Clinical and epidemiological features of myasthenia gravis in Chilean population.

OBJECTIVE: To provide an estimated prevalence and describe the clinical features of myasthenia gravis (MG) in Chile. METHOD: We carried out (i) a prevalence study of MG using the capture-recapture method and the hospital register of pyridostigmine prescription in South-East Santiago (ii) a nationwide survey of MG patients. RESULTS: Prevalence in adults in South-East Santiago was estimated to be 8.36/100 000 inhabitants (CI: 95%, 7.98-8.80). From the nationwide survey, 405 questionnaires were analysed, there was a female/male ratio of 2.2:1. The mean age of onset of symptoms was 38.7 years (range 1-89). The onset was ocular in 46.4%, oculobulbar in 11.6%, bulbar in 8.9%, limbs in 11.6% and generalized in 21.4%. Of the 13.3% of patients who had had a diagnosis of thymoma, only four of these patients were >60 years old at onset. Thymomas were commoner in patients living in mining counties. Patients ≥60 years old at onset of MG formed 19.5% of the sample, female/male ratio 0.97:1. Associated autoimmune diseases were reported in 14% of patients and in family members of 31.8% of patients. A total of 78 patients had to change work due to MG and 68 needed help in carrying out daily activities. CONCLUSIONS: This study reduces the gap in information about MG in South America. The prevalence of MG in Chile is within the range described worldwide. We did not see an increase in male frequency in the older age of onset group and thymoma was more frequent in the fifth and sixth decades.

The neuroblastoma tumour-suppressor TrkAI and its oncogenic alternative TrkAIII splice variant exhibit geldanamycin-sensitive interactions with Hsp90 in human neuroblastoma cells.

Hsp90 chaperones stabilize many tyrosine kinases including several oncogenes, which are inhibited or induced to degrade by the Hsp90 inhibitor geldanamycin (GA). As a consequence, GA has been developed for future chemotherapeutic use in several tumour types including neuroblastoma (NB). Alternative splicing of the neurotrophin receptor tyrosine kinase TrkA may have a pivotal function in regulating NB behaviour, with reports suggesting that tumour-suppressing signals from TrkA may be converted to oncogenic signals by stress-regulated alternative TrkAIII splicing. Within this context, it is important to know whether Hsp90 interacts with TrkA variants in NB cells and how GA influences this. Here, we report that both TrkAI and TrkAIII are Hsp90 clients in human NB cells. TrkAI exhibits GA-sensitive interaction with Hsp90 required for receptor endoplasmic reticulum export, maturation, cell surface stabilization and ligand-mediated activation, whereas TrkAIII exhibits GA-sensitive interactions with Hsp90 required for spontaneous activity and to a lesser extent stability. We show that GA inhibits proliferation and induces apoptosis of TrkAI expressing NB cells, whereas TrkAIII reduces the sensitivity of NB cells to GA-induced elimination. Our data suggest that GA-sensitive interactions with Hsp90 are critical for both TrkAI tumour suppressor and TrkAIII oncogenic function in NB and that TrkAIII expression exerts a negative impact on GA-induced NB cell eradication, which can be counteracted by a novel TrkAIII-specific peptide nucleic acid inhibitor.

What causes paramyotonia in the United Kingdom? Common and new SCN4A mutations revealed.

OBJECTIVE: To study the clinical and genetic features in a large cohort of UK patients with sodium channel paramyotonia congenita. METHODS: We conducted a UK-wide clinical and molecular genetic study of patients presenting with a phenotype suggestive of paramyotonia congenita. RESULTS: We identified 42 affected individuals (28 kindreds). All cases met our core criteria for a clinical diagnosis of paramyotonia congenita. Seventy-five percent of patients (32 patients/20 kindreds) had SCN4A mutations. Twenty-nine subjects from 18 kindreds had exon 22 and 24 mutations, confirming these exons to be hot spots. Unexpectedly, 3 of these subjects harbored mutations previously described with potassium-aggravated myotonia (G1306A, G1306E). We identified two new mutations (R1448L and L1436P). Ten cases (8 kindreds) without mutations exhibited paramyotonia congenita with prominent pain and weakness. CONCLUSIONS: This study identifies two new mutations, confirms SCN4A as a common cause of paramyotonia congenita in the UK, and suggests further allelic and possibly genetic heterogeneity.

Fatiga del material de los sistemas de ventilación mecanica como factor de riesgo en neumonía asociada a ventilación mecanica / Waste of material employed in mechanical ventilator systems as a risk factor for ventilator-associated pneumonia

La neumonía asociada a ventilación mecanica (NAVM) en Chile, es una de las infecciones intrahospitalarias (IIH) mas frecuentes y de mayor impacto en morbimortalidad. A pesar de las medidas habituales de prevención de IIH aplicadas en nuestro hospital, se presentó en el año 2002 un aumento en la tasa de NAVM, junto al aislamiento de un mayor porcentaje de Acinetobacter baumannii, cepa endémica en nuestro hospital. Con el fin de identificar posibles nichos de microorganismos nosocomiales, se realizó un plan de estudio, que involucró al paciente (secreción traqueal) y los sistemas de ventilación, humidificadores, tubo endotraqueal, tubo en Y, mangueras del sistema de ventilación. Se estudió por microscopia de barrido las mangueras de ventilación para precisar características del material. Se observó, al cabo de 7 días, tiempo de recambio establecido por el Comité Nacional de IIH, colonización por A. baumannii, Pseudomonas aeruginosa y Klebsiella pneumoniae, agentes asociados a NAVH en 2 pacientes. Se estudió el circuito de ventilación mecanica perteneciente a un paciente con NAVM tanto preesterilización como postesterilización, aislandose en ambos cultivos microorganismos multiresistentes. Al analizar porciones del circuito por microscopia de barrido se observó un desgaste de las mangueras con múltiples grietas con formas cocoides y bacilares incluidas en la trama. Al estudiar diferentes circuitos pre y posesterilización, se observó en 2 circuitos cultivos positivos con posterioridad a la esterilización en oxido de etileno. Nuestros datos dan enfasis a la necesidad de incorporar en forma rutinaria dentro de las normas de control de IIH las relacionadas a material reutilizable.

[HTLV-I seronegative idiopathic progressive spastic paraparesis: clinical and neurophysiological study of the sensory features]. / Paraparesia espástica progresiva idiopática HTLV-I seronegativa: estudio clínico y neurofisiológico de las manifestaciones sensitivas.

BACKGROUND: HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a defined entity. However, there are many patients not well characterized with a similar clinical picture who are HTLV-I seronegative. OBJECTIVE: Clinical and neurophysiological description of patients with HTLV-I seronegative idiopathic paraparesis. PATIENTS AND METHODS: Seventeen patients (4 women and 13 men aged 24-67 years, average 52.3) were evaluated including clinical assessment, vibratory sensory analysis, quantitative somatosensory thermotest (QST), somatosensory evoked potentials (SSEPs), electromyography (EMG) and motor and sensory nerve conductions. RESULTS: In addition to the spastic paraparesis, 3 (17.6%) patients had pseudobulbar symptoms. Ten (58.8%) patients had a spastic gait but could walk unaided, 6 (35.2%) needed support and 1 patient could not walk. Bladder dysfunction was found in 10 (58.8) patients and sensory symptoms in 7 (41.1%). There was mild distal impairment of vibration and position sense, distal tactile and pinprick hypoesthesia in 4 (23.4%) patients. Tibial SSEPs were abnormal in 11 (64.7%). Nerve conduction studies and EMG were normal. QST showed cold hypoesthesia in 14 (82.4%) patients. Warm sensation and beat pain appeared unimpaired. CONCLUSIONS: All sensory abnormalities found were restricted to sensations carried by myelinated (A beta and A delta) channels. Sensory and motor abnormalities are similar to HAM/TSP patients suggesting a common pathogenesis.