Did Osler suffer from "paranoia antitherapeuticum baltimorensis"?: A comparative content analysis of The Principles and Practice of Medicine and Harrison's Principles of Internal Medicine, 11th edition

One of the most important legacies of Sir William Osler was his textbook The Principles and Practice of Medicine. A common criticism of the book when it was first published was its deficiency in the area of therapeutics. In this article, the 1st edition of The Principles and Practice of Medicine is compared with the 11th edition of Harrison''s Principles of Internal Medicine. The analysis focuses on the treatment recommendations for 4 conditions that were covered in both books (diabetes mellitus, ischemic heart disease, pneumonia and typhoid fever). Osler''s textbook dealt with typhoid fever and pneumonia at greater length, whereas Harrison''s placed more emphasis on diabetes mellitus and ischemic heart disease. Notwithstanding Osler''s reputation as a therapeutic nihilist, the 2 books devoted equivalent space to treatment (in terms of proportion of total sentences for the conditions). For all conditions except ischemic heart disease, Osler concentrated on general measures and symptomatic care. Throughout Osler''s textbook numerous negative comments are made about the medicinal treatment of various conditions. A more accurate statement about Osler''s therapeutic approach was that he was a "medicinal nihilist." His demand for proof of efficacy before use of a medication remains relevant.     

Osler and the Jewish people

In his writings and actions, Sir William Osler betrayed no evidence of anti-Semitism. In his era, this trait was unusual. Two of his articles, "Letter from Berlin" and "Israel and medicine," dealt directly with his thoughts on the Jewish people. In both he spoke out against anti-Semitism. Osler had friendships with Jewish colleagues--an example is the great regard in which he held US pediatrician Dr. Abraham Jacobi. Osler was not a saint, and he had his "rough side," but in his relationships with Jewish colleagues his example remains relevant.     

What's so special about Osler?

Sir William Osler was an outstanding figure in American and British Medicine during the early years of this century. Over fifty years after his death, his name is still remembered and honored, whereas other leaders who were equally important in the eyes of their contemporaries have been relegated to the realm of history. This brief review attempts to discover what special qualities have kept Osler''s memory vivid. No single characteristic of his skill, science, or personality seems in itself to explain his continuing reputation. Rather, a combination of his eminence in several different medical schools, his presence at a time of revolution in medical teaching and thought, his authorship of one of the most successful medical textbooks, and an enthusiastic claque of ex-students and colleagues seem to have combined to maintain his memory as a leader of medicine.     

The heritage of Sir William Osler: is there a message to plastic surgeons?

The medical achievements of Sir William Osler (1849-1919), although numerous and important in his time, contribute less to his continued presence in medical literature. What remains is his literary and historical heritage, which is preserved in numerous essays and addresses. Some of his thoughts, which might be worth reading by today's busy plastic surgeons, were chosen from his writings, and they are presented here.     

Osler usque ad mare: the SS William Osler

William Osler''s connections with the sea included a strong family history of seafaring, his own transatlantic crossings (of which there were at least 32) and the occasional use of nautical imagery in his inspirational writings. An unusual Oslerian connection with the sea emerged after his death in the form of a World War II Liberty ship. Through the SS William Osler and its sister ships, Osler was symbolically reunited with colleagues associated with the early days of the Johns Hopkins Hospital. The William Osler circumnavigated the globe in 1943 without engaging the enemy. She was then converted into an army hospital ship and renamed the USHS Wisteria.     

Sir William Jardine and the Ichnology of Annandale

ABSTRACT

Sir William Jardine was a polymath; he was one of the world's foremost ornithologists, and ichthyologists, as well as a knowledgeable geologist, entomologist and botanist. He was a talented and skilled artist and engraver and a keen hunter and fisherman. He was also the author of the book The Ichnology of Annandale that represents the first book ever published on the subject of ichnology. It was here in this volume that Jardine coined the word ichnology. It is also one of the rarest ichnology publications, as it is believed that only 135–140 copies were ever printed. This volume remains the most lavishly illustrated book in vertebrate ichnology literature. This paper discusses the work of Jardine, the finds from his estate and his role in defining ichnology as a science.     

p63 regulation by microRNAs

Wafik S. El-Deiry, M.D., Ph.D., American Cancer Society Research Professor at the University of Pennsylvania, organized and hosted in Philadelphia the 199th Meeting of the Interurban Clinical Club (interurbanclinicalclub.org) started by Sir William Osler in 1905. The Scientific Meeting was held at the College of Physicians of Philadelphia and featured outstanding presentations of the most exciting biomedical research in Philadelphia. The evening black-tie dinner event was held at the historic Union League of Philadelphia where Margaret Foti, Ph.D., M.D. (h.c.), Chief Executive Officer of the American Association for Cancer Research addressed the attendees.     

Past presidents join forces to refurbish gravesite of Sir Charles Tupper,first CMA president.

The CMA''s past presidents have donated a plaque and refurbished the headstone and plot at the Halifax gravesite of Sir Charles Tupper, the association''s first president. "Sir Charles Tupper was a very significant personality in the conception of a national medical association and the past presidents wanted that fact to be remembered," Dr. Athol Roberts says of the endeavour.     

Equitable maritime boundary delimitation,as exemplified in the work of the international court of justice during the presidency of sir Robert Yewdall Jennings and Beyond

The article contains a systematic survey of decisions rendered by the International Court of Justice (and its Chamber) under the presidency of Sir Robert Yewdall Jennings in three cases (Guinea Bissau v. Senegal, Gulf of Fonseca, and Denmark v. Norway,) involving equitable maritime delimitation, and in one case (East Timor) settled after Sir Robert's presidency. Distinct features, which are particularly pronounced in the landmark Denmark v. Norway Judgment, are the increased consistency and degree of predictability in the complex process of applying equity in maritime delimitation, of which Sir Robert has been a strong advocate. The important procedural aspects of the case law under Sir Robert's presidency are also analyzed. These are exemplified by the role of the Court as a partner in preventive diplomacy and by the precedential permission granted a third state to intervene as a nonparty. While highlighting the two presently pending cases (Qatar/Bahrain and Cameroon v. Nigeria), the author hopes that these settlements will significantly benefit from substantial and procedural solutions endorsed by the Court during Sir Robert's presidency.     

Dimerization of Sir3 via its C‐terminal winged helix domain is essential for yeast heterochromatin formation

Gene silencing in budding yeast relies on the binding of the Silent Information Regulator (Sir) complex to chromatin, which is mediated by extensive interactions between the Sir proteins and nucleosomes. Sir3, a divergent member of the AAA+ ATPase‐like family, contacts both the histone H4 tail and the nucleosome core. Here, we present the structure and function of the conserved C‐terminal domain of Sir3, comprising 138 amino acids. This module adopts a variant winged helix‐turn‐helix (wH) architecture that exists as a stable homodimer in solution. Mutagenesis shows that the self‐association mediated by this domain is essential for holo‐Sir3 dimerization. Its loss impairs Sir3 loading onto nucleosomes in vitro and eliminates silencing at telomeres and HM loci in vivo. Replacing the Sir3 wH domain with an unrelated bacterial dimerization motif restores both HM and telomeric repression in sir3Δ cells. In contrast, related wH domains of archaeal and human members of the Orc1/Sir3 family are monomeric and have DNA binding activity. We speculate that a dimerization function for the wH evolved with Sir3's ability to facilitate heterochromatin formation.     

Glycerol 3-phosphate dehydrogenase regulates heat shock response in Saccharomyces cerevisiae

The aim of this work was to identify elements of adaptive regulatory mechanism for basal level of yeast histone deacetylase Sir2. Heat shock response (HSR) was altered in the absence of the NAD-dependent glycerol 3-phosphate dehydrogenase (Gpd1). Increase in HSR was lower in ΔGpd1 cells than wild-type cells. An inverse correlation existed between Gpd1 and Sir2; Sir2-deleted cells showed higher expression of Gpd1 while deletion of Gpd1 led to higher expression of Sir2. In the absence of Gpd1, basal activity of Sir2 promoter was higher and was increased further upon heat shock, suggesting higher Sir2 levels. No interaction between Gpd1 and Sir2 was detected without or with heat shock using immunoprecipitation. The results show that Gpd1 regulates HSR in yeast cells and likely blocks its uncontrolled activation. As uncontrolled stress adversely affects the cellular adaptive response, Gpd1 may be a component of the cell's catalogue to ensure a balanced response to unmitigated thermal stress.     

Review of pharmacological therapies in fibromyalgia syndrome

This review addresses the current status of drug therapy for the management of fibromyalgia syndrome (FMS) and is based on interdisciplinary FMS management guidelines, meta-analyses of drug trial data, and observational studies. In the absence of a single gold-standard medication, patients are treated with a variety of drugs from different categories, often with limited evidence. Drug therapy is not mandatory for the management of FMS. Pregabalin, duloxetine, milnacipran, and amitriptyline are the current first-line prescribed agents but have had a mostly modest effect. With only a minority of patients expected to experience substantial benefit, most will discontinue therapy because of either a lack of efficacy or tolerability problems. Many drug treatments have undergone limited study and have had negative results. It is unlikely that these failed pilot trials will undergo future study. However, medications, though imperfect, will continue to be a component of treatment strategy for these patients. Both the potential for medication therapy to relieve symptoms and the potential to cause harm should be carefully considered in their administration.The desire to take medicine is perhaps the greatest feature which distinguishes man from animals.Sir William Osler (1849–1919)     

Public health in inner London.

One of Sir Bernard Tomlinson''s aims in his inquiry into London''s health services was to advise the secretary of state for health on the future balance of primary and secondary health care "taking account of the health needs of Londoners." Sir Bernard, however, also made it clear that "we have not seen it as part of our remit to carry out a comprehensive needs assessment for the whole of London," but concluded that the extremes of health need found in London were "unparalleled in the rest of England." Dr Jacobson highlights some of the major determinants of health inequality in inner London and assesses the extent to which the proposed solutions are likely to meet these needs.     

Robert Alexander Falla K.B.E., C.M.G., M.A., D.Sc., F.R.S.N.Z.

Abstract

On 23 February 1979 Sir Robert Falla collapsed and died at his home in Eastbourne. He was 77. His sudden death came as a great shock to his multitude of friends and colleagues, many of whom were still sharing with Sir Robert a deep sense of loss at the death on 31 May 1978, shortly after the couple's golden wedding anniversary, of his charming wife Molly.     

Twenty-four-hour and annual variation in onset of epistaxis in Osler disease

Osler disease is an autosomal dominant disorder of the fibrovascular tissue characterized by arteriovenous malformations with multi-systemic haemorrhages. Recurrent epistaxis is the predominant symptom in more than 90% of patients. Recent studies showed circadian and seasonal patterns in the onset of nosebleeds, similar to acute cardiovascular events, such as myocardial infarction and stroke. The aim of this study was to determine whether such patterns would also apply to the onset of epistaxis in patients with Osler disease. In all, 110 patients with Osler disease who were under treatment for recurrent epistaxis at the University Hospital of Mannheim were requested to complete a questionnaire addressing the intensity and frequency of epistaxis according to the classification of Bergler et al., as well as circadian and circannual rhythmicity in the occurrence of epistaxis according to visual analogue scales (VAS). More than half of the patients claimed to experience daily to weekly episodes of recurrent epistaxis. The occurrence of epistaxis showed a biphasic 24 h pattern, with a primary peak in the morning (05:00-8:00 h) and smaller secondary peaks in the evening (17:00-20:00 h and 21:00-00:00 h). No significant seasonal variation was found in the onset of epistaxis. However, a slight tendency, with a peak in winter months, was observed. Similar to other chronobiological studies on nosebleeds, this study showed that the 24 h pattern and seasonal tendency in the onset of epistaxis even applied to patients with Osler disease. Further investigations are necessary to determine the pathological mechanism underlying this phenomenon.     

Phylogenetic Conservation and Homology Modeling Help Reveal a Novel Domain within the Budding Yeast Heterochromatin Protein Sir1

The yeast Sir1 protein's ability to bind and silence the cryptic mating-type locus HMRa requires a protein-protein interaction between Sir1 and the origin recognition complex (ORC). A domain within the C-terminal half of Sir1, the Sir1 ORC interaction region (Sir1OIR), and the conserved bromo-adjacent homology (BAH) domain within Orc1, the largest subunit of ORC, mediate this interaction. The structure of the Sir1OIR-Orc1BAH complex is known. Sir1OIR and Orc1BAH interacted with a high affinity in vitro, but the Sir1OIR did not inhibit Sir1-dependent silencing when overproduced in vivo, suggesting that other regions of Sir1 helped it bind HMRa. Comparisons of diverged Sir1 proteins revealed two highly conserved regions, N1 and N2, within Sir1's poorly characterized N-terminal half. An N-terminal portion of Sir1 (residues 27 to 149 [Sir1^27-149]) is similar in sequence to the Sir1OIR; homology modeling predicted a structure for Sir1^27-149 in which N1 formed a submodule similar to the known Orc1BAH-interacting surface on Sir1. Consistent with these findings, two-hybrid assays indicated that the Sir1 N terminus could interact with BAH domains. Amino acid substitutions within or near N1 or N2 reduced full-length Sir1's ability to bind and silence HMRa and to interact with Orc1BAH in a two-hybrid assay. Purified recombinant Sir1 formed a large protease-resistant structure within which the Sir1OIR domain was protected, and Orc1BAH bound Sir1OIR more efficiently than full-length Sir1 in vitro. Thus, the Sir1 N terminus exhibited both positive and negative roles in the formation of a Sir1-ORC silencing complex. This functional duality might contribute to Sir1's selectivity for silencer-bound ORCs in vivo.     

Comparison of effects of a self management booklet and audiocassette for patients with asthma.

The effects on self management of asthma of a specially prepared book and audiocassette tape with similar contents were observed in a controlled study of 177 patients with asthma in general practice. After a run in period of six months patients were randomly given the book, the tape, both the book and tape, or neither. Patients'' knowledge of the use of drugs, perceptions of their disability, skill in using an inhaler, consumption of drugs, consultations with their general practitioners, morbidity (from patients'' entries on diary cards), and use of the educational material were measured. Knowledge about the use of drugs was significantly increased in the groups who received the material after three months and persisted after 12 months. Patients who had been given the tape or the book and tape increased their scores of knowledge of drugs more than patients given the book alone. Patients in all groups given the material considered that their disability was reduced. There were no other significant changes. Patients given both the book and the tape preferred the book. Patients with asthma can obtain useful information from such material. The paradoxical result whereby patients learnt more from the tape but preferred the book suggests that a distinction can be made between information that patients need, which may be acquired better from an audiocassette, and information that they want, which may be acquired better from a book.