William Osler: Original Papers 1881-1897

Part 1: 1881-1888 On Some Points in the Etiology and Pathology of Ulcerative Endocarditis, 1881 On Certain Parasites in the Blood of the Frog, 1883 The Third Corpuscle of the Blood, 1883 On the Use of Arsenic in Certain Forms of Anaemia, 1886 Antifebrin, 1887 Case of Arterio-Venous Aneurism of the Axillary Artery and Vein of Fourteen Year's Duration, 1887 Typhilitis and Appendicitis, 1888 Part 2: 1889-1892 Annual Address - License to Practice 1889 Case of Syphiloma of the Cord of the Cauda Equina-Death From Diffuse Central Myelitis, 1889 On a Case of Simple Idiopathic Muscular Atrophy, Involving the Face and the Scapulo-Humeral Muscles, 1889 Note on Intra-Thoracic Growths Developing from the Thyroid Gland, 1889 On the Value of Laveran's Organisms in the Diagnosis of Malaria, 1889 On the Form of Convulsive Tic Associated with Corprolalia, Etc., 1890 A Case of Sensory Aphasia Word-blindness with Hemianopsia, 1891 Rudolf Virchow: The Man and the Student, 1891 The Healing of Tuberculosis, 1892 The Cold-Bath Treatment of Typhoid Fever, 1892 Part 3: 1893 Remarks on the Varieties of Chronic Chorea, and a Report Upon Two Families of the Hereditary Form, With One Autopsy, 1893 Note on Arsenical Neuritis Following the use of Fowler's Solution, 1893 Note on a Remarkable House Epidemic of Typhoid Fever, 1893 Cases of Sub-Phrenic Abscess, 1893 On Sporadic Cretinism in America, 1893 Notes on Tuberculosis in Children, 1893 Part 4: 1849-1895 Parotitis in Pneumonia, Case of Pericarditis Treated by Incision and Drainage, 1894 The Army Surgeon, 1894 Introductory Remarks to Course of Clinical Demonstrations on Typhoid Fever, 1894 Cancer of the Stomach with Very Rapid Course, 1895 Case of Sporadic Cretinism (Infantile Myxcedema) Treated Successfully with Thyroid Extract, 1895 Visible Contractile Tumour of the Pylorus Following Ulcer of the Stomach, 1895 On the Association of Enormous Heart Hypertrophy, Chronic Proliferative Peritonitis, and Recurring Ascites, with Adherent Pericardium, 1895 Teaching and Thinking the Two Functions of a Medical School, 1895 The Practical Value of Laveran's Discoveries, 1895 Part 5 1896 Addison's Disease, 1896 On Six Cases of Addison's Disease, 1896 Hemiplegia in Typhoid Fever Thomas Dover (of Dover's Powder) Physician and Buccaneer, 1896 John Keats The Apothecary Poet, 1896 On The Classification of the Tics or Habit Movements, 1896 The Cerebral Complication of Raynaud's Disease, 1896 Part 6: 1897 On Certain Features in the Prognosis of Pneumonia, 1897 Clinical Lecture on Mitral Stenosis - Sudden Death - Ball Thrombus in the Left Auricle, 1897 The Diagnosis of Malarial Fever, 1897 The Functions of a State Faculty (President's Address), 1897 A Clinical Lecture on The Ball-Valve Gall-Stone in the Common Duct, 1897 Pneumonia (Review of Cases studied), 1897 Internal Medicine as a Vocation, 1897 Back Notes

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

Molecular markers of human papillomavirus (HPV) infection and epidemiologic risk factors for squamous intraepithelial lesions (SIL) of the cervix

Infection with certain types of HPV is a necessary event in the development of cervical carcinoma; however, not all women who become infected will progress. While much is known about the molecular influence of HPV E6 and E7 proteins on the malignant transformation, little is known about the additional factors needed to drive the process. Currently, conventional cervical screening is insufficient at identifying women who are likely to progress from premalignant lesions to carcinoma. Aneuploidy and chromatin texture from image cytometry have been suggested as quantitative measures of nuclear damage in premalignant lesions and cancer, and traditional epidemiologic studies have identified potential factors to aid in the discrimination of those lesions likely to progress. ^ In the current study, real-time PCR was used to quantitate mRNA expression of the E7 gene in women exhibiting normal epithelium, LSIL, and HSIL. Quantitative cytometry was used to gather information about the DNA index and chromatin features of cells from the same women. Logistic regression modeling was used to establish predictor variables for histologic grade based on the traditional epidemiologic risk factors and molecular markers. ^ Prevalence of mRNA transcripts was lower among women with normal histology (27%) than for women with LSIL (40%) and HSIL (37%) with mean levels ranging from 2.0 to 4.2. The transcriptional activity of HPV 18 was higher than that of HPV 16 and increased with increasing level of dysplasia, reinforcing the more aggressive nature of HPV 18. DNA index and mRNA level increased with increasing histological grade. Chromatin score was not correlated with histology but was higher for HPV 18 samples and those with both HPV 18 and HPV 16. However, chromatin score and DNA index were not correlated with mRNA levels. The most predictive variables in the regression modeling were mRNA level, DNA index, parity, and age, and the ROC curves for LSIL and HSIL indicated excellent discrimination. ^ Real-time PCR of viral transcripts could provide a more efficient method to analyze the oncogenic potential within cells from cervical swabs. Epidemiological modeling of malignant progression in the cervix should include molecular markers, as well as the traditional epidemiological risk factors. ^

Classification of cellular malignancy associated changes in cervical cancer

Cervical cancer is the leading cause of death and disease from malignant neoplasms among women in developing countries. Even though the Pap smear has significantly decreased the number of deaths from cervical cancer in the past years, it has its limitations. Researchers have developed an automated screening machine which can potentially detect abnormal cases that are overlooked by conventional screening. The goal of quantitative cytology is to classify the patient's tissue sample based on quantitative measurements of the individual cells. It is also much cheaper and potentially can take less time. One of the major challenges of collecting cells with a cytobrush is the possibility of not sampling any existing dysplastic cells on the cervix. Being able to correctly classify patients who have disease without the presence of dysplastic cells could improve the accuracy of quantitative cytology algorithms. Subtle morphologic changes in normal-appearing tissues adjacent to or distant from malignant tumors have been shown to exist, but a comparison of various statistical methods, including many recent advances in the statistical learning field, has not previously been done. The objective of this thesis is to use different classification methods applied to quantitative cytology data for the detection of malignancy associated changes (MACs). In this thesis, Elastic Net is the best algorithm. When we applied the Elastic Net algorithm to the test set, we combined the training set and validation set as "training" set and used 5-fold cross validation to choose the parameter for Elastic Net. It has a sensitivity of 47% at 80% specificity, an AUC 0.52, and a partial AUC 0.10 (95% CI 0.09-0.11).^