tbuckley/cabot-search huggingface dataset:
Guanine Analogues Enhance Antisense Oligonucleotide-induced Exon Skipping in Dystrophin Gene In Vitro and In Vivo
Authors: Yihong Hu, Bo Wu, Allen Zillmer, Peijuan Lu, Ehsan Benrashid, Mingxing Wang, Timothy Doran, Mona Shaban, Xiaohua Wu, Qi Long Lu
Journal: Molecular Therapy (2010)

Exon skipping has demonstrated great potential for treating Duchenne muscular dystrophy (DMD) and other diseases. We have developed a drug-screening system using C2C12 myoblasts expressing a reporter green fluorescent phosphate (GFP), with its reading frame disrupted by the insertion of a targeted dystrophin exon. A library of 2,000 compounds (Spectrum collection; Microsource Discovery System) was screened to identify drugs capable of skipping targeted dystrophin exons or enhancing the exon-skipping effect by specific antisense oligomers. The 6-thioguanine (6TG) was effective for inducing skipping of both human dystrophin exon 50 (hDysE50) and mouse dystrophin exon 23 (mDysE23) in the cell culture systems and increased exon skipping efficiency (more than threefolds) when used in combination with phosphorodiamidate morpholino oligomers (PMO) in both myoblasts and myotubes. Guanine and its analogues were unable to induce detectable skipping of exon 23 when used alone but enhanced PMO-induced exon skipping significantly (approximately two times) in the muscles of dystrophic mdx mouse in vivo. Our results demonstrate that small-molecule compounds could enhance specific exon skipping synergistically with antisense oligomers for experimental therapy to human diseases. Exon skipping has demonstrated great potential for treating Duchenne muscular dystrophy (DMD) and other diseases. We have developed a drug-screening system using C2C12 myoblasts expressing a reporter green fluorescent phosphate (GFP), with its reading frame disrupted by the insertion of a targeted dystrophin exon. A library of 2,000 compounds (Spectrum collection; Microsource Discovery System) was screened to identify drugs capable of skipping targeted dystrophin exons or enhancing the exon-skipping effect by specific antisense oligomers. The 6-thioguanine (6TG) was effective for inducing skipping of both human dystrophin exon 50 (hDysE50) and mouse dystrophin exon 23 (mDysE23) in the cell culture systems and increased exon skipping efficiency (more than threefolds) when used in combination with phosphorodiamidate morpholino oligomers (PMO) in both myoblasts and myotubes. Guanine and its analogues were unable to induce detectable skipping of exon 23 when used alone but enhanced PMO-induced exon skipping significantly (approximately two times) in the muscles of dystrophic mdx mouse in vivo. Our results demonstrate that small-molecule compounds could enhance specific exon skipping synergistically with antisense oligomers for experimental therapy to human diseases.
Endoscopic submucosal dissection for superficial rectal tumors: prospective evaluation in France
Authors: Gabriel Rahmi, Bilal Hotayt, Stanislas Chaussade, Vincent Lepilliez, Marc Giovannini, Dimitri Coumaros, Antoine Charachon, Franck Cholet, Arthur Laquière, Elia Samaha, Frédéric Prat, Thierry Ponchon, Erwan Bories, Michel Robaszkiewicz, Christian Boustière, Christophe Cellier
Journal: Endoscopy (2014)

<b>Background and study aims:</b> Endoscopic submucosal dissection (ESD) provides a high en bloc resection rate for superficial colorectal tumors. The aims of this study were to assess the feasibility of ESD in France and to evaluate the complete resection rate at 1 year. <b>Patients and methods:</b> Patients with superficial rectal tumors ≥ 10 mm in size were prospectively included in the study at nine French expert centers between February 2010 and June 2012. The study was stopped temporarily because of a high complication rate. Study recruitment resumed following remedial action. <b>Results:</b> A total of 45 patients were included (mean age 67 years; 24 males). The immediate perforation rate was 18 % (n = 8), and salvage surgery was not required. Six patients (13 %) had late bleeding, which was treated endoscopically in five patients and surgically in one patient who had required blood transfusion. The mortality rate was zero. The en bloc resection rate was 64 % (29/45), and the curative R0 resection rate was 53 % (24/45). Three patients (7 %) had an invasive tumor (two sm1, one T2). At 1-year follow-up, endoscopic examinations showed complete resection in 38 /43 patients (88 %). At the end of the study, after the remedial action, the en bloc resection rate had increased from 52 % to 82 %, and the perforation rate had decreased significantly from 34 % to 0 %. <b>Conclusions:</b> The study reflects the initial prospective experience of ESD in France, and suggests that curative R0 resection rates should increase and complication rates should decrease with experience and corrective actions.
Health Care Issues in Presidential Campaigns
Authors: D Blumenthal, R A Berenson
Journal: New England Journal of Medicine (1989)

Presidential campaigns are unique events in American political life. They provide the only opportunity for the public to express its views as one on a vast array of critical policy issues, including health care. For example, in his 1960 contest with Richard Nixon, John Kennedy emphasized his support for federally guaranteed health care for elderly Americans. His victory set the stage for the later enactment of Medicare and Medicaid legislation.1 However, health care issues have not figured prominently in any recent presidential election. Given the extraordinary problems of cost and equity that currently plague our health care system, many providers . . .
Sodium Valproate in Treatment of Epilepsy
Authors: P. M. Jeavons, J. E. Clark
Journal: BMJ (1974)

Sodium valproate has a simple chemical structure unlike other anticonvulsants. It has been given to 63 patients with various types of epilepsy whose attacks were frequent and of whom 40 had failed to respond to other anticonvulsants. Fits stopped completely in 27 patients (43%) and 14 (22%) showed a reduction of attacks by more than 50%. The best results were in patients with absences (typical and atypical) associated with spike and wave discharges on the electroencephalogram. Myoclonic epilepsies responded well and improvement occurred with tonic-clonic seizures and focal motor fits. There was little or no improvement in temporal lobe epilepsy. Sodium valproate given alone did not cause unwanted effects but it potentiated many other anticonvulsants. An unusual side effect was temporary hair loss. A number of patients became more alert, school performances improved, and the management of subnormal patients became easier.
Myocardosis and Cardiac Failure
Authors: Frank A. Walker
Journal: JAMA (1967)

<h3>To the Editor:</h3> In the studies initiated by Dow Breweries in Quebec concerning the recent episodes of myocardial degeneration, Drs. McDermott, Delaney, Egan, and Sullivan (<b>198</b>:253, 1966) describe a very similar picture affecting a group of patients in Omaha. In reviewing these reports, I am struck by the similarity of this disease to beriberi and its occurrence at a time when pasteurization of bottled beer is being replaced by Millipore filtration, thus removing the yeast and a large portion of the B vitamins from the beer. I think the solution to this problem can readily be found in two areas: (1) the vitamin B content of beers habitually consumed by the patients, and (2) the comparison of the vitamin B content of unpasteurized, unsterilized draft beer with that of pasteurized bottled beer and that of beer sterilized by filtration.
Serum Zinc Level in Diabetes
Authors: C. S. Reusch
Journal: JAMA (1969)

To the Editor:—  That a relationship could exist between zinc and insulin has been suspected since the crystallization of a zinc-insulin complex. It cannot be determined from physiological evidence if an insulin-zinc complex is necessary for biological activity. 1 It is now known that insulin can be crystallized by metals other than zinc. 2   Prout et al 3 in 1960 made a study of plasma zinc concentration in patients with diabetes. They found no significant relationship between plasma zinc concentration and the insulin requirement of the diabetic patients.  We have measured the serum zinc concentration in a series of patients receiving different orally administered hypoglycemic agents and in healthy control subjects. Zinc was measured by the atomic absorption spectrophotometer.  Results:—  In healthy control subjects, the zinc content of serum in 53 healthy males and 56 healthy females was not significantly different. The observed range of zinc of the combined males
Some Comments on the Occasion of the 1967 Passano Award to Dr. Irvine Page
Authors: James A. Shannon
Journal: JAMA (1967)

It is a great pleasure for me to be with you and to have an opportunity to comment on the accomplishments and talents of Dr. Irvine Page, a distinguished scientist and physician.  You will not be surprised if I talk briefly on some aspects of hypertension and atherosclerosis. Our increasing understanding of these diseases and the scientific contributions of Dr. Page are intimately entwined and interdependent. But I will talk about the diseases in a very general way and only touch lightly upon Dr. Page's role in their exploration.  Three major points might be made: (1) These are important diseases. These and immediately related diseases continue to account for about half of all deaths in the United States. (2) Substantial progress has been made in clarifying both their nature and their management. (3) Finally, our considerations at this meeting can be viewed as a brief pause at a way station
Traitement par prothèse métallique expansible couverte extractible de 14 fistules oesophagiennes bénignes
Authors: J Branche, P Bulois, A Duriez, G Piessen, S Truant, P Desurmont, P Houcke, J Boitard, V Maunoury
Journal: Endoscopy (2010)

Introduction: La mise à disposition sur le marché de prothèses oesophagiennes métalliques expansibles couvertes extractibles a rendu possible la prise en charge endoscopique des fistules et perforations oesophagiennes. Reste à en apprécier les résultats.
Endothelial Control of Arterial Distensibility Is Impaired in Chronic Heart Failure
Authors: M.W. Ramsey, J. Goodfellow, C.J.H. Jones, L.A. Luddington, M.J. Lewis, A.H. Henderson
Journal: Circulation (1995)

Background Vascular tone is a determinant of conduit artery distensibility. The aim of this study was to establish whether endothelium-derived relaxing factor (EDRF) influences the distensibility of conduit arteries and whether endothelium-mediated increases in distensibility are impaired in chronic heart failure (CHF). Methods and Results Conduit artery distensibility was measured by two methods in healthy subjects and in nine patients with CHF caused by dilated cardiomyopathy. In the first method, pulse-wave velocity (PWV) was measured in the right common iliac artery at rest and during local infusions of acetylcholine (10 −7 to 10 −5 mol/L) or adenosine (2×10 −7 to 2×10 −5 mol/L), with correction for systemic effects. Acetylcholine induced concentration-dependent local reductions of PWV in healthy subjects (−5%, −15%, and −26%) but not in CHF patients (3%, 1% , −4%, P &lt;.01), whereas adenosine induced similar reductions of PWV in healthy subjects and CHF patients. In the second method, brachial artery diameter, blood flow, and blood pressure were measured noninvasively by high-resolution ultrasound, continuous-wave Doppler, and photoplethysmography during reactive hyperemia in the hand and after sublingual glyceryl trinitrate (GTN, 400 μg). Hyperemic flow, similar in healthy subjects and CHF patients, was associated with increases in diameter and distensibility in healthy subjects (8.8% and 18.4%, respectively) but not in CHF patients (0.3% and −4.5%), whereas GTN induced similar effects in healthy subjects and CHF patients. Conclusions These data indicate that conduit artery distensibility is increased by acetylcholine and increased blood flow in healthy subjects but not in CHF patients, whereas the effects of adenosine and GTN on distensibility are preserved in CHF patients. This implies that EDRF-mediated increases in distensibility are impaired in CHF patients, thus adding to cardiac work.
‘We're all carrying a burden that we're not sharing’: a qualitative study of the impact of cutaneous T-cell lymphoma on the family
Authors: L.E. Selman, T. Beynon, E. Radcliffe, S. Whittaker, D. Orlowska, F. Child, R. Harding
Journal: British Journal of Dermatology (2014)

Cutaneous T-cell lymphoma (CTCL) is a rare, progressive cancer that can be life limiting and highly disfiguring. Patients with CTCL experience poor quality of life; however, there is little published about the experiences of their families.To describe the impact of CTCL on family members and how they cope and adjust, to inform support services.Semistructured qualitative interviews were conducted with adult informal caregivers of patients with CTCL recruited via a supraregional CTCL clinic. Interviews explored the history of each patient's illness, the impact of CTCL on the patient and the family, and views about family support. Data were analysed thematically using the Family Adjustment and Adaptation Response model as an interpretative framework.Fourteen caregivers were interviewed (11 spouses, one friend, two daughters; 10 women, four men; all white British; aged 39-85 years). Three key themes emerged: (i) demands of CTCL (the disease, caregiving, financial impact, physical and emotional intimacy); (ii) family capabilities (family support, information, healthcare provider support, other coping strategies); and (iii) adjustment and adaptation (acceptance, changes in patient-caregiver relationship and family dynamics). CTCL was central in many aspects of caregivers' lives, particularly relationships, communication and intimacy.Our findings demonstrate the multiple demands that CTCL places on caregivers, the capabilities and resources they draw upon to cope, and the significant impact of CTCL on the family. To support families and patients, easily accessible services are needed that include the family in the unit of care, provide support and information, and understand the process of family adjustment and adaptation.
Does facial sebum excretion really affect the development of acne?
Authors: S-W. Youn, E-S. Park, D-H. Lee, C-H. Huh, K-C. Park
Journal: British Journal of Dermatology (2005)

It is generally accepted that the severity of acne is correlated with facial sebum secretion. However, previous studies on the relation between seborrhoea and the development of acne did not consider topographical differences in facial sebum secretion and used relatively vague acne severity grading systems.To elucidate the relation between topographical variations in facial sebum secretion and the severity of acne in women.Forty-six female controls and 46 women with acne were included in this study. The Sebumeter was used to measure facial sebum secretion in the following facial areas: forehead, nose, chin, and right and left cheek. We counted noninflammatory comedones and inflammatory acne lesions in the same areas. We compared sebum secretion between patients with acne and controls, and analysed the relation between the quantity of sebum secreted and the number of acne lesions.Sebum secretions in the whole face and in the T- and U-zones (areas of high and low sebum secretion, respectively) were higher in patients with acne than in controls. There was no correlation between sebum quantity and acne lesion count in most facial regions.Increased levels of facial sebum secretion were observed in patients with acne. Our findings indicate that increased sebum levels do not directly cause development of acne lesions.
Sacrificed to Eddyism.
Authors: Scott P. Child
Journal: JAMA (1903)

Kansas City, Mo., July 14, 1903. <i>To the Editor</i>:—I presume my indignation over and antagonism to the body known as Christian Scientists is but that of other members of the medical profession who have come in contact with them in case of serious illness and death, where their great assurance of power, though ignorance in reality, and criminality are demonstrated. How we, an organized medical profession, and a civilized people, can or do permit them to continue to treat disease and surgical conditions in spite of common and frequent deaths due to their ignorance and neglect, is beyond comprehension! Yet I realize it is due no less to my tolerance than to that of thousands of others, both of the profession and the laity. We profess to have left behind us the Middle Ages with its superstitions, its atrocities and cruelties, but daily that period is being re-enacted in
Toxoplasmosis in Relation to Mental Deficiency
Authors: J. Burkinshaw, B. H. Kirman, A. Sorsby
Journal: BMJ (1953)

M feel that it is important to examine the stomach and duodenum carefully when clinical features such as we have described are encountered, since it may well be that these cases are less rare than a reading of the literature would suggest, and that this aspect of Crohn's disease has not received adequate attention.The x-ray changes we have described are in our opinion characteristic.Further comment on the radiological find- ings may be made as follows: First, had the changes in Case 1 been confined to the stomach they might have been -attributed to cancer of the diffusely infiltrating type (linitis plastica), but associated involvement of the duodenum and consideration of the age of the patient were of value in leading to a correct diagnosis.Secondly, the follow-up x-ray films of this case are also of interest in showing that the changes in the mucous membrane of the stomach and duodenum are not necessarily of a permanent nature, and that with the passage of time a return to a normal mucosal pattern is possible.It should also be noted that both these patients became very ill on account of inability to assimilate adequate quanti- ties of food.Case 2, which we have been able to observe in hospital, showed an upset in the protein content of the blood, and we feel,it is important to stress the need for adequate dietetic care.Both these patients became anaemic, both appeared at one time to be going to die.A high- protein diet, as well as the prescribing of iron and vitamins, appears to us to be of importance in the handling of these cases. SummaryTwo cases of Crohn's disease involving the stomach and duodenum are reported; one of them was con- firmed by biopsy of the gastric muicosa.The radiological changes are described in detail.We would like to thank Dr. H.
THE ROLE OF THE LYMPHATIC SYSTEM IN THE REJECTION OF HOMOGRAFTS: A STUDY OF LYMPH FROM RENAL TRANSPLANTS
Authors: Niels C. Pedersen, Bede Morris
Journal: The Journal of Experimental Medicine (1970)

The rejection of renal homografts has been studied in sheep by transplanting kidneys into the neck and preserving the renal lymphatic drainage intact. Chronic fistulae were established in the transplanted renal lymphatics and lymph collected throughout the life of the graft. The changes that occurred in homografts during the process of rejection were reflected in changes in the lymph. Large numbers of basophilic, blast, lymphoid cells appeared in the lymph, and lymph production in the grafted kidney increased 20-50 fold. Over a period of about 10 days, up to 60 g wet weight of lymphoid cells and up to 10 liters of lymph were collected from the graft. Within 24 hr of grafting, the host cells present in the renal lymph had become sensitized to the graft and transformed into blast cells when cultivated in Millipore chambers in vitro. When the cells leaving the graft during the first 18-48 hr were injected into distant nonstimulated lymph nodes of the host sheep, they evoked significant cellular and antibody responses in the nodes. Within the graft, the main pathological changes were found in the vascular endothelium and many of the peritubular capillaries become plugged with emboli comprised of blast cells. There was extensive infiltration of the renal parenchyma with lymphoid cells and evidence of their transformation and proliferation within the renal blood capillaries. When all the lymph and cells leaving the homograft were diverted from the body, there was a greatly decreased reaction in the regional prescapular lymph node, and no reaction in lymph nodes distant from the graft. In these circumstances, the survival of the graft was not prolonged, and it was rejected without involvement of the lymph nodes of the host. Humoral antibody was produced in the lymph node regional to the homograft within 48-60 hr of grafting. Antibody was not detected in the blood or in the renal lymph until near to the time the graft was rejected. It was thought that this was due to the binding of antibody by the kidney graft tissue. We conclude that all the events which lead to the recognition and rejection of renal homografts can occur centrally within the graft itself.
Sexual health, contraception, and teenage pregnancy
Authors: John Tripp, Russell Viner
Journal: BMJ (2005)

Sexual health becomes a new health priority in early adolescence.The sexual health of young people is a matter of intense public concern.The adverse consequences of unsafe sexual behaviour-such as pregnancy and sexually transmitted infections (STIs), including HIV infection-affect adolescents as well as adults."Risk taking" behaviours are common when adolescents start being sexually intimate and are often linked with other health risk behaviours, such as substance misuse. This is the sixth in a series of 12 articlesTeenagers assess and evaluate risk differently from adults and health professionals: they would rather reduce their risk of being excluded from the "in-group" or of looking immature than take notice of any perceived health risks Clinical review
Death during Dental Anaesthesia
Authors: J. G. Bourne
Journal: BMJ (1975)

said: "This will be the much needed break- through for disenchanted consultants.Hos- pital staffs know that the British Medical Association has for some time been pressing for a complete reappraisal of the consultants' contract by setting up a working party for this purpose.We welcome the fact that the Government has recognized the strength of our argument and we look forward to co- operating to the full."We know that the working
Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival
Authors: A Tefferi, T L Lasho, J Huang, C Finke, R A Mesa, C Y Li, W Wu, C A Hanson, A Pardanani
Journal: Leukemia (2008)
Plaque Composition and its Relationship With Acknowledged Shear Stress Patterns in Coronary Arteries
Authors: Gastón A. Rodriguez-Granillo, Héctor M. García-García, Jolanda Wentzel, Marco Valgimigli, Keiichi Tsuchida, Wim van der Giessen, Peter de Jaegere, Evelyn Regar, Pim J. de Feyter, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2006)