RESUMO
To investigate the long-term effects of excitatory amino acid microinjections into the basal forebrain and its correlation with a possible Ca2+ imbalance associated with the excitotoxic process, ibotenic acid, mainly an N-methyl-D-aspartate receptor agonist, and quisqualic acid, an agonist of non-N-methyl-D-aspartate receptors, were injected into two regions rich in cholinergic neurons, namely the medial septal nucleus and the ventral globus pallidus. Within the globus pallidus but not within the medial septal nucleus, 13 days and one year postlesion, nerve cell death was associated with the appearance of calcium deposits within the large putative GABAergic pallidal neurons, being more pronounced in ibotenic acid than quisqualic acid-lesioned rats. An intermediate two month post-lesion study with alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and ibotenic acid microinjections in globus pallidus demonstrated that the AMPA subtype of glutamate receptor may also be involved in this Ca2+ imbalance, together with the N-methyl-D-aspartate and metabotropic subtype receptors. Quisqualic acid lesions in globus pallidus and medial septum were associated with a substantial disappearance of cholinergic cell bodies and their nerve terminal networks within the cerebral cortex and hippocampal formation respectively, as assessed by choline acetyltransferase and acetylcholine esterase immunocytochemistry. Ibotenic acid lesions resulted in a lower reduction of cholinergic markers. One year after septal lesions induced either by ibotenic or quisqualic acid, a marked atrophy of the entire dorsolateral septal nucleus was observed. Our results support the hypothesis that brief and intense glutamate exposure can induce long-term neurodegenerative processes and give evidence that long-term excitotoxic lesions of the two areas studied result in marked differences in neuronal damage, including intracellular calcium deposits which do not correlate with the cholinergic deficits produced by multiple glutamate receptor subtypes.
Assuntos
Dano Encefálico Crônico/induzido quimicamente , Neurotoxinas/toxicidade , Animais , Cálcio , Imuno-Histoquímica , Masculino , Degeneração Neural , Prosencéfalo , Ácido Quisquálico/toxicidade , Ratos , Ratos Sprague-Dawley , Núcleos Septais , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/farmacologiaRESUMO
Ibotenic acid-induced lesion of the basal forebrain resulted after 13 days in a 90% reduction of octopamine (OA) in the frontoparietal cortex of adult rats, whereas dihydroxyphenylacetic (DOPAC), homovanillic (HVA) and 5-hydroxyindoleacetic (5-HIAA) acids were not modified as measured by microdialysis and high-performance liquid chromatography (HPLC) with electrochemical detection. At this time, cortical choline acetyltransferase (ChAT) activity was decreased by 34%. The results are discussed with respect to possible octopamine involvement in reduced age-associated performance in neurodegenerative processes.
Assuntos
Lobo Frontal/metabolismo , Octopamina/metabolismo , Lobo Parietal/metabolismo , Prosencéfalo/efeitos dos fármacos , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Colina O-Acetiltransferase/metabolismo , Cromatografia Líquida de Alta Pressão , Diálise , Ácido Homovanílico/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Ácido Ibotênico/toxicidade , Masculino , Microquímica , Prosencéfalo/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Laparoscopic splenectomy (LS) has been demonstrated as an effective and safe treatment for hematological disorders requiring spleen removal, especially in cases of normal-sized spleens. However, although results are promising, long-term outcome data are lacking. We reviewed our clinical experience with LS in a series of 255 cases, with particular attention to the long-term outcome related to the disease process requiring LS. METHODS: From February 1993 to October 2003, LS was attempted in 255 patients (100 males and 155 females with a mean age of 45 +/- 19 years) and clinical information was recorded in a prospective database. Indications for splenectomy included idiopathic thrombocytopenic purpura (ITP) (n = 115), HIV-ITP (n = 9), Evans syndrome (n = 6), autoimmune hemolytic anemia (AIHA) (n = 13), hereditary spherocytosis (HS) (n = 19), hematologic malignancy (n = 66), thrombotic thrombocytopenic purpura (n = 1), and others (n = 26). Long-term postoperative follow-up evaluation was obtained through clinical notes, follow-up visits by the referring hematologist, and by phone interviews both with patients and with the referring hematologist. RESULTS: A total of 186 patients (73%) were available for a mean follow-up of 35 months (range, 1-104). Of the ITP patients, 87 (76%) were followed up, with a remission rate of 89% (complete remission in 75%). A similar remission rate was observed in ITP-HIV; in patients available for follow-up (78%), complete remission was achieved in 83%. In Evans, complete remission was achieved in all patients available for follow-up (67%). Clinical response for hemolytic disease ranged between 70% for AIHA and 100% for HS. In the malignant group, the late mortality rate was 22%. The mortality rate in the miscellaneous group was 5%. No cases of splenectomy-related sepsis occurred during follow-up. CONCLUSIONS: LS offers advantages for all types of splenic diseases requiring surgery. It provides not only good clinical short-term outcome but also satisfactory long-term hematological results.
Assuntos
Doenças Hematológicas/cirurgia , Laparoscopia/métodos , Esplenectomia/métodos , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do TratamentoRESUMO
BACKGROUND: Initial experience with the laparoscopic repair of paraesophageal and type III mixed hiatal hernias showed that it is safe and feasible, with excellent immediate and short-term results. However, after a longer follow-up, a recurrence rate of < or =40% has been demonstrated. Data related to the outcome of paraesophageal hernia repair and the recurrence rate are still lacking. Quality-of-life scores may offer a better means of assessing the impact of surgical treatment on the overall health status of patients. Therefore, we performed prospective evaluation of anatomic and/or symptomatic recurrences after paraesophageal or large hiatal hernia repair. In addition, we investigated the correlation between recurrence and the patient's quality of life. METHODS: All patients after who had undergone repair of paraesophageal of mixed hiatal hernia were identified prospectively from a database consisting of all patients who had had laparoscopic operations for gastroesophageal pathology at our hospital between February 1998 and December 2002. The preoperative symptoms were taken from patients' clinical files. In March 2003, all patients with > or =6 months of follow-up had a barium swallow and were examined for radiological and clinical signs of recurrence. Thereafter, the patients' quality of life after surgery was evaluated using three standard questionnaires (Short Form 36 [SF-36], Glasgow Dyspepsia Severity Score [GDSS], and Gastrointestinal Quality of Life Index [GIQLI]. RESULT: During the study period, 46 patients had been operated on. The mean age was 63 years (range, 28-93). Thirty seven of them had a follow-up of > or =6 months. Eight patients (21%) had postoperative gastrointestinal symptoms. Barium swallow was performed in 30 patients (81%) and showed a recurrence in six of them (20%). According to SF-36 and GDSS, the patients' postoperative quality of life reached normal values and did not differ significantly from the standard values for the Spanish population of similar age and with similar comorbidities. Successfully operated patients reached a GIQLI value comparable to the standard population. However, symptomatic patients had significantly lower GIQLI scores than the asymptomatic or the Rx-recurrent group. CONCLUSION: The laparoscopic treatment of large paraesophageal and mixed hiatal hernias is not only feasible and safe but also offers a good quality of life on a midterm basis. However, the anatomic and functional recurrence rate is high. The next step is to identify the subset of patients who are at risk of failure and to establish technical alternatives that would ensure the durability of the repair.
Assuntos
Fundoplicatura/estatística & dados numéricos , Hérnia Hiatal/cirurgia , Laparoscopia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Dispepsia/epidemiologia , Dispepsia/etiologia , Estudos de Viabilidade , Feminino , Seguimentos , Fundoplicatura/métodos , Hérnia Hiatal/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Qualidade de Vida , Radiografia , Recidiva , Índice de Gravidade de Doença , Espanha/epidemiologia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
The aim of the study was to investigate the place of imaging in the diagnosis and treatment of acute appendicitis. The files of 2,427 children with suspected acute appendicitis were reviewed for clinical management and operative findings. The sample was divided into 3 groups at time of admission: (1) before diagnostic imaging was available in our department (1991-1994); (2) after the introduction of imaging studies on a random basis in equivocal cases (1995-1998); and (3) after a policy was formulated for ultrasound use in all equivocal cases followed by computed tomography if necessary (1999-2000). Results showed that the rate of misdiagnosis decreased from 13.2% in group 1 to 6.5% in group 2 and 6.1% in group 3. False-positive findings (normal appendix with positive scan) were noted in 16.7% of group 2 and 25% of group 3; false-negative findings (appendicitis at surgery with negative scan) in 23.8% and 9.5%, respectively. Computed tomography was performed in 8 children and prevented unnecessary surgery in 4 of them. We conclude that in equivocal cases of acute appendicitis, imaging studies performed by skilled operators can improve the accuracy of diagnosis, saving patients unnecessary surgery, and identifying other conditions that mimic appendicitis.
Assuntos
Abdome Agudo/diagnóstico , Apendicite/diagnóstico , Apendicite/cirurgia , Diagnóstico por Imagem/métodos , Abdome Agudo/cirurgia , Adolescente , Apendicectomia/métodos , Apendicectomia/estatística & dados numéricos , Apendicite/epidemiologia , Criança , Pré-Escolar , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Seguimentos , Humanos , Incidência , Masculino , Estudos Retrospectivos , Medição de Risco , Estudos de Amostragem , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia/métodosRESUMO
BACKGROUND: Our purpose was to know the use of psychoactive drugs including neuroleptics (NL), benzodiazepines (BNZ) and antidepressants (AD) in nursing homes (NH) in the city of Barcelona. METHOD: Cross-sectional descriptive study of 384 clinical records of people living in 19 NH. The correct use of drugs was estimated by Garrad's and Beers et al criteria. RESULTS: Average age (SD) of residents was 83 years (2.0). The average consumption of drugs was 5 (2.7); 248 individuals (64.6%) were taking at least one psychoactive drug: 81 (21%) consumed NL, 179 (46.6%) BNZ and 73 (19%) AD. 48 (12.5%) NH residents consumed long-acting BNZ and 26 (6.7%) had surpassed the recommended time of consumption for short-acting BNZ. In 21 (26%) NH residents who consumed NL, its use would not be justified. CONCLUSIONS: It is necessary to reduce the use of long-acting BNZ, to encourage a correct use of NL and to achieve a correct identification of depressive disorders in NH.
Assuntos
Instituição de Longa Permanência para Idosos , Casas de Saúde , Psicotrópicos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Benzodiazepinas , Estudos Transversais , Uso de Medicamentos , Feminino , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Humanos , Masculino , Casas de Saúde/estatística & dados numéricosRESUMO
The effects of L-leucine on jejunal and ileal D-galactose absorption have been studied at three different ages in rats using a perfusion system in vivo. Both, D-galactose and L-leucine have been perfused through the jejunum and the ileum at two concentrations, 5mM (low) and 20 mM (high). L-leucine induced a reversible inhibition of D-galactose absorption at the three ages studied and in both intestinal segments. The inhibition was higher at 20 mM when carriers were saturated. A lineal correlation exits between the inhibition percentage and the age of animals, increasing with growth in the jejunum and decreasing in the ileum. Attention is called to the possibility of different transport mechanisms at low concentration (5 mM), one of low affinity in the jejunum and the other of high affinity in the ileum.
Assuntos
Envelhecimento , Galactose/metabolismo , Íleo/metabolismo , Jejuno/metabolismo , Leucina/metabolismo , Absorção , Animais , Transporte Biológico Ativo , Galactose/antagonistas & inibidores , Leucina/farmacologia , Masculino , Ratos , Ratos EndogâmicosRESUMO
The mechanisms underlying amino acid neurotoxicity may involve a rise in the intracellular concentration of calcium. Some neurons appear to die as a consequence of increased intracellular calcium levels induced by excitatory amino acids. One month after injection of ibotenic acid in the rat basal forebrain, the induced formation of calcium deposits and concomitant glial reaction were studied. Alizarine Red-positive calcium deposits were observed after ibotenic acid injection in the ventral part of the globus pallidus, but not in the medial septum. These deposits were present in the globus pallidus, ventral pallidum, substantia innominata, zona incerta, lateral hypothalamic area, entopeduncular nucleus, medial amygdaloid nucleus and several thalamic nuclei. Three types of round shaped deposit were identified morphologically. Differential astroglial and microglial reactions, studied autoradiographically with the monoamine oxidase-B marker [3H]Ro19-6327 and the peripheral benzodiazepine receptor marker [3H]Ro5-4864 respectively, were observed after both lesions. Our data suggest that excitotoxic lesions in the globus pallidus and medial septum lead with time to different neurodegenerative consequences and glial reactions. This differential sensitivity is discussed on the basis of the presence of different glutamate receptor subtypes and calcium-binding proteins.
Assuntos
Encéfalo/fisiopatologia , Cálcio/metabolismo , Ácido Ibotênico/farmacologia , Neuroglia/fisiologia , Prosencéfalo/fisiopatologia , Animais , Autorradiografia , Encéfalo/patologia , Encefalopatias/induzido quimicamente , Encefalopatias/patologia , Encefalopatias/fisiopatologia , Masculino , Monoaminoxidase/metabolismo , Prosencéfalo/efeitos dos fármacos , Prosencéfalo/patologia , Ratos , Ratos Sprague-Dawley , Receptores de GABA-A/metabolismoRESUMO
Cholinergic basal forebrain (BF) lesions in experimental animals have been used as a potential model for cholinergic deficits in cortex and hippocampus that occur in normal aging and Alzheimer's disease (AD). Glutamatergic cortical neurons are also affected in AD and could be part of the neurodegenerative process. In the present study, the effect of bilateral BF lesion with ibotenic acid microinjection on cortical extracellular amino acid levels was determined. Samples were collected every 20 min with microdialysis probes in awake, freely moving rats under basal and potassium stimulation conditions and measured by HPLC with fluorescence detection. Microdialysis experiments were performed 13 days, 21 days, and 30 days after BF lesion. The effectiveness of the lesion was shown by a significant 30% depletion in acetyl-CoA:choline O-acetyltransferase (EC 2.3.1.6) activity in the frontal cortex. Under basal conditions at 13 days only extracellular levels of taurine (Tau) and Glu were significantly reduced. Tau and Glu levels were recovered after 21 days and 30 days, respectively. In contrast, increase in Gly levels reaches its significance only at 30 days after lesion. Significant increases of Gln levels were observed at 21 days and 30 days. Asp and Ser levels remained constant throughout the period studied. Potassium stimulation led to increased Asp, Glu, Gly, and Tau levels, whereas Gln content decreased and Ser remained unaltered. As Ser is not believed to be a neurotransmitter, its lack of variation in any of the experimental conditions studied supports specific neuronal changes of the other amino acids. Results are discussed with reference to data observed in AD patients and possible mechanisms underlying the changes are suggested.
Assuntos
Aminoácidos/metabolismo , Encefalopatias/metabolismo , Córtex Cerebral/metabolismo , Doença de Alzheimer/metabolismo , Aminoácidos/análise , Animais , Encefalopatias/induzido quimicamente , Encefalopatias/patologia , Córtex Cerebral/química , Córtex Cerebral/patologia , Cromatografia Líquida de Alta Pressão , Fluorescência , Ácido Glutâmico/análise , Ácido Glutâmico/metabolismo , Glicina/análise , Glicina/metabolismo , Ácido Ibotênico , Masculino , Microdiálise , Potássio/farmacologia , Ratos , Ratos Sprague-Dawley , Serina/análise , Serina/metabolismo , Taurina/análise , Taurina/metabolismo , Fatores de TempoRESUMO
Monoamine metabolites and amino acid concentration in cerebrospinal fluid (CSF) of 33 untreated patients with parkinsonian syndrome, and 20 control patients without specific neurological symptoms have been compared with those obtained in cerebrospinal fluid of rats intrastriatally lesioned with 1-methyl-4-phenylpyridinium ion (MPP+) and sham operated animals. Homovanillic acid content was found to be significantly lower in patients with severe parkinsonism (motor score of UPDRS > 24), but not in patients with mild symptoms (motor score < or = 24). A correlation between the loss of striatal dopamine and the decrease in cerebrospinal homovanillic acid has been established in rats treated with MPP+. The extrapolation of these results to those obtained from human patients could be important in assessing the degree of striatal dopamine loss shown by humans with parkinsonian syndrome at the moment of clinical diagnosis. No significant differences were found between the other monoamine metabolites analyzed and free amino acid content in human and rat CSF.
Assuntos
Aminoácidos/líquido cefalorraquidiano , Monoaminas Biogênicas/metabolismo , Doença de Parkinson Secundária/metabolismo , 1-Metil-4-fenilpiridínio , Idoso , Animais , Monoaminas Biogênicas/líquido cefalorraquidiano , Feminino , Ácido Homovanílico/líquido cefalorraquidiano , Ácido Homovanílico/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Ratos , Ratos Sprague-DawleyRESUMO
The stereotaxic administration of 1-methyl-4-phenylpyridinium ion (MPP+) into the neostriatum of male rats caused a lesion that resulted in a large dose-dependent loss of striatal fructose 2,6-bisphosphate; initial values were restored 5 days after the treatment. This effect was not protected by systemic administration of MK-801 or by nitroarginine. The content of hexose 6-phosphates and ATP was also reduced by MPP+ treatment, whereas lactate was increased. Biochemical and histological results suggested that MPP+ caused a nonselective cell death, followed by a pronounced astroglial response, parallel to fructose 2,6-bisphosphate recovery. The stereotaxic administration of rotenone showed a different time effect on fructose 2,6-bisphosphate cerebral content, with a significantly faster recovery. These results indicate that cerebral fructose 2,6-bisphosphate may be a sensitive metabolite related to brain damage caused by potent neurotoxins such as MPP+. On the other hand, they show that MPP+ acts in the brain through a quick, strong cytotoxic mechanism, which probably involves mechanisms other than mitochondrial chain blockage.