The Segond fracture occurs at the site of lowest sub-entheseal trabecular bone volume fraction on the tibial plateau.

In a series of human cadaveric experiments, Dr. Paul Segond first described the avulsion injury occurring at the anterolateral tibial plateau that later took his name. The fracture is thought to arise as a consequence of excessive tibia internal rotation which often also elicits damage to other connective tissue of the knee. The exact mechanism behind the avulsion is, however, unclear. A number of ligamentous structures have been proposed in separate studies to insert into the Segond fragment. Suggestions include the iliotibial band (ITB), biceps femoris and the controversial 'anterolateral ligament' (ALL). Despite increasing knowledge of tibial plateau bony microarchitecture in both healthy and disease states, no studies have yet, to our knowledge, considered the role of tibial sub-entheseal bone structure in pathogenesis of the Segond fracture. The goal of this study was thus to elucidate the differences in trabecular properties at regions across the tibial plateau in order to provide an explanation for the susceptibility of the anterolateral region to avulsion injury. Twenty human tibial plateaus from cadaveric donors were dissected and imaged using a Nikon-XTH225-µCT scanner with <80 µm isotropic voxel size. Scans were reconstructed using MicroView 3D Image Viewer and Analysis Tool. Subsequent virtual biopsy at ten anatomically defined regions of interest (ROI) generated estimates of bone volume fraction ('bone volume divided by total volume' (BV/TV)). The overall mean BV/TV value across all 20 tibiae and all 10 ROIs was 0.271. Univariate repeated-measurements ANOVA demonstrated that BV/TV values differed between ROIs. BV/TV values at the Segond site (Sα, Sß or Sγ) were lower than all other ROIs at 0.195, 0.192 and 0.193, respectively. This suggests that, notwithstanding inter- and intra-specimen variation, the Segond site tends to have a lower trabecular bone volume fraction than entheseal sites elsewhere on the tibia. Since BV/TV correlates with tensile and torsional strength, the lower BV/TV at the Segond site could equate to a region of local weakness in certain individuals which predisposes them to an avulsion injury following the application of force from excessive internal rotation. The low BV/TV recorded at the Segond site also challenges the idea that the fracture occurs due to pull from a discrete 'anterolateral ligament', as the tension exerted focally would be expected to elicit a hypertrophic response in line with Frost's Mechanostat hypothesis. Our data would instead agree with the aforementioned reports of the fibrous band at the Segond site being part of a broader insertion of an 'anterolateral complex'.

Assessing the accuracy of body mass estimation equations from pelvic and femoral variables among modern British women of known mass.

Femoral head diameter is commonly used to estimate body mass from the skeleton. The three most frequently employed methods, designed by Ruff, Grine, and McHenry, were developed using different populations to address different research questions. They were not specifically designed for application to female remains, and their accuracy for this purpose has rarely been assessed or compared in living populations. This study analyzes the accuracy of these methods using a sample of modern British women through the use of pelvic CT scans (n = 97) and corresponding information about the individuals' known height and weight. Results showed that all methods provided reasonably accurate body mass estimates (average percent prediction errors under 20%) for the normal weight and overweight subsamples, but were inaccurate for the obese and underweight subsamples (average percent prediction errors over 20%). When women of all body mass categories were combined, the methods provided reasonable estimates (average percent prediction errors between 16 and 18%). The results demonstrate that different methods provide more accurate results within specific body mass index (BMI) ranges. The McHenry Equation provided the most accurate estimation for women of small body size, while the original Ruff Equation is most likely to be accurate if the individual was obese or severely obese. The refined Ruff Equation was the most accurate predictor of body mass on average for the entire sample, indicating that it should be utilized when there is no knowledge of the individual's body size or if the individual is assumed to be of a normal body size. The study also revealed a correlation between pubis length and body mass, and an equation for body mass estimation using pubis length was accurate in a dummy sample, suggesting that pubis length can also be used to acquire reliable body mass estimates. This has implications for how we interpret body mass in fossil hominins and has particular relevance to the interpretation of the long pubic ramus that is characteristic of Neandertals.

Prenatal cocaine use and maternal depression: effects on infant neurobehavior.

OBJECTIVE: The present study examined the impact of both perinatal maternal depression and cocaine use on infant neurobehavior at 1 month of age in a large, multi-site study. METHODS: Infant neurobehavior was examined in 1053 infants at 1 month of age using the NICU Network Neurobehavioral Scale (NNNS). Mothers were interviewed using The Addiction Severity Index to determine present and past psychiatric history. Four groups were derived from the total sample: 385 prenatally cocaine-exposed infants, 76 whose mothers reported current postpartum depression (DEP/COC) and 309 without current postpartum depression (nonDEP/COC); 668 infants were not exposed to cocaine, 104 whose mothers reported current postpartum depression (DEP/nonCOC), 564 without current postpartum depression (nonDEP/nonCOC). A 2x2 Analysis of Covariance was used with covariates (birthweight, maternal age, SES, nicotine, alcohol, and research site) to examine infant neurobehavior in these four conditions. Secondary analyses were conducted to examine the effects of amount and timing of prenatal cocaine exposure. RESULTS: DEP group by COC exposure status interactions were significant; there was only a DEP effect in the nonCOC infants. Infants in the nonCOC/DEP group had poorer self-regulation and more stress signs, excitability, and arousal than infants in the other groups. CONCLUSIONS: Postpartum maternal depression has negative effects on infant neurobehavior at 1 month of age. Prenatal cocaine exposure may serve to suppress or buffer the effects of postpartum depression on infant neurobehavior. Maternal mood could explain some of the inconsistencies found in the prenatal cocaine exposure literature.

Homozygous Resistance to Thyroid Hormone ß: Can Combined Antithyroid Drug and Triiodothyroacetic Acid Treatment Prevent Cardiac Failure?

Resistance to thyroid hormone ß (RTHß) due to homozygous THRB defects is exceptionally rare, with only five kindreds reported worldwide. Cardiac dysfunction, which can be life-threatening, is recognized in the disorder. Here we describe the clinical, metabolic, ophthalmic, and cardiac findings in a 9-year-old boy harboring a biallelic THRB mutation (R243Q), along with biochemical, physiologic, and cardiac responses to carbimazole and triiodothyroacetic acid (TRIAC) therapy. The patient exhibits recognized features (goiter, nonsuppressed thyroid-stimulating hormone levels, upper respiratory tract infections, hyperactivity, low body mass index) of heterozygous RTHß, with additional characteristics (dysmorphic facies, winging of scapulae) and more markedly elevated thyroid hormone levels, associated with the homozygous form of the disorder. Notably, an older sibling with similar clinical features and probable homozygous RTHß had died of cardiac failure at age 13 years. Features of early dilated cardiomyopathy in our patient prompted combination treatment with carbimazole and TRIAC. Careful titration of therapy limited elevation in TSH levels and associated increase in thyroid volume. Subsequently, sustained reduction in thyroid hormones with normal TSH levels was reflected in lower basal metabolic rate, gain of lean body mass, and improved growth and cardiac function. A combination of antithyroid drug and TRIAC therapy may prevent thyrotoxic cardiomyopathy and its decompensation in homozygous or even heterozygous RTHß in which life-threatening hyperthyroid features predominate.

Resistance to thyroid hormone caused by a mutation in thyroid hormone receptor (TR)α1 and TRα2: clinical, biochemical, and genetic analyses of three related patients.

BACKGROUND: The thyroid hormone receptor α gene (THRA) transcript is alternatively spliced to generate either thyroid hormone receptor (TR)α1 or a non-hormone-binding variant protein, TRα2, the function of which is unknown. Here, we describe the first patients identified with a mutation in THRA that affects both TRα1 and TRα2, and compare them with patients who have resistance to thyroid hormone owing to a mutation affecting only TRα1, to delineate the relative roles of TRα1 and TRα2. METHODS: We did clinical, biochemical, and genetic analyses of an index case and her two sons. We assessed physical and radiological features, thyroid function, physiological and biochemical markers of thyroid hormone action, and THRA sequence. FINDINGS: The patients presented in childhood with growth failure, developmental delay, and constipation, which improved after treatment with thyroxine, despite normal concentrations of circulating thyroid hormones. They had similar clinical (macrocephaly, broad faces, skin tags, motor dyspraxia, slow speech), biochemical (subnormal ratio of free thyroxine:free tri-iodothyronine [T3], low concentration of total reverse T3, high concentration of creatine kinase, mild anaemia), and radiological (thickened calvarium) features to patients with TRα1-mediated resistance to thyroid hormone, although our patients had a heterozygous mis-sense mutation (Ala263Val) in both TRα1 and TRα2 proteins. The Ala263Val mutant TRα1 inhibited the transcriptional function of normal receptor in a dominant-negative fashion. By contrast, function of Ala263Val mutant TRα2 matched its normal counterpart. In vitro, high concentrations of T3 restored transcriptional activity of Ala263Val mutant TRα1, and reversed the dominant-negative inhibition of its normal counterpart. High concentrations of T3 restored expression of thyroid hormone-responsive target genes in patient-derived blood cells. INTERPRETATION: TRα1 seems to be the principal functional product of the THRA gene. Thyroxine treatment alleviates hormone resistance in patients with mutations affecting this gene, possibly ameliorating the phenotype. These findings will help the diagnosis and treatment of other patients with resistance to thyroid hormone resulting from mutations in THRA. FUNDING: Wellcome Trust, NIHR Cambridge Biomedical Research Centre, Marie Curie Actions, Foundation for Development of Internal Medicine in Europe.

Computed tomography of subchondral bone and osteophytes in hip osteoarthritis: the shape of things to come?

Bone is a fundamental component of the disordered joint homeostasis seen in osteoarthritis, a disease that has been primarily characterized by the breakdown of articular cartilage accompanied by local bone changes and a limited degree of joint inflammation. In this review we consider the role of computed tomography imaging and computational analysis in osteoarthritis research, focusing on subchondral bone and osteophytes in the hip. We relate what is already known in this area to what could be explored through this approach in the future in relation to both clinical research trials and the underlying cellular and molecular science of osteoarthritis. We also consider how this area of research could impact on our understanding of the genetics of osteoarthritis.