tbuckley/cabot-search huggingface dataset:
Letter: Encroachments on the patient's responsibility.
Authors: R F Duke
Journal: BMJ (1974)

ceivably be playing a part in the aetiology of other disease entities,9 and halogenated salicylanilides and related compounds may not be the only drugs retained in this manner.'0Dr. R. H. Champion, in the article "Diseases of the Skin: Drug Therapy of Urticaria" (22 December 1973, p. 730) states that "antihistamine drugs may, if necessary, be continued for months or years with safety."How can he be sure of this?How can we be certain that any of the photosensitizing drugs which cover a wide therapeutic range and include several anti- histamines are not retained in the dermis for long periods, eventually playing a part in the production of actinic reticuloid in sus- ceptible subjects?Promethazine, an anti- histamine, and chlorpromazine, a tran- quillizer, two phenothiazine derivatives, may cause persistent photodermatitis which depends upon concomitant oral administration and external application."'3The active photocontact sensitizers cause multiple cross- sensitivities'4 and it is conceivable that one or several photosensitizing drugs retained in the dermis might be immunologically activated by an external powerful sensitizer such as fenticlor, leading to actinic reticu- loid.-Iam, etc.,
Medical Choices, Medical Chances: How Patients, Families, and Physicians Can Cope With Uncertainty
Authors: Elizabeth Pease
Journal: JAMA (1981)

Even though medicine has undergone numerous changes since Hippocrates' time, many would agree that one of his observations still holds true: "A wise man should consider that health is the greatest of human blessings, and learn how by his own thought to derive benefit from his illnesses." In<i>Medical Choices, Medical Chances</i>, authors Harold Bursztajn, Richard I. Feinbloom, Robert M. Hamm, and Archie Brodsky examine how an understanding of the scientific theory behind medicine influences the thoughts and actions of physicians and patients as they make decisions that affect health and well-being. These authors provide much evidence to support their belief that two approaches to practicing medicine currently affect health care. These "paradigms," however, are "shifting." The older, mechanistic paradigm, inspired by the laws of Newton, is being challenged by the newer, probabilistic paradigm, the result of quantum mechanics. And, while mechanistic medical practice aims at "looking for 'hard,' 'scientific,'
Changes in the principal free intracellular amino acids in the Langendorf perfused guinea pig heart during arrest with calcium-free or high potassium media
Authors: M-S Suleiman, R A Chapman
Journal: Cardiovascular Research (1993)

Objective: Many amino acids have been shown to be cotransported with Na+ in a variety of tissues but evidence for an Na+ dependent efflux in the heart is restricted to taurine. The aim of this study was to determine the intracellular levels of the principal amino acids, alanine, glutamine, glutamate, and aspartate, when the heart was beating at normal or low temperature, during exposure to strophanthidin, and when the heart was arrested with either Ca2+, Mg2+-free Tyrode solution (a condition known to raise intracellular Na+) or with a high K+ Tyrode solution. Methods: Guinea pig hearts, mounted on a Langendorff apparatus, were perfused with a variety of media and the level of amino acids in the ventricles determined using high performance liquid chromatography. Results: During perfusion with normal Tyrode solution a time dependent fall in tissue glutamine, glutamate, and aspartate, but not alanine, was observed. Exposure of the beating heart to strophanthidin (0.2 mM) or cooling to 20°C, which should induce a similar increase in [Na+]i but have opposite effects on metabolism, had different effects on tissue amino acids. Cooling did not affect the level of amino acids whereas strophanthidin produced an effect consistent with an activation of a glutamate-alanine aminotransferase. Arresting the heart with Ca2+, Mg2+-free Tyrode solution provoked a marked fall in all amino acids which was associated with their appearance in the effluent. This loss of the amino acids was antagonised by conditions known to reduce the rise in intracellular Na+ concentration and increased by inhibition of the Na+ pump. Comparison of the beating heart with the heart arrested with high K+ Tyrode solution showed no difference in the levels of glutamate or aspartate, with a small fall in alanine and taurine and raised glutamine. Conclusions: The data from beating or arrested hearts are consistent with the presence of amino acid/Na+ cotransport systems but the levels of amino acids free in the sarcoplasm depend on an interaction between amino acid transport driven by the changes in the Na+gradient and the effects of metabolism. Cardiovascular Research 1993;27:1810-1814
The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA
Authors: Alan K. Burnett, Robert K. Hills, Claire Green, Sarah Jenkinson, Kenneth Koo, Yashma Patel, Carol Guy, Amanda Gilkes, Donald W. Milligan, Anthony H. Goldstone, Archibald G. Prentice, Keith Wheatley, David C. Linch, Rosemary E. Gale
Journal: Blood (2009)
Early Atheroma-Derived Agonists of Peroxisome Proliferator–Activated Receptor-γ Trigger Intramedial Angiogenesis in a Smooth Muscle Cell–Dependent Manner
Authors: Benoît Ho-Tin-Noé, Julien Le Dall, Delphine Gomez, Liliane Louedec, Roger Vranckx, Morad El-Bouchtaoui, Luc Legrès, Olivier Meilhac, Jean-Baptiste Michel
Journal: Circulation Research (2011)

Rationale: Neovascularization favors intraplaque hemorrhage and plaque rupture. Development of therapeutic strategies against atheromatous angiogenesis requires elucidation of its initiating factors. Objective: We investigated the contribution of smooth muscle cells (SMCs) and atheroma-derived lipids to the initiation of atheroma-associated neoangiogenesis. Methods and Results: Forty human aortic segments, each harvested from a different donor, were classified as healthy or as bearing early atheromatous lesions, including fatty streaks and fibrolipidic atheroma, according to their histological features. Immunostaining for blood vessels and vascular endothelial growth factor-A (VEGF-A), as well as measurement of VEGF-A protein and mRNA levels by ELISA and real-time PCR, revealed that angiogenesis and VEGF-A production were enhanced in the medial layer of atheromatous aortas. The intramedial vessel density and invasiveness and the production of VEGF-A by medial SMCs were indeed increased in atheromatous aortas compared with healthy aortas. Furthermore, intimal layers of atheromatous aortas were enriched in soluble lipid mediators capable of inducing a sustained increase in VEGF-A production by medial SMCs, turning these cells into potent inducers of angiogenesis when incorporated into mouse Matrigel implants. Both effects were inhibited by the peroxisome proliferator–activated receptor-γ inhibitor GW9662 and mimicked by its agonist, rosiglitazone. Conclusions: We show that VEGF-A production is upregulated in medial SMCs of human atheromatous aortas and that peroxisome proliferator–activated receptor-γ agonists derived from early intimal lesions are likely to contribute to this phenotypic change. Our findings suggest that medial SMCs are central organizers of an angiogenic response initiated by the subendothelial accumulation of atherogenic lipids.
The Extractability of Serum Lipids in Normal Subjects, Coronary Disease, Hyperlipemia, and Hypercholesteremia
Authors: D. S. AMATUZIO, FRANCISCO GRANDE, SHOHACHI WADA
Journal: Circulation (1962)

The lipid extraction of fasting serum samples was studied with various alcohol-ether solutions. The release of cholesterol and esterified fatty acids from the serum lipoproteins was found to be significantly different in the various disease states studied as compared to the normal subject. The fraction of lipid release from fasting serum was not related to the total level of the cholesterol or esterified fatty acids in normal subjects, coronary artery disease, and hypercholesteremia.
A NEW OPHTHALMIC VISITING CASE.
Authors: FRANCIS W. ALTER
Journal: JAMA (1903)

This little visiting case which I present to the profession and which is herein portrayed is of especial interest to oculists; it can, of course, be used by the physician in general work in connection with his ophthalmic cases. As will be seen by the cut, it contains all the essentials commonly used in the treatment of eye cases, each dropper being marked in a manner indicating its contents. The case contains cocain, atropin, eserin, homatropin, two bottles of silver nitrate in different strengths, a phial for toothpicks and a reservoir for cotton, beside a bottle intended to hold a relaxing tablet, a spud and a pair of epilating forceps, a pocket in the side of the case for prescription blanks, cards, etc. While the case is primarily intended as a visiting case it
The Oregon experiment re-examined: the need to bolster primary care
Authors: John Heintzman, Rachel Gold, Steffani R Bailey, Jennifer E DeVoe
Journal: BMJ (2014)

The intestinal epithelium serves as a barrier to the intestinal flora. In response to pathogens, intestinal epithelial cells (IEC) secrete proinflammatory cytokines. To aid in defense against bacteria, IEC also secrete antimicrobial peptides, termed defensins. The aim of our studies was to understand the role of TLR signaling in regulation of β-defensin expression by IEC. The effect of LPS and peptidoglycan on β-defensin-2 expression was examined in IEC lines constitutively or transgenically expressing TLRs. Regulation of β-defensin-2 was assessed using promoter-reporter constructs of the human β-defensin-2 gene. LPS and peptidoglycan stimulated β-defensin-2 promoter activation in a TLR4- and TLR2-dependent manner, respectively. A mutation in the NF-κB or AP-1 site within the β-defensin-2 promoter abrogated this response. In addition, inhibition of Jun kinase prevents up-regulation of β-defensin-2 protein expression in response to LPS. IEC respond to pathogen-associated molecular patterns with expression of the antimicrobial peptide β-defensin-2. This mechanism may protect the intestinal epithelium from pathogen invasion and from potential invaders among the commensal flora.
Prognosis and early management of birth injuries to the brachial plexus.
Authors: G C Bennet, A J Harrold
Journal: BMJ (1976)

Twenty-four cases of birth injury to the brachial plexus were seen in 21 infants over 15 years. Obstetric complications were common, and in 11 cases traction was needed to deliver the shoulders. Three out of every four arms fully recovered after exercises. Splints were not needed. Reconstructive procedures were performed on three permanently paralysed arms when the children were aged about 4. There was no way of predicting which patients would recover. The muscles supplied by the suprascapular nerve were paralysed in all patients, and this paralysis persisted in those whose arms failed to recover fully.
When cells get stressed: an integrative view of cellular senescence
Authors: Ittai Ben-Porath, Robert A. Weinberg
Journal: Journal of Clinical Investigation (2004)

Cells entering a state of senescence undergo a permanent cell cycle arrest, accompanied by a set of functional and morphological changes. Senescence of cells occurs following an extended period of proliferation in culture or in response to various physiologic stresses, yet little is known about the role this phenomenon plays in vivo. The study of senescence has focused largely on its hypothesized role as a barrier to extended cell division, governed by a division-counting mechanism in the form of telomere length. Here, we discuss the biological functions of cellular senescence and suggest that it should be viewed in terms of its role as a general cellular stress response program, rather than strictly as a barrier to unlimited cycles of cell growth and division. We also discuss the relative roles played by telomere shortening and telomere uncapping in the induction of senescence.
The Origins, History, and Design of the Resident Match
Authors: Alvin E. Roth
Journal: JAMA (2003)

In the early 1900s, competition among hospitals for interns and among medical students for good internships led to increasingly early offers of internships to students. By the 1940s, appointments were often made as early as the beginning of the junior year of medical school. Hospitals thus had little information about students' performance, and students frequently had to make a final decision to accept or reject an offer without knowing which other offers might be forthcoming. From 1945 through 1951, efforts were made to enforce a uniform date for accepting offers. However, students were still faced with offers having very short deadlines, compelling them to accept or reject offers without knowing what other offers might be forthcoming. Hospitals often had to scramble for available students, since if an offer was rejected, it was often too late for them to reach their next preferred candidate. A centralized clearinghouse was thus developed as a way of alleviating this chaos and allowing a larger role to the preferences of both students and hospitals. This evolved into the current matching program, whose algorithm continues to be updated to take account of changing needs of applicants, such as growth in the number of couples who seek 2 positions in the same vicinity.
Activity-Dependent Gating of Calcium Spikes by A-type K+ Channels Controls Climbing Fiber Signaling in Purkinje Cell Dendrites
Authors: Yo Otsu, Païkan Marcaggi, Anne Feltz, Philippe Isope, Mihaly Kollo, Zoltan Nusser, Benjamin Mathieu, Masanobu Kano, Mika Tsujita, Kenji Sakimura, Stéphane Dieudonné
Journal: Neuron (2014)

In cerebellar Purkinje cell dendrites, heterosynaptic calcium signaling induced by the proximal climbing fiber (CF) input controls plasticity at distal parallel fiber (PF) synapses. The substrate and regulation of this long-range dendritic calcium signaling are poorly understood. Using high-speed calcium imaging, we examine the role of active dendritic conductances. Under basal conditions, CF stimulation evokes T-type calcium signaling displaying sharp proximodistal decrement. Combined mGluR1 receptor activation and depolarization, two activity-dependent signals, unlock P/Q calcium spikes initiation and propagation, mediating efficient CF signaling at distal sites. These spikes are initiated in proximal smooth dendrites, independently from somatic sodium action potentials, and evoke high-frequency bursts of all-or-none fast-rising calcium transients in PF spines. Gradual calcium spike burst unlocking arises from increasing inactivation of mGluR1-modulated low-threshold A-type potassium channels located in distal dendrites. Evidence for graded activity-dependent CF calcium signaling at PF synapses refines current views on cerebellar supervised learning rules.
Intramuscular Injection of Trypsin: Its Value as a Thrombolytic and Anti-Inflammatory Agent
Authors: Kenneth M. Moser
Journal: New England Journal of Medicine (1957)

Acute Deep ThrombophlebitisFifteen patients with acute, deep, unilateral thrombophlebitis received intramuscular injections of trypsin. Significant features are presented in Table 4.The upper extremity was involved in 3 patients, and the lower extremity in the remainder. None of the former group and 10 of the latter received anticoagulants. A single pulmonary embolus occurred (Case 13). This preceded trypsin therapy, the patient being on Dicumarol at the time.The average duration of symptoms before trypsin therapy was six and seven-tenths days, with a range of one day to three weeks.In the 14 patients with heat and tenderness present, both disappeared . . .
Sex Differences in Platelet Reactivity and Response to Low-Dose Aspirin Therapy
Authors: Diane M. Becker, Jodi Segal, Dhananjay Vaidya, Lisa R. Yanek, J. Enrique Herrera-Galeano, Paul F. Bray, Taryn F. Moy, Lewis C. Becker, Nauder Faraday
Journal: JAMA (2006)

ContextRecent randomized trials suggest that women may not accrue the same cardioprotective benefits as men do from low-dose aspirin therapy used in primary prevention. Failure of aspirin to suppress platelet aggregation in women is one hypothesized mechanism.ObjectiveTo examine differential platelet reactivity to low-dose aspirin therapy by sex.Design, Setting, and ParticipantsA clinical trial of aspirin at 81 mg/d for 14 days was conducted in 571 men and 711 women. Baseline and post–aspirin therapy measures included platelet aggregation to arachidonic acid, adenosine diphosphate, epinephrine, and platelet function analyzer closure time.Main Outcome MeasureSex differences in cyclooxygenase 1 (COX-1) direct and indirect platelet activation pathways before and after administration of aspirin.ResultsIn 10 of the 12 platelet agonist exposures, women's platelets were significantly more reactive at baseline. However, after aspirin therapy, the percent aggregation to arachidonic acid (the direct COX-1 pathway) decreased more in women than in men (P&lt;.001) and demonstrated near total suppression of residual platelet reactivity in both men and women. In COX-1 indirect pathways, women experienced the same or more platelet inhibition than men in 8 of the 9 assays yet retained modestly greater platelet reactivity after aspirin therapy. In multivariable analysis, female sex significantly predicted aggregation to 2 μM and 10 μM of adenosine diphosphate (P = .02 and &lt;.001, respectively) and collagen at 5 μg/mL (P&lt;.001) independent of risk factors, age, race, menopausal status, and hormone therapy.ConclusionsWomen experienced the same or greater decreases in platelet reactivity after aspirin therapy, retaining modestly more platelet reactivity compared with men. However, most women achieved total suppression of aggregation in the direct COX-1 pathway, the putative mechanism for aspirin's cardioprotection.
P3-15-02: The Change of Bone Turnover Markers during Neoadjuvant Anastrozole Versus Exemestane: A Randomized Single-Center Study.
Authors: H Jinno, K Shimada, M Takahashi, T Hayashida, S Hirose, T Ikeda, Y Kitagawa
Journal: Cancer Research (2011)

Abstract Background: Non-steroidal aromatase inhibitors including anastrozole and letrozole have been reported to increase the rate of bone turnover, accelerate loss of bone, and increase the incidence of fractures. Although steroidal inactivator exemestane has similar inhibitory effect on the aromatization, animal studies have shown a weak but potentially important anabolic effect of exemestane metabolites, which might lead to decreased bone resorption. This randomized trial was conducted to compare the effect of exemestane and anastorozole on bone turnover markers. Patients and Methods: Fifty-two postmenopausal women with ER-positive, HER2−negative, invasive, nonmetastatic, and operable breast cancer were randomly assigned to neoadjuvant exemestane (25 mg daily) or anastrozole (1 mg daily) for 4 months. The primary endpoint was change in bone turnover markers including resorption markers urinary and serum N-telopeptide (NTX) and the formation markers serum bone alkaline phosphatase (BAP). The secondary endpoint was tumor objective response (OR) assessed by both caliper and ultrasound. Comparisons were also made of breast conservation rate and adverse events. Results: The changes in serum NTX from baseline to week 16 were not statistically different between anastrozole and exemestane. The changes in urinary NTX from baseline to week 16 were also not statistically different between both groups .BAP did not show any significant increase in the exemestane group (10.8%; p=0.21), whereas the increase in BAP from baseline to week 16 in the anastrozole group was 15.0% and marginally significant (p=0.05). There were no significant differences in OR in the intent-to-treat population between patients receiving anastrozole or exemestane (45.8% vs. 39.2%; p=0.63). The OR was similar between the patients with a baseline Ki67 index of ≥15% and &amp;lt;15% in exemestane group (37.5% vs. 41.2%; p=0.86). In anastrozole group the OR in patients with a baseline Ki67 index of ≥15% and &amp;lt;15% was 44.4% and 53.8%, respectively(p=0.66). Breast conservation rate was similar between anastrozole and exemestane (62.5% vs. 67.9%; p=0.68). Treatment was well tolerated and much the same for both groups. Conclusions: There is no significant differences of the change in bone turnover markers between anastrozole and exemestane. These results indicate exemestane had no anabolic effects which would lead to fewer adverse effects on bone. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-15-02.
For many, endemic goiter remains a baffling problem
Authors: Terra Ziporyn
Journal: JAMA (1985)

Before iodine prophylaxis began in 1924, endemic goiter was a major problem in areas of the United States. Today, iodized salt and other measures have largely alleviated this problem, supplementing the iodine washed away by glaciation in areas such as the Great Lakes. But in many areas of the world—even a few in the United States—endemic goiter remains a major public health problem. And, as recent research in one state indicates, iodine deficiency may not always be a prerequisite for goiter. This intriguing research is being conducted in some coal-rich areas of Kentucky that still are reporting a high prevalence of goiter in spite of sufficient iodine intake. In these areas, iodine supplementation appears to be of little help. At the American Thyroid Association meeting in New York City, Eduardo Gaitan, MD, presented initial results of this study, which reassessed the situation by contrasting goiter occurrence in two Kentucky counties.
ARTIFICIAL LIGHT THERAPY IN TUBERCULOSIS
Authors: EDGAR MAYER
Journal: JAMA (1924)

The curative rôle of light in rickets and tetany is now commonly accepted. Under the influence of light, the blood in rickets shows an increased phosphorus content, and calcium deposition in the epiphyses of the long bones readily takes place. The blood in tetany shows an increased calcium and phosphorus content and, clinically, the disappearance of such symptoms as carpopedal spasms, laryngospasms and convulsions after a few exposures to quartz mercury vapor radiations. Lupus vulgaris of the skin is healed by combined local and general light exposures in almost 90 per cent, of cases. Extrapulmonary tuberculosis in many forms yields to treatment with sunlight and artificial light radiations. These results have been so clear cut in a large number of cases and yield so much promise that a knowledge of light and its clinical applications has become a requisite not only of the physiotherapist but also of the general practitioner.