tbuckley/cabot-search huggingface dataset:
A major histocompatibility complex class II restriction for BioBreeding/Worcester diabetes-inducing T cells.
Authors: K E Ellerman, A A Like
Journal: The Journal of Experimental Medicine (1995)

Inbred diabetes-prone (DP) BioBreeding/Worcester (BB/Wor) (RT1u) rats develop spontaneous autoimmune diabetes, which, like human insulin-dependent diabetes mellitus, is mediated by autoreactive T lymphocytes. Breeding studies have shown an absolute requirement for at least one copy of the major histocompatibility complex (MHC) RT1u haplotype for spontaneous diabetes expression. Concanavalin A-activated spleen cells from acutely diabetic DP rats adoptively transfer diabetes only to recipients that express at least one RT1u haplotype. To investigate the basis for the MHC requirement in BB/Wor autoimmunity, diabetes-inducing T cell lines were derived from the spleens of acutely diabetic DP rats. Upon activation in vitro with islet cells, the T cell lines adoptively transfer insulitis and diabetes into young DP recipients and non-diabetes-prone RT1 congenic rat strains that are class IIu. Recipients that are RT1u at only the class I A or C locus, but not at the class II B/D loci, do not develop diabetes after T cell transfer. The adoptive transfer of diabetes by Concanavalin A-activated diabetic DP spleen cells also requires that donor and recipient share class II B/Du gene products. Furthermore, the adoptive transfer of diabetes into MHC class IIu congenic rats is independent of the class I haplotype; i.e., it occurs in the presence of class I Aa Cu or Au Ca gene products. BB/Wor T cells can be activated in vitro for the transfer of diabetes with islet cell antigens and class II-positive but not class IIu-negative antigen-presenting cells. The inductive phase of BB diabetes is therefore MHC class II restricted, and this appears to operate at the level of interaction between inducing T cells and class IIu antigen-presenting cells. These results may explain the well-documented, but not yet understood, MHC class II genetic contribution to insulin-dependent diabetes mellitus pathogenesis, and they may facilitate the development of protocols designed to prevent diabetes onset in susceptible individuals.
Nanoparticles Modified With Tumor-targeting scFv Deliver siRNA and miRNA for Cancer Therapy
Authors: Yunching Chen, Xiaodong Zhu, Xiaoju Zhang, Bin Liu, Leaf Huang
Journal: Molecular Therapy (2010)

Targeted delivery of RNA-based therapeutics for cancer therapy remains a challenge. We have developed a LPH (liposome-polycation-hyaluronic acid) nanoparticle formulation modified with tumor-targeting single-chain antibody fragment (scFv) for systemic delivery of small interfering RNA (siRNA) and microRNA (miRNA) into experimental lung metastasis of murine B16F10 melanoma. The siRNAs delivered by the scFv targeted nanoparticles efficiently downregulated the target genes (c-Myc/MDM2/VEGF) in the lung metastasis. Two daily intravenous injections of the combined siRNAs in the GC4-targeted nanoparticles significantly reduced the tumor load in the lung. miRNA-34a (miR-34a) induced apoptosis, inhibited survivin expression, and downregulated MAPK pathway in B16F10 cells. miR-34a delivered by the GC4-targeted nanoparticles significantly downregulated the survivin expression in the metastatic tumor and reduced tumor load in the lung. When miR-34a and siRNAs were co-formulated in GC4-targeted nanoparticles, an enhanced anticancer effect was observed. Targeted delivery of RNA-based therapeutics for cancer therapy remains a challenge. We have developed a LPH (liposome-polycation-hyaluronic acid) nanoparticle formulation modified with tumor-targeting single-chain antibody fragment (scFv) for systemic delivery of small interfering RNA (siRNA) and microRNA (miRNA) into experimental lung metastasis of murine B16F10 melanoma. The siRNAs delivered by the scFv targeted nanoparticles efficiently downregulated the target genes (c-Myc/MDM2/VEGF) in the lung metastasis. Two daily intravenous injections of the combined siRNAs in the GC4-targeted nanoparticles significantly reduced the tumor load in the lung. miRNA-34a (miR-34a) induced apoptosis, inhibited survivin expression, and downregulated MAPK pathway in B16F10 cells. miR-34a delivered by the GC4-targeted nanoparticles significantly downregulated the survivin expression in the metastatic tumor and reduced tumor load in the lung. When miR-34a and siRNAs were co-formulated in GC4-targeted nanoparticles, an enhanced anticancer effect was observed.
Old and unwashed: bathing problems in the over 70s.
Authors: N. D. Penn, P. W. Belfield, B. H. Muscie-Taylor, G. P. Mulley
Journal: BMJ (1989)

The efficacy of and complication rates associated with balloon tamponade have been reported from centres experienced in using the procedure.'3This prospective survey was carried out to assess the value and complica- tion rates of balloon tamponade when used in hospitals with limited experience of managing acute variceal bleeding.
Obama's team hopes to lower healthcare costs and increase insurance coverage
Authors: B. Roehr
Journal: BMJ (2009)

The opportunity for health reform in the United States is greater now than it has been in more than 50 years, according to a government adviser on health in the country.

The director of the White House Office of Health Reform, Nancy-Ann DeParle, told a breakfast meeting of reporters this week that the twin goals are to lower costs and extend coverage to people who are uninsured.

Ms DeParle, whose background includes Harvard Law School, a master’s degree from Oxford University as a Rhodes Scholar, and extensive national experience with healthcare finance, is a counsellor to the president, Barack Obama.

“All of the groups who were at different sides of the table 15 years ago are …
Continuous Narcotic Infusion with Patient-Controlled Analgesia for Chronic Cancer Pain in Outpatients
Authors: IAN G. KERR
Journal: Annals of Internal Medicine (1988)

To determine the feasibility and safety of outpatient continuous narcotic infusions with additional bolus capabilities (patient-controlled analgesia) in patients with cancer pain.A single arm (non-randomized) series.Outpatient with contact by telephone and through outpatient clinic.Consecutive series of 18 patients with poorly controlled cancer pain or significant side effects from regular administration of various narcotics.Patients taught and supervised to use portable pump capable of delivering a continuous narcotic infusion with bolus capabilities.All patients had improvement in pain control as judged by the use of a linear analogue scale. Side effects and safety profile were highly acceptable. Narcotics used and maximum doses were meperidine, 50 mg/h; morphine, 80 mg/hr; and hydromorphone, 60 mg/hr. Infusion duration ranged from 7 to 225 days (mean, 54 days).Continuous narcotic infusions using a programmable portable pump with bolus capabilities is a safe and reliable method of delivering narcotics to outpatients.
Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the systemic hemostatic profile
Authors: George Dangas, Juan J Badimon, Donald A Smith, Allen H Unger, Daniel Levine, John H Shao, Perwaiz Meraj, Carl Fier, John T Fallon, John A Ambrose
Journal: Journal of the American College of Cardiology (1999)

OBJECTIVES The study sought to determine the effects of lipid-lowering with pravastatin on the systemic fibrinolytic profile and on thrombus formation under dynamic flow conditions. BACKGROUND Lowering cholesterol (C) decreases clinical events in coronary artery disease (CAD) patients, but an analysis of the effects of lipid-lowering on the entire hemostatic and thrombotic profile has not been conducted. METHODS We prospectively studied 93 stable patients with untreated low-density lipoprotein cholesterol (LDL-C) >145 mg/dl. The CAD patients received pravastatin, and non-CAD patients were randomized to pravastatin versus placebo (double-blind). Thrombus formation upon an injured vascular surface was assessed in a substudy of 40 patients with a previously validated ex vivo perfusion chamber system. Systemic hemostatic markers and thrombus formation were evaluated at baseline, three and six months. RESULTS Placebo produced no changes in either the lipid profile, any of the hemostatic markers, or the ex vivo thrombus formation. Both pravastatin groups (CAD and non-CAD) showed decreased LDL-C by 30% within 6 weeks (188 to 126 mg/dl, p < 0.001 vs. baseline), and decreased plasminogen activator inhibitor-1 at 3- and 6-month follow-up compared to baseline (15% to 18% decrease at 3 months and 21% to 23% at 6 months). For the tissue plasminogen activator antigen, CAD and non-CAD groups showed significant decreases at 6 months compared to baseline (10% and 13%, respectively). No significant changes were observed with treatment in d-dimer, fibrinopeptide A, prothrombin fragment F1.2, factor VIIa, von Willebrand factor, or C-reactive protein. Fibrinogen levels were significantly increased at 6 months compared to baseline, though still below the upper normal limit. In the perfusion chamber substudy, there was a decrease in thrombus area in non-CAD patients treated with pravastatin at both 3 and 6 months compared to baseline (by 21% and 34%, respectively). The CAD patients showed decreases in thrombus formation by 13% at 3 months, and by 16% at 6 months. The change in LDL-C- correlated modestly with the change in thrombus formation (r = 0.49; p < 0.01). CONCLUSIONS Pravastatin therapy significantly decreased thrombus formation and improved the fibrinolytic profile in patients with and without CAD. These early effects may, in part, explain the benefit rendered in primary and secondary prevention of CAD.
Anticoagulation may be beneficial in high risk factor V Leiden carriers
Authors: T. Baglin, C. Baglin, K. Brown, R. Luddington
Journal: BMJ (1998)

EDITOR—Sarasin and Bounameaux's decision analysis model of treatment in factor V Leiden carriers1 is in keeping with the results of our cohort study.2 In our study the annual rate of recurrence when treatment with warfarin was stopped was 11.1 per 100 patient-years. Patients who had an idiopathic first event were more likely to have a recurrence than those whose first event was precipitated (log rank=4.76, P=0.029). The recurrence …
Fatal Cerebral Hypoxemia after Cardiac Arrest
Authors: Jesper Kelsen, Annette Obel
Journal: New England Journal of Medicine (2003)

A 50-year-old woman suddenly became unconscious during her birthday celebration; there was no measurable pulse or blood pressure. Breathing and circulation returned spontaneously within a few minutes, but the exact time was unknown. On admission, she was comatose with bilateral dilated pupils and pronated limbs. Electrocardiography revealed signs of acute inferior myocardial ischemia and sinus tachycardia. The creatine kinase level was 770 U per liter; the level of the MB isoenzyme of creatine kinase was 44 U per liter; and the troponin T level was 0.65 per liter. A computed tomographic (CT) scan of the brain obtained one hour after . . .
The thin layer rapid use epicutaneous test (TRUE-test), a new patch test method with high accuracy
Authors: T.I. FISCHER, H.I. MAIBACH
Journal: British Journal of Dermatology (1985)

The thin layer rapid use epicutaneous test (TRUE-test) is a new patch test, in which the allergens are incorporated in a thin, flexible solid vehicle on a water impermeable backing. The vehicle shows good stability for allergens, which are crystallized, micronized or emulsified into a gel. The TRUE-test produces an exact dosage, even surface spread and high bioavailability for the allergens. This solves the problems of low bioavailability, uncertain dosage and uneven surface distribution which are commonly seen when petrolatum is used as the vehicle.
Esophageal Achalasia: Intrasphincteric Injection of Botulinum Toxin A Versus Balloon Dilation
Authors: S. M. Muehldorfer, T. H. Schneider, J. Hochberger, P. Martus, E. G. Hahn, C. Ell
Journal: Endoscopy (1999)

Background and Study Aims: In patients with esophageal achalasia, pneumatic dilation is the treatment of choice, but it bears the risk of perforation in about 4 % of cases. A new nonsurgical method, intrasphincteric injection of botulinum toxin A, has shown promising initial results, and we thus undertook this study to compare the long-term outcome of these two methods.
Dye Dilution Curves and Cardiac Output in Newborn Infants
Authors: KLARA J. PREC, DONALD E. CASSELS
Journal: Circulation (1955)

The pattern of dye dilution curves and the cardiac output was studied in 29 healthy newborn infants during the first 26 hours of life by the method of Wood and his associates. Thirty-six per cent of all infants studied had curves of normal contour which occurred mostly in infants older than 15 hours. Infants younger than 15 hours tended to have curves of abnormal shape. These were either diphasic or had the appearance of curves associated with left-to-right shunts and were probably caused by a patent ductus arteriosus. The mean cardiac output was 540 cc. per minute.
Moral Medicine and Universal Health Care-Reply
Authors: Arthur L. Caplan, Robert A. Baker, Linda L. Emanuel, Stephen R. Latham
Journal: JAMA (1997)

Dr Emanuel is surely correct to observe that American medicine must "use its influence to promote a universal health care system" in the United States. Since this nation has decided to rely on free-market approaches in the provision of services, we maintain that free-market medicine is not moral medicine until universal access is secured. Exactly how that goal is to be attained in the context of market-based medicine is open to debate. That it is the central feature of what makes a medical system a moral one is not.
High dose interleukin-2 registry, PROCLAIM™; higher center-specific IL-2 dose density correlates with higher response rates
Authors: Michael K Wong, Gregory A Daniels, Howard L Kaufman, David F McDermott, Michael A Morse, Sandra Aung, James N Lowder
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts High dose interleukin-2 (Proleukin®) is an FDA-approved treatment for metastatic melanoma (mM) and renal cell carcinoma (mRCC) that consistently delivers durable CRs in up to 10% of patients. PROCLAIM™ is a HD IL-2 observational database that was initiated in 2011 to capture
In vivo evidence for apoptosis in the bone marrow in systemic lupus erythematosus
Authors: A. L Hepburn, I. A Lampert, J. J Boyle, D. Horncastle, W F. Ng, M. Layton, T. J Vyse, M. Botto, J. C Mason
Journal: Annals of the Rheumatic Diseases (2007)

An increase in leucocyte apoptosis and impaired clearance of apoptotic cells has been observed in patients with systemic lupus erythematosus (SLE). Apoptotic cells are likely to be a key source of autoantigens in SLE as they express many of the nuclear autoantigens (in surface blebs and apoptotic bodies) that are relevant to this disease. The clearance of apoptotic cells is usually a rapid process, such that few cells are usually seen in the extracellular environment <i>in vivo</i>. We report a case in which multiple apoptotic bodies were observed in the bone marrow of a patient with SLE that was complicated by an immune-mediated pancytopenia. We have subsequently examined the frequency of apoptotic cells, identified morphologically, and by caspase-3 staining in bone-marrow trephine samples taken from patients with SLE over a 10-year period of follow-up. A high proportion of bone marrows contained apoptotic debris. The novel demonstration of apoptotic bodies <i>in vivo</i> in patients with SLE is unusual and supports the notion that the marrow may be a target organ in the disease. Their abundance is also consistent with the hypothesis that normal clearance mechanisms are defective and/or overwhelmed in SLE.
Lentil Aspiration Pneumonia
Authors: Pablo R. Ros
Journal: JAMA (1984)

To the Editor.—Report of a Case.—  A 14-year-old boy housed at a special educational school had had cerebral palsy since birth and psychosis that deepened with adolescence. This patient was admitted with respiratory distress, fever, and cough, as well as anemia. On admission, a chest roentgenogram (Fig 1) was taken. After aggressive antibiotic therapy, the radiographic abnormalities were still present. To establish a definitive diagnosis, the patient underwent open-lung biopsy. Postsurgically, he suffered an acute bout of respiratory distress with cardiac arrest and died four weeks after admission.  On the admission chest roentgenogram there was a bright, fine interstitial nodular pattern, diffusely distributed over the pulmonary parenchyma with miliary characteristics (Fig 1). The open-lung biopsy disclosed a chronic granulomatous pneumonia secondary to aspiration of food, primarylegumen pulse.  A postmortem examination revealed a confluent nodular pneumonia in both lungs, pathologically characteristic of lentil aspiration pneumonia.  Comment.—  Lentil pneumonia is a
Bone Marrow–Derived Cells Contribute to Vascular Inflammation but Do Not Differentiate Into Smooth Muscle Cell Lineages
Authors: Hiroshi Iwata, Ichiro Manabe, Katsuhito Fujiu, Tetsufumi Yamamoto, Norifumi Takeda, Kosei Eguchi, Akiko Furuya, Makoto Kuro-o, Masataka Sata, Ryozo Nagai
Journal: Circulation (2010)

It has been proposed that bone marrow-derived cells infiltrate the neointima, where they differentiate into smooth muscle (SM) cells; however, technical limitations have hindered clear identification of the lineages of bone marrow-derived "SM cell-like" cells.Using a specific antibody against the definitive SM cell lineage marker SM myosin heavy chain (SM-MHC) and mouse lines in which reporter genes were driven by regulatory programs for either SM-MHC or SM α-actin, we demonstrated that although some bone marrow-derived cells express SM α-actin in the wire injury-induced neointima, those cells did not express SM-MHC, even 30 weeks after injury. Likewise, no SM-MHC(+) bone marrow-derived cells were found in vascular lesions in apolipoprotein E(-/-)mice or in a heart transplantation vasculopathy model. Instead, the majority of bone marrow-derived SM α-actin(+) cells were also CD115(+)CD11b(+)F4/80(+)Ly-6C(+), which is the surface phenotype of inflammatory monocytes. Moreover, adoptively transferred CD11b(+)Ly-6C(+) bone marrow cells expressed SM α-actin in the injured artery. Expression of inflammation-related genes was significantly higher in neointimal subregions rich in bone marrow-derived SM α-actin(+) cells than in other regions.It appears that bone marrow-derived SM α-actin(+) cells are of monocyte/macrophage lineage and are involved in vascular remodeling. It is very unlikely that these cells acquire the definitive SM cell lineage.
Professional and popular views of chronic fatigue syndrome
Authors: G MacLean, S Wessely
Journal: BMJ (1994)

Objective : To study the coverage of the chronic fatigue syndrome in the popular and professional press. Design : Search of all original research papers on the chronic fatigue syndrome published in British journals from 1980 onwards and of professional trade papers, national newspapers, and women's magazines. Interviews with six medical journalists. Setting : British scientific, medical, and popular press. Results : 37 (49%) articles in research journals did not favour organic causes and 23 (31%) favoured organic causes. By contrast 31 (55%) articles in the medical trade press and 118 (69%) in national newspapers and women's magazines favoured organic causes. Conclusions : Press coverage of chronic fatigue syndrome has amplified and distorted divisions in the research community concerning the chronic fatigue syndrome. Articles in the press concentrate on a simple medical model of illness reinforcing the stigma of psychological illness and dissatisfaction with traditional medical authority.
Effectively Costing Out Options
Authors: Jeanette M. Smith
Journal: JAMA (1996)

Physicians who received medical training during the early days of Medicare may recall when patients with newly diagnosed uncomplicated diabetes and hypertension were admitted for leisurely workups. Disputing the attending physician's decision to transfer a patient to the intensive care unit for "observation" may have succeeded only in incurring his or her warth—the issue of cost was seemingly irrelevant at the time. Cost-effectiveness not taught on rounds. See also p 1172. That medical education milieu likely did not preprare many of today's clinicians for making decisions about medical care costs, and caring for patients' needs more appropriately the physician's first concern. How infuriating it is to have expended considerable mental and emotional resources in a difficult case, only to be second-suggestand badgered about the cost by an insurance company or utilization reviewer. However, the reality is that cost has to be dealt with. For example, based onrojections put forth by federal analysts, Peterson<sup>1</sup>suggests that if program operations continue as currently, by the year 2030, there will be a combined cash deficit of $1.7 trillion for Medicare Hospital Insurance and Social Security.
THE COUNCIL ON PHYSICAL MEDICINE AND REHABILITATION
Authors: Ralph E. De Forest
Journal: JAMA (1952)

A resolution passed by the House of Delegates of the American Medical Association in 1925 empowered the Board of Trustees to appoint a council on "'nonmedicinal agents' similar to the Council on Pharmacy and Chemistry."<sup>1</sup>The council appointed by the Board of Trustees was originally named the Council on Physical Therapy. At its first meeting, on Oct. 16, 1925, the following members were present: Drs. W. R. Bovie, Boston, biophysicist; Arthur Compton, Chicago, physicist; Ralph Pemberton, Philadelphia, internist; Harry E. Mock, Chicago, surgeon and the Council's first Chairman; George Miller MacKee, New York, dermatologist; Arthur U. Desjardins, Rochester, Minn., radiologist; A. S. Warthin, Ann Arbor, Mich., pathologist; Francis Carter Wood, New York, pathologist; and Walter B. Cannon, Boston, physiologist.<sup>1</sup> In 1944, the name was changed to the Council on Physical Medicine because this was a more inclusive term and, as stated in an editorial inThe Journal,<sup>2</sup>because