RESUMO
We examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [11C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide (11C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy controls. Regional-binding potential (BPND) was calculated using the simplified reference-tissue model with four alternative reference inputs. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to examine between-group BPND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis tested for BPND associations with gray matter volume, peripheral cytokines and clinical variables. The null hypothesis of equality in BPND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison or region. Across all subjects, BPND was positively correlated to age in the thalamus (r=0.43, P=0.008, false discovery rate). No correlations with regional gray matter, peripheral cytokine levels or clinical symptoms were detected. We therefore found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. While the possibility of 11C-(R)-PK11195-binding differences in certain patient subgroups remains, the patient cohorts in our study, who also displayed normal peripheral cytokine profiles, do not substantiate the assumption of microglial activation in schizophrenia as a regular and defining feature, as measured by 11C-(R)-PK11195 BPND.
Assuntos
Encéfalo/metabolismo , Microglia/metabolismo , Transtornos Psicóticos/complicações , Transtornos Psicóticos/metabolismo , Receptores de GABA/metabolismo , Esquizofrenia/complicações , Esquizofrenia/metabolismo , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Radioisótopos de Carbono , Feminino , Humanos , Isoquinolinas , Masculino , Tomografia por Emissão de Pósitrons , Fatores de Risco , Esquizofrenia/diagnóstico , Adulto JovemRESUMO
Chrysanthemum white rust (CWR), caused by Puccinia horiana, is pathogenic on many Chrysanthemum spp. and close relatives, and infects commercially important florist chrysanthemum cultivars (Chrysanthemum × morifolium) throughout the world. Due to regulations, most research and observations with CWR are done in vitro with symptomatic plants. In contrast, research presented herein is based on microscopic examination of symptomatic and asymptomatic plants collected from natural outbreaks in the field. We observed scattered (not in a linear pattern) telial sori on infected chrysanthemum leaves, stems, and flowers that coalesced at high infection levels. Teliospores were mainly two-celled but occasionally one- or three-celled. Promycelia arose from the apical teliospore cell, the basal cell, or both. The number of basidiospores on promycelia varied from one to four. Germ tubes, arising from P. horiana basidiospores, penetrated the host epidermis directly without appressoria. A mucilaginous exudate formed at the site of attachment and penetration of leaf and stem tissue, as well as on internal cell walls. P. horiana colonization was systemic, with intercellular mycelium and intracellular M-haustoria in both symptomatic and asymptomatic infected host tissue. Hyphal anastomosis was observed within infected plants, suggesting that asexual fusion between different P. horiana pathotypes or genotypes might occur.
RESUMO
Chrysanthemum white rust (CWR) is a quarantine-significant pest in the United States (Title 7, Code of Federal Regulations, Part 319.37-2). The causal agent of CWR, Puccinia horiana Henn., is an autoecious, microcyclic rust that is pathogenic on chrysanthemum species (Chrysanthemum spp.) and close relatives within the family Asteraceae. CWR is indigenous to Japan, where it was first reported in 1895 (4). By the 1960s, CWR was found throughout Europe and later spread to Africa, Oceana, South America, and other parts of Asia. In North America, CWR was reported in Mexico and in the United States (New Jersey and Pennsylvania [1977], Oregon and Washington [1990], and California [1991]). Additional detections of CWR were later reported in 22 Pennsylvania counties (2004, 2006 to 2010) (3). These later Pennsylvania reports stated that eradication was attempted at some sites, but unconfirmed observations suggested that the rust pathogen might overwinter in volunteer plants (3). Since "CWR is known to overwinter in Europe where chrysanthemums overwinter (average minimum temperatures ranging from -10°F to 10°F)" (2), the unconfirmed Pennsylvania observations prompted us to determine if P. horiana can overwinter in Pennsylvania. During October 2010, we identified CWR on perennial mums planted at six outdoor garden locations in University Park, PA. Symptomatic plants were quarantined and eradication attempted. Eradicated sites were routinely surveyed and CWR confirmed in July 2011 on volunteer plants at two of the originally infested sites. An additional outdoor garden site with CWR was observed in State College, PA, during October 2011 and eradication attempted. The three infested sites were surveyed throughout the fall and winter of 2011 to 2012. During February 2012, two asymptomatic volunteer plants arising from root pieces were collected from each of the three sites. Each sample was washed with tap water to remove excess soil, examined morphologically, surface sterilized with 10% bleach, and divided into two subsamples. One subsample from each site was divided into crown and root portions and DNA extracted using a Qiagen DNeasy Plant Mini Kit. Molecular analysis was performed using modifications of published primers ITS 5 and Rust1 (1,4). Puccinia horiana was detected in plant roots from one site and in plant crowns from two sites. The remaining two subsamples from each site were transplanted into sterilized potting soil and placed in a clean controlled environment chamber at 18°C and 85% relative humidity (RH). After 6 weeks, six actively growing plants were transferred to a second clean controlled environment chamber at 17°C and 90 to 100% RH. On 6 April 2012, CWR symptoms and signs were confirmed morphologically on two plants that had been removed from one site. On 19 April 2012, CWR signs and symptoms were confirmed morphologically and by molecular analysis on leaves of volunteer plants at one University Park site. DNA extractions were sequenced and shared a 100% maximum identity to a known P. horiana accession (EU816920.1) in GenBank. To our knowledge, this is the first confirmed report of P. horiana overwintering in Pennsylvania. References: (1) H. Alaei et al. Mycol. Res. 113:668, 2009. (2) Anon. Chrysanthemum White Rust Bulletin, Syngenta Flowers Inc., Gilroy, CA, 2010. (3) S. Kim et al. Phytopathology 101:S91, 2011. (4) K. Pedley. Plant Dis. 93:1252, 2009.
RESUMO
BACKGROUND: The in vivo diagnosis of cerebral amyloid angiopathy (CAA) is inferred from clinical and structural imaging features. (11)C-Pittsburgh compound B (PIB) is a PET ligand that binds to beta-amyloid in extracellular plaques and vessel walls. We hypothesized that patients with a clinical diagnosis of CAA-related hemorrhage (CAAH) have increased (11)C-PIB uptake and that the pattern differs from Alzheimer disease (AD). METHODOLOGY: Patients with CAAH based on established clinical criteria were studied using (11)C-PIB PET and were compared with age-matched controls and patients with AD. Distribution volume ratio (DVR) parametric maps were created using the cerebellar cortex as a reference region. RESULTS: Twelve patients with CAAH of mean age 73.9 (range 58-93) years were compared with 22 normal controls and 13 patients with AD of mean age 71.8 (59-83) and 73.8 (56-90) years, respectively. CAAH PIB median DVR binding was higher in cortical regions (1.69, interquartile range 1.44-1.97) compared with controls (1.32, 1.21-1.44, p = 0.002) but lower than AD (2.04, 1.93-2.26, p = 0.004). The occipital-global uptake ratio was lower among patients with AD than among patients with CAAH (p = 0.008), and the frontal-global uptake ratio was higher (p = 0.012). CONCLUSION: (11)C-Pittsburgh compound B (PIB) binding is moderately increased in most patients with probable cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage. The distribution may differ from that seen in Alzheimer disease. (11)C-PIB PET may assist in the in vivo diagnosis of CAA and serve as a surrogate marker for future therapeutic studies.
Assuntos
Benzotiazóis/metabolismo , Radioisótopos de Carbono/metabolismo , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Hemorragia/complicações , Hemorragia/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Estudos Retrospectivos , Inquéritos e Questionários , TiazóisRESUMO
Extensive experimental and neuropathological evidence supports the general hypothesis that decline in the basal forebrain cholinergic system contributes significantly to age-related cognitive impairment. Postmortem studies suggest reductions in neuronal nicotinic acetylcholine receptors (nAChRs, particularly the alpha(4)beta(2) subtype) with aging. This study aimed to determine the distribution of alpha(4)beta(2)-subtype nAChRs in vivo by 2-FA PET in healthy subjects (aged 21-83) and to establish whether there is an age-related decline in nAChRs. Furthermore, the relationship between PET measures of 2-FA binding and neurobehavioral measures of cognitive function was investigated. All participants were nonsmokers and underwent extensive cognitive testing and a PET scan after injection of 2-FA (200 MBq). Brain regional 2-FA binding was assessed through a simplified estimation of distribution volume (DV(S)). As expected, increasing age was associated with poorer cognitive performance, particularly on tasks assessing episodic memory and attentional processes. No significant age-related differences in regional nAChR DV(S) were found. Furthermore, no significant correlations were found between cognitive measures and nAChR DV(S). These results are consistent with recent studies suggesting the stability of cholinergic markers during senescence. It is plausible that changes in alpha(4)beta(2) nAChRs do occur with advancing age, but are beyond detection by the clinical 2-FA PET approach adopted here. However, this approach may be appropriate for use in pathologies considered to undergo extensive nAChR loss such as Alzheimer's disease and Parkinson's disease.
Assuntos
Acetilcolina/metabolismo , Envelhecimento/metabolismo , Encéfalo/metabolismo , Transtornos Cognitivos/metabolismo , Transtornos da Memória/metabolismo , Receptores Nicotínicos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Azetidinas , Ligação Competitiva/efeitos dos fármacos , Ligação Competitiva/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/fisiopatologia , Feminino , Radioisótopos de Flúor , Humanos , Masculino , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/fisiopatologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Receptores Nicotínicos/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: Mutations of the neuronal nicotinic acetylcholine (nACh) receptor identified in patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) lead to increased sensitivity to ACh. As activation of presynaptic nicotinic receptors augments the release of dopamine in the striatum and the prefrontal regions, we tested the hypothesis that that the alpha4-Ser248Phe mutation affects dopaminergic transmission. METHODS: We measured D(1) receptor binding using [(11)C]-SCH23390 and PET in 12 subjects with the alpha4-Ser248Phe mutation (3 men, mean age 41 +/- 16 years) and 19 controls (8 men, mean age 36 +/- 13 years) matched for gender, smoking status, and age. Parametric images were produced using the simplified reference region method. Both MRI-based regions of interest and voxel based analyses were used. RESULTS: Reduced striatal [(11)C]-SCH23390 binding occurred with the mutation (controls 1.1 +/- 0.1; ADNFLE 0.97 +/- 0.2; p < 0.01). Statistical parametric mapping confirmed a region of reduced [(11)C]-SCH23390 binding in the right putamen in alpha4-Ser248Phe subjects compared to controls (309 voxels, local maxima 20 16 -2 mm; Z(score) 3.57, p < 0.05). CONCLUSIONS: Reduced D(1) receptor binding may represent increased extracellular dopamine levels or, more likely, receptor downregulation. Alterations in mesostriatal dopaminergic circuits may contribute to nocturnal paroxysmal motor activity in autosomal dominant nocturnal frontal lobe epilepsy.
Assuntos
Corpo Estriado/metabolismo , Epilepsia do Lobo Frontal/genética , Epilepsia do Lobo Frontal/metabolismo , Receptores de Dopamina D1/metabolismo , Adulto , Feminino , Genes Dominantes/genética , Humanos , Masculino , Pessoa de Meia-Idade , Distonia Paroxística Noturna/genética , Distonia Paroxística Noturna/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Ligação Proteica/fisiologia , Receptores de Dopamina D1/antagonistas & inibidoresRESUMO
Neuronal nicotinic acetylcholine receptors (nAChRs) are critical for higher order cognitive processes. Post-mortem studies suggest reductions in nAChRs (particularly the alpha(4)beta(2) subtype) with ageing and in Alzheimer's disease (AD). This study aimed to; (1) quantify nAChR distribution in vivo with 2-[18F]fluoro-A-85380 (2-FA) in 15 early AD patients compared to 14 age-matched, healthy controls (HC) and (2) correlate nAChR distribution with cognitive performance in both groups. All participants were non-smokers and underwent cognitive testing along with a dynamic PET scan after injection of 200 MBq of 2-FA. Brain regional 2-FA binding was assessed through a simplified estimation of Distribution Volume (DV(S)). The AD group differed significantly from HC on all cognitive measures employed, with impairments on measures of attention, working memory, language, executive function, visuospatial ability, verbal learning and verbal memory (p<.05). Contrary to post-mortem data this study found no evidence of in vivo nAChR loss in early AD despite significant cognitive impairment. Furthermore, no correlation between nAChR and cognitive performance was found for either group. The findings of the current study suggest preservation of nAChRs early in AD supporting previous studies. It is possible that while the clinical 2-FA PET method described here may be insensitive in detecting changes in early AD, such changes may be detected in more advanced stages of the illness.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Receptores Nicotínicos/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/classificação , Atenção/fisiologia , Encéfalo/diagnóstico por imagem , Comportamento de Escolha/fisiologia , Aprendizagem por Discriminação/fisiologia , Feminino , Radioisótopos de Flúor , Humanos , Inibição Psicológica , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Orientação/fisiologia , Resolução de Problemas/fisiologia , Desempenho Psicomotor/fisiologia , Piridinas , Tempo de Reação/fisiologia , Aprendizagem Verbal/fisiologiaRESUMO
BACKGROUND: Neuropathological studies have reported varying amounts of amyloid pathology in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). [11C]PIB positron emission tomography (PET) is a marker of brain amyloid deposition. The aim of this study was to quantify in vivo amyloid load in DLB and PDD compared with control subjects and subjects with Parkinson's disease (PD) without dementia. METHODS: 13 DLB, 12 PDD, 10 PD subjects and 41 age matched controls (55-82 years) were recruited. Each subject underwent clinical evaluation, neuropsychological assessment, T1 and T2 MRI, and [11C]PIB PET. The amyloid load was estimated from 60-90' target region:cerebellar [11C]PIB uptake ratios. Object maps were created by segmenting individual MRIs and convolving them with a probabilistic atlas. Cortical [11C]PIB uptake was assessed by region of interest analysis. RESULTS: The DLB cohort showed a significant increase in mean brain [11C]PIB uptake and individually 11 of the 13 subjects with DLB had a significantly increased amyloid load. In contrast, mean [11C]PIB uptake was normal for the PDD group although two of 12 patients with PDD individually showed a raised amyloid load. Where significant increases in [11C]PIB uptake were found, it was increased in cortical association areas, cingulate and striatum. None of the subjects with PD showed significantly raised cortical [11C]PIB uptake. CONCLUSION: This study suggests that amyloid load is significantly raised in over 80% of subjects with DLB, while amyloid pathology is infrequent in PDD. These in vivo PET findings suggest that the presence of amyloid in DLB could contribute to the rapid progression of dementia in this condition and that anti-amyloid strategies may be relevant.
Assuntos
Amiloide/fisiologia , Doença por Corpos de Lewy/genética , Doença de Parkinson/genética , Idoso , Idoso de 80 Anos ou mais , Amiloide/metabolismo , Radioisótopos de Carbono/farmacologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Doença por Corpos de Lewy/diagnóstico , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neuropsicologia/métodos , Doença de Parkinson/diagnóstico , Tomografia por Emissão de Pósitrons/métodosRESUMO
Approximately 30% of healthy persons aged over 75 years show Abeta deposition at autopsy. It is postulated that this represents preclinical Alzheimer's disease (AD). We evaluated the relationship between Abeta burden as assessed by PiB PET and cognitive decline in a well-characterized, non-demented, elderly cohort. PiB PET studies and cognitive tests were performed on 34 elderly participants (age 73+/-6) from the longitudinal Melbourne Healthy Aging Study (MHAS). Subjects were classified as being cognitively 'stable' or 'declining' by an independent behavioural neurologist based on clinical assessment and serial word-list recall scores from the preceding 6-10 years. Decline was calculated from the slope of the word-list recall scores. Abeta burden was quantified using Standardized Uptake Value normalized to cerebellar cortex. Ten subjects were clinically classified as declining. At the time of the PET scans, three of the declining subjects had mild cognitive impairment, one had AD, and six were declining but remained within the normal range for age on cognitive tests. Declining subjects were much more likely to show cortical PiB binding than stable subjects (70% vs. 17%, respectively). Neocortical Abeta burden correlated with word-list recall slopes (r=-0.78) and memory function (r=-0.85) in the declining group. No correlations were observed in the stable group. Abeta burden correlated with incident memory impairment and the rate of memory decline in the non-demented ageing population. These observations suggest that neither memory decline nor Abeta deposition are part of normal ageing and likely represent preclinical AD. Further longitudinal observations are required to confirm this hypothesis.
Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/metabolismo , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Mapeamento Encefálico , Transtornos Cognitivos/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de PósitronsRESUMO
PURPOSE: To assess the contribution of concurrent low-dose, noncontrast CT in the assessment of the malignant potential of incidental focal 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-avid colonic lesions on positron emission tomography/computed tomography (PET/CT). PROCEDURES: Routine FDG-PET/CT scans were reviewed for identification of focal FDG-avid colon lesions, and the CT component was independently reviewed for an anatomical lesion and malignant potential based on CT criteria. Clinical, endoscopic, and histopathology follow-up was obtained. RESULTS: A total of 85/2,916 (3%) oncology FDG-PET/CT scans had incidental focal colon lesions. Clinical and/or endoscopic follow-up was available in 83/85 (98%) patients. Focal, corresponding CT lesions were found in 44/83 (53%) patients, but features of malignancy were not assessable. Of the 44 patients with a final diagnosis, 32/44 (73%) were FDG-PET/CT true positives; 5/44 (11%) were false positives; and 7/44 (16%) had inconclusive FDG-PET/CT findings. CONCLUSIONS: Concurrent low-dose, noncontrast CT improves localization, but does not provide independent information on the malignant potential of incidental focal colonic activity on FDG-PET/CT.
Assuntos
Doenças do Colo/diagnóstico , Meios de Contraste/metabolismo , Fluordesoxiglucose F18 , Achados Incidentais , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Endoscopia , Reações Falso-Positivas , Seguimentos , HumanosRESUMO
BACKGROUND: Accurate staging of lung cancer is essential in determining the most appropriate management plan, as detection of occult metastasis can significantly alter management. AIMS: The aims of this study are to determine the prevalence of occult metastasis in patients undergoing 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET) for evaluation of suspected/proven lung carcinoma and correlate pre-PET TNM stage with prevalence of metastasis. METHODS: FDG-PET, which identified patients with metastasis on institutional database, was re-evaluated by a nuclear medicine physician blinded to clinical information. The confidence level of metastasis was scored on a 5-point scale, with a score of >/=4 considered positive. RESULTS: There were 67 of 645 (10%) patients identified with suspected occult metastasis on FDG-PET. Twelve patients scoring =3 were excluded. Prevalence of occult metastasis was 10/156 (6%) in solitary pulmonary nodules (SPN); 22/319 (7%) and 23/170 (14%) in proven and suspected lung cancer, respectively. Positive predictive value of FDG-PET for metastasis was 8/10 (80%) in solitary pulmonary nodules, 14/20 (70%) and 17/21 (81%) in proven and suspected lung cancer, respectively. (18)F-FDG-avid lesions classified as false positives were patients with cholelithiasis, rib fractures and those with equivocal/negative bone scans or computed tomography on follow up. There was a higher incidence of true positive occult metastasis in patients in all stages of disease, particularly stage III disease. CONCLUSION: (18)F-FDG PET is predictive for occult metastatic disease in patients with solitary pulmonary nodules and proven or suspected lung cancer and is more likely to be present in all stages, particularly in stage III. PET findings should be actively pursued with correlative investigation to identify benign pathology in patients who remain candidates for curative treatment.
Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Metástase Neoplásica/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Prevalência , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Nódulo Pulmonar Solitário/patologiaRESUMO
OBJECTIVE: To compare brain beta-amyloid (Abeta) burden measured with [(11)C]Pittsburgh Compound B (PIB) PET in normal aging, Alzheimer disease (AD), and other dementias. METHODS: Thirty-three subjects with dementia (17 AD, 10 dementia with Lewy bodies [DLB], 6 frontotemporal dementia [FTD]), 9 subjects with mild cognitive impairment (MCI), and 27 age-matched healthy control subjects (HCs) were studied. Abeta burden was quantified using PIB distribution volume ratio. RESULTS: Cortical PIB binding was markedly elevated in every AD subject regardless of disease severity, generally lower and more variable in DLB, and absent in FTD, whereas subjects with MCI presented either an "AD-like" (60%) or normal pattern. Binding was greatest in the precuneus/posterior cingulate, frontal cortex, and caudate nuclei, followed by lateral temporal and parietal cortex. Six HCs (22%) showed cortical uptake despite normal neuropsychological scores. PIB binding did not correlate with dementia severity in AD or DLB but was higher in subjects with an APOE-epsilon4 allele. In DLB, binding correlated inversely with the interval from onset of cognitive impairment to diagnosis. CONCLUSIONS: Pittsburgh Compound B PET findings match histopathologic reports of beta-amyloid (Abeta) distribution in aging and dementia. Noninvasive longitudinal studies to better understand the role of amyloid deposition in the course of neurodegeneration and to determine if Abeta deposition in nondemented subjects is preclinical AD are now feasible. Our findings also suggest that Abeta may influence the development of dementia with Lewy bodies, and therefore strategies to reduce Abeta may benefit this condition.
Assuntos
Envelhecimento/metabolismo , Peptídeos beta-Amiloides/análise , Compostos de Anilina , Química Encefálica , Radioisótopos de Carbono , Transtornos Cognitivos/diagnóstico por imagem , Demência/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tiazóis , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Apolipoproteínas E/genética , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Demência/metabolismo , Demência/patologia , Feminino , Giro do Cíngulo/química , Giro do Cíngulo/diagnóstico por imagem , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/metabolismo , Doença por Corpos de Lewy/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neocórtex/química , Neocórtex/diagnóstico por imagem , CintilografiaRESUMO
UNLABELLED: Anterior cingulate (ACC) hypo-activity is commonly observed in chronically ill schizophrenia patients. However, it is unclear whether this is secondary to persistent illness and/or medication. METHOD: We examined eight antipsychotic-naïve first-episode patients and matched healthy controls undergoing PET scanning while performing the Stroop task. RESULTS: Group-averaged and single-subject analyses showed ACC activation in both controls and patients, albeit in different sub-regions (paracingulate and cingulate respectively). A direct comparison revealed relative under-activity of the left paracingulate cortex in patients. CONCLUSION: These findings suggest that the more pervasive hypo-activation observed in chronic patients may be secondary to persistent illness and/or medication.
Assuntos
Antipsicóticos/uso terapêutico , Giro do Cíngulo/metabolismo , Giro do Cíngulo/fisiopatologia , Tomografia por Emissão de Pósitrons , Esquizofrenia , Adulto , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Doença Crônica , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Tempo de Reação , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologiaRESUMO
Toll-like receptor 4 (TLR-4) is required for detection of Gram negative bacterial infections by binding lipopolysaccharide (LPS) and for the initiation of inflammatory signaling. Recent studies have demonstrated that a nonsynonymous single-nucleotide polymorphism (Asp299Gly, A+896G) is associated with decreased endotoxin responsiveness and poor outcomes from sepsis. We show that human carriers of this polymorphism show no deficit in LPS induced peripheral blood mononuclear cell (PBMC) mitogen-activated protein kinase (MAPK) activity, no reduction in sensitivity to endotoxin, and variable differences in whole-blood inflammatory cytokine production. These results indicate that this mutation is not a primary determinant of human endotoxin sensitivity.
Assuntos
Substituição de Aminoácidos/genética , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/fisiologia , Lipopolissacarídeos/farmacologia , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de Superfície Celular/genética , Substituição de Aminoácidos/fisiologia , Células Cultivadas , Citocinas/biossíntese , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Glicoproteínas de Membrana/metabolismo , Polimorfismo de Nucleotídeo Único/fisiologia , Receptores de Superfície Celular/metabolismo , Receptor 4 Toll-Like , Receptores Toll-LikeRESUMO
This paper is motivated by a clinical requirement to utilise ictal SPECT images for target localisation in stereotactic radiosurgery treatment planning using the xknife system which only supports CT and MRI images. To achieve this, the SPECT images were converted from raw (pixel data only) format into a part 10 compliant DICOM CT fileset. The minimum requirements for the recasting of a raw format image as DICOM CT or MRI data set are described in detail. The method can be applied to the importation of raw format images into any radiotherapy treatment planning system that supports CT or MRI import. It is demonstrated that the combination of the low spatial resolution SPECT images, depicting functional information, with high spatial resolution MRI images, which show the structural information, is suitable for stereotactic radiosurgery treatment planning.
Assuntos
Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Interpretação de Imagem Assistida por Computador/métodos , Radiocirurgia/métodos , Radioterapia Assistida por Computador/métodos , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Algoritmos , Humanos , Cuidados Pré-Operatórios/métodos , Radiografia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Software , Técnica de Subtração , Interface Usuário-ComputadorRESUMO
Positron emission tomography (PET) and the ligand [(18)F]fluoromisonidazole ((18)F-FMISO) have been used to image hypoxic tissue in the brain following acute stroke. Existing region of interest (ROI)-based methods of analysis are time consuming and operator-dependent. We describe and validate a method of statistical parametric mapping to identify regions of increased (18)F-FMISO uptake. The (18)F-FMISO PET images were transformed into a standardized coordinate space and intensity normalized. Then t statistic maps were created using a pooled estimate of variance. Statistical inference was based on the theory of Gaussian Random Fields. We examined the homogeneity of variance in normal subjects and the influence of normalization by mean whole brain activity versus mean activity in the contralateral hemisphere. Validity of the distributional assumptions inherent in parametric analysis was tested by comparison with a non-parametric method. The results of parametric analysis were also compared with those obtained with the existing ROI-based method. Variance in uptake at each voxel in normal subjects was homogeneous and not affected by mean voxel activity or distance from the centre of the image. The method of normalization influenced results significantly. Normalization by whole brain mean activity resulted in a smaller volume of tissue being classified as hypoxic compared to normalisation by mean activity in the contralateral hemisphere. The ROI-based method was subject to interobserver variability with a coefficient of variability of 16%. The volumes of hypoxic tissue identified by parametric and nonparametric methods were highly correlated (r = 0.99). These findings suggest that using a pooled variance and contralateral hemisphere normalisation, statistical parametric mapping can be used to objectively identify regions of increased (18)F-FMISO uptake following acute stroke in individual subjects.
Assuntos
Encéfalo/diagnóstico por imagem , Hipóxia/diagnóstico por imagem , Misonidazol/análogos & derivados , Estatística como Assunto/métodos , Tomografia Computadorizada de Emissão , Doença Aguda , Idoso , Isquemia Encefálica/complicações , Feminino , Radioisótopos de Flúor , Humanos , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Valores de Referência , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND: Recent studies suggest that low computed tomography (CT) attenuation values can be used to differentiate benign adrenal adenomas from non-adenomas. We examined the utility of non-enhanced CT attenuation values of Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem
, Tomografia Computadorizada por Raios X
, Adenoma/diagnóstico por imagem
, Adulto
, Humanos
, Pessoa de Meia-Idade
RESUMO
BACKGROUND: Protective ventilation, in general, includes low tidal volume ventilation and maintaining end-inspiratory plateau pressures less than 35 cmH2O. Recent clinical studies have determined that such an approach results in improved survival in patients with moderate to severe acute lung injury and acute respiratory distress syndrome. However, experimental evidence suggests that repeated end-expiratory collapse and reexpansion contributes to ventilator-induced lung injury. We sought to determine the immediate effects of specific tidal volume-PEEP combinations upon oxygenation and static compliance in patients with moderate to severe acute lung injury. METHODS: Fourteen patients were prospectively studied and were treated with each of 10 tidal volume-PEEP combinations, applied in random order. After 5 minutes at each tidal volume-PEEP combination, PaO2/FIO2 and static compliance were recorded. Comparisons were made between low and high tidal volume ventilation as well as across five PEEP levels. RESULTS: At both low (6 mL/kg) and high (10 mL/kg) tidal volume ventilation, PaO2/FIO2 increased with increasing PEEP, up to 20 cmH2O. Similar changes in static compliance were not evident. Static compliance was highest at PEEP of 10 and 15 cmH2O, regardless of tidal volume. With PEEP set at 5 cmH2O, static compliance was significantly lower with 6 mL/kg than with 10 mL/kg tidal volumes. Overall, static compliance was lowest for both tidal volume conditions with PEEP set at 25 cmH2O. CONCLUSION: Low tidal volume ventilation with PEEP set at 5 cmH2O results in poor oxygenation and compliance in patients with moderate to severe acute lung injury. Similarly, PEEP set at 25 cmH2O did not improve oxygenation or compliance.
Assuntos
Cooperação do Paciente , Respiração com Pressão Positiva , Troca Gasosa Pulmonar , Síndrome do Desconforto Respiratório/terapia , Volume de Ventilação Pulmonar , Adolescente , Adulto , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Alzheimer's disease (AD) is a progressive dementing neurologic illness, and the most frequent cause of dementia in the elderly. Neuritic plaques are one of the main neuropathological findings in AD, and the major protein component is the beta-amyloid protein (A beta). Another striking feature of neuritic plaques is the presence of activated microglia, cytokines, and complement components, suggestive of "inflammatory foci" within AD brain. In this review, we will examine the mechanisms by which microglia become activated in AD, emphasizing the role in the A beta protein and proinflammatory cytokines. As well, pathways for suppression of microglial activation by immunosuppressive cytokines will be described. Inflammation mediated by activated microglia is an important component of AD pathophysiology, and strategies to control this response could provide new therapeutic approaches for the treatment of AD.
Assuntos
Doença de Alzheimer/fisiopatologia , Microglia/imunologia , Adjuvantes Imunológicos/fisiologia , Animais , Antígenos CD40/fisiologia , Citocinas/fisiologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Inflamação/fisiopatologia , Interleucina-4/farmacologia , Fator de Crescimento Transformador beta/farmacologiaRESUMO
Chronic exposure to nitrous oxide (N2O) is known to be associated with hematologic and neurologic abnormalities. When this syndrome occurs, it is generally seen in health care workers, especially dentists and anesthesiologists, who have access to nitrous oxide. Here, however, we report a case of a 55-year-old non-healthcare worker who presented with multiple neurological abnormalities. His serum vitamin B12 level was low but his Shilling test was normal. His neurologic symptoms improved after cessation of inhaling nitrous oxide and starting vitamin B12 therapy. Physicians should consider nitrous oxide abuse in non-healthcare workers presenting with neurologic symptom of unclear cause.