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The postmortem diagnosis of drowning death and understanding the mechanisms leading to drowning require a comprehensive judgment based on numerous morphological findings in order to determine the pathogenesis and epidemiological characteristics of the findings. Effortful breathing during the drowning process can result in intramuscular hemorrhage in respiratory and accessory respiratory muscles. However, the characteristics of this phenomenon have not been investigated. We analyzed the epidemiological characteristics of 145 cases diagnosed as drowning, in which hemorrhage, not due to trauma, was found in the respiratory muscles and accessory respiratory muscles. Hemorrhage was observed in 31.7% of these cases, and the incidence did not differ by gender or drowning location. The frequency of hemorrhage was significantly higher in months with a mean temperature below 20°C than in months above 20°C, suggesting a relationship between the occurrence of hemorrhage and low environmental temperature. Moreover, the frequency of hemorrhage was significantly higher in the elderly (aged ≥65 years) compared to those <65 years old. In the elderly, the weakening of muscles due to aging may contribute to the susceptibility for intramuscular hemorrhage. Moreover, these intramuscular hemorrhages do not need to be considered in cases of a potential bleeding tendency due to disease such as cirrhosis or medication such as anticoagulants. Our results indicate that intramuscular hemorrhage in respiratory and accessory respiratory muscles can serve as an additional criterion to differentiate between fatal drowning and other causes of death, as long as no cutaneous or subcutaneous hematomas above the muscles with hemorrhages are observed. In addition, the epidemiological features that such intramuscular hemorrhage is more common in cold environments and in the elderly may provide useful information for the differentiation., Competing Interests: All authors declare no conflict of interest related to this study.

Background: Few studies have examined respiratory dysfunction in patients with Becker muscular dystrophy (BMD)., Objective: This study aimed to examine the characteristics of respiratory dysfunction in patients with BMD., Methods: The present retrospective study assessed respiratory parameters of adult BMD patients using medical records and compared these parameters with various patient characteristics to identify correlations. BMD patients aged 17 years and older who had been diagnosed genetically and/or pathologically were included in the analysis., Results: Of the source population of 133 patients, respiratory function was assessed in 85. Two of these patients had no symptoms, and eight had died. Mean % forced vital capacity (% FVC) was 94.2+/-21.7% (median, 96.1%; range, 5.1-134.1%). In 16 (19%) of the 85 patients, % FVC was <80%. Of these, seven were non-ambulant. Age, ambulation, and cardiac function did not significantly differ between patients with or without respiratory dysfunction, whereas age at onset was significantly lower in patients with respiratory dysfunction (7.7+/-4.7 years vs. 14.4+/-11.9 years; p = 0.001). One non-ambulant patient was a continuous NPPV user, and one patient had been recommended NPPV use but refused. Autopsy of one patient revealed that the diaphragm and intercostal muscles were less affected than proximal skeletal muscles., Conclusion: BMD patients are at risk of developing respiratory dysfunction due to dystrophic changes in respiratory muscles. Respiratory function should be carefully and periodically monitored in these patients.

Acquired abdominal intercostal hernia (AAIH) is an infrequent occurrence whereby intra-abdominal contents herniate into intercostal space directly from the peritoneal cavity through an acquired defect in the abdominal wall musculature and fascia. These hernias are difficult to diagnose and should always be suspected when a chest wall swelling occur after major or minor trauma. Surgical repair is warranted in symptomatic patients. The majority of AAIHs are repaired through an open approach using tension-free mesh, with significant recurrence risk. Recently, laparoscopic and robot-assisted repairs have been proposed. We discuss a 49-year-old man presented through outpatient setting with a 5-year history of ongoing left subcostal discomfort and a reducible lump. His history included a workplace accident 5 years ago. Contrast-enhanced abdominal CT confirmed AAIH with omentum herniation into the sac. A successful laparoscopic repair with intraperitoneal onlay mesh technique using composite mesh was performed., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Limb muscle wasting is one of main systemic manifestation of chronic obstructive pulmonary disease (COPD). However, the change of respiratory muscle is unclear., Objectives: This study assessed the cross-sectional area (CSA) of the intercostal muscles (ICMs) in patients with COPD, using chest computed tomography (CT) and determined its association with the clinical characteristics of COPD., Methods: They retrospectively reviewed 60 patients with stable COPD and compared them with 30 controls. CSA (mm 2 ) of the ICM on chest CT was measured at the midline level of the lateral arch of the bilateral first rib with a 3-mm slice thickness by using CT histogram software. The association with the clinical characteristics of COPD and with the control groups was assessed., Results: CSA of the ICM and the CSA/body mass index (BMI) were lower in the COPD group than in the control group. Patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 4 had a significantly lower CSA of the ICM than patients with stage 1, 2, and 3. CSA of the ICM was positively associated with FEV 1 , %FEV 1 predicted, FEV 1 /FVC ratio, and BMI and negatively associated with age. However, there were no associations with PaO 2 , PaCO 2 , smoking status, 6-minute walk test, frequency of acute exacerbation of COPD, and serum C-reactive protein level., Conclusion: Intercostal muscle atrophy occurs in COPD patients and is associated with severity of airway obstruction, BMI, and increasing age., (© 2017 John Wiley & Sons Ltd.)

Background: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease with no available therapy. Components of the innate immune system are activated in the spinal cord and central nervous system of ALS patients. Studies in the SOD1(G93A) mouse show deposition of C1q and C3/C3b at the motor end-plate before neurological symptoms are apparent, suggesting that complement activation precedes neurodegeneration in this model. To obtain a better understanding of the role of complement at the motor end-plates in human ALS pathology, we analyzed post-mortem tissue of ALS donors for complement activation and its regulators., Methods: Post-mortem intercostal muscle biopsies were collected at autopsy from ALS (n = 11) and control (n = 6) donors. The samples were analyzed for C1q, membrane attack complex (MAC), CD55, and CD59 on the motor end-plates, using immunofluorescence or immunohistochemistry., Results: Here, we show that complement activation products and regulators are deposited on the motor end-plates of ALS patients. C1q co-localized with neurofilament in the intercostal muscle of ALS donors and was absent in controls (P = 0.001). In addition, C1q was found deposited on the motor end-plates in the intercostal muscle. MAC was also found deposited on motor end-plates that were innervated by nerves in the intercostal muscle of ALS donors but not in controls (P = 0.001). High levels of the regulators CD55 and CD59 were detected at the motor end-plates of ALS donors but not in controls, suggesting an attempt to counteract complement activation and prevent MAC deposition on the end-plates before they are lost., Conclusions: This study provides evidence that complement activation products are deposited on innervated motor end-plates in the intercostal muscle of ALS donors, indicating that complement activation may precede end-plate denervation in human ALS. This study adds to the understanding of ALS pathology in man and identifies complement as a potential modifier of the disease process.

Congenital myasthenic syndromes (CMSs) are a group of rare genetic disorders of the neuromuscular junction resulting in structural or functional causes of fatigable weakness that usually begins early in life. Mutations in pre-synaptic, synaptic and post-synaptic proteins have been demonstrated in human cases, with more than half involving aberrations in nicotinic acetylcholine receptor (AChR) subunits. CMS was first recognized in dogs in 1974 as an autosomal recessive trait in Jack Russell Terriers (JRTs). A deficiency of junctional AChRs was demonstrated. Here we characterize a CMS in 2 contemporary cases of JRT littermates with classic clinical and electromyographic findings, and immunochemical confirmation of an approximately 90% reduction in AChR protein content. Loci encoding the 5 AChR subunits were evaluated using microsatellite markers, and CHRNB1 and CHRNE were identified as candidate genes. Sequences of the splice sites and exons of both genes revealed a single base insertion in exon 7 of CHRNE that predicts a frameshift mutation and a premature stop codon. We further demonstrated this pathogenic mutation in CHRNE in archival tissues from unrelated JRTs studied 34 years ago., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A polymer based material was developed to act as an embolic agent and drug reservoir for the treatment of arteriovenous malformations (AVM) and hyper vascularized solid tumors. The aim was to combine the blocking of blood supply to the target region and the inhibition of the embolization-stimulated angiogenesis. The material is composed of an ethanolic solution of a linear acrylate based copolymer and acrylate calibrated microparticles containing nanospheres loaded with sunitinib, an anti-angiogenic agent. The precipitation of the linear copolymer in aqueous environment after injection through microcatheter results in the formation of an in-situ embolization gel whereas the microparticles serve to increase the cohesive properties of the embolization agent and to form a reservoir from which the sunitinib-loaded nanospheres are released post-embolization. The swollen state of the microparticles in contact with aqueous medium results in the release of the nanospheres out of microparticles macromolecular structure. After the synthesis, the formulation and the characterization of the different components of the material, anti-angiogenic activity was evaluated in vitro using endothelial cells and in vivo using corneal neovascularization model in rabbit. The efficiency of the arterial embolization was tested in vivo in a sheep model. Results proved the feasibility of this new system for vascular embolization in association with an in situ delivery of anti-angiogenic drug. This combination is a promising strategy for the management of arteriovenous malformations and solid tumors., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Rationale and Objectives: Chronic obstructive pulmonary disease (COPD) is characterized by progressive respiratory function impairment and respiratory muscle dysfunction. We hypothesized that the mass and fat infiltration of respiratory muscles correlates with COPD severity and emphysema extent., Materials and Methods: Ninety-eight male patients with COPD underwent chest computed tomography (CT) and spirometry. The mass and fat infiltrations of intercostal and latissimus muscles were quantified as the cross-sectional area (CSA) and attenuation of these muscles using CT histogram analysis. Intercostal index and latissimus index were defined as intercostal CSAs and latissimus CSAs divided by body mass index. The emphysema extent was measured as the ratio of the emphysematous lung volume to the total lung volume using a density-mask technique. Pearson correlation analyses were performed to evaluate the relationships between these parameters. Multiple regression analysis was performed using forced expiratory volume in 1 second (FEV1) as the dependent parameter and the clinical and CT data as the independent parameters., Results: FEV1 was significantly correlated with intercostal index (r = 0.57), latissimus index (r = 0.34), intercostal attenuation (r = 0.62), and latissimus attenuation (r = 0.38). Emphysema extent was significantly correlated with intercostal index (r = -0.36) and intercostal attenuation (r = -0.50). Multiple regression analysis showed that FEV1 was predicted by intercostal attenuation (B = 0.40), intercostal CSA (B = 0.23), emphysema extent (B = -0.23), and age (B = -0.21, R(2) = 0.64, P < .001)., Conclusions: A decrease in intercostal mass and an increase in intercostal fat are associated with worsening of COPD severity., (Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.)

Intramuscular myxomas are benign soft-tissue tumors that often develop in the thigh. A 66-year-old woman was referred with an abnormal shadow on chest roentgenogram. The tumor was well defined and smooth and originated from the second intercostal space. Positron emission tomography showed no accumulation of 18F-fluorodeoxyglucose in the tumor. The patient attended the outpatient department for follow-up care. Because the mass grew slightly after 52 months, the patient underwent complete removal by video-assisted thoracoscopic surgery. On histopathological examination, the tumor was diagnosed as an intramuscular myxoma in the chest wall. The patient has had no recurrence 3 years after surgery. A case of intramuscular myxoma in the chest wall, completely resected by video-assisted thoracoscopic surgery, is reported. A well-defined, smooth, homogeneous mass in the chest wall may therefore be intramuscular myxoma.

Dogs homozygous for missense mutations in the SOD1 gene develop a late-onset neuromuscular disorder called degenerative myelopathy (DM) that has many similarities to amyotrophic lateral sclerosis (ALS). Both disorders are characterized by widespread progressive declines in motor functions, accompanied by atrophic changes in the descending spinal cord tracts. Some forms of ALS are also associated with SOD1 mutations. In end-stage ALS, death usually occurs as a result of respiratory failure from severe functional impairment of respiratory muscles. The mechanisms that lead to this loss of function are not known. Dogs with DM are euthanized at all stages of disease progression, providing an opportunity to characterize the onset and progression of any pathological changes in the respiratory muscles that may precede respiratory failure. To characterize such potential disease-related pathology, we evaluated intercostal muscles from Boxer and Pembroke Welsh Corgi dogs that were euthanized at various stages of DM disease progression. DM was found to result in intercostal muscle atrophy, fibrosis, increased variability in muscle fiber size and shape, and alteration in muscle fiber type composition. This pathology was not accompanied by retraction of the motor neuron terminals from the muscle acetylcholine receptor complexes, suggesting that the muscle atrophy did not result from physical denervation. These findings provide a better understanding of the mechanisms that likely lead to respiratory failure in at least some forms of ALS and will be useful in the development and evaluation of potential therapeutic interventions using the DM model., (Copyright © 2013 Wiley Periodicals, Inc.)

Background and Objective: Oxidative stress and inflammation contribute to the diaphragm contractile dysfunction observed in animal models of sepsis and endotoxemia. In septic patients, molecular events have never been explored in their respiratory muscles. Levels of oxidative stress and inflammation were evaluated in a respiratory muscle, the external intercostal, and a limb muscle, the vastus lateralis, of patients with sepsis., Patients and Methods: Levels of oxidized and nitrated proteins, protein adducts of malondialdehyde and hydroxinonenal, antioxidant enzymes catalase and Mn-superoxide dismutase, tumor necrosis factor (TNF)-α, TNF-α receptors i and ii, interleukin (IL)-1 and IL-6, the panleukocyte marker CD18, and fiber type composition were explored using immunoblotting, real time-polymerase chain reaction, and immunohistochemistry in the external intercostal and vastus lateralis of patients with severe sepsis and/or septic shock., Results: Compared to the controls, in septic patients, levels of oxidized and nitrated proteins were increased in the vastus lateralis, but not in the external intercostal, while those of the antioxidant enzymes did not differ, and the proportions and sizes of the muscle fibers were not significantly different in any muscle between patients and controls., Conclusions: Differences in activity between the respiratory and limb muscles may account for the differential pattern of oxidative stress and inflammation observed among patients with severe sepsis. These findings may have relevant implications for the clinical and therapeutic management of these patients., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)

A tumor shadow was identified in the chest X-ray of a 40-year-old Korean man and he was referred to our hospital. The computed tomographic (CT) scan of his chest showed a 3-cm rounded pleural-based mass lesion with calcification, which was growing into the intercostal muscles. Thoracoscopic surgery was performed to resect the tumor. From the histological findings, the tumor was diagnosed as an intramuscular lipoma. The patient displayed no evidence of recurrence for more than 18 months. As well-circumscribed type of intramuscular lipoma is a rare tumor, we report this case with a literature review in this paper.

Aging is associated with loss of skeletal muscle mass, strength and endurance. The aim of this study was to determinate age related changes in human muscles with different function and location in the body (vastus lateralis muscle and intercostal internus muscle). Our results suggest that age related muscle atrophy affect both human skeletal muscles. Also, the results showed the increase in percentage of muscle fibers with high oxidative activity during aging.

We report a case of an 11-year-old girl who presented with a slowly enlarging mass in the right posterolateral chest wall. Computed tomography showed a soft-tissue mass 8.5 × 7.5 × 5.5 cm in size, arising from the right posterolateral 9th, 10th, and 11th intercostal spaces. Magnetic resonance imaging confirmed a vascular mass. The patient underwent complete resection of the tumor, together with the right 8th, 9th, 10th, 11th, and 12th ribs and their intercostal muscles. Reconstruction of the chest wall was performed with methyl methacrylate and Marlex mesh. Histopathologic examination of the tumor confirmed an intercostal cavernous hemangioma. At last examination, 6 months after the operation, the child was doing well, with no evidence of recurrence.

We report a case of desmoid tumor of the chest wall in a 79-year-old woman. The patient was referred to our hospital for management of a chest wall mass. Four months previously, the patient noted a small lump in the right lateral chest wall that had rapidly increased in size. Magnetic resonance imaging of the chest revealed a soft tissue tumor in the right lateral chest wall with unclear margins that extended into the intercostal muscles. Positron emission tomography with (18)F-fluorodeoxyglucose (FDG) showed slight FDG accumulation at the lesion. Because open biopsy suggested a desmoid tumor, full-thickness chest wall resection with reconstruction was performed. The final diagnosis was desmoid tumor of the chest wall. Wide surgical resection during the initial operation is an essential element in the treatment of this tumor.

Objective: There is disagreement regarding the local action of cytokines in the respiratory muscles of patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to analyze the relationships between cytokine expression and genetic activation of the mechanisms of muscle repair., Patients and Methods: Twenty-five patients with severe COPD and in stable condition were enrolled in the study. We performed a biopsy of the external intercostal muscle of the patients and analyzed the specimen for signs of muscle lesion (morphometry), infiltration of inflammatory cells (immunohistochemistry), and expression of selected genes (real-time polymerase chain reaction technique) corresponding to the cytokines (tumor necrosis factor alpha [TNF-alpha] and its type 1 and 2 receptors [TNFR1 and TNFR2], and interleukin [IL] 1beta, IL-6, and IL-10), a pan-leukocyte marker (CD18), and key molecules in the repair-myogenesis pathways (Pax7, M-cadherin, and MyoD)., Results: Expression of TNFR2 is directly related to inspiratory muscle function (represented by maximum sustainable inspiratory pressure; r=0.496; P<.05), whereas expression of CD18 is inversely related (r=0.462; P<.05). Moreover, expression of the 2 TNF-alpha receptors was directly related to that of the key molecules of the repair pathways analyzed (TNFR1 to Pax7 [r=0.650; P<.001] and M-cadherin [r=0.678; P<.001]; TNFR2 to Pax7 [r=0.395; P<.05], M-cadherin [r=0.409; P<.05], and MyoD [r=0.418; P<.05])., Conclusions: Expression of TNF-alpha receptors bears a close relationship both to activation of the myogenesis programs and to inspiratory muscle function. This reinforces our hypothesis that some local cytokines take part in the repair of respiratory muscles in patients with COPD.

Chest wall tumors are uncommon, but intercostal hemangioma is even more so: There have been only a handful of reports on it to date. We report on a 32-year-old man with a left-side chest wall mass detected on a chest roentgenogram and computed tomography scans. The tumor was completely resected by means of video-assisted thoracic surgery. Two years after the surgery, the patient is doing well with no evidence of recurrence.

Soft tissues' infections involve fascia and musculature which permit to define different anatomic entities as necrotizing fasciitis or myositis. We describe here the case of an infectious myositis whose initial clinical approach did not allow to get the right diagnosis. The tomodensitometry showed typical lesions which induced an accurate management, but could not avoid the death of the patient because of major wounds and a poor general background.

Objective: The respiratory muscles of patients with chronic obstructive pulmonary disease (COPD) display evidence of structural damage in parallel with signs of adaptation. We hypothesized that this can only be explained by the simultaneous activation of satellite cells. The aim of this study was to analyze the number and activation of those cells along with the expression of markers of microstructural damage that are frequently associated with regeneration., Patients and Methods: The study included 8 patients with severe COPD (mean [SD] forced expiratory volume in 1 second, 33% [9%] of predicted) and 7 control subjects in whom biopsies were performed of the external intercostal muscle. The samples were analyzed by light microscopy to assess muscle fiber phenotype, electron microscopy to identify satellite cells, and real-time polymerase chain reaction to analyze the expression of the following markers: insulin-like growth factor 1, mechano growth factor, and embryonic and perinatal myosin heavy chains (MHC) as markers of microstructural damage; Pax-7 and m-cadherin as markers of the presence and activation of satellite cells, respectively; and MHC-I, IIa, and IIx as determinants of muscle fiber phenotype., Results: The patients had larger fibers than healthy subjects (54 [6] vs 42 [4] microm(2); P< .01) with a similar or slightly increased proportion of satellite cells, as measured by ultrastructural analysis (4.3% [1%] vs 3.7% [3.5%]; P>.05) or expression of Pax-7 (5.5 [4.1] vs 1.6 [0.8] arbitrary units [AU]; P< .05). In addition, there was greater activation of satellite cells in the patients, as indicated by increased expression of m-cadherin (3.8 [2.1] vs 1.0 [1.2] AU; P=.05). This was associated with increased expression of markers of microstructural damage: insulin-like growth factor 1, 0.35 (0.34) vs 0.09 (0.08) AU (P< .05); mechano growth factor, 0.45 (0.55) vs 0.13 (0.17) AU (P=.05)., Conclusions: The intercostal muscles of patients with severe COPD show indirect signs of microstructural damage accompanied by satellite cell activation. This suggests the presence of ongoing cycles of lesion and repair that could partially explain the maintenance of the structural properties of the muscle.

This study aimed at describing the epidemiology, clinical features and prognosis of post-circumcision tetanus at the infectious diseases clinic in Fann Hospital in Dakar. Data were collected retrospectively for analysis from patients' files recorded from January 1, 1999 to December 31, 2006. 54 cases were included, accounting for 4% of all tetanus cases admitted to the clinic during the study period (54 cases/1291). The patients' average age was 9 +/- 3.7 years old (range = 1-17 years) and 52% of them were schoolboys. In most cases (76%), tetanus symptoms occurred beyond 7 days after circumcision. The average delay from onset of the disease to admission was 2.3 days (range = 0-6 days). The circumcision took place at home in 39% of cases, in health center in 35% of cases and in unspecified area in 26% of cases. The majority of patients (85%) had never received tetanus vaccine and, in 72% of the cases, the circumciser was designated as a male nurse. Generalized tetanus was observed in all cases, most of which was a mild form of the disease (63%). During hospitalisation, thirteen patients (24%) had complications among which diaphragmatic and intercostal muscle spasms (3 cases), bacteraemia (5 cases), respiratory infection (4 cases), urinary tract infection (4 cases), and fracture of the vertebrae (1 case). The case fatality rate was 7.4% (4 deaths). Vaccination together with health education of the population as well as a better sensitization of the practitioners are necessary to eradicate tetanus after circumcision.

Objectives: The present study was undertaken to investigate the significance of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake in the intercostal muscles (ICM) and prominent visualization of right ventricle (RV) in FDG-positron emission tomography (PET) scans and its implications., Methods: Patients identified to have FDG uptake in the ICM with or without prominent visualization of the RV either incidentally or in the background of an existing explanatory cause at the time of FDG-PET studies were included in this retrospective study. These patients had undergone FDG-PET either for ruling out malignancy or for disease monitoring purposes in setting a proven malignancy. We reviewed the clinical and investigational records (including computed tomography [CT] thorax, chest X-ray, 2-D echo and pulmonary function tests, and arterial blood gas analysis) of the group with incidental FDG uptake for revelation of a pathology explaining such uptake., Results: A total of 14 cases with 16 FDG-PET studies were identified from the retrospective examination of case records. One patient had three FDG-PET at different time points of his disease course. The patient population included 13 males and one female with age range 46-88 years. The patients were classified into two groups: (1) cases with isolated ICM uptake (n=10); (2) cases with both ICM and RV uptake (n=4). Among 10 patients with isolated ICM uptake, in six patients it was a serendipitous observation, whereas four patients had existing explanatory cause at the time of FDG-PET. The causes found to be associated included COPD, asthma, recent heart failure, interstitial lung disease (post external radiotherapy) and pulmonary embolism, atelectasis with pleural effusion. In all four cases with associated RV uptake, there was evidence of pulmonary hypertension (PH). Among these, in one patient this was a serendipitous observation. He had evidence of interstitial lung disease (ILD) in CT thorax, and 2-D echo showed moderate PH. The remaining three patients had cor pulmonale secondary to COPD, pneumoconiosis, and Swyer James Syndrome with associated severe PH. The SUVmax ratio of the RV-to-LV free wall ranged from 0.53 to 1.04 in the cases with prominent RV uptake. One patient had multiple FDG-PET studies and have shown reduction of RV uptake in the last scan consistent with the clinical impression of improvement of cor pulmonale., Conclusion: Both intercostal muscle and prominent RV uptake in FDG-PET can be associated with a spectrum of causes (including both obstructive and restrictive airway diseases) that lead to breathing exertion. These are important markers, which could signify underlying pulmonary disease and pulmonary hypertension, respectively. Associated prominent RV uptake strongly indicates presence of pulmonary hypertension and the uptake in the right heart can subserve a valuable surrogate marker in the treatment-monitoring scenario of a known PH.

Objective: Vascular abnormalities associated with neurofibromatosis Type 1 (NF-1) are well known, but arteriovenous fistulae (AVF) are rare and usually involve vertebral AVF. A case of intercostal AVF associated with NF-1 and manifesting as congestive myelopathy is described., Clinical Presentation: A 62-year-old woman with a medical history of NF-1 experienced gradually worsening gait disturbance. Neurological examination at the time of admission found spastic paraparesis, decrease of sensation in the bilateral lower extremities, and vesicorectal disturbance. Magnetic resonance imaging scans revealed flow void sign and a congestive lesion of the thoracolumbar spinal cord, as well as a huge mass in the paravertebral region at T10-T12. Spinal angiography revealed an intercostal AVF with a large paravertebral varix, which drained to the spinal medullary vein and caused dilation of the intradural venous plexus of the spinal cord resulting in congestive myelopathy., Intervention: Direct surgery was selected for the occlusion of the draining point of the medullary vein, located in the entry of the dura. The patient underwent hemilaminectomy at T10-T12, and the dural entry of the draining vein was occluded. Postoperative angiography revealed no dilated venous plexus of the spinal cord and reduced paravertebral varix. The symptoms were gradually relieved after the surgery., Conclusion: The present case of a very rare intercostal AVF with an unusual manifestation of congestive myelopathy occurred in a relatively rare association with NF-1. Accurate evaluation of the vascular anomaly allowed selection of the appropriate surgical method.

Previous studies have shown a blunted ventilatory response to hypercapnia in mdx mice older than 7 months. We test the hypothesis that in the mdx mice ventilatory response changes with age, concomitantly with the increased functional impairment of the respiratory muscles. We thus studied the ventilatory response to CO(2) in 5 and 16 month-old mdx and C57BL10 mice (n = 8 for each group). Respiratory rate (RR), tidal volume (VT), and minute ventilation (VE) were measured, using whole-body plethysmography, during air breathing and in response to hypercapnia (3, 5 and 8% CO(2)). The ventilatory protocol was completed by histological analysis of the diaphragm and intercostals muscles. During air breathing, the 16 month-old mdx mice showed higher RR and, during hypercapnia (at 8% CO(2) breathing), significantly lower RR (226 +/- 26 vs. 270 +/- 21 breaths/min) and VE (1.81 +/- 0.35 vs. 3.96 +/- 0.59 ml min(-1) g(-1)) (P < 0.001) in comparison to C57BL10 controls. On the other hand, 5 month-old C57BL10 and mdx mice did not present any difference in their ventilatory response to air breathing and to hypercapnia. In conclusion, this study shows similar ventilation during air breathing and in response to hypercapnia in the 5 month-old mdx and control mice, in spite of significant pathological structural changes in the respiratory muscles of the mdx mice. However in the 16 month-old mdx mice we observed altered ventilation under air and blunted ventilation response to hypercapnia compared to age-matched control mice. Ventilatory response to hypercapnia thus changes with age in mdx mice, in line with the increased histological damage of their respiratory muscles.

Critically ill patients treated for multiple organ failure often develop muscle dysfunction. Here we test the hypothesis that mitochondrial and energy metabolism are deranged in leg and intercostal muscle of critically ill patients with sepsis-induced multiple organ failure. Ten critically ill patients suffering from sepsis-induced multiple organ failure and requiring mechanical ventilation were included in the study. A group (n = 10) of metabolically healthy age- and sex-matched patients undergoing elective surgery were used as controls. Muscle biopsies were obtained from the vastus lateralis (leg) and intercostal muscle. The activities of citrate synthase and mitochondrial respiratory chain complexes I and IV and concentrations of ATP, creatine phosphate, and lactate were analyzed. Morphological evaluation of mitochondria was performed by electron microscopy. Activities of citrate synthase and complex I were 53 and 60% lower, respectively, in intercostal muscle of the patients but not in leg muscle compared with controls. The activity of complex IV was 30% lower in leg muscle but not in intercostal muscle. Concentrations of ATP and creatine phosphate were, respectively, 40 and 34% lower, and lactate concentrations were 43% higher in leg muscle but not in intercostal muscle. We conclude that both leg and intercostal muscle show a twofold decrease in mitochondrial content in intensive care unit patients with multiple organ failure, which is associated with lower concentrations of energy-rich phosphates and an increased anaerobic energy production in leg muscle but not in intercostal muscle.

Studies in experimental animals indicate that chronic increases in neural drive to limb muscles elicit a fast-to-slow transformation of fiber-type proportions and myofibrillar proteins. Since neural drive to the parasternal intercostal muscles (parasternals) is chronically increased in patients with severe chronic obstructive pulmonary diseases (COPDs), we carried out the present study to test the hypothesis that the parasternals of COPD patients exhibit an increase in the proportions of both slow fibers and slow myosin heavy chains (MHCs). Accordingly, we obtained full thickness parasternal muscle biopsies from the third interspace of seven COPD patients (mean +/- SE age: 59 +/- 4 yr) and seven age-matched controls (AMCs). Fiber typing was done by immunohistochemistry, and MHC proportions were determined by SDS-PAGE followed by densitometry. COPD patients exhibited higher proportions of slow fibers than AMCs (73 +/- 4 vs. 51 +/- 3%; P < 0.01). Additionally, COPD patients exhibited higher proportions of slow MHC than AMCs (56 +/- 4 vs. 46 +/- 4%, P < 0.04). We conclude that the parasternal muscles of patients with severe COPD exhibit a fast-to-slow transformation in both fiber-type and MHC proportions. Previous workers have demonstrated that remodeling of the external intercostals, another rib cage inspiratory muscle, elicited by severe COPD is characterized by a slow-to-fast transformation in both fiber types and MHC isoform proportions. The physiological significance of this difference in remodeling between these two inspiratory rib cage muscles remains to be elucidated.

The imaging features of 16 cases of pathologically proven atypical thoracic Castleman disease (CD) were retrospectively reviewed. Thirteen out of 16 tumors originated from atypical locations, including eight from the pleura and one each from the axilla, supraclavicular fossa, intercostal space, pericardium, and lung. Six out of 16 tumors revealed atypical enhancement, including poor CT enhancement in three tumors, target-like CT enhancement in two tumors, and concentric MR enhancement pattern in one tumor. These atypical enhancement patterns were histopathologically corresponded to various degrees of degeneration, necrosis, and fibrosis.

Myogenic regulatory factors (MRFs), muscle-specific transcription factors, are implicated in the activity-dependent regulation of nicotinic acetylcholine receptor (AChR) subunit genes. Here we show, with immunohistochemistry, Western blotting, and electron microscopy that MyoD, a member of the MRF family, also plays a role in fetal synapse formation. In the diaphragm of 14.5 d gestation (E14.5) wild-type and MyoD-/- mice, AChR clusters (the formation of which is under a muscle intrinsic program) are confined to a centrally located endplate zone. This distribution persists in wild-type adult muscles. However, beginning at E15.5 and extending to the adult, innervated AChR clusters are distributed all over the diaphragm of MyoD-/- mice, extending as far as the insertion of the diaphragm into the ribs. In wild-type muscle, motor axons terminate on clusters adjacent to the main intramuscular nerve; in MyoD-/- muscle, axonal bundles form extensive secondary branches that terminate on the widely distributed clusters. The number of AChR clusters on adult MyoD-/- and wild-type diaphram muscles is similar. Junctional fold density is reduced at MyoD-/- endplates, and the transition from the fetal (alpha, beta, gamma, delta) to adult-type (alpha, beta, delta, epsilon) AChRs is markedly delayed. However, MyoD-/- mice assemble a complex postsynaptic apparatus that includes muscle-specific kinase (MuSK), rapsyn, erbB, and utrophin.

The present study was aimed at evaluating the effects of a specific inspiratory muscle training protocol on the structure of inspiratory muscles in patients with chronic obstructive pulmonary disease. Fourteen patients (males, FEV1, 24 +/- 7% predicted) were randomized to either inspiratory muscle or sham training groups. Supervised breathing using a threshold inspiratory device was performed 30 minutes per day, five times a week, for 5 consecutive weeks. The inspiratory training group was subjected to inspiratory loading equivalent to 40 to 50% of their maximal inspiratory pressure. Biopsies from external intercostal muscles and vastus lateralis (control muscle) were taken before and after the training period. Muscle samples were processed for morphometric analyses using monoclonal antibodies against myosin heavy chain isoforms I and II. Increases in both the strength and endurance of the inspiratory muscles were observed in the inspiratory training group. This improvement was associated with increases in the proportion of type I fibers (by approximately 38%, p < 0.05) and in the size of type II fibers (by approximately 21%, p < 0.05) in the external intercostal muscles. No changes were observed in the control muscle. The study demonstrates that inspiratory training induces a specific functional improvement of the inspiratory muscles and adaptive changes in the structure of external intercostal muscles.

Chemokines are involved in a number of pathophysiological conditions, such as inflammatory processes and are divided in two major subfamilies, C-X-C and C-C chemokines. The C-C chemokines are monocyte chemotactic protein 1-2-3-4-5, while C-X-C chemokines include MIP-2, IL-8, etc. We studied the levels of MCP-1 and MIP-2 in diaphragmatic and intercostal muscle tissue and serum in Trichinella spiralis infected mice treated and not treated with 4-deoxypyridoxine, a potent Vit. B6 antagonist which inhibits humoral and cellular immune response. MCP-1 and MIP-2 were measured in homogenized tissue and serum and determined by a specific ELISA. Here we found the levels of MCP-1 and MIP-2 in diaphragmatic and intercostal muscle tissue of T. spiralis infected mice were significantly increased after 10 days and peaked on day 20 post-infection; however, the levels of MIP-2 in mice treated with 4-DPD was lower than that of untreated mice at day 20. MCP-1 also peaked at days 20 and 40. Animals treated with 4-DPD also inhibited the production of MCP-1, compared with untreated animals. The maximum inhibition was at day 40. These inhibitory effects on MIP-2 and MCP-1 were also repeated in the serum determinations, but were not significant. This study demonstrates that MIP-2 and MCP-1 are stimulated in serum and tissue of T. spiralis infected mice and 4-DPD-treated animals significantly inhibited them.

Purpose: The purpose of this work is to describe the CT and MR appearance of primary malignant fibrous histiocytoma (MFH) of the chest wall., Method: Eleven men and eight women (45-76 years old) with primary MFH of the chest wall who underwent both CT and MRI were enrolled, and the imaging interpretation was retrospectively compared to the pathologic specimen., Results: All tumors were inhomogeneous in appearance on CT scans. All tumors showed high signal intensity on T2-weighted images. On T1-weighted MR images, tumors displayed inhomogeneous isosignal intensity in 15 cases (79%) and low signal intensity in 5 (21%) compared with the surrounding muscle. Tumors exhibited inhomogeneous enhancement in all except three localized tumors on enhanced CT and MRI. Invasion of intercostal muscle was noted on MR images in 18 patients (95%) and on CT in 11 patients (58%)., Conclusion: There might be various radiologic appearances of MFH. However, CT and MRI are able to demonstrate the exact localization and disease extent of MFH arising in the chest wall.

Introduction: The external intercostal muscle is a relevant contributor to ventilatory work in situations of overloading. Like other respiratory muscles, the external intercostal muscle seems to undergo a process of structural remodeling to adapt to a situation of functional disadvantage. However, findings from published studies of morphology have differed to a certain degree. On the one hand, the proportion of fibers involved in anaerobic metabolism increases; on the other hand, the number of capillaries also increases, an occurrence that would facilitate aerobic metabolism., Objective: This study was designed to analyze the activity of several key enzymes involved in the principal metabolic pathways in the external intercostal muscles of patients with COPD., Methodology: We studied 6 patients with COPD (65 +/- 8 years, BMI 23 +/- 3 kg/m2, FEV1 51 +/- 9% ref, RV 184 +/- 38% ref, PaO2 81 +/- 10 mmHg) and 6 control subjects matched for age and anthropometric variables but with normal lung function. External intercostal muscle samples were taken from each patient (fifth intercostal space, non-dominant side). The samples were treated by conventional spectrophotometry to determine enzyme activity as follows: citrate synthase (CS, Krebs cycle), phosphofructokinase (PFK, by common glycolysis), lactate dehydrogenase (LDH, anaerobic glycolysis) and creatine phosphokinase (CPK, use of energy reserves)., Results: Patients with COPD showed greater PFK enzyme activity (93 +/- 25 versus 44 +/- 9 micromol/min/g of fresh weight; p = 0.001) and LDH (308 +/- 42 versus 231 +/- 29 micromol/min/g; p < 0.01) than did control subjects. However, CS and CPK activity was similar in both groups (82 +/- 31 versus 90 +/- 20 micromol/min/g and 4017 +/- 1734 versus 3048 +/- 464 micromol/min/g, respectively), although the latter displayed noteworthy dispersion of values among COPD patients, with levels in some patients being three-fold greater than in controls. RV was directly related to glycolytic enzyme activity (with PFK, r = 0.716, p < 0.01; with LDH r = 0.697, p < 0.05) and PFK and LDH also correlated with each other (r = 0.737, p < 0.01)., Conclusions: Based on the enzyme activity studied, oxidative activity seems to be conserved in the external intercostal muscle of patients with COPD. Activity in the glycolytic pathway seems to increase and the increase is proportional to the severity of COPD. These findings are probably the expression of a combination of adaptive structural factors.

A 29-year-old woman who underwent evaluation for a 3-month history of left-sided back pain proved to have a left pleural tumor accompanied by a bloody pleural effusion (cytological class II). Three years previously, a chest roentgenogram had been normal. The tumor originated from the parietal pleura at the level of the first three intercostal muscles and was excised completely in continuity with these muscles, including a margin of normal muscle. The tumor measured 15x12 cm and the pathologic diagnosis was benign solitary fibrous tumor; while the tumor invaded the intercostal muscles, no histologically malignant features were present. Long-term follow-up is planned because a possibility of local recurrence exists.

A 57-year-old woman suffered from generalized muscular weakness without diplopia or dysphagia for about 2 years. An abnormal decremental response on low frequency nerve stimulation and improvement upon administration of edrophonium chloride suggested a diagnosis of myasthenia gravis. However, this diagnosis remained uncertain, since repeated tests for antiacetylcholine receptor antibodies were negative. In addition, the patient reported that she was never able to keep up with peers in prolonged physical activities since childhood. For this reason, a congenital myasthenic syndrome was suspected and an intercostal muscle biopsy performed for special end-plate studies. Immunohistochemistry of the muscle biopsy revealed membrane attack complex deposits at the end-plates. This finding definitely confirmed the diagnosis of autoimmune myasthenia gravis. In conclusion, immunohistochemistry for complement deposits at the end-plates is a simple and reliable method of confirming the diagnosis of myasthenia gravis in uncertain cases.

We report a case of herniation of abdominal contents into the left hemithorax in a patient hospitalized with an acute exacerbation of asthma accompanied by paroxysms of coughing. There was no history of trauma. We believe this is the first reported case of diaphragmatic rupture complicating an asthma exacerbation. We review clinical features, pathophysiology, diagnosis, and treatment of diaphragmatic rupture in its most common setting, trauma, and discuss its occasional "spontaneous" occurrence.

Intramuscular haemangiomas of the chest wall are rare. We present the case of a 33-year-old man with an intramuscular haemangioma of the left side of the anterior chest wall located in the left sixth intercostal space. We resected the tumour and surrounding tissue. Histopathological examination of the tumour demonstrated an intramuscular haemangioma of small-vessel type. The patient has been free of recurrence for 5 years after surgery., (Copyright 2000 The British Association of Plastic Surgeons.)

Receptor tyrosine kinase erbB2, which is activated by neuregulin, is expressed in Schwann and muscle cells in the developing neuromuscular junction (NMJ). In vitro studies have shown that neuregulin promotes the survival and migration of Schwann cells and stimulates acetylcholine receptor gene transcription in cultured muscle cells. These findings suggest an important role for erbB2 in the development of the NMJ. Here we examine erbB2-deficient mice to determine whether erbB2 is required for NMJ development in vivo. Our analysis shows that there are pre- and postsynaptic defects of developing NMJ in erbB2-deficient embryos. The presynaptic defects include defasciculation and degeneration of the motor nerves, and an absence of Schwann cells. The postsynaptic defect features an impairment of junctional folds at the neuromuscular synapse in the mutants. These results demonstrate that erbB2 is essential for in vivo development of the NMJ.

A 32-year-old female presented with a 2-year history of fluctuating generalized weakness including extraocular, bulbar, and limb muscles, suggesting myasthenia gravis, but with poor response to pyridostigmine and unusual electromyographic findings. After rest, power increased on repeated maximal contractions, followed by progressive weakness. There were decremental responses at low-frequency stimulation, but incremental responses at high frequencies, and single stimuli evoked repetitive compound muscle action potentials. Plasmapheresis was ineffective. In a conventional assay, antibodies against acetylcholine receptors (AChRs) were borderline. However, in an assay using cells expressing mainly adult-type human AChRs, the patient's serum was positive. Thymectomy revealed a hyperplastic thymus. An intercostal muscle specimen revealed small miniature end-plate potentials, 0.22+/-0.02 mV instead of 0.56+/-0.05 mV in controls. The number of 125I-alpha-bungarotoxin binding sites was normal. The decay time constant of end-plate potentials was increased from 5.3+/-0.6 msec in controls to 23+/-3.6 msec in the patient. Ultrastructurally, there was no destruction of the end plate. Transfer of the patient's plasma to mice in vivo produced similar physiological changes in their diaphragms. We conclude that the patient has an immune-mediated disorder, in which an antibody specific to the adult form of the AChRs alters the channel properties, reducing total current and slowing the closure. We propose the name "acquired slow-channel syndrome" for this variant of myasthenia gravis.

N lines can be seen by electron microscopy within the I band of skeletal muscle, but are poorly visualized in conventional preparations. We present a case of acute quadriplegic myopathy with myosin loss and prominent N lines. The only other reported cases of N lines were also seen in patients with myosin loss from diverse etiologies. Myosin loss and the subsequent detachment of titin from myosin may result in the formation of prominent N lines.

The general morphometric characteristics of the external intercostal muscle (EIM) of patients with chronic respiratory disease have been well described. Because this muscle is highly accessible, it can provide an ideal model for longitudinal studies using consecutive biopsies of both sides. Whether or not the EIM fiber phenotype is homogeneous on dominant (D) and non dominant (ND) sides is unknown, however. To evaluate possible structural differences in right and left EIM in patients with COPD, eight patients (63 +/- 7 years of age) were enrolled. Lung function, respiratory muscle power, general muscle power and nutritional state were evaluated. Biopsies of the fifth EIM were taken from both sides. Specimens were processed in parallel manner to determine conventional morphometry (hematoxylin-eosin staining), including minimum diameter (Dm) and fiber area (Ar) in cross sections. Fibers were typed by ATPase (at pH 4.2, 4.6 and 9.4) and NADH-TR staining. Nutrition was normal in all patients. All patients had severe COPD (FEV1 27 +/- 7% of reference, limits 13 to 38% of reference) with air entrapment (RV 163 +/- 36% of reference, limits 181 to 276% of reference). None of the patients showed respiratory insufficiency at rest (PaO2 72 +/- 7 mmHg). Peripheral musculoskeletal power measured by manual dynamometer showed no significant right-left differences: D 29 +/- 2 and ND 28 +/- 3 dynes. Morphometric study of 16 muscle specimens showed no significant differences between fiber size on D and ND sides. DmD was 47 +/- 10 microns and ArD, was 2,595 +/- 1,249 microns2. DmD was 49 +/- 9 microns and ArD was 2,636 +/- 953 microns2. Likewise, no significant differences were found between D and ND fiber types: type ID 51 +/- 4% and type IID 49 +/- 5% versus type IND 52 +/- 4% and type IIND 48 +/- 4%. EIM on N and ND sides is homogeneous at the fifth intercostal space. This finding, along with the scarcely invasive nature of the technique for collecting specimens leads us to suggest that longitudinal studies might be performed on the structural effects of various pharmacological or physical treatments followed by COPD patients

Chest wall tumors are uncommon and there have been only a few reports of intercostal hemangioma during the past 20 years. We treated a 33-year-old man who presented with intercostal hemangioma. We resected tumor and surrounding muscles beyond the limits of the lesion without removing any bone or lung tissue. The patient is free of any recurrence 3 years after surgery.