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1.
Ear Hear ; 45(2): 276-296, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37784231

RESUMO

BACKGROUND: Chronic substance misuse is an ongoing and significant public health concern. Among a myriad of health complications that can occur, substance misuse potentially causes ototoxic effects. Case reports, retrospective chart data, and a few cohort studies suggest that certain prescription opioids and illicit drugs can have either temporary or permanent effects on auditory and/or vestibular function. Given the steady rise of people with a substance-use disorder (SUD), it is of growing importance that audiologists and otolaryngologists have an insight into the potential ototoxic effects of substance misuse. OBJECTIVES: A systematic review was conducted to (1) synthesize the literature on the illicit drugs, prescription opioids, and alcohol misuse on the auditory and vestibular systems, (2) highlight common hearing and vestibular impairments for each substance class, and (3) discuss the limitations of the literature, the potential mechanisms, and clinical implications for clinicians who may encounter patients with hearing or vestibular loss related to substance misuse, and describe opportunities for further study. DESIGN: Systematic searches were performed via PubMed, Scopus, and Google Scholar, and the final updated search was conducted through March 30, 2022. Inclusion criteria included peer-reviewed articles, regardless of study design, from inception until the present that included adults with chronic substance misuse and hearing and/or vestibular complaints. Articles that focused on the acute effects of substances in healthy people, ototoxicity from already known ototoxic medications, the relationship between hearing loss and development of a SUD, articles not available in English, animal work, and duplicates were excluded. Information on the population (adults), outcomes (hearing and/or vestibular data results), and study design (e.g., case report, cohort) were extracted. A meta-analysis could not be performed because more than 60% of the studies were single-case reports or small cohort. RESULTS: The full text of 67 studies that met the eligibility criteria were selected for the review. Overall, 21 studies reported associations between HL/VL related to illicit drug misuse, 28 studies reported HL/VL from prescription opioids, and 20 studies reported HL/VL related to chronic alcohol misuse (2 studies spanned more than one category). Synthesis of the findings suggested that the misuse and/or overdose of amphetamines and cocaine was associated with sudden, bilateral, and temporary HL, whereas HL from the combination of a stimulant and an opioid often presented with greater HL in the mid-frequency range. Reports of temporary vertigo or imbalance were mainly associated with illicit drugs. HL associated with misuse of prescription opioids was typically sudden or rapidly progressive, bilateral, moderately severe to profound, and in almost all cases permanent. The misuse of prescription opioids occasionally resulted in peripheral VL, especially when the opioid misuse was long term. Chronic alcohol misuse tended to associate with high-frequency sudden or progressive sensorineural hearing loss, or retrocochlear dysfunction, and a high occurrence of central vestibular dysfunction and imbalance. CONCLUSIONS: Overall, chronic substance misuse associates with potential ototoxic effects, resulting in temporary or permanent hearing and/or vestibular dysfunction. However, there are notable limitations to the evidence from the extant literature including a lack of objective test measures used to describe hearing or vestibular effects associated with substance misuse, small study sample sizes, reliance on case studies, lack of controlling for confounders related to health, age, sex, and other substance-use factors. Future large-scale studies with prospective study designs are needed to further ascertain the role and risk factors of substance misuse on auditory and vestibular function and to further clinical management practices.


Assuntos
Alcoolismo , Drogas Ilícitas , Transtornos Relacionados ao Uso de Substâncias , Adulto , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Alcoolismo/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Analgésicos Opioides/efeitos adversos
3.
Clin Neuropharmacol ; 46(2): 79-81, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36735548

RESUMO

OBJECTIVE: Phenibut is a widely available gamma-aminobutyric acid B receptor agonist. When taken chronically, phenibut causes dependence and subsequent withdrawal if stopped. Baclofen, a gamma-aminobutyric acid B receptor agonist structurally related to phenibut, has been used to manage phenibut withdrawal (PW), although baclofen doses for PW are not well defined and may exceed Food and Drug Administration-approved doses. Little data described outcomes from baclofen use. METHODS: This case details a patient who experienced a seizure while on baclofen 10 mg thrice daily as monotherapy for PW and highlights a potential risk of underdosing baclofen as monotherapy in the management of PW. RESULTS: A man in his early 30s with anxiety, depression, and substance use disorder presented to the emergency department by family for lethargy and confusion starting earlier that day. He had been using 25-30 g of phenibut daily for the past 6 months. On arrival, he was hypertensive, tachycardic, tachypneic, and lethargic. The patient received 1 mg of intravenous lorazepam and was admitted to the hospital for presumed PW. His symptoms improved overnight, and he was discharged on 10 mg of baclofen thrice daily. He returned 28 hours later after having a seizure and required intensive care admission in addition to multimodal drug therapy. CONCLUSIONS: Phenibut use is rising, and treatment options for PW, such as baclofen, warrant additional study. Potential risks of underdosing baclofen if used as monotherapy in PW may include seizures as withdrawal progresses. Baclofen's role in therapy may be more appropriate as an adjunct than a cornerstone of therapy. Treatment done in consultation with providers experienced in managing withdrawal such as a toxicologist may help reduce this risk.


Assuntos
Síndrome de Abstinência a Substâncias , Transtornos Relacionados ao Uso de Substâncias , Masculino , Humanos , Baclofeno/efeitos adversos , Ácido gama-Aminobutírico/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Convulsões/tratamento farmacológico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/etiologia
4.
BMC Psychiatry ; 23(1): 23, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627601

RESUMO

BACKGROUND: Illicit amphetamine-type stimulants (ATS) trafficking activities have increased substantially in Saudi Arabia over the last 10 years. In the period 2013-2017 Saudi Arabia seized the largest quantities of amphetamine at the global level. The current study examines whether the increased quantity of ATS seizures has an impact on amphetamine use disorder admissions. METHOD: This is an ecological study combining two datasets, the first dataset was obtained from United Nations Office on Drugs and Crime (UNODC), and the Al-Amal Hospital Electronic Health Record System in the city of Dammam, Eastern region of Saudi Arabia from 2005 to 2018. The annual incidence of patients diagnosed with amphetamine use was the dependent variable. The independent variable was the annual reported count of seized quantities of ATS in Saudi Arabia. We used a random intercept Negative Binomial model to predict the yearly count of amphetamine use disorder admission rates. RESULTS: A total of 910 amphetamine disorder admission patients in Al-Amal rehabilitation and addiction center, and the quantity equivalent to 200 tons of ATS was seized from 2005 to 2018. The amphetamine disorder admission rate has increased from 1.33% in 2005 to 18.27% in 2018. For each one-unit increase in the amphetamine confiscated quantities, the amphetamine use disorder admission rate increased by 49 to 88%. CONCLUSION: The current study found that reported amphetamine seized quantities were significantly and positively associated with the increase of amphetamine use disorder-related admission rates. In 2018, both ATS seized quantities and admission rates significantly increased, nearly doubling from the previous year. Rigorous, and multidisciplinary interventional studies to evaluate factors associated with increasing abuse of ATS should be a priority for policymakers and researchers in Saudi.


Assuntos
Estimulantes do Sistema Nervoso Central , Transtornos Relacionados ao Uso de Substâncias , Humanos , Anfetamina , Arábia Saudita/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estimulantes do Sistema Nervoso Central/efeitos adversos , Convulsões
5.
Psychopharmacology (Berl) ; 239(10): 3237-3248, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35933518

RESUMO

RATIONALE: Synthetic cannabinoid receptor agonists (SCRAs) are found in illicit smoking products, such as "K2" or "Spice." Convulsions are commonly reported adverse effects of SCRAs but are poorly understood. OBJECTIVES: We determined convulsant effects of SCRAs AB-PINACA, and 5F-ADB-PINACA in adult male NIH Swiss mice, and then determined if convulsant effects of AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, and JWH-018 elicited seizure-like effects using EEG. METHODS: Mice were administered SCRAs or pentylenetetrazole (PTZ) and placed in observation chambers where convulsant effects were scored. The capacity of the CB1R antagonist rimonabant, the benzodiazepine diazepam, or the non-specific CYP450 inhibitor 1-aminobenzotriazole (1-ABT) to attenuate convulsant effects was determined. Other mice were prepared with EEG headmounts to ascertain whether observed convulsions occurred concurrently with seizure-like effects by assessing root-mean-square (RMS) power, high amplitude EEG spike analysis, and videography. RESULTS: Mice receiving AB-PINACA or 5F-ADB-PINACA exhibited dose-dependent convulsant effects that were blocked by 10 mg/kg rimonabant pretreatment but not by pretreatment with 10 mg/kg diazepam; these convulsant effects were not altered in the presence of 100 mg/kg 1-ABT. Repeated administration of 10 mg/kg AB-PINACA and 3 mg/kg 5F-ADB-PINACA produced partial tolerance to convulsant effects but did not lead to cross-tolerance to PTZ-induced convulsions. In EEG studies, convulsant doses of AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, and JWH-018 did not produce seizures concomitantly with convulsions. CONCLUSIONS: These data extend previous findings of convulsant effects of SCRAs and suggest that convulsant effects of AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, and JWH-018 are CB1R-mediated but are not associated with electroencephalographic seizures. These results further suggest that benzodiazepines may not effectively treat convulsions elicited by SCRA use in humans.


Assuntos
Canabinoides , Transtornos Relacionados ao Uso de Substâncias , Animais , Benzodiazepinas , Agonistas de Receptores de Canabinoides/farmacologia , Canabinoides/farmacologia , Convulsivantes , Diazepam , Eletroencefalografia , Humanos , Indazóis , Indóis , Masculino , Camundongos , Naftalenos , Pentilenotetrazol/toxicidade , Receptor CB1 de Canabinoide , Rimonabanto , Convulsões/induzido quimicamente , Valina/análogos & derivados
6.
BMC Med ; 20(1): 183, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35570266

RESUMO

BACKGROUND: This study examines mental, neurological, and substance use (MNS) service usage within refugee camp primary health care facilities in low- and middle-income countries (LMICs) by analyzing surveillance data from the United Nations High Commissioner for Refugees Health Information System (HIS). Such information is crucial for efforts to strengthen MNS services in primary health care settings for refugees in LMICs. METHODS: Data on 744,036 MNS visits were collected from 175 refugee camps across 24 countries between 2009 and 2018. The HIS documented primary health care visits for seven MNS categories: epilepsy/seizures, alcohol/substance use disorders, mental retardation/intellectual disability, psychotic disorders, severe emotional disorders, medically unexplained somatic complaints, and other psychological complaints. Combined data were stratified by 2-year period, country, sex, and age group. These data were then integrated with camp population data to generate MNS service utilization rates, calculated as MNS visits per 1000 persons per month. RESULTS: MNS service utilization rates remained broadly consistent throughout the 10-year period, with rates across all camps hovering around 2-3 visits per 1000 persons per month. The largest proportion of MNS visits were attributable to epilepsy/seizures (44.4%) and psychotic disorders (21.8%). There were wide variations in MNS service utilization rates and few consistent patterns over time at the country level. Across the 10 years, females had higher MNS service utilization rates than males, and rates were lower among children under five compared to those five and older. CONCLUSIONS: Despite increased efforts to integrate MNS services into refugee primary health care settings over the past 10 years, there does not appear to be an increase in overall service utilization rates for MNS disorders within these settings. Healthcare service utilization rates are particularly low for common mental disorders such as depression, anxiety, post-traumatic stress disorder, and substance use. This may be related to different health-seeking behaviors for these disorders and because psychological services are often offered outside of formal health settings and consequently do not report to the HIS. Sustained and equitable investment to improve identification and holistic management of MNS disorders in refugee settings should remain a priority.


Assuntos
Epilepsia , Sistemas de Informação em Saúde , Refugiados , Transtornos Relacionados ao Uso de Substâncias , Criança , Epilepsia/epidemiologia , Epilepsia/terapia , Feminino , Humanos , Masculino , Saúde Mental , Atenção Primária à Saúde , Convulsões , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Nações Unidas
7.
Curr Pharm Des ; 28(15): 1213-1220, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35538799

RESUMO

Discovered in the United States of America (USA) in the 1960s, ketamine was introduced as an anaesthetic drug to specifically replace phencyclidine. Briefly, the substance moved from the medical world to recreational users, since it was discovered that intense psychedelic experiences were obtained with dosages lower than those prescribed for anesthesia. At the end of the 90's, it was circulated in London nightclubs as a drug itself and as counterfeit 3,4-methylenedioxymethamphetamine tablets. In 1997, the Drug Enforcement Administration (DEA) alerted the United States (US) government about the increasing diffusion of ketamine in American 'clubs', and in 1999, the substance was added to Schedule III of drugs controlled by federal authorities. In 2002, ketamine epidemics moved to Europe, and the European Monitoring Centre for Drugs and Drug Addiction carried out a risk assessment monitoring of the phenomenon. An estimated ninety-nine percent of all global ketamine seizures occurred in Asia. Its growing popularity is due to the fact that this new psychoactive substance is cheaper than other stimulants, such as MDMA. Moreover, the amount used for recreational purposes does not cause respiratory depression and its legal use as a drug makes it widely available for a diversion towards illicit markets. Nevertheless, acute intoxication and several deaths have been related to exclusive ketamine use both in Europe and internationally. Since 2015, there has been an increasing rise in the illicit ketamine market, and currently, the drug is being used with unprecedented peaks and a consequent significant increase in seizures and clinical cases worldwide.


Assuntos
Anestésicos , Ketamina , Transtornos Relacionados ao Uso de Substâncias , Fármacos do Sistema Nervoso Central , Humanos , Ketamina/efeitos adversos , Prescrições , Convulsões
8.
Epilepsy Behav ; 125: 108419, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34837845

RESUMO

RATIONALE: Recreational substance use (RSU) has been associated with seizure. There is limited knowledge on prevalence of seizures in patients with concomitant RSU in U.S. Thus, we aimed to investigate the prevalence of concomitant RSU in patients with seizures at a university based tertiary healthcare system. METHODS: We conducted a retrospective observational study from 01/01/2013 to 02/28/2021. Data from patient cohort explorer (a de-identified database) were used to select patients with seizure and a positive drug test (either urine or serum) obtained during the same encounter. The prevalence of RSU for individual substance was reported as percentage of number of encounters. RESULTS: There were 226,613 encounters with seizure(s) for a total of 40,459 subjects. Of the total, 5787 (2.5%) encounters with 4,342 subjects concomitantly tested positive for RSU. Mean age was 40.1 (±16.9) years, 58.4% were males, 59.1% were African Americans, and 38.3% were Caucasians. Gender and race of subjects with concomitant RSU for individual drug class was studied for all age groups and for subjects older than 16 years. CONCLUSIONS: Overall, the most common concomitantly positively tested RSU during seizure encounters was cannabinoid (40.7%) followed by benzodiazepine (38.7%). There was a higher proportion of males' encounters with concomitant seizure and RSU regardless of type of drug class. Amphetamine use was more common in Caucasians, while the remaining studied RSU were more common in African Americans. Similar trends were seen in the subgroup of subjects older than 16 years.


Assuntos
Transtornos Relacionados ao Uso de Substâncias , Adolescente , Adulto , Humanos , Masculino , Prevalência , Convulsões/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Centros de Atenção Terciária , População Branca
9.
Neurol India ; 69(5): 1241-1246, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34747791

RESUMO

BACKGROUND: Dizziness is a typical manifestation of vestibular pathologies. Clinical studies have shown that it affects 1.82% of young adults to more than 30% older adults. Habituation and compensation are some traditional rehabilitation protocols. OBJECTIVE: Yoga is also known to have a significant effect on vestibulopathy. Hence, a need arises to compare the above two maneuvers. MATERIALS AND METHODS: Participants were recruited (n = 32) after screening using the Dix-Hallpike and head impulse test. They were then divided into two groups (n = 16). The first one, Group A, received yogasanas, and the second one, Group B, received gaze stabilization and habituation exercises for 4 days a week for 3 weeks. Pre- and post intervention outcome measures were taken using the motion sensitivity quotient (MSQ) score and Dizziness Handicap Inventory (DHI) scale. RESULTS: In reducing symptoms of dizziness, the between-group comparison shows that Group A has shown greater improvement (12.37% ±1.43%) in MSQ and Group B has shown greater improvement (16.12 ± 3.56) in DHI. Within-group comparison shows that both the interventions are effective in reducing symptoms of dizziness (P < 0.05). CONCLUSION: Both gaze stabilization along with habituation exercises and yogasanas are effective in improving the symptoms of dizziness in patients with peripheral vestibular dysfunction. When compared between the groups, yogasanas had a superior hand in the MSQ score, whereas gaze stabilization and habituation exercises had a superior hand in the DHI scale.


Assuntos
Tontura , Vestíbulo do Labirinto , Idoso , Tontura/terapia , Terapia por Exercício , Habituação Psicofisiológica , Humanos , Vertigem , Adulto Jovem
10.
Am J Public Health ; 111(11): 2046-2049, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34618543

RESUMO

Objectives. To determine whether there have been shifts in nonmedical ketamine use, poisonings ("exposures"), and seizures. Methods. We used generalized additive models to detect trends in past-year use (2006-2019), exposures (1991-2019), and seizures (2000-2019) involving ketamine in the United States. Results. There was a quarterly increase in self-reported past-year nonmedical ketamine use in 2006 to 2014 (Β = 0.21; P = .030) and an increase in 2015 to 2019 (Β = 0.29; P = .036), reaching a peak of 0.9% in late 2019. The rate of exposures increased from 1991 through 2019 (Β = 0.87; P = .006), and there was an increase to 1.1 exposures per 1 000 000 population in 2014, with rates remaining stable through 2019. The rate of ketamine seizures increased from 2000 through 2019 (Β = 2.27; P < .001), with seizures reaching a peak in 2019 at 3.2 per 1000 seizures. Conclusions. Indicators suggest that ketamine use and availability has increased, including before increased medical indications, but nonmedical use is still currently uncommon despite increased acceptance and media coverage. (Am J Public Health. 2021;111(11):2046-2049. https://doi.org/10.2105/AJPH.2021.306486).


Assuntos
Analgésicos/intoxicação , Ketamina/intoxicação , Convulsões/induzido quimicamente , Convulsões/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Estados Unidos/epidemiologia
11.
Am J Med Genet A ; 185(3): 894-900, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33369065

RESUMO

Neuroligin 4 X-linked (NLGN4X) is an X-linked postsynaptic scaffolding protein, with functional role in excitatory synapsis development and maintenance, that has been associated with neuropsychiatric disorders such as intellectual disability, autism spectrum disorders (ASD), anxiety, attention deficit hyperactivity disorder (ADHD), and Tourette's syndrome. Chromosomal microarray analysis identified a paternally inherited, 445 Kb deletion on Xp22.3 that includes the entire NLGN4X in a 2.5 year old female (46,XX) with congenital hypotonia, strabismus, ASD, and increased aggressive behavioral issues. Her family history is significant for a mother with learning disabilities, a father with anxiety, major depressive disorder, and substance abuse, as well as two maternal half-brothers with developmental delays. X-inactivation studies in the proband's blood showed random X-inactivation despite the presence of an abnormal X chromosome. Furthermore, trio exome sequencing did not reveal any other deleterious variant that could explain her phenotype. Our report describes the first example of a paternally inherited NLGN4X microdeletion as the genetic etiology of ASD in a female proband, and the psychiatric phenotypes in the father. It also provides further evidence that NLGN4X is sensitive to dosage changes in females, and can contribute to a variety of psychiatric features within the same family.


Assuntos
Moléculas de Adesão Celular Neuronais/genética , Cromossomos Humanos X/genética , Deficiências do Desenvolvimento/genética , Deleção de Genes , Genes Ligados ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Síndrome de Tourette/genética , Adulto , Agressão , Ansiedade/genética , Transtorno do Espectro Autista/genética , Transtornos do Comportamento Infantil/genética , Pré-Escolar , Feminino , Humanos , Hibridização in Situ Fluorescente , Deficiências da Aprendizagem/genética , Masculino , Anamnese , Análise em Microsséries , Herança Paterna , Convulsões/genética , Estrabismo/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Sequenciamento do Exoma , Inativação do Cromossomo X
12.
BMC Pediatr ; 20(1): 552, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287753

RESUMO

BACKGROUND: In contrast to intoxications in toddlers which can be due to accidental ingestions, many intoxications in infants are due to medication errors. To our knowledge, this is the first case report of a citalopram intoxication in an infant, and may offer new insight on possible screening methods for intoxication as well as pharmacokinetics of citalopram in small infants. CASE PRESENTATION: This case report describes an unintentional citalopram intoxication in a 4 week old infant due to a vitamin D drops 'look alike' error. The infant showed extreme jitteriness and opisthotonus at presentation, as well as prolonged signs of gastro-oesophageal reflux. No cardiac rhythm disturbances or convulsions were seen. The clinical course combined with Finnegan scores was correlated to and supported by pharmacokinetic and pharmacokinetic data of citalopram in the patient. CONCLUSIONS: Using Finnegan scores in general pediatric practice could help objectify follow-up of acute intoxications in young infants with neurological symptoms.


Assuntos
Refluxo Gastroesofágico , Transtornos Relacionados ao Uso de Substâncias , Criança , Citalopram , Humanos , Lactente , Convulsões
13.
J Toxicol Sci ; 45(7): 391-399, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612007

RESUMO

This study was aimed at examining propofol- (a known anesthetic) induced emotion-related behavioral disorders in mice, and exploring the possible molecular mechanisms. A total of 60 mice were divided into two groups: control and propofol group. Mice were injected with propofol (150 mg/kg, ip) at 8:00 a.m. (once a day, lasting for 30 days). During the 30 days, loss of righting reflex (LORR) and return of righting reflex (RORR) of mice were recorded every day. At the 1st (T1) and 30th (T2) day of drug discontinuance (T2), 15 mice of each group were selected to perform the open field test; then the mice underwent perfusion fixation, and the midbrain and corpus striatum were separated for immunofluorescence assay with anti-tyrosine hydroxylase (Th) and anti- dopamine transporter (DAT) antibodies. Results showed that after propofol injection, LORR and RORR increased and decreased, respectively. Long-term use of propofol resulted in decreased activities of mice (activity trajectory, line crossing, rearing time, scratching times and defecating frequency). Immunofluorescence assay showed long-term use of propofol induced decrease of Th and DAT. Collectively, our present work suggested long-term abuse of propofol induces neuropsychiatric function impairments, and the possible mechanisms are related to dopamine dyssynthesis via down-regulating tyrosine hydroxylase and dopamine transporter.


Assuntos
Anestésicos/toxicidade , Comportamento Animal/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Neurônios Dopaminérgicos/patologia , Transtornos Mentais/induzido quimicamente , Propofol/toxicidade , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/patologia , Tirosina 3-Mono-Oxigenase/metabolismo , Área Tegmentar Ventral/metabolismo , Área Tegmentar Ventral/patologia , Anestésicos/efeitos adversos , Animais , Neurônios Dopaminérgicos/metabolismo , Emoções/efeitos dos fármacos , Masculino , Transtornos Mentais/metabolismo , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Camundongos Endogâmicos C57BL , Propofol/efeitos adversos , Reflexo de Endireitamento/efeitos dos fármacos
14.
Neurology ; 95(6): e643-e652, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32690794

RESUMO

OBJECTIVE: To investigate the hypothesis that patients diagnosed with psychogenic nonepileptic seizures (PNES) on video-EEG monitoring (VEM) have increased mortality by comparison to the general population. METHODS: This retrospective cohort study included patients evaluated in VEM units of 3 tertiary hospitals in Melbourne, Australia, between January 1, 1995, and December 31, 2015. Diagnosis was based on consensus opinion of experienced epileptologists and neuropsychiatrists at each hospital. Mortality was determined in patients diagnosed with PNES, epilepsy, or both conditions by linkage to the Australian National Death Index. Lifetime history of psychiatric disorders in PNES was determined from formal neuropsychiatric reports. RESULTS: A total of 5,508 patients underwent VEM. A total of 674 (12.2%) were diagnosed with PNES, 3064 (55.6%) with epilepsy, 175 (3.2%) with both conditions, and 1,595 (29.0%) received other diagnoses or had no diagnosis made. The standardized mortality ratio (SMR) of patients diagnosed with PNES was 2.5 (95% confidence interval [CI] 2.0-3.3). Those younger than 30 had an 8-fold higher risk of death (95% CI 3.4-19.8). Direct comparison revealed no significant difference in mortality rate between diagnostic groups. Among deaths in patients diagnosed with PNES (n = 55), external causes contributed 18%, with 20% of deaths in those younger than 50 years attributed to suicide, and "epilepsy" was recorded as the cause of death in 24%. CONCLUSIONS: Patients diagnosed with PNES have a SMR 2.5 times above the general population, dying at a rate comparable to those with drug-resistant epilepsy. This emphasizes the importance of prompt diagnosis, identification of risk factors, and implementation of appropriate strategies to prevent potential avoidable deaths.


Assuntos
Transtorno Conversivo/mortalidade , Convulsões/mortalidade , Adolescente , Adulto , Distribuição por Idade , Transtornos de Ansiedade/mortalidade , Causas de Morte , Criança , Pré-Escolar , Comorbidade , Transtorno Conversivo/fisiopatologia , Transtorno Depressivo/mortalidade , Grupos Diagnósticos Relacionados , Transtornos Dissociativos/mortalidade , Eletroencefalografia , Epilepsia/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Convulsões/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Suicídio/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos , Vitória/epidemiologia , Gravação em Vídeo , Adulto Jovem
15.
Aerosp Med Hum Perform ; 91(4): 326-331, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32493554

RESUMO

BACKGROUND: Aerobatic flight is a challenge for the vestibular system, which is likely to lead to adaptive changes in the vestibular responses of pilots. We investigated whether aerobatic pilots, as individuals who experience intense vestibular stimulation, present modifications of the vestibular-ocular reflex, motion sickness susceptibility and intensity, visual vertical estimation, and visual dependence as compared to normal volunteers.METHODS: To evaluate vestibulo-ocular reflexes, eye movements were recorded with videonystagmography while subjects were rotated on a rotatory chair with the axis of rotation being vertical (canal-ocular reflex) or inclined to 17° (otolith-ocular reflex). Motion sickness was evaluated after the rotatory test using the Graybiel diagnostic criteria. General motion sickness susceptibility and visual field dependence were also evaluated.RESULTS: Averaged data did not show significant difference in canal-ocular reflex and otolith ocular-reflex between groups. However, a significant asymmetry in otolith-driven ocular responses was found in pilots (CW 0.50 ± 1.21° · s-1 vs. CCW 1.59 ± 1.12° · s-1), though visual vertical estimation was not altered in pilots and both groups were found field independent. Pilots were generally less susceptible to motion sickness (MSSQ scores: 2.52 ± 5.59 vs. 13.5 ± 11.36) and less affected by the nauseogenic stimulation (Graybiel diagnostic criteria 3.36 ± 3.81 vs. 8.39 ± 7.01).DISCUSSION: We did not observe the expected habituation in the group of aerobatic pilots. However, there was a significant asymmetry in the otolith-driven ocular responses in pilots, but not in the controls, which may result from the asymmetry in piloting protocols.Kuldavletova O, Tanguy S, Denise P, Quarck G. Vestibulo-ocular responses, visual field dependence, and motion sickness in aerobatic pilots. Aerosp Med Hum Perform. 2020; 91(4):326-331.


Assuntos
Medicina Aeroespacial , Habituação Psicofisiológica , Enjoo devido ao Movimento/fisiopatologia , Pilotos , Reflexo Vestíbulo-Ocular/fisiologia , Campos Visuais/fisiologia , Adolescente , Adulto , Estudos de Casos e Controles , Medições dos Movimentos Oculares , Feminino , Humanos , Masculino , Testes de Função Vestibular , Adulto Jovem
16.
Int J Occup Med Environ Health ; 33(4): 497-506, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32519680

RESUMO

OBJECTIVES: The authors formulated a hypothesis that, on completion of the training program by cadets, their vestibular habituation would increase, measured by the time of the duration of the test on the unlocked looping, in contrast to the initial values and the control group. MATERIAL AND METHODS: The research involved 35 male cadets, first-year students of the Polish Air Force Academy in Deblin. The examined persons were on average 20 years of age. They were divided into 2 groups. Group A (N = 25, tested) continued training on Special Aviation Gymnastic Instruments (SAGI). The cadets were a homogeneous group of participants in the jet pilot course, selected by the Military Aeromedical Board. Group B (N = 10, control) conducted the standard physical military education program. Groups A and B were tested on the unlocked looping before and after the training process. In the training process, the groups had heart rate (HR) monitored. RESULTS: The cadets in group A on the test in the unlocked looping, at the beginning of the training period, had an average score of 468.5±96.6 s, and on completion of the training period 575.6±47.9 s, which is a statistically significant difference at p < 0.000001. Similarly, the examined individuals in group B received an average score of 396.2±31.8 s, and at the end of the training period 473.4±72.0 s, which is a statistically significant difference at p < 0.01. In group A, a statistically significant decrease in the average HR value was observed. In group B, there was a statistically significant increase in the average HR value. CONCLUSIONS: The exercises on SAGI have a beneficial impact on improving the habituation of the vestibular organ in training cadets in examination II, as opposed to examination I and the control group. Int J Occup Med Environ Health. 2020;33(4):497-506.


Assuntos
Medicina Aeroespacial , Habituação Psicofisiológica , Militares/educação , Vestíbulo do Labirinto/fisiologia , Ginástica/fisiologia , Frequência Cardíaca , Humanos , Masculino , Polônia , Estudantes , Testes de Função Vestibular , Adulto Jovem
17.
Rev. colomb. psiquiatr ; 49(2): 116-120, abr.-jun. 2020. graf
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1115652

RESUMO

RESUMEN Introducción: El síndrome de Otelo, epónimo del personaje de Shakespeare, es un término diagnóstico transnosológico que designa un cuadro caracterizado por delirios de infidelidad respecto a la pareja que, por consiguiente, puede acarrear actitudes celotípicas y conductas violentas hacia ella. En su forma pura, corresponde al trastorno delirante de infidelidad, pero también puede ser secundario a organicidad cerebral y a consumo de drogas. Métodos: Reporte de caso y revisión no sistemática de la literatura relevante. Presentación del caso: Varón de 26 arios con antecedente de consumo de drogas y víctima de maltrato infantil, 3 años antes había sufrido crisis convulsivas tónico-clónicas e hipertensión intracraneal, por lo que se sometió a una craneotomía, en la que se halló un tuberculoma cerebral frontal derecho. Tras un lapso, comenzó con delirios de infidelidad y conductas violentas hacia su pareja. Revisión de la literatura: Los celos delirantes se asocian, como otros delirios, a lesiones del lóbulo frontal derecho. Pese a la elevada y creciente prevalencia mundial de tuberculosis, no se han publicado casos de síndrome de Otelo secundario a tuberculoma cerebral. Conclusiones: El síndrome de Otelo, aunque no es la principal causa de violencia doméstica, puede asociarse con manifestaciones particularmente violentas y ser secundario a tuberculoma cerebral. Este es el primer caso de tal índole que se publica.


ABSTRACT Introduction: Othello syndrome, an eponym of Shakespeare's character, is a transnosological diagnostic term that designates a clinical picture characterised by the presence of delusions of infidelity with respect to a partner and that, consequently, can lead to typical jealousy attitudes and violent behaviour towards the partner. In its pure form, it corresponds to delusional disorder of infidelity, but it may also be secondary to brain organicity and drug use. Methods: Case report and non-systematic review of the relevant literature. Case presentation: A 26-year-old man, with a history of drug abuse and a victim of domestic violence as a child, presented with tonic-clonic seizures and intracranial hypertension three years ago, for which he underwent a craniotomy with the finding of a right frontal cerebral tuberculoma. After a lapse, he developed a clinical picture of delusions of infidelity regarding his partner and violent behaviour towards her. Literature review: Delusional jealousy is associated, like other delusions, with lesions of the right frontal lobe. Despite the high and growing prevalence of tuberculosis worldwide, there are no reported cases of Othello syndrome secondary to cerebral tuberculoma in the literature. Conclusion: Othello syndrome, although not the main cause of domestic violence, can be associated with particularly violent manifestations and be secondary to cerebral tuberculoma. This is the first published case of its kind.


Assuntos
Humanos , Masculino , Adulto , Síndrome , Transtornos Relacionados ao Uso de Substâncias , Ciúme , Esquizofrenia Paranoide , Convulsões , Atitude , Prevalência , Violência Doméstica , Hipertensão Intracraniana , Craniotomia , Diagnóstico , Epônimos , Lobo Frontal
18.
J Pharmacol Exp Ther ; 374(2): 273-282, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385092

RESUMO

Methylenedioxypyrovalerone (MDPV) is an abused synthetic cathinone, commonly referred to as a "bath salt." Because the dopamine (DA) transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2) are key regulators of both the abuse and neurotoxic potential of structurally and behaviorally related agents, the impact of MDPV on these transporters was investigated. Results revealed that a single in vivo MDPV administration rapidly (within 1 hour) and reversibly increased both rat striatal DAT and VMAT-2 activity, as assessed via [3H]DA uptake in synaptosomes and synaptic vesicles, respectively, prepared from treated rats. There was no evidence of an MDPV-induced increase in plasmalemmal membrane DAT surface expression. Plasma concentrations of MDPV increased dose-dependently as assessed 1 hour after 2.5 and 5.0 mg/kg (s.c.) administration and returned to levels less than 10 ng/ml by 18 hours after 2.5 mg/kg (s.c.). Neither pretreatment with a D1 receptor (SCH23390), a D2 receptor (eticlopride), nor a nicotinic receptor (mecamylamine) antagonist attenuated the MDPV-induced increase in DAT activity. In contrast, eticlopride pretreatment attenuated both the MDPV-induced increase in VMAT-2-mediated DA uptake and an associated increase in cytoplasmic-associated vesicle VMAT-2 immunoreactivity. SCH23390 did not attenuate the MDPV-induced increase in VMAT-2 activity. Repeated MDPV injections did not cause persistent DAergic deficits, as assessed 7 to 8 days later. The impact of MDPV on striatal and hippocampal serotonergic assessments was minimal. Taken together, these data contribute to a growing pharmacological rubric for evaluating the ever-growing list of designer cathinone-related stimulants. The profile of MDPV compared with related psychostimulants is discussed. SIGNIFICANCE STATEMENT: Pharmacological characterization of the synthetic cathinone, 3,4-methylenedioxypyrovalerone (MDPV; commonly referred to as a "bath salt"), is critical for understanding the abuse liability and neurotoxic potential of this and related agents. Accordingly, the impact of MDPV on monoaminergic neurons is described and compared with that of related psychostimulants.


Assuntos
Benzodioxóis/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Drogas Desenhadas/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Pirrolidinas/farmacologia , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , Animais , Benzodioxóis/farmacocinética , Temperatura Corporal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacocinética , Drogas Desenhadas/farmacocinética , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Feminino , Masculino , Neostriado/efeitos dos fármacos , Neostriado/metabolismo , Pirrolidinas/farmacocinética , Ratos , Ratos Sprague-Dawley , Catinona Sintética
19.
Rev. otorrinolaringol. cir. cabeza cuello ; 80(1): 54-62, mar. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1099202

RESUMO

La vestibulopatía bilateral es poco frecuente, se caracteriza principalmente por inestabilidad al caminar o al estar de pie, visión borrosa inducida por el movimiento u oscilopsia al caminar o al realizar movimientos rápidos de la cabeza o del cuerpo, empeoramiento de la estabilidad en la oscuridad o terrenos irregulares, reducción de los síntomas al estar en condiciones estáticas, ganancia del reflejo vestíbulo-ocular angular reducida de forma bilateral, entre otros. Existen múltiples causas. Dentro de las causas identificables, se describen principalmente medicamentos ototóxicos, meningitis y enfermedad de Ménière. Se presenta el caso de una paciente de 64 años diagnosticada con vestibulopatía bilateral posterior a tratamiento intramuscular con gentamicina por sobreinfección bacteriana cutánea de las manos. La evaluación vestibular complementada con videonistagmografía y prueba de impulso cefálico asistida por video confirman el diagnóstico y se inicia tratamiento con rehabilitación vestibular enfocada en promover la compensación central a través de estrategias de sustitución principalmente; además de habituación y adaptación vestibular, favoreciendo la estabilización de la mirada, mantención del equilibrio, control postural, marcha y reducción de los síntomas.


Bilateral vestibulopathy is infrequent, and it is characterized mostly by unstable walking or when standing, blurred vision induced by movement, or oscillopsia when walking or performing fast movements; worsening of the stability in darkness or uneven ground, but with lack of symptoms in static conditions. Other symptoms may include bilateral reduction of the oculo-vestibular reflex. Among the identifiable causes, there is the use of ototoxic medication, meningitis, Ménière's disease, although it can be idiopathic or have a neurological cause. We hereby describe the case of a 64-year-old woman, diagnosed with bilateral vestibulopathy secondary to intramuscular treatment with gentamicin due to a bacterial hand infection. Vestibular assessment was complemented with video-nystagmography and video head impulse test which confirmed the diagnosis, and therapy was started with vestibular rehabilitation focused on promoting central compensation mainly, through substitution strategies. Also, habituation exercise and vestibular adaptation strategies were used, thus promoting sight stabilization, balance maintenance, postural control, walking, and reduction of the symptoms.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Gentamicinas/efeitos adversos , Vestibulopatia Bilateral/induzido quimicamente , Vestibulopatia Bilateral/reabilitação , Antibacterianos/efeitos adversos , Audiometria , Superinfecção , Eletronistagmografia , Teste do Impulso da Cabeça , Vestibulopatia Bilateral/diagnóstico , Vestibulopatia Bilateral/fisiopatologia
20.
Genes Brain Behav ; 19(5): e12634, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31898856

RESUMO

A subset of people exposed to a traumatic event develops post-traumatic stress disorder (PTSD), which is associated with dysregulated fear behavior. Genetic variation in SLC18A2, the gene that encodes vesicular monoamine transporter 2 (VMAT2), has been reported to affect risk for the development of PTSD in humans. Here, we use transgenic mice that express either 5% (VMAT2-LO mice) or 200% (VMAT2-HI mice) of wild-type levels of VMAT2 protein. We report that VMAT2-LO mice have reduced VMAT2 protein in the hippocampus and amygdala, impaired monoaminergic vesicular storage capacity in both the striatum and frontal cortex, decreased monoamine metabolite abundance and a greatly reduced capacity to release dopamine upon stimulation. Furthermore, VMAT2-LO mice showed exaggerated cued and contextual fear expression, altered fear habituation, inability to discriminate threat from safety cues, altered startle response compared with wild-type mice and an anxiogenic-like phenotype, but displayed no deficits in social function. By contrast, VMAT2-HI mice exhibited increased VMAT2 protein throughout the brain, higher vesicular storage capacity and greater dopamine release upon stimulation compared with wild-type controls. Behaviorally, VMAT2-HI mice were similar to wild-type mice in most assays, with some evidence of a reduced anxiety-like responses. Together, these data show that presynaptic monoamine function mediates PTSD-like outcomes in our mouse model, and suggest a causal link between reduced VMAT2 expression and fear behavior, consistent with the correlational relationship between VMAT2 genotype and PTSD risk in humans. Targeting this system is a potential strategy for the development of pharmacotherapies for disorders like PTSD.


Assuntos
Medo , Transtornos de Estresse Pós-Traumáticos/genética , Proteínas Vesiculares de Transporte de Monoamina/genética , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/fisiologia , Animais , Sinais (Psicologia) , Dopamina/metabolismo , Feminino , Habituação Psicofisiológica , Hipocampo/metabolismo , Hipocampo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Comportamento Social , Proteínas Vesiculares de Transporte de Monoamina/metabolismo
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