Journal of Clinical Medicine

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Open AccessReview

Bioengineering and Stem Cell Technology in the Treatment of Congenital Heart Disease

by Alexis Bosman, Michael J. Edel, Gillian Blue, Rodney J. Dilley, Richard P. Harvey and David S. Winlaw

J. Clin. Med. 2015, 4(4), 768-781; https://doi.org/10.3390/jcm4040768 - 22 Apr 2015

Cited by 2 | Viewed by 6527

Abstract

Congenital heart disease places a significant burden on the individual, family and community despite significant advances in our understanding of aetiology and treatment. Early research in ischaemic heart disease has paved the way for stem cell technology and bioengineering, which promises to improve [...] Read more.

Congenital heart disease places a significant burden on the individual, family and community despite significant advances in our understanding of aetiology and treatment. Early research in ischaemic heart disease has paved the way for stem cell technology and bioengineering, which promises to improve both structural and functional aspects of disease. Stem cell therapy has demonstrated significant improvements in cardiac function in adults with ischaemic heart disease. This finding, together with promising case studies in the paediatric setting, demonstrates the potential for this treatment in congenital heart disease. Furthermore, induced pluripotent stems cell technology, provides a unique opportunity to address aetiological, as well as therapeutic, aspects of disease. Full article

(This article belongs to the Special Issue iPS Cells for Modelling and Treatment of Human Diseases)

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Open AccessReview

Diagnosis and Management of Hyponatremia in Patients with Aneurysmal Subarachnoid Hemorrhage

by Neena I. Marupudi and Sandeep Mittal

J. Clin. Med. 2015, 4(4), 756-767; https://doi.org/10.3390/jcm4040756 - 21 Apr 2015

Cited by 17 | Viewed by 12251

Abstract

Hyponatremia is the most common, clinically-significant electrolyte abnormality seen in patients with aneurysmal subarachnoid hemorrhage. Controversy continues to exist regarding both the cause and treatment of hyponatremia in this patient population. Lack of timely diagnosis and/or providing inadequate or inappropriate treatment can increase [...] Read more.

Hyponatremia is the most common, clinically-significant electrolyte abnormality seen in patients with aneurysmal subarachnoid hemorrhage. Controversy continues to exist regarding both the cause and treatment of hyponatremia in this patient population. Lack of timely diagnosis and/or providing inadequate or inappropriate treatment can increase the risk of morbidity and mortality. We review recent literature on hyponatremia in subarachnoid hemorrhage and present currently recommended protocols for diagnosis and management. Full article

(This article belongs to the Special Issue Hyponatremia: Advances in Diagnosis and Management)

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Open AccessReview

Histamine and Skin Barrier: Are Histamine Antagonists Useful for the Prevention or Treatment of Atopic Dermatitis?

by Anna De Benedetto, Takeshi Yoshida, Sade Fridy, Joo-Eun S. Park, I.-Hsin Kuo and Lisa A. Beck

J. Clin. Med. 2015, 4(4), 741-755; https://doi.org/10.3390/jcm4040741 - 21 Apr 2015

Cited by 29 | Viewed by 10445

Abstract

Atopic Dermatitis (AD), the most common chronic inflammatory skin disease, is characterized by an overactive immune response to a host of environmental allergens and dry, itchy skin. Over the past decade important discoveries have demonstrated that AD develops in part from genetic and/or [...] Read more.

Atopic Dermatitis (AD), the most common chronic inflammatory skin disease, is characterized by an overactive immune response to a host of environmental allergens and dry, itchy skin. Over the past decade important discoveries have demonstrated that AD develops in part from genetic and/or acquired defects in the skin barrier. Histamine is an aminergic neurotransmitter involved in physiologic and pathologic processes such as pruritus, inflammation, and vascular leak. Enhanced histamine release has been observed in the skin of patients with AD and antihistamines are often prescribed for their sedating and anti-itch properties. Recent evidence suggests that histamine also inhibits the terminal differentiation of keratinocytes and impairs the skin barrier, raising the question whether histamine might play a role in AD barrier impairment. This, coupled with the notion that histamine’s effects mediated through the recently identified histamine receptor H4R, may be important in allergic inflammation, has renewed interest in this mediator in allergic diseases. In this paper we summarize the current knowledge on histamine and histamine receptor antagonists in AD and skin barrier function. Full article

(This article belongs to the Special Issue Epidemiology and Treatment of Atopic Eczema)

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Open AccessReview

Endoplasmic Reticulum Stress in the Diabetic Kidney, the Good, the Bad and the Ugly

by Robyn Cunard

J. Clin. Med. 2015, 4(4), 715-740; https://doi.org/10.3390/jcm4040715 - 20 Apr 2015

Cited by 60 | Viewed by 8469

Abstract

Diabetic kidney disease is the leading worldwide cause of end stage kidney disease and a growing public health challenge. The diabetic kidney is exposed to many environmental stressors and each cell type has developed intricate signaling systems designed to restore optimal cellular function. [...] Read more.

Diabetic kidney disease is the leading worldwide cause of end stage kidney disease and a growing public health challenge. The diabetic kidney is exposed to many environmental stressors and each cell type has developed intricate signaling systems designed to restore optimal cellular function. The unfolded protein response (UPR) is a homeostatic pathway that regulates endoplasmic reticulum (ER) membrane structure and secretory function. Studies suggest that the UPR is activated in the diabetic kidney to restore normal ER function and viability. However, when the cell is continuously stressed in an environment that lies outside of its normal physiological range, then the UPR is known as the ER stress response. The UPR reduces protein synthesis, augments the ER folding capacity and downregulates mRNA expression of genes by multiple pathways. Aberrant activation of ER stress can also induce inflammation and cellular apoptosis, and modify signaling of protective processes such as autophagy and mTORC activation. The following review will discuss our current understanding of ER stress in the diabetic kidney and explore novel means of modulating ER stress and its interacting signaling cascades with the overall goal of identifying therapeutic strategies that will improve outcomes in diabetic nephropathy. Full article

(This article belongs to the Special Issue Diabetic Nephropathy)

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Open AccessReview

Concise Review: Methods and Cell Types Used to Generate Down Syndrome Induced Pluripotent Stem Cells

by Youssef Hibaoui and Anis Feki

J. Clin. Med. 2015, 4(4), 696-714; https://doi.org/10.3390/jcm4040696 - 15 Apr 2015

Cited by 8 | Viewed by 7868

Abstract

Down syndrome (DS, trisomy 21), is the most common viable chromosomal disorder, with an incidence of 1 in 800 live births. Its phenotypic characteristics include intellectual impairment and several other developmental abnormalities, for the majority of which the pathogenetic mechanisms remain unknown. Several [...] Read more.

Down syndrome (DS, trisomy 21), is the most common viable chromosomal disorder, with an incidence of 1 in 800 live births. Its phenotypic characteristics include intellectual impairment and several other developmental abnormalities, for the majority of which the pathogenetic mechanisms remain unknown. Several models have been used to investigate the mechanisms by which the extra copy of chromosome 21 leads to the DS phenotype. In the last five years, several laboratories have been successful in reprogramming patient cells carrying the trisomy 21 anomaly into induced pluripotent stem cells, i.e., T21-iPSCs. In this review, we summarize the different T21-iPSCs that have been generated with a particular interest in the technical procedures and the somatic cell types used for the reprogramming. Full article

(This article belongs to the Special Issue iPS Cells for Modelling and Treatment of Human Diseases)

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Open AccessReview

Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

by Nestor R. Ramos, Clifton C. Mo, Judith E. Karp and Christopher S. Hourigan

J. Clin. Med. 2015, 4(4), 665-695; https://doi.org/10.3390/jcm4040665 - 10 Apr 2015

Cited by 95 | Viewed by 14637

Abstract

The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden [...] Read more.

The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for “complete” remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or refractory AML is generally poor. In this review, we outline the commonly utilized salvage cytotoxic therapy interventions and then highlight novel investigational efforts currently in clinical trials using both pathway-targeted agents and immunotherapy based approaches. We conclude that there is no current standard of care for adult relapsed or refractory AML other than offering referral to an appropriate clinical trial. Full article

(This article belongs to the Special Issue AML in the Molecular Age: From Biology to Clinical Management)

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Rational Combinations of Targeted Agents in AML

by Prithviraj Bose and Steven Grant

J. Clin. Med. 2015, 4(4), 634-664; https://doi.org/10.3390/jcm4040634 - 10 Apr 2015

Cited by 22 | Viewed by 9012

Abstract

Despite modest improvements in survival over the last several decades, the treatment of AML continues to present a formidable challenge. Most patients are elderly, and these individuals, as well as those with secondary, therapy-related, or relapsed/refractory AML, are particularly difficult to treat, owing [...] Read more.

Despite modest improvements in survival over the last several decades, the treatment of AML continues to present a formidable challenge. Most patients are elderly, and these individuals, as well as those with secondary, therapy-related, or relapsed/refractory AML, are particularly difficult to treat, owing to both aggressive disease biology and the high toxicity of current chemotherapeutic regimens. It has become increasingly apparent in recent years that coordinated interruption of cooperative survival signaling pathways in malignant cells is necessary for optimal therapeutic results. The modest efficacy of monotherapy with both cytotoxic and targeted agents in AML testifies to this. As the complex biology of AML continues to be elucidated, many “synthetic lethal” strategies involving rational combinations of targeted agents have been developed. Unfortunately, relatively few of these have been tested clinically, although there is growing interest in this area. In this article, the preclinical and, where available, clinical data on some of the most promising rational combinations of targeted agents in AML are summarized. While new molecules should continue to be combined with conventional genotoxic drugs of proven efficacy, there is perhaps a need to rethink traditional philosophies of clinical trial development and regulatory approval with a focus on mechanism-based, synergistic strategies. Full article

(This article belongs to the Special Issue AML in the Molecular Age: From Biology to Clinical Management)

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Open AccessReview

Safety and Efficacy Data on Vaccines and Immunization to Human Papillomavirus

by Natalie Kash, Michael A. Lee, Ramya Kollipara, Christopher Downing, Jacqueline Guidry and Stephen K. Tyring

J. Clin. Med. 2015, 4(4), 614-633; https://doi.org/10.3390/jcm4040614 - 03 Apr 2015

Cited by 73 | Viewed by 12008

Abstract

Since the discovery of the causal association between human papillomavirus (HPV) and cervical cancer, efforts to develop an effective prophylactic vaccine to prevent high-risk HPV infections have been at the forefront of modern medical research. HPV causes 530,000 cervical cancer cases worldwide, which [...] Read more.

Since the discovery of the causal association between human papillomavirus (HPV) and cervical cancer, efforts to develop an effective prophylactic vaccine to prevent high-risk HPV infections have been at the forefront of modern medical research. HPV causes 530,000 cervical cancer cases worldwide, which is the second most common cause of cancer deaths in women; a worldwide collaboration among epidemiologists, molecular biologists, vaccinologists, virologists, and clinicians helped lead to the development of two highly effective prophylactive HPV vaccines. The first, Gardasil, is a quadrivalent vaccine made up of recombinant HPV L1 capsid proteins from the two high-risk HPV types (16/18) responsible for 70% of cervical cancer cases as well as two low-risk HPV types (6/11) which are the causative agent for genital warts. The second, Cervarix, is a bivalent vaccine that was FDA approved three years after Gardasil and is also composed of L1 capsid proteins from HPV types 16/18. This review article focuses on the safety and efficacy data of both FDA-approved vaccines, as well as highlighting a few advances in future HPV vaccines that show promise in becoming additional treatment options for this worldwide disease. Full article

(This article belongs to the Special Issue Clinical Advances of Human Papillomaviruses)

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Open AccessReview

Biological Treatments in Atopic Dermatitis

by Andrea Montes-Torres, Mar Llamas-Velasco, Alejandra Pérez-Plaza, Guillermo Solano-López and Javier Sánchez-Pérez

J. Clin. Med. 2015, 4(4), 593-613; https://doi.org/10.3390/jcm4040593 - 03 Apr 2015

Cited by 53 | Viewed by 11316

Abstract

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases that affect both children and adults with a prevalence of 30% and 10%, respectively. Even though most of patients respond satisfactory to topical anti-inflammatory drugs, about 10% require one or [...] Read more.

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases that affect both children and adults with a prevalence of 30% and 10%, respectively. Even though most of patients respond satisfactory to topical anti-inflammatory drugs, about 10% require one or more systemic treatments to achieve good control of their illness. The progressive and increasingly detailed knowledge in the immunopathogenesis of AD has allowed research on new therapeutic targets with very promising results in the field of biological therapy. In this article, we will review the different biological treatments with a focus on novel drugs. Their mechanism of action, current status and results from clinical trials and observational studies will be specified. Full article

(This article belongs to the Special Issue Epidemiology and Treatment of Atopic Eczema)

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Open AccessReview

The Interaction between Human Immunodeficiency Virus and Human Papillomaviruses in Heterosexuals in Africa

by Anna-Lise Williamson

J. Clin. Med. 2015, 4(4), 579-592; https://doi.org/10.3390/jcm4040579 - 02 Apr 2015

Cited by 49 | Viewed by 6989

Abstract

Sub-Saharan Africa has the highest incidence of human papillomavirus (HPV) and cervical cancer in the world, which is further aggravated by the burden of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) disease with invasive cervical cancer being an AIDS-defining cancer. The prevalence of HPV [...] Read more.

Sub-Saharan Africa has the highest incidence of human papillomavirus (HPV) and cervical cancer in the world, which is further aggravated by the burden of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) disease with invasive cervical cancer being an AIDS-defining cancer. The prevalence of HPV infection and associated disease is very high in HIV-infected people and continues to be a problem even after anti-retroviral therapy. In the genital tract, the interaction between HPV and HIV is complex, with infection with multiple HPV types reported to make both women and men more susceptible to HIV infection. Besides the national programmes to vaccinate girls against HPV and screen women for cervical cancer, there should be targeted cervical cancer screening, treatment and prevention programmes introduced into HIV treatment centres. There is evidence that in high HIV prevalence areas, HIV-positive women could cause increases in the prevalence of genital HPV infection in HIV-negative men and so increase the HPV circulating in the community. Condom use and circumcision reduce the acquisition of HIV-1, and also to some extent of HPV. This review will highlight what is known about the interaction of HIV and HPV, with an emphasis on research in Africa. Full article

(This article belongs to the Special Issue Clinical Advances of Human Papillomaviruses)

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Patient-Specific iPSC-Derived RPE for Modeling of Retinal Diseases

by Huy V. Nguyen, Yao Li and Stephen H. Tsang

J. Clin. Med. 2015, 4(4), 567-578; https://doi.org/10.3390/jcm4040567 - 31 Mar 2015

Cited by 26 | Viewed by 7140

Abstract

Inherited retinal diseases, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world. Currently, treatments for these conditions are limited. Recently, considerable attention has been given to the possibility of using patient-specific induced pluripotent stem [...] Read more.

Inherited retinal diseases, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world. Currently, treatments for these conditions are limited. Recently, considerable attention has been given to the possibility of using patient-specific induced pluripotent stem cells (iPSCs) as a treatment for these conditions. iPSCs reprogrammed from adult somatic cells offer the possibility of generating patient-specific cell lines in vitro. In this review, we will discuss the current literature pertaining to iPSC modeling of retinal disease, gene therapy of iPSC-derived retinal pigmented epithelium (RPE) cells, and retinal transplantation. We will focus on the use of iPSCs created from patients with inherited eye diseases for testing the efficacy of gene or drug-based therapies, elucidating previously unknown mechanisms and pathways of disease, and as a source of autologous cells for cell replacement. Full article

(This article belongs to the Special Issue iPS Cells for Modelling and Treatment of Human Diseases)

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Using iPS Cells toward the Understanding of Parkinson’s Disease

by Roger Torrent, Francesca De Angelis Rigotti, Patrizia Dell'Era, Maurizio Memo, Angel Raya and Antonella Consiglio

J. Clin. Med. 2015, 4(4), 548-566; https://doi.org/10.3390/jcm4040548 - 30 Mar 2015

Cited by 43 | Viewed by 12856

Abstract

Cellular reprogramming of somatic cells to human pluripotent stem cells (iPSC) represents an efficient tool for in vitro modeling of human brain diseases and provides an innovative opportunity in the identification of new therapeutic drugs. Patient-specific iPSC can be differentiated into disease-relevant cell [...] Read more.

Cellular reprogramming of somatic cells to human pluripotent stem cells (iPSC) represents an efficient tool for in vitro modeling of human brain diseases and provides an innovative opportunity in the identification of new therapeutic drugs. Patient-specific iPSC can be differentiated into disease-relevant cell types, including neurons, carrying the genetic background of the donor and enabling de novo generation of human models of genetically complex disorders. Parkinson’s disease (PD) is the second most common age-related progressive neurodegenerative disease, which is mainly characterized by nigrostriatal dopaminergic (DA) neuron degeneration and synaptic dysfunction. Recently, the generation of disease-specific iPSC from patients suffering from PD has unveiled a recapitulation of disease-related cell phenotypes, such as abnormal α-synuclein accumulation and alterations in autophagy machinery. The use of patient-specific iPSC has a remarkable potential to uncover novel insights of the disease pathogenesis, which in turn will open new avenues for clinical intervention. This review explores the current Parkinson’s disease iPSC-based models highlighting their role in the discovery of new drugs, as well as discussing the most challenging limitations iPSC-models face today. Full article

(This article belongs to the Special Issue iPS Cells for Modelling and Treatment of Human Diseases)

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Open AccessArticle

Sick Leave and Factors Influencing Sick Leave in Adult Patients with Atopic Dermatitis: A Cross-Sectional Study

by Harmieke Van Os-Medendorp, Simone Appelman-Noordermeer, Carla Bruijnzeel-Koomen and Marjolein De Bruin-Weller

J. Clin. Med. 2015, 4(4), 535-547; https://doi.org/10.3390/jcm4040535 - 27 Mar 2015

Cited by 11 | Viewed by 6190

Abstract

Background: Little is known about the prevalence of sick leave due to atopic dermatitis (AD). The current literature on factors influencing sick leave is mostly derived from other chronic inflammatory diseases. This study aimed to determine the prevalence of sick leave due to [...] Read more.

Background: Little is known about the prevalence of sick leave due to atopic dermatitis (AD). The current literature on factors influencing sick leave is mostly derived from other chronic inflammatory diseases. This study aimed to determine the prevalence of sick leave due to AD and to identify influencing factors. Methods: A cross-sectional study was carried out in adult patients with AD. Outcome measures: sick leave during the two-week and one-year periods, socio-demographic characteristics, disease severity, quality of life and socio-occupational factors. Logistic regression analyses were used to determine influencing factors on sick leave over the two-week period. Results: In total, 253 patients were included; 12% of the patients had to take sick leave in the last two weeks due to AD and 42% in the past year. A higher level of symptom interference (OR 1.26; 95% CI 1.13–1.40) or perfectionism/diligence (OR 0.90; 95% CI 0.83–0.96) may respectively increase or decrease the number of sick leave days. Conclusion: Sick leave in patients with AD is a common problem and symptom interference and perfectionism/diligence appeared to influence it. Novel approaches are needed to deal with symptoms at work or school to reduce the amount of sick leave due to AD. Full article

(This article belongs to the Special Issue Epidemiology and Treatment of Atopic Eczema)

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Open AccessReview

The Potential of Vitamin D-Regulated Intracellular Signaling Pathways as Targets for Myeloid Leukemia Therapy

by Elzbieta Gocek and George P. Studzinski

J. Clin. Med. 2015, 4(4), 504-534; https://doi.org/10.3390/jcm4040504 - 25 Mar 2015

Cited by 15 | Viewed by 10280

Abstract

The current standard regimens for the treatment of acute myeloid leukemia (AML) are curative in less than half of patients; therefore, there is a great need for innovative new approaches to this problem. One approach is to target new treatments to the pathways [...] Read more.

The current standard regimens for the treatment of acute myeloid leukemia (AML) are curative in less than half of patients; therefore, there is a great need for innovative new approaches to this problem. One approach is to target new treatments to the pathways that are instrumental to cell growth and survival with drugs that are less harmful to normal cells than to neoplastic cells. In this review, we focus on the MAPK family of signaling pathways and those that are known to, or potentially can, interact with MAPKs, such as PI3K/AKT/FOXO and JAK/STAT. We exemplify the recent studies in this field with specific relevance to vitamin D and its derivatives, since they have featured prominently in recent scientific literature as having anti-cancer properties. Since microRNAs also are known to be regulated by activated vitamin D, this is also briefly discussed here, as are the implications of the emerging acquisition of transcriptosome data and potentiation of the biological effects of vitamin D by other compounds. While there are ongoing clinical trials of various compounds that affect signaling pathways, more studies are needed to establish the clinical utility of vitamin D in the treatment of cancer. Full article

(This article belongs to the Special Issue AML in the Molecular Age: From Biology to Clinical Management)

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J. Clin. Med., Volume 4, Issue 4 (April 2015) – 14 articles , Pages 504-781

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