A History of Orthognathic Surgery in North America.

This review highlights the contributions of American oral and maxillofacial surgeons to the field of orthognathic surgery. The present state of the art and science of orthognathic surgery is the harvest of yesterday's innovation and research. An improved understanding of the biological and surgical principles and the routine involvement of orthodontics have fueled widespread adoption of a coordinated approach to the treatment of dentofacial problems. Technologic advances in rigid internal fixation, virtual surgical planning with computer-aided manufacturing of occlusal splints and cutting guides, custom implants, and worldwide interest in the correction of dentofacial and craniofacial deformities have resulted in highly predictable, efficient, and safe treatment, which scarcely resembles the situation 70 years ago.

A Historical Report on Preparing Sustained Release Dosage Forms for Addicts in Medieval Persia, 16th Century AD.

For several centuries, opium addiction has been a social problem all over the world. It has been prevalent in Iran from the Safavid era (1501-1736 A.D). During this period, Hakim Imad al-Din Mahmud ibn-Mas'ud Shirazi (1515-1592 A.D), also known as Imad was one of the Persian physicians who wrote one of the earliest books in the field of opium and addiction (called Afiounieh) in history. In this book, he introduced two sustained release rectal (suppository) and oral (pill) dosage forms for Muslim addicts who fast in the month of Ramadan. He aimed to formulate them for these people so that they could keep fasting by using the slow release drugs. In these formulations, his innovation has important impacts in the history of both addiction and pharmaceutical sciences.

Antoine Ritti (1844-1920), forgotten alienist and innovative theorist on the pathophysiology of hallucinations.

Antoine Ritti (1844-1920), now forgotten, was an "alienist" or psychiatrist who formulated a theory of hallucination based on thalamic dysfunction, as described in his thesis defended in 1874. Ritti was a student of Jules Luys and used the anatomical-functional discoveries of his teacher to explain that an automatic activity in the thalamus, by stimulating the cortex without reception of sensory information, created autonomous representations, perceived by the patient but not by his entourage, a process occurring spontaneously to some degree. Hence, Ritti seems the first author to introduce the concept of sensory deprivation and release of subcortical function into the pathophysiology of hallucinations. This innovative theory, which gave subcortical structures a role in high-level cognitive function, is very resonant today but was ignored for several decades after Ritti published his work.

From closed ranks to open doors: Elaine and John Cummings' mental health education experiment in 1950s Saskatchewan.

During late 1951 and early 1952, married couple, social biologist Elaine Cumming and psychiatrist John Cumming, led a mental health education experiment in Indian Head, Saskatchewan. The study, which was intended to inform strategies toward deinstitutionalization, sought to determine if attitudes regarding mental illness could be changed through commonly used educational practices. It was shaped by the shared interests of powerful philanthropic, charitable, psychiatric, academic and governmental bodies to create healthier citizens and a stronger democratic nation through expert knowledge. However, in addition to the disappointing findings indicating that attitudes remained unchanged, the town appeared to close ranks against the research team. Nonetheless, the Cummings' later association with sociologists at Harvard University enabled them to interpret the results in a way that lent the study credibility and themselves legitimacy, thus opening the door to their careers as very successful researchers and policy-makers.

Drugging the "Undruggable" MYCN Oncogenic Transcription Factor: Overcoming Previous Obstacles to Impact Childhood Cancers.

Effective treatment of pediatric solid tumors has been hampered by the predominance of currently "undruggable" driver transcription factors. Improving outcomes while decreasing the toxicity of treatment necessitates the development of novel agents that can directly inhibit or degrade these elusive targets. MYCN in pediatric neural-derived tumors, including neuroblastoma and medulloblastoma, is a paradigmatic example of this problem. Attempts to directly and specifically target MYCN have failed due to its similarity to MYC, the unstructured nature of MYC family proteins in their monomeric form, the lack of an understanding of MYCN-interacting proteins and ability to test their relevance in vivo, the inability to obtain structural information on MYCN protein complexes, and the challenges of using traditional small molecules to inhibit protein-protein or protein-DNA interactions. However, there is now promise for directly targeting MYCN based on scientific and technological advances on all of these fronts. Here, we discuss prior challenges and the reasons for renewed optimism in directly targeting this "undruggable" transcription factor, which we hope will lead to improved outcomes for patients with pediatric cancer and create a framework for targeting driver oncoproteins regulating gene transcription.

Dega Transiliac Pelvic Osteotomy: the History of Surgical Technique Development.

BACKGROUND: Wiktor Dega originally described the surgical technique of transiliac osteotomy in 1969 in the Polish Orthopaedics and Trauma Surgery Journal. Its worldwide popularity spread just after it was presented in English by Grudziak and Ward in 2001 [1]. This paper aims to describe the development of the technique by Wiktor Dega's team. MATERIAL AND METHODS: An analysis of original papers published by Dega between 1929-1974 was performed to clarify the chronology of development of the technique. RESULTS: Dega's interest in developmental dysplasia of the hip (DDH) had begun as early as 1929, when he presented in Vilnius a paper about the aetiology and pathogenesis of the disease. The concept of transiliac osteotomy had been initially based on König's idea of shelf procedure. Dega called this procedure plastic surgery of the acetabular roof and performed it between 1927 and 1930. In 1964, Dega published a paper that described the basic concept of DDH treatment with a pelvic osteotomy termed supraacetabular semi-circular osteotomy. This procedure differed from transiliac osteotomy because it did not involve cutting the inner cortex of the ilium. In 1968 the first 'technically proper' transiliac osteotomy was performed and then described in 1969. In 1974, Dega emphasized that both the outer and inner iliac walls should be osteotomized in the transiliac osteotomy. CONCLUSION: The political situation of the 1950s and the 1960s made it difficult to freely exchange views and clinical experiences between the Western and Eastern political camps. Despite this, Wiktor Dega became a precursor of effective surgical treatment in DDH worldwide.

CAR-T therapy and historical trends in effectiveness and cost-effectiveness of oncology treatments.

Aim: This study examines how chimeric antigen receptor T-cell (CAR-T) therapy's incremental effectiveness and cost-effectiveness profile fits into the recent history of anticancer treatments. Materials & methods: We conducted graphical and multivariable analyses using data from the Cost-Effectiveness Analysis Registry of the Tufts Medical Center and the Institute for Clinical and Economic Review's analysis of CAR-T therapies. We collected additional information including the US FDA approval years for pharmacologic innovations. Results: CAR-T provided 5.03 (95% CI: 3.88-6.18) more incremental quality-adjusted life-years than the average pharmaceutical intervention and 4.61 (95% CI: 1.67-7.56) more than the average nonpharmaceutical intervention, while retaining similar cost-effectiveness. There was evidence of worsening cost-effectiveness by approval year for pharmaceutical interventions. Limitations: Analysis is limited to anticancer treatments studied in cost-utility analyses, estimated to cover approximately 60% of FDA-approved antineoplastic agents. Conclusion: CAR-T therapy breaks a pattern of stagnant efficacy growth in pharmaceutical innovation and demonstrates significantly greater incremental effectiveness and similar cost-effectiveness to prior innovations.

[Gene-based therapies of spinal muscular atrophy: a piece of history of medicine]. / Thérapies géniques de l'amyotrophie spinale infantile - Un morceau d'histoire de la médecine.

It is worth stating that a generation is needed to bring about a new family of drugs. After the deciphering of the genetic cause in 1995, two innovative classes of therapeutics are now available for spinal muscular atrophy (SMA): the repeated administration of antisens oligonucleotides and the one-shot administration of a scAAV9-SMN as a gene therapy. By addressing the genetic mechanisms of the disease, these drugs fundamentally change its course. These major advances in an extremely severe disease, often fatal before the age of 18 months in the type 1 form (50% of patients), pave the way for the treatment of other serious pathologies of the nervous or neuromuscular system, and provide unambiguous evidence of the effectiveness of these new classes of drugs called to address a number of genetic or acquired diseases. These breakthroughs raise also new scientific and technological questions (limited production yields of gene therapy drugs) but also ethical issues (access of patients to these innovative therapies) that resonate beyond this disease alone.

TITLE: Thérapies géniques de l'amyotrophie spinale infantile - Un morceau d'histoire de la médecine. ABSTRACT: On convient de dire qu'une génération est nécessaire pour faire émerger une nouvelle famille de médicaments. L'amyotrophie spinale infantile (SMA), après l'élucidation du gène causal en 1995, dispose depuis peu de deux classes innovantes de thérapeutiques : l'administration répétée d'oligonucléotides antisens et l'administration unique d'une thérapie génique par scAAV9-SMN. En s'adressant aux mécanismes génétiques de la maladie, elles en modifient fondamentalement le cours. Ces avancées majeures dans une maladie extrêmement sévère, mortelle souvent avant l'âge de 18 mois dans les formes de type 1 (50 % des malades), ouvrent la voie pour d'autres pathologies graves du système nerveux ou neuromusculaire, et apportent une preuve déterminante de l'efficacité de ces classes nouvelles de produits appelés à s'adresser à de nombreuses maladies génétiques ou acquises. Elles génèrent aussi de nouvelles questions d'ordre scientifique et technologique (capacités limitées de production des quantités nécessaires en thérapie génique) mais également d'ordre éthique (conditions d'accès des malades à ces thérapies innovantes), qui résonnent au-delà de cette seule maladie.

The Lillehei Heart Institute: building on the shoulders of giants.

Scientific revolutions require a series of paradigm shifts that are promoted by a series of discoveries. These discoveries, paradigm shifts, and scientific revolutions are dependent on timing, environment, and innovative pioneers. More than 50 years ago, a series of discoveries led to such a paradigm shift at the University of Minnesota which in turn revolutionized the field of cardiovascular medicine forever. Today, this spirit of innovation and discovery is alive and thriving at the Lillehei Heart Institute at the University of Minnesota.

Preimplantation genetic screening: "established" and ready for prime time?

Unless attempts to improve pregnancy rates and/or diminish miscarriage rates through preimplantation genetic screening (PGS) are applied to only carefully selected patients, they will fail. Because specific PGS indications have remained undefined, PGS should be considered an experimental procedure.

Contribuição do estudo de Zigman Brener (1961) para a terapia da doença de Chagas / Contribution of the study of Zigman Brener (1961) for the treatment of Chagas disease

Revisões históricas aos avanços científicos para o controle da doença, o Simpósio Internacional Comemorativo do Centenário da Descoberta da Doença de Chagas (1909-2009).

Atividade terapêutica do 5-nitrofuraldeído-semicarbazona (nitrofurazona) em esquemas de duração prologada na infeccção experimental do camundongo pelo Trypanosoma cruzi / Therapeutic activity of 5-nitrofuraldeído-semicarbazone (nitrofurazone) in schemes prolong the duration of infectious disease in experimental mice by Trypanosoma cruzi

Revisões históricas aos avanços científicos para o controle da doença, o Simpósio Internacional Comemorativo do Centenário da Descoberta da Doença de Chagas (1909-2009).