Journal of Clinical Medicine

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Open AccessReview

The Dual Role of Neutrophils in Inflammatory Bowel Diseases

by Odile Wéra, Patrizio Lancellotti and Cécile Oury

J. Clin. Med. 2016, 5(12), 118; https://doi.org/10.3390/jcm5120118 - 17 Dec 2016

Cited by 191 | Viewed by 14383

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are characterised by aberrant immunological responses leading to chronic inflammation without tissue regeneration. These two diseases are considered distinct entities, and there is some evidence that neutrophil behaviour, above all other aspects of [...] Read more.

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are characterised by aberrant immunological responses leading to chronic inflammation without tissue regeneration. These two diseases are considered distinct entities, and there is some evidence that neutrophil behaviour, above all other aspects of immunity, clearly separate them. Neutrophils are the first immune cells recruited to the site of inflammation, and their action is crucial to limit invasion by microorganisms. Furthermore, they play an essential role in proper resolution of inflammation. When these processes are not tightly regulated, they can trigger positive feedback amplification loops that promote neutrophil activation, leading to significant tissue damage and evolution toward chronic disease. Defective chemotaxis, as observed in Crohn’s disease, can also contribute to the disease through impaired microbe elimination. In addition, through NET production, neutrophils may be involved in thrombo-embolic events frequently observed in IBD patients. While the role of neutrophils has been studied in different animal models of IBD for many years, their contribution to the pathogenesis of IBD remains poorly understood, and no molecules targeting neutrophils are used and validated for the treatment of these pathologies. Therefore, it is crucial to improve our understanding of their mode of action in these particular conditions in order to provide new therapeutic avenues for IBD. Full article

(This article belongs to the Special Issue Neutrophil Functions: From Immunity to Disease)

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Open AccessArticle

Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center

by Mark B. Detweiler, Bhuvaneshwar Pagadala, Joseph Candelario, Jennifer S. Boyle, Jonna G. Detweiler and Brian W. Lutgens

J. Clin. Med. 2016, 5(12), 117; https://doi.org/10.3390/jcm5120117 - 16 Dec 2016

Cited by 33 | Viewed by 11731

Abstract

The effectiveness of medications for PTSD in general has been well studied, but the effectiveness of medicatio.ns prescribed specifically for post-traumatic stress disorder (PTSD) nightmares is less well known. This retrospective chart review examined the efficacy of various medications used in actual treatment [...] Read more.

The effectiveness of medications for PTSD in general has been well studied, but the effectiveness of medicatio.ns prescribed specifically for post-traumatic stress disorder (PTSD) nightmares is less well known. This retrospective chart review examined the efficacy of various medications used in actual treatment of PTSD nightmares at one Veteran Affairs Hospital. Records at the Salem, VA Veterans Affairs Medical Center (VAMC) were examined from 2009 to 2013 to check for the efficacy of actual treatments used in comparis.on with treatments suggested in three main review articles. The final sample consisted of 327 patients and 478 separate medication trials involving 21 individual medications plus 13 different medication combinations. The three most frequently utilized medications were prazosin (107 trials), risperidone (81 trials), and quetiapine (72 trials). Five medications had 20 or more trials with successful results (partial to full nightmare cessation) in >50% of trials: risperidone (77%, 1.0–6.0 mg), clonidine (63%, 0.1–2.0 mg), quetiapine (50%, 12.5–800.0 mg), mirtazapine (50%; 7.5–30.0 mg), and terazosin (64%, 50.0–300.0 mg). Notably, olanzapine (2.5–10.0) was successful (full remission) in all five prescription trials in five separate patients. Based on the clinical results, the use of risperidone, clonidine, terazosin, and olanzapine warrants additional investigation in clinically controlled trials as medications prescribed specifically for PTSD nightmares. Full article

(This article belongs to the Special Issue Post-Traumatic Stress Disorder)

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Open AccessReview

Technical Developments and Clinical Use of Telemedicine in Sleep Medicine

by Marie Bruyneel

J. Clin. Med. 2016, 5(12), 116; https://doi.org/10.3390/jcm5120116 - 13 Dec 2016

Cited by 7 | Viewed by 5803

Abstract

The use of assistive technology and telemedicine is likely to continue to shape our medical practice in the future, notably in the field of sleep medicine, especially within developed countries. Currently, the number of people suffering from obstructive sleep apnea syndrome (OSAS) is [...] Read more.

The use of assistive technology and telemedicine is likely to continue to shape our medical practice in the future, notably in the field of sleep medicine, especially within developed countries. Currently, the number of people suffering from obstructive sleep apnea syndrome (OSAS) is increasing. Telemedicine (TM) can be used in a variety of ways in sleep medicine: telediagnostics, teleconsultation, teletherapy and telemonitoring of patients being treated with positive pressure devices. In this review, we aim to summarize the recent scientific progresses of these techniques and their potential clinical applications and give consideration to the remaining problems related to TM application. Full article

(This article belongs to the Special Issue Telemedicine - Technical Developments and Clinical Practice)

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Open AccessReview

Bronchiectasis in the Last Five Years: New Developments

by Jun Keng Khoo, Victoria Venning, Conroy Wong and Lata Jayaram

J. Clin. Med. 2016, 5(12), 115; https://doi.org/10.3390/jcm5120115 - 08 Dec 2016

Cited by 17 | Viewed by 7629

Abstract

Bronchiectasis, a chronic lung disease characterised by cough and purulent sputum, recurrent infections, and airway damage, is associated with considerable morbidity and mortality. To date, treatment options have been limited to physiotherapy to clear sputum and antibiotics to treat acute infections. Over the [...] Read more.

Bronchiectasis, a chronic lung disease characterised by cough and purulent sputum, recurrent infections, and airway damage, is associated with considerable morbidity and mortality. To date, treatment options have been limited to physiotherapy to clear sputum and antibiotics to treat acute infections. Over the last decade, there has been significant progress in understanding the epidemiology, pathophysiology, and microbiology of this disorder. Over the last five years, methods of assessing severity have been developed, the role of macrolide antibiotic therapy in reducing exacerbations cemented, and inhaled antibiotic therapies show promise in the treatment of chronic Pseudomonas aeruginosa infection. Novel therapies are currently undergoing Phase 1 and 2 trials. This review aims to address the major developments within the field of bronchiectasis over this time. Full article

(This article belongs to the Special Issue Chronic Respiratory Diseases)

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Open AccessReview

A Review of Targeted Pulmonary Arterial Hypertension-Specific Pharmacotherapy

by Ali Ataya, Jessica Cope and Hassan Alnuaimat

J. Clin. Med. 2016, 5(12), 114; https://doi.org/10.3390/jcm5120114 - 06 Dec 2016

Cited by 13 | Viewed by 5364

Abstract

Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the [...] Read more.

Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways. Full article

(This article belongs to the Special Issue Novel Therapeutic Approaches for Pulmonary Arterial Hypertension)

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Open AccessReview

Diaphragm Dysfunction: Diagnostic Approaches and Management Strategies

by Bruno-Pierre Dubé and Martin Dres

J. Clin. Med. 2016, 5(12), 113; https://doi.org/10.3390/jcm5120113 - 05 Dec 2016

Cited by 109 | Viewed by 17457

Abstract

The diaphragm is the main inspiratory muscle, and its dysfunction can lead to significant adverse clinical consequences. The aim of this review is to provide clinicians with an overview of the main causes of uni- and bi-lateral diaphragm dysfunction, explore the clinical and [...] Read more.

The diaphragm is the main inspiratory muscle, and its dysfunction can lead to significant adverse clinical consequences. The aim of this review is to provide clinicians with an overview of the main causes of uni- and bi-lateral diaphragm dysfunction, explore the clinical and physiological consequences of the disease on lung function, exercise physiology and sleep and review the available diagnostic tools used in the evaluation of diaphragm function. A particular emphasis is placed on the clinical significance of diaphragm weakness in the intensive care unit setting and the use of ultrasound to evaluate diaphragmatic action. Full article

(This article belongs to the Special Issue Chronic Respiratory Diseases)

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Open AccessArticle

Hyaluronic Acid Gel-Based Scaffolds as Potential Carrier for Growth Factors: An In Vitro Bioassay on Its Osteogenic Potential

by Masako Fujioka-Kobayashi, Benoit Schaller, Eizaburo Kobayashi, Maria Hernandez, Yufeng Zhang and Richard J. Miron

J. Clin. Med. 2016, 5(12), 112; https://doi.org/10.3390/jcm5120112 - 30 Nov 2016

Cited by 19 | Viewed by 6255

Abstract

Hyaluronic acid (HA) has been utilized for a variety of regenerative medical procedures due to its widespread presence in connective tissue and perceived biocompatibility. The aim of the present study was to investigate HA in combination with recombinant human bone morphogenetic protein 9 [...] Read more.

Hyaluronic acid (HA) has been utilized for a variety of regenerative medical procedures due to its widespread presence in connective tissue and perceived biocompatibility. The aim of the present study was to investigate HA in combination with recombinant human bone morphogenetic protein 9 (rhBMP9), one of the most osteogenic growth factors of the BMP family. HA was first combined with rhBMP9 and assessed for the adsorption and release of rhBMP9 over 10 days by ELISA. Thereafter, ST2 pre-osteoblasts were investigated by comparing (1) control tissue culture plastic, (2) HA alone, and (3) HA with rhBMP9 (100 ng/mL). Cellular proliferation was investigated by a MTS assay at one, three and five days and osteoblast differentiation was investigated by alkaline phosphatase (ALP) activity at seven days, alizarin red staining at 14 days and real-time PCR for osteoblast differentiation markers. The results demonstrated that rhBMP9 adsorbed within HA scaffolds and was released over a 10-day period in a controlled manner. While HA and rhBMP9 had little effect on cell proliferation, a marked and pronounced effect was observed for cell differentiation. rhBMP9 significantly induced ALP activity, mRNA levels of collagen1α2, and ALP and osteocalcin (OCN) at three or 14 days. HA also demonstrated some ability to induce osteoblast differentiation by increasing mRNA levels of OCN and increasing alizarin red staining at 14 days. In conclusion, the results from the present study demonstrate that (1) HA may serve as a potential carrier for various growth factors, and (2) rhBMP9 is a potent and promising inducer of osteoblast differentiation. Future animal studies are now necessary to investigate this combination approach in vivo. Full article

(This article belongs to the Special Issue Bone Cell Biology and Transcriptional Regulation)

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Open AccessReview

Proteinase-Activated Receptor 2 Is a Novel Regulator of TGF-β Signaling in Pancreatic Cancer

by David Witte, Franziska Zeeh, Thomas Gädeken, Frank Gieseler, Bernhard H. Rauch, Utz Settmacher, Roland Kaufmann, Hendrik Lehnert and Hendrik Ungefroren

J. Clin. Med. 2016, 5(12), 111; https://doi.org/10.3390/jcm5120111 - 30 Nov 2016

Cited by 12 | Viewed by 7225

Abstract

TGF-β has a dual role in tumorigenesis, acting as a tumor suppressor in normal cells and in the early stages of tumor development while promoting carcinogenesis and metastasis in advanced tumor stages. The final outcome of the TGF-β response is determined by cell-autonomous [...] Read more.

TGF-β has a dual role in tumorigenesis, acting as a tumor suppressor in normal cells and in the early stages of tumor development while promoting carcinogenesis and metastasis in advanced tumor stages. The final outcome of the TGF-β response is determined by cell-autonomous mechanisms and genetic alterations such as genomic instability and somatic mutations, but also by a plethora of external signals derived from the tumor microenvironment, such as cell-to-cell interactions, growth factors and extracellular matrix proteins and proteolytic enzymes. Serine proteinases mediate their cellular effects via activation of proteinase-activated receptors (PARs), a subclass of G protein-coupled receptors that are activated by proteolytic cleavage. We have recently identified PAR2 as a factor required for TGF-β1-dependent cell motility in ductal pancreatic adenocarcinoma (PDAC) cells. In this article, we review what is known on the TGF-β-PAR2 signaling crosstalk and its relevance for tumor growth and metastasis. Since PAR2 is activated through various serine proteinases, it may couple TGF-β signaling to a diverse range of other physiological processes, such as local inflammation, systemic coagulation or pathogen infection. Moreover, since PAR2 controls expression of the TGF-β type I receptor ALK5, PAR2 may also impact signaling by other TGF-β superfamily members that signal through ALK5, such as myostatin and GDF15/MIC-1. If so, PAR2 could represent a molecular linker between PDAC development and cancer-related cachexia. Full article

(This article belongs to the Special Issue Biological and Clinical Aspects of TGF-beta in Carcinogenesis)

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Open AccessCase Report

Burkholderia contaminans Colonization from Contaminated Liquid Docusate (Colace) in a Immunocompetent Adult with Legionnaire’s Disease: Infection Control Implications and the Potential Role of Candida pellucosa

by Burke A. Cunha, John Gian, Bertamaria Dieguez, Elsa Santos-Cruz, Daniela Matassa, Steve Gerson, Pat Daniels, Carlos Rosales and Rodger P. Silletti

J. Clin. Med. 2016, 5(12), 110; https://doi.org/10.3390/jcm5120110 - 30 Nov 2016

Cited by 3 | Viewed by 5025

Abstract

Objective: B. contaminans was cultured from respiratory secretions and liquid docusate (Colace) in a Neurosurgical Intensive Care Unit (NICU) patient with community-acquired Legionnaire’s disease but not from another bottle given to the patient. Unexpectedly, C. pelliculosa was cultured from two bottles, but not [...] Read more.

Objective: B. contaminans was cultured from respiratory secretions and liquid docusate (Colace) in a Neurosurgical Intensive Care Unit (NICU) patient with community-acquired Legionnaire’s disease but not from another bottle given to the patient. Unexpectedly, C. pelliculosa was cultured from two bottles, but not the B. contaminans bottle or respiratory secretions. Methods: B. cepacia, later identified as B. contaminans, was cultured from a bottle of liquid docusate (Colace) dispensed to a non-cystic fibrosis patient. His respiratory secretions were colonized with B. contaminans. Results: Eradication of B. contaminans colonization in the patient’s respiratory secretions was attempted. With levofloxacin, B. contaminans developed multidrug resistance (MDR). Subsequent TMP-SMX therapy did not result in further MDR. Nine other ICU patients were given docusate from the same lot, but there were no other B. contaminans isolates. Conclusion: B. contaminans colonization of respiratory secretion may be difficult to eliminate. The significance of C. pelliculosa cultured from liquid docusate (Colace) remains to be elucidated. In this case, it appeared that B. contaminans may have inhibited the growth of C. pelliculosa in the same bottle. Others should be alerted to the possibility that C. pelliculosa may be present in B. contaminans–contaminated lots of liquid docusate (Colace). Full article

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Open AccessReview

Switching Roles of TGF-β in Cancer Development: Implications for Therapeutic Target and Biomarker Studies

by Nan Sun, Ayumu Taguchi and Samir Hanash

J. Clin. Med. 2016, 5(12), 109; https://doi.org/10.3390/jcm5120109 - 30 Nov 2016

Cited by 26 | Viewed by 5197

Abstract

TGF-β induces complicated and even opposite responses in numerous biological processes, e.g., tumor suppression in pre-malignant cells and metastasis promotion in cancer cells. However, the cellular contextual determinants of these different TGF-β roles remain elusive, and the driver genes triggering the determinants’ changes [...] Read more.

TGF-β induces complicated and even opposite responses in numerous biological processes, e.g., tumor suppression in pre-malignant cells and metastasis promotion in cancer cells. However, the cellular contextual determinants of these different TGF-β roles remain elusive, and the driver genes triggering the determinants’ changes have not been identified. Recently, however, several findings have provided new insights on the contextual determinants of Smads in TGF-β’s biological processes. These novel switches and their effectors may serve as prognostic biomarkers and therapeutic targets of TGF-β-mediated cancer progression. Full article

(This article belongs to the Special Issue Biological and Clinical Aspects of TGF-beta in Carcinogenesis)

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Open AccessArticle

Monitoring of Physiological Parameters to Predict Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review

by Ahmed M. Al Rajeh and John R. Hurst

J. Clin. Med. 2016, 5(12), 108; https://doi.org/10.3390/jcm5120108 - 25 Nov 2016

Cited by 47 | Viewed by 9184

Abstract

Introduction: The value of monitoring physiological parameters to predict chronic obstructive pulmonary disease (COPD) exacerbations is controversial. A few studies have suggested benefit from domiciliary monitoring of vital signs, and/or lung function but there is no existing systematic review. Objectives: To conduct a [...] Read more.

Introduction: The value of monitoring physiological parameters to predict chronic obstructive pulmonary disease (COPD) exacerbations is controversial. A few studies have suggested benefit from domiciliary monitoring of vital signs, and/or lung function but there is no existing systematic review. Objectives: To conduct a systematic review of the effectiveness of monitoring physiological parameters to predict COPD exacerbation. Methods: An electronic systematic search compliant with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. The search was updated to April 6, 2016. Five databases were examined: Medical Literature Analysis and Retrieval System Online, or MEDLARS Online (Medline), Excerpta Medica dataBASE (Embase), Allied and Complementary Medicine Database (AMED), Cumulative Index of Nursing and Allied Health Literature (CINAHL) and the Cochrane clinical trials database. Results: Sixteen articles met the pre-specified inclusion criteria. Fifteen of these articules reported positive results in predicting COPD exacerbation via monitoring of physiological parameters. Nine studies showed a reduction in peripheral oxygen saturation (SpO₂%) prior to exacerbation onset. Three studies for peak flow, and two studies for respiratory rate reported a significant variation prior to or at exacerbation onset. A particular challenge is accounting for baseline heterogeneity in parameters between patients. Conclusion: There is currently insufficient information on how physiological parameters vary prior to exacerbation to support routine domiciliary monitoring for the prediction of exacerbations in COPD. However, the method remains promising. Full article

(This article belongs to the Special Issue Chronic Respiratory Diseases)

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Open AccessReview

Inebilizumab, a B Cell-Depleting Anti-CD19 Antibody for the Treatment of Autoimmune Neurological Diseases: Insights from Preclinical Studies

by Ding Chen, Sandra Gallagher, Nancy L. Monson, Ronald Herbst and Yue Wang

J. Clin. Med. 2016, 5(12), 107; https://doi.org/10.3390/jcm5120107 - 24 Nov 2016

Cited by 73 | Viewed by 9310

Abstract

Exaggerated or inappropriate responses by B cells are an important feature in many types of autoimmune neurological diseases. The recent success of B-cell depletion in the treatment of multiple sclerosis (MS) has stimulated the development of novel B-cell-targeting therapies with the potential for [...] Read more.

Exaggerated or inappropriate responses by B cells are an important feature in many types of autoimmune neurological diseases. The recent success of B-cell depletion in the treatment of multiple sclerosis (MS) has stimulated the development of novel B-cell-targeting therapies with the potential for improved efficacy. CD19 has emerged as a promising target for the depletion of B cells as well as CD19-positive plasmablasts and plasma cells. Inebilizumab (MEDI-551), an anti-CD19 antibody with enhanced antibody-dependent cell-mediated cytotoxicity against B cells, is currently being evaluated in MS and neuromyelitis optica. This review discusses the role of B cells in autoimmune neurological disorders, summarizes the development of inebilizumab, and analyzes the recent results for inebilizumab treatment in an autoimmune encephalitis mouse model. The novel insights obtained from these preclinical studies can potentially guide future investigation of inebilizumab in patients. Full article

(This article belongs to the Special Issue B Cells in Autoimmunity)

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J. Clin. Med., Volume 5, Issue 12 (December 2016) – 12 articles

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