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1.
Am Surg ; 89(8): 3612-3613, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36951139

RESUMO

Gallstone ileus is a rare complication of complicated gallbladder disease. Typically the result of a cholecystocholeduodenal fistula, a gallstone enters the small bowel and impacts in the ileum causing an obstruction. In this case study, a 74-year-old male presented to the emergency department with nausea, vomiting, and constipation for 2 weeks. CT revealed pneumobilia and a 3.1 cm calcified mass in the terminal ileum. The patient was successfully treated with a robotic-assisted enterotomy alone without complications.


Assuntos
Cálculos Biliares , Íleus , Obstrução Intestinal , Masculino , Humanos , Idoso , Íleus/diagnóstico por imagem , Íleus/etiologia , Cálculos Biliares/complicações , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/cirurgia , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Intestino Delgado , Íleo
2.
Am Surg ; 88(9): 2176-2181, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35839280

RESUMO

INTRODUCTION: Operative rib fixation is becoming more common in the management of rib fractures, with studies showing benefits of surgery in decreasing time on mechanical ventilation, ICU and total hospital length of stay, and mortality. This paper will review the data from our institution to determine if these benefits were seen in our trauma population. METHODS: A retrospective review of the institution's trauma database was conducted, including operative patients (n = 36), control patients (nonoperative patients from October 2018 to October 2019, n = 207), and selected control patients based on similar injury severity score range as operative patients (n = 181). Data reviewed included time on mechanical ventilation, ICU and total hospital length of stay, and disposition at discharge, including mortalities. Operative complications were also reviewed. RESULTS: The operative group had a higher ISS compared to both controls, longer average time on mechanical ventilation, longer average ICU and total hospital length of stay, and a higher percentage of patients discharged to inpatient facilities. However, the operative group had lower mortality compared to the control groups. The operative group had 3 surgical site infections requiring readmission and hardware removal. DISCUSSION: Unlike other studies, our operative patients did not see improvements in time on mechanical ventilation, ICU and total hospital length of stay, or disposition at discharge, but did see a mortality benefit. Confounding factors include higher average ISS in the operative group, and over-sedation in the ICU. Data collection is ongoing, and refinements are being made to perioperative and ICU management to minimize these confounding variables.


Assuntos
Fraturas das Costelas , Centros de Traumatologia , Humanos , Tempo de Internação , Estudos Retrospectivos , Fraturas das Costelas/complicações , Costelas
3.
J Gerontol A Biol Sci Med Sci ; 77(4): 673-682, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34671810

RESUMO

We examined the association between differential diagnoses of major stroke and probable Alzheimer's disease (AD) and mixed AD on C-reactive protein (CRP) in older adults with and without depression. Secondary data analyses examined associations between blood-based measures of probable peripheral inflammation using CRP collected from dried blood spots in the Health and Retirement Study, a nationally representative sample of individuals aged 50 and older. A validated pattern-recognition algorithm was utilized to identify cognitive decline indicative of probable AD, mixed AD, and major stroke. Negative binomial regressions were utilized to model concentrations of serologic CRP. On average, participants (N = 4 601) were 70 years old, female, and non-Hispanic White. Mixed AD participants had a 0.26 mg/dL increase in CRP compared to unimpaired participants, controlling for demographics, health behaviors, and comorbidities. Those with mixed AD had 2.14 times increased odds of having high CRP (odds ratio = 2.14 [1.19-3.85]). In analyses stratified by depression, adults with mixed AD and without depression had an additional 0.37 mg/dL increase in CRP (SE = 0.06; p < .001) compared to unimpaired adults. Those with AD without depression had a 0.20 mg/dL increase in CRP (SE = 0.07; p < .01). Age was not associated with increased CRP in nondepressed older adults. Depressed adults with major stroke had a -0.26 mg/dL decrease in CRP (SE = 0.11; p = .02), controlling for hypertension, alcoholic drinks/beverages per week, and smoking status. Concentration modeling revealed that participants with major stroke, probable AD, and probable mixed AD without depression had significantly higher CRP concentrations when compared to unimpaired older adults.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Idoso , Doença de Alzheimer/diagnóstico , Proteína C-Reativa/análise , Depressão/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Receptores Imunológicos , Aposentadoria
4.
Psychiatry Res Neuroimaging ; 302: 111109, 2020 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-32480044

RESUMO

There is a growing need for optimizing treatment selection and response prediction in individuals with major depressive disorder (MDD). Prior investigations have shown that changes in electroencephalographic (EEG)-based measures precede symptom improvement and could serve as biomarkers of treatment outcome. One such method is cordance, a computation of regional brain activity based on a combination of absolute and relative resting EEG activity. Specifically, early reduction in prefrontal (PF) and midline right frontal (MRF) theta (4-8Hz) cordance has been shown to predict response to various antidepressants, though replication is required. Thus, this study examined early changes (baseline to week 1) in PF and MRF cordance in 47 MDD patients undergoing antidepressant treatment. Early changes in cordance and in Montgomery Åsberg Depression Rating Scale (MADRS) scores were assessed alone, and in combination, to predict eventual (by week 12) treatment response and remission. Models combining early changes in theta cordance (PF and MRF) and depressive symptoms were most predictive of response to treatment at week 12; remission models (cordance, MADRS, and their combination) were weaker, though provided modest prediction values. These results suggest that antidepressant response may be optimally predicted by combining both EEG and symptom-based measures after one week of treatment.


Assuntos
Antidepressivos/uso terapêutico , Depressão/psicologia , Transtorno Depressivo Maior/tratamento farmacológico , Córtex Pré-Frontal/fisiopatologia , Ritmo Teta , Adulto , Bupropiona/uso terapêutico , Citalopram/uso terapêutico , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Eletroencefalografia/métodos , Feminino , Lobo Frontal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Resultado do Tratamento
6.
Adv Radiat Oncol ; 4(4): 559-565, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681862

RESUMO

PURPOSE: To present a systematic approach to the reirradiation special medical physics consult (ReRT-SMPC) process. MATERIALS AND METHODS: An in-house reirradiation committee of physicians and physicists was formed to develop a streamlined and well-documented approach to ReRT-SMPCs. Dosimetric goals and considerations for tissue repair were generated by the committee with input from the literature, clinical trial guidelines, and physician experience. Procedural workflow was also defined. RESULTS: The total number of ReRT-SMPCs performed in our department in 2018 was 401, corresponding to 369 unique patients and 16% of the total number of patients receiving external beam radiation in our department that year. This constituted a large increase over the 183 ReRT-SMPCs performed in 2017. We have found that a standardized ReRT-SMPC workflow helps to safeguard patients, documents the clinical decision-making process for medical and legal purposes, and facilitates the peer-review process. The data being collected from each consult along with toxicity and outcomes data can be used to help inform future re-treatment guidelines. CONCLUSIONS: As the number of patients returning for additional courses of radiation continues to increase, a uniform method for the ReRT-SMPC workflow and analysis is a powerful tool for ensuring patient safety, understanding and predicting treatment toxicity, and refining reirradiation dosimetric limits.

7.
Pharmacol Biochem Behav ; 184: 172739, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31283908

RESUMO

The high prevalence of concomitant cannabis and nicotine use has implications for sensory and cognitive processing. While nicotine tends to enhance function in these domains, cannabis use has been associated with both sensory and cognitive impairments, though the underlying mechanisms are unclear. Additionally, the interaction of the nicotinic (nAChR) and cannabinoid (CB1) receptor systems has received limited study in terms of sensory/cognitive processes. This study involving healthy volunteers assessed the acute separate and combined effects of nabilone (a CB1 agonist) and nicotine on sensory processing as assessed by auditory deviance detection and indexed by the mismatch negativity (MMN) event-related potential. It was hypothesized that nabilone would impair auditory discriminability as shown by diminished MMN amplitudes, but not when administered in combination with nicotine. 20 male non-smokers and non-cannabis-users were assessed using a 5-stimulus 'optimal' multi-feature MMN paradigm within a randomized, placebo controlled design (placebo; nabilone [0.5 mg]; nicotine [6 mg]; and nicotine + nabilone). Treatment effects were region- and deviant-dependent. At the temporal regions (mastoid sites), MMN was reduced by nabilone and nicotine separately, whereas co-administration resulted in no impairment. At the frontal region, MMN was enhanced by co-administration of nicotine and nabilone, with no MMN effects being found with separate treatment. These neural effects have relevance for sensory/cognitive processes influenced by separate and simultaneous use of cannabis and tobacco and may have treatment implications for disorders associated with sensory dysfunction and impairments in endocannabinoid and nicotinic cholinergic neurotransmission.


Assuntos
Agonistas de Receptores de Canabinoides/farmacologia , Dronabinol/análogos & derivados , Potenciais Evocados Auditivos/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Estimulação Acústica/métodos , Adulto , Agonistas de Receptores de Canabinoides/administração & dosagem , Método Duplo-Cego , Dronabinol/administração & dosagem , Dronabinol/farmacologia , Quimioterapia Combinada/métodos , Eletroencefalografia/métodos , Eletroculografia/métodos , Lobo Frontal/efeitos dos fármacos , Voluntários Saudáveis , Humanos , Masculino , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/metabolismo , Receptores Nicotínicos/metabolismo , Esquizofrenia/tratamento farmacológico , Lobo Temporal/efeitos dos fármacos , Adulto Jovem
8.
J Psychopharmacol ; 33(6): 688-699, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30920339

RESUMO

BACKGROUND: Schizophrenia (SCZ) patients and relatives have deficits in early cortical sensory gating (SG) typically measured by suppression of electroencephalography-derived P50 event-related potentials (ERPs) in a conditioning-testing (S1-S2) paradigm. Associated with alpha 7 nicotinic acetylcholine receptor (α7 nAChR) dysfunction and shown to be improved with nicotine and α7 nAChR agonists, SG has recently been shown to be improved in low P50 suppressing SCZ patients following acute CDP-choline treatment. AIMS: This pilot study in healthy humans assessed the SG effects of an α7 nAChR strategy combining CDP-choline with galantamine, a positive allosteric modulator (PAM) of nAChRs, aimed at increasing and prolonging nicotinic receptor activity. METHODS: The combined effect of CDP-choline (500 mg) and galantamine (16 mg) on speech P50 gating indices rP50 (S2/S1) and dP50 (S1-S2) was examined in 30 healthy participants stratified into low and high baseline P50 suppressors in a randomized, double-blind, placebo-controlled and counterbalanced design. RESULTS: In low suppressors, CDP-choline/galantamine (vs. placebo) improved rP50 and dP50 gating, and reduced S2P50 amplitudes. No P50 gating effects were observed in high suppressors; however, CDP-choline/galantamine (vs. placebo) increased their S2P50 amplitudes. CONCLUSION: Findings from this pilot study with CDP-choline/galantamine in a healthy, SCZ-like surrogate deficient gating sample are consistent with the association of α7 nAChR mechanisms in SG impairment in SCZ and support further research trials with CDP-choline and galantamine targeting sensory processes.


Assuntos
Citidina Difosfato Colina/uso terapêutico , Galantamina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Filtro Sensorial/efeitos dos fármacos , Fala/efeitos dos fármacos , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Adulto , Cognição/efeitos dos fármacos , Método Duplo-Cego , Potenciais Evocados/efeitos dos fármacos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Nicotina/metabolismo , Nootrópicos/uso terapêutico , Fonética , Projetos Piloto , Receptores Nicotínicos/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo
9.
Hum Psychopharmacol ; 34(1): e2684, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30488987

RESUMO

OBJECTIVE: The effects of GABA modulating drugs and nicotine, the prototypical nicotinic cholinergic agonist, on attention have been investigated using subcomponents of the P300 event-related potentials (ERP), which index involuntary (P3a) and voluntary attention (P3b). However, investigations into how such pharmacologic effects interact with genetic features in the GABA system remain unclear. This study examined the moderating effects of a single nucleotide polymorphism (rs7557793) in the glutamic acid decarboxylase 67 (GAD1) gene, which is implicated in the conversion of glutamate to GABA, on P300-indices of auditory attentional processing; the influence of nicotine administration was also assessed. METHODS: The effects of GAD1 genotype (TT/CC/CT) were examined on the P3a/b in response to an auditory selective attention task in healthy, nonsmoking male volunteers (N = 126; 18-40 years). Participants responded to rare target stimuli (P3b-eliciting) and ignored frequent nontarget stimuli as well as rare distractor stimuli (P3a-eliciting). In a subsample (N = 59), P3a/b profiles to acute nicotine (vs. placebo) administration were examined as a function of GAD1 genotype. As a secondary aim, earlier sensory processes were assessed with N200 ERP subcomponents elicited by novel (N2a) and target (N2b) auditory stimuli. RESULTS: GAD1 allelic variation moderated early sensory processes, enhancing N2a amplitudes in CT versus TT carriers. Further, TT homozygotes exhibited larger P3b amplitudes than CC homozygotes in the placebo versus nicotine condition. Regardless of genotype, nicotine versus placebo moderated the N200 ERP. CONCLUSION: These findings expand our knowledge regarding the attentional effects of GAD1 genetic variants in relation to nicotine.


Assuntos
Atenção/efeitos dos fármacos , Potenciais Evocados P300/efeitos dos fármacos , Glutamato Descarboxilase/genética , Nicotina/farmacologia , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Potenciais Evocados P300/fisiologia , Genótipo , Voluntários Saudáveis , Humanos , Masculino , Adulto Jovem , Ácido gama-Aminobutírico/fisiologia
10.
Sci Rep ; 8(1): 8036, 2018 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-29795273

RESUMO

A new synthesis approach for aluminum particles enables an aluminum core to be passivated by an oxidizing salt: aluminum iodate hexahydrate (AIH). Transmission electron microscopy (TEM) images show that AIH replaces the Al2O3 passivation layer on Al particles that limits Al oxidation. The new core-shell particle reactivity was characterized using laser-induced air shock from energetic materials (LASEM) and results for two different Al-AIH core-shell samples that vary in the AIH concentration demonstrate their potential use for explosive enhancement on both fast (detonation velocity) and slow (blast effects) timescales. Estimates of the detonation velocity for TNT-AIH composites suggest an enhancement of up to 30% may be achievable over pure TNT detonation velocities. Replacement of Al2O3 with AIH allows Al to react on similar timescales as detonation waves. The AIH mixtures tested here have relatively low concentrations of AIH (15 wt. % and 6 wt. %) compared to previously reported samples (57.8 wt. %) and still increase TNT performance by up to 30%. Further optimization of AIH synthesis could result in additional increases in explosive performance.

11.
Papillomavirus Res ; 5: 38-45, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29272853

RESUMO

BACKGROUND: Women with cervical cancer often have anal human papillomavirus (HPV) infection and anal dysplasia. However, effectiveness of anal HPV screening is unknown. METHODS: A dynamic model was constructed using STELLA. Populations are represented as "stocks" that change according to model rates. Initial anal cytology in new cervical cancer patients, dysplasia progression and regression, cost of treating high-grade squamous intraepithelial lesions (HSIL), and lifetime costs for anal cancer care were extrapolated from the literature. Local costs of anal HPV testing and cytology were obtained. Outcomes included anal cancer rates, anal cancer deaths, screening costs and cancer care. RESULTS: Benefits in the screened group included reduction in anal cancers after three years and anal cancer deaths after four years. After 10 years, predicted costs per anal cancer prevented and anal cancer deaths were $168,796 and $210,057 and were $98,631 and $210,057 at 20 years. Predicted costs per quality of life year saved at 10 and 20 years were $9785 and $1687. Sensitivity analysis demonstrated cost-effectiveness of screening for a variety of cure rates HSIL with electrocautery. CONCLUSION: Screening for anal HPV and treatment of anal HSIL in patients with cervical cancer is cost-effective, prevents anal cancer and reduces anal cancer deaths.


Assuntos
Canal Anal/patologia , Canal Anal/virologia , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/economia , Detecção Precoce de Câncer/economia , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Ânus/virologia , Carcinoma in Situ , Colposcopia/economia , Simulação por Computador , Análise Custo-Benefício , DNA Viral/isolamento & purificação , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Programas de Rastreamento/economia , Modelos Econômicos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Projetos Piloto , Qualidade de Vida , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/virologia , Displasia do Colo do Útero/virologia
12.
Psychiatry Res ; 256: 444-447, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28709058

RESUMO

Our aim was to explore the association between blood cadmium (BCd) and depressive symptoms, adjusting for pack years and blood cotinine, and also stratifying by smoking status. Using data from the US National Health and Nutrition Examination Survey (NHANES) 2005-2012, we categorized depressive symptoms using the PHQ-9 (Patient Health Questionnaire-9) survey and modeled depressive symptoms in relation to BCd adjusted for blood cotinine, pack years of smoking, and other covariates. We also stratified by self-reported smoking status (current, former, never). There were 11,209 subjects from 2005 to 2012, age ≥ 18 with PHQ-9, smoking, and blood cadmium data available. 876 (7.8%) met criteria for depressive symptoms. Depressive symptoms were associated with BCd levels in a crude model and with adjustment for pack years and cotinine. The association disappeared when analyzed among current, former, or never smokers. Consistent with the literature, we found an association between BCd and depressive symptoms; however, that association disappears in analyses stratified by smoking status. This suggests residual confounding may be present. It is important to stratify by smoking status when investigating health outcomes associated with BCd.


Assuntos
Cádmio/sangue , Fumar Cigarros/sangue , Depressão/sangue , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Autorrelato , Inquéritos e Questionários
13.
J Vis Exp ; (117)2016 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-27842354

RESUMO

Tetraiodine nonoxide (I4O9) has been synthesized using a dry approach that combines elemental oxygen and iodine without the introduction of hydrated species. The synthesis approach inhibits the topochemical effect promoting rapid hydration when exposed to the relative humidity of ambient air. This stable, amorphous, nano-particle material was analyzed using differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) and showed an exothermic energy release at low temperature (i.e., 180 °C) for the transformation of I4O9 into I2O5. This additional exothermic energy release contributes to an increase in overall reactivity of I4O9 when dry mixed with nano-aluminum (Al) powder, resulting in a minimum of 150% increase in flame speed compared to Al + I2O5. This study shows that as an oxidizer, I4O9 has more reactive potential than other forms of iodine(V) oxide when combined with Al, especially if I4O9 can be passivated to inhibit absorption of water from its surrounding environment.


Assuntos
Alumínio , Varredura Diferencial de Calorimetria , Cinética , Nanopartículas , Óxidos , Água
14.
Phys Chem Chem Phys ; 18(16): 11243-50, 2016 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-27052472

RESUMO

Iodine oxide is a highly reactive solid oxidizer and with its abundant generation of iodine gas during reaction, this oxidizer also shows great potential as a biocidal agent. A problem with using I2O5 in an energetic mixture is its highly variable reactive behavior. This study isolates the variable reactivity associated with I2O5 as a function of its chemical reaction in various environments. Specifically, aluminum fuel and iodine oxide powder are combined using a carrier fluid to aid intermixing. The carrier fluid is shown to significantly affect the oxidation state of iodine oxide, thereby affecting the reactivity of the mixture. Four carrier fluids were investigated ranging in polarity and water miscibility in increasing order from hexane < acetone < isopropanol < water as well as untreated, dry-mixed reactants. Oxidation state and reactivity were examined with experimental techniques including X-ray photoelectric spectroscopy (XPS) and differential scanning calorimetry (DSC). Results are compared with thermal equilibrium simulations. Flame speeds increased with polarity of the fluid used to intermix the powder and ranged from 180 to 1202 m s(-1). The I2O5 processed in the polar fluids formed hydrated states of iodine oxide: HIO3 and HI3O8; and, the nonpolar and dry-mixed samples formed: I2O4 and I4O9. During combustion, the hydrated iodine oxides rapidly dehydrated from HIO3 to HI3O8 and from HI3O8 to I2O5. Both steps release 25% of their mass as vapor during combustion. Increased gas generation enhances convective energy transport and accounts for the increase in reactivity seen in the mixtures processed in polar fluids. These results explain the chemical mechanisms underlying the variable reactivity of I2O5 that are a function of the oxide's highly reactive nature with its surrounding environment. These results will significantly impact the selection of carrier fluid in the synthesis approach for iodine containing reactive mixtures.

15.
Ochsner J ; 16(1): 37-40, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27046402

RESUMO

BACKGROUND: In the United States and in New York State, individuals with no health insurance have consistently lower screening rates for breast and cervical cancer than those with health insurance and are also more likely to be diagnosed with advanced stages of cancer. Our objective was to compare the cancer screening rates among patients at a free student-run clinic to state and national data. To our knowledge, ours is the first study examining breast and cervical screening rates and their relation to insurance status, income level, education level, race, and marital status in a suburban free student-run clinic. METHODS: As part of their intake from fall 2012 to spring 2013, patients at the Stony Brook Health Outreach and Medical Education Clinic in Stony Brook, NY, filled out a 26-item survey that included questions about race, income, education level, marital status, and cancer screening status. We compared the screening rates reported by our patients to published state and national rates. RESULTS: Breast and cervical cancer screening rates reported by 165 patients treated at our free student-run clinic were lower than the overall state and national averages. No significant associations between race, income, education level, or marital status and cancer screening rates were detected. CONCLUSION: Cancer screening rates at our free student-run clinic for the uninsured were lower than the overall state and national rates. These findings are consistent with previous reports of lower cancer preventive care utilization among the uninsured and suggest that insurance status has been a significant barrier to obtaining cancer screenings among our clinic population. Increasing cancer screening rates at student-run clinics may be a cost-effective secondary prevention activity that can decrease cancer mortality.

16.
J Psychopharmacol ; 30(1): 56-62, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26537155

RESUMO

While nicotine is often associated with the neuropsychological effects of tobacco smoke, the robust monoamine oxidase (MAO) inhibition observed in chronic smokers is also likely to play a role. Electroencephalographically-indexed alterations in baseline neural oscillations by nicotine have previously been reported in both smokers and non-smokers, however, little is known about the effects of MAO inhibition in combination with nicotine on resting state EEG. In a sample of 24 healthy non-smoking males, the effects of 6 mg nicotine gum, as well as MAO-A inhibition via 75 mg moclobemide, were investigated in separate and combined conditions over four separate test sessions. Drug effects were observed in the alpha2, beta2, and theta band frequencies. Nicotine increased alpha2 power, and moclobemide decreased beta2 power. Theta power was decreased most robustly by the combination of both drugs. Therefore, this study demonstrated that the nicotinic and MAO inhibiting properties of tobacco may differentially influence fast-wave oscillations (alpha2 and beta2), while acting in synergy to influence theta oscillations.


Assuntos
Moclobemida/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Interações Medicamentosas , Sinergismo Farmacológico , Eletroencefalografia , Humanos , Masculino , Moclobemida/administração & dosagem , Inibidores da Monoaminoxidase/administração & dosagem , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Dispositivos para o Abandono do Uso de Tabaco
17.
Pharmacol Biochem Behav ; 137: 44-52, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26226350

RESUMO

The mismatch negativity (MMN) auditory event-related potential (ERP) has been extensively studied as a potential biomarker for abnormal auditory processing in schizophrenia (SZ), a population which exhibits abnormally high smoking rates. The relationship between nicotinic activation and cognition in SZ may be related to underlying nicotinic and NMDA receptor dysfunction within the disease. However, transient cognitive improvements via smoking in patients may also result from monoamine oxidase (MAO) inhibition, achieved through tobacco smoke. In 24 healthy non-smoking males, we investigated the separate and combined effects of nicotine and MAO-A inhibition via moclobemide (75mg) on the optimal-5 variation of the MMN paradigm. No significant drug effects were observed in our total sample, however, stratification of individuals into low (N=12) and high (N=12) baseline MMN amplitude groups revealed increases in duration MMN amplitude relative to placebo by nicotine, as well as moclobemide, but not after the combination of the two. Because previous research has shown there was no effect of monoamine modulation on MMN, this study shows an unexpected effect of moclobemide on duration MMN.


Assuntos
Potenciais Evocados/efeitos dos fármacos , Moclobemida/administração & dosagem , Inibidores da Monoaminoxidase/administração & dosagem , Monoaminoxidase , Nicotina/administração & dosagem , Adulto , Estudos Cross-Over , Método Duplo-Cego , Combinação de Medicamentos , Potenciais Evocados/fisiologia , Humanos , Masculino , Monoaminoxidase/metabolismo , Estimulação Luminosa/métodos
18.
Psychopharmacology (Berl) ; 232(11): 1911-20, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25466703

RESUMO

INTRODUCTION: The cognitive effects of nicotine in humans remain a topic of great interest, due to the continued prevalence of cigarette smoking in society as well as the hypothesis that cognitively impaired populations such as schizophrenia patients use nicotine as a means of self-medicating against deficits of sensory gating. However, chronic smoking can predispose individuals to robust monoamine oxidase (MAO) inhibition, and thus far, the effect of MAO inhibition on human sensory gating is unknown. METHODS: In this study, we investigated the effects of both nicotine (6-mg gum) and pharmacologically induced MAO-A inhibition via moclobemide (75 mg) on P50 event-related potential-indexed sensory gating in a sample of 24 healthy non-smoking males. RESULTS: Ratio score (rP50) measured gating revealed significant improvement in auditory stimulus suppression after combined nicotine and MAO-A inhibition compared to placebo and to the nicotine-alone condition. This nicotine + MAO-A inhibition-induced efficient gating was consistent regardless of participants' baseline (placebo) gating efficiency, despite the observation that nicotine in the absence of MAO-A inhibition exhibited a detrimental effect on gating in participants with high baseline suppression ratios. CONCLUSION: Nicotine and monoamine oxidase-inhibiting agents in tobacco smoke appear to exert a synergistic effect on sensory gating, which may contribute to the elevated dependence rates seen in populations with cognitive deficits such as schizophrenia.


Assuntos
Potenciais Evocados/efeitos dos fármacos , Moclobemida/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Nicotina/farmacologia , Filtro Sensorial/efeitos dos fármacos , Adulto , Estudos Cross-Over , Método Duplo-Cego , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Esquizofrenia/fisiopatologia , Fumar/genética , Dispositivos para o Abandono do Uso de Tabaco
19.
Hum Psychopharmacol ; 29(5): 446-58, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25196041

RESUMO

OBJECTIVE: Cognitive enhancement resulting from nicotinic acetylcholine receptor stimulation may be evidenced by increased efficiency of the auditory-frontal cortex network of auditory discrimination, which is impaired in schizophrenia, a cognitive disorder associated with excessive tobacco use. Investigating automatic (preattentive) detection of acoustic change with the mismatch negativity (MMN) brain event-related potential in response to nicotine in individuals with varying baseline levels of auditory discrimination may provide useful insight into the cholinergic regulation of this neural network and its potential amelioration with novel nicotinic agents. METHODS: Sixty healthy, non-smoking male volunteers were presented with an 'optimal' multi-feature MMN paradigm in a randomized, placebo controlled double-blind design with 6 mg of nicotine gum. RESULTS: Participants with low, medium, and high baseline amplitudes responded differently to nicotine (vs. placebo), and nicotine response was feature specific. Whereas MMN in individuals with high amplitudes was diminished by nicotine, MMN increased in those with low amplitudes. Nicotine effects were not shown in medium amplitude participants. CONCLUSIONS: These findings provide preliminary support for the role of nicotinic neurotransmission in sensory memory processing of auditory change and suggest that nicotinic receptor modulation can both enhance and diminish change detection, depending on baseline MMN and its eliciting stimulus feature.


Assuntos
Percepção Auditiva/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Nicotina/farmacologia , Psicotrópicos/farmacologia , Detecção de Sinal Psicológico/efeitos dos fármacos , Estimulação Acústica , Adolescente , Adulto , Percepção Auditiva/fisiologia , Encéfalo/fisiologia , Método Duplo-Cego , Eletroencefalografia , Potenciais Evocados , Humanos , Masculino , Agonistas Nicotínicos/farmacologia , Detecção de Sinal Psicológico/fisiologia , Adulto Jovem
20.
Pharmacol Biochem Behav ; 122: 107-17, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24690514

RESUMO

Cholinergic stimulation produces cognitive effects that vary across individuals, and stimulus/task conditions. As of yet, the role of individual differences in moderating the effects of the nicotinic acetylcholine receptor agonist nicotine on specific attentional functions and their neural and behavioral correlates is not fully understood. In this randomized, double-blind, placebo-controlled study of 64 healthy non-smokers, we address the contribution of baseline-dependence to inter-individual variability in response to nicotine gum (6 mg) assessed with event-related brain potential (ERP) indices of involuntary (the anteriorly distributed P3a) and voluntary (the posteriorly distributed P3b) attention derived from an active 3-stimulus auditory oddball paradigm involving listening to standard and novel stimuli and detection and response to target stimuli. Nicotine enhanced the amplitude of P3a elicited during the processing of novel stimuli but only in individuals with relatively low baseline P3a amplitudes. Exhibiting an inverted-U nicotine response profile, target P3b and standard N1 amplitudes were increased and decreased in participants with low and high baseline amplitudes, respectively. In all, the findings corroborate the involvement of nicotinic mechanisms in attention, generally acting to increase attentional capacity in relatively low attentional functioning (reduced baseline ERPs) individuals, while having negative or detrimental effects in those with medium/high attentional levels (increased baseline ERPs), and in a manner that is differentially expressed during bottom-up (involuntary) attentional capture and top-down (voluntary) attentional allocation.


Assuntos
Atenção/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Potenciais Evocados P300/efeitos dos fármacos , Nicotina/administração & dosagem , Dispositivos para o Abandono do Uso de Tabaco , Adolescente , Adulto , Atenção/fisiologia , Encéfalo/fisiologia , Estudos Cross-Over , Método Duplo-Cego , Potenciais Evocados P300/fisiologia , Humanos , Masculino , Adulto Jovem
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