vacuole. The data suggest that C. pneumoniae retains amphiphysin IIm on the vacuole to survive within the macrophage.
American Medical Society for Sports Medicine (AMSSM) position statement: interventional musculoskeletal ultrasound in sports medicine
Authors: Jonathan T Finnoff, Mederic M Hall, Erik Adams, David Berkoff, Andrew L Concoff, William Dexter, Jay Smith
Journal: British Journal of Sports Medicine (2014)

Background The use of diagnostic and interventional ultrasound has significantly increased over the past decade. A majority of the increased utilisation is by non-radiologists. In sports medicine, ultrasound is often used to guide interventions such as aspirations, diagnostic or therapeutic injections, tenotomies, releases and hydrodissections. Objective Critically review the literature related to the accuracy, efficacy and cost-effectiveness of ultrasound-guided injections (USGIs) in major, intermediate and small joints; and soft tissues. Design Systematic review of the literature. Results USGIs are more accurate than landmark-guided injections (LMGIs; strength of recommendation taxonomy (SORT) Evidence Rating=A). USGIs are more efficacious than LMGIs (SORT Evidence Rating=B). USGIs are more cost-effective than LMGIs (SORT Evidence Rating=B). Ultrasound guidance is required to perform many new procedures (SORT Evidence Rating=C). Conclusions The findings of this position statement indicate there is strong evidence that USGIs are more accurate than LMGI, moderate evidence that they are more efficacious and preliminary evidence that they are more cost-effective. Furthermore, ultrasound-guided (USG) is required to perform many new, advanced procedures and will likely enable the development of innovative USG surgical techniques in the future.
Effect of insulating existing houses on health inequality: cluster randomised study in the community
Authors: Philippa Howden-Chapman, Anna Matheson, Julian Crane, Helen Viggers, Malcolm Cunningham, Tony Blakely, Chris Cunningham, Alistair Woodward, Kay Saville-Smith, Des O'Dea, Martin Kennedy, Michael Baker, Nick Waipara, Ralph Chapman, Gabrielle Davie
Journal: BMJ (2007)

To determine whether insulating existing houses increases indoor temperatures and improves occupants' health and wellbeing.Community based, cluster, single blinded randomised study.Seven low income communities in New Zealand.1350 households containing 4407 participants.Installation of a standard retrofit insulation package.Indoor temperature and relative humidity, energy consumption, self reported health, wheezing, days off school and work, visits to general practitioners, and admissions to hospital.Insulation was associated with a small increase in bedroom temperatures during the winter (0.5 degrees C) and decreased relative humidity (-2.3%), despite energy consumption in insulated houses being 81% of that in uninsulated houses. Bedroom temperatures were below 10 degrees C for 1.7 fewer hours each day in insulated homes than in uninsulated ones. These changes were associated with reduced odds in the insulated homes of fair or poor self rated health (adjusted odds ratio 0.50, 95% confidence interval 0.38 to 0.68), self reports of wheezing in the past three months (0.57, 0.47 to 0.70), self reports of children taking a day off school (0.49, 0.31 to 0.80), and self reports of adults taking a day off work (0.62, 0.46 to 0.83). Visits to general practitioners were less often reported by occupants of insulated homes (0.73, 0.62 to 0.87). Hospital admissions for respiratory conditions were also reduced (0.53, 0.22 to 1.29), but this reduction was not statistically significant (P=0.16).Insulating existing houses led to a significantly warmer, drier indoor environment and resulted in improved self rated health, self reported wheezing, days off school and work, and visits to general practitioners as well as a trend for fewer hospital admissions for respiratory conditions.
Efficacy and safety of granisetron, a selective 5-hydroxytryptamine-3 receptor antagonist, in the prevention of nausea and vomiting induced by high-dose cisplatin.
Authors: R M Navari, H G Kaplan, R J Gralla, S M Grunberg, R Palmer, D Fitts
Journal: Journal of Clinical Oncology (1994)

PURPOSE To assess the antiemetic effects and safety profile of four different doses of granisetron (Kytril; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) when administered as a single intravenous (IV) dose for prophylaxis of cisplatin-induced nausea and vomiting. PATIENTS AND METHODS One hundred eighty-four chemotherapy-naive patients receiving high-dose cisplatin (81 to 120 mg/m2) were randomized to receive one of four granisetron doses (5, 10, 20, or 40 micrograms/kg) administered before chemotherapy. Patients were observed on an inpatient basis for 18 to 24 hours, and vital signs, nausea, vomiting, retching, and appetite were assessed. Safety analyses included incidence of adverse experiences and laboratory parameter changes. RESULTS After granisetron doses of 5, 10, 20, and 40 micrograms/kg, a major response (&lt; or = two vomiting or retching episodes, and no antiemetic rescue) was recorded in 23%, 57%, 58%, and 60% of patients, respectively, and a complete response (no vomiting or retching, and no antiemetic rescue) in 18%, 41%, 40%, and 47% of patients, respectively. There was a statistically longer time to first episode of nausea (P = .0015) and vomiting (P = .0001), and fewer patients were administered additional antiemetic medication in the 10-micrograms/kg dosing groups than in the 5-micrograms/kg dosing group. As granisetron dose increased, appetite return increased (P = .040). Headache was the most frequently reported adverse event (20%). CONCLUSION A single 10-, 20-, or 40-micrograms/kg dose of granisetron was effective in controlling vomiting in 57% to 60% of patients who received cisplatin at doses greater than 81 mg/m2 and totally prevented vomiting in 40% to 47% of patients. There were no statistically significant differences in efficacy between the 10-micrograms/kg dose and the 20- and 40-micrograms/kg doses. Granisetron was well tolerated at all doses.
Applied Pharmacogenomics in Cardiovascular Medicine
Authors: Peter Weeke, Dan M. Roden
Journal: Annual Review of Medicine (2013)

Interindividual heterogeneity in drug response is a central feature of all drug therapies. Studies in individual patients, families, and populations over the past several decades have identified variants in genes encoding drug elimination or drug target pathways that in some cases contribute substantially to variable efficacy and toxicity. Important associations of pharmacogenomics in cardiovascular medicine include clopidogrel and risk for in-stent thrombosis, steady-state warfarin dose, myotoxicity with simvastatin, and certain drug-induced arrhythmias. This review describes methods used to accumulate and validate these findings and points to approaches--now being put in place at some centers--to implementing them in clinical care.
New Anticoagulant Therapy
Authors: Lori-Ann Linkins, Jeffrey I. Weitz
Journal: Annual Review of Medicine (2004)

The development of new anticoagulants is expanding the list of drugs that can be used to prevent and treat venous and arterial thrombosis. New parenteral anticoagulants have been developed to overcome the limitations of heparin and low-molecular-weight heparin, whereas novel orally active anticoagulants have been designed to provide more streamlined therapy than vitamin K antagonists. This review identifies the molecular targets of new anticoagulants, describes the results of clinical trials, and provides clinical perspective on the opportunities for new anticoagulants.
Detection of Early Prostate Cancer Using a Hepsin-Targeted Imaging Agent
Authors: Kimberly A. Kelly, Sunita R. Setlur, Robert Ross, Rajesh Anbazhagan, Peter Waterman, Mark A. Rubin, Ralph Weissleder
Journal: Cancer Research (2008)

Abstract Early detection and diagnosis of prostate cancer is key to designing effective treatment strategies. Microarrays have resulted in the discovery of hepsin (HPN) as a biomarker for detection of prostate cancer. In this study, we explore the development of HPN imaging probes for detection of prostate cancer. We used phage display to isolate HPN binding peptides with 190 + 2.2 nmol/L affinity in monomeric form and high specificity. The identified peptides were able to detect human prostate cancer on tissue microarrays and in cell-based assays. HPN-targeted imaging agents were synthesized by conjugating multiple peptides to fluorescent nanoparticles to further improve avidity through multivalency and to improve pharmacokinetics. When injected into mouse xenograft models, HPN-targeted nanoparticles bound specifically to HPN-expressing LNCaP xenografts compared with non–HPN-expressing PC3 xenografts. HPN imaging may provide a new method for detection of prostate cancer. [Cancer Res 2008;68(7):2286–91]
Understanding the Structure and Mechanism of Formation of a New Magnetic Microbubble Formulation
Authors: Joshua Owen, Bin Zhou, Paul Rademeyer, Meng-Xing Tang, Quentin Pankhurst, Robert Eckersley, Eleanor Stride
Journal: Theranostics (2012)

Magnetic nanoparticles and ultrasound contrast agents have both been used as vehicles for therapeutic delivery.More recently, magnetic microbubbles have been developed as a new theranostic agent which combines the advantages of the individual carriers and overcomes many of their limitations.In a previous study of gene delivery using magnetic microbubbles, it was found that a combination of magnetic liquid droplets and non-magnetic phospholipid microbubbles produced higher transfection rates than magnetic microbubbles.The reasons for this were not fully understood, however.The aim of this study was to investigate the hypothesis that conjugation between the droplets and the microbubbles occurred.A combination of optical and fluorescence microscopy and ultrasound imaging studies in a flow phantom were performed.No interaction between magnetic droplets and microbubbles was observed under optical microscopy but the results from the fluorescence and acoustic imaging indicated that magnetic droplets and microbubbles do indeed combine to form a new magnetically and acoustically responsive particle.Theoretical calculations indicate that the driving force of the interaction is the relative surface energy and thus thermodynamic stability of the microbubbles and the droplets.The new particles were resistant to centrifugation, of comparable echogenicity to conventional ultrasound contrast agents and could be retained by a magnetic field (0.2T) in a flow phantom at centre line velocities of ~6 cm s -1 and shear rates of ~60 s -1 .
Ageing eyes retain their mystery
Authors: Andrew F Smith
Journal: The Lancet (1999)

In Kathryn Senior's March 6 news item (p 818),1Senior K Ageing eyes retain their mystery.Lancet. 1999; 353: 818Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar she records developments that aim to uncover the mechanism for the formation of age-related macular degeneration (ARMD), and points out the necessity for further epidemiological studies on the environmental and genetic risk factors involved in ARMD. Although emphasis must be maintained on the pursuit of eventual treatments, in the absence of an effective treatment for ARMD, Alan Bird of Moorfields Eye Hospital (London, UK), who she quotes, is right to argue for the allocation of greater resources for population-based studies aimed at elucidating potential risk factors in the development of ARMD. Too often, scarce health-care resources have been targeted towards the cure of vision loss and blindness due to ARMD, and have failed to provide funding for the pursuit of public health and preventive ophthalmological initiatives. Perhaps now in view of the urgency affecting the rising tide of age-related blindness, it is time for epidemiology to play a leading part in providing answers to the plight of persons affected with ARMD and other age-related eye disease, such as cataract. One strategy, which might achieve rapid results in the elucidation of potential risk factors for ARMD, is for highly sensitive measurements of possible environmental and biological processes to be taken. Such an approach, which focuses on small in-vivo changes to the retina during the development of ARMD in relation to minute environmental or biological changes or exposures, could well illuminate promising preventive or treatment pathways in a more immediate time frame than by use of traditional exposure measurements. By identifying single or multiple risk factors of even the slightest magnitude (either protective or causative) subsequent efforts could then be directed towards understanding and hopefully rectifying underlying biological mechanisms associated with ARMD. A lack of creativity in the study design and sensitivity of the techniques in epidemiological studies to evaluate the risk factors for ARMD could well translate into years, if not decades, of unrealised clinical potential for the provision of an effective means of delaying or halting the visual loss in patients with ARMD. Clearly, if ARMD could be successfully prevented through potential lifestyle modifications to smoking status, diet, and exercise, then this is important information that should reside within the public domain, where it would have the added effect of reducing the demands for costly and currently unsuccessful ophthalmic care for patients with ARMD.