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Purpose: Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited disorder that involves epistaxis, mucocutaneous telangiectases, and visceral arteriovenous malformations (AVMs). This study aims to investigate the genetic causes in a Chinese family with HHT. Methods: HHT was confirmed according to Curaçao's diagnostic criteria. Three patients diagnosed with HHT and healthy members were recruited. Whole-exome sequencing (WES) and sanger sequencing were performed to define the patient's genetically pathogenic factor. Results: The proband presented with recurrent epistaxis, hepatopulmonary arteriovenous malformation, and adenocarcinoma. A novel frameshift mutation (c.1376_1377delAC, p.H459Lfs*41) of the ENG gene was revealed in affected individuals by WES. There was no report of this variant and predicted to be highly damaging by causing truncation of the ENG protein. Conclusion: We report a novel variant in the ENG gene in Chinese that extends the mutational and phenotypic spectra of the ENG gene, and also demonstrates the feasibility of WES in the application of genetic diagnosis of HHT. [ABSTRACT FROM AUTHOR]

The study included 32 women with PAS and 20 with normally implanted placenta as a control group. Vascular endothelial cell growth factor (VEGF), Soluble FMS Like Tyrosine Kinase (sFLT-1/sVEGFR1), and Endoglin (ENG) were measured in placenta tissue by ELISA. Granzyme B (GrzB) expression in trophoblastic and stromal mesenchymal cells was evaluated by immunohistochemistry. MAIT, NK, and NKT cells were assessed in blood and placenta by flow cytometry. Alterations were observed in levels of MAIT cells, NK cell subsets, and NKT cells in patients compared with controls. Several significant correlations were detected between these cells and GrzB scores, VEGF, ENG, and sFLT-1 levels. This is the first study analysing these cells in PAS patients and correlating their levels with changes in some angiogenic and antiangiogenic factors implicated in trophoblast invasion and with GrzB distribution in trophoblast and stroma. Interrelation between these cells probably plays an important role in pathogenesis of PAS. [ABSTRACT FROM AUTHOR]

Hereditary haemorrhagic telangiectasia (HHT) is supposedly rare in Africa, with only three pathogenic variants documented to date. We describe the clinical and genetic features of HHT patients in central South Africa, who fulfilled the Curaçao criteria. Sixteen patients (median age 38.5 years, range 12–65 years), from six families were included. Fifteen patients were of African descent and one was of Afrikaner descent. The mean epistaxis severity score was 3.18, and the median haemoglobin was 9.5 g/dL (range 3.5–13.5 g/dL). On transthoracic contrast echocardiography 69% had a shunt grade ≥ 1, but only 20% had pulmonary arteriovenous malformations (AVMs) on computed tomography of the chest. Hepatic AVMs were found in 13% of patients, while 13% had brain vascular malformations. Four patients were HIV positive, of whom two had worsening epistaxis while they had opportunistic infections and poor HIV control. We identified six pathogenic variants (four in ENG and two in ACVRL1) in the six probands, three of which had been described previously. Three variants have apparently not been reported previously: ENG c.[1336_1337dup];[ =] p.[(Asp446fs)];[(=)], ENG c.[ 690?_816+?del] p.[(?)], and ACVRL1 c.[268_274delins57];[ =] p.[(Cys90fs)];[(=)]. We confirmed the diagnosis of HHT in sixteen patients and identified pathogenic variants in ENG or ACVRL1 in all six probands in central South Africa, where HHT has been underreported. We describe three pathogenic variants: two of ENG and one of ACVRL1. We will be able to implement pre-symptomatic screening of patients in our area, and improve their management. [ABSTRACT FROM AUTHOR]

Neural interfaces have great potential to treat disease and disability by modulating the electrical signals within the nervous system. However, whilst neural stimulation is a well-established technique, current neural interfaces are limited by poor recording ability. Low signal amplitudes necessitate the use of highly invasive techniques that divide or penetrate the nerve, and as such are unsuitable for chronic implantation. In this paper, we present the first application of the velocity selective recording technique to the detection of respiration activity in the vagus nerve, which is involved with treatments for epilepsy, depression, and rheumatoid arthritis. Further, we show this using a chronically implantable interface that does not divide the nerve. We also validate our recording setup using electrical stimulation and we present an analysis of the recorded signal amplitudes. The recording interface was formed from a cuff containing ten electrodes implanted around the intact right vagus nerve of a Danish Landrace pig. Nine differential amplifiers were connected to adjacent electrodes, and the resulting signals were processed to discriminate neural activity based on conduction velocity. Despite the average single channel signal-to-noise ratio of - 5.8 dB, it was possible to observe distinct action potentials travelling in both directions along the nerve. Further, contrary to expectation given the low signal-to-noise ratio, we have shown that it was possible to identify afferent neural activity that encoded respiration. The significance of this is the demonstration of a chronically implantable method for neural recording, a result that will transform the capabilities of future neuroprostheses. [ABSTRACT FROM AUTHOR]

Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %. [ABSTRACT FROM AUTHOR]

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by vascular malformations. The genes known to be associated with HHT include ENG (HHT1), ACVRL1 (HHT2) and SMAD4 (JPHT). It has been reported that circulating CD34 cell subsets repair damaged vessels. To investigate whether mobilization of these cells is present in the peripheral blood (PB) of HTT patients, we analyzed CD34 cells, CD34VEGFR-2 progenitor or mature endothelial cells, and CD34CD133VEGFR-2 hematopoietic progenitor cells (HPCs). Cytofluorimetric analysis was performed in 150 HTT patients and 43 healthy subjects (CTRLs). In HTT patients, PB CD34 cells were significantly increased; the frequency of endothelial cells was higher ( P = 0.002), while the frequency of CD34CD133VEGFR-2 HPCs was lower ( P = 0.00007) than in CTRLs. Results were comparable in patients with ENG or ACVRL1 gene mutation; in patients with ENG mutation, the frequency of the cell subsets inversely correlated with the age of the patients at time of sampling (CD34), disease duration (CD34VEGFR-2), and age at disease onset (CD34CD133 VEGFR-2). In conclusion, HHT patients show an increase of circulating endothelial cells and a decrease of HPCs. In patients with ENG mutation, the frequency of CD34 endothelial cells correlates with specific clinical characteristics suggesting that their active turnover characterizes the initial phase of the disease. [ABSTRACT FROM AUTHOR]

Arteriovenous malformations occur when abnormalities of vascular patterning result in the flow of blood from arteries to veins without an intervening capillary bed. Recent work has revealed the importance of the Notch and TGF-β signaling pathways in vascular patterning. Specifically, Notch signaling has an increasingly apparent role in arterial specification and suppression of branching, whereas TGF-β is implicated in vascular smooth muscle development and remodeling under angiogenic stimuli. These physiologic roles, consequently, have implicated both pathways in the pathogenesis of arteriovenous malformation. In this review, we summarize the studies of endothelial signaling that contribute to arteriovenous malformation and the roles of genes implicated in their pathogenesis. We further discuss how endothelial signaling may contribute to vascular smooth muscle development and how knowledge of signaling pathways may provide us targets for medical therapy in these vascular lesions. [ABSTRACT FROM AUTHOR]

The carpal tunnel syndrome - compression of the median nerve by the transverse ligament of the wrist - is a serious disease of the human hand. The electrophysiological changes in the median nerve can be easily followed by electroneurography (ENG). The degenerative changes in the collagen structures of the carpal ligament cause shrinking of the ligament and compression of the nerve. According to the present study we could demonstrate that DSC is a useful and well applicable method for the investigation of collagen tissue of the human carpal transverse ligament. DSC scans clearly demonstrated significant differences between the different types and conditions of samples (control: Tm=61.3°C and Δ Hcal=4.04 J g−1, mild: Tm=62°C and Δ Hcal=4.3 J g−1, middle: Tm=61.5°C and ΔHcal=5.17 J g−1 as well as severe: Tm=61.85°C and Δ Hcal=8.44 J g−1). After these investigations we can choose the optimal time of surgical therapy of different clinical level carpal tunnel syndrome too. [ABSTRACT FROM AUTHOR]

Using a multi-electrode nerve-signal recording cuff and a method of signal processing described previously, activity in axons with different propagation velocities can be distinguished, and the relative amplitude of the small-fibre signals increased. This paper is, largely, an analysis of the selectivity and noise of this system though impedance measurements from an actual cuff are included. The signal processor includes narrow band-pass filters. It is shown that the selectivity and noise both increase with the centre frequencies of these filters. A convenient approach is to make the filter frequencies inversely related to the artificial time delays so that the filter ‘ Q’s are approximately constant and the noise densities are equal for all velocity filters. Numerical calculations, using formulae for this system and for the conventional tripole, based on a fixed cuff size and tissue resistivity, find the number of action potentials per second that must pass through the cuff so that the signal power equals the noise power. For slow fibres (20 m/s), the rate is 14 times lower for the multi-electrode cuff than the tripole, a significant advantage for recording from these fibres. [ABSTRACT FROM AUTHOR]

A dizzy patient always remains a challenge to an E.N.T. surgeon. History is the key role and may be the only positive clue. An overall neurological assesment with special emphasis on nystagmus should be given. A comprehensive workout has been attempted in this study of vestibular disorders. [ABSTRACT FROM AUTHOR]

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The article presents the author's experience with CCG & ENG in diagnosis brain-stem & cerebellar tumors over a period of one year. [ABSTRACT FROM AUTHOR]

The effect of Ginkgo Biloba Extract (GBE) on normal volunteers and vertiginous patients in two separate, randomised trials is described. The drug was administered orally as well as intravenously. Results were monitored using both electronystagmography and cranio-corpography. An analysis of both groups indicates a beneficial, 'stabilising' effect of the compound on the vestibular system. [ABSTRACT FROM AUTHOR]