Charcot foot in diabetes: farewell to the neurotrophic theory.

Neuropathic osteoarthropathy is characterised by relatively painless swelling together with extensive damage in bones and joints, predominantly in the feet and ankles. The uncontrolled natural course of the condition leads to gross foot deformity, skin pressure ulceration, spreading infections, and sometimes amputation. Jean-Martin Charcot in 1883 described "Charcot foot" named after him in patients with tabes dorsalis insensitivity. Charcot believed that intrinsic bone weakness was the underlying condition, and was caused by neurogenic deficiencies in bone nutrition. His followers believed such dystrophy to be mediated by sympathetic denervation of the bone vasculature (neurotrophic, or neurovascular theory). Attempts to prove this theory were futile. A neurogenic circulatory disorder potentially relevant to bone nutrition could not be identified. Nowadays, Charcot foot is mostly seen in diabetic neuropathy, which has replaced syphilis as a frequent cause of peripheral nerve dysfunction. Recent studies in the diabetic Charcot foot and bone turnover indicate that the neurotrophic theory is a myth. The assumption of bone resorption due to sympathetic denervation proved to be false--sympathetic activity increases osteoclastic activity and thereby bone loss (sympathomimetic bone resorption). Except for the transient, inflammatory stage of the diabetic Charcot foot, there is no evidence of relevant osteoporosis or demineralisation of the foot skeleton in diabetes.     

Un premier schéma de l’inconscient par Charcot dès 1892

The recent discovery of a drawing of the mind sheds new light on Charcot’s contribution to the discovery of the unconscious. This particular drawing, given by his son Jean-Baptiste, was found in Charcot’s personal notes related to a lecture he gave in June 1892 and was kept in the Salpêtrière historical collection of the University Pierre and Marie Curie. Is this drawing an anticipation of Freud’s first topology of the Unconscious? This is the main issue raised. In order to understand its full meaning, we will focus on Charcot’s scientific thoughts, the specific position he held on hypnosis, his studies on the force of the idea and experimental paralysis, his relationships with Pierre Janet and Sigmund Freud during the years 1885–1992, and finally, his view on Sigmund Freud that is shared in their correspondences.     

Chronobiology meets the need for integration in a reductionist climate of biology and medicine.

One of us introduces a chronobiology course to students at the University of Milan, Italy, with a succinct statement that may well serve to summarize the foregoing 24 points. Its few lines distill the preceding details and formulate the raison d'être of Chronobiology: Chronobiology is: not only a science in its own right; not only a methodology; not only a new kind of statistical analysis; not just an aspect of biology, but a new way of invariably approaching any problem in biology, notably medicine.     

Biostatistical collaboration in medical research

There has been an explosive growth in the development of statistical methodology over the past several decades. Research in both medicine and public health, in which the involvement of biostatisticians has increased dramatically during this period, has been both a beneficiary of this new methodology as well as a source of new problems. The contributions of statistical methodology in design, implementation, and analysis as they relate to the role that biostatistics and biostatisticians now play in the field of medical research are addressed. We comment on: (1) the acceptance by the medical community that biostatistical concepts are an integral part of sound medical research; (2) the sometimes unrealistic expectations placed on biostatistics and biostatisticians given limited resources and/or limited control; (3) some controversies among biostatisticians; and (4) the need for emphasizing the design and implementation phases of medical investigations.     

Dr. PIAS: an integrative system for assessing the druggability of protein-protein interactions

Background  

The amount of data on protein-protein interactions (PPIs) available in public databases and in the literature has rapidly expanded in recent years. PPI data can provide useful information for researchers in pharmacology and medicine as well as those in interactome studies. There is urgent need for a novel methodology or software allowing the efficient utilization of PPI data in pharmacology and medicine.     

Quality of Life Improvement Following Reconstruction of Midtarsal Charcot Foot Deformity: A Five Year Follow-Up

BackgroundThere is increasing interest in reconstruction of diabetes-associated Charcot foot arthropathy with the goal of improving quality of life.MethodsTwenty-four patients who completed the Short Musculoskeletal Function Assessment (SMFA) at baseline and one year following Charcot foot reconstruction were contacted and asked to complete the survey at five years following surgery.ResultsFourteen of the 24 patients completed the SMFA preoperatively, one year following surgery and five years postoperatively. Two patients underwent below knee amputation in the interim. Improvement was noted in all domains measured by the SMFA, with a statistically significant improvement in difficulty with daily activities at five years.ConclusionCorrection of non-plantigrade Charcot foot arthropathy results in clinically meaningful improvement in health-related quality of life at both one and five years postoperatively, including independence with daily activities. The improvement is maintained when reevaluated at five years. This supports the modern paradigm shift towards reconstruction of this deformity. Level of Evidence: III     

Integrate personalized medicine into clinical practice to improve patient safety

Medical practice is based on the experience of practitioners and on learned medical knowledge. This knowledge is based on studies of patient's population. Modern medicine is facing a variety of clinical forms and also variable patients’ responses to treatment. Pharmacogenomics has brought insights to this variability and has led to the development of personalized medicine. The adoption of personalized medicine is slowed down by a number of technical and methodology barriers. The concept of personalized medicine should not be only limited to genetics but must reuse all patient information to get the most suitable patient profile. In this paper we present a methodology for the integration of personalized medicine into clinical practice.     

Differential diagnosis of Charcot arthropathy and osteomyelitis

Foot problems are common causes of morbidity in patients with diabetes mellitus. Foot ulcers are the leading cause of hospitalization in diabetic patients. Bones may be involved in two different clinical conditions: osteomyelitis and Charcot osteoarthropathy. Osteomyelitis usually develops by spreading from contiguous soft tissue to underlying bone. Charcot foot is deformation of foot as a result of muscle athrophy, bone and joint structure changes in a joint as a secondary complication of neuropathy. To distinguish bone infection from non-infectious bone disorders as in Charcot joint may be difficult, especially if there is no skin ulceration. So, the mere absence of skin ulcers does not exclude the diagnosis of osteomyelitis.     

Zonage radiologique d’un service de médecine nucléaire : exemple de l’hôpital d’instruction des armées Sainte-Anne

According to the ministerial order of May 15th, 2006 (transposition of the EURATOM directive 96/29 from May 13th, 1996), each person in charge of a medical institution is compelled to classify the working areas dealing with sources of ionizing radiation. The approach to the delineation of radiological areas should appear in an internal document combining the analysis of heath risks. Without waiting for the publication of the official guidelines as announced in the notice DGT/ASN no. 1 of January 18th, 2008 and in accordance with the above mentioned order, we have already formalized the different steps towards a zoning in the new nuclear medicine department in the Military Hospital Ste Anne of Toulon by using a detailed methodology to measure exposition and contamination levels. The methodology is largely based on measurements and consideration of normal envelopes. Analysis of integrated doses over an hour in a room can ultimately determine radiological areas. We apply the new recommended values to define the different classified zones according to their specificity and discuss this new way of assessment of exposure risks as well as the consequences on the different staff categories concerned.     

Making sense of shadows: Dr. James Third and the introduction of x-rays, 1896 to 1902.

The discovery of x-rays was announced by German physicist Wilhelm Conrad Röntgen in December 1895. This review of the introduction of the use of x-rays in Kingston, Ont., shows the rapidity of their adoption in Canadian medicine. By February 1896 "x-ray photographs" were being taken by Captain John Cochrane of the Royal Military College of Canada in Kingston. Initially a scientific and popular curiosity, the new rays were quickly applied to medicine, and by the fall of 1896 the Kingston General Hospital had acquired its own x-ray apparatus. The hospital superintendent, Dr. James Third, became a leading practitioner and promoter of radiographic diagnosis and radiation therapy. He published, in 1902, the first comprehensive review of the diagnostic and therapeutic uses of x-rays by a Canadian physician. Third''s writings reveal his technical knowledge, his organized approach to the application of radiography to clinical medicine and his cautious attitude. Like other physicians who have witnessed the introduction of new diagnostic techniques, Third feared that the new technology would usurp the physician''s clinical skills.     

Protocol for Development of American Association of Clinical Endocrinology Clinical Practice Guidelines and Consensus Statements: Summary of Methodology,Process, and Policy – 2023 Update

ObjectiveThis 2023 updated protocol summarizes the American Association of Clinical Endocrinology’s (AACE’s) new framework for the development of clinical practice guidelines and other guidance documents that includes changes to methodology, processes, and policies.MethodsAACE has critically reviewed its development processes for guidance documents over the last several years against the National Academy of Medicine Standards for Developing Trustworthy Clinical Practice Guidelines and the Council of Medical Specialty Societies Principles for Development of Specialty Society Clinical Guidelines to determine areas for improvement.ResultsThe new AACE framework for development of guidance documents incorporates many changes, including a revised conflicts of interest (COI) policy; strengthened commitment to collection of disclosures and management of relevant COI during development; open calls to membership for authors; new requirements for authors; new diversity, equity, and inclusion (DEI) policy; new empanelment process that incorporates consideration of DEI; and adoption of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to increase the quality of evidence assessment and standardize recommendation grades and statements, among other improvements.ConclusionsAACE has revised its policies and adopted a completely new methodology for guideline development in support of the mission to elevate the practice of clinical endocrinology to improve patient care. With the use of an evidence-based medicine framework and by continually assessing and improving its processes for development of guidance, AACE strives to deliver trustworthy, unbiased, and up-to-date information that ensures clinician and patient confidence in AACE content. Further, AACE hopes that these enhancements foster a more collaborative approach to development and increase engagement with the worldwide medical community to improve global health.     

Methods for the absolute quantification of N-glycan biomarkers

BackgroundMany treatment options especially for cancer show a low efficacy for the majority of patients demanding improved biomarker panels for patient stratification. Changes in glycosylation are a hallmark of many cancers and inflammatory diseases and show great potential as clinical disease markers. The large inter-subject variability in glycosylation due to hereditary and environmental factors can complicate rapid transfer of glycan markers into the clinical practice but also presents an opportunity for personalized medicine.Scope of reviewThis review discusses opportunities of glycan biomarkers in personalized medicine and reviews the methodology for N-glycan analysis with a specific focus on methods for absolute quantification.Major conclusionsThe entry into the clinical practice of glycan markers is delayed in large part due to a lack of adequate methodology for the precise and robust quantification of protein glycosylation. Only absolute glycan quantification can provide a complete picture of the disease related changes and will provide the method robustness required by clinical applications.General significanceGlycan biomarkers have a huge potential as disease markers for personalized medicine. The use of stable isotope labeled glycans as internal standards and heavy-isotope labeling methods will provide the necessary method precision and robustness acceptable for clinical use. This article is part of a Special Issue entitled “Glycans in personalized medicine” Guest Editor: Professor Gordan Lauc.     

Duchenne,Charcot and Babinski,three neurologists of La Salpetrière Hospital,and their contribution to concepts of the central organization of motor synergy

Many currently accepted notions of motor control originate from a few seminal concepts developed in the latter half of the 19th century (see Bennett and Hacker, 2002). The goal of this review is to retrace some current ideas about motor control back to the thought of three French neurologists of Hospital of the Salpetrière hospital in Paris during the latter half of the 19th century and early 20th century (Fig. 1): Guillaume Duchenne de Boulogne (1806–1875), Jean-Martin Charcot (1825–1893), and Babinski, 1886, Babinski, 1896, Babinski, 1898, Babinski, 1899, Babinski, 1900, Babinski, 1902, Babinski, 1903, Babinski, 1909, Babinski, 1913. A common theoretical and methodological thread unites these three men as Charcot was taught neurology by Duchenne, and Babinski was trained by Charcot. The influential concepts developed by these pioneering French neurologists have been neglected for nearly a century and only rediscovered recently. We intend to highlight how these astute clinicians used their meticulous clinical observations of patients to reveal novel and original perspectives of motor co-ordination. Between 1850 and 1930, all three men played a major role in developing and shaping the entire field of normal and pathological motor control in addition to making important contributions to three major scientific issues; the centralist view of muscle sense, the emerging concept of muscle synergy in voluntary movements and in locomotion and finally the specific role of the cerebellum in muscle synergy. The important contributions of these men will be considered in the context of other significant schools of neurology from other countries. Finally, the concept of cerebellar asynergy as proposed by Babinski anticipated the development of the internal models which much later were able to provide a theoretical basis for understanding the mechanism of learned motor co-ordination involving the cerebellum.     

Natural,modified DNA bases

The four canonical bases that make up genomic DNA are subject to a variety of chemical modifications in living systems. Recent years have witnessed the discovery of various new modified bases and of the enzymes responsible for their processing. Here, we review the range of DNA base modifications currently known and recent advances in chemical methodology that have driven progress in this field, in particular regarding their detection and sequencing. Elucidating the cellular functions of modifications remains an ongoing challenge; we discuss recent contributions to this area before exploring their relevance in medicine.     

Répartiteur de dose des médicaments radiopharmaceutiques : contrôle qualité sur deux sites hospitaliers et comparaison avec la législation en vigueur en France

An increasing number of nuclear medicine departments are equipped with automated measurement systems for the preparation of radiopharmaceuticals, with the main aim of minimising technician's irradiation. However, the automatic measurement of the patient activity differs from the manual measurement in material and method. In this context, the objective of the present study was to test the performances of one of these systems, the Unidose by TRASIS^®, in two newly equipped hospitals. The particularity of these systems is they are made up of two dose calibrators: the entrance calibrator (well chamber) and the exit calibrator (probe). Controls were performed on both of these dose calibrators. The results obtained, as well as the methodology employed, were then compared with the regulatory requirements in France. The results found are coherent between the two sites and have highlighted several non-conformities compared to the current regulations, part of which concerning the carpule dose calibrator, which is actually a probe. These results raise the question of a suitable regulation for the new automated measurement systems in nuclear medicine.     

M.S. Gilyarov's Scientific School of Soil Zoology

The role of M.S. Gilyarov's scientific school in the development of the subject and methodology of a new complex discipline formed in the mid 20th century—soil zoology—was considered. The establishment and evolution of the proper scientific school was periodized. The creative continuity and development of the basic laws and technical approaches included in the teacher's scientific program was demonstrated by scientific historical analysis.     

Using journal impact factors to correct for the publication bias of medical studies

Publication bias of the results of medical studies can invalidate evidence-based medicine. The existing methodology for modeling this essentially relies upon the symmetry of the funnel plot. We present a new method of modeling publication bias that uses this information plus the impact factors of the publishing journals. A simple model of the publication process enables the estimation of bias-corrected intervention effects. The procedure is illustrated using a meta-analysis of the effectiveness of single-dose oral aspirin for acute pain, and results are also obtained for five other meta-analyses. The method enables the fitting of a wide range of models and is considered more flexible than other ways of compensating for publication bias. The model also provides the basis of a statistical test for the existence of publication bias. Use of the new methodology to supplement existing methods is recommended, in the context of a sensitivity analysis.     

Coordination of Locomotor Activity in Transgenic C57Bl/6 Mice with Hereditary Neuropathy

Neurophysiology - Locomotor activity of C57Bl/6 mice with hereditary motor and sensory neuropathy (HMSN; an animal model of Charcot–Marie–Tooth, CMT, disease) was investigated in males...