William Osler: Original Papers 1898-1906

Part 1: 1898-1899 On Chronic Symmetrical Enlargement of the Salivary and Lachrymal Glands, 1898 Leprosy in the United States, with the Report of a Case, 1898 An Acute Myxaedematous Condition, with Tachycardia, Glycosuria, Melaena, Mania and Death, 1898 On some of the Intestinal Features of Typhoid Fever, 1898 Cerebro-Spinal Fever, 1898 The Arthritis of Cerebro-Spinal Fever, 1898 In Memoriam, William Pepper, 1899 After Twenty-Five Years, 1899 The Diagnosis of Typhoid Fever, 1899 Interstitial Processes in the Central Nervous System, 1899 Part 2: 1900 The Home Treatment of Consumption, 1900 On Splenic Anaemia, 1900 The Chronic Intermittent Fever of Endocarditis, 1900 A Case of Multiple Gangrene in Malarial Fever, 1900 Latent Cancer of the Stomach, 1900 On the Study of Tuberculosis, 1900 Fatal Angina Pectoris without Lesions of the Coronary Arteries of a Young Man, 1900 On the Advantages of a Trace of Albumin and a Few Casts in the Urine of Certain Men above Fifty Years of Age, 1900 Part 3: 1901-1902 Congenital Absence of the Abdominal Muscles with Distended Hypertrophied Urinary Bladder, 1901 Intermittent Claudication, 1902 On the Diagnosis of Bilateral Cystic Kidney, 1902 On Amebic Abscess of the Liver, 1902 Note on the Occurrence of Ascites in Solid Abdominal Tumors, 1902 Amebic Dysentery, 1902 Notes on Aneurism, 1902 William Beaumont; a Pioneer American Physiologist, 1902 Part 4: 1903 On the Educational Value of the Medical Society, 1903 On obliteration of the Superior Vena Cava,1903 Chronic Cyanosis, with Polycythemia and Enlarged Spleen: A New Clinical Entity, 1903 The Home and its Relation to the Tuberculosis Problem, 1903 Unity, Peace, and Concord, 1903 Typhoid Fever and Tuberculosis, 1903 Part 5: 1904-1906 Ochronosis, 1904 The “Phthisiologia” of Richard Morton, M.D., 1904 On the Surgical Importance of the Visceral Crises In the Erythema Group of Skin Diseases, 1904 Aneurysm of the Abdominal Aorta, 1905 Back Notes

William Osler: Original Papers 1907-1919

Part 1: 1907-1908 The Royal Medical Society of Edinburg, 1907 On the Library of a Medical School, 1907 On Telangiectasis Circumscripta Universalis, 1907 A Clinical Lecture on Abdominal Tumours Associated with Disease of the Testicle, 1907 A Clinical Lecture on Erythraemia, 1908 Vienna after Thirty-Four Years, 1908 Endocardites Infectieuses Chroniques, 1908 Part 2: 1909 Chronic Infectious Endocarditis, 1909 What the Public Can Do in the Fight Against Tuberculosis, 1909 Annual Oration on the Occasion of the Opening of the New Building of the Medical and Chirurgical Faculty of the State of Maryland, May 13, 1909 The Medical Library in Post-Graduate Work, 1909 The Treatment of Disease, 1909 Part 3: 1910-1911 The Pupil Symptoms in Thoracic Aneurysm, 1910 The Lumleian Lectures on Angina Pectoris, 1910 Certain Vasomotor, Sensory, and Muscular Phenomena Associated with Cervical Rib, 1910 An Address on the Hospital Unit in University Work, 1911 Sulle Telangiectasie Emorragiche Ereditarie, 1911 Transient Attacks of Aphasia and Paralyses in States of High Blood Pressure and Arterio-Sclerosis, 1911 The Pathological Institute of a General Hospital, 1911 Part 4: 1912-1914 An Address on High Blood Pressure: its Associations, Advantages, and Disadvantages, 1912 Specialism in the General Hospital, 1913 Syphilis of the Liver with the Picture of Banti’s Disease, 1913 An Introductory Address on Examinations, Examiners, and Examinees, 1913 The Medical Clinic: a retrospect and a Forecast, 1914 Part 5: 1915-1919 Remarks on the Diagnosis of Polycystic Kidney, 1915 The War and Typhoid Fever, 1914/15 The Cerebro-Spinal Fever in Camps and Barracks, 1915 Remarks on Arterio-Venous Aneurysm, 1915 Nerve & “Nerves”, 1915 Intensive Work in Science at the Public Schools in Relation to the Curriculum, 1916 Creators, Transmuters, and Transmitters, 1916 Annual Oration on the Campaign Against Syphilis, 1917 The First Printed Documents relating to Modern Surgical Anaesthesia, 1918 Observations on the Severe Anaemias of Pregnancy and the Post-Partum State, 1919 Typhoid Spine, 1919

Platelet nitric oxide responsiveness - A novel prognostic marker in acute coronary syndromes

Objectives - Nitric oxide (NO) is critically important in the regulation of vascular tone and the inhibition of platelet aggregation. We have shown previously that patients with acute coronary syndromes (ACS) or stable angina pectoris have impaired platelet responses to NO donors when compared with normal subjects. We tested the hypotheses that platelet hyporesponsiveness to NO is a predictor of (1) cardiovascular readmission and/or death and (2) all-cause mortality in patients with ACS (unstable angina pectoris or non-Q-wave myocardial infarction). Methods and Results - Patients (n = 51) with ACS had evaluation of platelet aggregation within 24 hours of coronary care unit admission using impedance aggregometry. Patients were categorized as having normal (>= 32% inhibition of ADP-induced aggregation with the NO donor sodium nitroprusside; 10 mu mol/L; n = 18) or impaired (>= 32% inhibition of ADP-induced aggregation; n = 33) NO responses. We then compared the incidence of cardiovascular readmission and death during a median of 7 years of follow-up in these 2 groups. Using a Cox proportional hazards model adjusting for age, sex, index event, postdischarge medical treatment, revascularization status, left ventricular systolic dysfunction, concurrent disease states, and cardiac risk factors, impaired NO responsiveness was associated with an increased risk of the combination of cardiovascular readmission and/or death (relative risk, 2.7; 95% CI, 1.03 to 7.10; P = 0.041) and all-cause mortality (relative risk, 6.3; 95% CI, 1.09 to 36.7; P = 0.033). Conclusions - Impaired platelet NO responsiveness is a novel, independent predictor of increased mortality and cardiovascular morbidity in patients with high-risk ACS.

Inflammation, complement activation and endothelial function in stable and unstable coronary artery disease

Background: Endothelial dysfunction plays an important role in the pathogenesis of coronary artery disease (CAD). Apart from traditional risk factors complement activation and inflammation may trigger and sustain endothelial dysfunction. We sought to assess the association between endothelial function, high sensitivity C-reactive protein (hs-CRP) and markers of complement activation in patients with either stable or unstable coronary artery disease. Methods: We prospectively recruited 78 patients, 35 patients with stable angina pectoris (SAP) and 43 patients with unstable angina pectoris (UAP). Endothelial function was assessed as brachial artery reactivity (BAR). Hs-CRP, C3a, C5a, and C1-Inhibitor (C1 inh.) were measured enzymatically. Results: Patients with IJAP showed higher median levels of hs-CRP and C3a compared to patients with SAP, while BAR was not significantly different between patient groups. In UAP patients, hs-CRP was significantly correlated with cholesterol (r = 0.27, p < 0.02), C3a (r = 0.32, p < 0.001) and C1 INH.(r = 0.41, p < 0.003), but not with flow mediated dilatation (r = 0.09, P = 0.41). Hs-CRP and C1 INH.were found to be independant predictors of IJAP in a backward stepwise logistic regression model. Conclusions: We conclude that both hs-CRP, a marker of inflammation and C3a, a marker of complement activation are elevated in patients with UAP, but not in patients with SAP. (c) 2005 Elsevier B.V. All rights reserved.

Work disability and depressive disorders:impact on the European population

OBJECTIVE: Our aim was to study the impact of depressive disorders on work disability to discover the determinants of depression for work disability in the European countries. DESIGN: The sample was composed of 31,126 individuals from 29 countries included in the 2002 World Health Survey of the World Health Organization. National representative samples of countries from all regions of Europe and with different levels of economic development and health coverage were selected. RESULTS: Estimates of people not working because of ill health did not differ among European countries in relation to levels of economic development or health coverage. Significant determinants of people with diagnosis of depression not working because of ill health (reference category) versus working were age (odds ratio = 0.97), female sex (odds ratio = 1.71), education (odds ratio = 1.11), marital status (being unmarried indicating less probability), lowest income level, and comorbidity with angina pectoris (odds ratio = 0.51). Moreover, according to previous studies, we found some determinants (comorbidity with other diseases, young age, and unemployment) impacting on health status. CONCLUSIONS: Depression is a substantial cause of work disability and it is a complex phenomenon that involves many variables. Investigation into this relationship should improve, focusing on the role of determinants.

Assessing the immune phenotype of cardiac syndrome x: a prospective study of biomarkers

Cardiac Syndrome X (CSX), the presence of angina pectoris with objective signs of myocardial ischaemia despite angiographically normal epicardial coronary arteries, appears to be due to coronary microvascular dysfunction and is known to be associated with an elevation of several inflammatory biomarkers, suggesting a possible role for inflammation in its pathogenesis. We aimed to further characterise this relationship by prospectively analysing a wide variety of molecular biomarkers in a cohort of CSX patients thereby charting the changes in biomarkers throughout the natural history of CSX from its initial diagnosis to eventual disease quiescence. We found that CSX patients, when compared to healthy controls, have a persistent low-grade systemic inflammatory response characterised by an elevation of Tumour Necrosis Factor and Interferon-gamma, regardless of the presence of contemporaneous signs or symptoms of disease activity. Interleukin-6 and C-reactive Protein (CRP) are only elevated when patients have clinical evidence of disease activity and may be state markers in CSX. Moreover, CRP levels appear to correlate with signals of disease severity such as the time taken to develop symptoms during exercise stress testing. We have also demonstrated that the enzyme Indoleamine-2,3- dioxygenase is upregulated in active disease thus providing a possible explanation for the increased burden of psychological disease encountered in CSX. Analysis of the microRNA transcriptome showed that miR-143 is significantly under-expressed in CSX patients. This could allow phenotype switching in vascular smooth muscle cells with the resultant vascular remodelling causing reduced vessel responsiveness to local rheological stimuli and reduced luminal diameter with consequent increased microvascular resistance during times of increased myocardial oxygen demand, thereby limiting maximal hyperaemia during exercise. Our findings corroborate many previous hypotheses regarding the role of inflammation in CSX, generate new insights into possible pathogenic mechanisms and offer new therapeutic targets for the future management of this important cardiological condition.

Drugs for hypertension, angina and heart failure

12.1 Drugs for hypertension 12.1.1 Epidemiology and pathophysiology 12.1.2 Diuretics for hypertension 12.2.3 Vasodilators for hypertension 12.4.4 β-Adrenoceptor blockers for hypertension 12.2. Drugs for angina 12.2.1 Typical angina 12.2.2 Drugs to treat an attack of typical angina 12,2.3 Drugs to prevent an attack of typical angina 12.2.4 Atypical angina 12.3 Drugs for heart failure 12.3.1 The heart failure epidemic 12.3.2 Compensatory changes in heart failure 12.3.3 Diuretics for heart failure 12.3.4 ACE inhibitors and AT1-receptor antagonists 12.3.5 β-adrenoceptor antagonists 12.3.6 Digoxin

Qutting and restarting smoking: cohort study of patients with angina in primary care

Objective To examine variations in self-reported smoking habit among a cohort of individuals with chronic coronary heart disease over a five year period. Design Cross-sectional cohort; interviews at baseline, 2 years and 5 years. Setting Primary care. Participants A cross-sectional sample of 688 patients previously diagnosed as having angina, identified from 18 general practices in the Greater Belfast Area; a cohort of 487 were followed for five years. Outcome measures Changes in self-reported smoking habits; breath carbon monoxide measurement. Results Initially 92 of the 487 participants (19%) reported smoking, 34 (27%) subsequently reported non-smoking. Of the 395 self-reported non-smokers at baseline, 21 (5%) subsequently reported smoking. The prevalence of self-reported smoking amongst the cohort was 19% and 15% at two and five years respectively. However, changes in reported smoking habits indicating periods of abstinence and resumption were reported by 55/487 (11%) participants. Of the 21 non-smokers who changed their report, 20 had smoked previously, five reported having stopped for less than one year but nine for more than five years. Of the initial sample twice as many smokers as non-smokers had died by 2 years (10% v 5%; p