The striatal cholinergic system in L-dopa-induced dyskinesias.

Cholinergic signaling plays a key role in regulating striatal function. The principal source of acetylcholine in the striatum is the cholinergic interneurons which, although low in number, densely arborize to modulate striatal neurotransmission. This modulation occurs via strategically positioned nicotinic and muscarinic acetylcholine receptors that influence striatal dopamine, GABA and other neurotransmitter release. Cholinergic interneurons integrate multiple striatal synaptic inputs and outputs to regulate motor activity under normal physiological conditions. Consequently, an imbalance between these systems is associated with basal ganglia disorders. Here, we provide an overview of how striatal cholinergic interneurons modulate striatal activity under normal and pathological conditions. Numerous studies show that nigrostriatal damage such as that occurs with Parkinson's disease affects cholinergic receptor-mediated striatal activity. This altered cholinergic signaling is an important contributor to Parkinson's disease as well as to the dyskinesias that develop with L-dopa therapy, the gold standard for treatment. Indeed, multiple preclinical studies show that cholinergic receptor drugs may be beneficial for the treatment of L-dopa-induced dyskinesias. In this review, we discuss the evidence indicating that therapeutic modulation of the cholinergic system, particularly targeting of nicotinic cholinergic receptors, may offer a novel approach to manage this debilitating side effect of dopamine replacement therapy for Parkinson's disease.

Cell-cycle arrest biomarkers in urine to predict acute kidney injury in septic and non-septic critically ill patients.

PURPOSE: To analyse the usefulness of the composite index of the tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as urinary biomarkers for the early prediction of AKI in septic and non-septic patients. METHODS: This is a prospective, observational study including patients admitted to ICU from acute care departments and hospital length of stay <48 h. The main exclusion criteria were pre-existing eGFR <30 mL/min/1.73 m2 and hospitalisation 2 months prior to current admission. The [TIMP-2]·[IGFBP7] index was analysed twice, within the first 12 h of ICU admission. RESULTS: The sample included 98 patients. AKI incidence during ICU stay was 50%. Sepsis was diagnosed in 40.8%. Baseline renal variables were comparable between subgroups except for a higher baseline eGFR in non-septic patients. Patients were stratified based on the presence of AKI and their highest level of [TIMP-2]·[IGFBP7] within the first 12 h of stay. [TIMP-2]·[IGFBP7] index values were dependent on the incidence of AKI but not of sepsis. [TIMP-2]·[IGFBP7] values were significantly related to AKI severity according to AKIN criteria (p < 0.0001). The AUROC curve to predict AKI of the worst [TIMP-2]·[IGFBP7] index value was 0.798 (sensitivity 73.5%, specificity 71.4%, p < 0.0001). Index values below 0.8 ruled out any need for renal replacement (NPV 100%), whereas an index >0.8 predicted a rate of AKI of 71% and AKIN ≥ 2 of 62.9%. CONCLUSIONS: In our study, urinary [TIMP-2]·[IGFBP7] was an early predictor of AKI in ICU patients regardless of sepsis. Besides, index values <0.8(ng/mL)2/1000 ruled out the need for renal replacement.

[Validation, adaptation and translation of the MacCAT-T into Spanish: a tool to assess the ability to make health decisions]. / Validación, adaptación y traducción al castellano del MacCAT-T: herramienta para evaluar la capacidad en la toma de decisiones sanitarias.

INTRODUCTION: Capacity assessment is an essential element of the informed consent process and is the duty of the physician. The MacCAT-T instrument explores four skills needed to consent a treatment. There is no Spanish version, and the main objective of this work is to validate, adapt and translate the MacCAT-T into Spanish. MATERIAL AND METHODS: The MacCAT-T was translated into Spanish and then back-translated into English. It was validated as regards its appearance and content (by 15 experts), construct (inter-rater reliability and internal consistency) and criteria (the validity of an instrument by comparing it to some external criterion, in this case the Mini Examen Cognoscitivo de Lobo). Ninety medical and surgical outpatients over 18 years were included with no deficits of expression and/or severe disorders of consciousness that did not allow them to be interviewed. RESULTS: They have been optimal considering different types of validity. The average application time was between 9 and 13minutes. DISCUSSION: Data are consistent with those obtained in other applications of MacCAT-T in the English language and facilitate the provision of a Spanish tool for assessing capacity.

[GEITDAH consensus on attention deficit hyperactivity disorder]. / Consenso del GEITDAH sobre el trastorno por deficit de atencion/hiperactividad.

In this article, the GEITDAH -the Spanish abbreviation of the Special Interest Group on Attention Deficit Hyper-activity Disorder (ADHD)- presents a consensus reached by experts in the management of ADHD from all over Spain. The consensus concerns fundamental aspects that should be the starting point for future local or regional consensus guides. Another aim of this consensus is also to reduce the amount of variability that occurs in the health care offered to patients with ADHD in our country, as well as to act as a stimulus in educational matters. That fact that it is not very long will make it more popular among greater numbers of people and this will allow these goals to be reached more effectively. The conclusions in the consensus guide have been constructed around an introduction dealing with basic aspects and recommendations for diagnosis, treatment (both pharmacological and psychotherapeutic), patient flow and organisational aspects.

[PET/CT with (11)C-choline and (18)F-FDG in patients with elevated PSA after radical treatment of a prostate cancer]. / PET/TAC con (11)C-colina y (18)F-FDG en pacientes con elevación de PSA tras tratamiento radical de un cáncer de próstata.

OBJECTIVE: To compare the diagnostic accuracy of PET/CT with (18)F-FDG and (11)C-choline for early detection and localization of recurrent prostate cancer. MATERIAL AND METHODS: Thirty-eight patients with increased PSA levels (0.8-9.5 ng/ml) after radical treatment for prostate cancer (surgery n = 20/radiation therapy n = 18) were included. Ten patients were on hormone therapy. All patients underwent a PET/CT with (11)C-choline and (18)F-FDG, respectively, on the same day. The PET imaging findings were compared with histopathology (n = 10); PSA monitoring (n = 21) and/ or other methods (n = 7). RESULTS: Focal uptake of (11)C-choline was detected in 26 patients (68%), and focal uptake of (18)F-FDG was detected in 13 patients (34%). The (11)C-choline uptake in 14 patients was suggested local recurrence, whereas this was true in only 4 patients (48%) with (18)F-FDG. Pelvic lymph nodes were detected with (11)C-choline PET/CT in 8 patients and only in 4 patients (50%) with (18)F-FDG. Mediastinal involvement was detected in 5 patients with (11)C-choline and 3 patients (60%) with (18)F-FDG. Focal bone involvement was detected in 3 patients with (11)C-choline and (18)F-FDG. (11)C-choline was able to detect 40% of recurrences in patients with PSA < 1 ng/ml, 50% of recurrences in patients with PSA 1-4 ng/ml and 87% of recurrences with PSA > 4 ng/ml. Sensitivity of (11)C-choline was higher for surgically treated patients, with no significant differences found between patients with and without hormone therapy. CONCLUSIONS: (11)C-choline PET/CT was useful for the detection of biochemical recurrence of prostate cancer, with higher yielding as compared to (18)F-FDG. (11)C-choline sensitivity was clearly related to PSA levels, was higher in patients with surgery and did not seem to be modified by hormonal therapy. Disease staging with (11)C-choline showed direct impact for the selection of the most appropriate therapeutic approach.

Compensation in pre-synaptic dopaminergic function following nigrostriatal damage in primates.

Clinical symptoms of Parkinson's disease only become evident after 70-80% reductions in striatal dopamine. To investigate the importance of pre-synaptic dopaminergic mechanisms in this compensation, we determined the effect of nigrostriatal damage on dopaminergic markers and function in primates. MPTP treatment resulted in a graded dopamine loss with moderate to severe declines in ventromedial striatum (approximately 60-95%) and the greatest reductions (approximately 95-99%) in dorsolateral striatum. A somewhat less severe pattern of loss was observed for striatal nicotinic receptor, tyrosine hydroxylase and vesicular monoamine transporter expression. Declines in striatal dopamine uptake and transporter sites were also less severe than the reduction in dopamine levels, with enhanced dopamine turnover in the dorsolateral striatum after lesioning. The greatest degree of adaptation occurred for nicotine-evoked [(3)H]dopamine release from striatal synaptosomes, which was relatively intact in ventromedial striatum after lesioning, despite > 50% declines in dopamine. This maintenance of evoked release was not due to compensatory alterations in nicotinic receptor characteristics. Rather, there appeared to be a generalized preservation of release processes in ventromedial striatum, with K(+)-evoked release also near control levels after lesioning. These combined compensatory mechanisms help explain the finding that Parkinson's disease symptomatology develops only with major losses of striatal dopamine.

[Brain metastasis and the carcinoembryonic antigen]. / Metástasis cerebrales y antígeno carcinoembrionario.

INTRODUCTION: Neurological complications have a notable repercussion on the quality of life of patients with systemic cancer, and can even become the direct cause of death. The complication that causes most concern is undoubtedly brain metastasis, because of its difficult management and because there has been an upward tendency in its incidence in the last few years. AIMS: The aim of this study is to provide a review of the literature about brain metastases and, more particularly, about the carcinoembryonic antigen (CEA) as a marker of these pathologies. DEVELOPMENT: In general it is reckoned that 60% of all brain metastases start from the lung and most of them are multiple when they are diagnosed, which suggests a possibly mistaken staging of these patients. The carcinoembryonic antigen is the prototypical tumour marker, and it is usually found in higher concentrations in the cerebrospinal fluid of patients with metastatic tumours in the central nervous system. As the CEA goes through the blood brain barrier, it behaves in a similar way to IgA due to their having homologous molecular weights. This allows us to employ the same hyperbolic distribution curve that is used as a reference for lgA to distinguish between intrathecally synthesized CEA and that which diffuses from the systemic circulation. CONCLUSIONS: In spite of the progress that has been obtained with the new therapies, brain metastases continue to have a poor prognosis. Hence, there is a need to identify new tumour markers that allow a diagnosis to be established before the clinical methods and presentations.

[IgG subclasses intrathecal synthesis patterns in eosinophilic meningoencephalitis due to Angiostrongylus cantonensis]. / Patrones de síntesis intratecal de subclases de IgG en meningoencefalitis eosinofílica por Angiostrongylus cantonensis.

INTRODUCTION: There is a growing interest to know the characteristics of meningoencephalitis due to Angiostrongylus cantonensis because of it is an emergent disease. OBJECTIVE: To describe the intrathecal synthesis pattern of IgG subclasses in pediatric patients suffering from eosinophilic meningoencephalitis due to Angiostrongylus cantonensis. PATIENTS AND METHODS: Ten pediatric patients with the disease were studied. During the firs diagnostic lumbar puncture an eosinophilic pleocitosis was found. Simultaneously a serum sample was taken. Eight days later, a second lumbar and venous puncture was performed. To every serum and cerebrospinal fluid sample IgA, IgM, IgG, albumin and the four subclasses of IgG were quantified by immunodiffusion and a differential cell count. RESULTS: During the first diagnostic lumbar puncture, all the cases had blood cerebrospinal fluid barrier dysfunction with absence of immunoglobulins intrathecal synthesis with a mean of 450 106cells/L and 48% of eosinophils average. In the second lumbar punction there was a 40% patients with dysfunction of the blood cerebrospinal fluid barrier and with a synthesis pattern IgA+IgM+IgG in the 50% o patients and with IgA+IgG in four patients. The synthesis pattern of IgG subclasses was IgG1+IgG2 in six patients, IgG1+IgG2+IgG3 in one patient, IgG1+IgG2+IgG4 in one more patient and two patients without intrathecal synthesis. CONCLUSION: The intrathecal synthesis pattern of IgG subclasses can contribute to eosinophilic meningoencephalitis diagnosis due to Angiostrongylus cantonensis.

Clinical pattern and therapeutic results achieved in 1490 patients with germ-cell tumours of the testis: the experience of the Spanish Germ-Cell Cancer Group (GG).

OBJECTIVE: To describe the clinical characteristics and treatment results obtained with the application of a homogeneous treatment protocol in 1490 patients with germ-cell tumours (GCT) registered in the 55 hospitals belonging to the Spanish Germ-Cell Cancer Group (GG) during the period between January 1994 and April 2001. METHODS: In general, surveillance was the common policy for stage I patients without local poor prognosis factors, whereas they received adjuvant chemotherapy in case those factor were present. Chemotherapy schedules used in advanced cases were cisplatin and etoposide (EP) for seminoma and BEP or BOMP-EPI in non-seminoma, according to whether the patient was in the good or poor prognosis IGCCCG (International Germ-Cell Cancer Collaborative Group) group. Excision of residual masses was mandatory in non-seminomatous germ-cell tumour (NSGCT). RESULTS: Initial local symptomatology was increased testis size in 90% of cases. Sonography was an excellent diagnostic tool to suggest tumour. Non-seminoma (64.2%) was more frequent than seminoma (35.8%). Approximately 10% had the antecedent of cryptorchidism. Non-seminoma patients were 7 years younger than seminoma. Right testis was involved predominantly. Pre-orchidectomy tumour markers were elevated in 21% of seminoma (betaHGC) and 79% in non-seminoma (alphaFP and/or betaHGC). Scrotum violation occurred in only 1.8%. There were significant differences among stage I and the IGCCCG prognosis groups related to a longer interval between the first symptom and orchiectomy. Eighteen percent of non-seminomatous germ-cell tumour belonged to the poor prognosis IGCCCG group. With a median follow-up to 33 months, this series has achieved a 3 year overall survival of 98% for seminoma and 94% for non-seminoma. Only 10% of excised residual masses present after chemotherapy contained malignant cells. CONCLUSION: Spanish GCT have a similar clinical pattern to that described in the other occidental countries except for a slight increased proportion of non-seminoma upon seminoma. Co-operative groups as GG are unique structures to obtain quick and wide experience on the treatment of testis tumours, contributing to achieve a high cure rate.

[Intrathecal synthesis pattern of immunoglobulins in meningoencephalitis epidemic due to echovirus 9]. / Patrones de síntesis intratecal de inmunoglobulinas en epidemia de meningoencefalitis por echovirus 9.

INTRODUCTION: Epidemics of meningoencephalitis due to echovirus 9 were commonly occurred when a children population become susceptible for the first time in front the virus. OBJECTIVE: To present the intrathecal synthesis pattern of immunoglobulins of the epidemic that affected Cuba in 1999 and to probe the usefulness of reibergram and antibody index in the diagnostic and characterization of the outbreak. PATIENTS AND METHODS: 23 pediatric patients suffering from viral meningoencephalitis due to echovirus 9 were studied in the income moment. Serum and cerebrospinal fluid IgA, IgM, IgG, albumin and glucose were quantified. Cerebrospinal fluid total protein content and lactate were quantified. Titles of antibodies against echo 9 and Coxsackie A9 and differential cell count were performed. RESULTS: A mean of 555 cells/10 6 L mainly lymphocytes were obtained. Glucose in cerebrospinal fluid was over 50%, serum glucose and lactate levels below 2.1 mmol/L. In the reibergram an absence of intrathecal synthesis was predominant (15/23), IgM synthesis (6/23) and IgM+IgA (2/23). Blood cerebrospinal fluid dysfunction was observed in 15 patients. The mean antibody index was 1,8 for echo 9 and 0,9 for Coxsackie A9. CONCLUSIONS: The intrathecal synthesis pattern of immunoglobulins was different from other enterovirus and from echovirus 9 in non epidemic situations before this epidemic, probably with alteration of viral genome.

[Neuroimmune epidemiological value of reibergram in the first echovirus 16 meningoencephalitis outbreak in Cuba]. / Valor neuroinmunoepidemiologico del reibergrama en la primera epidemia de meningoencefalitis por echovirus 16 en Cuba.

INTRODUCTION: During the third quarter of 2000, an outbreak of echovirus 16 meningoencephalitis was firstly occurred in Cuba and produced vomiting, headache, fever and exanthem that differentiate it from other enterovirus epidemies. OBJECTIVE: To describe the intrathecal immunoglobulin synthesis pattern of the epidemie from the reibergram. PATIENTS AND METHODS: Diagnostic serum and cerebrospinal fluid from 18 children during the acute phase by nephelometrie assay, besides cytochemical and virological study. RESULTS: A predominant absence of intrathecal immunoglobulin synthesis and two patients with IgA and IgM synthesis was produced. 66% of cerebrospinal blood barrier dysfunction, 6.26 10 3 mean albumin ratio, lactate below 2.1 mmol/L and glucose concentration in cerebrospinal fluid was 50% over glucose blood content and 168 cells 10 6 L mainly lymphocytes were observed. CONCLUSIONS: The intratecal immunoglobulin synthesis pattern differs from other enterovirus outbreaks that have affected this population and it seems the one found for the diagnostic period in adults. This finding alerts the possibility of genetic changes in echovirus 16 strain, interesting from the neuroimmunoepidemiological point of view.

Cells overexpressing fructose-2,6-bisphosphatase showed enhanced pentose phosphate pathway flux and resistance to oxidative stress.

Changes in the content of fructose-2,6-bisphosphate, a modulator of glycolytic flux, also affect other metabolic fluxes such as the non-oxidative pentose phosphate pathway. Since this is the main source of precursors for biosynthesis in proliferating cells, PFK-2/FBPase-2 has been proposed as a potential target for neoplastic treatments. Here we provide evidence that cells with a low content of fructose-2,6-bisphosphate have a lower energy status than controls, but they are also less sensitive to oxidative stress. This feature is related to the activation of the oxidative branch of the pentose phosphate pathway and the increased production of NADPH.

[Patterns of immunoglobulin synthesis in pediatric patients with Coxsackie A9 meningoencephalitis during the neuropathy epidemic in Cuba]. / Patrones de síntesis de inmunoglobulinas en pacientes pediátricos con meningoencefalitis por Coxsackie A9 durante la epidemia de neuropatía en Cuba.

INTRODUCTION: Simultaneously with the origin and development of the Cuban epidemic neuropathy, cases of viral meningoencephalitis with particular characteristics due to Coxsackie were found. This virus and Inoue-Melnick virus were found too in patients suffering from Cuban epidemic neuropathy. PATIENTS AND METHODS: 31 pediatric patients suffering from viral meningoencephalitis were studied. Albumin, IgA, IgM and IgG were quantified in serum and cerebrospinal fluid by nephelometry. Cytochemical studies and reibergrams were performed. RESULTS: There was a lymphocyte predominance in cerebrospinal fluid. A dysfunction of blood-cerebrospinal fluid barrier was shown in 10 patients. Twenty patients have no immunoglobulins intrathecal synthesis. The synthesis patterns were: five patients with local IgM synthesis, two patients with local IgG synthesis and IgA + IgM. IgA + IgG and IgA + IgM pattern was synthesized in one patient respectively. Two patients with low IgG synthesis percentage or IgG intrathecal fractions were reported. CONCLUSIONS: The absence of immunoglobulins intrathecal synthesis and the immunoglobulins synthesis patterns differ from other pediatric patients with enterovirus meningoencephalitis. These patterns may have relationship with modified antigenic characteristics of the virus, also found in Cuban epidemic neuropathy.

IgG2 immunodeficiency: association to pediatric patients with bacterial meningoencephalitis.

An IgG subclass deficiency is often associated with bacterial infections. We studied four pediatric patients suffering from meningoencephalitis, two of them due to Streptococcus pneumoniae and two due to Haemophilus influenzae type b. Simultaneous diagnostic serum and cerebrospinal fluid samples were taken during income. The four subclasses of IgG and albumin were quantified in both biologic fluids by radial immunodiffusion. Very low levels of seric IgG2 with non detectable cerebrospinal fluid IgG2 were found in the patients. No intrathecal IgG subclass synthesis was found in two patients. One patient with S. pneumoniae had IgG3 intrathecal synthesis. Intrathecal IgG1, IgG3 and IgG4 synthesis was found in one patient suffering from H. influenzae according with reibergrams. Substitutive therapy with intravenous gammaglobulin was given to the patients as part of the treatment.

[Haptoglobin in cerebrospinal fluid as a marker of infectious process in central nervous system]. / Haptoglobina en líquido cefalorraquídeo como marcador de procesos infecciosos en el sistema nervioso central.

INTRODUCTION: Haptoglobin is a transport protein and protects organism against iron loss and it should be involved in central nervous system infectious process. PATIENTS AND METHODS: Simultaneous serum and cerebrospinal fluid were obtained of 39 pediatric patients, 14 suffering from viral meningoencephalitis and 25 from bacterial meningoencephalitis. Five control cases were examined too. Haptoglobin, IgG and albumin were quantified in both fluids by radial immunodiffusion. Haptoglobin cerebrospinal fluid/serum ratio, haptoglobin index and haptoglobin/IgG index were calculated. Local IgG intrathecal synthesis was determined by reibergram. RESULTS: Haptoglobin index was higher not statistically significant in viral meningoencephalitis in comparison with bacterial disease but both were statistically significant with respect to control group. Increased haptoglobin/IgG index were statistically significant in bacterial meningoencephalitis in relation with viral meningoencephalitis. There were no association between haptoglobin and polymorphonuclear cells count and globular sediment speed. CONCLUSION: Haptoglobin should be considered a relevant marker of central nervous system infectious process.

El procuramiento de órganos en un servicio de urgencia de la Región Metropolitana / Organ provision at an emergency service, Región Metropolitana

La unidad de emergencia del área occidente tiene una población asignada de 800.000 habitantes y es el centro de derivación de urgencias para adultos. Estadísticas extranjeras establecen que un 2 por ciento de los fallecidos o 45 individuos por millón de habitantes por año deberían ser donantes potenciales. De acuerdo a esto, en nuestra unidad debería ser posible de obtener entre 15 y 20 donantes efectivos por año. En 1992, se inició un programa de procuramiento a nivel local, basado en: educación y motivación, implementación básica y obtención de recursos y evaluación periódica de resultados. El objetivo de esta comunicación fue presentar los resultados y motivar al personal de salud que labora en otros puntos del país para que inicien esta actividad. El número de donantes potenciales aumentó de 2 a 45 por año y el número de donantes efectivos de 1 a 15 por año. El número de órganos procurados fue de 88 riñones, 7 hígados, 11 donantes de válvulas cardíacas, 10 donantes de córneas, 2 donantes cardíacos y 1 donante óseo. El número de riñones entregados al pool nacional supera a los riñones recibidos de otras partes. Desde 1993 se ha incrementado el número de donantes multiorgánicos. La motivación del personal médico y paramédico, el apoyo del neurólogo y el respaldo de la dirección de la unidad, han sido elementos importantes para esta mejoría. Estos resultados demuestran que pese a las limitaciones y deficiencias existentes en los servicios de urgencias públicos en Chile, es posible implementar el procuramiento de órganos como una actividad médica habitual

[Intrathecal humoral immune response in pediatric patients with meningoencephalitis due to Coxsackie B5]. / Respuesta inmune humoral intratecal en pacientes pediátricos con meningoencefalitis por Coxsackie B5.

INTRODUCTION: Childhood is sensibly affected by viral meningoencephalitis outbreaks. OBJECTIVE: To study the intrathecal humoral immune response in a group of children suffering from Coxsackie B5 meningoencephalitis outbreak. Patients and methods. Forty eight sick children were studied. Serum and cerebrospinal IgA, IgM, IgG and albumin were quantified by radial immunodiffusion. It had been evaluated by reibergrams. RESULTS: Seventeen children has blood-cerebrospinal fluid barrier dysfunction. Four different patterns of intrathecal immune humoral response were observed mainly IgG and three major immunoglobulins class. Mean cell counts was 624 +/- 517 x 10(6) cells/l with a lymphocyte predominance. CONCLUSION: An intrathecal humoral response were reported as an early patterns like in delayed non-diagnostic puncture and in evolutive puncture in adults patterns with viral meningoencephalitis.