ResearchPad - vertigo https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Is postural dysfunction related to sarcopenia? A population-based study]]> https://www.researchpad.co/article/elastic_article_7695 Postural dysfunction is one of the most common community health symptoms and frequent chief complaints in hospitals. Sarcopenia is a syndrome characterized by degenerative loss of skeletal muscle mass, muscle quality, and muscle strength, and is the main contributor to musculoskeletal impairment in the elderly. Previous studies reported that loss of muscle mass is associated with a loss of diverse functional abilities. Meanwhile, there have been limited studies concerning postural dysfunction among older adults with sarcopenia. Although sarcopenia is primarily a disease of the elderly, its development may be associated with conditions that are not exclusively seen in older persons. Also, recent studies recognize that sarcopenia may begin to develop earlier in life. The objective of this paper was to investigate the association between the prevalence of sarcopenia and postural dysfunction in a wide age range of adults using data from a nationally representative cohort study in Korea. Korean National Health & Nutrition Exhibition Survey V (KNHANES V, 2010–2012) data from the fifth cross-sectional survey of the South Korean population performed by the Korean Ministry of Health and Welfare were used. Appendicular skeletal muscle mass (ASM)/height (ht)2 was used to define sarcopenia, and the Modified Romberg test using a foam pad (“foam balance test”) was performed to evaluate postural dysfunction. ASM/ht2 was lower in women and significantly decreased with age in men. Subjects with sarcopenia were significantly more likely to fail the foam balance test, regardless of sex and age. Regression analysis showed a significant relationship between sarcopenia and postural dysfunction (OR: 2.544, 95% CI: 1.683–3.846, p<0.001). Multivariate regression analysis revealed that sarcopenia (OR: 1.747, 95% CI: 1.120–2.720, p = 0.014) and age (OR: 1.131, 95% CI: 1.105–1.158, p<0.001) are independent risk factors for postural instability. In middle age subjects, the adjusted OR for sarcopenia was 3.344 (95% CI: 1.350–8.285) (p = 0.009). The prevalence of postural dysfunction is higher in sarcopenia patients, independent of sex and age.

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<![CDATA[Comparison of acute vertigo diagnosis and treatment practices between otolaryngologists and non-otolaryngologists: A multicenter scenario-based survey]]> https://www.researchpad.co/article/5c9902a2d5eed0c484b982b9

Acute vertigo is a common problem in emergency departments. However, clinical strategies of acute vertigo care vary among care providers. The aim of the study was to investigate differences in diagnosis [Dix-Hallpike test, the head impulse, nystagmus, and the test of skew (HINTS) procedure, and imaging modalities] and treatment (pharmacological treatments and the Epley maneuver) by otolaryngologists and non-otolaryngologists in emergency medicine settings. We used a multicenter case-based survey for the study. Four clinical vignettes of acute vertigo (posterior canal benign paroxysmal positional vertigo, vestibular neuritis, Meniere disease, and nonspecific vertigo) were used. Total 151 physicians from all study sites participated in the study. There were 84 non-otolaryngologists (48 emergency physicians and 36 internists) and 67 otolaryngologists. The multivariate analysis indicated that otolaryngologists ordered fewer CT scans (odds ratio (OR), 0.20; 95% confidence interval (CI), 0.07–0.53) and performed fewer HINTS procedures (OR, 0.17; 95% CI, 0.06–0.46), but used the Dix-Hallpike method more often (OR, 2.36; 95% CI, 1.01–5.52) for diagnosis compared to non-otolaryngologists. For treatment, otolaryngologists were less likely to use the Epley method (OR, 0.19; 95% CI, 0.07–0.53) and metoclopramide (OR, 0.09; 95% CI, 0.01–0.97) and more likely to use sodium bicarbonate (OR, 20.50; 95% CI, 6.85–61.40) compared to non-otolaryngologists. We found significant differences in the acute vertigo care provided by non-otolaryngologists and otolaryngologists from a vignette-based research. To improve acute vertigo care, educational systems focusing on acute vertigo are needed.

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<![CDATA[Who gets lost and why: A representative cross-sectional survey on sociodemographic and vestibular determinants of wayfinding strategies]]> https://www.researchpad.co/article/5c5b52bdd5eed0c4842bcf61

When we think of our family and friends, we probably know someone who is good at finding their way and someone else that easily gets lost. We still know little about the biological and environmental factors that influence our navigational ability. Here, we investigated the frequency and sociodemographic determinants of wayfinding and their association with vestibular function in a representative cross-sectional sample (N = 783) of the adult German-speaking population. Wayfinding was assessed using the Wayfinding Strategy Scale, a self-report scale that produces two scores for each participant representing to what degree they rely on route-based or orientation (map-based) strategies. We were interested in the following research questions: (1) the frequency and determinants of wayfinding strategies in a population-based representative sample, (2) the relationship between vestibular function and strategy choice and (3) how sociodemographic factors influence general wayfinding ability as measured using a combined score from both strategy scores. Our linear regression models showed that being male, having a higher education, higher age and lower regional urbanization increased orientation strategy scores. Vertigo/dizziness reduced the scores of both the orientation and the route strategies. Using a novel approach, we grouped participants by their combined strategy scores in a multinomial regression model, to see whether individuals prefer one strategy over the other. The majority of individuals reported using either both or no strategy, instead of preferring one strategy over the other. Young age and reduced vestibular function were indicative of using no strategy. In summary, wayfinding ability depends on both biological and environmental factors; all sociodemographic factors except income. Over a third of the population, predominantly under the age of 35, does not successfully use either strategy. This represents a change in our wayfinding skills, which may result from the technological advances in navigational aids over the last few decades.

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<![CDATA[Bilateral delayed endolymphatic hydrops evaluated by bilateral intratympanic injection of gadodiamide with 3T-MRI]]> https://www.researchpad.co/article/5c117b60d5eed0c484698ee1

The purpose of this study was to assess the diagnostic performance of 3T MRI after intratympanic injection of gadodiamide for delayed endolymphatic hydrops (DEH), and assess the relationship between endolymphatic hydrops (ELH) and vestibular function in patients diagnosed with DEH and confirmed by 3T MRI. Nineteen patients clinically diagnosed with DEH (11 ipsilateral DEH, 8 contralateral DEH) participated in this study. Diluted gadodiamide was administered to the bilateral tympanic cavity by injection through the tympanic membrane. At 24 hours post-injection, the ELH was evaluated by MRI. Patient vestibular functions were evaluated by caloric testing and cVEMP. ELH was observed in all patients (19/19: positive rate 100%). The distribution patterns of ELH varied between the cochlear or vestibular region. Vestibular ELH was observed in the affected ear in all ipsilateral DEH patients. In the contralateral DEH patients, however, there were individual differences in the distribution patterns of ELH. Six patients (1 ipsilateral DEH, 5 contralateral DEH) had bilateral ELH. No obvious relationships were observed between ELH and vestibular function. ELH distribution was complicated, particularly in the contralateral DEH cases. It was difficult to identify the existence of ELH by vestibular functional testing alone; therefore, 3T MRI is thought to be useful for identifying the affected ear. A significant number of cases had “bilateral” DEH, particularly among the contralateral DEH cases, indicating that we should pay careful attention to this pathology when treating DEH.

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<![CDATA[Baroreflex function, haemodynamic responses to an orthostatic challenge, and falls in haemodialysis patients]]> https://www.researchpad.co/article/5c12cf76d5eed0c48491469a

Background

Stage 5 chronic kidney disease patients on haemodialysis (HD) often present with dizziness and pre-syncopal events as a result of the combined effect of HD therapy and cardiovascular disease. The dysregulation of blood pressure (BP) during orthostasis may be implicated in the aetiology of falls in these patients. Therefore, we explored the relationship between baroreflex function, the haemodynamic responses to a passive orthostatic challenge, and falls in HD patients.

Methods

Seventy-six HD patients were enrolled in this cross-sectional study. Participants were classified as “fallers” and “non-fallers” and completed a passive head up tilting to 60o (HUT-60°) test on an automated tilt table. ECG signals, continuous and oscillometric BP measurements and impedance cardiography were recorded. The following variables were derived from these measurements: heart rate (HR) stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), number of baroreceptor events, and baroreceptor effectiveness index (BEI).

Results

The forty-four participants who were classified as fallers (57.9%) had a lower number of baroreceptor events (6.5±8.5 vs 14±16.7, p = .027) and BEI (20.8±24.2% vs 33.4±23.3%, p = .025). In addition, fallers experienced a significantly larger drop in systolic (-6.4±10.9 vs -0.4±7.7 mmHg, p = .011) and diastolic (-2.7±7.3 vs 1.8±6 mmHg, p = .027) oscillometric BP from supine to HUT-60° compared with non-fallers. None of the variables taken for the analysis were significantly associated with falls in multivariate logistic regression analysis.

Conclusions

This cross-sectional comparison indicates that, at rest, HD patients with a positive history of falls present with a lower count of baroreceptor sequences and BEI.

Short-term BP regulation warrants further investigation as BP drops during a passive orthostatic challenge may be implicated in the aetiology of falls in HD.

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<![CDATA[Effectiveness of betahistine (48 mg/day) in patients with vestibular vertigo during routine practice: The VIRTUOSO study]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc5b2

Background

Vestibular vertigo is associated with substantially reduced quality of life. Betahistine is effective in improving vertigo-associated symptoms, with longer treatment periods leading to greater improvements; however, it is not known whether these effects persist after treatment cessation.

Methods

VIRTUOSO was a prospective, multinational, non-comparative, post-marketing observational programme investigating the effectiveness of betahistine (48 mg/day) and the course of vertigo after the discontinuation of treatment. Patients with vestibular vertigo who were prescribed 48 mg/day betahistine were enrolled in Russia and Ukraine. Treatment duration was up to 2 months, and patients were followed up for 2 months after discontinuation of betahistine. Efficacy endpoints included clinical response (assessed by change in vertigo severity), monthly attack frequency, and physician and patient grading of overall clinical response and improvement of vertigo-associated symptoms.

Results

Overall, 309 patients were enrolled and 305 completed the study. Clinical response was rated as good, very good or excellent in 74.1% of patients at end of treatment, with vertigo severity significantly decreased from baseline (p < 0.001). Monthly vertigo attack frequency decreased significantly during the 2 months of treatment (p < 0.001 from baseline) and further decreased during the 2-month follow-up (p < 0.001 from end of treatment). Overall, clinical response was graded as good or excellent by 94.4% of physicians and 95.4% of patients. Clinical improvement was considered either good or excellent by 82.6–90.5% of physicians and patients for nausea, vomiting and faintness. Only one adverse event was reported, with no serious adverse events.

Conclusion

Our findings suggest that betahistine (48 mg/day) therapy is effective in treating vertigo in routine clinical settings. The observed effects persisted for 2 months after treatment cessation, suggesting that betahistine may facilitate lasting vestibular compensation.

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<![CDATA[Direct Acoustic Stimulation at the Lateral Canal: An Alternative Route to the Inner Ear?]]> https://www.researchpad.co/article/5989da11ab0ee8fa60b7995c

Severe to profound mixed hearing loss is associated with hearing rehabilitation difficulties. Recently, promising results for speech understanding were obtained with a direct acoustic cochlear implant (DACI). The surgical implantation of a DACI with standard coupling through a stapedotomy can however be regarded as challenging. Therefore, in this experimental study, the feasibility of direct acoustic stimulation was investigated at an anatomically and surgically more accessible inner ear site. DACI stimulation of the intact, blue-lined and opened lateral semicircular canal (LC) was investigated and compared with standard oval window (OW) coupling. Additionally, stapes footplate fixation was induced. Round window (RW) velocity, as a measure of the performance of the device and its coupling efficiency, was determined in fresh-frozen human cadaver heads. Using single point laser Doppler vibrometry, RW velocity could reliably be measured in low and middle frequency range, and equivalent sound pressure level (LE) output was calculated. Results for the different conditions obtained in five heads were analyzed in subsequent frequency ranges. Comparing the difference in RW membrane velocity showed higher LE in the LC opened condition [mean: 103 equivalent dB SPL], than in LC intact or blue-lined conditions [63 and 74 equivalent dB SPL, respectively]. No difference was observed between the LC opened and the standard OW condition. Inducing stapes fixation, however, led to a difference in the low frequency range of LE compared to LC opened. In conclusion, this feasibility study showed promising results for direct acoustic stimulation at this specific anatomically and surgically more accessible inner ear site. Future studies are needed to address the impact of LC stimulation on cochlear micromechanics and on the vestibular system like dizziness and risks of hearing loss.

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<![CDATA[Coenzyme Q10 Protects Hair Cells against Aminoglycoside]]> https://www.researchpad.co/article/5989da7cab0ee8fa60b98d04

It is well known that the production of free radicals is associated with sensory cell death induced by an aminoglycoside. Many researchers have reported that antioxidant reagents protect sensory cells in the inner ear, and coenzyme Q10 (CoQ10) is an antioxidant that is consumed as a health food in many countries. The purpose of this study was to investigate the role of CoQ10 in mammalian vestibular hair cell death induced by aminoglycoside. Cultured utricles of CBA/CaN mice were divided into three groups (control group, neomycin group, and neomycin + CoQ10 group). In the neomycin group, utricles were cultured with neomycin (1 mM) to induce hair cell death. In the neomycin + CoQ10 group, utricles were cultured with neomycin and water-soluble CoQ10 (30–0.3 µM). Twenty-four hours after exposure to neomycin, the cultured tissues were fixed, and vestibular hair cells were labeled using an anti-calmodulin antibody. Significantly more hair cells survived in the neomycin + CoQ10 group than in the neomycin group. These data indicate that CoQ10 protects sensory hair cells against neomycin-induced death in the mammalian vestibular epithelium; therefore, CoQ10 may be useful as a protective drug in the inner ear.

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<![CDATA[Neurogenic Potential of the Vestibular Nuclei and Behavioural Recovery Time Course in the Adult Cat Are Governed by the Nature of the Vestibular Damage]]> https://www.researchpad.co/article/5989da66ab0ee8fa60b91d9b

Functional and reactive neurogenesis and astrogenesis are observed in deafferented vestibular nuclei after unilateral vestibular nerve section in adult cats. The newborn cells survive up to one month and contribute actively to the successful recovery of posturo-locomotor functions. This study investigates whether the nature of vestibular deafferentation has an incidence on the neurogenic potential of the vestibular nuclei, and on the time course of behavioural recovery. Three animal models that mimic different vestibular pathologies were used: unilateral and permanent suppression of vestibular input by unilateral vestibular neurectomy (UVN), or by unilateral labyrinthectomy (UL, the mechanical destruction of peripheral vestibular receptors), or unilateral and reversible blockade of vestibular nerve input using tetrodotoxin (TTX). Neurogenesis and astrogenesis were revealed in the vestibular nuclei using bromodeoxyuridine (BrdU) as a newborn cell marker, while glial fibrillary acidic protein (GFAP) and glutamate decarboxylase 67 (GAD67) were used to identify astrocytes and GABAergic neurons, respectively. Spontaneous nystagmus and posturo-locomotor tests (static and dynamic balance performance) were carried out to quantify the behavioural recovery process. Results showed that the nature of vestibular loss determined the cellular plastic events occurring in the vestibular nuclei and affected the time course of behavioural recovery. Interestingly, the deafferented vestibular nuclei express neurogenic potential after acute and total vestibular loss only (UVN), while non-structural plastic processes are involved when the vestibular deafferentation is less drastic (UL, TTX). This is the first experimental evidence that the vestibular complex in the brainstem can become neurogenic under specific injury. These new data are of interest for understanding the factors favouring the expression of functional neurogenesis in adult mammals in a brain repair perspective, and are of clinical relevance in vestibular pathology.

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<![CDATA[Somatic Symptoms: Prevalence, Co-Occurrence and Associations with Self-Perceived Health and Limitations Due To Physical Health – A Danish Population-Based Study]]> https://www.researchpad.co/article/5989d9feab0ee8fa60b73126

A high number of somatic symptoms have been associated with poor health status and increased health care use. Previous studies focused on number of symptoms without considering the specific symptoms. The aim of the study was to investigate 1) the prevalence of 19 somatic symptoms, 2) the associations between the symptoms, and 3) the associations between the somatic symptoms, self-perceived health and limitations due to physical health accounting for the co-occurrence of symptoms. Information on 19 somatic symptoms, self-perceived health and limitations due to physical health was achieved from a population-based questionnaire survey of 36,163 randomly selected adults in the Capital Region of Denmark in 2006/07. Chain graph models were used to transparently identify and describe the associations between symptoms, self-perceived health and limitations due to physical health. In total, 94.9% of the respondents were bothered by one or more of the 19 somatic symptoms. The symptoms were associated in a complex structure. Still, recognisable patterns were identified within organ systems/body parts. When accounting for symptom co-occurrence; dizziness, pain in legs, respiratory distress and tiredness were all strongly directly associated with both of the outcomes (γ>0.30). Chest pain was strongly associated with self-perceived health, and other musculoskeletal symptoms and urinary retention were strongly associated with limitations due to physical health. Other symptoms were either moderate or not statistically associated with the health status outcomes. Opposite, almost all the symptoms were strongly associated with the two outcomes when not accounting for symptom co-occurrence. In conclusion, we found that somatic symptoms were frequent and associated in a complex structure. The associations between symptoms and health status measures differed between the symptoms and depended on the co-occurrence of symptoms. This indicates an importance of considering both the specific symptoms and symptom co-occurrence in further symptom research instead of merely counting symptoms.

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<![CDATA[Adverse effects of mefloquine for the treatment of uncomplicated malaria in Thailand: A pooled analysis of 19, 850 individual patients]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdba85

Mefloquine (MQ) has been used for the treatment of malaria since the mid-1980s, first as monotherapy or as fixed combination with sulfadoxine-pyrimethamine (MSP) and since the mid-1990s in combination with artesunate. There is a renewed interested in MQ as part of a triple therapy for the treatment of multi-drug resistance P. falciparum malaria. The widespread use of MQ beyond south-East Asia has been constrained by reports of poor tolerability. Here we present the side effect profile of MQ for the treatment of uncomplicated malaria on the Thai-Myanmar/Cambodia borders. In total 19,850 patients received seven different regimens containing either 15 or 24–25 mg/kg of MQ, the latter given either as a single dose, or split over two or three days. The analysis focused on (predominantly) gastrointestinal and neuropsychiatric events as compared to the new fixed dose combination of MQ plus artesunate given as equal doses of 8 mg/kg MQ per day over three days. Gastrointestinal side effects were dose-dependent and associated with the severity of malaria symptoms. Serious neuropsychiatric side effects associated with MQ use were rare: for a single 25 mg/kg dose it was 11.9 per 10,000 treatments (95% confidence interval, CI, 4–285) vs. 7.8 (3–15) for the 15 mg/kg dose. The risk with 25 mg/kg was much higher when it was given as repeat dosing in patients who had failed treatment with 15 mg/kg MQ in the preceding month; (RR 6.57 (95% CI 1.33 to 32.4), p = 0.0077). MQ was best tolerated as 15 mg/kg or as 24 mg/kg when given over three days in combination with artesunate. We conclude that the tolerance of a single dose of MQ in the treatment of uncomplicated malaria is moderate, but can be improved by administering it as a split dose over three days.

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<![CDATA[Examining the construct and known-group validity of a composite endpoint for The Older Persons and Informal Caregivers Survey Minimum Data Set (TOPICS-MDS); A large-scale data sharing initiative]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc782

Background

Preference-weighted multi-faceted endpoints have the potential to facilitate comparative effectiveness research that incorporates patient preferences. The Older Persons and Informal Caregivers Survey—Composite endpoint (TOPICS-CEP) is potentially a valuable outcome measure for evaluating interventions in geriatric care as it combines multiple outcomes relevant to older persons in a single metric. The objective of this study was to validate TOPICS-CEP across different study settings (general population, primary care and hospital).

Methods

Data were extracted from TOPICS Minimum Dataset (MDS), a pooled public-access national database with information on older persons throughout the Netherlands. Data of 17,603 older persons were used. Meta-correlations were performed between TOPICS-CEP indexed scores, EuroQol5-D utility scores and Cantril’s ladder life satisfaction scores. Mixed linear regression analyses were performed to compare TOPICS-CEP indexed scores between known groups, e.g. persons with versus without depression.

Results

In the complete sample and when stratified by study setting TOPICS-CEP and Cantril’s ladder were moderately correlated, whereas TOPICS-CEP and EQ-5D were highly correlated. Higher mean TOPICS-CEP scores were found in persons who were: married, lived independently and had an education at university level. Moreover, higher mean TOPICS-CEP scores were found in persons without dementia, depression, and dizziness with falls, respectively. Similar results were found when stratified by subgroup.

Conclusion

This study supports that TOPICS-CEP is a robust measure which can potentially be used in broad settings to identify the effect of intervention or of prevention in elderly care.

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<![CDATA[Autoimmunity as a Candidate for the Etiopathogenesis of Meniere's Disease: Detection of Autoimmune Reactions and Diagnostic Biomarker Candidate]]> https://www.researchpad.co/article/5989db2bab0ee8fa60bd1339

Meniere's disease is an inner ear disorder that can manifest as fluctuating vertigo, sensorineural hearing loss, tinnitus, and aural fullness. However, the pathologic mechanism of Meniere's disease is still unclear. In this study, we evaluated autoimmunity as a potential cause of Meniere's disease. In addition we tried to find useful biomarker candidates for diagnosis. We investigated the protein composition of human inner ear fluid using liquid column mass spectrometry, the autoimmune reaction between circulating autoantibodies in patient serum and multiple antigens using the Protoarray system, the immune reaction between patient serum and mouse inner ear tissues using western blot analysis. Nine proteins, including immunoglobulin and its variants and interferon regulatory factor 7, were found only in the inner ear fluid of patients with Meniere's disease. Enhanced immune reactions with 18 candidate antigens were detected in patients with Meniere's disease in Protoarray analysis; levels of 8 of these antigens were more than 10-fold higher in patients than in controls. Antigen-antibody reactions between mouse inner ear proteins with molecular weights of 23–48 kDa and 63–75 kDa and patient sera were detected in 8 patients. These findings suggest that autoimmunity could be one of the pathologic mechanisms behind Meniere's disease. Multiple autoantibodies and antigens may be involved in the autoimmune reaction. Specific antigens that caused immune reactions with patient's serum in Protoarray analysis can be candidates for the diagnostic biomarkers of Meniere's disease.

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<![CDATA[Arterial Spin Labeling Perfusion Study in the Patients with Subacute Mild Traumatic Brain Injury]]> https://www.researchpad.co/article/5989da0dab0ee8fa60b78434

Background

This study uses a MRI technique, three-dimension pulse continuous arterial spin labeling (3D-PCASL), to measure the patient’s cerebral blood flow (CBF) at the subacute stage of mild traumatic brain injury (MTBI) in order to analyze the relationship between cerebral blood flow and neurocognitive deficits.

Objective

To provide the relationship between cortical CBF and neuropsychological dysfunction for the subacute MTBI patients.

Methods

After MTBI, perfusion MR imaging technique (3D-PCASL) measures the CBF of MTBI patients (n = 23) within 1 month and that of normal controls (n = 22) to determine the quantity and location of perfusion defect. The correlation between CBF abnormalities and cognitive deficits was elucidated by combining the results of the neuropsychological tests of the patients.

Result

We observed a substantial reduction in CBF in the bilateral frontal and left occipital cortex as compared with the normal persons. In addition, there were correlation between post concussive symptoms (including dizziness and simulator sickness) and CBF in the hypoperfused areas. The more severe symptom was correlated with higher CBF in bilateral frontal and left occipital lobes.

Conclusion

First, this study determined that despite no significant abnormality detected on conventional CT and MRI studies, hypoperfusion was observed in MTBI group using 3D-PCASL technique in subacute stage, which suggested that this approach may increase sensitivity to MTBI. Second, the correlation between CBF and the severity of post concussive symptoms suggested that changes in cerebral hemodynamics may play a role in pathophysiology underlies the symptoms.

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<![CDATA[Safety and tolerability of high-dose ulinastatin after 2-hour intravenous infusion in adult healthy Chinese volunteers: A randomized, double-blind, placebo-controlled, ascending-dose study]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf6e8

Ulinastatin, is a broad-spectrum protease inhibitor purified from human urine, inhibits endogenous proteases such as trypsin, α-chymotrypsin, hyaluronidase, and plasmin. It is widely being used at increasingly higher doses for the treatment of acute or chronic pancreatitis, severe infection, and acute organ failure. We aimed to evaluate the safety and tolerability of high-dose ulinastatin in healthy volunteers in our single center, randomized, double-blind, placebo-controlled, single-dose escalation study. Fifty-one healthy Chinese subjects were enrolled in 9 dose cohorts (3×105 U, 6×105 U, 12×105 U, 20×105 U, 30×105 U, 45×105 U, 60×105 U, 70×105 U, or 80×105 U of ulinastatin) and randomized to UTI or matching placebo (n = 1). Each dose cohort was composed of 3–7 subjects. All subjects were required to have 2 h of intravenous infusion. Safety and tolerability were assessed throughout the study via monitoring of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms, and interviews with the subjects about adverse events. Fifty-one subjects (35 men and 16 women) completed the study. A total of 13 AEs were reported by 10 subjects: 11 adverse events in the ulinastatin groups and 2 adverse events in the placebo group. Twelve of the adverse events were possibly related to the study drug. The most common drug-related adverse events included dizziness, pain at injection site, and a decrease in white blood cell count. All adverse events were of mild severity; none were serious. In conclusion, 2 hours of intravenous infusion of ulinastatin (3×105 to 80×105 U) was well tolerated by healthy Chinese subjects.

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<![CDATA[Cupulin Is a Zona Pellucida-Like Domain Protein and Major Component of the Cupula from the Inner Ear]]> https://www.researchpad.co/article/5989da77ab0ee8fa60b9716c

The extracellular membranes of the inner ear are essential constituents to maintain sensory functions, the cupula for sensing torsional movements of the head, the otoconial membrane for sensing linear movements and accelerations like gravity, and the tectorial membrane in the cochlea for hearing. So far a number of structural proteins have been described, but for the gelatinous cupula precise data are missing. Here, we describe for the first time a major proteinogenic component of the cupula structure with an apparent molecular mass of 45 kDa from salmon. Analyses of respective peptides revealed highly conserved amino-acid sequences with identity to zona pellucida-like domain proteins. Immunohistochemistry studies localized the protein in the ampulla of the inner ear from salmon and according to its anatomical appearance we identified this glycoprotein as Cupulin. Future research on structure and function of zona pellucida-like domain proteins will enhance our knowledge of inner ear diseases, like sudden loss of vestibular function and other disturbances.

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<![CDATA[Involving Patients in Weighting Benefits and Harms of Treatment in Parkinson's Disease]]> https://www.researchpad.co/article/5989d9f1ab0ee8fa60b6e9e8

Introduction

Little is known about how patients weigh benefits and harms of available treatments for Parkinson’s Disease (oral medication, deep brain stimulation, infusion therapy). In this study we have (1) elicited patient preferences for benefits, side effects and process characteristics of treatments and (2) measured patients’ preferred and perceived involvement in decision-making about treatment.

Methods

Preferences were elicited using a best-worst scaling case 2 experiment. Attributes were selected based on 18 patient-interviews: treatment modality, tremor, slowness of movement, posture and balance problems, drowsiness, dizziness, and dyskinesia. Subsequently, a questionnaire was distributed in which patients were asked to indicate the most and least desirable attribute in nine possible treatment scenarios. Conditional logistic analysis and latent class analysis were used to estimate preference weights and identify subgroups. Patients also indicated their preferred and perceived degree of involvement in treatment decision-making (ranging from active to collaborative to passive).

Results

Two preference patterns were found in the patient sample (N = 192). One class of patients focused largely on optimising the process of care, while the other class focused more on controlling motor-symptoms. Patients who had experienced advanced treatments, had a shorter disease duration, or were still employed were more likely to belong to the latter class. For both classes, the benefits of treatment were more influential than the described side effects. Furthermore, many patients (45%) preferred to take the lead in treatment decisions, however 10.8% perceived a more passive or collaborative role instead.

Discussion

Patients weighted the benefits and side effects of treatment differently, indicating there is no “one-size-fits-all” approach to choosing treatments. Moreover, many patients preferred an active role in decision-making about treatment. Both results stress the need for physicians to know what is important to patients and to share treatment decisions to ensure that patients receive the treatment that aligns with their preferences.

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<![CDATA[Betahistine Exerts a Dose-Dependent Effect on Cochlear Stria Vascularis Blood Flow in Guinea Pigs In Vivo]]> https://www.researchpad.co/article/5989d9eeab0ee8fa60b6d9bc

Objective

Betahistine is a histamine H1-receptor agonist and H3-receptor antagonist that is administered to treat Menière’s disease. Despite widespread use, its pharmacological mode of action has not been entirely elucidated. This study investigated the effect of betahistine on guinea pigs at dosages corresponding to clinically used doses for cochlear microcirculation.

Methods

Thirty healthy Dunkin-Hartley guinea pigs were randomly assigned to five groups to receive betahistine dihydrochloride in a dose of 1,000 mg/kg b. w. (milligram per kilogram body weight), 0.100 mg/kg b. w., 0.010 mg/kg b. w., 0.001 mg/kg b. w. in NaCl 0.9% or NaCl 0.9% alone as placebo. Cochlear blood flow and mean arterial pressure were continuously monitored by intravital fluorescence microscopy and invasive blood pressure measurements 3 minutes before and 15 minutes after administration of betahistine.

Results

When betahistine was administered in a dose of 1.000 mg/kg b. w. cochlear blood flow was increased to a peak value of 1.340 arbitrary units (SD: 0.246; range: 0.933–1.546 arb. units) compared to baseline (p<0.05; Two Way Repeated Measures ANOVA/Bonferroni t-test). The lowest dosage of 0.001 mg/kg b. w. betahistine or NaCl 0.9% had the same effect as placebo. Nonlinear regression revealed that there was a sigmoid correlation between increase in blood flow and dosages.

Conclusions

Betahistine has a dose-dependent effect on the increase of blood flow in cochlear capillaries. The effects of the dosage range of betahistine on cochlear microcirculation corresponded well to clinically used single dosages to treat Menière’s disease. Our data suggest that the improved effects of higher doses of betahistine in the treatment of Menière’s disease might be due to a corresponding increase of cochlear blood flow.

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<![CDATA[Oculomotor Deficits after Chemotherapy in Childhood]]> https://www.researchpad.co/article/5989da35ab0ee8fa60b85e9a

Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years) treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years). Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS) and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy) was markedly poorer (p<0.001) and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence) (p = 0.004), whereas smooth pursuit and saccade onset times were shorter (p = 0.004) in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%), unsteadiness, light-headedness and that things around them were spinning or moving (87%). Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects’ self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of neurological complications following chemotherapy.

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<![CDATA[Amelioration of Acute Sequelae of Blast Induced Mild Traumatic Brain Injury by N-Acetyl Cysteine: A Double-Blind, Placebo Controlled Study]]> https://www.researchpad.co/article/5989dabbab0ee8fa60baec46

Background

Mild traumatic brain injury (mTBI) secondary to blast exposure is the most common battlefield injury in Southwest Asia. There has been little prospective work in the combat setting to test the efficacy of new countermeasures. The goal of this study was to compare the efficacy of N-acetyl cysteine (NAC) versus placebo on the symptoms associated with blast exposure mTBI in a combat setting.

Methods

This study was a randomized double blind, placebo-controlled study that was conducted on active duty service members at a forward deployed field hospital in Iraq. All symptomatic U.S. service members who were exposed to significant ordnance blast and who met the criteria for mTBI were offered participation in the study and 81 individuals agreed to participate. Individuals underwent a baseline evaluation and then were randomly assigned to receive either N-acetyl cysteine (NAC) or placebo for seven days. Each subject was re-evaluated at 3 and 7 days. Outcome measures were the presence of the following sequelae of mTBI: dizziness, hearing loss, headache, memory loss, sleep disturbances, and neurocognitive dysfunction. The resolution of these symptoms seven days after the blast exposure was the main outcome measure in this study. Logistic regression on the outcome of ‘no day 7 symptoms’ indicated that NAC treatment was significantly better than placebo (OR = 3.6, p = 0.006). Secondary analysis revealed subjects receiving NAC within 24 hours of blast had an 86% chance of symptom resolution with no reported side effects versus 42% for those seen early who received placebo.

Conclusion

This study, conducted in an active theatre of war, demonstrates that NAC, a safe pharmaceutical countermeasure, has beneficial effects on the severity and resolution of sequelae of blast induced mTBI. This is the first demonstration of an effective short term countermeasure for mTBI. Further work on long term outcomes and the potential use of NAC in civilian mTBI is warranted.

Trial Registration

ClinicalTrials.gov NCT00822263

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