tbuckley/cabot-search huggingface dataset:
Exenatide versus Insulin Glargine in Patients with Suboptimally Controlled Type 2 Diabetes
Authors: Robert J. Heine, Luc F. Van Gaal, Don Johns, Michael J. Mihm, Mario H. Widel, Robert G. Brodows
Journal: Annals of Internal Medicine (2005)

Background: Physicians may use either insulin or exenatide injections for patients with type 2 diabetes mellitus who have poor glycemic control despite taking oral blood glucose–lowering drugs. Objective: To compare effects of exenatide and insulin glargine on glycemic control in patients with type 2 diabetes mellitus that is suboptimally controlled with metformin and a sulfonylurea. Design: 26-week multicenter, open-label, randomized, controlled trial. Setting: 82 outpatient study centers in 13 countries. Patients: 551 patients with type 2 diabetes and inadequate glycemic control (defined as hemoglobin A1c level ranging from 7.0% to 10.0%) despite combination metformin and sulfonylurea therapy. Intervention: Exenatide, 10 µg twice daily, or insulin glargine, 1 daily dose titrated to maintain fasting blood glucose levels of less than 5.6 mmol/L (<100 mg/dL). Measurements: Hemoglobin A1c level, fasting plasma glucose level, body weight, 7-point self-monitored blood glucose, standardized test-meal challenge, safety, and tolerability. Results: Baseline mean hemoglobin A1c level was 8.2% for patients receiving exenatide and 8.3% for those receiving insulin glargine. At week 26, both exenatide and insulin glargine reduced hemoglobin A1c levels by 1.11% (difference, 0.017 percentage point [95% CI, −0.123 to 0.157 percentage point]). Exenatide reduced postprandial glucose excursions more than insulin glargine, while insulin glargine reduced fasting glucose concentrations more than exenatide. Body weight decreased 2.3 kg with exenatide and increased 1.8 kg with insulin glargine (difference, −4.1 kg [CI, −4.6 to −3.5 kg]). Rates of symptomatic hypoglycemia were similar, but nocturnal hypoglycemia occurred less frequently with exenatide (0.9 event/patient-year versus 2.4 events/patient-year; difference, −1.6 events/patient-year [CI, −2.3 to −0.9 event/patient year]). Gastrointestinal symptoms were more common in the exenatide group than in the insulin glargine group, including nausea (57.1% vs. 8.6%), vomiting (17.4% vs. 3.7%) and diarrhea (8.5% vs. 3.0%). Limitations: The trial was open-label and did not assess clinical complications related to diabetes. Of the 551 participants, 19.4% of those receiving exenatide and 9.7% of those receiving insulin glargine withdrew from the study. Only 21.6% of the insulin glargine group and 8.6% of the exenatide group achieved the target level for fasting plasma glucose of less than 5.6 mmol/L (<100 mg/dL). Conclusions: Exenatide and insulin glargine achieved similar improvements in overall glycemic control in patients with type 2 diabetes that was suboptimally controlled with oral combination therapy. Exenatide was associated with weight reduction and had a higher incidence of gastrointestinal adverse effects than insulin glargine. *For members of the GWAA Study Group, see the Appendix.
Twenty four hour care in inner cities.
Authors: J. N. Hardy, R. M. Patel
Journal: BMJ (1989)

during the first vear.TFhe ouitpatient waiting time stands at two weeks, and sincc it opened the waiting time at the longer established unit has declined steadilI to an average of three months.We believe that providing adequate facilities of this type is a much more satisfactory solution to the problem of delays in fitting hearing aids than the proposal suggested in the Royal National Institute for the Deaf document entitled Hearing Aids -The Case for Change.
Clinical Evaluation of Adriamycin, a New Antitumour Antibiotic
Authors: G. Bonadonna, S. Monfardini, M. de Lena, F. Fossati-Bellani
Journal: BMJ (1969)

Adriamycin, a new antitumour antibiotic of the anthracycline group with a structural formula very similar to daunorubicin, has proved to have potent tumour-growth-inhibiting properties, and to be particularly effective in childhood malignancies. Though adriamycin produces a higher percentage of side-effects than daunorubicin-namely, stomatitis and alopecia-a lower dosage may be used for therapy.
CORONARY OBSTRUCTION FOLLOWING TRANSCATHETER AORTIC VALVE IMPLANTATION: INSIGHTS ON BASELINE PATIENTS’ CHARACTERISCTICS, MANAGEMENT AND CLINICAL OUTCOMES
Authors: Henrique Barbosa Ribeiro, Luis Nombela–Franco, Marina Urena, Michael Mok, Sergio Pasian, Daniel Doyle, Robert De Larochellière, Melanie Cote, Louis Laflamme, Hugo De Larochelliere, Eric Dumont, Josep Rodes–Cabau
Journal: Journal of the American College of Cardiology (2013)
A PHYSICO-CHEMICAL THEORY OF FERTILIZATION.
Authors: MARTIN F. FISCHER
Journal: JAMA (1906)

<h3>INTRODUCTION.</h3> Within the last few years our conceptions of the physical state of protoplasm have undergone a series of changes in consequence of which a number of long-debated physiologic problems have been settled. No one advance has contributed nor promised to contribute more toward the understanding of certain cell phenomena, both from their morphologic and physiologic aspects, than the recognition of the colloidal nature of protoplasm. It is our purpose in the following pages to show, if possible, that the fertilization of the ovum by the spermatozoön represents another cell process which finds its explanation in the colloidal nature of the egg protoplasm, and it is to the arguments which point in this direction that we wish to call attention. As it is impossible in the limited time allowed to meet all the various criticisms which might be raised against our theory of fertilization, we would refer the interested listener
1026-91 The Effect of First Phase Polarity of Biphasic Shocks on the Defibrillation Threshold with a Single Transvenous Lead System
Authors: S. Adam Strickberger, K. Ching Man, Emile G. Daoud, Laura E. Horwood, Mark J. Niebauer, Brian D. Williamson, John D. Hummel, Fred Morady
Journal: Journal of the American College of Cardiology (1995)
Fine‐scale mapping of type I allergy candidate loci suggests central susceptibility genes on chromosomes 3q, 4q and Xp
Authors: A. Haagerup, A. D. Børglum, H. G. Binderup, T. A. Kruse
Journal: Allergy (2003)

Background: Type I allergy globally affects an increasing number of individuals with the consequence of considerable personal morbidity and socio‐economic costs. Identification of disease susceptibility genes would render enormous medical perspectives in terms of improved diagnosis, treatment and prevention. Like for other complex disorders, achievement of the knowledge necessary depends on confirmation of reported genomic candidate regions. Methods: We performed a two‐stage fine‐scale linkage analysis in 11 selected candidate regions on chromosome 3p, 3q, 4p, 4q, 5q, 6p, 9p, 12q, 12qter, 18q and Xp. We analysed 97 polymorphic markers in 424 individuals from 100 sib‐pair families and evaluated the data for five phenotypes: Allergic asthma, atopic dermatitis, allergic rhinitis and total and specific immunoglobulin E. Results: The highest maximum likelihood scores (MLS) were obtained on chromosomes 3q (MLS = 2.69), 4p (MLS = 2.34), 4q (MLS = 2.75), 6p (MLS = 2.22), 12qter (MLS = 2.15) and Xp (MLS = 2.23). All five phenotypes showed MLS ≥ 2 in one or more of the candidate regions. Conclusions: Susceptibility genes in the 3q, 4q and Xp regions may play a central role in the inheritance of allergic disease, as positive results were obtained for all five phenotypes in these three regions.
Cytochemical localization of lysosomal enzymes in rat megakaryocytes and platelets.
Authors: M E Bentfeld, D F Bainton
Journal: Journal of Clinical Investigation (1975)

Platelets secrete lysosmal enzymes during the "platelet release reaction" early in clot formation. This study was undertaken to identify primary lysosomes of platelets and to detemine their origin in megakaryocytes. Using electron microscopy and cytochemistry, we localized two lysosomal enzymes, arylsulfatase and acid phosphatase, in megakaryocytes and platelets of normal and thrombocytopenic rats. In platelets and mature megakaryocytes, reaction product for both enzymes is confined to vesicles measuring 175-250 nm. These vesicles, which are primary lysosmes, first appear in the earliest recognizable megakaryocytes and increase in number during cellular maturation. In immature and maturing megakaryocytes, arylsulfatase and acid phosphatase can also be demonstrated in an organell similar to GERL (Golgi-endoplasmic reticulumlysosome), i.e., single smooth-surfaced cisternal with associated vesicles near the stacked Golgi cisternae. Scant reaction product for acid phosphatase is also sometimes seen in Golgi cisternae and endoplasmic reticulum. No reaction product was found in alpha-granules at any stage of megakaryocyte maturation, nor in alpha- or serotonin granules of platelets. Thus, our findings indicate that the primay lysosomes of megakaryocytes and platelets are small vesicles derived from GERL early in megakaryocyte differentiation. They can be indentified only after cytochemical staining and are distinct from both alpha- and serotonin granules.
Factor VIII Inhibitors
Authors: Daniel Deykin
Journal: New England Journal of Medicine (1974)

Physicians not engaged in the treatment of patients with bleeding disorders may not fully appreciate the magnitude of the revolution that has occurred in the management of classic hemophilia. Before 1964 the mainstay of therapy was fresh-frozen plasma. Limited by the volume of plasma that could be given, treatment was usually inadequate. Elective surgery was rarely performed, and crippling joint deformities were the hallmark of the disorder. The discovery by Pool and her associates, in 1964,1 that factor VIII, the anti-hemophilic globulin, could readily be concentrated from frozen plasma has completely altered the treatment of hemophilia. Not only can serious . . .
TREATMENT OF ECTOPIC GESTATION.Read in the Section of Obstetrics and Diseases of Women, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May, 1891.
Authors: E. E. MONTGOMERY
Journal: JAMA (1891)

While it is important in every class of disease to have definite ideas as to the methods of treatment, it is particularly so in the condition under consideration. The obscure character of the symptoms often presented, the difficulty of diagnosis, the grave lesions resulting from development and rupture, render such cases so important, that time devoted to their consideration, even though it may lead to frequent reiteration, is not time lost. A fierce conflict has been waged during the last few years between the advocates of surgical procedure and those who favor palliative measures. The latter class, recognizing the dangers of a surgical procedure which necessitates the opening of the abdominal cavity, the separation of vascular adhesions, and the increased avenues for septic infection, have endeavored to seek some way by which they may be averted. To accomplish this, the general methods of procedure have been the injection into the
Patient-Reported Health Status in Coronary Heart Disease in the United States
Authors: Jipan Xie, Eric Q. Wu, Zhi-Jie Zheng, Patrick W. Sullivan, Lin Zhan, Darwin R. Labarthe
Journal: Circulation (2008)

Background— Coronary heart disease (CHD) affects 15.8 million Americans. However, data on the national impact of CHD on health-related quality of life, particularly among people of different age, sex, racial, and ethnic groups, are limited. Methods and Results— Using data from the 2000 and 2002 Medical Expenditure Panel Survey, we examined various measures of patient-reported health status, including health-related quality of life, in the CHD and non-CHD populations and differences in the measures among demographic subgroups. These measures included short-form generic measures (Short Form 12; Mental Component Summary-12 and Physical Component Summary-12) and EuroQol Group measures (EQ-5D index and EQ visual analog scale). Ordinary least-squares regressions were used to adjust for sociodemographic characteristics, risk factors, comorbidities, and proxy report. The adjusted difference between the CHD and non-CHD populations was −1.2 for Mental Component Summary-12 (2.4% of the score in the non-CHD population), −4.6 for Physical Component Summary-12 (9.2%), −0.04 for EQ-5D (4.6%), and −7.3 for EQ visual analog scale (9.0%) (all P &lt;0.05). Differences among demographic subgroups were observed. Particularly, compared with whites, the differences between CHD and non-CHD in blacks were bigger in all measures except Physical Component Summary-12. A significantly bigger difference in Mental Component Summary-12 also was observed among Hispanics compared with non-Hispanics. Conclusions— CHD is associated with significant impairment of health-related quality of life and other patient-reported health status in the US adult population. Differences in the impairment associated with CHD exist across different age, racial, and ethnic groups. In addition to preventing CHD, effective public health interventions should be aimed at improving health-related quality of life and perceived health status in the CHD population, especially the most vulnerable groups.
Efficacy and Safety of Mexiletine in the Treatment of Painful Diabetic Neuropathy. The Mexiletine Study Group
Authors: Per Oskarsson, Jan-Gustaf Ljunggren, Per-Eric Lins
Journal: Diabetes Care (1997)

To investigate the efficacy and safety of mexiletine in the treatment of painful diabetic neuropathy.A total of 216 insulin-treated diabetes patients with painful diabetic neuropathy were randomly allocated to three dosages of mexiletine or placebo. The Visual Analog Scale (VAS) for pain/discomfort was scored each day during daytime and nighttime, and sleeping disturbances were also recorded by the patients. Plasma levels of mexiletine and 24-h electrocardiogram (ECG) mapping were assessed before and during the 3-week study period.A significant reduction in sleep disturbances and pain during nighttime was observed in the group of patients taking the highest dosages (675 mg/day) of mexiletine compared with the other groups. No significant correlation was found between plasma concentration of mexiletine and the therapeutic effect or adverse events. No serious adverse events were seen. The 24-h ECG mapping did not disclose onset of significant arrhythmias in any patient.Mexiletine in a dosage of 675 mg daily can reduce pain caused by diabetic neuropathy, and the effect of this drug appears to have a rapid onset.
Current Status of Therapy in the Nephrotic Syndrome in Adults
Authors: Francis P. Chinard
Journal: JAMA (1961)

THE nephrotic syndrome in adults occurs mainly as a distressing manifestation of certain types of renal disease. For the present purposes, the syndrome is defined as the complex of the following signs and laboratory findings: edema or anasarca, hypoalbuminemia, proteinuria, and hypercholesterolemia. The usual complaint of patients with the nephrotic syndrome is edema. The edema is a reflection of the retention of salt and water; the proteinuria and the consequent depletion of the plasma proteins play an important role in its development. The proteinuria is the result of an abnormally high permeability of the glomerular capillaries to proteins. The usual therapeutic goal is to rid the patient of edema. Therapy designed to reach this goal can be directed to the reversal of the increased glomerular permeability or to the relief of the edema without necessarily achieving reduction of the glomerular permeability. The nephrotic syndrome that occurs in adults differs in
Suicide and Euthanasia: Historical and Contemporary Themes
Authors: Allen D. Verhey
Journal: JAMA (1990)

Medical technology has made some ancient questions urgent. The question of choosing death, whether for oneself or for another, is a very old question; it is raised today within medical ethics in novel circumstances, but it remains an old question. Enamored of novelty, contemporary bioethics has given a good deal more—and a good deal more serious—attention to the novelty of the circumstances than to the historic traditions of moral wisdom and reflection that have considered old questions and that might provide a resource for contemporary discernment. This volume attends to some of these traditions about suicide and euthanasia; moreover, it attends to them in ways that offer fresh insight into the traditions, correction to some conventional but flawed accounts of the same traditions, and sometimes new insight into the contemporary debate in the light of this reexamination of historic moral arguments. In the opening essay, for example, John M. Cooper
Community health doctors need not "rage and despair"
Authors: P. Tizard, D. Irvine
Journal: BMJ (1984)

neurology to develop in this way has led to the limited development of academic neurology so that currently there are very few professorial units.Such units should have neurosurgical units associated with them.The inadequacy of academic promotional prospects in the UK has led to many neurologists interested in research seeking careers in other countries.The difficulty neurology faces over its service role, as described by Dr Hopkins, is one that requires urgent consideration.Its resolution, however, is unlikely to depend purely on neurologists but will require an overview from other groups including the Department of Health and Social Security.
Gene Transfer Corrects Acute GM2 Gangliosidosis—Potential Therapeutic Contribution of Perivascular Enzyme Flow
Authors: M Begoña Cachón-González, Susan Z Wang, Rosamund McNair, Josephine Bradley, David Lunn, Robin Ziegler, Seng H Cheng, Timothy M Cox
Journal: Molecular Therapy (2012)

The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay-Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosaminidase α (HEXA) and β (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity-as opposed to tremor-ataxia-were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of β-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue-long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system.
Rheumatoid Arthritis and Related Conditions
Authors: M. I. V. Jayson
Journal: Annals of the Rheumatic Diseases (1982)

Society and no mean intellect and an observant clinician, even he in his Bowman lecture on gout and conditions of the eye confesses, 'I must admit little or no evidence as to deposits of urate of soda in any ocular structures....I doubt if it has been shown even in a single case though several observers have suggested its presence....I trust, however, that we are long past the stage of belief which regards such deposit as essential to a gouty inflammation'.It would seem at this point in time that William Heberden's and A. B. Garrod's observations had fallen on relatively stony ground.Even Sherlock Holmes would have had dif- ficulties in this misty diagnostic jungle, and his creator was merely following up current ideas.
Two different mutations in codon 97 of the β-globin gene cause Hb Malmö in Sweden
Authors: Britta Landin, Stig Berglund, Kristina Wallman
Journal: American Journal of Hematology (1996)

An abnormal hemoglobin with increased oxygen affinity, Hb Malmö [alpha 2 beta 297(FG4)His-->Gln], was found to cause erythrocytosis in two apparently unrelated Swedish families. Direct nucleotide sequencing of amplified DNA demonstrated a CAC-->CAA substitution in one family and a CAC-->CAG substitution in the other. Both mutations resulted in a His-->Gln substitution in codon 97. This finding prompted us to examine the possible point mutations underlying the different hemoglobin variants reported in the literature.
Preserving the Physician-Patient Relationship in the Era of Managed Care
Authors: Ezekiel J. Emanuel
Journal: JAMA (1995)

Even without comprehensive health care reform legislation, the US health care system is undergoing significant changes. Probably the most important change is the expansion of managed care with significant price competition. One of the major concerns about this change is the effect of managed care on the physician-patient relationship. To provide a normative standard for evaluating the effect of changes, we need an ideal conception of the physician-patient relationship. This ideal can be summarized by six C's: choice, competence, communication, compassion, continuity, and (no) conflict of interest. For the 37 million uninsured Americans there is little chance of realizing the ideal physician-patient relationship, since they lack the choice of practice setting and physician, receive care in a rushed atmosphere that undermines communication and compassion, and have no continuity of care. While many insured Americans may believe they have an ideal physician-patient relationship, the relationship is threatened by lack of a regular assessment of competence, by financial incentives that undermine good communication, and by the persistence of conflict of interest. The shift to managed care may improve the choice of practice settings, especially in sections of the country that currently lack managed care; increase choice of preventive services; make quality assessments more routine; and improve communication by making greater use of primary care physicians and nonphysician providers. However, the expansion of managed care and the imposition of significant cost control have the potential to undermine all aspects of the ideal physician-patient relationship. Choice could be restricted by employers and by managed care selection of physicians; poor quality indicators could undermine assessments of competence; productivity requirements could eliminate time necessary for communication; changing from one to another managed care plan to secure the lowest costs could produce significant disruption in continuity of care; and use of salary schemes that reward physicians for not using medical services could increase conflict of interest. (<i>JAMA</i>. 1995;273:323-329)
Perspective on Vitamin E as Therapy
Authors: Hyman J. Roberts
Journal: JAMA (1981)

IN A recent editorial on vitamin E therapy, Oski<sup>1</sup>stated: "Fortunately, large doses of this vitamin appear to be tolerated with relative impunity." The purported safety of vitamin E also is repeatedly underscored by physicians in popular health-oriented publications. Wright asserted: "There's never been a case reported of vitamin E toxicity. None of my patients have ever had any problems" (<i>Prevention</i>, February 1978, p 74). This widely held attitude deserves scrutiny because it could pose a major public health concern. I continue to encounter patients with problems that seem to have been caused or aggravated by self-medication with vitamin E (used here to designate the various tocopherols) in high dosages.<sup>2-4</sup>The more serious ones include the following: (1) thrombophlebitis, pulmonary embolism, or both (my series now exceeds 80 such patients, averaging 62 years of age; four had recurrences on resuming vitamin E treatment); (2) hypertension (22 patients), generally