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Journal of Oral Biology and... 2022The conventional surgical procedures for the closure of cleft-lip and palate are based on proven plastic-surgical procedures from tumour surgery or traumatology. These...
Cleft lip, alveolus and palate: Defect or dislocation malformation? Importance of adopting a physiological concept for surgical repair in achieving optimal outcomes in LMICs. Part 1: Physiological processes in facial development.
The conventional surgical procedures for the closure of cleft-lip and palate are based on proven plastic-surgical procedures from tumour surgery or traumatology. These flap surgeries take little account of the fact that the treatment of such malformations takes place during the time of a child's increased growth and is known to lead to pronounced scarring and skeletal growth disorders. It is therefore imperative to develop modified surgical procedures based on physiological growth processes. These physiological procedures must include the reconstruction of all facial structures such as orofacial, palatal and pharyngeal muscles, complete nose, upper jaw and palate. Transfer of this know how to low resource LMIC and training is essential if optimal outcomes are to be achieved.
PubMed: 34820255
DOI: 10.1016/j.jobcr.2021.11.001 -
JIMD Reports 2013In 2010, we reported the successful clinical outcome related to a 20-month course of intravenous, cyclical ceftriaxone, in a patient with adult-onset Alexander's...
In 2010, we reported the successful clinical outcome related to a 20-month course of intravenous, cyclical ceftriaxone, in a patient with adult-onset Alexander's disease. We now provide evidence that the progression of the patient's signs/symptoms was halted and reversed with a 4-year-long extension of the trial.The patient's clinical signs/symptoms were evaluated before the start and every 6 months for 6 years. For the early 2 years, without therapy, and for the following 4 years, after intravenous ceftriaxone 2 g daily, for 3 weeks monthly during the initial 4 months, then for 15 days monthly.Gait ataxia and dysarthria were assessed clinically on a 0 to 4 scale. Palatal myoclonus and nystagmus/oscillopsia were monitored by videotape and a self-evaluation scale. The degree of disability, measured by a modified Rankin scale, and the brain MRI were periodically evaluated.Before ceftriaxone therapy, in a 2-year period, gait ataxia and dysarthria worsened from mild to marked, palatal myoclonus spread from the soft palate to lower facial muscles, and the patient complained of oscillopsia. After 4 years of ceftriaxone therapy, gait ataxia and dysarthria improved, from marked to mild at clinical rating scales. The palatal myoclonus was undetectable; the patient did not complained of oscillopsia and declared a progressively better quality of life. Ceftriaxone was safe.This case report provides Class IV evidence that intravenous cycles of ceftriaxone may halt and/or reverse the progression of neurodegeneration in patients with adult-onset Alexander's disease and may significantly improve their quality of life.
PubMed: 23430549
DOI: 10.1007/8904_2012_180 -
Anatomical Record (Hoboken, N.J. : 2007) Nov 2018Although minor salivary glands play a significant functional role in the oral cavity, their developmental morphology and cell differentiation has been scarcely studied....
Although minor salivary glands play a significant functional role in the oral cavity, their developmental morphology and cell differentiation has been scarcely studied. This study aimed to describe the development of rat palatine glands with regard to the ultrastructural morphology of the secretory cells and surrounding myoepithelial cells (MECs). Palatine glands from rats at embryonic ages (E) 18 and 20 days, and postnatal days (PN) 0, 3, 7, 10, 13, 21, 30, 42, and 60 were fixed and prepared for morphological analysis and immunocytochemical labeling of alpha-smooth muscle actin (α-SMA). At E18, epithelial cords were observed extending from the palatal epithelium and showed negative reactivity to α-SMA. After luminization at E20, the cells of immature acini accumulated secretory granules of various densities: electron-dense, electron-lucent and some empty-appearing granules. MECs were poorly differentiated at E20 and exhibited only slight α-SMA expression. At birth, mucous and serous cells were typically located around a common lumen. Thereafter, serous cells began to move to the periphery to form demilunes by PN7. The mucous secretory granules of intermediate electron density became predominant around PN13. At PN21, these granules were dramatically reduced in number and most of the acini in adults contained acinar cells with numerous electron-lucent granules, and a few serous demilune cells with electron-dense granules. After birth, MECs progressively accumulated actin microfilaments until prominent α-SMA expressing MECs invested the acini and the proximal part of the intercalated ducts in the adult. Anat Rec, 301:1820-1833, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Animals; Animals, Newborn; Embryonic Development; Female; Male; Microscopy, Electron; Palate; Rats; Rats, Sprague-Dawley; Salivary Glands
PubMed: 30290073
DOI: 10.1002/ar.23927 -
Frontiers in Physiology 2016Defects in mid-facial development, including cleft lip/palate, account for a large number of human birth defects annually. In many cases, aberrant gene expression...
Defects in mid-facial development, including cleft lip/palate, account for a large number of human birth defects annually. In many cases, aberrant gene expression results in either a reduction in the number of neural crest cells (NCCs) that reach the frontonasal region and form much of the facial skeleton or subsequent failure of NCC patterning and differentiation into bone and cartilage. While loss of gene expression is often associated with developmental defects, aberrant upregulation of expression can also be detrimental. microRNAs (miRNAs) are a class of non-coding RNAs that normally repress gene expression by binding to recognition sequences located in the 3' UTR of target mRNAs. miRNAs play important roles in many developmental systems, including midfacial development. Here, we take advantage of high throughput RNA sequencing (RNA-seq) from different tissues of the developing mouse midface to interrogate the miRs that are expressed in the midface and select a subset for further expression analysis. Among those examined, we focused on four that showed the highest expression level in in situ hybridization analysis. Mir23b and Mir24.1 are specifically expressed in the developing mouse frontonasal region, in addition to areas in the perichondrium, tongue musculature and cranial ganglia. Mir23b is also expressed in the palatal shelves and in anterior epithelium of the palate. In contrast, Mir133b and Mir128.2 are mainly expressed in head and trunk musculature. Expression analysis of mir23b and mir133b in zebrafish suggests that mir23b is expressed in the pharyngeal arch, otic vesicle, and trunk muscle while mir133b is similarly expressed in head and trunk muscle. Functional analysis by overexpression of mir23b in zebrafish leads to broadening of the ethmoid plate and aberrant cartilage structures in the viscerocranium, while overexpression of mir133b causes a reduction in ethmoid plate size and a significant midfacial cleft. These data illustrate that miRs are expressed in the developing midface and that Mir23b and Mir133b may have roles in this developmental process.
PubMed: 27471470
DOI: 10.3389/fphys.2016.00281 -
International Journal of Molecular... Feb 2024Heterozygous variants in the Poly(U) Binding Splicing Factor 60kDa gene () have been associated with Verheij syndrome, which has the key features of coloboma, short...
Heterozygous variants in the Poly(U) Binding Splicing Factor 60kDa gene () have been associated with Verheij syndrome, which has the key features of coloboma, short stature, skeletal abnormalities, developmental delay, palatal abnormalities, and congenital heart and kidney defects. Here, we report five novel patients from unrelated families with -related disorders exhibiting novel genetic and clinical findings with three truncating variants, one splice-site variant with likely reduced protein expression, and one missense variant. Protein modeling of the patient's missense variant in the PUF60 AlphaFold structure revealed a loss of polar bonds to the surrounding residues. Neurodevelopmental disorders were present in all patients, with variability in speech, motor, cognitive, social-emotional and behavioral features. Novel phenotypic expansions included movement disorders as well as immunological findings with recurrent respiratory, urinary and ear infections, atopic diseases, and skin abnormalities. We discuss the role of PUF60 in immunity with and without infection based on recent organismic and cellular studies. As our five patients showed less-severe phenotypes than classical Verheij syndrome, particularly with the absence of key features such as coloboma or palatal abnormalities, we propose a reclassification as -related neurodevelopmental disorders with multi-system involvement. These findings will aid in the genetic counseling of patients and families.
Topics: Humans; Coloboma; Mutation, Missense; Neurodevelopmental Disorders; Phenotype; RNA Splicing Factors
PubMed: 38396730
DOI: 10.3390/ijms25042053 -
Acta Otorhinolaryngologica Italica :... Dec 2022To describe a clear and intuitive way to analyse the anatomical meaning of images observed in Drug-induced Sleep Endoscopy (DISE) to fully understand the obstructive...
OBJECTIVE
To describe a clear and intuitive way to analyse the anatomical meaning of images observed in Drug-induced Sleep Endoscopy (DISE) to fully understand the obstructive dynamics and therefore opt for a tailor-made pharyngeal surgical technique.
METHODS
From January 2016 to December 2020, 298 patients who underwent DISE were selected according to inclusion criteria.
RESULTS
The case series consisted of 204 males and 94 females with a mean age of 56 years. Body mass index ranged from 19 kg/m to 34 kg/m with a median of 26.5 kg/m. Median Apnoea-Hypopnea Index (AHI) was 27 (range 5-62.3). The authors also observed four palate pharyngeal phenotypic patterns of collapse and clarify the morphology and role of the main muscles involved in upper airway collapse.
CONCLUSIONS
DISE is fundamental to determine the collapse site in patients affected by obstructive sleep apnoea syndrome. The velopharyngeal region is the most common site of obstruction and lateral pharyngeal wall collapse is the major determining factor. DISE can lead to a deeper understanding of the obstructive dynamic patterns and a more precise identification of the muscle bundles responsible for upper airway collapse.
Topics: Male; Female; Humans; Middle Aged; Airway Obstruction; Sleep Apnea, Obstructive; Pharynx; Endoscopy; Sleep
PubMed: 36654522
DOI: 10.14639/0392-100X-N2143 -
PloS One 2020Parkinson disease (PD) is associated with speech and swallowing difficulties likely due to pathology in widespread brain and nervous system regions. In post-mortem...
Parkinson disease (PD) is associated with speech and swallowing difficulties likely due to pathology in widespread brain and nervous system regions. In post-mortem studies of PD, pathology has been reported in pharyngeal and laryngeal nerves and muscles. However, it is unknown whether PD is associated with neuromuscular changes in the tongue. Prior work in a rat model of PD (Pink1-/-) showed oromotor and swallowing deficits in the premanifest stage which suggested sensorimotor impairments of these functions. The present study tested the hypothesis that Pink1-/- rats show altered tongue function coinciding with neuromuscular differences within tongue muscles compared to wildtype (WT). Male Pink1-/- and WT rats underwent behavioral tongue function assays at 4 and 6 months of age (n = 7-8 rats per group), which are time points early in the disease. At 6 months, genioglossus (GG) and styloglossus (SG) muscles were analyzed for myosin heavy chain isoforms (MyHC), α-synuclein levels, myofiber size, centrally nucleated myofibers, and neuromuscular junction (NMJ) innervation. Pink1-/- showed greater tongue press force variability, and greater tongue press forces and rates as compared to WT. Additionally, Pink1-/- showed relative increases of MyHC 2a in SG, but typical MyHC profiles in GG. Western blots revealed Pink1-/- had more α-synuclein protein than WT in GG, but not in SG. There were no differences between Pink1-/- and WT in myofiber size, centrally-nucleated myofibers, or NMJ innervation. α-synuclein protein was observed in nerves, NMJ, and vessels in both genotypes. Findings at these early disease stages suggest small changes or no changes in several peripheral biological measures, and intact motor innervation of tongue muscles. Future work should evaluate these measures at later disease stages to determine when robust pathological peripheral change contributes to functional change, and what CNS deficits cause behavioral changes. Understanding how PD affects central and peripheral mechanisms will help determine therapy targets for speech and swallowing disorders.
Topics: Animals; Disease Models, Animal; Gene Knockout Techniques; Male; Myosin Heavy Chains; Palatal Muscles; Parkinson Disease; Protein Kinases; Rats; Tongue
PubMed: 33064741
DOI: 10.1371/journal.pone.0240366 -
Indian Journal of Otolaryngology and... Dec 2022OSMF is a precancerous condition of the oral cavity. Cons umption of Areca nut in quid has been proved to be the most consistent factor. To assess middle ear function in...
OSMF is a precancerous condition of the oral cavity. Cons umption of Areca nut in quid has been proved to be the most consistent factor. To assess middle ear function in OSMF patients by audiometry and tympanometry. Two Hundred patients of < 40 years of age with OSMF were examined and followed by PTA and impedance audiometry. Impaired mobility was seen in 20(10%) ears, and retraction of tympanic membrane was found in 36(18%) ears. Clinical staging was done in four stages. Majority of the patients were males (58%) in the age group of 21-30 years belonging to stage III (38%) and IV (26%) respectively. PTA showed varying degrees of hearing loss in 73 (36.5%) ears. In Grade I, mild hearing loss was seen in 10 (35.71%) ears and moderately severe hearing loss was in 5 (11.36%) ears whereas in Grade II mild hearing loss in 11(25%) ears. Grade III and IV showed mild hearing loss in 11(14.47%) and 12 (23.07%) respectively. Tympanometry revealed type A curve in 126 (63%) ears followed by C curve in 50 (25%) and B curve in 24 (12%) ears. In patients of OSMF, there is involvement of palatal/paratubal muscles in the fibrosis process, which causes eustachian tube malfunction leading to disturbed middle ear functions and negative middle ear pressure. Most patients of oral submucous fibrosis showed direct association with grade of hearing impairment and eustachian tube dysfunction. Higher clinical grades, both clinically and histologically showed similar findings thereby we concluded that if the disease is treated early, preventing patients from having higher grades of disease, involvement of ear can be avoided, and patients can be saved from hearing impairment.
PubMed: 36742817
DOI: 10.1007/s12070-022-03077-2 -
BMJ Case Reports Sep 2021A 16-year-old patient presented with sudden-onset difficulty in swallowing food especially for liquids with nasal regurgitation and rhinolalia with no history of fever...
A 16-year-old patient presented with sudden-onset difficulty in swallowing food especially for liquids with nasal regurgitation and rhinolalia with no history of fever and limb weakness. Examination revealed bilateral palatal palsy with absence of gag reflex. Other neurological examinations were normal. Investigations were done to rule out any known pathology leading to such a presentation. The symptoms were attributed to an idiopathic acute-onset-acquired bilateral palatal palsy, in the absence of any identifiable cause. This is a rare presentation in adolescent age with no case reported in the literature so far in this age group. Medical management was started and patient showed complete improvement within 2 weeks of his symptoms. Early diagnosis and aggressive management of this condition lead to a favourable prognosis.
Topics: Adolescent; Humans; Muscle Weakness; Palate; Paralysis; Speech Disorders
PubMed: 34479886
DOI: 10.1136/bcr-2021-243467 -
Anatomical Record (Hoboken, N.J. : 2007) Apr 2020Herbivorous dinosaurs exhibited diverse cranial feeding mechanisms. Although osteological, microwear, and biomechanical research has revealed some of this diversity, the...
Herbivorous dinosaurs exhibited diverse cranial feeding mechanisms. Although osteological, microwear, and biomechanical research has revealed some of this diversity, the evolutionary reorientation of cranial musculature throughout nonavian herbivorous Dinosauria and its influence on feeding mechanisms requires more study. Here, cranial muscle reconstructions in herbivorous dinosaurs are reviewed and informative anatomical characters are compared across 142 dinosaur genera (84 ornithischians, 36 sauropodomorphs, and 22 herbivorous nonavian theropods), both through examination of specimens and literature. Traits include those relating to the temporal region, adductor chamber, palate, and mandibular attachments, such as the coronoid elevation and retroarticular process. Findings reveal many combinations of anatomical traits influencing a diversity of feeding mechanisms. Some primarily more orthal feeders, including herbivorous theropods, nonsauropod sauropodomorphs, basal ornithischians, and derived stegosaurs (which also show varying degrees of coinciding slight palinal motion and long-axis hemimandibular rotation), possess traits indicative of more prominent temporal musculature and moderately sized palatal musculature. However, orthal feeding sauropods and pachycephalosaurs possess traits indicative of greatly reduced, low-angled temporal musculature, and enhanced palatal musculature producing a primarily vertical, orthal feeding vector. Among ankylosaurs, hadrosaurids, and neoceratopsians, a rostrolabial temporal muscle expansion is present (with a tall coronoid elevation in hadrosaurids and ceratopsids) for greater temporal muscle support and mechanical advantage for complex palinal feeding motions. This also aids in long-axis hemimandibular rotation against the predentary in hadrosaurs and ankylosaurs. This diversity in cranial muscle architecture provides an informative spectrum of numerous adaptations acquired given the evolution of various anatomical constraints in the skull. Anat Rec, 303:1104-1145, 2020. © 2019 American Association for Anatomy.
Topics: Animals; Biological Evolution; Dinosaurs; Feeding Behavior; Fossils; Herbivory; Muscle, Skeletal; Skull
PubMed: 31675182
DOI: 10.1002/ar.24283