tbuckley/cabot-search huggingface dataset:
Abstract 3199: Miniaturized, multiplexed, highly sensitive protein NanoArray assay for measuring biomarkers in dried blood spot (DBS) samples
Authors: Douglas B. Dixon, Ivan D. Ivanov, Earl J. Gubbins, Richard R. Harris, Michael L. Coen, Rosalind Helfrich, Haris Jamil
Journal: Cancer Research (2012)

Abstract As the utility of new biomarkers for diagnosis and treatment of disease become better understood, physicians and researchers are faced with increasingly critical decisions regarding how to best distribute their valuable patient samples. While simply taking more blood would seem a reasonable solution, a recent publication in the Archives of Internal Medicine (Salisbury, et.al., Arch Intern Med. 2011;171(18):1646-1653) addresses the very real problem of hospital-acquired anemia (HAA) brought on by blood loss resulting from blood drawn for clinical assays. Also in many resource constrained countries, the lack of adequate infrastructure such as hospitals, laboratories, transportation systems as well as qualified personnel pose major obstacles for patient access to clinical testing. This has revived interest in collecting dried blood spots (DBS) for clinical testing. DBS samples provide a number of benefits when compared with drawing venous blood: they require minimal blood volume (usually 50µl per spot), they can easily be collected from infants and children, and they can be used to collect blood samples where collection and storage of serum or plasma is not feasible. However for DBS samples to be a viable solution for clinical assay, the assay method must be sensitive and yet require very small sample volumes. NanoInk, Inc. has developed a highly sensitive assay based on dip-pen nanolithography (DPN™) using the NanoArrayer3000™. Utilizing a 48 subarray slide platform printed with a nano-scale antibody array we have created a miniaturized multiplexed sandwich ELISA with sensitivities as low as the 100's of femtograms/ml while using sample volumes that range from 2-4µl/well. Using our proprietary elution protocol, we are able to elute biomarkers from a standard 3.2mm DBS card punch sufficient to provide triplicate assay values while still keeping the samples concentrated enough to measure lower concentration biomarkers. Our NanoInk DBS cytokine assay has been validated using eluted blood standards and QC samples and shows good well-to-well and slide-to-slide variability. NanoInk's multiplexed assay format can also be customized to include a wide array of biomarkers. This multiplex capability, in combination with our proprietary sample and standard elution protocol, now allows clinicians to accurately measure the concentration of multiple biomarkers using convenient small-volume DBS samples. The results of an ongoing study for measuring biomarker levels in patient samples using our 5-cytokine DBS assay will be presented. 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 3199. doi:1538-7445.AM2012-3199
Physiologic and Physical Factors that Govern the Clinical Appreciation of Cardiac Thrills
Authors: TIMOTHY B. COUNIHAN, MAURICE B. RAPPAPORT, HOWARD B. SPRAGUE
Journal: Circulation (1951)

Palpable cardiac thrills have been considered valuable diagnostic findings. The present study indicates that they add little information to that obtained by careful evaluation of auscultatory findings, and that the quality of cardiac murmurs is a much safer guide in diagnosis than are the palpable vibrations produced by the same mechanism.
POINTS IN THE DIAGNOSIS AND TREATMENT OF SOME COMMON NEUROSES.
Authors: ROBERT T. EDES
Journal: JAMA (1896)

There are few occasions in medical practice where it is of more importance for the reputation of the physician, the satisfaction of friends, the attainment of the ends of justice, the advancement of therapeutic science, and the welfare of the patient, to establish a correct diagnosis than when the practitioner has to decide between organic and functional disease. The line between them, as is being constantly demonstrated, is indeed a shifting one; as new methods are invented new lesions are found where before it was thought none existed; organs that to the naked eye have presented no morbid changes reveal to the microscope and the test tube alterations minute and hitherto imperceptible or evanescent, but none the less fatally standing in the way of normal activity than than those grosser ones which have until quite recent times engrossed the attention of the morbid anatomist. Conditions hitherto known to us only
A DIVING APPARATUS FOR LIFE SAVING WORK
Authors: Christian J. Lambertsen
Journal: JAMA (1941)

Frequently drownings occur in spite of apparently adequate patrolling of beaches and lakes by trained lifeguards. A swimmer who, because of panic or exhaustion, sinks beneath the surface of the water is usually quickly lost to sight. The task of the lifeguard is to swim down under water, holding his breath, in an attempt to locate the drowning person. Holding the breath while undergoing the exertion of swimming under water is extremely tiring. Rarely can an untrained person remain under water in this manner for more than one minute or dive deeper than about 30 feet. When the lifeguard does come to the surface for air he is exhausted, and his successive dives will necessarily be shorter and shallower until finally he can no longer continue. Valuable time is wasted in coming to the surface for air, and time is an all-important factor in an emergency of this sort.  An
Joseph Callistus Devlin
Authors: Maureen Carnighan
Journal: BMJ (2007)

There are a million deaths by suicide every year and by 2020 it is expected to be 1.53 million. The global burden of disease by suicide is also expected to increase from 1.8% to 2.4% signifying that suicide is a major public health problem. Around 60% of suicides occur in Asia. Suicide is a complex human behaviour resulting from a maze of biological, psychological, socio cultural and environmental risk and protective factors that interact intricately. The resulting behaviour varies in patterns and the responses it elicits in different countries and regions. In developed countries, the male to female ratio for suicide is between 2 and 4 to 1. Asian countries, show much lower male to female ratio. Mental disorders occupy a premier position in the matrix of causation of suicide, however in developing countries like China and India, social and environmental factors appear more significant. Exposure to violence and Intimate partner violence is also strongly linked to suicide. Worldwide, suicide by ingestion of pesticides is the commonest method accounting for 30% of suicides. It is more so in rural areas of the developing world. Hence, restriction of access to pesticide through safer individual and community storage and stopping sales of more toxic preparations has the potential to reduce suicide. A 10% reduction in pesticide suicide would result in 30 000 lives saved. Several developed countries have established national suicide prevention programmes, but their effectiveness has not been conclusively proven. The enormity of the problem needs a global movement towards significant reduction of suicides. Suicide prevention should not be viewed as a traditional exercise in health sector but as a social objective.
Molecular biology and evolution of resistance of toxicants
Authors: M. Taylor, R. Feyereisen
Journal: Molecular Biology and Evolution (1996)

To the prevailing biochemical/physiological classification of mechanisms of organismal resistance to toxicants, an additional molecular dimension is proposed. Predictions are developed regarding the relative prevalence of different classes of mutations and are found to compare favorably with reports from the literature. In particular, point mutations in target loci were the dominant form of resistance for both lab and field selection. Amplifications of target loci were less common than structural mutations, and more common for lab-selected than for field-selected strains. Amplification was the most common mechanism of up-regulation of metabolizing enzymes. In comparison, only one mutation involving cis-regulation and several involving trans-acting regulation were found. Mutations involving gene disruption and down-regulation were uncommon, but were found in appropriate cases, i.e., when toxicants stimulated rather than inhibited target function and when metabolizing enzymes converted toxicants into more toxic metabolites. Additional phenomena of likely but uncertain importance are genetic "succession," recombinational limitation, and negative cross-resistance. More work on these phenomena and on quantification of fitness costs of resistance is recommended.
Idola Fori and Scientific Expression
Authors: Robert O'Leary
Journal: New England Journal of Medicine (1972)

Among the classes of error to which mankind is prone, Francis Bacon listed as the third those of the market place. As set forth in the Novum Organum more than 350 years ago, his "idola fori" represented the fallacies (idols) of the word market: meanings that change, seldom for the better, as words are used in the communication of ideas. In an age when literary expression in general seems to follow the permissiveness typified by Webster III, a caveat against imprecise diction may be worthy of consideration by those who share their medical and scientific knowledge with their peers.New . . .
A REAGENT FOR DEMONSTRATING FUNGI IN SKIN SCRAPINGS AND HAIR
Authors: Theodore Cornbleet
Journal: JAMA (1930)

Fungous disorders of the skin are being seen in such increasing numbers that they are becoming a problem of public health. The first means of prevention is the quick recognition of existing cases. This can most rapidly and conveniently be done by knowing the distinct clinical forms which the different mycoses assume. While, to the expert, clinical means are generally sufficient, he too often needs the aid of the laboratory to be certain of his diagnosis. It is natural, therefore, that improved methods for demonstrating fungi in keratotic structures should be desirable. There are two laboratory procedures in general use by physicians for examining the skin and hair for fungi. The first is the cultural means and the second is the direct method of maceration with fixed alkalis. The cultural method does not lend itself to routine use by the physician because it requires too much time, material and special
Effects of CPAP on lung mechanics in infants with acquired tracheobronchomalacia.
Authors: H B Panitch, J L Allen, B E Alpert, D V Schidlow
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Continuous positive airway pressure (CPAP) has been used in the treatment of infants with tracheobronchomalacia (TBM). However, the effects of CPAP on lung mechanics in these infants are unknown. We hypothesized that CPAP prevents airway collapse and improves forced exhalation. We studied respiratory mechanics of nine infants (age 15 +/- 3 mo, SEM) with acquired TBM documented by bronchoscopy, during quiet respiration and forced exhalation, using the esophageal balloon and rapid thoracic compression techniques, respectively. Measurements were made when infants received no CPAP and repeated when 5 and 8 cm H2O CPAP were applied to the airway opening via a modified Mapleson anesthesia circuit. Expiratory resistance (RL), midexpiratory tidal flow (VE50), and maximal flow at functional residual capacity (Vmax FRC) were compared at each level of CPAP. Vmax FRC increased threefold from baseline to 8 cm H2O CPAP (p < 0.005). In contrast, there was no difference in expiratory RL or in VE50 at any level of CPAP. These data suggest that in infants with acquired TBM, assessments of forced expiratory flow reflect the amount of CPAP necessary to prevent airway collapse during forced exhalation better than can measurements of tidal mechanics.
Ideas and Trends: Medical Informatics and Health Care Computing
Authors: Chris Dwyer
Journal: Annals of Internal Medicine (1999)

Currents19 January 1999Ideas and Trends: Medical Informatics and Health Care ComputingChris DwyerChris DwyerSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-2-199901190-00102 SectionsAboutFull Text ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail New York City internist and cardiologist Michael W. Jacobson, MD, MPH, suggests that “if patient records are computerized and general medical knowledge is also made available on-line, we should be able to handle the information demands of our profession in a radically improved fashion.”Jacobson envisions a scenario in which clinicians use information technology to:• choose a practice guideline that they feel is reasonable and see how well their own patient management follows it• automatically review all patient records for major quality-of-care issues• screen all patients for drug interactions• read an article in a medical journal ... Author, Article, and Disclosure InformationAffiliations: Corresponding Author: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByUse of the Internet by patients: not a threat to nursing, but an opportunity? 19 January 1999Volume 130, Issue 2Page: 170-172KeywordsAdverse reactionsComputersDrug interactionsElectronic medical recordsHealth careHealth informaticsHealth information technologyInformation technologyInternetTreatment guidelines Issue Published: 19 January 1999 CopyrightCopyright © 1999 by American College of Physicians. All Rights Reserved.Loading ...
Chronic lung allograft rejection and airway microvasculature: Is HIF-1 the missing link?
Authors: David S. Wilkes
Journal: Journal of Clinical Investigation (2011)

Chronic lung allograft rejection, known as obliterative bronchiolitis (OB), is the leading cause of death in lung transplant patients. Although OB pathogenesis is not fully understood, in this issue of the JCI, Jiang and colleagues report that tissue hypoxia resulting in dysfunctional airway microvasculature precedes the airway fibrosis characteristic of OB. In addition, a relative deficiency of allograft endothelial cell-derived HIF-1α contributes to this process. Data showing that overexpressing HIF-1α restores the microvascular airway normoxia and prevents airway fibrosis highlight a novel role for vascular biology in OB pathogenesis.
IMPROVED TECHNIC IN THE APPLICATION OF PLASTER-OF-PARIS CASTS IN THE TREATMENT OF CONGENITAL CLUBFOOT
Authors: Philip Lewin
Journal: JAMA (1928)

The illustration accompanying this clinical note indicates a modification of the technic of the application of plaster-of-paris casts used in the treatment of clubfoot. In addition to the routine application of casts, one applies a crossbar of plaster with a foundation consisting of two wooden tongue depressors cut to the required length. One tongue depressor is placed over and the other under the completed casts at a point about 1 inch (2.5 cm.) above the internal malleolus. A few turns of plaster bandage are then applied, making a solid but very light crossbar connection. This may be used to hold the legs in any position of external rotation which is usually desirable. It is noteworthy that after treatment and correction of clubfoot there often remains an inward rotation of the lower legs or entire lower extremities which causes disability and a visible deformity.
Evaluation of the beta 2 adrenoceptor agonist/antagonist activity of formoterol and salmeterol.
Authors: A. Grove, B. J. Lipworth
Journal: Thorax (1996)

BACKGROUND: Salmeterol and formoterol have a lower intrinsic activity at beta 2 receptors than isoprenaline in human bronchus in vitro. The aim of the present study was to evaluate in vivo the beta 2 agonist/antagonist activity of salmeterol and formoterol at rest with low endogenous adrenergic tone, on exercise with raised endogenous adrenergic tone, and in the presence of fenoterol, an exogenous full beta 2 receptor agonist. METHODS: Eight normal subjects were randomised to receive single doses of placebo, salmeterol 300 micrograms, formoterol 72 micrograms, or propranolol 80 mg at weekly intervals. beta 2 adrenoceptor responses were evaluated at rest, at peak exercise, and after treatment with fenoterol 2.4 mg. RESULTS: At rest salmeterol and formoterol exhibited equivalent beta 2 agonist activity with regard to decrease in serum potassium levels and increase in finger tremor, with propranolol having no effect. Salmeterol and formoterol, like propranolol, potentiated the hyperkalaemic delta response to exercise compared with placebo, consistent with beta 2 antagonism: (mean difference and 95% confidence interval (CI) compared with placebo) salmeterol 0.20 (0.02 to 0.38) mmol/l, formoterol 0.17 (0.00 to 0.34) mmol/l, propranolol 0.45 (0.08 to 0.82) mmol/l. Propranolol blunted the heart rate delta response to exercise, consistent with beta 1 blockade, whilst salmeterol and formoterol had no effect. Salmeterol and formoterol, like propranolol, attenuated the hypokalaemic, tremor, and heart rate delta responses to fenoterol compared with placebo, in keeping with beta 2 blockade: potassium, salmeterol 0.18 (0.0 to 0.36) mmol/l, formoterol 0.17 (-0.03 to 0.37) mmol/l, propranolol 0.80 (0.54 to 1.06) mmol/l; tremor, salmeterol -0.69 (-1.26 to -0.12) log units, formoterol -0.71 (-1.53 to 0.11) log units, propranolol -0.85 (-1.66 to -0.04) log units; heart rate, salmeterol -6 (-13 to 1) beats/min, formoterol -10 (-19 to -1) beats/min, propranolol -18 (-29 to -7) beats/min. CONCLUSIONS: At rest with low endogenous adrenergic tone salmeterol and formoterol showed equivalent beta 2 mediated agonist activity in terms of serum potassium and finger tremor responses. In the presence of raised endogenous adrenergic tone at peak exercise and in the presence of fenoterol (an exogenous full beta 2 receptor agonist), salmeterol and formoterol, like propranolol, exhibited beta 2 receptor antagonism as evidenced by their attenuation of beta 2 receptor mediated responses. The degree of beta 2 blockade with formoterol and salmeterol was comparable but less than with propranolol. The relevance of these findings at extrapulmonary beta 2 receptors with regard to airway beta 2 responses remains unclear and warrants further investigation.
A specific and sensitive assay for blood levels of glycated CD59: A novel biomarker for diabetes
Authors: Pamela Ghosh, Rupam Sahoo, Anand Vaidya, Sonia Cantel, Amol Kavishwar, Allison Goldfine, Neil Herring, Lynn Bry, Michael Chorev, Jose A. Halperin
Journal: American Journal of Hematology (2013)

Increasing evidence links the complement system with complications of human diabetes. The complement regulatory protein CD59, an inhibitor of formation of membrane attack complex (MAC), is inhibited by hyperglycemia‐induced glycation fostering increased deposition of MAC, a major effector of complement‐mediated tissue damage. CD59, an ubiquitous GPI‐anchored membrane protein, is shed from cell membranes by phospholipases generating a soluble form present in blood and urine. We established an enzyme‐linked immunosorbent assay (ELISA) to measure serum/plasma glycated human CD59 (hCD59) (GCD59) and evaluated its potential as a diabetes biomarker. We used a synthetic peptide strategy to generate (a) a mouse monoclonal antibody to capture hCD59, (b) a rabbit monoclonal antibody to detect GCD59, and (c) a GCD59 surrogate for assay standardization. ELISA conditions were optimized for precision, reproducibility, and clinical sensitivity. The clinical utility of the assay was initially evaluated in 24 subjects with or without diabetes and further validated in a study that included 100 subjects with and 90 subjects without a diagnosis of diabetes. GCD59 (a) was significantly higher in individuals with than in individual without diabetes, (b) was independently associated with HbA1c, and (c) identified individuals with diabetes with high specificity and sensitivity. We report the development and standardization of a novel, sensitive, and specific ELISA for measuring GCD59 in blood. The assay distinguished individuals with diabetes from those without, and showed strong correlation between GCD59 and HbA1c. Because GCD59 likely contributes to the pathogenesis of diabetes complications, measurement of blood levels of GCD59 may be useful in the diagnosis and management of diabetes. Am. J. Hematol. 88:670–676, 2013. © 2013 Wiley Periodicals, Inc.
Two-dimensional J-resolved nuclear magnetic resonance spectral study of two bromobenzene glutathione conjugates.
Authors: J A Ferretti, R J Highet, L R Pohl, T J Monks, J A Hinson
Journal: Environmental Health Perspectives (1985)

The application of two-dimensional J-resolved nuclear magnetic resonance spectroscopy to determine the structure of two bile metabolites isolated from rats injected interperitoneally with bromobenzene is described. The structures of the two molecules are obtained unambiguously from the proton-proton spin coupling constants. This paper discusses the fundamentals of the technique and demonstrates the resolution of small long-range coupling constants.
TREATMENT OF PERNICIOUS ANAEMIA WITH DESICCATED HOG'S STOMACH
Authors: A. Renshaw
Journal: BMJ (1930)

HOG'S STOMACH.THEBDICAITJOSHAL highily concentrated uirine during thc height of the fever; (8) the inconclusive Widal reactions of the serum; (9) the negative blood culture; (10) the faillure to isolate organisms of the enteric or dyscitery group from tChe stools; (11) thei negative report upon thc splutUmI1.CASE IV.(Rerort by Dr. E. L. Elliott.)On Janiuary 17tli the patient, a gardener, aged 55, sought my advice for g'eneral mralaise.He liad been out of sorts for thiree or four days, but liad been able to cairry on hiis work.I found Ihinm with a temperature of 10.lO F., and ordered hiim to bed.For the first four d-ays the temperature was r-aised, varying from 990 to 1010, and the pulse was sliglhtly intermitterit.During
Hydrogen Peroxide, an Endogenous Endothelium-Derived Hyperpolarizing Factor, Plays an Important Role in Coronary Autoregulation In Vivo
Authors: Toyotaka Yada, Hiroaki Shimokawa, Osamu Hiramatsu, Tatsuya Kajita, Fumiyuki Shigeto, Masami Goto, Yasuo Ogasawara, Fumihiko Kajiya
Journal: Circulation (2003)

Recent studies in vitro have demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor (EDHF) in animals and humans. The aim of this study was to evaluate our hypothesis that endothelium-derived H2O2 is an EDHF in vivo and plays an important role in coronary autoregulation.To test this hypothesis, we evaluated vasodilator responses of canine (n=41) subepicardial small coronary arteries (> or =100 microm) and arterioles (<100 microm) with an intravital microscope in response to acetylcholine and to a stepwise reduction in coronary perfusion pressure (from 100 to 30 mm Hg) before and after inhibition of NO synthesis with N(G)-monomethyl-L-arginine (L-NMMA). After L-NMMA, the coronary vasodilator responses were attenuated primarily in small arteries, whereas combined infusion of L-NMMA plus catalase (an enzyme that selectively dismutates H2O2 into water and oxygen) or tetraethylammonium (TEA, an inhibitor of large-conductance K(Ca) channels) attenuated the vasodilator responses of coronary arteries of both sizes. Residual arteriolar dilation after L-NMMA plus catalase or TEA was largely attenuated by 8-sulfophenyltheophylline, an adenosine receptor inhibitor.These results suggest that H2O2 is an endogenous EDHF in vivo and plays an important role in coronary autoregulation in cooperation with NO and adenosine.
Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons
Authors: David M Dietz, Haosheng Sun, Mary Kay Lobo, Michael E Cahill, Benjamin Chadwick, Virginia Gao, Ja Wook Koo, Michelle S Mazei-Robison, Caroline Dias, Ian Maze, Diane Damez-Werno, Karen C Dietz, Kimberly N Scobie, Deveroux Ferguson, Daniel Christoffel, Yoko Ohnishi, Georgia E Hodes, Yi Zheng, Rachael L Neve, Klaus M Hahn, Scott J Russo, Eric J Nestler
Journal: Nature Neuroscience (2012)