Advances in the neurophysiology of magnocellular neuroendocrine cells

Hypothalamic magnocellular neuroendocrine cells have unique electrical properties and a remarkable capacity for morphological and synaptic plasticity. Their large somatic size, their relatively uniform and dense clustering in the supraoptic and paraventricular nuclei, and their large axon terminals in the neurohypophysis make them an attractive target for direct electrophysiological interrogation. Here, we provide a brief review of significant recent findings in the neuroplasticity and neurophysiological properties of these neurones that were presented at the symposium “Electrophysiology of Magnocellular Neurons” during the 13th World Congress on Neurohypophysial Hormones in Ein Gedi, Israel in April 2019. Magnocellular vasopressin (VP) neurones respond directly to hypertonic stimulation with membrane depolarisation, which is triggered by cell shrinkage‐induced opening of an N‐terminal‐truncated variant of transient receptor potential vanilloid type‐1 (TRPV1) channels. New findings indicate that this mechanotransduction depends on actin and microtubule cytoskeletal networks, and that direct coupling of the TRPV1 channels to microtubules is responsible for mechanical gating of the channels. Vasopressin neurones also respond to osmostimulation by activation of epithelial Na⁺ channels (ENaC). It was shown recently that changes in ENaC activity modulate magnocellular neurone basal firing by generating tonic changes in membrane potential. Both oxytocin and VP neurones also undergo robust excitatory synapse plasticity during chronic osmotic stimulation. Recent findings indicate that new glutamate synapses induced during chronic salt loading express highly labile Ca²⁺‐permeable GluA1 receptors requiring continuous dendritic protein synthesis for synapse maintenance. Finally, recordings from the uniquely tractable neurohypophysial terminals recently revealed an unexpected property of activity‐dependent neuropeptide release. A significant fraction of the voltage‐dependent neurohypophysial neurosecretion was found to be independent of Ca²⁺ influx through voltage‐gated Ca²⁺ channels. Together, these findings provide a snapshot of significant new advances in the electrophysiological signalling mechanisms and neuroplasticity of the hypothalamic‐neurohypophysial system, a system that continues to make important contributions to the field of neurophysiology.     

Focal midbrain tumors in children.

The clinical and neuroradiological features of focal midbrain tumors in 12 children are described, and the results of their surgical management are presented. Patients with a focal midbrain tumor usually exhibit either symptoms and signs of raised intracranial pressure caused by an obstructive hydrocephalus (50%) or symptoms and signs caused by pressure on the tegmentum and cerebral peduncles. The lesions are confined to the tectal plate or tegmentum with possible extension upward to the thalamus and downward to the pons, displacing but not invading these structures. The edges of the tumor are well defined, and the large majority have a solid consistency with intense regular enhancement after intravenous contrast. Radical resection is hardly ever feasible in brain stem tumors, but in this series, significant reduction of the tumor mass was obtained in 75% of the patients, with no surgical mortality and minimal surgical morbidity and with the majority of patients showing clinical improvement postoperatively. All tumors were nonpilocytic, low-grade astrocytomas. Six patients received adjunctive radiotherapy. The mean follow-up period is 2.5 years, and all patients are alive and doing well. We conclude that focal midbrain tumors in children appear to be a distinct subgroup of brain stem tumors and are very amenable to surgical resection with an excellent long-term prognosis.     

The spatial patterns of β/A4 deposit subtypes in Down's syndrome

The spatial patterns of diffuse, primitive and classic /A4 deposits were studied in coronal sections of the hippocampus and adjacent gyri in 11 cases of Down's syndrome (DS) varying in age from 38 to 67 years. The objectives of the study were first, to compare the spatial patterns of /A4 deposits revealed in DS with those reported in cases of Alzheimer's disease (AD) and second, to study how the spatial patterns of /A4 deposits may develop in the tissue. The spatial patterns revealed in DS exhibited a number of similarities with those reported in AD: (1) the range and frequency of the different types of spatial pattern revealed were similar, (2) /A4 deposits occurred in clusters and in many cortical tissues, the clusters were distributed in a regular pattern parallel to the pia, (3) the clusters of diffuse and primitive /A4 deposits occurred in an alternating pattern along the cortex, and (4) the clusters of classic /A4 deposits were not correlated with the clusters of the diffuse and primitive deposits. Primitive deposits may develop from the diffuse deposits in regions of the cortex where extracellular paired helical filaments were formed. However, clusters of the classic /A4 deposits, which are formed in older cases, appear to develop independently of the diffuse and primitive deposits.Supported in part by the Alzheimer's Disease Society, UK     

Predictive value of respiratory symptoms and bronchial hyperresponsiveness to diagnose asthma in New Zealand

Respiratory symptoms are often used as the only diagnostic criteria for asthma in epidemiological surveys and the clinical diagnosis of asthma relies primarily on a detailed history. The aim of this study is to predict the diagnostic value of 11 different respiratory symptoms to diagnose asthma, and to determine if bronchial hyperresponsiveness (BHR) improves the predictive value of these respiratory symptoms. A random sample of 1257 subjects aged 20-44 years old in 3 different areas of New Zealand were selected between March 1991 and December 1992 to answer the European Community Respiratory Health Survey questionnaire on respiratory symptoms. Of these, 784 underwent bronchial challenge with methacholine. The prevalence of current doctor diagnosed asthma (DDA) defined as asthma confirmed by a physician and an asthma attack in the last 12 months was 8.3%. Wheezing with dyspnoea is the single best predictor of diagnosed asthma with a sensitivity of 82%, a specificity of 90% and a Youden's index of 0.72. Wheezing alone is more sensitive (94%) but less specific (76%), with a Youden's index of 0.70. The addition of BHR to asthma symptoms decreases sensitivity and increases specificity with a small increase in Youden's index to 0.75. In New Zealand adults, a history of wheezing with BHR best predicts a diagnosis of asthma but wheezing alone or with dyspnoea are the two best symptoms for predicting asthma.     

Uptake of preventive health care among Mediterranean migrants in Belgium.

STUDY OBJECTIVE--The aim was to investigate the influence of ethnicity on the demand for preventive care by Mediterranean migrants in Belgium. DESIGN--This was a survey of patient contacts with general practitioners. SETTING AND PATIENTS--33 general practitioners working in Belgian localities with the highest migrant density collaborated in the study. During two months they recorded information on consultations with an estimated 72,600 clients. Participation was obtained from all subjects attending for preventive care or for a new episode of illness (n = 6256). MAIN RESULTS--An average of 30% of the patients sought preventive care, but multivariate analysis showed ethnicity to be a strong independent predictor of this type of demand. The higher primary preventive uptake by female Moroccans and Turks and the higher secondary preventive uptake by males from the same ethnic groups, as compared with the Belgian reference population, contrasted with a lower demand for tertiary prevention in migrants of either gender. The relative demand for preventive care by the more acculturated migrants was, however, quite similar to the demand of the Belgian population. CONCLUSIONS--The differential uptake of primary preventive care could be partly explained by the higher fertility rates of immigrant women, and the differential secondary uptake by a lower incidence of tuberculosis in the indigenous population. The meagre demand for tertiary prevention by Moroccan and Turkish migrants could be due to weaker compliance with treatments for chronic disorders, which is related to the perceptions of illness in these ethnic groups. The establishment of cross cultural mechanisms of dialogue should enhance compliance and improve the access of immigrants to the benefits of tertiary preventive care.     

Dysfunctional eating patterns and symptoms of pica in children and adolescents with sickle cell disease

The objective of this study was to examine the incidence and relationship of pica symptoms and dysfunctional eating patterns in children and adolescents with sickle cell disease (SCD). Children and caregivers (n = 146) completed questionnaires assessing eating difficulties and symptoms of pica. Information also was collected from medical records and analyzed for relationships with dysfunctional eating patterns. Incidence of problems and their association with disease parameters of SCD were examined. Dysfunctional eating patterns were found in those with no symptoms of pica and those with severe symptoms of pica. Caregiver-reported dysfunctional eating patterns were associated with caregiver- and child-reported frequency of painful episodes.     

导致儿童期肥胖的生命早期危险因素：队列研究

目的 确定早年（3岁以内）导致英国儿童肥胖的危险因素。设计 前瞻性队列研究。方法 Avon英国父母及儿童纵向调查研究。参与者 参与队列研究的8234名年龄为7岁的儿童以及亚组的909名重点儿童，后者需额外提供与早期发育有关并涉及可能导致肥胖的各种资料。诊断标准 7岁儿童体重指数≥95百分位确定为肥胖，参考1990年英国人口调查的诊断标准。结果 经过最终验证，在假设的25项危险因素中有8项与肥胖有关：父母肥胖（父母双方校正后的相对危险度10．44，95％可信区间5．11～21．32）；最早期（43个月内）的体重指数或体重反弹升高（校正后的相对危险度15．00，95％可信区间5．32～42．30）；3岁时每周看电视的时间超过8小时（校正后的相对危险度1．55，95％可信区间1．13～2．12）；追赶性生长（校正后的相对危险度2．60，95％可信区间1．09～6．16）；8个月（校正后的相对危险度3．13，95％可信区间1．43～6．85）和18个月（校正后的相对危险度2．65，95％可信区间l，25～5．59）时体重的标准差值；1岁时体重增加值（校正后的相对危险度1．06，95％可信区间1．02～1．10，体重每增加100g）；出生体重，每100g（校正后的相对危险度1．05，95％可信区间1．03～1．07）；3岁时睡眠不足（〈10．5小时，校正后的相对危险度1．45，95％可信区间1．10～1．89）。结论儿童期肥胖可能与8项危险因素有关。