tbuckley/cabot-search huggingface dataset:
Abnormal Hemoglobins with High and Low Oxygen Affinity
Authors: G Stamatoyannopoulos, A J Bellingham, C Lenfant, C A Finch
Journal: Annual Review of Medicine (1971)

The reaction of hemoglobin with oxygen and the mechanisms of adapta­ tion to hypoxia have intrigued scientists for almost a century. Differences in the oxygen equilibria of myoglobin and hemoglobin have been appreci­ ated for about seventy years, and various kinetic interpretations of oxygen­ ation have been presented for nearly half a century. Nevertheless, a deeper understanding of hemoglobin function has only recently emerged, based on the elucidation of the tertiary and quaternary structure of hemoglobin, an appreciation of the allosteric behavior of hemoglobin during oxygenation, and the finding of hemoglobin mutants with altered oxygen dissociation characteristics. These variant structural forms have served as reagents in testing hypotheses relating the structure to the function of normal hemoglo­ bin. They have revealed the functional role of specific portions of the mole­ cule and have provided further insight into certain types of human disease. The present review calls particular attention to the effects of hemoglobin variants on oxygen transport.
Potential of Immuno–Positron Emission Tomography for Tumor Imaging and Immunotherapy Planning
Authors: Michael R. Zalutsky
Journal: Clinical Cancer Research (2006)

In this issue of Clinical Cancer Research , Borjesson et al. ([1][1]) report the results of the first clinical trial using the long-lived positron emitter 89Zr for immuno–positron emission tomography (PET). A series of 20 patients with squamous cell carcinoma of the head and neck were imaged up
Improved Survival After Resection of Colorectal Liver Metastases
Authors: Eddie K. Abdalla, Jean-Nicolas Vauthey
Journal: Journal of Clinical Oncology (2006)

.The authors are to be commended for their results (51% 5-year sur-vival) in this small cohort of patients with colorectal liver metastases(CLM) treated by hepatic resection with long-term follow-up (me-dian, 64 months). Although they attribute their results to treatmentwith adjuvant radioimmunotherapy (RAIT) with iodine-131 labetu-zumab, their results must be reassessed in the setting of recent out-comedatainﬁvelargerseries(includingamulticentertrial)thatrevealresults comparable to or better than those reported in their studywithouttheuseofRAIT.Despite expanding indications for resection of colorectal livermetastases, several studies have shown marked improvement in sur-vival compared with historical series. Figueras et al
Intervention strategies to reduce the burden of non-communicable diseases in Mexico: cost effectiveness analysis
Authors: J. A. Salomon, N. Carvalho, C. Gutierrez-Delgado, R. Orozco, A. Mancuso, D. R. Hogan, D. Lee, Y. Murakami, L. Sridharan, M. E. Medina-Mora, E. Gonzalez-Pier
Journal: BMJ (2012)

<b>Objective</b> To inform decision making regarding intervention strategies against non-communicable diseases in Mexico, in the context of health reform. <b>Design</b> Cost effectiveness analysis based on epidemiological modelling. <b>Interventions</b> 101 intervention strategies relating to nine major clusters of non-communicable disease: depression, heavy alcohol use, tobacco use, cataracts, breast cancer, cervical cancer, chronic obstructive pulmonary disease, cardiovascular disease, and diabetes. <b>Data sources</b> Mexican data sources were used for most key input parameters, including administrative registries; disease burden and population estimates; household surveys; and drug price databases. These sources were supplemented as needed with estimates for Mexico from the WHO-CHOICE unit cost database or with estimates extrapolated from the published literature. <b>Main outcome measures</b> Population health outcomes, measured in disability adjusted life years (DALYs); costs in 2005 international dollars ($Int); and costs per DALY. <b>Results</b> Across 101 intervention strategies examined in this study, average yearly costs at the population level would range from around ≤$Int1m (such as for cataract surgeries) to &gt;$Int1bn for certain strategies for primary prevention in cardiovascular disease. Wide variation also appeared in total population health benefits, from &lt;1000 DALYs averted a year (for some components of cancer treatments or aspirin for acute ischaemic stroke) to &gt;300 000 averted DALYs (for aggressive combinations of interventions to deal with alcohol use or cardiovascular risks). Interventions in this study spanned a wide range of average cost effectiveness ratios, differing by more than three orders of magnitude between the lowest and highest ratios. Overall, community and public health interventions such as non-personal interventions for alcohol use, tobacco use, and cardiovascular risks tended to have lower cost effectiveness ratios than many clinical interventions (of varying complexity). Even within the community and public health interventions, however, there was a 200-fold difference between the most and least cost effective strategies examined. Likewise, several clinical interventions appeared among the strategies with the lowest average cost effectiveness ratios—for example, cataract surgeries. <b>Conclusions</b> Wide variations in costs and effects exist within and across intervention categories. For every major disease area examined, at least some strategies provided excellent value for money, including both population based and personal interventions.
Physician spending and subsequent risk of malpractice claims: observational study
Authors: Anupam B Jena, Lena Schoemaker, Jay Bhattacharya, Seth A Seabury
Journal: BMJ (2015)

<b>Study question</b> Is a higher use of resources by physicians associated with a reduced risk of malpractice claims? <b>Methods</b> Using data on nearly all admissions to acute care hospitals in Florida during 2000-09 linked to malpractice history of the attending physician, this study investigated whether physicians in seven specialties with higher average hospital charges in a year were less likely to face an allegation of malpractice in the following year, adjusting for patient characteristics, comorbidities, and diagnosis. To provide clinical context, the study focused on obstetrics, where the choice of caesarean deliveries are suggested to be influenced by defensive medicine, and whether obstetricians with higher adjusted caesarean rates in a year had fewer alleged malpractice incidents the following year. <b>Study answer and limitations</b> The data included 24 637 physicians, 154 725 physician years, and 18 352 391 hospital admissions; 4342 malpractice claims were made against physicians (2.8% per physician year). Across specialties, greater average spending by physicians was associated with reduced risk of incurring a malpractice claim. For example, among internists, the probability of experiencing an alleged malpractice incident in the following year ranged from 1.5% (95% confidence interval 1.2% to 1.7%) in the bottom spending fifth ($19 725 (£12 800; €17 400) per hospital admission) to 0.3% (0.2% to 0.5%) in the top fifth ($39 379 per hospital admission). In six of the specialties, a greater use of resources was associated with statistically significantly lower subsequent rates of alleged malpractice incidents. A principal limitation of this study is that information on illness severity was lacking. It is also uncertain whether higher spending is defensively motivated. <b>What this study adds</b> Within specialty and after adjustment for patient characteristics, higher resource use by physicians is associated with fewer malpractice claims. <b>Funding, competing interests, data sharing</b> This study was supported by the Office of the Director, National Institutes of Health (grant 1DP5OD017897-01 to ABJ) and National Institute of Aging (R37 AG036791 to JB). The authors have no competing interests or additional data to share.
Horse versus Rabbit Antithymocyte Globulin in Acquired Aplastic Anemia
Authors: Phillip Scheinberg, Olga Nunez, Barbara Weinstein, Priscila Scheinberg, Angélique Biancotto, Colin O. Wu, Neal S. Young
Journal: New England Journal of Medicine (2011)

In severe acquired aplastic anemia, hematopoietic failure is the result of immune-mediated destruction of bone marrow stem and progenitor cells. Immunosuppressive therapy with antithymocyte globulin (ATG) plus cyclosporine is an effective alternative to stem-cell transplantation and improves blood counts and survival. Although horse ATG is the standard therapy, rabbit ATG is more potent in depleting peripheral-blood lymphocytes and is preferred in other clinical circumstances.
Clonotypic heterogeneity in experimental interstitial nephritis. Restricted specificity of the anti-tubular basement membrane B cell repertoire is associated with a disease-modifying crossreactive idiotype.
Authors: M D Clayman, M J Sun, L Michaud, J Brill-Dashoff, R Riblet, E G Neilson
Journal: The Journal of Experimental Medicine (1988)

Experimental anti-tubular basement membrane (anti-TBM) disease is an autoimmune interstitial nephritis elicited in susceptible rodents after immunization with renal tubular antigen. The nephritogenic antigen in the immunizing preparation is 3M-1, a 48,000 Mr noncollagenous glycoprotein. The hallmarks of the renal lesion are the presence of anti-TBM antibodies (anti-TBM-Ab) and a dense mononuclear cell infiltrate. The anti-TBM B cell repertoire in this disease was analyzed using a library of 22 anti-TBM mAbs generated in a prototypically susceptible Brown Norway rat. These anti-TBM mAbs were all demonstrated to be 3M-1 specific and their characterization formed the basis for the following observations: (a) The size of the anti-TBM B cell population is estimated at 58 distinct clones; (b) by competitive inhibition criteria, all anti-TBM mAbs recognize the same (or spatially close) epitope(s) on 3M-1. This focused recognition was maintained in spite of considerable variability in affinity. Epitopic dominance could also be demonstrated in human polyclonal anti-TBM antisera from a patient with anti-TBM disease; and (c) a crossreactive idiotype was documented, and antisera directed toward this set of variable region determinants was shown to be effective as a prophylactic regimen to abrogate disease, and as a therapeutic modality to arrest the progression of disease; (d) analysis of VH gene families suggested biased usage of Q52- and 7183-like families, although at least three gene families are used in the anti-TBM-Ab response. Thus, the anti-TBM B cell compartment in BN rats is moderately large, but is primarily focused to a single epitope on the nephritogenic antigen and is associated with a disease-modifying crossreactive idiotype.
Limitation of joint mobility (cheiroarthropathy) in adult noninsulin-dependent diabetic patients.
Authors: M A Fitzcharles, S Duby, R W Waddell, E Banks, J Karsh
Journal: Annals of the Rheumatic Diseases (1984)

Joint mobility was assessed in 80 consecutive adult noninsulin-dependent diabetic (NIDD) patients and 47 nondiabetic controls matched for age and sex. Impairment of mobility was observed in 36 NIDD patients but only 7 controls (p less than 0.01). There was no significant differences between diabetic patients with and without impaired mobility with regards to age, duration of diabetes, mean daily insulin dose, or overall diabetic control as assessed by the measurement of glycosylated haemoglobin (HbA1C). However, NIDD patients with impaired joint mobility had a significantly increased frequency of microvascular disease, as shown by retinopathy and/or nephropathy (42% versus 22%, p less than 0.05), were more often on insulin treatment (86% versus 63%, p less than 0.05) and more frequently had additional rheumatic disorders such as Dupuytren9s contracture and osteoarthritis (36% versus 18%, p less than 0.05). In addition tight waxy skin over the phalanges was commonly associated with impaired mobility (58% versus 22%, p less than 0.01). Limitation of joint mobility was most prominent in the hands but caused no functional impairment. This finding may be an additional marker of microvascular disease in the adult diabetic patient.
Nutrition and Fitness, Obesity, The Metabolic Syndrome, Cardiovascular Disease and Cancer (Vol 94)
Authors: Peter Baquie
Journal: British Journal of Sports Medicine (2007)

Edited by A P Simpopoulas. Published by S Karger AG: Basle, Switzerland; 2005, £136.57, pp 195. ISBN 3-8055-7945-4

The magnitude of the epidemic of obesity and its medical consequences, rising public awareness and the need for providing up-to-date information for health workers underpins the importance of this collection of reviews. It provides an authoritative and contemporary approach, featuring an Olympic link, a collection of current multinational experts and sound …
Long-term follow-up after first-line bronchoscopic therapy in patients with bronchial carcinoids
Authors: Hes A P Brokx, Marinus A Paul, Pieter E Postmus, Thomas G Sutedja
Journal: Thorax (2015)

Carcinoid of the lung is considered to be a low-grade malignancy. A subgroup presents as an endobronchial tumour. Surgical resection is considered the standard approach because of its metastatic potential and the possibility of an iceberg phenomenon for the endobronchial subgroup. Advances in non-invasive and minimally invasive technologies seem to justify a more lung parenchyma-sparing approach.In patients presenting with bronchial carcinoids, initial bronchoscopic treatment (IBT) is first attempted for complete tumour eradication and sufficient tissue sampling for the proper differentiation of typical (TC) versus atypical (AC) histological type. Furthermore in cases with postobstruction problems the desobstruction is aimed at improving the patient's condition and by that alleviate surgery if that is needed. High resolution CT is performed 6 weeks post IBT to determine local tumour growth. Surgical resection follows in case of extraluminal disease, residual carcinoid inaccessible for IBT, or late recurrences not salvaged by repeat IBT.Minimum follow-up was 5 years from start of treatment for 112 patients (65 women, 47 men), with a median age of 47 years (range 16-77 years). Eighty-three patients (74%) had TC, and 29 (26%) AC. IBT only was ultimately curative in 42% of the cases (47/112): 42 TC, 5 AC. Disease-specific mortality including surgical mortality has been 2.6% (3/112) in patients with extraluminal carcinoids (3 AC).IBT, if with unsuccessful rescue surgery, is justifiable with excellent long-term outcome. IBT made surgery unnecessary in 42% of the cases. Iceberg phenomenon and metastatic potential in this group of patients with bronchial carcinoids are clinically insignificant.
Cue fascination: A new vulnerability in drug addiction
Authors: John Sarnecki, Rebecca Traynor, Michael Clune
Journal: Behavioral and Brain Sciences (2008)

Abstract Redish et al. propose a constellation of vulnerabilities inherent in the brain's decision-making system. They allow over-attention to cues a minor role in drug addiction. We think this is inadequate. Using the established links among drug cues, dopamine, and novelty, we propose a fuller account of this key feature of addiction, which we call the phenomenon of cue fascination.
Hypoxia-responsive polymeric nanoparticles for tumor-targeted drug delivery
Authors: Thavasyappan Thambi, V.G. Deepagan, Hong Yeol Yoon, Hwa Seung Han, Seol-Hee Kim, Soyoung Son, Dong-Gyu Jo, Cheol-Hee Ahn, Yung Doug Suh, Kwangmeyung Kim, Ick Chan Kwon, Doo Sung Lee, Jae Hyung Park
Journal: Biomaterials (2013)
Human Disease Models in<i>Drosophila melanogaster</i>and the Role of the Fly in Therapeutic Drug Discovery
Authors: Udai Bhan Pandey, Charles D. Nichols
Journal: Pharmacological Reviews (2011)

The common fruit fly, <i>Drosophila melanogaster</i>, is a well studied and highly tractable genetic model organism for understanding molecular mechanisms of human diseases. Many basic biological, physiological, and neurological properties are conserved between mammals and <i>D. melanogaster</i>, and nearly 75% of human disease-causing genes are believed to have a functional homolog in the fly. In the discovery process for therapeutics, traditional approaches employ high-throughput screening for small molecules that is based primarily on in vitro cell culture, enzymatic assays, or receptor binding assays. The majority of positive hits identified through these types of in vitro screens, unfortunately, are found to be ineffective and/or toxic in subsequent validation experiments in whole-animal models. New tools and platforms are needed in the discovery arena to overcome these limitations. The incorporation of <i>D. melanogaster</i> into the therapeutic discovery process holds tremendous promise for an enhanced rate of discovery of higher quality leads. <i>D. melanogaster</i> models of human diseases provide several unique features such as powerful genetics, highly conserved disease pathways, and very low comparative costs. The fly can effectively be used for low- to high-throughput drug screens as well as in target discovery. Here, we review the basic biology of the fly and discuss models of human diseases and opportunities for therapeutic discovery for central nervous system disorders, inflammatory disorders, cardiovascular disease, cancer, and diabetes. We also provide information and resources for those interested in pursuing fly models of human disease, as well as those interested in using <i>D. melanogaster</i> in the drug discovery process.
Relationships Between Daily Acute Glucose Fluctuations and Cognitive Performance Among Aged Type 2 Diabetic Patients
Authors: Maria Rosaria Rizzo, Raffaele Marfella, Michelangela Barbieri, Virginia Boccardi, Francesco Vestini, Biagio Lettieri, Silvestro Canonico, Giuseppe Paolisso
Journal: Diabetes Care (2010)

OBJECTIVE The mean amplitude of glycemic excursions (MAGE) is a significant determinant of overall metabolic control as well as increased risk for diabetes complications. Older individuals with type 2 diabetes are more likely to have moderate cognitive deficits and structural changes in brain tissue. Considering that poor metabolic control is considered a deranging factor for cognitive performance in diabetic patients, we evaluated whether the contributions of MAGE to cognitive status in older patients with type 2 diabetes were independent from the main markers of glycemic control, such as sustained chronic hyperglycemia (A1C), postprandial glycemia (PPG), and fasting plasma glucose (FPG). RESEARCH DESIGN AND METHODS In 121 older patients with type 2 diabetes, 48-h continuous subcutaneous glucose monitoring (CSGM) were assessed. MAGE and PPG were evaluated during CSGM. The relationship of MAGE to performance on cognitive tests was assessed, with adjustment for age, glycemic control markers, and other determinants of cognitive status. The cognitive tests were a composite score of executive and attention functioning and the Mini Mental Status Examination (MMSE). RESULTS MAGE was significantly correlated with MMSE (r = 0.83; P &amp;lt; 0.001) and with cognition composite score (r = 0.68; P &amp;lt; 0.001). Moreover, MAGE was associated with the MMSE (P &amp;lt; 0.001) and cognition composite score (P &amp;lt; 0.001) independently of age, sex, BMI, waist-to-hip (WHR) ratio, drug intake, physical activity, mean arterial blood pressure, FPG, PPG, and A1C. CONCLUSIONS MAGE during a daily period was associated with an impairment of cognitive functioning independent of A1C, FPG, and PPG. The present data suggest that interventional trials in older patients with type 2 diabetes should target not only A1C, PPG, and FPG but also daily acute glucose swings.
Monitoring access to out-of-hours care services in Scotland – a review
Authors: Sylvia Godden, Simon Hilton, Allyson M Pollock
Journal: Journal of the Royal Society of Medicine (2011)

Objectives Changes in the contractual responsibilities of primary care practitioners and health boards have resulted in a plethora of arrangements relating to out-of-hours healthcare services. Rather than being guaranteed access to a GP (usually either their own or another through a local GP co-operative), patients have a number of alternative routes to services. Our objective was to identify and assess the availability and adequacy of relevant standards, responsibilities and information systems in Scotland to monitor the impact of contractual changes to out-of-hours healthcare services on equity of access. Design Cross-sectional study. Setting All providers of primary care out-of-hours services in Scotland. Participants Not applicable. Main outcome measures First, identification and policy review of current standards and performance monitoring systems, data and information, primarily through directly contacting national and local organizations responsible for monitoring out-of-hours care, supplemented by literature searches to highlight specific issues arising from the review; and second, mapping of data items by out-of-hours provider type to identify overlap and significant gaps. Results In Scotland, data monitoring systems have not kept pace with changes in the organization of out-of-hours care, so the impact on access to services for different population groups is unknown. There are significant gaps in information collected with respect to workforce, distribution of services, service utilisation and clinical outcomes. Conclusions Since 2004 there have been major changes to the way patients access out-of-hours healthcare in the UK. In Scotland, none of the current systems provide information on whether the new services satisfy the key NHS principle of equity of access. There is an urgent need for a comprehensive review of data standards and systems relating to out-of-hours care in order to monitor and evaluate inputs, processes and outcomes of care not least in respect of access and fairness of distribution of resources.
Joint recognition by cytotoxic T cells of inactivated Sendai virus and products of the major histocompatibility complex.
Authors: J W Schrader, G M Edelman
Journal: The Journal of Experimental Medicine (1977)

Cytotoxic T cells specific for Sendai virus were generated by culturing murine spleen cells in vitro together with UV-inactivated Sendai virus. In vivo immunization of donor mice with UV-inactivated Sendai virus resulted in an in vitro secondary response of increased magnitude. Cytotoxic activity was demonstrated in a short-term 51Cr-release assay, using syngeneic tumor cells which had been coated with inactivated Sendai virus by incubation at 4 degrees C for 30 min. The lysis of Sendai virus-coated target cells was restricted by the H-2 haplotype of the target cells, suggesting that the H-2 genes of the target cell contributed to the specificity of the lysis. Kinetic experiments showed that susceptibility to lysis by cytotoxic T cells specific for Sendai virus appeared within 30 min after coating target cells with inactivated virus. Furthermore, there was no detectable synthesis of new proteins in cells treated with UV-inactivated Sendai virus. For these reasons, we suggest that neither viral replication nor the synthesis of new proteins are necessary for the production of the antigen recognized by cytotoxic cells specific for Sendai virus. We infer that the virus-specific component on the target cells is probably a preformed virion antigen adsorbed onto or integrated into the cell membrane. These results imply that, if the cytotoxic T cell recognizes a single antigenic determinant specified both by viral and H-2 genes, this determinant is formed by the physical association of H-2 and Sendai virus antigens rather than by their alteration during the processes of synthesis.