tbuckley/cabot-search huggingface dataset:
Treatment of refractory obesity with fenfluramine.
Authors: J. F. Munro, D. A. Seaton, L. J. Duncan
Journal: BMJ (1966)

Fenfluramine hydrochloride (Ponderax) is a recently marketed appetite-depressant.Although it has some chemical resem- blance to the amphetamines, it is not metabolized by the body to produce amphetamine and is excluded from the Drugs (Pre- vention of Misuse) Act, 1964.We report the results of a 12- weeks double-blind clinical trial of this drug in a group of women having refractory obesity. Materials and MethodsThe 60 women who started the trial were mostly middle- aged housewives, none of whom had oedema or were known to have any cardiac disorder.All were clinically obese, over- weight by at least 20% of their standard (U.S.A. Medico- Actuarial Investigation, 1912), and had " refractory obesity " as previously defined (Duncan et al., 1960).Thus they had regularly attended the Diabetic and Dietetic Department during the previous year for dietetic advice and supervision, but had not lost weight appreciably in the three months before the study or taken any anorectic drug in the previous six months.The patients were matched by age, standard weight, and excess weight to form two comparable groups.By chance 25 subjects in each group completed the study, and Table I sets out their relevant data.TABLE I.-Mean Figures and Range for the 50 the 12-Week Trial Patients who Completed Group A Group B (Fenfluramine) (Dummy) 25 Patients 25 PatientsAge (years) ..49-3 (22 to 72) 49-6 (25 to 66) Weight at start (lb.) ..
New centre is set up to promote evidence based surgery in the United Kingdom
Authors: Zosia Kmietowicz
Journal: BMJ (2004)

What is thought to be the world's first centre to help coordinate clinical trials into surgical interventions opened this week in the United Kingdom.

The de Lotbiniere Facial Surgery Research Centre is the brainchild of Mr Iain Hutchison, consultant in oral and maxillofacial surgery at St Bartholomew's Hospital and the Royal London Hospital.

The centre aims to stimulate research and provide rapid answers to important questions about the value of surgical techniques for treating conditions affecting the mouth and face. Unlike drug interventions, surgical treatments—:for a number of reasons—:are rarely covered by randomised trials, said Mr Hutchison,

One of the problems is that surgeons tend to work on their …
Urokinase Receptor Counteracts Vascular Smooth Muscle Cell Functional Changes Induced by Surface Topography
Authors: Yulia Kiyan, Kestutis Kurselis, Roman Kiyan, Hermann Haller, Boris N. Chichkov, Inna Dumler
Journal: Theranostics (2013)

Current treatments for human coronary artery disease necessitate the development of the next generations of vascular bioimplants.Recent reports provide evidence that controlling cell orientation and morphology through topographical patterning might be beneficial for bioimplants and tissue engineering scaffolds.However, a concise understanding of cellular events underlying cell-biomaterial interaction remains missing.In this study, applying methods of laser material processing, we aimed to obtain useful markers to guide in the choice of better vascular biomaterials.Our data show that topographically treated human primary vascular smooth muscle cells (VSMC) have a distinct differentiation profile.In particular, cultivation of VSMC on the microgrooved biocompatible polymer E-shell induces VSMC modulation from synthetic to contractile phenotype and directs formation and maintaining of cell-cell communication and adhesion structures.We show that the urokinase receptor (uPAR) interferes with VSMC behavior on microstructured surfaces and serves as a critical regulator of VSMC functional fate.Our findings suggest that microtopography of the E-shell polymer could be important in determining VSMC phenotype and cytoskeleton organization.They further suggest uPAR as a useful target in the development of predictive models for clinical VSMC phenotyping on functional advanced biomaterials.
BICHLORID OF MERCURY IN THE TREATMENT OF DIPHTHERIA.Read in the Section on Laryngology and Otology, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: CHARLES F. McGAHAN
Journal: JAMA (1893)

I wish to call attention to the treatment of diphtheria by the bichlorid of mercury, not that I regard it as a specific in the disease, for I am sure that all of us who have had much experience with this most treacherous malady will agree with me that there is no such thing as a specific for it. Various modes of treatment have been followed by me, and frequently with such success in different epidemics that I felt on several occasions I had found a cure, but each time my hopes were crushed by having the treatment fail entirely in the next series of cases which fell under my observation. I have made this statement so that all can see that I am not reviving this treatment, in the expectation of having it considered a "cure-all" for the disease, but simply because I believe that if the profession would
Living donor liver transplantation for early hepatocellular carcinoma: A life-expectancy and cost-effectiveness perspective
Authors: F Sarasin
Journal: Hepatology (2001)

Cadaveric liver transplantation (CLT) is an excellent treatment for early hepatocellular carcinoma (HCC). Its use, however, is limited by the shortage of grafts, with up to 30% of patients developing contraindications to the procedure while waiting for a donor. Living donor liver transplantation (LDLT) has emerged as an alternative to overcome this limitation. We compared the consequences of LDLT versus CLT using a Markov model balancing the gains and losses in life expectancy among donors and recipients. For a 60-year-old recipient with a 70% 5-year survival after transplantation, a 4% monthly drop-out rate, and a donor with 1% mortality, LDLT became more effective than CLT after 3.5 months on the waiting list. These results varied with the probability of developing contraindications to transplantation, the survival after transplantation, and the donor's mortality. For a 12-month delay saved on the waiting list, the gain in survival provided by LDLT compared with CLT ranged between 0 and 2.8 life years depending on survival after transplantation, time spent on the waiting list, and drop-out rate. LDLT was cost-effective (less than $50,000 per quality-adjusted life year saved) in all scenarios of waiting lists exceeding 7 months, and this figure ranged from 2 to 16 months when varying the drop-out rate. LDLT for early HCC offered substantial gains in life expectancy with acceptable cost-effectiveness ratios when the waiting list exceeds 7 months. The gain in life expectancy and the cost-effectiveness of LDLT were more dependent on the drop-out rate and the outcome after transplantation than on donor's mortality.
NLRR1 Enhances EGF-Mediated <i>MYCN</i> Induction in Neuroblastoma and Accelerates Tumor Growth <i>In Vivo</i>
Authors: Shamim Hossain, Atsushi Takatori, Yohko Nakamura, Yusuke Suenaga, Takehiko Kamijo, Akira Nakagawara
Journal: Cancer Research (2012)

Neuronal leucine-rich repeat protein-1 (NLRR1), a type-1 transmembrane protein highly expressed in unfavorable neuroblastoma, is a target gene of MYCN that is predominately expressed in primary neuroblastomas with MYCN amplification. However, the precise biological role of NLRR1 in cell proliferation and tumor progression remains unknown. To investigate its functional importance, we examined the role of NLRR1 in EGF and insulin growth factor-1 (IGF-1)-mediated cell viability. We found that NLRR1 positively regulated cell proliferation through activation of extracellular signal-regulated kinase mediated by EGF and IGF-1. Interestingly, EGF stimulation induced endogenous MYCN expression through Sp1 recruitment to the MYCN promoter region, which was accelerated in NLRR1-expressing cells. The Sp1-binding site was identified on the promoter region for MYCN induction, and phosphorylation of Sp1 was important for EGF-mediated MYCN regulation. In vivo studies confirmed the proliferation-promoting activity of NLRR1 and established an association between NLRR1 expression and poor prognosis in neuroblastoma. Together, our findings indicate that NLRR1 plays an important role in the development of neuroblastoma and therefore may represent an attractive therapeutic target for cancer treatment.
What and where is the word?
Authors: Catherine McBride-Chang, Hsuan-Chih Chen, Benjawan Kasisopa, Denis Burnham, Ronan Reilly, Paavo Leppänen
Journal: Behavioral and Brain Sciences (2012)

Abstract Examples from Chinese, Thai, and Finnish illustrate why researchers cannot always be confident about the precise nature of the word unit. Understanding ambiguities regarding where a word begins and ends, and how to model word recognition when many derivations of a word are possible, is essential for universal theories of reading applied to both developing and expert readers.
Medical journals are corrupted by dependence on drug companies
Authors: Zosia Kmietowicz
Journal: BMJ (2005)

Medical journals are no more than “an extension of the marketing arm of pharmaceutical companies” because a large proportion of their revenue comes from drug advertisements and reprints of company funded trials, claims former BMJ editor, Richard Smith.

Dr Smith argues that although medical journals make a sizeable income from drug advertisements this is the least of their “corrupting form of dependence” on the industry since the advertisements are “there for all to see and criticize” ( PLoS Medicine 2005;2:e138; www.plosmedicine.org, doi: 10.1371/journal.pmed.0020138).

Dr Smith's strongest criticism is levelled at the fact that journals publish …
What sort of "health checks" for older people?
Authors: E G Buckley, J Williamson
Journal: BMJ (1988)

Cyclists need helmetsCycling has many attractions.It provides independence, needs no licence, has an extremely high mechanical efficiency, produces no pollution, and seldom causes injury to others.Injuries to riders are, however, all too common-about 300 deaths and over 5000 serious injuries in Britain annually.Pedal cycling is second only to motorcycling as the most dangerous form of travel per mile.The Transport and Road Research Laboratory has shown that many of the cycle accidents that include a second vehicle occur at T junctions, and often the cyclist is travelling straight ahead and therefore should have priority.'As the report states, "In over half of these accidents the other vehicle was turning, suggesting that a significant number of these vehicles either did not see the cycle, saw it but misjudged its speed, or saw it but unreasonably expected it to give way."Many injuries to cyclists could be prevented if other road users gave them a better opportunity to ride safely.For instance, stones and other rubbish tend to find their way into the sides of the road-but it is here that cyclists are often forced to ride by the bulk ofother vehicles.The bicycle wheel is particularly vulnerable to irregular surfaces, and the rider may easily be thrown off and injured.The speed of the cycle may contribute little to the impact, but the height of the fall from the riding position is important.Injuries to the head are an important cause of death and are present in about three quarters of seriously injured cyclists.In many accidents the cycle is struck by the front of a car, and experiments show that modifying the front ofcars to reduce their "aggressivity" to pedestrians also helps prevent serious injuries to cyclists.A recent study from a large accident and emergency
Ireland fears blood shortage with new ban on donors
Authors: D. Payne
Journal: BMJ (2001)

The board of the Irish Blood Transfusion Service will discuss at its next meeting whether it can go ahead with plans to ban blood donations—from this month—from anyone who spent a year in the United Kingdom between 1980 and 1996.

In March this year, in response to concerns about the dangers of patients contracting variant Creutzfeldt-Jakob disease (vCJD) from donated blood, the service banned donations from anyone who had spent five years in Britain, which led to a drop of 20% in blood supplies and growing concern …
Incidence of Trichinosis
Authors: Raymond E. Moldow
Journal: JAMA (1963)

To the Editor:—  In Facets of Trichinosis, an editorial in the April 6 issue ofThe Journal( 184 :56), it is stated that 1 of every 6 Americans harbors Trichinella spiralis .  A recent study (summer, 1962) conducted here at the University of Pittsburgh, in which 100 human diaphragm specimens were examined microscopically for T spiralis larvae, indicated that the prevalence of trichinosis may be considerably lower than has been suggested by prevalence studies conducted during the 1940's.  In the study mentioned, larvae were detected in five of the 100 specimens. This decreased prevalence of trichinosis is in part attributable to the use of grain or cooked garbage in the feeding of hogs, and also to thorough cooking of pork products by a better-informed public.
Membrane phenotype and response to deoxycoformycin in mature T cell malignancies.
Authors: C E Dearden, E Matutes, A V Hoffbrand, K Ganeshaguru, M Brozovic, H J Williams, N Traub, M Mills, D C Linch, D Catovsky
Journal: BMJ (1987)

The adenosine deaminase inhibitor deoxycoformycin was used in low doses to treat 19 patients with clinically aggressive T cell malignancy with a mature membrane phenotype. The patients comprised eight with prolymphocytic leukaemia, two with chronic lymphocytic leukaemia, four with adult T cell leukaemia-lymphoma, three with Sézary syndrome, and two with T cell lymphoma. Two thirds of the patients had been resistant or minimally responsive to combination chemotherapy. Complete remission was obtained in five patients (two with prolymphocytic leukaemia and one each with chronic lymphocytic leukaemia, adult T cell leukaemia-lymphoma, and Sézary syndrome) and partial remission in two others. Unmaintained complete remission lasting more than one year was seen in three patients. Responses were obtained only in patients with CD4+,CD8-membrane markers (seven out of 10), and no responses were recorded in any of the nine patients with a different phenotype. In this series remission appeared to correlate with the membrane phenotype of the neoplastic cell and not with the cytopathological diagnosis. Future studies should establish the biochemical basis for the greater sensitivity of CD4+ lymphoid cells to deoxycoformycin.
Heterosexual AIDS: Myth or Epidemic?
Authors: Stephen E. Godfrey
Journal: JAMA (1990)

To  Editor.—  Several observations by Dr Sherer about acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) transmission through heterosexual contact 1 are inaccurate.  He expresses concern that the continued slow but steady rise in heterosexually transmitted cases of AIDS in  United States has been represented as a  in Michael Fumento's recent book The Myth of Heterosexual AIDS . 2 An inference is made there that heterosexual cases of AIDS acquired through sexual contact are increasing disproportionately, although  latest statistics from  Centers for Disease Control hardly seem to show this. 3 Adult/adolescent cases of AIDS through heterosexual contact constitute only 5% of all US cases of AIDS to date and only 6% of those diagnosed in  last year. Fumento's book states that  myth is not that there is no heterosexual AIDS transmission but rather that there is epidemic heterosexual AIDS transmission, for which there
Napoleone Ferrara receives the 2010 Lasker~DeBakey Clinical Award for breakthroughs in angiogenesis research
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2010)

When Napoleone Ferrara was a medical student in Italy in the 1970s, he became interested in reproductive endocrinology. Although his training never specifically focused on angiogenesis, he is recognized today for shaping the field through the discovery of its core signaling molecule, VEGF, and for exploiting VEGF for the first successful clinical treatments of wet age-related macular degeneration (AMD) and cancer. On September 21, 2010, the Albert and Mary Lasker Foundation announced they will present Ferrara (Figure ​(Figure1)1) with the 2010 Lasker~DeBakey Clinical Medical Research Award for his work on VEGF, which led to an effective therapy for neovascular AMD. Ferrara spoke with the JCI about his journey from discovery to treatment. 



Figure 1

Napoleone Ferrara, winner of the 2010 Lasker~DeBakey Clinical Award.
Tumor necrosis factor α production by peripheral blood mononuclear cells of patients with chronic liver disease
Authors: Kentaro Yoshioka, Shinichi Kakumu, Motohiro Arao, Yasuhiko Tsutsumi, Masaki Inoue
Journal: Hepatology (1989)

We investigated the production of tumor necrosis factor α by peripheral blood mononuclear cells of patients with chronic liver disease and its association with hepatitis activity. Tumor necrosis factor α production was measured with an enzyme-linked immunosorbent assay. Tumor necrosis factor α production by peripheral blood mononuclear cells stimulated with recombinant γ-interferon of patients with chronic active hepatitis (5.8 ± 4.0 units per ml, p < 0.05) and patients with cirrhosis (4.1 ± 2.1 units per ml, p < 0.05) was significantly increased when compared with controls (2.5 ± 1.6 units per ml). Tumor necrosis factor α production by peripheral blood mononuclear cells stimulated with a combination of recombinant γ-interferon and recombinant interleukin 2 of patients with chronic persistent hepatitis (5.8 ± 3.8 units per ml, p < 0.05), patients with chronic active hepatitis (8.9 ± 3.0 units per ml, p < 0.001) and patients with cirrhosis (6.7 ± 3.2 units per ml, p < 0.05) was significantly increased in comparison with controls (3.3 ± 1.8 units per ml). Tumor necrosis factor α production of patients with chronic active hepatitis was significantly higher than that of patients with chronic persistent hepatitis ( p < 0.05). There was a significant correlation (r = 0.5699, p < 0.005) between tumor necrosis factor α production and histologic activity index in patients with chronic persistent hepatitis or chronic active hepatitis. These findings show that tumor necrosis factor α production is increased in chronic liver disease and that the increased tumor necrosis factor α production is related to hepatitis activity.
Increased expression of factor XIII-A in patients with chronic rhinosinusitis with nasal polyps
Authors: Tetsuji Takabayashi, Atsushi Kato, Anju T. Peters, Kathryn E. Hulse, Lydia A. Suh, Roderick Carter, James Norton, Leslie C. Grammer, Bruce K. Tan, Rakesh K. Chandra, David B. Conley, Robert C. Kern, Shigeharu Fujieda, Robert P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2013)
A new scalp formulation of calcipotriol plus betamethasone dipropionate compared with each of its active ingredients in the same vehicle for the treatment of scalp psoriasis: a randomized, double-blind, controlled trial
Authors: P.C.M. van de Kerkhof, V. Hoffmann, A. Anstey, L. Barnes, C. Bolduc, K. Reich, S. Saari, S. Segaert, L. Vaillant
Journal: British Journal of Dermatology (2008)

There is a need for new treatments for scalp psoriasis, as many topical treatments are cosmetically unacceptable and difficult to apply, resulting in poor compliance.To compare the efficacy and safety of a new, once-daily, two-compound scalp formulation (Xamiol; LEO Pharma A/S, Ballerup, Denmark) containing calcipotriol 50 microg g(-1) plus betamethasone 0.5 mg g(-1) (as dipropionate), with the active ingredients as single compounds in the same vehicle.This 8-week, multicentre, double-blind, parallel-group study, randomized adult patients with scalp psoriasis involving > 10% of the scalp to the two-compound scalp formulation (n = 568), betamethasone dipropionate 0.5 mg g(-1) (n = 563), or calcipotriol 50 microg g(-1) (n = 286). The primary efficacy measure was the proportion of patients with 'absence of disease' or 'very mild disease' according to investigators' assessments at week 8.The proportion of patients with 'absence of disease' or 'very mild disease' at week 8 was significantly higher in the two-compound group (68.4%) than the betamethasone dipropionate (61.0%, P = 0.0079) or calcipotriol (43.4%, P < 0.0001) groups. The proportion of patients rating their scalp psoriasis as 'clear' or 'almost clear' was significantly higher for the two-compound scalp formulation (69.6%) than for betamethasone dipropionate (59.9%, P = 0.0006) or calcipotriol (44.7%, P < 0.0001). The incidence of lesional/perilesional adverse events was lower in the two-compound and betamethasone dipropionate groups than the calcipotriol group.The two-compound scalp formulation was well tolerated and more effective in the treatment of scalp psoriasis than either of its individual components in the same vehicle.
Body Composition and Prevalence of Left Ventricular Hypertrophy
Authors: Bernhard Kuch, Hans-Werner Hense, Birgit Gneiting, Angela Döring, Michael Muscholl, Ulrich Bröckel, Heribert Schunkert
Journal: Circulation (2000)

Background —Fat-free mass (FFM) has been proposed as an optimal normalization of left ventricular (LV) mass to body size. We sought to evaluate the novel FFM-based criteria of LV hypertrophy (LVH). Methods and Results —A population sample of 1371 men and women aged 25 to 74 years was examined by echocardiography and bioelectrical impedance analysis. Internal partition values for LVH were generated in a healthy population subgroup on the basis of LV mass divided by FFM and by the traditional indexations to body height, height 2.7 , and body surface area. In contrast to the sex-specific criteria required by traditional indexations, the value of LV mass/FFM that divided individuals with and without LVH was identical for men and women (4.1 g/kg). Estimates of LVH prevalence varied significantly by type of indexation used, internally or externally derived cut points, and by population subgroups. Differences were pronounced among hypertensives and the obese. Thus, the application of LV mass/FFM more than halved the risk of LVH in obese versus nonobese women (odds ratio, 2.5; 95% confidence interval, 1.6 to 4.0) compared with criteria based on LV mass/height 2.7 (odds ratio, 5.5; 95% confidence interval, 3.6 to 8.3). Implications among hypertensives were less marked. Conclusions —Indexation of LV mass to FFM eliminates sex-specific LVH criteria. The proportion of individuals defined as having LVH using the new criteria deviate markedly from traditional indexations. Prospective investigations will be needed to identify the prognostic implications of different indexations, especially in subgroups such as the obese.
CXCR4 downregulation of let-7a drives chemoresistance in acute myeloid leukemia
Authors: Ye Chen, Rodrigo Jacamo, Marina Konopleva, Ramiro Garzon, Carlo Croce, Michael Andreeff
Journal: Journal of Clinical Investigation (2013)

We examined the role of microRNAs (miRNAs) in targeting the stromal-derived factor 1α/CXCR4 (SDF-1α/CXCR4) axis to overcome chemoresistance of AML cells. Microarray analysis of OCI-AML3 cells revealed that the miRNA let-7a was downregulated by SDF-1α-mediated CXCR4 activation and increased by CXCR4 inhibition. Overexpression of let-7a in AML cell lines was associated with decreased c-Myc and BCL-XL protein expression and enhanced chemosensitivity, both in vitro and in vivo. We identified the transcription factor Yin Yang 1 (YY1) as a link between SDF-1α/CXCR4 signaling and let-7a, as YY1 was upregulated by SDF-1α and downregulated by treatment with a CXCR4 antagonist. ChIP assay confirmed the binding of YY1 to unprocessed let-7a DNA fragments, and treatment with YY1 shRNA increased let-7a expression. In primary human AML samples, high CXCR4 expression was associated with low let-7a levels. Xenografts of primary human AML cells engineered to overexpress let-7a exhibited enhanced sensitivity to cytarabine, resulting in greatly extended survival of immunodeficient mice. Based on these data, we propose that CXCR4 induces chemoresistance by downregulating let-7a to promote YY1-mediated transcriptional activation of MYC and BCLXL in AML cells.