tbuckley/cabot-search huggingface dataset:
Over-the-Counter Analgesic Use
Authors: Marc E. De Broe, Monique M. Elseviers
Journal: Journal of the American Society of Nephrology (2009)

Chronic analgesic nephropathy, particularly chronic interstitial nephritis and renal papillary necrosis, results from daily use for many years of mixtures containing at least two analgesics and caffeine or dependence-inducing drugs. Computed tomography scan can accurately diagnose this disease even in the absence of reliable information on previous analgesic use. The occasion to moderate regular use of aspirin and nonsteroidal anti-inflammatory drugs is without renal risk when renal function is normal. Paracetamol use is less clear although the risk is not great. The continued use of non-phenacetin-combined analgesics with or without nonsteroidal anti-inflammatory drugs is associated with faster progression toward renal impairment. As long as high-risk analgesic mixtures are available over the counter, analgesic nephropathy will continue to be a problem.
Removal of endobronchial mucormycosis lesion through a rigid bronchoscope.
Authors: S al-Majed, F al-Kassimi, M Ashour, M O Mekki, S Sadiq
Journal: Thorax (1992)

A 44 year old man with poorly controlled diabetes mellitus developed endobronchial mucormycosis, which totally obstructed the right lower lobe bronchus. The lesion was removed through a rigid bronchoscope. Two weeks later the bronchus was free of mucormycosis histologically and on culture.
Combined effect of retinoic acid and basic FGF on PAI-1 gene expression in vascular smooth muscle cells
Authors: Atai Watanabe, Masahiko Kurabayashi, Masashi Arai, Kenichi Sekiguchi, Ryozo Nagai
Journal: Cardiovascular Research (2001)

Aberrant regulation of the synthesis and degradation of the extracellular matrix (ECM) is associated with the pathophysiology of vascular disease. Plasminogen activator inhibitor-1 (PAI-1) plays a crucial role in regulating the quantity and composition of ECM. However, regulatory mechanisms underlying the expression of the PAI-1 gene remain unclear. We examined the effects of all-trans-retinoic acid (atRA), either alone or in combination with mitogenic growth factor, basic fibroblast growth factor (bFGF), on the PAI-1 expression in cultured vascular smooth muscle cells (SMCs).Cultures of the rabbit vascular smooth muscle cell line C2/2 were used to study the effects of atRA and bFGF separately or together.Treatment of vascular SMCs with atRA in combination with bFGF resulted in an additional increase in PAI-1 expression both at the mRNA and protein levels. In contrast, tissue-type plasminogen activator, urokinase-type plasminogen activator and tissue factor mRNA levels were only minimally affected. The all-trans-RA- and bFGF-mediated increases in PAI-1 mRNA levels were markedly attenuated by the tyrosine kinase inhibitor genistein, but not by MEK1 or p38MAP kinase inhibitors. The rate of decrease in PAI-1 mRNA levels after actinomycin D treatment was not affected by atRA and bFGF. Transient transfection of the PAI-1 promoter-luciferase reporter gene, which contains 967 bp of the 5'-flanking region of the human PAI-1 gene, revealed that atRA and bFGF additionally increased transcription from this promoter. Progressive 5'-deletion revealed that the promoter region required for such an effect lies between -967 and -260, which contains no canonical sequence for the RA-response element. In agreement with the role of PAI-1 in the inhibition of fibrinolytic activity which stimulates ECM degradation, cell migration was inhibited by treatment with atRA and bFGF.These results indicate that atRA and bFGF can function in a combined fashion and induce PAI-1 synthesis in vascular SMCs, and suggest a role for these two compounds in regulating SMC migration.
Suppression of apolipoprotein B production during treatment of cholesteryl ester storage disease with lovastatin. Implications for regulation of apolipoprotein B synthesis.
Authors: H N Ginsberg, N A Le, M P Short, R Ramakrishnan, R J Desnick
Journal: Journal of Clinical Investigation (1987)

Cholesteryl ester storage disease (CESD) is characterized by the deficient activity of lysosomal cholesteryl ester (CE) hydrolase, accumulation of LDL-derived CE in lysosomes, and hyperlipidemia. We studied the kinetics of VLDL and LDL apolipoprotein B (apoB), using 125I-VLDL and 131I-LDL, in a 9-yr-old female with CESD and elevated total cholesterol (TC) (271.0 +/- 4.4 mg/dl), triglyceride (TG) (150.0 +/- 7.8 mg/dl), and LDL cholesterol (184.7 +/- 3.4 mg/dl). These studies demonstrated a markedly elevated production rate (PR) of apoB, primarily in LDL, with normal fractional catabolism of apoB in VLDL and LDL. Urine mevalonate levels were elevated, indicative of increased synthesis of endogenous cholesterol. Treatment with lovastatin, a competitive inhibitor of hydroxymethylglutaryl coenzyme A reductase, resulted in significant reductions in TC (196.8 +/- 7.9 mg/dl), TG (100.8 +/- 20.6 mg/dl), and LDL cholesterol (102.0 +/- 10.9 mg/dl). Therapy reduced VLDL apoB PR (5.2 vs. 12.2 mg/kg per d pretreatment) and LDL apoB PR (12.7 vs. 24.2 mg/kg per d pretreatment). Urine mevalonate levels also decreased during therapy. These results indicate that, in CESD, the inability to release free cholesterol from lysosomal CE resulted in elevated synthesis of endogenous cholesterol and increased production of apoB-containing lipoproteins. Lovastatin reduced both the rate of cholesterol synthesis and the secretion of apoB-containing lipoproteins.
Childhood traumas: an outline and overview
Authors: L C Terr
Journal: American Journal of Psychiatry (1991)

Childhood psychic trauma appears to be a crucial etiological factor in the development of a number of serious disorders both in childhood and in adulthood. Like childhood rheumatic fever, psychic trauma sets a number of different problems into motion, any of which may lead to a definable mental condition. The author suggests four characteristics related to childhood trauma that appear to last for long periods of life, no matter what diagnosis the patient eventually receives. These are visualized or otherwise repeatedly perceived memories of the traumatic event, repetitive behaviors, trauma-specific fears, and changed attitudes about people, life, and the future. She divides childhood trauma into two basic types and defines the findings that can be used to characterize each of these types. Type I trauma includes full, detailed memories, "omens," and misperceptions. Type II trauma includes denial and numbing, self-hypnosis and dissociation, and rage. Crossover conditions often occur after sudden, shocking deaths or accidents that leave children handicapped. In these instances, characteristics of both type I and type II childhood traumas exist side by side. There may be considerable sadness. Each finding of childhood trauma discussed by the author is illustrated with one or two case examples.
Digital Genomic Quantification of Tumor-Infiltrating Lymphocytes
Authors: Harlan S. Robins, Nolan G. Ericson, Jamie Guenthoer, Kathy C. O’Briant, Muneesh Tewari, Charles W. Drescher, Jason H. Bielas
Journal: Science Translational Medicine (2013)

A digital DNA-based assay demonstrates an association between higher TIL counts and improved survival among women with ovarian cancer.
A CASE OF CYCLOPIA
Authors: D. Dougal, T. M. Bride
Journal: BMJ (1914)

IMEDICALJO 13 _~~~~~~~~~~~~~~~~~~~~~~~EIAJUN~1 compared with otlher methods of examination for the estimation of glucose in saccharine urines.Appenided for reference are given the parts per 1,000, and the percentages (grains by weight in 100 minims) corresponding to the number of grains per ounce (480 minims).The former is calculated by dividilng the number of grains per oz.by 0.4375.The latter by multiplying the number of grains per ounce by j1, a result of simple proportion.The coloured test glasses in a pocket-case can be obtained from Messrs. Down Brothers, St. Thomas's Street, Borough, S&.
Single-Molecule Detection of Epidermal Growth Factor Receptor Mutations in Plasma by Microfluidics Digital PCR in Non–Small Cell Lung Cancer Patients
Authors: Tony K.F. Yung, K.C. Allen Chan, Tony S.K. Mok, Joanna Tong, Ka-Fai To, Y.M. Dennis Lo
Journal: Clinical Cancer Research (2009)

Abstract Purpose: We aim to develop a digital PCR-based method for the quantitative detection of the two common epidermal growth factor receptor (EGFR) mutations (in-frame deletion at exon 19 and L858R at exon 21) in the plasma and tumor tissues of patients suffering from non-small cell lung cancers. These two mutations account for &amp;gt;85% of clinically important EGFR mutations associated with responsiveness to tyrosine kinase inhibitors. Experimental Design: DNA samples were analyzed using a microfluidics system that simultaneously performed 9,180 PCRs at nanoliter scale. A single-mutant DNA molecule in a clinical specimen could be detected and the quantities of mutant and wild-type sequences were precisely determined. Results: Exon 19 deletion and L858R mutation were detectable in 6 (17%) and 9 (26%) of 35 pretreatment plasma samples, respectively. When compared with the sequencing results of the tumor samples, the sensitivity and specificity of plasma EGFR mutation analysis were 92% and 100%, respectively. The plasma concentration of the mutant sequences correlated well with the clinical response. Decreased concentration was observed in all patients with partial or complete clinical remission, whereas persistence of mutation was observed in a patient with cancer progression. In one patient, tyrosine kinase inhibitor was stopped after an initial response and the tumor-associated EGFR mutation reemerged 4 weeks after stopping treatment. Conclusion: The sensitive detection and accurate quantification of low abundance EGFR mutations in tumor tissues and plasma by microfluidics digital PCR would be useful for predicting treatment response, monitoring disease progression and early detection of treatment failure associated with acquired drug resistance.
Tc99m-Noet: a new myocardial perfusion imaging agent that demonstrates redistribution. Comparison with Thallium-201 in patients with coronary artery disease
Authors: G. Vanzetto, P.Y. Marie, D. Leguludec, F. Brunotte, L. Philippe, R. Itti, J.L. Baral, R. Pasqualini, F. Chossat, J. Machecourt, D. Fagret
Journal: Journal of the American College of Cardiology (1998)
Re: Tamoxifen for Prevention of Breast Cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study
Authors: R. R. Love
Journal: JNCI Journal of the National Cancer Institute (1999)

What this portrayal of absolute events shows is that, in high-risk cohorts under and 50 years of age or more, the numbers of prevented breast cancers over a 5-year period are small; the number of prevented events in women under 50 years of age markedly exceeds the number of unfavorable events (ignoring symptoms); the number of prevented events in women aged 50 years or more is marginally fewer than the number of unfavorable events (without or with the excess uterine cancer numbers); and 15%‐25% (depending on how one looks at the data on symptoms) of all treated women will have what they view as substantial toxicity. With breast cancer prevention, preclinical hormone receptor-positive lesions are treated; the prognosis is excellent for women with clinically diagnosed, small hormone receptor-positive cancers (4). While, in the P-1 study, no endometrial cancer deaths occurred, in the meta-analysis of adjuvant therapy with tamoxifen (4), an excess of endometrial cancer mortality was found.
Photodynamic Therapy of Normal and Balloon-Injured Rat Carotid Arteries Using 5-Amino-Levulinic Acid
Authors: Isaac Nyamekye, Sandra Anglin, Jean McEwan, Alexander MacRobert, Stephen Bown, Christopher Bishop
Journal: Circulation (1995)

Although the management of atherosclerotic disease by the use of balloon angioplasty is widespread, the treatment is limited by restenosis in 30% to 50% of cases. Fibrocellular intimal hyperplasia, the main cause of restenosis, arises from proliferation and migration of medial smooth muscle cells (SMC) into the intimal layer. Factors leading to intimal hyperplasia are incompletely understood, and drugs have universally failed to influence clinical restenosis. Photodynamic therapy (PDT), the light activation of photosensitizing drugs to generate cytotoxic mediators, may have potential as prophylaxis for intimal hyperplasia. 5-Amino-levulinic acid-induced protoporphyrin IX (ALA-PPIX), a naturally occurring porphyrin precursor, and its product, -PPIX, offers a novel method of sensitization for PDT. We have investigated the pharmacokinetics of ALA in arteries and the effects of ALA-PPIX-sensitized PDT on normal and balloon-injured arteries.ALA (20 to 200 mg/kg) was injected into healthy rats, and PPIX fluorescence was measured in the carotid arteries. In a second group of rats, the exposed carotid artery was laser illuminated (50 J/cm2, 630 nm) 30 to 90 minutes after sensitization. Three and 14 days after PDT, histological sections from treated arteries were analyzed by light microscopy. Subsequently, two new groups of rats underwent PDT (ALA, 100 mg/kg; laser, 50 J/cm2, 630 nm [at 60 to 90 minutes]). The left carotid arteries underwent balloon angioplasty by intraluminal passage of a Fogarty FG2 catheter immediately before irradiation. These rats were killed at 14 and 28 days together with laser-only, ALA-only, and untreated control rats. The arteries were perfusion-fixed in vivo. ALA-PPIX induced arterial media fluorescence in a dose-dependent manner. In the normal arteries, PDT produced a dose-dependent cellular depletion in the treated arterial segment at 3 days, and this was complete with 100 and 200 mg/kg of ALA. At 14 days, the media remained acellular, although the endothelial lining had regenerated. In the balloon-injured arteries, PDT produced complete inhibition of intimal hyperplasia at both 14 and 28 days (0%). This was significantly greater than that produced by any of the control rats (34% to 69% and 37% to 66% at the two times, respectively). Significance was at 99% using ANOVA and Fisher's PLSD test. No hemorrhage, thrombosis, or aneurysm formation was seen.ALA-PPIX-sensitized PDT applied at the time of angioplasty effectively inhibits experimental intimal hyperplasia development in rats. This may offer a new approach to the management of angioplasty restenosis in patients.
Abstract LB-78: Effects of rapamycin and fasting-cycles therapy on differential stress resistance and sensitization in breast cancer mouse models
Authors: Stefano D. Biase, Sebastian Brandorst, Min Wei, Valter Longo
Journal: Cancer Research (2014)

Abstract Short-term starvation (STS) has been shown to be effective in both protection of normal cell and tissues and the sensitization of a variety of tumors during chemotherapy treatment. This condition of protection/sensitization of different cell types under the same condition has been named differential stress resistance (DSR). Although the effects of fasting have been mainly attributed to reduced glucose and circulating IGF1 levels, the involvement of signaling genes regulated by glucose and growth factors in these effects of fasting remain poorly understood. In this study we have administered the mTor inhibitor rapamycin in combination with STS and with the chemotherapy drug doxorubicin to shed light on the role of mTOR in the STS response and on its role in mediating DSR. In a mouse allograft model for breast cancer (4T1) we show that STS and rapamycin have an additive effect in reducing tumor progression, which confirms the possibility that STS-mediated effects on cancer cells are not due to the up-regulation of mTOR. Surprisingly, we observed that the administration of rapamycin during chemotherapy sensitizes the mice to the drug leading to an increased mortality. However, this sensitizing effect could be reversed by STS. In summary, the combination of mTor inhibition by rapamycin and STS have additive effects in retarding breast cancer tumor growth and also prevent the chemotherapy-dependent sensitization of normal cells caused by rapamycin alone. Because rapamycin is used for the treatment of certain tumors in humans, these results may have important implications for the safety of therapies using a combination of rapamycin and chemotherapy and indicate that the combination of Tor inhibitors and STS should be tested clinically. Citation Format: Stefano Di Biase, Sebastian Brandorst, Min Wei, Valter Longo. Effects of rapamycin and fasting-cycles therapy on differential stress resistance and sensitization in breast cancer mouse models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-78. doi:10.1158/1538-7445.AM2014-LB-78
Clinical Consequences and Management of Hypomagnesemia
Authors: Kevin J. Martin, Esther A. González, Eduardo Slatopolsky
Journal: Journal of the American Society of Nephrology (2008)

Magnesium deficiency and hypomagnesemia remain quite prevalent, particularly in patients in intensive care units, and may have important clinical consequences. Magnesium should be measured directly in clinical circumstances in which a risk for magnesium deficiency exists and appropriately corrected when found. This commentary reviews the current knowledge of magnesium homeostasis and the risk factors and clinical consequences of magnesium deficiency and outlines approaches to therapy.
Effect of Tumor Microenvironment Modulation on the Efficacy of Oncolytic Virus Therapy
Authors: Kazuhiko Kurozumi, Jayson Hardcastle, Roopa Thakur, Ming Yang, Gregory Christoforidis, Giulia Fulci, Fred H. Hochberg, Ralph Weissleder, William Carson, E. Antonio Chiocca, Balveen Kaur
Journal: JNCI Journal of the National Cancer Institute (2007)

The tumor microenvironment is being increasingly recognized as an important determinant of tumor progression as well as of therapeutic response. We investigated oncolytic virus (OV) therapy-induced changes in tumor blood vessels and the impact of modulating tumor vasculature on the efficacy of oncolytic virus therapy.Rat glioma cells (D74/HveC) were implanted intracranially in immune-competent rats. Seven days later, the rats (groups of 3-7 rats) were treated with oncolytic virus (hrR3), and, 3 days later, brains were harvested for evaluation. Some rats were treated with angiostatic cRGD peptide 4 days before oncolytic virus treatment. Some rats were treated with cyclophosphamide (CPA), an immunosuppressant, 2 days before oncolytic virus treatment. Changes in tumor vascular perfusion were evaluated by magnetic resonance imaging of live rats and by fluorescence microscopy of tumor sections from rats perfused with Texas red-conjugated lectin immediately before euthanasia. Leukocyte infiltration in tumors was evaluated by anti-CD45 immunohistochemistry, and the presence of oncolytic virus in tumors was evaluated by viral titration. Changes in cytokine gene expression in tumors were measured by quantitative real-time polymerase chain reaction-based microarrays. Survival was analyzed by the Kaplan-Meier method. All statistical tests were two-sided.Oncolytic virus treatment of experimental rat gliomas increased tumor vascular permeability, host leukocyte infiltration into tumors, and intratumoral expression of inflammatory cytokine genes, including interferon gamma (IFN-gamma). The increase in vascular permeability was suppressed in rats pretreated with cyclophosphamide. Compared with rats treated with hrR3 alone, rats pretreated with a single dose of cRGD peptide before hrR3 treatment had reduced tumor vascular permeability, leukocyte infiltration, and IFN-gamma protein levels (mean IFN-gamma level for hrR3 versus hrR3 + cRGD = 203 versus 65.6 microg/mg, difference = 137 microg/mg, 95% confidence interval = 72.7 to 202.9 microg/mg, P = .006); increased viral titers in tumor tissue; and longer median survival (21 days versus 17 days, P<.001).A single dose of angiostatic cRGD peptide treatment before oncolytic virus treatment enhanced the antitumor efficacy of oncolytic virus.
How to Evaluate Drugs
Authors: J.Robert Beck
Journal: JAMA (1990)

The merchandisers of new pharmaceuticals have three principal features to consider when promoting a new drug: (1) Is it more effective than a competitor against the condition being treated? (2) Is it less costly? (3) Does it exhibit fewer side effects? With the costs of drug development, approval, and marketing continually increasing,<sup>1</sup>it is rare to find a new medication that is less expensive than its predecessors. Advertisements in this and similar journals trumpet increased efficacy as the easiest concept to grasp in choosing among new drugs. Unfortunately for the manufacturers, not all new preparations can demonstrate increased potency, enhanced bioavailability, or better clinical results. In some recent cases, fewer adverse reactions are the distinguishing features of newer products. How do you sell a medication that might be more costly, just as effective, and have fewer side effects? Cost-effectiveness analysis offers an answer. This technology compares the health effects
Accumulation of Foam Cells in Liver X Receptor-Deficient Mice
Authors: Gertrud U. Schuster, Paolo Parini, Ling Wang, Siegfried Alberti, Knut R. Steffensen, Göran K. Hansson, Bo Angelin, Jan-Åke Gustafsson
Journal: Circulation (2002)

Background— The nature of some of the target genes for liver X receptors (LXRs)-α and -β, such as sterol regulatory element binding protein-1 and ATP-binding cassette transporter proteins, suggests a pivotal role of these nuclear receptors in the regulation of fatty acid and cholesterol homeostasis. The present study aimed to elucidate the physiological relevance of both LXRs with regard to lipid metabolism and macrophage cholesterol efflux. Methods and Results— Mice depleted for LXRα, LXRβ, or both were fed low-fat rodent chow for 18 months before investigations. The combined deficiency of LXRα and LXRβ was linked to impaired triglyceride metabolism, increased LDL and reduced HDL cholesterol levels, and cholesterol accumulation in macrophages (foam cells) of the spleen, lung, and arterial wall. Conclusions— Our data demonstrate the physiological importance of both LXRs in lipid metabolism and strongly indicate that both LXRs have a protective role against the development of atherosclerosis.