tbuckley/cabot-search huggingface dataset:
Light and electron microscopic localization of brain natriuretic peptide in relation to atrial natriuretic peptide in porcine atrium. Immunohistocytochemical study using specific monoclonal antibodies.
Authors: K Hasegawa, H Fujiwara, H Itoh, K Nakao, T Fujiwara, H Imura, C Kawai
Journal: Circulation (1991)

BACKGROUND Although first isolated from the porcine brain, brain natriuretic peptide (BNP) is also found in the heart, particularly in the atria. METHODS AND RESULTS We examined the immunocytochemical localization of BNP in relation to atrial natriuretic peptide (ANP) in five porcine atria using highly specific monoclonal antibodies. With the use of an indirect immunoperoxidase method, serial sections examined by light microscopy showed foci of multihormonal myocytes containing both ANP and BNP localized in the subendocardium. Monohormonal myocytes containing ANP only were observed in the subepicardium and part of the subendocardium. The staining intensity of ANP and BNP showed a transmural gradient from the subendocardium to the subepicardium. At the electron microscopic level, double immunocytochemistry using a two-face immunogold-staining method revealed two types of granules: Type 1 is a monohormonal granule containing ANP alone, and type 2 is a multihormonal granule containing both ANP and BNP. Although most atrial myocytes contained both, type 1 granules were frequently observed in the epicardial side, and type 2 granules were frequently observed in the endocardial side. We observed a few type 2 granules even in the light microscopically monohormonal myocytes. CONCLUSIONS These data suggest that the atrial myocyte population comprises single, multipotential cells able to synthesize both natriuretic peptides in varying proportions. The atrial transmural gradient of BNP and ANP may be related to responses to wall stress.
Fresh frozen plasma has no beneficial effect on the hemostatic system in children receiving <scp>L</scp>‐asparaginase
Authors: Jacqueline M. Halton, Lesley G. Mitchell, Patsy Vegh, Marilyn Eves, Maureen E. Andrew
Journal: American Journal of Hematology (1994)

Abstract L ‐Asparaginase (ASP), a chemotherapeutic agent used in the treatment of children with acute lymphoblastic leukaemia (ALL), is linked to thromboembolic complications secondary to an acquired deficiency of antithrombin III (ATIII). Fresh frozen plasma (FFP) is used to prevent and/or treat thrombotic complications in these children. However, the effect of FFP on plasma concentrations of ATIII and biochemical markers of activation of coagulation has never been tested. In this study, FFP (20 ml/kg) was administered to eight children with ALL receiving ASP in the consolidation phase of their treatment. Plasma samples were drawn pre‐infusion, and following infusion at 1, 24, and 48 hr. Prior to the FFP infusions, plasma concentrations of prothrombin, fibrinogen, α 2 ‐macroglobulin, heparin cofactor II, protein C, and protein S were similar to levels in healthy children. Only plasma concentrations of ATIII were significantly decreased (0.55 U/ml). Following FFP infusions, there was no statistical or clinically important increase in plasma concentrations of any coagulation protein at any time point. Pre‐infusion plasma concentrations of markers of endogenous thrombin generation (thrombin‐antithrombin III complexes (TAT)) and activation of the fibrinolytic system in response to activation of the coagulation system (D‐dimer levels) were significantly increased. However, FFP had no statistical or clinically important effect on concentrations of these markers. We conclude that FFP administration for the prevention and treatment of acquired ATIII deficiency secondary to ASP has no demonstrable benefit on plasma levels of coagulation proteins and is unlikely to be of clinical benefit. © 1994 Wiley‐Liss, Inc.
Superiority of combined diltiazem and propranolol therapy for angina pectoris.
Authors: W E Strauss, A F Parisi
Journal: Circulation (1985)

Twenty-four patients with stable angina were evaluated in a 14 week crossover trial. A single-blind placebo period (baseline 1) was followed by two double-blind periods evaluating maximum tolerated doses of diltiazem (up to 360 mg daily) vs placebo. Over the next 1 to 4 weeks, propranolol was started and increased until clinically documented beta-blockade was achieved (baseline 2). The final phase consisted of a pair of evaluation periods comparing propranolol plus the maximum tolerated dose of diltiazem to propranolol and placebo. The daily rate of angina attack was 1.6 during baseline, was unchanged during placebo therapy, but fell during treatment with diltiazem to 0.6 (p less than .005). With the addition of diltiazem to propranolol, the angina rate was improved (0.3) compared with that with either propranolol alone (0.6) or propranolol and placebo (0.5) (p less than .01). Total exercise duration during baseline 1 was 360 sec and increased to 497 sec with diltiazem, 481 sec with propranolol, and 527 sec with the combination of diltiazem and propranolol. Two patients with reduced ejection fractions developed congestive heart failure with propranolol. The combination of diltiazem and propranolol similarly resulted in congestive heart failure in one patient who had tolerated both drugs alone.
Soluble CD40 Ligand, Soluble P-Selectin, Interleukin-6, and Tissue Factor in Diabetes Mellitus
Authors: Hoong Sern Lim, Andrew D. Blann, Gregory Y.H. Lip
Journal: Circulation (2004)

Background— High levels of the soluble fragment of CD40 ligand (sCD40L) have previously been associated with adverse cardiovascular outcomes. CD40L–CD40 interaction has been linked to the pathogenesis of atherothrombotic complications in cardiovascular disease (CVD). We sought to determine whether a “package of care” of intensified multifactorial cardiovascular risk intervention could reduce indices of platelet activation, inflammation, and coagulation in diabetes and whether patients with overt CVD would derive similar benefit compared with those without. Methods and Results— We measured plasma sCD40L, soluble P-selectin (sP-sel, an index of platelet activation), interleukin-6 (IL-6, a proinflammatory cytokine), and tissue factor (TF, an initiator of coagulation) in 97 patients with diabetes mellitus (41 with and 56 without overt CVD) and 39 comparable healthy control subjects. Thirty-six patients with and 32 without overt CVD then participated in a package of care of cardiovascular risk intervention over a period of 1 year. Plasma levels of sCD40L ( P &lt;0.001), sP-sel ( P &lt;0.001), IL-6 ( P =0.001), and TF ( P &lt;0.001) were higher in patients with diabetes than in control subjects, with TF levels highest in patients with overt CVD. Multifactorial intervention was associated with significant reductions in sCD40L in both patient groups (both P &lt;0.001), but reductions in sP-sel and TF were seen only in patients without overt CVD. There was no significant change in IL-6 levels in both patient groups. Conclusions— Intensive multifactorial risk management can reduce high levels of sCD40L but can only partially correct abnormal platelet activation, inflammation, and coagulation in diabetes, particularly in patients with overt CVD.
1148-208 Psychological stress increases heterogeneity of repolarization in patients with structural heart disease and ventricular arrhythmias
Authors: Rachel Lampert, Vladimir Shusterman, Matthew M Burg, Forrester A Lee, Christine Earley, Anna Goldberg, Craig A McPherson, William P Batsford, Robert Soufer
Journal: Journal of the American College of Cardiology (2004)
Tsunami threats: the long and short of it
Authors: Stacie Bloom
Journal: Journal of Clinical Investigation (2005)

We now know that the catastrophe of December 26, 2004, was one of the greatest natural disasters in history. The tsunami that ripped through the Indian Ocean stole more than 150,000 lives and left thousands more injured, homeless, orphaned, and desperate. What we don't yet know are the long-term threats to public health that the tsunami will leave in its wake.

The primary effects of the sea surge have been made clear in the weeks that have passed. The majority of deaths were a direct result of drowning and traumatic injuries. The force of the waves washed away houses, medical facilities, fisheries, and food supplies. The impact of this devastation is tangible and evident, but the long-term threats to public health are more uncertain, and the threat of an epidemic looms. Damage to sewer systems and contamination of drinking water supplies poses the gravest threat and can lead to a multitude of water- and food-borne diseases such as cholera, hepatitis A and E, diarrhea, typhoid fever, shigellosis, rotavirus, and leptospirosis. Pools of standing water pose the threat of mosquito-borne diseases such as malaria and dengue fever. Overcrowding in refugee camps raise the risk of pneumonia and other respiratory ailments.

Preventive measures are in place to ensure the safety of area inhabitants – careful surveillance, distribution of health kits and chlorine tablets, vaccinations, education, organization of resources, and relief efforts will all help to keep epidemics at bay and preserve the heath of survivors. “Now that the crisis is weeks old, the risk of major outbreaks directly resulting from the tsunami . . . may already be behind us, and will probably be almost gone by the end of three months,” says Les Roberts, a water engineer and disaster expert at the Johns Hopkins Bloomberg School of Public Health. But, he adds, “Disasters which ravage economies can elevate infant mortality and disease transmission patterns for years.”

The mental consequences of this catastrophe also pose an insidious threat. Although psychosocial services are being provided in some areas by international organizations, the long-term effects can only be speculated. The incidence of posttraumatic stress disorder and depression is expected to be very high. Survivors also face a lasting sense of loss, fear, helplessness, and shell shock, says Carol Etherington, former president of the US board of Doctors Without Borders and an expert on international volunteer efforts who has worked with the International Medical Corps and the Red Cross. Adults can cope with and make sense of a natural disaster, she explains, but children will have a harder time putting the horror into context. But, she adds hopefully, “people are resilient.”
The temporal pattern of respiratory and heart disease mortality in response to air pollution.
Authors: Antonella Zanobetti, Joel Schwartz, Evi Samoli, Alexandros Gryparis, Giota Touloumi, Janet Peacock, Ross H Anderson, Alain Le Tertre, Janos Bobros, Martin Celko, Ayana Goren, Bertil Forsberg, Paola Michelozzi, Daniel Rabczenko, Santiago Perez Hoyos, H Erich Wichmann, Klea Katsouyanni
Journal: Environmental Health Perspectives (2003)

Short-term changes in ambient particulate matter with aerodynamic diameters < 10 micro m (PM10) have been associated with short-term fluctuations in mortality or morbidity in many studies. In this study, we tested whether those deaths are just advanced by a few days or weeks using a multicity hierarchical modeling approach for all-cause, respiratory, and cardiovascular deaths, for all ages and stratifying by age groups, within the APHEA-2 (Air Pollution and Health: A European Approach) project. We fit a Poisson regression and used an unconstrained distributed lag to model the effect of PM10 exposure on deaths up to 40 days after the exposure. In baseline models using PM10 the day of and day before the death, we found that the overall PM10 effect (per 10 micro g/m3) was 0.74% [95% confidence interval (95% CI), -0.17 to 1.66] for respiratory deaths and 0.69% (95% CI, 0.31-1.08) for cardiovascular deaths. In unrestricted distributed lag models, the effect estimates increased to 4.2% (95% CI, 1.08-7.42) for respiratory deaths and to 1.97% (95% CI, 1.38-2.55) for cardiovascular deaths. Our study confirms that most of the effect of air pollution is not simply advanced by a few weeks and that effects persist for more than a month after exposure. The effect size estimate for PM10 doubles when we considered longer-term effects for all deaths and for cardiovascular deaths and becomes five times higher for respiratory deaths. We found similar effects when stratifying by age groups. These larger effects are important for risk assessment.
L-Type Ca <sup>2+</sup> Current Downregulation in Chronic Human Atrial Fibrillation Is Associated With Increased Activity of Protein Phosphatases
Authors: T. Christ, P. Boknik, S. Wöhrl, E. Wettwer, E.M. Graf, R.F. Bosch, M. Knaut, W. Schmitz, U. Ravens, D. Dobrev
Journal: Circulation (2004)

Although downregulation of L-type Ca2+ current (I(Ca,L)) in chronic atrial fibrillation (AF) is an important determinant of electrical remodeling, the molecular mechanisms are not fully understood. Here, we tested whether reduced I(Ca,L) in AF is associated with alterations in phosphorylation-dependent channel regulation.We used whole-cell voltage-clamp technique and biochemical assays to study regulation and expression of I(Ca,L) in myocytes and atrial tissue from 148 patients with sinus rhythm (SR) and chronic AF. Basal I(Ca,L) at +10 mV was smaller in AF than in SR (-3.8+/-0.3 pA/pF, n=138/37 [myocytes/patients] and -7.6+/-0.4 pA/pF, n=276/86, respectively; P<0.001), though protein levels of the pore-forming alpha1c and regulatory beta2a channel subunits were not different. In both groups, norepinephrine (0.01 to 10 micromol/L) increased I(Ca,L) with a similar maximum effect and comparable potency. Selective blockers of kinases revealed that basal I(Ca,L) was enhanced by Ca2+/calmodulin-dependent protein kinase II in SR but not in AF. Norepinephrine-activated I(Ca,L) was larger with protein kinase C block in SR only, suggesting decreased channel phosphorylation in AF. The type 1 and type 2A phosphatase inhibitor okadaic acid increased basal I(Ca,L) more effectively in AF than in SR, which was compatible with increased type 2A phosphatase but not type 1 phosphatase protein expression and higher phosphatase activity in AF.In AF, increased protein phosphatase activity contributes to impaired basal I(Ca,L). We propose that protein phosphatases may be potential therapeutic targets for AF treatment.
THE PUBLIC HEALTH ASPECTS OF LEPROSY IN THE UNITED STATES
Authors: RUPERT BLUE
Journal: JAMA (1913)

On account of the communicability of leprosy and its mutilating effects on individuals affected, the presence of the disease in any community is a matter for concern. Leprosy is known to exist in many states and in all of our island possessions. By reason of this prevalence and the enormous volume of traffic carried on between the United States and other countries, the control of the disease becomes a problem of national importance. <h3>PAST PREVALENCE</h3> The infection was undoubtedly introduced into the United States from abroad, but the time of its introduction is problematical. Cases were undoubtedly imported into the Gulf States by maritime routes. The disease gained access to Pacific Coast ports through Chinese immigration, and to the north central states by means of Scandinavian immigrants. In some of these sections the prevalence of the disease evidently attracted more attention many years ago than at the present time. In Louisiana, where leprosy
A Clinical Comparison of MDP and DMAD
Authors: LEONARD ROSENTHALL, JERRY STERN, ARTIN ARZOUMANIAN
Journal: Clinical Nuclear Medicine (1982)

Tc-99m labeled dimethyl-amino-diphosphonate (DMAD) was compared with methylene diphosphonate (MDP) in five healthy volunteers and 28 patients with a variety of bony afflictions. Although the normal bone uptake of DMAD is less than MDP, the lesion-to-normal bone ratio is significantly higher with DMAD. All 71 lesions detected with MDP were also seen with DMAD. However, 10 lesions were disclosed with DMAD that were not seen with MDP. These lesions tended to have low grade concentrations of the radiopharmaceutical and were detected with DMAD by virtue of the lower normal bone uptake rather than higher lesion uptake.
Africans die in pain because of fears of opiate addiction
Authors: Dorothy Logie, Mhoira Leng
Journal: BMJ (2007)

Attempts to improve palliative care services in Africa are being hampered by the fear that many African professionals have of using morphine therapeutically and by poor access to the drug, a conference was told last month.⇓





Many countries in Africa have no access to morphine so that palliative care is reduced to the level of supportive care without pain relief, delegates from 35 countries heard. They were attending the second palliative care conference for Africa, in Nairobi.

While the world's 20 richest countries consume 86% of global therapeutic morphine, countries such as Rwanda use just 0.039 mg per …
A Post-Graduate Lecture ON THE ESTIMATION OF HEART POWER: AND THE TERMS BLOOD PRESSURE; HYPERTENSION; HYPERPIESIS; HYPERTONUS
Authors: W. Russell
Journal: BMJ (1912)

1 U~~~~~~~~~~~~~~~~~MuvwALUNA to mere a^idity, to the positive ion H. Stronger solitions drive it into iiaor.Dr. Fletcher has sho,wn tllat by. a previouis application of oxygen these 'effets can be pre-- ventel.The mammalian heart lying after death in ajii at-splhera of oxygen does not become acid, or but s' iglitly so; and after p3rfusion with oxygenized Ringer's selutioni,.evensome lhours after, no trace of lactic-acid appears.Dr. Flet-cher has shown in9 lhow mnany ocecult flaws there may possibly be in the balance of c)lloidal mechanisms in tlle cardiac mnuscle; and inore than tliis-that thc heart may have-abundant fatty (deposit in it, and yet the muscle cell on the motor side be intrinsically intact, and prove no more vulnerable than one hiistologically normal; and this lie illtustrated by tlle figure of an engine clogged with dirt and grease, which iiotNviths'anding may do better work than another engine briglit and clean but with tiaht bearings, or an unseen crack in its cylinder.When beyond unequal metabolismiis we pass into the region of toxic influences we recognize again lIow near the edge our gyroscope may be revolvilng.Finllly we know that the heart's balance depends on Ilha'; of many other parts also; tlle gaseotus exchanges are not in the myocardium only, not even in the lungs only; they are burning in every muscular area, in every viscus.Thus, even if the haemoglobin be constant in (quality and quantity, if velocity begins to fall we are in a vicious circle; velocity-which me.ans oxygen ex- chanuge-slows down in every organ, especially in those whlichi, beside the lungs, have a double capillary machinery, such as tlle liver and the kidneys; in these areas we very .;eonfind evidences of stasis.And retardation ini the lymph system also is not to be forgotten.Such defauilts as these mnay for wliiles m:ss or neutralize eaclh other, but Wheln at som3 unhappy moment a summation of adverse alternating conditions comes about-capillary retardations in tlhe viscera, tissue calls, lymnph pressures, vagus and vasomotor wvaves, psychic thrills in such cases as tllese, cases not without their prior forebodings, we shall not be at a loss to comprehend at last the suddenness of death.But the riddle, whlicll I have done so little to read, is the frequent suddenness of death in one wlho scarcely having, klnown illness expires under no extraordinary effort; or in the peace of his own bed or elbow chair passes silently away.
Safer administration of insulin: summary of a safety report from the National Patient Safety Agency
Authors: T. Lamont, D. Cousins, R. Hillson, A. Bischler, M. Terblanche
Journal: BMJ (2010)

Insulin has been identified as one of the top 10 high risk medicines worldwide.1 Errors are common—the first national audit of over 14 000 inpatients with diabetes in England and Wales published recently showed prescribing errors in 19.5% of cases.2 Not only are mistakes common, they often lead to harm. One comprehensive five year study of adverse drug events in the United States found that 3% of medication errors related to insulin, but these errors were also twice as likely to cause harm as errors for other prescribed drugs.3 Errors relating to insulin arise because insulin has a narrow therapeutic range and requires precise dose adjustments with careful administration and monitoring.4 Over 20 different types of insulin are in use, in various strengths and forms, and with a range of delivery devices, including insulin syringes (from vials), insulin pens (prefilled or reusable), or infusion pumps ( British National Formulary , http://bnf.org/bnf/index.htm). Staff may not be familiar with the safe use of different devices or the complex range of products now available. Studies show knowledge gaps among non-specialist staff in hospitals5 and in community settings.6

From August 2003 to August 2009, the National Patient Safety Agency (NPSA) received 3881 incident reports involving wrong insulin doses. The NPSA identified two common preventable errors relating to dose errors: using abbreviations when prescribing insulin; and failing to use insulin syringes. Reports described one death and one incident of severe harm caused by administering doses at 10 times the correct dose (errors that arose from abbreviating the term “unit”) and three deaths and 17 other incidents as a result of inappropriate use of intravenous syringes.⇓ ⇓ These incidents …
Study and Course of the Psychological Profile in 77 Patients Experiencing Panic Disorder with Agoraphobia after Cognitive Behaviour Therapy with or without Buspirone
Authors: M. Bouvard, E. Mollard, J. Guerin, J. Cottraux
Journal: Psychotherapy and Psychosomatics (1997)

Background: The change of psychopathological dimensions during treatment of panic disorder is attracting increasing interest. Methods: A population of subjects experiencing panic disorder with agoraphobia is evaluated with the French version of the factor structure of the Symptom Checklist 90 R (SCL 90 R). Two groups of patients are compared: a group receiving cognitive behaviour therapy (CBT) combined with buspirone and a group receiving cognitive behaviour therapy combined with placebo. Results: Comparative analysis of pre- and post-test changes between both groups completing treatment showed that the combination cognitive behaviour therapy plus buspirone provided better results than those in patients who had received cognitive behaviour therapy plus placebo. This difference between treatments did not persist at the 1-year follow-up, since, while results had been effectively maintained in the CBT plus buspirone group, the CBT plus placebo group continued to improve significantly for the target dimensions of treatment. Conclusions: Psychopathological dimensions on the SCL 90 R show that combination of buspirone and cognitive behaviour therapy accelerates the behaviour modification process only in the short term.
755 SUSTAINED VIROLOGICAL RESPONSE AFTER 4-WEEK TREATMENT WITH DEBIO 025 MONOTHERAPY OR COADMINISTERED WITH PEG-IFNα2A IN HCV GENOTYPE 1 AND 3 PATIENTS
Authors: A. Horban, H. Berak, A. Kolakowska-Rzadzka, H. Patel, R. Flisiak, R. Crabbé, J.S. Liz, J.E. Heathcote
Journal: Journal of Hepatology (2010)