tbuckley/cabot-search huggingface dataset:
Long-term exclusive zinc monotherapy in symptomatic Wilson disease: Experience in 17 patients
Authors: Francisca H. H. Linn, Roderick H. J. Houwen, Jan van Hattum, Stefan van der Kleij, Karel J. van Erpecum
Journal: Hepatology (2009)

Exclusive monotherapy with zinc in symptomatic Wilson disease is controversial. Seventeen symptomatic patients with Wilson disease were treated with zinc only. The mean age at diagnosis and start of treatment was 18 years (range 13-26) with approximately half presenting as adolescents. Presentation was exclusively hepatic, exclusively neurologic, and combined in seven, five, and five patients, respectively. The median follow-up was 14 years (range 2-30). At baseline, two of the 12 patients with hepatic disease exhibited decompensated cirrhosis, five exhibited compensated cirrhosis, and five had less severe disease. Both patients with decompensated cirrhosis improved to a compensated state after initiation of therapy. Two of the five patients with initial compensated cirrhosis progressed to decompensated state, and three remain stable. Three of the five patients with moderate or mild liver disease remain stable and two improved. Apart from decreasing bilirubin levels, no significant changes occurred in the liver biochemistry or function during long-term follow-up. Nine of 10 neurologic patients improved markedly and one deteriorated. Two patients with exclusively neurologic presentation developed liver disease during zinc treatment. Two patients with exclusively hepatic presentation developed mild neurologic symptoms. According to 24-hour urinary copper excretions (213 +/- 38 versus 91 +/- 23 microg: P = 0.01) and serum non-ceruloplasmin-bound copper concentrations (11 +/- 2 versus 7 +/- 1 microg/dL: P = 0.1) at the end of follow-up, the efficacy of decoppering was less in the exclusively hepatic than in the neurologic group. The prescribed zinc dose and 24-hour urinary zinc excretions tended to be less in the exclusively hepatic group.The outcome of exclusive zinc therapy is generally good in cases of neurologic disease. A less satisfactory outcome in hepatic disease may relate to less efficient decoppering.
Reducing Deaths Caused by Bronchial Asthma
Authors: Howard S. Rubenstein
Journal: JAMA (1986)

<h3>To the Editor.—</h3> Strunk et al<sup>1</sup>retrospectively compared the psychological and physiological characteristics of two groups of children with severe bronchial asthma, those who died vs those who did not. The national figures for all deaths from asthma are 2,326 deaths in 1972, 1,876 in 1974, 1,975 in 1976, 1,872 in 1978, 2,891 in 1980, and 3,154 in 1982 (National Center for Health Statistics, written communication, 1985). The authors reported no deaths in their own hospital during this period. Nonetheless, their study unintentionally raises serious questions about patient care, especially about the follow-up plans the hospital arranged and the actual care the patients received after discharge, since patients "died in their home communities after being discharged": Many patients who went on to die had become sicker during the week prior to discharge. Why, then, did the hospital discharge them? Was follow-up care arranged within one or two
The photoprotective potential of the new superpotent sunscreens
Authors: Kays H. Kaidbey
Journal: Journal of the American Academy of Dermatology (1990)

A sun protection factor (SPF)-15 and an SPF-30 sunscreen were compared with regard to their ability to prevent sunburn cell formation after the exposure of human skin to a standardized dose of solar-simulated radiation. The SPF-30 sunscreen provided a significantly superior degree of photoprotection and almost prevented sunburn cell induction. Because sunburn cells may be markers of ultraviolet radiation-induced damage to DNA, the new superpotent sunscreens should offer an advantage in the prevention of skin cancer and long-term actinic damage to skin.
Discharging patients into the community
Authors: J. Knowles
Journal: BMJ (1993)

pattern of pain is of no value in localising the site of the lesion.2We advocate consultation with a senior doctor and consideration of early computed tomography for patients with a good history of neck rotation at the time of impact.This increases the chance of bony injury,2 particularly between the occiput and C2, which is often poorly visualised in plain films.Computed tomography should also be considered in those with a fixed abnormal neck position, particularly if pain does not seem to be the restricting factor, and those with definite neurological signs and symptoms, even if their presenta- tion is delayed.
Lymphocyte Transformation in Multiple Sclerosis Induced by Cerebrospinal Fluid
Authors: Ira Fowler, Charles E. Morris, Thomas Whitley
Journal: New England Journal of Medicine (1966)

HUMAN peripheral blood lymphocytes have the capacity to undergo morphologic transformation under the influence of several agents. Initially, Nowell1 observed that phytohemagglutinin stimulated a large proportion of cultured lymphocytes, usually 70 to 90 per cent, to enlarge and divide. The morphologic change leading to mitosis has been variously described as an alteration to a blastic cell, a change to a plasma cell or merely an enlargement. The mechanism of action of phytohemagglutinin has not been established but may be nonspecific. A number of specific antigens to which the cell donor is sensitive has been shown to stimulate peripheral blood lymphocytes . . .
Modulation of CD59 Expression by Restrictive Silencer Factor–Derived Peptides in Cancer Immunotherapy for Neuroblastoma
Authors: Rossen M. Donev, Lisa C. Gray, Baalasubramanian Sivasankar, Timothy R. Hughes, Carmen W. van den Berg, B. Paul Morgan
Journal: Cancer Research (2008)

Abstract Tumor cells escape clearance by complement by abundantly expressing CD59 and other membrane complement regulators. Existing strategies for blocking/knocking down these regulators can contribute to tumor immunoclearance in vitro; however, there are numerous difficulties restricting their use in vivo. Here, we report a new strategy for suppression of CD59 expression in neuroblastoma using peptides that target regulators of CD59 expression. We identified the neural-restrictive silencer factor (REST) as a target for modulation of CD59 expression in neuroblastoma. We next designed plasmids that encoded peptides comprising different DNA-binding domains of REST and transfected them into neuroblastoma cell lines. These peptides suppressed CD59 expression, sensitizing neuroblastoma to complement-mediated killing triggered by anti-GD2 therapeutic monoclonal antibody. These CD59-modulating peptides might be effective therapeutic adjuvants to therapeutic monoclonal antibodies used for treatment of neuroblastoma and other cancer types sharing the same mechanism for regulation of CD59 expression. [Cancer Res 2008;68(14):5979–87]
Endothelins and pulmonary hypertension, what directions for the near future?
Authors: S. Eddahibi, S. Adnot
Journal: European Respiratory Journal (2001)

Among the various vasoactive molecules or growth factors that have been tentatively implicated in pulmonary hypertension (PH), endothelin (ET) is particularly important because the potential therapeutic efficacy of ET-receptor antagonists is being investigated in patients with PH 1. ET was discovered in 1988 and found to be the most potent vasoconstrictor ever known 2. The discovery that ET was abundantly expressed in the lung directed attention toward its potential role in the initiation or progression of PH. Beneficial effects of chronic treatment with specific ET-receptor antagonists in experimental PH were first reported in 1994–1995 3, 4. ET-receptor antagonists now hold considerable promise for the treatment of human PH 1, illustrating how fast basic research has moved to clinical use in this specific area.

Experimental studies of the expression and effects of lung ET have contributed substantially to the current fund of knowledge about the pathophysiological role of ET in PH and are in good agreement with those obtained in human PH. The current understanding of the ET system in the pathogenesis of PH can be summarized as follows: 1) the ET system seems activated in all forms of human PH 5 and in all animal models of PH 6, 7; 2) ET may contribute to the development of PH through its potent vasoconstricting properties, or its promitogenic properties 8–10; 3) ET-receptor blockade protects against PH and, more convincingly, reverses established sustained experimental PH 3, 4, 11–14. Each of these effects has been documented by a large number of studies. However, several questions of crucial importance when considering ET as a therapeutic target remain unanswered. 1) Why is the lung ET system activated during PH? 2) Why is lung ET well tolerated in the normal lung …
But, on the Other Hand: High Blood Pressure, Economics and Equity
Authors: Rashi Fein
Journal: New England Journal of Medicine (1977)

The story is told that some years ago the publisher of the New York Times was asked why the Times did not print any cartoons alongside its editorials. His explanation was that in a cartoon one couldn't say, "But, on the other hand."It is said that Harry Truman once expressed the wish that he could have a one-armed economist as an adviser. When asked why, Truman explained that he was tired of hearing economists respond, "But, on the other hand."The reader, therefore, will not be surprised when he finds that the remarks that follow, in relation to the . . .
Notification of tuberculosis
Authors: M. J Dlugolecka
Journal: BMJ (1988)

<h3>Abstract</h3> Single-cell gene expression data provide invaluable resources for systematic characterization of cellular hierarchy in multi-cellular organisms. However, cell lineage reconstruction is still often associated with significant uncertainty due to technological constraints. Such uncertainties have not been taken into account in current methods. We present ECLAIR, a novel computational method for the statistical inference of cell lineage relationships from single-cell gene expression data. ECLAIR uses an ensemble approach to improve the robustness of lineage predictions, and provides a quantitative estimate of the uncertainty of lineage branchings. We show that the application of ECLAIR to published datasets successfully reconstructs known lineage relationships and significantly improves the robustness of predictions. In conclusion, ECLAIR is a powerful bioinformatics tool for single-cell data analysis. It can be used for robust lineage reconstruction with quantitative estimate of prediction accuracy.
Normal joint mobility in mitral valve prolapse
Authors: J. S. Marks, J. Sharp, S. G. Brear, J. D. Edwards
Journal: Annals of the Rheumatic Diseases (1983)

Thirty-seven adults (19 male, 18 female) with mitral valve prolapse (MVP) were examined for evidence of joint hypermobility scored on a 0-9 scale. None of the patients had hypermobility scores exceeding 3, and comparison with 37 healthy age and sex matched controls recruited from hospital staff failed to show an increased prevalence of hypermobility in MVP. There was no evidence that the MVP syndrome is a forme fruste of a heritable disorder of connective tissue.
Extracellular superoxide dismutase and cardiovascular disease
Authors: T Fukai
Journal: Cardiovascular Research (2002)

Excessive production and/or inadequate removal of reactive oxygen species, especially superoxide anion (O2•−), have been implicated in the pathogenesis of many cardiovascular diseases, including atherosclerosis, hypertension, diabetes, and in endothelial dysfunction by decreasing nitric oxide (NO) bioactivity. Since the vascular levels of O2•− are regulated by the superoxide dismutase (SOD) enzymes, a role of SOD in the cardiovascular disease is of substantial interest. Particularly, a major form of SOD in the vessel wall is the extracellular SOD (ecSOD). This review will discuss the characteristics of ecSOD and the role of ecSOD in cardiovascular diseases.
Fibre and prevention of chronic diseases
Authors: A. Tjonneland, A. Olsen
Journal: BMJ (2011)

Fibre specifically from cereals and whole grains is most effective in reducing risk

In the linked systematic review and meta-analysis (doi:10.1136/bmj.d6617), Aune and colleagues assess the association between the intake of dietary fibre and whole grains and the risk of colorectal cancer.1

It was first hypothesised in 1988 that food items rich in dietary fibre may prevent colorectal cancer,2 but randomised trials studying dietary fibre have not supported the association.3 This is a classic situation within nutritional epidemiology; a food item is related to decreased incidence of disease and the biological effect is attributed to a single component, but when this component is tested in randomised trials the results are not what was expected. This ought to have taught researchers to study the dietary sources and not only one specific component, which is exactly what Aune and colleagues have done.1 Their systematic review and meta-analysis of prospective observational studies clearly shows that a high intake of fibre from cereals and high consumption of wholegrain foods is …
Lesson of the week Difficulties in diagnosing acute rheumatic fever---arthritis may be short lived and carditis silent
Authors: L. Williamson
Journal: BMJ (2000)

Think of rheumatic fever in all cases of acute childhood arthritis 

The incidence of acute rheumatic fever has increased in the developed world.1-4 Although the criteria for diagnosis are well known, the clinical symptoms needed to make a diagnosis do not always arise concurrently and the initial illness may be mild and short lived. Isolated arthritis is the presenting symptom in 14-42% of patients.3-5 There may be no history of sore throat, or this symptom may not be mentioned by the patient,5 and the carditis may be silent. 6 7 The diagnosis will be missed if appropriate investigations are not carried out during the acute illness. These patients are susceptible to recurrent attacks of rheumatic fever, and damage to heart valves becomes increasingly severe with each subsequent attack. 8 9 Children are affected more than adults and may present to their general practitioners or to accident and emergency, orthopaedic, rheumatology, or paediatric departments. To highlight potential diagnostic problems, we describe three cases of rheumatic fever in young people who presented to one musculoskeletal centre in a six month period.

### Case 1

A 3 year old girl was taken to an accident and emergency department with a painful swelling of her right knee that came on quickly. She had had a mild cough, sore throat, and low grade temperature for 10 days. There was no history of trauma. No fracture was seen on a radiograph, and the girl was sent home. Two days later the girl's right wrist swelled. She was admitted to the Nuffield Orthopaedic Centre for assessment. When she was examined her temperature was 37.4°C and her pulse was regular (80 beats per minute). She had large infected tonsils, posterior cervical lymphadenopathy, and a grade 2/6 basal ejection systolic murmur. Her wrist and knee were warm, red, swollen, …
Mechanism of Synergy of Levamisole and Fluorouracil: Induction of Human Leukocyte Antigen Class I in a Colorectal Cancer Cell Line
Authors: E. E. AbdAlla, G. E. Blair, R. A. Jones, H. M. Sue-Ling, D. Johnston
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Mechanism of Synergy of Levamisole and Fluorouracil: Induction of Human Leukocyte Antigen Class I in a Colorectal Cancer Cell Line Get access Elmuataz E. AbdAlla, Elmuataz E. AbdAlla Department of Biochemistry and Molecular Biology University of LeedsEngland Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Eric Blair, G. Eric Blair Department of Biochemistry and Molecular Biology University of LeedsEngland Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard A. Jones, Richard A. Jones Haematological Malignancies Diagnostic Services, Leeds General Infirmary University of LeedsEngland Search for other works by this author on: Oxford Academic PubMed Google Scholar Henry M. Sue-Ling, Henry M. Sue-Ling Division of Surgery, Leeds General Infirmary University of LeedsEngland Search for other works by this author on: Oxford Academic PubMed Google Scholar David Johnston David Johnston Division of Surgery, Leeds General Infirmary University of LeedsEngland Correspondence to: G. E. Blair, Ph.D., Department of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, England. Permanent address: EIMuataz E. AbdAlla, Faculty of Medicine, University of Khartoum, Sudan Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 7, 5 April 1995, Pages 489–496, https://doi.org/10.1093/jnci/87.7.489 Published: 05 April 1995 Article history Received: 08 July 1994 Revision received: 18 November 1994 Accepted: 09 January 1995 Published: 05 April 1995
Fluoxetine and Sexual Dysfunction
Authors: Michael J. Silverglat
Journal: JAMA (1995)

To the Editor.  —Dr Hollander 1 noted that sexual dysfunction occurs in up to 1.9% of patients taking fluoxetine with less than 1% experiencing impotence or ejaculatory problems. These figures are significantly lower than reflected in the recent literature.  Balon and colleagues 2 reviewed the existing literature on sexual dysfunction caused by antidepressants and reported a series of their own. The previously reported incidence of sexual dysfunction had ranged from as low as 1.9% for fluoxetine to as high as 92% for clomipramine.  They found alterations in sexual functioning in 65% of their 60 patients, classifying 43.3% of these changes as sexual dysfunction. Of their 14 patients receiving fluoxetine, six (five female, one male) experienced one or more dysfunctions including decreased libido, more time to reaching orgasm, or difficulty reaching orgasm. Two became anorgasmic.  Improvements in sexual function occurred in 16.6% of their patients, including two taking fluoxetine. Three patients
Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial
Authors: Lorraine A. Chantrill, Adnan M. Nagrial, Clare Watson, Amber L. Johns, Mona Martyn-Smith, Skye Simpson, Scott Mead, Marc D. Jones, Jaswinder S. Samra, Anthony J. Gill, Nicole Watson, Venessa T. Chin, Jeremy L. Humphris, Angela Chou, Belinda Brown, Adrienne Morey, Marina Pajic, Sean M. Grimmond, David K. Chang, David Thomas, Lucille Sebastian, Katrin Sjoquist, Sonia Yip, Nick Pavlakis, Ray Asghari, Sandra Harvey, Peter Grimison, John Simes, Andrew V. Biankin
Journal: Clinical Cancer Research (2015)

Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices of the International Cancer Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets of patients with aberrations in their tumor genome that could be targeted with currently available therapies.
Depressed transient outward current in single hypertrophied cardiomyocytes isolated from the right ventricle of ferret heart
Authors: D. Potreau, J. P. Gomez, N. Fares
Journal: Cardiovascular Research (1995)

Objective: The aim of this study was to investigate transient outward potassium current (Ito) changes as a basis for the prolongation of the action potential associated with cardiac hypertrophy. Methods: Right ventricular hypertrophy was induced by chronic pulmonary artery constriction in adult male ferrets. After 4–6 weeks, hearts were excised and single myocytes were isolated from the right ventricles of banded and sham-operated (control) animals by enzymatic dissociation. Ito was recorded by means of the whole cell patch clamp technique. Results: Heart weight:body weight ratio and cell membrane capacitance, as indications of hypertrophy, were increased by 17% (P < 0.05) and 32% (P < 0.01) respectively in the banded group. Analysis of Ito showed that in hypertrophied myocytes compared to normal controls: (1) the density of current was significantly reduced; (2) both the time to peak and the time constant of inactivation were increased; (3) the voltage-dependent steady-state availability was not changed, with similar potentials for half activation (30.4 ± 6.8 mV in control and 33.9 ± 8.5 mV in hypertrophied cells) and half inactivation (−12.3 ± 3.3 mV in control and −11.4 ± 2.7 mV in hypertrophied cells); (4) the time constant for recovery from inactivation was significantly increased regardless of the holding potentials (−50 mV, −70 mV or −90 mV). Conclusions: Alterations of the transient outward potassium current with respect to its density, kinetics and recovery from inactivation can explain the prolongation of the action potential in myocytes isolated from pressure-overload hypertrophied heart and may thus be an important step in such cardiac adaptation.
Lifestyle Factors and Risk for New-Onset Diabetes
Authors: Jared P. Reis, Catherine M. Loria, Paul D. Sorlie, Yikyung Park, Albert Hollenbeck, Arthur Schatzkin
Journal: Annals of Internal Medicine (2011)

Background: Epidemiologic data on the combined influence of several lifestyle factors on diabetes risk are rare, particularly among older adults. Objective: To examine how combinations of lifestyle risk factors relate to the 11-year risk for incident diabetes. Design: Population-based prospective cohort study. Setting: National Institutes of Health (NIH)–AARP Diet and Health Study. Participants: 114 996 men and 92 483 women, aged 50 to 71 years in 1995 to 1996, without evidence of heart disease, cancer, or diabetes. Measurements: A comprehensive survey of demographic characteristics and lifestyle factors, including dietary intake, body weight and height, physical activity, smoking, and alcohol consumption at baseline (1995 to 1996). Low-risk groups were formed by dichotomizing each lifestyle factor. Incident self-reported, physician-diagnosed diabetes was identified with a follow-up survey in 2004 to 2006. Results: 11 031 men (9.6%) and 6969 women (7.5%) developed new-onset diabetes. For each additional lifestyle factor in the low-risk group, the odds for diabetes were 31% lower (odds ratio [OR], 0.69 [95% CI, 0.68 to 0.71]) among men and 39% lower (OR, 0.61 [CI, 0.60 to 0.63]) among women. Men and women whose diet score, physical activity level, smoking status, and alcohol use were all in the low-risk group had ORs for diabetes of 0.61 (CI, 0.56 to 0.66) and 0.43 (CI, 0.34 to 0.55), respectively. When absence of overweight or obesity was added, the respective ORs were 0.28 (CI, 0.23 to 0.34) and 0.16 (CI, 0.10 to 0.24) for men and women. Results did not differ by family history of diabetes or level of adiposity. Limitation: The study was observational, with potential for residual confounding. Conclusion: Lifestyle factors, when considered in combination, are associated with a substantial reduction in risk for diabetes. Primary Funding Source: The NIH-AARP Diet and Health Study was supported by the Intramural Research Program of the NIH.
NON-SELECTIVE BETA-BLOCKERS DECREASE THROMBOTIC EVENTS IN PATIENTS WITH HEART FAILURE
Authors: Olav R. De Peuter, Patrick C. Souverein, Olaf H. Klungel, Gregory Y. Lip, Harry R. Büller, Anthonius De Boer, Pieter W. Kamphuisen
Journal: Journal of the American College of Cardiology (2010)