Search

Synthesized chemical defenses have broadly evolved across countless taxa and are important in shaping evolutionary and ecological interactions within ecosystems. However, the underlying genomic mechanisms by which these organisms synthesize and utilize their toxins are relatively unknown. Herein, we use comparative transcriptomics to uncover potential toxin synthesizing genes and pathways, as well as interspecific patterns of toxin synthesizing genes across 10 species of North American true toads (Bufonidae). Upon assembly and annotation of the 10 transcriptomes, we explored patterns of relative gene expression and possible protein–protein interactions across the species to determine what genes and/or pathways may be responsible for toxin synthesis. We also tested our transcriptome dataset for signatures of positive selection to reveal how selection may be acting upon potential toxin producing genes. We assembled high-quality transcriptomes of the bufonid parotoid gland, a tissue not often investigated in other bufonid-related RNAseq studies. We found several genes involved in metabolic and biosynthetic pathways (e.g., steroid biosynthesis, terpenoid backbone biosynthesis, isoquinoline biosynthesis, and glucosinolate biosynthesis) that were functionally enriched and/or relatively expressed across the 10 focal species that may be involved in the synthesis of alkaloid and steroid toxins, as well as other small metabolic compounds that cause distastefulness in bufonids. We hope that our study lays a foundation for future studies to explore the genomic underpinnings and specific pathways of toxin synthesis in toads, as well as at the macroevolutionary scale across numerous taxa that produce their own defensive toxins.

The corona mortis (CM) is a vascular connection between the obturator and external iliac or internal epigastric vessels that has historically been identified as a source of hemorrhage in pelvic surgery. However, its frequency, location, proximity to the osteotomies performed, vascular contributions and impact on blood loss in patients undergoing periacetabular osteotomy (PAO) are unknown. We sought to identify the frequency, origin, location relative to osteotomies performed during surgery and impact on blood loss of the CM. Preoperative magnetic resonance imaging (MRI) of the hips of 28 adolescent patients (56 hips) undergoing PAO was retrospectively reviewed for the presence of a CM. When identifiable, the size, nature (arterial or venous), orientation, position relative to the iliopectineal eminence (IPE) and associated estimated blood loss (EBL) were recorded. 75% (21/28) of patients possessed an identifiable, ipsilateral CM to the site of PAO, 90% of which were venous and 10% arterial. The vessel was typically 8.3 ± 3.8 mm medial and 11.1 ± 5.3 mm caudal from the anterosuperomedial edge of the IPE. There was no significant difference in the amount of EBL (519 ± 260 versus 694 ± 369 ml) or need for post-op transfusions (1/21 versus 0/7) between patients who possessed a CM and those who did not, respectively (P = 0.21). CM was more prevalent in this study than previously reported. However, the presence of an ipsilateral CM was not associated with an increase in EBL or transfusion during routine PAO surgery using modern surgical techniques.

Mitonuclear discordance is a frequently encountered pattern in phylogeographic studies and occurs when mitochondrial and nuclear DNA display conflicting signals. Discordance among these genetic markers can be caused by several factors including confounded taxonomies, gene flow, and incomplete lineage sorting. In this study, we present a strong case of mitonuclear discordance in a species complex of toads (Bufonidae: Incilius coccifer complex) found in the Chortís Block of Central America. To determine the cause of mitonuclear discordance in this complex, we used spatially explicit genetic data to test species limits and relationships, characterize demographic history, and quantify gene flow. We found extensive mitonuclear discordance among the three recognized species within this group, especially in populations within the Chortís Highlands of Honduras. Our data reveal nuclear introgression within the Chortís Highlands populations that was most probably driven by cyclical range expansions due to climatic fluctuations. Though we determined introgression occurred within the nuclear genome, our data suggest that it is not the key factor in driving mitonuclear discordance in the entire species complex. Rather, due to a lack of discernible geographic pattern between mitochondrial and nuclear DNA, as well as a relatively recent divergence time of this complex, we concluded that mitonuclear discordance has been caused by incomplete lineage sorting. Our study provides a framework to test sources of mitonuclear discordance and highlights the importance of using multiple marker types to test species boundaries in cryptic species.

Background Rotation of the humerus out of the coronal plane is presumed to alter the Baumann angle (BA) value. Identifying the rotational limits of the humerus at which the BA can be accurately and reliably measured will circumvent repeated radiographs and unnecessary exposure to radiation, may improve patient comfort, and save time and medical resources. Methods A retrospective chart review was performed to identify patients under the age of 18 who underwent an elbow computed tomography (CT) scan without any humeral pathology and with an open distal humeral physis. For each patient, a 3-dimensional (3D) computerized model was generated with 30% transparency to mimic a plain radiograph. These models were rotated in 10-degree increments and the BA was measured on each position. In addition, the measurements were taken on an anteroposterior radiograph for each patient. Analysis of variance and the Pearson tests were performed to locate differences and define associations. Results Fifteen 3D CT reconstructions were generated from 14 patients. The mean BA on the neutral position was found to be 72.2±3 degrees, which correlated with the 70.6±5.91 degrees measurement obtained on radiographs. The most extreme rotational positions on which the BA values were consistent with the neutral position values were +40 external rotation (70.97±7.01 degrees, P=1) and -70 degrees internal rotation (68.4±7.47 degrees, P=0.14). A negative correlation was found between the BA values and the extent at which the humerus was rotated from the neutral position. The variability of the BA between patients, implied by the SD of measurements on each position increased with increasing rotation from the neutral position (r=1, P Conclusions On the basis of 3D CT images, the BA is the most accurate when the arm is positioned at an exact anteroposterior position. It is reliable to measure the BA when the humerus is rotated no more than +40 degrees external rotation to -70 degrees internal rotation. This range of rotation can act as an "accurate zone" and help avoiding multiple radiographs. Level of evidence Level III.

Survivors of domestic violence (DV) and of violence perpetrated by organized gangs (GV) face barriers to legal protection under U.S. asylum law. We abstracted data from 132 affidavits based on forensic medical evaluations of asylum seekers granted legal protection in the U.S. on the basis of DV and/or GV. We described claimants’ trauma exposures and resilience factors and used multiple logistic regression to quantify associations with Diagnostic and Statistical Manual-5 (DSM-5) diagnoses and improvement in mental health. People seeking asylum based on DV and/or GV have endured multiple types of trauma with significant impacts on their mental health. New experiences of trauma following migration to the U.S. were common and associated with DSM-5 diagnoses. Conversely, resilience factors were associated with improved mental health. Policies that aim to reduce ongoing trauma in the U.S. and to bolster resilience factors may promote asylee mental health and well-being.

Acknowledgements: The authors would like to acknowledge Drs. Matthew Milewski, Yi-Meng Yen, and Adam Yanke for their contributions. Background: Surgical decision-making and pre-operative planning for children and adolescents with patellofemoral instability relies heavily on skeletal maturity status. In order to be clinically useful, radiologic assessments of skeletal maturity must demonstrate acceptable interrater reliability and accuracy. Purpose: The purpose of this study was to evaluate the interrater reliability among surgeons of varying experience levels and specialty training backgrounds when evaluating skeletal maturity in the distal femur and proximal tibia of children and adolescents with patellofemoral instability. Study Design: Cross-sectional study Methods: Six fellowship-trained orthopedic surgeons (4 pediatric orthopedic, 2 sports medicine) who perform a high volume of patellofemoral instability surgery examined 20 blinded and randomized knee radiographs and MR images. They assessed these images for clinically relevant growth (open physis) or clinically insignificant growth (closing/closed physis) remaining in the distal femoral and proximal tibial physes. Fleiss’s kappa was calculated for each measurement. After initial ratings, raters discussed consensus methods to improve reliability and assessed the images again in order to determine if training and new criteria improved interrater reliability. Results: Reliability for initial assessments of distal femoral and proximal tibial physeal status was poor (Kappa range: 0.01 – 0.58). After consensus building, all assessments demonstrated almost perfect interrater reliability (Kappa = 0.99 for all measurements). Conclusion: Surgical decision-making and pre-operative planning for children and adolescents with patellofemoral instability relies heavily on radiologic assessment of skeletal maturity. This study found that initial interrater reliability of physeal status and clinical decision making was unacceptably low. However, with the addition of new criteria, a consensus-building process, and training, these variables became highly reliable. Clinical Relevance: Lack of assessment reliability can jeopardize patient care, both when determining surgical indications as well as choosing an appropriate procedure based upon skeletal maturity. Surgeons should focus on using reliable imaging metrics in children and adolescents with patellofemoral instability, and measurements that remain unreliable after consensus building and training should be removed from clinical decision-making algorithms. What is known about the subject: Treatment of patellofemoral instability heavily relies on skeletal maturity status. Physeal assessments of the knee must be reliable and clinically relevant to ensure optimal patient care. What this study adds to existing knowledge: Physeal assessment of the knee without training can be unreliable among fellowship trained orthopedic surgeons. With consensus building and training in the use of the methods described in this manuscript, physeal assessments can demonstrate almost perfect reliability.

We examine the nature of thermal flow during the annealing process of a recently reported method to produce films of the high-T c superconducting compound YBa 2 Cu 3 O x wherein the oxygen content (x) spatially varies across the length of the sample. In this context, we discuss contrasting annealing results that can be expected under differing annealing configurations-including the formation of discrete regions of pressure stabilized oxygen content associated with known lattice superstructures. We also examine characteristic energy scales associated with the corresponding normal and superconducting states of these stabilized superstructures. A relationship between ratios of the superconducting gap energy, superconducting electronic kinetic energy, and the BCS-Eliashberg coupling constant associated with each lattice superstructure is found. The near integer ratios observed suggest that the superstructures can be viewed as “quantum structural” lattice states in the sense that oxygen doping levels in between are composed of a superposition of ordered structures.

Background:Surgical decision making and preoperative planning for children and adolescents with patellofemoral instability rely heavily on a patient’s skeletal maturity. To be clinically useful, radiologic assessments of skeletal maturity must demonstrate acceptable interrater reliability and accuracy.Purpose:The purpose of this study was to examine the interrater reliability among surgeons of varying experience levels and specialty training backgrounds when evaluating the skeletal maturity of the distal femur and proximal tibia of children and adolescents with patellofemoral instability.Study Design:Cohort study (diagnosis); Level of evidence, 3.Methods:Six fellowship-trained orthopaedic surgeons (3 pediatric orthopaedic, 2 sports medicine, and 1 with both) who perform a high volume of patellofemoral instability surgery examined 20 blinded knee radiographs and magnetic resonance images in random order. They assessed these images for clinically relevant growth (open physis) or clinically insignificant growth (closing/closed physis) remaining in the distal femoral and proximal tibial physes. Fleiss’ kappa was calculated for each measurement. After initial ratings, raters discussed consensus methods to improve reliability and assessed the images again to determine if training and new criteria improved interrater reliability.Results:Reliability for initial assessments of distal femoral and proximal tibial physeal patency was poor (kappa range, 0.01-0.58). After consensus building, all assessments demonstrated almost-perfect interrater reliability (kappa, 0.99 for all measurements).Conclusion:Surgical decision making and preoperative planning for children and adolescents with patellofemoral instability rely heavily on radiologic assessment of skeletal maturity. This study found that initial interrater reliability of physeal patency and clinical decision making was unacceptably low. However, with the addition of new criteria, a consensus-building process, and training, these variables became highly reliable.

Phalangeal microgeodic disease is a rare and benign self-limited condition involving the phalanges, often in the setting of cold exposure, with characteristic MR imaging abnormalities. Radiographic case descriptions are predominantly from Asia and Europe, with only seven cases using MR to characterize phalangeal microgeodic disease. In this study we describe the MR imaging appearance of unusual and striking phalangeal signal abnormality compatible with phalangeal microgeodic disease at our institution in North America. We retrospectively reviewed cases presenting at our institution with unusual or unexplained phalangeal signal abnormalities between 2001 and 2014. We reviewed the MR imaging appearances in conjunction with radiographs and any other available imaging investigations. Of 189 examinations reviewed during the study period, 8 imaging studies in 6 patients met the study inclusion criteria. Signal abnormality was present in 57 of 112 phalanges (51%), frequently involving the distal phalanges (70%, 28 of 40), followed by the middle phalanges (56%, 18 of 32) and the proximal phalanges (28%, 11 of 40). The pattern of involvement was most commonly diaphysis (38%), followed by metaphysis (32%) and epiphysis (30%). The extent of MR signal abnormality was greater than that suspected based on clinical presentation or on radiographs. The presence of unexplained diffuse characteristic marrow involvement of multiple painful phalanges on MR images, often in the setting of cold exposure, should raise the possibility of phalangeal microgeodic disease. Consideration of this diagnosis based on MR findings would lead to a more conservative management and avoid unnecessary invasive diagnostic procedures.

Shape memory polymer (SMP) foams were synthesized with three different nanoparticles (tungsten, silicon dioxide, and aluminum oxide) for embolization of cerebral aneurysms. Ultra-low density SMP foams have previously been utilized for aneurysm occlusion, resulting in a rapid, stable thrombus. However, the small cross section of foam struts can potentially lead to fracture and particulate generation, which would be a serious adverse event for an embolic device. The goal of this study was to improve the mechanical properties of the system by physically incorporating fillers into the SMP matrix. Thermal and mechanical characterization suggested minimal changes in thermal transition of the SMP nanocomposites and improved mechanical strength and toughness for systems with low filler content. Actuation profiles of the three polymer systems were tuned with filler type and content, resulting in faster SMP foam actuation for nanocomposites containing higher filler content. Additionally, thermal stability of the SMP nanocomposites improved with increasing filler concentration, and particulate count remained well below accepted standard limits for all systems. Extraction studies demonstrated little release of silicon dioxide and aluminum oxide from the bulk over 16 days. Tungstun release increased over the 16 day examination period, with a maximum measured concentration of approxiately 2.87 μg/mL. The SMP nanocomposites developed through this research have the potential for use in medical devices due to their tailorable mechanical properties, thermal resisitivity, and actuation profiles.

A previously healthy 3-week-old boy presented with 5 hours of marked fussiness, abdominal distention, and poor feeding. He was afebrile and well perfused. His examination was remarkable for localized abdominal tenderness and distention. He was referred to the emergency department in which an abdominal radiograph revealed gaseous distention of the bowel with a paucity of gas in the pelvis. Complete blood cell count and urinalysis were unremarkable. His ongoing fussiness and abnormal physical examination prompted consultation with surgery and radiology. Our combined efforts ultimately established an unexpected diagnosis.

Prior literature, limited to small case series and case reports, suggests that rotator cuff tears are rare in adolescents. However, we have identified rotator cuff tears in numerous children and adolescents who have undergone shoulder MRI evaluation. The purpose of this study is to describe the prevalence and characteristics of rotator cuff tears in children and adolescents referred for MRI evaluation of the shoulder at a large pediatric hospital and to correlate the presence of rotator cuff tears with concurrent labral pathology, skeletal maturity and patient activity and outcomes. We reviewed reports from 455 consecutive non-contrast MRI and magnetic resonance arthrogram examinations of the shoulder performed during a 2-year period, and following exclusions we yielded 205 examinations in 201 patients (ages 8–18 years; 75 girls, 126 boys). Rotator cuff tears were classified by tendon involved, tear thickness (partial or full), surface and location of tear (when partial) and presence of delamination. We recorded concurrent labral pathology when present. Physeal patency of the proximal humerus was considered open, closing or closed. Statistical analysis was performed to evaluate for a relationship between rotator cuff tears and degree of physeal patency. We obtained patient activity at the time of injury, surgical reports and outcomes from clinical records when available. Twenty-five (12.2%) rotator cuff tears were identified in 17 boys and 7 girls (ages 10–18 years; one patient had bilateral tears). The supraspinatus tendon was most frequently involved (56%). There were 2 full-thickness and 23 partial-thickness tears with articular-side partial-thickness tears most frequent (78%). Insertional partial-thickness tears were more common (78%) than critical zone tears (22%) and 10 (43%) partial-thickness tears were delamination tears. Nine (36%) patients with rotator cuff tears had concurrent labral pathology. There was no statistically significant relationship between rotator cuff tears and physeal patency (P > 0.05). Most patients were athletes (76%). Five tears were confirmed at surgery. Poor clinical follow-up limited evaluation of patient outcomes. Rotator cuff tears can be identified during MRI examination of symptomatic child and adolescent shoulders and often consist of tear patterns associated with repetitive microtrauma in overhead athletic activities or with single traumatic events. Rotator cuff tears are seen throughout the range of skeletal maturity, often coexist with labral tears and typically are found in athletes.

Introduction Over recent decades, two prominent trends have been observed in Canada and elsewhere: increasing prevalence of childhood overweight and obesity, and increasing participation of women (including mothers) in the paid labour force and resulting demand for child care options. While an association between child care and children's body mass index (BMI) is plausible and would have policy relevance, its existence and nature in Canada is not known. Methods Using data from the National Longitudinal Survey of Children and Youth, we examined exposure to three types of care at age 2/3 years (care by non-relative, care by relative, care in a daycare centre) in relation to change in BMI percentile (continuous and categorical) between age 2/3 years and age 6/7 years, adjusting for health and sociodemographic correlates. Results Care by a non-relative was associated with an increase in BMI percentile between age 2/3 years and age 6/7 years for boys, and for girls from households of low income adequacy. Conclusion Considering the potential benefits of high-quality formal child care for an array of health and social outcomes and the potentially adverse effects of certain informal care options demonstrated in this study and others, our findings support calls for ongoing research on the implications of diverse child care experiences for an array of outcomes including those related to weight.

London in the first half of the 19th century was a centre of scientific and medical interest. For example, the Royal Society, the Linnean Society, the Geological Society, the Chemical Society and the Royal Astronomical Society were all centred on Burlington House and, not far away, in Berner's Street was the Medical and Chirurgical Society, which in 1834 became the Royal Medical and Chirurgical Society and later the Royal Society of Medicine. It was also in this period that Edward Meryon became a member of the latter society and subsequently a Council Member, Librarian and Vice-President. His research led to the clear identification for the first time of the disease Duchenne muscular dystrophy and he published his results in the Transactions of the Royal Medical and Chirurgical Society in 1852.

The clinical course of juvenile dermatomyositis (JDMS) is unpredictable. MRI is used to determine muscle biopsy site and to monitor disease activity. It is unknown whether soft-tissue features on MRI obtained at diagnosis correlate with clinical outcome. The purpose of our study is to determine whether initial MRI findings in the pelvis and thighs in children with JDMS can predict clinical disease course.Forty-five children (31 girls and 14 boys; median age, 6 years; range, 1-18 years) with clinically diagnosed biopsy-proven JDMS and at least 24 months of clinical follow-up were included. Clinical outcome was categorized as limited or chronic disease, according to the established Crowe clinical classification scheme. Pretreatment MRI examinations of the pelvis and thighs were evaluated for signal abnormalities of muscle and fascia and reticulated signal changes in subcutaneous fat; associations with clinical outcome were examined.Twenty-two patients had limited disease and 23 had chronic disease. Signal intensity ranged from normal (n = 3) to floridly increased in all muscle compartments (n = 17). Muscle and fascial involvement were not associated with clinical outcome. Controlling for duration of symptoms, the adjusted odds of progressing to chronic disease were higher for patients with abnormal subcutaneous fat signal than for those with normal fat signal (odds ratio, 9.0; 95% CI, 1.5-53.5; p0.02).MRI findings of muscle or fascia involvement do not predict clinical outcome in children with newly diagnosed JDMS. Abnormal subcutaneous fat signal appears to have a significant association with a more aggressive chronic disease course.

Synovial diseases in children can be classified into normal structures as potential sources of pathology (synovial folds: plicae, infrapatellar fat pad clefts); noninfectious synovial proliferation (juvenile idiopathic arthritis, hemophilic arthropathy, lipoma arborescens, synovial osteochondromatosis, pigmented villonodular synovitis, reactive synovitis), and infectious synovial proliferation, deposition disease, vascular malformations, malignancy (including metastasis) and intra-articular/periarticular cysts and cyst-like structures (ganglia). Familiarity with characteristic MR imaging findings of synovial diseases in children and young adults will enable a more confident diagnosis for earlier intervention and directed therapy. The first part of this paper will cover potential pathology of normal synovial structures as well as noninfectious synovial proliferation.

Background: The medial patellofemoral ligament (MPFL), a chief medial restraint preventing lateral patellar dislocation, often is reconstructed in children with recurrent dislocation. The femoral MPFL attachment can be difficult to delineate at surgery. Therefore, the origin of the medial collateral ligament (MCL) frequently is used to approximate the reattachment site. The purpose of our study was to compile normative data from MR imaging examinations over different patient ages, to determine the effect of growth on the relationship of the MCL origin site to the distal femoral physis and medial femoral condyle (MFC). Subjects and Methods: This HIPAA-compliant study was IRB approved. Informed consent requirement was waived. Three hundred knee MR imaging examinations (143 boys, 157 girls, 0―20 y) were evaluated. MCL origin to femoral physis distance, MFC height, and MCL origin-physis distance: MFC height ratio (MCL:MFC ratio) were calculated. Relationships between these values and age, gender, and physeal patency were assessed using linear regression models. Results: With physeal patency, MCL origin-physis distance was significantly associated with increasing age in boys (P = 0.0394), and trended toward significance in girls (P = 0.0557). Distance increased 0.01 cm/y in both genders. MFC height increased 0.15 cm/y in boys and 0.13 cm/y in girls (P 0.0001). MCL: MFC ratio decreased 0.01/y (P < 0.0001). With physeal closure, no significant change was measured for any variable. Conclusions: During growth, there are statistically significant, albeit minimal, changes of the MCL origin-physis distance and MFC height. As these changes are essentially negligible, no adjustment for age is needed during restorative MPFL surgery in growing children. Clinical Relevance: As there is neglible change in location of the origin of the MCL relative to the distal femoral physis during skeletal growth in both boys and girls, no adjustment for patient age is necessary when using the origin of the MCL as a landmark to locate the site of femoral reattachment of a disrupted MPFL.

The liver is the largest organ in the abdomen taking up a relatively greater area in infants and young children. It is a unique organ with a dual blood supply and amazing regenerative capacity. The liver has a number of important functions with regard metabolism, detoxification, and immune function. The internal anatomy of this organ is orderly and highly structured around the basic functional unit--the hepatic lobule and portal triad. Numerous pathologic conditions can involve the liver. In this article, we will focus on etiologic, clinical, and cross-sectional imaging features of several childhood congenital and acquired disorders of one component of the portal triad--the biliary system.

Various congenital and acquired disorders can affect the upper extremity in pediatric and adolescent patients. MR imaging can provide unique anatomic and diagnostic information in the evaluation of many of these disorders, including inflammatory, infectious, neoplastic, and arthritic conditions. This article rounds out the issue on pediatric musculoskeletal MR imaging. It focuses on the evaluation of more common congenital disorders, and mainly sports-related injuries of the shoulder, elbow, and wrist in children. MR imaging can be more challenging in diagnosis of some of these disorders. Features of overuse injuries in skeletally immature athletes are a unifying theme throughout the article.

The original Virginia family with X-linked muscular dystrophy with early contractures and cardiomyopathy (Emery-Dreifuss type) has been reinvestigated 25 years later. The findings confirm that a cardiomyopathy, presenting most often as atrioventricular block, is a significant feature of the disease, which is characterized by the triad of: 1) slowly progressive muscle wasting and weakness with a humero-peroneal distribution in the early stages; 2) early contractures of the elbows, Achilles tendons, and post-cervical muscles; and 3) a cardiomyopathy usually presenting as heart block (some female carriers may also develop heart block). Other reported families with X-linked Emery-Dreifuss muscular dystrophy as well as a rare autosomal variant are reviewed, and differentiation from scapulo-peroneal muscular dystrophy and the rigid spine syndrome is discussed.

In a survey carried out to determine the incidence of Duchenne muscular dystrophy in the South East of Scotland, 47 cases were ascertained among 177,413 live male births for the years 1953 to 1968. The overall incidence is 1 case in 3,775 live male births (26.5 +/- 3.2 X 10(-5)). This incidence figure has been compared with those reported in nine other studies, and any differences appear likely to be due to varying degrees of ascertainment. So far there is no evidence of any decrease in incidence of the disease in S.E. Scotland as a result of genetic counselling and antenatal foetal sexing.

One possible explanation for the apparently high birth incidence of Duchenne muscular dystrophy (DMD), a lethal X-linked disorder, is genetic heterogeneity. As a first step in possibly demonstrating genetic heterogeneity, affected boys were sub-divided into those with and without severe mental handicap. In those with severe mental handicap, ages at onset and of becoming confined to a wheelchair were later, the fall in SCK level with age was less marked, and the urinary excretion of certain aminoacids was greater than in affected boys with normal intelligence. Though the number of subjects investigated was relatively small (15 in each group) and further studies are therefore needed, the results suggest that DMD may not be a single disease entity.

Ten extensive families with benign (Becker type) X-linked muscular dystrophy have been studied, in which there was a total of 67 affected males. Reliable information was available on 41 of these males, 29 of whom were alive at the time of the study. The disorder was characterised by a predominantly proximal myopathy, associated with pseudohypertrophy of the calf muscles, particularly in the early stages of the disease. The early development of contractures was not a feature of the disease in these families and cardiac involvement, when present, was a late manifestation. The clinical findings in these patients are discussed in detail and compared with those in a large unselected group of patients with Duchenne muscular dystrophy. The results indicate that the best criterion for distinguishing between these two disorders is the age of becoming chair-bound. Electrocardiographic studies revealed no consistent abnormality and no evidence of an abnormal algebraic sum of the R and S waves in lead Vi, as is found in patients with Duchenne muscular dystrophy. Serum creatine kinase levels are significantly elevated, particularly in the early stages of the disease, and in this way preclinical cases may be identified.

In tissue culture of muscle from five normal foetuses and four male foetuses at risk for Duchenne muscular dystrophy, no differences were found with regard to the ease with which cultures could be established and maintained, or in gross morphology or rate of growth and differentiation in culture. Yet before culture, muscle histology was clearly abnormal in at least one of the at-risk foetuses. The identification of the particular conditions of culture which prevent the full expression of the dystrophic process might be profitably pursued as a possible first step to finding a treatment.

Quadriceps muscle samples taken from four therapeutically aborted male fetuses (16 to 21 weeks gestation) at risk of developing Duchenne muscular dystrophy have been examined histologically. Two of the four samples were indistinguishable from normal fetal muscle of comparable gestation. A slight increase in variability of fibre size and in mean fibre diameter was found in the third fetus. The fourth fetus, of 16 weeks gestation, showed a marked increase in variability of fibre size and in mean fibre diameter. There was also a significant number of hyaline fibres present. These changes are so similar to those reported in early pre-clinical Duchenne muscular dystrophy, that it is suggested they represent the earliest histological signs of the disorder which is already manifest in utero.

A form of spinal muscular atrophy (S. M. A.) intermediate in severity between the infantile (Werd-nig-Hoffmann or type I) and juvenile (Kugelberg-Welander or type III) forms of this disease has been defined. This is referred to as intermediate or type II S. M. A. and is characterized by proximal muscle weakness with onset usually between 3 and 15 months and survival beyond 4 years and usually into adolescence or later. The finclings in 14 patients with this type of S. M. A. are described. It seems possible that it is inherited as an autosomal recessive trail.

In the mid 1990s, the fast spin-echo (FSE) and turbo spin-echo (TSE) T2-weighted (T2-W) sequences became available and are now widely accepted alternatives to conventional spin-echo sequences since they result in reduced acquisition times while maintaining tissue contrast. Since that time, there has been continued development of new sequences to further decrease acquisition times, minimize artifacts, and preserve lesion detection. The purpose of this pictorial essay is to qualitatively illustrate the newly available fast recovery (FR) FSE T2-W MR images of the abdomen compared with the images acquired using the routine FSE T2-W sequence in non-breath-hold studies in children.

We report a neonate with 4S neuroblastoma and MYCN amplification, but favorable Shimada histology, successfully treated with chemotherapy and 13-cis-retinoic acid without stem cell transplantation. MYCN amplification in neuroblastoma is usually associated with unfavorable Shimada histology; the presence of these features in infants with 4S disease confers a poor prognosis. A small number of infants with 4S neuroblastoma and MYCN amplification have favorable Shimada histology. In this subgroup of infants, histopathology may be equally important in predicting outcome.

Chapter 3 explores the first systematic study of the condition by Edward Meryon in the early 1850s. He lived during a very interesting period in English history, namely from 1807 to 1880, a time when much was changing in society and in the practice of medicine.

Chapter 9 attempts to resolve problems of heterogeneity are described as the situation appeared when this resource was first published in 1995.

Chapter 1 discusses the history of Duchenne muscular dystrophy, a serious condition and the second most common genetic disorder in many countries. Its cause was unknown until relatively recently and there has been no effective treatment. However, the responsible gene and its protein product have now been identified and gene therapy is under serious consideration.

Chapter 11 discusses ideas of pathogenesis and how at the beginning, the field of research of the disease was dominated by neurologists.

Chapter 12 discusses finding the basic biochemical defect in a disorder by first identifying the mutant gene itself, which was a quantum leap in the study and understanding of genetic disorders.

Chapter 4 discusses the life of Edward Meryon (1807–1880).

Chapter 7 discusses the problem of heterogeneity and the attempts that were made to resolve it.

Chapter 8 discusses the evidence available by the end of the last century that there was more than one type of dystrophy and the subsequent problem of classifying them.

Chapter 5 discusses Guillaume Benjamin Amand Duchenne, or Duchenne de Boulogne, who played a singularly important role in the history of muscular dystrophy.

This resource traces the history of Duchenne Muscular Dystrophy in detail along with a commentary of Edward Meryon's research, which has led to our current understanding of the disease, with full references and informative, historically relevant illustrations.

Chapter 2 discusses how Duchenne muscular dystrophy was observed and perhaps even recorded in earlier times.

Chapter 13 briefly summarizes some of the current areas of research and future possibilities with regard to the muscular dystrophies as a group of related conditions.