RESUMEN
BACKGROUND: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. METHODS: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000-2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing-remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers' characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. RESULTS: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. DISCUSSION: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers' characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.
Asunto(s)
Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Femenino , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple Crónica Progresiva/complicaciones , Esclerosis Múltiple Crónica Progresiva/epidemiología , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Fenotipo , Recurrencia , Derivación y ConsultaRESUMEN
OBJECTIVE: To investigate risk factors for delayed sputum culture conversion to negative during anti-tuberculosis treatment, with an emphasis on smoking. DESIGN: Nested case-control study of adults with non-cavitary, culture-confirmed pulmonary tuberculosis (TB) participating in an anti-tuberculosis treatment trial in Brazil. A case of delayed culture conversion was a patient who remained culture-positive after 2 months of treatment. Odds ratios with 95% confidence intervals were calculated. RESULTS: Fifty-three cases and 240 control patients were analyzed. Smokers had three-fold greater odds of remaining culture-positive after 2 months of treatment (P = 0.007) than non-smokers, while smokers and ex-smokers who smoked >20 cigarettes a day had two-fold greater odds of remaining culture-positive after 2 months of treatment (P = 0.045). CONCLUSION: Cigarette smoking adversely affects culture conversion during anti-tuberculosis treatment. Support for smoking cessation should be considered to improve outcomes in TB control programs.
Asunto(s)
Mycobacterium tuberculosis/aislamiento & purificación , Cese del Hábito de Fumar , Fumar/efectos adversos , Esputo/microbiología , Tuberculosis/tratamiento farmacológico , Adolescente , Adulto , Antituberculosos/uso terapéutico , Brasil/epidemiología , Intervalos de Confianza , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Oportunidad Relativa , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Fumar/epidemiología , Prevención del Hábito de Fumar , Resultado del Tratamiento , Tuberculosis/epidemiología , Tuberculosis/microbiología , Adulto JovenRESUMEN
Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 16/genética , Obesidad/genética , Obesidad/fisiopatología , Penetrancia , Adolescente , Adulto , Edad de Inicio , Envejecimiento , Índice de Masa Corporal , Estudios de Casos y Controles , Niño , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/genética , Estudios de Cohortes , Europa (Continente) , Femenino , Estudio de Asociación del Genoma Completo , Heterocigoto , Humanos , Patrón de Herencia/genética , Masculino , Mutación/genética , Obesidad/complicaciones , Reproducibilidad de los Resultados , Caracteres Sexuales , Adulto JovenRESUMEN
The research moves from the current global and local context and from shared development strategies. From the observation and the analysis of contemporary environmental and energy issues and redefined directions of growth of human activity, it is addressing the question of environmental sustainability and energy conservation of building hospital systems. The work has developed a field survey relating the specific topic of energy saving and efficiency of the Park Hospital in the Italian Lombardy Region. This has been articulated in a diagnosis of technology and efficiency of regional hospitals, implemented through a census, and in a subsequent identification of interventional cases, in order to show its economic, environmental and health performance of the energy efficiency consumption and the environmentally sound.
Asunto(s)
Conservación de los Recursos Naturales , Monitoreo del Ambiente , Contaminación Ambiental/prevención & control , Instituciones de Salud/normas , Eficiencia Organizacional , Fuentes Generadoras de Energía , Monitoreo del Ambiente/métodos , Hospitales/normas , Humanos , ItaliaRESUMEN
Fatal insomnia is a rare human prion disease characterised by sleep-wake disturbances, thalamic degeneration and deposition of type 2 disease-specific prion protein (PrP(Sc)). This report details a patient with sporadic fatal insomnia who exhibited cerebral deposition of type 1 PrP(Sc) and neuropathological changes largely in the basal ganglia. Previous damage of this brain region by a surgically removed colloid cyst and the insertion of two intracerebral shunts may have influenced the distribution of PrP(Sc) through a chronic inflammatory process. These findings add to our knowledge of the phenotypic variability of human prion diseases with prominent sleep disturbances.
Asunto(s)
Insomnio Familiar Fatal/patología , Proteínas PrPSc/metabolismo , Western Blotting , Encéfalo/patología , Síndrome de Creutzfeldt-Jakob/patología , Electroencefalografía , Humanos , Inmunohistoquímica , Insomnio Familiar Fatal/genética , Insomnio Familiar Fatal/metabolismo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Proteínas PrPSc/genética , Tomografía Computarizada por Rayos XRESUMEN
Slow oscillations of cytosolic calcium ion concentration - [Ca(2+)](c) - typically originate from release by intracellular stores, but in some cell types can be triggered and sustained by Ca(2+) influx as well. In this study we simultaneously monitored changes in [Ca(2+)](c) and in the electrical activity of the cell membrane by combining indo-1 and patch-clamp measurements in single rat chromaffin cells. By this approach we observed a novel type of spontaneous [Ca(2+)](c) oscillations, much faster than those previously described in these cells. These oscillations are triggered and sustained by complex electrical activity (slow action potentials and spike bursts), require Ca(2+) influx and do not involve release from intracellular stores. The possible physiological implications of this new pathway of intracellular signalling are discussed.
Asunto(s)
Potenciales de Acción , Señalización del Calcio/fisiología , Calcio/metabolismo , Células Cromafines/fisiología , Animales , Calcio/análisis , Canales de Calcio/fisiología , Membrana Celular/fisiología , Células Cultivadas , Células Cromafines/química , Fluorometría , Permeabilidad , RatasRESUMEN
This study analyzed the macrostructure and microstructure of sleep in 12 parkinsonian patients under basal conditions (T0) and during 1-night treatment (T1) with a new formulation of apomorphine. This new formulation consisted in a microemulsion of apomorphine administered by the transdermal route, able to provide a constant release of the drug over several hours (APO-TD). Sleep analysis at T1 compared with T0 revealed a 16% increment of total sleep time, a 12% increment of sleep efficiency, a 16% increment of stage 3 and 4 non-REM sleep, a 15% reduction of periodic limb movements index, a 22% reduction of arousal index, and a 23% reduction of cycling alternating patterns/non-REM. We conclude that APO-TD may be able to reduce nocturnal anomalous movements, akinesia, and rigidity in Parkinson's disease, and may reduce the disturbed sleep typical of Parkinson's disease.
Asunto(s)
Antiparkinsonianos/uso terapéutico , Apomorfina/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Sueño/efectos de los fármacos , Administración Cutánea , Anciano , Nivel de Alerta/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Preparaciones de Acción Retardada , Esquema de Medicación , Quimioterapia Combinada , Humanos , Levodopa/uso terapéutico , Persona de Mediana Edad , Movimiento/efectos de los fármacos , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/fisiopatología , Polisomnografía/métodos , Síndrome de las Piernas Inquietas/tratamiento farmacológico , Síndromes de la Apnea del Sueño/tratamiento farmacológicoRESUMEN
Brain metastases (BrM) are tumours that originate in tissues outside the central nervous system and spread secondarily to involve mainly the brain. The management of patients with cerebral metastases is complex, costly, and in some instances controversial. Furthermore, even in patients with widespread systemic cancer, the symptoms of the disease are often controllable while the symptoms of the BrM may be disabling. The treatment of BrM is one of the few areas of neuro-oncology where real progress has been made in the last twenty years. Moreover, the costs of managing this disease are rising, as therapies become more intensive and the number of patients with BrM increases. Modern neuroradiological imaging techniques, which are able to discover BrM earlier in the course of systemic cancer, and the greater efficacy of specific treatments, which lengthens survival, have increased the prevalence. The aggressive treatment of BrM may add some benefits to the patient, but its excessive cost leads to the necessity for accurate cost-effectiveness analysis. The latter begins with a complete understanding of the disease: its diagnosis, natural history and results of various modalities of treatment. While the development of BrM usually indicates a poor prognosis for the patient, advances in supportive care have made it possible to reverse most of the neurological symptoms and to give patients a meaningful extension of useful life.
Asunto(s)
Neoplasias Encefálicas/fisiopatología , Neoplasias Encefálicas/secundario , Apoyo Social , Neoplasias Encefálicas/terapia , HumanosRESUMEN
Electromyography (EMG) could be useful in defining regional motor neuron vulnerability in ALS. We performed EMG in 36 sporadic ALS patients (9 with bulbar-onset and 27 with limb-onset symptoms). Active denervation was more frequent in limb than in corresponding paraspinal muscles, in the thoracic paraspinal, and in the bulbo-cervical muscles in patients with bulbar-onset symptoms. These results are consistent with a regional motor neuron vulnerability along with a nerve length-dependent liability.
Asunto(s)
Esclerosis Amiotrófica Lateral/fisiopatología , Músculos/fisiopatología , Adulto , Anciano , Interpretación Estadística de Datos , Electromiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa/fisiologíaRESUMEN
The N-type voltage-operated calcium channel has been characterized over the years as a high-threshold channel, with variable inactivation kinetics, and a unique ability to bind with high affinity and specificity omega-conotoxin GVIA and related toxins. This channel is particularly expressed in some neurons and endocrine cells, where it participates in several calcium-dependent processes, including secretion. Omega-conotoxin GVIA was instrumental not only for the biophysical and pharmacological characterization of N-type channels but also for the development of in vitro assays for studying N-type VOCC subcellular localization, biosynthesis, turnover, as well as short-and long-term regulation of its expression. We here summarize our studies on N-type VOCC expression in neurosecretory cells, with a major emphasis on recent data demonstrating the presence of N-type channels in intracellular secretory organelles and their recruitment to the cell surface during regulated exocytosis.
Asunto(s)
Canales de Calcio Tipo N , Canales de Calcio/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Sistemas Neurosecretores/metabolismo , Péptidos/farmacología , Animales , Transporte Biológico , Calcio/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/efectos de los fármacos , Señalización del Calcio/efectos de los fármacos , Membrana Celular/metabolismo , Regulación hacia Abajo , Humanos , Potenciales de la Membrana , Proteínas del Tejido Nervioso/efectos de los fármacos , Sistemas Neurosecretores/efectos de los fármacos , Células PC12/metabolismo , Péptidos/metabolismo , Ratas , Regulación hacia Arriba , omega-Conotoxina GVIARESUMEN
Intracranial hypotension (IH) is essential or, more frequently, secondary. This syndrome is characterized by severe postural headache and low opening cerebrospinal fluid (CSF) pressure; although other symptoms may exist. In this study five patients are investigated. Neuroimaging showed: on computerized tomography scan (CT), poor visualization of the cerebral sulci with small ventricles; on magnetic resonance imaging (MRI), subdural fluid collections with enhancement on the convexity, along the tentorium and in the upper cervix after administration of contrast medium and downward displacement of the brain. Radionuclide cisternography was normal in the two patients who underwent this treatment as well as the meningeal biopsy in another patient. In all patients the opening CSF pressure was low or unmeasurable. The clinical syndrome spontaneously recovered contextually to normalization of neuroradiological findings. The possible pathogenesis (dural border cell layer tear) was discussed and the importance of diagnostic confirmation with MRI and measurement of CSF pressure when IH is thought to be present was underlined.
Asunto(s)
Encéfalo/diagnóstico por imagen , Hipotensión Intracraneal/diagnóstico , Adulto , Encéfalo/patología , Presión del Líquido Cefalorraquídeo , Diagnóstico Diferencial , Femenino , Cefalea/etiología , Humanos , Hipotensión Intracraneal/etiología , Hipotensión Intracraneal/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Postura , Síndrome , Tomografía Computarizada por Rayos XRESUMEN
Human motor neuron (MN) isolation provides a critical tool to study neurophysiological properties and the effects of molecules of clinical relevance on isolated neurons. We developed an immunomagnetic separation technique based on specific MN antigen recognition for nerve growth factor receptor (p75-NGFR). We cultured an average of 250,000 cells from the anterior horns of a single cord (four specimens at postconception Weeks 6.0, 7.2, 8.0, and 8.3). At day 7 in vitro (DIV), choline acetyltransferase (ChAT) and/or p75-NGFR-expressing cells (MNs) represented 72 +/- 2% of the total growing cells. MNs survived for at least 4 weeks in biochemically defined medium. The immunomagnetic separation method has been demonstrated to be effective, reproducible, and quantitative for separation of MNs.
Asunto(s)
Separación Inmunomagnética , Neuronas Motoras/inmunología , Médula Espinal/embriología , Células Cultivadas , Humanos , Inmunohistoquímica , Reproducibilidad de los Resultados , Médula Espinal/citologíaRESUMEN
Inward rectification, an important determinant of cell excitability, can result from channel blockade by intracellular cations, including Ca2+. However, mostly on the basis of indirect arguments, Ca2+-mediated rectification of inward rectifier K+ current (IK1) is claimed to play no role in the mammalian heart. The present study investigates Ca2+-mediated IK1 rectification during the mammalian ventricular action potential. Guinea pig ventricular myocytes were patch-clamped in the whole-cell configuration. The action potential waveform was recorded and then applied to reproduce normal excitation under voltage-clamp conditions. Subtraction currents obtained during blockade of K+ currents by either 1 mmol/L Ba2+ (IBa) or K+-free solution (I0K) were used to estimate IK1. Similar time courses were observed for IBa and I0K; both currents were strongly reduced during depolarization (inward rectification). Blockade of L-type Ca2+ current by dihydropyridines (DHPs) increased systolic IBa and I0K by 50.7% and 254.5%, respectively. beta-Adrenergic stimulation, when tested on I0K, had an opposite effect; ie, it reduced this current by 66.5%. Ryanodine, an inhibitor of sarcoplasmic Ca2+ release, increased systolic IBa by 47.7%, with effects similar to those of DHPs. Intracellular Ca2+ buffering (BAPTA-AM) increased systolic IBa by 87.7% and blunted the effect of DHPs. Thus, IK1 may be significantly reduced by physiological Ca2+ transients determined by both Ca2+ influx and release. Although Ca2+-induced effects may represent only a small fraction of total IK1 rectification, they are large enough to affect excitability and repolarization. They may also contribute to facilitation of early afterdepolarizations by conditions increasing Ca2+ influx.
Asunto(s)
Calcio/fisiología , Potasio/fisiología , Función Ventricular , Potenciales de Acción , Animales , Bario/fisiología , Bloqueadores de los Canales de Calcio/farmacología , Células Cultivadas , Dihidropiridinas/farmacología , Ácido Egtácico/análogos & derivados , Ácido Egtácico/farmacología , Conductividad Eléctrica , Cobayas , Magnesio/fisiología , Potenciales de la Membrana , Receptores Adrenérgicos beta/fisiología , Retículo Sarcoplasmático/fisiologíaRESUMEN
Transient sixth cranial nerves palsy may occur in rare cases after lumbar puncture, spinal anesthesia and myelography as well as in more rare cases of spontaneous intracranial hypotension. We report three cases of spontaneous intracranial hypotension with sixth cranial nerves palsy. One of these patients presented also third cranial nerve palsy, never reported in spontaneous intracranial hypotension.
Asunto(s)
Nervio Abducens , Enfermedades de los Nervios Craneales/etiología , Hipotensión Intracraneal/complicaciones , Enfermedades del Nervio Oculomotor/etiología , Parálisis/etiología , Adulto , Femenino , Humanos , Hipotensión Intracraneal/diagnóstico , Imagen por Resonancia Magnética , Persona de Mediana EdadRESUMEN
We report a series of four patients in whom the onset of systemic cancer was heralded by dysautonomic symptoms and a neurological non-metastatic complication mediated by immunological and endocrine factors. The series includes: a patient with acute leukaemia and autonomic sensory-motor polyradiculoneuropathy, a patient affected by colon carcinoma and autonomic neuropathy and limbic encephalitis, a patient with lung cancer and autonomic neuropathy and hypercalcaemic encephalopathy, a patient with small cell lung cancer associated with autonomic neuropathy in Lambert-Eaton Myasthenic Syndrome (LEMS) and syndrome of inappropriate ADH secretion (SIADH). We underline the prognostic importance and discuss the possible etiopathogenetic role of autonomic dysfunction, which is frequently associated with paraneoplastic neurologic syndromes of autoimmune and/or dysendocrine origin.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/inmunología , Síndromes Paraneoplásicos/inmunología , Anciano , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Neoplasias del Colon/inmunología , Neoplasias del Colon/fisiopatología , Humanos , Leucemia/inmunología , Leucemia/fisiopatología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Síndromes Paraneoplásicos/fisiopatologíaRESUMEN
1. The contribution of various ionic currents to diastolic depolarization (DD) in rabbit sinoatrial myocytes was evaluated by the action potential clamp technique. Individual currents were identified, during sustained pacemaking activity reproduced under voltage clamp conditions, according to their sensitivity to specific channel blockers. 2. The current sensitive to dihydropyridines (DHPs), blockers of L-type Ca2+ current (ICa,L), was small and outward during most of DD. Diastolic DHP-sensitive current was affected by changes in the driving force for K+, but it was insensitive to E-4031, which blocks the current termed IK,r; it was abolished by cell dialysis with a Ca2+ chelator. 3. The current sensitive to 2 mM Cs+ (ICs), a blocker of hyperpolarization-activated current (I(f)), was inward during the whole DD and it was substantially larger than the net inward current flowing during this phase. However, diastolic IK,r, identified in the same cells as the current sensitive to the blocker E-4031, exceeded ICs 2-fold. 4. These findings suggest that: (a) Ca2+ influx during the pacemaker cycle increases a K+ conductance, thus inverting the direction of the net current generated by L-type Ca2+ channel activity during DD; (b) the magnitude of I(f) would be adequate to account fully for DD; however, the coexistence of a larger IK,r suggests that other channels besides I(f) contribute inward current during this phase.
Asunto(s)
Canales Iónicos/fisiología , Canales de Potasio con Entrada de Voltaje , Nodo Sinoatrial/fisiología , Potenciales de Acción/fisiología , Animales , Canales de Calcio/efectos de los fármacos , Canales de Calcio/fisiología , Canales de Potasio de Tipo Rectificador Tardío , Dihidropiridinas/farmacología , Femenino , Técnicas In Vitro , Canales Iónicos/efectos de los fármacos , Técnicas de Placa-Clamp , Canales de Potasio/efectos de los fármacos , Canales de Potasio/fisiología , Conejos , Nodo Sinoatrial/citologíaRESUMEN
Central pontine myelinolysis (CPM), a rare condition first observed by Adams et al. in 1959 in a group of malnourished chronic alcoholic subjects, has subsequently been seen in patients treated with thiazide diuretics, patients hyperhydrated postoperatively, and in other clinical situations. it is characterized by quadriplegia and pseudobulbar palsy which sometimes evolves into a locked-in syndrome. The rapid correction of severe hyponatremia (> 12 mmol/L/24 h) seems to be the causal factor, with consequent osmotic edema in the richly vascularized white matter of the pons as the proposed pathogenetic mechanism. We describe the case of a chronic psychotic man with nutritional disorders and inappropriate water intake who came to our attention for a clinical picture of CPM. Neuroradiological findings and postmortem studies revealed a slow-growing cerebellar astrocytoma in addition to the typical features of CPM. We discuss the hypothesis that damage to the nervous pathways and centers involved in water and electrolyte regulation could be the causal factor of CPM pathogenesis in this case.
Asunto(s)
Astrocitoma/complicaciones , Neoplasias Cerebelosas/complicaciones , Mielinólisis Pontino Central/etiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Primary or spontaneous intracranial hypotension (SIH) is a rare syndrome which causes postural headache associated with spinal fluid hypotension. We report three cases of SIH, characterised on magnetic resonance imaging (MRI) by pachymeningeal enhancement not only at cerebral level, but also in the cervical spinal cord, which subsequently resolved completely and spontaneously. We discuss the possible pathogenetic mechanisms of the dural alterations and underline the radiological aspects.
Asunto(s)
Hipotensión Ortostática/patología , Presión Intracraneal , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Femenino , Humanos , Hipotensión Ortostática/fisiopatología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Parkinson's disease (PD) is characterized by the degeneration of the mesencephalic dopaminergic (mesDA) neurons innervating the striatum. Neurotrophic factor(s) that prevents the degeneration and increases the functional activity of the remaining mesDA neurons are of substantial clinical interest. The origin and development of mesDA neurons were characterized in the human mesencephalon from 5.0 to 12 Postconception (PC) weeks. Tyrosine Hydroxylase (TH) immunoreactive cells were first demonstrated at 5.5 PC weeks next to the ventricular zone. In primary culture, TH immunoreactive neurons represent 3 to 5% of the total cells at days 7 in vitro and basic Fibroblast growth factor (bFGF) was demonstrated to induce a significant increase of both TH immunoreactive cell number and TH enzymatic activity. This effect was mediated by proliferating glial fibrillary acidic protein immunoreactive cells. Nerve growth factor treatment did not have any appreciable effect. The effect of bFGF on TH positive cells described in this human bioassay is only a preliminary evidence that, if confirmed by experiments in vivo, may provide a starting rationale for investigating alternative strategies in the treatment of PD.