tbuckley/cabot-search huggingface dataset:
Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial
Authors: A. D Hay, C. Costelloe, N. M Redmond, A. A Montgomery, M. Fletcher, S. Hollinghurst, T. J Peters
Journal: BMJ (2008)

Objective To investigate whether paracetamol (acetaminophen) plus ibuprofen are superior to either drug alone for increasing time without fever and the relief of fever associated discomfort in febrile children managed at home. Design Individually randomised, blinded, three arm trial. Setting Primary care and households in England. Participants Children aged between 6 months and 6 years with axillary temperatures of at least 37.8°C and up to 41.0°C. Intervention Advice on physical measures to reduce temperature and the provision of, and advice to give, paracetamol plus ibuprofen, paracetamol alone, or ibuprofen alone. Main outcome measures Primary outcomes were the time without fever (<37.2°C) in the first four hours after the first dose was given and the proportion of children reported as being normal on the discomfort scale at 48 hours. Secondary outcomes were time to first occurrence of normal temperature (fever clearance), time without fever over 24 hours, fever associated symptoms, and adverse effects. Results On an intention to treat basis, paracetamol plus ibuprofen were superior to paracetamol for less time with fever in the first four hours (adjusted difference 55 minutes, 95% confidence interval 33 to 77; P<0.001) and may have been as good as ibuprofen (16 minutes, −7 to 39; P=0.2). For less time with fever over 24 hours, paracetamol plus ibuprofen were superior to paracetamol (4.4 hours, 2.4 to 6.3; P<0.001) and to ibuprofen (2.5 hours, 0.6 to 4.4; P=0.008). Combined therapy cleared fever 23 minutes (2 to 45; P=0.025) faster than paracetamol alone but no faster than ibuprofen alone (−3 minutes, 18 to −24; P=0.8). No benefit was found for discomfort or other symptoms, although power was low for these outcomes. Adverse effects did not differ between groups. Conclusion Parents, nurses, pharmacists, and doctors wanting to use medicines to supplement physical measures to maximise the time that children spend without fever should use ibuprofen first and consider the relative benefits and risks of using paracetamol plus ibuprofen over 24 hours. Trial registration Current Controlled Trials [ISRCTN26362730][1]. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN26362730
Genetic Variation in the One-Carbon Transfer Pathway and Ovarian Cancer Risk
Authors: Linda E. Kelemen, Thomas A. Sellers, Joellen M. Schildkraut, Julie M. Cunningham, Robert A. Vierkant, V. Shane Pankratz, Zachary S. Fredericksen, Madhura K. Gadre, David N. Rider, Mark Liebow, Ellen L. Goode
Journal: Cancer Research (2008)

Dysfunction in enzymes involved in one-carbon (1-C) metabolism can lead to increased chromosomal strand breaking and abnormal methylation patterns, which are both associated with cancer risk. Availability of 1-C units may modify risk. We investigated the association of single-nucleotide polymorphisms (SNP) in 21 genes in the 1-C transfer pathway among 829 Caucasian cases with primary epithelial ovarian cancer and 941 frequency-matched unaffected controls enrolled at Mayo Clinic (Rochester, MN) and Duke University (Durham, NC) and examined risk modification by multivitamin supplement use. Multivariable-adjusted SNP-specific logistic regression and haplotype analyses were done for 180 SNPs and false positive report probabilities (FPRP) were calculated. Each copy of the minor allele in SHMT1 intron 5 A>G (rs9909104) was associated with epithelial ovarian cancer [odds ratio (OR), 1.2; 95% confidence interval (95% CI), 1.0-1.4; P trend = 0.02; FPRP = 0.16] and a 5-SNP SHMT1 haplotype was associated with decreased risk (P = 0.01; FPRP = 0.09). Three SNPs in DNMT3A were associated with risk among multivitamin supplement users: 3' untranslated region (UTR) C>G (rs13420827: OR, 0.8; 95% CI, 0.6-1.0; P interaction = 0.006; FPRP = 0.54), intron 6 G>A (rs11887120: OR, 0.8; 95% CI, 0.7-1.0; P interaction = 0.007; FPRP = 0.57), and intron 22 A>T (rs11695471: OR, 1.2; 95% CI, 1.0-1.5; P interaction = 0.01; FPRP = 0.66). These data extend previous findings from other cancers of a role for SHMT1 in ovarian cancer, and provide evidence that SNPs in methylation and DNA synthesis reactions are associated with risk of ovarian cancer. Interventions with modifiable factors such as multivitamin intake may reduce risk.
General practitioner management of intimate partner abuse and the whole family: qualitative study
Authors: Angela Taft, Dorothy H Broom, David Legge
Journal: BMJ (2004)

Abstract Objective To explore management by general practitioners of victimised female patients, male partners who abuse, and children in the family. Design Triangulated qualitative study comparing doctors' reported management with current recommendations in the literature. Participants 28 general practitioners attending continuing medical education about management of domestic violence. Results Doctors perceived partner abuse in diverse ways. Their gender, perceptions, and attitudes could all affect identification and management of this difficult problem. A few doctors practised in recommended ways, but many showed stress and aversion, difficulties in resolving the tensions involved in managing all family members, and neglect of the risks to children. Some doctors used contraindicated practices, such as breaking confidentiality and undertaking or referring for couple counselling. Doctors who were not familiar with community based agencies were reluctant to use them. A lack of expertise and support could have a negative impact on doctors themselves. Conclusions General practitioners managing partner abuse need to be more familiar with and apply the central principles of confidentiality and safety of women and children. Recommended guidelines for managing the whole family should be developed. Doctors should consider referring one partner elsewhere and avoid couple counselling; always ask about and act on the children's welfare; refer to specialist family violence agencies; and seek training, supervision, and support for the inherent stress. Medical education and administration should ensure comprehensive training and support for doctors undertaking this difficult work.
A study of cutaneous photosensitivity induced by amiodarone
Authors: J. FERGUSON, H.A. ADDO, S. JONES, B.E. JOHNSON, W. FRAIN-BELL
Journal: British Journal of Dermatology (1985)

Amiodarone-induced cutaneous photosensitivity was studied in 12 subjects treated with the drug. The action spectrum for the abnormal response to sunlight was shown to be within the range of 335-460 (+/- 30) nm. The clinical features of the photosensitivity response suggested that it was most probably a phototoxic reaction, a conclusion supported by the results of in vitro studies which indicated activity mainly against cell membranes. Of the five in vitro models used, three--namely photohaemolysis, the inhibition of DNA synthesis in PHA stimulated lymphocytes and the killing of mouse peritoneal macrophages--provided unequivocal evidence of the phototoxic potential of both amiodarone and its major metabolite, desethylamiodarone. In each model desethylamiodarone produced a greater effect by a factor of between 2 and 10. In vitro, UV-B wavelengths produced a greater effect than UVA but the difference between the effective wavelengths in vivo and in vitro might be explained by the greater absorption of the shorter wavelength UV-B in the epidermis. Zinc oxide-containing preparations appeared to be the most effective in reducing the cutaneous photosensitivity. It is suggested that the long-term cutaneous pigmentation resulting from oral amiodarone has a significant photosensitivity component.
Evidence of a CJD epidemic may still be missed
Authors: J. Lowe
Journal: BMJ (2000)

EDITOR—The United Kingdom faces the possibility of an epidemic of new variant Creutzfeldt-Jakob disease as a result of bovine spongiform encephalopathy,1 but the referral of brain tissue to neuropathologists to determine the cause of degenerative diseases of the brain has virtually stopped. Public concerns over the retention of tissues for investigation after postmortem examination make it is easy to see how this has happened.2

In the United Kingdom most postmortem examinations on adults are performed because …
The First Psychiatric Hospital of the Western World
Authors: RUBEN D. RUMBAUT
Journal: American Journal of Psychiatry (1972)

Although the historic beginnings of genuine psychiatric hospital treatment are still a matter of controversy, evidence is accumulating that the first authentic psychiatric hospitals in the Western world were founded in Spain during the 15th century. This paper describes the first of those hospitals, opened in 1410 by Father Juan Gilabert Jofré, a Mercedarian friar, and a group of concerned citizens of Valencia. The hospital is still in operation.
Detection of asthma and chronic obstructive pulmonary disease in primary care
Authors: C.P. van Schayck, N.H. Chavannes
Journal: European Respiratory Journal (2003)

Chronic obstructive pulmonary disease (COPD) and asthma are major health problems, the number of patients with these diseases is still rising and only 25–50% of these patients are known to their doctors. Lung function gradually decreases in COPD and asthmatic patients during their lives. Due to adaptation of the patients or due to the doctor being unaware of the symptoms, COPD is often diagnosed late in its course and when finally diagnosed, lung function is often relatively poor. Underdiagnosis and consequently undertreatment might play an important role in the increase in morbidity and mortality as a result of COPD and asthma. Early detection and treatment might improve the long-term prognosis of these patients and this secondary prevention may also prevent irreversible loss of function. The identification of patients is useless if no effective preventive measures are available. In asthma, inhaled corticosteroids have been shown to have distinct effects on the progression of the disease. However, in COPD inhaled corticosteroids have only been shown to have some effects and the long-term effects on lung function have been disappointing. At present, the most effective treatment available for COPD is the cessation of smoking. It appears that a smoker at risk of developing COPD is more motivated to stop smoking than someone who is not at risk and this may help a physician in encouraging an attempt to quit. General practitioners appear to be already using this knowledge, as they seem more likely to advise smokers to quit smoking if they perceive their problems to be smoking related.
DIABETES MELLITUS ASSOCIATED WITH STATUS LYMPHATICUS
Authors: Ralph H. Major
Journal: JAMA (1926)

A great many complications have been described as occurring in diabetes mellitus. Many of these complications may be regarded simply as coexisting conditions, while others seem to bear a definite, direct relationship to the disease itself. The following complication, which we have recently observed, probably belongs to the latter group and is apparently very unusual. <h3>REPORT OF CASE</h3> D. D., a girl, aged 11, who was admitted to the medical service of Bell Memorial Hospital, Oct. 22, 1925, at 7 a. m., and who died four hours later, had suffered from diabetes for approximately two years. During this time she had had a moderately severe form of the disease, but had been kept in good condition by dieting and insulin therapy. She had gained weight and grown in height at a satisfactory rate. In September, 1923, her height was 44½ inches (113 cm.) and her weight 44 pounds (20 Kg.);
Do transplanted human livers regenerate?
Authors: Katherine S. Koch, Hyam L. Leffert
Journal: Hepatology (1989)

Two individuals undergoing orthotopic hepatic transplantation received livers from donors who were on average 10 kg smaller than themselves based on recipient ideal body weight. As a result, the donor livers in these 2 cases were 29%-59% smaller than would be expected had the donor liver and recipient been matched ideally. The liver grafts in the recipients steadily increased in size, as determined by serial computed tomography scanning, to achieve new volumes consistent with those that would have been expected in a normal individual of the recipient’s size, sex, and age. Fasting plasma levels of amino acids, glucagon, insulin, and standard liver injury tests were monitored to determine which measure best reflected the changes observed in the size of the grafts over time. No relationship between the changes observed in any of these parameters and hepatic growth was apparent. In both cases, the liver increased in volume at a rate of ˜ 70 ml/day. These data demonstrate that a small-for-size liver transplanted into a larger recipient increases in size at a rate of ˜ 70 ml/day until it achieves a liver volume consistent with that expected given the recipient’s size, age, and sex.
326. A Versatile Tool for Conditional Gene Expression and Knockdown
Authors: Jolanta Szulc, Maciej Wiznerowicz, Friedrich Beermann, Didier Trono, Patrick Aebischer
Journal: Molecular Therapy (2006)

Drug-inducible systems allowing the control of gene expression in mammalian cells are invaluable tools for genetic research, and could also fulfill essential roles in gene- and cell-based therapy. However, currently available systems often exhibit limited in vivo functionality due to leakiness, insufficient levels of induction, lack of tissue specificity or prohibitively complicated designs. To overcome these limitations we have developed a lentivector-based, conditional gene expression system for tetracycline-controllable repression of polymerase II-driven transgenes or polymerase III- controlled sequences encoding small inhibitory hairpin RNAs (shRNAs). Our system allows for tightly controlled, robust, and fully reversible gene expression or knockdown in cell lines, primary human haemopoietic progenitor cells and embryonic mouse stem cells (ES) in vitro, in both Tet-on or Tet-off configurations. Tight and efficient conditional expression of human Glial Cell Line Derived Neurotrophic Factor (GDNF) in the rat striatum and substantia nigra was achieved using this vector offering numerous opportunities for gene therapy approaches, modeling human diseases or studying gene function in central nervous system. When used for conditional knockdown this system allows for robust and fully reversible control of endogenous TP53 tumor supressor in human cancer cells xenotransplanted into nude mice, thus opening promising possibilities for both basic and applied cancer research. Finally, we probed the potential of our system by generating transgenic mice either by infection of fertilized oocytes with LV vectors or blastocyst transfer of transduced ES cells. These results pave the novel ways for basic or translational research, the development of gene-based therapeutics, and for creation of animal models of human diseases. M.W. and D.T. patented part of the technology described in this article.
ABC of Oxygen: Acute oxygen therapy
Authors: N T Bateman, R M Leach
Journal: BMJ (1998)

<b>Objective.</b> To explore the social and academic experiences of students identifying as underrepresented racial minorities (URMs) in a pharmacy school, how they made meaning of their experiences, and the strategic actions they took to navigate towards degree completion. <b>Methods.</b> Twenty students from a school of pharmacy within a research-intensive institution participated in semi-structured interviews. Data were analyzed through several rounds of coding. Trustworthiness procedures included the use of multiple coders, a dependability audit, and analytic memos to promote reflexivity. <b>Results.</b> The study yields a conceptual model. Pre-pharmacy school factors such as pipeline programs, work experiences, family, and URM health professionals impacted students' interest in and encouragement to attend pharmacy school. Students reported experiences including a lack of diversity, feeling unwelcomed, and concerns about cultural competency and group work challenges. Students were motivated by URM faculty members, self-efficacy, and a sense of purpose. Students were inhibited by the mental impact of sociopolitical events, the pressures of representing their race/ethnicity, and feeling inferior. Students took several actions to navigate the school including "code-switching," finding solace and support with other URMs, seeking cultural competence-related experiences to complement the curriculum, and strategically remaining silent or speaking up during group work conflicts. <b>Conclusion.</b> This exploratory study provides a roadmap to better understand URM students' journey to pharmacy school and experiences therein. Findings could be used by pharmacy schools to create a more inclusive environment for URM students and provide future directions for scholars pursing diversity-related research agendas in health professions education.
Comparison of Loperamide With Bismuth Subsalicylate for the Treatment of Acute Travelers' Diarrhea
Authors: Philip C. Johnson, Charles D. Ericsson, Herbert L. DuPont, Donna R. Morgan, Jo Ann M. Bitsura, Lindsey V. Wood
Journal: JAMA (1986)

Loperamide hydrochloride was compared with bismuth subsalicylate for the treatment of acute nondysenteric travelers' diarrhea in 219 students visiting seven countries in Latin America. Subjects whose condition was not improved with therapy could elect to take trimethoprim-sulfamethoxazole. Persons receiving loperamide passed fewer unformed stools when compared with the bismuth subsalicylate group during the first four hours of therapy, from four to 24 hours, and from 24 to 48 hours after therapy was initiated. Among subjects with disease due to enterotoxigenic Escherichia coli, Shigella sp, other pathogens, and unknown agents, fewer unformed stools were passed by the loperamide-treated subjects than the bismuth subsalicylate-treated subjects for all time periods studied. No significant prolongation of disease was seen in subjects with shigellosis treated with loperamide. Eight of the loperamide-treated subjects experienced constipation compared with one in the bismuth subsalicylate-treated group; otherwise, there was no difference in minor side effects experienced between both treatment groups. We conclude that loperamide is a safe and effective alternative to bismuth subsalicylate for the treatment of nondysenteric travelers' diarrhea.
Poverty reduction policies targeting poor people are not enough, UN warns
Authors: John Zarocostas
Journal: BMJ (2010)

Current approaches taken by governments and international agencies to cut poverty by targeting only poor people or adopting measures separate from broader aspects of economic development fail to tackle the underlying causes, a United Nations report warns. Such failure could leave about one billion people destitute by 2015, it says.

The report analyses the causes and persistence of poverty and looks at what works and what doesn’t in current policy planning and practice.

“The evidence shows that poverty is reduced when economic and social policies, institutions and political arrangements are mutually supportive,” the report says. “Simple prescriptions may …
Idiopathic Dilatation of the Pulmonary Artery
Authors: MADHUKAR DESHMUKH, SULAHATTIN GUVENC, LAMBERTO BENTIVOGLIO, HARRY GOLDBERG
Journal: Circulation (1960)

Thirteen patients with idiopathic dilatation of the pulmonary artery are described and their clinical, roentgenologic, electrocardiographic, and hemodynamic features are elaborated. Absence or mildness of symptoms was the most significant finding in this series. A pulmonic systolic murmur was constantly present. The roentgenogram showed various degrees of dilatation of the pulmonary artery in the presence of normal heart size. The electrocardiogram was normal. The hemodynamic studies showed a mild systolic pressure gradient across the pulmonic valve in some cases in the presence of normal right ventricular pressure. A possible explanation of this finding is discussed. Idiopathic dilatation of the pulmonary artery is a benign lesion and does not affect cardiac function to any appreciable degree.
THE CAUSE OF DEATH OF PROMINENT PERSONS.
Authors: RALPH S. MICHEL
Journal: JAMA (1896)

A curious interest attaches to the demise of a friend. When "the rider on the pale horse" stops at the house of a friend, we seldom fail to inquire the cause of death. Death is to us so deep a mystery. It changes a being full of energy and life and hope, into an inanimate object, with a rapidity that is appalling. We stand aghast in its presence. The friend, whose welcome smile we meet to-day, is dead to-morrow. We eagerly inquire the cause. So it seemed to me that it would be of interest to make a collection of facts in regard to the death of celebrated persons; those whom we have learned to know and love from their written pages; and those whose deeds have moved men's hearts, in the times in which they lived. It is impossible to ascertain the cause of death in many instances. Diagnosis
Justice and medical ethics.
Authors: R Gillon
Journal: BMJ (1985)

Justice, in the sense of fair adjudication between conflicting claims, is held to be relevant to a wide range of issues in medical ethics. Several differing concepts of justice are briefly described, including Aristotle's formal principle of justice, libertarian theories, utilitarian theories, Marxist theories, the theory of John Rawls, and the view--held, for example, by W.D. Ross--that justice is essentially a matter of reward for individual merit.
Radical Cystectomy for Bladder Cancer Today—A Homogeneous Series Without Neoadjuvant Therapy
Authors: Stephan Madersbacher, Werner Hochreiter, Fiona Burkhard, George N. Thalmann, Hansjörg Danuser, Regula Markwalder, Urs E. Studer
Journal: Journal of Clinical Oncology (2003)

To investigate the effect of pelvic lymph node dissection and radical cystectomy for transitional cell cancer of the bladder on recurrence-free and overall survival, pelvic recurrences, and metastatic patterns in a homogeneous group.A consecutive series of patients undergoing pelvic lymphadenectomy and radical cystectomy between 1985 and 2000 was analyzed. All patients were staged N0, M0 preoperatively, and no patient received neoadjuvant radio/chemotherapy. Pathologic characteristics based on the 1997 tumor-node-metastasis system, recurrence-free/overall survival, and metastatic patterns were determined.Five hundred seven patients (age 66 +/- 12 years) with a mean follow-up time of 45 months (range, 0.1 to 176 months) were analyzed. Five-year recurrence-free and overall survival were, respectively, 73% and 62% for patients with organ-confined, lymph node-negative tumors (n = 217; < or = pT2, pN0) and 56% and 49% for non-organ-confined, lymph node-negative tumors (n = 166; > pT2, pN0). Positive lymph nodes were found in 124 (24%) patients who had a 5-year recurrence-free (33%) or overall (26%) survival. Isolated local recurrences were observed in 3% of patients with organ-confined tumors (< or = pT2, pN0), 11% with non-organ-confined tumors (> pT2, pN0), and 13% with positive lymph nodes (any pT, pN+). Distant metastases developed in 25% of patients with organ-confined tumors, 37% with non-organ-confined tumors, and 51% with positive lymph nodes.Despite negative preoperative staging, pelvic lymphadenectomy and cystectomy for bladder cancer reveal a high percentage of unsuspected nodal metastases (24%) that have a 25% chance for long-term survival. This procedure also ensures a low pelvic recurrence rate even in lymph node-positive patients, and patients with locally advanced cancer have a 56% probability of 5-year recurrence-free survival.