Forty years of calcitonin--where are we now? A tribute to the work of Iain Macintyre, FRS

Calcitonin was discovered as a hypocalcemic principal that was initially thought to originate from the parathyroid gland. This view was corrected subsequently, and an origin from the thyroid C cells was documented. The purification and sequencing of various calcitonins soon followed. Calcitonin is a 32-amino-acid-long peptide with an N-terminal disulfide bridge and a C-terminal prolineamide residue. The peptide was shown to potently inhibit bone resorption; however, a direct osteoclastic action of the peptide was confirmed only in the early 1980s. Several osteoclast calcitonin receptors have subsequently been cloned and sequenced. Specific regions of the receptor necessary for ligand binding and intracellular signaling through cyclic AMP and calcium have been identified through systematic deletion mutagenesis and chimeric receptor studies. Calcitonin's potent antiresorptive effect has led to its use in treating Paget's disease of bone, osteoporosis, and hypercalcemia. This review retraces key aspects of the synthesis and structure of calcitonin, its cellular and molecular actions, and its therapeutic uses as they have emerged over the 40 years since its discovery. The review also examines the implications of these findings for future clinical applications as a tribute to early workers to whom credit must be given for creation of an important and expanding field. Notable are the new approaches currently being used to enhance calcitonin action, including novel allosteric activators of the calcitonin receptor, modulation of the release of endogenous calcitonin by calcimimetic agents, as well as the development of oral calcitonins.     

Application of artificial intelligence to imaging interpretations in the musculoskeletal area: Where are we? Where are we going?

The interest of researchers, clinicians and radiologists, in artificial intelligence (AI) continues to grow. Deep learning is a subset of machine learning, in which the computer algorithm itself can determine the optimal imaging features to answer a clinical question. Convolutional neural networks are the most common architecture for performing deep learning on medical images. The various musculoskeletal applications of deep learning are the detection of abnormalities on X-rays or cross-sectional images (CT, MRI), for example the detection of fractures, meniscal tears, anterior cruciate ligament tears, degenerative lesions of the spine, bone metastases, classification of e.g., dural sac stenosis, degeneration of intervertebral discs, assessment of skeletal age, and segmentation, for example of cartilage. Software developments are already impacting the daily practice of orthopedic imaging by automatically detecting fractures on radiographs. Improving image acquisition protocols, improving the quality of low-dose CT images, reducing acquisition times in MRI, or improving MR image resolution is possible through deep learning. Deep learning offers an automated way to offload time-consuming manual processes and improve practitioner performance. This article reviews the current state of AI in musculoskeletal imaging.     

Radiation exposure to the hands of orthopaedic surgeons: are we underestimating the risk?

Introduction Previous studies reported that the radiation exposure to the hands of orthopaedic surgeons was far below the acceptable limit. However, the risk could have been underestimated as some factors were overlooked, namely monitoring trainees during average workload, placing dosimeters over the most susceptible locations, measuring the cumulative dosage of radiation and considering the dose limit for non-classified workers.Materials and methods We performed a prospective study in two centres to estimate the radiation dose to the hands of two consultant trauma surgeons and two trainees (one assisting and one operating) while performing 47 fluoroscopy-assisted procedures. We used validated thermoluminescent dosimeters (TLDs) rings and fingerstalls for monitoring the cumulative dosage.Results Trainees were at higher risk while performing intramedullary nailing and during assistance. Higher radiation doses were recorded from dominant index fingers and particularly fingertips.Conclusion The risk of radiation exposure appears to be higher than previously reported. Fingertips are more susceptible to radiation exposure and should therefore be monitored in forthcoming studies.     

Allotransplantation of the face: how close are we?

Reconstruction of patients with severe facial disfigurements due to burns, trauma, or cancer is a challenging task for plastic surgeons. Currently, available reconstructive options rarely result in satisfactory functional and aesthetic outcomes. In this article the authors present the rationale and experimental basis for the introduction of composite facial allograft transplantation in humans. They outline the ethical, social, and media-related issues in facial allograft transplantation.     

Presidential address to the 1998 American Venous Forum: Where are we now? Where are we going? Inching forward

J Vasc Surg 1998;28:761-6.     

Prevention of secondary osteoporotic fractures--why are we ignoring the evidence?

Osteoporosis is a major problem world-wide. In the UK, it costs the NHS about £1.7 billion per annum. Admission to orthopaedic units for treatment and rehabilitation with fractured necks of femur makes up a large proportion of the cost. The evidence suggests simple, cost-effective treatments can reduce fractures and re-fractures attributable to osteoporosis by up to 50%, and easy to follow guidelines exist.Our study, of a typical large district general hospital suggests that ideally placed orthopaedic surgeons are however not taking the opportunity to start these treatments or offer advice about this common condition. Commencing these treatments could prevent more than 7000 fractures per year in the UK.     

Self-neglect in the case of the elderly. Where are we now?

Self-neglect in an elderly person is a behavior that threatens his/her own health and safety. It is present when a person refuses to adequately feed, water, shelter, or clothe himself, refuses medication or medical care, and personal safety measures. MATERIAL AND METHOD: This is a multicentric study of self-neglect in three geriatric units from Finland, Greece and Romania The medical, social, psychological and behavioral profile analysis was based on a questionnaire; this questionnaire relied on existing studies and social, economic and medical facts in the three countries. The cognitive function, nutritional status, and the presence or absence of depression have also been assessed. RESULTS AND DISCUSSIONS: The data obtained until now support the importance of self-neglect among the elderly. The social-medical network should not only identify, diagnose, prevent, and treat the elderly affected by the phenomenon of self-neglect, but also educate the society to help them and, moreover, to prevent their marginalization.     

Why are diabetics at reduced risk for prostate cancer? A review of the epidemiologic evidence

A large body of epidemiologic evidence provides strong support for the notion that type-2 diabetics are at decreased risk for prostate cancer. In this review article, we summarize the epidemiologic literature that explores the role of diabetes mellitus and related biomarkers in prostate cancer risk and detection, in order to create a better understanding of the potential mechanisms that underlie this inverse association. The bulk of the data supporting this association comes from the USA, as evidence for this association is less consistent in many other regions of the world. The relationship between diabetes and prostate cancer is suspected to be causal due to evidence of decreasing prostate cancer risk with increasing diabetes duration and lack of evidence for any confounding of this association. Hypothesized mechanisms for decreased prostate cancer risk among diabetics include (1) decreased levels of hormones and other cancer-related growth factors among diabetics, (2) the impact of diabetes on detection-related factors, such as prostate size, circulating prostate-specific antigen (PSA), and health-care seeking behaviors, (3) protective effects of diabetes medications, and (4) a protective effect of diabetes-induced vascular damage in the prostate. The evidence for screening-related factors is compelling, as diabetics appear to have reduced PSA and lower levels of health-care seeking behavior compared with nondiabetics. Furthermore, the inverse association between diabetes and prostate cancer is much less apparent in populations that do not perform biopsies based on PSA levels and in studies restricted to biopsied individuals. The inverse association appears to be stronger for low-grade disease, as compared with high-grade (Gleason >7), which is consistent with the observation that among patients receiving biopsy or prostate cancer treatment, diabetics are more likely to have high-grade disease as compared to nondiabetics, potentially resulting in worse outcomes for diabetics. Epidemiological research has reveals a great deal regarding the relationship between diabetes and prostate cancer risk, but additional research is needed to further clarify the mechanisms underlying this inverse association.