tbuckley/cabot-search huggingface dataset:
Importance of sympathetic innervation in the positive inotropic effects of bradykinin and ramiprilat.
Authors: R D Minshall, V P Yelamanchi, A Djokovic, D J Miletich, E G Erdös, S F Rabito, S M Vogel
Journal: Circulation Research (1994)

Isolated rat left atria or right ventricular strips were electrically stimulated at a constant frequency. The amplitude of twitch contractions, thus elicited, rose as a function of stimulation intensity because of increases in the evoked release of sympathetic catecholamines. Bradykinin had no effect on contractile force in preparations paced at a minimal intensity (threshold). By contrast, bradykinin (1 nmol/L to 1 mumol/L) markedly increased twitch contractile force when the preparations were paced at a high intensity (two to three times threshold). The EC50 for the positive inotropic action of bradykinin averaged 42 nmol/L. Ramiprilat (1 mumol/L), an angiotensin I-converting enzyme/kinase II inhibitor, shifted the EC50 for bradykinin to approximately 2 nmol/L. Ramiprilat (1 mumol/L) per se also produced a modest positive inotropic effect. The effects of bradykinin and/or ramiprilate were inhibited by HOE 140 (300 nmol/L), a bradykinin B2-receptor antagonist. Propranolol (1 mumol/L), a beta-adrenoceptor blocker, abolished the effects of bradykinin. After the destruction of sympathetic nerve endings by use of 6-hydroxydopamine, bradykinin no longer exerted a positive inotropic action. Cocaine (10 micrograms/mL), an inhibitor of catecholamine reuptake, potentiated the effect of bradykinin. Bradykinin did not affect the positive inotropic response to tyramine (10 mumol/L), whereas cocaine blocked it. Furthermore, bradykinin did not modify the dose-response curves for added norepinephrine. omega-Conotoxin (100 nmol/L) inhibited the positive inotropic effect of intensified stimulation and bradykinin potentiation. Bradykinin is suggested to facilitate the evoked release of sympathetic catecholamines and thereby cause a positive inotropic effect.
Forefoot eczema—a review
Authors: E. Young, D.S. Wilkinson
Journal: British Journal of Dermatology (1985)

Twenty-eight cases of forefoot eczema attending our department in the past 10 years have been reviewed. Factors investigated were: (a) the incidence of atopy in the patients and the presence of sibling involvement; (b) the natural course of the disease and age of clearance; (c) seasonal incidence, if any; (d) treatment and effect; and (e) other factors involved including the role of friction and footwear. Twenty-five per cent of patients gave a personal history of atopic disease. Ten per cent had an affected sibling. Natural progression of the disease was of gradual improvement and clearance by the age of 15 years. Fourteen per cent found their condition worse in the winter months and 50% suffered more in summer. The remainder showed no seasonal variation. This variation could largely be explained by frictional factors from footwear or sport and leisure activities. Topical treatment was most effective when frictional factors were minimized.
Abstract 5665: New alternatives to photodynamic therapy based on light-enabled drug delivery.
Authors: M. Michael Dcona, Deboleena Mitra, Rachel W. Goehe, David A. Gewirtz, Deborah A. Lebman, Matthew C.T. Hartman
Journal: Cancer Research (2013)

Abstract Conventional photodynamic therapy (PDT) aims to achieve tumor drug targeting by selectively killing cells upon illumination. PDT serves as a non-invasive treatment option for many types of non-metastatic, light-accessible cancers such as those involving the head and neck, lung, bladder, prostate, or esophagus. The various types of PDT all use the same basic strategy for killing cells; photosensitizing molecules are taken up by cancer cells, and, upon illumination, singlet oxygen is generated in the vicinity of the photosensitizer, killing the cell. A new alternative to PDT is photochemical internalization, in which singlet oxygen generated by a photosensitizer disrupts endosomes containing a toxin, releasing it into the cytoplasm and killing the cell. A drawback to both of these approaches is that moderate levels of oxygen are required, yet tumors are often hypoxic environments. Moreover, during PDT treatment, oxygen levels drop even further as the singlet oxygen is consumed; this can compromise treatment effectiveness. We have sought to address these challenges by developing new strategies for light-based treatment of cancer that are oxygen independent. In the first approach, which we call photocaged permeability, we have attached the anticancer drug doxorubicin to a cell impermeable small molecule via a light-cleavable linker. We show using flow cytometry and confocal microscopy that this conjugate is cell impermeable in the dark, yet upon illumination, doxorubicin is released and enters the cells. The IC50 for our conjugate in JH-EsoAd1 cells using non-cytotoxic doses of light is 1.6 μM, identical to that of doxorubicin alone. No cytotoxicity is observed at doses 30-fold higher in the dark. In a second approach, we have attached doxorubicin to folate receptor and PSMA ligands via a light cleavable linker in order to enable dual cancer cell targeting with both light and ligand specificity. The ability of the resulting conjugates to selectively kill cells expressing the requisite receptors with light will be described. Citation Format: M. Michael Dcona, Deboleena Mitra, Rachel W. Goehe, David A. Gewirtz, Deborah A. Lebman, Matthew C.T. Hartman. New alternatives to photodynamic therapy based on light-enabled drug delivery. [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 5665. doi:10.1158/1538-7445.AM2013-5665
The Reliability and Validity of a Brief Diabetes Knowledge Test
Authors: James T Fitzgerald, Martha M Funnell, George E Hess, Patricia A Barr, Robert M Anderson, Roland G Hiss, Wayne K Davis
Journal: Diabetes Care (1998)

OBJECTIVE To examine the reliability and validity of a brief diabetes knowledge test. The diabetes knowledge test has two components: a 14-item general test and a 9-item insulin-use subscale. RESEARCH DESIGN AND METHODS Two populations completed the test. In one population, patients received diabetes care in their community from avariety of providers, while the other population received care from local health departments. Cronbach's coefficient a was used to calculate scale reliability for each sample. To determine validity, patient group differences were examined. It was hypothesized that test scores would be higher for patients with type 1 diabetes, for patients with more education, and for patients who had received diabetes education. RESULTS The coefficient as for the general test and the insulin-use subscale indicate that both are reliable, α ≥ 0.70. In the community sample, patients with type 1 diabetes scored higher than patients with type 2 diabetes on the general test and the insulin-use subscale. In the health department sample, patients with type 1 scored higher than patients with type 2 on the insulin-use subscale. For both samples, scores increased as the years of formal education completed increased, and patients who received diabetes education scored higher than patients who did not. CONCLUSIONS Although the samples differed demographically, the reliability and validity of the test were supported in both the community andthe health department samples. This suggests that the test is appropriate for a variety of settings and patient populations.
Intravenous Tubing With Burettes Can Be Safely Changed at 48-Hour Intervals
Authors: Hector F. Gorbea
Journal: JAMA (1984)

No studies of safety in changing intravenous systems containing in-line burettes at 48 hours in an intensive care setting have been performed. Patients entering a surgical intensive care unit were alternatively assigned to have any line with an in-line burette changed at either 24-hour (64 patients) or 48-hour (59 patients) intervals. Daily quantitative cultures with a 2-mL aliquot of burette fluid were obtained. Contaminated burette fluid was detected in nine of 452 (2.0%; 95% confidence interval, 0.7% to 3.3%) samples from 24-hour interval burettes and in nine of 224 (4.0%; 95% confidence interval, 1.4% to 6.6%) samples from 48-hour interval burettes. Bacterial contamination of burette fluid with ten or more colonies per milliliter occurred in only five (1.1%) cultures from patients in the 24-hour interval group compared with only two cultures (0.9%) in the 48-hour group. None of the contaminated burette fluids was associated with primary bacteremia. Change of in-line burettes in intensive care at 48-hour intervals is safe and should result in substantial cost savings.
Internal Cardioversion of Atrial Fibrillation
Authors: Randolph A. S. Cooper, William M. Smith, Raymond E. Ideker
Journal: Circulation (1997)

Background The ultimate acceptance of a fully automatic atrial defibrillator will depend on the reduction of pain to acceptable levels, requiring a marked decrease in defibrillation thresholds. The purpose of this study was to determine whether atrial defibrillation thresholds can be reduced by sequential shocks delivered through two current pathways. Methods and Results Sustained atrial fibrillation was induced with rapid atrial pacing in 12 adult sheep. Defibrillation electrodes were positioned in the right atrial appendage (RAap), distal coronary sinus (DCS), proximal coronary sinus (CSos), main/left pulmonary artery junction (PA), and right ventricular apex (RV). Single-capacitor biphasic waveforms (3/1 ms) were delivered through combinations of these electrodes. Probability-of-success curves were determined for single shocks with a single current pathway and sequential shocks with either single- or dual current pathways. The ED 50 for delivered energy for the dual current pathway RAap to DCS then CSos to PA was 0.36±0.13 J, which was significantly lower than the ED 50 of the standard single current pathway RAap to DCS (1.31±0.3 J) and was significantly lower than all other configurations tested. Conclusions Internal atrial defibrillation thresholds can be markedly reduced with two sequential biphasic shocks delivered over two current pathways compared with the standard single shock delivered over a single current pathway or with sequential shocks delivered over a single current pathway.
Intracolonic Vancomycin for Pseudomembranous Colitis
Authors: Miralem Pasic, Res Jost, Thierry Carrel, Ludwig Von Segesser, Marko Turina
Journal: New England Journal of Medicine (1993)

To the Editor: We report the use of intracolonic vancomycin to treat antibiotic-associated pseudomembranous colitis in a patient with paralytic ileus. An 80-year-old man underwent combined aortocoronary-bypass grafting, thromboendarterectomy of the left carotid artery, and insertion of a Y-shaped aortoiliac graft. The initial postoperative course was uneventful. Four days after surgery, a suspected lung infection was treated with parenteral imipenem and later with ceftazidime and ciprofloxacin. Nine days after surgery, abdominal discomfort, fever, and leukocytosis (42,600 cells per cubic millimeter) developed. This was followed by paralytic ileus and two episodes of voluminous bloody diarrhea. Pseudomembranous colitis was diagnosed by colonoscopy, . . .
Sideroblasts, Siderocytes, and Sideroblastic Anemia
Authors: George E. Cartwright, Andrew Deiss
Journal: New England Journal of Medicine (1975)

SMALL iron-containing granules, demonstrable by means of the Prussian blue reaction, have been recognized in erythrocytes and their precursors for at least 30 years.1 2 3 4 5 Only recently, through the use of electron microscopy,6 7 8 have two distinct series of iron-containing erythroid cells been distinguished: one in which the iron consists of cytoplasmic aggregates of ferritin and the other in which non-ferritin iron is contained within mitochondria (Table 1). The physiologic and pathologic implications of each are quite different, and the non-heme iron pools are disposed of in different ways.The purpose of this report is to describe the various types of iron-containing . . .
Bromocriptine for Cushing's disease.
Authors: A L Kennedy, D A Montgomery
Journal: BMJ (1977)

sites must be affected by some secondary mechanism (for example, allergy) it is likely that the intestinal lesions are of like origin rather than simple irritation.It is not easy to date onset.Cases observed in depth show symptoms in childhood which in retrospect can be ascribed to Crohn's disease.Thus it could well be that patients with "preclinical" Crohn's disease find cornflakes more acceptable than other cereals.Likewise, the cornflake hypothesis does not account for cases in my knowledge with florid features before the introduction (about 1920) of cornflakes.I would rather put my money on refined sugar-though in my observation alcohol can provoke acute exacerbations.
A piece of my mind. The last death song
Authors: S. F. Gordon
Journal: JAMA (1990)

Death came as no surprise to Mary. She lay in her bed and sang. The third floor of the deteriorating Indian Hospital rang with her voice. She was very old. When Mary had been born, the Battle of Wounded Knee was still news, and the Bureau of Indian Affairs' policy encouraged the sale of reservation lands to non-Indians. The memories of the tribe's five forced moves in 30 years were as strong in her society's memory as the memory of the Holocaust is today. The peyote church came to the reservation and replaced the warrior societies as the social organizing force when Mary was mastering literacy of her own language. The clan system was deteriorating at the beginning of World War II when her grandchildren started to arrive. English had replaced Hochungra as the reservation's main language at the end of the war, and by that time written Hochungra had
Artemis: guarding small children and, now, the genome
Authors: Vicky L. Brandt, David B. Roth
Journal: Journal of Clinical Investigation (2003)

Through careful analysis of young patients exhibiting radiosensitivity and inherited SCID of B and T lymphocytes, Despina Moshous and colleagues discovered a new DNA repair gene two years ago and named it after the Greek goddess Artemis, a guardian of young children and small animals (1). The same group has recently analyzed several patients with hypomorphic Artemis mutations, and their results, published in this issue of the JCI (2), along with a recent report by the group of Fred Alt (3), have proven Artemis to be a guardian of the genome as well. To appreciate the significance of this finding, it is necessary first to review what is known about how our large repertoire of antigen receptors is generated.
Bepotastine Besilate Ophthalmic Solution 1.5% Reduces Ocular Itching in a Clinical Model of Allergic Conjunctivitis
Authors: G.L. Torkildsen, P.J. Gomes, J.I. Williams, J.A. Gow, T.R. McNamara
Journal: Journal of Allergy and Clinical Immunology (2009)
The real Doctor Frankenstein?
Authors: C. Goulding
Journal: Journal of the Royal Society of Medicine (2002)

Mary Shelley's novel Frankenstein1 has become one of the most analysed literary texts of the modern age. Its central theme provides a metaphor conducive to almost limitless reinterpretation, drawn by different readings into the service of numerous ideologies including marxist economics, radical feminism, green politics, and, most recently, genetics and biotechnology.
Metabolic alkalosis in a patient with dyspnoea
Authors: R. Windsor, W. Petchey
Journal: BMJ (2013)

A 56 year old woman with poorly controlled asthma was admitted to hospital with a suspected lower respiratory tract infection, having become increasingly anxious and short of breath over the past 24 hours. She had been unwell for the past week, and her general practitioner had started her on amoxicillin and oral steroids. She was a never smoker, had a history of ischaemic heart disease and atrial fibrillation, and had a high body mass index. This was not the first time she had been admitted to hospital with an exacerbation of her asthma, having been admitted several times previously. Her regular drugs included fluticasone, salbutamol, furosemide, omeprazole, simvastatin, and diltiazem.

On examination she had a normal temperature, a respiratory rate of 26 breaths/min, sparse crackles at her left lung base, together with widespread expiratory wheeze. The table⇓ details her initial arterial blood gases on air and other blood test results.

View this table:

Initial arterial blood gases on …
Margery Lila Moncrieff (nee Allen)
Authors: C. Markham
Journal: BMJ (2008)

At school Margery loved botany, but perhaps because she had spent much of her childhood being ill herself—she had frequent episodes of pneumonia confining her to bed for many weeks at time—her interests turned to medicine. She needed to improve her physics, so spent a year at Bedford College doing so well that at the end of the year she was offered a place to read physics. She was not tempted by this, and took up the offer to do medicine at the Royal Free. This was post-war London, and, as the Royal Free Hospital and Medical School had been bombed during the war, she and her friends had to travel around various parts of London for their studies. It was during this time she developed her love of classical music. Her parents were shocked to see a picture of …
A New Prostatic Stent for the Treatment of Benign Prostatic Hyperplasia in High&amp;ndash;Risk Patients
Authors: Olivier Traxer, Maurice Anidjar, Fran&ccedil;ois Gaudez, Fran&ccedil;ois Saporta, Michel Daudon, Ariane Cortesse, Fran&ccedil;ois Desgrandchamps, Olivier Cussenot, Pierre Teillac, Alain Le Duc
Journal: European Urology (2000)
918. Rescue of Dystrophin in the GRMD Dog by Multi-Exon Skipping Using Engineered U7 snRNAs
Authors: Adeline Vulin, Aurelie Goyenvalle, Ines Barthelemy, France Leturcq, Jean-Claude Kaplan, Olivier Danos, Stephane Blot, Luis Garcia
Journal: Molecular Therapy (2006)

Mutations in the dystrophin gene that create frame-shifts or premature stop codons on the mRNA are responsible of the severe Duchenne Muscular Dystrophy (DMD), while mutations that preserve the reading frame result in either milder or asymptomatic phenotypes. The exon skipping stratagem makes use of compounds designed to target key motifs on pre-mRNA to re-direct splicing in order to eliminate detrimental exons and rescue the production of shorter-proteins still functional. We have achieved persistent |[ldquo]|on demand alternative splicing|[rdquo]| that removes several consecutive exons on the dystrophin mRNA of the GRMD dog, by single administration of AAV vectors expressing antisense sequences coupled to a modified U7 short nuclear (sn) RNA. We report the sustained production of dystrophin at physiological levels in entire groups of muscles at the scale of a large size animal model of DMD.
Road to Euthanasia or Right to Refuse Care?-Reply
Authors: Charles L. Sprung
Journal: JAMA (1990)

<h3>In Reply.—</h3> Ms Rouse suggests that there is a deficiency in providing palliative care at the end of life and that we insist on people enduring pain and agony because of our misguided moral conscience. Physicians have distinguished between curing diseases and caring and comforting their patients for many years. Most physicians do not fear addiction or shortening of life in providing pain relief if the prognosis is hopeless and the patient is in severe pain.<sup>1</sup>Although I believe in biblical ethics and the infinite value of human life, the priority for the relief of pain in dying patients is not theoretical but rather a daily reality practiced in my unit and others throughout the world. Dr Sananman does not view judicial attitudes as becoming more permissive but as affirming individual rights and self-determinism. My article was an attempt to note the changes in attitudes and practices in forgoing
Prevalence of hepatitis C virus infection in patients with antiphospholipid syndrome
Authors: Francisco José Muñoz-Rodríguez, Dolors Tàssies, Josep Font, Joan Carles Reverter, Ricard Cervera, José Maria Sánchez-Tapias, Roberto Mazzara, Antoni Ordinas, Miguel Ingelmo
Journal: Journal of Hepatology (1999)
Viral Infections and the Blood Supply
Authors: Paul V. Holland
Journal: New England Journal of Medicine (1996)

Transfusions are an indispensable part of medical and surgical therapies. Packed red cells, platelets, and plasma infusions allow patients to be treated intensively for cancer, undergo transplantation, survive surgery despite extensive blood loss, and recover from life-threatening diseases such as thrombotic thrombocytopenic purpura. Today, the serious risks from the blood components given to patients in transfusion are smaller than those from the underlying disease or the primary therapy.In this issue of the Journal, Schreiber et al.1 estimate the current risks of the major viral infections transmitted by transfusions from volunteers giving multiple donations (who provide over 80 percent of . . .
Nuclear transcription factors: potential targets for new modes of intervention in skin disease
Authors: L.A. MCKAY, P. WINYARD, I.M. LEIGH, S.A. BUSTIN
Journal: British Journal of Dermatology (1994)

Many drugs already in use for the treatment of skin disease, including steroids, retinoids, vitamin D derivatives and cyclosporin (CyA), exert effects on gene transcription. In this review we briefly outline how these drugs work, before proceeding to a consideration of how new drugs acting on the transcription process might be used to influence skin disease.
A Directory of English Country Doctors—1603-1643
Authors: John H. Talbott
Journal: JAMA (1962)

Social history is the most recent daughter of Historia. It is only within the past few decades that she has been received with approbation in historical circles. The reticence to cultivate this most recent daughter was due to the fact that most historians felt she smacked too much of antiquarianism and was without design, purpose, or techniques. The book, prepared by Dr. Raach and published by Dawsons of London who are particularly interested in publishing books on medical history, helps establish these 3 features for a segment of English life—the medical profession. It presents as complete a list of country physicians in early Stuart England as can be obtained 3 centuries later. The names of the physicians, their educational qualifications, the towns or villages where they practiced, and bibliographical notes are given in each instance. To assist those interested in early 17th century medicine, there is an excellent but short
Epithelial ovarian cancer: prevention, diagnosis, and treatment
Authors: E. E. Partridge, M. N. Barnes
Journal: CA A Cancer Journal for Clinicians (1999)

The leading cause of death from gynecologic malignancies in the United States is epithelial ovarian cancer. The significant risk factor for development of ovarian cancer is advancing age, although there is clearly a genetic predisposition—often associated with the BRCA1 and BRCA2 genes—in at least 5% to 10% of all epithelial ovarian cancers. Oral contraceptives are known to reduce the risk for development of ovarian cancer and should be considered as a method of birth control in women at increased risk. Currently, there is no acceptable method of screening for this disease, although measurement of CA-125 level and transvaginal ultrasound have been utilized. Ovarian cancer is a surgically staged disease. In apparent early-stage disease, complete surgical staging is critical for the selection of adjunctive therapy. In advanced-stage disease, the goal is primary cytoreduction. Standard postoperative therapy for advanced-stage ovarian cancer includes platinum-based chemotherapy with the substitution of paclitaxel for cyclophosphamide occurring in the last decade. Despite these advances in chemotherapy, ovarian cancer continues to be fatal in far too many cases.