tbuckley/cabot-search huggingface dataset:
Drug-Drug Interactions Among Elderly Patients Hospitalized for Drug Toxicity
Authors: David N. Juurlink, Muhammad Mamdani, Alexander Kopp, Andreas Laupacis, Donald A. Redelmeier
Journal: JAMA (2003)

Context Drug-drug interactions are a preventable cause of morbidity and mortality, yet their consequences in the community are not well characterized. Objective To determine whether elderly patients admitted to hospital with specific drug toxicities were likely to have been prescribed an interacting drug in the week prior to admission. Design Three population-based, nested case-control studies. Setting Ontario, Canada, from January 1, 1994, to December 31, 2000. Patients All Ontario residents aged 66 years or older treated with glyburide, digoxin, or an angiotensin-converting enzyme (ACE) inhibitor. Case patients were those admitted to hospital for drug-related toxicity. Prescription records of cases were compared with those of controls (matched on age, sex, use of the same medication, and presence or absence of renal disease) for receipt of interacting medications (co-trimoxazole with glyburide, clarithromycin with digoxin, and potassium-sparing diuretics with ACE inhibitors). Main Outcome Measure Odds ratio for association between hospital admission for drug toxicity (hypoglycemia, digoxin toxicity, or hyperkalemia, respectively) and use of an interacting medication in the preceding week, adjusted for diagnoses, receipt of other medications, the number of prescription drugs, and the number of hospital admissions in the year preceding the index date. Results During the 7-year study period, 909 elderly patients receiving glyburide were admitted with a diagnosis of hypoglycemia. In the primary analysis, those patients admitted for hypoglycemia were more than 6 times as likely to have been treated with co-trimoxazole in the previous week (adjusted odds ratio, 6.6; 95% confidence interval, 4.5-9.7). Patients admitted with digoxin toxicity (n = 1051) were about 12 times more likely to have been treated with clarithromycin (adjusted odds ratio, 11.7; 95% confidence interval, 7.5-18.2) in the previous week, and patients treated with ACE inhibitors admitted with a diagnosis of hyperkalemia (n = 523) were about 20 times more likely to have been treated with a potassium-sparing diuretic (adjusted odds ratio, 20.3; 95% confidence interval, 13.4-30.7) in the previous week. No increased risk of drug toxicity was found for drugs with similar indications but no known interactions (amoxicillin, cefuroxime, and indapamide, respectively). Conclusions Many hospital admissions of elderly patients for drug toxicity occur after administration of a drug known to cause drug-drug interactions. Many of these interactions could have been avoided.
Age as a Risk Factor for Inadequate Treatment
Authors: Terrie Wetle
Journal: JAMA (1987)

An age bias in treatment of breast cancer has been reported in a number of studies.<sup>1,2</sup>Alternative explanations for different treatment of older patients have been suggested, including presentation for treatment at a later stage of disease and higher levels of comorbidity among the old.<sup>2</sup>Greenfield et al<sup>3</sup>reported that older patients are more likely to be provided inadequate treatment for breast cancer, even when controlling for stage of disease, comorbidity, and functional status. What then are the reasons for systematic denial of optimal care for this important segment of the population? Is age an inadequate and inappropriate criterion on which to make treatment decisions? Although geriatricians have argued that the approach to elderly patients should be different from that for younger patients,<sup>4</sup>it is imperative that alterations in care of patients due to age be based on science and data, not on misinformation and mistaken
Human herpesvirus‐8 infection among heterosexual partners of patients with classical Kaposi’s sarcoma
Authors: L. Brambilla, V. Boneschi, S. Ferrucci, M. Taglioni, E. Berti
Journal: British Journal of Dermatology (2000)

DNA sequences of human herpesvirus-8 (HHV8) are found in lesions of Kaposi's sarcoma (KS).To verify the hypothesis of the sexual transmission of HHV8 infection.We used the immunoperoxidase assay to study the prevalence of serum antibodies to HHV8-related antigens in 27 consorts of patients with classical KS, and in a control group of 25 healthy women.Forty-four per cent of the study group were positive, compared with 8% of the controls.The sexual route may be one of the possible ways of transmission of the HHV8 virus.
Efficacy and safety of the <scp>SQ</scp>‐standardized grass allergy immunotherapy tablet in mono‐ and polysensitized subjects
Authors: H. Nelson, M. Blaiss, H. Nolte, S. Ø. Würtz, J. S. Andersen, S. R. Durham
Journal: Allergy (2012)

Abstract The efficacy of single‐allergen‐specific immunotherapy in polysensitized subjects is a matter of debate. We therefore performed a post hoc analysis of pooled data from six randomized, double‐blind, placebo‐controlled trials ( N = 1871) comparing the efficacy and safety of the SQ ‐standardized grass allergy immunotherapy tablet ( AIT ), Grazax ( Phleum pratense 75 000 SQ ‐T/2800 BAU , ALK , Denmark), in mono‐ and polysensitized subjects. A statistically significant reduction in the mean total combined symptom/medication score ( TCS ) of 27% was demonstrated in actively treated subjects compared with placebo ( P &lt; 0.0001). This was not dependent on sensitization status ( P = 0.5772), suggesting a similar treatment effect in mono‐ and polysensitized subjects (i.e. reductions of the TCS s of 28% and 26%, respectively, both P &lt; 0.0001). Finally, a comparable and favourable safety profile of grass AIT was demonstrated in the two subgroups. Thus, no difference in efficacy and safety of single‐allergen grass AIT was observed between mono‐ and polysensitized subjects.
Abstract 3543: Activation of the ERK pathways overcome the cisplatin-resistance in ovarian carcinoma cells
Authors: Michiko Nonaka, Hiroaki Itamochi, Wakae Kawaguchi, Kazunori Uegaki, Jun Naniwa, Shinya Sato, Muneaki Shimada, Tetsuro Oishi, Naoki Terakawa, Junzo Kigawa, Tasuku Harada
Journal: Cancer Research (2010)

Abstract Objective: Cisplatin (CDDP) is a key drug used to treat ovarian carcinoma that activates the mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling cascade and a phosphatidylinositol 3′-kinase (PI3K)-Akt pathway, both of which are considered pathways for cell proliferation and survival. The present study aimed to elucidate the roles of the MEK-ERK and PI3K-Akt pathways in regulating cytotoxicity in ovarian carcinoma cells induced by CDDP. Methods: Seven human ovarian serous adenocarcinoma cell lines were used in this study (KF, KFr, KOC-2S, SK-OV-3, SHIN-3, TU-OS-3, and TU-OS-4). We treated the cell lines with CDDP combined with PI3K inhibitor (LY294002 [LY]), MEK inhibitor (PD98059 [PD]), or ERK activator (phorbol 12-myristate 13-acetate [PMA]), then assessed cell viability by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The levels at which proteins expressed MEK, phosphorylated (p)MEK, ERK, pERK, Akt, pAkt, and cleaved caspase-9 were detected by western blotting. Cell cycle distribution and apoptotic cells were determined by flow cytometry, 5-bromo-2-deoxyuridine (BrdU) incorporation, and staining with Annexin V. Results: The range of IC50 to CDDP was 2.4 to 26.9 μM for those cell lines. KFr, a CDDP-resistant cell line, was established from KF cells, and the IC50 to CDDP was 9.6 μM. We defined the cell lines which had 9.6 μM or higher IC50 value as CDDP-resistance. Proteins MEK, pMEK, Akt, pAkt, ERK and pERK were expressed in all cell lines. CDDP combined with LY had an additive effect on inhibiting growth of cells in all lines. In contrast, we observed an antagonism for all cell lines when CDDP was combined with PD. Interestingly, growth of cells was dramatically suppressed when CDDP was combined with PMA in the CDDP-resistant cells (KFr, SK-OV-3, SHIN-3, TU-OS-3, TU-OS-4). Treatment with PMA upregulated protein expression levels of pERK and cleaved caspase-9 only in the CDDP-resistant cells. CDDP combined with PMA increased the S-phase fraction and apoptotic cells in the CDDP-resistant cells. Conclusion: ERK activated by PMA may overcome resistance to CDDP in ovarian carcinoma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3543.
Pirfenidone treatment in idiopathic pulmonary fibrosis: too much of a great expectation?
Authors: Spyros A. Papiris, Konstantinos Kagouridis, Likourgos Kolilekas, Christina Triantafillidou, Iraklis Tsangaris, Effrosyni D. Manali
Journal: European Respiratory Journal (2012)

To the Editors: 

Idiopathic pulmonary fibrosis (IPF) is a dreadful, chronic and irreversibly progressive fibrosing disease lacking any effective treatment and leading to death in all affected patients [1, 2]. The scientific community is becoming aware that corticosteroids and immunosuppressors have failed to prove any efficacy concerning both mortality and the prevention of devastating complications, such as IPF acute exacerbations [1, 3]. Not only has this approach proven ineffective, but also harmful. Recently, the National Heart, Lung, and Blood Institute (Bethesda, MD, USA) aborted the continuation of treatment of combined prednisone, azathioprine and N -acetylcysteine (one arm of the three-arm multicentre PANTHER-IPF clinical trial) due to safety concerns [4]. The results of the interim analyses revealed that patients with IPF receiving the conventionally used triple-drug therapy consisting of prednisone, azathioprine and N -acetylcysteine had worse outcomes than those who received matched placebos. Thus, the need for an effective and safe treatment for IPF is still being pursued in several clinical trials.

Pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone), a novel compound with anti-inflammatory, antifibrogenic and antioxidant properties, appears promising in IPF patients [1, 2 …
Fertility treatment regulator steps up warning about multiple births
Authors: Caroline White
Journal: BMJ (2006)

The UK fertility treatment regulator has stepped up its warnings to couples seeking treatment about the risks of multiple births as a result of assisted conception techniques.

The move came last week as the Human Fertilisation and Embryology Authority published its new guide on treatment options for patients and healthcare professionals and released its latest set of figures on the live birth rate achieved at 85 UK licensed clinics.

The cumulative figures show that between April 2003 and March 2004 the live birth rate rose 1.2 percentage points on the previous year to 21.6%. The increase was reflected across all age groups. …
Partner choice, fairness, and the extension of morality
Authors: Nicolas Baumard, Jean-Baptiste André, Dan Sperber
Journal: Behavioral and Brain Sciences (2013)

Abstract Our discussion of the commentaries begins, at the evolutionary level, with issues raised by our account of the evolution of morality in terms of partner-choice mutualism. We then turn to the cognitive level and the characterization and workings of fairness. In a final section, we discuss the degree to which our fairness-based approach to morality extends to norms that are commonly considered moral even though they are distinct from fairness.
The Role of the General Practitioner in Medical Teaching
Authors: Homer B. Martin
Journal: JAMA (1963)

THE CHANGING CHARACTER of American medicine has confronted physicians individually and collectively with a problem of great interest and concern. Is there a useful future for the general practitioner or does he represent only a sentimental remembrance of the past without value in modern times? All too often the varied answers have been highly charged with emotion, reflecting merely a personal viewpoint which is remarkably free of objective and constructive thinking. There are those individuals who feel every future family doctor should be a specialist. These prophets are quick to sound the death knell of the general practitioner and look upon his existence today as somewhat of an anachronism. To keep abreast of the rapid advance in modern medicine, they propose that the internist and pediatrician be fashioned into the future family physician. However, the idea of a general practitioner is so old fashioned, it is suggested that he
Sirt1 Extends Life Span and Delays Aging in Mice through the Regulation of Nk2 Homeobox 1 in the DMH and LH
Authors: Akiko Satoh, Cynthia S. Brace, Nick Rensing, Paul Cliften, David F. Wozniak, Erik D. Herzog, Kelvin A. Yamada, Shin-ichiro Imai
Journal: Cell Metabolism (2013)
Mildly dilated congestive cardiomyopathy.
Authors: A Keren, M E Billingham, D Weintraub, E B Stinson, R L Popp
Journal: Circulation (1985)

Five patients with only mildly dilated ventricles but other features typical of congestive cardiomyopathy underwent cardiac transplantation for class IV NYHA heart failure. The findings of clinical studies, cardiac catheterization, endomyocardial biopsy, and pathologic examination of the removed hearts in this group with mildly dilated congestive cardiomyopathy (MDCM) were compared with similar data in four patients with idiopathic restrictive cardiomyopathy (IRCM) and in 10 patients with typical dilated congestive cardiomyopathy (DCM). In comparison with the other groups, patients with MDCM had a higher incidence of familial cardiomyopathy (p = .02) and a shorter symptomatic period than patients with IRCM (p less than .02). Patients with both MDCM and DCM had globular hearts (with predominant left ventricular dilatation), congestive hemodynamics and poor left ventricular contractility (ejection fraction 12% to 19%), and high incidence of ventricular thrombi. Patients with IRCM showed normal ventricular size, marked atrial dilatation, restrictive hemodynamics, mild-to-moderate decrease in left ventricular contractility (ejection fraction 29% to 55%), and absence of ventricular thrombi. Cardiac index, ventricular wall thickness, and light microscopic findings were similar in the three groups of patients. Electron microscopy showed no myofibrillar loss in patients with IRCM but mild (partial) or moderate-to-severe (almost total) myofibrillar loss in those with MDCM and DCM, respectively. We conclude that end-stage congestive cardiomyopathy may occur without significant ventricular dilatation and patients with MDCM have heart sizes intermediate between those found in IRCM and DCM but their clinical, hemodynamic, and pathologic findings are virtually identical to those of patients with typical DCM.
Influence of applied stress on mitotic response of arteries to injury with a balloon catheter: quantitative study in rat thoracic aorta
Authors: L. CAPRON, P. BRUNEVAL
Journal: Cardiovascular Research (1989)

Proliferation of arterial smooth muscle cells is an important feature of atherosclerosis, and a well documented reaction to intimal injury. To assess the influence of the intensity of injury to rat thoracic aorta, we studied the effects of a soft or hard friction with a moderately or tightly inflated balloon catheter at 2, 14 and 30 d after operation. As compared with soft injury, hard injury (1) strongly enhanced the proliferating response of the aortic intima and media (median incorporation of tritiated thymidine into deoxyribonucleic acid on day 2 increase 2.8-fold, 95% confidence interval 2.3-3.3; median deoxyribonucleic acid content on day 14; 102.1 v 72.1 micrograms); (2) markedly delayed endothelial regeneration (median percentage of intimal area stained by Evans blue on day 14: 33.1 v 0.6%). On day 2, transmission and scanning electron microscopy showed that endothelial denudation was complete after a hard injury, but only partial after a soft one. However, macroscopic staining of the intima with Evans blue was complete in both instances. The extent of endothelial denudation appears to be a major determinant of the mitotic reaction of arteries to injury. In the experimental search for drugs to reduce muscular proliferation (of potential value in the prevention of restenosis after percutaneous transluminal angioplasty), endothelial injury with balloon catheters should be carefully standardised, and applied "blindly" to afford valid comparisons between treated and control groups of animals.
Transcriptional Effect of DEFB1 Gene 5′ Untranslated Region Polymorphisms
Authors: John Petros
Journal: Cancer Research (2007)

In Response: 

We wish to acknowledge the outstanding and careful work done by Prof. Milanese in assessing the functionality of 5′ untranslated region (UTR) single nucleotide polymorphisms (SNP) in the DEFB1 gene and are gratified that they agree with our assessment that these SNPs can modulate
Taking the Blood Pressure
Authors: Geoffrey E. King
Journal: JAMA (1969)

Some of the sources of error in sphygmomanometry have been clarified by recent research. High readings may result from the failure of the cuff bladder to completely encircle the arm. Observer bias in blood pressure readings may prove unimportant in view of the sampling error associated with infrequent determinations. The generation of Korotkoff sounds remains incompletely understood. Recent work suggests that the "silent" diastolic endpoint be the preferred index since it is associated with smaller random errors.
Spontaneous Bacterial Peritonitis: A Prospective Investigation in Predominantly Nonalcoholic Cirrhotic Patients
Authors: None Giovambattista, Rosa Giovanna Simonetti, Antonio Craxí, Sonia Di Piazza, Caterina Spanó, Luigi Pagliaro
Journal: Hepatology (1983)

Two hundred and twenty-four consecutive inpatients with cirrhosis, mostly of nonalcoholic etiology, and ascites were prospectively investigated on admission for spontaneous bacterial peritonitis (SBP) by culture, smear, and polymorphonuclear (PMN) counts of ascitic fluid. Positive cultures were found in 54 patients. A possible intraabdominal source of infection was apparent in five of them, all with clinically overt peritonitis (secondary peritonitis). No intraabdominal source of infection was identified in the remaining 49. These patients were classified into the following groups: (a) SBP , 27 patients (positive cultures plus PMN counts ± 250 per mm 3 ). Nine of them had no clinical features of peritonitis (silent SBP) in contrast to the other 18 (symptomatic SBP). (b) Bacteriascites (BA), 18 patients (positive culture with PMN counts less than 250 per mm 3 in the absence of clinical peritonitis). Four patients were unclassified. Among 170 patients with negative culture, six had an overt peritonitis plus a positive smear and PMNs ± 250 per mm 3 into ascites and were considered as probable SBP. The remaining 164 patients were classified as sterile ascites. A single strain of Gram-negative bacteria (usually of enteric origin) was recovered frequently in patients with symptomatic or silent SBP (79%) whereas Gram-positive bacteria were more frequently found in patients with BA (61%, p &lt; 0.01). In-hospital mortality showed a statistically significant difference among patients with SBP (48%) and those with BA (22%) or sterile ascites (18%) (p &lt; 0.05 and p &lt; 0.0005, respectively). We conclude that SBP is frequent event in nonalcoholic cirrhosis. Bacterial contamination of ascites may remain in balance or progress to overt peritonitis according to the pathogenicity of the agent. SBP carries a high mortality in comparison to sterile ascites or BA despite early antibiotic treatment.
Prognostic Importance of Ophthalmoscopic Findings in Essential Hypertension
Authors: Donald J. Breslin
Journal: JAMA (1966)

Analysis of data on 540 hypertensive patients grouped according to the retinal criteria of Keith, Wagener, and Barker and followed for at least 20 years, or until death, showed that (1) the survival rate in each ophthalmoscopic group was less than that expected in a normal population of the same age and sex distribution, and was poorer for men than for women, (2) there was a definite relationship between severity of retinal changes (ophthalmoscopic grouping) and survival rate and incidence of cardiac and renal complications of hypertension, and (3) for any given level of diastolic blood pressure the prognosis worsened with increase in severity of retinal changes (from lower to higher ophthalmoscopic grouping). It is concluded that changes in the optic fundi remain the simplest, most practical, and most accurate guide to prognosis in hypertension, with or without complications.
Aspects of database construction and interrogation of relevance to the accurate prediction of rodent carcinogenicity and mutagenicity.
Authors: J Ashby
Journal: Environmental Health Perspectives (1991)

Attempts to reconcile qualitative carcinogenicity databases with qualitative mutagenicity database continue to indicate that there is no useful relationship between mutagenicity/genotoxicity and rodent carcinogenicity. It is suggested that recognition of two classes of carcinogen, genotoxic and nongenotoxic, is the first step in finding meaningful correlations between the above parameters. This then leads to purposeful intervention into the databases, including rejecting low quality data, abandoning some assays from the database, and clustering certain end points as repetitive rather that independent of each other. Seeking specific correlations within a focused database may yield knowledge from the current wealth of information. The effort required to build databases, particularly quantitative ones, has so far prevented the equally arduous task of their correct interrogation. Preliminary indications are the mutagenicity is closely correlated with genotoxic carcinogenesis and completely independent of nongenotoxic carcinogenesis.
Whooping cough in Shetland.
Authors: G T Stewart
Journal: BMJ (1979)

phils, the theatre staff had 221 ±99 x 106/1 eosino- phils and the controls 79±63 x 106/1 (P<0001).When those with any kind of allergic history were excluded, a statistically significant difference remained between the groups.When the leucocyte and differential counts were checked six months later, the leucocyte count was 4900 ±780 x 106/1 in the theatre staff and 4500 ± 1090 x 106/1 in the controls.The proportion of eosinophils was 0 04 ±0-02 in the theatre staff and in the controls 0-02±0-02 (P<001), and the absolute eosinophil counts were 206±119x 106/1 and 96±72x 106/1 respectively (P<005).Summer holidays of one month in the theatre staff had no effect on the leucocyte and eosinophil counts.However, when the direct chamber method of Randolph7 was used, the eosinophil count in the theatre staff was 132 ±68 ( x 106/l) and 94 ± 67( x 106/1) in the controls (P> 005).To verify the previous finding of the increased eosinophil count in the theatre staff of Loimaa Regional Hospital, we studied the operating theatre personnel of Turku University Central Hospital.They included 125 nurses and doctors (117 women and eight men).The controls were 70 nurses from the wards.The proportion of eosinophils, 0 03 + 0-02 in the theatre staff, was higher than in the controls (0 02 ±0-02) (P <0-05); but the difference in the absolute numbers of eosinophils (173± 147 X 106/1 and 144± 122 x 106/1, respectively) was not statistically significant.This study suggests that operating theatre work increases the proportion of eosinophils.The same observation has been made by Werthmann,8 but in that study the eosinophil count decreased after six weeks' leave.The clinical significance of this finding remains to be established.
BASH-novel PKC-Raf-1 pathway of pre-BCR signaling induces κ gene rearrangement
Authors: Mutsumi Yamamoto, Katsuhiko Hayashi, Takuya Nojima, Yumi Matsuzaki, Yohei Kawano, Hajime Karasuyama, Ryo Goitsuka, Daisuke Kitamura
Journal: Blood (2006)