tbuckley/cabot-search huggingface dataset:
Bisphosphonates in the treatment of osteoporosis
Authors: K. E. Poole, J. E. Compston
Journal: BMJ (2012)

A 74 year old woman is admitted to hospital with a subtrochanteric hip fracture after a fall in her home. The T score for the bone mineral density (BMD) in her femoral neck is −3.2. She had a wrist fracture seven years ago but is otherwise healthy. Her 10 year absolute risk of any major osteoporotic fracture is 23% (calculated with the online WHO FRAX tool, www.shef.ac.uk/FRAX). The patient is treated surgically with internal fixation of the fracture. She is advised that she has a high risk of having further fractures, and the benefits and risks of possible treatment options to reduce this risk are discussed using a decision aid (http://musculoskeletal.cochrane.org/decision-aids). It is agreed that she will take alendronate, 70 mg once weekly for five years.

Bisphosphonates are analogues of inorganic pyrophosphate. They inhibit bone resorption by inducing apoptosis of osteoclasts,1 thus preventing age related bone loss and deterioration of bone microarchitecture. Bisphosphonates that contain nitrogen (such as alendronate, risedronate, ibandronate, and zoledronic acid) have the most potent antiresorptive properties and are the most commonly used drugs in the treatment of osteoporosis. The bisphosphonate etidronate does not contain nitrogen, and although it is approved for treatment of postmenopausal osteoporosis, the evidence base is weaker and it is rarely prescribed nowadays.

Large phase III randomised controlled trials in postmenopausal women with osteoporosis have shown significant reduction in vertebral fractures after three years of treatment with alendronate,2 risedronate,3 4 ibandronate,5 and zoledronic acid,6 and in non-vertebral fractures and hip fractures with alendronate,2 risedronate,7 and zoledronic acid.6 In the Fracture Intervention Trial, the incidence of vertebral fracture in women treated for three years with alendronate 5 mg daily for 24 months followed by 10 mg daily for 12 months was 8%, compared with 15% in …
Allogeneic T cells induce rapid CD34+ cell differentiation into CD11c+CD86+ cells with direct and indirect antigen-presenting function
Authors: Javaneh Abbasian, Dolores Mahmud, Nadim Mahmud, Sandeep Chunduri, Hiroto Araki, Pavan Reddy, Ronald Hoffman, Mario Arpinati, James L. M. Ferrara, Damiano Rondelli
Journal: Blood (2006)
Breast Tumor as the Presenting Sign of Multiple Myeloma
Authors: Benjamin Rosenberg, Joseph N. Attie, Harold L. Mandelbaum
Journal: New England Journal of Medicine (1963)

PLASMA-cell tumors may appear in a solitary form or as a manifestation of multiple myeloma. Extra-medullary plasmocytomas — that is, soft-tissue plasma-cell tumors in the absence of skeletal involvement — are rare and are often an early finding of generalized myeloma. These soft-tissue lesions have been described in many organs. However, there has been only 1 previously reported case1 in which the disease became apparent after investigation of a mass in the breast. In the patient described below, breast tumors were the earliest manifestation of this disease.Case ReportA.H., a 41-year-old housewife, entered Maimonides Hospital on March 25, 1962, . . .
654. Quantifying GDNF Levels in the Spinal Cord after Intracerebral Delivery of rAAV5 GDNF
Authors: Kevin D. Foust, Paul J. Reier, Ronald J. Mandel, Terence R. Flotte
Journal: Molecular Therapy (2005)

Top of pageAbstract
Neurodegenerative diseases such as Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) are characterized by a loss of the lower motor neurons in the spinal cord. Gene therapy is a possible treatment for these diseases. One promising approach is the use of multiple injections of recombinant adeno-associated virus to deliver secreted trophic factors to spinal motor neurons (Kaspar, et al 2003). However the relationship between the upper and lower motor neurons can potentially be utilized to deliver trophic factors to large areas of the spinal cord via a single intracerebral injection. Previously we have demonstrated GFP and GDNF immuno-staining of cervical and thoracic spinal cord after a single red nucleus injection of rAAV5 GFP or GDNF vector. To further characterize the GDNF expression in the spinal cord, normal rats were given a unilateral injection of rAAV5 GDNF and sacrificed 6 weeks post injection. The brains and spinal cords were extracted and analyzed by GDNF ELISA. GDNF was detected in all levels of spinal cord examined. A gradient of GDNF expression was clearly observed moving from cervical through to lumbar levels of spinal cord. This follows the pattern of rubrospinal tract fibers with the number of fibers comprising the tract lessening as it moves caudally. GDNF was not detectable in GFP injected controls. These results indicate that delivery of a transgene encoding a secreted trophic factor such as IGF1 or GDNF to a large portion of the spinal cord is possible after a single injection into the red nucleus. Future directions include delivery of rAAV5 GDNF or IGF1 to the motor cortex and red nucleus of normal and diseased animals to measure protein levels along the spinal cord and investigate the therapeutic effect of this novel gene delivery route. Supported by a grant from Families of Spinal Muscular Atrophy.
Platelet releasing activity in sera of patients with rheumatoid vasculitis.
Authors: T.J Cunningham, R.L Medcalf, J.D Mathews, K.D Muirden
Journal: Annals of the Rheumatic Diseases (1986)

Platelet releasing activity was found in sera fractionated by 30% ammonium sulphate in seven of 11 patients with systemic rheumatoid vasculitis, two of 16 patients with cutaneous rheumatoid vasculitis, and three of 18 patients with clinically uncomplicated rheumatoid arthritis. Serial studies in three patients suggest a key role of platelet activation by serum factors in the pathogenesis of systemic rheumatoid vasculitis. IgG rheumatoid factor or IgG containing immune complexes, or both, may be responsible for this platelet releasing activity.
Clinicopathologic Characteristics and Outcome of Diffuse Large B-Cell Lymphomas Presenting With an Associated Low-Grade Component at Diagnosis
Authors: Hervé Ghesquières, Françoise Berger, Pascale Felman, Evelyne Callet-Bauchu, Paul-André Bryon, Alexandra Traverse-Glehen, Catherine Thieblemont, Lucile Baseggio, Anne-Sophie Michallet, Bertrand Coiffier, Gilles Salles
Journal: Journal of Clinical Oncology (2006)

Some diffuse large B-cell lymphomas (DLBCL) present at diagnosis with associated morphologic features of small B-cell non-Hodgkin's lymphoma (NHL) and may arise from the transformation of a previously unknown indolent low-grade lymphoma. The characteristics and prognosis of these particular DLBCL are not well known.The strict morphologic review of consecutive DLBCL patients diagnosed over 12 years in our department (Hematology Department, Centre Hospitalier Lyon-Sud, Lyon, France) allowed to retrieve 60 DLBCL that could be have occurred from the transformation of marginal zone B-cell NHL (32 patients), follicular NHL (22 patients), and small lymphocytic NHL (6 patients). We compared them to 180 matched patients of de novo DLBCL.Patients median age was 55 years and presented the following clinical characteristics: poor performance status in 33%, disseminated disease in 97%, more than one extranodal site in 50%, and increased lactate dehydrogenase level in 55%. Complete remission with multidrug chemotherapy regimens was achieved in 60% of the patients, but 48% relapsed: 28% with aggressive and 20% with indolent histology, respectively. Overall survival (OS) and freedom-from-progression rates at 5 years were 57% and 33%, respectively. The matched-control analysis showed that patients with transformed NHL at diagnosis had lower complete response to chemotherapy (P = .004) and higher progression rate (P = .03), whereas no difference was observed in OS (P = .21).Compared to de novo DLBCL, transformed NHL at diagnosis have similar overall survival but lower complete response to initial treatment and higher risk of indolent relapses.
Variation of the fatty acid binding protein 2 gene is not associated with obesity and insulin resistance in Japanese subjects
Authors: Tetsuo Hayakawa, Yukihiro Nagai, Erika Nohara, Haruhisa Yamashita, Toshinari Takamura, Toshio Abe, Gakuji Nomura, Ken-ichi Kobayashi
Journal: Metabolism (1999)
UK drug regulator destroys all evidence after 15 years
Authors: P. C. Gotzsche
Journal: BMJ (2011)

Jorgensen and I recently gained access to clinical study reports and trial protocols of placebo controlled trials at the European Medicines Agency (EMA).1 Some drugs, however, have not been approved centrally, and in such cases the EMA advises contacting the relevant national drug agencies.

For the antidepressant drug fluoxetine, the United Kingdom acts as Reference Member State according to the Mutual Recognition …
Family participation in care to the critically ill: opinions of families and staff
Authors: �lie Azoulay, Fr�d�ric Pochard, Sylvie Chevret, Charles Arich, Fran�ois Brivet, Fr�d�ric Brun, Pierre-Emmanuel Charles, Thibaut Desmettre, Didier Dubois, Richard Galliot, Maite Garrouste-Orgeas, Dany Goldgran-Toledano, Patrick Herbecq, Luc-Marie Joly, Merc� Jourdain, Michel Kaidomar, Alain Lepape, Nicolas Letellier, Olivier Marie, Bernard Page, Antoine Parrot, Pierre-Andre Rodie-Talbere, Alain Sermet, Alain Tenaillon, Marie Thuong, Patrick Tulasne, Jean-Roger Le Gall, Benot Schlemmer
Journal: Intensive Care Medicine (2003)
Trauma Registries and Organ Transplantation-Reply
Authors: Daniel Pollock
Journal: JAMA (1990)

<h3>In Reply. —</h3> We appreciate Dr Evans' interest in trauma registries and his suggestion that registry data could be useful in estimating the size of the potential organ donor pool. Although Evans et al<sup>1</sup>and others<sup>2</sup>have provided point estimates using data abstracted from medical records, organ procurement agencies require ongoing surveillance of the potential and actual donor pools.<sup>3</sup> Trauma registries are used for ongoing surveillance of the quality of trauma care. The expansion suggested by Dr Evans could increase the value of the database, but not all registries are equipped to capture these additional data. A variety of practical obstacles, including insufficient staff and resources, impede the use of many registries for trauma care surveillance. Overcoming these obstacles is of paramount importance if registries are to serve their primary purpose and additional purposes, such as surveillance of potential organ donors. Data fields for the primary and
After After Many a Summer: A Modern Analysis of Ancient Lifetime Data
Authors: Martin Tanner
Journal: JAMA (1985)

<h3>To the Editor.—</h3> In the fifth chapter of the Book of Genesis, the direct male lineage from Adam to Noah is reported: Adam, Seth, Enosh, Kenan, Mahalalel, Jared, Hanoch, Methuselah, Lamech, and Noah. For nine of these individuals, we are told the age of the individual at which his succeeding son was born, the number of years from this date to the death of the individual, the total number of years that the individual survived, and the fact that the death of the individual was observed. However, for Hanoch no mention is made that his death was observed<sup>1</sup>: "And Hanoch lived sixty and five years, and begot Methuselah. And Hanoch walked with God after he begot Methuselah three hundred years, and begot sons and daughters. And all the days of Hanoch were three hundred sixty and five years. And Hanoch walked with God,<i>and he was not;</i>for God
THE VALUE OF STATE CONTROL AND VACCINATION IN THE MANAGEMENT OF SMALLPOX.
Authors: J. N. McCORMACK
Journal: JAMA (1902)

Vaccination became so popular and universal in all civilized countries in the decades following its introduction that the horrors of smallpox almost faded from the memory of men, and medical writers and teachers habitually wrote and spoke of it as possessing only an historic interest. It is probable that in this age vaccination became so general that more or less inherited immunity existed, as a rule, even where the individual himself had not been subjected to the operation. Then came the reaction against it, and an exaggeration and misrepresentation of the accidents and evils incident to any like remedy used by the laity, as well as by many careless medical men, who had no conception of the value of cleanliness, which philosophic minds should have anticipated. In this the anti-vaccinationist had his day, alongside of him who doubted if Shakespeare wrote his own plays, and the other countless freaks, literary
Relative Merits of Clinical and Didactic Teaching of Medicine.
Authors: L. Harrison Mettler
Journal: JAMA (1899)

Chicago, March 13, 1899. <h3>To the Editor:</h3> —The editor of the<i>Philadelphia Medical Journal</i>has spoken vehemently of the usefulness of clinical and the uselessness of didactic lectures in the teaching of medicine. I am glad to see the didactic lecture defended by two such able writers and lecturers as Barton Cooke Hirst (<i>Phila. Med. Jour.</i>) and Hobart Amory Hare (<i>Med. News</i>). I have recently, somewhere, seen some foreign utterances in behalf of the didactic lecture, and the statement that Virchow disapproved of the disfavor into which didactic teaching seems lately to have fallen. It is undoubtedly true, that at one time didactic teaching was greatly overdone and that there was a crying need of the system of quizzes and recitations. With the advance of medical science, the improvement in the instrumental and chemic means of diagnosis, and the desire for more exactness in all the departments of the art
An attempt to use vincristine and colcemid to measure proliferative rates in normal human epidermis in vivo
Authors: R.S. CAMPLEJOHN, S. GELFANT, DAN CHALKER
Journal: British Journal of Dermatology (1981)

A range of doses of vincristine (0.5–10 μg) or colcemid (5–100 μg) injected intradermally into normal volunteers failed to yield any significant accumulation of arrested mitoses. This was despite an apparently successful block of cells in metaphase by the highest three doses of each drug. Possible reasons for the failure to see accumulation are discussed. The results suggest that normal human epidermis is not a suitable system for application of the metaphase-arrest technique using intradermal injection.
Advice to a Moscow children's hospital.
Authors: S A McKenzie, O Kurtianyk, M Kidd, D Knowles, H Lipman
Journal: BMJ (1993)

At the request of the largest children's hospital in Moscow, McKenzie and colleagues made recommendations for improving the service. Restrictions on visiting and fears of contracting illness from non-disposable needles have discouraged the local population from using the hospital. Consequently the hospital is underused and overstaffed. Serious shortages of drugs and surgical supplies compromise care. Fundamental changes are needed in nursing and postgraduate education. The authors encouraged their Russian colleagues to address the health care needs of their local population and to develop family centred care, and they offered training in London.
Resistin and visfatin in steatotic and non-steatotic livers in the setting of partial hepatectomy under ischemia-reperfusion
Authors: Maria Elias-Miró, Mariana Mendes-Braz, Ruben Cereijo, Francesc Villarroya, Mónica B Jiménez-Castro, Jordi Gracia-Sancho, Sergi Guixé-Muntet, Marta Massip-Salcedo, Joan Carles Domingo, Raquel Bermudo, Juan Rodés, Carmen Peralta
Journal: Journal of Hepatology (2013)
Can cells other than Th17 lymphocytes be important sources of IL-17 in the lungs?
Authors: M. Brodlie, J. Lordan, C. Ward
Journal: Thorax (2011)

alveolar cell traffic, that Porter highlights, may not be readily made in mice.In sharp contrast to humans, mice lack a bronchial circulation.The dominance of the pulmonary circulation is reflected in the work carried out by Corry et al.These authors repeatedly emphasise that their studies concern parenchymal leucocytes.When egression is inhibited, leucocytes accumulate in pulmonary parenchymal tissues 'causing' severely impeded gas exchange. 4 Oxygen is an effective remedy in these lethally affected mice. 3 Corry et al 3 particularly underscore that 'differences in smooth muscle or other contractile cell function cannot explain the increased mortality observed.'Hence, Porter's statement that death in this model is by 'bronchoconstriction' is puzzling.Then Porter discusses data suggesting that mouse lung injury evoked by intratracheal bleomycin is caused by transepithelial neutrophil egression.We are not equally convinced.For example, n-formylneoleucyl-leucyl-phenylalanine (nFNLP) may not be used as a specific inducer of neutrophil egression, as quoted by Porter.nFNLPlike peptides are multipotent agents and avidly induce neutrophil toxicity as well.Nearly 130 years have passed since Julius Cohnheim held classic lectures on inflammation. 5 He discussed the resolution of inflammatory infiltrates in mucosally lined organs, specifically noting the advantageous outward transport available to bronchi and lung alveoli.Cohnheim's contemporary and perpetual authority, Henry Hyde Salter, observed cell-rich sputum production at resolution of severe asthma.Salter intriguingly analysed how the most peripheral airways could be cleared of cellular exudates since coughing would have little impact here.
Cytokine gene transcription in vascularised organ grafts: analysis using semiquantitative polymerase chain reaction.
Authors: M J Dallman, C P Larsen, P J Morris
Journal: The Journal of Experimental Medicine (1991)

Cytokine gene transcription has been analyzed by direct analysis of RNA obtained from mouse heterotopic cardiac transplants. The level of expression of the cytokine genes was assessed using semiquantitative polymerase chain reaction (PCR). Expression of the cytokines investigated fell into three groups. The first group included interleukin 1 beta (IL-1 beta), IL-5, IL-6, and interferon gamma (IFN gamma). These genes were expressed in normal heart tissue at low level and were upregulated following both syngeneic and allogeneic transplantation. Genes in the second group (IL-1 alpha, IL-3) were not expressed at detectable levels in normal heart but were induced following either syngeneic or allogeneic heart grafting. IL-2, IL-4, and tumor necrosis factor beta (IFN beta) comprised the third group and these cytokines were expressed only in allogeneic grafts after transplantation.
De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly
Authors: Jeong Ho Lee, My Huynh, Jennifer L Silhavy, Sangwoo Kim, Tracy Dixon-Salazar, Andrew Heiberg, Eric Scott, Vineet Bafna, Kiley J Hill, Adrienne Collazo, Vincent Funari, Carsten Russ, Stacey B Gabriel, Gary W Mathern, Joseph G Gleeson
Journal: Nature Genetics (2012)
Is duodenal diverticulum a risk factor for sphincterotomy?
Authors: D Vaira, J F Dowsett, A R Hatfield, S R Cairns, A A Polydorou, P B Cotton, P R Salmon, R C Russell
Journal: Gut (1989)

It is uncertain whether ERCP and associated procedures are more difficult when the papilla is inside or adjacent to a duodenal diverticulum. We have therefore reviewed the data from 2458 consecutive, prospectively reported ERCPs between November 1983 and March 1988. Three hundred and eight patients (12.5%) had periampullary diverticula and in 21 the papilla was located deep within the diverticulum of whom 227 had undergone endoscopic sphincterotomy (73.7%). Comparison was made with the 2150 patients without diverticula of whom 1223 (56.9%) had undergone sphincterotomy. The success rate of specific duct cannulation was 94.2% in the diverticulum group and 96.7% in those without diverticula (p less than 0.05). The overall success rate of endoscopic sphincterotomy was 95.2% in the diverticulum group, as compared with 98.0% in those without diverticula (p less than 0.05). The procedure related morbidity and mortality of sphincterotomy were 5.2%/0.9% and 4.0%/0.7% respectively (NS). If only those who had successful cholangiography were included there was no difference in sphincterotomy success between those with and without diverticula. The group of patients with papilla deep within diverticula had a slightly higher failure rate of pure endoscopic sphincterotomy (11.8% v 5.7%: NS) but did not have a higher complication rate. In the subgroup of patients with choledocholithiasis, duct clearance of stones was as successful after sphincterotomy in those with diverticula as in those without. Medium term complications (mean 26 months) occurred in 1.4% of patients with diverticula and in 0.7% of patients without diverticula. We conclude that diagnostic cholangiography is more difficult when the papilla is closely associated with a diverticulum but that if diagnostic cholangiography is obtained, sphincterotomy may be performed as successfully and as safely in those with or without diverticula.
Dispensing in Rural Areas
Authors: J. Wright
Journal: BMJ (1967)

<h3>Abstract</h3> Gene expression alterations occur in all mouse tissues during aging, but recent works highlight minor rather than major dysregulation amplitude for most genes, questioning whether differentially expressed genes on their own provide deep insight into aging biology. To clarify this issue, we have combined differential gene expression with weighted gene correlation network analysis (WGCNA) to identify expression signatures accounting for the pairwise relations between gene expression profiles and the cumulative effect of genes with small fold- changes during aging in the brain, heart, liver, skeletal muscle, and pancreas of C57BL/6 mice. Functional enrichment analysis of the overlap of genes identified in both approaches showed that immunity-related responses, mitochondrial energy metabolism, tissue regeneration and detoxification are prominently altered in the brain, heart, muscle, and liver, respectively, reflecting an age-related global loss of tissue function. While data showed little overlap among the age-dysregulated genes between tissues, aging triggered common biological processes in distinct tissues, particularly proteostasis-related pathways, which we highlight as important features of murine tissue physiological aging.
AMONG PATIENTS WITH ST ELEVATION MYOCARDIAL INFARCTION ANEMIA PREDICTS LONG-TERM MORTALITY, INDEPENDENTLY OF CO-MORBIDITY AND ANTI-PLATELET TREATMENT
Authors: Gaetano M. De Ferrari, Andrea Baldo, Claudia Pavesi, Gabriele Crimi, Silvia Pica, Antonella Potenza, Marco Ferlini, Massimiliano Gnecchi, Rita Camporotondo
Journal: Journal of the American College of Cardiology (2014)