tbuckley/cabot-search huggingface dataset:
Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in β-thalassemia
Authors: Ilaria V. Libani, Ella C. Guy, Luca Melchiori, Raffaella Schiro, Pedro Ramos, Laura Breda, Thomas Scholzen, Amy Chadburn, YiFang Liu, Margrit Kernbach, Bettina Baron-Lühr, Matteo Porotto, Maria de Sousa, Eliezer A. Rachmilewitz, John D. Hood, M. Domenica Cappellini, Patricia J. Giardina, Robert W. Grady, Johannes Gerdes, Stefano Rivella
Journal: Blood (2008)
Surgery of Repair as Applied to Hand Injuries
Authors: Robert A. Chase
Journal: JAMA (1969)

In its first two editions this book firmly established itself as an important contribution to the literature on primary reparative surgery of the hand. The new third edition reports progress made in the field and develops seasoned thoughts and conclusions of the senior authors, after a decade and a half of experience since the first edition. It adds a new scholarly and imaginative author, J. T. Hueston. The book has not lost its unique flavor as a volume with which one may spend hours and feel that he has conversed with the authors. The emphasis on primary care of hand injuries is unique to the volume, and I find little disagreement with the principles and most of the techniques described. Although I might disagree in some of the details on such things as donor sites for split grafts (the forearm), local pedicle flaps (the radial side of the index digit
Assessment of left ventricular function in severe aortic regurgitation.
Authors: A D Johnson, J S Alpert, G S Francis, V R Vieweg, I Ockene, A D Hagan
Journal: Circulation (1976)

Echocardiographic (echo) measurements of left ventricular ejection phase indices--ejection fraction, percent shortening of the minor diameter (%deltaD), and velocity of circumferential fiber shortening (Vcf)--are said to be accurate reflections of their angiographic (angio) counterparts. Most studies correlating echo and angio left ventricular function parameters have included relatively few patients with aortic regurgitation. Echo and angio measurements of left ventricular ejection phase indices thus might not correlate in these patients in whom left ventricular geometry may have been altered due to the volume overload. To test this hypothesis, left ventricular ejection phase indices were determined by angiography and echocardiography and compared in 20 patients with isolated, symptomatic, severe aortic regurgitation. Ejection fraction, %deltaD, and Vcf by LAO cineangiograms and echo were uniformly higher than corresponding measurements from RAO angio, and were often normal in the presence of other indicators of significant left ventricular dysfunction. We conclude that the usual, linear echocardiographic measurement of left ventricular wall motion may not reflect significant myocardial dysfunction in patients with severe aortic regurgitation.
Bacteria and the Liver
Authors: James P. Nolan
Journal: New England Journal of Medicine (1978)

For an organ exposed to bacteria from both the systemic and portal circulations, it is surprising that bacterial infections of the liver are so rare. Although viral invasion of hepatic tissue is common, the extensive network of reticuloendothelial or von Kupffer cells that line the sinusoids is capable normally of clearing bacteria presented from elsewhere,1 and repeated studies have confirmed that healthy liver tissue is sterile.Abnormalities of liver function in systemic infections are common but are usually due to toxic products rather than bacterial presence. In pneumococcal pneumonia, hepatic function is impaired commonly, and jaundice may be seen in . . .
Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC
Authors: Lois M. Mulligan, Charis Eng, Catherine S. Healey, David Clayton, John B.J. Kwok, Emily Gardner, Margaret A. Ponder, Andrea Frilling, Charles E. Jackson, Hendrik Lehnert, Hartmut P.H. Neumann, Stephen N. Thibodeau, Bruce A.J. Ponder
Journal: Nature Genetics (1994)
The Treatment of Diabetes with Special Reference to Accessory Forms of Treatment
Authors: WALTER M. BARTLETT
Journal: Annals of Internal Medicine (1928)

Article1 October 1928The Treatment of Diabetes with Special Reference to Accessory Forms of TreatmentWALTER M. BARTLETT, M. D.WALTER M. BARTLETT, M. D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-2-4-334 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptUnder ordinary circumstances it is simple to determine the specific value of a certain method of treatment of any common disease. The usual procedure is to set aside a group of cases which have been thoroughly investigated, employ the treatment in question in one half of the cases and not in the other half. The results are then compared by some suitable unit of comparison and the statistics resulting are presented to a group of competent judges for inspection and criticism. By this method the comparison is of value only to the extent of the validity and reliability of the...(1) ALLEN FM: Blueberry Leaf Extract, physiologic and Clinical Properties in Relation to Carbohydrate Metabolism, Journal A. M. A., Nov 5, 1927, lxxxix. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bernardsville, New Jersey PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1928Volume 2, Issue 4Page: 334-340KeywordsReproducibility Issue Published: 1 October 1928 PDF downloadLoading ...
Sublingual immunotherapy: a double‐blind, placebo‐controlled trial with <i>Parietaria judaica </i>extract standardized in mass units in patients with rhinoconjunctivitis, asthma, or both
Authors: F. Purello‐D'Ambrosio, S. Gangemi, S. Isola, N. La Motta, L. Ricciardi, P. Puccinelli, S. Parmiani, E. Savi
Journal: Allergy (1999)

Background : New routes of administering immunotherapy in respiratory allergy are being studied as an alternative to conventional injective immunotherapy. We carried out a study to evaluate the clinical efficacy and effects of sublingual immunotherapy in patients with Parietaria judaica ‐induced respiratory allergy. Methods : A double‐blind, placebo‐controlled design was followed. Thirty patients with P. judaica rhinoconjunctivitis, mild asthma, or both were randomly chosen for sublingual immuno‐therapy (14 patients) or placebo treatment (16 patients). The patients underwent preseasonal rush induction treatment followed by coseasonal maintenance treatment during the Parietaria pollen season. Symptom and drug scores, as well as specific IgE and specific IgG4, were recorded. Results : Significantly lower symptom and drug scores were found ( P =0.04), especially during the Parietaria pollination period, in the immunotherapy group. No significant difference in specific IgE and specific IgG4 was detected between the active and placebo groups; a statistically significant increase of specific IgE was detected in both groups ( P =0.05). No patient undergoing active sublingual immunotherapy reported local or systemic side‐effects. Conclusions : Our data suggest that sublingual immunotherapy is both clinically effective and safe in treating patients with Parietaria ‐induced rhinoconjunctivitis and mild asthma.
Overuse of animal antibiotics threatens human health
Authors: R. Woodman
Journal: BMJ (1999)

Giving antibiotics to farm animals results in the emergence of resistant bacteria with potentially calamitous consequences for human health, warns a report from the United Kingdom Advisory Committee on the Micro-biological Safety of Food

The committee, which was set up to provide the government with independent expert advice, says that it is clear that some of the resistant strains seen in food animals are capable of infecting humans Moreover, the ability of micro-organisms …
Child Care in General Practice: "Normal Development"
Authors: R. S. Illingworth
Journal: BMJ (1964)

All children are different.They differ in their intelligence, rate of development, their interests and aptitudes, and in their behaviour.In addition, the home environment of one child is very different from that of another and the environment has a profound effect on development.Various illnesses and mechanical or sensory defects greatly affect the course of development.In consequence, developmental assessment is fraught with difficulties.There is no place for spot diagnosis and no place for diagnosis based purely on clinical impressions.Each child has to be considered in detail, in order to avoid serious and unnecessary mistakes.Mistakes may be tragic in some circumstances-as in the assessment of suitability for adoption-a process undertaken far too lightly by many with no experience or knowledge of developmental assessment.
Clinical modeling of T cell vaccination against autoimmune diseases in rats. Selection of antigen-specific T cells using a mitogen.
Authors: F Mor, A W Lohse, N Karin, I R Cohen
Journal: Journal of Clinical Investigation (1990)

Effective T cell vaccination against experimental autoimmune diseases involves treatment with activated, autoimmune T lymphocytes. The present study was undertaken to learn whether antigen-specific T cells present in low frequency could be selected in vitro without using the specific antigen. The rat models of adjuvant arthritis and experimental autoimmune encephalomyelitis were investigated using proliferation assays and limiting dilution techniques to quantify the changes in reactivity of a heterogenous population of lymphocytes to the relevant antigen. Stimulation with concanavalin A for 2 d and then culture in IL-2-containing medium led to a substantial increase in the activity and frequency of the specific autoimmune T cells. Enrichment of antigen-specific T cells could be demonstrated using lymph node, spleen, or peripheral blood lymphocytes, from rats late in the course of disease. The effect was not evident in lymphocytes from the thymus. These results are relevant to the clinical application of T cell vaccination and to investigation of self-antigens in autoimmune disease.
Obesity and climate change
Authors: F. Godlee
Journal: BMJ (2012)

“Childhood obesity, perhaps like climate change, is at times in danger of inciting an ennui borne out of a repetition of problems without answers, a long latency before problems become apparent, and a perception that solutions are out of reach.” So say Lee Hudson and Russell Viner in an editorial this week (doi:10.1136/bmj.e5457). They are commenting on a systematic review which concludes that the adverse effects of obesity on children’s health are greater than previously thought (doi:10.1136/bmj.e4759).

Based on data from nearly 50 000 children the review’s authors found that, compared with children of normal weight, those with a raised body …
Functional characterization of natural killer cells in type I leukocyte adhesion deficiency
Authors: Roberta Castriconi, Alessandra Dondero, Claudia Cantoni, Mariella Della Chiesa, Carola Prato, Marina Nanni, Maurilia Fiorini, Lucia Notarangelo, Silvia Parolini, Lorenzo Moretta, Luigi Notarangelo, Alessandro Moretta, Cristina Bottino
Journal: Blood (2007)
Abstract 4837: Tumor microenvironment contributes to RAF-inhibitor resistance through HGF secretion
Authors: Ravid Straussman, Teppei Morikawa, Kevin Shee, Michal Barzily-Ronki, Jinyan Du, Ashli Davis, Joshua Gould, Keith T. Flaherty, Shuji Ogino, Jennifer A. Wargo, Todd R. Golub
Journal: Cancer Research (2012)

Abstract Drug resistance remains a vexing problem in the treatment of cancer patients. While many studies have focused on cell autonomous mechanisms of drug resistance, we hypothesized that the tumor microenvironment may confer innate resistance to therapy. We employed a novel co-culture assay to systematically assay the ability of 23 stromal cell types to influence the sensitivity of 45 cancer cell lines to 35 anti-cancer drugs testing more than 15,000 cancer-stroma-drug combinations. We found that stroma-mediated resistance is surprisingly common - particularly to targeted chemotherapies. We decided to further characterize the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibition because most patients exhibit some degree of innate resistance. Proteomic analysis showed that stromal secretion of the growth factor hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the MAPK and PI3K/AKT pathways, and immediate resistance to RAF inhibition. Immunohistochemistry confirmed tumor stromal HGF expression in 11 out of 15 patients with BRAF-mutant melanoma. Among these patients, only one experienced a complete response, and that patient was negative for stromal HGF, consistent with our prediction of HGF-mediated RAF-inhibitor resistance. In contrast, of 6 evaluable patients with stable disease 4 had particularly high levels of stromal HGF expression. Dual inhibition of RAF and MET in BRAF-mutant melanoma cell lines resulted in reversal of drug resistance, suggesting RAF/MET combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. Interestingly, the activation of MET in these cell lines was cell autonomous, caused, for example, by autocrine secretion of HGF and resulting in complete resistance to RAF inhibitors even in the absence of stromal cells. Treatment with a MET inhibitor re-sensitized these cell lines to RAF inhibitors suggesting the same RAF/MET combination therapy for non-melanoma BRAF mutant cancers as well. More generally, these studies indicate that the systematic dissection of tumor-microenvironment interactions may reveal important mechanisms underlying drug resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4837. doi:1538-7445.AM2012-4837
TRACHOMA AMONG THE INDIANS OF THE SOUTHWEST
Authors: WILLIAM CAMPBELL POSEY
Journal: JAMA (1927)

Two years ago the Secretary of the Interior, Dr. Hubert Work, requested the American Medical Association to appoint a committee of ophthalmologists from the Association with whom he might confer as occasion demanded on the spread of trachoma among the Indians. The trustees accordingly appointed Drs. Wilder of Chicago, Knapp of New York and me to serve on such a committee, Dr. Proctor of Boston being added to our number later on account of his familiarity with the Indian problem in the Southwest. Last summer Dr. Wilder, the chairman of the committee, with Dr. Holloway of Philadelphia and others, visited some of the reservations in Oklahoma, and last autumn, in order to be in a better position to advise the secretary by making a personal survey and study of the situation at close range, Dr. Proctor and I visited the Southwest and inspected the most important Indian schools and hospitals
Abstract 3933: Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling
Authors: Nikhil Wagle, Caroline Emery, Michael F. Berger, Matthew J. Davis, Allison Sawyer, Panisa Pochanard, Sarah M. Kehoe, Cory M. Johannessen, Laura E. Macconaill, William C. Hahn, Matthew Meyerson, Levi A. Garraway
Journal: Cancer Research (2011)

Abstract Although targeted anticancer agents often result in dramatic responses, tumors invariably become resistant to these agents. A detailed understanding of the mechanisms by which tumors acquire resistance to such inhibitors should speed the development of more durable treatment strategies. The promise of RAF inhibition in metastatic melanoma is exemplary in this regard. Mutations in the BRAF oncogene have been detected in more than 50% of metastatic melanomas, and inhibition of mutant BRAF has shown high response rates in early clinical trials of patients with melanoma. However, resistance to RAF inhibition invariably develops. Mechanisms of de novo and acquired resistance to RAF inhibition remain poorly understood. Moreover, the clinical application of genomic approaches that might be capable of diagnosing salient resistance mechanisms remains underdeveloped. Here, we describe an approach to characterize genetic mechanisms of resistance through systematic tumor mutation profiling. We performed massively parallel sequencing of 138 cancer genes in a tumor specimen from a melanoma patient who developed resistance to PLX4032 after a dramatic initial response. The resulting profile identified a novel mutation in the downstream kinase MEK1 that was absent in the corresponding pre-treatment tumor. This MEK1 mutation was shown to increase kinase activity and confer robust resistance to both RAF and MEK inhibition in vitro. Our results provide an instructive framework both for assessing mechanisms of acquired resistance to kinase inhibition and deploying new technologies for elaboration of resistance mechanisms in a manner that may accelerate personalized cancer medicine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3933. doi:10.1158/1538-7445.AM2011-3933
Tacrine for Alzheimer's Disease
Authors: Margaret A. Winker
Journal: JAMA (1994)

The efficacy and toxicity of tacrine have been debated since dramatic improvement of cognition in patients with Alzheimer's disease after treatment with tacrine was reported in 1986.<sup>1</sup>The scientific validity of this study was contested<sup>2</sup>and cases of hepatotoxicity were reported<sup>3,4</sup>; the first major trial of tacrine was suspended after 2 months.<sup>5</sup>In an attempt to reduce toxicity, the design of several large trials<sup>6-8</sup>incorporated a lower maximum dosage (usually 80 mg/d), but results demonstrated considerably smaller benefits still accompanied by significant adverse effects and high drop-out rates. See also pp 985 and 992. In this issue ofTHE JOURNAL, Knapp et al<sup>9</sup>report the first large randomized controlled study to use a higher dosage of tacrine (maximum dosage, 160 mg/d) in a 30-week trial. Although hepatotoxicity and adverse effects produced high dropout rates, the results eventually led to Food and Drug Administration approval
Compliance as a Determinant of Serum Digoxin Concentration
Authors: M. Weintraub, W. Y. W. Au, L. Lasagna
Journal: JAMA (1973)

Serum digoxin concentrations were measured in 101 outpatients by radioimmunoassay with radioactive iodine 125 to evaluate factors affecting these concentrations. Patient compliance, ascertained by asking how often patients missed taking digoxin, was the most important determinant of serum digoxin concentrations. Compliant patients had mean serum digoxin concentrations (±SD) of 1.2±0.8 ng—l; noncompliant patients had a mean of 0.7±0.7 ng/ml(P ( P  P   Analysis of relationships between serum concentration of digoxin and renal function, age, and dosage in outpatients should include compliance as a variable. Physicians should find out if patients are adhering to the prescribed regimen and search for correctable causes of noncompliance.
Pruritus and underlying cancer: is targeted screening feasible?
Authors: E.A. Langan
Journal: British Journal of Dermatology (2015)

Journal Article Pruritus and underlying cancer: is targeted screening feasible? Get access E.A. Langan E.A. Langan Department of Dermatology University of Lübeck Lübeck Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 6, 1 June 2015, Pages 1685–1686, https://doi.org/10.1111/bjd.13686 Published: 01 June 2015
Safety and clinical impact of ergonovine stress echocardiography for diagnosis of coronary vasospasm
Authors: Jae-Kwan Song, Seong-Wook Park, Duk-Hyun Kang, Myeong-Ki Hong, Jae-Joong Kim, Cheol-Whan Lee, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2000)
Preparation of pegylated lumbrokinase and an evaluation of its thrombolytic activity both in vitro and in vivo
Authors: Mingji Jin, Wei Chen, Wei Huang, Long Rong, Zhonggao Gao
Journal: Acta Pharmaceutica Sinica B (2013)

Lumbrokinase (LK) is a group of serine proteases with strong fibrinolytic and thrombolytic activities. In clinical practice, LK can only be administered orally because of its antigenicity, immunogenicity and potential to produce anaphylactic reactions after injection. However, many useful drugs such as interferon, insulin, erythropoietin and interleukin have been modified with polyethylene glycol (PEG) to prepare injectable formulations. In this study, LK was modified with methoxy PEG succinimidyl carbonate (mPEG-SC) with molecular weights of 5000, 10,000 and 20,000 and the pegylated products were isolated and purified using the Akta protein purification system. The extent of pegylation was determined by HPLC. Fibrinolytic activities of pegylated and unmodified LK were measured both in vitro against urokinase on fibrin plates and in vivo using a mouse carageenan black tail model. Optimal pegylation was obtained using mPEG-SC5000 in a buffer pH 8.0 with a reaction time of 5 h, reaction temperature of 0 °C and LK:mPEG-SC molar ratio of 1:25. The results show that mPEG modified LK has strong fibrinolytic and thrombolytic activities both in vitro and in vivo. It is suggested that the pegylated LK is a promising injectable thrombolytic agent for the treatment of thrombotic diseases in clinical practice.
Role of the Two-Year School in Easing the Shortage of Physicians
Authors: Carleton B. Chapman, David C. House, Rachmiel Levine, David E. Haft
Journal: New England Journal of Medicine (1970)

Abstract The two-year medical school is based on the premise that basic science but not clinical facilities limit student output by four-year medical schools. As a matter of fact, the number of two-year schools declined from 10 in 1940 to three in 1966; during the last five years the third-year classes of 25 medical schools had a net increase of 528 students, but in 51 other schools, the total number of students decreased by 1299, and 65 schools do not expect to increase the number of third-year transfers through 1974. These data suggest that the role of traditional, independent two-year schools in easing the doctor shortage is limited, that the elasticity of current clinical teaching facilities is overestimated and that other mechanisms are needed to increase the number of medical-school graduates.