tbuckley/cabot-search huggingface dataset:
The International Pharmaceutical Market as a Source of Low-Cost Prescription Drugs for U.S. Patients
Authors: Aaron S. Kesselheim, Niteesh K. Choudhry
Journal: Annals of Internal Medicine (2008)

In response to increasing prescription drug costs, more U.S. patients and policymakers are importing less-expensive pharmaceutical products from other countries. Large-scale prescription drug importation is currently illegal, but the U.S. Food and Drug Administration permits individuals to bring in 90-day supplies of drugs for personal use. As patient use of foreign-bought drugs has increased, federal legislators have continued to debate the full legalization of importation. Three factors help guide whether U.S. patients and policymakers can rely on other countries as sources of imported prescription drugs: whether the safety of the product can be ensured, how the import price compares with domestic prices, and how importation might affect the exporting country's pharmaceutical market. In wealthier countries with active regulatory systems, drug safety can be adequately ensured, and brand-name products are usually less expensive than in the United States (although generic drugs may be more expensive). However, implementing large-scale importation can negatively impact the originating country's market and can diminish the long-term cost savings for U.S. consumers. In low- and middle-income countries, prices may be reduced for both brand-name and generic drugs, but the prevalence of unauthorized products on the market makes ensuring drug safety more difficult. It may be reasonable for individual U.S. consumers to purchase essential medicines from certain international markets, but the most effective way to decrease drug costs overall is the appropriate use of domestic generic drugs, which are available for almost every major therapeutic class.
Comparison of the new miniature Wright peak flow meter with the standard Wright peak flow meter.
Authors: H G Oldham, M M Bevan, M McDermott
Journal: Thorax (1979)

Preproduction and current models of the miniature Wright peak flow meter have been compared with the standard Wright peak flow meter on normal and abnormal subjects. Early problems in production appear to have been overcome, and the current model agrees to within 3% with the standard peak flow meter, which is as close as the agreement between two standard instruments. The new mini-meter may be enclosed in a case, making direct comparisons with other instruments possible.
Twin- versus single-bag disconnect systems
Authors: D C Harris, E J Yuill, K Byth, J R Chapman, C Hunt
Journal: Journal of the American Society of Nephrology (1996)

Although twin-bag disconnect fluid-transfer systems for continuous ambulatory peritoneal dialysis (CAPD) have a lower rate of catheter-related infection than single-bag systems, their greater monetary purchase cost has prevented universal adoption. Therefore, a single-center randomized study was performed in 63 adult patients to compare the efficiency and total cost of Freeline Solo (FS, twin-bag) and Basic Y (BY, single-bag) systems. Patients were new to CAPD (N = 39), or had a new CAPD catheter, or had had no episodes of peritonitis or exit-site infection in the previous 12 months (N = 24). Total follow-up was 631 patient months (pt.mon), and 53 patients were still on the trial at its termination. Patients rated FS as easier to use than BY (P < 0.001). Peritonitis occurred on 23 occasions in 12 out of 30 patients using BY, and on seven occasions in five of 33 patients using FS. Time to first infection was less with BY than FS (hazard ratio, 2.4; 95% confidence interval (CI), 1.0 to 5.3; P < 0.04). Cumulative incidence of peritonitis was 1 per 14.0 pt.mon with BY and 1 per 46.5 pt.mon with FS (odds ratio, 3.6; 95% CI 1.5 to 8.5; P = 0.004). Length of hospitalization for peritonitis or exit-site infection was 98 days in six patients with BY, versus 17 days in two patients with FS. With BY, four catheters were removed because of infection, but none with FS (P < 0.05). With BY, the total cost of infection was $AUD127,079 ($5033 per pt.yr) versus $19,250 ($704 per pt.yr) with FS, which offset the higher purchase cost of FS. The total cost of CAPD was $AUD956 per pt.yr less with FS than BY. In conclusion, the higher purchase cost of the FS twin-bag system is more than offset by savings from its lower incidence of peritonitis.
Immunotoxins: An Update
Authors: Gerald R. Thrush, Laura R. Lark, Birgitta C. Clinchy, Ellen S. Vitetta
Journal: Annual Review of Immunology (1996)

The use of immunotoxins (ITs) in the therapy of cancer, graft-vs-host disease (GvHD), autoimmune diseases, and AIDS has been ongoing for the past two decades. ITs contain a targeting moiety for delivery and a toxic moiety for cytotoxicity. Theoretically, one molecule of a toxin, routed to the appropriate cellular compartment, will be lethal to a cell. Newly developed MoAbs, toxins, and molecular biological technologies have enabled researchers to construct ITs that can effectively kill many different cell types. In fact, phase I/II clinical trials have given promising results. Although nonspecific toxicity and immunogenicity still limit the use of IT therapy, these agents hold enormous promise in an optimal setting to treat minimal disease.
IMPACT OF PLAQUE DISTRIBUTION ON SIDE BRANCH COMPROMISE AFTER STENT DEPLOYMENT IN BIFURCATION
Authors: Masahiro Yamawaki, Toshiya Muramatsu, Reiko Tsukahara, Yoshiaki Ito, Hiroshi Ishimori, Keisuke Hirano, Masatsugu Nakano, Motoharu Araki, Shinya Sasaki, Hideyuki Takimura, Yasunari Sakamoto, Ikki Komatsu, Takuro Takama
Journal: Journal of the American College of Cardiology (2011)
Breathless in the bath
Authors: G P Whyte, M Harries, J Dickinson, M I Polkey
Journal: British Journal of Sports Medicine (2006)

The case is reported of a male track and field athlete with breathing difficulties at rest and during exercise, which were exacerbated in the supine position and during water immersion. Right hemidiaphragmatic paralysis was diagnosed. The cause of this relatively benign disorder is not known and there are no serious clinical implications. There is no treatment, but a continuation of exercise together with interventions to strengthen the subsidiary inspiratory muscles is recommended.
Behaviour of effector cells, synovial fluids, and sera from rheumatoid arthritis patients in antibody-dependent cell-mediated cytotoxicity.
Authors: L A Cooke, F C Hay, R Perumal
Journal: Annals of the Rheumatic Diseases (1979)

Antibody-dependent cell-mediated cytotoxicity (ADCC) was examined in patients with rheumatoid arthritis (RA). The cytotoxicity of peripheral blood leucocytes from patients with RA was similar to that found in normal persons, whereas ADCC was less effective in RA synovial fluid cells. It is possible that the activity in these cells is lower because of immune complexes and other factors being absorbed from the synovial fluid itself. Although patients' sera had little effect on normal peripheral blood leucocytes, synovial fluid from RA patients was markedly inhibitory in ADCC. The degree of inhibition correlated significantly with the clinical status of the patients.
Short course of antibiotic treatment in acute exacerbations of COPD
Authors: R. Wilson
Journal: Thorax (2008)

such a high cure and completion rate.Firstly, no outcome was reported in 18.1% (2364) of cases, and the demographics of the non-reported cases showed higher age and higher proportions of white ethnicity and pulmonary tuberculosis, all of which are more associated with adverse outcome.These individuals, if they had had reports, are likely to reduce the overall success figures as the authors themselves accept.Secondly, enhanced surveillance reports outcome if properly recorded but may miss important process errors, which would only be apparent as later relapse or drug resistance.The pilot for enhanced surveillance showed less than half were getting an appropriate four drug regimen, 11% were not on combination tablets and only 41% had minimum compliance monitoring, 18 all factors potentially lead- ing to later relapse.Relapse is not recorded under enhanced surveillance but between 5% and 10% of notifications have a history of prior tuberculosis treatment, suggesting their current episode is a relapse.Relapse rates after treatment are seldom reported in the UK, 29 but would be expected to be between 0% and 3% from data from controlled clinical trials. 3 Modification of the reporting criteria for the UK enhanced tuberculosis surveillance system seems appropriate from the analysis 26 but strenuous efforts need to be made to increase the level of outcome reporting above the current 82%, ideally to 100%.Short cross sectional audits may also be needed to confirm appropriate regimens, combination tablets and adequate adherence monitoring are being used.
Treatment and prevention of acute respiratory viral infections in patients with chronic obstructive pulmonary disease
Authors: Ekaterina Makarova, Nikolay Menkov, Ludmila Baronina, Galina Varvarina
Journal: European Respiratory Journal (2013)

Background.  Acute respiratory viral infections (ARVI) are aetiological triggers of exacerbations of chronic obstructive pulmonary disease (COPD).    Aim:  To study the efficacy and safety of complex medicine with antiviral and anti-inflammatory activity containing ultralow doses of antibodies (ULD AB) against interferon-γ (IFN-γ), CD-4 and histamine molecules (ergoferon) in treatment and prevention of ARVI in COPD patients.    Patients and methods:  The open comparative prospective clinical trial in parallel groups involving 48 adult patients was performed. The 1st group (25 patients) received the investigated medicine (ergoferon) in preventive regimen (1 pill 1 time in a day for 1 month), and with the appearance of ARVI - in treatment regimen (1pill 3 times in a day for 5 days, in 1st day additionally 5 pills). The 2nd group (23 patients) didn’t receive antiviral prevention/treatment. All patients obtained also treatment of COPD. The number and duration of the ARVI, and number of COPD exacerbations during 4 month follow-up period in groups were estimated.    Results:  The mean number and duration of ARVI episodes in the 1st group (0,6±0,3; 8,9±1,2 days) was less than in control group (1,1±0,4; 12,5±2,1 days). The number of moderate and severe COPD exacerbations during the follow-up period was decreased in the 1st group compared with the 2nd group. There were not registered any adverse effects in a patients taking investigated medicine.    Conclusion:  The administration of medicine containing ULD AB to IFN-γ, CD4 and histamine (ergoferon) in COPD patients leads to reduction in the frequency of COPD exacerbations caused by ARVI.
<i>LKB1</i> and Lung Cancer: More Than the Usual Suspects
Authors: Usman Shah, Norman E. Sharpless, D. Neil Hayes
Journal: Cancer Research (2008)

Abstract Often, the problem in cancer research is figuring out how a gene or pathway works in regulating cellular transformation. The question of what RAS activates or PTEN inhibits have been classic dilemmas of modern cancer biology. In these cases, biochemical and genetic studies have provided us with a fairly clear picture of the cancer relevant functions of these genes. For LKB1, a more recently identified human tumor suppressor gene, however, the problem is different. This serine-threonine kinase that is conserved from yeast to mammals seems to play a role in many diverse cellular pathways. Therefore, although elegant functional and genetic approaches have established critical roles for LKB1 in the regulation of metabolism, motility, polarity, and the cell cycle, the role(s) responsible for its true tumor suppressor function(s) is unknown. One is reminded of an Agatha Christie murder mystery where nearly every character in the book has reason to be suspected of committing the crime—there are too many suspects for how LKB1 might repress lung cancer. [Cancer Res 2008;68(10):3562–5]
Epidemiology of tuberculosis on Gran Canaria: a 4 year population study using traditional and molecular approaches
Authors: M J Pena
Journal: Thorax (2003)

In recent years several population based studies using restriction fragment length polymorphism (RFLP) analysis have shown a higher rate of recent transmission of tuberculosis than previously thought. This study was undertaken to determine the transmission patterns of tuberculosis and the potential causes of recent transmission on the island of Gran Canaria (Spain).The strains of all patients diagnosed with tuberculosis confirmed by culture between 1 January 1993 and 31 December 1996 were typed by RFLP using the insertion sequence IS6110. A cluster was defined as two or more isolates with an identical RFLP pattern. Epidemiological linkage through contact tracing was investigated.Of the total of 719 patients, 153 (21.3%) were excluded because there was inadequate bacterial DNA for genotyping (n=129) or the isolates of Mycobacterium tuberculosis had less than five copies of IS6110 (n=24). The isolates from 409 patients (72.3%) were grouped into 78 different clusters with an estimated 58.5% of the cases being due to recent transmission. Young age was the only significant predictor of clustering. Only in 147 (35.9%) of the 409 patients belonging to a cluster could an epidemiological link be found. 111 patients (19.6%) were identified as having had previous contact with a tuberculosis patient and 81 of them (72.9%) belonged to a cluster. The three largest clusters included 75, 49 and 20 patients, respectively.Recent transmission is frequent among patients with tuberculosis on Gran Canaria and could be associated with certain aspects of control measures. Some of the clusters described in the study could be due to the prevalence of particular strains of M tuberculosis on the island.
Recombinant Peptides as Biomarkers for Tumor Response to Molecular Targeted Therapy
Authors: Ralph J. Passarella, Li Zhou, John G. Phillips, Hongmei Wu, Dennis E. Hallahan, Roberto Diaz
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Phage display technology can be used to identify peptide sequences that bind rapidly and specifically to tumors responding to sunitinib therapy. These peptides may help to address problems with current methods of assessing tumor response to therapy that can be slow and have limited usage. Experimental Design: The peptide of interest was isolated after four rounds of biopanning in MDA-MB-231 and MCF-7 xenografted tumors. The binding location of the peptide was investigated with immunohistochemistry. Its in vivo ability to bind to breast tumors responding to therapy was determined by treating nude mice, xenografted with various tumor cell lines, with sunitinib and using near IR imaging to assess the ability of the peptide conjugated to Alexafluor-750 to bind tumors. Results: EGEVGLG was the dominant sequence isolated from biopanning. This peptide showed increased binding relative to control groups in two cancer cell lines (MDA-MB-435 and MCF-7 human breast) responding to sunitinib treatment, whereas no elevated binding occurred in vitro when samples were incubated with tumor cells that are unresponsive to sunitinib treatment (B16 melanoma and BxPC3 pancreatic). Mice xenografted with tumors that are responsive to sunitinib therapy showed increased peptide binding when compared with untreated control. Mice bearing tumors unresponsive to sunitinib therapy showed no increased peptide binding between treated and untreated groups. Conclusion: The use of recombinant peptides to assess the pharmacodynamic response of cancer holds promise in minimizing the duration of ineffective treatment regimens in patients, potentially providing a more rapid and less invasive assessment of cancer response to systemic therapy. (Clin Cancer Res 2009;15(20):6421–9)
Dermatitis herpetiformis and celiac disease: association with glomerulonephritis, hypocomplementia, and circulating immune complexes
Authors: A. V. Moorthy
Journal: JAMA (1978)

DERMATITIS herpetiformis is a disease of unknown cause, which is characterized by recurrent bullous eruptions of the skin often associated with gluten-sensitive enteropathy (celiac disease). Cutaneous deposition of IgA, the presence of circulating immune complexes, and an increased incidence of histocompatibility antigen HLA-B8 as well as an association with immunologic disorders, eg, thyroid disease, rheumatoid arthritis, chronic liver disease, cutaneous vasculitis, Addison's disease, systemic lupus erythematosus (SLE), and ulcerative colitis, have led to the speculation of immunologic alterations in dermatitis herpetiformis.<sup>1</sup>Glomerular deposition of immune complexes is a major pathogenic mechanism of mediation of injury in patients with glomerulonephritis.<sup>2</sup> <h3>Materials and Methods</h3> Biopsy material was processed as previously described.<sup>3</sup>Briefly, tissue for light microscopic examination was fixed in buffered 4% formaldehyde solution (10% formalin) embedded in paraffin sectioned at 2 μ, and stained with hematoxylin
Inhibition of phosphodiesterase 4 enhances lung alveolarisation in neonatal mice exposed to hyperoxia
Authors: K. Woyda, S. Koebrich, I. Reiss, S. Rudloff, S. S. Pullamsetti, A. Rühlmann, N. Weissmann, H. A. Ghofrani, A. Günther, W. Seeger, F. Grimminger, R. E. Morty, R. T. Schermuly
Journal: European Respiratory Journal (2008)

Bronchopulmonary dysplasia (BPD) is characterised by impaired alveolarisation, inflammation and aberrant vascular development. Phosphodiesterase (PDE) inhibitors can influence cell proliferation, antagonise inflammation and restore vascular development and homeostasis, suggesting a therapeutic potential in BPD. The aim of the present study was to investigate PDE expression in the lung of hyperoxia-exposed mice, and to assess the viability of PDE4 as a therapeutic target in BPD. Newborn C57BL/6N mice were exposed to normoxia or 85% oxygen for 28 days. Animal growth and dynamic respiratory compliance were reduced in animals exposed to hyperoxia, paralleled by decreased septation, airspace enlargement and increased septal wall thickness. Changes were evident after 14 days and were more pronounced after 28 days of hyperoxic exposure. At the mRNA level, PDE1A and PDE4A were upregulated while PDE5A was downregulated under hyperoxia. Immunoblotting confirmed these trends in PDE4A and PDE5A at the protein expression level. Treatment with cilomilast (PDE4 inhibitor, 5 mg·kg −1 ·day −1 ) between days 14 and 28 significantly decreased the mean intra-alveolar distance, septal wall thickness and total airspace area and improved dynamic lung compliance. Pharmacological inhibition of phosphodiesterase improved lung alveolarisation in hyperoxia-induced bronchopulmonary dysplasia, and thus may offer a new therapeutic modality in the clinical management of bronchopulmonary dysplasia.
Brain stimulation modulates the autonomic nervous system, rating of perceived exertion and performance during maximal exercise
Authors: Alexandre Hideki Okano, Eduardo Bodnariuc Fontes, Rafael Ayres Montenegro, Paulo de Tarso Veras Farinatti, Edilson Serpeloni Cyrino, Li Min Li, Marom Bikson, Timothy David Noakes
Journal: British Journal of Sports Medicine (2013)

Background The temporal and insular cortex (TC, IC) have been associated with autonomic nervous system (ANS) control and the awareness of emotional feelings from the body. Evidence shows that the ANS and rating of perceived exertion (RPE) regulate exercise performance. Non-invasive brain stimulation can modulate the cortical area directly beneath the electrode related to ANS and RPE, but it could also affect subcortical areas by connection within the cortico-cortical neural networks. This study evaluated the effects of transcranial direct current stimulation (tDCS) over the TC on the ANS, RPE and performance during a maximal dynamic exercise. Methods Ten trained cyclists participated in this study (33±9 years; 171.5±5.8 cm; 72.8±9.5 kg; 10–11 training years). After 20-min of receiving either anodal tDCS applied over the left TC (T3) or sham stimulation, subjects completed a maximal incremental cycling exercise test. RPE, heart rate (HR) and R–R intervals (as a measure of ANS function) were recorded continuously throughout the tests. Peak power output (PPO) was recorded at the end of the tests. Results With anodal tDCS, PPO improved by ∼4% (anodal tDCS: 313.2±29.9 vs 301.0±19.8 watts: sham tDCS; p=0.043), parasympathetic vagal withdrawal was delayed (anodal tDCS: 147.5±53.3 vs 125.0±35.4 watts: sham tDCS; p=0.041) and HR was reduced at submaximal workloads. RPE also increased more slowly during exercise following anodal tDCS application, but maximal RPE and HR values were not affected by cortical stimulation. Conclusions The findings suggest that non-invasive brain stimulation over the TC modulates the ANS activity and the sensory perception of effort and exercise performance, indicating that the brain plays a crucial role in the exercise performance regulation.
IL-7 receptor signaling is necessary for stage transition in adult B cell development through up-regulation of EBF
Authors: Kazu Kikuchi, Anne Y. Lai, Chia-Lin Hsu, Motonari Kondo
Journal: The Journal of Experimental Medicine (2005)

Cytokine receptor signals have been suggested to stimulate cell differentiation during hemato/lymphopoiesis. Such action, however, has not been clearly demonstrated. Here, we show that adult B cell development in IL-7−/− and IL-7Rα2/− mice is arrested at the pre–pro-B cell stage due to insufficient expression of the B cell–specific transcription factor EBF and its target genes, which form a transcription factor network in determining B lineage specification. EBF expression is restored in IL-7−/− pre–pro-B cells upon IL-7 stimulation or in IL-7Rα−/− pre–pro-B cells by activation of STAT5, a major signaling molecule downstream of the IL-7R signaling pathway. Furthermore, enforced EBF expression partially rescues B cell development in IL-7Rα−/− mice. Thus, IL-7 receptor signaling is a participant in the formation of the transcription factor network during B lymphopoiesis by up-regulating EBF, allowing stage transition from the pre–pro-B to further maturational stages.
Biophysical Correlates of Cognition Among Depressed and Nondepressed Type 2 Diabetic Patients
Authors: Virginia Elderkin-Thompson, Gerhard Hellemann, Rakesh K. Gupta, Anand Kumar
Journal: Diabetes Care (2008)

Caudate magnetization transfer (MT) ratios have indicated an abnormality in the macromolecular protein pool of diabetic patients. This study examined the relationship between MT ratios of the caudate and cognitive performance.Diabetic patients, diabetic and depressed patients, and healthy comparison subjects completed magnetic resonance imaging and a neuropsychological battery. Magnetization transfer ratios of caudate and three comparison regions were computed. The neuropsychological battery was aggregated into a global index of cognitive function and correlated with MT ratios.MT ratios of the caudate correlated with cognitive performance, and the correlations were stronger among diabetic patients than healthy control subjects. Comorbid depression increased the strength of the correlation compared with diabetes alone. Comparison regions showed no evidence of a diabetes effect on cognition.One mechanism precipitating cognitive loss during diabetes appears to be associated with cellular changes occurring in the macromolecular protein pool of the caudate.