tbuckley/cabot-search huggingface dataset:
Epidemiology and comorbidity of psoriasis in children
Authors: M. Augustin, G. Glaeske, M.A. Radtke, E. Christophers, K. Reich, I. Schäfer
Journal: British Journal of Dermatology (2009)

Background Psoriasis is a common disease affecting all age groups. In contrast to adult psoriasis, only few studies on the epidemiology of childhood psoriasis have been published. Objectives Assessment of prevalence and comorbidities of juvenile psoriasis in Germany based on health insurance data. Methods Data were collected from a database of about 1·3 million nonselected individuals from a German statutory health insurance organization which covers all geographical regions. Individuals with psoriasis were identified by ICD-10 codes applied to all outpatient and inpatient visits. The present analysis consists of all patients who were enlisted throughout the year 2005. The diagnosis of psoriasis was registered whenever there was at least one documented patient contact using code L40.* and subcodes. Comorbidities were also evaluated by ICD-10 diagnoses. Results In total, 33 981 patients with the diagnosis of psoriasis were identified. The prevalence in 2005 was 2·5%. The total rate of psoriasis in children younger than 18 years was 0·71%. The prevalence rates increased in an approximately linear manner from 0·12% at the age of 1 year to 1·2% at the age of 18 years. The overall rate of comorbidity in subjects with psoriasis aged under 20 years was twice as high as in subjects without psoriasis. Juvenile psoriasis was associated with increased rates of hyperlipidaemia, obesity, hypertension, diabetes mellitus, rheumatoid arthritis and Crohn disease. Conclusions Psoriasis is a common disease in children. Like in adults, it is associated with significant comorbidity. Increased attention should be paid to the early detection and treatment of patients affected.
Congenital Long-QT Syndrome Caused by a Novel Mutation in a Conserved Acidic Domain of the Cardiac Na <sup>+</sup> Channel
Authors: Jian Wei, Dao W. Wang, Marco Alings, Frank Fish, Mark Wathen, Dan M. Roden, Alfred L. George
Journal: Circulation (1999)

Background —Congenital long-QT syndrome (LQTS) is an inherited condition of abnormal cardiac excitability characterized clinically by an increased risk of ventricular tachyarrhythmias. One form, LQT3, is caused by mutations in the cardiac voltage–dependent sodium channel gene, SCN5A . Only 5 SCN5A mutations have been associated with LQTS, and more work is needed to improve correlations between SCN5A genotypes and associated clinical syndromes. Methods and Results —We researched a 3-generation white family with autosomal dominant LQTS who exhibited a wide clinical spectrum from mild bradycardia to sudden death. Molecular genetic studies revealed a single nucleotide substitution in SCN5A exon 28 that caused the substitution of Glu1784 by Lys (E1784K). The mutation occurs in a highly conserved domain within the C-terminus of the cardiac sodium channel containing multiple, negatively charged amino acids. Two-electrode voltage-clamp recordings of a recombinant E1784K mutant channel expressed in Xenopus oocytes revealed a defect in fast inactivation characterized by a small, persistent current during long membrane depolarizations. Coexpression of the mutant with the human sodium channel β 1 -subunit did not affect the persistent current, even though we did observe shifts in the voltage dependence of steady-state inactivation. Neutralizing multiple, negatively charged residues in the same region of the sodium channel C-terminus did not cause a more severe functional defect. Conclusions —We characterized the genetics and molecular pathophysiology of a novel SCN5A sodium channel mutation, E1784K. The functional defect exhibited by the mutant channel causes delayed myocardial repolarization, and our data on the effects of multiple charge neutralizations in this region of the C-terminus suggest that the molecular mechanism of channel dysfunction involves an allosteric rather than a direct effect on channel gating.
Public health and medicolegal implications of sleep apnoea
Authors: J Krieger, W T McNicholas, P Levy, W De Backer, N Douglas, O Marrone, J Montserrat, J H Peter, D Rodenstein
Journal: European Respiratory Journal (2002)

⇓The sleep apnoea syndrome represents something of a paradox in clinical medicine. On the one hand, this disorder has been recognised only in recent decades, and is still regarded as a niche interest by many clinicians, particularly those from clinical disciplines other than respiratory medicine, neurology and otolaryngology. On the other hand, the syndrome is now recognised as being very common and current epidemiological data indicate that sleep apnoea syndrome is second only to asthma in the prevalence league table of chronic respiratory disorders 1. Furthermore, there is increasing evidence that sleep apnoea syndrome is associated with a considerable number of adverse sequelae, both behavioural and physical. Behavioural consequences include daytime sleepiness, impaired concentration and neuropsychological dysfunction, whereas physical consequences include cardiovascular disorders, particularly hypertension.

In 1997, the European Respiratory Society (ERS) established a Task Force to examine the Public Health and Medicolegal Implications of the Sleep Apnoea Syndrome with particular reference to the impact of sleepiness on patient and public safety. The following report represents the outcome of several meetings and discussions of the Task Force membership and also includes a review of current European Regulations concerning driver licensing prepared by one of the members (J. Krieger).

Obstructive sleep apnoea syndrome (OSAS) is a condition characterised by repetitive obstruction of the upper airway, often resulting in oxygen desaturation and arousals from sleep. The principal daytime manifestation is excessive sleepiness but other symptoms such as unrefreshing sleep, poor concentration and fatigue are commonly reported. Early definitions of the syndrome were based on an apnoea frequency without reference to symptoms 2. However, as epidemiological data from many studies made it clear that apnoeas during sleep are very common in the general population, the definition of a clinical syndrome was revised to include certain symptoms, particularly daytime sleepiness. Hypopnoeas …
GPs should not profit personally from NHS reforms, say doctors' leaders
Authors: A. O'Dowd
Journal: BMJ (2010)

GPs should not gain any personal profit from commissioning budgets under the proposed reforms to the NHS, say doctors’ leaders.

The BMA’s General Practitioners Committee has published what it says should be the fundamental principles underlying the development of GP commissioning.

In the committee’s first position statement on GP commissioning since the publication in July of the government white paper Equity and Excellence: Liberating the NHS , the BMA says that its principles should be used to define policy, inform debate and negotiations, and ensure that good medical practice is guaranteed.

The government’s reforms of the NHS will see the abolition of England’s primary care trusts and strategic health authorities, as new consortiums of GPs take direct …
"Patients First" and the clinician's influence in management
Authors: W I. Jones
Journal: BMJ (1980)

Atypical glucose tolerance curve in dogs SIR,-The recent article of Mr Paul McMaster and others (16 February, p 444) gave the results of preoperative and postoperative intravenous glucose tolerance tests in dogs immunosuppressed by cyclosporin A with segmental pancreatic allografts.The results of these tests were highlighted by the presence of an unusually delayed glucose peak occurring at 30 minutes in both the untreated and the allografted dogs.This delayed glucose response was observed after an intravenous injection of 0-5 g glucose per kg body weight.In our experience of 50 intravenous glucose tolerance tests in normal dogs, using a rapid infusion of 05 g glucose per kg body weight, the peak glucose response always occurred five to 10 minutes after the administration of glucose.These results are in agreement with the findings of other workersl-3 who used this dose and mode of administration of glucose.As the beta cells in the pancreatic islets are known to have an instantaneous response to a glucose challenge4 it is of great interest to us to ascertain how the apparently significantly delayed response after a glucose load was achieved.Furthermore, it would be important to know if the use of the drug cyclosporin A may have contributed to the delayed glucose response in the allografted dogs, although this seems unlikely in view of the similar responses found before operation in the same dogs.
NFκB activation and stimulation of chemokine production in normal human macrophages by the gadolinium-based magnetic resonance contrast agent Omniscan: possible role in the pathogenesis of nephrogenic systemic fibrosis
Authors: Francesco Del Galdo, Peter J Wermuth, Sankar Addya, Paolo Fortina, Sergio A Jimenez
Journal: Annals of the Rheumatic Diseases (2010)

Objective Nephrogenic systemic fibrosis (NSF) is a generalised fibrotic disorder occurring in certain individuals with renal insufficiency exposed to gadolinium-based contrast agents (GdBCA) for MRI. Histopathological examination of affected tissues shows increased numbers of activated macrophages. To elucidate the mechanisms responsible for macrophage activation, the effects of the GdBCA Omniscan on normal human macrophage global gene expression, chemokine production and nuclear factor κB (NFκB) activation was examined. Methods Normal human monocyte-derived macrophages were incubated with Omniscan (50 mM) and their gene expression analysed by microarrays and real-time PCR. Macrophage chemokine production was assayed by multiplex ELISA. NFκB activation was assessed by NFκB nuclear localisation and quantitation of intracellular levels of inducible nitric oxide synthase (iNOS) protein. A specific cell-permeable NFκB peptide inhibitor was used to abrogate NFκB stimulation of chemokine and iNOS protein levels. CCL8/MCP-2 in affected skin of patients with NSF was examined by indirect immunofluorescence. Results Omniscan caused a profound change in the transcriptome of differentiated human normal macrophages in vitro, including a large increase in the expression of genes encoding CC and CXC chemokines. It induced rapid nuclear localisation of NFκB and stimulation of iNOS protein levels and chemokine production which were blocked by an NFκB inhibitory peptide. CCL8/MCP-2, the most upregulated chemokine following in vitro macrophage exposure to Omniscan, was strongly increased in NSF-affected skin. Conclusion The GdBCA Omniscan induces potent stimulation of macrophage gene expression, NFκB activation and increased NFκB-mediated production of CC and CXC chemokines and iNOS. These alterations may play a crucial role in the pathogenesis of NSF.
Adipokines and Risk of Type 2 Diabetes in Older Men
Authors: S. Goya Wannamethee, Gordon D.O. Lowe, Ann Rumley, Lynne Cherry, Peter H. Whincup, Naveed Sattar
Journal: Diabetes Care (2007)

OBJECTIVE—The aim was to assess the relationship between adipokines, including interleukin (IL)-6, leptin, and adiponectin, with development of type 2 diabetes and assess the role of obesity and insulin resistance in these relationships. RESEARCH DESIGN AND METHODS—We conducted a prospective study of 3,599 nondiabetic men aged 60–79 years and followed up for a mean period of 5 years, during which time there were 108 incident cases of type 2 diabetes. RESULTS—Elevated IL-6, leptin, and low adiponectin were associated with increased risk of type 2 diabetes even after adjustment for BMI, lifestyle factors, preexisting cardiovascular disease, and systolic blood pressure. The relative risks (RRs) (top vs. bottom third) were 2.02 (95% CI 1.14–3.58) for IL-6, 1.91 (0.97–3.76) for leptin, and 0.40 (0.23–0.70) for adiponectin. Further adjustment for insulin resistance made minor differences to the IL-6 diabetes relationship (adjusted RR 2.12 [1.18–3.81]), weakened the associations with adiponectin (0.59 [0.33–1.04]), and abolished the association between leptin and diabetes (1.12 [0.55–2.26]). The inverse relation between low adiponectin and diabetes was significantly stronger in men who were obese (waist circumference &amp;gt;102 cm or BMI ≥30 kg/m2) (0.30 [0.11–0.79]) relative to leaner men (0.93 [0.44–1.96]) (test for interaction P = 0.04). CONCLUSIONS—The association between leptin and incident diabetes is mediated by insulin resistance. By contrast, the positive association between IL-6 and diabetes appeared to be independent of obesity and insulin resistance. Finally, the association between low adiponectin and increased risk of diabetes appears to be significantly stronger in obese men than in leaner counterparts.
Should bronchoscopy be advocated to study airway remodelling and inflammation in adults with cystic fibrosis?: Figure 1
Authors: Pierre-Régis Burgel, Clémence Martin, Isabelle Fajac, Daniel J Dusser
Journal: Thorax (2011)

We read with interest the article by Regamey et al who reviewed the relationship of airway remodelling to inflammation in cystic fibrosis (CF).1 The authors suggested that endobronchial biopsy studies are useful for studying airway remodelling in CF. Four studies were conducted in 91 children who underwent bronchoscopy for clinical reasons or annual routine surveillance. These studies confirmed that airway remodelling in CF appeared early in life and this is indeed of more than academic interest. However, while the authors have previously shown …
Metastatic Cancer Cell
Authors: Marina Bacac, Ivan Stamenkovic
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

Metastasis is the result of cancer cell adaptation to a tissue microenvironment at a distance from the primary tumor. Metastatic cancer cells require properties that allow them not only to adapt to a foreign microenvironment but to subvert it in a way that is conducive to their continued proliferation and survival. Recent conceptual and technological advances have contributed to our understanding of the role of the host tissue stroma in promoting tumor cell growth and dissemination and have provided new insight into the genetic makeup of cancers with high metastatic proclivity.
The normal range and determinants of the intrinsic heart rate in man
Authors: A. D. Jose, D. Collison
Journal: Cardiovascular Research (1970)

Normal standards for the intrinsic heart rate (IHR) were measured in 432 healthy adult subjects aged 16 to 70 years. At rest, with normal body temperature, the IHR was highly reproducible. In different subjects, age was the only important determinant. Differences in IHR between individuals may correspond to differences in functional capacity of the myocardium, whether determined genetically, by age, or by disease.
Bridging the gap between science and drug policy: From “what” and “how” to “whom” and “when”
Authors: Robert J. MacCoun
Journal: Behavioral and Brain Sciences (2008)

Abstract For all its problems, the microeconomic “rational addiction” theory had the appeal of making clear predictions about the effects of various drug policies. The emerging picture of the “what” and “how” of addiction is far more complex. Addiction scientists might help bridge the science–policy gap by devoting more attention to the “whom” and “when” of addiction.
Efficacy of intravenous Ig therapy in juvenile dermatomyositis
Authors: C. G. Lam, C. Manlhiot, E. M. Pullenayegum, B. M. Feldman
Journal: Annals of the Rheumatic Diseases (2011)

Intravenous immunoglobulin (IVIg) is an adjunctive therapy for juvenile dermatomyositis (JDM) patients with poor response to first-line therapy (corticosteroid resistant; SR) or who are corticosteroid dependent (SD). Patients requiring IVIg are generally expected to have poorer outcomes, leading to confounding by indication in observational studies. Few studies have evaluated IVIg efficacy in JDM.Compared with similar matched controls, to determine if JDM IVIg recipients achieve quiescence sooner and have less disease activity. For SD patients, to determine if IVIg recipients exhibit less disease activity than IVIg-naive patients.A retrospective inception cohort of 78 JDM patients was studied. Kaplan-Meier survival determined time to quiescence. Marginal structural modelling was used to account for confounding by indication by incorporating inverse probability of treatment weights to handle patients' unequal likelihood of receiving IVIg.While similar demographically, the 30 IVIg patients demonstrated weaker muscle strength and more had photosensitivity at baseline than the 48 controls. As expected, IVIg patients achieved quiescence later than controls in unadjusted analysis. However, although IVIg patients started with greater disease activity, after accounting for confounding as best possible, they maintained similar or lower disease activity than controls from 30 days to 4 years post-diagnosis. This improvement was most marked in SR patients. Among SD patients, IVIg recipients maintained lower disease activity than IVIg-naive patients.This study, involving the largest JDM cohort receiving IVIg to date, applied bias-reduction methods and demonstrated IVIg efficacy in controlling JDM disease activity, particularly for SR patients.
VIIth EULAR Postgraduate Course in Rheumatology
Authors: J A P da Silva
Journal: Annals of the Rheumatic Diseases (2003)

The VIIth EULAR Postgraduate Course in Rheumatology took place in Budapest from the 22nd to the 27th September 2002.

The programme was designed to offer a comprehensive review and discussion of the scientific basis and clinical practice in the diagnosis and management of a large spectrum of rheumatic conditions, …
Resorption of implanted bone prepared from normal and warfarin-treated rats.
Authors: J B Lian, M Tassinari, J Glowacki
Journal: Journal of Clinical Investigation (1984)

Bone that was virtually depleted of the vitamin K-dependent protein, osteocalcin, and 93% reduced in the concentration of its characteristic amino acid, gamma-carboxyglutamic acid, was obtained from rats treated with warfarin for 6 wk. Osteocalcin-deficient bone particles were resistant to resorption when implanted subcutaneously in normal rats. The relative resorption was 60% of control bone, as measured by histomorphometry as percent of bone particles in the field. Additionally, the number of multinucleated cells around the bone particles was reduced by 54%. These data suggest that osteocalcin is an essential component for bone matrix to elicit progenitor-cell recruitment and differentiation necessary for bone resorption.
Influence of scar on left ventricular performance at the onset of myocardial ischemia: shock versus heart failure
Authors: Timothy J. Regan, Anthony J. Passannante, Mohammad I. Khan, Henry A. Oldewurtel, Mohan U. Jesrani
Journal: Journal of Clinical Investigation (1971)

Obstruction of a major branch of the left coronary artery in a previously normal ventricle is not usually associated with shock, experimentally or clinically. To examine the early hemodynamic alterations which may determine the course of ischemia when myocardial scar exists from previous infarction, 16 animals were successfully studied 9 wk after obstruction of the left circumflex artery. Acute ischemia during thrombus formation in the anterior descending artery of intact anesthetized dogs with scar was compared with animals undergoing the same procedure in the absence of scar (group 1). In the chronic animals, two types of hemodynamic responses were observed. Group 2 was characterized by heart failure usually persisting through 3 hr, and group 3 by a different ventricular volume response and rapidly developing shock. The weight of ischemic and scar areas were comparable and coronary blood flow (85Kr method) to the ischemic site was reduced to a similar extent. Animals in groups 1 and 2 remained normotensive and had similar elevations of left ventricular enddiastolic volume (indicator dilution method) during the initial 60 min of ischemia. Group 2 had a significantly larger rise of end-diastolic pressure, presumably related to altered elastic properties associated with scar of subendocardial distribution.
Statin-Induced Expression of Decay-Accelerating Factor Protects Vascular Endothelium Against Complement-Mediated Injury
Authors: Justin C. Mason, Zahra Ahmed, Rivka Mankoff, Elaine A. Lidington, Saifur Ahmad, Vinay Bhatia, Anne Kinderlerer, Anna M. Randi, Dorian O. Haskard
Journal: Circulation Research (2002)

Complement-mediated vascular injury is important in the pathophysiology of atherosclerosis and myocardial infarction. Because recent evidence shows that statins have beneficial effects on endothelial cell (EC) function independent of lipid lowering, we explored the hypothesis that statins modulate vascular EC resistance to complement through the upregulation of complement-inhibitory proteins. Human umbilical vein and aortic ECs were treated with atorvastatin or simvastatin, and decay-accelerating factor (DAF), membrane cofactor protein, and CD59 expression was measured by flow cytometry. A dose-dependent increase in DAF expression of up to 4-fold was seen 24 to 48 hours after treatment. Statin-induced upregulation of DAF required increased steady-state mRNA and de novo protein synthesis. L-Mevalonate and geranylgeranyl pyrophosphate reversed the effect, confirming the role of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition and suggesting that constitutive DAF expression is negatively regulated by geranylgeranylation. Neither farnesyl pyrophosphate nor squalene inhibited statin-induced DAF expression, suggesting that the effect is independent of cholesterol lowering. Statin-induced DAF upregulation was mediated by the activation of protein kinase Calpha and inhibition of RhoA and was independent of phosphatidylinositol-3 kinase and NO activity. The increased DAF expression was functionally effective, resulting in significant reduction of C3 deposition and complement-mediated lysis of antibody-coated ECs. These observations provide evidence for a novel cytoprotective action of statins on vascular endothelium that is independent of the effect on lipids and results in enhanced protection against complement-mediated injury. Modulation of complement regulatory protein expression may contribute to the early beneficial effects of statins in reducing the morbidity and mortality associated with atherosclerosis.