tbuckley/cabot-search huggingface dataset:
Increased brain serotonin function in men with chronic fatigue syndrome
Authors: M Sharpe, K Hawton, A Clements, P. Cowen
Journal: BMJ (1997)

Objective: To examine the incidence of cardiovascular diseases and cancer from published clinical trials that studied other outcomes of postmenopausal hormone therapy as some surveys have suggested that it may decrease the incidence of cardiovascular diseases and increase the incidence of hormone dependent cancers.Design: Trials that compared hormone therapy with placebo, no therapy, or vitamins and minerals in comparable groups of postmenopausal women and reported cardiovascular or cancer outcomes were searched from the literature.Subjects: 22 trials with 4124 women were identified.In each group, the numbers of women with cardiovascular and cancer events were summed and divided by the numbers of women originally allocated to the groups.Results: Data on cardiovascular events and cancer were usually given incidentally, either as a reason for dropping out of a study or in a list of adverse effects.The calculated odds ratios for women taking hormones versus those not taking hormones was 1.39 (95% confidence interval 0.48 to 3.95) for cardiovascular events without pulmonary embolus and deep vein thrombosis and 1.64 (0.65 to 4.18) with them.It is unlikely that such results would have occurred if the true odds ratio were 0.7 or less.For cancers, the numbers of reported events were too low for a useful conclusion. Conclusions:The results of these pooled data do not support the notion that postmenopausal hormone therapy prevents cardiovascular events.
Proangiogenic Factor PlGF Programs CD11b+ Myelomonocytes in Breast Cancer during Differentiation of Their Hematopoietic Progenitors
Authors: Julien Laurent, Eveline Faes-van't Hull, Cedric Touvrey, François Kuonen, Qiang Lan, Girieca Lorusso, Marie-Agnès Doucey, Laura Ciarloni, Natsuko Imaizumi, Gian Carlo Alghisi, Ernesta Fagiani, Khalil Zaman, Roger Stupp, Masabumi Shibuya, Jean-François Delaloye, Gerhard Christofori, Curzio Ruegg
Journal: Cancer Research (2011)

Abstract Tumor-mobilized bone marrow–derived CD11b+ myeloid cells promote tumor angiogenesis, but how and when these cells acquire proangiogenic properties is not fully elucidated. Here, we show that CD11b+ myelomonocytic cells develop proangiogenic properties during their differentiation from CD34+ hematopoietic progenitors and that placenta growth factor (PlGF) is critical in promoting this education. Cultures of human CD34+ progenitors supplemented with conditioned medium from breast cancer cell lines or PlGF, but not from nontumorigenic breast epithelial lines, generate CD11b+ cells capable of inducing endothelial cell sprouting in vitro and angiogenesis in vivo. An anti–Flt-1 mAb or soluble Flt-1 abolished the generation of proangiogenic activity during differentiation from progenitor cells. Moreover, inhibition of metalloproteinase activity, but not VEGF, during the endothelial sprouting assay blocked sprouting induced by these proangiogenic CD11b+ myelomonocytes. In a mouse model of breast cancer, circulating CD11b+ cells were proangiogenic in the sprouting assays. Silencing of PlGF in tumor cells prevented the generation of proangiogenic activity in circulating CD11b+ cells, inhibited tumor blood flow, and slowed tumor growth. Peripheral blood of breast cancer patients at diagnosis, but not of healthy individuals, contained elevated levels of PlGF and circulating proangiogenic CD11b+ myelomonocytes. Taken together, our results show that cancer cells can program proangiogenic activity in CD11b+ myelomonocytes during differentiation of their progenitor cells in a PlGF-dependent manner. These findings impact breast cancer biology, detection, and treatment. Cancer Res; 71(11); 3781–91. ©2011 AACR.
No benefit of surgery over physiotherapy for meniscal tears in adults with knee osteoarthritis
Authors: Steven J Kamper, Nicholas Henschke
Journal: British Journal of Sports Medicine (2014)

This section features a recent randomised controlled trial that is indexed on PEDro, the Physiotherapy Evidence Database (http://www.pedro.org.au). PEDro is a free, web-based database of evidence relevant to physiotherapy.

▸ Surgery versus physical therapy for meniscal tear and osteoarthritis. New Engl J Med 2013;368:1675–84.

Many people with osteoarthritis (OA) of the knee have damage to the meniscus,1 which is commonly treated by surgical excision of the damaged fragment; a procedure known as partial meniscectomy. However, it is not clear whether surgery of symptomatic meniscal tears improves pain and function in people with knee OA compared to conservative treatment.

To assess whether adding arthroscopic meniscectomy to physiotherapy leads to greater improvements in pain and function than physiotherapy alone in older people with mild-to-moderate OA of the knee and a defined meniscus tear.

Participants were recruited from tertiary referral centres in the USA. Patients over 45 years old with knee OA who reported symptoms consistent with a meniscus tear that had persisted for more than 1 month were eligible. Meniscus pathology and OA were confirmed by MRI. Clinical symptoms of a meniscus tear included at least one of the following: clicking, catching, popping, giving way, pain with pivot or torque, pain …
The bidirectional capacity of bacterial antigens to modulate allergy and asthma
Authors: H. Renz, U. Herz
Journal: European Respiratory Journal (2002)

In recent decades, the prevalence of allergic diseases including bronchial asthma, hay fever and atopic dermatitis, has risen steadily in high-income countries. The underlying mechanisms for this phenomenon remain largely unknown. Since the natural mutation rate is low, altered environmental and lifestyle conditions are thought to play an important role. Epidemiological and clinical studies have provided indirect evidence that infections may prevent the development of atopy and atopic disease. This is referred to as the “hygiene hypothesis”. According to the hygiene hypothesis, viral and/or bacterial infections could inhibit the T-helper (Th)-2 immune response associated with atopic reactions by stimulating a Th-1 response involved in defence of bacterial infections and delayed-type hypersensitivity reactions. In particular, the prenatal period and early childhood are considered to be critical for the establishment and maintenance of a normal Th-1/Th-2 balance. On the other hand, several studies suggested that infections exacerbate established allergic diseases, e.g. bronchial asthma, airway hyperresponsiveness and atopic dermatitis. Therefore, viral and/or microbial infections and/or their products may have bidirectional effects on the development of allergy and asthma. This review will focus on recent findings related to the interaction between allergic disorders and infectious diseases, with the main emphasis on bacterial infections.
RENAL COLIC AND HAEMATURIA FOLLOWING RECUMBENCY
Authors: W. E. Wilson
Journal: BMJ (1931)

sturgeoni stands in front and manipulates the fragments till reduction is perfect.The assistant retains this by maintainin-g the traction.The plaster slab is then applied by the surgeon in front.E-ach extremity is moulded so as to be crutch-ended and to fit into the delto-pectoral hollow in front of each shoulder.It is made to come well down into the axilla beneath the shoulder so as to obtain sufficient upward lift.Owing to the prearranged length of the-slab, the central part, which is in front of the sternum and inner portionis of the clavicles, is bowed out from the skin surface slightly.Over the outer half to two-thirds of the clavicle the slab is moulded exactly to the contour of the bone in its corrected alignment.It thus embraces the fra,gments on both sides of the fracture.The plaster is held till set.A nurse tllhei applies bandages in the following faslion.First, a double " figure of eight " is applied round both shoulders, with the intersection in front over the centre of the slab.The assistant then relinquishes his -hold.The effect of this bandage, very firmly applied, is to' exert a force backwards, outwards, and upwards on the centre of the bow-shaped slab.The plaster here stands, off a short distance from the sternum, so that this pressure is transmitted through the crutch- enids of the slab and puthcs the shoulders and outer ends Fie.2.--Photo-raph of a patient with the moulded plaster sMA in position.of the clavicles backwards, outwards, and upwards.The slab acts, indeed, exactly as an adventitious clavicle, replacinig the bone both in position and function as closely as is possible.It constitutes an efficient substitute till the continiuity of the prototype is restored.Properly
Uric Acid Is a Danger Signal Activating NALP3 Inflammasome in Lung Injury Inflammation and Fibrosis
Authors: Pamela Gasse, Nicolas Riteau, Sabine Charron, Sandra Girre, Lizette Fick, Virginie Pétrilli, Jürg Tschopp, Vincent Lagente, Valérie F. J. Quesniaux, Bernhard Ryffel, Isabelle Couillin
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Lung injury leads to pulmonary inflammation and fibrosis through myeloid differentiation primary response gene 88 (MyD88) and the IL-1 receptor 1 (IL-1R1) signaling pathway. The molecular mechanisms by which lung injury triggers IL-1beta production, inflammation, and fibrosis remain poorly understood.To determine if lung injury depends on the NALP3 inflammasome and if bleomycin (BLM)-induced lung injury triggers local production of uric acid, thereby activating the NALP3 inflammasome in the lung.Inflammation upon BLM administration was evaluated in vivo in inflammasome-deficient mice. Pulmonary uric acid accumulation, inflammation, and fibrosis were analyzed in mice treated with the inhibitor of uric acid synthesis or with uricase, which degrades uric acid.Lung injury depends on the NALP3 inflammasome, which is triggered by uric acid locally produced in the lung upon BLM-induced DNA damage and degradation. Reduction of uric acid levels using the inhibitor of uric acid synthesis allopurinol or uricase leads to a decrease in BLM-induced IL-1beta production, lung inflammation, repair, and fibrosis. Local administration of exogenous uric acid crystals recapitulates lung inflammation and repair, which depend on the NALP3 inflammasome, MyD88, and IL-1R1 pathways and Toll-like receptor (TLR)2 and TLR4 for optimal inflammation but are independent of the IL-18 receptor.Uric acid released from injured cells constitutes a major endogenous danger signal that activates the NALP3 inflammasome, leading to IL-1beta production. Reducing uric acid tissue levels represents a novel therapeutic approach to control IL-1beta production and chronic inflammatory lung pathology.
Microbial evaluation of proton-pump inhibitors and the risk of pneumonia
Authors: S. C. A. Meijvis, M. C. A. Cornips, G. P. Voorn, P. C. Souverein, H. Endeman, D. H. Biesma, H. G. M. Leufkens, E. M. W. van de Garde
Journal: European Respiratory Journal (2011)

Recent initiation of proton-pump inhibitor (PPI) treatment may increase the risk of community-acquired pneumonia (CAP), hypothetically by allowing colonisation of the oropharynx by gastrointestinal bacteria. The aim of this study was to assess the causal pathway by considering microbial aetiology of pneumonia and indications for initiation of PPI treatment. This was a population-based, case-control study with 430 cases with pneumonia and 1,720 matched controls. An elaborate diagnostic protocol was used to identify the causative microorganism of pneumonia. For patients recently starting PPI treatment, indications for treatment were assessed. Recent initiation of PPI treatment (<30 days) was associated with an increased risk of CAP (adjusted OR 3.1, 95% CI 1.4-7.1). Oropharyngeal bacteria were evenly distributed among current users, past users and nonusers of PPIs (p=0.41). Gastrointestinal bacteria were identified in only five (1.2%) patients with pneumonia (two current users and three nonusers). Excluding patients who were possibly prescribed PPI treatment for early symptoms of pneumonia (protopathic bias) did not alter the study findings. This study reaffirmed that use of PPIs is associated with an increased risk of CAP, especially when treatment has recently been started. Neither protopathic bias nor shifts in microbial aetiology seem to explain the association.
Anti-EMMPRIN Monoclonal Antibody as a Novel Agent for Therapy of Head and Neck Cancer
Authors: Nichole R. Dean, J. Robert Newman, Emily E. Helman, Wenyue Zhang, Seena Safavy, D.M. Weeks, Mark Cunningham, Linda A. Snyder, Yi Tang, Li Yan, Lacey R. McNally, Donald J. Buchsbaum, Eben L. Rosenthal
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Extracellular matrix metalloprotease inducer (EMMPRIN) is a tumor surface protein that promotes growth and is overexpressed in head and neck cancer. These features make it a potential therapeutic target for monoclonal antibody (mAb)–based therapy. Because molecular therapy is considered more effective when delivered with conventional cytotoxic agents, anti-EMMPRIN therapy was assessed alone and in combination with external beam radiation. Experimental Design: Using a murine flank model, loss of EMMPRIN function was achieved by transfection with a small interfering RNA against EMMPRIN or treatment with a chimeric anti-EMMPRIN blocking mAb. Cytokine expression was assessed for xenografts, tumor cells, fibroblasts, and endothelial cells. Results: Animals treated with anti-EMMPRIN mAb had delayed tumor growth compared with untreated controls, whereas treatment with combination radiation and anti-EMMPRIN mAb showed the greatest reduction in tumor growth (P = 0.001). Radiation-treated EMMPRIN knockdown xenografts showed a reduction in tumor growth compared with untreated knockdown controls (P = 0.01), whereas radiation-treated EMMPRIN–expressing xenografts did not show a delay in tumor growth. Immunohistochemical evaluation for Ki67 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) resulted in a reduction in proliferation (P = 0.007) and increased apoptosis in anti-EMMPRIN mAb–treated xenografts compared with untreated controls (P = 0.087). In addition, we provide evidence that EMMPRIN suppression results in decreased interleukin 1β (IL-1β), IL-6, and IL-8 cytokine production, in vitro and in vivo. Conclusions: These data suggest that anti-EMMPRIN antibody inhibits tumor cell proliferation in vivo and may represent a novel targeted treatment option in head and neck squamous cell carcinoma.
VAGOTOMY—FIVE YEARS LATER
Authors: WILLIAM M. SHANAHAN
Journal: American Journal of Psychiatry (1955)

On an average of 5 years after complete vagotomy, 24 of 25 peptic ulcer patients had no physical recurrence; 6, or 64%, of all men, achieved an excellent functional result with improved vigor, amiability, and total adjustment. No new psychiatric morbidity of any type has appeared in these patients. Eight, or 32%, 3 of whom were women, while anatomically cured, are dissatisfied with vagotomy, maladjusted, and incapacitated by hypochondriasis, other psychosomatic disorder, or working under duress. Study indicates that the patient who will probably get a good functional result from vagotomy can be psychiatrically identified prior to surgery. Suggested criteria for the identification of those who may get a poor functional result are also presented. This does not mean that these cases should not be operated upon if the accomplishment of an anatomical result is deemed of sufficient importance. In addition to the individuals who accept their dependency and those who present reaction formation, there would appear to be a third group, namely, those who are independent at work and dependent at home. In peptic ulcer patients with satisfactory reaction formation, it seems that some characteristics previously considered a part of the patient's personality are really pathoneurotic reactions to frustration of neurotic equilibrium and that they will vanish with successful vagotomy. Intensive study of individual cases of functional success and failure after vagotomy will amplify our understanding of the psychodynamics involved and improve our ability to assist the surgeon in selecting cases.
Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme
Authors: Todd D. Camenisch, Andrew P. Spicer, Tammy Brehm-Gibson, Jennifer Biesterfeldt, Mary Lou Augustine, Anthony Calabro, Steven Kubalak, Scott E. Klewer, John A. McDonald
Journal: Journal of Clinical Investigation (2000)

We identified hyaluronan synthase-2 (Has2) as a likely source of hyaluronan (HA) during embryonic development, and we used gene targeting to study its function in vivo. Has2–/– embryos lack HA, exhibit severe cardiac and vascular abnormalities, and die during midgestation (E9.5–10). Heart explants from Has2–/– embryos lack the characteristic transformation of cardiac endothelial cells into mesenchyme, an essential developmental event that depends on receptor-mediated intracellular signaling. This defect is reproduced by expression of a dominant-negative Ras in wild-type heart explants, and is reversed in Has2–/– explants by gene rescue, by administering exogenous HA, or by expressing activated Ras. Conversely, transformation in Has2–/– explants mediated by exogenous HA is inhibited by dominant-negative Ras. Collectively, our results demonstrate the importance of HA in mammalian embryogenesis and the pivotal role of Has2 during mammalian development. They also reveal a previously unrecognized pathway for cell migration and invasion that is HA-dependent and involves Ras activation.
Long-Term Effects of In Utero Exposure to Cyclosporin A on Renal Function in the Rabbit
Authors: Anai[Combining Diaeresis]s Tendron-Franzin, Jean-Bernard Gouyon, Jean-Pierre Guignard, Ste[Combining Acute Accent]phane Decramer, Eve Justrabo, Thierry Gilbert, Denis Salomon Semama
Journal: Journal of the American Society of Nephrology (2004)

The number of pregnant women who receive cyclosporin A (CsA) after transplantation or for autoimmune disease has increased. CsA and its metabolites can cross the placental barrier and thus interfere with fetal development. It was shown previously that rabbits that were exposed <i>in utero</i> to 10 mg/kg per d CsA from the 14th to the 18th day of gestation presented a 25% nephron reduction. Thus, this study was conducted to assess the long-term systemic and renal effects of a CsA-induced nephron reduction. Twenty-two pregnant New Zealand white rabbits were randomly divided into two groups: Twelve received 10 mg/kg per d CsA from day 14 to day 18 of gestation, and 10 were used as controls. Rabbits that were born to these animals were evaluated at 4, 11, 18, and 35 wk of life. Pups that were exposed antenatally to CsA presented first a permanent nephron deficit; second, glomerular, tubular, and intrarenal hemodynamics dysfunction; third, enlarged kidneys with numerous tubular and glomerular lesions; and, fourth, an endothelin-dependent systemic hypertension that worsened with age. <i>In utero</i> exposure to CsA induced a nephron reduction that led to systemic hypertension and progressive chronic renal insufficiency in adulthood. A long-term clinical survey is mandatory in infants who are born to mothers who were treated with cyclosporin during pregnancy.
Renal effects of aspirin and low dose methotrexate in rheumatoid arthritis.
Authors: P Seideman, R Müller-Suur
Journal: Annals of the Rheumatic Diseases (1993)

The aim of this investigation was to study the glomerular and tubular effects of low doses (15 mg) of methotrexate in patients with rheumatoid arthritis with and without combined treatment with aspirin (2 g single dose). Renal function was measured by the plasma clearance of EDTA labelled with chromium-51 (51Cr-EDTA) and mercaptoacetyltriglycine labelled with technetium-99m (99mTc-MAG-3). Clearance of 51Cr-EDTA was reduced from 98 (6) to 87 (5) ml/min (mean (SEM)) for patients receiving methotrexate only and further reduced to 76 (5) ml/min for patients receiving methotrexate and aspirin. This effect was reversible as 51Cr-EDTA increased to 85 (6) ml/min during continued treatment with methotrexate alone. Clearance of 99mTc-MAG-3 also decreased from 366 (18) to 315 (17) ml/min in patients receiving methotrexate alone and further to 295 (17) ml/min during treatment with aspirin and methotrexate. Continued treatment with methotrexate alone resulted in a further decrease in the 99mTc-MAG-3 clearance to 253 (17) ml/min. The study shows that treatment with low doses of methotrexate particularly when combined with aspirin affects glomerular and tubular function. These effects may be of clinical importance and renal function should therefore be monitored with more sensitive methods than serum creatinine as this may not reflect these changes.
Value of biomarkers in osteoarthritis: current status and perspectives
Authors: M Lotz, J Martel-Pelletier, C Christiansen, M-L Brandi, O Bruyère, R Chapurlat, J Collette, C Cooper, G Giacovelli, J A Kanis, M A Karsdal, V Kraus, W F Lems, I Meulenbelt, J-P Pelletier, J-P Raynauld, S Reiter-Niesert, R Rizzoli, L J Sandell, W E Van Spil, J-Y Reginster
Journal: Annals of the Rheumatic Diseases (2013)

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the 'omics' (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.