tbuckley/cabot-search huggingface dataset:
Book: Adrenaline and the Inner World
Authors: Simon L Bacon
Journal: BMJ (2006)

Before even opening this book, two things struck me. Firstly, a renowned American physician at the National Institutes of Health is writing a book about adrenaline (the British approved name for the international non-proprietary name epinephrine), and secondly, the book claims to cover fields as diverse as philosophy, biochemistry, and alternative medicine. In my general experience, a book that claims to be so diverse generally ends up being so “thin” that it serves no one. In such a world, this book is an exception.​exception.




Figure 1



David S Goldstein

Johns Hopkins University Press, $25/£16.60, pp 328 ISBN 0 8018 8289 3 www.press.jhu.edu

Rating: ★★★★




Although only adrenaline appears in the title, the book deals with all members of the catecholamine family. Even though, as the author admits, much has been written about catecholamines, few have attempted to draw together the myriad of effects and interactions these molecules have on the body. In this book, issues ranging from the history of the catecholamine family to interventions to deal with dysautonomias (dysfunctional catecholamine disorders) are covered. Scientific fact is brought to life by real world occurrences and incidences. In the final chapter, Dr Goldstein explains the principles of scientific integrative medicine and does an excellent job of using the concepts developed in the book to explain the basis and utility of the integrative approach to medicine.

The author glides through complex structures, functions, and systems, providing a readable and entertaining summary of the area. Some omissions are evident and anyone who wishes to find a reference to go with a specific tantalising topic, such as the interaction of the sympathetic nervous system and the hypothalamus-pituitaryadrenal axis, will be disappointed.

In spite of its minor shortcomings, the book is an enjoyable read and would provide an excellent accompaniment to a more rigorous and academic work.
Time to reassess strategies for improving health in developing countries
Authors: David B Evans, Taghreed Adam, Tessa Tan-Torres Edejer, Stephen S Lim, Andrew Cassels, Timothy G Evans
Journal: BMJ (2005)

A girl born today in Malawi is 35 times more likely to die before reaching the age of 5 years than a girl born in the United Kingdom. If she reaches her fifth birthday, she can look forward to a life in which she has a 37 times greater chance of contracting tuberculosis than her British counterpart and is 180 times more likely to die during pregnancy or childbirth.1 Malawian girls can expect a life span of only 42 years, 39 years less than that of British girls.1 These differences are typical of the health gaps between rich and poor countries. Contributing factors are numerous and complex and include poverty, low levels of education (particularly for women), environmental hazards, limited access to health services, and the low volumes, unpredictability, and volatility of aid flows. In recognition, after a decade of discussion, 189 countries committed to accelerate development in poor countries by endorsing an interrelated set of development goals, outlined in the Millennium Declaration of September 2000.2

Improving health received considerable prominence in the millennium development goals. Three of the eight goals focused on reducing key causes of mortality in poor countries: maternal and perinatal conditions, diseases affecting children and infants, and the major communicable diseases (box 1). These remain priorities, although non-communicable diseases and injuries are increasingly important even in poor countries (table 1).

View this table:

Table 1 
Leading causes of death in developing and developed countries, 20004



Targets and indicators for each goal were developed to help monitor and evaluate progress (table 2). Tuberculosis is the only disease other than HIV and AIDS and malaria specifically mentioned in the last health goal.

View this table:

Table 2 
Targets and indicators for millennium development health goals3



The millennium development goals have been criticised on several fronts: that they are too ambitious and therefore …
Abstract 12016: An Enhanced Collagen-Based Matrix Promotes Cardiomyocytic Differentiation of Embryonic Stem Cells
Authors: Diba Ebadi, Drew Kuraitis, Donna T Padavan, Ashraf Al Madhoun, Marc Ruel, Ilona Skerjanc, Erik J Suuronen
Journal: Circulation (2011)

Background:  Previous studies have incorporated the oligosaccharide sialyl Lewis X  (sLe X ) into an injectable collagen matrix for regeneration of ischemic muscle. It was hypothesized that this material may support differentiation of progenitors towards a cardiac lineage. This study sought to characterize its elastic and hydropolar properties that are conducive towards myogenesis, and its potential for generating cardiomyocytes.   Methods:  Elastic moduli and water contact angles (WCA) of matrices were measured. Mouse embryonic bodies were cultured on: 1) collagen matrix; or, 2) sLe X -collagen matrix; and compared to 3) tissue culture plastic substrate (TCPS) controls. After 15 days, cells were harvested and analyzed for cardiac markers using immunofluorescence, qPCR and Western blotting.   Results:  Collagen matrices did not produce a detectable WCA, but incorporation of sLe X  reliably produced regions with WCA of  P =0.9); values ranged from 9.0-19.9kPa, which supports maximal myogenic differentiation. L-Selectin, the receptor for sLe X , was expressed in cells from days 0 to 15, indicating potential interaction with the sLe X -collagen matrix. Spontaneously beating cells were observed on all substrates. At day 15, cells on both collagen and sLe X -collagen matrices had greater expression of cardiac myogenesis markers GATA4 (1.8-fold;  P  P  X -matrix culture induced increased transcription of cardiac markers Nkx2.5 (2.3-fold;  P =0.009) and atrial natriuretic factor (3.1-fold;  P =0.02) in cells, compared to TCPS. Immunofluorescence demonstrated a greater presence of cardiac α-actinin on the sLe X -collagen matrix.   Conclusions:  These results demonstrate that the physical properties of the sLe X -collagen matrix are optimal for myogenesis. In addition to having regenerative effects  in vivo , these injectable materials may be useful for generating functional cardiomyocytes for transplantation, without the need for genetic or viral manipulation.
Abstract 3239: Edge-to-edge Repair of Functional Tricuspid Regurgitation is Safe and Durable
Authors: Vincent Chan, Anthony Tran, Marc Ruel, Dominique Grisoli, Ladislaus Ressler, Thierry Mesana
Journal: Circulation (2009)

Introduction: The edge-to-edge repair technique has been well described for the treatment of functional mitral regurgitation, but few data exist describing its use in functional tricuspid regurgita...
Abstract 2655: Polymorphisms in the Gene Encoding for Cyclooxygenase-2 and the Risk of Recurrent Atherothrombotic Events
Authors: Jeroen Jaspers Focks, Nick Clappers, Martijn G van Oijen, Wilbert H Peters, Rene H te Morsche, Hennie M Roelofs, Joost P Drenth, Freek W Verheugt
Journal: Circulation (2008)

Multiple single nucleotide polymorphisms (SNP’s) in the gene encoding for cyclooxygenase-2 (COX-2) have been identified. These SNP’s may modify risk of atherothrombotic events. The COX-2 -765G-&gt;C SNP has been associated with decreased COX-2 activity and with significantly lower odds of a first atherothrombotic event. The − 1195G-&gt;A SNP on the other hand seems to be correlated with increased COX-2 activity, but has not been investigated in relation to atherothrombotic events. Our aim is to investigate whether these two functional COX-2 SNP’s are associated with the risk of recurrent atherothrombotic events. Patients hospitalized between Apr 2002 and Jan 2004 with acute coronary syndrome were genotyped for the COX-2 − 765G-&gt;C and − 1195G-&gt;A SNP’s and followed up to July 2008. The primary endpoint was a composite of cardiovascular death, myocardial infarction and/or stroke. Multivariate analysis was performed. We included a cohort of 379 consecutive patients (median age 66 y (IQR 55–73), 66% were males). Genotyping for the − 765G-&gt;C showed frequencies of 72% GG, 27% GC and 1% CC. For the − 1195G-&gt;A frequencies were 5% GG, 35% GA and 60% AA. There was strong linkage disequilibrium (D’=−1.0) between both SNP’s. The primary endpoint occurred in 82 patients (22%). The unadjusted hazard ratio for the − 765GC/CC genotypes was 1.33 (95% confidence intervals [CI] 0.84 –2.10, p= 0.22) compared with − 765GG , the adjusted hazard ratio was 1.16 (95% CI 0.72–1.88, p=0.54). Haplotype analysis of the combination of −1195- and −765-genotypes, revealed no genetic subgroup at significantly increased risk either. Previously, the COX-2 − 765G-&gt;C SNP was associated with a reduced risk for first atherothrombotic event. For the risk of recurrent events we found no effect for this SNP. In addition we studied the combination with the functional − 1195G-&gt;A SNP of COX-2, which did not show a significant effect on recurrent events either.
Abstract 17934: Phosphoprotein Profiling Unravels Novel Phosphoproteins That Distinguish Intracellular cGMP Signaling by Natriuretic Peptide- and Nitric Oxide-Activated Guanylyl Cyclases
Authors: Kumar Kotlo, Bahar Hesabi, Robert Danziger
Journal: Circulation (2010)

Intracellular cGMP regulates vascular smooth muscle cell (VSMC) growth and proliferation. Cellular guanylyl cyclases (GCs) are generally divided into two groups: natriuretic peptide- activated-GCs ...
Abstract 1940: Diastolic Untwisting is Altered in Tetralogy of Fallot Patients: A Novel MR Speckle Tracking Method for Cine-MRI
Authors: Petra S Niemann, David J Sahn
Journal: Circulation (2009)

Background: In tetralogy of Fallot (TOF), satisfactory post-op outcome is not solely dependent on systolic right and left ventricular (RV,LV) function. Early signs of LV diastolic dysfunction need ...
506. LPS-Induced Lung Inflammation and Bronchial Hyperreactivity: Effects of Murine IL-10 When Injected in the Airways or Generated in the Circulation after Muscle Electrotransfer of Murine IL-10 Encoding Plasmid
Authors: Virginie Deleuze, Jean Lefort, Michel-Francis Bureau, Daniel Scherman, B. Boris Vargaftig
Journal: Molecular Therapy (2004)

When administered to mice systemically or via the airways, LPS induces bronchoconstriction (BC) and/or bronchopulmonary hyperreactivity (BHR), associated to inflammation. Accordingly, a relation between inflammation and allergic and non-allergic BHR can be hypothesized. We therefore studied the interference of the anti-inflammatory cytokine murine IL-10 (mIL-10) with LPS-induced lung inflammation, BC and BHR. mIL-10 was administered directly into the airways by intranasal instillation or generated in vivo after muscle electrotransfer of mIL-10-encoding plasmid. Electrotransfer led to high mIL-10 circulating levels for a longer time than after the injection of recombinant mIL-10 (rmIL-10). rmIL-10 administered intra-nasally reduced lung inflammation and BHR following LPS administration into airways. Two days after electrotransfer, mIL-10 blood levels were elevated, but lung inflammation, BC and BHR persisted unaffected. Blood mIL-10 reaches the airways poorly, which probably accounts for the ineffectiveness of mIL-10-encoding plasmid electrotransfer. When LPS was aerosolized 15 days after electrotransfer, lung inflammation persisted but BHR was significantly reduced, an effect which may be related to the longer exposure of the relevant cells to mIL-10. The dissociation between inflammation and BHR indicates that both are not directly correlated. In conclusion, this study shows that mIL-10 is efficient against BHR when present in the airway compartment. Despite this, the muscle electrotransfer with mIL-10-encoding plasmid showed a protective effect against BHR after a delay of two weeks that should be further investigated.
Doublespeak
Authors: Des Spence
Journal: BMJ (2008)

“Lively” (disruptive), “independent” (selfish), “spirited” (appallingly spoilt), “enjoys maths” (no friends), “energetic at sport” (hopelessly uncoordinated), “special aptitude at art” (innumerate), “enjoys listening to music” (tone deaf), “a delight” (will never amount to anything), “making headway with reading” (stupid and slow)—welcome to the doublespeak of school report cards and the noxious “all positive” feedback.

Gone are the comments that spurred a generation. Our coffee stained report cards were at least honest. “Desmond would do much better if he occasionally listened.” “Desmond’s English would improve if he learnt to spell and occasionally used something we call punctuation.” “Please provide Desmond with a gag next term.” “Desmond is a clumsy boy.” But now there is nothing worth hanging in your downstairs toilet to entertain your guests. Why has our society become so fake and lost the ability to be honest?

Many professional groups have suffered a succession of high profile inquiries, berated for perceived failings and accused of a catalogue of institutional “isms.” The reaction of service directors has been to make their organisations ever more risk averse. But by introducing increasingly restrictive protocols, institutions are eroding the core values of professionalism: discretion and judgment. In turn power has shifted away from the professional to the client, the patient, the pupil, and even the pet. Some changes were of course overdue, much of the criticism justified—but we have gone too far. We have created a complaint economy with a hyperinflation in skewed and stupid feedback questionnaires and wads of bankrupt unrepresentative users groups.

We doctors are now so fearful of criticism and complaints that we are no longer able to be honest in consultations, assessments, reports, or referrals. This makes our job increasingly difficult. Being patient centred is important, but we struggle to challenge (even sensitively) people’s lifestyles, parenting skills, behaviour—resulting in ever increasing medicalisation. In removing a sense of personal responsibility our society is in danger of decapitating our moral selves, leaving just a flailing corpse of entitlement, bleeding out the last of our self esteem.

Medicine isn’t just another service industry, and the customer isn’t always right. We don’t need to return to the paternalism of the past, but for the sake of our patients we need to be able to be open and honest without the threat of unfounded complaints. We have the ability, but it may be too late; we should have done our homework, worked harder, and applied ourselves.
Abstract 11305: Isolated Left Anterior Fascicular Block is Associated With an Increased Risk of Atrial Fibrillation and Heart Failure
Authors: Mala C Mandyam, Elsayed Z Soliman, Susan R Heckbert, Eric Vittinghoff, Thomas A Dewland, Gregory M Marcus
Journal: Circulation (2012)

Introduction: Isolated left anterior fascicular block (LAFB) can be caused by fibrosis of the conduction system. This ECG finding may therefore represent an early manifestation of diffuse myocardia...
Abstract 3488: Hyperuricemia and the Risk of Isolated Hypertension among Young People without Cardiovascular and Metabolic Risk Factors: The CARDIA Study
Authors: Eswar Krishnan, Hyon K Choi, Lewis H Kuller, Kiang Liu
Journal: Circulation (2007)

PURPOSE: The association between higher serum uric acid (SUA) levels and hypertension in the context of the metabolic syndrome is well known. If such an association was causal, one would expect to demonstrate a link between hyperuricemia and incidence of isolated hypertension - a hypothesis that has not been tested so far. METHODS: We used the 15-year limited-access data from the prospective cohort study of Coronary Artery Risk Development in young adults (CARDIA), sponsored by the National Institutes of Health, to identify a group of non-smoking young people with normal blood pressure and free of insulin resistance, hyperlipidemia, obesity, and a family history of cardiovascular diseases. These young people aged between 18 and 30 years at baseline were followed-up for a period of 15 years by 6 study visits where all cardiovascular risk factors were reassessed. Incidence of JNC-7 hypertension was the outcome of interest in Cox proportional hazards models where age, gender, race, lipid levels, blood pressure, alcohol, body mass index, smoking and serum insulin levels (time-varying where appropriate) were the covariates. Baseline serum uric acid (continuous) was the independent variable of interest. A second set of Cox regression analyses was performed among the subgroup of these individuals who remained free of all cardiovascular risk factors (except for hypertension) over the 15-year follow up. RESULTS: Out of the 5113 CARDIA participants at baseline, 2057 subjects were free of cardiovascular risk factors at baseline and were available for evaluation at year 15. Over the follow-up period, 828 subjects developed hypertension. In multivariate Cox models, each mg/dl increase in serum uric acid was associated with a hazard ratio of 1.45 (1.09–1.91). In the second set of analyses, 753 were free of all cardiovascular risk factors at baseline and remained free of any of the components of the metabolic syndrome except hypertension (n = 122 incident cases of hypertension) were studied. In these analyses each mg/dl increasse in SUA was associated with a risk adjusted hazard ratio of 1.60 (95% CI 1.02–2.49). CONCLUSIONS: Unrelated to the other features of the metabolic syndrome, higher levels of SUA among young people predicts isolated hypertension.
"True" schizotypal personality disorder: a study of co-twins and relatives of schizophrenic probands
Authors: S Torgersen, S Onstad, I Skre, J Edvardsen, E Kringlen
Journal: American Journal of Psychiatry (1993)

The aim of the study was to investigate the type and nature of personality disorders among biological relatives of schizophrenic probands.A total of 176 nonschizophrenic co-twins and other first-degree relatives of schizophrenic probands were compared to 101 co-twins and first-degree relatives of probands with major depression.Schizotypal personality disorders were more common and histrionic personality disorders less common among the biological relatives of schizophrenic probands than among relatives of probands with major depression. A further exploration of the schizotypal criteria revealed that the so-called "negative" criteria such as odd speech, inappropriate affect, and odd behavior, as well as excessive social anxiety, were significantly more common among the relatives of schizophrenic probands. The latter criterion seems particularly important. The so-called "positive" schizotypal criteria were partly, although not statistically significantly, more common among the relatives of probands with major depression. There were only minor differences in frequencies of the negative criteria between monozygotic co-twins, dizygotic co-twins, and other first-degree relatives of schizophrenic probands.The present study suggests that DSM-III-R schizotypal disorder is defined by a set of criteria that partly describe a "true" schizophrenia-related personality disorder and partly features that are not specific for relatives of schizophrenic probands. Furthermore, the genetic relationship between schizophrenia and "true" schizotypal personality disorder seems weak. Excessive social anxiety may be a marker of a possible genetic link between the disorders.
More on albumin
Authors: I. Roberts, P. Edwards, B. McLelland, B. J Fogarty, K. Khan
Journal: BMJ (1999)

Editor—After publication of the Cochrane Injuries Group Albumin Reviewers’ systematic review of albumin administration in critically ill patients1 the Committee on Safety of Medicines convened an expert working party to consider the implications for the use of albumin in the United Kingdom. To date the committee has not made any announcement. The results of the review were widely reported in the medical and lay press,2 and this may have influenced the use of albumin.

We requested data on the monthly issues of albumin solutions to regional blood centres and hospitals between 1993 and 1999 from the Bio Products Laboratory (which serves England and Wales) and the Protein Fractionation Centre of the Scottish National Blood Transfusion Service (which serves Scotland and Northern Ireland). Issues were expressed in kg of albumin, reflecting the total albumin content of the various dose units. A three month moving average of albumin issues was calculated.

From May 1993 to June 1998 albumin issues from the Scottish National Blood Transfusion Service increased by about 17%. In July 1998, after publication in the BMJ and Cochrane Library of the systematic review, issues fell steeply, from 180 kg in June to 62 kg in December (figure). Issues from Bio Products Laboratory had been stable from January 1994 to July 1998, after which they fell dramatically. By the end of December 1998 issues of albumin from the Bio Products Laboratory had levelled out, those of 4.5% albumin having dropped by 40-45% and those of 20% albumin by around 40% (figure). 

The Protein Fractionation Centre’s data reflect virtually all albumin used in Scotland and Northern Ireland. Data on Bio Products Laboratory’s share of the market in England and Wales are not available.

Demand for albumin fell steeply after publication of the systematic review. This raises important questions about the alternatives being used—non-albumin colloids (gelatins, starches, dextrans) and crystalloid solutions. Although the review included trials comparing albumin with crystalloids, there should be some concern that albumin may have been replaced by non-albumin colloids as there is no compelling evidence that these are superior and these products may also have important adverse effects.3,4 In view of the rapid and substantial changes in albumin issues there is a case for monitoring changing patterns of use of colloid and providing guidance for clinicians on fluid management.
Characterization of p53 Abnormalities in CLL Patients in Relation to IGVH Mutation Status and Previous Treatment.
Authors: M. Trbusek, V. Kuhrova, J. Malcikova, J. Smardova, H. Francova, D. Mentzlova, S. Bukovska, M. Svitakova, P. Kuglik, V. Linkova, M. Doubek, Y. Brychtova, J. Kujickova, S. Pospisilova, D. Dvorakova, J. Mayer
Journal: Blood (2005)
Epidemiology of fine particulate air pollution and human health: biologic mechanisms and who's at risk?
Authors: C A Pope
Journal: Environmental Health Perspectives (2000)

This article briefly summarizes the epidemiology of the health effects of fine particulate air pollution, provides an early, somewhat speculative, discussion of the contribution of epidemiology to evaluating biologic mechanisms, and evaluates who's at risk or is susceptible to adverse health effects. Based on preliminary epidemiologic evidence, it is speculated that a systemic response to fine particle-induced pulmonary inflammation, including cytokine release and altered cardiac autonomic function, may be part of the pathophysiologic mechanisms or pathways linking particulate pollution with cardiopulmonary disease. The elderly, infants, and persons with chronic cardiopulmonary disease, influenza, or asthma are most susceptible to mortality and serious morbidity effects from short-term acutely elevated exposures. Others are susceptible to less serious health effects such as transient increases in respiratory symptoms, decreased lung function, or other physiologic changes. Chronic exposure studies suggest relatively broad susceptibility to cumulative effects of long-term repeated exposure to fine particulate pollution, resulting in substantive estimates of population average loss of life expectancy in highly polluted environments. Additional knowledge is needed about the specific pollutants or mix of pollutants responsible for the adverse health effects and the biologic mechanisms involved.