tbuckley/cabot-search huggingface dataset:
Gene-expression profiling of the response of peripheral blood mononuclear cells and melanoma metastases to systemic IL-2 administration
Authors: Monica C Panelli, Ena Wang, Giao Phan, Markus Puhlmann, Lance Miller, Galen A Ohnmacht, Harvey G Klein, Francesco M Marincola
Journal: Genome biology (2002)

Interleukin-2 (IL-2) has direct pluripotent effects on cells with immune and inflammatory function. Which of these effects has a critical role in mediating tumor regression remains enigmatic. In this study, we compared early changes in transcriptional profiles of circulating mononuclear cells with those occurring within the microenvironment of melanoma metastases following systemic IL-2 administration.The results suggest that the immediate effects of IL-2 administration on the tumor microenvironment is transcriptional activation of genes predominantly associated with monocyte cell function; minimal effects were noted on migration, activation and proliferation of T cells. However, production of chemokines and markers of adhesion and migration within few hours of IL-2 administration may be responsible for a secondary recruitment of immune cells to the tumor site later.Our results suggest that IL-2 induces inflammation at tumor sites with three predominant secondary effects: activation of antigen-presenting monocytes; massive production of chemoattractants that may recruit other immune cells to the tumor (including MIG and PARC, which are specific for T cells); and activation of cytolytic mechanisms in monocytes (calgranulin, grancalcin) and NK cells (NKG5, NK4).
Trends in Human Leptospirosis in Denmark, 1980 to 2012
Authors: L B van Alphen, A Lemcke Kunoe, T Ceper, J Kähler, C Kjelsø, S Ethelberg, K A Krogfelt
Journal: Eurosurveillance (2015)

Binary file ES_Abstracts_Final_ECDC.txt matches
The effect of sports specific training on reducing the incidence of hamstring injuries in professional Australian Rules football players
Authors: G M Verrall, J P Slavotinek, P G Barnes
Journal: British Journal of Sports Medicine (2005)

Objectives: To assess in a single team of Australian Rules football players the effect of a specific intervention program on the incidence and consequence of hamstring muscle strain injuries. Method: A prospective study was performed with a single team being followed for four playing seasons for hamstring injury. Magnetic resonance imaging was used to confirm the diagnosis of hamstring muscle injury. After two playing seasons an intervention program was implemented with the number of athletes with hamstring injury, competition days missed, and incidence of hamstring match injuries per 1000 h of playing time being compared pre- and post-intervention. The intervention program involved stretching whilst fatigued, sport specific training drills, and an emphasis on increasing the amount of high intensity anaerobic interval training. Results: In the seasons prior to the intervention, nine and 11 athletes sustained hamstring injury compared to two and four following intervention. Competition days missed reduced from 31 and 38 to 5 and 16 following intervention and match incidence decreased from 4.7 to 1.3 per 1000 h of playing time. A beneficial effect was demonstrated with a smaller number of players having hamstring injuries (p = 0.05), a lower number of competition games missed being recorded (p&lt;0.001), and a decrease in hamstring strain incidence per 1000 h of playing time (p = 0.01) following the intervention program. Conclusions: Increasing the amount of anaerobic interval training, stretching whilst the muscle is fatigued, and implementing sport specific training drills resulted in a significant reduction in the number and consequences of hamstring muscle strain injuries.
Carbon Monoxide Poisoning
Authors: Lindell K. Weaver, Karen J. Valentine, Ramona O. Hopkins
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Carbon monoxide poisoning is common and causes cognitive sequelae. Hyperbaric oxygen (HBO2) reduces cognitive sequelae incidence, but which patients may benefit from HBO2 is unclear.Objectives: Risk factor determination for 6-wk cognitive sequelae from CO poisoning and risk modification with HBO2.Methods: Patients were from a randomized controlled trial, enrolling acutely CO-poisoned patients more than 15 years of age. Patients eligible but not enrolled in the randomized trial, and not receiving HBO2, were followed during the study interval. In patients not receiving HBO2, we performed univariate analyses including risk factors identified by randomized trial subgroup analyses. A multivariable analysis was performed using univariate results with and without HBO2.Measurements and Main Results: In 163 patients not receiving HBO2, 68 (42%) manifested sequelae. Risk factors for sequelae from subgroup analyses were loss of consciousness, age of 36 years or more, and carboxyhemoglobin levels greater than or equal to 25%. By univariate analyses, risks for sequelae were age of 36 years or more (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.3–4.9; P = 0.005), and exposure intervals greater than or equal to 24 hours (OR, 2.4; 95% CI, 1.2–4.8; P = 0.019). Including 75 patients receiving HBO2, cognitive sequelae was reduced in patients age of 36 years or more (OR, 0.3; 95% CI, 0.2–0.6; P < 0.001). Exposure intervals greater than or equal to 24 hours are an independent risk factor for sequelae (OR, 2.0; 95% CI, 1.0–3.8; P = 0.046).Conclusions: HBO2 oxygen is indicated for patients with acute CO poisoning who are 36 years or older or have exposure intervals greater than or equal to 24 hours. In addition, subgroup analyses support that patients with loss of consciousness or higher carboxyhemoglobin levels warrant HBO2.
Persistent Urinary Salmonella Dublin Carrier with Bilharziasis
Authors: W. S. Miller
Journal: BMJ (1952)

HYPOTHYROIDISM MBR1flSHThe serum cholesterol affords an approximate indication of thyroid status, but seems liable to unaccountable fluctuations.It is a pleasure to thank Mr. A. V. Bridgland, Chairman of the Trustees of the London Clinic, for granting facilities for this investigation.The thyroxine derivative used was
A randomized, double-blind, placebo-controlled study of high-dose bosentan in patients with stage IV metastatic melanoma receiving first-line dacarbazine chemotherapy
Authors: Richard Kefford, Philip R Clingan, Benjamin Brady, Andrea Ballmer, Adele Morganti, Peter Hersey
Journal: Molecular Cancer (2010)

The endothelin system is implicated in the pathogenesis of melanoma. We evaluated the effects of bosentan - a dual endothelin receptor antagonist - in patients receiving first-line dacarbazine therapy for stage IV metastatic cutaneous melanoma in a phase 2, proof-of-concept study. Eligible patients had metastatic cutaneous melanoma naïve to chemotherapy or immunotherapy, no central nervous system involvement, and serum lactate dehydrogenase <1.5 × upper limit of normal. Treatment comprised bosentan 500 mg twice daily or matching placebo, in addition to dacarbazine 1000 mg/m2 every three weeks. Eighty patients were randomized (double-blind) and 38 in each group received study treatment. Median time to tumor progression (primary endpoint) was not significantly different between the two groups (placebo, 2.8 months; bosentan, 1.6 months; bosentan/placebo hazard ratio, 1.144; 95% CI, 0.717-1.827; p = 0.5683). Incidences of most adverse events and clinically relevant increases in hepatic transaminases were similar between treatment groups although hemoglobin decrease to >8 and ≤ 10 g/dL and ≤ 8 g/dL was more common in the bosentan group. In patients receiving dacarbazine as first-line chemotherapy for metastatic melanoma, the addition of high-dose bosentan had no effect on time to tumor progression or other efficacy parameters. There were no unexpected safety findings. This study is registered in ClinicalTrials.gov under the unique identifier NCT01009177.
Case of 'Red Softening' of the Surface of the Left Hemisphere of the Brain: With Sudden Loss of Speech and Hemiplegia
Authors: H. C. Bastian
Journal: BMJ (1867)

She had never had acute rheumatism; she had been ailing six or seven years; her face was sallow and tintless; she complained of being soon out of breath, and on exertion or excitement was seized with pain in the proecordial region and epigastrium, extending to the back, and down
Dr John McLoughlin
Authors: J. Richard Raines
Journal: JAMA (1982)

<h3>To the Editor.—</h3> The article on "Medical Numismatics" by C. R. Allen, Jr, MD, MPH (1981;246:2347), gives a fine overview of this interesting subject. The mention of John McLoughlin deserves amplification because he is the only physician portrayed on a US coin, having his likeness on the Fort Vancouver centennial half-dollar issued in 1925. It is documented that McLoughlin was a physician, trained by preceptorship in Quebec and licensed by examination in Montreal in 1803.<sup>1</sup>He was employed as a contract physician by the Northwest Company, which later became the Hudson's Bay Company. His duties gradually became more administrative, and he was named a chief factor of the Hudson's Bay Company supervising the Northwest Territory. He established Fort Vancouver (in Washington, not British Columbia) in 1825 as the northwest headquarters of the company and administered the far-flung empire from that location for about 20 years. He is credited with
TMEM16A Induces MAPK and Contributes Directly to Tumorigenesis and Cancer Progression
Authors: Umamaheswar Duvvuri, Daniel J. Shiwarski, Dong Xiao, Carol Bertrand, Xin Huang, Robert S. Edinger, Jason R. Rock, Brian D. Harfe, Brian J. Henson, Karl Kunzelmann, Rainer Schreiber, Raja S. Seethala, Ann Marie Egloff, Xing Chen, Vivian W. Lui, Jennifer R. Grandis, Susanne M. Gollin
Journal: Cancer Research (2012)

Frequent gene amplification of the receptor-activated calcium-dependent chloride channel TMEM16A (TAOS2 or ANO1) has been reported in several malignancies. However, its involvement in human tumorigenesis has not been previously studied. Here, we show a functional role for TMEM16A in tumor growth. We found TMEM16A overexpression in 80% of head and neck squamous cell carcinoma (SCCHN), which correlated with decreased overall survival in patients with SCCHN. TMEM16A overexpression significantly promoted anchorage-independent growth in vitro, and loss of TMEM16A resulted in inhibition of tumor growth both in vitro and in vivo. Mechanistically, TMEM16A-induced cancer cell proliferation and tumor growth were accompanied by an increase in extracellular signal-regulated kinase (ERK)1/2 activation and cyclin D1 induction. Pharmacologic inhibition of MEK/ERK and genetic inactivation of ERK1/2 (using siRNA and dominant-negative constructs) abrogated the growth effect of TMEM16A, indicating a role for mitogen-activated protein kinase (MAPK) activation in TMEM16A-mediated proliferation. In addition, a developmental small-molecule inhibitor of TMEM16A, T16A-inh01 (A01), abrogated tumor cell proliferation in vitro. Together, our findings provide a mechanistic analysis of the tumorigenic properties of TMEM16A, which represents a potentially novel therapeutic target. The development of small-molecule inhibitors against TMEM16A may be clinically relevant for treatment of human cancers, including SCCHN.
Metabolic Effects of Human Growth Hormone and of Estrogens in Boys with Duchenne Muscular Dystrophy
Authors: Daniel Rudman, Samuel B. Chyatte, Joseph H. Patterson, Glynda G. Gerron, Irma O'Beirne, Joan Barlow, Ashby Jordan, Joel S. Shavin
Journal: Journal of Clinical Investigation (1972)

Metabolic balance studies were conducted in seven boys with Duchenne-type muscular dystrophy, and in six normal boys of similar age, during a 12 day control period and during a 12 day period of treatment with human growth hormone (HGH) at the following doses: 0.0168, 0.0532, and 0.168 U/kg body weight (BW)((3/4)) per day (doses A, B, and C, respectively). In five of the six normals, dose C caused positive balances in N, P, Na, and K; doses B and A had anabolic effects in two and one normal subjects, respectively. In six of the seven Duchenne cases, dose C caused negative balances of N and K, and sometimes of P. Negative balances were produced in three of the Duchenne subjects by dose B, and in one by dose A. None of the dystrophy cases exhibited an anabolic response to any dosage of HGH tested. The release of endogenous HGH in response to insulin, after 2 days' pretreatment with diethylstilbestrol, was similar in both groups of subjects. In the course of these tests, a marked anabolic effect of diethylstilbestrol in the Duchenne patients was apparent. Therefore metabolic balance studies were repeated, in both Duchenne and normal cases, during a 12 day control period and during 12 days of treatment with diethylstilbestrol (0.106 mg/kg BW((3/4)) per day). In three of the normal children, diethylstilbestrol had no effect on the elemental balances; in two cases, a retention of Na was observed. In all seven Duchenne cases, diethylstilbestrol caused positive balances in N, P, Na, and K. Ethinyl estradiol (0.0106 mg/kg BW((3/4)) per day) produced positive N, P, Na, and K balances in all three Duchenne cases tested with this agent. The data show that exogenous HGH causes a catabolic effect in boys with Duchenne dystrophy. These patients are hyperresponsive to the anabolic effect of diethylstilbestrol. The latter phenomenon may reflect the inhibitory effect of estrogen upon the peripheral actions of these boys' endogenous HGH.
Effects of High-Dose Simvastatin Therapy on Glucose Metabolism and Ectopic Lipid Deposition in Nonobese Type 2 Diabetic Patients
Authors: Julia Szendroedi, Christian Anderwald, Martin Krssak, Michaela Bayerle-Eder, Harald Esterbauer, Georg Pfeiler, Attila Brehm, Peter Nowotny, Astrid Hofer, Werner Waldhäusl, Michael Roden
Journal: Diabetes Care (2008)

Statins may exert pleiotropic effects on insulin action that are still controversial. We assessed effects of high-dose simvastatin therapy on peripheral and hepatic insulin sensitivity, as well as on ectopic lipid deposition in patients with hypercholesterolemia and type 2 diabetes.We performed a randomized, double-blind, placebo-controlled, single-center study. Twenty patients with type 2 diabetes received 80 mg simvastatin (BMI 29 +/- 4 kg/m2, age 55 +/- 6 years) or placebo (BMI 27 +/- 4 kg/m2, age 58 +/- 8 years) daily for 8 weeks and were compared with 10 healthy humans (control subjects; BMI 27 +/- 4 kg/m2, age 55 +/- 7 years). Euglycemic-hyperinsulinemic clamp tests combined with D-[6,6-d2]glucose infusion were used to assess insulin sensitivity (M) and endogenous glucose production (EGP). 1H magnetic resonance spectroscopy was used to quantify intramyocellular and hepatocellular lipids.High-dose simvastatin treatment lowered plasma total and LDL cholesterol levels by approximately 33 and approximately 48% (P < 0.005) but did not affect M, intracellular lipid deposition in soleus and tibialis anterior muscles and liver, or basal and insulin-suppressed EGP. In simvastatin-treated patients, changes in LDL cholesterol related negatively to changes in M (r = -0.796, P < 0.01). Changes in fasting free fatty acids (FFAs) related negatively to changes in M (r = -0.840, P < 0.01) and positively to plasma retinol-binding protein-4 (r = 0.782, P = 0.008).High-dose simvastatin treatment has no direct effects on whole-body or tissue-specific insulin action and ectopic lipid deposition. A reduction in plasma FFAs probably mediates alterations in insulin sensitivity in vivo.
Role of endothelial and smooth muscle cells in the physiopathology and treatment management of pulmonary hypertension
Authors: C Veyssier-Belot
Journal: Cardiovascular Research (1999)

Pulmonary hypertension can occur either as primary or secondary disease following cardiac or pulmonary illnesses. In either cases, histological lung biopsies reveal vascular remodelling i.e. smooth muscle cells proliferation with medial hypertrophy, arteriolar muscularization and endothelial cell proliferation. Subsequent intimal thickening, fibrosis and in situ thrombosis, altogether lead to vaso-occlusive alterations referred to as plexiform lesions. Theories concerning the detailed physiopathology of pulmonary hypertension have focused on endothelial and smooth muscle cells' chemical factors production and response to different mediators. The endothelium produces vasoconstrictor and growth-promoting factor such as endothelin-1 (ET-1) as well as vasodilator and growth-inhibitor factors like prostacyclin and nitric oxide (NO). ET-1 has been noted in high concentrations in some clinical cases and experimental models of pulmonary hypertension, coupled with ET-1 receptors' modulation and altered endothelin converting enzyme activities, suggesting their active role in both arteriolar vasoconstriction and occlusion. Vascular thrombosis which has been noted by pathologists in pulmonary hypertension, could be related to an imbalance between thrombotic inducing factors (such as anti-phospholipid antibodies, ET-1 and thromboxane) and decreased fibrinolytic activity and antiaggregant endothelial factors (like prostacyclin, NO, thrombomodulin). The discovery of an endothelial cells' monoclonal proliferation in plexiform lesions of patients with primary pulmonary hypertension may reinforce the cellular proliferation hypothesis to understand the histopathology of this disease. In view of these new findings, the treatments available for pulmonary hypertension have been expanded from the previously employed oxygen therapy, calcium-channel blockers and anticoagulants, to intravenous prostacyclin analogues (epoprostenol) and inhaled nitric oxide.
Incomplete sulphomucin-secreting intestinal metaplasia for gastric cancer. Preliminary data from a prospective study from three centres.
Authors: M I Filipe, F Potet, W V Bogomoletz, P A Dawson, B Fabiani, P Chauveinc, A Fenzy, B Gazzard, D Goldfain, R Zeegen
Journal: Gut (1985)

A joint prospective long term study of gastric biopsies has been undertaken to survey intestinal metaplasia Types I, II, and III in terms of their incidence, distribution and value in the selection of high risk cancer patients. This study is based on protocols agreed between three centres for endoscopy, histological interpretation, and mucin histochemistry. The results on the first 1350 gastric biopsies examined during 1981-1982 are presented. Intestinal metaplasia was found in 267 biopsies (20%), being common in association with carcinoma (71%), less so in benign conditions such as gastric ulcer (39%), and chronic gastritis (24%), but rare in 'normal' (3%). Type I intestinal metaplasia was predominant (73%) in all the biopsies with intestinal metaplasia and was most common in benign conditions, 70% in gastric ulcer and 76% in chronic gastritis. Type III intestinal metaplasia (incomplete sulphomucin-secreting intestinal metaplasia) was recorded in only 9.8% of all the biopsies with intestinal metaplasia and had a higher incidence in carcinoma (35%), than in benign conditions (7%) (p less than 0.0001). These results suggest that intestinal metaplasia types may have different malignant potential and their identification may be useful in screening patients for early detection of cancer.
The Sun is My Enemy
Authors: N. S. Plummer
Journal: Annals of the Rheumatic Diseases (1973)

This is the personal story of one young woman who suffered from systemic lupus erythematosus for 17 years.Despite renal damage, recovery occurred while she was being treated with nicotinic acid injections along with chloroquine.The doleful but not uncommon story is told of the slowness in recognizing the part played by hypersensitivity to sulphonamides (including Diamox), to many other drugs, and to vaccination against smallpox.The patient goes through all the treatments and even- tually finds her salvation in a Bulgarian doctor and his use of nicotinic acid.She received wonderful care and understanding from some well-known physicians in Boston, Massachusetts.Her personal courage is remark- able and led to her doing much research into the diseaseno doubt mainly with the object of finding a cure.The reviewer is a firm believer in the wider knowledge of medicine and in the understanding of patients to be obtained from plays and television, from the Sunday newspapers, and from the reading of novels.The same is true of personal stories of both common and rare chronic diseases such as this one.He believes that all students of the connective tissue disorders should read this wellwritten story.
Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma
Authors: Robert J. Motzer, Thomas E. Hutson, David Cella, James Reeves, Robert Hawkins, Jun Guo, Paul Nathan, Michael Staehler, Paul de Souza, Jaime R. Merchan, Ekaterini Boleti, Kate Fife, Jie Jin, Robert Jones, Hirotsugu Uemura, Ugo De Giorgi, Ulrika Harmenberg, Jinwan Wang, Cora N. Sternberg, Keith Deen, Lauren McCann, Michelle D. Hackshaw, Rocco Crescenzo, Lini N. Pandite, Toni K. Choueiri
Journal: New England Journal of Medicine (2013)

Pazopanib and sunitinib provided a progression-free survival benefit, as compared with placebo or interferon, in previous phase 3 studies involving patients with metastatic renal-cell carcinoma. This phase 3, randomized trial compared the efficacy and safety of pazopanib and sunitinib as first-line therapy. We randomly assigned 1110 patients with clear-cell, metastatic renal-cell carcinoma, in a 1:1 ratio, to receive a continuous dose of pazopanib (800 mg once daily; 557 patients) or sunitinib in 6-week cycles (50 mg once daily for 4 weeks, followed by 2 weeks without treatment; 553 patients). The primary end point was progression-free survival as assessed by independent review, and the study was powered to show the noninferiority of pazopanib versus sunitinib. Secondary end points included overall survival, safety, and quality of life. Pazopanib was noninferior to sunitinib with respect to progression-free survival (hazard ratio for progression of disease or death from any cause, 1.05; 95% confidence interval [CI], 0.90 to 1.22), meeting the predefined noninferiority margin (upper bound of the 95% confidence interval, <1.25). Overall survival was similar (hazard ratio for death with pazopanib, 0.91; 95% CI, 0.76 to 1.08). Patients treated with sunitinib, as compared with those treated with pazopanib, had a higher incidence of fatigue (63% vs. 55%), the hand-foot syndrome (50% vs. 29%), and thrombocytopenia (78% vs. 41%); patients treated with pazopanib had a higher incidence of increased levels of alanine aminotransferase (60%, vs. 43% with sunitinib). The mean change from baseline in 11 of 14 health-related quality-of-life domains, particularly those related to fatigue or soreness in the mouth, throat, hands, or feet, during the first 6 months of treatment favored pazopanib (P<0.05 for all 11 comparisons). Pazopanib and sunitinib have similar efficacy, but the safety and quality-of-life profiles favor pazopanib. (Funded by GlaxoSmithKline Pharmaceuticals; COMPARZ ClinicalTrials.gov number, NCT00720941.).
Haemoptysis associated with pulmonary varices: demonstration using computed tomographic angiography
Authors: GR Ferretti, F Arbib, B Bertrand, M Coulomb
Journal: European Respiratory Journal (1998)

A 67 yr old female with mitral stenosis presented with an acute haemoptysis caused by the rupture of pulmonary varices. Chest radiography and bronchoscopy showed nonspecific abnormalities. The diagnosis of this rare but potentially lethal complication was made using computed tomographic angiography with three-dimensional volume rendering.