tbuckley/cabot-search huggingface dataset:
Medecins Sans Frontieres campaigns to increase treatment of Chagas disease
Authors: P. Moszynski
Journal: BMJ (2009)

The charity Medecins Sans Frontieres last week launched an international campaign to raise awareness of the parasitic Chagas disease, to encourage patients to seek help and doctors to treat the disease in both its acute and chronic stages.

Because the disease has previously been considered incurable, many patients who realise they are infected do not seek help, the charity says. And many other patients don’t know they have the disease.

Gemma Ortiz, head of the charity’s Chagas campaign, said, “Patients aren’t presenting, doctors aren’t prescribing, so manufacturers don’t know how many drugs to produce. Now, knowing that the majority of those infected by the parasite [that …
Clinical Outcomes and Cost-Effectiveness of Retinopathy Screening in Youth With Type 1 Diabetes
Authors: Betty Huo, Amy T. Steffen, Karena Swan, Kristin Sikes, Stuart A. Weinzimer, William V. Tamborlane
Journal: Diabetes Care (2007)

Since type 1 diabetes can lead to asymptomatic microvascular disease, regular screening for diabetic retinopathy (DR) in youth with type 1 diabetes has been recommended. The American Diabetes Association (ADA) (1) advises annual retinopathy screening once a child is 10 years old and has had type 1 diabetes for 3–5 years. This recommendation may have been appropriate in the pre-intensive treatment era, when elevated A1C levels were associated with early development of DR (2). However, results of the Diabetes Control and Complications Trial (3) demonstrated that intensive treatment in adolescents markedly delayed early microvascular changes in the retina. Since A1C levels in youth with type 1 diabetes are much lower now than they were 20 years ago (4,5), the yield from such screening examinations is also likely to be reduced.

Most DR screening studies have been carried out by retinal specialists using state-of-the-art technology (6). In many pediatric diabetes clinics like ours, however, general ophthalmologists and optometrists do not use advanced techniques to perform most routine eye screening, which may reduce the likelihood of identifying early retinal changes. The aim of this study was to examine the prevalence of positive DR exams in our Pediatric Diabetes Clinic population in comparison to the yield from blood pressure and microalbuminuria screening in the same patients.

Charts of all type 1 diabetic patients in our Diabetes Clinic were …
Sleeping and Breathing
Authors: Gerard M. Turino, Roberta M. Goldring
Journal: New England Journal of Medicine (1978)

He sleeps well who knows not that he sleeps ill. (Latin proverb)Clinical investigation has provided many examples of disturbances in normal physiology and biochemistry in which the function of a carefully integrated system is disrupted because of circumscribed defects in one component or link in the system. It is remarkable in this regard that discrete defects in the complex process of the regulation of pulmonary ventilation were late in coming to the attention of physiologists and clinicians. The concept of respiratory failure in the presence of normal lungs emerged conceptually in the middle 1950's as a result of case . . .
The Smoke Ring: Tobacco, Money, and Multinational Politics
Authors: Ronald M. Davis
Journal: JAMA (1985)

Tobacco was listed as a drug in the 1890 edition of the<i>US Pharmacopeia</i>, the official compendium of drug standards for the United States, but was dropped from the 1905 edition and never reappeared. According to political legend, tobacco was banished from the pages of the<i>Pharmacopeia</i>in exchange for the votes of tobacco state congressmen for the original Food and Drug Act.<sup>1</sup>Eighty years later, in the words of Peter Taylor, "the [tobacco] problem remains political." Taylor is a British investigative journalist with five film documentaries on the smoking issue to his credit. The best known of these is<i>Death in the West</i>, which featured interviews with six real cowboys in the American West dying of lung cancer or emphysema. After its first showing on British television in 1976, the Philip Morris tobacco company filed an injunction, and the film was locked in a vault under court order.
CLINICAL EXPERIENCE WITH 99mTc-HEXAMETHYLPROPYLENE-AMINEOXIME FOR LABELLING LEUCOCYTES AND IMAGING INFLAMMATION
Authors: A.M. Peters, S. Osman, B.L. Henderson, J.D. Kelly, H.J. Danpure, R.J. Hawker, H.J. Hodgson, R.D. Neirinckx, J.P. Lavender
Journal: The Lancet (1986)
Measurements of coronary flow reserve: defining pathophysiology versus making decisions about patient care.
Authors: F J Klocke
Journal: Circulation (1987)

THE POTENTIAL ATTRACTIVENESS of measure- ment of coronary flow reserve in an area ofmyocardium supplied by a stenosed coronary artery has long been recognized.As options for quantifying flow reserve in man have improved, there has been increasing interest in the use of flow reserve measurements to make indi- vidual patient care decisions as well as to define pathophysiology in patient groups.The requirements for effective use in individual patients are in many ways more stringent than in patient groups.Factors that must be considered on an individual rather than group basis include effects of variables potentially affecting flow reserve independently of degree of stenosis, theoretical and practical limitations of specific measurement tech- niques, and confidence limits for procedurally satis- factory measurements. Factors underlying interest in measurements of flow reserve in manLimitations of arteriographic estimates of stenosis severity.Despite the acknowledged pivotal role of coronary arteriography in management decisions in patients with coronary heart disease, the functional significance of an arteriographic lesion often cannot be settled from the arteriogram alone.This point has been emphasized by a number of experimental studies of stenosis behavior, particularly those of Gould.1 It is generally agreed that limitations of arteriographic measurements are most troublesome for stenoses ofmoderate-to-severe degree, i.e., 50% to 90% diameter narrowing.Because
Low molecular weight components of polymers used in packaging.
Authors: S G Gilbert
Journal: Environmental Health Perspectives (1975)

The increasing use of polymers in packaging of foods and drugs focuses attention on the possible chronic toxicity relations of migrants from these polymers to the contents. Such migrants can arise from residues and additives in the polymers from manufacturing processes used in fabrication of packages. The origin and chemical nature of potential migrants, the methods of transfer, and principles involved in development of safety criteria for their regulation are discussed.
Tuberculosis in Anergic HIV-Infected Drug Users
Authors: Hans Abeles
Journal: JAMA (1993)

<h3>To the Editor.</h3> —Selwyn et al<sup>1</sup>report important information for the prevention of tuberculosis in addicts infected with the human immunodeficiency virus (HIV). We would like to make the following comments based on our experience at the Albert Einstein College of Medicine Methadone Maintenance Clinic at Bronx (NY) Municipal Hospital Center, which was established 26 years ago specifically for the treatment of addicts with tuberculosis. In 1985, we reported that 27% of our patients were positive for purified protein derivative (PPD) and 9% were anergic.<sup>2</sup>In 1989, again 97 (27%) of 355 patients who were tested were PPD-positive. Of these 97 patients, 20 (20%) had a history of treated tuberculosis. Of the remaining 77 PPD-positive patients, 61 (80%) had received preventive isoniazid treatment. Sixteen (20%) had no preventive treatment for one of the following reasons: they were HIV-negative and over 35 years of age; they had elevated, unstable
Effect of Cyclosporine on Colchicine Secretion by A Liver Canalicular Transporter Studied In Vivo
Authors: Vincent K. Speeg, Alma L. Maldonado, Julie Liaci, Donna Muirhead
Journal: Hepatology (1992)

The multidrug resistance transport protein is a normal constituent of the liver canalicular membrane, although its function has not been defined in vivo. Colchicine, a multidrug resistance substrate, is eliminated mainly by the liver. Cyclosporine reverses multidrug resistance in vitro, presumably by inhibiting the multidrug resistance transporter. This study assesses biliary colchicine elimination and the effect of cyclosporine on this process. After cyclosporine administration biliary colchicine clearance decreased from 11.6 +/- 0.8 to 2.2 +/- 0.4 ml/min.kg (p less than 0.05), and the colchicine bile/plasma ratio decreased from 166 +/- 9 to 38 +/- 5 (p less than 0.05). Cremophor EL (a cyclosporine vehicle) transiently inhibited biliary colchicine clearance and colchicine bile/plasma ratio, but to a much smaller extent than cyclosporine in vehicle. Biliary cyclosporine clearance was 0.122 and 0.024 ml/min.kg after bolus doses of 2 or 10 mg/kg intravenously, respectively. Cyclosporine bile/plasma ratio was 1.3 to 5.2. When cyclosporine was given 16 hr before colchicine infusion, biliary colchicine clearance decreased 39% (p less than 0.05), and colchicine bile/plasma ratio decreased 51% (p less than 0.05). Thus colchicine is actively secreted into bile and will be useful in the study of the multidrug transporter in vivo. Cyclosporine profoundly inhibits colchicine secretion into bile but is itself mainly metabolized rather than secreted. If competition for a common carrier is the basis for the interaction, then cyclosporine represents a drug that binds to but is not transported by the canalicular transporter.
Differential expression of CD45RO (UCHL1) and its functional relevance in two subpopulations of circulating TCR-gamma/delta+ lymphocytes.
Authors: T Miyawaki, Y Kasahara, K Taga, A Yachie, N Taniguchi
Journal: The Journal of Experimental Medicine (1990)

We examined the developmental profile of TCR-gamma/delta+ cells with respect to CD45RO expression. Although total TCR-gamma/delta+ cells were negligible in the neonatal blood and increased with advancing age, most blood TCR-gamma/delta+ cells markedly expressed CD45RO without a distinction of age, probably reflecting a different CD45RO expression of two subsets defined by BB3 and delta TCS1 mAbs. The vast majority of BB3+ cells expressed CD45RO, whereas expression of CD45RO was virtually absent in the delta TCS1+ population. Functional studies revealed that, while both TCR-gamma/delta+ cell subsets showed CD3-mediated activation, only BB3+ (or Ti gamma A+) cells, but not delta TCS1+ cells, appeared to proliferate in response to PPD in PPD-reactive individuals. The results suggested that the CD45RO+ (BB3+ or Ti gamma A+) subset among blood TCR-gamma/delta+ cells may be mainly involved in the memory or primed component of the immune system responding to some foreign antigens.
Personality of Students with Acne Vulgaris
Authors: C. J. Lucas
Journal: BMJ (1961)

BEHAVIOUR DISORDERS IN CHILDHOODBORrsH measures should be developed to help them achieve socially and mentally a healthy childhood and adult life.Information is needed about the proportion of children from broken homes who develop normally and the characteristics of their rearing which result in this healthy development, since we would like to emulate them in our foster homes and children's homes.I am grateful to Dr. Wilfred Warren for permission to make use of his cases and for the facilities at Brixton Child Guidance Unit.I am
Abstract 5299: VEGF receptor-3 interacts with PI3K directly to regulate lymphangiogenesis
Authors: Sanja Coso, Yiping Zeng, Kenneth Opeskin, Elizabeth D. Williams
Journal: Cancer Research (2012)

Abstract Dissemination of malignant cells into the regional lymph nodes is a common occurrence in many cancers. The vascular endothelial growth factor (VEGF) family is a major regulator spread of cancer to lymph nodes via induction of lymphangiogenesis. We have used primary lymphatic endothelial cells and clinical material to investigate VEGF-C/VEGF receptor (VEGFR)-3 signalling pathways. We found that treatment with VEGF-C induced activation of PI3K/Akt and MEK/Erk in lymphatic endothelial cells. Furthermore, activation of PI3K/Akt by VEGF-C/VEGFR-3 resulted in phosphorylation of P70S6K, eNOS, PLCγ1, and Erk1/2. Importantly, a direct interaction between PI3K and VEGFR-3 in lymphatic endothelial cells was demonstrated both in vitro and in clinical specimens, where it was associated with the presence of lymph node metastases in small cell carcinoma of the lung. Blocking PI3K abolished VEGF-C-stimulated lymphatic endothelial cell tube formation and migration. Our findings demonstrate that specific VEGFR-3 signalling pathways are activated in lymphatic endothelial cells by VEGF-C. The importance of PI3K in VEGF-C/VEGFR-3-mediated lymphangiogenesis provides a potential therapeutic target for tumor lymphatic metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5299. doi:1538-7445.AM2012-5299
Weekly Moxifloxacin and Rifapentine Is More Active Than the Denver Regimen in Murine Tuberculosis
Authors: Ian M. Rosenthal, Kathy Williams, Sandeep Tyagi, Andrew A. Vernon, Charles A. Peloquin, William R. Bishai, Jacques H. Grosset, Eric L. Nuermberger
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Treatment of tuberculosis with an efficacious once-weekly regimen would be a significant achievement in improving patient adherence. Currently, the only recommended once-weekly continuation phase regimen of isoniazid plus rifapentine (10 mg/kg) is inferior to standard twice-weekly therapy with isoniazid plus rifampin and is, therefore, restricted to non-high-risk patients. The substitution of moxifloxacin, a new 8-methoxyfluoroquinolone, for isoniazid and an increase in the dose of rifapentine could augment the activity of once-weekly regimens.To test this hypothesis we evaluated the sterilizing activity of improved once-weekly rifapentine-based continuation phase regimens in a murine model that mimics the treatment of high-risk patients with tuberculosis. The bactericidal activity of standard daily therapy and standard intermittent therapy ("Denver" regimen) was also assessed to evaluate the effect of intermittent drug administration during the initial phase of therapy.After 2 mo of treatment, lung colony-forming unit counts were 1 log(10) lower in mice treated with standard daily therapy than with the Denver regimen. During the continuation phase, the sterilizing activity of once-weekly moxifloxacin plus rifapentine (15 mg/kg) was significantly greater than that of the predominantly twice-weekly Denver regimen of isoniazid plus rifampin. No significant difference in sterilizing activity was detected between once-weekly isoniazid plus rifapentine (15 mg/kg) and the Denver regimen.These results suggest that the efficacy of the once-weekly isoniazid plus rifapentine continuation phase regimen can be increased by substituting moxifloxacin for isoniazid and by increasing the dose of rifapentine to a clinically acceptable level of 15 mg/kg.
Physiologic and Pathophysiologic Effects of Anemia
Authors: James W. Linman
Journal: New England Journal of Medicine (1968)

TWO 24-year-old women of similar height and weight were hospitalized on the same day; each was subsequently shown to have had, at the time of admission, a total red-cell mass that was 70 per cent of normal. The first patient sought medical attention because of pallor, progressive fatigability of several months' duration and some intolerance to cold. She was Cooperative and in no apparent distress. Vital signs were within normal limits (the pulse rate was 58). Physical examination revealed nothing significant except slight pallor and a cool, dry skin. The hemoglobin was 9.8 gm per 100 ml, the hematocrit 31 . . .
Encouragement of breast-feeding
Authors: M. Aylett
Journal: BMJ (1976)

menses in each patient, one before treatment, two while on ethamsylate (500 mg four times daily from five days before the anticipated onset of menstruation for 10 days) and two while on indistinguishable doses of placebo with double-blind random allocation of each of the tablets.The Wilcoxon signed rank test was used in statistical analysis of the results.Mean blood loss was 64-8 ml before treatment and 64-6 ml during placebo therapy (P>010) but was significantly less (53-5 ml; P <0-05) during administration of ethamsylate.The mean percentage reduction in blood loss was 18-6+4-7, giving a range at the 95% con- fidence level of 8-4-28-8.Such results, if confirmed by a longer series, would suggest that a patient with an IUD in situ who complained of menorrhagia should be offered ethamsylate as primary treatment.This could prove sufficiently effective in controlling the cycle to make further manipulation unnecessary.
Nanoparticle-directed sub-cellular localization of doxorubicin and the sensitization breast cancer cells by circumventing GST-Mediated drug resistance
Authors: Xianghui Zeng, Ralf Morgenstern, Andreas M. Nyström
Journal: Biomaterials (2013)

Resistance to single or multiple chemotherapeutic drugs is a major complication in clinical oncology and is one of the most common treatment limitations in patients with reoccurring cancers. Nanoparticle (NP)-based drug delivery systems (DDS's) have been shown to overcome drug resistance in cancer cells mainly by avoiding the activation of efflux pumps in these cells. We demonstrate in this work that polyester-based hyperbranched dendritic-linear (HBDL)-based NPs carrying doxorubicin (Dox) can effectively overcome microsomal glutathione transferase 1 (MGST1)-mediated drug resistance in breast cancer cells. Our DDS was much more effective at considerably lower intracellular Dox concentrations (IC50 6.3 μm vs. 36.3 μm) and achieved significantly greater reductions in viability and induced higher degrees of apoptosis (31% vs. 14%) compared to the free drug in the resistant cells. Dox-loaded HBDL NPs were found to translocate across the membranes of resistant cells via active endocytic pathways and to be transported to lysosomes, mitochondria, and the endoplasmic reticulum. A significantly lower amount of Dox accumulated in these cytoplasmic compartments in resistant cells treated with free Dox. Moreover, we found that Dox-HBDL significantly decreased the expression of MGST1 and enhanced mitochondria-mediated apoptotic cell death compared to free Dox. Dox-HBDL also markedly activated the JNK pathway that contributes to the apoptosis of drug-resistant cells. These results suggest that HBDL NPs can modulate subcellular drug distribution by specific endocytic and trafficking pathways and that this results in drug delivery that alters enzyme levels and cellular signaling pathways and, most importantly, increases the induction of apoptosis. Our findings suggest that by exploiting the cell transport machinery we can optimize the polymeric vehicles for controlled drug release to overcome drug resistance combat drug resistance with much higher efficacy.
Abstract 4495: Treatment effects of the novel mTOR kinase inhibitor AZD8055 in prostate cancer cell models
Authors: Yao Dai, Dietmar Siemann
Journal: Cancer Research (2011)

Abstract The mTOR pathway is frequently hyperactivated in prostate cancer due to PTEN loss of function, hence rendering prostate cancer cells sensitive to mTOR inhibitors. Although the classic allosteric mTOR inhibitor rapamycin has shown considerable preclinical efficacy, clinical results suggest that rapamycin alone is insufficient to inhibit tumor growth in prostate cancer patients. AZD8055 is an ATP-competitive mTOR kinase inhibitor that efficiently blocks activation of both mTOR complex (mTORC) 1 and 2. In this study we evaluated the effects of AZD8055 in prostate cancer cell models. Cell proliferation after drug treatment was determined by MTT assay and cell cycle was analyzed using propidium iodide staining followed by flow cytometry. Protein expression was detected by Western blot. In both PC-3 (PTEN null) and DU145 (PTEN wildtype) cells, AZD8055 suppressed cell proliferation at the nanomolar level in a dose dependent manner. At the same concentration (100 nM), AZD8055 induced greater G1 phase arrest than rapamycin and the expression of proteins related to G1 progression (cyclin D1, c-Myc) was significantly decreased by AZD8055 while only slightly reduced by rapamycin. Mechanistically, although both drugs blocked phosphorylation of mTORC1 downstream targets S6K and S6, only AZD8055 inhibited phosphorylation of 4E-BP1, another mTORC1 downstream molecule, and Akt, a typical target of mTORC2. Importantly, cells that were able to survive and proliferate under rapamycin (100 nM) selective pressure remained responsive to AZD8055, even at the lowest dose (10 nM). Furthermore in a PC-3 cell line established to be highly resistant to rapamycin (PC-3RR), AZD8055 could still potently decrease cell proliferation, with an IC50 of 0.5 nM. Taken together, these findings indicate that a) AZD8055 is superior to rapamycin in growth inhibition of prostate cancer cells irrespective of PTEN status, b) AZD8055 is able to deactivate rapamycin-insensitive complexes involved in the mTOR signaling, and c) AZD8055 treatment can overcome rapamycin treatment-associated resistance. In summary, the novel mTOR kinase inhibitor AZD8055 may have significant therapeutic potential in prostate cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4495. doi:10.1158/1538-7445.AM2011-4495
SPINAL CORD ISCHEMIA IN SURGICALLY TREATED ACUTE AORTIC DISSECTION: WHO'S AT RISK?
Authors: Anton Camaj, Santi Trimarchi, Daniel Montgomery, Elise Woznicki, Christoph A. Neinauber, Truls Myrmel, Kevin Greason, Nicole Corriveau, Shyamli Sinha, Rosell Fattori, Eva Kline-Rogers, James B. Froehlich, Kim A. Eagle
Journal: Journal of the American College of Cardiology (2011)
Oral Verapamil for Paroxysmal Supraventricular Tachycardia
Authors: D. R. Mauritson, M. D. Winniford, W. S. Walker, R. E. Rude, J. R. Cary, L. D. Hillis
Journal: Annals of Internal Medicine (1982)

The effectiveness and safety of orally administered verapamil was tested in 11 patients with frequent paroxysmal supraventricular tachycardia. In a 4-month randomized, double-blind, placebo-controlled trial, the frequency of paroxysmal supraventricular tachycardia fell from 0.3 +/- 0.3 (mean +/- SD) to 0.1 +/- 0.1 episodes per day by patient diary (p less than 0.05) and from 0.7 +/- 0.7 to 0.3 +/- 0.5 episodes per day by Holter monitor (p less than 0.05) for placebo and verapamil treatment periods, respectively. Verapamil caused a decrease in the duration of paroxysmal supraventricular tachycardia (in minutes per day): placebo 27 +/- 51 by dairy, 67 +/- 111 by Holter; verapamil, 3 +/- 3 by diary, 1 +/- 2 by Holter (p less than 0.05). Five patients required a total of 35 pharmacologic cardioversions for sustained tachycardia: two during verapamil and 33 during placebo (p less than 0.001). No verapamil treatment period was shortened due to unacceptable paroxysmal supraventricular tachycardia, but five of 22 placebo treatment periods were shortened (p equal to 0.02). Verapamil was well-tolerated, causing mild constipation in five patients and headache in one. Oral verapamil is both safe and effective in the long-term treatment of patients with paroxysmal supraventricular tachycardia.