tbuckley/cabot-search huggingface dataset:
Caffeine: A Cause of Insulin Resistance?
Authors: Italo Biaggioni, Stephen N. Davis
Journal: Diabetes Care (2002)

Caffeine is arguably the most widely consumed drug in Western society. The annual world consumption of coffee exceeds 4 million tons. Caffeine constitutes 1–2% of roasted coffee beans and is present in many over-the-counter preparations for the treatment of cold and allergies, headaches, diuretics, and stimulants. In general, one cup of coffee is assumed to contain 100 mg of caffeine, and soft drinks contain ∼10–50 mg of caffeine per 12-oz serving. The per capita consumption of caffeine averages ∼200 mg/day, but in some countries, it can exceed 400 mg/day (1). There has been great interest, therefore, in defining the mechanism of action of caffeine and determining the health consequences of its consumption. Progress has been made on both accounts, but not without controversy.

It is now evident that caffeine acts as an antagonist of adenosine receptors (1,2). Only concentrations reaching toxic effects are effective in increasing intracellular calcium or inhibiting cyclic nucleotide phosphodiesterases (1), the alternative mechanisms of action. Caffeine (1,3,7-trimethylxanthine) and the closely related theophylline (1,3-dimethylxanthine) are relatively poor adenosine receptor antagonists, with EC50 values in the low μmol/l range. These concentrations, however, are readily achieved during habitual caffeine consumption. In experimental studies in humans, an oral dose of caffeine at 250 mg t.i.d. (∼5–7 cups of coffee/day), which is well tolerated, produced plasma caffeine concentrations in excess of …
Pain in the Back and Legs Caused by Cervical Spinal Cord Compression
Authors: Thomas W. Langfitt
Journal: JAMA (1967)

Cervical spinal cord compression by tumor or degenerated disk material can cause low back and leg pains which simulate the lumbar disk syndrome. If the patient has roentgenographic evidence of both cervical and lumbar disk disease, the differential diagnosis can be difficult. The pain caused by cord compression tends to be diffuse, involves both legs, and is burning or aching in quality. Lumbosacral nerve root compression produces a sharp, radiating pain in the distribution of the involved root. The results of neurologic examination may be normal at a time when cord compression is sufficient to produce severe pain. The mechanical signs of lumbar disk herniation, limitation in back mobility, and a positive reaction to the straight leg raising test are absent with cord compression.
QBleed predicted risk for gastrointestinal and intracranial bleeding
Authors: Graeme J. Hankey
Journal: Annals of Internal Medicine (2014)

Source Citation Hippisley-Cox J, Coupland C. Predicting risk of upper gastrointestinal bleed and intracranial bleed with anticoagulants: cohort study to derive and validate the QBleed scores. BMJ. 2014;349:g4606. 25069704
Augmented myocardial perfusion reserve after coronary angioplasty quantified by positron emission tomography with H215O
Authors: Mary Norine Walsh, Edward M. Geltman, Robert L. Steele, Joseph L. Kenzora, Philip A. Ludbrook, Burton E. Sobel, Steven R. Bergmann, M.M.A. Weinheimer, Carla J. Weinheimer
Journal: Journal of the American College of Cardiology (1990)
S63 F alpha-1 antitrypsin polymerises and promotes an exaggerated inflammatory response
Authors: S Alam, R Mahadeva
Journal: Thorax (2013)

<h3></h3> Alpha-1 antitrypsin (AT) is the most important anti-elastase in the lung. Z-AT (342Glu&gt;Lys) polymerises within the hepatocyte resulting in severe plasma deficiency and is the commonest genetic reason for the development of COPD. The F α<sub>1</sub>-antitrypsin variant (223Arg&gt;Cys) has been associated with mild plasma deficiency, and when found in association with the Z allele linked to emphysema and liver cirrhosis. We investigated the properties of F-AT in a cell-model. Human F-AT cDNA was generated by site-directed mutagenesis and overexpressed into hepatocytes (HepG2 cells). Supernatants, lysates and inclusion bodies were assessed for total AT. F-AT cells were assessed for polymeric-AT, PERK, NF-kB, AP-1, TNF-α and IL-6 by ELISA, immunoblot or RT-PCR in comparison with normal (non-polymerising) M-AT and Z AT (polymerising control). F-AT cells had no cell cytotoxicity or apoptosis upto 72h. At 24h (unless stated) F-AT secretion was slightly lower, but comparable to M-AT secretion (1479.3 ± 142pg/ml vs. 1745.5 ± 102.3pg/ml, P = 0.413) Secreted F-AT had significantly reduced elastase inhibitory capacity compared to M-AT (0.972 ± 0.069(OD at 405nm) vs. 0.449 ± 0.085, P &lt; 0.001). F-AT formed insoluble aggregates of polymeric-AT (375 ± 32pg/ml vs. undetectable), upregulated PERK mRNA (at 3h) and significantly increased NF-κB (at 16h), AP-1, TNF-α (34.5 ± 5.3pg/ml vs. 10.53 ± 3.2, P = 0.023) and IL-6 (at 48h) (132.3 ± 20.8pg/ml vs. 23.9 ± 16) (P = 0.006). All of which were inhibited by treatment with an inhibitor of polymerisation (P &lt; 0.001 for all). In comparison to Z-AT, F-AT secretion was greater (P &lt; 0.001) but had significantly reduced anti-elastase activity (P = 0.032) and lower ER accumulation of polymeric-F-AT (P &lt; 0.001). In the F-AT cell, PERK mRNA was upregulated at 3h compared to 0.5h in Z-AT. Although elevated compared to M-AT cells, F-AT cells had lower NF-κB activity (P &lt; 0.001), TNF-a production (P = 0.046) and IL-6 production (P = 0.012) compared to Z-AT. In conclusion, F-AT secretion was comparable to M-AT. However, secreted F-AT was defective as an anti-elastase. F-AT was found to polymerise and aggregate in inclusion bodies. ER accumulation of F-AT activated the ER overload response; PERK-dependant-NF-κB mediated inflammatory response, greater than M-AT but to a lesser degree than Z-AT. This data indicate that FZ phenotype may be at risk for liver and lung disease.
Immunoresponsiveness in endometriosis: implications of estrogenic toxicants.
Authors: S E Rier, D C Martin, R E Bowman, J L Becker
Journal: Environmental Health Perspectives (1995)

Endometriosis is a reproductive disease characterized by the growth of endometrial cells at sites outside the uterus. This disease is a serious disorder associated with chronic pain and infertility, which may be present in 6 million women in this country. Traditional medical therapy has consisted of hormonal regimens that limit the action of endogenous estrogen. The etiology of endometriosis is unknown, but studies suggest that soluble factors known as cytokines play a role in disease pathogenesis. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is an environmental toxicant that alters the action of estrogen in reproductive organs and adversely affects immunocompetence. The incidence of endometriosis was determined in rhesus monkeys that were chronically exposed to dioxin for a period of approximately 4 years. Ten years after termination of dioxin treatment, the presence and severity of endometriosis was assessed by surgical laparoscopy. The incidence of endometriosis correlated with dioxin exposure and disease severity was dependent upon the dose administered. Moderate to severe endometriosis was not found in control animals but was documented in three of seven animals exposed to 5 ppt dioxin (43%) and in five of seven animals exposed to 25 ppt dioxin (71%). The frequency of spontaneous disease in the control group was 33%, similar to an overall prevalence of 30% in 304 rhesus monkeys with no history of dioxin exposure. This study indicates that endometriosis may be associated with dioxin exposure in the rhesus. In view of overwhelming evidence that cytokines participate in the mediation of reproductive-endocrine phenomena and regulation of endometrial growth, future assessment of the effects of environmental toxicants on reproductive health may depend upon our understanding of the bidirectional cytokine network between the immune and endocrine systems.
MARATHON RUNNERS HAVE INCREASED AORTIC STIFFNESS
Authors: Despina Kardara, Charalambos Vlachopoulos, Aris Anastasakis, Katerina Baou, Dimitrios Terentes-Printzios, Ioanna Dima, Georgios Antoniou, Athanasios Gravos, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2010)
TCT-267 Lower Mortality of Paclitaxel-Coated Balloon Compared with Paclitaxel-Eluting Stent for the Treatment of DES In-Stent Restenosis: Two-Year Follow-Up of the PEPCAD China ISR Trial
Authors: Yelin Zhao, Bo Xu, Junbo Ge, Yuejin Yang, Jian'an Wang, Shao Liang Chen, Bin Liu, Fang Chen, Run-Lin Gao
Journal: Journal of the American College of Cardiology (2014)
Male pseudohermaphroditism caused by mutations of testicular 17β–hydroxysteroid dehydrogenase 3
Authors: Wayne M. Geissler, Daphne L. Davis, Ling Wu, Karen D. Bradshaw, Sushma Patel, Berenice B. Mendonca, Keith O. Elliston, Jean D. Wilson, David W. Russell, Stefan Andersson
Journal: Nature Genetics (1994)
Platelet Transfusions from Single Donors
Authors: Charles A. Schiffer, Sherrill J. Slichter
Journal: New England Journal of Medicine (1982)

As a consequence of the increasingly intensive therapy administered to patients with leukemia and other types of cancer, there has been a dramatic increase in the use of platelet transfusions in the United States in the past five years.1 Most transfusions consist of pooled platelet concentrates prepared from the blood of multiple donors as a byproduct of whole-blood donation. The optimal conditions for platelet separation and storage have been well characterized, and it is quite clear that platelet recovery, survival, and hemostatic effectiveness can be maintained at nearly normal levels for up to 72 hours after collection.2 4 5 More recently, new . . .
Diagnosis of Proliferative Diabetic Retinopathy
Authors: Bruce E. Spivey
Journal: JAMA (1982)

<h3>To the Editor.—</h3> Sussman et al (1982; 247:3231) are to be commended for their well-designed study of errors in the diagnosis of proliferative diabetic retinopathy. This is a treatable disease, and timely, correct diagnoses can help prevent serious visual loss or blindness. The authors correctly suggest that many physicians may need additional training in eye examination skills and that referral for ophthalmologic opinion is sometimes appropriate.
Physiologic and Psychologic Aspects of the Gravity Spectrum
Authors: Cleto Di Giovanni, Randall M. Chambers
Journal: New England Journal of Medicine (1964)

Musculoskeletal AspectsIncreased urinary calcium, with the occasional formation of urinary calculi, and muscular atrophy are not uncommon clinical occurrences among long-term bedridden patients.28 The concern has been expressed in the literature38, 49 and at meetings and conferences that the same problems may occur in prolonged space flight, either because of the lack of gravity and weight bearing or because of extended periods of confinement in a relatively immobile position. Adequate bone growth is dependent upon muscular contraction and the forces of weight bearing. Failure of either or both to occur in sufficient quantity may result in bone demineralization.Thus far, . . .
Doctor in the lab: what is it like for a doctor to work with scientists?
Authors: C. M Jorm, J. A Stamford, L. Strunin
Journal: BMJ (1996)

As clinical academic medical departments strive to improve the quality of their research, clinicians and scientists are forced into closer liaison.In many cases, clinical departments now have research laboratories directed by "basic scien- tists" but often staffed, in part at least, by doctors.To someone who has not worked in one, these laboratories may seem uncompromising and forbidding work environments.
Accident with Therapeutic Electric Lamp.
Authors: Henry F. Langhorst
Journal: JAMA (1907)

Elmhurst, Ill., Sept. 6, 1907. <h3>To the Editor:</h3> —I wish to report a mishap which occurred during the use of a therapeutic lamp. The lamp used was a small portable one. While administering a treatment over the abdomen, for a diffuse peritonitis, without any known cause the globe exploded, severely frightening and burning the patient. The therapeutic lamp is frequently used about the face in the treament of boils, infections, eczema, neuralgia, enlarged glands, etc. Since the incandescent globe may explode, light and heat should be administered through a different medium.
Abstract 5347: MiRNA expression profile of tumor microenvironment in murine liver metastatic model.
Authors: Joana Marquez, Arianne Schaub, Maite Unzurrunzaga, Patricia Garcia, Iker Badiola
Journal: Cancer Research (2013)

Abstract Colorectal cancer (CRC) is the second most recurrent cancer type and one of the most lethal diseases around the worldwide. The lethality of the CRC is due to the metastasis and the principal target is the liver. Although the main responsible of the metastasis is the cancer cell we can not obviate the crucial role of the host organ and how the cells of the host organ support the progression of the disease. The crosstalk of the tumor microenvironment with the tumor has been deeply studied from the cellular point of view but the regulatory pathways of these processes still remain unknown. The epigenetic regulation has been postulated as one important process implicated in the regulation of cellular changes. The microRNA (miRNA) expression is one of the variants of the epigenetic regulation. In this work we study the deregulation of the miRNA expression in the metastasized liver respect to healthy condition using a murine in vivo liver metastasis model. We inoculated CT26 murine colon carcinoma cell intrasplenically in BALB/c mice and after 15 days we sacrificed the animals to obtain four liver cell types (hepatocytes, liver sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells). Then we isolated the total RNA and performed gene expression and miRNA expression microarrays (Agilent) comparing the tumor received cells with control cells (PBS injected animal's cells). The gene expression microarray helps us finding the biological and cellular sense of the deregulated miRNAs and could be an important data source to elucidate the therapeutic option of each deregulated miRNAs. An in vivo approach is a more realistic model that can show more elements implicated in the crosstalk of the different liver cell types. This fact show us several results in the different cell types with expected and unexpected new miRNA deregulations. For instance downregulation of miR-16 and miR-15b and upregulation of miR-138 has been found in hepatic stellate cells with important role in activation proliferation and apoptosis of this cell type and we also observed deregulation of miR-135 in liver sinusoidal cells. These are some of the examples of a large amount of miRNA identified. Nowadays we are checking the role of each deregulated miRNA in the cellular processes to verify their implication in the metastatic progression and postulate them as therapeutic targets. Citation Format: Joana Marquez, Arianne Schaub, Maite Unzurrunzaga, Patricia Garcia, Iker Badiola. MiRNA expression profile of tumor microenvironment in murine liver metastatic model. [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 5347. doi:10.1158/1538-7445.AM2013-5347
Newly Identified Actions of the Vitamin D Endocrine System*
Authors: MARIAN R. WALTERS
Journal: Endocrine Reviews (1992)

VITAMIN D is a seco-steroid in which the B-ring of the cyclopentanoperhydrophenanthrene structure is cleaved. The vitamin is either obtained from the diet or is synthesized in the skin from 7-dehydrocholesterol (Fig. 1) and is itself biologically inert (for reviews see Refs. 1–8). Vitamin D and its metabolites circulate in the blood primarily bound to and in equilibrium association with the vitamin D-binding globulin [DBP]. In the liver, the enzyme 25-hydroxylase converts the vitamin to the inactive hormonal precursor 25-hydroxyvitamin D [25(OH)D]. Subsequently, the renal lα-hydroxylase enzyme converts 25(OH)D to the biologically active form 1,25-dihydroxyvitamin D [1,25(OH)2D]. Both hydroxylase enzymes are cytochrome P450-containing enzymes. la-Hydroxylase activity is tightly controlled by a number of ionic and endocrine factors including stimulation by PTH and reduced plasma Ca2+ or inhibition by 1,25(OH)2D in a classic negative feedback loop. Although not illustrated in Fig. 1, under conditions of adequate plasma Ca2+ levels, 25(OH)D is alternatively converted to 24,25(OH)2D by the reciprocally regulated renal P450- dependent 24-hydroxylase enzyme. Whether this metabolite of vitamin D is biologically effective or whether its production simply initiates a catabolic pathway has been a topic of active debate (2, 4, 5, 9). The seco-steroid hormone 1,25(OH)2D exerts its principal biological activities through specific intracellular receptors (Fig. 1), which are nuclear transcription factors of the steroidthyroid receptor gene superfamily (7, 10), a relationship previously postulated on the basis of the biochemical similarities between all these receptor species (1, 11). As now considered likely for many of these ligand-dependent transcription factors, the 1,25(OH)2D receptor (VDR) (12, 13), seems to be predominately a nuclear protein (1), a fact that will be of importance in later discussions of its signal transduction mechanisms. The mechanism of action of the VDR is similar to that of the other steroid hormone receptors (Fig. 2), involving specific interactions of the receptor zinc-finger regions with specific nucleotide sequences (hormone response elements) usually in the 5′-regulatory region of the affected genes (1, 7, 10, 15). Similarly, 1,25(OH)2D regulation of cell function by altering gene transcription and mRNA and protein synthesis is similar to that of the other members of this gene family (1).
Platelet‐activating factor (<scp>PAF</scp>) induces wheal and flare skin reactions independent of mast cell degranulation
Authors: K. Krause, A. Giménez‐Arnau, E. Martinez‐Escala, M. Farré‐Albadalejo, M. Abajian, M. K. Church, M. Maurer
Journal: Allergy (2013)

Platelet-activating factor (PAF) causes wheal and flare responses which are abrogated by H1-antihistamines giving rise to the hypothesis that PAF-induced wheal development is secondary to histamine release from dermal mast cells. But is this hypothesis correct?Wheal and flare responses were induced by intradermal injection of PAF, codeine and histamine in 14 healthy volunteers. Dermal histamine and PGD2 contractions were measured using microdialysis.PAF, unlike histamine and codeine, did not cause a statistically significant rise in mean histamine levels with ten persons showing negligible histamine release. Codeine caused a significant but variable histamine release, ranging from 29 to 282 ng/ml. Codeine, but not PAF or histamine, caused a small but statistically significant release of PGD2.Wheal and flare reactions in human skin induced by PAF are not associated with histamine release and, therefore, appear to be independent of mast cell degranulation.
“Zero Ischemia” Partial Nephrectomy: Novel Laparoscopic and Robotic Technique
Authors: Inderbir S. Gill, Manuel S. Eisenberg, Monish Aron, Andre Berger, Osamu Ukimura, Mukul B. Patil, Vito Campese, Duraiyah Thangathurai, Mihir M. Desai
Journal: European Urology (2010)
Factors Associated With Decisions to Undergo Surgery Among Patients With Newly Diagnosed Early-Stage Lung Cancer
Authors: Samuel Cykert, Peggye Dilworth-Anderson, Michael H. Monroe, Paul Walker, Franklin R. McGuire, Giselle Corbie-Smith, Lloyd J. Edwards, Audrina Jones Bunton
Journal: JAMA (2010)

Lung cancer is the leading cause of cancer death in the United States. Surgical resection for stage I or II non-small cell cancer remains the only reliable treatment for cure. Patients who do not undergo surgery have a median survival of less than 1 year. Despite the survival disadvantage, many patients with early-stage disease do not receive surgical care and rates are even lower for black patients.
Acute Liver Injury due to Flavocoxid (Limbrel), a Medical Food for Osteoarthritis
Authors: Naga Chalasani
Journal: Annals of Internal Medicine (2012)

Background: Flavocoxid is a prescription medical food that is used to treat osteoarthritis. It is a proprietary blend of 2 flavonoids, baicalin and catechins, which are derived from the botanicals Scutellaria baicalensis and Acacia catechu, respectively. Objective: To describe characteristics of patients with acute liver injury suspected of being caused by flavocoxid. Design: Case series. Setting: Drug-Induced Liver Injury Network Prospective Study ongoing at multiple academic medical centers since 2004. Patients: Four adults with liver injury. Measurements: Clinical characteristics, liver biochemistry values, and outcomes. Results: Among 877 patients enrolled in the prospective study, 4 had liver injury suspected to have been caused by flavocoxid. All were women; ages ranged from 57 to 68 years. All developed symptoms and signs of liver injury within 1 to 3 months after initiating flavocoxid. Liver injury was characterized by marked elevations in levels of alanine aminotransferase (mean peak, 1268 U/L; range, 741 to 1540 U/L), alkaline phosphatase (mean peak, 510 U/L; range, 286 to 770 U/L), and serum bilirubin (mean peak, 160.7 µmol/L [9.4 mg/dL]; range, 34.2 to 356 µmol/L [2.0 to 20.8 mg/dL]). Liver biochemistry values decreased to the normal range within 3 to 12 weeks after flavocoxid was stopped, and all patients recovered without experiencing acute liver failure or chronic liver injury. Causality was adjudicated as highly likely in 3 patients and as possible in 1 patient. Limitation: The frequency and mechanism of liver injury could not be assessed. Conclusion: Flavocoxid can cause clinically significant liver injury, which seems to resolve within weeks after cessation. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases.
Ultrasonic screening for small for dates fetuses.
Authors: C R Whitfield, J P Neilson
Journal: BMJ (1984)

But does this mean that we should have a national grocery board and a series of general managers to control the grocery industry in each district ?This would be as relevant to the grocery industry as it is to the National Health Service.It is now too late to turn back, however, and we must continue to divert our energies and some of our best brains into devising a meaningful job description for general managers and in trying to devise ways of measuring their effectiveness.