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Skeletal Radiology Apr 2019Following the thalidomide disaster (1958-62), Henkel and Willert analysed the pattern of dysmelia in the long bones (J Bone Joint Surg Br. 51:399-414, 1969) and the... (Review)
Review
BACKGROUND
Following the thalidomide disaster (1958-62), Henkel and Willert analysed the pattern of dysmelia in the long bones (J Bone Joint Surg Br. 51:399-414, 1969) and the extremities, Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970). Willert's material from deformed extremities is re-examined here asking "How does thalidomide reduce the skeleton?"
MATERIALS AND METHODS
We reviewed the original data collection of Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970), comprising musculoskeletal histology slides from 30 children affected by thalidomide with radiographs of hands (19 cases) and feet (4 cases).
RESULTS
All original observations by Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970), were verified. Radial rays of the hand disappeared early, but the foot was spared until late. Radiology confirms that bone reduction in the hand (aplasia or hypoplasia in the thumb and index finger) coincides with sensory segmental nerve C6. In the foot, reduction of the toes is rare, but mesenchymal excess (polydactyly) occurs in the hallux (L5 sclerotome), usually associated with absent tibia (L4 sclerotome). Histology confirms skeletal mesenchymal components to be unremarkable, contrasting with grossly abnormal bony architecture, a striking discordance between microscopic and macroscopic findings. No necrosis or vascular pathology was seen.
CONCLUSION
The basic lesion was an abnormal quantity rather than quality of mesenchyme. Cell populations result from cellular proliferation, controlled in early limb bud formation by neurotrophism. Thalidomide is a known sensory neurotoxin in adults. In the embryo, sensorineural injury alters neurotrophism, causing increased or diminished cell proliferation in undifferentiated mesenchyme. Differentiation into normal cartilage occurs later, but within an altered mesenchymal mass. Reduction or excess deformity results, with normal histology, a significant finding. The primary pathological condition is not in the skeleton, but in the nerves.
Topics: Abnormalities, Drug-Induced; Extremities; Humans; Infant, Newborn; Limb Deformities, Congenital; Peripheral Nervous System Diseases; Thalidomide
PubMed: 30341712
DOI: 10.1007/s00256-018-3086-2 -
Italian Journal of Pediatrics Jun 2021Positional plagiocephaly frequently affects healthy babies. It is hypothesized that manual therapy tailored to pediatrics is more effective in improving plagiocephalic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Positional plagiocephaly frequently affects healthy babies. It is hypothesized that manual therapy tailored to pediatrics is more effective in improving plagiocephalic cranial asymmetry than just repositioning and sensory and motor stimulation.
METHODS
Thirty-four neurologically healthy subjects aged less than 28 weeks old with a difference of at least 5 mm between cranial diagonal diameters were randomly distributed into 2 groups. For 10 weeks, the pediatric integrative manual therapy (PIMT) group received manual therapy plus a caregiver education program, while the controls received the same education program exclusively. Cranial shape was evaluated using anthropometry; cranial index (CI) and cranial vault asymmetry index (CVAI) were calculated. Parental perception of change was assessed using a visual analogue scale (- 10 cm to + 10 cm).
RESULTS
CVAI presented a greater decrease in PIMT group: 3.72 ± 1.40% compared with 0.34 ± 1.72% in the control group (p = 0.000). CI did not present significant differences between groups. Manual therapy led to a more positive parental perception of cranial changes (manual therapy: 6.66 ± 2.07 cm; control: 4.25 ± 2.31 cm; p = 0.004).
CONCLUSION
Manual therapy plus a caregiver education program improved CVAI and led to parental satisfaction more effectively than solely a caregiver education program.
TRIAL REGISTRATION
Trial registration number: NCT03659032 ; registration date: September 1, 2018. Retrospectively registered.
Topics: Cephalometry; Female; Humans; Infant; Infant, Newborn; Male; Musculoskeletal Manipulations; Plagiocephaly, Nonsynostotic
PubMed: 34090515
DOI: 10.1186/s13052-021-01079-4 -
Trends in Biotechnology Feb 2014Clinicians and scientists working in the field of regenerative engineering are actively investigating a wide range of methods to promote musculoskeletal tissue... (Review)
Review
Clinicians and scientists working in the field of regenerative engineering are actively investigating a wide range of methods to promote musculoskeletal tissue regeneration. Small-molecule-mediated tissue regeneration is emerging as a promising strategy for regenerating various musculoskeletal tissues and a large number of small-molecule compounds have been recently discovered as potential bioactive molecules for musculoskeletal tissue repair and regeneration. In this review, we summarize the recent literature encompassing the past 4 years in the area of small bioactive molecules for promoting repair and regeneration of various musculoskeletal tissues including bone, muscle, cartilage, tendon, and nerve.
Topics: Drug Discovery; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Regenerative Medicine
PubMed: 24405851
DOI: 10.1016/j.tibtech.2013.12.002 -
European Cells & Materials Jan 2015Foetal movements commence at seven weeks of gestation, with the foetal movement repertoire including twitches, whole body movements, stretches, isolated limb movements,... (Review)
Review
Foetal movements commence at seven weeks of gestation, with the foetal movement repertoire including twitches, whole body movements, stretches, isolated limb movements, breathing movements, head and neck movements, jaw movements (including yawning, sucking and swallowing) and hiccups by ten weeks of gestational age. There are two key biomechanical aspects to gross foetal movements; the first being that the foetus moves in a dynamically changing constrained physical environment in which the freedom to move becomes increasingly restricted with increasing foetal size and decreasing amniotic fluid. Therefore, the mechanical environment experienced by the foetus affects its ability to move freely. Secondly, the mechanical forces induced by foetal movements are crucial for normal skeletal development, as evidenced by a number of conditions and syndromes for which reduced or abnormal foetal movements are implicated, such as developmental dysplasia of the hip, arthrogryposis and foetal akinesia deformation sequence. This review examines both the biomechanical effects of the physical environment on foetal movements through discussion of intrauterine factors, such as space, foetal positioning and volume of amniotic fluid, and the biomechanical role of gross foetal movements in human skeletal development through investigation of the effects of abnormal movement on the bones and joints. This review also highlights computational simulations of foetal movements that attempt to determine the mechanical forces acting on the foetus as it moves. Finally, avenues for future research into foetal movement biomechanics are highlighted, which have potential impact for a diverse range of fields including foetal medicine, musculoskeletal disorders and tissue engineering.
Topics: Biomechanical Phenomena; Computer Simulation; Fetal Movement; Gestational Age; Humans; Models, Biological; Musculoskeletal Abnormalities
PubMed: 25552425
DOI: 10.22203/ecm.v029a01 -
American Journal of Medical Genetics.... May 2017Craniosynostosis, the premature ossification of one or more skull sutures, is a clinically and genetically heterogeneous congenital anomaly affecting approximately one... (Review)
Review
Craniosynostosis, the premature ossification of one or more skull sutures, is a clinically and genetically heterogeneous congenital anomaly affecting approximately one in 2,500 live births. In most cases, it occurs as an isolated congenital anomaly, that is, nonsyndromic craniosynostosis (NCS), the genetic, and environmental causes of which remain largely unknown. Recent data suggest that, at least some of the midline NCS cases may be explained by two loci inheritance. In approximately 25-30% of patients, craniosynostosis presents as a feature of a genetic syndrome due to chromosomal defects or mutations in genes within interconnected signaling pathways. The aim of this review is to provide a detailed and comprehensive update on the genetic and environmental factors associated with NCS, integrating the scientific findings achieved during the last decade. Focus on the neurodevelopmental, imaging, and treatment aspects of NCS is also provided.
Topics: Congenital Abnormalities; Cranial Sutures; Craniosynostoses; Humans; Ossification, Heterotopic; Phenotype
PubMed: 28160402
DOI: 10.1002/ajmg.a.38159 -
Current Osteoporosis Reports Sep 2014The normal human chromosome complement consists of 46 chromosomes comprising 22 morphologically different pairs of autosomes and one pair of sex chromosomes. Variations... (Review)
Review
The normal human chromosome complement consists of 46 chromosomes comprising 22 morphologically different pairs of autosomes and one pair of sex chromosomes. Variations in either chromosome number and/or structure frequently result in significant mental impairment and/or a variety of other clinical problems, among them, altered bone mass and strength. Chromosomal syndromes associated with specific chromosomal abnormalities are classified as either numerical or structural and may involve more than one chromosome. Aneuploidy refers to the presence of an extra copy of a specific chromosome, or trisomy, as seen in Down's syndrome (trisomy 21), or the absence of a single chromosome, or monosomy, as seen in Turner syndrome (a single X chromosome in females: 45, X). Aneuploidies have diverse phenotypic consequences, ranging from severe mental retardation and developmental abnormalities to increased susceptibility to various neoplasms and premature death. In fact, trisomy 21 is the prototypical aneuploidy in humans, is the most common genetic abnormality associated with longevity, and is one of the most widespread genetic causes of intellectual disability. In this review, the impact of trisomy 21 on the bone mass, architecture, skeletal health, and quality of life of people with Down syndrome will be discussed.
Topics: Down Syndrome; Humans; Musculoskeletal Abnormalities; Osteoarthritis, Spine; Osteoporosis
PubMed: 24980541
DOI: 10.1007/s11914-014-0221-4 -
Osteoporosis International : a Journal... Dec 2018Notch (Notch1 through 4) are transmembrane receptors that play a fundamental role in cell differentiation and function. Notch receptors are activated following... (Review)
Review
Notch (Notch1 through 4) are transmembrane receptors that play a fundamental role in cell differentiation and function. Notch receptors are activated following interactions with their ligands in neighboring cells. There are five classic ligands termed Jagged (Jag)1 and Jag2 and Delta-like (Dll)1, Dll3, and Dll4. Recent work has established Notch as a signaling pathway that plays a critical role in the differentiation and function of cells of the osteoblast and osteoclast lineages and in skeletal development and bone remodeling. The effects of Notch are cell-context dependent, and the four Notch receptors carry out specific functions in the skeleton. Gain- and loss-of-function mutations of components of the Notch signaling pathway result in a variety of congenital disorders with significant craniofacial and skeletal manifestations. The Notch ligand Jag1 is a determinant of bone mineral density, and Notch plays a role in the early phases of fracture healing. Alterations in Notch signaling are associated with osteosarcoma and with the metastatic potential of carcinoma of the breast and of the prostate. Controlling Notch signaling could prove useful in diseases of Notch gain-of-function and in selected skeletal disorders. However, clinical data on agents that modify Notch signaling are not available. In conclusion, Notch signaling is a novel pathway that regulates skeletal homeostasis in health and disease.
Topics: Abnormalities, Multiple; Bone Diseases; Bone Neoplasms; Bone Remodeling; Humans; Osteoblasts; Osteoclasts; Receptors, Notch; Signal Transduction; Skeleton
PubMed: 30194467
DOI: 10.1007/s00198-018-4694-3 -
Human Mutation Jul 2022Different pathogenic variants in the fibrillin-1 gene (FBN1) cause Marfan syndrome and acromelic dysplasias. Whereas the musculoskeletal features of Marfan syndrome... (Review)
Review
Different pathogenic variants in the fibrillin-1 gene (FBN1) cause Marfan syndrome and acromelic dysplasias. Whereas the musculoskeletal features of Marfan syndrome involve tall stature, arachnodactyly, joint hypermobility, and muscle hypoplasia, acromelic dysplasia patients present with short stature, brachydactyly, stiff joints, and hypermuscularity. Similarly, pathogenic variants in the fibrillin-2 gene (FBN2) cause either a Marfanoid congenital contractural arachnodactyly or a FBN2-related acromelic dysplasia that most prominently presents with brachydactyly. The phenotypic and molecular resemblances between both the FBN1 and FBN2-related disorders suggest that reciprocal pathomechanistic lessons can be learned. In this review, we provide an updated overview and comparison of the phenotypic and mutational spectra of both the "tall" and "short" fibrillinopathies. The future parallel functional study of both FBN1/2-related disorders will reveal new insights into how pathogenic fibrillin variants differently affect the fibrillin microfibril network and/or growth factor homeostasis in clinically opposite syndromes. This knowledge may eventually be translated into new therapeutic approaches by targeting or modulating the fibrillin microfibril network and/or the signaling pathways under its control.
Topics: Brachydactyly; Fibrillin-1; Fibrillin-2; Humans; Marfan Syndrome; Musculoskeletal Abnormalities; Phenotype
PubMed: 35419902
DOI: 10.1002/humu.24383 -
Reumatologia Clinica 2015
Topics: Diagnosis, Differential; Diagnostic Errors; Female; Fractures, Compression; Humans; Magnetic Resonance Imaging; Middle Aged; Musculoskeletal Abnormalities; Osteoporotic Fractures; Spinal Fractures; Thoracic Vertebrae
PubMed: 24582140
DOI: 10.1016/j.reuma.2014.01.001 -
Orthopaedic Surgery Oct 2019Os acromiale is a developmental defect which results from the lack of an osseous union between the ossification centers of the acromion, leading to the... (Review)
Review
Os acromiale is a developmental defect which results from the lack of an osseous union between the ossification centers of the acromion, leading to the fibrocartilaginous tissue connection. The prevalence of os acromiale is 1% to 15%, and is quite common in the African American population. Os acromiale in adults is easily diagnosed by symptoms and X-ray, particularly on the axillary view; however, the differential diagnosis of adolescents may require MRI or SPECT-CT. Generally, nonoperative therapy for symptomatic os acromiale should be started, including physiotherapy, nonsteroidal anti-inflammatory drugs, and injections. Surgical treatment is indicated after failed conservative treatment. In symptomatic patients with fixable acromiale, the tension band technique should be used to make the anterior aspect of the acromion elevated from the humerus head. In patients with small fragments which are unsuitable for reattachment, excision might be the best therapeutic option and lead to good outcomes. Whether using internal fixation or resection, the arthroscopic technique results in a better outcome and fewer complications, especially in older patients or athletes with overhead movement, because of the high incidence of shoulder impingement or rotator cuff tears which can be treated concurrently.
Topics: Acromion; Arthroscopy; Diagnosis, Differential; Humans; Internal Fixators; Musculoskeletal Abnormalities; Radiography
PubMed: 31486589
DOI: 10.1111/os.12518