DOCSLIB.ORG

Olfactory Disturbances —Pathophysiological Findings and the Development of New Therapeutic Procedures—

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Olfactory Disturbances —Pathophysiological Findings and the Development of New Therapeutic Procedures— Ⅵ Sensory Organ Disorders Olfactory Disturbances —Pathophysiological findings and the development of new therapeutic procedures— JMAJ 47(1): 38–43, 2004 Mitsuru FURUKAWA Professor, Department of Otorhinolaryngology, Graduate School of Medicine and School of Medicine, Kanazawa University Abstract: Chronic rhinosinusitis is the most frequent cause of hyposmia. We established a new experimental animal model to investigate pathological findings in the olfactory epithelium and olfactory bulb of rats and describe the possible etiology of hyposmia due to rhinosinusitis. Not only dysfunction of the olfactory epithelium but a central type of hyposmia caused by disorders of the olfactory bulb was demonstrated by immunohistochemistry. The possible etiology of hyposmia after common colds and dysosmia after traumatic olfactory disorders is also described based on recent studies. Hyposmia after common colds is strongly associated with nasal obstruction, swelling of the nasal mucosa, and edema of the mucosa of the olfactory cleft observed by nasal fiberscopy. Viral infection is consid- ered one of the etiologies of anosmia after common colds, especially in women from 40 to 60 years old, and results in a poor outcome. One possible explanation of olfactory dysosmia is misdirected connections during reinnervation of the olfac- tory bulb by olfactory nerve fibers after apoptotic change of olfactory receptor neurons and traumatic amputations of olfactory filla at the level of ethmoid lamina cribrosa. These findings suggested new ideas for the treatment of patients with different types of olfactory disturbances. Key words: Pathophysiology; Olfactory disturbances; Paranasal sinusitis; Common cold; Parosmia Introduction everyday life. Due to hearing difficulty, aged people tend to be isolated from their commu- The research on gustatory and olfactory senses nities and also from participating in social have not been fully developed as compared to activities. Considering these aspects, gustatory those on visual and auditory functions. Yet these and olfactory disturbances among them may senses contribute significantly to one’s QOL in interfere with their desire to live and enjoy This article is a revised English version of a paper originally published in the Journal of the Japan Medical Association (Vol. 127, No. 9, 2002, pages 1483–1486). 38 JMAJ, January 2004—Vol. 47, No. 1 OLFACTORY DISTURBANCES AND TREATMENT their lives. (PCNA) antibody, anti-single-stranded DNA At the beginning of the 21st century, our (ssDNA) antibody, and anti-inducible nitric aging society continues to be complex and faces oxide synthase (iNOS) antibody. To ascertain further problems to be solved. The patho- the presence (or absence) of changes to the physiological elucidation of various olfactory central olfactory system, an immunohistologi- disturbances and the development of new ther- cal study was conducted on the olfactory bulb apeutic methodology are much desired. The samples of the rats affected by paranasal sinus- current situation is presented in this literature. itis by using an anti-tyrosine hydroxylase (TH) antibody. Chronic Paranasal Sinusitis The results of these observations may be summarized as follows: The onset of paranasal Paranasal sinusitis is the most frequent cause sinusitis was confirmed in 6 animals after 3 of olfactory disturbances in Japan.1) It is true days, 7 animals after 7 days, 6 animals after 14 that sequential changes that occur at the olfac- days, 6 animals after 21 days, and 7 animals tory mucosa caused by paranasal sinusitis have after 28 days following exposure to Staphylo- not been investigated sufficiently. Nor have coccus aureus. Inflammation developed in the appropriate animal models been found that are olfactory epithelium that was affected by para- suitable for such studies. Therefore, we pre- nasal sinusitis within 3 days and the inflamma- pared a model for experimental paranasal tory condition persisted even after 28 days. The sinusitis by using rats to elucidate the mecha- thickness of the olfactory epithelium, the num- nism by which olfactory disturbances develop ber of olfactory cell layers, and the count of and to conduct histological observations of the the olfactory cells per 100␮m2 of the olfactory olfactory epithelium and olfactory bulb.2) epithelium continued to be markedly reduced until after 21 days. The olfactory neurofibril 1. Pathophysiology bundles became elongated and scarce in pro- (1) Olfactory disturbance portion to the time (i.e., number of days) that (direct effects of sinusitis) the foreign body was retained in the nasal A foreign material (polyvinyl acetal) coated cavity. The olfactory cell regenerating activity with Staphylococcus aureus was inserted into was markedly reduced for the initial 7 days and one of the nasal cavities of rats and 3, 7, 14, 21, hardly recognized on the 21st or 28th day. and 28 days later, samples from the nasal cavity Apoptosis of the olfactory cells was most pro- and olfactory bulb were collected (from 10 ani- nounced on the 3rd and 7th days, after which mals at each experiment) to prepare coronal the activity was reduced and became barely sections. HE stain was applied to the samples recognizable on the 21st or 28th day. The from the nasal cavity to examine the maxillary iNOS expression in the olfactory epithelium sinus and ascertain the onset of paranasal was hardly noted in the normal olfactory epi- sinusitis. thelium. The enzyme expression was abundant The HE-stained nasal sinus section obtained around the basal cells of the samples obtained from the rats affected by paranasal sinusitis from the animals with paranasal sinusitis; but it was used to measure the thickness of the olfac- was somewhat reduced where the olfactory tory epithelium. The sections from the nasal epithelium had undergone marked degenera- cavity of the rats with paranasal sinusitis were tion. In the olfactory bulb, the TH expression of used for immunohistological observation of the the juxtaglomerular cells began to be reduced olfactory epithelium by using the following anti- on the 7th day and became much reduced on bodies: anti-protein gene product 9.5 (PGP9.5) the 21st and 28th days. antibody, anti-proliferating cell nuclear antigen It has been shown for the first time that in JMAJ, January 2004—Vol. 47, No. 1 39 M. FURUKAWA addition to the olfactory epithelium, histologi- position for about 5 minutes. If no improve- cal changes develop in the olfactory bulb and ment is seen within one month, the medication central olfactory disturbances may occur in is discontinued. When the patient is unable to chronic paranasal sinusitis. hold his head in the specified position or he has (2) Olfactory disturbance chronic sinusitis or has recently undergone (indirect effects of sinusitis) surgery, the same preparation is sprayed from Inflammatory changes in the olfactory cleft, an atomizer twice a day. Topical application of nasal polyps, especially those of the olfactory 2mg/0.5 mlV of dexamethasone or 40 mg/1mlV cleft, and excessive secretion that are caused of methylprednisolone to the olfactory mucosa by sinusitis have been pointed out. It is well is also recommended. Both are applied once known that these conditions are also accompa- every 2 weeks and repeated 4 to 6 times. nied by morphological deviations of the nasal (ii) Oral medication cavity, such as accentuated curved nasal sep- Recently, long-term application of a small tum and nodules of the nasal septum. The patho- amount of macrolide antibiotics has been re- physiology of olfactory disturbances caused by commended as a conservative or postoperative chronic paranasal sinusitis may therefore be adjuvant therapy for chronic paranasal sinus- summed up as the so-called mixed olfactory itis. This medication is usually combined with dysfunctions, where the aforementioned olfac- ethyl L-cysteine hydrochloride (Cystanin®) or tory epithelial changes and respiratory olfac- L-carbocysteine (Mucodyne®). tory dysfunction — due to deviations in air flow (iii) Therapeutic modalities projected in within the nasal cavity — are involved. the near future For the etiology of chronic paranasal sinus- 2. Treatment itis, it has been proven that inflammatory cyto- Needless to add, the treatment of chronic kines (e.g., IL-1␤, TNF-␣, GM-CSF, and IL-6) paranasal sinusitis, the cause of olfactory dis- are involved. Therefore, much is expected from turbances, also constitutes the basis of treat- gene therapy to control the genes responsible ment of the latter. for the expression of these cytokines at the (1) Surgical treatment genetic level or chemotherapy targeted at these Surgical correction of morphological devia- genes. tions of the nasal cavity — e.g., modification of the nasal septum, excision of the turbinate, and Olfactory Disturbances Following a elimination of nasal polyps — and endoscopic Common Cold surgery of the paranasal sinus are effective in improving respiratory or mixed olfactory dis- It is understood that olfactory disturbances turbances. However, complete recovery from complicating upper respiratory inflammation extensive and multiple polyps is difficult. It has are caused by nasal occlusion, swelling of the been reported that the recovery rate is about nasal mucosa, or edema of the mucosa of the 50%.3) olfactory cleft. Most of these symptoms are (2) Drug therapy transient, being eliminated in 2 to 3 days. How- (i) Nasal instillation, nasal spraying, or local ever, in some instances they may develop after injection of adrenal cortex hormones a cold and their prognosis is considered to be With the patient in the head-down (chin-up) poor. The condition frequently affects women position, 1 to 2 drops of a 0.1% solution of between 40 to 69 years of age.4) The question betamethasone sodium (Rinderon®) are instilled of the exaggerated susceptibility to infection in the nasal cavity 3 to 4 times a day, during by viruses from the olfactory nerve and the which time the patient is instructed to hold the resistance to recovery from disturbances in this 40 JMAJ, January 2004—Vol. 47, No. 1 OLFACTORY DISTURBANCES AND TREATMENT age range, as well as the higher frequency of disturbances of the same function.
Load more

Recommended publications
  • Treating Dysosmia, from Saline to Surgery
    日鼻誌４７!：５１～５２，２００８ 特別講演２ TREATING DYSOSMIA, FROM SALINE TO SURGERY Donald A. Leopold, MD, FACS University of Nebraska Medical Center, Omaha, Nebraska, United States of America The sense of smell begins with airflow through the nose. The exact path of this airflow has only recently been investigated. Some of this data comes from models, both life size and enlarged models using measurements of airflow. Additional information comes from computerized airflow models of the nasal cavities. The neural pathways of olfaction begin with the olfactory receptors high in the nasal cavity. After transduction from the chemical to the electrical information, this information is transferred through the olfactory bulb and into the central brain. Patients typically present with one of three different types of dysosmia. The first is simply a decreased ability to perceive smells（hyposmia and anosmia）. The two remaining types of dysosmia relate to distortions of perceived smells. One of these（parosmia）is a distortion of smell odorants that are actually in the environment. The third type is theperceptionofanodorwhenthereisnoodorantintheenvironment（phantosmia or hallucination）. The clinical task of the physician seeing these patients is to decide on the etiology of the problem and to recom- mend therapy if possible. The clinical history is one of the best tools the clinician has, but the physical examination, sensory testing and imaging can also be helpful. Diagnostic categories for these patients are many, but the most com- mon include nasal inflammatory disease for about a third of these patients, the losses that occur after an upper respira- tory infection in about 25 percent of the patients and head trauma in about 15 percent of patients.
    [Show full text]
  • Taste and Smell Disorders in Clinical Neurology
    TASTE AND SMELL DISORDERS IN CLINICAL NEUROLOGY OUTLINE A. Anatomy and Physiology of the Taste and Smell System B. Quantifying Chemosensory Disturbances C. Common Neurological and Medical Disorders causing Primary Smell Impairment with Secondary Loss of Food Flavors a. Post Traumatic Anosmia b. Medications (prescribed & over the counter) c. Alcohol Abuse d. Neurodegenerative Disorders e. Multiple Sclerosis f. Migraine g. Chronic Medical Disorders (liver and kidney disease, thyroid deficiency, Diabetes). D. Common Neurological and Medical Disorders Causing a Primary Taste disorder with usually Normal Olfactory Function. a. Medications (prescribed and over the counter), b. Toxins (smoking and Radiation Treatments) c. Chronic medical Disorders ( Liver and Kidney Disease, Hypothyroidism, GERD, Diabetes,) d. Neurological Disorders( Bell’s Palsy, Stroke, MS,) e. Intubation during an emergency or for general anesthesia. E. Abnormal Smells and Tastes (Dysosmia and Dysgeusia): Diagnosis and Treatment F. Morbidity of Smell and Taste Impairment. G. Treatment of Smell and Taste Impairment (Education, Counseling ,Changes in Food Preparation) H. Role of Smell Testing in the Diagnosis of Neurodegenerative Disorders 1 BACKGROUND Disorders of taste and smell play a very important role in many neurological conditions such as; head trauma, facial and trigeminal nerve impairment, and many neurodegenerative disorders such as Alzheimer’s, Parkinson Disorders, Lewy Body Disease and Frontal Temporal Dementia. Impaired smell and taste impairs quality of life such as loss of food enjoyment, weight loss or weight gain, decreased appetite and safety concerns such as inability to smell smoke, gas, spoiled food and one’s body odor. Dysosmia and Dysgeusia are very unpleasant disorders that often accompany smell and taste impairments.
    [Show full text]
  • Paroxysmal Bilateral Dysosmia Treated by Resection of the Olfactory Bulbs
    160 Surg Neurol 1993 ;40:160-3 Paroxysmal Bilateral Dysosmia Treated by Resection of the Olfactory Bulbs J.M. Markert, M.D., D.O. Hartshorn, M.D., and S.M. Farhat, M.D. Department of Surgery, Section of Neurosurgery and Department of Otolaryngology, Head and Neck Surgery, University of Michigan Medical Center, and Catherine McAuley Health Center, Ann Arbor, Michigan Markert JM, Hartshorn DO, Farhat SM. Paroxysmal bilateral Case Report dysosmia treated by resection of the olfactory bulbs. Surg Neurol 1993;40:160-3. P.G., a 37-year-old woman, was seen in November 1988. She reported a 17 year history of dysosmia with paroxysms of peculiar sensations of smell. These sensa- Dysosmia, or the distortion of olfaction, is most commonly tions were usually brought on by inhalation of other preceded by viral illness or head trauma, but has a variety strong odors, such as cigars, perfume, or onions; how- of etiologies. The precise nature of the disease process remains obscure. Medical management is largely empiric, ever, they also could be triggered by sudden turning of and has been aimed at treating underlying illnesses, re- the head, a big sniff, or emotional and physical stress. stricting triggering medications, as well as various phar- The common cold or flu would also exacerbate the sensa- macologic interventions. Successful eradication of a severe tion. Dysosmia paroxysms were described as unlike any case of persistent unilateral paroxysmal dysosmia with other odor, and always the same: of a hot, foul and resection of the ipsilateral olfactory bulb has been re- smoky nature on the right, and a sickeningly sweet, ported.
    [Show full text]
  • Critical Illness and Changes in Sensory Perception
    Proceedings of the Nutrition Society (2007), 66, 331–345 DOI:10.1017/S0029665107005599 g The Author 2007 Critical illness and changes in sensory perception Susan S. Schiffman Department of Psychiatry, 54212 Woodhall Building, Duke University Medical Center, Durham, NC 27710–3259, USA Impairments of sensory perception that occur during a period of critical care can seriously impact on health and nutritional status, activities of daily living, independence, quality of life and the possibility of recovery. It is emphasized from the outset that sensory losses in critically- ill patients may or may not be related to their current medical condition. The present paper provides an overview of all five senses (vision, hearing, taste, smell and touch) and describes the factors that contribute to sensory losses in critically-ill patients, including medications, medical conditions and treatments and the process of aging itself. Cancer and stroke are two critical illnesses in which profound sensory decrements often occur. Many sensory complaints in patients with cancer are related to alteration in sensory signals caused by damage to the sensory receptors. However, some complaints, such as taste aversions in patients with cancer, are not related to altered sensory physiology per se but to learned aversions that arise during the noxious effects of radiotherapy and chemotherapy. The paper also reviews a study in which the sensory performance (of all five senses) was compared in three groups of elderly subjects: (1) patients who had undergone coronary artery bypass surgery; (2) patients with cardio- vascular conditions but with no history of surgery; (3) healthy non-medicated age-matched controls.
    [Show full text]
  • Clinical Diagnosis and Treatment of Olfactory Dysfunction
    Clinical Diagnosis and Treatment of Olfactory Dysfunction Seok Hyun Cho Hanyang Med Rev 2014;34:107-115 http://dx.doi.org/10.7599/hmr.2014.34.3.107 Department of Otorhinolaryngology-Head and Neck Surgery, Hanyang University College of Medicine, Seoul, Korea pISSN 1738-429X eISSN 2234-4446 Olfactory dysfunction is a relatively common disorder that is often under-recognized by Correspondence to: Seok Hyun Cho Department of Otorhinolaryngology-Head both patients and clinicians. It occurs more frequently in older ages and men, and decreases and Neck Surgery, Hanyang University patients’ quality of life, as olfactory dysfunction may affect the emotion and memory func- Hospital, 222 Wangsimni-ro, Seongdong-gu, tions. Three main causes of olfactory dysfunction are sinonasal diseases, upper respiratory Seoul 133-792, Korea Tel: +82-2-2290-8583 viral infection, and head trauma. Olfactory dysfunction is classified quantitatively (hypos- Fax: +82-2-2293-3335 mia and anosmia) and qualitatively (parosmia and phantosmia). From a pathophysiologi- E-mail: [email protected] cal perspective, olfactory dysfunction is also classified by conductive or sensorineural types. All patients with olfactory dysfunction will need a complete history and physical examina- Received 17 April 2014 Revised 23 June 2014 tion to identify any possible or underlying causes and psychophysical olfactory tests are Accepted 3 July 2014 essential to estimate the residual olfactory function, which is the most important prognos- This is an Open Access article distributed under tic factor. CT or MRI may be adjunctively used in some indicated cases such as head trauma the terms of the Creative Commons Attribution and neurodegenerative disorders.
    [Show full text]
  • Olfactory Dysfunction
    Olfactory Dysfunction: By Steven Sobol, MD, MSc; Saul Frenkiel, MD, FRCSC; and Debbie Mouadeb he sense of smell plays an important role in protecting Tman from environmental dangers, such as fire, natural gas leaks and spoiled food. Physiologically, the chemical senses aid in normal digestion by triggering gastrointestinal secretions.1 Smell influences the palatability of food. Defects in the sense of smell are associated with alterations in perceptions of flavor, leading to anorexia and weight loss. Psychologically, smell is powerful in establishing strong positive and negative memories, and affects socialization and interpersonal relationships. Smell dysfunctions often mean considerable disability and a lower quality of life. Loss or decreased olfactory function affects approximately one per cent of Americans under the age of 60 and more than half the population over that age.2 Aside from having a substantial impact on an individual’s quality of life, olfactory dysfunction may signal an underlying disease. Smell disorders have been largely overlooked by the medical community because of a lack of knowledge and understanding of the sense of smell and its disease states, as well its diagnosis and management. Patients with olfactory disorders need to be clinically assessed, and the etiology and anatomical location of their disorder should be sought out. The Canadian Journal of Diagnosis / August 2002 55 Olfactory Dysfunction Summary What are the causes of olfactory dysfunction? 1.Conductive olfactory loss is any process that causes sufficient obstruction in the nose preventing odorant molecules from reaching the olfactory epithelium. 2.Sensorineural olfactory loss is any process that directly affects and impairs either the olfactory epithelium or the central olfactory pathways.
    [Show full text]
  • Alteration, Reduction and Taste Loss: Main Causes and Potential Implications on Dietary Habits
    nutrients Review Alteration, Reduction and Taste Loss: Main Causes and Potential Implications on Dietary Habits Davide Risso 1,* , Dennis Drayna 2 and Gabriella Morini 3 1 Ferrero Group, Soremartec Italia Srl, 12051 Alba, CN, Italy 2 National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA; [email protected] 3 University of Gastronomic Sciences, Piazza Vittorio Emanuele 9, Bra, 12042 Pollenzo, CN, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-0173-313214 Received: 3 September 2020; Accepted: 23 October 2020; Published: 27 October 2020 Abstract: Our sense of taste arises from the sensory information generated after compounds in the oral cavity and oropharynx activate taste receptor cells situated on taste buds. This produces the perception of sweet, bitter, salty, sour, or umami stimuli, depending on the chemical nature of the tastant. Taste impairments (dysgeusia) are alterations of this normal gustatory functioning that may result in complete taste losses (ageusia), partial reductions (hypogeusia), or over-acuteness of the sense of taste (hypergeusia). Taste impairments are not life-threatening conditions, but they can cause sufficient discomfort and lead to appetite loss and changes in eating habits, with possible effects on health. Determinants of such alterations are multiple and consist of both genetic and environmental factors, including aging, exposure to chemicals, drugs, trauma, high alcohol consumption, cigarette smoking, poor oral health, malnutrition, and viral upper respiratory infections including influenza. Disturbances or loss of smell, taste, and chemesthesis have also emerged as predominant neurological symptoms of infection by the recent Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus strain 2 (SARS-CoV-2), as well as by previous both endemic and pandemic coronaviruses such as Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and SARS-CoV.
    [Show full text]
  • Calcification of the Olfactory Bulbs in Three Patients with Hyposmia
    AJNR Am J Neuroradiol 24:2097–2101, November/December 2003 Case Report Calcification of the Olfactory Bulbs in Three Patients with Hyposmia Stacey L. Ishman, Todd A. Loehrl, and Michelle M. Smith Summary: An estimated two million Americans suffer from Patient 2 chemosensory disorders. We present the clinical and imag- A 49-year-old African-American female patient presented ing findings in three hyposmic patients with bilateral ol- with altered flavor perception and frontal headaches. She did factory bulb calcification detected by CT. To our knowl- not have specific olfactory complaints. Her medical history was edge, these are the first cases of olfactory bulb calcification significant for hypertension, diabetes, seizures, and migraines. reported in the literature. A review of the literature con- She denied any tobacco use, nasal obstruction, rhinorrhea, or facial pain. Physical examination findings were unremarkable, cerning calcification of cranial nerves, olfactory neuritis, as were those at nasal endoscopy. On UPSIT, the patient and the potential etiology and clinical significance of olfac- correctly identified 87.5% (35/40) of odors on each side, which tory bulb calcification in our patients is presented. classified her condition as mildly hyposmic when her score was adjusted for age. Taste testing results were normal. CT of the sinonasal cavities revealed bilateral olfactory bulb calcification An estimated two million Americans suffer from (Fig 2A). MR images showed no abnormalities of the anterior taste and smell disorders, and as many as 25% of skull base or cerebrum; however, hypointense signal on cases are classified as idiopathic (1). We present three long-TR images was noted in the olfactory bulbs (Fig 2B), patients with hyposmia and olfactory bulb calcifica- corresponding to the dense calcifications shown by CT.
    [Show full text]
  • Long-Term Follow-Up of Surgically Treated Phantosmia
    ORIGINAL ARTICLE Long-term Follow-up of Surgically Treated Phantosmia Donald A. Leopold, MD; Todd A. Loehrl, MD; James E. Schwob, MD, PhD Objectives: To determine whether transnasal excision Results: Of 8 patients, 7 have complete and permanent of olfactory epithelium is a safe, effective therapy and to resolution of their phantosmia. Postoperatively, the learn more of the pathogenesis of phantosmia by study- single nostril olfactory ability in the operated-on nostril ing the histological features of the excised mucosa. is decreased in 2 nostrils, remains unchanged in 7, and is improved in 1. The excised olfactory mucosa gener- Design: A retrospective study consisting of a medical re- ally shows a decreased number of neurons, a greater ra- cord review and telephone survey. Follow-up ranged from tio of immature to mature neurons, and disordered 1 to 11 years (average, 5.4 years). Excised tissues were his- growth of axons with some intraepithelial neuromas. tologically processed and descriptively compared with nor- mal and other abnormal olfactory tissues. Conclusions: Surgical excision of olfactory epithelium Setting: Tertiary university medical referral centers. is an effective and safe method to relieve phantosmia while Patients: All patients who presented to the primary au- potentially preserving olfactory ability. The abnormal his- thor (D.A.L.) from 1988 to 1999 with unremitting phan- tological features of the excised olfactory tissue suggest tosmia lasting longer than 4 years. at least some pathological condition in the peripheral ol- factory system. This nasal surgery requires intensive ol- Intervention: Olfactory testing and transnasal endo- factory evaluation and follow-up. It is also extremely dif- scopic excision of olfactory mucosa.
    [Show full text]
  • Supplementary Materials Contents: • Supplementary Methods O App Development O Testing Kits • Supplementary Results O Tables: ▪ Supplementary Table S1
    Supplementary Materials Contents: • Supplementary Methods o App development o Testing Kits • Supplementary Results o Tables: ▪ Supplementary Table S1. List of symptom questions asked by the COVID Symptom Study app. ▪ Supplementary Table S2. List of local symptoms caused by the COVID Symptom Study app, caused by vaccination. ▪ Supplementary Table S3: Properties and features of models used in this study. ▪ Supplementary Table S4. Listing of clinical symptoms grouping. ▪ Supplementary Table S5. Profiles of illness in symptomatic individuals after the 1st dose of vaccination (N=145) and 2nd dose (N=4). ▪ Supplementary Table S6. Symptom prevalence and distribution during the first week after vaccination, in symptomatic individuals testing positive for SARS-CoV-2 infection. ▪ Supplementary Table S7. Symptom prevalence and distribution during the first week after vaccination, in symptomatic individuals testing negative for SARS-CoV-2 infection (1:1 matched cohort). ▪ Supplementary Table S8. Duration of individual symptoms after first vaccination (irrespective of symptom prevalence) in individuals testing positive or negative for SARS-CoV-2 (N=145 for each cohort). ▪ Supplementary Table S9. Demographic information of vaccinated individuals testing positive (N=149) and a constructed cohort of equal size created by bootstrapping testing negative for SARS-CoV-2. o Figures: ▪ Supplementary Figure S1. Profiles of illness in symptomatic individuals early post-vaccination, comparing symptom prevalence (symptom reported at any time during first week) in positive vs. negative cases (N=145 for each cohort), using bootstrapping to construct the negative cohort. ▪ Supplementary Figure S2. Profiles of illness in symptomatic individuals early post-vaccination, comparing symptom prevalence (symptom reported at any time during first week) in individuals testing positive (N=145) vs.
    [Show full text]
  • Handbook on Clinical Neurology and Neurosurgery
    Alekseenko YU.V. HANDBOOK ON CLINICAL NEUROLOGY AND NEUROSURGERY FOR STUDENTS OF MEDICAL FACULTY Vitebsk - 2005 УДК 616.8+616.8-089(042.3/;4) ~ А 47 Алексеенко Ю.В. А47 Пособие по неврологии и нейрохирургии для студентов факуль­ тета подготовки иностранных граждан: пособие / составитель Ю.В. Алексеенко. - Витебск: ВГМ У, 2005,- 495 с. ISBN 985-466-119-9 Учебное пособие по неврологии и нейрохирургии подготовлено в соответствии с типовой учебной программой по неврологии и нейрохирургии для студентов лечебного факультетов медицинских университетов, утвержденной Министерством здравоохра­ нения Республики Беларусь в 1998 году В учебном пособии представлены ключевые разделы общей и частной клиниче­ ской неврологии, а также нейрохирургии, которые имеют большое значение в работе врачей общей медицинской практики и системе неотложной медицинской помощи: за­ болевания периферической нервной системы, нарушения мозгового кровообращения, инфекционно-воспалительные поражения нервной системы, эпилепсия и судорожные синдромы, демиелинизирующие и дегенеративные поражения нервной системы, опу­ холи головного мозга и черепно-мозговые повреждения. Учебное пособие предназначено для студентов медицинского университета и врачей-стажеров, проходящих подготовку по неврологии и нейрохирургии. if' \ * /’ L ^ ' i L " / УДК 616.8+616.8-089(042.3/.4) ББК 56.1я7 б.:: удгритний I ISBN 985-466-119-9 2 CONTENTS Abbreviations 4 Motor System and Movement Disorders 5 Motor Deficit 12 Movement (Extrapyramidal) Disorders 25 Ataxia 36 Sensory System and Disorders of Sensation
    [Show full text]
  • Centrin 2 Is Required for Mouse Olfactory Ciliary Trafficking and Development of Ependymal Cilia Planar Polarity
    The Journal of Neuroscience, April 30, 2014 • 34(18):6377–6388 • 6377 Development/Plasticity/Repair Centrin 2 Is Required for Mouse Olfactory Ciliary Trafficking and Development of Ependymal Cilia Planar Polarity Guoxin Ying,1 Prachee Avasthi,1 Mavis Irwin,3 Cecilia D. Gerstner,1 Jeanne M. Frederick,1 Mary T. Lucero,3 and Wolfgang Baehr1,2,4 Departments of 1Ophthalmology, and 2Neurobiology and Anatomy, University of Utah Health Science Center, Salt Lake City, Utah 84132, and Departments of 3Physiology and 4Biology, University of Utah, Salt Lake City, Utah 84112 Centrins are ancient calmodulin-related Ca 2ϩ-binding proteins associated with basal bodies. In lower eukaryotes, Centrin2 (CETN2) is required for basal body replication and positioning, although its function in mammals is undefined. We generated a germline CETN2 knock-out (KO) mouse presenting with syndromic ciliopathy including dysosmia and hydrocephalus. Absence of CETN2 leads to olfac- tory cilia loss, impaired ciliary trafficking of olfactory signaling proteins, adenylate cyclase III (ACIII), and cyclic nucleotide-gated (CNG) channel, as well as disrupted basal body apical migration in postnatal olfactory sensory neurons (OSNs). In mutant OSNs, cilia base- anchoring of intraflagellar transport components IFT88, the kinesin-II subunit KIF3A, and cytoplasmic dynein 2 appeared compro- mised. Although the densities of mutant ependymal and respiratory cilia were largely normal, the planar polarity of mutant ependymal cilia was disrupted, resulting in uncoordinated flow of CSF. Transgenic expression of GFP-CETN2 rescued the Cetn2-deficiency pheno- type. These results indicate that mammalian basal body replication and ciliogenesis occur independently of CETN2; however, mouse CETN2 regulates protein trafficking of olfactory cilia and participates in specifying planar polarity of ependymal cilia.
    [Show full text]