tbuckley/cabot-search huggingface dataset:
The degree of natural allergen exposure modifies eosinophil activity markers in the circulation of patients with mild asthma
Authors: E. Fernvik, R. Grönneberg, J. Lundahl, J. Hed, O. Andersson, S. G. O. Johansson, G. Halldén
Journal: Allergy (1996)

We have previously found that CD9, CD11b, and intracellular ECP (EG2) may be used as activity markers for eosinophils in vitro. The main object of the present study was to determine whether these markers can reflect eosinophil activation in vivo in relation to allergen exposure. for this purpose, six patients with a history of allergic rhinitis and occasional asthma symptoms during the pollen season participated. Blood donors served as controls. Peripheral blood eosinophils were analyzed according to the FOG method and flow cytometry, before and during one birch pollen season with high pollen load (HPL) and one with low pollen load (LPL). The CD9 expression on peripheral eosinophils from the patients was significantly increased both before (P < 0.05) and during (P < 0.01) HPL season, and CD11b expression solely during HPL season (P = 0.01) as compared to controls. The intracellular expression of the EG2 epitope was increased before (P < 0.01) and during (P < 0.05) HPL season, and increased significantly (P < 0.05) during season as compared to before. No changes were observed before and during LPL season. The proportion of eosinophils was increased both before (P < 0.05) and during (P < 0.001) the HPL season as compared to controls. The markers CD9, EG2, and, to a lesser extent, CD11b seem to detect activated eosinophils in the circulation, whereas EG2 may also reflect increased antigen exposure during season.
Prognostic value of brain natriuretic peptide in the management of patients receiving cardiac resynchronization therapy
Authors: Maria Vittoria Pitzalis, Massimo Iacoviello, Francesca Di Serio, Roberta Romito, Pietro Guida, Elisabetta De Tommasi, Giovanni Luzzi, Matteo Anaclerio, Lucia Varraso, Cinzia Forleo, Nicola Pansini
Journal: European Journal of Heart Failure (2006)
A CASE OF PAPYRACEOUS FETUS
Authors: J. L. Mills
Journal: JAMA (1923)

A woman, aged 38, housewife, well developed and well nourished, now in her fourth pregnancy, gave a negative family history, with no record of multiple pregnancies on either side of the family. The youngest child was 7 years old. The last menstruation was on July 15. For the first three months, the patient was nauseated in the morning and vomited occasionally. Other than that, she felt perfectly well during the entire course of her pregnancy. At no time did she have any bloody vaginal discharge or excessive leukorrhea. Quickening occurred, November 23, and from then on, fetal movement was felt every day. Examination, February 5, showed the fundus half way between the umbilicus and the ensiform cartilage. The posi
France proposes overhaul of drug regulatory system
Authors: P. Benkimoun
Journal: BMJ (2011)

The French Ministry of Health has initiated a national consultation to overhaul the regulation of prescription drugs, after the very critical first report by the national drug agency into the appetite suppressant benfluorex (marketed in France as Mediator).

The ministry launched a public investigation last year into how the drug, which was withdrawn in 2009 and has been linked to around 500 deaths, remained on the market for more than 30 years ( BMJ 2010;341:c6882, doi:10.1136/bmj.c6882). 

The consultation, which will continue until the end of May, includes six working groups representing different stakeholders. Participants are expected to make proposals on the assessment, monitoring, use, and promotion of drugs.

At the same time the independent drug review journal Prescrire has published 57 recommendations on how to improve the …
THE USE OF SPINAL ANESTHESIA IN UROLOGY
Authors: ARTHUR L. CHUTE
Journal: JAMA (1931)

At a meeting of this section held in St. Louis in 1922, I presented a paper entitled "Spinal Anesthesia in Prostatectomy." In reading over that paper I am surprised and, I will confess, rather chagrined, to find that my use of spinal anesthesia has not materially changed, so far as the great essentials go, in the interval that has elapsed. In the first place I must state that perhaps my title is a little misleading in that I have never used spinal anesthesia for kidney operations but have confined my use of it to operations on the lower part of the urinary tract. My reason for this is that to me the special indication for spinal anesthesia is the great susceptibility to injury from the use of inhalation anesthesia, especially ether, that comes when both kidneys have been, for a considerable time, subjected to urinary back pressure; this condition usually
Cytotoxic T cells both produce and respond to interleukin 2
Authors: L Andrus, A Granelli-Piperno, E Reich
Journal: The Journal of Experimental Medicine (1984)

Interleukin 2 (IL-2) is a T cell-derived lymphokine that serves as a cofactor for the in vitro response of T lymphocytes to antigen and plays an important role in regulating the growth and/or differentiation of these cells (1, 2). It has been postulated (2, 3) that IL-2 is produced by a discrete regulatory T cell subset, with its effects being exerted on a second, functionally distinct subpopulation of T cells. Cytotoxic T cells have been included in the IL-2-responsive subset (3). Several models of immune regulation have further assumed that the T lymphocyte pool is divided into a complex array of genetically preprogrammed T cell subtypes, each performing a specific regulatory or effector function (4, 5). However, recent results from several laboratories (6-8) have failed to support such a strict functional subdivision of the T cell pool. The availability of highly purified mouse IL-2 (1) prompted us to reevaluate the distinction, if any, between IL-2-producing and IL-2- responsive T cells. For this purpose, we resorted to a cell-cloning procedure using activated T lymphocytes that were maintained only for short periods in culture. T cell clones were tested for cytotoxic activity, responsiveness to IL-2, and for the capacity to produce IL-2 after appropriate stimulation. We found no evidence for the existence of a major functional subdivision involving these parameters among alloantigen-activated T cells: the majority of clones analyzed could perform all three functions.
Deep venous thrombosis and occult malignancy: an epidemiological study
Authors: M Nordstrom, B Lindblad, H Anderson, D Bergqvist, T Kjellstrom
Journal: BMJ (1994)

To determine the risk of subsequent cancer in patients with deep venous thrombosis confirmed by venography.Follow up of all patients who had venography for suspected deep venous thrombosis during 1984-88. Patients were traced through a cancer registry up to 1 January 1991.4399 patients who had phlebography in one hospital.General hospital in Malmö, Sweden, serving a population of 230,000.Number of cancers recorded.4399 patients had venography for suspected deep venous thrombosis; 604 were known to have a malignancy at the time of venography and were excluded from further analysis. 1383 had deep venous thrombosis, 150 of whom subsequently developed cancer. 182 of the 2412 patients without thrombosis developed cancer. During the first six months after venography 66 patients with thrombosis developed malignancy compared with 37 patients without thrombosis (P < 0.0001). 38 of the cancers in the deep venous thrombosis group were detected by history, physical examination, and laboratory tests. Three patients had postoperative or post-traumatic deep venous thromboses. Only two of the remaining patients would have benefited from early detection by extensive screening. After six months the incidence of cancer was identical in patients with and without thrombosis.Deep venous thrombosis is associated with a significantly higher frequency of malignancy during the first six months after diagnosis. Malignancies can be found with simple clinical and diagnostic methods and extensive screening is not required.
Relationship between the angiotensin-converting enzyme genotype and the forearm vasodilator response to estrogen replacement therapy in postmenopausal women
Authors: Mitsuhiro Sanada, Yukihito Higashi, Keigo Nakagawa, Shota Sasaki, Ichiro Kodama, Mikio Tsuda, Nobutaka Nagai, Koso Ohama
Journal: Journal of the American College of Cardiology (2001)
European Perspective on the Costs and Cost-Effectiveness of Cancer Therapies
Authors: Michael F. Drummond, Anne R. Mason
Journal: Journal of Clinical Oncology (2007)

In Europe, the vast majority of the costs of cancer therapy fall on third-party payers, normally the government, or sickness funds. Therefore, the main focus of cost-effectiveness studies is to assist payers in deciding whether new therapies are worthwhile, despite their high cost. Drug budgets are regulated in most European countries. The main form of central control is price setting, with some form of reference pricing being the most common approach. This sets the price of drugs, either to an international standard, or to a common price for drugs in the same group or cluster. At the hospital level, the main control over cancer drugs is the hospital formulary. Studies have shown a wide variation among European countries in access to cancer drugs. Explanations for these variations include differences in research funding, the drug approval process, the role of health economics in decision making, and budgetary issues. Several countries in Europe now require economic data in making decisions about the reimbursement of new drugs. An examination of decisions made by the National Institute for Health and Clinical Excellence in the United Kingdom suggests that cancer drugs have fared quite well, with most recommendations being positive. This could be because of the seriousness of the health condition and the lack of alternative therapies for some cancer patients. If the policy of requesting cost-effectiveness evidence for pricing and reimbursement decisions becomes more popular, a major implication for the pharmaceutical industry is that studies should be conducted during phase III of clinical development to generate the required data.
CLINICAL EFFECTS OF INTRODUCING HIGH SENSITIVE CARDIAC TROPONIN T INTO CLINICAL PRACTICE: DATA FROM 48,594 PATIENTS IN THE SWEDEHEART REGISTRY
Authors: Dina Melki, Per Johanson, Johan Lugnegård, Joakim Alfredsson, Suzanne Lind, Kai M. Eggers, Bertil Lindahl, Tomas Jernberg
Journal: Journal of the American College of Cardiology (2014)
Recurrent <i>PRDM10</i> Gene Fusions in Undifferentiated Pleomorphic Sarcoma
Authors: Jakob Hofvander, Johnbosco Tayebwa, Jenny Nilsson, Linda Magnusson, Otte Brosjö, Olle Larsson, Fredrik Vult von Steyern, Nils Mandahl, Christopher D.M. Fletcher, Fredrik Mertens
Journal: Clinical Cancer Research (2014)

Undifferentiated pleomorphic sarcoma (UPS) is defined as a sarcoma with cellular pleomorphism and no identifiable line of differentiation. It is typically a high-grade lesion with a metastatic rate of about one third. No tumor-specific rearrangement has been identified, and genetic markers that could be used for treatment stratification are lacking. We performed transcriptome sequencing (RNA-Seq) to search for novel gene fusions.RNA-Seq, FISH, and/or various PCR methodologies were used to search for gene fusions and rearrangements of the PRDM10 gene in 84 soft tissue sarcomas.Using RNA-Seq, two cases of UPS were found to display novel gene fusions, both involving the transcription factor PRDM10 as the 3' partner and either MED12 or CITED2 as the 5' partner gene. Further screening of 82 soft tissue sarcomas for rearrangements of the PRDM10 locus revealed one more UPS with a MED12/PRDM10 fusion. None of these genes has been implicated in neoplasia-associated gene fusions before.Our results suggest that PRDM10 fusions are present in around 5% of UPS. Although the fusion-positive cases in our series showed the same nuclear pleomorphism and lack of differentiation as other UPS, it is noteworthy that all three were morphologically low grade and that none of the patients developed metastases. Thus, PRDM10 fusion-positive sarcomas may constitute a clinically important subset of UPS.
Abstract B41: Thymoquinone induces-cell cycle non-specific-cell death in cisplatin-resistant ovarian cancer cell through up-regulation of PTEN expression
Authors: El-Shaimaa A. Arafa, Altaf A. Wani
Journal: Clinical Cancer Research (2012)

Abstract Ovarian carcinoma is one of the most prevalent and lethal gynecological malignancies, and is the fifth leading cause of cancer death among women in the United Stat. Like most malignancies, ovarian cancer is a heterogeneous disease characterized by multiple molecular alterations. These include loss of function of tumor suppressor genes, deregulation of Bcl-2 family proteins, inhibition of caspase activation, and activation of cellular survival signaling pathways, such as HER-2/neu and phosphatidylinositol-3 kinase PI3K/Akt. Over years the use of natural compounds as anticancer agents acquired great importance. Thymoquinone (TQ) is the main bioactive component of the volatile oil of the black seed (Nigella sativa, Ranunclulaceae family). TQ has been used as antioxidant, anti-inflammatory, and antineoplastic medicines for more than 2,000 years. Previous studies reported that TQ exhibited inhibitory effects on cell proliferation of many types of cancer cell lines, including breast adenocarcinoma, lung adenocarcinoma, colorectal cancer, etc. Here, we report that TQ greatly inhibited cell proliferation of cisplatin-resistant ovarian cancer cells (A2780/CP70) 24, 48 and 72 hours after treatment in a concentration-dependent manner. However, our flow cytometry data revealed that TQ is a cell cycle non-specific for CP70 cells. Our results also showed that TQ upregulated PTEN and p53 in CP70 cells while downregulated phospho-Akt in a dose-dependent manner. Current investigations are ongoing to fully understand the mechanism of action of TQ in cisplatin-resistant ovarian cancer cells.
Messenger RNA expression and synthesis of endothelin-1 along rat nephron segments.
Authors: K Ujiie, Y Terada, H Nonoguchi, M Shinohara, K Tomita, F Marumo
Journal: Journal of Clinical Investigation (1992)

The kidney both produces and responds to endothelin. We examined the production and the expression of mRNA of endothelin-1 (ET-1) in tubule suspensions and microdissected nephron segments. ET-1 production was measured by RIA using an ET-1-specific antibody. We applied the reverse transcription and polymerase chain reaction (PCR) technique to detect ET-1 mRNA along the nephron segments. Stimulation of ET-1 production was observed in the presence of FCS and transforming growth factor-beta (TGF-beta) in inner medullary tubules but not in cortical or outer medullary tubule suspensions. Among dissected nephron segments, ET-1 production was observed in glomeruli and inner medullary collecting ducts (IMCD), whereas it was negligible in proximal convoluted tubules (PCT) and medullary thick ascending limbs (MAL). In addition, the PCR product of ET-1 mRNA was also higher in glomeruli and IMCD, whereas it was undetectable in PCT and MAL. Furthermore, FCS and TGF-beta increased ET-1 mRNA in microdissected glomeruli and IMCD. These data clearly demonstrated that the production sites of ET-1 are glomeruli and IMCD among the nephron segments. ET-1 is an autocrine factor in these sites.
Ultraconservation identifies a small subset of extremely constrained developmental enhancers
Authors: Axel Visel, Shyam Prabhakar, Jennifer A Akiyama, Malak Shoukry, Keith D Lewis, Amy Holt, Ingrid Plajzer-Frick, Veena Afzal, Edward M Rubin, Len A Pennacchio
Journal: Nature Genetics (2008)
Cardiologists Broaden Use of Stents
Authors: Marsha F. Goldsmith
Journal: JAMA (1997)

STENTING IS A wide-open field. Implanting minute metallic mesh expandable cages to keep coronary arteries patent "is one of the hottest things in cardiology right now," agreed numerous speakers at the 69th Scientific Sessions of the American Heart Association (AHA), held in New Orleans, La. And even as many cardiologists are documenting the ways in which stents provide what one called "a smoother ride" for patients with plaque-prone arteries, others are experimenting with newer models, improved placement methods, and adjunct therapies. In the 2 years since the Food and Drug Administration (FDA) gave the go-ahead to the Palmaz-Schatz stent (made by Johnson &amp; Johnson, New Brunswick, NJ) —the first and so far only stent approved for use in the United States—the percentage of postangioplasty patients in whom the device is used has risen from approximately 9% to 39%, said Daniel B. Mark, MD, MPH, director of the Outcomes Research
Incidence and Prevalence of Childhood Diabetes in Slovakia (1985–1992)
Authors: Dagmar M Michalková, Jozef Černay, Anna Danková, Martin Rusnák, Katarína Fandáková
Journal: Diabetes Care (1995)

OBJECTIVE To provide reliable data on the incidence and prevalence of insulin–dependent diabetes mellitus (IDDM) in children in Slovakia. RESEARCH DESIGN AND METHODS A total of 754 Slovak children with IDDM, aged 0–14 years, were identified during an 8-year study period. There were 369 boys and 385 girls from an average population of 1,363,499 children. All patients were prospectively recorded. The primary ascertainment was based on notifications by physicians from outpatient departments. The second independent source of information was from all hospitals where the diabetic patients were hospitalized. The completeness of ascertainment was based on the capture-recapture procedure. RESULTS The completeness of the ascertainment was 95%. In 1992, the annual incidence rate of IDDM (per 100,000) in the 0- to 14-year-old age-group was 8.92 for both sexes (7.95 for boys and 9.93 for girls). In the youngest age-group, an increase in the incidence rates from 2.89 in 1985 to 6.54 in 1992 was observed. Seasonality, with a higher incidence in autumn and winter, was observed in children older than 4 years. The prevalence rates of IDDM (per 1,000) were 0.28–0.50% in the 8-year period. CONCLUSIONS The incidence of IDDM in Slovak children (0–14 years) is similar to what has been found in other Central European countries. In children younger than 4 years of age, in the last 2 years (1991 and 1992) more patients with diabetes were found than in any period during the preceding 6 years. The recent conspicuous increase in the incidence of IDDM among the younger children in Slovakia urges us to study its mechanisms, so far unknown, and to search for possible means of prevention.
1185 ELTROMBOPAG IN CHRONIC LIVER DISEASE PATIENTS WITH THROMBOCYTOPENIA UNDERGOING AN ELECTIVE INVASIVE PROCEDURE: RESULTS FROM ELEVATE, A RANDOMISED CLINICAL TRIAL
Authors: N. Afdhal, E. Giannini, G.N. Tayyab, A. Mohsin, J.W. Lee, A. Andriulli, L. Jeffers, J. McHutchison, F. Campbell, N. Blackman, D. Hyde, A. Brainsky, D. Theodore
Journal: Journal of Hepatology (2010)
Clinical Trial Transparency — Antidote to Weaker Off-Label-Promotion Rules?
Authors: Kevin Outterson
Journal: New England Journal of Medicine (2014)

Interview with Professor Kevin Outterson on the FDA’s guidance on off-label promotion and the move toward clinical trial transparency. (09:14)Download As the FDA's regulatory authority is weakened by challenges from drug companies claiming that restrictions on off-label promotion violate their First Amendment rights, the need for clinical trial transparency becomes more urgent.
Resident Research in Internal Medicine Training Programs
Authors: Patrick C. Alguire
Journal: Annals of Internal Medicine (1996)

Objective: To determine how well medical residency programs are prepared to meet the new Accreditation Council of Graduate Medical Education (ACGME) accreditation guidelines for resident scholarly activity. Design: Cross-sectional study using a mailed survey. Participants: Program directors of all ACGME-accredited internal medicine residency programs. Measurements: Program directors were asked to list the scholarly activities and products of their residents and their programs' minimal expectations for resident research; available academic, faculty, technical, and personnel support for resident research; perceived barriers to resident research; and the desired educational and skill outcomes of resident research. The responses of university-based training programs were compared with those of non-university-based programs. Results: 271 program directors returned the survey, yielding a response rate of 65%. Ninety-seven percent of all programs have established scholarly guidelines consistent with accreditation requirements. Although only 37% of programs reported having an organized, comprehensive research curriculum, 70% taught skills important to research. Technical support and resources were generally available for resident research; the most frequently cited barrier to resident research was lack of resident time. University-based and non-university-based training programs differed in important ways. Generally, non-university-based programs had more research activity and structure, and they exceeded university-based programs in the number of oral and poster presentations given at local, state, and national professional meetings. Conclusions: Most programs have in place the basic elements conducive to resident research. Program directors have identified and teach educational outcomes and skills that are likely to have lifelong benefits for most of their graduates.
Review: Self-collected samples are less accurate for HPV testing than clinician-collected samples
Authors: David A. Frank, Jeanne Marrazzo
Journal: Annals of Internal Medicine (2014)

Source Citation Arbyn M, Verdoodt F, Snijders PJ, et al. Accuracy of human papillomavirus testing on self-collected versus clinician-collected samples: a meta-analysis. Lancet Oncol. 2014;15:172-83. 24433684
Pioglitazone Reduces Atherogenic Dense LDL Particles in Nondiabetic Patients With Arterial Hypertension
Authors: Karl Winkler, Thomas Konrad, Stefanie Füllert, Isolde Friedrich, Ramadan Destani, Manfred W. Baumstark, Kristin Krebs, Heinrich Wieland, Winfried März
Journal: Diabetes Care (2003)

OBJECTIVE—The oral antidiabetic agent pioglitazone improves insulin sensitivity and glycemic control and appears to lower atherogenic dense LDL in type 2 diabetes. Insulin resistance may occur frequently in nondiabetic patients with hypertension. This study is the first to report the effect of pioglitazone on LDL subfractions in normolipidemic, nondiabetic patients with arterial hypertension. RESEARCH DESIGN AND METHODS—We performed a monocentric, double-blind, randomized, parallel-group comparison of 45 mg pioglitazone (n = 26) and a placebo (n = 28), each given once daily for 16 weeks. Fifty-four moderately hypertensive patients (LDL cholesterol, 2.8 ± 0.8 mmol/l; HDL cholesterol, 1.1 ± 0.3 mmol/l; triglycerides, 1.4 mmol/l (median; range 0.5–7.1) were studied at baseline and on treatment. RESULTS—At baseline, dense LDLs were elevated (apolipoprotein [apo]B in LDL-5 plus LDL-6 &amp;gt;250 mg/l) in 63% of all patients. Sixteen weeks of treatment with pioglitazone did not significantly change triglycerides, total, LDL, and HDL cholesterol. However, pioglitazone reduced dense LDLs by 22% (P = 0.024). The mean diameter of LDL particles increased from 19.83 ± 0.30 to 20.13 ± 0.33 nm (P &amp;lt; 0.001 vs. placebo), whereas the mean LDL density decreased from 1.0384 ± 0.0024 to 1.0371 ± 0.0024 kg/l (P = 0.005 vs. placebo). The effect of pioglitazone on LDL size and density was independent of fasting triglycerides and HDL cholesterol at baseline and of changes in fasting triglycerides and HDL cholesterol. CONCLUSIONS—The prevalence of atherogenic dense LDL in nondiabetic, hypertensive patients is similar to patients with type 2 diabetes. Pioglitazone significantly reduces dense LDL independent from fasting triglycerides and HDL cholesterol. The antiatherogenic potential of pioglitazone may thus be greater than that expected from its effects on triglycerides, LDL, and HDL cholesterol alone.