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.     

Complex regional pain syndromes in children and adolescents

Background: The purpose of the present paper was to assess efficiency of treatment and long-term functional outcome of complex regional pain syndromes (CRPS) in children who were treated in the chronic pain clinic at a major tertiary hospital in Israel.
Methods: The files of 14 children with CRPS were analyzed retrospectively. Demographic data, initiating event, referring source, time needed for referral to pain clinic, clinical evaluation, treatment, recurrence and complications were recorded.
Results: Fourteen children with CRPS types I and II were included in the study. Girls were affected in 71%. Lower extremities were affected in 57%. The median time from onset of symptoms to seeking medical help was 4.46 weeks (range 2–82 weeks). The median time to referral to pain clinic was 24.51 weeks (range 1.2–94). In 45% the referral source was the pediatrician. A total of 85.8% of patients were referred to various consultations before the pain clinic. Most children had reduced pain and improved function on non-invasive treatment approach. Invasive treatments were used in 28.5%. Full or partial recovery was accomplished in 93%. Recurrence was observed in 29%.
Conclusions: CRPS in children and adolescents is still underdiagnosed, although many of the epidemiologic features of pediatric CRPS are similar in different countries/cultures. Early recognition and management is the major factor in improving outcome and preventing resistant CRPS, but even children with delayed diagnosis still have a good outcome. The management of this disease by an experienced multidisciplinary team is recommended. Because psychosocial factors play an important role, it is recommended to provide psychological evaluation and cognitive behavioral treatment as soon as possible.     

Evaluation of semiautomated measurements of mesothelioma tumor thickness on CT scans

RATIONALE AND OBJECTIVES: To evaluate the clinical acceptability of semiautomated methods for the measurement of mesothelioma tumor thickness in computed tomography (CT) scans. MATERIALS AND METHODS: A computer interface was developed to allow the acquisition of semiautomated mesothelioma tumor thickness measurements, which require the manual selection of a point along the outer margin of the tumor in a CT section. After application of an automated lung segmentation method, the computer automatically identifies a corresponding point along the inner margin of the tumor (as represented by the lung boundary), constructs a line segment between the manually selected outer tumor margin point and the computer-determined inner tumor margin point, and computes tumor thickness as the length of this line segment. Three radiologists and oncologists independently reviewed line segments representing the semiautomated measurements generated by three different algorithms at 134 measurement sites in the CT scans of 22 mesothelioma patients. The observers either accepted a measurement line segment or modified it through the interface. Differences between the initial semiautomated measurements and the measurements as modified by the observers were analyzed. RESULTS: The frequency with which observers accepted the semiautomated measurements without modification was as high as 86%. Of all measurements across all observers and methods (1,206 measurements), 89% were changed by 2 mm or less. CONCLUSION: We have developed semiautomated methods to measure mesothelioma tumor thickness. The potential of these methods has been demonstrated through an observer study. We expect these methods to become important tools for the efficient quantification of tumor extent.     

Analysis of prostate-specific antigen rebound interval in patients with prostate cancer receiving hormonal therapy and external-beam radiation therapy

The goal of this investigation is to characterize the clinical significance of the rebound interval (RI) after neoadjuvant short-course hormonal therapy (HT) and external-beam radiation therapy (RT), during which the prostate-specific antigen (PSA) may rise because of hormone withdrawal prior to full RT efficacy. The charts of 257 consecutive patients with localized prostate cancer who received short-course neoadjuvant HT and RT were reviewed. A piecewise-linear log PSA versus time curve was generated for each patient and averaged over the population to facilitate identification of the RI start and end dates. Existing definitions of biochemical failure--American Society for Therapeutic Radiology and Oncology (ASTRO), Vancouver and Houston--were applied, as were these same definitions modified to exclude failures during the RI. Sensitivity and specificity were analyzed, using no evidence (by digital rectal examination or radiology) of disease failure as the gold standard. The 5-year biochemical survival with different failure definitions were ASTRO versus ASTRO-modified: 81.6% versus 86.7%; Houston versus Houston-modified: 71.4% versus 76.7%; and Vancouver versus Vancouver-modified: 83.5% versus 85.6%. The sensitivity and specificity comparisons were ASTRO versus ASTRO-modified 58.3% versus 33.3%; 91.4% versus 94.3%, Vancouver versus Vancouver-modified: 50% versus 50%; 92.7% versus 95.5%, Houston versus Houston-modified: 100% versus 66.7%; 90.6% versus 92.2%. The RI after HT and RT is likely not merely an artifact of hormone withdrawal but is correlated with ultimate clinical outcome. Excluding RI failures can marginally improve specificity but may possibly have an unacceptable risk of lowering sensitivity. Further work is needed to design and validate definitions of failure, which account for the RI.     

Retrocaval ureter

Two cases of retrocaval ureter are reported. A 22 years old male patient presented to us with the complaints of right flank pain and hematuria and a child of 2 years referred to us for evaluation of right side moderate hydronephrosis detected on ultrasound. The diagnosis was confirmed on intravenous urography and retrograde pyelography. Both the ends were transected and anastomosed above a JJ stent in front of the inferior vena cava. Postoperatively the patients remained asymptomatic and the hydronephrosis improved.     

Reproducibility and Sources of Variability in Radiographic Texture Analysis of Densitometric Calcaneal Images

Radiographic texture analysis (RTA) is a computerized analysis of the spatial pattern of radiographic images used as a way of evaluating bone structure. We have shown that RTA performed on high-resolution heel images obtained using a portable densitometer differentiates subjects with and without osteoporotic fractures. In the present study, short-term precision of RTA was examined on densitometric heel images obtained from 33 subjects scanned 8 times each, with 3 observers placing a region of interest (ROI) 3 times on each image. The long-term precision was examined on images obtained from 10 subjects 3 times on each of 3 days separated by 1 week, with 2 observers placing an ROI on each image. The RTA features examined included the root mean square (RMS) variation, a measure of the contrast between the light and dark areas of the image, the first moment of the power spectrum, a measure of the spatial frequency of the trabecular pattern, and Minkowski fractal (MINK), a measure of roughness/smoothness of the trabecular pattern. The precision of the RTA features expressed as coefficient of variation ranged between the lowest of 0.5–0.7% for MINK and the highest of 14–16% for RMS. The short- and long-term precision was similar, and was not significantly influenced by repositioning and rescanning, or by ROI placement by the same or different observers. Significant sources of variability of RTA were the between-subject differences and differences between regions of the heel, but not differences due to repositioning, rescanning in the same position, or ROI placement by the same or different observers. We conclude that technical aspects of image acquisition and processing are adequate to allow further development of RTA of the densitometric images for clinical application as a method for noninvasive assessment of bone structure.     

“I Don’t Understand”: Who Is Missed When We Ask Early Adolescents, “Are You Transgender”?

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