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- Shah, Farhan, 1975-
(författare)
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Neuromuscular injuries and pharyngeal dysfunction in snorers and sleep apnea patients : a study on pathological changes in the human soft palate and its relationship with swallowing dysfunction
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Obstructive sleep apnea (OSA) is a prevalent progressive sleep disorder with serious negative health consequences. Although several risk factors such as obesity can make an individual vulnerable to develop OSA, the pathophysiological mechanism for the collapse of the upper airway is unclear. Moreover, the etiology of the commonly occurring swallowing dysfunction in snorers and sleep apnea patients is not understood. In the light of this, we aimed to investigate whether muscle and nerve changes in upper airway contributes to pharyngeal dysfunction in snorers and sleep apnea patients.Twenty-two patients (1 female, 21 males, mean age 45 years) undergoing soft palate surgery because of snoring and sleep apnea were included in the study. Ten healthy non-snoring males, mean age 38 years, were recruited as controls. Biopsies from the uvula were obtained from both patients and voluntary controls. Control autopsies from both uvula and palatopharyngeus muscles were taken post mortem from 6 previously healthy adult subjects (3 males, 3 females, mean age 52 years) and two male infants (age 4 months and 1.4 years). Overnight sleep registration and videoradiographic examinations of pharyngeal swallowing function were performed in both patients and voluntary controls.Enzyme and immunohistochemistry and morphometric techniques were used to investigate cytoskeletal and membrane proteins desmin and dystrophin and two neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). The nerve fascicles in the soft palate were explored for changes in axon and Schwann cell density and for signs of axon regeneration. All patients were snores, and 14 patients had OSA with a mean apnea-hypopnea index 24, range 5-84. Sixteen of the 22 patients had swallowing dysfunction. None of the 10 voluntary controls had sleep apnea or swallowing dysfunction. In both controls and patients, a subgroup of muscle fibers in the soft palate lacked immunoreaction for desmin and the C-terminus of dystrophin, and these fibers were more common in patients than in controls (p<0.001). Moreover, muscle fibers with disorganized desmin were commonly observed in patients, but not in controls (p<0.001). Thus, overall, desmin abnormalities were significantly more frequent in patients (46 vs. 15%, p<0.001), and some of these fibers showed upregulation of BDNF. In addition, nerve fascicles from the soft palate of patients displayed lower density of axons (p<0.02) and a smaller area occupied by Schwann cells (p=0.001) compared to controls. The axon density within nerve fascicles as well as the cytoskeletal abnormalities in muscles correlated significantly with swallowing dysfunction (rs=0.50 and 0.76, respectively, p≤0.03).To conclude, human soft palate muscles seem to be of a unique allotype. In the soft palate of snorers and sleep apnea patients, cytoskeletal myopathy and neuropathy were frequently observed, and these changes correlate significantly with pharyngeal swallowing dysfunction. The upregulation of BDNF in muscle fibers of patients may relate to a regenerative attempt after injury. Consequently, a disturbed sensorimotor function and muscle weakness may contribute to development and progression of swallowing dysfunction and OSA. Traumatic snoring vibrations and muscle overload are plausible causes of the neuromuscular injuries.
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| 2. |
- Spang, Christoph, 1984-
(författare)
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The plantaris tendon in relation to the Achilles tendon in midportion Achilles tendinopathy : studies on morphology, innervation and signalling substances
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Midportion Achilles tendinopathy (tendinosis) is a troublesome painful condition, often characterised by pain, local swelling, tenderness and functional disability. Despite extensive research, the pathogenesis is poorly understood and treatment remains challenging. Features related to the peritendinous connective tissue can be of importance. Recently it has been suggested that the plantaris tendon might be involved in this condition. Furthermore, it has been hypothesised that tendon pain and the tendinosis-related tissue changes in tendinopathy might be mediated by signalling substances such as glutamate and acetylcholine. A clinical observation, not scientifically evaluated, has been that unilateral treatment for bilateral Achilles tendinosis can lead to an effect on the contralateral side. The aim of this work was to examine the morphology and innervation patterns in the plantaris tendon and the peritendinous connective tissue in between the Achillles and plantaris tendons in midportion Achilles tendinopathy, and to evaluate if plantaris tendon removal has an effect on Achilles tendon structure. Another aim was to determine if unilateral treatment for Achilles tendinopathy targeting the peritendinous connective tissue can result in bilateral recovery. Furthermore the presence of non-neuronal cholinergic and glutamate systems was examined. Sections of plantaris tendons with adjacent peritendinous connective tissue from patients with midportion Achilles tendinopathy were stained for morphology (H&E), and innervation patterns were evaluated using antibodies against general nerve marker (PGP9.5), sensory (CGRP) and sympathetic (TH) nerve fibres and Schwann cells (S-100β). Furthermore immunostainings against non-neuronal aceylcholine (ChAT) and glutamate signalling components (glutamate, VGluT2, NMDAR1) were performed. Plantaris tendon cells were cultured and also stained for glutamate signalling components, and were stimulated with glutamate and glutamate receptor agonist NMDA. Furthermore, Ultrasound Tissue Characterisation (UTC) was used to monitor the integrity of the Achilles tendon collagen structure after plantaris tendon removal. Plantaris tendons exhibited tendinosis-like tissue patterns such as hypercellularity, collagen disorganisation and large numbers of blood vessels. The peritendinous connective tissue between the plantaris and Achilles tendons contained large numbers of fibroblasts and blood vessels and to some extent macrophages and mast cells. A marked innervation was found in the peritendinous connective tissue and there were also nerve fibres in the loose connective tissue spaces within the tendon tissue proper. Most nerve fibres were identified as sensory fibres. Some nerve fascicles in the peritendinous connective tissue showed absence of axons but homogenous reactions for Schwann cell marker. Tenocytes and cells in the peritendinous connective tissue expressed ChAT, glutamate, VGluT2 and NMDAR1. Tendon cells in vitro expressed VGluT2, NMDAR1 and glutamate. UTC showed significant improvement of Achilles tendon integrity 6 months after surgical plantaris tendon removal and scraping procedure. Eleven out of thirteen patients reported of a bilateral recovery after unilateral surgical treatment. The results of this work show that plantaris tendons exhibit tendinosis-like tissue changes, internal innervation and features that suggest occurrence of glutamate and acetylcholine production and signalling. Plantaris removal improves Achilles tendon structure suggesting possible compressive/shearing interference between the Achilles and plantaris tendons in tendinopathy. The peritendinous connective tissue shows marked innervation, which thus might transmit pain when being compressed. The partial absence of axons indicates a possible nerve degeneration. On the whole, the study gives new evidence favouring that the plantaris tendon and the peritendinous connective tissue might be of importance for pain and the tendinopathy process in midportion Achilles tendinopathy.
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