tbuckley/cabot-search huggingface dataset:
Sir Percivall Pott—the first sports neurologist?
Authors: P R McCrory
Journal: British Journal of Sports Medicine (2001)

“A young man playing at cudgels in Moorfields received a stroke on his forehead; it did not seem to himself to be a particular severe one, but as it produced blood it was deemed by the laws of the game to be a broken head, and he was obliged to yield to his antagonist . . .as it gave him no trouble, he took no notice of it and was for several nights afterward engaged in the same diversion which followed his daily labour...on the ninth day from that on which he received the blow, he thought that his forehead was somewhat swollen and felt tender to touch . . .the swelling and pain increased and he found himself much out of order . . .an incision was made into the tumour . . .a circular piece of the scalp was removed which discovered a fracture . . .a trephine was passed into the fracture line and the bone was removed . . ..the dura mater was found discoloured and beginning to have matter on its surface . . .he was let blood . . .until his pulse failed . . .by proper care he was brought to himself . . .it is very clear that unless the cranium had been perforated he must have perished” (Case XVIII)1

This case report, published in 1768 by Percivall Pott, represents the first example in the medical literature of sports neurology. Now popularised by current day neurologists and neurosurgeons such as Jordan and Cantu, sports neurology has slowly evolved into a distinct subspecialty of neurology.2–6

The case report described above also illustrates a number of other features. It is the first demonstration of the “blood rule” in action and serves to graphically illustrate the perilous nature of head injuries …
Soft Sweeps II—Molecular Population Genetics of Adaptation from Recurrent Mutation or Migration
Authors: Pleuni S. Pennings, Joachim Hermisson
Journal: Molecular Biology and Evolution (2006)

In the classical model of molecular adaptation, a favored allele derives from a single mutational origin. This ignores that beneficial alleles can enter a population recurrently, either by mutation or migration, during the selective phase. In this case, descendants of several of these independent origins may contribute to the fixation. As a consequence, all ancestral haplotypes that are linked to any of these copies will be retained in the population, affecting the pattern of a selective sweep on linked neutral variation. In this study, we use analytical calculations based on coalescent theory and computer simulations to analyze molecular adaptation from recurrent mutation or migration. Under the assumption of complete linkage, we derive a robust analytical approximation for the number of ancestral haplotypes and their distribution in a sample from the population. We find that so-called "soft sweeps," where multiple ancestral haplotypes appear in a sample, are likely for biologically realistic values of mutation or migration rates.
Allergic rhinitis management pocket reference 2008*
Authors: J. Bousquet, J. Reid, C. Van Weel, C. Baena Cagnani, G. W. Canonica, P. Demoly, J. Denburg, W. J. Fokkens, L. Grouse, K. Mullol, K. Ohta, T. Schermer, E. Valovirta, N. Zhong, T. Zuberbier
Journal: Allergy (2008)

Allergic rhinitis is a major chronic respiratory disease because of its prevalence, impacts on quality of life and work/school performance, economic burden, and links with asthma. Family doctors (also known as ‘primary care physicians’ or ‘general practitioners’) play a major role in the management of allergic rhinitis as they make the diagnosis, start the treatment, give the relevant information, and monitor most of the patients. Disease management that follows evidence‐based practice guidelines yields better patient results, but such guidelines are often complicated and may recommend the use of resources not available in the family practice setting. A joint expert panel of the World Organization of Family Doctors (Wonca), the International Primary Care Airways Group (IPAG) and the International Primary Care Respiratory Group (IPCRG), offers support to family doctors worldwide by distilling the globally accepted, evidence‐based recommendations from the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative into this brief reference guide. This guide provides tools intended to supplement a thorough history taking and the clinician’s professional judgment in order to provide the best possible care for patients with allergic rhinitis. A diagnostic Questionnaire specifically focuses the physician’s attention on key symptoms and markers of the disease. When questionnaire responses suggest a diagnosis of allergic rhinitis, a Diagnosis Guide and a simple flowchart then lead the clinician through a series of investigations commonly available in primary care to support the diagnosis. In addition, key aspects of differential diagnosis are illuminated. According to ARIA, allergic rhinitis may be classified as Intermittent or Persistent, and as Mild or Moderate/Severe. The classification of rhinitis determines the treatment necessary, as set out in an ARIA flowchart included in this guide. The guide also includes information about the strength of evidence for efficacy of certain rhinitis treatments, a brief discussion of pediatric aspects, and a glossary of allergic rhinitis medications to assist the clinician in making medication choices for each individual patient. Finally, many patients with allergic rhinitis also have concomitant asthma, and this must be checked. The World Organization of Family Doctors has been delegated by WHO as the group that will be taking primary responsibility for education about chronic respiratory diseases among primary care physicians globally. This document will be a major resource in this educational program.
Effects of Low Dose Sympathetic Inhibition on Glomerulosclerosis and Albuminuria in Subtotally Nephrectomized Rats
Authors: KERSTIN AMANN, LARS CHRISTIAN RUMP, AURELIA SIMONAVICIENE, VITUS OBERHAUSER, SABINE WESSELS, STEPHAN R. ORTH, MARIE-LUISE GROSS, ANDREAS KOCH, GERHARD W. BIELENBERG, JORGE P. VAN KATS, HEIMO EHMKE, GERHARD MALL, EBERHARD RITZ
Journal: Journal of the American Society of Nephrology (2000)

Abstract. A potential role of the sympathetic nervous system in progression of renal failure has received little attention. This study examined whether nonhypotensive doses of moxonidine, an agent that reduces sympathetic activity, affects glomerulosclerosis, urine albumin excretion, and indices of renal handling of norepinephrine (NE) in subtotally nephrectomized (SNX) rats. Sprague Dawley rats were SNX or sham-operated (control). SNX rats were either left untreated or treated with moxonidine in a dose (1.5 mg/kg body wt per d) that did not modify telemetrically monitored 24-h BP. Glomerular and renal morphology were evaluated by quantitative histology, immunohistochemistry, and in situ hybridization. Urine albumin excretion rate was analyzed by enzyme-linked immunosorbent assay, and kidney angiotensin II and NE content were measured using HPLC, 3 H-NE uptake, and release. Body and kidney weight and BP were not significantly different between SNX with or without moxonidine. The glomerulosclerosis index was significantly lower in moxonidine-treated (0.88 ± 0.09) compared with untreated (1.55 ± 0.28) SNX rats, as was the index of vascular damage (0.32 ± 0.14 versus 0.67 ± 0.16). The number of proliferating cell nuclear antigen-positive glomerular and tubular cells per area was significantly higher in untreated SNX rats than in controls and moxonidine-treated SNX rats. The same was true for urine albumin excretion rate. Renal angiotensin II tissue concentration was not affected by moxonidine. In untreated SNX rats, renal nerve stimulation and exogenous NE induced an increase in isolated kidney perfusion pressure (102 ± 21 versus 63 ± 8 mmHg). Renal endogenous NE content was significantly lower in SNX rats than in controls (86 ± 14 versus 140 ± 17 pg/mg wet weight). Cortical uptake of [ 3 H]-NE was not different, but cortical NE release was significantly higher in SNX rats than in controls. Reduced function of presynaptic inhibitory α-adreno-receptors is unlikely because an α 2 -adrenoceptor antagonist increased NE release. At subantihypertensive doses, moxonidine ameliorates renal structural and functional damage in SNX animals, possibly through central inhibition of efferent sympathetic nerve traffic. In kidneys of SNX rats, indirect evidence was found for increased activity of a reduced number of nerve fibers.
Does a home-based strength and balance programme in people aged ≥80 years provide the best value for money to prevent falls? A systematic review of economic evaluations of falls prevention interventions
Authors: J C Davis, M C Robertson, M C Ashe, T Liu-Ambrose, K M Khan, C A Marra
Journal: British Journal of Sports Medicine (2010)

Objectives To investigate the value for money of strategies to prevent falls in older adults living in the community. Design Systematic review of peer reviewed journal articles reporting an economic evaluation of a falls prevention intervention as part of a randomised controlled trial or a controlled trial, or using an analytical model. MEDLINE, PUBMED, EMBASE and NHS EED databases were searched to identify cost-effectiveness, cost–utility and cost–benefit studies from 1945 through July 2008. Main outcome measures The primary outcome measure was incremental cost-effectiveness, cost–utility and cost–benefit ratios in the reported currency and in pounds sterling at 2008 prices. The quality of the studies was assessed using two instruments: (1) an economic evaluation checklist developed by Drummond and colleagues and (2) the Quality of Health Economic Studies instrument. Results Nine studies meeting our inclusion criteria included eight cost-effectiveness analyses, one cost–utility and one cost–benefit analysis. Three effective falls prevention strategies were cost saving in a subgroup of participants: (1) an individually customised multifactorial programme in those with four or more of the eight targeted fall risk factors, (2) the home-based Otago Exercise Programme in people ≥80 years and (3) a home safety programme in the subgroup with a previous fall. These three findings were from six studies that scored ≥75% on the Quality of Health Economic Studies instrument. Conclusions Best value for money came from effective single factor interventions such as the Otago Exercise Programme which was cost saving in adults 80 years and older. This programme has broad applicability thus warranting warrants health policy decision-makers’ close scrutiny.
D<scp>IETARY</scp>R<scp>EGULATION OF</scp>E<scp>XPRESSION OF</scp>G<scp>LUCOSE</scp>-6-P<scp>HOSPHATE</scp>D<scp>EHYDROGENASE</scp>
Authors: Lisa M Salati, Batoul Amir-Ahmady
Journal: Annual Review of Nutrition (2001)

▪ Abstract The family of enzymes involved in lipogenesis is a model system for understanding how a cell adapts to dietary energy in the form of carbohydrate versus energy in the form of triacylglycerol. Glucose-6-phosphate dehydrogenase (G6PD) is unique in this group of enzymes in that it participates in multiple metabolic pathways: reductive biosynthesis, including lipogenesis; protection from oxidative stress; and cellular growth. G6PD activity is enhanced by dietary carbohydrates and is inhibited by dietary polyunsaturated fats. These changes in G6PD activity are a consequence of changes in the expression of the G6PD gene. Nutrients can regulate the expression of genes at both transcriptional and posttranscriptional steps. Most lipogenic enzymes undergo large changes in the rate of gene transcription in response to dietary changes; however, G6PD is regulated at a step subsequent to transcription. This step is involved in the rate of synthesis of the mature mRNA in the nucleus, specifically regulation of the efficiency of splicing of the nascent G6PD transcript. Understanding the mechanisms by which nutrients alter nuclear posttranscriptional events will help uncover new information on the breadth of mechanisms involved in gene regulation.
Focal Lesions in the Canine Bundle of His: THEIR EFFECT ON VENTRICULAR EXCITATION
Authors: Thomas B. Watt, Raymond D. Pruitt
Journal: Circulation Research (1972)

The alterations in ventricular excitation resulting from production of discrete punctate electrocautery lesions in the canine bundle of His were studied. Electrocardiographic changes were correlated with lesions identified anatomically by microscopic examination of the atrioventricular bundle. Although partial or complete atrioventricular block developed from lesions at several levels of the atrioventricular bundle, changes in the form of the QRS complex appeared only when lesions involved the distal portion of the bundle. Such QRS changes were recorded in 21 of 32 instances when the lesion involved the branching portion of the common bundle but in none of 6 instances when the lesion involved only the nonbranching portion of the common bundle. This study, then, provides evidence for functionally distinct longitudinal fascicles only within the distal portion of the common bundle. The syncytial character of the terminal fascicular (Purkinje) network may minimize the electrocardiographic evidence for such functional specificity within the common bundle.
Specialized functions of major histocompatibility complex class I molecules. II. Hmt binds N-formylated peptides of mitochondrial and prokaryotic origin.
Authors: S M Shawar, J M Vyas, J R Rodgers, R G Cook, R R Rich
Journal: The Journal of Experimental Medicine (1991)

The physiological functions of the mouse telomeric major histocompatibility complex (MHC) class I molecules, including Hmt, are unknown. Hmt presents a polymorphic, N-formylated peptide encoded by the mitochondrial gene ND1 forming the cell surface maternally transmitted antigen (Mta). Because the N-formyl moiety is required for Hmt binding, we proposed that Hmt may function generally in presentation of N-formylated antigens. This hypothesis was validated by a competitive binding assay, demonstrating that synthetic N-formyl peptides from other mitochondrial genes also bound Hmt. Bacteria similarly initiate protein synthesis with N-formylmethionine; indeed, we established that Hmt can also present prokaryotic peptides in an N-formyl-dependent manner. These results indicate biochemical specialization of this MHC-peptide interaction and suggest a unique role for Hmt in prokaryotic host defenses.
Abrogation of p21 Expression by Flavopiridol Enhances Depsipeptide-Mediated Apoptosis in Malignant Pleural Mesothelioma Cells
Authors: Dao M. Nguyen, William D. Schrump, G. Aaron Chen, Wilson Tsai, Phuongmai Nguyen, Jane B. Trepel, David S. Schrump
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Recent insights regarding the pathogenesis of malignant pleural mesothelioma (MPM) provide new opportunities for targeted molecular therapies for this highly lethal disease. The present study was undertaken to examine the effects of the histone deacetylase inhibitor, Depsipeptide (DP) FK228, in conjunction with the cyclin-dependent kinase inhibitor, Flavopiridol (FLA), in cultured MPM cells. Experimental Design: Proliferation and apoptosis in drug-treated, virally transduced, or control cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Apo-bromodeoxyuridine techniques. Western blot and ELISA techniques were used to examine signal transduction and cell cycle-related protein levels in MPM cells exposed to DP and/or FLA in the presence or absence of calphostin, phorbol-12,13-dibutyrate, 5,6-dichloro-1-β-d-ribofuranosyl-benzimidazole, or adenoviral p21 transduction. Results: DP (1–50 ng/ml × 6 h) or FLA (100–200 nm × 72 h) alone, mediated low-level, dose-dependent growth inhibition in MPM cells. In contrast, sequential DP/FLA treatment mediated marked growth inhibition and apoptosis in these cell lines. The cytotoxic effects of DP/FLA were considerably less pronounced in cultured normal cells. The proapoptotic effects of DP/FLA treatment coincided with inhibition of DP-mediated induction of p21 by FLA. Overexpression of p21 by adenoviral gene transfer techniques rendered MPM cells refractory to the cytotoxic effects of this treatment regimen. In p21 reporter assays, promoter activation by DP was antagonized by FLA. The magnitude of inhibition of DP-mediated p21 induction by FLA exceeded that observed with the pTEFb antagonist 5,6-dichloro-1-β-d-ribofuranosyl-benzimidazole. Calphostin C abrogated p21 induction mediated by DP and enhanced DP-mediated apoptosis in a manner comparable with FLA in MPM cells; in contrast, phorbol-12,13-dibutyrate blocked FLA-mediated inhibition of p21 induction by DP and markedly protected these cells from the apoptotic effects of sequential DP/FLA. Conclusions: FLA abrogates DP-mediated induction of p21 expression, in part, via inhibition of protein kinase C signaling and markedly potentiates the cytotoxic effects of DP in MPM cells.
Identification of PMF1 Methylation in Association with Bladder Cancer Progression
Authors: Ainel Aleman, Virginia Cebrian, Miguel Alvarez, Virginia Lopez, Esteban Orenes, Lidia Lopez-Serra, Ferran Algaba, Joaquin Bellmunt, Antonio López-Beltrán, Pilar Gonzalez-Peramato, Carlos Cordon-Cardo, Javier García, Javier García del Muro, Manel Esteller, Marta Sánchez-Carbayo
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Polyamines are important regulators of cell growth and death. The polyamine modulated factor-1 (PMF-1) is involved in polyamine homeostasis. After identifying an enriched CpG island encompassing the PMF1 promoter, we aimed at evaluating the clinical relevance of PMF1 methylation in bladder cancer. Experimental Design: The epigenetic silencing of PMF1 by hypermethylation was tested in bladder cancer cells (n = 11) after azacytidine treatment. PMF1 methylation status was evaluated in 507 bladder tumors and 118 urinary specimens of bladder cancer patients and controls. PMF1 protein expression was analyzed by immunohistochemistry on tissue arrays containing bladder tumors for which PMF1 methylation was assessed (n = 218). Results: PMF1 hypermethylation was associated with gene expression loss, being restored in vitro by a demethylating agent. An initial set of 101 primary frozen bladder tumors served to identify PMF1 hypermethylation in 88.1% of the cases. An independent set of 406 paraffin-embedded tumors also revealed a high PMF1 methylation rate (77.6%). PMF1 methylation was significantly associated with increasing stage (P = 0.025). Immunohistochemical analyses revealed that PMF1 methylation was associated with cytoplasmic PMF1 expression loss (P = 0.032). PMF1 protein expression patterns were significantly associated with stage (P &amp;lt; 0.001), grade (P &amp;lt; 0.001), and poor overall survival using univariate (P &amp;lt; 0.001) and multivariate (P = 0.011) analyses. Moreover, PMF1 methylation in urinary specimens distinguished bladder cancer patients from controls (area under the curve = 0.800). Conclusion: PMF1 was identified to be epigenetically modified in bladder cancer. The association of PMF1 methylation with tumor progression and its diagnostic ability using urinary specimens support including PMF1 assessment for the clinical management of bladder cancer patients.
Generation of cytotoxic T lymphocytes in vitro. IV. Functional activation of memory cells in the absence of DNA synthesis.
Authors: H R MacDonald, B Sordat, J C Cerottini, K T Brunner
Journal: The Journal of Experimental Medicine (1975)

Re-exposure of day 14 mixed leukocyte culture (MLC) cells to the original stimulating alloantigens (secondary response) has previously been shown to result in significant proliferation and in rapid reappearance of high levels of cytolytic T-lymphocyte (CTL) activity within the next 4 days. Moreover, evidence has been presented that CTL precursor cells in day 14 MLC populations, while they derived from cells were large at peak of the primary response (day 4) were themselves small lymphocytes which developed into large CTL after restimulation. In this study, inhibition of DNA synthesis by cytosine arabinoside (ARA-C) was used to investigate whether CTL formation could be dissociated from proliferation during the secondary response. It was found that within the first 24 h after restimulation (a) CTL activity increased 6-to-20-fold, (b) 60-70% of the small T lymphocytes became medium- to large-sized cells, and (c) both events were independent of DNA synthesis. By using two successive cell separations by velocity sedimentation at unit gravity, before and after stimulation of day 14 MLC cells for 24 h in the presence or absence of ARA-C, direct evidence was obtained that small CTL precursor cells developed into large CTL, irrespective of DNA synthesis. The presence of ARA-C for periods longer than 24 h inhibited any further increase in CTL activity, in contrast to a parallel increase in lytic activity and cell number from day 1 to day 4 in control restimulated cultures. Taken together with the finding that 90% of the medium- and large-sized lymphoid cells in control restimulated cultures underwent DNA synthesis within 24 h, these results thus suggest that during a secondary MLC response there is initially a differentiation step leading to the formation of CTL which, although it can be clearly dissociated from DNA synthesis, is under normal conditions followed by proliferation of these effector cells.
Physician Assistants and Health System Reform
Authors: P. Eugene Jones, James F. Cawley
Journal: JAMA (1994)

NATIONAL efforts to reform the health care system will likely result in changes in the roles and responsibilities, practice combinations, and distribution of health professionals, including midlevel providers such as physician assistants (PAs), nurse practitioners (NPs), and certified nurse-midwives. Although recent studies have addressed differing scenarios of the projected roles of midlevel providers,<sup>1-5</sup>implementation of initiatives that involve PAs may be influenced by an overall shortage of PAs, existing barriers to PA practice, and the need for commitment to physician-dependent practice relationships in a team-oriented health care delivery system. This article reviews the history, academic preparation, clinical capabilities, distribution, and practice activities of PAs and discusses the potential roles of PAs in the changing health system environment. The origin of the PA can be traced to the new health practitioner movement of the 1960s, during which the PA concept emerged from a combination of events. As experienced hospital corpsmen
An ecological analysis of incidence of tuberculosis and per capita gross domestic product
Authors: J-P. Janssens, H. L. Rieder
Journal: European Respiratory Journal (2008)

To the Editor: 

In 2006, an estimated 9 million new cases of tuberculosis (TB) emerged worldwide 1. Of these, only 1% occurred in the European Union and North America combined, while Africa and South-East Asia contributed >65%. Among the 22 high-burden countries, 17 were in Africa, 16 of which were in the lowest quartile in terms of per capita gross domestic product (GDP). Since 2001, the fight against poverty has been a major theme in the World Health Organization’s (WHO) “Stop TB” strategy. Indeed, poverty “fuels” TB by facilitating transmission through crowded working and living conditions, it may increase the risk of progression to disease through malnutrition, and imposes barriers to accessing health services.

The aim of the present analysis …