tbuckley/cabot-search huggingface dataset:
Combination Therapy in NIDDM
Authors: Philip Raskin
Journal: New England Journal of Medicine (1992)

The use of a combination of oral hypoglycemic drugs and insulin to treat patients with non-insulin-dependent diabetes mellitus (NIDDM) that is refractory to treatment with oral hypoglycemic drugs alone has long been of great interest to practitioners. I cannot remember when I last gave a lecture on diabetes without being asked my opinion of the merits of combination therapy.Combination therapy makes good pathophysiologic sense. NIDDM has two main pathophysiologic features: relative insulin deficiency1 and decreased peripheral and hepatic sensitivity to insulin.2 The combination of a sulfonylurea drug that increases insulin sensitivity3 and exogenous insulin should theoretically correct both defects . . .
What are all the things that aspirin does?
Authors: R. Flower
Journal: BMJ (2003)

This fascinating but simple and cheap drug has an assured future 

Ask any medical student and he or she will tell you that aspirin reduces fever, pain, and inflammation but may cause ulcers. Students may also recollect that it prolongs bleeding, and may prevent strokes and heart attacks, but would be unlikely to know of its use in cancer or Alzheimer's disease.

A defining point in the history of aspirin was the discovery that it inhibited the prostaglandin forming cyclooxygenase.1 Prostaglandins cause inflammation, fever, and pain; have gastric cytoprotective actions; and are implicated in platelet aggregation, so this discovery provided a unified explanation for the effects of aspirin (and most other non-steroidal anti-inflammatory drugs). However, events took an even more interesting turn when a further isoform of cyclo-oxygenase, cyclooxygenase-2, was discovered.2 While similar in many ways to the original enzyme (COX 1) there were important differences, including the fact that COX 2 was induced in cells by inflammatory insults. COX 2 therefore seemed to be the most relevant target in inflammation, which led …
Excess Deaths From Nine Chronic Diseases in the United States, 1986
Authors: Robert A. Hahn
Journal: JAMA (1990)

To assess excess mortality from chronic disease in the United States, state age-adjusted combined mortality rates for nine chronic diseases in 1986 were compared with three "minimum" rates--two calculated from rates actually achieved in states and a third estimated as the mortality remaining after elimination of one risk factor for each disease. Hawaii had the lowest mortality rate of combined diseases (305/100,000); state excesses ranged from 0% to 37%. The sum of lowest disease-specific rates in any state was 284 per 100,000, indicating excesses of between 7% and 41%. A minimum mortality rate of 224 per 100,000 was estimated to result from elimination of one risk factor for each of the nine diseases, indicating state excesses from 26% to 54%, or 524,000 US deaths. Reduction of US mortality from the nine diseases to the risk factor--eliminated rate is estimated to be associated with an increased life expectancy at birth of 4 years.
Elaboration of toxic oxygen by-products by neutrophils in a model of immune complex disease.
Authors: R B Johnston, J E Lehmeyer
Journal: Journal of Clinical Investigation (1976)

Contact between human neutrophils and aggregated immunoglobulin G bound to micropore filters has been studied as a model of the pathogenesis of tissue damage in immune complex disease. Contact with this surface, as well as with plain filters and polystyrene petri dishes, induced neutrophils to elaborate superoxide anion and hydrogen peroxide and to generate chemiluminescence, which has been attributed to singlet oxygen. Pretreatment of the cells with cytochalasin B decreased these activities but increased release of lysosomal beta-glucuronidase, suggesting that degranulation and the burst of oxygen metabolism that characterizes phagocytes are independently regulated functions. Toxic oxygen metabolites released from neutrophils are highly reactive and could mediate tissue injury at sites of inflammation.
On Recurrent Fibromata of the Neck, and their Relation to the Branchial Arches
Authors: H. W Freeman
Journal: BMJ (1884)

I PROPOSE to deal shortly with this subject under the following heads:1.The history of a typical case of recurrent fibromata of the neck; 2. The pathology of these growths;3. The morphology of the branchial arches, and their probable rela- tion to these fibromas.G. B., a labourer, was first admitted into the Bath United Hospital on MIarch 1st, 1882, with a lump on the left side of the neck the lower jaw, of six months' duration.The tumour was hard, rounded, freely movable, and about the size of a hen's egg, deeply situated in the anterior triangle of theneck, posterior to, but on with, the body of the hyoid bone and thyroid cartilage, lying deep vessels of the neck, and moving up and down during deglItition.It was removed without difficulty, and, after dividing the layers deep cervical fascia over a director, it shelled out easily.naked eye, the growth looked like a young rapidly developing The man, after a sharp attack of quinsy, made a good recovery, left the hospital a fortnight after the operation.On August 25th, 1883, eighteen months after his discharge, he applied for admission, this time for a much larger growth under jaw of the same side, situate on a higher plane, and involving cicatrix of the previous tumour.It had been growing for six months, the interval of freedom being only a year.It was now lobulated anteriorly, hard to the feel, moved easily about on the underlying structures, placed obliquely to, and overlapping the carotid vessels front, attached sparingly to the body of the lower jaw, and
Abstract A49: The ERK/MAPK scaffold IQGAP1 is a tumor-selective target
Authors: Katherine L. Jameson, Ashley M. Zehnder, Paul A. Khavari
Journal: Cancer Research (2011)

Abstract To advance insight into skin biology and pathophysiology, our lab has focused on understanding how the normal processes of cell division and migration are regulated and how they become dysregulated in pathological states, including cancer. One particular pathway of interest in the lab is the extracellular-regulated kinase/mitogen-activated protein kinase (Erk/MAPK) pathway. This highly conserved pathway is critical to epidermal homeostasis and tumorigenesis, but its mechanisms of action remain unclear. This research explores how the Erk/MAPK-interacting protein IQGAP1 mediates signaling in tumorigenesis. IQGAP1 physically interacts with canonical Erk/MAPK pathway members in order to precisely modulate their signal output and in its absence, signaling through this pathway is severely diminished. We recently found that depleting expression of IQGAP1, a Mek- and Erk-binding MAPK-IP, exerted no effect on normal tissue but effectively blocked invasive neoplasia. We are currently working to define the functional domains of IQGAP1 required for Erk MAPK-driven epidermal neoplasia. These efforts will help identify potentially important and therapeutically relevant neoplasia-selective interactions of IQGAP1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A49.
Neonatal and Pediatric Cardiovascular Crisis
Authors: Moshe Steier
Journal: JAMA (1976)

<h3>To the Editor.—</h3> We enjoyed the timely, factual, and brilliant note by Warren G. Guntheroth, MD (232:168, 1975), that helpfully summarized the current management of neonatal and pediatric cardiovascular crisis. We believe that a few clarifying comments are in order. The statement, "A cuff too large will produce a reading that may suggest shock in the presence of a normal circulatory state," is proved to be not true by an excellent study of Steinfeld et al<sup>1</sup>: "In human investigations, unusually wide bladder, extending from the axilla to a level 1 or 2 cm above the antecubital crease, failed to elicit previously reported low peak systolic values, when direct and indirect pressures were compared." "These clinical results are in agreement with the analytic prediction of the nonexistence of the socalled wide cuff effect."<sup>2</sup> On the basis of the above clinical experimental studies I would suggest that a too-wide cuff
Persistent Limb Pain in Below-Knee Amputee
Authors: Ronald M. Lawrence
Journal: JAMA (1976)

<h3>To the Editor.—</h3> This information relates to a recent letter (234:649, 1975). We have used a technique that consists of stimulation of the periosteum of the bone in treatment of phantom limb pain with excellent results over the last four years. In treating approximately ten patients with this technique, we have had 100% success in either reducing or limiting pain in those individuals who have had no prior neurosurgical procedure performed on them. The technique is simple and consists mainly of implantation of hypodermic needles into the periosteum of the bone at various preselected areas. These needles are then attached to an electrical apparatus, and the patient is stimulated for 45 minutes. If anyone is interested, we can send them the details of the technique.
THE ROLE OF ELECTRICITY IN TREATMENT
Authors: E. P. Cumberbatch
Journal: BMJ (1932)

a HE EIIECTRICAL I)EPARTIMENT, s1r.BART HOLOMEW'S IHOSP'ITAL Various diseases can be cured or relieved, not only by electricity, but also by other physical agents or by pharmacological or surgical methods.When we speak of the role of electricity we should exclude the maladies wvhich respond to simple forms of treatInent.
Classification and Analysis of Fetal Deaths in Massachusetts
Authors: Edward J. Lammer, Lisa E. Brown, Marlene T. Anderka, Bernard Guyer
Journal: JAMA (1989)

Fetal deaths, in contrast to infant deaths, have been subject to epidemiologic analysis infrequently. We characterized 574 Massachusetts resident fetal deaths from 1982 and assessed the accuracy of cause-of-death information available from vital records compared with that from corresponding fetal autopsies. The fetal death rate exceeded the neonatal mortality rate. Fetal mortality was higher among black, unmarried, and older mothers. Fetuses of multiple-gestation pregnancies had an unusually high risk of fetal death. Autopsy reports were obtained for 61% of fetal deaths. The underlying cause of death from the fetal death record differed from that on the autopsy report in 55% of cases. Systematic collection of population-based autopsy data is a useful approach for improving the quality and accuracy of mortality statistics on fetal deaths. Many stillbirths remain unexplained, however, and research is needed to identify pathological markers that might reduce the heterogeneity within the fetal deaths currently ascribed to unknown causes.
Plasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronic HCV patients
Authors: Jérémie Decalf, Sandrine Fernandes, Randy Longman, Mina Ahloulay, Françoise Audat, François Lefrerre, Charles M. Rice, Stanislas Pol, Matthew L. Albert
Journal: The Journal of Experimental Medicine (2007)

Plasmacytoid dendritic cells (pDCs) are the professional type I interferon (IFN)-producing cells, and upon activation they traffic to lymph organs, where they bridge innate and adaptive immunity. Using multianalyte profiling (MAP), we have mapped the key chemokines and cytokines produced in response to pDC activation, taking into consideration the role of autocrine IFN, as well as paracrine effects on other innate cells (e.g., monocytes and conventional DCs). Interestingly, we identify four distinct cytokine/chemokine loops initiated by Toll-like receptor engagement. Finally, we applied this analytic approach to the study of pDC activity in chronic hepatitis C patients. Based on the activation state of pDCs in fresh blood, the lack of agonistic activity of infectious virions, the production of a broad array of cytokines/chemokines once stimulated, and the direct effects of pDCs on other PBMCs, we conclude that the pDCs from hepatitis C virus (HCV)-infected individuals are fully functional and are, indeed, a viable drug target. In sum, this study provides insight into the use of MAP technology for characterizing cytokine networks, and highlights how a rare cell type integrates the activation of other inflammatory cells. Furthermore, this work will help evaluate the therapeutic application of pDC agonists in diseases such as chronic HCV infection.
ABDOMINOPERINEAL OPERATION FOR CANCER OF THE RECTUM
Authors: T. E. JONES
Journal: JAMA (1930)

A review of the history of cases of cancer of the rectum shows that there is still neglect of digital or proctoscopic examination of patients who present themselves for relief of bleeding from the rectum. Occasionally a patient does not seek medical advice until he is in a hopeless condition, but in this series of cases it was found that, while most of the patients did consult a physician from three to six months previously for the relief of rectal bleeding, the physician was misled by coexisting hemorrhoids and advised only palliative treatment. As a result, the patient left with a false sense of security and did not again seek relief for several weeks or months. That this is true is well borne out by the statistics, which show that in the past four years, from among 185 cases of cancer of the rectum seen at the Cleveland Clinic, 70
The interaction between propranolol and epinephrine as observed in patients undergoing Mohs' surgery
Authors: Leonard M. Dzubow
Journal: Journal of the American Academy of Dermatology (1986)

The blood pressure response to the administration of epinephrine-containing local anesthetics was studied prospectively in ten patients taking propranolol and in ten control patients. While no significant alteration in blood pressure was documented for the patients taking propranolol, the blood pressures of the control group tended to decrease following injection of anesthetic. The variation in blood pressure response between the two groups was statistically significant and represents a mild manifestation of the blockade of beta-2 receptors of the vascular beds from the propranolol. The uncommon occurrence of a malignant hypertensive response from a propranolol-epinephrine reaction is probably a dose-related, somewhat idiosyncratic sensitivity of the peripheral vasculature to the alpha pressor effect of epinephrine unmasked by the blockade of beta receptors. The risk of this catastrophic event must be weighed against the risk of precipitating a myocardial ischemic event from too rapid an alteration in propranolol dosage. Malignant hypertension is probably uncommon in patients receiving low doses of epinephrine during most dermatologic procedures.
Estradiol-type activity of coumestrol in mature and immature ovariectomized rat uterotrophic assays.
Authors: H Tinwell, A R Soames, J R Foster, J Ashby
Journal: Environmental Health Perspectives (2000)

Makaverich et al. [Environ Health Perspect 103:574-581 (1995)] reported that the uterotrophic activity of the phytoestrogen coumestrol in the immature ovariectomized rat was atypical in that it was not associated with increased uterine hyperplasia and DNA content. We previously reported that coumestrol gave a typical estradiol-type uterotrophic response in the immature intact rat, yielding increases in uterine epithelial cell height, glandular formation, cell labeling, and DNA content. These papers did not answer the question of whether there is a basic difference between the ovariectomized and the intact rat uterotrophic assays. In this paper, we report that coumestrol gives a typical estradiol-type uterotrophic response in uterotrophic assays using immature intact, immature ovariectomized, and mature ovariectomized rats. We concluded that the uterotrophic activity of coumestrol is typical of the natural estrogen estradiol.
Aneurysmal Bone Cyst of the Patella
Authors: RAKESH KUMAR, BHARATHI DASAN J, ARUN MALHOTRA
Journal: Clinical Nuclear Medicine (2000)

The authors report a rare case of aneurysmal bone cyst of the patella in a 16-year-old girl who had swelling of the left knee joint. Radiographs of the left knee joint suggested giant cell tumor or aneurysmal cyst of the patella. A three-phase bone scan revealed increased vascularity in initial blood-flow and blood-pool images and a doughnut-shaped appearance in delayed images, in keeping with the final histopathologic diagnosis of aneurysmal bone cyst of the patella. This case highlights the importance of obtaining lateral views in possible disease of the patella and various differential diagnoses of doughnut-shaped appearance on a patellar bone scintigram.
Frequency of immunoglobulin E class switching is autonomously determined and independent of prior switching to other classes.
Authors: S Jung, G Siebenkotten, A Radbruch
Journal: The Journal of Experimental Medicine (1994)

Both, in humans and in mice, a major fraction of immunoglobulin E (IgE)-expressing B lymphocytes develops by sequential Ig class switching from IgM via IgG to IgE. This sequential class switch might have functional implications for the frequency and repertoire of IgE+ cells. Here we show that in mutant mice, in which sequential switching to IgE via IgG1 is blocked, the frequency of cells switching to IgE is not affected. Thus, sequential class switching to IgE merely reflects the simultaneous accessibility of two acceptor switch regions for switch recombination, induced by one cytokine, but with markedly distinct efficiency. Analysis of switch recombination on both IgH alleles of switched cells shows that the low frequency of switching to IgE is an inherent feature of the S epsilon switch region and its control elements.
Muscular Endurance in Long-Term IDDM Patients
Authors: Henning Andersen
Journal: Diabetes Care (1998)

OBJECTIVE To determine the short-term muscular endurance and working capacity of leg muscles in long-term IDDM patients in relation to neuropathic complications, muscle strength, and metabolic control. RESEARCH DESIGN AND METHODS The muscular endurance of extensors and flexors at the ankle and knee was assessed in 44 IDDM patients and in 44 matched control subjects during 30 maximal isokinetic movements. The endurance index was the work performance of the last 5 movements relative to the first 5 movements. Total work was the summated work of all movements. All patients underwent a neurological evaluation, nerve conduction studies, and quantitative sensory tests. RESULTS The combined endurance index of the ankle extensors and flexors was 70% (51–88) (median [range]) in the diabetic group and 65% (55–82) in the control group (P &amp;lt; 0.01). For knee extensors and flexors the combined endurance index was 65% (55–103) for the diabetic patients and 63% (48–75) in the control subjects (P &amp;lt; 0.01). The endurance index related neither to the severity of neuropathy nor to the metabolic control (blood glucose and HbA1c) for any of the muscle groups. Diabetic patients had reduced strength of all muscle groups (14–24%, P &amp;lt; 0.02) and impaired total work performance (15–20%, P &amp;lt; 0.01) for ankle movements. CONCLUSIONS Long-term IDDM patients have increased endurance but reduced strength and work performance of leg muscles. The combined effect of the motor abnormalities is suggested to give rise to functional impairment, including an increased risk of falls and injuries.
NADPH‐oxidation activities in subcellular fractions isolated from resting or phagocytozing human polymorphonuclears
Authors: Christian Auclair, Martine Torres, Jacques Hakim, Huguette Troube
Journal: American Journal of Hematology (1978)

Using a fluorometric assay for the determination of oxidized pyridine nucleotides (NAD[P]+), total and cyanide-resistant NADPH-oxidative activities have been measured in subcellular fractions isolated from resting and phagocytosing human polymorphonuclears. Enzymatic activies responsible for the oxidation of the NADPH have been recovered in the heavy particles (15,000g/15 min), the low-density particles (100,000g/30 min), and the cytosolic fraction. Stimulation of the cells with opsonized zymosan had a different effect on the NADPH-oxidative activities of these subcellular fractions, which suggests the involvement of various types of enzymatic systems in the oxidation of NADPH. The cytosolic fraction interacted strongly with the enzymatic activities occurring in the sedimentable fractions and is therefore thought to play a central role in the regulation of the activation of the oxidative metabolism associated with phagocytosis.
North American Loxoscelism
Authors: Calvin J. Dillaha, G. Thomas Jansen, W. Mage Honeycutt, Carson R. Hayden
Journal: JAMA (1964)

North American loxoscelism caused by the bite of the<i>Loxosceles reclusus</i>, the brown recluse spider, can produce a gangrenous slough at the site of envenomation and a severe systemic reaction. In 16 cases the local reaction included pain, bleb formation, erythema, ecchymosis, necrosis ending in an eschar, and ulceration. The systemic reactions may include fever, nausea, malaise, hemolysis, and thrombocytopenia. Two deaths have been reported in small children. This spider is indigenous throughout the South Central US.
Granulomatous cheilitis and Crohn's disease
Authors: Y. KANO, T. SHIOHARA, A. YAGITA, M. NAGASHIMA
Journal: British Journal of Dermatology (1990)

Journal Article Granulomatous cheilitis and Crohn's disease Get access Y. KANO, Y. KANO Division of Dermatology, National Okura Hospital and Departments of Tokyo, JapanDivision of Dermatology Tokyo, Japan Dr Yoko Kano, Division of Dermatology, National Okura Hospital, 2–10–1 Okura, Setagaya, Tokyo 157, Japan. Search for other works by this author on: Oxford Academic Google Scholar T. SHIOHARA, T. SHIOHARA Division of Dermatology Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar A. YAGITA, A. YAGITA Division of Surgery, Kyorin University School of Medicine, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar M. NAGASHIMA M. NAGASHIMA Division of Dermatology Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 123, Issue 3, 1 September 1990, Pages 409–412, https://doi.org/10.1111/j.1365-2133.1990.tb06303.x Published: 01 September 1990
Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer
Authors: Richard S Houlston, Emily Webb, Peter Broderick, Alan M Pittman, Maria Chiara Di Bernardo, Steven Lubbe, Ian Chandler, Jayaram Vijayakrishnan, Kate Sullivan, Steven Penegar, Luis Carvajal-Carmona, Kimberley Howarth, Emma Jaeger, Sarah L Spain, Axel Walther, Ella Barclay, Lynn Martin, Maggie Gorman, Enric Domingo, Ana S Teixeira, David Kerr, Jean-Baptiste Cazier, Iina Niittymäki, Sari Tuupanen, Auli Karhu, Lauri A Aaltonen, Ian P M Tomlinson, Susan M Farrington, Albert Tenesa, James G D Prendergast, Rebecca A Barnetson, Roseanne Cetnarskyj, Mary E Porteous, Paul D P Pharoah, Thibaud Koessler, Jochen Hampe, Stephan Buch, Clemens Schafmayer, Jurgen Tepel, Stefan Schreiber, Henry Völzke, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner, Brent W Zanke, Alexandre Montpetit, Thomas J Hudson, Steven Gallinger, Harry Campbell, Malcolm G Dunlop
Journal: Nature Genetics (2008)