Abstract Myostatin (MSTN) is a negative regulator of muscle growth even if some studies have shown a counterintuitive positive correlation between MSTN and muscle mass (MM). Our aim was to investigate the influence of 2 months of resistance training (RT) and diets with different protein contents on plasma MSTN, interleukin 1 beta (IL-1?), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-?), and insulin-like growth factor 1 (IGF-1). Eighteen healthy volunteers were randomly divided in two groups: high protein (HP) and normal protein (NP) groups. Different protein diet contents were 1.8 and 0.85?g of protein·kg bw(-1)·day(-1) for HP and NP, respectively. Subjects underwent 8 weeks of standardized progressive RT. MSTN, IGF-1, IL-1?, IL-6, and TNF-? were analyzed before and after the first and the last training sessions. Lean body mass, MM, upper-limb muscle area, and strength were measured. Plasma MSTN showed a significant increase (P<.001) after the last training in the HP group compared with NP group and with starting value. IGF-1 plasma concentration showed a positive correlation with MSTN in HP after the last training (r(2)=0.6456; P=.0295). No significant differences were found between NP and HP for IL-1?, IL-6, TNF-?, and strength and MM or area. These findings suggest a "paradoxical" postexercise increase of plasma MSTN after 8 weeks of RT and HP diets. This MSTN elevation correlates positively with IGF-1 plasma level. This double increase of opposite (catabolic/anabolic) mediators could explain the substantial overlapping of MM increases in the two groups.
No second-line treatment significantly prolongs the survival of malignant mesothelioma patients who have a high unmet medical need. Here, we comment on the therapeutic potential of cytotoxic T-lymphocyte-associated protein (CTLA)4-blockade by the anti-CTLA4 monoclonal antibody (mAb) tremelimumab of refractory malignant mesothelioma patients. We also focus on the critical role of an accurate tumor assessment in the course of treatment with immunomodulating mAb. Finally, treatment with potentially effective, second-generation checkpoint(s) inhibiting mAb, as well future combination strategies in this deadly disease, will be discussed.
The frequency of suboccipital injections to treat headaches has increased. The third segment of the vertebral artery is located in the suboccipital triangle and its main muscular branch, the suboccipital artery of Salmon (SAS), supplies blood to the suboccipital muscles. The purpose of this study was to radiographically investigate the morphology and territory of distribution of SAS.
In our study, we evaluated the feasibility of a new sampling method for splenic stiffness (SS) measurement by Quantitative Acoustic Radiation Force Impulse Elastography (Virtual Touch Tissue Quantification (VTTQ)).We measured SS in 54 patients with HCV-related cirrhosis of whom 28 with esophageal varices (EV), 27 with Chronic Hepatitis C (CHC) F1-F3, and 63 healthy controls. VTTQ-SS was significantly higher among cirrhotic patients with EV (3.37?m/s) in comparison with controls (2.19?m/s, P<0.001), CHC patients (2.37?m/s, P<0.001), and cirrhotic patients without EV (2.7?m/s, P<0.001). Moreover, VTTQ-SS was significantly higher among cirrhotic patients without EV in comparison with both controls (P<0.001) and CHC patients (P<0.01). The optimal VTTQ-SS cut-off value for predicting EV was 3.1?m/s (AUROC=0.96, sensitivity 96.4%, specificity 88.5%, positive predictive value 90%, negative predictive value 96%, positive likelihood ratio 8.36, and negative likelihood ratio 0.04). In conclusion, VTTQ-SS is a promising noninvasive and reliable diagnostic tool to screen cirrhotic patients for EV and reduce the need for upper gastrointestinal endoscopy. By using our cut-off value of 3.1?m/s, we would avoid endoscopy in around 45% of cirrhotic subjects, with significant time and cost savings.
Monoclonal antibodies to cytotoxic T-lymphocyte antigen 4 (CTLA4) have therapeutic activity in different tumour types. We aimed to investigate the efficacy, safety, and immunological activity of the anti-CTLA4 monoclonal antibody, tremelimumab, in advanced malignant mesothelioma.
Although the plantar fascia (PF) has been studied quite well from a biomechanical viewpoint, its microscopic properties have been overlooked: nothing is known about its content of elastic fibers, the features of the extracellular matrix or the extent of innervation. From a functional and clinical standpoint, the PF is often correlated with the triceps surae muscle, but the anatomical grounds for this link are not clear. The aim of this work was to focus on the PF macroscopic and microscopic properties and study how Achilles tendon diseases might affect it. Twelve feet from unembalmed human cadavers were dissected to isolate the PF. Specimens from each PF were tested with various histological and immunohistochemical stains. In a second stage, 52 magnetic resonance images (MRI) obtained from patients complaining of aspecific ankle or foot pain were analyzed, dividing the cases into two groups based on the presence or absence of signs of degeneration and/or inflammation of the Achilles tendon. The thickness of PF and paratenon was assessed in the two groups and statistical analyses were conducted. The PF is a tissue firmly joined to plantar muscles and skin. Analyzing its possible connections to the sural structures showed that this fascia is more closely connected to the paratenon of Achilles tendon than to the Achilles tendon, through the periosteum of the heel. The PF extended medially and laterally, continuing into the deep fasciae enveloping the abductor hallucis and abductor digiti minimi muscles, respectively. The PF was rich in hyaluronan, probably produced by fibroblastic-like cells described as fasciacytes. Nerve endings and Pacini and Ruffini corpuscles were present, particularly in the medial and lateral portions, and on the surface of the muscles, suggesting a role for the PF in the proprioception of foot. In the radiological study, 27 of the 52 MRI showed signs of Achilles tendon inflammation and/or degeneration, and the PF was 3.43 ± 0.48 mm thick (99%CI and SD = 0.95), as opposed to 2.09 ± 0.24 mm (99%CI, SD = 0.47) in the patients in which the MRI revealed no Achilles tendon diseases; this difference in thickness of 1.29 ± 0.57 mm (99%CI) was statistically significant (P < 0.001). In the group of 27/52 patients with tendinopathies, the PF was more than 4.5 mm thick in 5, i.e. they exceeded the threshold for a diagnosis of plantar fasciitis. None of the other 25/52 paitents had a PF more than 4 mm thick. There was a statistically significant correlation between the thicknesses of the PF and the paratenon. These findings suggest that the plantar fascia has a role not only in supporting the longitudinal arch of the foot, but also in its proprioception and peripheral motor coordination. Its relationship with the paratenon of the Achilles tendon is consistent with the idea of triceps surae structures being involved in the PF pathology, so their rehabilitation can be considered appropriate. Finally, the high concentration of hyaluronan in the PF points to the feasibility of using hyaluronan injections in the fascia to treat plantar fasciitis.
The aim of this paper was to examine the macroscopic and microscopic characteristics of the paratendineous tissues (paratenon, epitenon and endotenon) of the calcaneal tendon to better understand their role in the pathogenesis of "tendinopathy". Ten non-embalmed legs from cadavers were used. Histological and immunohistochemical studies were done at the middle third of the tendon. Magnetic resonance images of the hind foot were made in 60 living subjects to analyze the morphological alterations of tendon and paratenon. The paratenon is a thick fibrous layer with few elastic fibers, continuous with the crural fascia, well vascularized and innervated. It forms a sheath around the tendon similar to a synovial layer, but less organized. Indeed, it has no complete epithelium, but only some cells producing hyaluronan, called fasciacytes. Crural fascia and paratenon can be clearly observed by MRI, appearing as homogeneous, low signal intensity bands, sharply defined in the context of subcutaneous tissue in T1-weighted sequences. The mean thickness of the crural fascia was 1.11 mm in healthy subjects and 1.30 mm in patients (p < 0.005). The mean value of paratenon thickness in patients was 1.34 mm, 0.85 in healthy (p < 0.0001). The paratenon is more highly vascularized and innervated than the tendon, supporting the hypothesis that it is the origin of pain in tendinopathy. The imaging study suggests that, an increase in the thickness of the paratenon more than 1.35 mm is predictive of paratendinopathy, even before tendon damage.
Clinical and neuroimaging parameters predictive of the changing clinical course of multiple sclerosis (MS) from relapsing-remitting to secondary progressive have not been clarified yet. We specifically designed a prospective 5-year longitudinal study aimed at assessing demographic, clinical, and magnetic resonance imaging (MRI) parameters that could predict the changing clinical course of MS.
The extradural space is currently investigated through fluoroscopy and ultrasound for surgical approach, whereas magnetic resonance imaging has been used to provide detailed information. The aim of the present paper is to describe the radiologic anatomy of the sacral canal through a review of its appearance in the different radiologic techniques. CT is able to visualise also the sacrum and the content of the sacral canal, triangular in shape in the transverse images, being able to establish the measurement of the transverse area of the dural sac and of the canal diameter. On the sagittal CT scans, the sacrococcygeal membrane appears as a hypodense structure, between the posterior end of the sacral vertebra and the posterior tip of the coccyx. In magnetic resonance imaging, on T2-sagittal plane images, the sacral canal appears hyperintense, due to the presence of the liquor. The dural sac appears as a hypointense band and its termination as hypointense cul de sac in the context of the hyperintensity of the sacral canal. The sacrococcygeal membrane appears as a hypointense band between the posterior end of the sacral vertebra and the posterior tip of the coccyx. On ultrasound imaging, in the transverse sonographic view, two hyperechoic reversed U-shaped structures correspond to the two bony prominences of sacral cornua, between which there were two hyperechoic band-like structures. The band-like structure on top is the sacrococcygeal ligament. The band-like structure at the bottom is the dorsal surface of the sacrum. The sacral hiatus corresponds to the hypoechoic region observed between the two hyperechoic band-like structures.
When the anomalous origin of coronary arteries (AOCA) is suspected in children (especially athletes), due to signs and symptoms of myocardial ischemia or on the basis of echocardiographic assessment, three-dimensional coronary magnetic resonance angiography (3D-CMRA) can be proposed for the fine morphological evaluation of coronary branches anatomy and course. We tested the diagnostic potential of CMRA angiography in a prospective study on AOCA in young patients. Between July 2005 and June 2008, 15 patients aged 6-29 years (mean age, 13.5 years+/-5.6 S.D.; median, 14) with clinical and echocardiographic suspicion of AOCA underwent CMRA (1.5 T), 3D whole-heart, free-breathing technique, without the use of contrast medium and beta-blockers, with a mean examination time of 30 min. We acquired a second scan of all patients to ameliorate the quality of the acquisition and to improve our experience. AOCA was confirmed by 3D-CMRA in 8 out of 15 cases (53%) and three different anatomical variants were demonstrated, that is, ectopic origin of the left circumflex artery arising from the right coronary artery with retro-aortic course in four cases, single coronary artery arising from the right sinus of Valsalva with interarterial course in one case, ectopic right coronary artery arising from the left sinus of Valsalva with interarterial course in one case; in two patients without anomalies of origin of the coronary arteries, elongated LMCA with angulation of the proximal segment of the left circumflex artery was present. When AOCA is suspected particularly in children (especially athletes), CMRA without the use of contrast medium is an effective diagnostic technique, which is useful to clarify the spatial position of the anomalous course of the main coronary branches in order to suggest the most convenient management of the disease. CMRA does not need contrast medium, needles, and beta-blockers; is repeatable in the same examination without the exposure to X-rays; allows a parent to stay near the child; and needs low collaboration in low-stress conditions.
This report presents a case of a 16-year-old hypertensive boy who presented to our clinic. Laboratory findings showed severe hypokalemia and markedly increased plasma renin activity. Abdominal ultrasonography and contrast-enhanced computed tomography of the abdomen revealed a well-circumscribed, solid, hypoenhancing cortical lesion (2 cm) in the lower pole of the left kidney. The patient underwent nephron-sparing surgery. Histopathologic examination gave a diagnosis of juxtaglomerular cell tumor. Reninoma is an uncommon cause of hypertension in a young adult and should be included in the differential diagnosis as a potential life-threatening and curable condition. The conservative surgical management is the gold standard for small, circumscribed lesions.
Fibromuscular dysplasia (FMD) is one of the most common causes of renovascular hypertension in children and women. It is characterized by short multiple stenoses alternated to focal expansions that usually involve the lateral third of the renal artery. Digital subtraction angiography is considered the most accurate method in the diagnosis of renal artery FMD. An indirect sign of FMD-the notches on the ureter secondary to the hypertrophy of the branches of ureteric arteries "climbing" along the ureters-can be visualised during urography. We report the case of a 38-years-old woman with hypertension and no history of familiar predisposition, in which the multidetector computed tomography angiography was able to show both direct and indirect radiological signs of renal artery FMD. 2D and 3D visualisations are useful to suggest the diagnosis of FMD and in the follow-up in patients who underwent to percutaneous transluminal angioplasty.
Recent fMRI evidence indicates that both the execution and the observation of hand actions in multiple sclerosis (MS) patients increase recruitment of a portion of the so-called mirror neuron system. However, it remains unclear whether this is the expression of a compensatory mechanism for the coding of observed action or whether such a mechanism represents a rather unspecific functional adaptation process. Here we used fMRI on early relapsing remitting MS (RRMS) patients to clarify this issue. Functional images of 15 right-handed early RRMS patients and of 15 sex- and age-matched right-handed healthy controls were acquired using a 1.5 T scanner. During scanning, participants simply observed images depicting a human hand either grasping an object or resting alongside an object. As shown by a between-group analysis, when compared to controls, RRMS patients revealed a robust increase of activation in an extensive network of brain regions including frontal, parietal, temporal and visual areas usually activated during action observation. However, this pattern of hemodynamic activity was completely independent of the type of observed hand-object interaction as revealed by the lack of any significant between-group interaction. Our findings are in line with previous fMRI evidence demonstrating cortical reorganization in MS patients during action observation. However, based on our findings we go one step further and suggest that such functional cortical changes may be the expression of a generalized and unspecific compensatory mechanism, that is not necessarily involved in action understanding.
Obesity is associated with structural alterations in subcutaneous small resistance arteries. The aim of the present work is to study modifications of perforators vessels of abdominal wall and subcutaneous tissue characteristics in obese patients after massive weight loss. An anatomo-radiologic study was carried out on 15 patients (5M, 10F, mean age 54.9y), who underwent abdominoplasty after massive weight loss. Their pre-operative Computed Tomographic results (CT) of the anterior abdominal wall were compared with CT of 15 normal weighted controls. Anatomo-microscopic and morphometric examinations were conducted on full-thickness specimens of panniculectomy samples. 10 right panniculectomy were sampled from donor cadavers. All the measurements were taken on transverse sections. In patients, at CT the mean luminal diameter (LD) and standard deviation of perforator branches of the deep inferior epigastric artery (DIEA) was 3.7 ± 0.4 mm (control 2.2 ± 0.1 mm; p < 0.05). At microscopic examination, the wall thickness of perforator arteries was 212.7 ? ± 83.9 versus 143.9 ± 32.8 (p < 0.05) deep to the superficial fascia and 120.4 ? ± 74.8 versus 72.3 ± 23.5 (p < 0.05) superficial to it. A thickening of the muscular layer was observable and the tunica media represented 71.4% ± 5.6 of the whole area of the wall (controls 37.1% ± 3.5, p < 0.0001). Our data demonstrate that the major LD of the perforators in patients matches with hypertrophy of the tunica media and we think that the major thickness of perforator walls can facilitate the microsurgical technique in free microsurgical flap reconstruction.
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