High prevalence of hyposalivation in individuals with neurofibromatosis 1: a case-control study
TL;DR: Hyposalivation may be a consequence of NF1, as occurs in other genetic diseases, and more studies are necessary to understand if there is and what is the relationship between NF1 and hyposalivation.
Abstract: Background
Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases in humans and has widely variable expressivity. Oral manifestations are common, but there are no studies that investigated functional alterations in salivary glands in NF1. Our aim was to evaluate the salivary flow rate in NF1 individuals, comparing to a control group, and to investigate the possible causes and some consequences of salivary gland alteration.
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TL;DR: In this article, the authors investigated the expression levels and distribution of neurofibromin in acinar and ductal cells of major and minor salivary glands of adult individuals without NF1.
Abstract: Neurofibromin, a protein encoded by the NF1 gene, is mutated in neurofibromatosis 1, one of the most common genetic diseases. Oral manifestations are common and a high prevalence of hyposalivation was recently described in individuals with neurofibromatosis 1. Although neurofibromin is ubiquitously expressed, its expression levels vary depending on the tissue type and developmental stage of the organism. The role of neurofibromin in the development, morphology, and physiology of salivary glands is unknown and a detailed expression of neurofibromin in human normal salivary glands has never been investigated. To investigate the expression levels and distribution of neurofibromin in acinar and ductal cells of major and minor salivary glands of adult individuals without NF1. Ten samples of morphologically normal major and minor salivary glands (three samples of each gland: parotid, submandibular and minor salivary; and one sample of sublingual gland) from individuals without neurofibromatosis 1 were selected to assess neurofibromin expression through immunohistochemistry. Immunoquantification was performed by a digital method. Neurofibromin was expressed in the cytoplasm of both serous and mucous acinar cells, as well as in ducts from all the samples of salivary glands. Staining intensity varied from mild to strong depending on the type of salivary gland and region (acini or ducts). Ducts had higher neurofibromin expression than acinar cells (p = 0.003). There was no statistical association between the expression of neurofibromin and the type of the salivary gland, considering acini (p = 0.09) or ducts (p = 0.50) of the four salivary glands (parotid, submandibular, minor salivary, and sublingual gland). Similar results were obtained comparing the acini (p = 0.35) and ducts (p = 0.50) of minor and major salivary glands. Besides, there was no correlation between the expression of neurofibromin and age (p = 0.08), and sex (p = 0.79) of the individuals, considering simultaneously the neurofibromin levels of acini and duct (n = 34). Neurofibromin is expressed in the cytoplasm of serous and mucous acinar cells, and ductal cells of salivary glands, suggesting that this protein is important for salivary gland function.
1 citations
TL;DR: This is a sporadic case of cutaneous neurofibromatosis 1 in a 78-year-old female patient who presented with extremely severe cutaneous neuroscience, making this case at least rather peculiar.
Abstract: Abstract Neurofibromatosis-1 (NF1) is one of the most common hereditary multisystemic disorders. The disease manifests a variety of characteristic features that include: hyperpigmentary abnormalities of the skin (café-au-lait macules, freckles in the axillae, and iris Lisch nodules) and growth of benign peripheral nerve sheath tumors (neurofibromas) in the skin. Associated extracutaneous clinical features include: skeletal abnormalities, neurological, cardiovascular, endocrine and other malformations. NF1 is caused by mutation in the neurofibromatosis-1 gene, which codes for the protein neurofibromin. The inheritance of NF1 follows an autosomal dominant trait, although about 50% of patients present with new („de novo“) mutations, and represent the first member of their family. No difference in the severity of the disease can be found in patients with familial mutations versus those with new mutations. We present a 78-year-old female patient with an extreme cutaneous form of neurofibromatosis who reported no affected family member. Apart from skin problems, she had no major health issues in childhood and adolescence, but in recent decades she had frequent headaches, occasional abdominal pain, and vision and hearing impairment. About 10 to 14 days before admission, she developed a severe cough, shortness of breath, and chest and abdominal pain. On examination, the patient of short stature (hight: 152 cm, weight: 49 kg) presented with thousands of soft nodules dispersed over the whole body, except on extensor sides of thighs and lower legs; the nodules varied in color from skin-colored, livid erythematous, to brown-grey; the nodules on the abdomen were moist, partly bleeding from the base, and accompanied by an unpleasant odor. Her feet were also densely covered by dark purple lumps, with dystrophic changes of the toe nails that were thickened, frayed, and yellowish. The skeletal abnormalities included: short stature, severe osteoporosis and osteosclerosis of the head bone structure; degenerative arthropathc-spondylotic changes of the thoracolumbar spine segment with signs of diffuse skeletal hyperostosis; pronounced degenerative changes of the lumbar spine. CT scans of the head, chest and abdomen showed the following abnormalities: flattening of the paraventricular gyri and reduction of brain parenchyma with hypodensity of the white matter in terms of cortical atrophy; periventricular bilateral small post-ischemic microvascular brain lesions of varying chronicity; in the parenchyma of the upper left lung lobe the apical presence of small areas of pleural effusion with consequent subatelectic region; distended stomach and a small inner wall herniation; hypotrophic right kidney; atherosclerotic lesions of the abdominal aorta; low grade infrarenal kinking of the abdominal aorta. Pathohistological analysis of biopsy specimen taken from the nodule corresponded with cutaneous neurofibroma. Consultative examinations of various specialists pointed to the existence of the following comorbidities: obstructive respiratory syndrome and right lobe pneumonia that were treated by antibiotics, aminophylline and dexamethasone infusions; psycho-organic syndrome without focal neurological deficit; Lisch nodules in each eye, and senile cataract. Considering the age and medical presentation of the patient, no other treatment was considered. In conclusion, this is a sporadic case of cutaneous neurofibromatosis 1 in a 78-year-old female patient who presented with extremely severe cutaneous neurofibromas, making this case at least rather peculiar.
1 citations
01 Jan 2020
TL;DR: About 80% of children with NF1 exhibit various speech and language disorders: slow early speech development, slower vocabulary enrichment, syntactic, semantic and phonological speech disorders, and about one-third of these persons have emotional and social problems.
Abstract: Neurofibromatoses are a set of different genetic disorders that have a common characteristic of the appearance of nervous system tumors. There are three forms of the disease, of which type 1 neurofibromatosis (NF 1) is the most common. NF 1 is an inherited autosomal-dominant disease, with a high rate of new mutations. In addition to the many physical manifestations and complications that occur in persons with NF 1, there are also numerous cognitive difficulties, including lower general intellectual functioning, learning difficulties, but also problems in attention, visual abilities, executive functions, and speech. Attention disorders are up to three times more common in people with NF 1, while learning disabilities are present in more than half of these subjects. Disturbances in the field of visuospatial perception are recognisable even in the preschool period. About 80% of children with NF1 exhibit various speech and language disorders: slow early speech development, slower vocabulary enrichment, syntactic, semantic and phonological speech disorders. Disruption of executive functions will manifest itself in the areas of working memory, organisation, planning / problem solving. This will reflect as the underperformance in academic achievement. Nearly one-third of these persons have emotional and social problems.
TL;DR: In this paper, the authors evaluated the mandibular condyles of individuals without facial plexiform neurofibroma using cone beam computed tomography images (CCT images).
Abstract: The aim of this study was to evaluate the mandibular condyles of neurofibromatosis 1 (NF1) individuals without facial plexiform neurofibroma using cone beam computed tomography images Eighty cone beam computed tomography scans (160 mandibular condyles) were analyzed: 40 from NF1 individuals (study group) and 40 from individuals without NF1 (control group) The anteroposterior and mediolateral dimensions, height, and volume of the mandibular condyles were measured The mandibular condyles were classified according to their morphology: healthy (absence of morphological changes), with flattening (loss of rounded contour of at least one of the surfaces), with erosion (loss of continuity of the cortical bone), with osteophyte (exophytic formation of the condyle surface), and with sclerosis (any increase in the cortical thickness in the load-bearing areas) Furthermore, the position of the mandibular condyles in relation to the joint fossa in an anteroposterior view was classified as anterior, concentric, or posterior The study group had a higher anteroposterior dimension of the mandibular condyles compared with the control group (p 005) The morphological alterations were not associated with sex or age in any group evaluated (p > 005) For both groups, the concentric position was the most common For the study group, there was a significant difference in the condylar position between the sides (p < 005) NF1 individuals without facial plexiform neurofibroma present a high prevalence of condyles with a large anteroposterior dimension and asymmetric position in the joint fossa However, no morphological and volumetric changes were observed in the mandibular condyles of them The knowledge of the TMJ alterations in individuals with NF1 is important to establish an evaluation protocol, which would allow early intervention if indicated
01 Jan 2020
TL;DR: The COVID-19 pandemic is becoming unfortunately traumatic for many, which is especially what authors from the USA and Israel are writing about, and which often manifests itself in our country, faced us on a personal and collective level with the crisis as a chance and a challenge for the emergence and deepening of awareness of basic values in life as discussed by the authors.
Abstract: The COVID-19 pandemic is becoming unfortunately traumatic for many, which is especially what authors from the USA and Israel are writing about, and which often manifests itself in our country, faced us on a personal and collective level with the crisis as a chance and a challenge for the emergence and deepening of awareness of basic values in life, for the emergence and deepening of a sense of gratitude for the basic things we have in life, but also for the analytical processing of earlier and the earliest personal and collective traumas that the actual trauma brought to the surface and allowed us to approach them. Commitment to working with patients means keeping our mental world and the mental world of our patients working together all the time, even before, after and during turbulences. That work involves discovering the patient's life force because, especially in a critical, crisis, stressful age, the role of creativity is essential. The psychotherapist's creativity also changes under the influence of the pandemic, as does his / her ability to trigger his / her own anxieties and fear of death. Therefore now, during this crisis, we are giving to the unconscious its place more than ever. It is important that we all the time maintain and nurture listening to the unconscious with our patients. This is a basic principle in the face of trauma, and the current pandemic provides a chance to relive all the trauma.
References
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TL;DR: To deal with the exceedingly difficult health care issues posed by frail elderly persons, health professionals need to collect, organize, and use a vast array of clinically relevant information.
Abstract: he population of elderly persons in the developed nations is growing with extraordinary rapidity. Although the majority enjoy good T health, many older people suffer from multiple illnesses and significant disability. Comprehensive assessment methodologies, while not solely applicable to frail elderly persons, are believed to be particularly suited to their situation. These individuals tend to exhibit great medical complexity and vulnerability; have illnesses with atypical and obscure presentations; suffer major cognitive, affective, and functional problems; are especially vulnerable to iatrogenesis; are often socially isolated and economically deprived; and are at high risk for premature or inappropriate institutionalization. To deal with the exceedingly difficult health care issues posed by frail elderly persons, health professionals need to collect, organize, and use a vast array of clinically relevant information. This process, compre-
1,353 citations
01 Jan 2017
TL;DR: The Plummer-Vinson syndrome has come increasingly rare with the availabil¬ ity of iron supplements, but nonetheless it should be suspected in the setting of dysphagia and iron deficiency.
Abstract: Plummer-Vinson syndrome is characterized by dysphagia, iron-deficiency anemia, and esophageal webs. The webs are best diagnosed by cineradiography. Iron repletion often improves the dysphagia, although some patients require esophageal dilatation or bougienage. The syndrome is associated with an increased incidence of postcricoid carcinoma, and surveillance endoscopy is recommended. (Arch Intern Med. 1995;155:2008-2011) The Plummer-Vinson syndrome has be¬ come increasingly rare with the availabil¬ ity of iron supplements, but nonetheless it should be suspected in the setting of dysphagia and iron deficiency. The follow¬ ing case illustrates the clinical, radiographic, and endoscopie presentation of this syndrome.
792 citations
TL;DR: The prevalence of oral and radiographic findings in this sample was 72%, which is much higher than previously reported and the five most common findings are oral neurofibromas, enlarged fungiform papillae, intrabony lesions, wide inferior alveolar canals, and enlarged mandibular foramina.
123 citations
TL;DR: No relationship between the appearance of the tongue and salivary bacterial load could be detected and there was no difference in bacterial load between the healthy/gingivitis and the periodontitis group within the present study population.
Abstract: Background The papillary structure of the dorsum of the tongue forms a unique ecological site that provides a large surface area favoring the accumulation of oral debris and microorganisms. These micro-organisms of the tongue may be of influence on the flora of the entire oral cavity. The normal appearance of the dorsum of the tongue is either pinkish or has a thin white coating. For the present study a scoring method was developed to describe the appearance of the dorsum of the tongue in relation to the extent of color and thickness of tongue coating. Aim The purpose of this study was to investigate the discoloration and coating of the tongue in healthy/gingivitis subjects and periodontitis patients. Furthermore, to determine the relationship between the appearance of the tongue and the bacterial load in salivary samples. Material and methods 2 groups of patients were studied, 70 healthy/gingivitis subjects and 56 periodontitis patients. After scoring of the tongue a salivary sample of each patient was taken and analyzed using a phase-contrast microscope. Results This investigation showed that most discoloration was found on the distal part of the tongue. The mean number of bacteria per ml sample in relation to a pink, white and yellow appearance of the tongue was 948, 855 and 900 (x 10(6)) respectively. The mean number of bacteria per ml sample in relation to no, thin and thick coating was 948, 863, and 895 (x 10(6)), respectively. Analysis did not reveal a relationship between discoloration, coating thickness and total bacterial load. The mean number of bacteria per ml in healthy/gingivitis subjects was 860 and in periodontitis patients 918 (x 10(6)). Conclusion No relationship between the appearance of the tongue and salivary bacterial load could be detected. There was no difference in bacterial load between the healthy/gingivitis and the periodontitis group within the present study population.
116 citations
TL;DR: Evidence of alternative splicing in this region of the NF1 gene is identified using reverse transcription-polymerase chain reaction (RT-PCR) analyses with primers located in exons 7 and 13, and an isoform bearing an extra 30 bp sequence between exons 9 and 10a is proposed to be called exon 9br.
Abstract: The neurofibromatosis 1 gene seems to play essential roles at several different stages of life. During embryogenesis, it is involved in cardiac development while in the adult, neurofibromin (the corresponding protein) is mainly expressed in the nervous system, and therein, essentially in neurons, non-myelinating Schwann cells and oligodendrocytes. In addition, the NF1 gene is considered a tumor suppressor gene, since mutations have been associated with the occurrence of benign and malignant tumors in neuralcrest-derived tissues. Using reverse transcription-polymerase chain reaction (RT-PCR) analyses with primers located in exons 7 and 13, we have identified evidence of alternative splicing in this region of the NF1 gene. Cloning and sequencing of cDNA allowed the characterization of an isoform bearing an extra 30 bp sequence between exons 9 and 10a, leading to the insertion of 10 amino acids between residues 420 and 421 of neurofibromin. The insertion is conserved in the mouse. Examination of the pattern of expression of this isoform demonstrated a high level of expression in the central nervous system and an absence of expression in all the other normal tissues tested including peripheral nervous tissues derived from the neural crest. Analysis of brain tumors indicated a reduced expression of the alternative exon in medulloblastomas and oligodendrogliomas. The results presented here are consistent with tissue-specific expression of this alternative exon which we propose to call exon 9br.
94 citations