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Aim: Early/follow-up durability of superior mesenteric artery (SMA) stent-grafts is crucial after fenestrated/branched endografting (FB-EVAR) in complex abdominal aortic aneurysms (CAAAs) and thoracoabdominal aortic aneurysms (TAAAs). The study aimed to report early/midterm outcomes of SMA incorporated during FB-EVAR procedures. Methods: FB-EVAR procedures performed between 2016 and 2021 in a single institution were reviewed. Anatomical SMA characteristics were analyzed. The SMA configuration was classified into three types according to the angle between the SMA main trunk and the aorta: (A) perpendicular, (B) downward, and (C) upward. SMA-related technical success (SMA-TS: cannulation and stenting, patency at completion angiography without endoleak, stenosis/kinking, dissection, bleeding, and 24-h mortality) and SMA-adverse events (SMA-AEs: one among bowel ischemia, stenosis, occlusion, endoleak, reinterventions, or SMA-related mortality) were assessed. Results: Two hundred FB-EVAR procedures with SMA as the target artery were performed. The indication for FB-EVAR was CAAAs and TAAAs in 99 (49%) and 101 (51%) cases, respectively. The SMA configuration was A, B, and C in 132 (66%), 63 (31%), and 5 (3%) cases, respectively. SMA was incorporated with fenestrations and branches in 131 (66%) and 69 (34%) cases, respectively. Directional branch (P < .001), aortic diameter ≥35â mm at the SMA level (P < .001), and ≥2 SMA bridging stent-grafts (P = .001) were more frequent in TAAAs. Relining of the SMA stent-graft with a bare metal stent was necessary in 41 (21%) cases to correct an acute angle between the stent-graft and native artery (39), stent-graft stenosis (1), or SMA dissection (1). Relining was associated with type A or C SMA configuration (OR: 17; 95% CI: 1.8-157.3; P = .01). SMA-TS was achieved in all cases. Overall, 15 (7.5%) patients had SMA-AEs [early: 9 (60%), follow-up: 6 (40%)] due to stenosis (2), endoleak (8), and bowel ischemia (5). Aortic diameter ≥35â mm at the SMA level was an independent risk factor for SMA-AEs (OR: 4; 95% CI: 1.4-13.8; P = .01). Fourteen (7%) patients died during hospitalization with 10 (5%) events within the 30-postoperative day. Emergency cases (OR: 33; 95% CI: 5.7-191.3; P = .001), peripheral arterial occlusive disease (OR: 14; 95% CI: 2.3-88.8; P = .004), and bowel ischemia (OR: 41; 95% CI: 1.9-87.9; P = .01) were risk factors for 30-day/in-hospital mortality. The mean follow-up was 32 ± 24 months; estimated 3-year survival was 81%, with no case of late SMA-related mortality or occlusion. The estimated 3-year freedom from overall and SMA-related reinterventions was 74% and 95%, respectively. Conclusion: SMA orientation determines the necessity of stent-graft relining. Aortic diameter ≥35â mm at the SMA level is a predictor of SMA-AEs. Nevertheless, SMA-related outcomes of FB-EVAR are satisfactory, with excellent technical success and promising clinical outcomes during the follow-up.
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OBJECTIVE: The contribution of psychological and psychiatric symptoms in the development of Functional Neurological Disorders (FND) is unclear. We therefore aimed to investigate the role of different attachment styles (AS) and their relationship with psychiatric symptoms in FND patients as compared with both subjects with neurological disorders (ND) and healthy controls (HC); and the possible differences between patients with functional movement disorders (FMD) and with functional seizures. METHODS: In this case-control study, forty-six patients with FND were compared to 34 with ND and 30 HC, by means of an extensive battery to investigate the presence of alexithymia, depression, anxiety, dissociation and to explore their AS using the Revised Experiences in Close Relationships instrument (ECR-R). RESULTS: Patients with FND had higher depression and alexithymia as well as an avoidant pattern on the ECR-R than patients with ND. In the FND group, ECR-R avoidance was an independent predictor of psychiatric symptoms and, altogether, ECR-R avoidance, the somatic-affective component of depression and difficulty identifying feelings were independent predictors of FND. Gender, anxiety and difficulty identifying feelings predicted the presence of functional seizures. CONCLUSION: The avoidant AS may be an important psychological factor influencing the presence of mood disorders and alexithymia. Their co-occurence might drive maladaptive responses underlying the presence of FND. Although we demonstrated a large overlap between FND phenotypes, patients with functional seizures might have higher alexithymia, which in turn could explain a defensive response less anchored to body reactions and physical symptoms.
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Sintomas Afetivos , Ansiedade , Transtornos de Ansiedade , Estudos de Casos e Controles , Humanos , ConvulsõesRESUMO
Anesthetics and other products used during the perioperative period may influence immune function not only merely by reducing the HPA-axis stress response but also by directly modulating innate and adaptive immune responses. Most of the literature on the immune effects of anesthetics has been derived from in vitro or animal studies, due to the number of confounding variables in real life surgical settings. These immunosuppressive effects might not normally have clinical consequences for an immune-competent patient, but may act as important modifiers in postoperative morbidity and mortality. Furthermore, some inhibitory effects on neutrophil functions may provide a therapeutically beneficial effect under specific surgical clinical conditions, such as ischemia-reperfusion injury.
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Sistema Imunitário/fisiologia , Período Perioperatório , Analgésicos Opioides/farmacologia , Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Anestésicos Locais/farmacologia , Animais , Humanos , Sistema Imunitário/efeitos dos fármacosRESUMO
Produced formation waters (PFWs) represent the largest aqueous wastes that are normally discharged into the marine environment during the offshore gas production processes. The chemical additive diethylene glycol (DEG) is widely used in the gas production line and therefore can be found in the PFW, becoming of environmental concern. In this study, a new method has been developed for trace determination of DEG in sea water samples collected around offshore gas platforms. The method is based on liquid chromatography coupled to electrospray ionization mass spectrometry (LC-ESI-MS). Prior to analysis, water samples were derivatized using the Schotten-Baumann method for the benzoylation of glycols. The derivatization procedure allowed us to maximize the ESI-MS response of DEG and minimize the influence of interfering compounds. The method was validated and allowed a quantification of DEG in sea water samples with a method LOD of 0.4 ng/mL. The applicability of the procedure was demonstrated by analyzing sea water samples collected around eight gas platforms located in the Adriatic Sea (Italy).
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Cromatografia Líquida/métodos , Etilenoglicóis/análise , Água do Mar/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Poluentes Químicos da Água/análise , Benzoatos/química , Etilenoglicóis/química , Resíduos Industriais/análise , Itália , Modelos Químicos , Estrutura Molecular , Reprodutibilidade dos Testes , Água do Mar/químicaRESUMO
Water pollution by organochlorine pesticides (OCPs) is considered as an analytical challenge, since these persistent and nonbiodegradable pollutants are not amenable by liquid chromatography coupled to atmospheric pressure ionization mass spectrometry (LC/API-MS). This represents a significant constraint in multiresidue analysis of real samples, when high polar, poorly volatile compounds are present as well. This paper reports the development of an innovative single-step method for the simultaneous determination of OCPs and polar pesticides belonging to the class of phenoxy acids in water samples. The method is based on an off-line solid-phase extraction (SPE) procedure with Carbograph 4 followed by liquid chromatography coupled to a direct electron ionization mass spectrometer (LC/direct-EI-MS). The direct-EI capability of acquiring high-quality EI spectra and operation in selected ion monitoring mode allowed a precise quantification of OCPs and phenoxy acids in a single chromatographic run without derivatization. The instrumental response was characterized by excellent sensitivity, linearity, and precision. The SPE recovery rates in river water gave values equal or better than 80% for most of the compounds. The method limits of detection (LODs) span from 0.002 to 0.052 microg/L, allowing the detection of the selected pesticides at the limits required by the European Union (EU) legislation for drinking water.
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Contrary to common believing, the prevalence of the intolerance to food additives in the general population is rather low. Nowadays many doubts persist with regard both to the pathogenetic mechanisms and to the clinical and diagnostic aspects in this field. Symptoms due to, or exacerbated from, food additives usually involve non-IgE-mediate mechanisms (pseudo-allergic reactions, PAR) and are usually less severe of those induced by food allergy. The most frequent clinical feature of the intolerance to food additives still remains the urticaria-angioedema syndrome, although these substances are really involved only in a minority of patients. Other possible clinical features include anaphylaxis, atopic eczema, behaviour disturbances, asthma and non-allergic rhinitis. The diagnostic approach consists in diary cards, reporting symptoms and food habits, elimination diet and double blinded placebo-controlled oral challenge with suspected additives. However, such procedure still remains poorly standardized and numerous uncertainties persist with regard to optimal conditions for performing and interpret the challenge results. The therapeutic approach consists in the exclusion of foods and products containing the additive involved, and, in patients not compliant to the diet, in treatment with symptomatic drugs.
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Aditivos Alimentares/efeitos adversos , Hipersensibilidade Alimentar , Alérgenos , Criança , Aditivos Alimentares/análise , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/dietoterapia , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/terapia , Humanos , Prevalência , Testes Cutâneos , Fatores de Tempo , Urticária/etiologiaRESUMO
In an attempt to investigate the neoplastic progression in different stages of actinic keratosis (AK), a standardized AgNOR analysis was performed in 94 cases of AK, 35 of which were associated with squamous cell carcinoma (SCC) or basal cell carcinoma (BCC), and in 31 cases of SCC and 22 cases of BCC. The cases were subdivided into low- and high-AgNOR-expressing (AgNOR status) AK by using the mean area of AgNORs per cell (NORA) value (3.996 micro(2)) as the cut-off. In AK samples, a progressive increase of the mean NORA value from Stage I to Stage IV was encountered. In addition, a significantly higher mean NORA value was found in the AK cases associated with SCC, in comparison to those without SCC; by contrast, no significant differences in the mean NORA value were noted between AK cases with or without BCC. A highly significant association between a high AgNOR quantity and the coexistence of SCC was encountered in AK; no association was appreciable between the AgNOR quantity and the co-occurrence of BCC. Moreover, when the co-existence of SCC in AK was considered as the reference point, the AK cases associated with SCC mostly (95.5%) presented a high AgNOR quantity (high sensitivity), but only 57.6% of cases without SCC displayed a low AgNOR quantity (low specificity). Additionally, our data document that the standardised AgNOR analysis represents a strong negative predictor for the association between SCC and AK. Indeed, a low AgNOR quantity mostly is associated with AK cases without SCC.
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Antígenos Nucleares/análise , Carcinoma Basocelular/química , Carcinoma de Células Escamosas/química , Ceratose/metabolismo , Região Organizadora do Nucléolo/química , Neoplasias Cutâneas/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Feminino , Humanos , Ceratose/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Coloração pela Prata , Neoplasias Cutâneas/patologiaRESUMO
Contamination of water resources by organochlorine pesticides (OCPs) continues to receive widespread attention because of the increasing concern regarding their high persistence and bioaccumulation. These organic pollutants are not amenable by liquid chromatography (LC) coupled to atmospheric pressure ionization-mass spectrometry, which represents the method of choice for the characterization of pesticide residues in water. Gas chromatography-mass spectrometry provides excellent response for OCPs, but it falls short when complex, multiresidue analyses are required. As recently demonstrated, an efficient EI-based LC-MS interface can generate very good spectra for an extremely wide range of small-medium molecular weight molecules of different polarity and can represent a valid tool in solving the analytical challenge of analyzing OCPs by LC-MS. Based on this assumption, we present a new approach for the determination of 12 OCPs in water samples. The method requires a solid-phase extraction preconcentration step followed by nanoscale liquid chromatography coupled to a direct-electron ionization direct interface (Direct-EI). Direct-EI is a miniaturized interface for efficiently coupling a liquid chromatograph with an EI mass spectrometer. The capability to acquire high-quality EI spectra in a wide range of concentrations, and to operate in selected ion monitoring mode during analyses, allowed a precise quantification of the OCPs. Without sample injection enrichment, limits of detection of the method span from 0.044 to 0.33 microg/L, corresponding to an instrumental detection limit of 120-850 pg. In addition, a careful evaluation of the matrix effect showed that the response of the Direct-EI interface was never affected by sample interferences. From our knowledge, the proposed method represents the first application of LC-MS in the analysis of organochlorine pesticides.
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Cromatografia Líquida/métodos , Hidrocarbonetos Clorados/análise , Espectrometria de Massas/métodos , Praguicidas/análise , Poluentes Químicos da Água/análiseRESUMO
Produced formation waters (PFWs), a by-product of both oil and gas extraction, are separated from hydrocarbons onboard oil platforms and then discharged into the sea through submarine outfalls. The dispersion of PFWs into the environment may have a potential impact on marine ecosystems. We reproduce the initial PFW-seawater mixing process by means of the UM3 model applied to offshore natural gas platforms currently active in the Northern Adriatic Sea (Mediterranean Sea). Chemical analyses lead to the identification of a chemical tracer (diethylene glycol) which enables us to follow the fate of PFWs into receiving waters. The numerical simulations are realized in different seasonal conditions using both measured oceanographic data and tracer concentrations. The numerical results show the spatial and temporal plume development in different stratification and ambient current conditions. The analytical approach measures concentrations of the diethylene glycol at a maximum sampling distance of 25 m. The results show a good agreement between field observations and model predictions in the near-field area. The integration of numerical results with chemical analyses also provides new insight to plan and optimize PFW monitoring and discharge.
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Etilenoglicóis/análise , Modelos Teóricos , Água do Mar/química , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/análise , Simulação por Computador , Monitoramento Ambiental , Oceanos e Mares , Estações do Ano , Movimentos da ÁguaRESUMO
Major progress in interfacing liquid chromatography and electron ionization mass spectrometry is presented. The minimalism of the first prototype, called the Direct-EI interface, has been widely refined, improved, and applied to modern instrumentation. The simple interfacing principle is based on the straight connection between a nanoHPLC system and a mass spectrometer equipped with an EI source forming a solid and reliable unicum resembling the immediacy and straightforwardness of GC/MS. The interface shows a superior performance in the analysis of small-medium molecular weight compounds, especially when compared to its predecessors, and a unique trait that excels particularly in the following aspects: (1) It delivers high-quality, fully library matchable mass spectra of most sub-1 kDa molecules amenable by HPLC. (2) It is a chemical ionization free interface (unless operated intentionally) with accurate reproduction of the expected isotope ion abundances. (3) Response is never influenced by matrix components in the sample or in the mobile phase (nonvolatile salts are also well accepted). A deep evaluation of these aspects is presented and discussed in detail. Other characteristics of the interface performance such as limits of detections, range of linear response, and intra- and interday signal stability were also considered. The usefulness of the interface has been tested in a few real-world applications where matrix components played a detrimental role with other LC/MS techniques.
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The massive accumulation of organic matter, which periodically occurs in the northern Adriatic Sea, and in other locations worldwide, is presently thought to be the results of the aggregation of dissolved organic matter (DOM) into particulate organic matter (POM). This phenomenon is the result of human activities and propitious weather conditions. Although many aspects of the phenomenon are well understood, the trigger mechanisms leading to mucilage formation have not been clarified yet, probably as a consequence of inadequate analytical approaches. In this context, the recent advancements in LC-MS interfacing might contribute in clarifying the mechanism of mucilage formation. In the present paper, hydrophilic interaction liquid chromatography coupled with electrospray tandem mass spectrometry (HILC-ESI-MS/MS) is proposed as an innovative method for the investigation of underivatized oligosaccharides in mucilage samples. Recent findings suggest that the significant presence of these compounds in seawater can play an important role in the initial steps of the agglomeration processes forming gelatinous material. Our results reveal the presence of several maltodextrines in the water-soluble fraction of mucilage macroaggregates, collected in various locations of the northern Adriatic Sea. In our knowledge, the proposed method is the first application of LC-MS in the investigation of marine mucilage.
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Adesivos/química , Oligossacarídeos/química , Água do Mar/química , Espectrometria de Massas por Ionização por Electrospray , Cromatografia Líquida , Oceanos e Mares , Poluição da ÁguaRESUMO
I. Introduction 88 II. Cap-EI Interface 90 A. Interface Performance 92 III. Direct-EI Interface 93 A. Interface Performance 97 IV. Conclusions 103 Acknowledgments 103 References 103 --Two recent approaches for coupling capillary scale liquid chromatography and electron ionization mass spectrometry are reviewed and discussed. The first one, Cap-EI, is the latest evolution of the micro-scale particle beam interface, in which the nebulizer has been optimized to overcome the limitations of the former approach, in terms of sensitivity and linearity. It can be easily hosted in pre-existing instruments without major modifications and can use helium and the less-expensive nitrogen to generate library-matchable electron ionization spectra. The second one is a miniaturized interface for nano- and micro-HPLC, in which the interfacing process takes place into a suitably modified ion source. Because the eluate from the column is completely transferred into the ion source for ionization, superior sensitivity, linearity, and reproducibility are obtained. No signs of chemical ionization are observed at flow rates up to 1.5 microL/min. These two interfaces demonstrate that electron ionization can be successfully used for the analysis of small-medium molecules of various polarities, and also at the trace level. The possibility to record library-matchable electron ionization spectra offers the analyst a powerful tool that can be particularly useful in real-world applications.
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Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Cafeína/química , Cromatografia Líquida de Alta Pressão/instrumentação , Herbicidas/química , Espectrometria de Massas/instrumentação , Propanil/química , Vitamina K/químicaRESUMO
A new solid-phase extraction on-line device for micro-HPLC is presented. This device optimizes the injection of very dilute samples into a packed capillary column. It consists of two capillary, reversed-phase, HPLC columns of different length that can be linked together as a single chromatographic column. The first segment, only 2 cm long is connected to the HPLC injector. When disconnected from the longer column, several milliliters of an aqueous sample can be passed through at a high flow rate for fast trapping. On the basis of the retention mechanism, all suitable compounds are focused on the short column head in a sharp band. As soon as the chromatographic column is recomposed, the trapped analytes are eluted and separated at the optimal flow rate and gradient conditions. Due to the high preconcentration factor, trace-level analysis can be performed successfully. Different classes of analytes of various polarities and molecular weights can be determined, depending on the stationary phase and on the detector used. Some pesticides belonging to different classes were chosen to evaluate the performance of the device using an electron ionization mass spectrometer as HPLC detector. A fungicide in an irrigation canal water was determined at a concentration level of 4.5 microg x L(-1).
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The use of a new LC-MS interface (cap-EI), part of a Waters Integrity system, capable of generating EI spectra at micro flow rates is presented. The cap-EI interface relies on the production of a fine aerosol by means of a nebulizer and supported by a nitrogen jet. Sensitivity, response linearity, reproducibility, and LC compatibility of the interface were thoroughly examined using testosterone, caffeine, a mixture of antiinflammatory drugs, and 3,4-dihydroxybenzoic acid as test compounds. The interface is fully compatible with LC requirements such as high-water- and/or -buffer-content mobile phases. Reproducibility, high sensitivity in scan mode, as well, to produce library-searchable EI spectra, 2 orders of magnitude linearity, together with an intrinsic simplicity of the entire system are the key features of cap-EI interface.
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Recent reports have demonstrated an improvement in 5-year actuarial survival of patients with resected ductal adenocarcinoma. The purpose of this study was to determine the factors favoring long-term survival after pancreaticoduodenectomy. Between 1974 and 1995, 75 patients with pancreatic head carcinoma underwent pancreaticoduodenectomy in our department. The overall postoperative mortality rate was 5.3% and morbidity was 24%. Median survival following resection was 17 months. The estimated 1-, 2- and 5-year survival rates were 68%, 46.7% and 18.7%, respectively. Five-year survival was significantly greater for node-negative versus node-positive patients (41.7% vs 7.8%, P < 0.001), for smaller (< 3 cm) versus larger tumours (33.3% vs 8.8%, P < 0.006), and for negative versus positive resection margins (23.3% vs 0, P < 0.001). Other factors, including gender, age, and blood transfusion had no significant effect on survival. The multivariate analysis was done using the Cox proportional hazards model to determine independent prognostic determinants of survival. The presence of positive resection margins was the strongest independent predictor of decreased survival. Lymph node metastasis, tumour size > 3 cm, and poor histologic differentiation were also independent predictors of poor survival. The most favorable subset consisted in 17 patients who had negative resection margins, negative lymph nodes, and tumor size < 3 cm. Their 5-year survival rate was 52.9%.
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Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/cirurgia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Fatores de TempoRESUMO
BACKGROUND AND OBJECTIVES: Recent reports have demonstrated improvement in the 5-year actuarial survival for patients with resected ductal adenocarcinoma. The purpose of this study is to determine the factors favoring long-term survival after pancreaticoduodenectomy. METHODS: Between 1974 and 1995, 75 patients with pancreatic head carcinoma underwent pancreaticoduodenectomy in our department. RESULTS: Overall postoperative mortality rate was 5. 3% and morbidity was 24%. Median survival following resection was 17 months. Estimated 1-, 2-, and 5-year survival rates were 68%, 46.7%, and 18.7%, respectively. Five-year survival was greater for node-negative than for node-positive patients (41.7% vs. 7.8%, P < 0. 001) and for smaller (<3 cm) than for larger tumors (33.3% vs. 8.8%, P < 0.006). The 5-year survival in patients with negative margins (n = 60) was 23.3%, whereas no patient with positive margins (n = 15) survived at 13 months (P < 0.001). Multivariate analysis, performed by the Cox proportional hazards model, indicated that margin status, lymph node metastasis, tumor size, and poor histological differentiation were independent predictors of poor survival. CONCLUSIONS: Five-year survival for patients undergoing pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas was 18.7%. Survival was greater in the group of patients with negative lymph nodes, tumor size <3 cm, and negative margin status.
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Adenocarcinoma/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Análise Atuarial , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adulto , Idoso , Coledocostomia/efeitos adversos , Coledocostomia/métodos , Feminino , Seguimentos , Previsões , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Pancreaticojejunostomia/efeitos adversos , Pancreaticojejunostomia/métodos , Complicações Pós-Operatórias , Modelos de Riscos Proporcionais , Análise de Sobrevida , Taxa de SobrevidaRESUMO
BACKGROUND: The cognitive, behavioral, and mood effects of N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine, have been used to study the effects of NMDA receptor dysfunction. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia. Preclinical studies indicate that some ketamine effects may be mediated through increased glutamate release. In this study, we tested the hypothesis that lamotrigine, a drug reported to inhibit glutamate release, will reduce the neuropsychiatric effects of ketamine in humans. METHOD: Healthy subjects (n = 16) completed 4 test days involving the administration of lamotrigine, 300 mg by mouth, or placebo 2 hours prior to administration of ketamine (0.26 mg/kg by intravenous bolus and 0.65 mg/kg per hour by intravenous infusion) or placebo in a randomized order under double-blind conditions. Behavioral and cognitive assessments were performed at baseline and after administration of the medications. RESULTS: Lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician-Administered Dissociative States Scale (P<.001); positive symptoms of schizophrenia as assessed by the Brief Psychiatric Rating Scale positive symptoms subscale (P<.001); negative symptoms as assessed by the Brief Psychiatric Rating Scale negative symptoms subscale (P<.05); and learning and memory impairment as assessed by the Hopkins Verbal Learning Test (P<.05). However, lamotrigine increased the immediate mood-elevating effects of ketamine (P<.05). CONCLUSIONS: Glutamate release-inhibiting drugs may reduce the hyperglutamatergic consequences of NMDA receptor dysfunction implicated in the pathophysiologic processes of neuropsychiatric illnesses such as schizophrenia. Further study is needed.
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Antagonistas de Aminoácidos Excitatórios/farmacologia , Ketamina/farmacologia , Transtornos Mentais/induzido quimicamente , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Triazinas/farmacologia , Adulto , Afeto/efeitos dos fármacos , Escalas de Graduação Psiquiátrica Breve/estatística & dados numéricos , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/prevenção & controle , Método Duplo-Cego , Feminino , Glutamatos/metabolismo , Glutamatos/fisiologia , Humanos , Ketamina/antagonistas & inibidores , Lamotrigina , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/prevenção & controle , Transtornos da Percepção/induzido quimicamente , Transtornos da Percepção/diagnóstico , Transtornos da Percepção/prevenção & controle , Placebos , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/fisiologia , Esquizofrenia/metabolismo , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Aprendizagem Verbal/efeitos dos fármacosRESUMO
BACKGROUND: A growing body of preclinical research suggests that brain glutamate systems may be involved in the pathophysiology of major depression and the mechanism of action of antidepressants. This is the first placebo-controlled, double-blinded trial to assess the treatment effects of a single dose of an N-methyl-D-aspartate (NMDA) receptor antagonist in patients with depression. METHODS: Seven subjects with major depression completed 2 test days that involved intravenous treatment with ketamine hydrochloride (.5 mg/kg) or saline solutions under randomized, double-blind conditions. RESULTS: Subjects with depression evidenced significant improvement in depressive symptoms within 72 hours after ketamine but not placebo infusion (i.e., mean 25-item Hamilton Depression Rating Scale scores decreased by 14 +/- SD 10 points vs. 0 +/- 12 points, respectively during active and sham treatment). CONCLUSIONS: These results suggest a potential role for NMDA receptor-modulating drugs in the treatment of depression.
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Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Ketamina/uso terapêutico , Adulto , Antidepressivos/farmacologia , Transtorno Depressivo Maior/diagnóstico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Ácido Glutâmico/metabolismo , Humanos , Injeções Intravenosas , Ketamina/farmacologia , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Alterations in benzodiazepine receptor function have long been hypothesized to play a role in anxiety. Animal models of anxiety involving exposure to chronic stress have shown a specific decrease in benzodiazepine receptor binding in frontal cortex and hippocampus. The purpose of this study was to examine benzodiazepine receptor binding patients with panic disorder and comparison subjects. METHODS: A quantitative measure related to benzodiazepine receptor binding (Distribution Volume (DV)) was obtained with single photon emission computed tomography (SPECT) imaging of [123I]iomazenil and measurement of radioligand concentration in plasma in patients with panic disorder and healthy controls. DV image data were analyzed using statistical parametric mapping (spm96). RESULTS: A decrease in measures of benzodiazepine receptor binding (DV) was found in left hippocampus and precuneus in panic disorder patients relative to controls. Panic disorder patients who had a panic attack compared to patients who did not have a panic attack at the time of the scan had a decrease in benzodiazepine receptor binding in prefrontal cortex. CONCLUSIONS: Findings of a decrease in left hippocampal and precuneus benzodiazepine receptor binding may be related to alterations in benzodiazepine receptor binding, or other factors including changes in GABAergic transmission or possible endogenous benzodiazepine compounds. Benzodiazepine receptor function in prefrontal cortex appears to be involved in changes in state-related panic anxiety.
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Flumazenil/análogos & derivados , Radioisótopos do Iodo , Transtorno de Pânico/diagnóstico por imagem , Transtorno de Pânico/metabolismo , Receptores de GABA-A/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Adolescente , Adulto , Idoso , Feminino , Moduladores GABAérgicos/metabolismo , Hipocampo/diagnóstico por imagem , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/patologiaRESUMO
A capillary-scale particle beam interface was used to detect 18 phenolic compounds in red wine samples. This technique allows reproducible, library searchable electron ionization spectra at only 1 microliter/min mobile phase flow-rate for a sensitive detection of the analytes in complex matrices. The method makes use of a narrow bore, reversed-phase packed capillary column for sample separation. Detection limits were in the low picogram range for most compounds. Sensitivity and response linearity were evaluated for eight phenolic acids, which are often encountered in red wines. The phenolic compound composition was outlined in two red wines obtained using different aging processes.