tbuckley/cabot-search huggingface dataset:
Chronic cerebral hypoperfusion induces ABCA1 and apolipoprotein A I mediated cellular cholesterol efflux by activating LXR/RXR in aging rat brain
Authors: Linhui Wang, Mingyuan Tian, Li Tang, Bin Liu, Yu Li
Journal: Molecular Neurodegeneration (2012)

Background Chronic cerebral hypoperfusion has been associated with cognitive decline in aging and Alzheimer’s disease. Vascular dementia produced by permanent, bilateral occlusion of the common carotid arteries in aging rats involves progressive deterioration of intellectual and cognitive function in rats, which are closely associated with the hippocampus. In recent years, it was believed that vascular dementia results from corporation of several factors, in which cholesterol homeostasis and lipoprotein disturbances appear to play an important role. Liver X receptor-b(LXR-b), retinoic X receptor-a(RXR-a), ABCA1 and apolipoprotein A I are thought to be important factors in the mechanism of neurological disease, such as Alzheimer’s disease. But the exact mechanism about vascular dementia is not clear. Here we focus on the mechanism of vascular dementia and offer some new and useful methods in the design of early diagnostic and therapeutic approaches to treat and prevent the progression in vascular dementia. Method Fifty aging male Sprague-Dawley rats aged 12 months and weighing 460~530g, were randomly divided into five groups: as ham-operated group, 1, 2, 3, 4w eeks after 2VO, with 10 rats in each group. The brain tissue lysates were collected for RT-PCR, Western blot assay detecting the expression of LXR-b ,R XR-a ,A BCA1 and aopA I undering the low blood perfusion. Immunofluorescent double labeled analysis was used to detect the expression and location of LXR-b and RXR-a in the hippocampus in a vascular dementia model. The serum levels of HDL, TC were measured by automatic biochemical analyzer. Results RT-PCR and Western blot results showed that the expression of LXR-b ,R XR-a ,A BCA1, apoA Im RNA and protein mildly decrease in the 1 weeks after permanent ligation of the bilateral common carotid arteries, compared with a sham-operated group (P<0.05). However, the protein expression peaked at 2 weeks post-surgery (P<0.05), accompanied by severe ischemia. The expression of these proteins decrease at 3 and 4 weeks, accompanied by recovery of cerebral blood flow. Meanwhile, the dynamic alterations of serum levels of HDL and TC were also found (P<0.05). Immunofluorescent staining results not only confirmed the above changes, but also showed that the LXR/RXR heterodimers function as sensors for cellular oxysterols flow in vascular dementia.
CORNEAL ULCERATION FOLLOWING USE OF LASH-LURE
Authors: A. W. McCally
Journal: JAMA (1933)

There has been much agitation recently against the unbridled use of harmful cosmetics, and many case reports have appeared demonstrating some of the consequences of this practice. We report a case in which a woman had her eyebrows and eyelashes dyed with a preparation called Lash-Lure, a product manufactured in Los Angeles by the Lash-Lure Research Laboratory, Inc. As the ingredients of the cosmetic were unknown and could not be learned from the local beautician who applied it, an analysis was made by a competent chemist. He qualified his report by stating that the dye was one of the paraphenylenediamine group. No neutralizing antidote was known and no report of similar cases could be found in the literature as a guide to treatment at the time the patient came under observation. Since then a report of a somewhat similar case, though apparently without such extensive involvement, has been made by
Miliary tuberculosis in association with chronic cutaneous tuberculosis
Authors: D.E. BATEMAN, W. MAKEPEACE, M. LESNA
Journal: British Journal of Dermatology (1980)

A case of miliary tuberculosis associated with two different forms of cutaneous tuberculosis and a negative Heaf tuberculin test is reported. The value of skin biopsy and culture in helping to establish an early diagnosis is discussed. The unusual finding of a negative Heaf tuberculin test is commented upon.
Niclosamide Inhibits Androgen Receptor Variants Expression and Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer
Authors: Chengfei Liu, Wei Lou, Yezi Zhu, Nagalakshmi Nadiminty, Chad T. Schwartz, Christopher P. Evans, Allen C. Gao
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Enzalutamide, a second-generation antiandrogen, was recently approved for the treatment of castration-resistant prostate cancer (CRPC) in patients who no longer respond to docetaxel. Despite these advances that provide temporary respite, resistance to enzalutamide occurs frequently. Androgen receptor (AR) splice variants such as AR-V7 have recently been shown to drive castration-resistant growth and resistance to enzalutamide. This study was designed to identify inhibitors of AR variants and test its ability to overcome resistance to enzalutamide. Experimental Design: The drug screening was conducted using luciferase activity assay to determine the activity of AR-V7 after treatment with the compounds in the Prestwick Chemical Library, which contains about 1,120 FDA-approved drugs. The effects of the identified inhibitors on AR-V7 activity and enzalutamide sensitivity were characterized in CRPC and enzalutamide-resistant prostate cancer cells in vitro and in vivo. Results: Niclosamide, an FDA-approved antihelminthic drug, was identified as a potent AR-V7 inhibitor in prostate cancer cells. Niclosamide significantly downregulated AR-V7 protein expression by protein degradation through a proteasome-dependent pathway. Niclosamide also inhibited AR-V7 transcription activity and reduced the recruitment of AR-V7 to the PSA promoter. Niclosamide inhibited prostate cancer cell growth in vitro and tumor growth in vivo. Furthermore, the combination of niclosamide and enzalutamide resulted in significant inhibition of enzalutamide-resistant tumor growth, suggesting that niclosamide enhances enzalutamide therapy and overcomes enzalutamide resistance in CRPC cells. Conclusions: Niclosamide was identified as a novel inhibitor of AR variants. Our findings offer preclinical validation of niclosamide as a promising inhibitor of AR variants to treat, either alone or in combination with current antiandrogen therapies, patients with advanced prostate cancer, especially those resistant to enzalutamide. Clin Cancer Res; 20(12); 3198–210. ©2014 AACR.
Potomac Fever or White House Wisdom?-Reply
Authors: Burton J. Lee
Journal: JAMA (1990)

<h3>In Reply. —</h3> My statements do reflect my views. I am not cynical about the majority of physicians in America, but there is no question that a few of them, with their billing practices, have severely damaged fee-for-service private practice of medicine for the rest of us. For confirmation, please listen to the public, big business, big labor, and the insurance companies. The exact amount that physician greed adds to health care costs is unknown to me. It is also unknown to Dr Woody, so I am not sure why he assumes it is "minor." Historically, the American Medical Association<i>has</i>behaved as a physicians'union, fighting tooth and nail any attempt to cut physicians' fees in any way. I was in practice for 30 years, and I loved the American Medical Association for it. But current reimbursement problems related to health care financing are changing matters for all of us,
Prostatism: how useful is routine imaging of the urinary tract?
Authors: G. de Lacey, S. Johnson, D. Mee
Journal: BMJ (1988)

The clinical effects of routinely imaging the renal tract (by intravenous urography and ultrasonography) were evaluated prospectively in 128 consecutive patients with prostatism. Patients with haematuria, previous renal disease, or infection were excluded. Urologists completed a standard questionnaire in the patient's notes stating the diagnosis and the intended management. The patient then had intravenous urography and abdominal ultrasonography, urine was analysed, and plasma urea and serum creatinine concentrations and acid phosphatase activity were determined. From six months to a year later the eventual management was compared with the intended management to see the effect of these routine investigations on the outcome. For four out of 28 patients whose management was intended to be conservative the decision was changed; for only three of them was this because of the results of urography, ultrasonography, and biochemical determinations. For 31 patients the management was to be decided by cystoscopic findings, and for none of these was the final decision altered by the results from the investigations after the initial consultation. Similarly for five patients who were assessed urodynamically the final management was not changed by the results of these investigations. The planned management was changed in three of the remaining 64 patients but not because of the results of the initial investigations. Thus no indication was found for either routine urography or ultrasonography, but the total abandonment of imaging of the renal tract would be unwise. Patients scheduled for conservative management (about a quarter of the patients in this study) should have ultrasonography to detect unsuspected hydronephrosis, but in all other patients urography or ultrasonography, or both, is an unhelpful ritual. Moreover, urography is becoming more expensive, and has a recognised (albeit small) mortality.
NOTE ON MILITARY MEDICINE
Authors: Alan Gregg
Journal: JAMA (1953)

The rosters of all military medical services at present show a disturbing ratio between career men and civilians on relatively short turns of duty; a ratio in which the number of career men is already too small for the optimum utilization of the services of either group. Since the percentage of doctors of medicine on full time or part time salaries is increasing, and since, therefore, the various characteristics of medical careers are receiving attention from an increasing number of prospective aspirants for salaried positions, some of the elements of medical careers deserve review. This assertion carries additional weight because the falling purchasing power of the dollar has disturbed what used to be a stable factor in the calculations that could be made about any type of medical career. Some reflections on what, generically, will be called military medical careers seem to be in order. From the range of motivations
TREATMENT OF COLD ABSCESSES AND SINUSES IN TUBERCULOUS BONE LESIONS.
Authors: V. P. GIBNEY
Journal: JAMA (1904)

Paradoxical as it may appear, cold abscess and sinuses with all kinds of mixed infection furnish a fascination for me that years of experience in their treatment can not satisfy. Year after year, as requests from chairmen and secretaries come to present a paper for discussion, the topic chosen to-day comes first into mind, and because of its inexhaustibility it pleads for further discussion. To the practitioner remote from large cities, abscesses and sinuses appear insignificant, perhaps, because out-of-door life and good hygiene contribute so much to the storing up of vital resistance, and almost any surgical measure leads to satisfying results. In largely populated centers, however, where the tenement house plays so important a part, vital resistance is lowered and results are far from satisfactory. My connection for nearly a third of a century with a hospital whose in- and out-patient service is second to none prompts me to
Wellcome exhibition explores magic, religion, beauty, and eroticism
Authors: A. Ferriman
Journal: BMJ (2003)

These two exhibits are from the collection of Henry Wellcome, the pharmaceutical entrepreneur and philanthropist who co-founded the company Burroughs-Wellcome & Co.

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Wellcome was a compulsive collector and world traveller, and at the beginning of the 20th century, when his collecting mania was at …

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Leucocyte expression of complement C5a receptors exacerbates infarct size after myocardial reperfusion injury
Authors: Vince C. De Hoog, Leo Timmers, Amerik Van Duijvenvoorde, Saskia C. A. De Jager, Ben J. Van Middelaar, Mirjam B. Smeets, Trent M. Woodruff, Pieter A. Doevendans, Gerard Pasterkamp, C. Erik Hack, Dominique P.V. De Kleijn
Journal: Cardiovascular Research (2014)

Early reperfusion is mandatory for the treatment of acute myocardial infarction. This process, however, also induces additional loss of viable myocardium, called ischaemia–reperfusion (IR) injury. Complement activation plays an important role in IR injury, partly through binding of C5a to its major receptor (C5aR). We investigated the role of C5aR on infarct size and cardiac function in a model for myocardial IR injury. BALB/c (WT) mice and C5aR−/− mice underwent coronary occlusion for 30 min, followed by reperfusion. Infarct size, determined 24 h after IR, was reduced in C5aR−/− mice compared with WT mice (28.5 ± 2.1 vs. 35.7 ± 2.5%, P = 0.017). Bone marrow (BM) chimaera experiments showed that this effect was due to the absence of C5aR on circulating leucocytes, since a similar reduction in infarct size was observed in WT mice with C5aR-deficient BM cells (25.3 ± 2.2 vs. 34.6 ± 2.8%, P < 0.05), but not in C5aR−/− mice with WT BM cells. Reduced infarct size was associated with fewer neutrophils, T cells, and macrophages in the infarcted area 24 h after IR in C5aR−/− mice, and also with lower levels of Caspase-3/7 indicating less inflammation and apoptosis. Echocardiography 4 weeks after IR showed an improved ejection fraction in C5aR−/− mice (25.8 ± 5.5 vs. 19.2 ± 5.4%, P < 0.001). The absence of C5aR on circulating leucocytes reduces infarct size, is associated with reduced leucocyte infiltration and with less apoptosis in the infarcted myocardium, and improves cardiac function in a mouse model of myocardial IR injury. Selective blocking of C5aR might be a promising strategy to prevent myocardial IR injury.
Antileukemic activity of the HSP70 inhibitor pifithrin-μ in acute leukemia
Authors: M Kaiser, A Kühnl, J Reins, S Fischer, J Ortiz-Tanchez, C Schlee, L H Mochmann, S Heesch, O Benlasfer, W-K Hofmann, E Thiel, C D Baldus
Journal: Blood Cancer Journal (2011)

Heat shock protein (HSP) 70 is aberrantly expressed in different malignancies and has emerged as a promising new target for anticancer therapy. Here, we analyzed the in vitro antileukemic effects of pifithrin-μ (PFT-μ), an inhibitor of inducible HSP70, in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) cell lines, as well as in primary AML blasts. PFT-μ significantly inhibited cell viability at low micromolar concentrations in all cell lines tested, with IC50 values ranging from 2.5 to 12.7 μ, and was highly active in primary AML blasts with a median IC50 of 8.9 μ (range 5.7-37.2). Importantly, higher IC50 values were seen in normal hematopoietic cells. In AML and ALL, PFT-μ induced apoptosis and cell cycle arrest in a dose-dependent fashion. PFT-μ also led to an increase of the active form of caspase-3 and reduced the intracellular concentrations of AKT and ERK1/2 in NALM-6 cells. Moreover, PFT-μ enhanced cytotoxicity of cytarabine, 17-(allylamino)-17-desmethoxygeldanamycin, suberoylanilide hydroxamic acid, and sorafenib in NALM-6, TOM-1 and KG-1a cells. This is the first study demonstrating significant antileukemic effects of the HSP70 inhibitor PFT-μ, alone and in combination with different antineoplastic drugs in both AML and ALL. Our results suggest a potential therapeutic role for PFT-μ in acute leukemias.
Dabigatran Versus Warfarin in Patients With Atrial Fibrillation
Authors: Rangadham Nagarakanti, Michael D. Ezekowitz, Jonas Oldgren, Sean Yang, Michael Chernick, Timothy H. Aikens, Greg Flaker, Josep Brugada, Gabriel Kamenský, Amit Parekh, Paul A. Reilly, Salim Yusuf, Stuart J. Connolly
Journal: Circulation (2011)

The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial compared dabigatran 110 mg BID (D110) and 150 mg BID (D150) with warfarin for stroke prevention in 18 113 patients with nonvalvular atrial fibrillation.Cardioversion on randomized treatment was permitted. Precardioversion transesophageal echocardiography was encouraged, particularly in dabigatran-assigned patients. Data from before, during, and 30 days after cardioversion were analyzed. A total of 1983 cardioversions were performed in 1270 patients: 647, 672, and 664 in the D110, D150, and warfarin groups, respectively. For D110, D150, and warfarin, transesophageal echocardiography was performed before 25.5%, 24.1%, and 13.3% of cardioversions, of which 1.8%, 1.2%, and 1.1% were positive for left atrial thrombi. Continuous treatment with study drug for ≥3 weeks before cardioversion was lower in D110 (76.4%) and D150 (79.2%) compared with warfarin (85.5%; P<0.01 for both). Stroke and systemic embolism rates at 30 days were 0.8%, 0.3%, and 0.6% (D110 versus warfarin, P=0.71; D150 versus warfarin, P=0.40) and similar in patients with and without transesophageal echocardiography. Major bleeding rates were 1.7%, 0.6%, and 0.6% (D110 versus warfarin, P=0.06; D150 versus warfarin, P=0.99).This study is the largest cardioversion experience to date and the first to evaluate a novel anticoagulant in this setting. The frequencies of stroke and major bleeding within 30 days of cardioversion on the 2 doses of dabigatran were low and comparable to those on warfarin with or without transesophageal echocardiography guidance. Dabigatran is a reasonable alternative to warfarin in patients requiring cardioversion.
Antihypertensive medication use is associated with increased organ system involvement and hospitalization in emergency department patients with anaphylaxis
Authors: Sangil Lee, Erik P. Hess, David M. Nestler, Venkatesh R. Bellamkonda Athmaram, M. Fernanda Bellolio, Wyatt W. Decker, James T.C. Li, John B. Hagan, Veena Manivannan, Samuel C. Vukov, Ronna L. Campbell
Journal: Journal of Allergy and Clinical Immunology (2013)
Practice nursing Free nurses from taking blood
Authors: M R Williamson, J Stevenson
Journal: BMJ (1994)

EDITOR, - I agree with David Jewell and Pat Turton that practice nurses should be encouraged towards greater professionalism.1 However, their assessment of the practice nurse's present role was a glossy representation of the York census,2 and they failed to suggest radical enough solutions to the problems of how to create and fund this change.

At present practice nurses spend much of their time performing predominantly simple tasks; grade F or G nurses are overtrained to do these tasks. Their expensive time is a resource which should be being used to run health promotion and chronic disease management programmes. The York survey …
History of Depression Increases Risk of Type 2 Diabetes in Younger Adults
Authors: Lauren C. Brown, Sumit R. Majumdar, Stephen C. Newman, Jeffrey A. Johnson
Journal: Diabetes Care (2005)

OBJECTIVE—The purpose of this study was to assess the history of previous depression in people with incident diabetes compared with people without diabetes. RESEARCH DESIGN AND METHODS—We conducted a population-based nested case-control study using the administrative databases of Saskatchewan Health to assess the study objective. We identified cases of type 2 diabetes based on diagnostics codes and prescription records for individuals over the age of 20 years. For each case subject, two control subjects were randomly selected from the nondiabetic population during the same index year. History of depression, based on diagnostic codes and antidepressant prescription, was ascertained up to 3 years before index date. Simple and multivariate logistic regression analysis was used to estimate the odds ratio (OR) and 95% CIs, after adjusting for age, sex, and frequency of physician visits. RESULTS—Individuals with newly diagnosed diabetes (1,622 of 33,257; 4.9%) were 30% more likely to have had a previous history of depression compared with people without diabetes (2,279 of 59,420; 3.8%). This increased risk remained after controlling for sex and number of physician visits but was limited to subjects 20–50 years of age (adjusted OR 1.23 [95% CI 1.10–1.37]) and not in those aged ≥51 years (0.92 [0.84–1.00]). CONCLUSIONS—Depression appears to increase the risk of developing diabetes by ∼23% in younger adults. This provides information regarding the temporality of the relationship between diabetes and depression.
Results of Proton Beam Therapy without Concurrent Chemotherapy for Patients with Unresectable Stage III Non-small Cell Lung Cancer
Authors: Yoshiko Oshiro, Masashi Mizumoto, Toshiyuki Okumura, Takayuki Hashimoto, Nobuyoshi Fukumitsu, Ayako Ohkawa, Ayae Kanemoto, Haruko Hashii, Toshiki Ohno, Takeji Sakae, Koji Tsuboi, Hideyuki Sakurai
Journal: Journal of Thoracic Oncology (2011)
Abstract A59: Block/homo polyplex micelle-based GM-CSF gene therapy via intraperitoneal administration elicits antitumor immunity against peritoneal dissemination and exhibits safety potentials in mice and monkeys.
Authors: Masahiro Ohgidani, Koichi Furugaki, Shinkai Kentaro, Yumi Kunisawa, Keiji Itaka, Kazunori Kataoka, Kenji Nakano
Journal: Cancer Research (2013)

Abstract A block/homo-mixed polyplex micelle, comprising of cationic homo polymer: {N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} P[Asp(DET)] and block copolymer: polyethylene glycol (PEG) -P[Asp(DET)], has been reported to exhibit the efficient transgene expression in vivo by intratracheal and systemic administration. In the present study, we investigated the potential of immunogene therapy by intraperitoneal (i.p.) administration of block/homo polyplex micelles for peritoneal dissemination. For evaluation of transgene expression in vivo, block/homo polyplex micelles showed 12-fold higher level in luciferase expression evaluated by bioluminescence imaging system at 24 h after the i.p. administration compared with block polyplex micelles in nude mice bearing peritoneal dissemination. The distribution of polyplex micelles in tumor nodules was similarly present for both polyplex micelles, where the intracellular uptake of plasmid DNA was detected for block/home polyplex micelles but little for block polyplex micelles. The i.p. administration of block/homo polyplex micelles encapsulating granulocyte macrophage colony stimulating factor (GM-CSF) gene elicited GM-CSF expression dominantly in tumors and less in normal organs (liver and spleen), inhibited the tumor growth and prolonged survival rate for the mice harboring disseminated pancreatic cancer more significantly compared with the mock. The antitumor effect of GM-CSF gene therapy was mediated via the activation of natural killer cells. For safety evaluation, block/homo polyplex micelles indicated almost no adverse events for patho-physical findings and blood examinations in mice and cynomolgus monkeys, although slight increases in serum fibrinogen were observed in the monkey model. In conclusion, block/homo polyplex micelle-based immunogene therapy via i.p. administration may be a safe and effective approach for suppressing intractable peritoneal dissemination. Citation Format: Masahiro Ohgidani, Koichi Furugaki, Shinkai Kentaro, Yumi Kunisawa, Keiji Itaka, Kazunori Kataoka, Kenji Nakano. Block/homo polyplex micelle-based GM-CSF gene therapy via intraperitoneal administration elicits antitumor immunity against peritoneal dissemination and exhibits safety potentials in mice and monkeys. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A59.