tbuckley/cabot-search huggingface dataset:
Pre-treatment with trimetazidine increases sarcolemmal mechanical resistance in reoxygenated myocytes
Authors: M. Ruiz-Meana, D. Garcia-Dorado, M. Julia, M. A. Gonzalez, J. Inserte, J. Soler-Soler
Journal: Cardiovascular Research (1996)

Cytoskeletal and sarcolemmal fragility secondary to anoxia may contribute to sarcolemmal rupture and cell death during reoxygenation of cardiomyocytes. This study investigated the influence of trimetazidine (TMZ), a drug with effects on lipid metabolism and cell membranes, on reoxygenation-induced sarcolemmal rupture.Methods: Isolated adult rat myocytes were submitted to 60 min of metabolic inhibition and 5 min of hypo-osmotic reoxygenation to simulate reperfusion edema in situ. Cells were allocated to 3 groups of treatment: in one group, TMZ 100 μmol/1 was added to both the metabolic inhibition and reoxygenation buffers (group TMZ); another group was submitted to the same treatment but cells had previously been incubated with TMZ 100 μmol/1 for 3 h (group TMZ-Pre); a control group underwent metabolic inhibition and hypo-osmotic reoxygenation without any treatment. Cell morphology was monitored throughout the experiment and sarcolemmal integrity was assessed by quantification of LDH activity and trypan blue exclusion test.Results: After 60 min of metabolic inhibition most cells (83.1 ± 2%) presented rigor contracture without between-group differences. Reoxygenation resulted in hypercontracture of 84.2 ± 2.3, 91.2 ± 1.4 and 84.1 ± 2.1% of cells in TMZ, TMZ-Pre and control groups, P =NS. The trypan blue exclusion test revealed a higher proportion of cells with sarcolemmal integrity in TMZ and TMZ-Pre groups than in controls (12.7 ± 2.0, 10.0 ± 1.5 and 6.3 ± 0.8%, respectively, P = 0.002). No between-group differences in LDH activity in the extracellular medium were observed at the onset or at the end of metabolic inhibition. However, LDH release was significantly lower (P = 0.002) in the TMZ-Pre group (1.6 ± 0.1 IU/1000 cells) than in the TMZ and control groups (1.9 ± 0.2 and 2.2 ± 0.1 IU/1000 cells).Conclusion: Preincubation of cardiomyocytes with TMZ does not prevent rigor contracture induced by metabolic inhibition or hypercontracture during subsequent reoxygenation, but does improve sarcolemmal resistance to reoxygenation-induced mechanical stress. This could help to explain the beneficial effect of TMZ on infarct size.
Abstract 3622: Preclinical characterization of EMD1214063, a potent and highly selective inhibitor of the c-Met kinase in Phase I clinical trials
Authors: Friedhelm Bladt, Andree Blaukat, Dieter Dorsch, Claus Fittschen, Manja Friese-Hamim, Ulrich Graedler, Michael Meyring, Wilfried Rautenberg, Oliver Schadt, Frank Stieber
Journal: Cancer Research (2010)

Abstract c-Met, the receptor for hepatocyte growth factor (HGF), is a well characterized receptor tyrosine kinase, which is crucial for cell functions, such as survival, proliferation, motility and migration. Activating point mutations of c-Met have been identified in human malignancies, including renal carcinoma and lung cancer and constitutive activation of the HGF/c-Met pathway leads to tumor development and progression in cancer animal models. In the light of these findings, c-Met has become a key target for oncology therapeutics. In order to develop c-Met specific inhibitors, we have conducted a biochemical HTS run with the recombinant kinase domain of c-Met. This approach has enabled us to identify a new class of c-Met inhibitors. Our report will focus on pharmacological and pre-clinical data, characterising EMD1214063, a promising therapeutic candidate currently under clinical testing. Inhibition of the c-Met kinase by EMD1214063 was potent and highly selective. In in vitro kinase reactions and binding assays, EMD1214063 at a dose of 1μM, inhibited only 5 additional kinases in a panel of more than 250 different potential off-targets more than 50%. In vitro, EMD1214063 interfered with survival, anchorage-independent growth and HGF-induced migration of tumor cells, by blocking HGF-dependent as well as constitutive phosphorylation of c-Met. In vivo, oral administration of EMD1214063 resulted in a strong inhibition - ranging from delayed growth to complete regression - of HGF-dependent and -independent c-Met driven tumor xenografts. Such anti-tumor activity was observed at a broad dose range, suggesting that EMD1214063 has a wide therapeutic index. The inhibitor was well tolerated, as indicated by the lack of significant weight loss in treated mice. The mechanism of action of EMD1214063 was investigated in vivo in a series of PK/PD studies. Administration of a single dose of EMD1214063 induced a complete and long-lasting inhibition of c-Met phosphorylation in the tumor xenografts. Furthermore, it strongly reduced the plasma levels of tumor-derived IL-8. c-Met phosphorylation and plasma IL-8 levels decreased as a function of the drug concentration in the tumor and plasma. Taken together, the high c-Met selectivity, potency and in vivo efficacy of EMD1214063 render this compound a very promising candidate for the treatment of patients bearing c-Met-driven tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3622.
Asymmetric Edema of the Upper Lung Due to Mitral Valvular Dysfunction
Authors: Siva Raman, Sudhakar Pipavath
Journal: New England Journal of Medicine (2009)

This 80-year-old woman with chronic obstructive pulmonary disease and mitral-valve prolapse presented with dyspnea, orthopnea, and dry cough. A chest radiograph showed mild cardiomegaly and air-space disease in the upper lobes, more on the right than on the left.
Stress Hormone–Mediated Invasion of Ovarian Cancer Cells
Authors: Anil K. Sood, Robert Bhatty, Aparna A. Kamat, Charles N. Landen, Liz Han, Premal H. Thaker, Yang Li, David M. Gershenson, Susan Lutgendorf, Steven W. Cole
Journal: Clinical Cancer Research (2006)

Abstract Purpose: There is growing evidence that stress and other behavioral factors may affect cancer progression and patient survival. The underlying mechanisms for this association are poorly understood. The purpose of this study is to determine the effects of stress-associated hormones norepinephrine, epinephrine, and cortisol on the invasive potential of ovarian cancer cells. Experimental Design: The ovarian cancer cells EG, SKOV3, and 222 were exposed to increasing levels of either norepinephrine, epinephrine, or cortisol, and the in vitro invasive potential was determined using the membrane invasion culture system. Additionally, the effects of these stress hormones on matrix metalloproteinase-2 (MMP-2) and MMP-9 were determined by ELISA. The effects of the β-adrenergic agonist isoproterenol on in vivo tumor growth were determined using nude mice. Results: Stress levels of norepinephrine increased the in vitro invasiveness of ovarian cancer cells by 89% to 198%. Epinephrine also induced significant increases in invasion in all three cell lines ranging from 64% to 76%. Cortisol did not significantly affect invasiveness of the EG and 222 cell lines but increased invasion in the SKOV3 cell line (P = 0.01). We have previously shown that ovarian cancer cells express β-adrenergic receptors. The β-adrenergic antagonist propanolol (1 μmol/L) completely blocked the norepinephrine-induced increase in invasiveness. Norepinephrine also increased tumor cell expression of MMP-2 (P = 0.02 for both SKOV3 and EG cells) and MMP-9 (P = 0.01 and 0.04, respectively), and pharmacologic blockade of MMPs abrogated the effects of norepinephrine on tumor cell invasive potential. Isoproterenol treatment resulted in a significant increase in tumor volume and infiltration in the SKOV3ip1 in vivo model, which was blocked by propranolol. Conclusions: These findings provide direct experimental evidence that stress hormones can enhance the invasive potential of ovarian cancer cells. These effects are most likely mediated by stimulation of MMPs.
P31. Genomic profiling and functional characterisation of a new myeloid cell type enriched in renal cell carcinoma
Authors: D Brech, M Irmler, T Straub, P Bruns, C Jaekel, E Noessner
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Dendritic cells (DCs) are central players of the immune response because they regulate both innate and adaptive immune cells. As part of the leukocyte infiltrate of various tumours they can initiate antitumour immune responses through the activation of tumour-specific T cells.
A registry of drug funding policies would be more useful for patients than one of doctors' competing interests
Authors: R. Thornett, H. Thornett, J. Haswell, A. Thornett
Journal: BMJ (2014)

Although we understand the proposed reasons for setting up a register of GPs’ competing interests,1 this aspect of practice is not the one of most concern to us as patients. When we visit our GP or practice nurse, we do not sit in the waiting room wondering whether our health …
Pleasures of medical writing.
Authors: J Apley
Journal: BMJ (1976)

In Stockholm  little while ago I was introduced to  charming, grey-haired lady doctor who said: I'm so glad to meet you. I've had you on my bookshelf for years. Could anything but writing match so great  pleasure  A novelist remarked that authors go through three stages in the writing process. Firstly, euphoria, the stage of ideas when they say to themselves  will come out all right. Just  few more hours. No trouble at all. Secondly, the stage of depression or anxiety, when they chain-smoke, nibble their nails, kick the dog, and quarrel with the wife. Will it ever come out ? This is the stage when they might recall Nietzsche's cruel comment on Brahms's music: The melancholy of impotence. Thirdly, and lastly, is the stage of relief, when they pat the dog, kiss the wife, and ask themselves Now, what do I write next ? But, perhaps you say, novelists and medical writers are different. I began to wonder when I heard  novelist defined as a man who puts  notebook under the bed on his wedding night, but on reflection I did not think modern novelists bother with  wedding night. No, writers are writers, even though they may be grouped, like teeth, into incisors and grinders.
Screening for HTLV-III Antibodies: The Relation Between Prevalence and Positive Predictive Value and Its Social Consequences
Authors: C. E. Miller
Journal: JAMA (1985)

To the Editor.—  Weiss et al, 1 in their article on a screening test for human T-cell leukemia (lymphotropic) retrovirus type III (HTLV-III) antibodies, reported a specificity of 98.6% and a sensitivity of 97.3%, excluding borderline test results. These values of specificity and sensitivity are quite impressive, but they are, in reality, not practical. Borderline results cannot be excluded in actual practice. As the authors point out, if borderline results are considered positive, the specificity and sensitivity are 92.6% and 96.7%, respectively. If the borderline results are considered negative, the specificity and sensitivity are 98.7% and 81.7%, respectively. Excluding the borderline results may give an erroneous impression of the performance of the test.  It would seem that, for the present state of the art, borderline results should be considered positive in screening blood donors. The specificity and sensitivity of a test are applicable only to populations represented by the group
THE USE OF GELATO-GLYCERIN BOUGIES IN THE TREATMENT OF ACUTE EARACHE IN YOUNG CHILDREN.
Authors: GEO. L. RICHARDS
Journal: JAMA (1903)

It is commonly stated that remedies applied to the external canal in the treatment of acute earache are of very little use, since, owing to the fact that the canal and tympanic membrane are lined with epithelium, which is an extension inward of the skin, the absorption is so slight that remedies of this class can do but very little good. While it is true that absorption is much less and slower than is the case when remedies can be applied to a mucous membrane, I am nevertheless fully persuaded that absorption of medicaments can take place through the external surface of the tympanic membrane, and that many remedies can be exhibited in this way to the comfort of the patient. In my early experience I often used morphin and atrophin solutions in the form of drops, and various oils and other external ear drops are in universal use. Acute earache in young children is sudden and severe
Bladder cancer as a prescribed industrial disease: a guide for clinicians.
Authors: S M Somerville, J M Davies, W F Hendry, G Williams
Journal: BMJ (1980)

Urologists, radiotherapists, general surgeons, and family doctors concerned with the care of patients with urothelial tumours need to be alert for cases where the disease is occupational. The aim of this paper is to advise clinicians how to identify patients with occupational tumours and help them obtain compensation; it expands and updates an earlier guidance note of 1961 by the British Association of Urological Surgeons.1
One patient, two unusual conditions and three basic lessons.
Authors: J M Gardner-Medwin, R J Powell
Journal: Annals of the Rheumatic Diseases (1996)

Case reportA 54 year old woman presented with Raynaud's phenomenon, stiff fingers, and generalised thinning of her hair.She had a long history of pain in the knees and a past history of asthma controlled with inhalers.Examination revealed active digital vasculitis, marked facial telangiectasia, difficulty in fully opening her mouth, and osteoarthritis of the knees, subsequently confirmed radiographically.She was strongly positive for antinuclear antibody, and was anti-Sm positive, with a further undefined extractable nuclear antibody, but was negative for double stranded DNA.The table lists other initial investigations from 1989.A quadriceps muscle biopsy specimen taken for investigation of the increased creatine kinase (CK) concentration (462 U/1) showed only type 2 atrophy and small vessel thickening.An undifferentiated connective tissue disease was diagnosed, and treated with oral prednisolone and continuing azathioprine treatment at a starting dose of 100 mg/day, with a good clinical response, resolution of the vasculitis, and a return of the CK concentration to 156 U/A.After two years, the digital vasculitis recurred and responded to an increase of the dose of azathioprine to 200 mg/day, but this was subsequently withdrawn because of suspected drug induced neutropenia (1-58 x 109/1).The patient received no drugs during the next six months as she declined to transfer her medical care to Spanish physicians during her annual visit over the winter months to the southern coast of Spain.She returned prematurely to England at Christmas 1991 with active digital vasculitis (table), and restarted azathioprine
CILOSTAZOL IMPROVES PRIMARY PATENCY AFTER FEMOROPOPLITEAL STENTING WITH SELF-EXPANDABLE NITINOL STENT
Authors: Yoshimitsu Soga, Osamu Iida, Keisuke Hirano, Kenji Suzuki, Hiroyoshi Yokoi, Shinsuke Nanto, Toshiya Muramatsu, Naoto Inoue
Journal: Journal of the American College of Cardiology (2011)
Secondary prevention in CAD: A significant correlation between LDL-cholesterol (LDL-C) achieved therapeutically and extent of progression reduction claims for LDL-C target levels &lt; 100 mg/dl
Authors: H.P. Bestehom, U.F.E. Rensing, H. Roskamm, L. Benesch, G. Blümchen, P. Mathes, L. Kappenberger
Journal: Journal of the American College of Cardiology (1996)
Exome sequencing identifies GRIN2A as frequently mutated in melanoma
Authors: Xiaomu Wei, Vijay Walia, Jimmy C Lin, Jamie K Teer, Todd D Prickett, Jared Gartner, Sean Davis, Katherine Stemke-Hale, Michael A Davies, Jeffrey E Gershenwald, William Robinson, Steven Robinson, Steven A Rosenberg, Yardena Samuels
Journal: Nature Genetics (2011)
Cardiac Resuscitation And Vertebral Fracture
Authors: Yune-Gill JEONG
Journal: JAMA (1975)

To the Editor.—  A compression fracture of the thoracic veterbrae during cardiac resuscitation by countershock and external cardiac massage appears to be an extremely unusual but serious complication. We know of only one previous report in the literature (203:369, 1968), and the article by Atcheson and Fred, 1 which recently reviewed very thoroughly the complications of cardiac resuscitation, did not point out this extraordinary complication.  Report of a Case.—  A 54-year-old woman with acute anterior myocardial infarction lost consciousness in the ambulance, and ventricular fibrillation developed on arrival at the hospital. She was successfully resuscitated by external cardiac massage and two direct-current countershocks of 400 joules.  Following the resuscitation, the patient complained of severe midback pain particularly when supine. There was diffuse swelling in the region of the sixth, seventh, and eighth thoracic vertebrae, and tenderness was elicited by deep palpation. The x-ray film of the thoracic spine demonstrated a
Outcomes and Costs of Elective Surgery for Diverticular Disease
Authors: Kyle J. Van Arendonk, Kevin M. Tymitz, Susan L. Gearhart, Miloslawa Stem, Anne O. Lidor
Journal: JAMA Surgery (2012)

<h3>Objective</h3>To compare outcomes and costs of elective surgery for diverticular disease (DD) with those of other diseases commonly requiring colectomy.<h3>Design</h3>Multivariable analyses using the Nationwide Inpatient Sample to compare outcomes across primary diagnosis while adjusting for age, sex, race, year of admission, and comorbid disease.<h3>Setting</h3>A sample of US hospital admissions from 2003-2009.<h3>Patients</h3>All adult patients (≥18 years) undergoing elective resection of the descending colon or subtotal colectomy who had a primary diagnosis of DD, colon cancer (CC), or inflammatory bowel disease (IBD).<h3>Main Outcome Measures</h3>In-hospital mortality, postoperative complications, ostomy placement, length of stay, and hospital charges.<h3>Results</h3>Of the 74 879 patients, 50.52% had DD, 43.48% had CC, and 6.00% had IBD. After adjusting for other variables, patients with DD were significantly more likely than patients with CC to experience in-hospital mortality (adjusted odds ratio, 1.90; 95% CI, 1.37-2.63; P &lt; .001), develop a postoperative infection (1.67; 1.48-1.89; P &lt; .001), and have an ostomy placed (1.87; 1.65-2.11; P &lt; .001). The adjusted total hospital charges for patients with DD were $6678.78 higher (95% CI, $5722.12-$7635.43; P &lt; .001) and length of stay was 1 day longer (95% CI, 0.86-1.14; P &lt; .001) compared with patients with CC. Patients with IBD had the highest in-hospital mortality, highest rates of complications and ostomy placement, longest length of stay, and highest hospital charges.<h3>Conclusions</h3>Despite undergoing the same procedure, patients with DD have significantly worse and more costly outcomes after elective colectomy compared with patients with CC but better than patients with IBD. These relatively poor outcomes should be recognized when considering routine elective colectomy after successful nonoperative management of acute diverticulitis.
An Elevated Breathing Reserve Index at the Lactate Threshold Is a Predictor of Mortality in Patients with Cystic Fibrosis Awaiting Lung Transplantation
Authors: Kelan G. Tantisira, David M. Systrom, Leo C. Ginns
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The proportion of cystic fibrosis (CF) patients dying while on the lung transplant wait list remains high; identification of such patients remains difficult. The breathing reserve index (BRI = minute ventilation/maximal voluntary ventilation) at the lactate threshold (LT) is a predictor of a pulmonary mechanical limit to incremental exercise. We hypothesized that an elevated BRI at the LT in patients with CF awaiting lung transplantation would be a predictor of wait list mortality. Forty-five consecutive patients with CF completed cardiopulmonary exercise testing as part of their pretransplant assessment. We evaluated BRI at LT, baseline demographic characteristics, pulmonary function, and other exercise parameters via Cox proportional hazards modeling. Fifteen patients died while awaiting transplant. Twenty one were transplanted, and nine still awaited transplantation. Relative risks from the multivariate model included (95% confidence interval in parentheses) BRI at LT, 17.52 (2.45–123.97); resting PaCO2, 1.29 (1.10–1.49); resting PaO2, 0.97 (0.90–1.05); and forced expiratory volume at one second as a percent of predicted, 1.19 (1.05–1.34). BRI at LT not only provided the highest point estimate of risk for wait list mortality but also identified a physiologically significant threshold value (0.70 or more) for those at risk. This measurement may allow improved timing of listing for transplantation, including consideration for living donor transplantation.
<i>Mycobacterium mucogenicum</i>Infection Following Dacryocystorhinostomy and Crawford Tube Placement
Authors: Mark Tye Haeberle, Patricia Todd, Jeffrey P. Callen, Soon Bahrami
Journal: JAMA Dermatology (2014)

Nontuberculous mycobacterial infections of the skin can be seen in cases of immunosuppression and/or traumatic implantation of contaminated objects. Surgical settings with appropriate sterilization techniques have been immune to these types of infections. We report a case of nosocomially derived infection from a sterile procedure.A woman in her 70s presented with a facial lesion after an ophthalmologic procedure that was discovered to be a nontuberculous mycobacterial infection. It was successfully treated with oral antibiotics.Nontuberculous mycobacterial infections should be considered in the differential diagnosis of new lesions arising after invasive procedures, even in immunocompetent patients in seemingly sterile settings.
Superiority of Tandem Autologous Transplantation Over Standard Therapy for Previously Untreated Multiple Myeloma
Authors: Bart Barlogie, Sundar Jagannath, David H. Vesole, Sally Naucke, Bruce Cheson, Sandy Mattox, Dwayne Bracy, Sydney Salmon, Joth Jacobson, John Crowley, Guido Tricot
Journal: Blood (1997)
Volunteering Overseas — Lessons from Surgical Brigades
Authors: Adam J. Wolfberg
Journal: New England Journal of Medicine (2006)

Interview with Dr. Mark Migliori on his work as a volunteer surgeon in developing countries. (07:22)Download Dr. Mark Migliori's approach to international surgical care is minimalist. With another surgeon, two anesthesiologists, and two or three nurses, he travels to a rural hospital in Guatemala. The group evaluates dozens of children from the surrounding villages whom local health care workers have identified as potential candidates for surgery — primarily the repair of cleft lips and palates. Each surgeon operates on as many as 15 children each day with the use of local hospital equipment augmented with supplies brought from home. When they leave, local health care workers provide follow-up care, consulting with Migliori by e-mail as necessary. . . .
Uterine Sarcoma Associated with Tamoxifen Use
Authors: Diane K. Wysowski, Susan Flamm Honig, Julie Beitz
Journal: New England Journal of Medicine (2002)

To the Editor: Between 1978, when tamoxifen was first marketed in the United States, and April 2001, there were 43 cases, reported either to the Food and Drug Administration (FDA) or in the medical...
Long-Term Effects of Clofibrate (Atromid-S) on Serum Lipids in Man
Authors: DONALD B. HUNNINGHAKE, DONALD R. TUCKER, DANIEL L. AZARNOFF
Journal: Circulation (1969)

Clofibrate was administered to 45 patients for varying periods of time up to 4 years with no evidence of chronic toxicity. Clofibrate was more effective in lowering serum triglycerides than serum cholesterol, with more than 75% of all patients with elevated triglycerides having at least a 25% reduction in triglycerides, the absolute reduction in triglycerides being directly correlated with pretreatment values. A reduction in serum cholesterol of 15% or more was obtained in 50% of all patients, those individuals with elevations of triglycerides having the greatest reduction in serum cholesterol as well as being most likely to respond.