tbuckley/cabot-search huggingface dataset:
Relationship of partially purified factor concentrates to immune tests and AIDS
Authors: Janine Jason, Robert C. Holman, Bruce L. Evatt Group
Journal: American Journal of Hematology (1990)

Abstract We evaluated those members of a cohort of 203 hemophilic men providing all necessary information at their 1984 and 1985 evaluations, to determine whether non‐heated or &lt; 80°C dry heat‐treated partially purified factor products were associated with 1) the development of AIDS in human immunodeficiency virus (HIV)‐infected persons or 2) abnormal immune test results in participants seroconverting or remaining HIV seronegative. We found no relationship between type of factor (VIII vs. IX) (n = 162), frequency of usage (≧once a week vs. &lt; once a week) (n = 141), or yearly doses of non‐heated or dry heat‐treated partially purified factor (n = 118) and the development of AIDS. Seroconverting participants using partially purified factor products ≧once a week in 1984 had lower T‐helper cell numbers in 1985 than those receiving factor less frequently (median 515 vs. 772/mm 3 , n = 9), as did those using factor ≧once a week in 1985 (median 515 vs. 726/mm 3 , n = 10). A similar relation was seen between 1984 frequency and 1985 T‐helper cell numbers of seronegative participants (median 741 vs. 1037/mm 3 , n = 31). The yearly dose of heat‐treated products was not associated with any immune test result or changes in results between years. These findings suggested that frequency of administration of partially purified factor materials may have had an effect upon the immune system, but that total yearly dose did not. Previously used partly purified, dry heat‐treated factor concentrates were not associated with the development of AIDS.
Acute Gouty Arthritis Precipitated by Chlorothiazide
Authors: A. Aronoff
Journal: New England Journal of Medicine (1960)

CHLOROTHIAZIDE has recently been shown to be a potent diuretic agent1 for oral use and to have an important antihypertensive effect2 given in conjunction with other hypotensive agents. In addition to its saluretic action, there is a tendency to potassium depletion3 and ammonia retention.4 More recently many authors3 , 5 6 7 8 9 10 have shown that there is a tendency to an elevation of the serum uric acid in patients receiving chlorothiazide in the treatment of hypertension or congestive heart failure and that this was due to a decreased clearance of urate by the renal tubule.5 Serum uric acid levels in the range of 3 . . .
<scp>l</scp>-Arginine Depletion Blunts Antitumor T-cell Responses by Inducing Myeloid-Derived Suppressor Cells
Authors: Matthew Fletcher, Maria E. Ramirez, Rosa A. Sierra, Patrick Raber, Paul Thevenot, Amir A. Al-Khami, Dulfary Sanchez-Pino, Claudia Hernandez, Dorota D. Wyczechowska, Augusto C. Ochoa, Paulo C. Rodriguez
Journal: Cancer Research (2014)

Abstract Enzymatic depletion of the nonessential amino acid l-Arginine (l-Arg) in patients with cancer by the administration of a pegylated form of the catabolic enzyme arginase I (peg-Arg I) has shown some promise as a therapeutic approach. However, l-Arg deprivation also suppresses T-cell responses in tumors. In this study, we sought to reconcile these observations by conducting a detailed analysis of the effects of peg-Arg I on normal T cells. Strikingly, we found that peg-Arg I blocked proliferation and cell-cycle progression in normal activated T cells without triggering apoptosis or blunting T-cell activation. These effects were associated with an inhibition of aerobic glycolysis in activated T cells, but not with significant alterations in mitochondrial oxidative respiration, which thereby regulated survival of T cells exposed to peg-Arg I. Further mechanistic investigations showed that the addition of citrulline, a metabolic precursor for l-Arg, rescued the antiproliferative effects of peg-Arg I on T cells in vitro. Moreover, serum levels of citrulline increased after in vivo administration of peg-Arg I. In support of the hypothesis that peg-Arg I acted indirectly to block T-cell responses in vivo, peg-Arg I inhibited T-cell proliferation in mice by inducing accumulation of myeloid-derived suppressor cells (MDSC). MDSC induction by peg-Arg I occurred through the general control nonrepressed-2 eIF2α kinase. Moreover, we found that peg-Arg I enhanced the growth of tumors in mice in a manner that correlated with higher MDSC numbers. Taken together, our results highlight the risks of the l-Arg–depleting therapy for cancer treatment and suggest a need for cotargeting MDSC in such therapeutic settings. Cancer Res; 75(2); 275–83. ©2014 AACR.
Abstract 4593: Expression of Ecdysoneless in breast cancer progression predicts poor outcome in breast cancer patients
Authors: Sameer Mirza, Xiangshan Zhao, Alaa Alshareeda, Ying Zhang, Channabasavaiah Basavaraju Gurumurthy, Aditya Bele, Jun Hyun Kim, Shakur Mohibi, Monica Goswami, Subodh Lele, William West, Fang Qiu, Ian O. Ellis, Andrew R. Green, Hamid Band, Vimla Band
Journal: Cancer Research (2012)

Abstract Breast cancer is the most common type of cancer and second leading cause of cancer-related deaths in women in the United States. Our laboratory has identified the protein hEcd (human ortholog of Drosophila Ecdysoneless) as a novel regulator of cell cycle. Previous studies showed that Ecd regulates cell cycle by regulating the Rb-E2F pathway. Given the dysregulation of the cell cycle machinery in cancer, we examined expression of Ecd in normal, benign, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of breast. In first cohort, we showed while normal and hyperplasia of breast barely showed Ecd expression, high Ecd expression was observed in DCIS and IDC patient tissue specimens. In this cohort of 104 IDC patents, Ecd expression was positively associated with higher grade (p=0.04).We then analyzed Ecd expression in a second larger cohort (954) and observed similar results, where increased Ecd expression was associated with tumors of higher histological grade (p=0.013), mitotic count (p=0.032), and Nottingham Prognostic Index score (p=0.014). Notably, Ecd expression was positively associated with HER2/neu (p=0.002) overexpression. Significantly, a positive association between Ecd expression and shorter breast cancer specific survival (BCSS) (p=0.008) and disease-free survival (DFS) (p=0.003) was observed in HER2/neu overexpressing patients. Taken together, our results demonstrate Ecd expression as a novel marker for breast cancer progression that predicts tumor progression and the clinical outcome in breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4593. doi:1538-7445.AM2012-4593
Anticholinergic Therapy vs. OnabotulinumtoxinA for Urgency Urinary Incontinence
Authors: Anthony G. Visco, Linda Brubaker, Holly E. Richter, Ingrid Nygaard, Marie Fidela R. Paraiso, Shawn A. Menefee, Joseph Schaffer, Jerry Lowder, Salil Khandwala, Larry Sirls, Cathie Spino, Tracy L. Nolen, Dennis Wallace, Susan F. Meikle
Journal: New England Journal of Medicine (2012)

Anticholinergic medications and onabotulinumtoxinA are used to treat urgency urinary incontinence, but data directly comparing the two types of therapy are needed.
Abstract 2689: Drivers of cancer cell invasion and metastasis.
Authors: Ghada M. Sharif, Marcel O. Schmidt, Casey Shuptrine, Louis M. Weiner, Zhang-Zhi Hu, Anna T. Riegel, Anton Wellstein
Journal: Cancer Research (2013)

Abstract Metastatic spread of cancer cells from their primary site requires invasion into the vasculature, evasion at the distant organ site and colonization of the distant organ. Here we studied mechanisms of attachment and invasion into endothelial monolayers by cancer cells to identify driver molecules and signaling pathways that are crucial for the invasive and metastatic phenotype. Different human and mouse cancer cell lines were transduced with lentiviral-based, genome-wide or kinome-targeted shRNA libraries. Cancer cell populations of different invasive and metastatic phenotype were then selected for their loss- or gain-of-function respectively in endothelial invasion in vitro or by tumor growth and metastasis selection in vivo. After several rounds of selection, the respective shRNA targeted genes were identified from the selected cancer cell populations or from clonal cell lines. Eighteen different genes targeted by two to four distinct shRNAs each were identified in the in vitro selection for endothelial attachment and invasion. The function of the genes as well as the clinical significance appear to explain their phenotypic selection. Citation Format: Ghada M. Sharif, Marcel O. Schmidt, Casey Shuptrine, Louis M. Weiner, Zhang-Zhi Hu, Anna T. Riegel, Anton Wellstein. Drivers of cancer cell invasion and metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2689. doi:10.1158/1538-7445.AM2013-2689
Headache: Physiopathological and Clinical Concepts
Authors: Charles M. Poser
Journal: JAMA (1983)

The papers that constitute this volume were presented and discussed at an international symposium on headache held in Florence, Italy, in 1980. One hundred thirteen contributors from 19 countries provided 54 chapters in this state-of-the-art compendium. The book has been divided into six sections, which deal with clinical aspects, serotonin and its role in the pathogenesis of migraine, the important, but yet still mysterious, role of opiate receptors in the brain, the interrelationship between headache and other functions, the possible role of platelet aggregation in the migraine syndrome, and clinical and preclinical pharmacology of migraine.  Friedman's introductory chapter is a masterpiece of conciseness, common sense, and lucidity. As one might expect in this type of compilation, the quality of the contributions varies considerably: there are good discussions of the relationship between the endorphins and pain modulation, neuronal sensitivity, and opiate tolerance and dependence, as well as several interesting reports on
Hepatitis C virus replication cycle
Authors: Ralf Bartenschlager, Francois-Loic Cosset, Volker Lohmann
Journal: Journal of Hepatology (2010)

Hepatitis C virus (HCV) is a positive strand RNA virus forming the genus Hepacivirus in the Flaviviridae family. Replication of HCV starts with the virus binding to hepatocytes, which are the primary, if not exclusive host cells. HCV entry is a multi-step and slow process (Panel 1). Interactions between HCV E1–E2 envelope glycoproteins and glycosaminoglycans (GAGs) contribute to primary binding of the virus particles to host cells. Owing to the association of HCV with (very) low-density-lipoproteins [(V)LDL] [1], the LDL receptor (LDLr) has also been proposed as a capture molecule.
Refractory acute leukaemia in adults treated with sequential colaspase and high-dose methotrexate
Authors: B.-S. Yap, K. B McCredie, R. S Benjamin, G. P Bodey, E. J Freireich
Journal: BMJ (1978)

Thirty-nine adults with acute leukaemia who had relapsed when receiving extensive chemotherapy were treated with a combination of methotrexate and colaspase (L-asparaginase) given sequentially. Patients initially received 50-80 mg/m(2) methotrexate, followed three hours later by intravenous colaspase, 40 000 IU/m(2). Seven days later intravenous methotrexate, 120 mg/m(2) was given. Each dose of methotrexate was followed 24 hours later by colaspase, and the two-day course of treatment was repeated every 7-14 days. The methotrexate dose was increased to tolerance by increments of 40 mg/m(2) with each course, while the colaspase dose remained constant unless abnormal liver function developed, when it was reduced by half.Overall, 18 out of 39 patients achieved complete remission (46%). Of these, 13 out of 21 (62%) had acute lymphoblastic leukaemia, three out of seven (43%) acute undifferentiated leukaemia, and two out of 11 (18%) acute myeloblastic leukaemia. The median duration of complete remission was 20 weeks and the median duration of survival in complete responders was 45 weeks. The median number of courses needed to achieve complete remission was three. The maximum tolerated dose of methotrexate was 400 mg/m(2) (median 200 mg/m(2)). Major side effects were due to colaspase. Methotrexate in doses of up to 400 mg/m(2) caused minimal myelosuppression and stomatitis, which suggested that colaspase given sequentially provides relative protection from methotrexate toxicity without the need for folinic acid (citrovorum factor) rescue.The combination of sequential colaspase and methotrexate is highly effective in reinducing remission in patients with acute lymphoblastic leukaemia or acute undifferentiated leukaemia. The regimen is easy to administer and relatively non-toxic, so it is suitable for use in outpatients, either alone or combined with other agents.
Association Between Ratio of Sodium to Potassium in Random Urine Samples and Renal Dysfunction and Mortality in Patients With Decompensated Cirrhosis
Authors: Evangelos Cholongitas, John Goulis, George Arsos, Charis Birtsou, Theodora Nakouti, Sophia Papadopoulou, Parthenis Chalevas, Konstantinos Karakatsanis, Evangelos Akriviadis
Journal: Clinical Gastroenterology and Hepatology (2013)
Postoperative pain control in children.
Authors: N. S. Morton, L. R. McNicol
Journal: BMJ (1992)

Protocol for postoperative observationSedation and pain score-record hourly Level Sedation Pain I Awake Pain free 2 Drowsy Comfortable except on moving 3 Asleep but moves spontaneously Uncomfortable 4 Asleep responds to stimulation Distressed but can be comforted 5 Hard to rouse Distressed Action: Action: Level 4: Stop infusion until return to level 3 Level 2: NCA-give bolus PCA-encourage bolus (10 minutes before activity) Epidural-increase rate Level 5: Stop infusion.Call pain service Level 3: Contact pain service NCA-give bolus PCA -encourage bolus Epidural-increase rate Naloxone 4 tg/kg to be available at all times Level 4: Contact pain service NCA-give bolus or increase background infusion PCA -encourage bolus or increase background infusion Epidural-give bolus or increase rate Level 5: Contact pain service NCA=Nurse controlled analgesia.PCA=Patient controlled analgesia.
Performing Arts Medicine
Authors: Richard J. Lederman
Journal: New England Journal of Medicine (1989)

Performing artists have always had medical problems, and these have been attended to by practitioners using a wide variety of diagnostic and therapeutic techniques. Interest in the illnesses of the more celebrated artists of the past continues to the present day.Much has been written, for instance, on the deafness of Ludwig van Beethoven, who was, of course, not just a composer of some of the most sublime music ever conceived, but a preeminent pianist of his day. His deafness, which he first recognized at the age of 29, progressed inexorably until his death some 28 years later. Its precise . . .
Counsellors in general practice.
Authors: E. Martin
Journal: BMJ (1988)

spells of absence than the average, but even when there is verifiable disease the threshold for taking time off work will vary from person to person.Moreover, if patients say that they have migraine or gastroenteritis and describe the right symptoms it is hard to disprove their claims.This difficulty was recognised in 1982 when self certification was introduced for sickness absence lasting up to seven days.Where the doctor may play a more positive part is in ensuring that patients return to work promptly after long term absence for more serious illness.A prerequisite is to find out exactly what the patients' jobs entail.Even if they are not fit to return to their normal jobs their employers may be able to find them useful alternative work either temporarily or permanently.If the company has a medical department it is helpful to liaise with the doctor or nurse who will be familiar with the occupational environment.If not, a letter to the management should explain in simple terms what the employee can and cannot do.Specific advice such as to avoid kneeling or lifting weights over 5 kg is more useful than the vague prescription of "light" work.Timely and well managed return to work after illness is an important component of rehabilitation-good for the employer and good for the patient.
Skill mix in primary care
Authors: I Heath
Journal: BMJ (1994)

Subjects that breed euphemisms are usually contentious, and skill mix (reprofiling, grade mix, and multiskilling) is no exception. In her recent review of the topic, Leone Ridsdale has provided us with a much needed synopsis of the debate.1

The pursuit of skill mix in the new NHS has divided managers and health care professionals. With staffing accounting for 70% of NHS spending and managers under pressure to cut costs, the attractions of giving tasks to the lowest grades of staff who can perform them are obvious. In such an environment professionals fear the gradual erosion of the quality of care2,3 and trade unions see the spectre of redundancy.4 The debate over skill mix has heightened the belief among health professionals that managers do not understand the complexity of their knowledge and skill.5

The dangerously simplistic approach of the NHS Value for Money Unit's report Skill Mix in District Nursing did nothing to allay these fears.6 District nursing was reduced to a series of mechanistic tasks that could be counted and reallocated. In this model of skill mix highly qualified, …
Pemphigus vulgaris: the other half of the story
Authors: Richard S. Kalish
Journal: Journal of Clinical Investigation (2000)

Pemphigus vulgaris pathogenesis had been considered well understood and was in danger of being “finished,” as was physics at the end of the 19th century. With the publication in this issue of a paper by Nguyen and colleagues (1), the understanding of pemphigus pathogenesis must undergo a major revision. This turning point brings with it the promise of a more complete picture, as well as new therapeutic approaches for this serious disease.
Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon
Authors: Kevin M Haigis, Krystle R Kendall, Yufang Wang, Ann Cheung, Marcia C Haigis, Jonathan N Glickman, Michiko Niwa-Kawakita, Alejandro Sweet-Cordero, Judith Sebolt-Leopold, Kevin M Shannon, Jeffrey Settleman, Marco Giovannini, Tyler Jacks
Journal: Nature Genetics (2008)
Simultaneous measurement of cardiac output and its distribution with microspheres in the rat
Authors: D. G. MCDEVITT, A. S. NIES
Journal: Cardiovascular Research (1976)

Journal Article Simultaneous measurement of cardiac output and its distribution with microspheres in the rat Get access DENIS G. MCDEVITT, DENIS G. MCDEVITT 2 From the Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA 2Present address: Department of Therapeutics and Pharmacology, Queen's University, Belfast, Northern Ireland. Search for other works by this author on: Oxford Academic PubMed Google Scholar ALAN S. NIES ALAN S. NIES From the Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 10, Issue 4, July 1976, Pages 494–498, https://doi.org/10.1093/cvr/10.4.494 Published: 01 July 1976
Interleukin 18 causes hepatic ischemia/reperfusion injury by suppressing anti-inflammatory cytokine expression in mice
Authors: Dan Takeuchi, Hiroyuki Yoshidome, Atsushi Kato, Hiroshi Ito, Fumio Kimura, Hiroaki Shimizu, Masayuki Ohtsuka, Yasuhiro Morita, Masaru Miyazaki
Journal: Hepatology (2004)

Hepatic ischemia/reperfusion injury is a clinically important problem. While the mechanisms of the initial event and subsequent neutrophil-dependent injury are somewhat understood, little is known about the regulation of endogenous hepatoprotective effects on this injury. Interleukin 12 (IL-12) plays a role in the induction of this injury, but involvement of interleukin 18 (IL-18) has not been clarified. Using a murine model of partial hepatic ischemia and subsequent reperfusion, the aim of the current study was to determine whether IL-18 is up-regulated during hepatic ischemia/reperfusion and to determine the role of endogenous IL-18 in the development and regulation of inflammatory hepatic ischemia/reperfusion injury. Hepatic IL-18 expression was up-regulated from 1 to 8 hours after reperfusion. Hepatic ischemia/reperfusion induced nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) activation, as defined by electrophoretic mobility shift assay, and caused significant increases in liver neutrophil recruitment, apoptosis, hepatocellular injury, and liver edema as defined by liver myeloperoxidase content, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling (TUNEL) staining, serum aminotransferase levels, and liver wet-to-dry weight ratios. In mice treated with neutralizing antibody to IL-18, ischemia/reperfusion-induced increases in CXC chemokine expression, activation of NF-κB and AP-1, and apoptosis were greatly reduced. Furthermore, under blockade of IL-18, anti-inflammatory cytokines such as IL-4 and IL-10 were greatly up-regulated. Signal transducer and activator of transcription 6 (STAT6) was significantly activated under blockade of IL-18. These conditions also caused significant reduction in liver neutrophil sequestration and liver injury. In conclusion, the data suggest that IL-18 is required for facilitating neutrophil-dependent hepatic ischemia/reperfusion injury through suppressing anti-inflammatory cytokine expression. (Hepatology 2004;39:699-710.)
Risks of intrauterine contraceptive devices.
Authors: N Siddle
Journal: BMJ (1984)

stopping prednisolone 40 mg daily for three weeks.20If there has been a response the usual practice is to attempt to maintain symptomatic improvement by gradually withdrawing predni- solone while introducing inhaled steroids.If continued treatment with prednisolone is needed to maintain the improvement the benefits must be balanced against the hazards for the indi- vidual.Little evidence is available on the duration of response, the dose of steroid needed to maintain it, and the effect of long term treatment on prognosis.One possibility-as yet un- proved-is that long term treatment which reduced limitation of air flow might retard the development of cor pulmonale and thereby prolong survival.In our current state of knowledge a trial of corticosteroids is reasonable in patients with chronic limitation ofair flow who remain breathless despite treatment with maximum doses of bronchodilators.Measurements of air flow should be used to help in assessing the response.Steroids may also be helpful in acute exacerbations of bronchitis associated with increased limitation of air flow.
901-82 A Multicenter Controlled Trial of a Novel Metabolic Active Compound (Ranolazine) in Chronic Stable Angina Patients
Authors: William B. Smith, Steven Chrysant, William T. Garland, Thomas S. Parker, Howard T. Walpole, Carl J. Pepine, Ahmad Mokatrin, Daniel Gennevois
Journal: Journal of the American College of Cardiology (1995)