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J. Clin. Med., Volume 7, Issue 6 (June 2018)

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Cover Story (view full-size image) Dialysis associated steal syndrome (DASS) is a rare but debilitating complication of arteriovenous [...] Read more.
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Open AccessReview Prostate-Associated Gene 4 (PAGE4): Leveraging the Conformational Dynamics of a Dancing Protein Cloud as a Therapeutic Target
J. Clin. Med. 2018, 7(6), 156; https://doi.org/10.3390/jcm7060156
Received: 31 May 2018 / Revised: 13 June 2018 / Accepted: 15 June 2018 / Published: 17 June 2018
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Abstract
Prostate cancer (PCa) is a leading cause of mortality and morbidity globally. While genomic alterations have been identified in PCa, in contrast to some other cancers, use of such information to personalize treatment is still in its infancy. Here, we discuss how PAGE4,
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Prostate cancer (PCa) is a leading cause of mortality and morbidity globally. While genomic alterations have been identified in PCa, in contrast to some other cancers, use of such information to personalize treatment is still in its infancy. Here, we discuss how PAGE4, a protein which appears to act both as an oncogenic factor as well as a metastasis suppressor, is a novel therapeutic target for PCa. Inhibiting PAGE4 may be a viable strategy for low-risk PCa where it is highly upregulated. Conversely, PAGE4 expression is downregulated in metastatic PCa and, therefore, reinstituting its sustained expression may be a promising option to subvert or attenuate androgen-resistant PCa. Thus, fine-tuning the levels of PAGE4 may represent a novel approach for personalized medicine in PCa. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Prostate Cancer)
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Open AccessArticle Association of Low Fecal Elastase-1 and Non-Ulcer Dyspepsia
J. Clin. Med. 2018, 7(6), 155; https://doi.org/10.3390/jcm7060155
Received: 27 May 2018 / Revised: 11 June 2018 / Accepted: 15 June 2018 / Published: 16 June 2018
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Abstract
Non-ulcer dyspepsia (NUD) is a term used to define a set of symptoms that are believed to originate from the gastroduodenal region, and no underlying organic, systemic, or metabolic reason can be found. The majority of patients suffer from chronic symptoms although half
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Non-ulcer dyspepsia (NUD) is a term used to define a set of symptoms that are believed to originate from the gastroduodenal region, and no underlying organic, systemic, or metabolic reason can be found. The majority of patients suffer from chronic symptoms although half of the patients report improvement in symptoms with time. The potential role exocrine pancreatic insufficiency in NUD patients has not been clarified yet. We aimed to identify exocrine pancreas function with pancreatic fecal elastase-1 in patients diagnosed with non-ulcer dyspepsia and no typical exocrine pancreatic insufficiency (EPI) symptoms. Thirty-five patients referred to gastroenterology clinics with NUD and 35 people with no dyspeptic symptoms as a control group were included in this prospective study. Non-ulcer dyspepsia patients were classified as group 1 and control subjects classified as group 2. Upper gastrointestinal endoscopies were performed in both groups. Assessment of exocrine pancreatic function was performed by measuring fecal elastase-1 concentration with a commercial ELISA kit using polyclonal antibodies (BioServ Diagnostics) in NUD patients compared to control subjects. Mean fecal elastase-1 levels were significantly lower in group 1 patients compared with group 2 (367.47 ± 43.27; 502.48 ± 50.94 respectively; p = 0.04). The percentage of the patients with EPI was significantly higher in group 1 (p = 0.02). Patients with NUD should be re-evaluated if they do not show satisfactory improvement with treatment. Exocrine pancreatic insufficiency was significantly higher in patients with NUD in our study. Evaluation for the presence of EPI can be a cost effective approach in management of refractory patients during the process of ruling out organic reasons. Full article
Open AccessArticle Betulin Suppresses Osteoclast Formation via Down-Regulating NFATc1
J. Clin. Med. 2018, 7(6), 154; https://doi.org/10.3390/jcm7060154
Received: 30 May 2018 / Accepted: 10 June 2018 / Published: 15 June 2018
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Abstract
Osteoporosis is a disease characterized by osteoclast-mediated low bone mass. The modulation of osteoclasts is important for the prevention or therapeutic treatment of loss of bone mass. Osteoclasts, which are bone-resorbing multinucleated cells, are differentiated from the hematopoietic stem cell monocyte/macrophage lineage by
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Osteoporosis is a disease characterized by osteoclast-mediated low bone mass. The modulation of osteoclasts is important for the prevention or therapeutic treatment of loss of bone mass. Osteoclasts, which are bone-resorbing multinucleated cells, are differentiated from the hematopoietic stem cell monocyte/macrophage lineage by Receptor activator of nuclear factor kappa-B ligand (RANKL) expressed from osteoblasts and stromal cells. RANKL signaling ultimately activates nuclear factor of activated T Cells 1 (NFATc1), which is a master transcription factor in osteoclastogenesis. Betulin, a lupine type pentacyclic triterpenoid, was isolated from the bark of Betula platyphylla. Betulin inhibited RANKL-mediated osteoclast differentiation by downregulating NFATc1. Betulin may serve as a useful structural scaffold in the therapeutic agent development to prevention/treatment the osteoclast-mediated bone disorder. Full article
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Open AccessReview An Update on Predictive Biomarkers for Treatment Selection in Non-Small Cell Lung Cancer
J. Clin. Med. 2018, 7(6), 153; https://doi.org/10.3390/jcm7060153
Received: 17 May 2018 / Revised: 12 June 2018 / Accepted: 12 June 2018 / Published: 15 June 2018
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Abstract
It is now widely established that management of lung cancer is much more complex and cannot be centered on the binary classification of small-cell versus non-small cell lung cancer (NSCLC). Lung cancer is now recognized as a highly heterogeneous disease that develops from
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It is now widely established that management of lung cancer is much more complex and cannot be centered on the binary classification of small-cell versus non-small cell lung cancer (NSCLC). Lung cancer is now recognized as a highly heterogeneous disease that develops from genetic mutations and gene expression patterns, which initiate uncontrolled cellular growth, proliferation and progression, as well as immune evasion. Accurate biomarker assessment to determine the mutational status of driver mutations such as EGFR, ALK and ROS1, which can be targeted by specific tyrosine kinase inhibitors, is now essential for treatment decision making in advanced stage NSCLC and has shifted the treatment paradigm of NSCLC to more individualized therapy. Rapid advancements in immunotherapeutic approaches to NSCLC treatment have been paralleled by development of a range of potential predictive biomarkers that can enrich for patient response, including PD-L1 expression and tumor mutational burden. Here, we review the key biomarkers that help predict response to treatment options in NSCLC patients. Full article
Open AccessArticle Ganoderma lucidum Ameliorates Non-Alcoholic Steatosis by Upregulating Energy Metabolizing Enzymes in the Liver
J. Clin. Med. 2018, 7(6), 152; https://doi.org/10.3390/jcm7060152
Received: 24 May 2018 / Revised: 12 June 2018 / Accepted: 13 June 2018 / Published: 15 June 2018
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Abstract
Non-alcoholic steatosis is a common health problem worldwide due to altered food habits and life styles, and it is intimately linked with various metabolic disorders. In the present study, we investigated the molecular mechanism of Ganoderma lucidum (GL) against the development of non-alcoholic
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Non-alcoholic steatosis is a common health problem worldwide due to altered food habits and life styles, and it is intimately linked with various metabolic disorders. In the present study, we investigated the molecular mechanism of Ganoderma lucidum (GL) against the development of non-alcoholic steatosis using in vivo and in vitro settings. C57BL/6 mice fed with normal diet (ND) or high fat diet (HFD) were administered GL extract or vehicle for 16 weeks. HFD feeding increased serum alanine aminotransferase level and hepatic lipid droplet, but these increases were significantly attenuated by GL. GL inhibited the increases in epididymal and perirenal adipose tissue weights and serum cholesterol and LDL levels in HFD-fed mice. Fasting blood glucose levels were elevated in HFD-fed mice compared to ND-fed mice, and glucose and insulin sensitivities were deteriorated. These changes were markedly improved by GL. GL restored the reduction of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation in the liver of HFD-fed mice, and increased AMPK and ACC phosphorylation in HepG2 and 3T3-L1 cells. GL induced GLUT4 protein expression in 3T3-L1 cells. Finally, GL attenuated lipid accumulation induced by free fatty acid in HepG2 cells. Taken together, our results indicate that GL has a potential to improve non-alcoholic steatosis and the associated complicated disorders via the induction of energy metabolizing enzymes. Full article
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Open AccessReview Immunotherapy in Non-Small Cell Lung Cancer: Shifting Prognostic Paradigms
J. Clin. Med. 2018, 7(6), 151; https://doi.org/10.3390/jcm7060151
Received: 4 May 2018 / Revised: 8 June 2018 / Accepted: 12 June 2018 / Published: 14 June 2018
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Abstract
Immune checkpoint inhibitors have shown efficacy in the treatment of non-small cell lung cancer (NSCLC) in the adjuvant, first- and subsequent-line settings. In metastatic disease, they provide hope of durable response where “best-case” scenario has long been inadequate. This progress has highlighted the
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Immune checkpoint inhibitors have shown efficacy in the treatment of non-small cell lung cancer (NSCLC) in the adjuvant, first- and subsequent-line settings. In metastatic disease, they provide hope of durable response where “best-case” scenario has long been inadequate. This progress has highlighted the immunogenic nature of NSCLC and invigorated research into immunotherapy in the field. In this review we consider the foundations of immunotherapy in NSCLC, canvass the current research and summarise the evidence guiding clinical practice. Full article
Open AccessArticle Pharmacokinetics of Tedizolid and Pseudoephedrine Administered Alone or in Combination in Healthy Volunteers
J. Clin. Med. 2018, 7(6), 150; https://doi.org/10.3390/jcm7060150
Received: 6 June 2018 / Accepted: 13 June 2018 / Published: 14 June 2018
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Abstract
Therapeutic doses of tedizolid phosphate, an oxazolidinone antibiotic, lack monoamine oxidase inhibition in vivo, potentially resulting in an improved safety profile versus other oxazolidinones. This randomized, double-blind, placebo-controlled, 2-period, 2-sequence, crossover, phase 1 study (NCT01577459) assessed the potential for pharmacokinetic (PK) interactions between
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Therapeutic doses of tedizolid phosphate, an oxazolidinone antibiotic, lack monoamine oxidase inhibition in vivo, potentially resulting in an improved safety profile versus other oxazolidinones. This randomized, double-blind, placebo-controlled, 2-period, 2-sequence, crossover, phase 1 study (NCT01577459) assessed the potential for pharmacokinetic (PK) interactions between tedizolid and pseudoephedrine. Eighteen healthy volunteers (age: 18–45 years) were block-randomized to 1 of 2 treatment sequences containing 2 treatment periods (tedizolid phosphate or placebo once daily for 4 days; single dose of pseudoephedrine 60 mg on day 5) separated by a 2-day washout. Median time to maximum plasma concentration for tedizolid and pseudoephedrine ranged from 3 to 4 h, regardless of treatment coadministration. Steady-state tedizolid had no effect on the PK of pseudoephedrine; geometric mean ratio and 90% confidence interval remained within the no-effect 0.8 to 1.25 boundaries. The maximum observed concentration of tedizolid decreased by approximately 14% when pseudoephedrine was coadministered; no changes in the area under the plasma concentration-time curve or the minimum observed plasma concentration occurred. All adverse events (AEs) were mild, and there were no serious AEs or study drug discontinuations. No meaningful PK interactions occurred between tedizolid and pseudoephedrine, and tedizolid was well tolerated when administered in conjunction with pseudoephedrine. Full article
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Open AccessOpinion Complementary Medicine: Risks to Infants and Children
J. Clin. Med. 2018, 7(6), 149; https://doi.org/10.3390/jcm7060149
Received: 11 June 2018 / Accepted: 11 June 2018 / Published: 12 June 2018
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Abstract
Complementary Alternative Medicine (CAM) that targets infants and children can place them at grave risk. Our plan is to review some of the major cases of CAM used by parents, and by unlicensed and even licensed health professionals. Complications from CAM are rarely
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Complementary Alternative Medicine (CAM) that targets infants and children can place them at grave risk. Our plan is to review some of the major cases of CAM used by parents, and by unlicensed and even licensed health professionals. Complications from CAM are rarely the focus of regulatory bodies, or even the courts. Even regulated health professionals, who have profited by misrepresenting science-based evidence for treatment or prevention of disease, have been rarely sanctioned by their respective Boards or Colleges. This must change. In addition, there is a dire need for regulators, including the governments, who allow quack products and devices to be marketed in their respective countries, to prosecute them. Existing regulations must be coupled with more effective enforcement. Some of these cases have had a direct connection to me personally, while others are examples of just plain dangerous quackery. Full article
Open AccessReview The Role of Procalcitonin in the Diagnosis of Meningitis: A Literature Review
J. Clin. Med. 2018, 7(6), 148; https://doi.org/10.3390/jcm7060148
Received: 4 June 2018 / Accepted: 8 June 2018 / Published: 11 June 2018
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Abstract
Objective: To review the current published literature on the use of procalcitonin as a diagnostic and prognostic marker in adult patients with meningitis. Methods: We conducted a PubMed search to identify all relevant publications regarding the diagnostic and prognostic value of serum procalcitonin
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Objective: To review the current published literature on the use of procalcitonin as a diagnostic and prognostic marker in adult patients with meningitis. Methods: We conducted a PubMed search to identify all relevant publications regarding the diagnostic and prognostic value of serum procalcitonin in patients with a known or suspected central nervous system infection. We also reviewed the bibliographies of all identified manuscripts in an attempt to identify additional relevant references. Results: A significant body of evidence suggests that serum procalcitonin has a promising role and can be a useful biomarker in the assessment of patients with meningitis. Conclusions: Our literature review suggests that data on the role of Cerebrospinal Fluid (CSF) procalcitonin are limited, whereas serum procalcitonin (S–PCT) is probably a useful tool in the evaluation of patients with a known or suspected central nervous system infection and can help distinguish between bacterial and viral meningitis. Full article
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Open AccessArticle Randomized Controlled Trial Considering Varied Exercises for Reducing Proactive Memory Interference
J. Clin. Med. 2018, 7(6), 147; https://doi.org/10.3390/jcm7060147
Received: 17 May 2018 / Revised: 4 June 2018 / Accepted: 8 June 2018 / Published: 11 June 2018
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Abstract
We evaluated the effects of exercise on proactive memory interference. Study 1 (n = 88) employed a 15-min treadmill walking protocol, while Study 2 (n = 88) included a 15-min bout of progressive maximal exertion treadmill exercise. Each study included four
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We evaluated the effects of exercise on proactive memory interference. Study 1 (n = 88) employed a 15-min treadmill walking protocol, while Study 2 (n = 88) included a 15-min bout of progressive maximal exertion treadmill exercise. Each study included four distinct groups, in which groups of 22 participants each were randomly assigned to: (a) exercise before memory encoding, (b) a control group with no exercise, (c) exercise during memory encoding, and (d) exercise after memory encoding (i.e., during memory consolidation). We used the Rey Auditory Verbal Learning Test (RAVLT) to assess proactive memory interference. In both studies, the group that exercised prior to memory encoding recalled the most words from list B (distractor list) of the RAVLT, though group differences were not statistically significant for Study 1 (walking exercise) (p = 0.521) or Study 2 (high-intensity exercise) (p = 0.068). In this sample of young adults, high intensity exercise prior to memory encoding showed a non-significant tendency to attenuate impairments in recall attributable to proactive memory interference. Thus, future work with larger samples is needed to clarify potential beneficial effects of exercise for reducing proactive memory interference. Full article
(This article belongs to the Special Issue The Effects of Exercise on Cognitive Function)
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Open AccessArticle Experimental Effects of Acute Exercise on Iconic Memory, Short-Term Episodic, and Long-Term Episodic Memory
J. Clin. Med. 2018, 7(6), 146; https://doi.org/10.3390/jcm7060146
Received: 24 May 2018 / Revised: 4 June 2018 / Accepted: 10 June 2018 / Published: 11 June 2018
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Abstract
The present experiment evaluated the effects of acute exercise on iconic memory and short- and long-term episodic memory. A two-arm, parallel-group randomized experiment was employed (n = 20 per group; Mage = 21 year). The experimental group engaged in an acute
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The present experiment evaluated the effects of acute exercise on iconic memory and short- and long-term episodic memory. A two-arm, parallel-group randomized experiment was employed (n = 20 per group; Mage = 21 year). The experimental group engaged in an acute bout of moderate-intensity treadmill exercise for 15 min, while the control group engaged in a seated, time-matched computer task. Afterwards, the participants engaged in a paragraph-level episodic memory task (20 min delay and 24 h delay recall) as well as an iconic memory task, which involved 10 trials (at various speeds from 100 ms to 800 ms) of recalling letters from a 3 × 3 array matrix. For iconic memory, there was a significant main effect for time (F = 42.9, p < 0.001, η2p = 0.53) and a trend towards a group × time interaction (F = 2.90, p = 0.09, η2p = 0.07), but no main effect for group (F = 0.82, p = 0.37, η2p = 0.02). The experimental group had higher episodic memory scores at both the baseline (19.22 vs. 17.20) and follow-up (18.15 vs. 15.77), but these results were not statistically significant. These findings provide some suggestive evidence hinting towards an iconic memory and episodic benefit from acute exercise engagement. Full article
(This article belongs to the Special Issue The Effects of Exercise on Cognitive Function)
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Open AccessArticle Preoperative and Postoperative Assessment of Ultrasonographic Measurement of Inferior Vena Cava: A Prospective, Observational Study
J. Clin. Med. 2018, 7(6), 145; https://doi.org/10.3390/jcm7060145
Received: 19 April 2018 / Revised: 4 June 2018 / Accepted: 8 June 2018 / Published: 10 June 2018
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Abstract
Background: Ultrasound measurement of dynamic changes in inferior vena cava (IVC) diameter and collapsibility index (CI) are used to estimate the fluid responsiveness and intravascular volume status. We conducted an analysis to quantify the sonographic measurement of IVC diameter changes in adult patients
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Background: Ultrasound measurement of dynamic changes in inferior vena cava (IVC) diameter and collapsibility index (CI) are used to estimate the fluid responsiveness and intravascular volume status. We conducted an analysis to quantify the sonographic measurement of IVC diameter changes in adult patients at the preoperative and postoperative periods. Methods: Ultrasonography was performed on 72 patients scheduled for surgery with American Society of Anesthesiologists physical status I to III. Quantitative assessments of the end-expiration (Dmin), end-inspiration (Dmax), and CI at preoperative and postoperative period were compared in a prospective, observational study. The patients received intravenous fluid according to standard protocol regimes peroperatively. Results: Ultrasonography of IVC measurement was unsuccessful in 12.5% of patients and 63 patients remained for analyses. The mean age was 43.29 ± 17.22 (range 18–86) years. The average diameter of the Dmin, Dmax, and dIVC preoperative and postoperative were 1.99 ± 0.31 vs. 2.05 ± 0.29 cm, 1.72 ± 0.33 vs. 1.74 ± 0.32 cm, 14.0 ± 9.60% vs. 15.14 ± 11.18%, respectively (p > 0.05). CI was positively associated preoperatively and postoperatively (regression coefficient = 0.438, p < 0.01). Conclusion: The diameter of the IVC did not change preoperatively and postoperatively in adult patients with standard fluid regimens. The parameters of the IVC diameter increased postoperatively according to the preoperative period. Full article
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Open AccessReview Current and Future Molecular Testing in NSCLC, What Can We Expect from New Sequencing Technologies?
J. Clin. Med. 2018, 7(6), 144; https://doi.org/10.3390/jcm7060144
Received: 24 May 2018 / Revised: 5 June 2018 / Accepted: 6 June 2018 / Published: 9 June 2018
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Abstract
Recent changes in lung cancer care, including new approvals in first line and the introduction of high-throughput molecular technologies in routine testing led us to question ourselves on how deeper molecular testing may be helpful for the optimal use of targeted drugs. In
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Recent changes in lung cancer care, including new approvals in first line and the introduction of high-throughput molecular technologies in routine testing led us to question ourselves on how deeper molecular testing may be helpful for the optimal use of targeted drugs. In this article, we review recent results in the scope of personalized medicine in lung cancer. We discuss biomarkers that have a therapeutic predictive value in lung cancer with a focus on recent changes and on the clinical value of large scale sequencing strategies. We review the use of second- and third-generation EGFR and ALK inhibitors with a focus on secondary resistance alterations. We discuss anti-BRAF and anti-MEK combo, emerging biomarkers as NRG1 and NTRKs fusions and immunotherapy. Finally, we discuss the different technical issues of comprehensive molecular profiling and show how large screenings might refine the prediction value of individual markers. Based on a review of recent publications (2012–2018), we address promising approaches for the treatment of patients with lung cancers and the technical challenges associated with the identification of new predictive markers. Full article
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Open AccessArticle Platelet-Rich Plasma May Offer a New Hope in Suppressed Wound Healing When Compared to Mesenchymal Stem Cells
J. Clin. Med. 2018, 7(6), 143; https://doi.org/10.3390/jcm7060143
Received: 9 May 2018 / Revised: 30 May 2018 / Accepted: 6 June 2018 / Published: 8 June 2018
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Abstract
Background: The present study investigated the effectiveness of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) in wound healing suppressed by corticosteroid in rats. Methods: Forty rats were separated into four groups. To disrupt the wound-healing processes, intraperitoneal single dose 10 mg/kg methylprednisolone
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Background: The present study investigated the effectiveness of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) in wound healing suppressed by corticosteroid in rats. Methods: Forty rats were separated into four groups. To disrupt the wound-healing processes, intraperitoneal single dose 10 mg/kg methylprednisolone was administered to all rats with the exception of Sham-S group. Then, full-thickness incision was performed to the abdominal skin of all animals, and PRP or MSCs were applied to the incision line except the Sham-S and Sham-M group animals. Ten days later, all animals were sacrificed to investigate: tissue collagenization, inflammation, and re-epithelialization grades histopathologically; and tissue hydroxyproline (HP), interleukin-1β (IL-1β), tumor necrosis factor-α levels biochemically. Results: Collagenization (p = 0.003) and inflammation grade (p = 0.002) values were higher in PR group. Tissue HP level value was found to be high in MC group (p < 0.001). Tissue IL-1β level value of Sham-M group was lower than those of other groups (p < 0.001). Conclusions: This preliminary study revealed that PRP could improve the histopathological grades in wound healing which was suppressed by corticosteroid in rats, while MSCs could show their therapeutic effects via biochemical route. These positive effects were more salient in PR group. Full article
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Open AccessArticle A Neglected Issue in Ulcerative Colitis: Mesenteric Lymph Nodes
J. Clin. Med. 2018, 7(6), 142; https://doi.org/10.3390/jcm7060142
Received: 15 May 2018 / Revised: 29 May 2018 / Accepted: 6 June 2018 / Published: 8 June 2018
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Abstract
Data evaluating the presence and characteristics of mesenteric lymph nodes (LNs) in patients with ulcerative colitis (UC) are scarce. The aim of this study is to determine the presence and characteristics of LNs in UC. The LN characteristics in computed tomography (CT), including
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Data evaluating the presence and characteristics of mesenteric lymph nodes (LNs) in patients with ulcerative colitis (UC) are scarce. The aim of this study is to determine the presence and characteristics of LNs in UC. The LN characteristics in computed tomography (CT), including LN dimension and attenuation, were evaluated retrospectively in 100 patients with UC (61 active and 39 inactive cases). Clinical characteristics and laboratory parameters, including CBC, biochemical analysis, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were also compared. Mesenteric LNs were evident in all patients with UC. The attenuation and dimension of mesenteric LNs did not differ between active and inactive patients with UC. No correlation was found among patients with UC in terms of LN dimension, attenuation, ESR, CRP, leucocyte, and albumin (all with p > 0.05). The current study suggested that inflammation results in the development of mesenteric LN in UC, similar to Crohn’s disease and other inflammatory disorders. Full article
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