Papers by William McAlister
Journal of Bone and Mineral Research, 2015
Heritable disorders that feature high bone mass (HBM) are rare. The etiology is typically a mutat... more Heritable disorders that feature high bone mass (HBM) are rare. The etiology is typically a mutation(s) within a gene that regulates the differentiation and function of osteoblasts (OBs) or osteoclasts (OCs). Nevertheless, the molecular basis is unknown for approximately one-fifth of such entities. NF-κB signaling is a key regulator of bone remodeling and acts by enhancing OC survival while impairing OB maturation and function. The NF-κB transcription complex comprises five subunits. In mice, deletion of the p50 and p52 subunits together causes osteopetrosis (OPT). In humans, however, mutations within the genes that encode the NF-κB complex, including the Rela/p65 subunit, have not been reported. We describe a neonate who died suddenly and unexpectedly and was found at postmortem to have HBM documented radiographically and by skeletal histopathology. Serum was not available for study. Radiographic changes resembled malignant OPT, but histopathological investigation showed morphologically normal OCs and evidence of intact bone resorption excluding OPT. Furthermore, mutation analysis was negative for eight genes associated with OPT or HBM. Instead, accelerated bone formation appeared to account for the HBM. Subsequently, trio-based whole exome sequencing revealed a heterozygous de novo missense mutation (c.1534_1535delinsAG, p.Asp512Ser) in exon 11 of RELA encoding Rela/p65. The mutation was then verified using bidirectional Sanger sequencing. Lipopolysaccharide stimulation of patient fibroblasts elicited impaired NF-κB responses compared with healthy control fibroblasts. Five unrelated patients with unexplained HBM did not show a RELA defect. Ours is apparently the first report of a mutation within the NF-κB complex in humans. The missense change is associated with neonatal osteosclerosis from in utero increased OB function rather than failed OC action. These findings demonstrate the importance of the Rela/p65 subunit within the NF-κB pathway for human skeletal homeostasis and represent a new genetic cause of HBM. © 2015 American Society for Bone and Mineral Research.
Medicine, 1993
Spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of skeletal disorders that ca... more Spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of skeletal disorders that can have a genetic basis, but their classification and prognostication suffer because few families have been extensively studied. We describe a large kindred affected by a unique type of SEMD that is transmitted as an autosomal dominant trait. The propositus and his affected brother and first cousin were evaluated as inpatients. Other kindred members were screened by telephone interviews and lateral thoraco-lumbar spine radiographs, and then, in most cases, investigated by additional x-ray studies. Of the 29 living members of the kindred, 22 were studied radiologically. Among the 22 subjects investigated, 15 were affected, and the status of 1 individual with minor changes on x-ray was indeterminate. The deceased patriarch was presumed to be affected. These 16 affected subjects could usually, but not invariably, be distinguished from their unaffected sex-matched siblings by their smaller he...
AJNR. American journal of neuroradiology, 1994
To measure diagnostic performance and preference of two three-dimensional CT reconstruction modal... more To measure diagnostic performance and preference of two three-dimensional CT reconstruction modalities (voxel-gradient and surface-projection) displayed two ways (conventional and unwrapped) in craniosynostosis confirmed by surgical inspection and histologic analysis of resected sutures. High-resolution 2-mm contiguous CT sections were obtained and three-dimensional reconstruction images generated for 25 infants and children with skull deformities before surgical treatment of craniosynostosis. Two pediatric radiologists and two neuroradiologists first ranked images by their own preferences for diagnostic use. Then they diagnosed craniosynostosis from images presented in random order and blinded. The standard of reference was inspection during surgery and histologic evaluation of excised sutures. Finally, reviewers repeated their subjective preference tests. The least experienced radiologist had 100% sensitivity for all imaging modalities and specificities ranging from 43% to 83%. Th...
Pediatric Radiology, 1985
A young infant with vomiting associated with a gastric polyp is presented. The polyp proved to be... more A young infant with vomiting associated with a gastric polyp is presented. The polyp proved to be focal foveolar hyperplasia. These non-neoplastic polyps of unknown etiology are usually found in adults.
Pediatric Radiology, 2008
Cystic adenomyosis is a rare form of adenomyosis of the uterine myometrium that has been describe... more Cystic adenomyosis is a rare form of adenomyosis of the uterine myometrium that has been described in older adults. This condition has not previously been reported in the pediatric radiology literature. In this case report, we describe an adenomyotic cyst in an adolescent girl that was imaged with US, CT, and MR and proved by surgical pathology. Understanding of the radiologic features of cystic adenomyosis is important for noninvasive diagnosis and effective medical/surgical management.
New England Journal of Medicine, 1970
Original Article from The New England Journal of Medicine Endochondral Ossification in Achondro... more Original Article from The New England Journal of Medicine Endochondral Ossification in Achondroplastic Dwarfism.
The Journal of Pediatrics, 1974
Journal of Pediatric Orthopaedics, 1999
We evaluated the anatomic and functional consequences of psoas lengthening during operative inter... more We evaluated the anatomic and functional consequences of psoas lengthening during operative intervention for developmental dislocation of the hip (DDH). Possible anatomic changes were assessed by magnetic resonance imaging (MRI), and functional assessment included strength determination by an isokinetic dynamometer and gait analysis. Six girls and one boy, ranging in age from 15 to 20 months, had operative reduction of a unilateral DDH. One closed and six open reductions (three anteromedial and three anterolateral approaches) were performed. Follow-up ranged from 4 years 0 months to 9 years 2 months. The cross-sectional area determined by MRI of the lengthened psoas muscles was markedly reduced for all of the six open-reduction patients (three moderate and three severe). Atrophy of the iliacus muscle also was apparent by MRI in five of the six open-reduction patients. Maximum flexion torque, as determined by the isokinetic dynamometer, was diminished on the DDH side for the three patients whose hips were reduced open through the anteromedial approach. Average hip-flexion torque over the entire range of motion was decreased for both anteromedial and anterolateral groups on the operated-on side. Lengthening of the psoas tendon during open reduction of a DDH is associated with considerable atrophy of the psoas muscle.
The Journal of Clinical Endocrinology & Metabolism, 1977
A recent study using the photon absorption technique has revealed a high frequency of significant... more A recent study using the photon absorption technique has revealed a high frequency of significant bone loss in diabetic adults regardless of age or duration of diabetes. In this study 107 diabetic children age 4-18 were studied using cortical bone thickness and skeletal maturation as ...
Human Genetics, 2003
Human paternal uniparental disomy for chromosome 14 (upd(14)pat) presents with skeletal abnormali... more Human paternal uniparental disomy for chromosome 14 (upd(14)pat) presents with skeletal abnormalities, joint contractures, dysmorphic facial features and developmental delay/mental retardation. Distal human chromosome 14 (HSA14) is homologous to distal mouse chromosome 12 (MMU12) and both regions have been shown to contain imprinted genes. In humans, consistent radiographic findings include a narrow, bell-shaped thorax with caudal bowing of the anterior ribs, cranial bowing of the posterior ribs and flaring of the iliac wings without shortening or dysplasia of the long bones. Mice with upd(12)pat have thin ribs with delayed ossification of the sternum, skull and feet. In both mice and humans, the axial skeleton is predominantly affected. We hypothesize that there is an imprinted gene or genes on HSA14/MMU12 that specifically affects rib/thorax development and the maturation of ossification centers in the sternum, feet and skull with little effect on long bone development.
Bone, 2009
p = 0.006; and femoral neck BMD, rs16948767 (females only, MAF = 0.008), p = 0.004. There was no ... more p = 0.006; and femoral neck BMD, rs16948767 (females only, MAF = 0.008), p = 0.004. There was no association between the promoter polymorphisms and fracture, but an association was observed with femoral neck BMD in females (p = 0.035).
American Journal of Roentgenology, 1987
Forty-three control patients (neonate to 17 years old) were studied by upper gastrointestinal ser... more Forty-three control patients (neonate to 17 years old) were studied by upper gastrointestinal series to determine the position of key duodenal landmarks and the mobility of the duodenojejunal flexure with manual displacement. These results were compared with the duodenal positions of 35 children of similar ages with surgically documented malrotation. Nine criteria were identified as a useful means of detecting subtle abnormalities of duodenal position. The normal duodenojejunal flexure was found to be readily displaceable in neonates and could be pushed to the right of the spine in over two-thirds of patients less than 4 months old. Over 4 years of age, mobility was very limited. A mobile duodenum discovered on fluoroscopic examination or by positioning of a transpyloric feeding tube should not be considered indicative of malrotation in infancy.
American Journal of Roentgenology, 1989
We performed a prospective study of 70 infants and children with recurrent sinusitis. We compared... more We performed a prospective study of 70 infants and children with recurrent sinusitis. We compared plain radiographs with coronal CT scans of the sinuses to determine if plain radiographs can be used to accurately diagnose and localize residual sinus disease amenable to endoscopic surgery. This residual disease is thought to be important in the pathogenesis of recurrences of sinusitis. The patients were taking antibiotics and were clinically well at the time of the two examinations (performed on the same day). Findings on slightly over 80% of the CT scans were abnormal. In about 75% of the patients, the findings on plain radiographs did not correlate with those on CT scans. About 45% of the patients had normal findings on plain radiographs of at least one sinus with an abnormality of that sinus shown on CT scans. Almost 35% of the patients had what was interpreted as an abnormality of at least one sinus on plain radiographs, but that sinus was normal on CT scans. Sinusitis in infants and children is often underdiagnosed or overdiagnosed on the basis of findings on plain radiographs of the sinuses. Plain radiographs cannot be used to determine the need for, or to guide, endoscopic surgery on the sinuses.
The American Journal of Medicine, 1980
Three adult sisters with osteopetrosis in infancy had spontaneous resolution of bone modeling def... more Three adult sisters with osteopetrosis in infancy had spontaneous resolution of bone modeling defects and osteosclerosis. During adolescence, basal ganglia calcification developed in two. Renal tubular acidosis (type I) was diagnosed in each during early adulthood. The disorder was transmitted apparently as a recessive trait--the same mode of inheritance as for the "malignant" form of osteopetrosis which is usually fatal during childhood. Electron microscopy of bone suggested that osteoclasts failed to form "ruffled membranes" characteristic of active bone resorbing cells. Chronic systemic acidosis may have ameliorated the skeletal manifestations of this new syndrome.
Journal of the American Optometric Association
Cardiopulmonary resuscitation (CPR) certification requirements for optometric licensure were obta... more Cardiopulmonary resuscitation (CPR) certification requirements for optometric licensure were obtained from 49 states, the District of Columbia and Puerto Rico. It was found that 17 percent of the states required CPR certification for optometric licensure while 11 percent required certification to maintain licensure. For initial Diagnostic Pharmaceutical Agents (DPA) licensing 44 percent of the boards required CPR certification while less than 25 percent required maintaining that certification to sustain DPA licensure. Of those states having Therapeutic Pharmaceutical Agents (TPA) legislation, 36 percent required CPR certification for initial licensure but only 8 percent of them required maintenance of certification for license renewal. Optometry can take the lead in health care by requiring CPR certification for all forms of licensure and license renewal.
Background: Hypophosphatasia (HPP) is a rare, heritable, meta- bolic bone disease due to deficien... more Background: Hypophosphatasia (HPP) is a rare, heritable, meta- bolic bone disease due to deficient activity of the tissue-nonspecific isoenzymeofalkalinephosphatase.Theinfantileformfeaturessevere rickets often causing death in the first year of life from respiratory complications. There is no established medical treatment. In 1997, an 8-month-old girl with worsening and life-threatening infantile HPP improved considerably after marrow cell transplantation. Objective: Our aim was to
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2015
PURPOSE. Soldiers assigned overseas must meet vision standards to be considered deployable. Those... more PURPOSE. Soldiers assigned overseas must meet vision standards to be considered deployable. Those who do not meet standards without correction are required to have two pairs of spectacles and one pair of protective mask inserts. The U.S. Army Center for Health Promotion and Preventive Medicine (CHPPM) defines visually ready as having vision necessary to meet job standards, and optically ready as possessing all required optical devices. If soldiers do not maintain visual and optical readiness, last-minute preparations can be inefficient and time-consuming, potentially causing delayed deployment and logistical problems in fabricating and delivering eyewear. In a pilot study conducted by optometrists from CHPPM-Europe, results from two Soldier Readiness Program (SRP) exercises in Kaiserslautern, Germany, indicated that 2.5% of soldiers were not visually ready and 23% were not optically ready. METHODS. Unit commanders were advised that soldiers would continue to be required to prove the...
Uploads
Papers by William McAlister