tbuckley/cabot-search huggingface dataset:
Innovation fund supports video game to help stroke patients regain movement
Authors: J. Wise
Journal: BMJ (2012)

A video game designed to rehabilitate stroke patients, gene therapy for a form of blindness, and an implantable device to monitor pulmonary hypertension are some of the projects being supported by the Health Innovation Challenge Fund.

The fund was set up by the Department of Health and the Wellcome Trust in 2009 to stimulate the development of products and interventions for possible use in the NHS.1 So far around £55m (€68m; $87m) has been allocated, and there are 25 projects at various stages of development.

Speaking at a press conference in London on 16 May, Sally Davies, chief medical officer for England, said, “We are targeting areas of poorly met or unmet need. The fund is focusing on projects that will come to patients within three to five years and wouldn’t classically get research funding.”

The video game project is being led by Janet Eyre, …
What action should be taken to prevent spread of vancomycin resistant enterococci in European hospitals?
Authors: B. Ridwan
Journal: BMJ (2002)

Vancomycin resistant enterococci are important nosocomial pathogens with variable epidemiological characteristics. Infections are becoming increasingly common in American hospitals, although it is rare for healthy people to carry the bacterium. By contrast, infection with vancomycin resistant enterococci is uncommon in European hospitals but many healthy people carry the bacterium. We describe an outbreak of vancomycin resistant enterococci infection in a Dutch hospital that was controlled by costly, labour intensive infection control measures.1 We also discuss what should be done to prevent vancomycin resistant enterococci becoming endemic in European hospitals.

#### Summary points

Vancomycin resistant enterococci have low virulence but infection is difficult to treat

Infection is endemic in US hospitals but rare in European hospitals

An outbreak in a Dutch hospital was halted by strict infection control measures

These measures were expensive and at times stopped new admissions and surgery

It is unclear whether such strict measures are justified, and European guidelines are needed

In the United States, the incidence of infection with vancomycin resistant enterococci has increased greatly in the past 10 years. In the national nosocomial infection surveillance study, the proportion of vancomycin resistant enterococci among enterococcal bloodstream infections rose from 0% in 1989 to 25.9% in 1999.2 Although the initial rise was observed in intensive care patients, infections are also common among patients treated in general hospital wards.2

Enterococci have a low virulence but can cause serious infections in immunocompromised patients, such as transplant recipients or those in intensive care units.3 Infection usually occurs in the abdominal cavity or urinary tract, and the attributable mortality may be as high as 30%,4 although these figures have not been replicated. 5 6 New antibiotics (such as linezolid) that are effective against vancomycin resistant enterococci are available, but development of resistance has already been reported.7 Limiting further …
Evaluation of Psychiatric Disability and the Concept of Regression
Authors: Joseph Lerner
Journal: JAMA (1964)

In the review of thousands of psychiatric reports submitted in connection with applications for disability benefits under the social security law, it was found that many of these reports did not consider the concept of regression in evaluating the impact of the psychiatric illness. Our experience with physiological regression is illustrated by two cases which emphasize the concept that loss of function for an extended period of time should be associated with concomitant evidence of physiological regression. This furnishes a reasonable basis for the conclusion that the psychiatric impairment has resulted in a substantial and persistent loss of functional capacity.
Association of defensin β-1 gene polymorphisms with asthma
Authors: Hara Levy, Benjamin A. Raby, Stephen Lake, Kelan G. Tantisira, David Kwiatkowski, Ross Lazarus, Edwin K. Silverman, Brent Richter, Walter T. Klimecki, Donata Vercelli, Fernando D. Martinez, Scott T. Weiss
Journal: Journal of Allergy and Clinical Immunology (2005)
Autoantibodies to the HLA-B27 sequence cross-react with the hypothetical peptide from the arthritis-associated Shigella plasmid.
Authors: N Tsuchiya, G Husby, R C Williams, H Stieglitz, P E Lipsky, R D Inman
Journal: Journal of Clinical Investigation (1990)

We previously reported elevated serum antibody levels to a peptide representing the HLA-B27 polymorphic region (B27 peptide) in HLA-B27(+) ankylosing spondylitis (AS) patients. A plasmid (pHS-2) isolated from arthritogenic Shigella flexneri strains had been shown to encode an amino acid sequence homologous to HLA-B27. Rabbit antibody to this sequence (pHS-2 peptide) strongly cross-reacted with B27 peptide and, to a much lesser extent, with Klebsiella nitrogenase peptide. Serum antibody levels to pHS-2 peptide were studied in 160 spondylarthropathy patients. 12 of 115 (10.4%) AS patients, 2 of 45 (4.4%) patients with Reiter's syndrome or reactive arthritis as well as 6 of 147 (4.1%) normal controls were shown to have elevated anti-pHS-2 peptide antibodies. Antibody levels to B27 and pHS-2 peptides were significantly correlated in 134 HLA-B27(+) patients (r = 0.333, P less than 0.001). 13 of 15 affinity-purified anti-B27 peptide antibodies from patients strongly cross-reacted with pHS-2 peptide, whereas only 3 weakly cross-reacted to nitrogenase peptide. Leucine appeared to be a critical residue for this cross-reaction. AS patients' anti-B27 peptide antibodies reacted with HLA-B27 transfected L cells. These results may suggest that pHS-2 peptide more efficiently "mimics" B27 peptide than does nitrogenase peptide. Involvement of pHS-2 in pathogenesis of spondylarthropathy through molecular mimicry mechanisms requires further study.
Eye Strain from Convergence Insufficiency
Authors: R. S. Mahto
Journal: BMJ (1972)

Eye strain and headache are common ocular symptoms, and the main cause in persons aged 15 to 40 is convergence insufficiency. It is more common in females than in males. Many patients are supplied with glasses for eye strain without the causative convergence insufficiency being treated. The treatment in most cases is orthoptic exercises.
P1-08-03: Huge Improvement in Relapse-Free Breast Cancer Survival over the Last 25 Years.
Authors: SME Geurts, Dijck JAAM van, Vegt F de, Y Paquay, S Siesling, ALM Verbeek, VCG Tjan-Heijnen
Journal: Cancer Research (2011)

Abstract Introduction The purpose of this study was to evaluate the dwindling risk of relapse in breast cancer patients treated with curative intent since the 1970s. Patients and methods 8570 women diagnosed with invasive breast cancer in 2003 or 2004 were compared with 307 consecutively diagnosed patients with invasive breast cancer between 1972 and 1986 in the Netherlands. Five-year overall survival and 5-year risk of relapse, i.e. second primary breast cancer, locoregional recurrence or distant metastasis, were calculated using the Kaplan-Meier method. Multivariable Cox-proportional hazards modelling was applied to correct the period-specific risk of relapse for tumour size, lymph node involvement and age at diagnosis. Results Median (range) age at diagnosis was 52 years (27-82 years) in 1972–1986 and 58 years (20-96 years) in 2003–2004. Patients diagnosed in 1972–1986 had a larger tumour size and similar nodal involvement as compared to patients diagnosed in 2003–2004. In 2003–2004 more women were treated with breast conserving surgery, chemotherapy, and hormonal therapy as compared to 1972–1986. The 5-year overall survival rate increased from 71% (95% CI: 65% — 76%) in the period 1972–1986 to 85% (95% CI: 84% — 85%) in the years 2003–2004. Five-year risk of any relapse decreased from 37% to 16% across the calendar years (table 1). This decrease was observed for the risk of locoregional recurrence and the risk of distant metastasis (table 1). Risk of second primary breast cancer was similar for both periods of diagnosis (table 1). After adjustment for tumour size, nodal status and age at diagnosis the decrease in risk of relapse remained significant for patients diagnosed in 2003–2004 compared to 1972–1986 (HR= 0.5, 95% CI: 0.4 - 0.6). Conclusion Over the last decades, the risk of breast cancer relapse has tremendously decreased, also after adjustment for tumour stage and age at diagnosis. The improved prognosis can be explained by the more often administered and intensified systemic treatment procedures and, further, by an earlier detection. The similar nodal stage probably resulted from stage migration caused by a more thoroughly performed lymph node staging in 2003–2004 compared to 1972–1986. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-03.
An Address ON THE DRUG HABIT: Delivered at a Meeting of the Pharmaceutical Society
Authors: W. E. Dixon
Journal: BMJ (1921)

THE food custom-s of nmankind shouildnot be regarded as random practices adopted to please the palate, or to gratify an idle anid vicious appetite.Thev are more probably the result of experience and instinct which supply important waants in the animal economny.The natives in mnany different countries of the world uselherbs containing caffeine or one of its allies in the form-l of a decoction or infusion, althou(h suchi herbs possess neither clharacteristic taste or smlell.Caffeine is obtained most readily from tea, whlichl may contain anything from 3 to 5 per cent.; otlher plants are coffee from Arabia con- taining caffeine, cocoa from South America containiing tlheobronmine, Lola from Central Africa containing both caffeine and theobromine, guarana paste from Brazil, ParaguLay tea from the Argentine, and there are many othiers.Stimulants in some formn would appear to be even more essential to the exigencies of life under modern civiliza- tion.Caffeine, whichl is universal, is a powerful cerebral stimulant, but its action in banishing sleep and its effect on the heart effectually prevent it from being taken in excessive doses.Chronic poisoning by tea and coffee is not very uncomiimon and may occur when six or seven grains of caffeine are taken daily.The su-fferer is tremulous, shows loss of self-control, and exhibits fits of excitement and depression; lhe has a haggard appearance
US public service advertising could learn from the UK
Authors: Janice Hopkins Tanne
Journal: BMJ (2007)

Lester Crawford, former commissioner of the US Food and Drug Administration, was last week fined $89 377 (£45 800; €67 000), sentenced to three years of supervised probation, and required to do 50 hours of community service by Judge Deborah Robinson of the US District Court for the District of Columbia.Last October Dr Crawford (below) pleaded (below) pleaded pleaded guilty to two charges: failing to report that he and his wife owned shares in companies regulated by the agency and filing false
Long-term Results of Aortic Valve Replacement with the Starr-Edwards Valve
Authors: J. Fleming, J. Hamer, G. Hayward, O. S. Tubbs, I. Hill
Journal: BMJ (1969)

Review of the 74 patients undergoing aortic valve replacement with a Starr–Edwards ball-valve prosthesis between October 1963 and December 1967 showed that 16 died during surgery or within the first month after operation, usually owing to myocardial failure; and there were nine late deaths. The remaining patients developed few major complications, and the long-term results of operation are considered satisfactory, no patient being grossly incapacitated and most of them are leading active, symptom-free lives.
II. Treatment of Acute Respiratory Failure
Authors: Maurice S. Segal
Journal: New England Journal of Medicine (1966)

WHEN ventilatory failure occurs, the rapid recognition of the defect and its multiple complicating factors are necessary to provide adequate patient care. The more common acute respiratory failures seen at the Boston City Hospital are listed in Table 1.Clinical and Laboratory Evaluation of Ventilatory FunctionIn the clinical assessment the history and ertinent physical findings are useful, particularly the frequency of cough, sputum volume, dyspnea, wheezing or prolonged expiration and cyanosis. Dyspnea is present in patients with purely mechanical defects and in those with combined mechanical and alveolar respiratory insufficiency; cyanosis is usually seen in the latter.Immediate evaluation should . . .
Oral Hedgehog-Pathway Inhibitors for Basal-Cell Carcinoma
Authors: John T. Lear
Journal: New England Journal of Medicine (2012)

Basal-cell carcinoma of the skin is the most common cancer worldwide, and its prevalence is increasing, accounting for 80% of nonmelanoma skin cancers.1 In 2006, more than 2.1 million new cases of nonmelanoma skin cancer were treated in the United States.2 Basal-cell carcinoma has many clinical subtypes and can progress to an advanced state in which surgery or radiation therapy is not considered to be helpful (locally advanced basal-cell carcinoma). Such lesions arise either from earlier lesions that have not been treated or from a recurrence of aggressive basal-cell carcinoma. Metastatic basal-cell carcinoma is rare.1 Exposure to ultraviolet light is . . .
THE RENAL ASPECTS OF ESSENTIAL VASCULAR HYPERTENSION: (HYPERPIESIA OF CLIFFORD ALLBUTT)
Authors: W. W. D. Thomson
Journal: BMJ (1933)

TUBERCULOSIS OF BOVINE ORIGIN rMTETBRITURNAL milk, than demand that any known practicable methods which will remove this danger should be put into operation.Pasteurization is not a new, untried experiment; it operates over .large part of the United States and Canada, and there is much evidence showing its-extreme efficiency.
Carbon Monoxide: An Endogenous Modulator of the Nitric Oxide–Cyclic GMP Signaling System
Authors: Tatsuya Ingi, Julia Cheng, Gabriele V Ronnett
Journal: Neuron (1996)

Carbon monoxide (CO) is an activator of soluble guanylyl cyclase and is implicated as a neuronal messenger. CO production, nitric oxide synthase (NOS) activity, and guanosine 3′,5′-monophosphate (cGMP) levels were quantitated in cerebellar granule cell cultures. Metabolic labeling experiments enabled the direct measurement of neuronal CO production in vitro. CO production is significant, and peaked during early stages of culture. NOS activity and cGMP levels synchronously increased as cells matured. Whereas inhibition of NOS depleted cGMP in mature cultures, inhibitors of CO production potentiated the nitric oxide (NO)-mediated cGMP increase. Exogenous CO at similar concentrations to endogenous levels blocked the NO-mediated cGMP increase. These results directly demonstrate that endogenous neuronal CO production is high and indicate that while NO is the major regulator of cGMP in these neurons, CO may modulate the NO–cGMP signaling system.
Expression of Immunomodulatory Neutrophil-activating Protein of Helicobacter pylori Enhances the Antitumor Activity of Oncolytic Measles Virus
Authors: Ianko D Iankov, Cory Allen, Mark J Federspiel, Rae M Myers, Kah Whye Peng, James N Ingle, Stephen J Russell, Evanthia Galanis
Journal: Molecular Therapy (2012)

Helicobacter pylori neutrophil-activating protein (NAP) is a major virulence factor and powerful inducer of inflammatory reaction and Th1-polarized immune response. Here, we evaluated the therapeutic efficacy of measles virus (MV) strains engineered to express secretory NAP forms against metastatic breast cancer. Recombinant viruses encoding secretory NAP forms (MV-lambda-NAP and MV-s-NAP) efficiently infect and destroy breast cancer cells by cell-to-cell viral spread and large syncytia formation independently of hormone receptor status. Intrapleural administration of MV-s-NAP doubled the median survival in a pleural effusion xenograft model: 65 days as compared to 29 days in the control group (P < 0.0001). This therapeutic effect correlated with a brisk Th1 type cytokine response in vivo. Secretory NAP was expressed at high levels by infected tumor cells and increased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-12/23 cytokine concentrations were detected in the pleural effusion. In an aggressive model of lung metastatic breast cancer, MV-lambda-NAP and MV-s-NAP also significantly improved survival of the treated animals (P < 0.05) as compared to the control MV strain. These data suggest that potent immunomodulators of bacterial origin, such as H. pylori NAP, can enhance the antitumor effect of oncolytic viruses and support the feasibility and potential of a combined viroimmunotherapy approach.
TCTAP A-032 0/300 Impact of Bifurcation Technique on 2-Years Clinical Outcomes in Asian Patients with Distal Unprotected Left Main Coronary Artery Stenosis Treated with Drug-Eluting Stents
Authors: Jabar Ali, Byoung Geol Choi, Seung-Woon Rha, Se Yeon Choi, Shaopeng Xu, Harris Ngow, Ji Bak Kim, Cheol Ung Choi, Eung Ju Kim, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2015)
Uterine Insulin-Like Growth Factor-1: Regulation of Expression and Its Role in Estrogen-Induced Uterine Proliferation*
Authors: LIAM J. MURPHY, AZIZ GHAHARY
Journal: Endocrine Reviews (1990)

THE response of the uterus to estrogen is a complexphenomenon involving numerous biochemical events (1). The most dramatic outcome of estrogenization of the immature uterus is the proliferation of various cell types. It is customary to divide the response of the uterus to estrogen into two major temporal phases. In the early phase, within the first 4 h after estrogen administration, there is an increase in uterine wet weight (2), glucose metabolism (3), histamine depletion (4), and RNA polymerase activity (5). One of the early events that is likely to be important in the proliferative response of the uterus to estrogen is activation of protooncogenes which encode nuclear regulatory proteins (6–8) and the enhanced expression of growth factors and their receptors (9) and cAMP-independent protein kinase (10). The intermediate and late phase (4–48 h after estrogen) responses include increases in protein and RNA synthesis and an increase in uterine dry weight and DNA content (11, 12).
The prevalence of corticosteroid allergy in two U.K. centres: prescribing implications
Authors: K.F. Thomson, S.M. Wilkinson, S. Powell, M.H. Beck
Journal: British Journal of Dermatology (1999)

Journal Article The prevalence of corticosteroid allergy in two U.K. centres: prescribing implications Get access K.F. Thomson, K.F. Thomson Department of Dermatology, The General Infirmary, Leeds LS1 3EX, U.K. Search for other works by this author on: Oxford Academic Google Scholar S.M. Wilkinson, S.M. Wilkinson Department of Dermatology, The General Infirmary, Leeds LS1 3EX, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. Powell, S. Powell Churchill Hospital, Oxford OX3 7LJ, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.H. Beck M.H. Beck Hope Hospital, Salford M6 8HD, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 141, Issue 5, 1 November 1999, Pages 863–866, https://doi.org/10.1046/j.1365-2133.1999.03160.x Published: 01 November 1999
Letter: Antibiotic policy.
Authors: O J Gilmore, P J Sanderson
Journal: BMJ (1975)

general practice also.Of course, for the occasional complicated case of urinary tract infection CLED medium might be neces- sary, but dipslides are not intended for the full investigation of this relatively uncommon problem.Incidentally, Dr. Rosalind Maskell's letter (28 June, p. 752) appears to misinterpret the findings of Dr. Edwards and her colleagues and also to contain a serious non sequitur.They showed that it was the CLED surface (not the MacConkey) that produced most of the false positive results and so if Dr. Maskell wishes to avoid false positives she should be using MacConkey-only rather than CLED-only dipslides.-Iam, etc.,
CCR5 deficiency exacerbates T-cell-mediated hepatitis in mice — Clinical implications for CCR5 inhibition as antiretroviral therapy
Authors: Stefan Mauss, Massimo Puoti
Journal: Hepatology (2006)

To the Editor: In the paper authored by Christophe Moreno and colleagues, a more pronounced hepatotoxic reaction and an increased rate of liver associated mortality was observed in CCR5 deficient mice after exposure to Concanavalin A.1 This observation is of particular interest as CCR5 inhibitors are currently studied as antiretroviral drugs for the treatment of HIV infection.2, 3 However, the development of aplaviroc was stopped recently due to hepatotoxic adverse events associated with jaundice observed in four study participants.4 For maraviroc, another CCR5 inhibitor currently in phase III trials, at least one case of liver failure resulting in liver transplantation was observed (personal communication). However, details concerning this case were not disclosed by the manufacturer of the drug to the public. The mechanism for the possible hepatotoxic reactions under treatment with CCR5 inhibitors remains unknown. In this context, the paper by Moreno and colleagues provides an intriguing hypothesis.1 The results from the paper suggest an increased vulnerability to hepatotoxic agents due to CCR5 deficiency or pharmacological inhibition due to an imbalance in the cytokine response rather than a direct hepatotoxic action of the drug itself. The impact of CCR5-Δ32 mutation on the clinical course of hepatitis C is still controversial: increased susceptibility to chronic HCV infection, decreased necro-inflammatory activity and a reduced sensitivity to interferon monotherapy have all been reported in different populations.5, 6 Given the relevant proportion of HIV-seropositive patients with hepatitis B or C coinfection in addition to other conditions of liver injury prevalent in the HIV-infected individuals (drugs, alcohol, steatosis) the potential of CCR5 blockade or deficiency to affect liver inflammation and progression of fibrosis deserves further attention. In addition, the hypothetical vulnerability of patients with CCR5 deficiency due to the non-functional homozygous CCR5-Δ32 allele may explain why individuals with this mutation represent only a small minority of the population <2% in most parts of the world.7 Even in Northern Europe the prevalence is at most 10% of the population despite the partial protection against such deadly infections as the plague.7 Stefan Mauss*, Massimo Puoti , * Center for HIV and Hepatogastroenterology, Duesseldorf, Germany, University of Brescia, Italy.
Comment: The End Results
Authors: Philip Rubin
Journal: JAMA (1974)

THE ultimate measure of success in managing a cancer is the end results as they are measured by survival in specific stages. It is, therefore, important for the reader of publications offering statistics to be aware of the different measures of survival. Some guidelines for reporting cancer survival and end results have been issued by the American Joint Committee for Cancer Staging and End Results Reporting.<sup>45</sup>The simplest approach is calculation by the direct method; the survival rate is determined at the end of a specified interval, ie, five years. Under this procedure, the five-year survival rate is calculated on the basis of patients who were exposed to the risk of dying for at least five years. Two commonly used survival rates are defined as follows: minimum survival rate, which assumes untraced patients to be dead of the cancer; and maximum survival rate, which assumes that untraced patients are
The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery
Authors: Shimon Sakaguchi
Journal: Journal of Clinical Investigation (2003)

Naturally arising CD4+ regulatory T cells, which engage in the maintenance of immunologic self-tolerance, specifically express FOXP3, which encodes a transcription-repressor protein. Genetic defects in FOXP3 cause IPEX, an X-linked autoimmune/inflammatory syndrome. With FOXP3 as a specific marker for regulatory CD4+ T cells in humans, it is now possible to determine their origin and developmental pathway .