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Puccinia striiformis f. sp. tritici, which causes yellow (or stripe) rust on wheat, is a macrocyclic and heteroecious fungus. In this study, we investigated whether Berberis vulgaris subsp. seroi and B. vulgaris subsp. australis, which are indigenous in Spain, may serve as alternate hosts for P. striiformis f. sp. tritici. Wheat leaves bearing telia of an isolate of P. striiformis f. sp. tritici were harvested and used to inoculate plants of both barberry subspecies. Pycnia were observed on the adaxial side of the leaves from 10 days after inoculation (dai). Following successful fertilization, aecia were observed on the abaxial side of the leaves from 16 dai. At 27 dai, barberry leaves bearing aecia were detached and used to inoculate susceptible wheat seedlings of cultivar Morocco. Uredinia were observed on wheat seedlings from 12 days after aeciospore exposure. Eighty-three single lesions were recovered from individual wheat leaves, of which 43 were genotyped using 19 P. striiformis f. sp. tritici simple sequence repeat markers (SSR). In total, 19 multilocus genotypes (MLGs) were identified among the 43 progeny isolates. The SSR genotyping confirmed that all 43 isolates were derived from the parental isolate. Seven heterozygous SSR markers showed segregation among the progenies, whereas none of the 12 homozygous markers resulted in segregation. These results demonstrated that B. vulgaris subspp. seroi and australis can serve as alternate hosts for P. striiformis f. sp. tritici, which may result in novel virulence combinations that can have a detrimental impact on wheat production. Although P. striiformis f. sp. tritici has not been detected on these barberry species in nature, this study highlights the importance of rust surveillance in barberry areas where suitable conditions for completion of the sexual life cycle may be present.
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Basidiomycota , Berberis , Basidiomycota/genética , Doenças das Plantas , Puccinia , EspanhaRESUMO
INTRODUCTION: The analysis of the core biomarkers of Alzheimer's Disease (AD) in the cerebrospinal fluid (CSF) is recommended in the clinical units where it is available. Because of the absence of universal validated values, the determination of specific cut-off points for each center and its population is recommended. The main objective of the CORCOBIA study was to determine the cut-off points of core AD CSF biomarkers for several centers (Parc de Salut Mar, Barcelona and Hospital General de Granollers), which work with the same reference laboratory (Laboratori de Referència de Catalunya). METHODS: Prospective study including cognitively unimpaired individuals (CU, n = 42), subjects with amnestic mild cognitive impairment (aMCI, n = 35) and patients with dementia due to Alzheimer's Disease (AD, n = 48), in whom clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture to analyse amyloid beta peptides (Aß42, Aß40), total tau (tTau) and phosphorylated Tau (pTau181) using the Lumipulse G600II (Fujirebio) was performed. The values of sensitivity (SE), specificity (SP), predictive values and area under the curve (AUC) were calculated, determining the cut-off point according to the Youden index by comparing the CU and AD groups. RESULTS: The resulting cut-offs and their AUC were the following: Aß42 750 pg/mL (AUC 0.809); Aß42/Aß40 0.062 (AUC 0.78); pTau181 69.85 pg/mL (AUC 0.81); tTau 522.0 pg/mL (AUC 0.79); Aß42/tTau 1.76 (AUC 0.86); Aß42/pTau181 10.25 (AUC 0.86). CONCLUSIONS: The determination of cut-off points of core AD CSF biomarkers for the participating centers allows a better diagnostic accuracy. The ratio CSF Aß42/pTau181 shows the highest AUC and better balance between sensitivity and specificity.
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The turbulent impurity (nickel) transport dependence on the normalized electron temperature gradient has been analyzed in sawtooth-free electron cyclotron wave heated Tore Supra plasmas. In the core, our experimental analysis shows that the lower R/L((T)(e)), the lower the nickel diffusion coefficient. The latter decreases until the instability threshold is reached. The experimental threshold is in agreement with the one computed by a gyrokinetic model. Further out, R/L((T)(e)) plays no role in the impurity diffusion. This set of experimental results is consistent with a quasilinear gyrokinetic analysis.
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BACKGROUND: Malignancy is one of the most common long-term complications in renal transplant patients, often related to immunosuppressive treatment although other factors could be considered. Vitamin D plays an important role in reducing cancer risk. After kidney transplantation (KT), 25-hydroxyvitamin D (25OH-D, or calcidiol) insufficiency concerns >85%. The main aim of the present study was to determine the relationship between calcidiol blood levels and cancer development in KT recipients. METHODS: This was a retrospective observational case-control study including patients who received transplants in our hospital from 2003 to 2009 with a follow-up period to 2015. A total of 738 patients were included; 94 of them developed malignancy process, 80 of whose tumor data were analyzed in the cancer group, and the rest composed the control group. At the moment of cancer presentation, age, sex, primary kidney disease, time after surgery, immunosuppressant schedule, and 25OH-D blood levels were collected. RESULTS: The mean patient age was 57 years. The percentages of man and women were 59.5% and 41.5%. The predominant etiology of kidney disease was chronic glomerulonephritis in 31.9%. There were no significant differences between sex, primary kidney disease, immunosuppressant schedule, or incidence of neoplasm in each group of patients. There were no significant differences in 25OH-D blood levels. The incidence of cancer was 7.1%-13.7% per year. The mean time between the graft surgery and the event was 5.6 years. CONCLUSIONS: In patients with functioning KT, we found no correlation between blood levels of calcidiol and the incidence of cancer.
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Nefropatias/sangue , Transplante de Rim/efeitos adversos , Neoplasias/etiologia , Complicações Pós-Operatórias , Vitamina D/análogos & derivados , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Incidência , Nefropatias/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/epidemiologia , Estudos Retrospectivos , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/etiologiaRESUMO
OBJECTIVE: To investigate the cognitive and mental status of patients with basal ganglia calcification on a computed tomographic scan. DESIGN: Eighteen ambulatory patients with basal ganglia calcification and without other radiological findings who were identified from the computed tomography records of a general hospital in a 2-year period and 16 control subjects who were matched for age, education, sex, and premorbid IQ estimation consented to participate. All subjects underwent a neurological evaluation, a comprehensive neuropsychological battery, and tests with psychiatric rating scales. RESULTS: Significant differences for the control group were found in tests that evaluated motor speed and executive, visuospatial, and some memory functions. Four patients (22%) met criteria for organic mood disorder (minor depression, three patients; bipolar depression, one patient) according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, whereas six other patients (33%) met diagnostic criteria for obsessive-compulsive disorder. CONCLUSIONS: These results indicate that patients with basal ganglia calcifications frequently have a subcortical pattern of neuropsychological dysfunction and behavioral changes that are known to be associated with alterations of the frontal-limbic-basal ganglia circuits. The pattern of neuropsychological impairment is consistent with basal ganglia damage. However, poor performance in other neuropsychological tests suggest additional involvement of other connected networks.
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Doenças dos Gânglios da Base/diagnóstico por imagem , Doenças dos Gânglios da Base/psicologia , Calcinose/diagnóstico por imagem , Calcinose/psicologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: New medication is needed to treat essential tremor. Preliminary evidence suggests that gabapentin may be effective in the treatment of this disorder. OBJECTIVE: To study the effects of gabapentin in a comparative, double-blind, crossover, placebo-controlled trial of patients who have essential tremor. PATIENTS AND METHODS: 16 patients with essential tremor (6 with a new onset and 10 with a 2-week washout period of previous treatment with propranolol hydrochloride) received gabapentin (Neurontin), 400 mg 3 times daily; propranolol hydrochloride, 40 mg 3 times daily; and placebo for 15 days with a 1-week washout period between treatments. MAJOR OUTCOME MEASURES: Major outcome evaluations consisted of a Tremor Clinical Rating Scale, accelerometric recordings, and a self-reported disability scale obtained before drug intake on study days 1 and 15 of each treatment period. In addition, the initial (day 1) and superimposed (day 15) drug effects were studied before and 2, 4, 6, and 8 hours after drug intake. RESULTS: At day 15, both gabapentin and propranolol demonstrated significant and comparable efficacy in reducing tremor from baseline in all tremor measures. The initial drug effects evaluated through accelerometry revealed no significant changes with the use of a placebo, but gabapentin and propranolol use significantly reduced tremor power. CONCLUSION: Gabapentin may be useful for the treatment of essential tremor.
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Acetatos/uso terapêutico , Aminas , Antiparkinsonianos/uso terapêutico , Ácidos Cicloexanocarboxílicos , Propranolol/uso terapêutico , Simpatolíticos/uso terapêutico , Tremor/tratamento farmacológico , Ácido gama-Aminobutírico , Administração Oral , Idoso , Estudos Cross-Over , Método Duplo-Cego , Feminino , Gabapentina , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Tremor/patologia , Tremor/fisiopatologiaRESUMO
We describe a patient with episodic involuntary contraction in the lower facial and masseter muscles, in whom we recorded neuromyotonic discharges. The neuromyotonia was a delayed effect of radiation therapy and responded to carbamazepine therapy.
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Músculos Faciais , Nervo Facial , Miotonia/etiologia , Lesões por Radiação/complicações , Nervo Trigêmeo , Carbamazepina/uso terapêutico , Doenças dos Nervos Cranianos/tratamento farmacológico , Doenças dos Nervos Cranianos/etiologia , Neoplasias dos Nervos Cranianos/radioterapia , Nervo Glossofaríngeo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Formal studies examining the antiparkinsonian efficacy of levodopa and pergolide monotherapy in de novo Parkinson's disease (PD) are lacking. The authors conducted a preliminary, 6-month, open-label parallel experimental study with de novo consecutive PD patients who were randomly assigned to three daily doses of pergolide (n = 10; mean age, 63.7 years; mean Hohen & Yahr score, 1.5; mean final dose, 2.8 mg daily) or levodopa (n = 10; mean age, 67.3 years; mean Hohen & Yahr score, 1.8; mean final dose, 435 mg daily). Doses were titrated individually according to patients' evaluation of their own functional ability, known side-effects, and a monthly administration of the Unified Parkinson's Disease Rating Scale (UPDRS) by a clinician blind to the treatment regime. All patients completed the study. There were no significant basal differences between groups and no significant treatment ortreatment-by-time effects in UPDRS scores (according to two-way ANOVA). A clear time effect was observed for most of the functional and motor variables (p < 0.001), with significant improvement during the first month that was maintained for the duration of the study in both groups. Side effects were mild, transient, and comparable. In this preliminary study, pergolide and levodopa exhibited similar symptomatic efficacy and incidence of side effects in the short-term treatment of de novo PD patients at their usual age of clinical manifestation.
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Antiparkinsonianos/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Pergolida/uso terapêutico , Adulto , Idoso , Antiparkinsonianos/efeitos adversos , Feminino , Humanos , Levodopa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Destreza Motora/efeitos dos fármacos , Pergolida/efeitos adversos , Resultado do TratamentoRESUMO
PIP: In Argentina, an integrated program has been developed to provide health care to adolescents in a hospital setting. In order to describe the structure and operation of the program and the constitution and dynamics of the working team, data were gathered through observations and interviews. The objectives of the program are 1) to provide adolescents with health care which integrates their physical, psychological, and social needs; 2) to detect disorders in early stages; 3) to emphasize reproductive health; 4) to strengthen families; 5) to train health care professionals; 6) to extend the program; 7) to do research on the Argentine adolescent; and 8) to collaborate with professional organizations concerned with adolescents. This report relates the evolution of the program, which has its roots in a 1973 study on the effectiveness of hospital services to adolescents, and describes the building and equipment devoted to the adolescent program. The organization of the program is discussed in terms of administration, material and financial resources, and human resources. The functions of the program are detailed and, as indicated by its goals, include health care (clinical medicine, gynecology, obstetrics, and mental health), teaching (pre/post graduate workshops, annual intensive courses, and scientific meetings), research, and community outreach. Finally, each area of medical care is described, with data tabulated for the most frequent reasons for each type of clinical and gynecological consultation. Reproductive health care includes sex education, counseling, pregnancy or postabortion care, and social services to unmarried adolescent mothers. The mental health staff offers individual, family, linking, and group therapy as well as vocational guidance, parental guidance, and psychopedagogical diagnoses. The social workers on the team interact with the adolescent in question and other professionals. In conclusion, it is noted that adolescent medicine is developing as a distinct field, and there is a need for more medical centers to provide the range of services adolescents require as well as to afford training opportunities for health care professionals. The positive results of this program based on increasing demand and user satisfaction justify the work done to create the service.^ieng
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Adolescente , Atenção à Saúde , Planejamento em Saúde , Hospitais , Entrevistas como Assunto , Organização e Administração , Fatores Etários , América , Argentina , Coleta de Dados , Demografia , Países em Desenvolvimento , Saúde , Instalações de Saúde , América Latina , População , Características da População , Pesquisa , América do SulRESUMO
The initial treatment of Parkinson's disease should be addressed to improve symptoms, slow down the progression of the illness and avoid long and short term complications. Drugs currently available for symptomatic treatment are levodopa, dopaminergic agonists, anticholinergics and amantadine. Levodopa is still the goldstandard. Both the standard preparations of carbidopa/levodopa or benserazide/levodopa and the slow release preparations are suitable for initial treatment. However, when to start levodopa remains controversial. Dopaminergic agonists are useful symptomatic drugs. They can be used in monotherapy, but usually require the addition of levodopa to obtain a satisfactory long term therapeutic response. Used as adjuvant treatment to levodopa, they help lowering the dosage of levodopa. Anticholinergic drugs effectively improve symptoms such as tremor and rigidity but their use is limited by their side effects, particularly in older people. Amantadine may be a useful drug for initial treatment of Parkinson's disease when symptoms are not severe. Symptomatic treatment should be considered individually in each patient. If there is only slight disability, treatment may be started with amantadine alone or with a dopaminergic agonist. If there is greater disability, levodopa or the simultaneous use of levodopa and a dopaminergic agonist should be considered. Anticholinergic drugs should be reserved for young patients with tremor as the main symptom. The newer dopamine agonists and inhibitors of catachol-o-methyltransferase (COMT) are coming therapeutic options. Selegiline, a MAOB inhibitor with a possible neuroprotective effect, should also be considered as initial option for Parkinson's disease.
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Amantadina/uso terapêutico , Antagonistas Colinérgicos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Antioxidantes/uso terapêutico , Humanos , Levodopa/administração & dosagemRESUMO
During the period between Rajab 1405 and Jamad Thani 1407 (March 1985-January 1987) a total of 5280 babies were delivered at King Khalid Hospital, Al-Kharj, Saudi-Arabia. Out of these children, 345 i.e. 6.53% weighed less than 2500g. Seventy-three, i.e. 21% of the low birthweight (LBW) babies were born during the festival months of Ramadan and Hajj. When compared with the non-festival months, the number was statistically significant p less than 0.01; and Odds Ratio of 1.42. The perinatal mortality rate for the LBW infants was 176.8 per thousand compared with 25.82 for all deliveries during the same period of time. As in a previous report adolescent primiparae made a large contribution to the total number of LBW deliveries. Therefore there is a need for more vigilance in the care of pregnant patients and, more provisions for the care of LBW infants during the festival months.
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Jejum/efeitos adversos , Férias e Feriados , Mortalidade Infantil , Recém-Nascido de Baixo Peso , Islamismo , Humanos , Recém-Nascido , Estudos Retrospectivos , Arábia Saudita/epidemiologiaRESUMO
The allelic composition at five glutenin loci was assessed by one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis (1D SDS-PAGE) on a set of 155 landraces (from 21 Mediterranean countries) and 18 representative modern varieties. Gluten strength was determined by SDS-sedimentation on samples grown under rainfed conditions during 3 years in north-eastern Spain. One hundred and fourteen alleles/banding patterns were identified (25 at Glu-1 and 89 at Glu-2/Glu-3 loci); 0·85 of them were in landraces at very low frequency and 0·72 were unreported. Genetic diversity index was 0·71 for landraces and 0·38 for modern varieties. All modern varieties exhibited medium to strong gluten type with none of their 13 banding patterns having a significant effect on gluten-strength type. Ten banding patterns significantly affected gluten strength in landraces. Alleles Glu-B1e (band 20), Glu-A3a (band 6), Glu-A3d (bands 6 + 11), Glu-B3a (bands 2 + 4+15 + 19) and Glu-B2a (band 12) significantly increased the SDS-value, and their effects were associated with their frequency. Two alleles, Glu-A3b (band 5) and Glu-B2b (null), significantly reduced gluten strength, but only the effect of the latter locus could be associated with its frequency. Only three rare banding patterns affected gluten strength significantly: Glu-B1a (band 7), found in six landraces, had a negative effect, whereas banding patterns 2 + 4+14 + 15 + 18 and 2 + 4+15 + 18 + 19 at Glu-B3 had a positive effect. Landraces with outstanding gluten strength were more frequent in eastern than in western Mediterranean countries. The geographical pattern displayed from the frequencies of Glu-A1c is discussed.
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OBJECTIVE: To describe a novel mutation in exon 5 of the presenilin 1 gene (E120G)associated with early-onset autosomal dominant Alzheimer's disease (AD). PATIENT AND METHODS: The proband was a man who began with memory loss and progressive cognitive decline at the age of 34. His father and his sister suffered from early-onset cognitive decline. The genetic study performed on the blood sample using the single strand conformation polymorphism (SSCP) technique did not detect any abnormality suggestive of the presence of a mutation in PSEN1, PSEN2, and APP. In the last stage of the disease the patient had seizures and gait alteration. He died at the age of 44. Coding exons 3-12 of PSEN1 were studied by direct sequencing using isolated DNA from frozen brain tissue of the proband. RESULTS: The neuropathological examination showed the presence of frequent amyloid plaques and neurofibrillary tangles and severe amyloid angiopathy. The direct sequencing of the PSEN1 gene disclosed the presence of the E120G mutation. CONCLUSIONS: E120G is a novel mutation in PSEN1 that probably causes early-onset autosomal dominant AD. Absence of genetic alterations in screening techniques (SSCP) does not rule out the presence of mutations. We recommend direct sequencing for the genetic study of patients with early-onset autosomal dominant AD.
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Doença de Alzheimer/genética , Mutação , Presenilina-1/genética , Adulto , Sequência de Bases , Análise Mutacional de DNA , Éxons , Feminino , Humanos , Masculino , Dados de Sequência MolecularRESUMO
To explore the social context of drug use and sexual behaviours that put male-to-female (MTF) transgenders at risk for HIV, focus groups were conducted consisting of African American, Latina and Asian and Pacific Islander MTF transgenders (N = 48) who reside or work in San Francisco, California. Participants were likely to report having unprotected sex with primary partners to signify love and emotional connection, as well as to receive gender validation from their partners. In contrast, viewing sex work with customers as a business encouraged intentious to use condoms. Safer sex intentions with customers were frequently undermined by urgent financial needs, which stemmed from transphobia, employment discrimination and costly procedures associated with gender transition. Participants reported using drugs as a way to cope with or escape life stresses associated with relationships, sex work, transphobia and financial hardship. Interventions with at-risk MTF transgenders should address the interpersonal and social context of unsafe sex and drug use, particularly the unique roles of relationship issues with male partners, stigma, discrimination and community norms regarding sex work and drug use.
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Infecções por HIV/etnologia , Transexualidade/etnologia , Adulto , Negro ou Afro-Americano/etnologia , Asiático/etnologia , Atitude Frente a Saúde/etnologia , Grupos Focais , Identidade de Gênero , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Hispânico ou Latino/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sexo Seguro , São Francisco/epidemiologia , Comportamento Sexual/etnologia , Transtornos Relacionados ao Uso de Substâncias/etnologiaRESUMO
We have developed a proton magnetic resonance spectroscopy method that selectively can sample cortical gray matter and adjacent white matter in the frontal lobe. We have used this approach to study a group of patients (n = 7) infected with HIV and clinical manifestations of the AIDS dementia complex (ADC), a group of patients (n = 8) infected with HIV without any indications of ADC, and seven controls. The patients without ADC had a statistically significant increase in the ratio of myo-inositol to creatine in white matter compared with normal controls. In contrast, the group of patients with ADC had almost normal levels of myo-inositol to creatine in both gray matter and white matter and showed a statistically significant decrease in the N-acetylaspartate to creatine ratio in gray matter compared with either the normal controls or the patients without ADC. Patterns of spectral abnormalities correlated with neuropsychological measures of frontal lobe dysfunction, suggesting that the evaluation of frontal lobe metabolism by magnetic resonance spectroscopy can play a role in the early detection of ADC, in determining its progression, and in assessing responses to therapeutic interventions.
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Complexo AIDS Demência , Química Encefálica , Lobo Frontal/química , Infecções por HIV , HIV-1 , Complexo AIDS Demência/metabolismo , Adulto , Creatina , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/metabolismo , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Humanos , Inositol , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , RadiografiaRESUMO
There are few studies analyzing the incidence, clinical characteristics and diagnostic work-up of psychogenic tremor. We studied the clinical and electrophysiological characteristics and the associated psychopathology in a series of patients with psychogenic tremor. All patients (n = 8) diagnosed with documented or clinically established psychogenic tremor in the movement disorders section of our Department of Neurology in a two-years period were analysed. Psychogenic tremor was diagnosed in 9.5% of the patients that consulted for postural or action tremor of the upper limbs. In all cases tremor had a variable frequency and amplitude and improvement with distraction. Electrophysiological studies revealed asynchronic muscle activity and considerable variation of the dominant frequency when weight was added to the patient hands. Six patients were initially misdiagnosed of essential tremor (n = 3); Parkinson's disease (n = 1); and cerebrovascular disease (n = 2). Final psychiatric diagnoses were depression (n = 4); conversive disorder (n = 2); and malignering (n = 2). Psychogenic tremor is a relatively frequent cause of tremor in a Movement Disorders Clinic and has a characteristic clinical and electrophysiological pattern.
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Transtorno Conversivo/psicologia , Transtorno Depressivo/psicologia , Tremor/diagnóstico , Tremor/etiologia , Adulto , Idoso , Transtorno Conversivo/diagnóstico , Transtorno Depressivo/diagnóstico , Feminino , Humanos , Masculino , Simulação de Doença/diagnóstico , Simulação de Doença/psicologia , Pessoa de Meia-Idade , Escalas de Graduação PsiquiátricaRESUMO
OBJECTIVE: The effects of elevated blood lead levels on the development of children have been examined only in the context of behavioral and neuropsychological evaluations. No studies have examined the effects of lead on brain metabolism in vivo or on structural and/or functional correlates of brain function in children. In the human brain, magnetic resonance spectroscopy (MRS) provides a noninvasive, risk-free method to monitor the biochemistry of acute and chronic stages of disease. The purpose of this study was to examine in vivo the use of MRS for the evaluation of the neurotoxic effects of lead on the nervous system, by detection of brain metabolism, especially N-acetylaspartate, a metabolite shown to decrease in processes that involve neuronal loss. METHODOLOGY: Two male cousins who live in the same household and share the same socioeconomic background and home environment were studied. The subject, a 10-year-old boy, had elevated blood lead levels. His cousin, a 9-year-old boy, was not exposed to lead. Both underwent a comprehensive neuropsychological evaluation and both were evaluated using the magnetic resonance imaging (MRI) and MRS at the University of Pennsylvania Medical Center. High-resolution MRI and MRS were performed using a 3-in surface coil. Localized proton spectra were obtained from contiguous 6 x 6 x 10-mm voxels using one-dimensional phase encoding, with a 2000-millisecond repetition time and a 31-millisecond echo time. RESULTS: Neuropsychological evaluation demonstrated areas of impairment in the lead-exposed child, including difficulties in academic skills of reading, writing, and arithmetic, as well as deficient linguistic skills and attentional mechanism. By contrast, studies of the cousin, who was not exposed to lead, showed overall neuropsychological functioning within normal limits. Although both children had a normal MRI examination of the brain, studies of the lead-exposed boy showed a significant alteration in brain metabolites, with a reduction in the N-acetylaspartate:creatine ratio for both gray and white matter on the MRS examination, compared with his cousin. CONCLUSIONS: The present study is a first attempt to determine in vivo metabolic differences in the brain of a child exposed to lead compared with a healthy control subject. This is a unique case because these children were matched on a number of variables usually regarded as confounders in behavioral lead studies, and therefore can be regarded as matched controls. The present study demonstrates that MRS is a feasible, noninvasive technique for in vivo examination of the brains of children exposed to lead. We were able to obtain high-quality spectra from voxels as small as 0.36 cm at 1.5T. The spatial resolution used in the present study is sufficient to obtain spectra from voxels almost exclusively composed of gray matter. The one-dimensional phase-encoding approach used presents the advantage of obtaining several spectra simultaneously in a relatively short time. The present study has allowed us to examine the spectroscopic patterns of frontal gray and white matter after lead exposure relative to the normal pattern seen in healthy children and adults. The MRS study of the healthy, nonlead-exposed cousin demonstrated spectra entirely consistent with the spectral pattern reported in previous studies of healthy individuals. By contrast, the spectra obtained from the lead-exposed child deviated from the expected pattern in all metabolite ratios analyzed. Because N-acetylaspartate has been shown as a measure of neuronal viability, the level of N-acetylaspartate may enable us to evaluate the degree of neuronal loss in children exposed to lead. The MRI examination indicated no structural abnormalities or cortical thinning, and no abnormal findings in either case. By contrast, MRS indicated a significant change from normal values for the lead-exposed child. This supports the idea that lead neurodevelopmental toxicity may be related to inter
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Encéfalo/metabolismo , Intoxicação por Chumbo/metabolismo , Encéfalo/patologia , Criança , Humanos , Intoxicação por Chumbo/patologia , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , MasculinoRESUMO
OBJECTIVE: The effects of lead poisoning on the development of children have been examined primarily in the context of behavioral and neuropsychological studies. The purpose of this study was to examine the in vivo use of magnetic resonance spectroscopy (MRS) for the evaluation of the neurotoxic effects of lead on the nervous system. MRS has the ability to monitor brain metabolism by detecting a number of neurochemicals among which is N-acetylaspartate, a metabolite shown to decrease in processes that involve neuronal loss. METHODS: In the present study we evaluated the metabolism of gray and white matter of frontal cortex using MRS in individuals with elevated blood lead levels and compared the results with those obtained on nonlead-exposed controls. RESULTS: Although all of the participants had normal MRI examinations of the brain, the lead-exposed individuals exhibited a significant reduction in the N-acetylaspartate/creatine and phosphocreatine ratios in frontal gray matter compared with the nonlead-exposed controls. CONCLUSIONS: The findings of this study suggest that lead has an effect on brain metabolites as detected by MRS in vivo. More specifically, we have found statistically significant reduced levels of brain metabolites in gray but not white matter in lead-exposed individuals. These results imply that MRS is able to detect metabolic abnormalities in individuals with lead poisoning.
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Lobo Frontal/metabolismo , Intoxicação por Chumbo/diagnóstico , Intoxicação por Chumbo/metabolismo , Espectroscopia de Ressonância Magnética/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Ácido Aspártico/metabolismo , Criança , Pré-Escolar , Creatina/análise , Feminino , Lobo Frontal/química , Humanos , Lactente , Intoxicação do Sistema Nervoso por Chumbo/diagnóstico , Intoxicação do Sistema Nervoso por Chumbo/metabolismo , Intoxicação do Sistema Nervoso por Chumbo na Infância/metabolismo , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Fosfocreatina/análise , Fosfocreatina/metabolismo , Córtex Pré-Frontal/química , Córtex Pré-Frontal/metabolismoRESUMO
High-resolution MR imaging (312 microns in plane resolution) and MR spectroscopy (0.36 cm3 nominal voxel) have been performed on human frontal cortex using a 3 in surface coil. Localized proton spectra have been obtained from contiguous 6 x 6 x 10 mm voxels using one-dimensional phase encoding, TR 2000 ms and TE 31 ms. Seven healthy subjects were studied using this approach. The spectra from frontal gray matter showed a reproducible pattern characterized by a choline to creatine and N-acetylaspartate to creatine ratio significantly lower than those from cortical white matter. These metabolite ratio differences reflect the lower choline and higher creatine content in gray matter. These preliminary results show the potential of this high spatial-resolution approach for studying brain cortex.
Assuntos
Lobo Frontal/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Química Encefálica , Colina/análise , Creatina/análise , Humanos , Imageamento por Ressonância Magnética/instrumentação , Espectroscopia de Ressonância Magnética , Fosfocreatina/análise , Prótons , Valores de ReferênciaRESUMO
Elevated brain lactate has been observed by in vivo proton MRS in different pathological situations. The origin of this lactate remains controversial. The possibility that it was produced by the metabolism of phagocytic cells has been proposed. To investigate this hypothesis, the authors have employed high-resolution proton MRS to monitor changes in glucose, lactate, and other metabolites in the medium used to culture human monocyte-derived macrophages in vitro. Results show that the differentiation of human monocytes/macrophages in the presence of physiological stimulating factors (M-CSF or GM-CSF) was associated with an increase in lactate production and glucose utilization. The present results are consistent with the hypothesis that lactate detected by proton MRS in vivo may be produced by the metabolism of macrophages when infiltrates of these cells are present. The possible extrapolation of the authors' finding to the in vivo situation and its relevance are discussed.