Blimp-1–mediated CD4 T cell exhaustion causes CD8 T cell dysfunction during chronic toxoplasmosis

PubMed Central

Cobb, Dustin A.; Bhadra, Rajarshi

2016-01-01

CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported in Toxoplasma encephalitis (TE)–susceptible model, our current work demonstrates that CD4 not only become exhausted during chronic toxoplasmosis but this dysfunction is more pronounced than CD8 T cells. Exhausted CD4 population expressed elevated levels of multiple inhibitory receptors concomitant with the reduced functionality and up-regulation of Blimp-1, a transcription factor. Our data demonstrates for the first time that Blimp-1 is a critical regulator for CD4 T cell exhaustion especially in the CD4 central memory cell subset. Using a tamoxifen-dependent conditional Blimp-1 knockout mixed bone marrow chimera as well as an adoptive transfer approach, we show that CD4 T cell–intrinsic deletion of Blimp-1 reversed CD8 T cell dysfunction and resulted in improved pathogen control. To the best of our knowledge, this is a novel finding, which demonstrates the role of Blimp-1 as a critical regulator of CD4 dysfunction and links it to the CD8 T cell dysfunctionality observed in infected mice. The critical role of CD4-intrinsic Blimp-1 expression in mediating CD4 and CD8 T cell exhaustion may provide a rational basis for designing novel therapeutic approaches. PMID:27481131

Characterization of two homeodomain transcription factors with critical but distinct roles in virulence in the vascular pathogen Verticillium dahliae

USDA-ARS?s Scientific Manuscript database

Vascular wilt caused by Verticillium dahliae is a destructive disease that represents a chronic economic problem for crop production worldwide. In this work, we characterized two new regulators of pathogenicity in this species. Vph1 (VDAG_06555) was identified in a candidate gene approach as a putat...

The effects of chronic intracortical microstimulation on neural tissue and fine motor behavior.

PubMed

Rajan, Alexander T; Boback, Jessica L; Dammann, John F; Tenore, Francesco V; Wester, Brock A; Otto, Kevin J; Gaunt, Robert A; Bensmaia, Sliman J

2015-12-01

One approach to conveying sensory feedback in neuroprostheses is to electrically stimulate sensory neurons in the cortex. For this approach to be viable, it is critical that intracortical microstimulation (ICMS) causes minimal damage to the brain. Here, we investigate the effects of chronic ICMS on the neuronal tissue across a variety of stimulation regimes in non-human primates. We also examine each animal's ability to use their hand--the cortical representation of which is targeted by the ICMS--as a further assay of possible neuronal damage. We implanted electrode arrays in the primary somatosensory cortex of three Rhesus macaques and delivered ICMS four hours per day, five days per week, for six months. Multiple regimes of ICMS were delivered to investigate the effects of stimulation parameters on the tissue and behavior. Parameters included current amplitude (10-100 μA), pulse train duration (1, 5 s), and duty cycle (1/1, 1/3). We then performed a range of histopathological assays on tissue near the tips of both stimulated and unstimulated electrodes to assess the effects of chronic ICMS on the tissue and their dependence on stimulation parameters. While the implantation and residence of the arrays in the cortical tissue did cause significant damage, chronic ICMS had no detectable additional effect; furthermore, the animals exhibited no impairments in fine motor control. Chronic ICMS may be a viable means to convey sensory feedback in neuroprostheses as it does not cause significant damage to the stimulated tissue.

The effects of chronic intracortical microstimulation on neural tissue and fine motor behavior

NASA Astrophysics Data System (ADS)

Rajan, Alexander T.; Boback, Jessica L.; Dammann, John F.; Tenore, Francesco V.; Wester, Brock A.; Otto, Kevin J.; Gaunt, Robert A.; Bensmaia, Sliman J.

2015-12-01

Objective. One approach to conveying sensory feedback in neuroprostheses is to electrically stimulate sensory neurons in the cortex. For this approach to be viable, it is critical that intracortical microstimulation (ICMS) causes minimal damage to the brain. Here, we investigate the effects of chronic ICMS on the neuronal tissue across a variety of stimulation regimes in non-human primates. We also examine each animal’s ability to use their hand—the cortical representation of which is targeted by the ICMS—as a further assay of possible neuronal damage. Approach. We implanted electrode arrays in the primary somatosensory cortex of three Rhesus macaques and delivered ICMS four hours per day, five days per week, for six months. Multiple regimes of ICMS were delivered to investigate the effects of stimulation parameters on the tissue and behavior. Parameters included current amplitude (10-100 μA), pulse train duration (1, 5 s), and duty cycle (1/1, 1/3). We then performed a range of histopathological assays on tissue near the tips of both stimulated and unstimulated electrodes to assess the effects of chronic ICMS on the tissue and their dependence on stimulation parameters. Main results. While the implantation and residence of the arrays in the cortical tissue did cause significant damage, chronic ICMS had no detectable additional effect; furthermore, the animals exhibited no impairments in fine motor control. Significance. Chronic ICMS may be a viable means to convey sensory feedback in neuroprostheses as it does not cause significant damage to the stimulated tissue.

Managing painful chronic wounds: the Wound Pain Management Model.

PubMed

Price, Patricia; Fogh, Karsten; Glynn, Chris; Krasner, Diane L; Osterbrink, Jürgen; Sibbald, R Gary

2007-04-01

Chronic wound pain is not well understood and the literature is limited. Six of 10 patients venous leg ulcer experience pain with their ulcer, and similar trends are observed for other chronic wounds. Chronic wound pain can lead to depression and the feeling of constant tiredness. Pain related to the wound should be handled as one of the main priorities in chronic wound management together with addressing the cause. Management of pain in chronic wounds depends on proper assessment, reporting and documenting patient experiences of pain. Assessment should be based on six critical dimensions of the pain experience: location, duration, intensity, quality, onset and impact on activities of daily living. Holistic management must be based on a safe and effective mix of psychosocial approaches together with local and systemic pain management. It is no longer acceptable to ignore or inadequately document persistent wound pain and not to develop a treatment and monitoring strategy to improve the lives of persons with chronic wounds. Unless wound pain is optimally managed, patient suffering and costs to health care systems will increase.

Inhibition of p38 MAPK attenuates renal atrophy and fibrosis in a murine renal artery stenosis model.

PubMed

Wang, Diping; Warner, Gina M; Yin, Ping; Knudsen, Bruce E; Cheng, Jingfei; Butters, Kim A; Lien, Karen R; Gray, Catherine E; Garovic, Vesna D; Lerman, Lilach O; Textor, Stephen C; Nath, Karl A; Simari, Robert D; Grande, Joseph P

2013-04-01

Renal artery stenosis (RAS) is an important cause of chronic renal dysfunction. Recent studies have underscored a critical role for CCL2 (MCP-1)-mediated inflammation in the progression of chronic renal damage in RAS and other chronic renal diseases. In vitro studies have implicated p38 MAPK as a critical intermediate for the production of CCL2. However, a potential role of p38 signaling in the development and progression of chronic renal disease in RAS has not been previously defined. We sought to test the hypothesis that inhibition of p38 MAPK ameliorates chronic renal injury in mice with RAS. We established a murine RAS model by placing a cuff on the right renal artery and treated mice with the p38 inhibitor SB203580 or vehicle for 2 wk. In mice treated with vehicle, the cuffed kidney developed interstitial fibrosis, tubular atrophy, and interstitial inflammation. In mice treated with SB203580, the RAS-induced renal atrophy was reduced (70% vs. 39%, P < 0.05). SB203580 also reduced interstitial inflammation and extracellular matrix deposition but had no effect on the development of hypertension. SB203580 partially blocked the induction of CCL2, CCL7 (MCP-3), CC chemokine receptor 2 (CCR2), and collagen 4 mRNA expression in the cuffed kidneys. In vitro, blockade of p38 hindered both TNF-α and TGF-β-induced CCL2 upregulation. Based on these observations, we conclude that p38 MAPK plays a critical role in the induction of CCL2/CCL7/CCR2 system and the development of interstitial inflammation in RAS.

Elimination of the NLRP3-ASC Inflammasome Protects against Chronic Obesity-Induced Pancreatic Damage

PubMed Central

Youm, Yun-Hee; Adijiang, Ayinuer; Vandanmagsar, Bolormaa; Burk, David; Ravussin, Anthony

2011-01-01

Clinical evidence that the blockade of IL-1β in type-2 diabetic patients improves glycemia is indicative of an autoinflammatory mechanism that may trigger adiposity-driven pancreatic damage. IL-1β is a key contributor to the obesity-induced inflammation and subsequent insulin resistance, pancreatic β-cell dysfunction, and the onset of type 2 diabetes. Our previous studies demonstrated that the ceramides activate the Nod-like receptor family, pyrin domain containing 3 (Nlrp3) inflammasome to cause the generation of mature IL-1β and ablation of the Nlrp3 inflammasome in diet-induced obesity improves insulin signaling. However, it remains unclear whether the posttranslational processing of active IL-1β in pancreas is regulated by the NLRP3 inflammasome or whether the alternate mechanisms play a dominant role in chronic obesity-induced pancreatic β-cell exhaustion. Here we show that loss of ASC, a critical adaptor required for the assembly of the NLRP3 and absent in melanoma 2 inflammasome substantially improves the insulin action. Surprisingly, despite lower insulin resistance in the chronically obese NLRP3 and ASC knockout mice, the insulin levels were substantially higher when the inflammasome pathway was eliminated. The obesity-induced increase in maturation of pancreatic IL-1β and pancreatic islet fibrosis was dependent on the NLRP3 inflammasome activation. Furthermore, elimination of NLRP3 inflammasome protected the pancreatic β-cells from cell death caused by long-term high-fat feeding during obesity with significant increase in the size of the islets of Langerhans. Collectively, this study provides direct in vivo evidence that activation of the NLRP3 inflammasome in diet-induced obesity is a critical trigger in causing pancreatic damage and is an important mechanism of progression toward type 2 diabetes. PMID:21862613

Tobacco, the Common Enemy and a Gateway Drug: Policy Implications

ERIC Educational Resources Information Center

Torabi, Mohammad R.; Jun, Mi Kyung; Nowicke, Carole; Seitz de Martinez, Barbara; Gassman, Ruth

2010-01-01

For the four leading causes of death in the United States (heart disease, cancer, stroke and chronic respiratory disease), tobacco use is a common risk factor. Tobacco use is responsible for almost 450,000 deaths per year and impacts the health of every member of our society. Tobacco is a gateway drug for substance abuse. That role is critical to…

[Mental Health Promotion Among the Chronic Disabled Population in the Community].

PubMed

Huang, Hui-Chuan; Wang, Li-Hua; Chang, Hsiu-Ju

2015-08-01

Societal ageing and the rising prevalence of chronic disease are important causes that underlie the growth in the number of disabled individuals. The disease-induced psychological distress experienced by this population not only decreases quality of life but also increases demand for healthcare. The healthcare policy for the disabled population currently focuses on community healthcare. Therefore, developing appropriate programs to promote mental health among the disabled population in community settings is a critical issue. The present paper reviews current mental health promotion initiatives that target the disabled population in the community and addresses mental healthcare issues that are prevalent among the chronically disabled; strategies of mental health promotion that use music therapy, reminiscence therapy, and horticultural therapy; and the roles and responsibilities of community professionals in mental healthcare. We offer these perspectives as a reference to promote mental health and to establish holistic community healthcare for chronically disabled individuals.

Persistent inflammation, immunosuppression, and catabolism and the development of chronic critical illness after surgery.

PubMed

Efron, Philip A; Mohr, Alicia M; Bihorac, Azra; Horiguchi, Hiroyuki; Hollen, McKenzie K; Segal, Mark S; Baker, Henry V; Leeuwenburgh, Christiaan; Moldawer, Lyle L; Moore, Frederick A; Brakenridge, Scott C

2018-05-25

As early as the 1990s, chronic critical illness, a distinct syndrome of persistent high-acuity illness requiring management in the ICU, was reported under a variety of descriptive terms including the "neuropathy of critical illness," "myopathy of critical illness," "ICU-acquired weakness," and most recently "post-intensive care unit syndrome." The widespread implementation of targeted shock resuscitation, improved organ support modalities, and evidence-based protocolized ICU care has resulted in significantly decreased in-hospital mortality within surgical ICUs, specifically by reducing early multiple organ failure deaths. However, a new phenotype of multiple organ failure has now emerged with persistent but manageable organ dysfunction, high resource utilization, and discharge to prolonged care facilities. This new multiple organ failure phenotype is now clinically associated with the rapidly increasing incidence of chronic critical illness in critically ill surgery patients. Although the underlying pathophysiology driving chronic critical illness remains incompletely described, the persistent inflammation, immunosuppression, and catabolism syndrome has been proposed as a mechanistic framework in which to explain the increased incidence of chronic critical illness in surgical ICUs. The purpose of this review is to provide a historic perspective of the epidemiologic evolution of multiple organ failure into persistent inflammation, immunosuppression, and catabolism syndrome; describe the mechanism that drives and sustains chronic critical illness, and review the long-term outcomes of surgical patients who develop chronic critical illness. Copyright © 2018 Elsevier Inc. All rights reserved.

Host epithelial-viral interactions as cause and cure for asthma.

PubMed

Holtzman, Michael J; Patel, Dhara A; Zhang, Yong; Patel, Anand C

2011-08-01

Research on the pathogenesis of asthma has concentrated on initial stimuli, genetic susceptibilities, adaptive immune responses, and end-organ alterations (particularly in airway mucous cells and smooth muscle) as critical steps leading to disease. Recent evidence indicates that the innate immune cell response to respiratory viruses also contributes to the development of inflammatory airway disease. We further develop this concept by raising the issue that the interaction between host airway epithelial cells and respiratory viruses is another aspect of innate immunity that is also a critical determinant of asthma. We also introduce a rationale for how antiviral performance at the epithelial cell level might be improved to prevent acute infectious illness and chronic inflammatory disease caused by respiratory viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.

The PACE trial: It's time to broaden perceptions and move on.

PubMed

Petrie, Keith J; Weinman, John

2017-08-01

The continued critiques of the PACE trial highlight how differing beliefs about the causes of chronic fatigue syndrome still influence how scientific studies in this area are accepted and evaluated. Causal beliefs about chronic fatigue syndrome and a modern version of Cartesian dualism are important in understanding the reaction to the PACE trial. The continued debate on the PACE trial seems to miss the fact that science is incremental. An unfortunate outcome of the PACE controversy and intimidation of researchers may be less research in the area. It is time to move on from criticism and collect more data on effective treatments.

Chronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats.

PubMed

Hernández-Montiel, H L; Vásquez López, C M; González-Loyola, J G; Vega-Anaya, G C; Villagrán-Herrera, M E; Gallegos-Corona, M A; Saldaña, C; Ramos Gómez, M; García Horshman, P; García Solís, P; Solís-S, J C; Robles-Osorio, M L; Ávila Morales, J; Varela-Echavarría, A; Paredes Guerrero, R

2014-06-01

Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronic-degenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes.

Penalizing hospitals for chronic obstructive pulmonary disease readmissions.

PubMed

Feemster, Laura C; Au, David H

2014-03-15

In October 2014, the U.S. Centers for Medicare and Medicaid Services (CMS) will expand its Hospital Readmission Reduction Program (HRRP) to include chronic obstructive pulmonary disease (COPD). Under the new policy, hospitals with high risk-adjusted, 30-day all-cause unplanned readmission rates after an index hospitalization for a COPD exacerbation will be penalized with reduced reimbursement for the treatment of Medicare beneficiaries. In this perspective, we review the history of the HRRP, including the recent addition of COPD to the policy. We critically assess the use of 30-day all-cause COPD readmissions as an accountability measure, discussing potential benefits and then highlighting the substantial drawbacks and potential unintended consequences of the measure that could adversely affect providers, hospitals, and patients with COPD. We conclude by emphasizing the need to place the 30-day COPD readmission measure in the context of a reconceived model for postdischarge quality and review several frameworks that could help guide this process.

Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao Hongwei; Rahman, Irfan, E-mail: irfan_rahman@urmc.rochester.edu

Chronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-{kappa}B), autophagy and unfolded protein response leading to chronic lung inflammatorymore » response. Cigarette smoke also activates canonical/alternative NF-{kappa}B pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD.« less

Innate Immune Cytokines, Fibroblast Phenotypes, and Regulation of Extracellular Matrix in Lung.

PubMed

Richards, Carl D

2017-02-01

Chronic inflammation can be caused by adaptive immune responses in autoimmune and allergic conditions, driven by a T lymphocyte subset balance (TH1, TH2, Th17, Th22, and/or Treg) and skewed cellular profiles in an antigen-specific manner. However, several chronic inflammatory diseases have no clearly defined adaptive immune mechanisms that drive chronicity. These conditions include those that affect the lung such as nonatopic asthma or idiopathic pulmonary fibrosis comprising significant health problems. The remodeling of extracellular matrix (ECM) causes organ dysfunction, and it is largely generated by fibroblasts as the major cell controlling net ECM. As such, these are potential targets of treatment approaches in the context of ECM pathology. Fibroblast phenotypes contribute to ECM and inflammatory cell accumulation, and they are integrated into chronic disease mechanisms including cancer. Evidence suggests that innate cytokine responses may be critical in nonallergic/nonautoimmune disease, and they enable environmental agent exposure mechanisms that are independent of adaptive immunity. Innate immune cytokines derived from macrophage subsets (M1/M2) and innate lymphoid cell (ILC) subsets can directly regulate fibroblast function. We also suggest that STAT3-activating gp130 cytokines can sensitize fibroblasts to the innate cytokine milieu to drive phenotypes and exacerbate existing adaptive responses. Here, we review evidence exploring innate cytokine regulation of fibroblast behavior.

Anemia of Inflammation: A Review

PubMed Central

Fraenkel, Paula G.

2016-01-01

Impaired iron homeostasis and the suppressive effects of proinflammatory cytokines on erythropoiesis, together with alterations of the erythrocyte membrane that impair its survival, cause the anemia of inflammation. Recent epidemiologic studies have connected inflammatory anemia with critical illness, obesity, aging, and kidney failure, as well as with cancer, chronic infection, and autoimmune disease. The proinflammatory cytokine, interleukin-6, the iron regulatory hormone, hepcidin, and the iron exporter, ferroportin, interact to cause iron sequestration in the setting of inflammation. While severe anemia is associated with adverse outcomes in critical illness, experimental models suggest that iron sequestration is part of a natural defense against pathogens. In animal models and human patients, experimental therapeutic approaches targeting interleukin-6 or the ferroportin-hepcidin axis have shown efficacy in reversing anemia, although these agents have not yet been approved for the treatment of the anemia of inflammation. PMID:28189171

Infection in Venous Leg Ulcers: Considerations for Optimal Management in the Elderly.

PubMed

Pugliese, Douglas J

2016-02-01

Venous leg ulcers are the most common cause of chronic leg wounds, accounting for up to 70 % of all chronic leg ulcers and carrying with them a significant morbidity, especially for elderly patients. Among people aged 65 years and older, the annual prevalence is 1.7 %. Billions of dollars per year are spent caring for patients with these often difficult-to-heal and sometimes recurrent chronic wounds. Chronic non-healing wounds of the lower extremities are susceptible to microbial invasion and can lead to serious complications, such as delayed healing, cellulitis, enlargement of wound size, debilitating pain, and deeper wound infections causing systemic illness. Recognition and treatment of the infected venous leg ulcer is an essential skill set for any physician caring for geriatric patients. Most physicians rely on subjective clinical signs and patient-reported symptoms in the evaluation of infected chronic wounds. The conventional bacterial culture is a widely available tool for the diagnosis of bacterial infection but can have limitations. Systemic antibiotics, as well as topical antiseptics and antibiotics, can be employed to treat and control infection and critical colonization. Better understanding of microbial biofilms in the wound environment have caused them to emerge as an important reason for non-healing and infection due to their increased resistance to antimicrobial, immunological, and chemical attack. A sound understanding of the microbial-host environment and its complexities, as well as the pathophysiology of venous hypertension, must be appreciated to understand the need for a multimodality approach to treating an infected venous leg ulcer. Other treatment measures are often required, in addition to systemic and topical antibiotics, such as the application of wound bandages, compression therapy, and wound debridement, which can hasten clearance of the infection and help to promote healing.

Efficacy and safety of intravenous iron therapy as an alternative/adjunct to allogeneic blood transfusion.

PubMed

Muñoz, M; Breymann, C; García-Erce, J A; Gómez-Ramírez, S; Comin, J; Bisbe, E

2008-04-01

Anaemia is a common condition among patients admitted to hospital medicosurgical departments, as well as in critically ill patients. Anaemia is more frequently due to absolute iron deficiency (e.g. chronic blood loss) or functional iron deficiency (e.g. chronic inflammatory states), with other causes being less frequent. In addition, preoperative anaemia is one of the major predictive factors for perioperative blood transfusion. In surgical patients, postoperative anaemia is mainly caused by perioperative blood loss, and it might be aggravated by inflammation-induced inhibition of erythropoietin and functional iron deficiency (a condition that cannot be corrected by the administration of oral iron). All these mechanisms may be involved in the anaemia of the critically ill. Intravenous iron administration seems to be safe, as very few severe side-effects were observed, and may result in hastened recovery from anaemia and lower transfusion requirements. However, it is noteworthy that many of the recommendations given for intravenous iron treatment are not supported by a high level of evidence and this must be borne in mind when making decisions regarding its application to a particular patient. Nonetheless, this also indicates the need for further large, randomized controlled trials on the safety and efficacy of intravenous iron for the treatment of anaemia in different clinical settings.

Inhalable Antimicrobials for Treatment of Bacterial Biofilm-Associated Sinusitis in Cystic Fibrosis Patients: Challenges and Drug Delivery Approaches

PubMed Central

Kłodzińska, Sylvia Natalie; Priemel, Petra Alexandra; Rades, Thomas; Mørck Nielsen, Hanne

2016-01-01

Bacterial biofilm-associated chronic sinusitis in cystic fibrosis (CF) patients caused by Pseudomonas aeruginosa infections and the lack of available treatments for such infections constitute a critical aspect of CF disease management. Currently, inhalation therapies to combat P. aeruginosa infections in CF patients are focused mainly on the delivery of antimicrobials to the lower respiratory tract, disregarding the sinuses. However, the sinuses constitute a reservoir for P. aeruginosa growth, leading to re-infection of the lungs, even after clearing an initial lung infection. Eradication of P. aeruginosa from the respiratory tract after a first infection has been shown to delay chronic pulmonary infection with the bacteria for up to two years. The challenges with providing a suitable treatment for bacterial sinusitis include: (i) identifying a suitable antimicrobial compound; (ii) selecting a suitable device to deliver the drug to the sinuses and nasal cavities; and (iii) applying a formulation design, which will mediate delivery of a high dose of the antimicrobial directly to the site of infection. This review highlights currently available inhalable antimicrobial formulations for treatment and management of biofilm infections caused by P. aeruginosa and discusses critical issues related to novel antimicrobial drug formulation design approaches. PMID:27735846

Axon Transport and Neuropathy

PubMed Central

Tourtellotte, Warren G.

2017-01-01

Peripheral neuropathies are highly prevalent and are most often associated with chronic disease, side effects from chemotherapy, or toxic-metabolic abnormalities. Neuropathies are less commonly caused by genetic mutations, but studies of the normal function of mutated proteins have identified particular vulnerabilities that often implicate mitochondrial dynamics and axon transport mechanisms. Hereditary sensory and autonomic neuropathies are a group of phenotypically related diseases caused by monogenic mutations that primarily affect sympathetic and sensory neurons. Here, I review evidence to indicate that many genetic neuropathies are caused by abnormalities in axon transport. Moreover, in hereditary sensory and autonomic neuropathies. There may be specific convergence on gene mutations that disrupt nerve growth factor signaling, upon which sympathetic and sensory neurons critically depend. PMID:26724390

A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity

USGS Publications Warehouse

Lefebvre, Kathi A.; Frame, Elizabeth R.; Gulland, Frances; Hansen, John D.; Kendrick, Preston S.; Beyer, Richard P.; Bammler, Theo K.; Farin, Frederico M.; Hiolski, Emma M.; Smith, Donald R.; Marcinek, David J.

2012-01-01

The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity.

PubMed

Lefebvre, Kathi A; Frame, Elizabeth R; Gulland, Frances; Hansen, John D; Kendrick, Preston S; Beyer, Richard P; Bammler, Theo K; Farin, Frederico M; Hiolski, Emma M; Smith, Donald R; Marcinek, David J

2012-01-01

The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

Intestinal epithelial cells as producers but not targets of chronic TNF suffice to cause murine Crohn-like pathology

PubMed Central

Roulis, Manolis; Armaka, Maria; Manoloukos, Menelaos; Apostolaki, Maria; Kollias, George

2011-01-01

TNF plays a crucial role in the pathogenesis of Crohn disease. Dysregulated TNF production in mice that bear the genetic deletion of the TNF AU-rich regulatory elements (ARE) (TnfΔARE/+ mice) results in TNF receptor I (TNFRI)-dependent spontaneous Crohn-like pathology. Current concepts consider intestinal epithelial cell (IEC) responses to TNF to be critical for intestinal pathology, but the potential contribution of IEC-derived TNF in disease pathogenesis has not been addressed. In this study we examined whether IEC are sufficient as cellular targets or sources of TNF in the development of intestinal pathology. Using IEC-specific reactivation of a hypomorphic TnfΔAREneo allele in mice, we show that selective chronic overproduction of TNF by IEC suffices to cause full development of Crohn-like pathology. Epithelial TNF overexpression leads to early activation of the underlying intestinal myofibroblast, a cell type previously identified as a sufficient target of TNF for disease development in the TnfΔARE model. By contrast, restricted TNFRI expression on IEC although sufficient to confer IEC apoptosis after acute exogenous TNF administration, fails to induce pathology following chronic specific targeting of IEC by endogenous TNF in TnfΔARE/+ mice. Our results argue against IEC being early and sufficient responders to chronic TNF-mediated pathogenic signals and suggest that proinflammatory aberrations leading to chronic TNF production by IEC may initiate pathology in Crohn disease. PMID:21402942

Inflammation, cancer, and targets of ginseng.

PubMed

Hofseth, Lorne J; Wargovich, Michael J

2007-01-01

Chronic inflammation is associated with a high cancer risk. At the molecular level, free radicals and aldehydes, produced during chronic inflammation, can induce deleterious gene mutation and posttranslational modifications of key cancer-related proteins. Other products of inflammation, including cytokines, growth factors, and transcription factors such as nuclear factor kappaB, control the expression of cancer genes (e.g., suppressor genes and oncogenes) and key inflammatory enzymes such as inducible nitric oxide synthase and cyclooxygenase-2. These enzymes in turn directly influence reactive oxygen species and eicosanoid levels. The procancerous outcome of chronic inflammation is increased DNA damage, increased DNA synthesis, cellular proliferation, disruption of DNA repair pathways and cellular milieu, inhibition of apoptosis, and promotion of angiogenesis and invasion. Chronic inflammation is also associated with immunosuppression, which is a risk factor for cancer. Current treatment strategies for reactive species overload diseases are frequently aimed at treating or preventing the cause of inflammation. Although these strategies have led to some progress in combating reactive species overload diseases and associated cancers, exposure often occurs again after eradication, treatment to eradicate the cause fails, or the treatment has long-term side effects. Therefore, the identification of molecules and pathways involved in chronic inflammation and cancer is critical to the design of agents that may help in preventing the progression of reactive species overload disease and cancer associated with disease progression. Here, we use ginseng as an example of an antiinflammatory molecule that targets many of the key players in the inflammation-to-cancer sequence.

Mechanisms of Cachexia in Chronic Disease States

PubMed Central

Yoshida, Tadashi; Delafontaine, Patrice

2015-01-01

Sarcopenia and cachexia are muscle wasting syndromes associated with aging and with many chronic diseases such as congestive heart failure (CHF), diabetes, cancer, chronic obstructive pulmonary disease and chronic kidney disease (CKD). While mechanisms are complex these conditions are often accompanied by elevated angiotensin II (Ang II). Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme (ACE) inhibitor treatment improves weight loss. We found that Ang II infusion in rodents leads to skeletal muscle wasting. Ang II increases cytokines and circulating hormones such as tumor necrosis factor-α, interleukin-6, serum amyloid-A and glucocorticoids, which regulate muscle protein synthesis and degradation. Ang II-induced muscle wasting is caused by alterations in insulin-like growth factor-1 signaling, enhanced muscle protein breakdown via the ubiquitin-proteasome system, and decreased appetite resulting from downregulation of hypothalamic orexigenic neuropeptides such as Npy and orexin. Ang II also inhibits 5′ AMP-activated protein kinase (AMPK) activity and disrupts normal energy balance via activation of AMPK phosphatase PP2Cα. Furthermore, Ang II inhibits skeletal muscle stem (satellite) cell proliferation, leading to lowered muscle regenerative capacity. Distinct satellite cell angiotensin receptor subtypes have different effects on different stages of differentiation and are critical for regulation of muscle regeneration. These data suggest that the renin-angiotensin system (RAS) plays a critical role in mechanisms underlying cachexia in chronic disease states, and is a promising target for the treatment of muscle atrophy in patients with diseases such as CHF and CKD. PMID:26083652

Mechanisms of Cachexia in Chronic Disease States.

PubMed

Yoshida, Tadashi; Delafontaine, Patrice

2015-10-01

Sarcopenia and cachexia are muscle wasting syndromes associated with aging and with many chronic diseases, such as congestive heart failure (CHF), diabetes, cancer, chronic obstructive pulmonary disease and chronic kidney disease (CKD). While mechanisms are complex, these conditions are often accompanied by elevated angiotensin II (Ang II). Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme inhibitor treatment improves weight loss. It was found that Ang II infusion in rodents leads to skeletal muscle wasting. Ang II increases cytokines and circulating hormones, such as tumor necrosis factor-α, interleukin-6, serum amyloid-A and glucocorticoids, which regulate muscle protein synthesis and degradation. Ang II-induced muscle wasting is caused by alterations in insulin-like growth factor-1 signaling, enhanced muscle protein breakdown via the ubiquitin-proteasome system and decreased appetite resulting from the downregulation of hypothalamic orexigenic neuropeptides, such as Npy and orexin. Ang II also inhibits 5' adenosine monophosphate-activated protein kinase activity and disrupts normal energy balance via the activation of 5' adenosine monophosphate-activated protein kinase phosphatase PP2Cα. Furthermore, Ang II inhibits skeletal muscle stem (satellite) cell proliferation, leading to lowered muscle regenerative capacity. Distinct satellite cell angiotensin receptor subtypes have different effects on different stages of differentiation and are critical for the regulation of muscle regeneration. These data suggest that the renin-angiotensin system plays a critical role in mechanisms underlying cachexia in chronic disease states, and it is a promising target for the treatment of muscle atrophy in patients with diseases such as CHF and CKD.

Acute and Chronic Ethanol Exposure Differentially Regulate CB1 Receptor Function at Glutamatergic Synapses in the Rat Basolateral Amygdala

PubMed Central

Robinson, Stacey L.; Alexander, Nancy J.; Bluett, Rebecca J.; Patel, Sachin; McCool, Brian A.

2016-01-01

The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA. Chronic ethanol exposure significantly alters eCB system expression within regions critical to the expression of emotionality and anxiety-related behavior, including the BLA. Here, we investigated specific interactions between the BLA eCB system and its functional regulation of synaptic activity during acute and chronic ethanol exposure. In tissue from ethanol naïve-rats, a prolonged acute ethanol exposure caused a dose dependent inhibition of glutamatergic synaptic activity via a presynaptic mechanism that was occluded by CB1 antagonist/inverse agonists SR141716a and AM251. Importantly, this acute ethanol inhibition was attenuated following 10 day chronic intermittent ethanol vapor exposure (CIE). CIE exposure also significantly down-regulated CB1-mediated presynaptic inhibition at glutamatergic afferent terminals but spared CB1-inhibition of GABAergic synapses arising from local inhibitory-interneurons. CIE also significantly elevated BLA N-arachidonoylethanolamine (AEA or anandamide) levels and decreased CB1 receptor protein levels. Collectively, these data suggest a dynamic regulation of the BLA eCB system by acute and chronic ethanol. PMID:26707595

Airway mucus, inflammation and remodeling: emerging links in the pathogenesis of chronic lung diseases.

PubMed

Zhou-Suckow, Zhe; Duerr, Julia; Hagner, Matthias; Agrawal, Raman; Mall, Marcus A

2017-03-01

Airway mucus obstruction is a hallmark of many chronic lung diseases including rare genetic disorders such as cystic fibrosis (CF) and primary ciliary dyskinesia, as well as common lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), which have emerged as a leading cause of morbidity and mortality worldwide. However, the role of excess airway mucus in the in vivo pathogenesis of these diseases remains poorly understood. The generation of mice with airway-specific overexpression of epithelial Na + channels (ENaC), exhibiting airway surface dehydration (mucus hyperconcentration), impaired mucociliary clearance (MCC) and mucus plugging, led to a model of muco-obstructive lung disease that shares key features of CF and COPD. In this review, we summarize recent progress in the understanding of causes of impaired MCC and in vivo consequences of airway mucus obstruction that can be inferred from studies in βENaC-overexpressing mice. These studies confirm that mucus hyperconcentration on airway surfaces plays a critical role in the pathophysiology of impaired MCC, mucus adhesion and airway plugging that cause airflow obstruction and provide a nidus for bacterial infection. In addition, these studies support the emerging concept that excess airway mucus per se, probably via several mechanisms including hypoxic epithelial necrosis, retention of inhaled irritants or allergens, and potential immunomodulatory effects, is a potent trigger of chronic airway inflammation and associated lung damage, even in the absence of bacterial infection. Finally, these studies suggest that improvement of mucus clearance may be a promising therapeutic strategy for a spectrum of muco-obstructive lung diseases.

Predictors of long-term mortality following elective endovascular repair of abdominal aortic aneurysms.

PubMed

Marques-Rios, Guilherme; Oliveira-Pinto, José; Mansilha, Armando

2018-05-09

Endovascular aneurysm repair (EVAR) became the preferred modality for abdominal aortic aneurysm (AAA) repair. However, long term survival benefit may sometimes be questionable as many patients would die from other causes rather than aneurysm rupture. It is paramount to identify critical risk factors for late mortality after EVAR to understand its real benefit. The aim of this review is to identify most clinically relevant determinants of late mortality after elective EVAR. English literature was searched to identify publications on long-term predictors of mortality following elective EVAR. A follow-up extending for at least 5 years was the minimum required as inclusion criteria. Primary endpoint was all-cause mortality. We addressed clinical and demographic variables and observe if they had any associations with long-term all-cause mortality following EVAR. Thirteen studies were included describing more than 82306 patients, exploring at least one predictors of long-term mortality. All-cause mortality was associated to age (Hazard Ratio[HR] 1.06-3.34), gender (HR 1.07), aneurysm diameter (HR 1.09-1.64), smoking habits (HR 1.51-1.73), heart failure (HR 1.60-7.34), ischemic heart disease (HR 1.60), peripheral vascular disease (HR 1.30), cerebrovascular disease (HR 1.55), diabetes mellitus (HR 6.35), chronic obstructive pulmonary disease (HR 1.50-2.06) and chronic renal disease (HR 1.90-3.08). Risk factors associated with long-term mortality following elective EVAR remain scarcely published. Several demographic, anatomical, cardiovascular, pulmonary and renal co-morbidities seem to have an association with long-term mortality. Critical scrutiny of clinical patient status remains fundamental for a fair health resources allocation.

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

PubMed Central

Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

Effects of alcohol on the membrane excitability and synaptic transmission of medium spiny neurons in the nucleus accumbens

PubMed Central

Marty, Vincent N.; Spigelman, Igor

2013-01-01

Chronic and excessive alcohol drinking lead to alcohol dependence and loss of control over alcohol consumption, with serious detrimental health consequences. Chronic alcohol exposure followed by protracted withdrawal causes profound alterations in the brain reward system that leads to marked changes in reinforcement mechanisms and motivational state. These long-lasting neuroadaptations are thought to contribute to the development of cravings and relapse. The nucleus accumbens (NAcc), a central component of the brain reward system, plays a critical role in alcohol-induced neuroadaptive changes underlying alcohol-seeking behaviors. Here we review the findings that chronic alcohol exposure produces long-lasting neuroadaptive changes in various ion channels that govern intrinsic membrane properties and neuronal excitability, as well as excitatory and inhibitory synaptic transmission in the NAcc that underlie alcohol-seeking behavior during protracted withdrawal. PMID:22445807

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents.

PubMed

Eisenmann, Eric D; Rorabaugh, Boyd R; Zoladz, Phillip R

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions.

Cellular Therapies in Trauma and Critical Care Medicine: Forging New Frontiers

PubMed Central

Pati, Shibani; Pilia, Marcello; Grimsley, Juanita M.; Karanikas, Alexia T.; Oyeniyi, Blessing; Holcomb, John B.; Cap, Andrew P.; Rasmussen, Todd E.

2015-01-01

ABSTRACT Trauma is a leading cause of death in both military and civilian populations worldwide. Although medical advances have improved the overall morbidity and mortality often associated with trauma, additional research and innovative advancements in therapeutic interventions are needed to optimize patient outcomes. Cell-based therapies present a novel opportunity to improve trauma and critical care at both the acute and chronic phases that often follow injury. Although this field is still in its infancy, animal and human studies suggest that stem cells may hold great promise for the treatment of brain and spinal cord injuries, organ injuries, and extremity injuries such as those caused by orthopedic trauma, burns, and critical limb ischemia. However, barriers in the translation of cell therapies that include regulatory obstacles, challenges in manufacturing and clinical trial design, and a lack of funding are critical areas in need of development. In 2015, the Department of Defense Combat Casualty Care Research Program held a joint military–civilian meeting as part of its effort to inform the research community about this field and allow for effective planning and programmatic decisions regarding research and development. The objective of this article is to provide a “state of the science” review regarding cellular therapies in trauma and critical care, and to provide a foundation from which the potential of this emerging field can be harnessed to mitigate outcomes in critically ill trauma patients. PMID:26428845

Cellular Therapies in Trauma and Critical Care Medicine: Forging New Frontiers.

PubMed

Pati, Shibani; Pilia, Marcello; Grimsley, Juanita M; Karanikas, Alexia T; Oyeniyi, Blessing; Holcomb, John B; Cap, Andrew P; Rasmussen, Todd E

2015-12-01

Trauma is a leading cause of death in both military and civilian populations worldwide. Although medical advances have improved the overall morbidity and mortality often associated with trauma, additional research and innovative advancements in therapeutic interventions are needed to optimize patient outcomes. Cell-based therapies present a novel opportunity to improve trauma and critical care at both the acute and chronic phases that often follow injury. Although this field is still in its infancy, animal and human studies suggest that stem cells may hold great promise for the treatment of brain and spinal cord injuries, organ injuries, and extremity injuries such as those caused by orthopedic trauma, burns, and critical limb ischemia. However, barriers in the translation of cell therapies that include regulatory obstacles, challenges in manufacturing and clinical trial design, and a lack of funding are critical areas in need of development. In 2015, the Department of Defense Combat Casualty Care Research Program held a joint military-civilian meeting as part of its effort to inform the research community about this field and allow for effective planning and programmatic decisions regarding research and development. The objective of this article is to provide a "state of the science" review regarding cellular therapies in trauma and critical care, and to provide a foundation from which the potential of this emerging field can be harnessed to mitigate outcomes in critically ill trauma patients.

The epidemiology of chronic critical illness in the United States*.

PubMed

Kahn, Jeremy M; Le, Tri; Angus, Derek C; Cox, Christopher E; Hough, Catherine L; White, Douglas B; Yende, Sachin; Carson, Shannon S

2015-02-01

The epidemiology of chronic critical illness is not well characterized. We sought to determine the prevalence, outcomes, and associated costs of chronic critical illness in the United States. Population-based cohort study using data from the United States Healthcare Costs and Utilization Project from 2004 to 2009. Acute care hospitals in Massachusetts, North Carolina, Nebraska, New York, and Washington. Adult and pediatric patients meeting a consensus-derived definition for chronic critical illness, which included one of six eligible clinical conditions (prolonged acute mechanical ventilation, tracheotomy, stroke, traumatic brain injury, sepsis, or severe wounds) plus at least 8 days in an ICU. None. Out of 3,235,741 admissions to an ICU during the study period, 246,151 (7.6%) met the consensus definition for chronic critical illness. The most common eligibility conditions were prolonged acute mechanical ventilation (72.0% of eligible admissions) and sepsis (63.7% of eligible admissions). Among patients meeting chronic critical illness criteria through sepsis, the infections were community acquired in 48.5% and hospital acquired in 51.5%. In-hospital mortality was 30.9% with little change over the study period. The overall population-based prevalence was 34.4 per 100,000. The prevalence varied substantially with age, peaking at 82.1 per 100,000 individuals 75-79 years old but then declining coincident with a rise in mortality before day 8 in otherwise eligible patients. Extrapolating to the entire United States, for 2009, we estimated a total of 380,001 cases; 107,880 in-hospital deaths and $26 billion in hospital-related costs. Using a consensus-based definition, the prevalence, hospital mortality, and costs of chronic critical illness are substantial. Chronic critical illness is particularly common in the elderly although in very old patients the prevalence declines, in part because of an increase in early mortality among potentially eligible patients.

Vitamin D Status in Hospitalized Chronically Ill Patients.

PubMed

Botros, Raef Malak; AbdElsalam Besibes, Mona Mohamed; Bahaaeldin, Ahmed Mohamed; Abo Elyazed, Sherihan

2018-04-13

Vitamin D deficiency is rarely considered or treated in critically ill patients. Deficiency of 25-hydroxy vitamin D [25(OH)D] prior to hospital admission might be a significant predictor of short- and long-term all cause patient mortality in a critically ill patient. The aim of this work is to investigate the prevalence of vitamin D deficiency in hospitalized patients and its relation to the length of stay and outcome of hospitalization. Prospective cohort study performed on 80 patients admitted with acute deterioration of their chronic illness. Four groups of diseases were included, namely, chronic liver diseases (CLD), chronic obstructive pulmonary diseases (COPD), cerebrovascular stroke (CVS), and heart failure (HF). The patients were followed up until their discharge, or transfer, or death. Patients were sampled for their vitamin D level on admission and were divided according to their vitamin D status into sufficient, insufficient, and deficient. Statistical methods and analysis of the present study were conducted using the SPSS V17 program. Vitamin D level had a significant inverse correlation with length of hospital stay (r = -0.648) (p < 0.001). In vitamin D-deficient and -insufficient groups, there was a significant difference between survivors and nonsurvivors as regards vitamin D levels and an inverse correlation between vitamin D level and outcome of hospital admission. Vitamin D deficiency and insufficiency are significantly associated with a longer hospital stay and a poor outcome of hospital admission in comparison to control.

An Integrative Neuroscience Framework for the Treatment of Chronic Pain: From Cellular Alterations to Behavior.

PubMed

Greenwald, Jess D; Shafritz, Keith M

2018-01-01

Chronic pain can result from many pain syndromes including complex regional pain syndrome (CRPS), phantom limb pain and chronic low back pain, among others. On a molecular level, chronic pain syndromes arise from hypersensitization within the dorsal horn of the spinal cord, a process known as central sensitization. Central sensitization involves an upregulation of ionotropic and metabotropic glutamate receptors (mGluRs) similar to that of long-term potentiation (LTP). Regions of the brain in which LTP occurs, such as the amygdala and hippocampus, are implicated in fear- and memory-related brain circuity. Chronic pain dramatically influences patient quality of life. Individuals with chronic pain may develop pain-related anxiety and pain-related fear. The syndrome also alters functional connectivity in the default-mode network (DMN) and salience network. On a cellular/molecular level, central sensitization may be reversed through degradative glutamate receptor pathways. This, however, rarely happens. Instead, cortical brain regions may serve in a top-down regulatory capacity for the maintenance or alleviation of pain. Specifically, the medial prefrontal cortex (mPFC), which plays a critical role in fear-related brain circuits, the DMN, and salience network may be the driving forces in this process. On a cellular level, the mPFC may form new neural circuits through LTP that may cause extinction of pre-existing pain pathways found within fear-related brain circuits, the DMN, and salience network. In order to promote new LTP connections between the mPFC and other key brain structures, such as the amygdala and insula, we propose a holistic rehabilitation program including cognitive behavioral therapy (CBT) and revolving around: (1) cognitive reappraisals; (2) mindfulness meditation; and (3) functional rehabilitation. Unlike current medical interventions focusing upon pain-relieving medications, we do not believe that chronic pain treatment should focus on reversing the effects of central sensitization. Instead, we propose here that it is critical to focus on non-invasive efforts to promote new neural circuits originating from the mPFC.

Interventions to prevent respiratory diseases - Nutrition and the developing world.

PubMed

Karim, Tasneem; Muhit, Mohammad; Khandaker, Gulam

2017-03-01

Malnutrition is a major cause of morbidity and mortality in developing countries and nutrition plays a critical role in both acute and chronic respiratory conditions. Inadequacies in the nutritional requirements of a developing lung in utero and in early life can compromise the respiratory system integrity and result in poor lung function, reduced protection against infections, greater likelihood of acute illnesses in childhood and chronic illness in adulthood. Nutritional interventions harness great potential in reducing respiratory illness related morbidity and mortality in the developing world. In this review we have summarized the findings from published systematic reviews/meta-analysis, experimental and observational studies that looked into different nutritional interventions for preventing respiratory diseases in developing countries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Outcome and prognostic factors in critically ill patients with systemic lupus erythematosus: a retrospective study.

PubMed

Hsu, Chia-Lin; Chen, Kuan-Yu; Yeh, Pu-Sheng; Hsu, Yeong-Long; Chang, Hou-Tai; Shau, Wen-Yi; Yu, Chia-Li; Yang, Pan-Chyr

2005-06-01

Systemic lupus erythematosus (SLE) is an archetypal autoimmune disease, involving multiple organ systems with varying course and prognosis. However, there is a paucity of clinical data regarding prognostic factors in SLE patients admitted to the intensive care unit (ICU). From January 1992 to December 2000, all patients admitted to the ICU with a diagnosis of SLE were included. Patients were excluded if the diagnosis of SLE was established at or after ICU admission. A multivariate logistic regression model was applied using Acute Physiology and Chronic Health Evaluation II scores and variables that were at least moderately associated (P < 0.2) with survival in the univariate analysis. A total of 51 patients meeting the criteria were included. The mortality rate was 47%. The most common cause of admission was pneumonia with acute respiratory distress syndrome. Multivariate logistic regression analysis showed that intracranial haemorrhage occurring while the patient was in the ICU (relative risk = 18.68), complicating gastrointestinal bleeding (relative risk = 6.97) and concurrent septic shock (relative risk = 77.06) were associated with greater risk of dying, whereas causes of ICU admission and Acute Physiology and Chronic Health Evaluation II score were not significantly associated with death. The mortality rate in critically ill SLE patients was high. Gastrointestinal bleeding, intracranial haemorrhage and septic shock were significant prognostic factors in SLE patients admitted to the ICU.

The Use of Biologic Scaffolds in the Treatment of Chronic Nonhealing Wounds

PubMed Central

Turner, Neill J.; Badylak, Stephen F.

2015-01-01

Significance: Injuries to the skin as a result of illness or injury, particularly chronic nonhealing wounds, present a major healthcare problem. Traditional wound care approaches attempt to control the underlying causes, such as infection and ischemia, while the application of wound dressings aims to modify a poorly healing wound environment into a microenvironment more closely resembling an acute wound allowing the body to heal the wound naturally. Recent Advances: Regenerative medicine approaches, such as the use of biologic scaffold materials comprising an intact extracellular matrix (ECM) or individual components of the ECM, are providing new therapeutic options that focus upon the provision of biochemical cues that alter the wound microenvironment to facilitate rapid restoration of normal skin architecture. Critical Issues: The incidence of chronic nonhealing wounds continues to increase. For example, between 15% and 20% of diabetics are likely to develop chronic, nonhealing foot wounds creating an increasing burden on healthcare systems worldwide. Future Directions: Developing a thorough understanding of wound microenvironment and the mechanisms by which biologic scaffolds work in vivo has the potential to markedly improve outcomes in the clinical translation for the treatment of chronic wounds. PMID:26244105

Chronic Cocaine-Induced H3 Acetylation and Transcriptional Activation of CaMKIIα in the Nucleus Accumbens Is Critical for Motivation for Drug Reinforcement

PubMed Central

Wang, Lei; Lv, Zhigang; Hu, Zhaoyang; Sheng, Jian; Hui, Bin; Sun, Jie; Ma, Lan

2010-01-01

The regulation of gene expression in the brain reward regions is known to contribute to the pathogenesis and persistence of drug addiction. Increasing evidence suggests that the regulation of gene transcription is mediated by epigenetic mechanisms that alter the chromatin structure at specific gene promoters. To better understand the involvement of epigenetic regulation in drug reinforcement properties, rats were subjected to cocaine self-administration paradigm. Daily histone deacetylase (HDAC) inhibitor infusions in the shell of the nucleus accumbens (NAc) caused an upward shift in the dose-response curve under fixed-ratio schedule and increased the break point under progressive-ratio schedule, indicating enhanced motivation for self-administered drug. The effect of the HDAC inhibitor is attributed to the increased elevation of histone acetylation induced by chronic, but not acute, cocaine experience. In contrast, neutralizing the chronic cocaine-induced increase in histone modification by the bilateral overexpression of HDAC4 in the NAc shell reduced drug motivation. The association between the motivation for cocaine and the transcriptional activation of addiction-related genes by H3 acetylation in the NAc shell was analyzed. Among the genes activated by chronic cocaine experiences, the expression of CaMKIIα, but not CaMKIIβ, correlated positively with motivation for the drug. Lentivirus-mediated shRNA knockdown experiments showed that CaMKIIα, but not CaMKIIβ, in the NAc shell is essential for the maintenance of motivation to self-administered cocaine. These findings suggest that chronic drug-use-induced transcriptional activation of genes, such as CaMKIIα, modulated by H3 acetylation in the NAc is a critical regulatory mechanism underlying motivation for drug reinforcement. PMID:20010550

Effects of low-level chronic irradiation on radiosensitivity of mammals: modeling and experimental studies

NASA Astrophysics Data System (ADS)

Smirnova, O. A.; Yonezawa, M.

Effects of low dose rate chronic irradiation on radiosensitivity of mammals mice are studied by experimental and modeling methods Own and reference experiments show that priming chronic low-level short-term and long-term exposures to radiation induce respectively elevated radiosensitivity and lowered radiosensitivity radioresistance in mice The manifestation of these radiosensitization and radioprotection effects are respectively increased and decreased mortality of preirradiated specimens after challenge acute irradiation in comparison with those for previously unexposed ones Taking into account that the reason of the animal death in the experiments was the hematopoietic syndrome the biophysical models of the critical body system hematopoiesis are used to simulate the dynamics of the major hematopoietic lines in mice exposed to challenge acute irradiation following the chronic one Juxtaposition of the modeling results obtained and the relevant experimental data shows that the radiosensitization effect of chronic low-level short-term less than 1 month preirradiation on mice is due to increased radiosensitivity of lymphopoietic granulocytopoietic and erythropoietic systems accompanied by increased or close to the normal level radiosensitivity of thrombocytopoietic system which are induced by the above-indicated exposure In turn the radioprotection effect of chronic low-level long-term more than 1 month preirradiation on mice is caused by decreased radiosensitivity radioresistance of the granulocytopoietic system which

Effect of Chronic Diseases on Work Productivity: A Propensity Score Analysis.

PubMed

Fouad, Ahmed Mahmoud; Waheed, Amani; Gamal, Amira; Amer, Shaimaa Ahmed; Abdellah, Rasha Farouk; Shebl, Fatma Mohamed

2017-05-01

The aim of this study was to evaluate the effect of chronic disease(s) on work productivity. Using the Health & Work Performance Questionnaire, information was collected from 516 workers on chronic disease status and work productivity. Propensity-score matching was performed to identify matched-pairs of workers. In the propensity-score matched sample, workers with chronic diseases were more likely to have increased absenteeism and presenteeism rates, 6.34 and 2.36 times the rates if no chronic diseases, respectively. In addition, they had greater odds for getting negative critical work incidents and less odds for positive incidents than none or balanced status. Multimorbidity showed more significant increase in absenteeism and presenteeism rates, as well as increased odds for excess negative critical work incidents. Chronic disease(s) can significantly reduce work productivity by increasing absenteeism, presenteeism, and net negative critical incidents.

Resetting the transcription factor network reverses terminal chronic hepatic failure

PubMed Central

Nishikawa, Taichiro; Bell, Aaron; Brooks, Jenna M.; Setoyama, Kentaro; Melis, Marta; Han, Bing; Fukumitsu, Ken; Handa, Kan; Tian, Jianmin; Kaestner, Klaus H.; Vodovotz, Yoram; Locker, Joseph; Soto-Gutierrez, Alejandro; Fox, Ira J.

2015-01-01

The cause of organ failure is enigmatic for many degenerative diseases, including end-stage liver disease. Here, using a CCl4-induced rat model of irreversible and fatal hepatic failure, which also exhibits terminal changes in the extracellular matrix, we demonstrated that chronic injury stably reprograms the critical balance of transcription factors and that diseased and dedifferentiated cells can be returned to normal function by re-expression of critical transcription factors, a process similar to the type of reprogramming that induces somatic cells to become pluripotent or to change their cell lineage. Forced re-expression of the transcription factor HNF4α induced expression of the other hepatocyte-expressed transcription factors; restored functionality in terminally diseased hepatocytes isolated from CCl4-treated rats; and rapidly reversed fatal liver failure in CCl4-treated animals by restoring diseased hepatocytes rather than replacing them with new hepatocytes or stem cells. Together, the results of our study indicate that disruption of the transcription factor network and cellular dedifferentiation likely mediate terminal liver failure and suggest reinstatement of this network has therapeutic potential for correcting organ failure without cell replacement. PMID:25774505

Spouse criticism and hostility during marital interaction: effects on pain intensity and behaviors among individuals with chronic low back pain.

PubMed

Burns, John W; Post, Kristina M; Smith, David A; Porter, Laura S; Buvanendran, Asokumar; Fras, Anne Marie; Keefe, Francis J

2017-10-30

Individuals with chronic pain may experience negative responses from spouse, family, and friends. Responses such as overt criticism and hostility may be associated with worsening pain and function for chronic pain sufferers. We used a laboratory procedure to evaluate whether variability in spouse criticism/hostility exhibited toward chronic low back pain (CLBP) patients during a conflictual discussion predicted variability in patient pain and function during a subsequent pain-induction task. Chronic low back pain patients (n = 71) and their spouses (n = 71) participated in a 10-minute discussion followed by the patient undergoing a 10-minute structured pain behavior task (SPBT). Spouse criticism/hostility perceived by patients and patient Beck Depression Inventory-II (BDI) scores correlated significantly and positively with pain intensity during the SPBT, whereas perceived spouse hostility, patient BDI scores, and spouse trait hostility correlated significantly and positively with observed pain behaviors during the SPBT. Spouse criticism/hostility coded by raters from video recordings interacted significantly with patient BDI scores, such that observed spouse criticism/hostility was related significantly and positively with pain behaviors only for patients with high BDI scores. Patient sex interacted significantly with observed spouse criticism/hostility, such that observed spouse criticism/hostility was related significantly and positively with pain behaviors only for female patients. Results support the hypothesis that spouse criticism and hostility-actually expressed or perceived-may worsen CLBP patient symptoms. Further, women patients and patients high in depressive symptoms appeared most vulnerable to spouse criticism/hostility. Thus, negative marital communication patterns may be appropriate targets for intervention, especially among these 2 at risk groups.

Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury.

PubMed

Yang, Yi; Kimura-Ohba, Shihoko; Thompson, Jeffrey F; Salayandia, Victor M; Cossé, Melissa; Raz, Limor; Jalal, Fakhreya Y; Rosenberg, Gary A

2018-06-01

Vascular cognitive impairment is a major cause of dementia caused by chronic hypoxia, producing progressive damage to white matter (WM) secondary to blood-brain barrier (BBB) opening and vascular dysfunction. Tight junction proteins (TJPs), which maintain BBB integrity, are lost in acute ischemia. Although angiogenesis is critical for neurovascular remodeling, less is known about its role in chronic hypoxia. To study the impact of TJP degradation and angiogenesis during pathological progression of WM damage, we used the spontaneously hypertensive/stroke prone rats with unilateral carotid artery occlusion and Japanese permissive diet to model WM damage. MRI and IgG immunostaining showed regions with BBB damage, which corresponded with decreased endothelial TJPs, claudin-5, occludin, and ZO-1. Affected WM had increased expression of angiogenic factors, Ki67, NG2, VEGF-A, and MMP-3 in vascular endothelial cells and pericytes. To facilitate the study of angiogenesis, we treated rats with minocycline to block BBB disruption, reduce WM lesion size, and extend survival. Minocycline-treated rats showed increased VEGF-A protein, TJP formation, and oligodendrocyte proliferation. We propose that chronic hypoxia disrupts TJPs, increasing vascular permeability, and initiating angiogenesis in WM. Minocycline facilitated WM repair by reducing BBB damage and enhancing expression of TJPs and angiogenesis, ultimately preserving oligodendrocytes. Copyright © 2018 Elsevier Inc. All rights reserved.

Elevated plasma TGF-beta1 in renal diseases: cause or consequence?

PubMed

Junker, U; Haufe, C C; Nuske, K; Rebstock, K; Steiner, T; Wunderlich, H; Junker, K; Reinhold, D

2000-07-01

We previously reported elevated levels of TGF-beta1 in patients with renal carcinoma. Certain aspects led us to ask whether they might be caused by chronic damage to the kidney(s). Here we report on an extended set of patients with various renal diseases, lung cancer, humoral immunodeficiency and controls. For latent TGF-beta1 in plasma, we find that the control, immunodeficiency, lung cancer and kidney transplant groups do not differ significantly (means, 7.0-8.8 ng/ml). Also, acute short-term renal stress (extracorporal lithotrypsy) does not lead to an increase of TGF-beta1. However, the pyelonephritis patients present with levels of 19.0 ng/ml, chronic extracorporal dialysis patients with 15.5 ng/ml, and renal cell carcinoma patients with 22.8 ng/ml. For active TGF-beta1 these findings are exactly recovered. For serum levels, only the renal carcinoma group presents with significantly elevated levels of TGF-beta1. Kidney transplantation seems to normalize TGF-beta1 levels, while in the kidney cancer patients surgery has an effect only in part of the group. We conclude that elevated plasma TGF-beta1 levels are common in at least two chronic renal disease conditions, and that it normalizes with restoration of renal function. It is tempting to speculate that chronic elevation of TGF-beta1 in these patients may be critically involved in these conditions predisposing to renal cancer. Copyright 2000 Academic Press.

Salmonella Typhimurium gastroenteritis leading to chronic prosthetic vascular graft infection.

PubMed

Cullinan, Milo; Clarke, Michael; Dallman, Tim; Peart, Steven; Wilson, Deborah; Weiand, Daniel

2017-08-01

Introduction. It is estimated up to 6 % of prosthetic vascular grafts become infected. Staphylococcus aureus is predominant in early infection and coagulase-negative staphylococci are predominant in late infections. Enterobacteriaceae cause 14-40 % of prosthetic vascular graft infections. This is, to our knowledge the first reported case of Salmonella gastroenteritis causing chronic prosthetic vascular graft infection (PVGI). Case presentation. A 57 years old lady presented with signs and symptoms of prosthetic vascular graft infection. Three years earlier, she had undergone a prosthetic axillo-femoral bypass graft for critical limb ischaemia. The infected prosthetic vascular graft was removed and Salmonella Typhimurium was isolated on culture. In the intervening period, Salmonella Typhimurium was isolated from a faecal specimen, collected during an episode of acute gastroenteritis. Whole-genome sequencing (WGS) showed that the respective Salmonella Typhimurium isolates differed by only a single nucleotide polymorphism (SNP). Salmonella Typhimurium was not isolated on culture of a faecal specimen collected five days following cessation of antimicrobial therapy. Six months after removal of the prosthetic graft, the patient remains under follow-up for her peripheral vascular disease, which currently requires no further surgical intervention. Conclusion. This case has clear implications for the management of chronic PVGI. It is vital to collect high-quality surgical specimens for microbiological analysis and empirical choices of antibiotics are unlikely to cover all potential pathogens. It may also be prudent to enquire about a history of acute gastroenteritis when assessing patients presenting with chronic PVGI.

Chronic Alcohol Induces M2 Polarization Enhancing Pulmonary Disease Caused by Exposure to Particulate Air Pollution

PubMed Central

Thevenot, Paul; Saravia, Jordy; Giaimo, Joseph; Happel, Kyle I.; Dugas, Tammy R.; Cormier, Stephania A.

2013-01-01

Background Chronic alcohol consumption causes persistent oxidative stress in the lung, leading to impaired alveolar macrophage (AM) function and impaired immune responses. AMs play a critical role in protecting the lung from particulate matter (PM) inhalation by removing particulates from the airway and secreting factors which mediate airway repair. We hypothesized AM dysfunction caused by chronic alcohol consumption increases the severity of injury caused by particulate matter inhalation. Methods Age- and sex-matched C57BL6 mice were fed the Lieber-DeCarli liquid diet containing either alcohol or an iso-caloric substitution (control diet) for 8 weeks. Mice from both diet groups were exposed to combustion derived PM (CDPM) for the final 2 weeks. AM number, maturation, and polarization status were assessed by flow cytometry. Noninvasive and invasive strategies were used to assess pulmonary function and correlated with histomorphological assessments of airway structure and matrix deposition. Results Co-exposure to alcohol and CDPM decreased AM number and maturation status (CD11c expression) while increasing markers of M2 activation (IL-4Rα, Ym1, Fizz1 expression and IL-10 and TGF-β production). Changes in AM function were accompanied by decreased airway compliance and increased elastance. Altered lung function was attributable to elevated collagen content localized to the small airways and loss of alveolar integrity. Intranasal administration of neutralizing antibody to TGF-β during the CDPM exposure period improved changes in airway compliance and elastance while reducing collagen content caused by co-exposure. Conclusion CDPM inhalation causes enhanced disease severity in the alcoholic lung by stimulating the release of latent TGF-β stores in AMs. The combinatorial effect of elevated TGF-β, M2 polarization of AMs, and increased oxidative stress impairs pulmonary function by increasing airway collagen content and compromising alveolar integrity. PMID:23763452

Advance directives lessen the decisional burden of surrogate decision-making for the chronically critically ill.

PubMed

Hickman, Ronald L; Pinto, Melissa D

2014-03-01

To identify the relationships between advance directive status, demographic characteristics and decisional burden (role stress and depressive symptoms) of surrogate decision-makers (SDMs) of patients with chronic critical illness. Although the prevalence of advance directives among Americans has increased, SDMs are ultimately responsible for complex medical decisions of the chronically critically ill patient. Decisional burden has lasting psychological effects on SDMs. There is insufficient evidence on the influence of advance directives on the decisional burden of surrogate decision-makers of patients with chronic critical illness. The study was a secondary data analysis of cross-sectional data. Data were obtained from 489 surrogate decision-makers of chronically critically ill patients at two academic medical centres in Northeast Ohio, United States, between September 2005-May 2008. Data were collected using demographic forms and questionnaires. A single-item measure of role stress and the Center for Epidemiological Studies Depression (CESD) scale were used to capture the SDM's decisional burden. Descriptive statistics, t-tests, chi-square and path analyses were performed. Surrogate decision-makers who were nonwhite, with low socioeconomic status and low education level were less likely to have advance directive documentation for their chronically critically ill patient. The presence of an advance directive mitigates the decisional burden by directly reducing the SDM's role stress and indirectly lessening the severity of depressive symptoms. Most SDMs of chronically critically ill patients will not have the benefit of knowing the patient's preferences for life-sustaining therapies and consequently be at risk of increased decisional burden. Study results are clinically useful for patient education on the influence of advance directives. Patients may be informed that SDMs without advance directives are at risk of increased decisional burden and will require decisional support to facilitate patient-centred decision-making. © 2013 John Wiley & Sons Ltd.

Management of a rare case of arytenoid mucosa oedema inducing stridor and cough.

PubMed

De Corso, Eugenio; Pandolfini, Manlio; Battista, Maripina; Della Marca, Giacomo; Scarano, Emanuele

2013-09-01

Current guidelines recommend a multidisciplinary systematic integrated approach to patient with chronic cough in which nowadays otolaryngologists play an increasingly valuable role as new procedures are used for evaluation and treatment. Surgery has been never taken into consideration to treat refractory chronic cough. We present a rare case of arytenoid mucosa oedema inducing stridor and cough, lasting 8 months, that critically affected the quality of life of a 15-year-old adolescent arrived to our emergency department with prominent arytenoid oedema causing paroxysmal cough and laryngeal stridor and that was successfully treated by laryngeal debridement. In this case report we observed that prominent swelling of arytenoid mucosa might sustain a vicious cycle of cough persistence and that laryngeal surgical debridement might interrupt it resolving the particular clinical condition. The description of this case could be of some help for clinicians to draw new insight about diagnosis and therapy of rare selected cases of chronic refractory cough. Published by Elsevier Ireland Ltd.

Innate Immune Evasion Mediated by Flaviviridae Non-Structural Proteins.

PubMed

Chen, Shun; Wu, Zhen; Wang, Mingshu; Cheng, Anchun

2017-10-07

Flaviviridae-caused diseases are a critical, emerging public health problem worldwide. Flaviviridae infections usually cause severe, acute or chronic diseases, such as liver damage and liver cancer resulting from a hepatitis C virus (HCV) infection and high fever and shock caused by yellow fever. Many researchers worldwide are investigating the mechanisms by which Flaviviridae cause severe diseases. Flaviviridae can interfere with the host's innate immunity to achieve their purpose of proliferation. For instance, dengue virus (DENV) NS2A, NS2B3, NS4A, NS4B and NS5; HCV NS2, NS3, NS3/4A, NS4B and NS5A; and West Nile virus (WNV) NS1 and NS4B proteins are involved in immune evasion. This review discusses the interplay between viral non-structural Flaviviridae proteins and relevant host proteins, which leads to the suppression of the host's innate antiviral immunity.

Chronic and catastrophic natural mortality of three common Caribbean reef corals

NASA Astrophysics Data System (ADS)

Bythell, J. C.; Gladfelter, E. H.; Bythell, M.

1993-11-01

Compared to catastrophic impacts from storms, disease epidemics and bleaching events, little is known about the effects of more routine chronic mortality in reef corals. To monitor this ongoing mortality, monthly visual assessments of the cause of tissue damage were related to mortality rates (changes in planar surface area) of tagged colonies of three common reef corals: Montastrea annularis, Porites astreoides and Diploria strigosa at Buck Island Reef National Monument, St. Croix, US Virgin Islands. During the study Hurricane Hugo, the most powerful cyclone to affect the area in at least 60 y, made a direct impact on the site. Effects of the hurricane were extremely localized, with certain exposed sites being almost completely razed while others showed no detectable changes in community structure. Mortality caused both by the hurricane and by other factors during the 26 month study varied between species and also between site locations around the island. Differences in susceptibility were not dependent solely on gross morphology, because two robust, massive species showed opposite responses to hurricane damage and chronic mortality. Diploria strigosa was virtually unaffected by chronic factors, but was heavily damaged at exposed sites during the hurricane. In contrast, mortality from predation and tissue necrosis was high in Montastrea annularis, but it largely escaped damage from the hurricane because it was absent from the most severely scoured locations. Porites astreoides, with populations dominated by much smaller colonies, was affected by both chronic and hurricanerelated mortality. Differences in susceptibility to the various types of natural disturbance among species, coupled with high spatial and temporal variability in the effects of such disturbances, may be critical to the maintenance of species diversity on the reef.

Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis.

PubMed

Zhang, Yumin; Liu, Gang; Yan, Jingqi; Zhang, Yalin; Li, Bo; Cai, Dongsheng

2015-04-07

Metabolic homeostasis is regulated by the brain, but whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help in balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipid levels. Importantly, this function of metabolic learning requires not only the mushroom body but also the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting that the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate that the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis.

GPCR-autoantibodies in chronic heart failure.

PubMed

Boivin-Jahns, Valerie; Jahns, Roland

2018-06-01

Chronic heart failure (CHF) is a syndrome characterized by shortness of breath, fluid retention, and a progressive reduction in cardiac function. More than 60% of the cases are ischemic in origin (i.e., due to myo-cardial infarction) and about 30% are caused by non-ischemic myocardial damage (i.e., due to genetic or non-genetic causes like myocardial inflammation). Because of alterations in both cellular and humoral immunity patients with non-ischemic CHF often develop abnormal or misled immune responses, including cross-reacting antibodies and/or autoantibodies to various cardiac anti-gens. Non-ischemic myo-cardial damage was found to progress to CHF particularly, when associated (a) with the generation of autoantibodies directed against distinct myocyte membrane proteins critically involved in cardiac function - like G-protein coup-led membrane receptors (GPCRs), or (b) with virus persistence in the myocardium. This article will review current knowledge on the pathophysiological relevance of GPCR-autoreactivity in CHF by giving an overview on the so far available evidence from pre-clinical, clinical and epidemiological studies on the CHF-inducing potential of GPCR-autoantibodies and thereon based novel therapeutic approaches in GPCR autoantibody-associated CHF.

Mandibular Actinomyces osteomyelitis complicating florid cemento-osseous dysplasia: case report

PubMed Central

2011-01-01

Background Apart from neoplastic processes, chronic disfiguring and destructive diseases of the mandible are uncommon. Case Presentation We report, perhaps for the first time, the simultaneous occurrence of two such conditions in one patient, in a case that emphasizes the importance of bone biopsy in establishing the correct diagnosis. Florid cemento-osseous dysplasia (FCOD) is a chronic, disfiguring condition of the maxillofacial region. This relatively benign disease is primarily observed in middle-aged women of African ancestry. Cervicofacial actinomycosis is an uncommon and progressive infection caused by bacilli of the Actinomyces genus that typically involves intraoral soft tissues but may also involve bone. The accurate diagnosis of actinomycosis is critical for successful treatment. A diagnosis of osteomyelitis caused by Actinomyces bacteria was diagnosed by bone biopsy in a 53 year-old African-American woman with a longstanding history of FCOD after she presented with a new draining ulcer overlying the mandible. Conclusions Clinicians should be aware of the possibility of actinomycosis arising in the setting of FCOD, and the importance of bone biopsy and cultures in arriving at a definitive and timely diagnosis. PMID:21777471

Mandibular Actinomyces osteomyelitis complicating florid cemento-osseous dysplasia: case report.

PubMed

Smith, Miller H; Harms, Paul W; Newton, Duane W; Lebar, Bill; Edwards, Sean P; Aronoff, David M

2011-07-21

Apart from neoplastic processes, chronic disfiguring and destructive diseases of the mandible are uncommon. We report, perhaps for the first time, the simultaneous occurrence of two such conditions in one patient, in a case that emphasizes the importance of bone biopsy in establishing the correct diagnosis. Florid cemento-osseous dysplasia (FCOD) is a chronic, disfiguring condition of the maxillofacial region. This relatively benign disease is primarily observed in middle-aged women of African ancestry. Cervicofacial actinomycosis is an uncommon and progressive infection caused by bacilli of the Actinomyces genus that typically involves intraoral soft tissues but may also involve bone. The accurate diagnosis of actinomycosis is critical for successful treatment. A diagnosis of osteomyelitis caused by Actinomyces bacteria was diagnosed by bone biopsy in a 53 year-old African-American woman with a longstanding history of FCOD after she presented with a new draining ulcer overlying the mandible. Clinicians should be aware of the possibility of actinomycosis arising in the setting of FCOD, and the importance of bone biopsy and cultures in arriving at a definitive and timely diagnosis.

Rutin protects against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion.

PubMed

Qu, Jie; Zhou, Qiong; Du, Ying; Zhang, Wei; Bai, Miao; Zhang, Zhuo; Xi, Ye; Li, Zhuyi; Miao, Jianting

2014-08-01

Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion. We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion (BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses. BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin. Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer's disease. © 2014 The British Pharmacological Society.

Emerging pharmacotherapy for treatment of traumatic brain injury: targeting hypopituitarism and inflammation.

PubMed

Paterniti, Irene; Cordaro, Marika; Navarra, Michele; Esposito, Emanuela; Cuzzocrea, Salvatore

2015-01-01

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the developed world. In particular, TBI is an important cause of death and disability in young adults with consequences ranging from physical disabilities to long-term cognitive, behavioural, psychological and social defects. There is a large body of evidence that suggest that TBI conditions may adversely affect pituitary function in both the acute and chronic phases of recovery. Prevalence of hypopituitarism, from total to isolated pituitary deficiency, ranges from 5 to 90%. The time interval between TBI and pituitary function evaluation is one of the major factors responsible for variations in the prevalence of hypopituitarism reported. Diagnosis of hypopituitarism and accurate treatment of pituitary disorders offers the opportunity to improve mortality and outcome in TBI conditions. The aim of this paper is to review the history and pathophysiology of TBI and to summarize the best evidence of TBI as a cause of pituitary deficiency. Moreover, in this article we will describe the multiple changes which occur within the hypothalamic-pituitary-thyroid axis in critical illness, giving rise to 'sick euthyroid syndrome', focus our attention on thyroid hormones circulating levels from the initial insult to critical illness.

Spouse Criticism/Hostility Toward Partners with Chronic Pain: The Role of Spouse Attributions for Patient Control over Pain Behaviors.

PubMed

Burns, John W; Gerhart, James; Post, Kristina M; Smith, David A; Porter, Laura S; Buvanendran, Asokumar; Fras, Anne Marie; Keefe, Francis J

2018-06-01

Spouse attributions regarding displays of pain behaviors by their partners with chronic pain may account for subsequent increases in spouse critical/hostile responses toward their partners. People with chronic low back pain (n = 105) and their pain-free spouses (n = 105) completed electronic diary measures five times per day for 14 consecutive days. Key items assessed spouse observations of patient pain behavior, attributions regarding these behaviors, and spouse critical/hostile responses toward patients. Results were: a) spouse observations of patient pain behavior at Time 1 predicted high levels of spouse critical/hostile responses toward the patient at Time 2; b) "internal" attributions (e.g., the patient was attempting to influence spouse's feelings) at Time 1 predicted high levels of spouse critical/hostile responses toward the patient at Time 2; c) internal attributions mediated links between spouse observed pain behaviors at Time 1 and levels of spouse critical/hostile responses at Time 2. Spouse observations of patient pain behavior was also related to an "external" attribution (i.e., patient pain behavior was due to pain condition), but this attribution was not a significant mediator. A vital factor linking spouse scrutiny to spouse critical/hostile responses may be the spouse's ascribed reasons for the patient's grimacing, bracing, complaining, and so forth. Results indicate that spouse internal and negative attributions for pain behaviors of their partners with chronic pain may influence subsequent spouse critical/hostile reactions to them. Findings suggest that replacing spouse internal and negative attributions with external, compassionate and accepting explanations may be useful therapeutic targets for couples coping with chronic pain. Copyright © 2018. Published by Elsevier Inc.

Respiratory Diseases Caused by Coal Mine Dust

PubMed Central

Laney, A. Scott; Weissman, David N.

2015-01-01

Objective To provide an update on respiratory diseases caused by coal mine dust. Methods This article presents the results of a literature review initially performed for an International Conference on Occupational and Environmental Lung Disease held in summer 2013. Results Coal mine dust causes a spectrum of lung diseases collectively termed coal mine dust lung disease (CMDLD). These include Coal Workers’ Pneumoconiosis, silicosis, mixed dust pneumoconiosis, dust-related diffuse fibrosis (which can be mistaken for idiopathic pulmonary fibrosis), and chronic obstructive pulmonary disease. CMDLD continues to be a problem in the United States, particularly in the central Appalachian region. Treatment of CMDLD is symptomatic. Those with end-stage disease are candidates for lung transplantation. Because CMDLD cannot be cured, prevention is critical. Conclusions Coal mine dust remains a relevant occupational hazard and miners remain at risk for CMDLD. PMID:25285970

Acute exacerbations of chronic obstructive pulmonary disease: diagnosis, management, and prevention in critically ill patients.

PubMed

Dixit, Deepali; Bridgeman, Mary Barna; Andrews, Liza Barbarello; Narayanan, Navaneeth; Radbel, Jared; Parikh, Amay; Sunderram, Jag

2015-06-01

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and is a substantial source of disability in the United States. Moderate-to-severe acute exacerbations of COPD (AECOPD) can progress to respiratory failure, necessitating ventilator assistance in patients in the intensive care unit (ICU). Patients in the ICU with AECOPD requiring ventilator support have higher morbidity and mortality rates as well as costs compared with hospitalized patients not in the ICU. The mainstay of management for patients with AECOPD in the ICU includes ventilator support (noninvasive or invasive), rapid-acting inhaled bronchodilators, systemic corticosteroids, and antibiotics. However, evidence supporting these interventions for the treatment of AECOPD in critically ill patients admitted to the ICU is scant. Corticosteroids have gained widespread acceptance in the management of patients with AECOPD necessitating ventilator assistance, despite their lack of evaluation in clinical trials as well as controversies surrounding optimal dosage regimens and duration of treatment. Recent studies evaluating the safety and efficacy of corticosteroids have found that higher doses are associated with increased adverse effects, which therefore support lower dosing strategies, particularly for patients admitted to the ICU for COPD exacerbations. This review highlights recent findings from the current body of evidence on nonpharmacologic and pharmacologic treatment and prevention of AECOPD in critically ill patients. In addition, the administration of bronchodilators using novel delivery devices in the ventilated patient and the conflicting evidence surrounding antibiotic use in AECOPD in the critically ill is explored. Further clinical trials, however, are warranted to clarify the optimal pharmacotherapy management for AECOPD, particularly in critically ill patients admitted to the ICU. © 2015 Pharmacotherapy Publications, Inc.

Long-Term Temporal Imprecision of Information Coding in the Anterior Cingulate Cortex of Mice with Peripheral Inflammation or Nerve Injury

PubMed Central

Li, Xiang-Yao; Wang, Ning; Wang, Yong-Jie; Zuo, Zhen-Xing; Koga, Kohei; Luo, Fei

2014-01-01

Temporal properties of spike firing in the central nervous system (CNS) are critical for neuronal coding and the precision of information storage. Chronic pain has been reported to affect cognitive and emotional functions, in addition to trigger long-term plasticity in sensory synapses and behavioral sensitization. Less is known about the possible changes in temporal precision of cortical neurons in chronic pain conditions. In the present study, we investigated the temporal precision of action potential firing in the anterior cingulate cortex (ACC) by using both in vivo and in vitro electrophysiological approaches. We found that peripheral inflammation caused by complete Freund's adjuvant (CFA) increased the standard deviation (SD) of spikes latency (also called jitter) of ∼51% of recorded neurons in the ACC of adult rats in vivo. Similar increases in jitter were found in ACC neurons using in vitro brain slices from adult mice with peripheral inflammation or nerve injury. Bath application of glutamate receptor antagonists CNQX and AP5 abolished the enhancement of jitter induced by CFA injection or nerve injury, suggesting that the increased jitter depends on the glutamatergic synaptic transmission. Activation of adenylyl cyclases (ACs) by bath application of forskolin increased jitter, whereas genetic deletion of AC1 abolished the change of jitter caused by CFA inflammation. Our study provides strong evidence for long-term changes of temporal precision of information coding in cortical neurons after peripheral injuries and explains neuronal mechanism for chronic pain caused cognitive and emotional impairment. PMID:25100600

Patient- and family-centered performance measures focused on actionable processes of care for persistent and chronic critical illness: protocol for a systematic review.

PubMed

Rose, Louise; Istanboulian, Laura; Allum, Laura; Burry, Lisa; Dale, Craig; Hart, Nicholas; Kydonaki, Claire; Ramsay, Pam; Pattison, Natalie; Connolly, Bronwen

2017-04-17

Approximately 5 to 10% of critically ill patients transition from acute critical illness to a state of persistent and in some cases chronic critical illness. These patients have unique and complex needs that require a change in the clinical management plan and overall goals of care to a focus on rehabilitation, symptom relief, discharge planning, and in some cases, end-of-life care. However, existing indicators and measures of care quality, and tools such as checklists, that foster implementation of best practices, may not be sufficiently inclusive in terms of actionable processes of care relevant to these patients. Therefore, the aim of this systematic review is to identify the processes of care, performance measures, quality indicators, and outcomes including reports of patient/family experience described in the current evidence base relevant to patients with persistent or chronic critical illness and their family members. Two authors will independently search from inception to November 2016: MEDLINE, Embase, CINAHL, Web of Science, the Cochrane Library, PROSPERO, the Joanna Briggs Institute and the International Clinical Trials Registry Platform. We will include all study designs except case series/reports of <10 patients describing their study population (aged 18 years and older) using terms such as persistent critical illness, chronic critical illness, and prolonged mechanical ventilation. Two authors will independently perform data extraction and complete risk of bias assessment. Our primary outcome is to determine actionable processes of care and interventions deemed relevant to patients experiencing persistent or chronic critical illness and their family members. Secondary outcomes include (1) performance measures and quality indicators considered relevant to our population of interest and (2) themes related to patient and family experience. We will use our systematic review findings, with data from patient, family member and clinician interviews, and a subsequent consensus building process to inform the development of quality metrics and tools to measure processes of care, outcomes and experience for patients experiencing persistent or chronic critical illness and their family members. PROSPERO CRD42016052715.

Communication about chronic critical illness.

PubMed

Nelson, Judith E; Mercado, Alice F; Camhi, Sharon L; Tandon, Nidhi; Wallenstein, Sylvan; August, Gary I; Morrison, R Sean

2007-12-10

Despite poor outcomes, life-sustaining treatments including mechanical ventilation are continued for a large and growing population of patients with chronic critical illness. This may be owing in part to a lack of understanding resulting from inadequate communication between clinicians and patients and families. Our objective was to investigate the informational needs of patients with chronic critical illness and their families and the extent to which these needs are met. In this prospective observational study conducted at 5 adult intensive care units in a large, university-affiliated hospital in New York, New York, 100 patients with chronic critical illness (within 3-7 days of elective tracheotomy for prolonged mechanical ventilation) or surrogates for incapacitated patients were surveyed using an 18-item questionnaire addressing communication about chronic critical illness. Main outcome measures included ratings of importance and reports of whether information was received about questionnaire items. Among 125 consecutive, eligible patients, 100 (80%) were enrolled; questionnaire respondents included 2 patients and 98 surrogates. For all items, more than 78% of respondents rated the information as important for decision making (>98% for 16 of 18 items). Respondents reported receiving no information for a mean (SD) of 9.0 (3.3) of 18 items, with 95% of respondents reporting not receiving information for approximately one-quarter of the items. Of the subjects rating the item as important, 77 of 96 (80%) and 69 of 74 (93%) reported receiving no information about expected functional status at hospital discharge and prognosis for 1-year survival, respectively. Many patients and their families may lack important information for decision making about continuation of treatment in the chronic phase of critical illness. Strategies for effective communication in this clinical context should be investigated and implemented.

Communication About Chronic Critical Illness

PubMed Central

Nelson, Judith E.; Mercado, Alice F.; Camhi, Sharon L.; Tandon, Nidhi; Wallenstein, Sylvan; August, Gary I.; Morrison, R. Sean

2008-01-01

Background Despite poor outcomes, life-sustaining treatments including mechanical ventilation are continued for a large and growing population of patients with chronic critical illness. This may be owing in part to a lack of understanding resulting from inadequate communication between clinicians and patients and families. Our objective was to investigate the informational needs of patients with chronic critical illness and their families and the extent to which these needs are met. Methods In this prospective observational study conducted at 5 adult intensive care units in a large, university-affiliated hospital in New York, New York, 100 patients with chronic critical illness (within 3–7 days of elective tracheotomy for prolonged mechanical ventilation) or surrogates for incapacitated patients were surveyed using an 18-item questionnaire addressing communication about chronic critical illness. Main outcome measures included ratings of importance and reports of whether information was received about questionnaire items. Results Among 125 consecutive, eligible patients, 100 (80%) were enrolled; questionnaire respondents included 2 patients and 98 surrogates. For all items, more than 78% of respondents rated the information as important for decision making (>98% for 16 of 18 items). Respondents reported receiving no information for a mean (SD) of 9.0 (3.3) of 18 items, with 95% of respondents reporting not receiving information for approximately one-quarter of the items. Of the subjects rating the item as important, 77 of 96 (80%) and 69 of 74 (93%) reported receiving no information about expected functional status at hospital discharge and prognosis for 1-year survival, respectively. Conclusions Many patients and their families may lack important information for decision making about continuation of treatment in the chronic phase of critical illness. Strategies for effective communication in this clinical context should be investigated and implemented. PMID:18071175

Untethering an unusual cause of kidney injury in a teenager with Down syndrome.

PubMed

Yen, Elizabeth; Miele, Niel F; Barone, Joseph G; Tyagi, Rachana; Weiss, Lynne S

2014-11-01

Acute kidney injury (AKI) is characterized by the acute nature and the inability of kidneys to maintain fluid homeostasis as well as adequate electrolyte and acid-base balance, resulting in an accumulation of nitrogenous waste and elevation of serum blood urea nitrogen and creatinine values. Acute kidney injury may be a single isolated event, yet oftentimes, it results from an acute chronic kidney disease. It is critical to seek out the etiology of AKI and to promptly manage the underlying chronic kidney disease to prevent comorbidities and mortality that may ensue. We described a case of a 16-year-old adolescent girl with Down syndrome who presented with AKI and electrolyte aberrance.Abdominal and renal ultrasounds demonstrated a significantly dilated bladder as well as frank hydronephrosis and hydroureter bilaterally. Foley catheter was successful in relieving the obstruction and improving her renal function. However, a magnetic resonance imaging was pursued in light of her chronic constipation and back pain, and it revealed a structural defect (tethered cord) that underlies a chronic process that was highly likely contributory to her AKI. She was managed accordingly with a guarded result and required long-term and close monitoring.

Hyper-resting brain entropy within chronic smokers and its moderation by Sex.

PubMed

Li, Zhengjun; Fang, Zhuo; Hager, Nathan; Rao, Hengyi; Wang, Ze

2016-07-05

Cigarette smoking is a chronic relapsing brain disorder, and remains a premier cause of morbidity and mortality. Functional neuroimaging has been used to assess differences in the mean strength of brain activity in smokers' brains, however less is known about the temporal dynamics within smokers' brains. Temporal dynamics is a key feature of a dynamic system such as the brain, and may carry information critical to understanding the brain mechanisms underlying cigarette smoking. We measured the temporal dynamics of brain activity using brain entropy (BEN) mapping and compared BEN between chronic non-deprived smokers and non-smoking controls. Because of the known sex differences in neural and behavioral smoking characteristics, comparisons were also made between males and females. Associations between BEN and smoking related clinical measures were assessed in smokers. Our data showed globally higher BEN in chronic smokers compared to controls. The escalated BEN was associated with more years of smoking in the right limbic area and frontal region. Female nonsmokers showed higher BEN than male nonsmokers in prefrontal cortex, insula, and precuneus, but the BEN sex difference in smokers was less pronounced. These findings suggest that BEN mapping may provide a useful tool for probing brain mechanisms related to smoking.

Integrated management of depression: improving system quality and creating effective interfaces.

PubMed

Myette, Thomas L

2008-04-01

Depression is a chronic recurrent condition and is a leading cause of work disability. Improving occupational outcomes for depression will require an integrated approach that incorporates best practices from the clinical, community, and workplace systems. This article briefly reviews recent quality improvement initiatives and promising practices in each system and then shifts to the importance of systems integration. An integrated chronic care model uses a sophisticated case management process to support essential relationships, facilitate key plans, and efficiently link the three systems to optimize clinical, economic, and occupational outcomes. An expanded role for employers and their agents in the management of depression and other chronic diseases is seen as fundamental to maintaining a healthy and productive workforce. To improve occupational outcomes for depression by integrating best practices from the clinical, community, and workplace systems. After a brief review of quality improvement initiatives and promising practices in each system, an integrated chronic care model is introduced. A case management process that links critical systems, supports essential relationships, and facilitates key plans is expected to result in improvements in clinical, economic, and occupational outcomes. Employers should be more engaged with clinical and community partners in the prevention and control of depression in affected employees.

Dehydration as a Cause of Chronic Kidney Disease: Role of Fructokinase

DTIC Science & Technology

2016-10-01

1 AWARD NUMBER: W81XWH-14-1-0270 TITLE: Dehydration as a Cause of Chronic Kidney Disease: Role of Fructokinase PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Dehydration as a Cause of Chronic Kidney Disease: Role of Fructokinase 5b. GRANT NUMBER: W81XWH-14-1-0270 5c...SUPPLEMENTARY NOTES 14. ABSTRACT Our studies evaluate how recurrent dehydration can cause chronic kidney disease, an important question for the

Management of Chronic Kidney Disease Patients in the Intensive Care Unit: Mixing Acute and Chronic Illness.

PubMed

De Rosa, Silvia; Samoni, Sara; Villa, Gianluca; Ronco, Claudio

2017-01-01

Patients with chronic kidney disease (CKD) are at high risk for developing critical illness and for admission to intensive care units (ICU). 'Critically ill CKD patients' frequently develop an acute worsening of renal function (i.e. acute-on-chronic, AoC) that contributes to long-term kidney dysfunction, potentially leading to end-stage kidney disease (ESKD). An integrated multidisciplinary effort is thus necessary to adequately manage the multi-organ damage of those kidney patients and contemporaneously reduce the progression of kidney dysfunction when they are critically ill. The aim of this review is to describe (1) the pathophysiological mechanisms underlying the development of AoC kidney dysfunction and its role in the progression toward ESKD; (2) the most common clinical presentations of critical illness among CKD/ESKD patients; and (3) the continuum of care for CKD/ESKD patients from maintenance hemodialysis/peritoneal dialysis to acute renal replacement therapy performed in ICU and, vice-versa, for AoC patients who develop ESKD. © 2017 S. Karger AG, Basel.

Experience with ibrutinib for first-line use in patients with chronic lymphocytic leukemia.

PubMed

Itchaki, Gilad; Brown, Jennifer R

2018-01-01

Ibrutinib is the first in-class, orally administered, Bruton's tyrosine kinase (BTK) inhibitor that abrogates the critical signaling downstream of the B-cell receptor (BCR). This signaling is required for B-cell survival, proliferation and interaction with the microenvironment. Ibrutinib proved active in preclinical models of lymphoproliferative diseases and achieved impressive response rates in heavily pretreated relapsed and refractory (R/R) patients with chronic lymphocytic leukemia (CLL). Ibrutinib prolonged survival compared to standard therapy and mitigated the effect of most poor prognostic factors in CLL, thus becoming the main therapeutic option in high-risk populations. Moreover, compared with standard chemoimmunotherapy (CIT) for adults, ibrutinib causes fewer cytopenias and infections, while having its own unique toxicity profile. Its efficacy in relapsed patients as well as its tolerability have led to its increased use in previously untreated patients, especially in those with poor prognostic markers and/or the elderly. This review elaborates on ibrutinib's unique toxicity profile and the mechanisms of acquired resistance leading to progression on ibrutinib, since both are critical for understanding the obstacles to its first-line use. We will further evaluate the data from ongoing clinical trials in this setting and explore future options for combination therapy.

Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells

PubMed Central

Odorizzi, Pamela M.; Pauken, Kristen E.; Paley, Michael A.; Sharpe, Arlene

2015-01-01

Programmed Death-1 (PD-1) has received considerable attention as a key regulator of CD8+ T cell exhaustion during chronic infection and cancer because blockade of this pathway partially reverses T cell dysfunction. Although the PD-1 pathway is critical in regulating established “exhausted” CD8+ T cells (TEX cells), it is unclear whether PD-1 directly causes T cell exhaustion. We show that PD-1 is not required for the induction of exhaustion in mice with chronic lymphocytic choriomeningitis virus (LCMV) infection. In fact, some aspects of exhaustion are more severe with genetic deletion of PD-1 from the onset of infection. Increased proliferation between days 8 and 14 postinfection is associated with subsequent decreased CD8+ T cell survival and disruption of a critical proliferative hierarchy necessary to maintain exhausted populations long term. Ultimately, the absence of PD-1 leads to the accumulation of more cytotoxic, but terminally differentiated, CD8+ TEX cells. These results demonstrate that CD8+ T cell exhaustion can occur in the absence of PD-1. They also highlight a novel role for PD-1 in preserving TEX cell populations from overstimulation, excessive proliferation, and terminal differentiation. PMID:26034050

Improving Communication About Serious Illness

ClinicalTrials.gov

2017-01-07

Critical Illness; Chronic Disease; Terminal Care; Palliative Care; Communication; Advance Care Planning; Neoplasm Metastasis; Lung Neoplasms; Pulmonary Disease, Chronic Obstructive; Heart Failure; End Stage Liver Disease; Kidney Failure, Chronic

M2 Macrophages Play Critical Roles in Progression of Inflammatory Liver Disease in Hepatitis C Virus Transgenic Mice.

PubMed

Ohtsuki, Takahiro; Kimura, Kiminori; Tokunaga, Yuko; Tsukiyama-Kohara, Kyoko; Tateno, Chise; Hayashi, Yukiko; Hishima, Tsunekazu; Kohara, Michinori

2016-01-01

Macrophages in liver tissue are widely defined as important inflammatory cells in chronic viral hepatitis due to their proinflammatory activity. We reported previously that interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) play significant roles in causing chronic hepatitis in hepatitis C virus (HCV) transgenic mice (S. Sekiguchi et al., PLoS One 7:e51656, 2012, http://dx.doi.org/10.1371/journal.pone.0051656). In addition, we showed that recombinant vaccinia viruses expressing an HCV nonstructural protein (rVV-N25) could protect against the progression of chronic hepatitis by suppression of macrophage activation. Here, we focus on the role of macrophages in liver disease progression in HCV transgenic mice and examine characteristic features of macrophages following rVV-N25 treatment. The number of CD11b(+) F4/80(+) CD11c(-) CD206(+) (M2) macrophages in the liver of HCV transgenic mice was notably increased compared to that of age-matched control mice. These M2 macrophages in the liver produced elevated levels of IL-6 and TNF-α. rVV-N25 infection suppressed the number and activation of M2 macrophages in liver tissue. These results suggested that inflammatory cytokines produced by M2-like macrophages contribute to the induction of chronic liver inflammation in HCV transgenic mice. Moreover, the therapeutic effect of rVV-N25 might be induced by the suppression of the number and activation of hepatic macrophages. HCV causes persistent infections that can lead to chronic liver diseases, liver fibrosis, and hepatocellular carcinoma; the search for an HCV curative is the focus of ongoing research. Recently, effective anti-HCV drugs have been developed; however, vaccine development still is required for the prevention and therapy of infection by this virus. We demonstrate here that M2 macrophages are important for the pathogenesis of HCV-caused liver diseases and additionally show that M2 macrophages contribute to the therapeutic mechanism observed following rVV-N25 treatment. Copyright © 2015 Ohtsuki et al.

M2 Macrophages Play Critical Roles in Progression of Inflammatory Liver Disease in Hepatitis C Virus Transgenic Mice

PubMed Central

Ohtsuki, Takahiro; Kimura, Kiminori; Tokunaga, Yuko; Tsukiyama-Kohara, Kyoko; Tateno, Chise; Hayashi, Yukiko; Hishima, Tsunekazu

2015-01-01

ABSTRACT Macrophages in liver tissue are widely defined as important inflammatory cells in chronic viral hepatitis due to their proinflammatory activity. We reported previously that interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) play significant roles in causing chronic hepatitis in hepatitis C virus (HCV) transgenic mice (S. Sekiguchi et al., PLoS One 7:e51656, 2012, http://dx.doi.org/10.1371/journal.pone.0051656). In addition, we showed that recombinant vaccinia viruses expressing an HCV nonstructural protein (rVV-N25) could protect against the progression of chronic hepatitis by suppression of macrophage activation. Here, we focus on the role of macrophages in liver disease progression in HCV transgenic mice and examine characteristic features of macrophages following rVV-N25 treatment. The number of CD11b+ F4/80+ CD11c− CD206+ (M2) macrophages in the liver of HCV transgenic mice was notably increased compared to that of age-matched control mice. These M2 macrophages in the liver produced elevated levels of IL-6 and TNF-α. rVV-N25 infection suppressed the number and activation of M2 macrophages in liver tissue. These results suggested that inflammatory cytokines produced by M2-like macrophages contribute to the induction of chronic liver inflammation in HCV transgenic mice. Moreover, the therapeutic effect of rVV-N25 might be induced by the suppression of the number and activation of hepatic macrophages. IMPORTANCE HCV causes persistent infections that can lead to chronic liver diseases, liver fibrosis, and hepatocellular carcinoma; the search for an HCV curative is the focus of ongoing research. Recently, effective anti-HCV drugs have been developed; however, vaccine development still is required for the prevention and therapy of infection by this virus. We demonstrate here that M2 macrophages are important for the pathogenesis of HCV-caused liver diseases and additionally show that M2 macrophages contribute to the therapeutic mechanism observed following rVV-N25 treatment. PMID:26468521

Overview of the causes of chronic diarrhea in children

USDA-ARS?s Scientific Manuscript database

The major causes and the prevalence of chronic diarrhea differ between developed and developing countries. In the developing world, chronic diarrhea is typically associated with serial enteric infections and malnutrition; it is manifested by a chronic enteropathy, with impaired mucosal healing, and ...

Chronic Pain in the Classroom: Teachers' Attributions about the Causes of Chronic Pain

ERIC Educational Resources Information Center

Logan, Deirdre E.; Catanese, Sarah P.; Coakley, Rachael M.; Scharff, Lisa

2007-01-01

Background: School absenteeism and other impairments in school function are significant problems among children with chronic pain syndromes; yet, little is known about how chronic pain is perceived in the school setting. The purpose of this study was to examine teachers' attributions about the causes of chronic pain in adolescent students.…

Chronic hypersensitivity pneumonitis: important considerations in the work-up of this fibrotic lung disease.

PubMed

Glazer, Craig S

2015-03-01

Chronic hypersensitivity pneumonitis is increasingly recognized as an important mimic of other fibrotic lung diseases. This review will summarize recent data regarding the importance and difficulty of determining causative exposures both for accurate diagnosis and prognosis, and describe the expanded pathologic spectrum of the disease, the effects of fibrosis on prognosis and challenges in the diagnostic evaluation. Several recent publications show the potential pathologic patterns induced by chronic hypersensitivity pneumonitis are broader than the classic triad of bronchiolitis, interstitial infiltrates and granulomas. Other pathologic patterns include nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia, bronchiolitis and airway centric fibrosis. Detecting a causative antigen in fibrotic hypersensitivity pneumonitis is challenging but critically important both for accurate diagnosis and improved prognosis. The prognosis in hypersensitivity pneumonitis worsens in the presence of fibrosis, but it remains significantly better than idiopathic pulmonary fibrosis. Hypersensitivity pneumonitis is increasingly recognized as an important cause of fibrotic interstitial lung disease. Hypersensitivity pneumonitis demonstrates a remarkable tendency to mimic other idiopathic interstitial pneumonias. A detailed exposure history remains a cornerstone of diagnosis and management.

Monoamine Transporter Inhibitors and Substrates as Treatments for Stimulant Abuse

PubMed Central

Howell, Leonard L.; Negus, S. Stevens

2015-01-01

The acute and chronic effects of abused psychostimulants on monoamine transporters and associated neurobiology have encouraged development of candidate medications that target these transporters. Monoamine transporters in general, and dopamine transporters in particular, are critical molecular targets that mediate abuse-related effects of psychostimulants such as cocaine and amphetamine. Moreover, chronic administration of psychostimulants can cause enduring changes in neurobiology reflected in dysregulation of monoamine neurochemistry and behavior. The current review will evaluate evidence for the efficacy of monoamine transporter inhibitors and substrates to reduce abuse-related effects of stimulants in preclinical assays of stimulant self-administration, drug discrimination and reinstatement. In considering deployment of monoamine transport inhibitors and substrates as agonist-type medications to treat stimulant abuse, the safety and abuse liability of the medications are an obvious concern, and this will also be addressed. Future directions in drug discovery should identify novel medications that retain efficacy to decrease stimulant use but possess lower abuse liability, and evaluate the degree to which efficacious medications can attenuate or reverse neurobiological effects of chronic stimulant use. PMID:24484977

Influence of work-related psychosocial factors on the prevalence of chronic pain and quality of life in patients with chronic pain

PubMed Central

Yamada, Keiko; Matsudaira, Ko; Imano, Hironori; Kitamura, Akihiko; Iso, Hiroyasu

2016-01-01

Objectives Working is a common cause of chronic pain for workers. However, most of them need to continue working despite the pain in order to make a living unless they get a sick leave or retirement. We hypothesised that the therapeutic effect of vocational rehabilitation may depend on psychosocial factors related to the workplace. To test this hypothesis, we examined the association of work-related psychosocial factors with the prevalence of chronic pain or health-related quality of life (HRQoL) among workers with chronic pain. Methods We examined 1764 workers aged 20–59 years in the pain-associated cross-sectional epidemiological survey in Japan. The outcomes were (1) chronic pain prevalence among all workers and (2) low Euro QoL (EQ-5D <0.76; mean value of the current study) prevalence among workers with chronic pain according to the degree of workplace social support and job satisfaction. Workplace social support and job satisfaction were measured using the Brief Job Stress Questionnaire. Multivariable-adjusted ORs were calculated using a logistic regression model including age, sex, smoking, exercise, sleep time, work hours, body mass index, personal consumption expenditure, intensity of pain and the presence of severe depressive symptoms. Results Chronic pain prevalence was higher among males reporting job dissatisfaction compared with those reporting job satisfaction. No difference was observed among women. Chronic pain prevalence did not differ between workers of either sex reporting poor workplace social support compared with those reporting sufficient support. Among workers with chronic pain, low HRQoL was more frequent in those reporting job dissatisfaction. Similarly, low HRQoL was more frequent in patients with chronic pain reporting poor social support from supervisors or co-workers compared with patients reporting sufficient support. Conclusions Work-related psychosocial factors are critical for HRQoL in patients with chronic pain. PMID:27113235

Therapeutic-diagnostic Evaluation of Chronic Cough Amongst Adults: Causes, Symptoms and Management at the Primary Care Level, Malaysia.

PubMed

Nantha, Yogarabindranath Swarna

2014-07-01

Patients presenting with chronic cough pose a common diagnostic dilemma during routine consultations at public primary care clinics in Malaysia. To date, there has been little attempt at designing a standardized model or algorithm to facilitate an accurate diagnosis of chronic cough. This study proposes a clinical method to detect the causes of chronic cough in a primary care setting in Malaysia. A total of 117 patients aged above 18 at an urban primary care clinic were tracked over a span of 5 months to diagnose the cause of chronic cough. A therapeutic-diagnostic method was employed to help identify the causes of chronic cough. Subsequently, the demographic details of patients, the prevalence of the different causes of chronic cough and the relationship between history and diagnosis were analyzed statistically. Chronic cough had a slightly higher male preponderance (51.3% vs. 48.7%). Patients within the 'above 60' age category had the highest frequency of chronic cough. The most common cause of chronic cough was post-infectious cough (n = 42, 35.9%), followed closely by angiotensin-converting enzyme-inhibitor related cough (n = 14, 12%). Majority of patients had the symptom of phlegm production (n = 41, 54%). 33 patients (29.2%) had recent upper respiratory tract infection (<2 weeks ago) prior to the diagnosis of chronic cough. There were poor association between symptoms and the various entities comprising chronic cough. The exceptions were the following associations: (1) Bronchial asthma and itchiness of throat (P = 0021), (2) gastroesophageal reflux disease and heartburn (P < 0.001), (3) upper airway cough syndrome and running nose (P = 0.016) and (4) pulmonary tuberculosis and absence of weight loss (P = 0.004). This study demonstrates that the effectiveness of a therapeutic-diagnostic technique in the diagnosis of chronic cough. Consistent with previous studies, there was poor association between most symptoms and the causes of chronic cough. A study involving a larger primary care population is required to confirm the findings found in this analysis.

Management of acute, recurrent, and chronic meningitides in adults.

PubMed

Cho, Tracey A; Venna, Nagagopal

2010-11-01

Meningitis (inflammation of the pia, arachnoid, and sometimes dura) has diverse causes and presentations. Although viruses are the most common cause of acute meningitis, bacterial meningitides are more severe and important to exclude because morbidity and mortality are high. Chronic meningitis has a broader range of causes, including atypical bacteria, fungi, and noninfectious causes. Presentation is more insidious but, if untreated, significant damage or death may ensue. Recurrent meningitis has many of the same causes as chronic meningitis, but manifestations occur in discrete episodes. Distinguishing between acute, chronic, and recurrent meningitis is essential for proper diagnostic testing and treatment approaches. Copyright 2010 Elsevier Inc. All rights reserved.

The social and psychological impact of endometriosis on women's lives: a critical narrative review.

PubMed

Culley, Lorraine; Law, Caroline; Hudson, Nicky; Denny, Elaine; Mitchell, Helene; Baumgarten, Miriam; Raine-Fenning, Nick

2013-01-01

BACKGROUND Endometriosis is a chronic condition affecting between 2 and 17% of women of reproductive age. Common symptoms are chronic pelvic pain, fatigue, congestive dysmenorrhoea, heavy menstrual bleeding and deep dyspareunia. Studies have demonstrated the considerable negative impact of this condition on women's quality of life (QoL), especially in the domains of pain and psychosocial functioning. The impact of endometriosis is likely to be exacerbated by the absence of an obvious cause and the likelihood of chronic, recurring symptoms. The aims of this paper are to review the current body of knowledge on the social and psychological impact of endometriosis on women's lives; to provide insights into women's experience of endometriosis; to provide a critical commentary on the current state of knowledge and to make recommendations for future psycho-social research. METHODS The review draws on a method of critical narrative synthesis to discuss a heterogeneous range of both quantitative and qualitative studies from several disciplines. This included a systematic search, a structured process for selecting and collecting data and a systematic thematic analysis of results. RESULTS A total of 42 papers were included in the review; 23 used quantitative methods, 16 used qualitative methods and 3 were mixed methods studies. The majority of papers came from just four countries: UK (10), Australia (8), Brazil (6) and the USA (5). Key categories of impact identified in the thematic analysis were diagnostic delay and uncertainty; 'QoL' and everyday activities; intimate relationships; planning for and having children; education and work; mental health and emotional wellbeing and medical management and self-management. CONCLUSIONS Endometriosis has a significant social and psychological impact on the lives of women across several domains. Many studies have methodological limitations and there are significant gaps in the literature especially in relation to a consideration of the impact on partners and children. We recommend additional prospective and longitudinal research utilizing mixed methods approaches and endometriosis-specific instruments to explore the impact of endometriosis in more diverse populations and settings. Furthermore, there is an urgent need to develop and evaluate interventions for supporting women and partners living with this chronic and often debilitating condition.

Do We Know What Causes Chronic Myeloid Leukemia?

MedlinePlus

... Be Prevented? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

An aberrant parasympathetic response: a new perspective linking chronic stress and itch.

PubMed

Kim, Hei Sung; Yosipovitch, Gil

2013-04-01

Perceived stress has long been known to alter the dynamic equilibrium established between the nervous, endocrine and immune system and is widely recognised to trigger or enhance pruritus. However, the exact mechanism of how the major stress response systems, such as the hypothalamus-pituitary adrenal (HPA) axis and the autonomic nervous system induce or aggravate chronic itch, has not been elucidated. The limbic regions of the brain such as the prefrontal cortex and hippocampus are deeply involved in the regulation of the stress response and intersect with circuits that are responsible for memory and reward. According to the 'Polyvagal Theory', certain limbic structures that serve as a 'higher brain equivalent of the parasympathetic nervous system' play a foremost role in maintaining body homoeostasis by functioning as an active vagal brake. In addition, the limbic system has been postulated to regulate two distinct, yet related aspects of itch: (i) the sensory-discriminative aspect; and (ii) the affective-cognitive aspect. Chronic stress-induced itch is hypothesised to be caused by stress-related changes in limbic structure with subsequent rewiring of both the peripheral and central pruriceptive circuits. Herein, we review data suggesting that a dysfunctional parasympathetic nervous system associated with chronic stress may play a critical role in the regulatory control of key candidate molecules, receptors and brain structures involved in chronic itch. © 2012 John Wiley & Sons A/S.

Implication of mGlu5 receptor in the enhancement of morphine-induced hyperlocomotion under chronic treatment with zolpidem.

PubMed

Shibasaki, Masahiro; Ishii, Kazunori; Masukawa, Daiki; Ando, Koji; Ikekubo, Yuiko; Ishikawa, Yutori; Shibasaki, Yumiko; Mori, Tomohisa; Suzuki, Tsutomu

2014-09-05

Long-term exposure to zolpidem induces drug dependence, and it is well known that the balance between the GABAergic and glutamatergic systems plays a critical role in maintaining the neuronal network. In the present study, we investigated the interaction between GABAA receptor α1 subunit and mGlu5 receptor in the limbic forebrain including the N.Acc. after treatment with zolpidem for 7 days. mGlu5 receptor protein levels were significantly increased after treatment with zolpidem for 7 days, and this change was accompanied by the up-regulation of phospholipase Cβ1 and calcium/calmodulin-dependent protein kinase IIα, which are downstream of mGlu5 receptor in the limbic forebrain. To confirm that mGlu5 receptor is directly involved in dopamine-related behavior in mice following chronic treatment with zolpidem, we measured morphine-induced hyperlocomotion after chronic treatment with zolpidem in the presence or absence of an mGlu5 receptor antagonist. Although chronic treatment with zolpidem significantly enhanced morphine-induced hyperlocomotion, this enhancement of morphine-induced hyperlocomotion was suppressed by treating it with the mGlu5 receptor antagonist MPEP. These results suggest that chronic treatment with zolpidem caused neural plasticity in response to activation of the mesolimbic dopaminergic system accompanied by an increase in mGlu5 receptor. Copyright © 2014 Elsevier B.V. All rights reserved.

Lessons About the Pathogenesis and Management of Aspergillosis from Studies in Chronic Granulomatous Disease

PubMed Central

Gallin, John I.; Zarember, Kol

2007-01-01

Chronic Granulomatous Disease (CGD) is a rare disorder caused by mutations in the NADPH oxidase. The CGD phenotype includes granuloma formation and susceptibility to infection with microorganisms including Aspergillus. The immune adjuvant interferon-γ and the antifungal agent itraconazole have reduced the incidence of infections in CGD. Studies using CGD phagocytes have shown that reactive oxygen species (ROS), products of the NAPDH oxidase, are critical for killing Aspergillus hyphae. But despite lack of ROS production, CGD patients generally only get infected with Aspergillus after heavy exposure. To study why CGD patients are not infected with Aspergillus more frequently we studied host defense against this ubiquitous mold further. We found that neutrophil lactoferrin is fungistatic for Aspergillus fumigatus spores by chelation of iron, an essential growth factor. Thus, the neutrophil employs both nonoxidative (lactoferrin) and oxidative (hydrogen peroxide) defense mechanisms against A. fumigatus spores and hyphae, respectively. PMID:18528501

Epidemiology and Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: Risk Factors and Mechanisms.

PubMed

Medrek, Sarah; Safdar, Zeenat

2016-01-01

Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when thromboemboli travel to the pulmonary vasculature, fail to resolve, and cause elevated pulmonary arterial pressure. Untreated, this disease leads to progressive right heart failure and death. It develops in approximately 1% to 5% of patients who suffer an acute pulmonary embolism (PE) and has an overall incidence of 3 to 30 per million in the general population. While it is not entirely evident why most but not all people are able to clear this clot burden, there are known risk factors for the development of CTEPH. These include signs of right heart strain at the time of incident PE, inherited coagulopathies, inflammatory conditions, hypothyroidism, and a history of splenectomy. Since CTEPH can be treated both surgically and medically, it is critical to understand the pathophysiology of the disease so affected patients can be identified and diagnosed appropriately.

Diagnosis and management of neuropathic pain: a balanced approach to treatment.

PubMed

Nicholson, Bruce D

2003-12-01

To provide nurse practitioners with a conceptual framework from which to diagnose and manage chronic neuropathic pain, specifically postherpetic neuralgia (PHN). A current review of the available treatment options for the management of neuropathic pain and PHN is provided. A comprehensive literature review was conducted. Clinical articles, meta-analyses, and reviews were selected for their relevance to the diagnosis and management of chronic neuropathic pain and PHN. Managing patients with chronic neuropathic pain is a common clinical challenge due to variability in individual symptoms, mechanisms, and treatment responses. In patients with PHN, a balanced treatment approach focusing on efficacy, safety, and tolerability is recommended. With appropriate treatment, most patients are able to achieve clinically significant relief from neuropathic pain. Diagnosis and management of neuropathic pain syndromes is challenging. Because of the complexity of chronic pain, successful long-term treatment can be especially difficult (Nicholson, 2003b). While most acute pain is nociceptive (i.e., a response to noxious stimuli), chronic pain can be nociceptive, neuropathic, or of mixed origin. PHN is a chronic pain syndrome that can last for years, causing physical and social disability and psychological distress (Kanazi, 2000). Despite major recent advances in the treatment of PHN, many patients remain refractory to current therapy (Dworkin, 2003). For practicing clinicians, including nurse practitioners, viewing pain as a disease rather than a symptom is the first step towards its successful management. Understanding the pathophysiology of chronic pain and emerging treatment paradigms for the management of neuropathic pain and PHN is critical to optimal care.

Down-regulation of Decapping Protein 2 mediates chronic nicotine exposure-induced locomotor hyperactivity in Drosophila.

PubMed

Ren, Jing; Sun, Jinghan; Zhang, Yunpeng; Liu, Tong; Ren, Qingzhong; Li, Yan; Guo, Aike

2012-01-01

Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence.

Down-Regulation of Decapping Protein 2 Mediates Chronic Nicotine Exposure-Induced Locomotor Hyperactivity in Drosophila

PubMed Central

Ren, Jing; Sun, Jinghan; Zhang, Yunpeng; Liu, Tong; Ren, Qingzhong; Li, Yan; Guo, Aike

2012-01-01

Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence. PMID:23300696

Addressing Chronic Malnutrition through Multi-Sectoral, Sustainable Approaches: A Review of the Causes and Consequences

PubMed Central

Reinhardt, Kristina; Fanzo, Jessica

2014-01-01

Chronic malnutrition, including stunting, is an important example of a global challenge that spans multiple sectors, specifically health, agriculture, and the environment. The objective of this paper is to review current knowledge on the causes and consequences of chronic malnutrition and their relationship with multiple sectors. Understanding the causes includes approaching chronic malnutrition from the basic, underlying, and immediate levels. The causes reach from macro-level environmental influences to specific micronutrient intake. In order to effectively address stunting, it is important to understand the timing of stunting and the ability of individuals to catch up in terms of linear growth, cognitive ability, and immune function. The consequences of chronic malnutrition are transgenerational and they have an impact at the individual, community, and national level in the short- and long-term. There are still many gaps in knowledge regarding both the causes and consequences of chronic malnutrition, particularly when it comes to the interaction with agriculture and the environment, and understanding these gaps is important to addressing the burden of chronic malnutrition through evidence-based interventions. PMID:25988116

Pseudomonas aeruginosa rugose small-colony variants evade host clearance, are hyper-inflammatory, and persist in multiple host environments.

PubMed

Pestrak, Matthew J; Chaney, Sarah B; Eggleston, Heather C; Dellos-Nolan, Sheri; Dixit, Sriteja; Mathew-Steiner, Shomita S; Roy, Sashwati; Parsek, Matthew R; Sen, Chandan K; Wozniak, Daniel J

2018-02-01

Pseudomonas aeruginosa causes devastating infections in immunocompromised individuals. Once established, P. aeruginosa infections become incredibly difficult to treat due to the development of antibiotic tolerant, aggregated communities known as biofilms. A hyper-biofilm forming clinical variant of P. aeruginosa, known as a rugose small-colony variant (RSCV), is frequently isolated from chronic infections and is correlated with poor clinical outcome. The development of these mutants during infection suggests a selective advantage for this phenotype, but it remains unclear how this phenotype promotes persistence. While prior studies suggest RSCVs could survive by evading the host immune response, our study reveals infection with the RSCV, PAO1ΔwspF, stimulated an extensive inflammatory response that caused significant damage to the surrounding host tissue. In both a chronic wound model and acute pulmonary model of infection, we observed increased bacterial burden, host tissue damage, and a robust neutrophil response during RSCV infection. Given the essential role of neutrophils in P. aeruginosa-mediated disease, we investigated the impact of the RSCV phenotype on neutrophil function. The RSCV phenotype promoted phagocytic evasion and stimulated neutrophil reactive oxygen species (ROS) production. We also demonstrate that bacterial aggregation and TLR-mediated pro-inflammatory cytokine production contribute to the immune response to RSCVs. Additionally, RSCVs exhibited enhanced tolerance to neutrophil-produced antimicrobials including H2O2 and the antimicrobial peptide LL-37. Collectively, these data indicate RSCVs elicit a robust but ineffective neutrophil response that causes significant host tissue damage. This study provides new insight on RSCV persistence, and indicates this variant may have a critical role in the recurring tissue damage often associated with chronic infections.

Critical disease windows shaped by stress exposure alter allocation trade-offs between development and immunity.

PubMed

Kirschman, Lucas J; Crespi, Erica J; Warne, Robin W

2018-01-01

Ubiquitous environmental stressors are often thought to alter animal susceptibility to pathogens and contribute to disease emergence. However, duration of exposure to a stressor is likely critical, because while chronic stress is often immunosuppressive, acute stress can temporarily enhance immune function. Furthermore, host susceptibility to stress and disease often varies with ontogeny; increasing during critical developmental windows. How the duration and timing of exposure to stressors interact to shape critical windows and influence disease processes is not well tested. We used ranavirus and larval amphibians as a model system to investigate how physiological stress and pathogenic infection shape development and disease dynamics in vertebrates. Based on a resource allocation model, we designed experiments to test how exposure to stressors may induce resource trade-offs that shape critical windows and disease processes because the neuroendocrine stress axis coordinates developmental remodelling, immune function and energy allocation in larval amphibians. We used wood frog larvae (Lithobates sylvaticus) to investigate how chronic and acute exposure to corticosterone, the dominant amphibian glucocorticoid hormone, mediates development and immune function via splenocyte immunohistochemistry analysis in association with ranavirus infection. Corticosterone treatments affected immune function, as both chronic and acute exposure suppressed splenocyte proliferation, although viral replication rate increased only in the chronic corticosterone treatment. Time to metamorphosis and survival depended on both corticosterone treatment and infection status. In the control and chronic corticosterone treatments, ranavirus infection decreased survival and delayed metamorphosis, although chronic corticosterone exposure accelerated rate of metamorphosis in uninfected larvae. Acute corticosterone exposure accelerated metamorphosis increased survival in infected larvae. Interactions between stress exposure (via glucocorticoid actions) and infection impose resource trade-offs that shape optimal allocation between development and somatic function. As a result, critical disease windows are likely shaped by stress exposure because any conditions that induce changes in differentiation rates will alter the duration and susceptibility of organisms to stressors or disease. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

Deciding in the dark: advance directives and continuation of treatment in chronic critical illness.

PubMed

Camhi, Sharon L; Mercado, Alice F; Morrison, R Sean; Du, Qingling; Platt, David M; August, Gary I; Nelson, Judith E

2009-03-01

Chronic critical illness is a devastating syndrome for which treatment offers limited clinical benefit but imposes heavy burdens on patients, families, clinicians, and the health care system. We studied the availability of advance directives and appropriate surrogates to guide decisions about life-sustaining treatment for the chronically critically ill and the extent and timing of treatment limitation. Prospective cohort study. Respiratory Care Unit (RCU) in a large, tertiary, urban, university-affiliated, hospital. Two hundred three chronically critically ill adults transferred to RCU after tracheotomy for failure to wean from mechanical ventilation in the intensive care unit. None. We interviewed RCU caregivers and reviewed patient records to identify proxy appointments, living wills, or oral statements of treatment preferences, resuscitation directives, and withholding/withdrawal of mechanical ventilation, nutrition, hydration, renal replacement and vasopressors. Forty-three of 203 patients (21.2%) appointed a proxy and 33 (16.2%) expressed preferences in advance directives. Do not resuscitate directives were given for 71 patients (35.0%). Treatment was limited for 39 patients (19.2%). Variables significantly associated with treatment limitation were proxy appointment prior to study entry (time of tracheotomy/RCU transfer) (odds ratio = 6.7, 95% confidence interval [CI], 2.3-20.0, p = 0.0006) and palliative care consultation in the RCU (OR = 40.9, 95% CI, 13.1-127.4, p < 0.0001). Median (interquartile range) time to first treatment limitation was 39 (31.0-45.0) days after hospital admission and 13 (8.0-29.0) days after RCU admission. For patients dying after treatment limitation, median time from first limitation to death ranged from 3 days for mechanical ventilation and hydration to 7 days for renal replacement. Most chronically critically ill patients fail to designate a surrogate decision-maker or express preferences regarding life-sustaining treatments. Despite burdensome symptoms and poor outcomes, limitation of such treatments was rare and occurred late, when patients were near death. Opportunities exist to improve communication and decision-making in chronic critical illness.

Kidney-Heart Interactions in Acute Kidney Injury.

PubMed

Doi, Kent

2016-01-01

Acute kidney injury (AKI) is a common complication in critically ill patients treated in intensive care units. Renal replacement therapy (RRT)-requiring AKI occurs in approximately 5-10% patients in intensive care unit and their mortality rate is unacceptably high (50-60%), despite sufficient control of uremia using remarkably advanced modern RRT techniques. This suggests that there are unrecognized organ interactions following AKI that could worsen the outcomes. Cardiorenal syndrome has been defined based on clinical observations that acute and chronic heart failure causes kidney injury and AKI and that chronic kidney disease worsens heart diseases. Possible pathways that connect these 2 organs have been suggested; however, the precise mechanisms are yet to be clarified, particularly in AKI-induced cardiac dysfunction. This review focuses on acute cardiac dysfunction in the setting of AKI. A recent animal study demonstrated the dysregulation of mitochondrial dynamics caused by an increased dynamin-related protein 1 expression and cellular apoptosis of the heart in a renal ischemia reperfusion model. Although the precise mechanisms that induce cardiac mitochondrial injury in AKI remain unclear, cardiac mitochondria injury could be a novel candidate of drug targets against high mortality in severe AKI. © 2016 S. Karger AG, Basel.

First-rib stress fracture in two adolescent swimmers: a case report.

PubMed

Low, Sara; Kern, Michael; Atanda, Alfred

2016-01-01

First-rib stress fractures have been described in adolescent athletes in various sports, with only one prior case report of first-rib stress fractures in an adolescent female swimmer. There is a need for research on the cause, management, and prevention of these injuries as they lead to significant morbidity and critical time away from sport for these aspiring athletes. We aimed to describe first-rib stress fractures as a potential cause for non-specific atraumatic chronic shoulder pain in adolescent swimmers and to discuss the different presentations, unique risk factors, treatment, and potential injury prevention strategies of such fractures. We discussed two such cases which were successfully treated with activity modification with restriction of all overhead activity, gradually progressive physical therapy and a return to swimming protocol. First-rib stress fractures can vary in presentation and should be in the differential diagnosis in adolescent swimmers with chronic shoulder pain. These injuries can be successfully managed with rest from overhead activities and physical therapy. Gradual return to competitive swimming can be achieved even with non-union of a first-rib stress fracture. Emphasis on balanced strength training in different muscle groups and proper swimming technique is essential to prevent these injuries.

Chronic Broca's Aphasia Is Caused by Damage to Broca's and Wernicke's Areas

PubMed Central

Fridriksson, Julius; Fillmore, Paul; Guo, Dazhou; Rorden, Chris

2015-01-01

Despite being perhaps the most studied form of aphasia, the critical lesion location for Broca's aphasia has long been debated, and in chronic patients, cortical damage often extends far beyond Broca's area. In a group of 70 patients, we examined brain damage associated with Broca's aphasia using voxel-wise lesion-symptom mapping (VLSM). We found that damage to the posterior portion of Broca's area, the pars opercularis, is associated with Broca's aphasia. However, several individuals with other aphasic patterns had considerable damage to pars opercularis, suggesting that involvement of this region is not sufficient to cause Broca's aphasia. When examining only individuals with pars opercularis damage, we found that patients with Broca's aphasia had greater damage in the left superior temporal gyrus (STG; roughly Wernicke's area) than those with other aphasia types. Using discriminant function analysis and logistic regression, based on proportional damage to the pars opercularis and Wernicke's area, to predict whether individuals had Broca's or another types of aphasia, over 95% were classified correctly. Our findings suggest that persons with Broca's aphasia have damage to both Broca's and Wernicke's areas, a conclusion that is incongruent with classical neuropsychology, which has rarely considered the effects of damage to both areas. PMID:25016386

Can preeclampsia be considered a renal compartment syndrome? A hypothesis and analysis of the literature.

PubMed

Reuter, David G; Law, Yuk; Levy, Wayne C; Seslar, Stephen P; Zierler, R Eugene; Ferguson, Mark; Chattra, James; McQuinn, Tim; Liu, Lenna L; Terry, Mark; Coffey, Patricia S; Dimer, Jane A; Hanevold, Coral; Flynn, Joseph T; Stapleton, F Bruder

2016-11-01

The morbidity and mortality associated with preeclampsia is staggering. The physiology of the Page kidney, a condition in which increased intrarenal pressure causes hypertension, appears to provide a unifying framework to explain the complex pathophysiology. Page kidney hypertension is renin-mediated acutely and ischemia-mediated chronically. Renal venous outflow obstruction also causes a Page kidney phenomenon, providing a hypothesis for the increased vulnerability of a subset of women who have what we are hypothesizing is a "renal compartment syndrome" due to inadequate ipsilateral collateral renal venous circulation consistent with well-known variation in normal venous anatomy. Dynamic changes in renal venous anatomy and physiology in pregnancy appear to correlate with disease onset, severity, and recurrence. Since maternal recumbent position is well known to affect renal perfusion and since chronic outflow obstruction makes women vulnerable to the ischemic/inflammatory sequelae, heightened awareness of renal compartment syndrome physiology is critical. The anatomic and physiologic insights provide immediate strategies to predict and prevent preeclampsia with straightforward, low-cost interventions that make renewed global advocacy for pregnant women a realistic goal. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Myocyte enhancer factor 2D provides a cross-talk between chronic inflammation and lung cancer.

PubMed

Zhu, Hai-Xing; Shi, Lin; Zhang, Yong; Zhu, Yi-Chun; Bai, Chun-Xue; Wang, Xiang-Dong; Zhou, Jie-Bai

2017-03-24

Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are exposed to a higher risk of developing lung cancer. Chronic inflammation may play an important role in the lung carcinogenesis among those patients. The present study aimed at identifying candidate biomarker predicting lung cancer risk among patients with chronic respiratory diseases. We applied clinical bioinformatics tools to analyze different gene profile datasets with a special focus on screening the potential biomarker during chronic inflammation-lung cancer transition. Then we adopted an in vitro model based on LPS-challenged A549 cells to validate the biomarker through RNA-sequencing, quantitative real time polymerase chain reaction, and western blot analysis. Bioinformatics analyses of the 16 enrolled GSE datasets from Gene Expression Omnibus online database showed myocyte enhancer factor 2D (MEF2D) level significantly increased in COPD patients coexisting non-small-cell lung carcinoma (NSCLC). Inflammation challenge increased MEF2D expression in NSCLC cell line A549, associated with the severity of inflammation. Extracellular signal-regulated protein kinase inhibition could reverse the up-regulation of MEF2D in inflammation-activated A549. MEF2D played a critical role in NSCLC cell bio-behaviors, including proliferation, differentiation, and movement. Inflammatory conditions led to increased MEF2D expression, which might further contribute to the development of lung cancer through influencing cancer microenvironment and cell bio-behaviors. MEF2D might be a potential biomarker during chronic inflammation-lung cancer transition, predicting the risk of lung cancer among patients with chronic respiratory diseases.

Health education in Cuba: a preface.

PubMed

Tesh, S

1986-01-01

Critics of health education policy in the United States fault it for ignoring the unequal ability of Americans to adopt more healthy behavior and for underestimating the social, economic, and political causes of disease. Many critics hypothesize that health education in a less bourgeois society would be more equitable and less individualistic. This article tests that hypothesis by analyzing the current Cuban health education program aimed at the reduction of chronic diseases. It argues that while the Cuban program appears to be every bit as individualistic as the North American program, theirs may not be comparable to ours because Cubans are less likely than Americans to reify the state. At least among supporters of the revolution, Cubans do not automatically make a conceptual distinction between the individual and the society. Discussions about responsibility for disease prevention take on new meaning in this light.

Chemically modified tetracyclines an emerging host modulator in chronic periodontitis patients: A randomized, double-blind, placebo-controlled, clinical trial.

PubMed

Alyousef, Abdullah A; Divakar, Darshan Devang; Muzaheed

2017-09-01

Although periodontal diseases are caused by some of the specific pathogens, most of the tissue damage is caused by the host reaction to disease and not actually by the infections. Therefore, host modulatory therapy (HMT) has advanced benefit for the treatment of periodontitis, which works basically by reducing tissue destruction and regeneration in periodontium by altering the critical aspects of host response regulation and up regulating defensive regenerative responses. The present study was conducted with the goal to test an innovative therapeutic option using chemically modified tetracycline in patients affected with generalized, moderate and severe chronic periodontitis. We assumed that CMT might have the potential to provoke an assessable clinical result and pharmacologically impede the level inflammatory flow. CMT (incyclinide) treated group had significantly higher CAL (clinical attachment) values than Placebo Control suggesting an improved CAL in CMT treatment. Host modulation therapy width incyclinide can be as an adjunct to conventional nonsurgical therapies without antimicrobial resistance. Progress was noticed in the clinical parameters but not the serum CRP level in our study establishing the role of CMTs in controlling chronic periodontitis. Also CMT treatment indicates its role in anti-inflammatory process as it inhibited IL-12 and TNF alpha but IL-10 level was not affected. However, more randomized placebo-controlled clinical trials with large sample size are required in order to authenticate the usage of CMTs in chronic periodontitis treatment. Based on this understanding, exploration of the novel, low-cost synthetic inhibitors that can be used as potential therapeutic agents, has been tested. Copyright © 2017 Elsevier Ltd. All rights reserved.

Work-related stress and posttraumatic stress in emergency medical services.

PubMed

Donnelly, Elizabeth

2012-01-01

Recent research efforts in emergency medical services (EMS) has identified variability in the ability of EMS personnel to recognize their level of stress-related impairment. Developing a better understanding of how workplace stress may affect EMS personnel is a key step in the process of increasing awareness of the impact of work-related stress and stress-related impairment. This paper demonstrates that for those in EMS, exposure to several types of workplace stressors is linked to stress reactions. Stress reactions such as posttraumatic stress symptomatology (PTSS) have the potential to negatively influence the health of EMS providers. This research demonstrates that two different types of work-related stress and alcohol use influence the development of PTSS. A probability sample of nationally registered emergency medical technician (EMT)-Basics and EMT-Paramedics (n = 1,633) completed an Internet-based survey. Respondents reported their levels of operational and organizational types of chronic stress, critical incident stress, alcohol use, and PTSS. Ordinary least squares regression illustrated that when demographic factors were controlled, organizational and operational forms of chronic stress, critical incident stress, and alcohol use were all significant predictors of PTSS (p < 0.01). Inclusion of an interaction effect between operational stress and critical incident stress (p < 0.01) as well as between operational stress and alcohol use (p < 0.01) created a robust final model with an R(2) of 0.343. These findings indicate that exposure to both chronic and critical incident stressors increases the risk of EMS providers' developing a posttraumatic stress reaction. Higher levels of chronic stress, critical incident stress, and alcohol use significantly related to an increased level of PTSS. Further, for those reporting high levels of alcohol use or critical incident stress, interactions with high levels of chronic operational stress were associated with higher rates of PTSS. For those interested in the impact of work-related stress in EMS, these findings indicate that attention must be paid to levels of stress associated with both critical incident exposure as well as the chronic stress providers experience on a day-to-day basis.

Discontinuing treatment in children with chronic, critical illnesses.

PubMed

Mahon, M M; Deatrick, J A; McKnight, H J; Mohr, W K

2000-03-01

Decisions about optimal treatment for critically ill children are qualitatively different from those related to adults. Technological advances over the past several decades have resulted in myriad treatment options that leave many children chronically, critically ill. These children are often technology dependent. With new technologies and new patient populations comes the responsibility to understand how, when, and why these technologies are applied and when technology should not be used or should be withdrawn. Much has been written about ethical decision making in the care of chronically, critically ill adults and newborns. In this article, relevant factors about the care of children older than neonates are described: standards, decision makers, age of the child, and pain management. A case study is used as a mechanism to explore these issues. Dimensions of futility, discontinuing aggressive treatment, and a consideration of benefits and burdens are integrated throughout the discussion to inform nurse practitioner practice.

Integration of Palliative Care in Chronic Critical Illness Management

PubMed Central

Nelson, Judith E; Hope, Aluko A

2016-01-01

Palliative care is an essential component of comprehensive care for all patients with chronic critical illness, including those receiving restorative or life-sustaining therapies. Core elements include alleviation of symptom distress, communication about care goals, alignment of treatment with the patient’s values and preferences, transitional planning, and family support. Here we address strategies for assessment and management of symptoms, including pain, dyspnea, and depression, and for assisting patients to communicate while endotracheally intubated. We also discuss approaches to optimize communication among clinicians, patients, and families about care goals. Challenges for supporting families and planning for transitions between care settings are identified, while the value of interdisciplinary input is emphasized. We review “consultative” and “integrative” models for integrating palliative care and restorative critical care. Finally, we highlight key ethical issues that arise in the care of chronically critically ill patients and their families. PMID:22663973

Integration of Mobile Health Technology in the Treatment of Chronic Pain: A Critical Review.

PubMed

Sundararaman, Lalitha V; Edwards, Robert R; Ross, Edgar L; Jamison, Robert N

This article provides a critical overview and best-evidence synthesis of the use of mobile health (mHealth) technology among persons with chronic pain and their health care providers and examines the future benefits and barriers of implementing mHealth technology in clinical care. We critically review articles about electronic pain diaries, pain assessment programs, text messaging, and smartphone pain apps for management of persons with pain. Also presented are findings on the utility of activity trackers and use of telehealth to deliver cognitive behavioral therapy. Finally, barriers, study gaps, and future challenges of incorporating mobile technology for chronic pain are discussed. Although the future of mHealth technology and telemedicine in clinical practice is promising, this critical review highlights the need for rigorous studies to establish an association of the use of mHealth technology with improved quality of life, functional autonomy, and decreased hospital use.

Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ren, Zhenhua

Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanolmore » by gavage (5 g/kg, 25% ethanol w/v) daily for 3 days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3 days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas. - Highlights: • Chronic plus binge alcohol drinking causes more pancreatic injury. • Chronic plus binge alcohol drinking induces more pancreatic inflammation. • Chronic plus binge alcohol causes more endoplasmic reticulum stress and oxidative stress.« less

Hyper-resting brain entropy within chronic smokers and its moderation by Sex

PubMed Central

Li, Zhengjun; Fang, Zhuo; Hager, Nathan; Rao, Hengyi; Wang, Ze

2016-01-01

Cigarette smoking is a chronic relapsing brain disorder, and remains a premier cause of morbidity and mortality. Functional neuroimaging has been used to assess differences in the mean strength of brain activity in smokers’ brains, however less is known about the temporal dynamics within smokers’ brains. Temporal dynamics is a key feature of a dynamic system such as the brain, and may carry information critical to understanding the brain mechanisms underlying cigarette smoking. We measured the temporal dynamics of brain activity using brain entropy (BEN) mapping and compared BEN between chronic non-deprived smokers and non-smoking controls. Because of the known sex differences in neural and behavioral smoking characteristics, comparisons were also made between males and females. Associations between BEN and smoking related clinical measures were assessed in smokers. Our data showed globally higher BEN in chronic smokers compared to controls. The escalated BEN was associated with more years of smoking in the right limbic area and frontal region. Female nonsmokers showed higher BEN than male nonsmokers in prefrontal cortex, insula, and precuneus, but the BEN sex difference in smokers was less pronounced. These findings suggest that BEN mapping may provide a useful tool for probing brain mechanisms related to smoking. PMID:27377552

Chronic hypoxia stress-induced differential modulation of heat-shock protein 70 and presynaptic proteins.

PubMed

Fei, Guanghe; Guo, Conghui; Sun, Hong-Shuo; Feng, Zhong-Ping

2007-01-01

Chronic hypoxia exposure can cause neurobehavioral dysfunction, but the underlying cellular and molecular mechanisms remain unclear. Here, we found that adult Lymnaea stagnalis snails maintained in low O(2) (approximately 5%) for 4 days developed slowed reactions to light stimuli, and reduced righting movement. Semiquantitative immunoblotting analyses showed that hypoxia exposure induced increased expression of heat-shock protein (HSP)70 in ganglion preparations, and suppressed expression of the presynaptic proteins syntaxin I, synaptic vesicle protein 2 (SV2) and synaptotagmin I. Detailed time course analyses showed that an early moderate increase developed within 6 h, preceding a substantial up-regulation of HSP70 after 4 days; an early reduction of syntaxin I in the first 24 h; a delayed reduction of synaptotagmin I after 4 days; and a biphasic change in SV2. Using a double-stranded RNA interference approach, we demonstrated that preventing the hypoxia inducible HSP70 enhanced down-regulation of syntaxin and synaptotagmin, and aggravated motor and sensory suppression. Co-immunoprecipitation analysis revealed an interaction between HSP70 and syntaxin. We have thus provided the first evidence that early induction of HSP70 by chronic hypoxia is critical for maintaining expression levels of presynaptic proteins. These findings implicate a new molecular mechanism underlying chronic hypoxia-induced neurobehavioral adaptation and impairment.

Chronic hepatitis C and liver fibrosis

PubMed Central

Sebastiani, Giada; Gkouvatsos, Konstantinos; Pantopoulos, Kostas

2014-01-01

Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the next decades, posing a major health care challenge. This review provides a brief update on HCV epidemiology, summarizes basic mechanistic concepts of HCV-dependent liver fibrogenesis, and discusses methods for assessment of liver fibrosis that are routinely used in clinical practice. Liver biopsy was until recently considered as the gold standard to diagnose and stage liver fibrosis. However, its invasiveness and drawbacks led to the development of non-invasive methods, which include serum biomarkers, transient elastography and combination algorithms. Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic value and are cost-effective. Non-invasive methods for assessment of liver fibrosis are gradually being incorporated into new guidelines and are becoming standard of care, which significantly reduces the need for liver biopsy. PMID:25170193

OSTEOCYTE APOPTOSIS

PubMed Central

Jilka, Robert L.; Noble, Brendon; Weinstein, Robert S.

2012-01-01

Apoptotic death of osteocytes was recognized over 15 years ago, but its significance for bone homeostasis has remained elusive. A new paradigm has emerged that invokes osteocyte apoptosis as a critical event in the recruitment of osteoclasts to a specific site in response to skeletal unloading, fatigue damage, estrogen deficiency and perhaps in other states where bone must be removed. This is accomplished by yet to be defined signals emanating from dying osteocytes, which stimulate neighboring viable osteocytes to produce osteoclastogenic cytokines. The osteocyte apoptosis caused by chronic glucocorticoid administration does not increase osteoclasts; however, it does negatively impact maintenance of bone hydration, vascularity, and strength. PMID:23238124

Prolonged disturbance of consciousness caused by severe hypophosphatemia: a report of two cases.

PubMed

Murakami, Takaaki; Yoshida, Masanori; Funazo, Tomoko; Matsuda, Yuki; Matsuo, Koji; Nambu, Takuo; Yonemitsu, Shin; Muro, Seiji; Oki, Shogo

2014-01-01

We herein describe two patients with a prolonged disturbance of consciousness due to severe hypophosphatemia. Case one presented with pneumococcal infection and acute exacerbation of chronic obstructive pulmonary disease and asthma. Case two presented with diabetic foot infections and diabetic ketoacidosis. Both patients responded to initial therapy for their primary diseases, but consciousness became worse in both cases. Their test results for impaired consciousness revealed severe hypophosphatemia; therefore, phosphate replacement therapy was administered, thus resulting in complete alertness. These cases demonstrate that we should consider the possibility of hypophosphatemia in critically ill patients with an altered consciousness.

Exposed to events that never happen: Generalized unsafety, the default stress response, and prolonged autonomic activity.

PubMed

Brosschot, Jos F; Verkuil, Bart; Thayer, Julian F

2017-03-01

Based on neurobiological and evolutionary arguments, the generalized unsafety theory of stress (GUTS) hypothesizes that the stress response is a default response, and that chronic stress responses are caused by generalized unsafety (GU), independent of stressors or their cognitive representation. Three highly prevalent conditions are particularly vulnerable to becoming 'compromised' in terms of GU, and carry considerable health risks: Thus, GUTS critically revises and expands stress theory, by focusing on safety instead of threat, and by including risk factors that have hitherto not been attributed to stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

Investigating the Causes of Chronic Itch: New Advances Could Bring Relief

MedlinePlus

... on Research Investigating the Causes of Chronic Itch: New Advances Could Bring Relief By Kirstie Saltsman, Ph. ... touch, we could have the beginnings of a new treatment for chronic itch that would not impact ...

Living with the health and social inequities of a disability: a critical feminist study.

PubMed

Bethune-Davies, Patricia; McWilliam, Carol L; Berman, Helene

2006-03-01

Clients living at home with chronic disabling conditions together with their caregivers, service providers, and policymakers face major challenges in optimizing health care. In this critical feminist interpretive study we examined the experiences of women receiving home care for chronic disabling conditions. Five themes emerged: struggling with the embodied limitations of disabling chronic conditions; actively seeking health; struggling with service limitations; seeking ways to manage; and living with isolation and marginalization. Having done this study, we learned that home care services do not always contribute sufficiently to the overall health and well-being of women living with chronic disabling conditions and, in fact, may negatively impact upon their health.

Opening the Door: The Experience of Chronic Critical Illness in a Long-Term Acute Care Hospital.

PubMed

Lamas, Daniela J; Owens, Robert L; Nace, R Nicholas; Massaro, Anthony F; Pertsch, Nathan J; Gass, Jonathon; Bernacki, Rachelle E; Block, Susan D

2017-04-01

Chronically critically ill patients have recurrent infections, organ dysfunction, and at least half die within 1 year. They are frequently cared for in long-term acute care hospitals, yet little is known about their experience in this setting. Our objective was to explore the understanding and expectations and goals of these patients and surrogates. We conducted semi-structured interviews with chronically critically ill long-term acute care hospital patients or surrogates. Conversations were recorded, transcribed, and analyzed. One long-term acute care hospital. Chronically critically ill patients, defined by tracheotomy for prolonged mechanical ventilation, or surrogates. Semi-structured conversation about quality of life, expectations, and planning for setbacks. A total of 50 subjects (30 patients and 20 surrogates) were enrolled. Thematic analyses demonstrated: 1) poor quality of life for patients; 2) surrogate stress and anxiety; 3) optimistic health expectations; 4) poor planning for medical setbacks; and 5) disruptive care transitions. Nearly 80% of patient and their surrogate decision makers identified going home as a goal; 38% were at home at 1 year. Our study describes the experience of chronically critically ill patients and surrogates in an long-term acute care hospital and the feasibility of patient-focused research in this setting. Our findings indicate overly optimistic expectations about return home and unmet palliative care needs, suggesting the need for integration of palliative care within the long-term acute care hospital. Further research is also needed to more fully understand the challenges of this growing population of ICU survivors.

Dust Mite Allergy

MedlinePlus

... exposure to the allergen can cause the ongoing (chronic) inflammation associated with asthma. Dust mites eat organic matter ... their debris can cause complications. Sinus infections. Ongoing (chronic) inflammation of tissues in the nasal passages caused by ...

Postnatal Ablation of Foxm1 from Cardiomyocytes Causes Late Onset Cardiac Hypertrophy and Fibrosis without Exacerbating Pressure Overload-Induced Cardiac Remodeling

PubMed Central

Bolte, Craig; Zhang, Yufang; York, Allen; Kalin, Tanya V.; Schultz, Jo El J.; Molkentin, Jeffery D.; Kalinichenko, Vladimir V.

2012-01-01

Heart disease remains a leading cause of morbidity and mortality in the industrialized world. Hypertrophic cardiomyopathy is the most common genetic cardiovascular disorder and the most common cause of sudden cardiac death. Foxm1 transcription factor (also known as HFH-11B, Trident, Win or MPP2) plays an important role in the pathogenesis of various cancers and is a critical mediator of post-injury repair in multiple organs. Foxm1 has been previously shown to be essential for heart development and proliferation of embryonic cardiomyocytes. However, the role of Foxm1 in postnatal heart development and in cardiac injury has not been evaluated. To delete Foxm1 in postnatal cardiomyocytes, αMHC-Cre/Foxm1fl/fl mice were generated. Surprisingly, αMHC-Cre/Foxm1fl/fl mice exhibited normal cardiomyocyte proliferation at postnatal day seven and had no defects in cardiac structure or function but developed cardiac hypertrophy and fibrosis late in life. The development of cardiomyocyte hypertrophy and cardiac fibrosis in aged Foxm1-deficient mice was associated with reduced expression of Hey2, an important regulator of cardiac homeostasis, and increased expression of genes critical for cardiac remodeling, including MMP9, αSMA, fibronectin and vimentin. We also found that following aortic constriction Foxm1 mRNA and protein were induced in cardiomyocytes. However, Foxm1 deletion did not exacerbate cardiac hypertrophy or fibrosis following chronic pressure overload. Our results demonstrate that Foxm1 regulates genes critical for age-induced cardiomyocyte hypertrophy and cardiac fibrosis. PMID:23144938

Functional, communicative and critical health literacy of chronic disease patients and their importance for self-management.

PubMed

Heijmans, Monique; Waverijn, Geeke; Rademakers, Jany; van der Vaart, Rosalie; Rijken, Mieke

2015-01-01

To provide insight into the level of health literacy among chronic disease patients in the Netherlands, to identify subgroups with low literacy and to examine the associations between health literacy and self-management. Self-report questionnaires were sent to a nationwide sample of 1.341 chronic disease patients. The Dutch Functional Communicative and Critical Health Literacy scale (FCCHL), the Partners in Health scale (PIH) and Perceived Efficacy in Patient-Doctor Interactions (PEPPI-5) were used to assess health literacy and aspects of self-management. In general, health literacy skills were good. A higher age, lower education, lower income, multi-morbidity and/or functional limitations were associated with lower levels of health literacy. Communicative and critical health literacy were related to some aspects of self-management but not to all. Functional health literacy was less important. Communicative and critical health literacy play a role in successful self-management of chronic disease but the impact differs by context. Health literacy levels vary according to socio-demographic and disease characteristics of patients. Health care professionals should tailor their information and support to the health literacy skills and personal context of their patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Surveillance of US Death Rates from Chronic Diseases Related to Excessive Alcohol Use.

PubMed

Polednak, Anthony P

2016-01-01

To assess the utility of multiple-cause (MC) death records for surveillance of US mortality rates from chronic causes related to excessive alcohol use. The Alcohol-Related Disease Impact (ARDI) resource produced estimates of the population 'alcohol attributable fraction' (AAF) due to excessive drinking for each alcohol-related (AAF > 0%) cause of death, and used AAFs to estimate numbers of alcohol-related deaths from alcohol-related underlying causes (UC) in adults age 20-64 and 65+ years in 2006-2010. For surveillance, this study used MC death file to identify individual deaths (2006-2010) with an 'alcohol-induced' cause (AAF = 100%) anywhere on the certificate, and to obtain US rates of premature death (ages 15-64 and 65-74 years) for 1999-2012. Using the selected MC records, numbers of deaths from alcohol-related chronic UC (2006-2010) were 81% of ARDI estimates for age 20-64, but only 40% for 65+ years. The MC records identified substantial numbers of deaths from causes (e.g. certain infectious diseases) not included as alcohol-related in ARDI, but included in surveillance of premature death rates for chronic UC. Also, premature death rates for chronic alcohol-induced causes using only the UC (as in routine mortality statistics) were only about half the rates based on MC; all rates increased in recent years but some reached statistical significance only by using MC. Using MC records underestimated total US deaths from alcohol-related chronic causes as the UC, but enhanced surveillance of rates for premature deaths involving chronic causes that may be related to excessive alcohol use. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Mismatch between physicians and family members views on communications about patients with chronic incurable diseases receiving care in critical and intensive care settings in Georgia: a quantitative observational survey.

PubMed

Chikhladze, Nana; Janberidze, Elene; Velijanashvili, Mariam; Chkhartishvili, Nikoloz; Jintcharadze, Memed; Verne, Julia; Kordzaia, Dimitri

2016-07-22

Physicians working in critical and intensive care settings encounter death of chronic incurable patients on a daily basis; however they have scant skills on how to communicate with the patients and their family members. The aim of the present survey is to examine communication of critical and intensive care physicians with patients' family members receiving treatment due to chronic incurable diseases/conditions and to compare the views of families with physicians working in critical and intensive care settings. The survey was conducted in four cities of Georgia (Tbilisi, Kutaisi, Batumi and Telavi) in 2014. Physicians working in critical and intensive care settings and family members were asked to fill in separate questionnaires, covering various aspects of communication including patients' prognosis, ways of death occurrence, treatment plans and religion. Participants ranked their responses on a scale ranging from "0" to "10", where "0" represented "never" and "10"-"always". After data collection, responses were recoded into three categories: 0-3 = never/rarely, 4-7 = somewhat and 8-10 = often/always. Differences were tested using Pearson's chi-square or Fisher's exact test as appropriate. P value of < 0.05 was considered as significant. Sixty-five physicians and 59 patients' family members participated in this cross-sectional study. Majority of their responses was statistically significantly different. Only one quarter (23.7 %) of family members of patients receiving medical aid in critical and intensive care settings were satisfied with the communication level. In contrast, 78.5 % of physicians considered their communication with families as positive (p < 0.0001). The survey revealed the mismatch between the views on communication of critical and intensive care settings physicians and family members of the patients with chronic incurable diseases receiving care in critical and intensive care settings. In order to provide the best care for chronic incurable patients and their family members, physicians working in critical and intensive care settings must have relevant clinical knowledge and ability to provide effective communication. Present results reflect important potential targets for educational interventions including critical and intensive care physicians training through online modules.

Analysing the causes of chronic cough: relation to diesel exhaust, ozone, nitrogen oxides, sulphur oxides and other environmental factors

PubMed Central

Groneberg-Kloft, Beatrix; Kraus, Thomas; Mark, Anke van; Wagner, Ulrich; Fischer, Axel

2006-01-01

Air pollution remains a leading cause of many respiratory diseases including chronic cough. Although episodes of incidental, dramatic air pollution are relatively rare, current levels of exposure of pollutants in industrialized and developing countries such as total articles, diesel exhaust particles and common cigarette smoke may be responsible for the development of chronic cough both in children and adults. The present study analyses the effects of common environmental factors as potential causes of chronic cough. Different PubMed-based researches were performed that related the term cough to various environmental factors. There is some evidence that chronic inhalation of diesel can lead to the development of cough. For long-term exposure to nitrogen dioxide (NO2), children were found to exhibit increased incidences of chronic cough and decreased lung function parameters. Although a number of studies did not show that outdoor pollution directly causes the development of asthma, they have demonstrated that high levels pollutants and their interaction with sunlight produce ozone (O3) and that repeated exposure to it can lead to chronic cough. In summary, next to the well-known air pollutants which also include particulate matter and sulphur dioxide, a number of other indoor and outdoor pollutants have been demonstrated to cause chronic cough and therefore, environmental factors have to be taken into account as potential initiators of both adult and pediatric chronic cough. PMID:16722555

Patient-controlled analgesia: therapeutic interventions using transdermal electro-activated and electro-modulated drug delivery.

PubMed

Indermun, Sunaina; Choonara, Yahya E; Kumar, Pradeep; Du Toit, Lisa C; Modi, Girish; Luttge, Regina; Pillay, Viness

2014-02-01

Chronic pain poses a major concern to modern medicine and is frequently undertreated, causing suffering and disability. Patient-controlled analgesia, although successful, does have limitations. Transdermal delivery is the pivot to which analgesic research in drug delivery has centralized, especially with the confines of needle phobias and associated pain related to traditional injections, and the existing limitations associated with oral drug delivery. Highlighted within is the possibility of further developing transdermal drug delivery for chronic pain treatment using iontophoresis-based microneedle array patches. A concerted effort was made to review critically all available therapies designed for the treatment of chronic pain. The drug delivery systems developed for this purpose and nondrug routes are elaborated on, in a systematic manner. Recent developments and future goals in transdermal delivery as a means to overcome the individual limitations of the aforementioned delivery routes are represented as well. The approval of patch-like devices that contain both the microelectronic-processing mechanism and the active medicament in a small portable device is still awaited by the pharmaceutical industry. This anticipated platform may provide transdermal electro-activated and electro-modulated drug delivery systems a feasible attempt in chronic pain treatment. Iontophoresis has been proven an effective mode used to administer ionized drugs in physiotherapeutic, diagnostic, and dermatological applications and may be an encouraging probability for the development of devices and aids in the treatment of chronic pain. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Retrospective Analysis of Long-Term Outcomes After Combat Injury: A Hidden Cost of War.

PubMed

Stewart, Ian J; Sosnov, Jonathan A; Howard, Jeffrey T; Orman, Jean A; Fang, Raymond; Morrow, Benjamin D; Zonies, David H; Bollinger, Mary; Tuman, Caroline; Freedman, Brett A; Chung, Kevin K

2015-12-01

During the conflicts in Iraq and Afghanistan, 52,087 service members have been wounded in combat. The long-term sequelae of these injuries have not been carefully examined. We sought to determine the relation between markers of injury severity and the subsequent development of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease. Retrospective cohort study of critically injured US military personnel wounded in Iraq or Afghanistan from February 1, 2002 to February 1, 2011. Patients were then followed until January 18, 2013. Chronic disease outcomes were assessed by International Classification of Diseases, 9th edition codes and causes of death were confirmed by autopsy. From 6011 admissions, records were excluded because of missing data or if they were for an individual's second admission. Patients with a disease diagnosis of interest before the injury date were also excluded, yielding a cohort of 3846 subjects for analysis. After adjustment for other factors, each 5-point increment in the injury severity score was associated with a 6%, 13%, 13%, and 15% increase in incidence rates of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease, respectively. Acute kidney injury was associated with a 66% increase in rates of hypertension and nearly 5-fold increase in rates of chronic kidney disease. In Iraq and Afghanistan veterans, the severity of combat injury was associated with the subsequent development of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease. © 2015 American Heart Association, Inc.

Calcium Balance in Chronic Kidney Disease.

PubMed

Hill Gallant, Kathleen M; Spiegel, David M

2017-06-01

The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.

Unexplained dyspnea in a patient of chronic arsenicosis: A diagnostic challenge and learning curve for physicians

PubMed Central

Sengupta, Amitabha; Maji, Arnab; Jash, Debraj; Maikap, Malay

2015-01-01

Chronic arsenic exposure causes cutaneous effects like hyperkeratosis, peripheral vascular disease, hypertension, ischemic heart disease, non-cirrhotic portal hypertension, hepatomegaly, peripheral neuropathy, respiratory involvement, bad obstetrical outcome, hematological disturbances, and diabetes mellitus. Here we present a case of a 24-year-old lady, with chronic exposure to arsenic, presenting to us with progressive dyspnea. We found pulmonary arterial hypertension (PAH) as a cause of her dyspnea. PAH can occur in arsenicosis, secondary to arsenic-induced chronic obstructive pulmonary disease (COPD), lung fibrosis, and portal hypertension, which we excluded by appropriate investigations in our case. We also excluded a familial or heritable form of PAH. Thus, with the exclusion of all these secondary causes of PAH, as well as a hereditary cause, we came to a conclusion that this PAH might be due to chronic arsenic exposure. To the best of our knowledge, no case of PAH in chronic arsenicosis has been reported to date. PMID:25814805

Paracetamol, alcohol and the liver

PubMed Central

Prescott, Laurie F

2000-01-01

It is claimed that chronic alcoholics are at increased risk of paracetamol (acetaminophen) hepatotoxicity not only following overdosage but also with its therapeutic use. Increased susceptibility is supposed to be due to induction of liver microsomal enzymes by ethanol with increased formation of the toxic metabolite of paracetamol. However, the clinical evidence in support of these claims is anecdotal and the same liver damage after overdosage occurs in patients who are not chronic alcoholics. Many alcoholic patients reported to have liver damage after taking paracetamol with ‘therapeutic intent’ had clearly taken substantial overdoses. No proper clinical studies have been carried out to investigate the alleged paracetamol–alcohol interaction and acute liver damage has never been produced by therapeutic doses of paracetamol given as a challenge to a chronic alcoholic. The paracetamol–alcohol interaction is complex; acute and chronic ethanol have opposite effects. In animals, chronic ethanol causes induction of hepatic microsomal enzymes and increases paracetamol hepatotoxicity as expected (ethanol primarily induces CYP2E1 and this isoform is important in the oxidative metabolism of paracetamol). However, in man, chronic alcohol ingestion causes only modest (about twofold) and short-lived induction of CYP2E1, and there is no corresponding increase (as claimed) in the toxic metabolic activation of paracetamol. The paracetamol–ethanol interaction is not specific for any one isoform of cytochrome P450, and it seems that isoenzymes other than CYP2E1 are primarily responsible for the oxidative metabolism of paracetamol in man. Acute ethanol inhibits the microsomal oxidation of paracetamol both in animals and man. This protects against liver damage in animals and there is evidence that it also does so in man. The protective effect disappears when ethanol is eliminated and the relative timing of ethanol and paracetamol intake is critical. In many of the reports where it is alleged that paracetamol hepatotoxicity was enhanced in chronic alcoholics, the reverse should have been the case because alcohol was actually taken at the same time as the paracetamol. Chronic alcoholics are likely to be most vulnerable to the toxic effects of paracetamol during the first few days of withdrawal but maximum therapeutic doses given at this time have no adverse effect on liver function tests. Although the possibility remains that chronic consumption of alcohol does increase the risk of paracetamol hepatotoxicity in man (perhaps by impairing glutathione synthesis), there is insufficient evidence to support the alleged major toxic interaction. It is astonishing that clinicians and others have unquestion-ingly accepted this supposed interaction in man for so long with such scant regard for scientific objectivity. PMID:10759684

Endometrioid endometrial carcinoma indirectly caused by pituitary prolactinoma: a case report.

PubMed

Nishino, Kimihiro; Niwa, Yuri; Mizutani, Teruyuki; Shimizu, Ken; Hayashi, Kazumasa; Chaya, Jyunya; Kato, Noriko; Yamamuro, Osamu

2013-01-01

We present the case of a 44-year-old nulliparous woman who experienced irregular menstrual cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma. In premenopausal women, hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin-releasing hormone and thus suppressing luteinizing hormone levels, which can cause menstrual disorders ranging from amenorrhea, oligomenorrhea and chronic anovulatory cycle to short luteal phase of the menstrual cycle. A chronic anovulatory menstrual cycle is the most common cause of long-term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins, which can lead to endometrioid endometrial carcinoma. In this case, pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the endometrioid endometrial carcinoma. In patients for whom the cause of irregular menstruation and chronic anovulatory cycle is suspected to be hyperprolactinemia, explorations of both the hypophysis and endometrium are essential.

Endometrioid Endometrial Carcinoma Indirectly Caused by Pituitary Prolactinoma: A Case Report

PubMed Central

Nishino, Kimihiro; Niwa, Yuri; Mizutani, Teruyuki; Shimizu, Ken; Hayashi, Kazumasa; Chaya, Jyunya; Kato, Noriko; Yamamuro, Osamu

2013-01-01

We present the case of a 44-year-old nulliparous woman who experienced irregular menstrual cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma. In premenopausal women, hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin-releasing hormone and thus suppressing luteinizing hormone levels, which can cause menstrual disorders ranging from amenorrhea, oligomenorrhea and chronic anovulatory cycle to short luteal phase of the menstrual cycle. A chronic anovulatory menstrual cycle is the most common cause of long-term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins, which can lead to endometrioid endometrial carcinoma. In this case, pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the endometrioid endometrial carcinoma. In patients for whom the cause of irregular menstruation and chronic anovulatory cycle is suspected to be hyperprolactinemia, explorations of both the hypophysis and endometrium are essential. PMID:23467393

Neuroprotective Effects of Agomelatine and Vinpocetine Against Chronic Cerebral Hypoperfusion Induced Vascular Dementia.

PubMed

Gupta, Surbhi; Singh, Prabhat; Sharma, Brij Mohan; Sharma, Bhupesh

2015-01-01

Chronic cerebral hypoperfusion (CCH) has been considered as a critical cause for the development of cognitive decline and dementia of vascular origin. Melatonin receptors have been reported to be beneficial in improving memory deterioration. Phosphodiesterase-1 (PDE1) enzyme offers protection against cognitive impairments and cerebrovascular disorders. Aim of this study is to explore the role of agomelatine (a dual MT1 and MT2 melatonin receptor agonist) and vinpocetine (selective PDE1 inhibitor) in CCH induced vascular dementia (VaD). Two vessel occlusion (2VO) or bilateral common carotid arteries ligation method was performed to initiate a phase of chronic hypoperfusion in mice. 2VO animals have shown significant cognitive deficits (Morris water maze), cholinergic dysfunction (increased acetyl cholinesterase -AChE) activity alongwith increased brain oxidative stress (decreased brain catalase, glutathione, as well as superoxide dismutase with an increase in malondialdehyde levels), and significant increase in brain infarct size (2,3,5- triphenylterazolium chloride-TTC staining). Treatment of agomelatine and vinpocetine reduced CCH induced learning and memory deficits and limited cholinergic dysfunction, oxidative stress, and tissue damage, suggesting that agomelatine and vinpocetine may provide benefits in CCH induced VaD.

Targeting Obesity for the Prevention of Chronic Cardiovascular Disease Through Gut Microbiota-Herb Interactions: An Opportunity for Traditional Herbs.

PubMed

Chen, Feng; Jiang, Jun; Tian, Dan-Dan; Wen, Qi; Li, Yong-Hui; Zhang, Jun-Qing; Cheng, Chen; Wang, Tengfei

2017-01-01

Cardiovascular disease still remains the primary cause of death worldwide and obesity is becoming recognized as one of the most critical contributing risk factors. The increased prevalence of obesity casts a cloud over the global health and the whole societies and will still be burdened in the future. Therefore, prevention and therapy of obesity is a beneficial strategy for the prevention of chronic cardiovascular disease. Numerous studies have demonstrated that gut microbiota takes part in human health and disease including obesity. Traditional herbs hold great potential to improve people's health and wellness, particularly in the area of chronic inflammatory diseases although the mechanisms of action remain poorly understood. Emerging explorations of gut microbiotaherb interactions provide a potential to revolutionize the way we view herbal therapeutics. This review summarizes the experimental studies performed on animals and humans regarding the gut microbiota-herb interactions targeting obesity. This review also discusses the opportunity of herbs with potent activities but low oral bioavailability conundrum for prevention and therapy for obesity and related cardiovascular disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Deleterious Effects of Chronic Folate Deficiency in the Ts65Dn Mouse Model of Down Syndrome

PubMed Central

Helm, Susan; Blayney, Morgan; Whited, Taylor; Noroozi, Mahjabin; Lin, Sen; Kern, Semira; Green, David; Salehi, Ahmad

2017-01-01

Folate is an important B vitamin naturally found in the human diet and plays a critical role in methylation of nucleic acids. Indeed, abnormalities in this major epigenetic mechanism play a pivotal role in the pathogenesis of cognitive deficit and intellectual disability in humans. The most common cause of cognitive dysfunction in children is Down syndrome (DS). Since folate deficiency is very common among the pediatric population, we questioned whether chronic folate deficiency (CFD) exacerbates cognitive dysfunction in a mouse model of DS. To test this, adult Ts65Dn mice and their disomic littermates were chronically fed a diet free of folic acid while preventing endogenous production of folate in the digestive tract for a period of 8 weeks. Our results show that the Ts65Dn mouse model of DS was significantly more vulnerable to CFD in terms of plasma homocysteine and N5-methyltetrahydrofolate (5-MTHF) levels. Importantly, these changes were linked to degenerative alterations in hippocampal dendritic morphology and impaired nest building behavior in Ts65Dn mice. Based on our results, a rigorous examination of folate intake and its metabolism in individuals with DS is warranted. PMID:28649192

Exopolysaccharide Productivity and Biofilm Phenotype on Oral Commensal Bacteria as Pathogenesis of Chronic Periodontitis

DTIC Science & Technology

2012-01-01

2 Exopolysaccharide Productivity and Biofilm Phenotype on Oral Commensal Bacteria as Pathogenesis of Chronic Periodontitis Takeshi Yamanaka1...species biofilm in the oral cavity can cause persistent chronic periodontitis along with the importance of dental plaque formation and maturation...independent manner could be pathogenic for periodontal tissues and can cause chronic periodontitis lesions. 2.1 Initial colonizers on the tooth surface

Development and Validation of a Printed Information Brochure for Families of Chronically Critically Ill Patients

PubMed Central

Carson, Shannon S.; Vu, Maihan; Danis, Marion; Camhi, Sharon L.; Scheunemann, Leslie P.; Cox, Christopher E.; Hanson, Laura C.; Nelson, Judith E.

2012-01-01

Objective Families and other surrogate decision-makers for chronically critically ill patients often lack information about patient prognosis or options for care. This study describes an approach to develop and validate a printed information brochure about chronic critical illness aimed at improving comprehension of the disease process and outcomes for patients’ families and other surrogate decision-makers. Design Investigators reviewed existing literature to identify key domains of informational needs. Content of these domains was incorporated in a draft brochure that included graphics and a glossary of terms. Clinical sensibility, balance, and emotional sensitivity of the draft brochure were tested in a series of evaluations by cohorts of experienced clinicians (n=49) and clinical content experts (n=8), with revisions after each review. Cognitive testing of the brochure was performed through interviews of 10 representative family members of chronically critically ill patients with quantitative and qualitative analysis of responses. Measurements and Main Results Clinical sensibility and balance were rated in the two most favorable categories on a 5-point scale by more than two thirds of clinicians and content experts. After review, family members described the brochure as clear and readable and recommended that the brochure be delivered to family members by clinicians, followed by a discussion of its contents. They indicated that the glossary was useful and recommended supplementation by additional lists of local resources. After reading the brochure, their prognostic estimates became more consistent with actual outcomes. Conclusions We have developed and validated a printed information brochure that may improve family comprehension of chronic critical illness and its outcomes. The structured process that is described can serve as a template for the development of other information aids for use with seriously ill populations. PMID:21926610

Influence of work-related psychosocial factors on the prevalence of chronic pain and quality of life in patients with chronic pain.

PubMed

Yamada, Keiko; Matsudaira, Ko; Imano, Hironori; Kitamura, Akihiko; Iso, Hiroyasu

2016-04-25

Working is a common cause of chronic pain for workers. However, most of them need to continue working despite the pain in order to make a living unless they get a sick leave or retirement. We hypothesised that the therapeutic effect of vocational rehabilitation may depend on psychosocial factors related to the workplace. To test this hypothesis, we examined the association of work-related psychosocial factors with the prevalence of chronic pain or health-related quality of life (HRQoL) among workers with chronic pain. We examined 1764 workers aged 20-59 years in the pain-associated cross-sectional epidemiological survey in Japan. The outcomes were (1) chronic pain prevalence among all workers and (2) low Euro QoL (EQ-5D <0.76; mean value of the current study) prevalence among workers with chronic pain according to the degree of workplace social support and job satisfaction. Workplace social support and job satisfaction were measured using the Brief Job Stress Questionnaire. Multivariable-adjusted ORs were calculated using a logistic regression model including age, sex, smoking, exercise, sleep time, work hours, body mass index, personal consumption expenditure, intensity of pain and the presence of severe depressive symptoms. Chronic pain prevalence was higher among males reporting job dissatisfaction compared with those reporting job satisfaction. No difference was observed among women. Chronic pain prevalence did not differ between workers of either sex reporting poor workplace social support compared with those reporting sufficient support. Among workers with chronic pain, low HRQoL was more frequent in those reporting job dissatisfaction. Similarly, low HRQoL was more frequent in patients with chronic pain reporting poor social support from supervisors or co-workers compared with patients reporting sufficient support. Work-related psychosocial factors are critical for HRQoL in patients with chronic pain. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Anger arousal and behavioral anger regulation in everyday life among people with chronic low back pain: Relationships with spouse responses and negative affect.

PubMed

Burns, John W; Gerhart, James I; Bruehl, Stephen; Post, Kristina M; Smith, David A; Porter, Laura S; Schuster, Erik; Buvanendran, Asokumar; Fras, Anne Marie; Keefe, Francis J

2016-01-01

To determine the degree to which anger arousal and anger regulation (expression, inhibition) in the daily lives of people with chronic pain were related to spouse support, criticism, and hostility as perceived by patients and as reported by spouses. Married couples (N = 105, 1 spouse with chronic low back pain) completed electronic daily diaries, with assessments 5 times/day for 14 days. On these diaries, patients completed items on their own anger arousal, anger expression, and inhibition, and on perceived spouse support, criticism, and hostility. Spouses reported on their responses toward patients and their negative affect. Hierarchical linear modeling tested concurrent and lagged relationships. Patient-reported increases in anger arousal and anger expression were predominantly related to concurrent decreases in patient-perceived and spouse-reported spouse support, concurrent increases in patient-perceived and spouse-reported spouse criticism and hostility, and increases in spouse-reported negative affect. Relationships for anger expression remained significant with anger arousal controlled. These effects were especially strong for male patients. Spouses reported greater negative affect when patients were present than when they were not. Social support may facilitate adjustment to chronic pain, with declining support and overt criticism and hostility possibly adversely impacting pain and function. Results suggest that patient anger arousal and expression may be related to a negative interpersonal environment for married couples coping with chronic low back pain. (c) 2015 APA, all rights reserved).

Absenteeism due to Functional Limitations Caused by Seven Common Chronic Diseases in US Workers.

PubMed

Vuong, Tam D; Wei, Feifei; Beverly, Claudia J

2015-07-01

The study examined the relationship between functional limitation due to chronic diseases and absenteeism among full-time workers. The studied chronic diseases include arthritis/rheumatism, cancer, diabetes, heart disease, hypertension, lung disease, and stroke. We analyzed data from the 2011 to 2013 National Health Interview Survey. Economic impact was determined by workdays lost and lost income. Increase in absenteeism was observed for each studied condition. Employees with multiple conditions also saw increase absenteeism. Employers lose 28.2 million workdays annually ($4.95 billion in lost income) due to functional limitation caused by chronic diseases. The results show a burden on society due to functional limitation caused by studied chronic diseases. Employers should look into implementing intervention/prevention programs, such as the Chronic Disease Self-Management Programs, to help reduce the cost associated with absenteeism.

Transient urinary retention and chronic neuropathic pain associated with genital herpes simplex virus infection.

PubMed

Haanpää, Maija; Paavonen, Jorma

2004-10-01

Genital herpes (GH) causes genital ulcer disease, severe transient pain, and often paresthesias. Whether or not GH can cause urinary retention or chronic neuropathic pain is not well known. We present two immunocompetent patients with GH associated with neuropathic symptoms. We also review the literature on GH and associated neurologic problems. Patient 1 had primary herpes simplex virus (HSV)-2 infection with transient urinary retention and chronic bilateral neuropathic pain in the sacral area. Patient 2 had recurrent HSV-1 associated with unitaleral chronic neuropathic pain in the sacral area. Although transient urinary retention associated with GH is not uncommon, chronic neuropathic pain has not been reported previously. Our cases show that chronic neuropathic pain, that is "pain initiated or caused by a primary lesion or dysfunction in the nervous system," can follow genital HSV infection.

Generating protective immunity against genital herpes

PubMed Central

Shin, Haina; Iwasaki, Akiko

2013-01-01

Genital herpes is an incurable, chronic disease that affects millions of people worldwide. Not only does genital herpes cause painful, recurrent symptoms, it is also a significant risk factor for the acquisition of other sexually transmitted infections such as HIV-1. Antiviral drugs are used to treat herpes simplex virus (HSV) infection, but they cannot stop viral shedding and transmission. Thus, developing a vaccine that can prevent or clear infection will be critical in limiting the spread of disease. In this review, we outline recent studies that improve our understanding of host responses against HSV infection, discuss past clinical vaccine trials and highlight new strategies for vaccine design against genital herpes. PMID:24012144

Inflammation-induced lymphangiogenesis and lymphatic dysfunction

PubMed Central

Liao, Shan; von der Weid, Pierre-Yves

2014-01-01

The lymphatic system is intimately linked to tissue fluid homeostasis and immune cell trafficking. These functions are paramount in the establishment and development of an inflammatory response. In the past decade, an increasing number of reports has revealed that marked changes, such as lymphangiogenesis and lymphatic contractile dysfunction occur in both vascular and nodal parts of the lymphatic system during inflammation, as well as other disease processes. This review provides a critical update on the role of the lymphatic system in disease process such as chronic inflammation and cancer and examines the changes in lymphatic functions the diseases cause and the influence these changes have on the progression of the diseases. PMID:24449090

The Basics of Renal Allograft Pathology.

PubMed

Troxell, Megan L; Houghton, Donald C

2014-09-01

Renal allograft biopsy provides critical information in the management of renal transplant patients, and must be analyzed in close collaboration with the clinical team. The histologic correlates of acute T-cell mediated rejection are interstitial inflammation, tubulitis, and endothelialitis; polyomavirus nephropathy is a potential mimic. Evidence of antibody-mediated rejection includes C4d deposition; morphologic acute tissue injury; and donor specific antibodies. Acute tubular injury/necrosis is a reversible cause of impaired graft function, especially in the immediate post-transplant period. Drug toxicity, recurrent disease, chronic injury, and other entities affecting both native and transplant kidneys must also be evaluated. Copyright © 2014 Elsevier Inc. All rights reserved.

Physical activity and exercise attenuate neuroinflammation in neurological diseases.

PubMed

Spielman, Lindsay Joy; Little, Jonathan Peter; Klegeris, Andis

2016-07-01

Major depressive disorder (MDD), schizophrenia (SCH), Alzheimer's disease (AD), and Parkinson's disease (PD) are devastating neurological disorders, which increasingly contribute to global morbidity and mortality. Although the pathogenic mechanisms of these conditions are quite diverse, chronic neuroinflammation is one underlying feature shared by all these diseases. Even though the specific root causes of these diseases remain to be identified, evidence indicates that the observed neuroinflammation is initiated by unique pathological features associated with each specific disease. If the initial acute inflammation is not resolved, a chronic neuroinflammatory state develops and ultimately contributes to disease progression. Chronic neuroinflammation is characterized by adverse and non-specific activation of glial cells, which can lead to collateral damage of nearby neurons and other glia. This misdirected neuroinflammatory response is hypothesized to contribute to neuropathology in MDD, SCH, AD, and PD. Physical activity (PA), which is critical for maintenance of whole body and brain health, may also beneficially modify neuroimmune responses. Since PA has neuroimmune-modifying properties, and the common underlying feature of MDD, SCH, AD, and PD is chronic neuroinflammation, we hypothesize that PA could minimize brain diseases by modifying glia-mediated neuroinflammation. This review highlights current evidence supporting the disease-altering potential of PA and exercise through modifications of neuroimmune responses, specifically in MDD, SCH, AD and PD. Copyright © 2016 Elsevier Inc. All rights reserved.

RAGE and tobacco smoke: insights into modeling chronic obstructive pulmonary disease

PubMed Central

Robinson, Adam B.; Stogsdill, Jeffrey A.; Lewis, Joshua B.; Wood, Tyler T.; Reynolds, Paul R.

2012-01-01

Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by chronic airway inflammation and airspace remodeling, leading to airflow limitation that is not completely reversible. Smoking is the leading risk factor for compromised lung function stemming from COPD pathogenesis. First- and second-hand cigarette smoke contain thousands of constituents, including several carcinogens and cytotoxic chemicals that orchestrate chronic lung inflammation and destructive alveolar remodeling. Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors primarily expressed by diverse lung cells. RAGE expression increases following cigarette smoke exposure and expression is elevated in the lungs of patients with COPD. RAGE is responsible in part for inducing pro-inflammatory signaling pathways that culminate in expression and secretion of several cytokines, chemokines, enzymes, and other mediators. In the current review, new transgenic mouse models that conditionally over-express RAGE in pulmonary epithelium are discussed. When RAGE is over-expressed throughout embryogenesis, apoptosis in the peripheral lung causes severe lung hypoplasia. Interestingly, apoptosis in RAGE transgenic mice occurs via conserved apoptotic pathways also known to function in advanced stages of COPD. RAGE over-expression in the adult lung models features of COPD including pronounced inflammation and loss of parenchymal tissue. Understanding the biological contributions of RAGE during cigarette smoke-induced inflammation may provide critically important insight into the pathology of COPD. PMID:22934052

COPD and osteoporosis: links, risks, and treatment challenges.

PubMed

Inoue, Daisuke; Watanabe, Reiko; Okazaki, Ryo

2016-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease associated with various systemic comorbidities including osteoporosis. Osteoporosis and its related fractures are common and have significant impacts on quality of life and even respiratory function in patients with COPD. COPD-associated osteoporosis is however extremely undertreated. Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility, causing fractures in COPD patients. Various clinical risk factors of osteoporosis in COPD patients, including older age, emaciation, physical inactivity, and vitamin D deficiency, have also been described. It is critically important for pulmonologists to be aware of the high prevalence of osteoporosis in COPD patients and evaluate them for such fracture risks. Routine screening for osteoporosis will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage and give them appropriate treatment to prevent fracture, which may lead to improved quality of life as well as better long-term prognosis.

Liver pathology of hepatitis C, beyond grading and staging of the disease

PubMed Central

Dhingra, Sadhna; Ward, Stephen C; Thung, Swan N

2016-01-01

Liver biopsy evaluation plays a critical role in management of patients with viral hepatitis C. In patients with acute viral hepatitis, a liver biopsy, though uncommonly performed, helps to rule out other non-viral causes of deranged liver function. In chronic viral hepatitis C, it is considered the gold standard in assessment of the degree of necroinflammation and the stage of fibrosis, to help guide treatment and determine prognosis. It also helps rule out any concomitant diseases such as steatohepatitis, hemochromatosis or others. In patients with chronic progressive liver disease with cirrhosis and dominant nodules, a targeted liver biopsy is helpful in differentiating a regenerative nodule from dysplastic nodule or hepatocellular carcinoma. In the setting of transplantation, the liver biopsy helps distinguish recurrent hepatitis C from acute rejection and also is invaluable in the diagnosis of fibrosing cholestatic hepatitis, a rare variant of recurrent hepatitis C. This comprehensive review discusses the entire spectrum of pathologic findings in the course of hepatitis C infection. PMID:26819505

Disseminated Cryptococcal Disease in a Patient with Chronic Lymphocytic Leukemia on Ibrutinib.

PubMed

Okamoto, Koh; Proia, Laurie A; Demarais, Patricia L

2016-01-01

Cryptococcus is a unique environmental fungus that can cause disease most often in immunocompromised individuals with defective cell-mediated immunity. Chronic lymphocytic leukemia (CLL) is not known to be a risk factor for cryptococcal disease although cases have been described mainly in patients treated with agents that suppress cell-mediated immunity. Ibrutinib is a new biologic agent used for treatment of CLL, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. It acts by inhibiting Bruton's tyrosine kinase, a kinase downstream of the B-cell receptor critical for B-cell survival and proliferation. Ibrutinib use has not been associated previously with cryptococcal disease. However, recent evidence suggested that treatments aimed at blocking the function of Bruton's tyrosine kinase could pose a higher risk for cryptococcal infection in a mice model. Here, we report the first case of disseminated cryptococcal disease in a patient with CLL treated with ibrutinib. When evaluating possible infection in CLL patients receiving ibrutinib, cryptococcal disease, which could be life threatening if overlooked, could be considered.

From war on terror to war on weather? Rethinking humanitarianism in a new era of chronic emergencies.

PubMed

Munslow, Barry; O'Dempsey, Tim

2010-01-01

This special issue of Third World Quarterly makes a case for redirecting attention and resources away from the 'war on terror' and focussing as a matter of urgency on the causes and consequences of global climate change. Global climate change must be recognised as an issue of national and international security. Increased competition for scarce resources and migration are key factors in the propagation of many of today's chronic complex humanitarian emergencies. The relentless growth of megacities in natural disaster hotspots places unprecedented numbers of vulnerable people at risk of disease and death. The Earth's fragile ecosystem has reached a critical tipping point. Today's most urgent need is for a collective endeavour on the part of the international community to redirect resources, enterprise and creativity away from the war on terror and to earnestly redeploy these in seeking solutions to the far greater and increasingly imminent threats that confront us as a consequence of global climate change.

Low back pain - chronic

MedlinePlus

Nonspecific back pain; Backache - chronic; Lumbar pain - chronic; Pain - back - chronic; Chronic back pain - low ... Low back pain is common. Almost everyone has back pain at some time in their life. Often, the exact cause of ...

Time dependent effect of chronic embryonic exposure to ethanol on zebrafish: Morphology, biochemical and anxiety alterations.

PubMed

Ramlan, Nurul Farhana; Sata, Nurul Syafida Asma Mohd; Hassan, Siti Norhidayah; Bakar, Noraini Abu; Ahmad, Syahida; Zulkifli, Syaizwan Zahmir; Abdullah, Che Azurahanim Che; Ibrahim, Wan Norhamidah Wan

2017-08-14

Exposure to ethanol during critical period of development can cause severe impairments in the central nervous system (CNS). This study was conducted to assess the neurotoxic effects of chronic embryonic exposure to ethanol in the zebrafish, taking into consideration the time dependent effect. Two types of exposure regimen were applied in this study. Withdrawal exposure group received daily exposure starting from gastrulation until hatching, while continuous exposure group received daily exposure from gastrulation until behavioural assessment at 6dpf (days post fertilization). Chronic embryonic exposure to ethanol decreased spontaneous tail coiling at 24hpf (hour post fertilization), heart rate at 48hpf and increased mortality rate at 72hpf. The number of apoptotic cells in the embryos treated with ethanol was significantly increased as compared to the control. We also measured the morphological abnormalities and the most prominent effects can be observed in the treated embryos exposed to 1.50% and 2.00%. The treated embryos showed shorter body length, larger egg yolk, smaller eye diameter and heart edema as compared to the control. Larvae received 0.75% continuous ethanol exposure exhibited decreased swimming activity and increased anxiety related behavior, while withdrawal ethanol exposure showed increased swimming activity and decreased anxiety related behavior as compared to the respective control. Biochemical analysis exhibited that ethanol exposure for both exposure regimens altered proteins, lipids, carbohydrates and nucleic acids of the zebrafish larvae. Our results indicated that time dependent effect of ethanol exposure during development could target the biochemical processes thus leading to induction of apoptosis and neurobehavioral deficits in the zebrafish larvae. Thus it raised our concern about the safe limit of alcohol consumption for pregnant mother especially during critical periods of vulnerability for developing nervous system. Copyright © 2017 Elsevier B.V. All rights reserved.

Drinking patterns and beverage preferences of liver cirrhosis patients in Mexico.

PubMed

Campollo, O; Martínez, M D; Valencia, J J; Segura-Ortega, J

2001-02-01

The purpose of this study was to investigate the pattern of alcoholism in a special group of alcoholics (alcoholic cirrhotics) in a hospital-based population in west central Mexico and assess the role of regional spirits such as tequila. A complete alcohol drinking history and a structured questionnaire directed at investigating the pattern of alcohol consumption was applied to 124 adult patients with chronic liver disease caused by alcohol during January 1995 to January 1996. The mean age of onset was 27 +/- 3 years in women and 18 +/- 0.5 years in men. The mean alcohol intake per week was 749 +/- 192 g for women and 1113 +/- 151 g for men. On average, patients consumed alcohol for a mean of 24.5 years. The overall patient drinking preference was for tequila followed by 96 degree Gay Lusac (G.L.), alcohol, and beer. In a subset of 70 patients three phases of alcoholism could be identified (prealcoholic, critical, and chronic). Each phase had a mean duration of at least 11 years. Beer was the dominant beverage in the prealcoholic phase while tequila was consumed more often in the other phases. In the critical phase of alcoholism an average of 337 g of alcohol were consumed per week and in the chronic phase 1765 g/week. Tequila was the overall preferred beverage in this group of alcoholics. Other beverages included beer and straight alcohol with a clear trend from less to higher concentration of alcohol throughout the drinking history. Subtle gender differences in the patterns of alcoholism may be suspected. In this group of patients the role of tequila drinking is highlighted.

Hoxa9 and Hoxa10 induce CML myeloid blast crisis development through activation of Myb expression.

PubMed

Negi, Vijay; Vishwakarma, Bandana A; Chu, Su; Oakley, Kevin; Han, Yufen; Bhatia, Ravi; Du, Yang

2017-11-17

Mechanisms underlying the progression of Chronic Myeloid Leukemia (CML) from chronic phase to myeloid blast crisis are poorly understood. Our previous studies have suggested that overexpression of SETBP1 can drive this progression by conferring unlimited self-renewal capability to granulocyte macrophage progenitors (GMPs). Here we show that overexpression of Hoxa9 or Hoxa10 , both transcriptional targets of Setbp1 , is also sufficient to induce self-renewal of primary myeloid progenitors, causing their immortalization in culture. More importantly, both are able to cooperate with BCR/ABL to consistently induce transformation of mouse GMPs and development of aggressive leukemias resembling CML myeloid blast crisis, suggesting that either gene can drive CML progression by promoting the self-renewal of GMPs. We further identify Myb as a common critical target for Hoxa9 and Hoxa10 in inducing self-renewal of myeloid progenitors as Myb knockdown significantly reduced colony-forming potential of myeloid progenitors immortalized by the expression of either gene. Interestingly, Myb is also capable of immortalizing primary myeloid progenitors in culture and cooperating with BCR/ABL to induce leukemic transformation of mouse GMPs. Significantly increased levels of MYB transcript also were detected in all human CML blast crisis samples examined over chronic phase samples, further suggesting the possibility that MYB overexpression may play a prevalent role in driving human CML myeloid blast crisis development. In summary, our results identify overexpression of HOXA9 , HOXA10 , and MYB as critical drivers of CML progression, and suggest MYB as a key therapeutic target for inhibiting the self-renewal of leukemia-initiating cells in CML myeloid blast crisis patients.

The role of ions, heavy metals, fluoride, and agrochemicals: critical evaluation of potential aetiological factors of chronic kidney disease of multifactorial origin (CKDmfo/CKDu) and recommendations for its eradication.

PubMed

Wimalawansa, Sunil J

2016-06-01

The pollution of water and food through human waste and anthropogenic activities, including industrial waste and agricultural runoff, is a mounting problem worldwide. Water pollution from microbes causes identifiable diarrhoeal illnesses. The consumption of water contaminated with heavy metals, fluoride, and other toxins causes insidious illnesses that lead to protracted, non-communicable diseases and death. Chronic kidney disease of unusual/uncertain/unknown aetiology is one such example, began to manifest in the mid-1960s in several dry-zonal agricultural societies in developing economies that are located around the equator. In Sri Lanka, such a disease is affecting the North Central Province, the rice bowl of the country that first appeared in the mid-1990s. Several potential causes have been postulated, including heavy metals, fluoride, cyanobacterial and algae toxins, agrochemicals, and high salinity and ionicity in water, but no specific source or causative factor has been identified for CKD of multifactorial origin (CKDmfo). Three large studies conducted in the recent past failed to find any of the postulated components (heavy metals, cyanobacterial toxins, fluoride, salinity, or agrochemicals) at levels higher than those deemed safe by the World Health Organization and the US Environmental Protection Agency. At the reported low levels in water and with the heterogeneous geographical distribution, it is unrealistic to expect any of these components individually could cause this disease. However, the additive or synergistic effects of a combination of factors and components, even at lower exposure levels, together with malnutrition and harmful behaviours, and/or a yet-unidentified (or not investigated) toxin, can cause this epidemic. Because the cause is unknown, scientists need to work on broader hypotheses, so that key causative elements are not missed. Taken together the plausibility of multiple factors in the genesis of this disease, the appropriate terminology is CKDmfo, a name that also indicates the need for multi-disciplinary research programs to facilitate identifying the cause(s) and the need for multiple approaches to eradicate it. While some potential causes remain to be investigated, existing data point to polluted water as the main source of this disease. This article evaluates pros and cons of each hypothesis and highlights the importance of among others, providing clean water to all affected and surrounding communities. Available data do not support any of the postulated agents, chemicals, heavy metals, fluoride, salinity/ionicity, or individual agrochemical components, such as phosphate or glyphosate, as causative factors for CKDmfo in Sri Lanka. However, as the CKDmfo name implies, a combination of these factors (or an unknown toxin) together with harmful behaviour and chronic dehydration may cause this disease. Irrespective of the cause, prevention is the only way forward for eradication.

Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients

PubMed Central

Loftus, Tyler J; Mira, Juan C; Ozrazgat-Baslanti, Tezcan; Ghita, Gabriella L; Wang, Zhongkai; Stortz, Julie A; Brumback, Babette A; Bihorac, Azra; Segal, Mark S; Anton, Stephen D; Leeuwenburgh, Christiaan; Mohr, Alicia M; Efron, Philip A; Moldawer, Lyle L; Moore, Frederick A; Brakenridge, Scott C

2017-01-01

Introduction Sepsis is a common, costly and morbid cause of critical illness in trauma and surgical patients. Ongoing advances in sepsis resuscitation and critical care support strategies have led to improved in-hospital mortality. However, these patients now survive to enter state of chronic critical illness (CCI), persistent low-grade organ dysfunction and poor long-term outcomes driven by the persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Sepsis and Critical Illness Research Center (SCIRC) was created to provide a platform by which the prevalence and pathogenesis of CCI and PICS may be understood at a mechanistic level across multiple medical disciplines, leading to the development of novel management strategies and targeted therapies. Methods Here, we describe the design, study cohort and standard operating procedures used in the prospective study of human sepsis at a level 1 trauma centre and tertiary care hospital providing care for over 2600 critically ill patients annually. These procedures include implementation of an automated sepsis surveillance initiative, augmentation of clinical decisions with a computerised sepsis protocol, strategies for direct exportation of quality-filtered data from the electronic medical record to a research database and robust long-term follow-up. Ethics and dissemination This study has been registered at ClinicalTrials.gov, approved by the University of Florida Institutional Review Board and is actively enrolling subjects. Dissemination of results is forthcoming. PMID:28765125

[Chronic heart failure].

PubMed

Gosch, Markus

2008-08-01

As a consequence of the increasing life expectancy the number of patients suffering from chronic heart failure has been growing continuously in the past few decades, especially in the group of the old and oldest. Frailty is a clinical syndrome that geriatricians attach great importance to. Like many other diseases chronic heart failure can cause frailty. Based on the experience that we see only a small correlation between the functional capacity of patients with heart failure and the results of cardiological findings, the model of peripheral myopathy in chronic heart failure was developed. Different pathophysiological changes may cause the increasing exercise intolerance in patients with chronic heart failure. We can already consider different experimental approaches to the therapy of frailty caused by chronic heart failure. At the moment we have to focus our efforts on an optimal therapy of heart failure, especially with angiotensin-converting-enzyme inhibitors and beta-blockers, and on individual endurance and strength training.

Development of Burkholderia mallei and pseudomallei vaccines.

PubMed

Silva, Ediane B; Dow, Steven W

2013-01-01

Burkholderia mallei and Burkholderia pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. Chronic infection may develop after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. Symptoms for both meliodosis and glanders are non-specific, making diagnosis difficult. B. pseudomallei can be located in the environment, but in the host, B. mallei and B. psedomallei are intracellular organisms, and infection results in similar immune responses to both agents. Effective early innate immune responses are critical to controlling the early phase of the infection. Innate immune signaling molecules such as TLR, NOD, MyD88, and pro-inflammatory cytokines such as IFN-γ and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for both microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In contrast, the role of adaptive immune responses in controlling Burkholderia infection is less well understood. However, T cell responses are critical for vaccine protection from Burkholderia infection. At present, effective vaccines for prevention of glanders or meliodosis have not been developed, although recently development of Burkholderia vaccines has received renewed attention. This review will summarize current and past approaches to develop B. mallei and B. pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated bacteria provides the most effective and durable immunity, and it is important therefore to understand the immune correlates of protection induced by live attenuated vaccines. Subunit vaccines have typically provided less robust immunity, but are safer to administer to a wider variety of people, including immune compromised individuals because they do not reactivate or cause disease. The challenges facing B. mallei and B. pseudomalllei vaccine development include identification of broadly protective antigens, design of efficient vaccine delivery and adjuvant systems, and a better understanding of the correlates of protection from both acute and chronic infection.

Development of Burkholderia mallei and pseudomallei vaccines

PubMed Central

Silva, Ediane B.; Dow, Steven W.

2013-01-01

Burkholderia mallei and Burkholderia pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. Chronic infection may develop after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. Symptoms for both meliodosis and glanders are non-specific, making diagnosis difficult. B. pseudomallei can be located in the environment, but in the host, B. mallei and B. psedomallei are intracellular organisms, and infection results in similar immune responses to both agents. Effective early innate immune responses are critical to controlling the early phase of the infection. Innate immune signaling molecules such as TLR, NOD, MyD88, and pro-inflammatory cytokines such as IFN-γ and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for both microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In contrast, the role of adaptive immune responses in controlling Burkholderia infection is less well understood. However, T cell responses are critical for vaccine protection from Burkholderia infection. At present, effective vaccines for prevention of glanders or meliodosis have not been developed, although recently development of Burkholderia vaccines has received renewed attention. This review will summarize current and past approaches to develop B. mallei and B. pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated bacteria provides the most effective and durable immunity, and it is important therefore to understand the immune correlates of protection induced by live attenuated vaccines. Subunit vaccines have typically provided less robust immunity, but are safer to administer to a wider variety of people, including immune compromised individuals because they do not reactivate or cause disease. The challenges facing B. mallei and B. pseudomalllei vaccine development include identification of broadly protective antigens, design of efficient vaccine delivery and adjuvant systems, and a better understanding of the correlates of protection from both acute and chronic infection. PMID:23508691

[Language delay in children with chronic suppurative otitis media].

PubMed

Biurrún Unzué, Oscar; Biurrún Unzué, Ana; Villacorta Labairu, Begoña; Andrade Arriaga, Marcela

2003-01-01

The chronic serous otitis media is a well known cause of fluctuant moderated conduction deafness in childhood but not well studied in Castillian speaking areas, as a cause of alterations in the acquisition of language. In the present study we evaluate the chronic serous otitis media as a cause of alterations in the development of the language in childhood. We studied the semantic development level in a group of 18 four years old children affected of chronic serous otitis media of more than one year evolution. The incidence of alterations was of 27.7%. We discuss the results obtained and we propose a management for this pathology.

The neuropathology of traumatic brain injury.

PubMed

Mckee, Ann C; Daneshvar, Daniel H

2015-01-01

Traumatic brain injury, a leading cause of mortality and morbidity, is divided into three grades of severity: mild, moderate, and severe, based on the Glasgow Coma Scale, the loss of consciousness, and the development of post-traumatic amnesia. Although mild traumatic brain injury, including concussion and subconcussion, is by far the most common, it is also the most difficult to diagnose and the least well understood. Proper recognition, management, and treatment of acute concussion and mild traumatic brain injury are the fundamentals of an emerging clinical discipline. It is also becoming increasingly clear that some mild traumatic brain injuries have persistent, and sometimes progressive, long-term debilitating effects. Evidence indicates that a single traumatic brain injury can precipitate or accelerate multiple age-related neurodegenerations, increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease, and that repetitive mild traumatic brain injuries can provoke the development of a tauopathy, chronic traumatic encephalopathy. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus, septal abnormalities, and abnormal deposits of hyperphosphorylated tau (τ) as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy frequently occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including Alzheimer's disease, Lewy body disease, and motor neuron disease. Currently, chronic traumatic encephalopathy can be diagnosed only at autopsy; however, promising efforts to develop imaging, spinal fluid, and peripheral blood biomarkers are underway to diagnose and monitor the course of disease in living subjects. © 2015 Elsevier B.V. All rights reserved.

Effect of Chronic Kidney Diseases on Mortality among Digoxin Users Treated for Non-Valvular Atrial Fibrillation: A Nationwide Register-Based Retrospective Cohort Study.

PubMed

Sessa, Maurizio; Mascolo, Annamaria; Andersen, Mikkel Porsborg; Rosano, Giuseppe; Rossi, Francesco; Capuano, Annalisa; Torp-Pedersen, Christian

2016-01-01

This study investigated the impact of chronic kidney disease on all-causes and cardiovascular mortality in patients with atrial fibrillation treated with digoxin. All patients with non-valvular atrial fibrillation and/or atrial flutter as hospitalization diagnosis from January 1, 1997 to December 31, 2012 were identified in Danish nationwide administrative registries. Cox proportional hazard model was used to compare the adjusted risk of all-causes and cardiovascular mortality among patients with and without chronic kidney disease and among patients with different chronic kidney disease stages within 180 days and 2 years from the first digoxin prescription. We identified 37,981 patients receiving digoxin; 1884 patients had the diagnosis of chronic kidney disease. Cox regression analysis showed no statistically significant differences in all-causes (Hazard Ratio, HR 0.89; 95% confident interval, CI 0.78-1.03) and cardiovascular mortality (HR 0.88; 95%CI 0.74-1.05) among patients with and without chronic kidney disease within 180 days of follow-up period. No statistically significant differences was found using a 2 years follow-up period neither for all causes mortality (HR 0.90; 95%CI 0.79-1.03), nor for cardiovascular mortality (HR 0.87; 95%CI 0.74-1.02). No statistically significant differences was found comparing patients with and without estimated Glomerular Filtration Rate <30ml/min/1.73m2 and patients with different stages of chronic kidney disease, for all-causes and cardiovascular mortality within 180 days and 2 years from the first digoxin prescription. This study suggest no direct effect of chronic kidney disease and chronic kidney disease stages on all-causes and cardiovascular mortality within both 180 days and 2 years from the first digoxin prescription in patients treatment-naïve with digoxin for non-valvular atrial fibrillation.

Chronic Q Fever in the Netherlands 5 Years after the Start of the Q Fever Epidemic: Results from the Dutch Chronic Q Fever Database

PubMed Central

Delsing, Corine E.; Groenwold, Rolf H. H.; Wegdam-Blans, Marjolijn C. A.; Bleeker-Rovers, Chantal P.; de Jager-Leclercq, Monique G. L.; Hoepelman, Andy I. M.; van Kasteren, Marjo E.; Buijs, Jacqueline; Renders, Nicole H. M.; Nabuurs-Franssen, Marrigje H.; Oosterheert, Jan Jelrik; Wever, Peter C.

2014-01-01

Coxiella burnetii causes Q fever, a zoonosis, which has acute and chronic manifestations. From 2007 to 2010, the Netherlands experienced a large Q fever outbreak, which has offered a unique opportunity to analyze chronic Q fever cases. In an observational cohort study, baseline characteristics and clinical characteristics, as well as mortality, of patients with proven, probable, or possible chronic Q fever in the Netherlands, were analyzed. In total, 284 chronic Q fever patients were identified, of which 151 (53.7%) had proven, 64 (22.5%) probable, and 69 (24.3%) possible chronic Q fever. Among proven and probable chronic Q fever patients, vascular infection focus (56.7%) was more prevalent than endocarditis (34.9%). An acute Q fever episode was recalled by 27.0% of the patients. The all-cause mortality rate was 19.1%, while the chronic Q fever-related mortality rate was 13.0%, with mortality rates of 9.3% among endocarditis patients and 18% among patients with a vascular focus of infection. Increasing age (P = 0.004 and 0.010), proven chronic Q fever (P = 0.020 and 0.002), vascular chronic Q fever (P = 0.024 and 0.005), acute presentation with chronic Q fever (P = 0.002 and P < 0.001), and surgical treatment of chronic Q fever (P = 0.025 and P < 0.001) were significantly associated with all-cause mortality and chronic Q fever-related mortality, respectively. PMID:24599987

Factors influencing patient compliance with therapeutic regimens in chronic heart failure: A critical incident technique analysis.

PubMed

Strömberg, A; Broström, A; Dahlström, U; Fridlund, B

1999-01-01

The aim of this study was to identify factors influencing compliance with prescribed treatment in patients with chronic heart failure. A qualitative design with a critical incident technique was used. Incidents were collected through interviews with 25 patients with heart failure strategically selected from a primary health care clinic, a medical ward, and a specialist clinic. Two hundred sixty critical incidents were identified in the interviews and 2 main areas emerged in the analysis: inward factors and outward factors. The inward factors described how compliance was influenced by the personality of the patient, the disease, and the treatment. The outward factors described how compliance was influenced by social activities, social relationships, and health care professionals. By identifying the inward and outward factors influencing patients with chronic heart failure, health care professionals can assess whether intervention is needed to increase compliance.

Chronic Stress Exposure and Generation Are Related to the P-Factor and Externalizing Specific Psychopathology in Youth.

PubMed

Snyder, Hannah R; Young, Jami F; Hankin, Benjamin L

2017-05-25

Psychopathology is posited to be transdiagnostically linked to chronic stress. Yet efforts to understand the specificity and directionality of these links have been sparse, and the ubiquitous comorbidity of psychopathology has made the seemingly nonspecific links between psychological disorders and chronic stress difficult to interpret. The current study used a latent dimensional bifactor model of psychopathology to account for comorbidity and a multiwave prospective design to disentangle temporal associations between psychopathology and chronic stress longitudinally during the critical adolescent period for psychopathology risk and stress reactivity. A community sample of 567 youth (55.5% female, age M = 11.8 at baseline, M = 15.1 at end of study) were followed prospectively for 3 years, with chronic stress assessed with the Youth Life Stress Interview and psychopathology symptoms assessed via both self and parent report. Exposure to chronic stress predicted what is common across forms of psychopathology (the p factor), which in turn predicted generation of chronic stress over time. After accounting for comorbidity via the p factor, externalizing behaviors also had specific transactional links to chronic stress, whereas links between internalizing psychopathology and chronic stress were completely accounted for by common psychopathology. The results provide the first direct evidence that chronic stress is transdiagnostically and reciprocally linked to psychopathology, during a critical youth period for psychopathology onset and stress reactivity.

Disorders associated with systemic or local iron overload: from pathophysiology to clinical practice.

PubMed

Sebastiani, Giada; Pantopoulos, Kostas

2011-10-01

In healthy subjects, the rate of dietary iron absorption, as well as the amount and distribution of body iron are tightly controlled by hepcidin, the iron regulatory hormone. Disruption of systemic iron homeostasis leads to pathological conditions, ranging from anemias caused by iron deficiency or defective iron traffic, to iron overload (hemochromatosis). Other iron-related disorders are caused by misregulation of cellular iron metabolism, which results in local accumulation of the metal in mitochondria. Brain iron overload is observed in neurodegenerative disorders. Secondary hemochromatosis develops as a complication of another disease. For example, repeated blood transfusions, a standard treatment of various anemias characterized by ineffective erythropoiesis, promote transfusional siderosis, while chronic liver diseases are often associated with mild to moderate secondary iron overload. In this critical review, we discuss pathophysiological and clinical aspects of all types of iron metabolism disorders (265 references). This journal is © The Royal Society of Chemistry 2011

Aspergillus vertebral osteomyelitis in chronic leukocyte leukemia patient diagnosed by a novel panfungal polymerase chain reaction method.

PubMed

Dayan, Lior; Sprecher, Hannah; Hananni, Amos; Rosenbaum, Hana; Milloul, Victor; Oren, Ilana

2007-01-01

Vertebral osteomyelitis and disciitis caused by Aspergillus spp is a rare event. Early diagnosis and early antifungal therapy are critical in improving the prognosis for these patients. The diagnosis of invasive fungal infections is, in many cases, not straightforward and requires invasive procedures so that histological examination and culture can be performed. Furthermore, current traditional microbiological tests (ie, cultures and stains) lack the sensitivity for diagnosis of invasive aspergillosis. To present a case of vertebral osteomyelitis caused by Aspergillus spp diagnosed using a novel polymerase chain reaction (PCR) assay. Case report. Aspergillus DNA was detected in DNA extracted from the necrotic bone tissue by using a "panfungal" PCR novel method. Treatment with voriconazole was started based on the diagnosis. Using this novel technique enabled us to diagnose accurately an unusual bone pathogen that requires a unique treatment.

Failed medial patellofemoral ligament reconstruction: Causes and surgical strategies

PubMed Central

Sanchis-Alfonso, Vicente; Montesinos-Berry, Erik; Ramirez-Fuentes, Cristina; Leal-Blanquet, Joan; Gelber, Pablo E; Monllau, Joan Carles

2017-01-01

Patellar instability is a common clinical problem encountered by orthopedic surgeons specializing in the knee. For patients with chronic lateral patellar instability, the standard surgical approach is to stabilize the patella through a medial patellofemoral ligament (MPFL) reconstruction. Foreseeably, an increasing number of revision surgeries of the reconstructed MPFL will be seen in upcoming years. In this paper, the causes of failed MPFL reconstruction are analyzed: (1) incorrect surgical indication or inappropriate surgical technique/patient selection; (2) a technical error; and (3) an incorrect assessment of the concomitant risk factors for instability. An understanding of the anatomy and biomechanics of the MPFL and cautiousness with the imaging techniques while favoring clinical over radiological findings and the use of common sense to determine the adequate surgical technique for each particular case, are critical to minimizing MPFL surgery failure. Additionally, our approach to dealing with failure after primary MPFL reconstruction is also presented. PMID:28251062

Chronic consumption of a high-fat diet during pregnancy causes perturbations in the serotonergic system and increased anxiety-like behavior in nonhuman primate offspring.

PubMed

Sullivan, Elinor L; Grayson, Bernadette; Takahashi, Diana; Robertson, Nicola; Maier, Adriane; Bethea, Cynthia L; Smith, M Susan; Coleman, Kristine; Grove, Kevin L

2010-03-10

Childhood obesity is associated with increased risk of behavioral/psychological disorders including depression, anxiety, poor learning, and attention deficient disorder. As the majority of women of child-bearing age are overweight or obese and consume a diet high in dietary fat, it is critical to examine the consequences of maternal overnutrition on the development of brain circuitry that regulates offspring behavior. Using a nonhuman primate model of diet-induced obesity, we found that maternal high-fat diet (HFD) consumption caused perturbations in the central serotonergic system of fetal offspring. In addition, female infants from HFD-fed mothers exhibited increased anxiety in response to threatening novel objects. These findings have important clinical implications as they demonstrate that exposure to maternal HFD consumption during gestation, independent of obesity, increases the risk of developing behavioral disorders such as anxiety.

Chronic Consumption of a High Fat Diet During Pregnancy Causes Perturbations in the Serotonergic System and Increased Anxiety-like Behavior in Nonhuman Primate Offspring

PubMed Central

Sullivan, Elinor L.; Grayson, Bernadette; Takahashi, Diana; Robertson, Nicola; Maier, Adriane; Bethea, Cynthia L.; Smith, M. Susan; Coleman, Kristine; Grove, Kevin L.

2010-01-01

Childhood obesity is associated with increased risk of behavioral/psychological disorders including depression, anxiety, poor learning, and attention deficient disorder. As the majority of women of child-bearing age are overweight or obese and consume a diet high in dietary fat, it is critical to examine the consequences of maternal overnutrition on the development of brain circuitry that regulates offspring behavior. Using a nonhuman primate (NHP) model of diet-induced obesity, we found that maternal high-fat diet (HFD) consumption caused perturbations in the central serotonergic system of fetal offspring. In addition, female infants from HFD fed mothers exhibited increased anxiety in response to threatening novel objects. These findings have important clinical implications as they demonstrate that exposure to maternal HFD consumption during gestation, independent of obesity, increases the risk of developing behavioral disorders such as anxiety. PMID:20220017

Neutropenia during HIV Infection: Adverse Consequences and Remedies

PubMed Central

Shi, Xin; Sims, Matthew D; Hanna, Michel M; Xie, Ming; Gulick, Peter G; Zheng, Yong-Hui; Basson, Marc D; Zhang, Ping

2016-01-01

Neutropenia frequently occurs in patients with Human immunodeficiency virus (HIV) infection. Causes for neutropenia during HIV infection are multifactoral, including the viral toxicity to hematopoietic tissue, the use of myelotoxic agents for treatment, complication with secondary infections and malignancies, as well as the patient’s association with confounding factors which impair myelopoiesis. An increased prevalence and severity of neutropenia is commonly seen in advanced stages of HIV disease. Decline of neutrophil phagocytic defense in combination with the failure of adaptive immunity renders the host highly susceptible to developing fatal secondary infections. Neutropenia and myelosuppression also restrict the use of many antimicrobial agents for treatment of infections caused by HIV and opportunistic pathogens. In recent years, HIV infection has increasingly become a chronic disease because of progress in antiretroviral therapy (ART). Prevention and treatment of severe neutropenia becomes critical for improving the survival of HIV-infected patients. PMID:24654626

Muscle strengthening activity associates with reduced all-cause mortality in COPD.

PubMed

Loprinzi, Paul D; Sng, Eveleen; Walker, Jerome F

2017-06-01

Objective Emerging research suggests that aerobic-based physical activity may help to promote survival among chronic obstructive pulmonary disease patients. However, the extent to which engagement in resistance training on survival among chronic obstructive pulmonary disease patients is relatively unknown. Therefore, the purpose of this study was to examine the independent associations of muscle strengthening activities on all-cause mortality among a national sample of U.S. adults with chronic obstructive pulmonary disease. We hypothesize that muscle strengthening activities will be inversely associated with all-cause mortality. Methods Data from the 2003-2006 NHANES were employed, with follow-up through 2011. Aerobic-based physical activity was objectively measured via accelerometry, muscle strengthening activities engagement was assessed via self-report, and chronic obstructive pulmonary disease was assessed via physician-diagnosis. Results Analysis included 385 adults (20 + yrs) with chronic obstructive pulmonary disease, who represent 13.3 million chronic obstructive pulmonary disease patients in the USA. The median follow-up period was 78 months (IQR=64-90), with 82 chronic obstructive pulmonary disease patients dying during this period. For a two muscle strengthening activity sessions/week increase (consistent with national guidelines), chronic obstructive pulmonary disease patients had a 29% reduced risk of all-cause mortality (HR=0.71; 95% CI: 0.51-0.99; P = 0.04). Conclusion Participation in muscle strengthening activities, independent of aerobic-based physical activity and other potential confounders, is associated with greater survival among chronic obstructive pulmonary disease patients.

Type IV Pilus Expression Is Upregulated in Nontypeable Haemophilus influenzae Biofilms Formed at the Temperature of the Human Nasopharynx

PubMed Central

Mokrzan, Elaine M.; Ward, Michael O.

2016-01-01

ABSTRACT Nontypeable Haemophilus influenzae (NTHI), a commensal of the human nasopharynx (hNP), is a common cause of biofilm-associated diseases of the respiratory tract. However, NTHI biofilm biology at the average hNP temperature, i.e., 34°C, has not been well studied. Here we grew NTHI biofilms at 34°C and 37°C, to evaluate relative biofilm growth, expression, and function of the type IV pilus (Tfp), a critical adhesin important for NTHI biofilm formation. The kinetics and regulation of Tfp expression in NTHI biofilms are unclear, especially at 34°C. Tfp expression, as estimated by pilA promoter activity, was distributed throughout the biofilms, with a unique pattern that was dependent on temperature, time in culture, and position within the maturing biofilm. Tfp expression was required for the formation of the characteristic tower structures of NTHI biofilms and was significantly upregulated in NTHI biofilms formed at 34°C versus 37°C. This increase correlated with significantly greater twitching motility at 34°C than at 37°C. Treatment with antisera targeting the major subunit of Tfp (PilA) significantly inhibited NTHI biofilm formation at both temperatures, confirming the importance of this critical adhesin in biofilm formation. Additionally, treatment of preestablished biofilms with antisera against PilA significantly decreased biofilm biomass and mean thickness at both temperatures. These results demonstrated a pivotal role for Tfp in NTHI biofilm formation and stability at the temperature of the hNP, and they underscore the utility of PilA as a vaccine candidate for treatment and/or prevention of NTHI biofilm-associated diseases. IMPORTANCE NTHI is an important cause of chronic respiratory tract infections, including otitis media, chronic rhinosinusitis, and exacerbations of chronic obstructive pulmonary disease and cystic fibrosis. The chronic and recurrent nature of these diseases is attributed to the presence of bacterial biofilms, which are highly resistant to antimicrobials. We characterized NTHI biofilm growth and expression of PilA, the major subunit of the Tfp, at the temperature of the hNP, which is the commensal habitat of NTHI. Our results expand the current understanding of the role of Tfp during biofilm formation and maturation at the temperature of both the hNP and the middle ear, and they strengthen support for PilA as a vaccine candidate for the prevention and treatment of NTHI biofilm-associated diseases. PMID:27044626

Type IV Pilus Expression Is Upregulated in Nontypeable Haemophilus influenzae Biofilms Formed at the Temperature of the Human Nasopharynx.

PubMed

Mokrzan, Elaine M; Ward, Michael O; Bakaletz, Lauren O

2016-10-01

Nontypeable Haemophilus influenzae (NTHI), a commensal of the human nasopharynx (hNP), is a common cause of biofilm-associated diseases of the respiratory tract. However, NTHI biofilm biology at the average hNP temperature, i.e., 34°C, has not been well studied. Here we grew NTHI biofilms at 34°C and 37°C, to evaluate relative biofilm growth, expression, and function of the type IV pilus (Tfp), a critical adhesin important for NTHI biofilm formation. The kinetics and regulation of Tfp expression in NTHI biofilms are unclear, especially at 34°C. Tfp expression, as estimated by pilA promoter activity, was distributed throughout the biofilms, with a unique pattern that was dependent on temperature, time in culture, and position within the maturing biofilm. Tfp expression was required for the formation of the characteristic tower structures of NTHI biofilms and was significantly upregulated in NTHI biofilms formed at 34°C versus 37°C. This increase correlated with significantly greater twitching motility at 34°C than at 37°C. Treatment with antisera targeting the major subunit of Tfp (PilA) significantly inhibited NTHI biofilm formation at both temperatures, confirming the importance of this critical adhesin in biofilm formation. Additionally, treatment of preestablished biofilms with antisera against PilA significantly decreased biofilm biomass and mean thickness at both temperatures. These results demonstrated a pivotal role for Tfp in NTHI biofilm formation and stability at the temperature of the hNP, and they underscore the utility of PilA as a vaccine candidate for treatment and/or prevention of NTHI biofilm-associated diseases. NTHI is an important cause of chronic respiratory tract infections, including otitis media, chronic rhinosinusitis, and exacerbations of chronic obstructive pulmonary disease and cystic fibrosis. The chronic and recurrent nature of these diseases is attributed to the presence of bacterial biofilms, which are highly resistant to antimicrobials. We characterized NTHI biofilm growth and expression of PilA, the major subunit of the Tfp, at the temperature of the hNP, which is the commensal habitat of NTHI. Our results expand the current understanding of the role of Tfp during biofilm formation and maturation at the temperature of both the hNP and the middle ear, and they strengthen support for PilA as a vaccine candidate for the prevention and treatment of NTHI biofilm-associated diseases. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Chronic pelvic pain.

PubMed

Stein, Sharon L

2013-12-01

Chronic pelvic pain is pain lasting longer than 6 months and is estimated to occur in 15% of women. Causes of pelvic pain include disorders of gynecologic, urologic, gastroenterologic, and musculoskeletal systems. The multidisciplinary nature of chronic pelvic pain may complicate diagnosis and treatment. Treatments vary by cause but may include medicinal, neuroablative, and surgical treatments. Copyright © 2013 Elsevier Inc. All rights reserved.

Managing Chronic Conditions in College: Findings from Prompted Health Incidents Diaries

ERIC Educational Resources Information Center

Ravert, Russell D.; Russell, Luke T.; O'Guin, Monica B.

2017-01-01

Objective: This pilot study assessed an electronic health diary method designed to collect data about critical health incidents experienced by college students who have chronic health conditions. Participants: Nine university students with chronic medical conditions were recruited to complete a series of e-mail-based surveys, sent once every…

CRITICAL LOADS METHODS

EPA Science Inventory

I summarize the results of an interagency project that 1) defines a generic approach to quantifying and reporting critical loads, and 2) exercises that generic approach by examining a data rich system -- the critical loads of sulfur deposition and it's effect on the chronic acidi...

Phase transitions in pancreatic islet cellular networks and implications for type-1 diabetes

NASA Astrophysics Data System (ADS)

Stamper, I. J.; Jackson, Elais; Wang, Xujing

2014-01-01

In many aspects the onset of a chronic disease resembles a phase transition in a complex dynamic system: Quantitative changes accumulate largely unnoticed until a critical threshold is reached, which causes abrupt qualitative changes of the system. In this study we examine a special case, the onset of type-1 diabetes (T1D), a disease that results from loss of the insulin-producing pancreatic islet β cells. Within each islet, the β cells are electrically coupled to each other via gap-junctional channels. This intercellular coupling enables the β cells to synchronize their insulin release, thereby generating the multiscale temporal rhythms in blood insulin that are critical to maintaining blood glucose homeostasis. Using percolation theory we show how normal islet function is intrinsically linked to network connectivity. In particular, the critical amount of β-cell death at which the islet cellular network loses site percolation is consistent with laboratory and clinical observations of the threshold loss of β cells that causes islet functional failure. In addition, numerical simulations confirm that the islet cellular network needs to be percolated for β cells to synchronize. Furthermore, the interplay between site percolation and bond strength predicts the existence of a transient phase of islet functional recovery after onset of T1D and introduction of treatment, potentially explaining the honeymoon phenomenon. Based on these results, we hypothesize that the onset of T1D may be the result of a phase transition of the islet β-cell network.

Chronic Diseases Overview

MedlinePlus

... cases of blindness among adults. 6 Health Risk Behaviors that Cause Chronic Diseases Health risk behaviors are ... The Cost of Chronic Diseases and Health Risk Behaviors In the United States, chronic diseases and conditions ...

Chronic rhino-orbital mucormycosis caused by Mucor irregularis (Rhizomucor variabilis) in India

USDA-ARS?s Scientific Manuscript database

We describe a chronic case of rhino-orbital zygomycosis caused by Mucor irregularis, formerly known as Rhizomucor variabilis var. variabilis, a rare mycotic agent in humans. The infection caused progressive destruction of the nasal septum, soft and hard palate, leading to collapse of the nose bridge...

Death receptor-independent FADD signalling triggers hepatitis and hepatocellular carcinoma in mice with liver parenchymal cell-specific NEMO knockout.

PubMed

Ehlken, H; Krishna-Subramanian, S; Ochoa-Callejero, L; Kondylis, V; Nadi, N E; Straub, B K; Schirmacher, P; Walczak, H; Kollias, G; Pasparakis, M

2014-11-01

Hepatocellular carcinoma (HCC) usually develops in the context of chronic hepatitis triggered by viruses or toxic substances causing hepatocyte death, inflammation and compensatory proliferation of liver cells. Death receptors of the TNFR superfamily regulate cell death and inflammation and are implicated in liver disease and cancer. Liver parenchymal cell-specific ablation of NEMO/IKKγ, a subunit of the IκB kinase (IKK) complex that is essential for the activation of canonical NF-κB signalling, sensitized hepatocytes to apoptosis and caused the spontaneous development of chronic hepatitis and HCC in mice. Here we show that hepatitis and HCC development in NEMO(LPC-KO) mice is triggered by death receptor-independent FADD-mediated hepatocyte apoptosis. TNF deficiency in all cells or conditional LPC-specific ablation of TNFR1, Fas or TRAIL-R did not prevent hepatocyte apoptosis, hepatitis and HCC development in NEMO(LPC-KO) mice. To address potential functional redundancies between death receptors we generated and analysed NEMO(LPC-KO) mice with combined LPC-specific deficiency of TNFR1, Fas and TRAIL-R and found that also simultaneous lack of all three death receptors did not prevent hepatocyte apoptosis, chronic hepatitis and HCC development. However, LPC-specific combined deficiency in TNFR1, Fas and TRAIL-R protected the NEMO-deficient liver from LPS-induced liver failure, showing that different mechanisms trigger spontaneous and LPS-induced hepatocyte apoptosis in NEMO(LPC-KO) mice. In addition, NK cell depletion did not prevent liver damage and hepatitis. Moreover, NEMO(LPC-KO) mice crossed into a RAG-1-deficient genetic background-developed hepatitis and HCC. Collectively, these results show that the spontaneous development of hepatocyte apoptosis, chronic hepatitis and HCC in NEMO(LPC-KO) mice occurs independently of death receptor signalling, NK cells and B and T lymphocytes, arguing against an immunological trigger as the critical stimulus driving hepatocarcinogenesis in this model.

Chronic Kidney Disease (CKD)

MedlinePlus

... Donate Now Give Monthly Give In Honor Chronic kidney disease (CKD) www.kidneyfund.org > Kidney Disease > Chronic ... Kidney-friendly diet for CKD What causes chronic kidney disease (CKD)? Anyone can get CKD. Some people ...

Subacute and Chronic Meningitis

MedlinePlus

... infections can also cause chronic meningitis. They include Sarcoidosis Certain disorders that cause inflammation, such as systemic ... For disorders that are not infections, such as sarcoidosis and Behçet syndrome: Corticosteroids or other drugs that ...

Deletion of Ku80 causes early aging independent of chronic inflammation and Rag-1-induced DSBs.

PubMed

Holcomb, Valerie B; Vogel, Hannes; Hasty, Paul

2007-01-01

Animal models of premature aging are often defective for DNA repair. Ku80-mutant mice are disabled for nonhomologous end joining; a pathway that repairs both spontaneous DNA double-strand breaks (DSBs) and induced DNA DSBs generated by the action of a complex composed of Rag-1 and Rag-2 (Rag). Rag is essential for inducing DSBs important for assembling V(D)J segments of antigen receptor genes that are required for lymphocyte development. Thus, deletion of either Rag-1 or Ku80 causes severe combined immunodeficiency (scid) leading to chronic inflammation. In addition, Rag-1 induces breaks at non-B DNA structures. Previously we reported Ku80-mutant mice undergo premature aging, yet we do not know the root cause of this phenotype. Early aging may be caused by either defective repair of spontaneous DNA damage, defective repair of Rag-1-induced breaks or chronic inflammation caused by scid. To address this issue, we analyzed aging in control and Ku80-mutant mice deleted for Rag-1 such that both cohorts are scid and suffer from chronic inflammation. We make two observations: (1) chronic inflammation does not cause premature aging in these mice and (2) Ku80-mutant mice exhibit early aging independent of Rag-1. Therefore, this study supports defective repair of spontaneous DNA damage as the root cause of early aging in Ku80-mutant mice.

Age-associated chronic diseases require age-old medicine: role of chronic inflammation.

PubMed

Prasad, Sahdeo; Sung, Bokyung; Aggarwal, Bharat B

2012-05-01

Most chronic diseases--such as cancer, cardiovascular disease (CVD), Alzheimer disease, Parkinson disease, arthritis, diabetes and obesity--are becoming leading causes of disability and death all over the world. Some of the most common causes of these age-associated chronic diseases are lack of physical activity, poor nutrition, tobacco use, and excessive alcohol consumption. All the risk factors linked to these chronic diseases have been shown to up-regulate inflammation. Therefore, downregulation of inflammation-associated risk factors could prevent or delay these age-associated diseases. Although modern science has developed several drugs for treating chronic diseases, most of these drugs are enormously expensive and are associated with serious side effects and morbidity. In this review, we present evidence on how chronic inflammation leads to age-associated chronic disease. Furthermore, we discuss diet and lifestyle as solutions for age-associated chronic disease. Published by Elsevier Inc.

Timing of Acute Palliative Care Consultation in Critically Ill Patients

ClinicalTrials.gov

2016-08-03

Multiple Organ Failure; End Stage Cardiac Failure; End Stage Chronic Obstructive Airways Disease; Chronic Kidney Disease Stage 5; Hepatic Encephalopathy; Sepsis; Dementia; Multiple Sclerosis; Parkinson's Disease; In-Hospital Cardiac Arrest; Solid Organ Cancer

Critical tissue residue approach linking accumulated metals in aquatic insects to population and community-level effects

USGS Publications Warehouse

Schmidt, Travis S.; Clements, William H.; Zuellig, Robert E.; Mitchell, Katharine A.; Church, Stan E.; Wanty, Richard B.; San Juan, Carma A.; Adams, Monique; Lamothe, Paul J.

2011-01-01

Whole body Zn concentrations in individuals (n = 825) from three aquatic insect taxa (mayflies Rhithrogena spp. and Drunella spp. and the caddisfly Arctopsyche grandis) were used to predict effects on populations and communities (n = 149 samples). Both mayflies accumulated significantly more Zn than the caddisfly. The presence/absence of Drunella spp. most reliably distinguished sites with low and high Zn concentrations; however, population densities of mayflies were more sensitive to increases in accumulated Zn. Critical tissue residues (634 (mu or u)g/g Zn for Drunella spp. and 267 (mu or u)g/g Zn for Rhithrogena spp.) caused a 20% reduction in maximum (90th quantile) mayfly densities. These critical tissue residues were associated with exposure to 7.0 and 3.9 (mu or u)g/L dissolved Zn for Drunella spp. and Rhithrogena spp., respectively. A threshold in a measure of taxonomic completeness (observed/expected) was observed at 5.4 (mu or u)g/L dissolved Zn. Dissolved Zn concentrations associated with critical tissue residues in mayflies were also associated with adverse effects in the aquatic community as a whole. These effects on populations and communities occurred at Zn concentrations below the U.S. EPA hardness-adjusted continuous chronic criterion.

Functional changes in cerebral 5-hydroxytryptamine metabolism in the mouse induced by anticonvulsant drugs.

PubMed Central

Chadwick, D; Gorrod, J W; Jenner, P; Marsden, C D; Reynolds, E H

1978-01-01

1 Acute administration of clonazepam, diazepam, and diphenylhydantoin to mice elevated cerebral 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA); chronic administration had less effect. 2 Acute administration of clonazepam and diazepam but not diphenylhydantoin raised cerebral trytophan levels; chronic administration of clonazepam caused a smaller elevation of cerebral tryptophan but chronic administration of diazepam still caused a large rise in cerebral tryptophan. 3 Neither clonazepam nor diazepam caused induction of drug metabolizing enzymes on chronic administration but diphenylhydantoin had a marked effect. 4 These data suggest that the altered 5-HT metabolism caused by these compounds is unrelated to a common action on tryptophan levels, and that the reduced effect of clonazepam and diazepam on chronic administration cannot be attributed to increased metabolism of these compounds. 5 Clonazepam induced abnormal head movements in mice in a dose-dependent manner. Pretreatment of animals with tranylcypromine increased the intensity of movement, although pargyline was without effect. Similar effects were observed with diazepam and diphenylhydantoin, suggesting that the increase in cerebral 5-HT caused by these compounds is of functional significance in stimulating 5-HT receptors. PMID:620092

Insomnia

MedlinePlus

... can last for years. Common causes of chronic insomnia include: Stress. Concerns about work, school, health, finances or family ... stress. Stressful times and events can cause temporary insomnia. And major or long-lasting stress can lead to chronic insomnia. You don't ...

Quantifying Demyelination in NK venom treated nerve using its electric circuit model

NASA Astrophysics Data System (ADS)

Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

2016-03-01

Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

Quantifying Demyelination in NK venom treated nerve using its electric circuit model

PubMed Central

Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

2016-01-01

Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination. PMID:26932543

Quantifying Demyelination in NK venom treated nerve using its electric circuit model.

PubMed

Das, H K; Das, D; Doley, R; Sahu, P P

2016-03-02

Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

Matrix Remodeling in Pulmonary Fibrosis and Emphysema

PubMed Central

O’Reilly, Philip; Antony, Veena B.; Gaggar, Amit

2016-01-01

Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-β1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema. PMID:26741177

Confusion, Faciobrachial Dystonic Seizures, and Critical Hyponatremia in a Patient with Voltage-Gated Potassium Channel Encephalitis

PubMed Central

2017-01-01

Autoimmune limbic encephalitis is a rare cause of encephalitic disease. It is associated with various target antigens and is difficult to diagnose, and experience with its treatment is limited. This case report describes a 69-year-old man, who presented with life-threatening hyponatremia and confusion, following several months of gradually worsening faciobrachial dystonic seizures. Faciobrachial dystonic seizures are a well-described feature classically observed in voltage-gated potassium channel autoimmune encephalitis. The presence of chronic hyponatremia without cognitive dysfunction, eventually culminating in an acute episode of encephalopathy and severe hyponatremia, is a pattern of natural history not previously documented in this condition. PMID:28360986

The Impact of Chronic Illness on Psychosocial Stages of Human Development.

ERIC Educational Resources Information Center

Lapham, E. Virginia, Ed.; Shevlin, Kathleen M., Ed.

This book addresses critical issues regarding the impact of chronic illness and disability on human development. It was written for health care professionals who help chronically ill and disabled persons deal with the psychological and social as well as the biological aspects of their illness or disability. An expanded version of Erik Erikson's…

The Role of Reactive-Oxygen-Species in Microbial Persistence and Inflammation

PubMed Central

Spooner, Ralee; Yilmaz, Özlem

2011-01-01

The mechanisms of chronic infections caused by opportunistic pathogens are of keen interest to both researchers and health professionals globally. Typically, chronic infectious disease can be characterized by an elevation in immune response, a process that can often lead to further destruction. Reactive-Oxygen-Species (ROS) have been strongly implicated in the aforementioned detrimental response by host that results in self-damage. Unlike excessive ROS production resulting in robust cellular death typically induced by acute infection or inflammation, lower levels of ROS produced by host cells are increasingly recognized to play a critical physiological role for regulating a variety of homeostatic cellular functions including growth, apoptosis, immune response, and microbial colonization. Sources of cellular ROS stimulation can include “danger-signal-molecules” such as extracellular ATP (eATP) released by stressed, infected, or dying cells. Particularly, eATP-P2X7 receptor mediated ROS production has been lately found to be a key modulator for controlling chronic infection and inflammation. There is growing evidence that persistent microbes can alter host cell ROS production and modulate eATP-induced ROS for maintaining long-term carriage. Though these processes have yet to be fully understood, exploring potential positive traits of these “injurious” molecules could illuminate how opportunistic pathogens maintain persistence through physiological regulation of ROS signaling. PMID:21339989

Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion

PubMed Central

Ma, Jing; Zhang, Jing; Hou, Wei Wei; Wu, Xiao Hua; Liao, Ru Jia; Chen, Ying; Wang, Zhe; Zhang, Xiang Nan; Zhang, Li San; Zhou, Yu Dong; Chen, Zhong; Hu, Wei Wei

2015-01-01

Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion develops with progressive white matter and cognitive impairments, yet no effective therapy is available. We investigated the temporal effects of minocycline on an experimental SIVD exerted by right unilateral common carotid arteries occlusion (rUCCAO). Minocycline treated at the early stage (day 0–3), but not the late stage after rUCCAO (day 4–32) alleviated the white matter and cognitive impairments, and promoted remyelination. The actions of minocycline may not involve the inhibition of microglia activation, based on the effects after the application of a microglial activation inhibitor, macrophage migration inhibitory factor, and co-treatment with lipopolysaccharides. Furthermore, minocycline treatment at the early stage promoted the proliferation of oligodendrocyte progenitor cells (OPCs) in subventricular zone, increased OPC number and alleviated apoptosis of mature oligodendrocytes in white matter. In vitro, minocycline promoted OPC proliferation and increased the percentage of OPCs in S and G2/M phases. We provided direct evidence that early treatment is critical for minocycline to alleviate white matter and cognitive impairments after chronic cerebral hypoperfusion, which may be due to its robust effects on OPC proliferation and mature oligodendrocyte loss. So, early therapeutic time window may be crucial for its application in SIVD. PMID:26174710

mHealth For Aging China: Opportunities and Challenges.

PubMed

Sun, Jing; Guo, Yutao; Wang, Xiaoning; Zeng, Qiang

2016-01-01

The aging population with chronic and age-related diseases has become a global issue and exerted heavy burdens on the healthcare system and society. Neurological diseases are the leading chronic diseases in the geriatric population, and stroke is the leading cause of death in China. However, the uneven distribution of caregivers and critical healthcare workforce shortages are major obstacles to improving disease outcome. With the advancement of wearable health devices, cloud computing, mobile technologies and Internet of Things, mobile health (mHealth) is rapidly developing and shows a promising future in the management of chronic diseases. Its advantages include its ability to improve the quality of care, reduce the costs of care, and improve treatment outcomes by transferring in-hospital treatment to patient-centered medical treatment at home. mHealth could also enhance the international cooperation of medical providers in different time zones and the sharing of high-quality medical service resources between developed and developing countries. In this review, we focus on trends in mHealth and its clinical applications for the prevention and treatment of diseases, especially aging-related neurological diseases, and on the opportunities and challenges of mHealth in China. Operating models of mHealth in disease management are proposed; these models may benefit those who work within the mHealth system in developing countries and developed countries.

Protective effects of intercalated disk protein afadin on chronic pressure overload-induced myocardial damage

PubMed Central

Zankov, Dimitar P.; Shimizu, Akio; Tanaka-Okamoto, Miki; Miyoshi, Jun; Ogita, Hisakazu

2017-01-01

Adhesive intercellular connections at cardiomyocyte intercalated disks (IDs) support contractile force and maintain structural integrity of the heart muscle. Disturbances of the proteins at IDs deteriorate cardiac function and morphology. An adaptor protein afadin, one of the components of adherens junctions, is expressed ubiquitously including IDs. At present, the precise role of afadin in cardiac physiology or disease is unknown. To explore this, we generated conditional knockout (cKO) mice with cardiomyocyte-targeted deletion of afadin. Afadin cKO mice were born according to the expected Mendelian ratio and have no detectable changes in cardiac phenotype. On the other hand, chronic pressure overload induced by transverse aortic constriction (TAC) caused systolic dysfunction, enhanced fibrogenesis and apoptosis in afadin cKO mice. Afadin deletion increased macrophage infiltration and monocyte chemoattractant protein-1 expression, and suppressed transforming growth factor (TGF) β receptor signaling early after TAC procedure. Afadin also associated with TGFβ receptor I at IDs. Pharmacological antagonist of TGFβ receptor I (SB431542) augmented mononuclear infiltration and fibrosis in the hearts of TAC-operated control mice. In conclusion, afadin is a critical molecule for cardiac protection against chronic pressure overload. The beneficial effects are likely to be a result from modulation of TGFβ receptor signaling pathways by afadin. PMID:28045017

Absence from school related to cancer and other chronic conditions.

PubMed Central

Charlton, A; Larcombe, I J; Meller, S T; Morris Jones, P H; Mott, M G; Potton, M W; Tranmer, M D; Walker, J J

1991-01-01

Absence from school during the first year after starting major treatment for cancer or chronic or orthopaedic conditions was examined. Retrospective data were collected on 72 children and obtained from hospital records, school registers, and interviews with parents and teachers. Median initial absences caused by treatment were 91, 29-5, and 15 days for cancer, chronic, and orthopaedic patients respectively. The mean proportions of the remaining school time in the year occupied by absences caused by treatment and those not caused by treatment were respectively 17% and 17% for oncology patients, 8% and 12% for chronic patients, and 2% and 11% for orthopaedic patients. The only significant factor associated with the amount of absence caused by treatment was the type of illness. Increased absence not caused by treatment was associated with the amount of treatment time and the patient being a girl. The proportion of absence not caused by treatment decreased if the mother was educated beyond the age of 18. The possible reasons for and effects of excess absence are discussed. PMID:1953006

Severe Life Stress and Oxidative Stress in the Brain: From Animal Models to Human Pathology

PubMed Central

Jaquet, Vincent; Trabace, Luigia; Krause, Karl-Heinz

2013-01-01

Abstract Significance: Severe life stress (SLS), as opposed to trivial everyday stress, is defined as a serious psychosocial event with the potential of causing an impacting psychological traumatism. Recent Advances: Numerous studies have attempted to understand how the central nervous system (CNS) responds to SLS. This response includes a variety of morphological and neurochemical modifications; among them, oxidative stress is almost invariably observed. Oxidative stress is defined as disequilibrium between oxidant generation and the antioxidant response. Critical Issues: In this review, we discuss how SLS leads to oxidative stress in the CNS, and how the latter impacts pathophysiological outcomes. We also critically discuss experimental methods that measure oxidative stress in the CNS. The review covers animal models and human observations. Animal models of SLS include sleep deprivation, maternal separation, and social isolation in rodents, and the establishment of hierarchy in non-human primates. In humans, SLS, which is caused by traumatic events such as child abuse, war, and divorce, is also accompanied by oxidative stress in the CNS. Future Directions: The outcome of SLS in humans ranges from resilience, over post-traumatic stress disorder, to development of chronic mental disorders. Defining the sources of oxidative stress in SLS might in the long run provide new therapeutic avenues. Antioxid. Redox Signal. 18, 1475–1490. PMID:22746161

Is There a Relation between EEG-Slow Waves and Memory Dysfunction in Epilepsy? A Critical Appraisal

PubMed Central

Höller, Yvonne; Trinka, Eugen

2015-01-01

Is there a relationship between peri-ictal slow waves, loss of consciousness, memory, and slow-wave sleep, in patients with different forms of epilepsy? We hypothesize that mechanisms, which result in peri-ictal slow-wave activity as detected by the electroencephalogram, could negatively affect memory processes. Slow waves (≤4 Hz) can be found in seizures with impairment of consciousness and also occur in focal seizures without impairment of consciousness but with inhibited access to memory functions. Peri-ictal slow waves are regarded as dysfunctional and are probably caused by mechanisms, which are essential to disturb the consolidation of memory entries in these patients. This is in strong contrast to physiological slow-wave activity during deep sleep, which is thought to group memory-consolidating fast oscillatory activity. In patients with epilepsy, slow waves may not only correlate with the peri-ictal clouding of consciousness, but could be the epiphenomenon of mechanisms, which interfere with normal brain function in a wider range. These mechanisms may have transient impacts on memory, such as temporary inhibition of memory systems, altered patterns of hippocampal–neocortical interactions during slow-wave sleep, or disturbed cross-frequency coupling of slow and fast oscillations. In addition, repeated tonic–clonic seizures over the years in uncontrolled chronic epilepsy may cause a progressive cognitive decline. This hypothesis can only be assessed in long-term prospective studies. These studies could disentangle the reversible short-term impacts of seizures, and the impacts of chronic uncontrolled seizures. Chronic uncontrolled seizures lead to irreversible memory impairment. By contrast, short-term impacts do not necessarily lead to a progressive cognitive decline but result in significantly impaired peri-ictal memory performance. PMID:26124717

Biomimetic nanoparticles for siRNA delivery in the treatment of leukaemia.

PubMed

Guo, Jianfeng; Cahill, Mary R; McKenna, Sharon L; O'Driscoll, Caitriona M

2014-12-01

Leukaemia is a bone marrow cancer occurring in acute and chronic subtypes. Acute leukaemia is a rapidly fatal cancer potentially causing death within a few weeks, if untreated. Leukaemia arises as a result of disruption to haematopoietic precursors, caused either by acquired gene fusions, gene mutations or inappropriate expression of the relevant oncogenes. Current treatment options have made significant progress, but the 5 year survival for acute leukaemia remains under 10% in elderly patients, and less than 50% for some types of acute leukaemia in younger adults. For chronic leukaemias longer survival is generally expected and for chronic myeloid leukaemia patients on tyrosine kinase inhibitors the median survival is not yet reached and is expected to exceed 10 years. Chemotherapy and haematopoietic stem cell transplantation (HSCT) for acute leukaemia provide the mainstay of therapy for patients under 65 and both carry significant morbidity and mortality. Alternative and superior therapeutic strategies for acute leukaemias are urgently required. Recent molecular-based knowledge of recurring chromosome rearrangements, in particular translocations and inversions, has resulted in significant advances in understanding the molecular pathogenesis of leukaemia. Identification of a number of unique fusion genes has facilitated the development of highly specific small interfering RNAs (siRNA). Although delivery of siRNA using multifunctional nanoparticles has been investigated to treat solid cancers, the application of this approach to blood cancers is at an early stage. This review describes current treatments for leukaemia and highlights the potential of leukaemic fusion genes as therapeutic targets for RNA interference (RNAi). In addition, the design of biomimetic nanoparticles which are capable of responding to the physiological environment of leukaemia and their potential to advance RNAi therapeutics to the clinic will be critically evaluated. Copyright © 2014 Elsevier Inc. All rights reserved.

Chronic cough due to occupational factors

PubMed Central

Groneberg, David A; Nowak, Dennis; Wussow, Anke; Fischer, Axel

2006-01-01

Within the large variety of subtypes of chronic cough, either defined by their clinical or pathogenetic causes, occupational chronic cough may be regarded as one of the most preventable forms of the disease. Next to obstructive airway diseases such as asthma or chronic obstructive pulmonary disease, which are sometimes concomitant with chronic cough, this chronic airway disease gains importance in the field of occupational medicine since classic fiber-related occupational airway diseases will decrease in the future. Apart from acute accidents and incidental exposures which may lead to an acute form of cough, there are numerous sources for the development of chronic cough within the workplace. Over the last years, a large number of studies has focused on occupational causes of respiratory diseases and it has emerged that chronic cough is one of the most prevalent work-related airway diseases. Best-known examples of occupations related to the development of cough are coal miners, hard-rock miners, tunnel workers, or concrete manufacturing workers. As chronic cough is often based on a variety of non-occupational factors such as tobacco smoke, a distinct separation into either occupational or personally -evoked can be difficult. However, revealing the occupational contribution to chronic cough and to the symptom cough in general, which is the commonest cause for the consultation of a physician, can significantly lead to a reduction of the socioeconomic burden of the disease. PMID:16722562

Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection.

PubMed

Bellon, Marcia; Nicot, Christophe

2017-10-05

The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cells. Growing evidence suggests that this phenotype is recapitulated during chronic viral infection. The antigenic volume imposed by persistent and latent viruses exposes the immune system to unique challenges that lead to host T-cell exhaustion, characterized by impaired T-cell functions. These dysfunctional memory T cells lack telomerase, the protein capable of extending and stabilizing chromosome ends, imposing constraints on telomere dynamics. A deleterious consequence of this excessive telomere shortening is the premature induction of replicative senescence of viral-specific CD8+ memory T cells. While senescent cells are unable to expand, they can survive for extended periods of time and are more resistant to apoptotic signals. This review takes a closer look at T-cell exhaustion in chronic viruses known to cause human disease: Epstein-Barr virus (EBV), Hepatitis B/C/D virus (HBV/HCV/HDV), human herpesvirus 8 (HHV-8), human immunodeficiency virus (HIV), human T-cell leukemia virus type I (HTLV-I), human papillomavirus (HPV), herpes simplex virus-1/2(HSV-1/2), and Varicella-Zoster virus (VZV). Current literature linking T-cell exhaustion with critical telomere lengths and immune senescence are discussed. The concept that enduring antigen stimulation leads to T-cell exhaustion that favors telomere attrition and a cell fate marked by enhanced T-cell senescence appears to be a common endpoint to chronic viral infections.

The physiological consequences of exposure to chronic, sublethal waterborne nickel in rainbow trout (Oncorhynchus mykiss): exercise vs resting physiology.

PubMed

Pane, Eric F; Haque, Aziz; Goss, Greg G; Wood, Chris M

2004-03-01

In rainbow trout (Oncorhynchus mykiss), following chronic (42 day) exposure to both 384 microg Ni l(-1) and 2034 microg Ni l(-1), Ni accumulation was greatest in the gill, kidney and plasma, with the plasma as the main sink for Ni. Indeed, trapped plasma analysis revealed that extensive loading of Ni in the plasma accounted for substantial percentages of accumulated Ni in several tissues including the liver and heart. Accumulated Ni in the gill and kidney was less dependent on plasma Ni concentration, suggesting a more intracellular accumulation of Ni in these tissues. We present evidence for a clear, persistent cost of acclimation to chronic, sublethal Ni exposure. Chronic (40-99 day) exposure to sublethal waterborne Ni (243-394 microg Ni l(-1); approximately 1% of the 96 h LC(50)) impaired the exercise physiology, but not the resting physiology, of rainbow trout. Ni acted as a limiting stressor, decreasing maximal rates of oxygen consumption (MO2,max) during strenuous exercise in trout exposed for 34 days to sublethal Ni. This drop in high-performance gas exchange was attributed mainly to a reduction in relative branchial diffusing capacity (D(rel)) caused by thickening of secondary lamellae. Morphometric analysis of the gills of chronically exposed fish revealed overall swelling of secondary lamellae, as well as hypertrophic respiratory epithelia within secondary lamellae. Additionally, contraction of the lamellar blood pillar system and narrowing of interlamellar water channels occurred, possibly contributing to decreased high-performance gas exchange. Decreased aerobic capacity persisted in fish previously exposed to nickel despite a clean-water exposure period of 38 days and an almost complete depuration of gill Ni, suggesting that extrabranchial mechanisms of chronic Ni toxicity may also be important. Chronic impairment of such a dynamically active and critical organ as the gill may depress the overall fitness of a fish by impairing predator avoidance, prey capture and migration success with obvious environmental implications.

Status of industrial fluoride pollution and its diverse adverse health effects in man and domestic animals in India.

PubMed

Choubisa, Shanti Lal; Choubisa, Darshana

2016-04-01

Hydrofluorosis in humans and domestic animals is a worldwide health problem and caused by a prolonged period of fluoride exposure through drinking of fluoride contaminated water. But in recent years, due to rapid industrialization in India, diverse serious health problems among industrial workers and residents and domestic animals living in the industrial areas due to fluoride pollution are on the rise. A number of coal-burning and industrial activities such as power-generating stations, welding operations and the manufacturing or production of steel, iron, aluminum, zinc, phosphorus, chemical fertilizers, bricks, glass, plastic, cement, and hydrofluoric acid are generally discharging fluoride in both gaseous and particulate/dust forms into surrounding environments which create a industrial fluoride pollution and are an important cause of occupational exposure to fluoride in several countries including India. An industrial emitted fluoride contaminates not only surrounding soil, air, and water but also vegetation, crops and many other biotic communities on which man and animals are generally dependants for food. Long- time of inhalation or ingestion of industrial fluoride also causes serious health problems in the forms of industrial and neighborhood fluorosis. In India, whatever research works conducted so far on the chronic industrial fluoride intoxication or poisoning (industrial and neighborhood fluorosis) in man and various species of domestic animals due to a prolonged period of industrial fluoride exposure or pollution (contamination) are critically reviewed in the present communication. Simultaneously, we are also focused the various bio-indicators and bio-markers for chronic industrial fluoride intoxication or pollution.

Cancer and diet: How are they related?

PubMed Central

Sung, Bokyung; Prasad, Sahdeo; Yadav, Vivek R.; Lavasanifar, Afsaneh; Aggarwal, Bharat B.

2012-01-01

Extensive research in the past decade has revealed cancer to be a multigenic disease caused by perturbation of multiple cell signalling pathways and dysregulation of numerous gene products, all of which have been linked to inflammation. It is also becoming evident that various lifestyle factors, such as tobacco and alcohol use, diet, environmental pollution, radiation and infections, can cause chronic inflammation and lead to tumourigenesis. Chronic diseases caused by ongoing inflammation therefore require chronic, not acute, treatment. Nutraceuticals, compounds derived from fruits, vegetables, spices and cereals, can be used chronically. This study discusses the molecular targets of some nutraceuticals that happen to be markers of chronic inflammation and how they can prevent or treat cancer. These naturally-occurring agents in the diet have great potential as anti-cancer drugs, thus proving Hippocrates, who proclaimed 25 centuries ago, ‘Let food be thy medicine and medicine be thy food’. PMID:21651450

Chronic Cough: Evaluation and Management.

PubMed

Michaudet, Charlie; Malaty, John

2017-11-01

Although chronic cough in adults (cough lasting longer than eight weeks) can be caused by many etiologies, four conditions account for most cases: upper airway cough syndrome, gastroesophageal reflux disease/laryngopharyngeal reflux disease, asthma, and nonasthmatic eosinophilic bronchitis. Patients should be evaluated clinically (with spirometry, if indicated), and empiric treatment should be initiated. Other potential causes include angiotensin-converting enzyme inhibitor use, environmental triggers, tobacco use, chronic obstructive pulmonary disease, and obstructive sleep apnea. Chest radiography can rule out concerning infectious, inflammatory, and malignant thoracic conditions. Patients with refractory chronic cough may warrant referral to a pulmonologist or otolaryngologist in addition to a trial of gabapentin, pregabalin, and/or speech therapy. In children, cough is considered chronic if present for more than four weeks. In children six to 14 years of age, it is most commonly caused by asthma, protracted bacterial bronchitis, and upper airway cough syndrome. Evaluation should focus initially on these etiologies, with targeted treatment and monitoring for resolution.

The Immunological Basis of Hypertension

PubMed Central

Pons, Héctor; Quiroz, Yasmir; Johnson, Richard J.

2014-01-01

A large number of investigations have demonstrated the participation of the immune system in the pathogenesis of hypertension. Studies focusing on macrophages and Toll-like receptors have documented involvement of the innate immunity. The requirements of antigen presentation and co-stimulation, the critical importance of T cell–driven inflammation, and the demonstration, in specific conditions, of agonistic antibodies directed to angiotensin II type 1 receptors and adrenergic receptors support the role of acquired immunity. Experimental findings support the concept that the balance between T cell–induced inflammation and T cell suppressor responses is critical for the regulation of blood pressure levels. Expression of neoantigens in response to inflammation, as well as surfacing of intracellular immunogenic proteins, such as heat shock proteins, could be responsible for autoimmune reactivity in the kidney, arteries, and central nervous system. Persisting, low-grade inflammation in these target organs may lead to impaired pressure natriuresis, an increase in sympathetic activity, and vascular endothelial dysfunction that may be the cause of chronic elevation of blood pressure in essential hypertension. PMID:25150828

Activation of IκB Kinase β and NF-κB Is Essential for Helicobacter pylori-Induced Chronic Gastritis in Mongolian Gerbils▿

PubMed Central

Yanai, Ayako; Maeda, Shin; Shibata, Wataru; Hikiba, Yohko; Sakamoto, Kei; Nakagawa, Hayato; Ohmae, Tomoya; Hirata, Yoshihiro; Ogura, Keiji; Muto, Susumu; Itai, Akiko; Omata, Masao

2008-01-01

The Mongolian gerbil model of Helicobacter pylori infection resembles human gastritis. In this study, we investigated the role of NF-κB activation in H. pylori-infected gerbils. Activated macrophages were significantly increased in H. pylori-infected gastric mucosa and were identified as being important cells with potent activation of NF-κB, which plays an important part in producing proinflammatory cytokines. Macrophage depletion by the administration of clodronate resulted in milder inflammation in gerbils infected with H. pylori. In macrophages, the inhibition of IκB kinase β (IKKβ), which is a critical kinase for NF-κB activation, resulted in lower proinflammatory cytokine expression caused by heat-killed H. pylori cells. Furthermore, treatment with IKKβ inhibitor resulted in milder inflammation in gerbils with H. pylori gastritis. Collectively, our data suggest that H. pylori-mediated gastric inflammation critically depends on the efficient recruitment and activation of macrophages, with sufficient NF-κB activation. PMID:18070894

Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients.

PubMed

Loftus, Tyler J; Mira, Juan C; Ozrazgat-Baslanti, Tezcan; Ghita, Gabriella L; Wang, Zhongkai; Stortz, Julie A; Brumback, Babette A; Bihorac, Azra; Segal, Mark S; Anton, Stephen D; Leeuwenburgh, Christiaan; Mohr, Alicia M; Efron, Philip A; Moldawer, Lyle L; Moore, Frederick A; Brakenridge, Scott C

2017-08-01

Sepsis is a common, costly and morbid cause of critical illness in trauma and surgical patients. Ongoing advances in sepsis resuscitation and critical care support strategies have led to improved in-hospital mortality. However, these patients now survive to enter state of chronic critical illness (CCI), persistent low-grade organ dysfunction and poor long-term outcomes driven by the persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Sepsis and Critical Illness Research Center (SCIRC) was created to provide a platform by which the prevalence and pathogenesis of CCI and PICS may be understood at a mechanistic level across multiple medical disciplines, leading to the development of novel management strategies and targeted therapies. Here, we describe the design, study cohort and standard operating procedures used in the prospective study of human sepsis at a level 1 trauma centre and tertiary care hospital providing care for over 2600 critically ill patients annually. These procedures include implementation of an automated sepsis surveillance initiative, augmentation of clinical decisions with a computerised sepsis protocol, strategies for direct exportation of quality-filtered data from the electronic medical record to a research database and robust long-term follow-up. This study has been registered at ClinicalTrials.gov, approved by the University of Florida Institutional Review Board and is actively enrolling subjects. Dissemination of results is forthcoming. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Economic hardship associated with managing chronic illness: a qualitative inquiry

PubMed Central

Jeon, Yun-Hee; Essue, Beverley; Jan, Stephen; Wells, Robert; Whitworth, Judith A

2009-01-01

Background Chronic illness and disability can have damaging, even catastrophic, socioeconomic effects on individuals and their households. We examined the experiences of people affected by chronic heart failure, complicated diabetes and chronic obstructive pulmonary disease to inform patient centred policy development. This paper provides a first level, qualitative understanding of the economic impact of chronic illness. Methods Interviews were conducted with patients aged between 45 and 85 years who had one or more of the index conditions and family carers from the Australian Capital Territory and Western Sydney, Australia (n = 66). Content analysis guided the interpretation of data. Results The affordability of medical treatments and care required to manage illness were identified as the key aspects of economic hardship, which compromised patients' capacity to proactively engage in self-management and risk reduction behaviours. Factors exacerbating hardship included ineligibility for government support, co-morbidity, health service flexibility, and health literacy. Participants who were on multiple medications, from culturally and linguistically diverse or Indigenous backgrounds, and/or not in paid employment, experienced economic hardship more harshly and their management of chronic illness was jeopardised as a consequence. Economic hardship was felt among not only those ineligible for government financial supports but also those receiving subsidies that were insufficient to meet the costs of managing long-term illness over and above necessary daily living expenses. Conclusion This research provides insights into the economic stressors associated with managing chronic illness, demonstrating that economic hardship requires households to make difficult decisions between care and basic living expenses. These decisions may cause less than optimal health outcomes and increased costs to the health system. The findings support the necessity of a critical analysis of health, social and welfare policies to identify cross-sectoral strategies to alleviate such hardship and improve the affordability of managing chronic conditions. In a climate of global economic instability, research into the economic impact of chronic illness on individuals' health and well-being and their disease management capacity, such as this study, provides timely evidence to inform policy development. PMID:19818128

Hepatitis C as a cause of chronic liver disease in northern Pakistan.

PubMed

Malik, I A; Ahmad, N; Luqman, M; Legters, L J; Khalil-Ullah; Zaheeruddin; Ahmed, A; Bukhtiari, N; Nabi, S; Mubarik, A

1992-03-01

The antibodies to hepatitis C virus (HCV) were tested in 45 histologically confirmed cases of chronic liver disease. Twelve cases had chronic hepatitis, 24 cirrhosis and 9 hepatocellular carcinoma. Anti-HCV was detected in 6 patients. Two (16.67%) were suffering from chronic hepatitis, 3 (12.5%) had cirrhosis and one (11.11%) hepatocellular carcinoma. None of the anti-HCV positive cases had past history of blood transfusion. The patients of chronic liver disease in this study had a much higher prevalence of HBV infection which indicates that in northern Pakistan hepatitis C virus infection is not a common cause of chronic liver disease whereas HBV infection plays an aetiological role in a much larger number of these cases.

Chronic Broca's Aphasia Is Caused by Damage to Broca's and Wernicke's Areas.

PubMed

Fridriksson, Julius; Fillmore, Paul; Guo, Dazhou; Rorden, Chris

2015-12-01

Despite being perhaps the most studied form of aphasia, the critical lesion location for Broca's aphasia has long been debated, and in chronic patients, cortical damage often extends far beyond Broca's area. In a group of 70 patients, we examined brain damage associated with Broca's aphasia using voxel-wise lesion-symptom mapping (VLSM). We found that damage to the posterior portion of Broca's area, the pars opercularis, is associated with Broca's aphasia. However, several individuals with other aphasic patterns had considerable damage to pars opercularis, suggesting that involvement of this region is not sufficient to cause Broca's aphasia. When examining only individuals with pars opercularis damage, we found that patients with Broca's aphasia had greater damage in the left superior temporal gyrus (STG; roughly Wernicke's area) than those with other aphasia types. Using discriminant function analysis and logistic regression, based on proportional damage to the pars opercularis and Wernicke's area, to predict whether individuals had Broca's or another types of aphasia, over 95% were classified correctly. Our findings suggest that persons with Broca's aphasia have damage to both Broca's and Wernicke's areas, a conclusion that is incongruent with classical neuropsychology, which has rarely considered the effects of damage to both areas. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Management of Infrapopliteal Arterial Disease: Critical Limb Ischemia.

PubMed

Mustapha, Jihad A; Diaz-Sandoval, Larry J

2014-10-01

According to the TransAtlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease, "there is increasing evidence to support a recommendation for angioplasty in patients with critical limb ischemia and infrapopliteal artery occlusion." Management of infrapopliteal artery disease starts with diagnosis using modern preprocedural noninvasive and invasive imaging. Interventionalists need to learn the role of chronic total occlusion cap analysis and collateral zone recognition in angiosome-directed interventions for management of critical limb ischemia and be familiar with equipment and device selection and a stepwise approach for endovascular interventions. Interventionalists need to know which crossing tools to use to successfully cross-complex chronic total occlusion caps. Copyright © 2014 Elsevier Inc. All rights reserved.

[Prevention and management of refeeding syndrome in patients with chronic critical illness].

PubMed

Chen, Jun; Fan, Chaogang

2016-07-01

Nutritional support is an important means to treat the patients with chronic critical illness for commonly associated malnutrition. Refeeding syndrome is a serious complication during the process, mainly manifested as severe electrolyte with hypophosphataemia being the most common. Refeeding syndrome is not uncommon but it is often ignored. In our future clinical work, we need to recognize this chinical situation and use preventative and treatment measures. According to NICE clinical nutrition guideline, we discussed the risk factors, treatment methods and preventive measures of refeeding syndrome in patients with chronic critical illness. We argued that for patients with high risk refeeding syndrome, nutritional support treatment should be initially low calorie and slowly increased to complete requirement. Circulation capacity should be recovered, fluid balance must be closely monitored and supplement of vitamins, microelement, electrolytes should be noted. After the emergence of refeeding syndrome, we should reduce or even stop the calorie intake, give an active treatment for electrolyte disorder, provide vitamin B, and maintain the functions of multiple organs.

The Shared Decision Making Frontier: a Feasibility and Usability Study for Managing Non-Critical Chronic Illness by Combining Behavioural & Decision Theory with Online Technology.

PubMed

Russell, Amina; Van Woensel, William; Abidi, Samina Raza

2015-01-01

The objective of this study is to determine if shared decisions for managing non-critical chronic illness, made through an online biomedical technology intervention, us feasible and usable. The technology intervention incorporates behavioural and decision theories to increase patient engagement, and ultimately long term adherence to health behaviour change. We devised the iheart web intervention as a "proof of concept" in five phases. The implementation incorporates the Vaadin web application framework, Drools, EclipseLink and a MySQL database. Two-thirds of the study participants favoured the technology intervention, based on Likert-scale questions from a post-study questionnaire. Qualitative analysis of think aloud feedback, video screen captures and open-ended questions from the post-study questionnaire uncovered six main areas or themes for improvement. We conclude that online shared decisions for managing a non-critical chronic illness are feasible and usable through the iheart web intervention.

Critical role of tumor necrosis factor receptor 1 in the pathogenesis of pulmonary emphysema in mice.

PubMed

Fujita, Masaki; Ouchi, Hiroshi; Ikegame, Satoshi; Harada, Eiji; Matsumoto, Takemasa; Uchino, Junji; Nakanishi, Yoichi; Watanabe, Kentaro

2016-01-01

COPD is a major cause of chronic morbidity and mortality throughout the world. Although tumor necrosis factor-α (TNF-α) has a critical role in the development of COPD, the role of different TNF receptors (TNFRs) in pulmonary emphysema has not been resolved. We aimed to clarify the role of TNFRs in the development of pulmonary emphysema. TNF-α transgenic mice, a murine model of COPD in which the mice spontaneously develop emphysema with a large increase in lung volume and pulmonary hypertension, were crossed with either TNFR1-deficient mice or TNFR2-deficient mice. After 6 months, the gross appearance of the lung, lung histology, and pulmonary and cardiac physiology were determined. In addition, the relationship between apoptosis and emphysema was investigated. Pulmonary emphysema-like changes disappeared with deletion of TNFR1. However, slight improvements were attained with deletion of TNFR2. Apoptotic cells in the interstitium of the lung were observed in TNF-α transgenic mice. The apoptotic signals through TNFR1 appear critical for the pathogenesis of pulmonary emphysema. In contrast, the inflammatory process has a less important role for the development of emphysema.

The nutritional and metabolic support of heart failure in the intensive care unit.

PubMed

Meltzer, Joseph S; Moitra, Vivek K

2008-03-01

Heart failure and cardiovascular disease are common causes of morbidity and mortality, contributing to many ICU admissions. Nutritional deficiencies have been associated with the development and worsening of chronic heart failure. Nutritional and metabolic support may improve outcomes in critically ill patients with heart failure. This review analyzes the role of this support in the acute care setting of the ICU. Cardiac cachexia is a complex pathophysiologic process. It is characterized by inflammation and anabolic-catabolic imbalance. Nutritional supplements containing selenium, vitamins and antioxidants may provide needed support to the failing myocardium. Evidence shows that there is utility in intensive insulin therapy in the critically ill. Finally, there is an emerging metabolic role for HMG-CoA reductase inhibition, or statin therapy, in the treatment of heart failure. Shifting the metabolic milieu from catabolic to anabolic, reducing free radicals, and quieting inflammation in addition to caloric supplementation may be the key to nutritional support in the heart failure patient. Tight glycemic control with intensive insulin therapy plays an expanding role in the care of the critically ill. Glucose-insulin-potassium therapy probably does not improve the condition of the patient with heart failure or acute myocardial infarction.

Chronic obstructive pulmonary disease: knowing what we mean, meaning what we say.

PubMed

Joshi, J M

2008-01-01

Chronic obstructive pulmonary disease (COPD) is defined in several different ways using different criteria based on symptoms, physiological impairment and pathological abnormalities. While some use COPD to mean smoking related chronic airway disease, others include all disorders causing chronic airway obstruction. When COPD is used as a broad descriptive term, specific disorders that cause chronic airway obstruction remain under-diagnosed and the prevalence estimates vary considerably. The lack of agreement over the precise terminology and classification of COPD has resulted in widespread confusion. Terminology includes definition, diagnostic criteria, and a system for staging severity. Recently, COPD is defined more clearly and diagnosed using precise criteria that include tobacco smoking greater than 10 pack years, symptoms and airway obstruction on spirometry. A multi-dimensional severity grading system, the BODE (body mass index, obstruction, dyspnoea, and exercise tolerance) index has been designed to assess the respiratory and systemic expressions of COPD. This review proposes that the broad group of chronic disorders of the airways (with or without airway obstruction) be called chronic airway disease (CAD). The term COPD should be used exclusively for tobacco smoking related chronic airway disease. Chronic airway obstruction or obstructive lung disease may be used to define those conditions with airways obstruction caused by factors other than tobacco smoking. The aetiology may be appended to the label, for example, chronic airway obstruction/obstructive lung disease associated with bronchiectasis, chronic airway obstruction/obstructive lung disease associated with obliterative bronchiolitis or chronic airway obstruction/obstructive lung disease due to biomass fuel/occupational exposure.

Efficient zinc uptake is critical for the ability of Pseudomonas aeruginosa to express virulence traits and colonize the human lung.

PubMed

Mastropasqua, Maria Chiara; Lamont, Iain; Martin, Lois W; Reid, David W; D'Orazio, Melania; Battistoni, Andrea

2018-07-01

We have recently shown that Pseudomonas aeruginosa, an opportunistic pathogen that chronically infects the lungs of patients with cystic fibrosis (CF) and other forms of lung disease, is extremely efficient in recruiting zinc from the environment and that this capability is required for its ability to cause acute lung infections in mice. To verify that P. aeruginosa faces zinc shortage when colonizing the lungs of human patients, we analyzed the expression of three genes that are highly induced under conditions of zinc deficiency (zrmA, dksA2 and rpmE2), in bacteria in the sputum of patients with inflammatory lung disease. All three genes were expressed in all the analyzed sputum samples to a level much higher than that of bacteria grown in zinc-containing laboratory medium, supporting the hypothesis that P. aeruginosa is under zinc starvation during lung infections. We also found that the expression of several virulence traits that play a central role in the ability of P. aeruginosa to colonize the lung is affected by disruption of the most important zinc importing systems. Virulence features dependent on zinc intake include swarming and swimming motility and the ability to form biofilms. Furthermore, alterations in zinc assimilation interfere with the synthesis of the siderophore pyoverdine, suggesting that zinc recruitment could modulate iron uptake and affect siderophore-mediated cell signaling. Our results reveal that zinc uptake is likely to play a key role in the ability of P. aeruginosa to cause chronic lung infections and strongly modulates critical virulence traits of the pathogen. Taking into account the recent discovery that zinc uptake in P. aeruginosa is promoted by the release of a small molecular weight molecule showing high affinity for zinc, our data suggest novel and effective possibilities to control lung infections by these bacteria. Copyright © 2018 Elsevier GmbH. All rights reserved.

Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation.

PubMed

Ren, Zhenhua; Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

2016-10-01

Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5g/kg, 25% ethanol w/v) daily for 3days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas. Copyright © 2016 Elsevier Inc. All rights reserved.

CXCL10 Is Required to Maintain T-Cell Populations and to Control Parasite Replication during Chronic Ocular Toxoplasmosis

PubMed Central

Norose, Kazumi; Kikumura, Akitoshi; Luster, Andrew D.; Hunter, Christopher A.

2011-01-01

Purpose. Toxoplasma gondii is a major cause of ocular disease, which can lead to permanent vision loss in humans. T cells are critically involved in parasite control, but little is known about the molecules that promote T-cell trafficking and migration in the retina. Thus, the aim of this study was to image and dissect the T-cell response during chronic toxoplasmic retinochoroiditis. Methods. C57BL/6 mice were infected with the Me49 strain of T. gondii, and T cells that infiltrated the eye were analyzed by flow cytometry and imaged using multiphoton microscopy. IFN-γ, CXCL9, CXCL10, and CXCR3 mRNA levels were measured by real-time PCR. To investigate the role of CXCL10, mice were treated with anti–CXCL10 antibodies, and histopathology and immunohistochemistry were performed to monitor changes in pathology, cellular infiltration, and parasite burden in the eye. Results. Infection with T. gondii leads to the infiltration of highly activated motile T cells into the eye. These cells express CXCR3 and are capable of producing IFN-γ and TNF-α, and CD8+ T cells express granzyme B. The expression of CXCL9 and CXCL10 in the retina was significantly upregulated during chronic infection. Treatment of chronically infected mice with anti–CXCL10 antibodies led to decreases in the numbers of CD3+, CD4+, and CD8+ T cells and the amount of IFN-γ mRNA expression in the retina and an increase in replicating parasites and ocular pathology. Conclusions. The maintenance of the T-cell response and the control of T. gondii in the eye during chronic infection is dependent on CXCL10. PMID:20811054

Decreased expression of serum- and glucocorticoid-inducible kinase 1 (SGK1) promotes alpha-synuclein increase related with down-regulation of dopaminergic cell in the Substantia Nigra of chronic MPTP-induced Parkinsonism mice and in SH-SY5Y cells.

PubMed

Yeo, Sujung; Sung, Backil; Hong, Yeon-Mi; van den Noort, Maurits; Bosch, Peggy; Lee, Sook-Hyun; Song, Jongbeom; Park, Sang-Kyun; Lim, Sabina

2018-06-30

Parkinson's disease (PD) is a chronically progressive neurodegenerative disease, with its main pathological hallmarks being a dramatic loss of dopaminergic neurons predominantly in the Substantia Nigra (SN), and the formations of intracytoplasmic Lewy bodies and dystrophic neurites. Alpha-synuclein (α-syn), widely recognized as the most prominent element of the Lewy body, is one of the representative hallmarks in PD. However, the mechanisms behind the increased α-syn expression and aggregation have not yet been clarified. To examine what causes α-syn expression to increase, we analyzed the pattern of gene expression in the SN of mice intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), where down-regulation of dopaminergic cells occurred. We identified serum- and glucocorticoid-dependent kinase 1 (SGK1) as one of the genes that is evidently downregulated in chronic MPTP-intoxication. The results of Western blot analyses showed that, together with the down-regulation of dopaminergic cells, the decrease in SGK1 expression increased α-syn expression in the SN in a chronic MPTP-induced Parkinsonism mouse. For an examination of the expression correlation between SGK1 and α-syn, SH-5YSY cells were knocked down with SGK1 siRNA then, the downregulation of dopaminergic cells and the increase in the expression of α-syn were observed. These results suggest that decreased expression of SGK1 may play a critical role in increasing the expression of α-syn, which is related with dopaminergic cell death in the SN of chronic MPTP-induced Parkinsonism mice and in SH-SY5Y cells. Copyright © 2018. Published by Elsevier B.V.

In-depth behavioral characterization of the corticosterone mouse model and the critical involvement of housing conditions.

PubMed

Demuyser, Thomas; Deneyer, Lauren; Bentea, Eduard; Albertini, Giulia; Van Liefferinge, Joeri; Merckx, Ellen; De Prins, An; De Bundel, Dimitri; Massie, Ann; Smolders, Ilse

2016-03-15

Depression and anxiety are disabling and highly prevalent psychiatric disorders. To better understand the neurobiological basis of mood and anxiety disorders, relevant animal models are needed. The corticosterone mouse model is frequently used to study depression. Chronic stress and accompanying glucocorticoid elevation causes pathological changes in the central nervous system, which are related to psychiatric symptoms. Exogenous administration of corticosterone is therefore often used to induce depressive-like behavior in mice and in some cases also features of anxiety-like behavior are shown. However, a thorough characterization of this model has never been conducted and housing conditions of the used subjects often differ between the implemented protocols. We chronically administered a subcutaneous corticosterone bolus injection to single- and group-housed mice, and we subsequently evaluated the face validity of this model by performing a battery of behavioral tests (forced swim test, mouse-tail suspension test, saccharin intake test, novelty-suppressed feeding test, elevated plus maze, light/dark paradigm and open field test). Our results show that corticosterone treatment has a substantial overall effect on depressive-like behavior. Increases in anxiety-like behavior on the other hand are mainly seen in single housed animals, independent of treatment. The current study therefore does not only show a detailed behavioral characterization of the corticosterone mouse model, but furthermore also elucidates the critical influence of housing conditions on the behavioral outcome in this model. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of yoga on chronic neck pain: a systematic review of randomized controlled trials

PubMed Central

Kim, Sang-Dol

2016-01-01

[Purpose] The aim of this study was to investigate the effectiveness of yoga in the management of chronic neck pain. [Subjects and Methods] Five electronic databases were searched to identify randomized controlled trials (RCTs) of yoga intervention on chronic neck pain. The trials were published in the English language between January 1966 and December 2015. The Cochrane Risk of Bias Tool was used to assess the quality of the trials. [Results] Three trials were identified and included in this review. A critical appraisal was performed on the trials, and the result indicated a high risk of bias. A narrative description was processed because of the small number of RCTs. Neck pain intensity and functional disability were significantly lower in the yoga groups than in the control groups. [Conclusion] Evidence from the 3 randomly controlled trials shows that yoga may be beneficial for chronic neck pain. The low-quality result of the critical appraisal and the small number of trials suggest that high-quality RCTs are required to examine further the effects of yoga intervention on chronic neck pain relief. PMID:27512290

The AIMAR recommendations for early diagnosis of chronic obstructive respiratory disease based on the WHO/GARD model*

PubMed Central

2014-01-01

Respiratory diseases in Italy already now represent an emergency (they are the 3rd ranking cause of death in the world, and the 2nd if Lung cancer is included). In countries similar to our own, they result as the principal cause for a visit to the general practitioner (GP) and the second main cause after injury for recourse to Emergency Care. Their frequency is probably higher than estimated (given that respiratory diseases are currently underdiagnosed). The trend is towards a further increase due to epidemiologic and demographic factors (foremost amongst which are the widespread diffusion of cigarette smoking, the increasing mean age of the general population, immigration, and pollution). Within the more general problem of chronic disease care, chronic respiratory diseases (CRDs) constitute one of the four national priorities in that they represent an important burden for society in terms of mortality, invalidity, and direct healthcare costs. The strategy suggested by the World Health Organization (WHO) is an integrated approach consisting of three goals: inform about health, reduce risk exposure, improve patient care. The three goals are translated into practice in the three areas of prevention (1-primary, 2-secondary, 3-tertiary) as: 1) actions of primary (universal) prevention targeted at the general population with the aim to control the causes of disease, and actions of Predictive Medicine - again addressing the general population but aimed at measuring the individual’s risk for disease insurgence; 2) actions of early diagnosis targeted at groups or - more precisely - subgroups identified as at risk; 3) continuous improvement and integration of care and rehabilitation support - destined at the greatest possible number of patients, at all stages of disease severity. In Italy, COPD care is generally still inadequate. Existing guidelines, institutional and non-institutional, are inadequately implemented: the international guidelines are not always adaptable to the Italian context; the document of the Agency for Regional Healthcare Services (AGE.NA.S) is a more suited compendium for consultation, and the recent joint statement on integrated COPD management of the three major Italian scientific Associations in the respiratory area together with the contribution of a Society of General Medicine deals prevalently with some critical issues (appropriateness of diagnosis, pharmacological treatment, rehabilitation, continuing care); also the document “Care Continuity: Chronic Obstructive Pulmonary Disease (COPD)” of the Global Alliance against chronic Respiratory Diseases (GARD)-Italy does not treat in depth the issue of early diagnosis. The present document – produced by the AIMAR (Interdisciplinary Association for Research in Lung Disease) Task Force for early diagnosis of chronic respiratory disease based on the WHO/GARD model and on available evidence and expertise –after a general examination of the main epidemiologic aspects, proposes to integrate the above-mentioned existing documents. In particular: a) it formally indicates on the basis of the available evidence the modalities and the instruments necessary for carrying out secondary prevention at the primary care level (a pro-active,‘case-finding’approach; assessment of the individual’s level of risk of COPD; use of short questionnaires for an initial screening based on symptoms; use of simple spirometry for the second level of screening); b) it identifies possible ways of including these activities within primary care practice; c) it places early diagnosis within the “systemic”, consequential management of chronic respiratory diseases, which will be briefly described with the aid of schemes taken from the Italian and international reference documents. PMID:25473523

The AIMAR recommendations for early diagnosis of chronic obstructive respiratory disease based on the WHO/GARD model*.

PubMed

Nardini, Stefano; Annesi-Maesano, Isabella; Del Donno, Mario; Delucchi, Maurizio; Bettoncelli, Germano; Lamberti, Vincenzo; Patera, Carlo; Polverino, Mario; Russo, Antonio; Santoriello, Carlo; Soverina, Patrizio

2014-01-01

Respiratory diseases in Italy already now represent an emergency (they are the 3(rd) ranking cause of death in the world, and the 2(nd) if Lung cancer is included). In countries similar to our own, they result as the principal cause for a visit to the general practitioner (GP) and the second main cause after injury for recourse to Emergency Care. Their frequency is probably higher than estimated (given that respiratory diseases are currently underdiagnosed). The trend is towards a further increase due to epidemiologic and demographic factors (foremost amongst which are the widespread diffusion of cigarette smoking, the increasing mean age of the general population, immigration, and pollution). Within the more general problem of chronic disease care, chronic respiratory diseases (CRDs) constitute one of the four national priorities in that they represent an important burden for society in terms of mortality, invalidity, and direct healthcare costs. The strategy suggested by the World Health Organization (WHO) is an integrated approach consisting of three goals: inform about health, reduce risk exposure, improve patient care. The three goals are translated into practice in the three areas of prevention (1-primary, 2-secondary, 3-tertiary) as: 1) actions of primary (universal) prevention targeted at the general population with the aim to control the causes of disease, and actions of Predictive Medicine - again addressing the general population but aimed at measuring the individual's risk for disease insurgence; 2) actions of early diagnosis targeted at groups or - more precisely - subgroups identified as at risk; 3) continuous improvement and integration of care and rehabilitation support - destined at the greatest possible number of patients, at all stages of disease severity. In Italy, COPD care is generally still inadequate. Existing guidelines, institutional and non-institutional, are inadequately implemented: the international guidelines are not always adaptable to the Italian context; the document of the Agency for Regional Healthcare Services (AGE.NA.S) is a more suited compendium for consultation, and the recent joint statement on integrated COPD management of the three major Italian scientific Associations in the respiratory area together with the contribution of a Society of General Medicine deals prevalently with some critical issues (appropriateness of diagnosis, pharmacological treatment, rehabilitation, continuing care); also the document "Care Continuity: Chronic Obstructive Pulmonary Disease (COPD)" of the Global Alliance against chronic Respiratory Diseases (GARD)-Italy does not treat in depth the issue of early diagnosis. The present document - produced by the AIMAR (Interdisciplinary Association for Research in Lung Disease) Task Force for early diagnosis of chronic respiratory disease based on the WHO/GARD model and on available evidence and expertise -after a general examination of the main epidemiologic aspects, proposes to integrate the above-mentioned existing documents. In particular: a) it formally indicates on the basis of the available evidence the modalities and the instruments necessary for carrying out secondary prevention at the primary care level (a pro-active,'case-finding'approach; assessment of the individual's level of risk of COPD; use of short questionnaires for an initial screening based on symptoms; use of simple spirometry for the second level of screening); b) it identifies possible ways of including these activities within primary care practice; c) it places early diagnosis within the "systemic", consequential management of chronic respiratory diseases, which will be briefly described with the aid of schemes taken from the Italian and international reference documents.

Hepatitis B virus infection in Latin America: A genomic medicine approach

PubMed Central

Roman, Sonia; Jose-Abrego, Alexis; Fierro, Nora Alma; Escobedo-Melendez, Griselda; Ojeda-Granados, Claudia; Martinez-Lopez, Erika; Panduro, Arturo

2014-01-01

Hepatitis B virus (HBV) infection is the leading cause of severe chronic liver disease. This article provides a critical view of the importance of genomic medicine for the study of HBV infection and its clinical outcomes in Latin America. Three levels of evolutionary adaptation may correlate with the clinical outcomes of HBV infection. Infections in Latin America are predominantly of genotype H in Mexico and genotype F in Central and South America; these strains have historically circulated among the indigenous population. Both genotypes appear to be linked to a benign course of disease among the native and mestizo Mexicans and native South Americans. In contrast, genotypes F, A and D are common in acute and chronic infections among mestizos with Caucasian ancestry. Hepatocellular carcinoma is rare in Mexicans, but it has been associated with genotype F1b among Argentineans. This observation illustrates the significance of ascertaining the genetic and environmental factors involved in the development of HBV-related liver disease in Latin America, which contrast with those reported in other regions of the world. PMID:24966588

Wt-1 Expression Linked to Nitric Oxide Availability during Neonatal Obstructive Nephropathy

PubMed Central

Mazzei, Luciana; Manucha, Walter

2013-01-01

The wt-1 gene encodes a zinc finger DNA-binding protein that acts as a transcriptional activator or repressor depending on the cellular or chromosomal context. The wt-1 regulates the expression of a large number of genes that have a critical role in kidney development. Congenital obstructive nephropathy disrupts normal renal development and causes chronic progressive interstitial fibrosis, which contributes to renal growth arrest, ultimately leading to chronic renal failure. Wt-1 is downregulated during congenital obstructive nephropathy, leading to apoptosis. Of great interest, nitric oxide bioavailability associated with heat shock protein 70 (Hsp70) interaction may modulate wt-1 mRNA expression, preventing obstruction-induced cell death during neonatal unilateral ureteral obstruction. Moreover, recent genetic researches have allowed characterization of many of the complex interactions among the individual components cited, but the realization of new biochemical, molecular, and functional experiments as proposed in our and other research labs allows us to establish a deeper level of commitment among proteins involved and the potential pathogenic consequences of their imbalance. PMID:24288526

Lung Transplantation for Cystic Fibrosis: Results, Indications, Complications, and Controversies

PubMed Central

Lynch, Joseph P.; Sayah, David M.; Belperio, John A.; Weigt, S. Sam

2016-01-01

Survival in patients with cystic fibrosis (CF) has improved dramatically over the past 30 to 40 years, with mean survival now approximately 40 years. Nonetheless, progressive respiratory insufficiency remains the major cause of mortality in CF patients, and lung transplantation (LT) is eventually required. Timing of listing for LT is critical, because up to 25 to 41% of CF patients have died while awaiting LT. Globally, approximately 16.4% of lung transplants are performed in adults with CF. Survival rates for LT recipients with CF are superior to other indications, yet LT is associated with substantial morbidity and mortality (~50% at 5-year survival rates). Myriad complications of LT include allograft failure (acute or chronic), opportunistic infections, and complications of chronic immunosuppressive medications (including malignancy). Determining which patients are candidates for LT is difficult, and survival benefit remains uncertain. In this review, we discuss when LT should be considered, criteria for identifying candidates, contraindications to LT, results post-LT, and specific complications that may be associated with LT. Infectious complications that may complicate CF (particularly Burkholderia cepacia spp., opportunistic fungi, and nontuberculous mycobacteria) are discussed. PMID:25826595

Dynamics of Diabetes and Obesity: Epidemiological Perspective

PubMed Central

Boles, Annette; Kandimalla, Ramesh; Reddy, P. Hemachandra

2017-01-01

The purpose of this review article is to understand the current literature on obesity, diabetes and therapeutic avenues across the world. Diabetes is a chronic lifestyle condition that affects millions of people worldwide and it is a major health concern in our society. Diabetes and obesity are associated with various conditions, including non-modifiable and modifiable risk factors. Early detectable markers are not well established to detect pre-diabetes and as a result, it becomes diabetes. Several published epidemiological studies were assessed and the findings were summarized. Resources from published studies were used to identify criteria used for pre-diabetes, the role of diet in pre-diabetics and potential risks and characteristics associated with pre-diabetes. Preventive strategies are needed to combat diabetes. Individuals diagnosed with pre-diabetes need detailed education, need to fully understand the risk factors and have the ability to manage diabetes. Interventions exist that include chronic disease self-management programs, lifestyle interventions and pharmacological strategies. Obesity plays a large role in causing pre-diabetes and diabetes. Critical analysis of existing epidemiological research data suggests that additional research is needed to determine the efficacy of interventions. PMID:28130199

Rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model.

PubMed

Su, Wenru; Li, Zuohong; Jia, Yu; Zhuo, Yehong

2014-01-01

Glaucoma is a leading cause of irreversible blindness. Injury of retinal ganglion cells (RGCs) accounts for visual impairment of glaucoma. Here, we report rapamycin protects RGCs from death in experimental glaucoma model and the underlying mechanisms. Our results showed that treatment with rapamycin dramatically promote RGCs survival in a rat chronic ocular hypertension model. This protective action appears to be attributable to inhibition of neurotoxic mediators release and/or direct suppression of RGC apoptosis. In support of this mechanism, in vitro, rapamycin significantly inhibits the production of NO, TNF-α in BV2 microglials by modulating NF-κB signaling. In experimental animals, treatment with rapamycin also dramatically inhibited the activation of microglials. In primary RGCs, rapamycin was capable of direct suppression the apoptosis of primary RGCs induced by glutamate. Mechanistically, rapamycin-mediated suppression of RGCs apoptosis is by sparing phosphorylation of Akt at a site critical for maintenance of its survival-promoting activity in cell and animal model. These results demonstrate that rapamycin is neuroprotective in experimental glaucoma, possibly via decreasing neurotoxic releasing and suppressing directly apoptosis of RGCs.

Acute-on-chronic and Decompensated Chronic Liver Failure: Definitions, Epidemiology, and Prognostication.

PubMed

Olson, Jody C

2016-07-01

Chronic liver disease is the fifth leading cause of death worldwide and represents a major burden for the health care community. Cirrhosis is a progressive disease resulting in end-stage liver failure, which in the absence of liver transplantation is fatal. Acute-on-chronic liver failure carries high short-term mortality but is potentially reversible. Viral hepatitis, alcohol, and nonalcoholic fatty liver disease remain the principal causes of liver disease. Though treatments exist for hepatitis B and C, they remain unavailable to many with these diseases. This article reviews the epidemiology of advanced liver disease and the concept of acute-on-chronic liver failure. Copyright © 2016 Elsevier Inc. All rights reserved.

Under Pressure: Applying Practice-Based Learning and Improvement to the Treatment of Chronic Neuropathic Pain in Patients with Burns.

PubMed

Rapolti, Mihaela; Wu, Cindy; Schuth, Olga A; Hultman, Charles Scott

2017-10-01

Chronic neuropathic pain after burn injury may have multiple causes, such as direct nerve injury, nerve compression, or neuroma formation, and can significantly impair quality of life and limit functional recovery. Management includes a team-based approach that involves close collaboration between occupational and physical therapists, plastic surgeons, and experts in chronic pain, from neurology, anesthesia, psychiatry, and physiatry. Carefully selected patients with an anatomic cause of chronic neuropathic pain unequivocally benefit from surgical intervention. Self-reflection and analysis yield improvement in both efficiency and effectiveness when managing patients with burns with chronic neuropathic pain. Copyright © 2017 Elsevier Inc. All rights reserved.

How Is Chronic Myeloid Leukemia Diagnosed?

MedlinePlus

... Myeloid Leukemia? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

Dysphagia Caused by Chronic Laryngeal Edema.

PubMed

Delides, Alexander; Sakagiannis, George; Maragoudakis, Pavlos; Gouloumi, Αlina-Roxani; Katsimbri, Pelagia; Giotakis, Ioannis; Panayiotides, John G

2015-10-01

A rare case of a young female with chronic diffuse laryngeal edema causing severe swallowing difficulty is presented. The patient was previously treated with antibiotics and steroids with no improvement. Diagnosis was made with biopsy of the epiglottis under local anesthesia in the office.

Geometric phase transition in the cellular network of the pancreatic islets may underlie the onset of type 1diabetes

NASA Astrophysics Data System (ADS)

Wang, Xujing

Living systems are characterized by complexity in structure and emergent dynamic orders. In many aspects the onset of a chronic disease resembles phase transition in a dynamic system: quantitative changes accumulate largely unnoticed until a critical threshold is reached, which causes abrupt qualitative changes of the system. In this study we investigate this idea in a real example, the insulin-producing pancreatic islet β-cells and the onset of type 1 diabetes. Within each islet, the β-cells are electrically coupled to each other, and function as a network with synchronized actions. Using percolation theory we show how normal islet function is intrinsically linked to network connectivity, and the critical point where the islet cellular network loses site percolation, is consistent with laboratory and clinical observations of the threshold β-cell loss that causes islet functional failure. Numerical simulations confirm that the islet cellular network needs to be percolated for β-cells to synchronize. Furthermore, the interplay between site percolation and bond strength predicts the existence of a transient phase of islet functional recovery after disease onset and introduction of treatment, potentially explaining a long time mystery in the clinical study of type 1 diabetes: the honeymoon phenomenon. Based on these results, we hypothesized that the onset of T1D may be the result of a phase transition of the islet β-cell network. We further discuss the potential applications in identifying disease-driving factors, and the critical parameters that are predictive of disease onset.

Chronic Neck Pain: Making the Connection Between Capsular Ligament Laxity and Cervical Instability

PubMed Central

Steilen, Danielle; Hauser, Ross; Woldin, Barbara; Sawyer, Sarah

2014-01-01

The use of conventional modalities for chronic neck pain remains debatable, primarily because most treatments have had limited success. We conducted a review of the literature published up to December 2013 on the diagnostic and treatment modalities of disorders related to chronic neck pain and concluded that, despite providing temporary relief of symptoms, these treatments do not address the specific problems of healing and are not likely to offer long-term cures. The objectives of this narrative review are to provide an overview of chronic neck pain as it relates to cervical instability, to describe the anatomical features of the cervical spine and the impact of capsular ligament laxity, to discuss the disorders causing chronic neck pain and their current treatments, and lastly, to present prolotherapy as a viable treatment option that heals injured ligaments, restores stability to the spine, and resolves chronic neck pain. The capsular ligaments are the main stabilizing structures of the facet joints in the cervical spine and have been implicated as a major source of chronic neck pain. Chronic neck pain often reflects a state of instability in the cervical spine and is a symptom common to a number of conditions described herein, including disc herniation, cervical spondylosis, whiplash injury and whiplash associated disorder, postconcussion syndrome, vertebrobasilar insufficiency, and Barré-Liéou syndrome. When the capsular ligaments are injured, they become elongated and exhibit laxity, which causes excessive movement of the cervical vertebrae. In the upper cervical spine (C0-C2), this can cause a number of other symptoms including, but not limited to, nerve irritation and vertebrobasilar insufficiency with associated vertigo, tinnitus, dizziness, facial pain, arm pain, and migraine headaches. In the lower cervical spine (C3-C7), this can cause muscle spasms, crepitation, and/or paresthesia in addition to chronic neck pain. In either case, the presence of excessive motion between two adjacent cervical vertebrae and these associated symptoms is described as cervical instability. Therefore, we propose that in many cases of chronic neck pain, the cause may be underlying joint instability due to capsular ligament laxity. Currently, curative treatment options for this type of cervical instability are inconclusive and inadequate. Based on clinical studies and experience with patients who have visited our chronic pain clinic with complaints of chronic neck pain, we contend that prolotherapy offers a potentially curative treatment option for chronic neck pain related to capsular ligament laxity and underlying cervical instability. PMID:25328557

Chronic neck pain: making the connection between capsular ligament laxity and cervical instability.

PubMed

Steilen, Danielle; Hauser, Ross; Woldin, Barbara; Sawyer, Sarah

2014-01-01

The use of conventional modalities for chronic neck pain remains debatable, primarily because most treatments have had limited success. We conducted a review of the literature published up to December 2013 on the diagnostic and treatment modalities of disorders related to chronic neck pain and concluded that, despite providing temporary relief of symptoms, these treatments do not address the specific problems of healing and are not likely to offer long-term cures. The objectives of this narrative review are to provide an overview of chronic neck pain as it relates to cervical instability, to describe the anatomical features of the cervical spine and the impact of capsular ligament laxity, to discuss the disorders causing chronic neck pain and their current treatments, and lastly, to present prolotherapy as a viable treatment option that heals injured ligaments, restores stability to the spine, and resolves chronic neck pain. The capsular ligaments are the main stabilizing structures of the facet joints in the cervical spine and have been implicated as a major source of chronic neck pain. Chronic neck pain often reflects a state of instability in the cervical spine and is a symptom common to a number of conditions described herein, including disc herniation, cervical spondylosis, whiplash injury and whiplash associated disorder, postconcussion syndrome, vertebrobasilar insufficiency, and Barré-Liéou syndrome. When the capsular ligaments are injured, they become elongated and exhibit laxity, which causes excessive movement of the cervical vertebrae. In the upper cervical spine (C0-C2), this can cause a number of other symptoms including, but not limited to, nerve irritation and vertebrobasilar insufficiency with associated vertigo, tinnitus, dizziness, facial pain, arm pain, and migraine headaches. In the lower cervical spine (C3-C7), this can cause muscle spasms, crepitation, and/or paresthesia in addition to chronic neck pain. In either case, the presence of excessive motion between two adjacent cervical vertebrae and these associated symptoms is described as cervical instability. Therefore, we propose that in many cases of chronic neck pain, the cause may be underlying joint instability due to capsular ligament laxity. Currently, curative treatment options for this type of cervical instability are inconclusive and inadequate. Based on clinical studies and experience with patients who have visited our chronic pain clinic with complaints of chronic neck pain, we contend that prolotherapy offers a potentially curative treatment option for chronic neck pain related to capsular ligament laxity and underlying cervical instability.

Causes of unplanned hemodialysis initiation.

PubMed

Gomis Couto, A; Teruel Briones, J L; Fernández Lucas, M; Rivera Gorrin, M; Rodríguez Mendiola, N; Jiménez Álvaro, S; Quereda Rodríguez-Navarro, C

2011-01-01

Half of patients starting chronic hemodialysis used a transient vascular catheter as a vascular access (unplanned initiation). An objective of the Quality Management Group of the Spanish Society of Nephrology is to achieve that 80% of the patients starting hemodialysis do it with an arteriovenous fistula. We want to review the causes of non-planned hemodialysis nowadays. In 2010, 43 patients had started chronic hemodialysis in the Hospital Ramón y Cajal in Madrid (Spain). Mean age was 61 years, 79% were men, the most frequent cause of chronic renal disease was the diabetes (23%) and Charlson Comorbidity Index was 6.3 ± 2.6. The unplanned hemodialysis occurred in 20 patients (47%), without any differences with the 23 patients who began planned hemodialysis, in none of the clinical or demographic parameters analyzed. The main cause of unplanned hemodialysis was the acute exacerbation of chronic kidney disease stage 3 or 4, previously stable, secondary to an unforeseeable intercurrent process (8 patients, 40% of the cases). One patient began after a non-recovery acute renal failure and in other 6 patients, the reason of unplanned hemodialysis initiation was not attributable to the operation Health System (in 3 cases unknown kidney chronic disease and in the other 3 cases it was patient´s responsibility). Only in 5 cases (25%), the cause could be corrigible. Most causes of unplanned hemodialysis does not come from the healthcare organization and therefore not easy to resolve it. Consequently, the objective of the Quality Group will be difficult to be achieved.

Causes of chronic productive cough: An approach to management.

PubMed

Martin, Matthew J; Harrison, Tim W

2015-09-01

A chronic 'productive' or 'wet' cough is a common presenting complaint for patients attending the adult respiratory clinic. Most reviews and guidelines suggest that the causes of a productive cough are the same as those of a non-productive cough and as such the same diagnostic pathway should be followed. We suggest a different diagnostic approach for patients with a productive cough, focussing on the conditions that are the most likely causes of this problem. This review is intended to briefly summarise the epidemiology, clinical features, pathophysiology and treatment of a number of conditions which are often associated with chronic productive cough to aid decision making when encountering a patient with this often distressing symptom. The conditions discussed include bronchiectasis, chronic bronchitis, asthma, eosinophilic bronchitis and immunodeficiency. We also propose an adult version of the paediatric diagnosis of protracted bacterial bronchitis (PBB) in patients with idiopathic chronic productive cough who appear to respond well to low dose macrolide therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Time trends in the etiology of chronic pancreatitis in South India.

PubMed

Rajesh, Gopalakrishna; Girish, Banavara Narasimhamurthy; Panicker, Suprabha; Balakrishnan, Vallath

2014-01-01

Recent reports indicate a decline in prevalence of classical tropical chronic pancreatitis (TCP). We studied the etiologies and risk factors over a 14-year period at a tertiary care university hospital. We compared the etiology in chronic pancreatitis (CP) patients presenting and followed-up in our Pancreas Clinic over two time periods (2000-06 and 2007-13). Idiopathic chronic pancreatitis (ICP) was the predominant etiology seen over the two time periods. However an increase in prevalence of alcoholic chronic pancreatitis (ACP) during the latter time period suggests that it may be emerging as a dominant etiology over recent years. Hypertriglyceridemia and hyperparathyroidism were uncommon causes of non-alcoholic CP. Autoimmune pancreatitis was noted only during 2007-13, but remains a rare cause of CP. There are multiple risk factors for CP in our population. The high prevalence of ICP indicates need closer examination of risk factors and ICP pathogenesis. ACP appears to be emerging as a dominant cause of CP which suggests a need to reorient preventive strategies.

Update on Pediatric Cough.

PubMed

Kantar, Ahmad

2016-02-01

Despite the high prevalence of cough in children, the topic has been poorly researched. Although pediatricians recognize that chronic cough in children is different from that in adults, this difference seems less recognizable to other health professionals. During childhood, the respiratory tract and nervous system undergo a series of anatomical and physiological maturation processes that influence the cough reflex. Additionally, immunological responses undergo developmental and memorial processes that make infection and congenital abnormalities the overwhelming cause of cough in children. The lack of comprehensive clinical data regarding chronic cough in children has initially required pediatricians to adopt an adult approach to the problem. In the last 10 years, however, research has led to the reconsideration of the etiology of chronic cough in children. Currently, attention has focused on protracted bacterial bronchitis as a major cause of chronic cough in preschool-aged children and as a possible precursor of bronchiectasis. New research horizons are emerging for both the treatment and prevention of particular causes of chronic cough in children.

Autoimmune lymphoproliferative syndrome: more than a FAScinating disease

PubMed Central

Bride, Karen; Teachey, David

2017-01-01

Autoimmune lymphoproliferative syndrome (ALPS) is an inherited syndrome characterized by abnormal lymphocyte survival caused by failure of apoptotic mechanisms to maintain lymphocyte homeostasis. This failure leads to the clinical manifestations of non-infectious and non-malignant lymphadenopathy, splenomegaly, and autoimmune pathology, most commonly, autoimmune cytopenias. Since ALPS was first characterized in the early 1990s, insights in disease biology have improved both diagnosis and management of this syndrome. Sirolimus is the best-studied and most effective corticosteroid-sparing therapy for ALPS and should be considered first-line for patients in need of chronic treatment. This review highlights practical clinical considerations for the diagnosis and management of ALPS. Further studies could reveal new proteins and regulatory pathways that are critical for lymphocyte activation and apoptosis. PMID:29123652

A case report of pseudo grey platelet syndrome with citrate-induced pseudothrombocytopenia: those artifacts may interfere in the platelet numeration and lead to critical misdiagnosis.

PubMed

Herb, Agathe; Maurer, Maxime; Alamome, Isabelle; Bihl, Pierre-Adrien; Ghiura, Cosmina; Hurstel, Rémy

2017-08-01

The pseudo grey platelet syndrome is a rare artifact due to the degranulation of platelets caused, in vitro, by EDTA. This phenomenon is likely to disturb the platelet numeration and it is essential not to mistake it for a grey syndrome platelet, which is a constitutional thrombopathy with macrothrombopenia, in order to avoid specialized tests, or even misdiagnosis. Indeed, these two entities are cytologically alike, as grey platelets are found on the blood smear of a sample collected on EDTA in both cases. We here describe the case of a patient admitted in Colmar's Hospital for a chronic thrombocytopenia, associating both a pseudothrombocytopenia and a pseudo grey platelet syndrome.

Bioengineering Kidneys for Transplantation

PubMed Central

Madariaga, Maria Lucia L.; Ott, Harald C.

2014-01-01

One in ten Americans suffer from chronic kidney disease, and close to 90,000 people die each year from causes related to kidney failure. Patients with end-stage renal disease are faced with two options: hemodialysis or transplantation. Unfortunately, the reach of transplantation is limited because of the shortage of donor organs and the need for immunosuppression. Bioengineered kidney grafts theoretically present a novel solution to both problems. Herein we discuss the history of bioengineering organs, the current status of bioengineered kidneys, considerations for the future of the field, and challenges to clinical translation. We hope that by integrating principles of tissue engineering, and stem cell and developmental biology, bioengineered kidney grafts will advance the field of regenerative medicine while meeting a critical clinical need. PMID:25217267

[Recent achievements in the microbiological etiology of dental caries].

PubMed

Jing, Chen; Lei, Cheng; Xuedong, Zhou; Xian, Peng

2018-02-01

Dental caries is the most common chronic infectious disease of the oral cavity. The bacterium Streptococcus mutans is the sole pathogen that causes this disease. However, substantial evidence suggests that prevention and treatment strategies developed from traditional "cariogenic pathogen theory" are inefficient in reducing the prevalence of dental caries. An increasing number of individuals adopt the ecological view of the microbiota in the pathogenesis of dental caries. Recent technological improvements have enabled the detection and analysis of oral microorganisms, and many studies have focused on this area. The core microbiota is defined as a cluster of microbes playing critical roles in the initial and development phases of dental caries and may provide future direction for microorganism-related etiological studies.

Causes of death of prisoners of war during the Korean War (1950-1953).

PubMed

Lee, Myoung-Soon; Kang, Min-Jung; Huh, Sun

2013-03-01

This study aimed at analyzing the causes of death of prisoners of war (POWs) during the Korean War (1950-1953) who fought for the Communist side (North Korea and the People's Republic of China). In 1998, the United States Department of Defense released new information about the prisoners including, 7,614 deaths of the POW during the Korean War. The data on the causes of death of the POWs during the Korean War provides valuable information on the both the public health and history of the conflict. To analyze the causes of death of the POWs, we classified the clinical diagnosis and findings on 7,614 deaths into 22 chapters, as outlined in the International Statistical Classification of Diseases and Related Health Problems-10th Revision (ICD-10). Second, we traced changes in the monthly death totals of POWs as well as deaths caused by common infectious diseases and external causes of death including injury over time from August 1950 to September 1953. The most common category of causes of deaths of POWs was infectious disease, 5,013 (65.8%) out of 7,614 deaths, followed by external causes including injury, 817 (10.7%). Overall, tuberculosis and dysentery/diarrhea were the most common causes of death. Deaths caused by acute and chronic infection, or external causes showed different patterns of increases and decline over time during the Korean War. The information and data on POWs' deaths during the Korean War reflects the critical impact of the POWs' living conditions and the effect of public health measures implemented in POW camps during the war.

ESTIMATION OF AQUATIC SPECIES SENSITIVITY USING INTERSPECIES CORRELATION AND ACUTE TO CHRONIC TOXICITY MODELS

EPA Science Inventory

Abstract for presentation

Estimation of aquatic species sensitivity using interspecies correlation and acute to chronic toxicity models

Determining species sensitivity of aquatic organisms to contaminants is a critical component of criteria development and ecolog...

[Partsch's chronic granulomatous inflammation, the cutaneous manifestation of a dental cause].

PubMed

Buch, R S R; Fischer, B; Kleis, W K G; Reichert, T E

2003-08-01

Dentogenous inflammatory diseases can lead to typical dermatological facial symptoms with formation of cutaneous sinuses. Partsch's chronic granulomatous inflammation can result from conducted inflammation of a nonvital tooth via a chronic apical inflammation. In this rare disease, the granulomatous tissue perforates the bone, channels through the overlying skin, and drains via cutaneous or oral sinuses. A frequent localization of the cutaneous sinus is the skin inferior to the body of the mandible, and it is caused by an inflammation of the lower molars. Treatment consists of identifying the responsible teeth and eliminating the focus of infection. Chronically progressive periradicular granuloma and/or radicular cysts can be present with impressive dermatological symptoms. Therefore, X-ray examinations are necessary to exclude possible dentogenic causes in cases of badly healing processes of the face or neck.

THE RENIN-ANGIOTENSIN SYSTEM AND THE BIOLOGY OF SKELETAL MUSCLE: MECHANISMS OF MUSCLE WASTING IN CHRONIC DISEASE STATES.

PubMed

Delafontaine, Patrice; Yoshida, Tadashi

2016-01-01

Sarcopenia and cachexia are muscle-wasting syndromes associated with aging and with many chronic diseases such as congestive heart failure, diabetes, cancer, chronic obstructive pulmonary disease, and renal failure. While mechanisms are complex, these conditions are often accompanied by elevated angiotensin II (Ang II). We found that Ang II infusion in rodents leads to skeletal muscle wasting via alterations in insulin-like growth factor-1 signaling, increased apoptosis, enhanced muscle protein breakdown via the ubiquitin-proteasome system, and decreased appetite resulting from downregulation of hypothalamic orexigenic neuropeptides orexin and neuropeptide Y. Furthermore, Ang II inhibits skeletal muscle stem cell proliferation, leading to lowered muscle regenerative capacity. Distinct stem cell Ang II receptor subtypes are critical for regulation of muscle regeneration. In ischemic mouse congestive heart failure model skeletal muscle wasting and attenuated muscle regeneration are Ang II dependent. These data suggest that the renin-angiotensin system plays a critical role in mechanisms underlying cachexia in chronic disease states.

Associations between chronic diseases and choking deaths among older adults in the USA: a cross-sectional study using multiple cause mortality data from 2009 to 2013.

PubMed

Wu, Wen-Shiann; Sung, Kuan-Chin; Cheng, Tain-Junn; Lu, Tsung-Hsueh

2015-11-12

To examine whether the strengths of the associations between chronic diseases and overall choking differ from those of the associations between chronic diseases and only food-related choking. This cross-sectional study used nationwide multiple cause mortality files. The USA. Older adults aged 65 years or more died between 2009 and 2013. Mortality ratio (observed/expected) of number of deaths from both causes (chronic diseases and choking) and 95% CIs. We identified 76543 deaths for which the death certificates report choking (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes W78, W79 and W80 combined) as a cause of death and only 4974 (6.5%) deaths were classified as food-related choking (ICD-10 code W79). Schizophrenia, Parkinson's disease, Alzheimer's disease and oral cancer are four chronic diseases that had significant associations with both overall and food-related choking. Stroke, larynx cancer and mood (affective) disorders had significant associations with overall choking, but not with food-related choking. We suggest using overall choking instead of only food-related choking to better describe the associations between chronic diseases and choking. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Bladder Cancer

MedlinePlus

... have an elevated risk of developing bladder cancer. Chronic bladder inflammation. Chronic or repeated urinary infections or inflammations (cystitis), ... the world, squamous cell carcinoma is linked to chronic bladder inflammation caused by the parasitic infection known as schistosomiasis. ...

AB38. Microorganisms in Chronic prostatitis in outpatient clinic Mongolia

PubMed Central

Samdankhuu, Khongorzul; Sanjmyatav, Purevjal; Damiran, Naransukh; Naidan, Nansalmaa

2014-01-01

Background Recent years, morbidity of chronic prostatis is increasing in Mongolia. Most common cause of the chronic prostatis is Non-Gonococcal Urethritis (NGU) such as chlamydia trachomatis, mycoplasma hominis, mycoplasma genitalium, ureaplasma urealyticum and ureaplasma parvum or mixed infections. Purpose The purpose of the study was to research possible relationships between signs or symptoms of the chronic prostatitis and its cause. Method A total of 466 males who have possible signs of chronic prostatitis were enrolled in the study. All patients were checked for urinalysis and expressed prostate secretion (EPS) and Polymerase Chain Reaction (PCR) of EPS detection for neisser a gonorrhea, chlamydia trachomatis, mycoplasma hominis, mycoplasma genitalium, ureaplasma urealyticum and ureaplasma parvum at an outpatient center of andrology office, Ulaanbaatar, Mongolia. Results Two hundred and eighty three of all participants have positive PCR results. Mean age of in our study was 33.1±8 years. U. realyticum was the most common (48.6%), followed by M. hominis and C. trachomatis mixed infection. In Mach, April and August were highest episodes of morbidity were registered 16.2%, 11.69% and 10.71%. Chronic pelvic pain syndrome and lower urinary tract symptoms were the most common complaints of main reason to visit outpatient clinic. Conclusions U. urealyticum was most common infection detected by PCR analyses among men who have chronic prostatitis, who have chronic pelvic pain syndrome. Further research is needed to determine if there are associations between signs or symptoms and cause of the chronic prostatis.

Chronic Fatigue Syndrome: Searching for the Cause and Treatment.

ERIC Educational Resources Information Center

Eichner, Edward R.

1989-01-01

Chronic fatigue syndrome became known nationally in l985 with a pseudoepidemic in a Nevada resort community. Initially and erroneously linked to the Epstein-Barr virus, the cause of this puzzling syndrome and the mind-body connection are areas of controversy and research. (Author/SM)

An Unusual Cause of Acute Upper Gastrointestinal Bleeding: Acute Esophageal Necrosis

PubMed Central

Tokala, Madhusudhan R.; Dhillon, Sonu; Pisoh, Watcoun-Nchinda; Walayat, Saqib; Vanar, Vishwas; Puli, Srinivas R.

2016-01-01

Acute esophageal necrosis (AEN), also called “black esophagus,” is a condition characterized by circumferential necrosis of the esophagus with universal distal involvement and variable proximal extension with clear demarcation at the gastroesophageal junction. It is an unusual cause of upper gastrointestinal bleeding and is recognized with distinct and striking mucosal findings on endoscopy. The patients are usually older and are critically ill with shared comorbidities, which include atherosclerotic cardiovascular disease, diabetes mellitus, hypertension, chronic renal insufficiency, and malnutrition. Alcoholism and substance abuse could be seen in younger patients. Patients usually have systemic hypotension along with upper abdominal pain in the background of clinical presentation of hematemesis and melena. The endoscopic findings confirm the diagnosis and biopsy is not always necessary unless clinically indicated in atypical presentations. Herein we present two cases with distinct clinical presentation and discuss the endoscopic findings along with a review of the published literature on the management of AEN. PMID:27642529

Stepwise approach to myopathy in systemic disease.

PubMed

Chawla, Jasvinder

2011-01-01

Muscle diseases can constitute a large variety of both acquired and hereditary disorders. Myopathies in systemic disease results from several different disease processes including endocrine, inflammatory, paraneoplastic, infectious, drug- and toxin-induced, critical illness myopathy, metabolic, and myopathies with other systemic disorders. Patients with systemic myopathies often present acutely or sub acutely. On the other hand, familial myopathies or dystrophies generally present in a chronic fashion with exceptions of metabolic myopathies where symptoms on occasion can be precipitated acutely. Most of the inflammatory myopathies can have a chance association with malignant lesions; the incidence appears to be specifically increased only in patients with dermatomyositis. In dealing with myopathies associated with systemic illnesses, the focus will be on the acquired causes. Management is beyond the scope of this chapter. Prognosis is based upon the underlying cause and, most of the time, carries a good prognosis. In order to approach a patient with suspected myopathy from systemic disease, a stepwise approach is utilized.

Proteinuria and Hematuria in the Neonate

PubMed Central

Joseph, Catherine; Gattineni, Jyothsna

2016-01-01

Purpose of Review Neonatal proteinuria and hematuria while not common can have potentially devastating consequences if left undiagnosed and untreated. It is important to distinguish between inherited and acquired causes of proteinuria to initiate appropriate and timely treatment. In regards to hematuria, it is critical to identify true hematuria from pseudo-hematuria in order to balance between thorough investigation and unnecessary laboratory work up. This review provides an overview of the common causes of hematuria and proteinuria in a neonate. Recent Findings Identification of genetic mutations in nephrotic syndrome has improved our understanding of the role of various proteins that play an important role in maintaining the glomerular filtration barrier. With the advancement in our ability to provide care for extreme premature neonates, the incidence of acute kidney injury has increased in these neonates along with proteinuria and hematuria. Summary Persistent proteinuria after neonatal acute kidney injury would be of interest in regards to the risk of developing future chronic kidney disease and hypertension. PMID:26845146

Primary gingival tuberculosis in pregnancy: A rare combination.

PubMed

Sharma, Shweta; Ahad, Abdul; Gupta, Narinder Dev; Sharma, Vivek Kumar

2018-01-01

Tuberculosis (TB), a common chronic-specific granulomatous disease, has become rare in the developed countries. However, it is still a common cause of morbidity and mortality in India. Although it commonly involves the lungs, its presentation in the oral cavity is quite uncommon. The very rare incidence of primary gingival TB, particularly in the absence of active pulmonary involvement often leads to misdiagnosis. Clinical features of oral lesions may include ulceration, nodules, granulomas, and fissures. TB in pregnant women is a major cause of obstetric complications and increased risk of maternal and child mortality. This report highlights a rare case of primary TB of gingiva, presenting as severe gingival overgrowth in a patient with 4 th month of pregnancy. This case strongly suggests the importance of suspecting TB as the differential diagnosis of gingival overgrowth and therefore, playing a critical role in the early detection and treatment. Interdisciplinary collaboration for diagnosis and management resulted in the successful outcome and prevented the obstetric complications in this case.

HLA-DQB1*03 Confers Susceptibility to Chronic Hepatitis C in Japanese: A Genome-Wide Association Study

PubMed Central

Takahashi, Atsushi; Hayes, C. Nelson; Urabe, Yuji; Abe, Hiromi; Kawaoka, Tomokazu; Tsuge, Masataka; Hiraga, Nobuhiko; Imamura, Michio; Kawakami, Yoshiiku; Aikata, Hiroshi; Takahashi, Shoichi; Akuta, Norio; Suzuki, Fumitaka; Ikeda, Kenji; Kumada, Hiromitsu; Karino, Yoshiyasu; Toyota, Joji; Tsunoda, Tatsuhiko; Kubo, Michiaki; Kamatani, Naoyuki; Nakamura, Yusuke; Chayama, Kazuaki

2013-01-01

Hepatitis C virus (HCV) establishes a chronic infection in 70-80% of infected individuals. Many researchers have examined the effect of human leukocyte antigen (HLA) on viral persistence because of its critical role in the immune response against exposure to HCV, but almost all studies have proven to be inconclusive. To identify genetic risk factors for chronic HCV infection, we analyzed 458,207 single nucleotide polymorphisms (SNPs) in 481 chronic HCV patients and 2,963 controls in a Japanese cohort. Next, we performed a replication study with an independent panel of 4,358 cases and 1,114 controls. We further confirmed the association in 1,379 cases and 25,817 controls. In the GWAS phase, we found 17 SNPs that showed suggestive association (P < 1 × 10-5). After the first replication study, we found one intronic SNP in the HLA-DQ locus associated with chronic HCV infection, and when we combined the two studies, the association reached the level of genome-wide significance. In the second replication study, we again confirmed the association (P combined = 3.59 × 10−16, odds ratio [OR] = 0.79). Subsequent analysis revealed another SNP, rs1130380, with a stronger association (OR=0.72). This nucleotide substitution causes an amino acid substitution (R55P) in the HLA-DQB1 protein specific to the DQB1*03 allele, which is common worldwide. In addition, we confirmed an association with the previously reported IFNL3-IFNL4 locus and propose that the effect of DQB1*03 on HCV persistence might be affected by the IFNL4 polymorphism. Our findings suggest that a common amino acid substitution in HLA-DQB1 affects susceptibility to chronic infection with HCV in the Japanese population and may not be independent of the IFNL4 genotype. PMID:24376798

Kansas Primary Care Weighs In: A Pilot Randomized Trial of a Chronic Care Model Program for Obesity in 3 Rural Kansas Primary Care Practices

ERIC Educational Resources Information Center

Ely, Andrea C.; Banitt, Angela; Befort, Christie; Hou, Qing; Rhode, Paula C.; Grund, Chrysanne; Greiner, Allen; Jeffries, Shawn; Ellerbeck, Edward

2008-01-01

Context: Obesity is a chronic disease of epidemic proportions in the United States. Primary care providers are critical to timely diagnosis and treatment of obesity, and need better tools to deliver effective obesity care. Purpose: To conduct a pilot randomized trial of a chronic care model (CCM) program for obesity care in rural Kansas primary…

How Surrogate Decision-Makers for Patients With Chronic Critical Illness Perceive and Carry Out Their Role.

PubMed

Li, Lingsheng; Nelson, Judith E; Hanson, Laura C; Cox, Christopher E; Carson, Shannon S; Chai, Emily J; Keller, Kristine L; Tulsky, James A; Danis, Marion

2018-05-01

Family members commonly make medical decision for patients with chronic critical illness. This study examines how family members approach this decision-making role in real time. Qualitative analysis of interviews with family members in the intervention arm of a randomized controlled communication trial. Medical ICUs at four U.S. hospitals. Family members of patients with chronic critical illness (adults mechanically ventilated for ≥ 7 d and expected to remain ventilated and survive for ≥ 72 hr) who participated in the active arm of a communication intervention study. Family members participated in at least two content-guided, informational, and emotional support meetings led by a palliative care physician and nurse practitioner. Grounded theory was used for qualitative analysis of 66 audio recordings of meetings with 51 family members. Family members perceived their role in four main ways: voice of the patient, advocate for the patient, advocate for others, and advocate for oneself. Their decision-making was characterized by balancing goals, sharing their role, keeping perspective, remembering previous experiences, finding sources of strength, and coping with various burdens. Family members take a multifaceted approach as they participate in decision-making. Understanding how surrogates perceive and act in their roles may facilitate shared decision-making among clinicians and families during critical care.

Post-traumatic arthritis: overview on pathogenic mechanisms and role of inflammation

PubMed Central

Punzi, Leonardo; Galozzi, Paola; Luisetto, Roberto; Favero, Marta; Ramonda, Roberta; Oliviero, Francesca; Scanu, Anna

2016-01-01

Post-traumatic arthritis (PTA) develops after an acute direct trauma to the joints. PTA causes about 12% of all osteoarthritis cases, and a history of physical trauma may also be found in patients with chronic inflammatory arthritis. Symptoms include swelling, synovial effusion, pain and sometimes intra-articular bleeding. Usually, PTA recoveries spontaneously, but the persistence of symptoms after 6 months may be considered pathological and so-called chronic PTA. A variety of molecular, mechanobiological and cellular events involved in the pathogenesis and the progression of PTA have been identified. The activation of inflammatory mechanisms during the PTA acute phase appears to play a critical role in the chronic disease onset. Human studies and experimental models have revealed that a series of inflammatory mediators are released in synovial fluid immediately after the joint trauma. These molecules have been proposed as markers of disease and as a potential target for the development of specific and preventative interventions. Currently, chronic PTA cannot be prevented, although a large number of agents have been tested in preclinical studies. Given the relevance of inflammatory reaction, anticytokines therapy, in particular the inhibition of interleukin 1 (IL-1), seems to be the most promising strategy. At the present time, intra-articular injection of IL-1 receptor antagonist is the only anticytokine approach that has been used in a human study of PTA. Despite the fact that knowledge in this area has increased in the past years, the identification of more specific disease markers and new therapeutic opportunities are needed. PMID:27651925

Chronic Hypoxia Suppresses Pregnancy-Induced Upregulation of Large-Conductance Ca2+-Activated K+ Channel Activity in Uterine Arteries

PubMed Central

Hu, Xiang-Qun; Xiao, Daliao; Zhu, Ronghui; Huang, Xiaohui; Yang, Shumei; Wilson, Sean M.; Zhang, Lubo

2013-01-01

Our previous study demonstrated that increased Ca2+-activated K+ (BKCa) channel activity played a key role in the normal adaptation of reduced myogenic tone of uterine arteries in pregnancy. The present study tested the hypothesis that chronic hypoxia during gestation inhibits pregnancy-induced upregulation of BKCa channel function in uterine arteries. Resistance-sized uterine arteries were isolated from nonpregnant and near-term pregnant sheep maintained at sea level (≈300 m) or exposed to high-altitude (3801 m) hypoxia for 110 days. Hypoxia during gestation significantly inhibited pregnancy-induced upregulation of BKCa channel activity and suppressed BKCa channel current density in pregnant uterine arteries. This was mediated by a selective downregulation of BKCa channel β1 subunit in the uterine arteries. In accordance, hypoxia abrogated the role of the BKCa channel in regulating pressure-induced myogenic tone of uterine arteries that was significantly elevated in pregnant animals acclimatized to chronic hypoxia. In addition, hypoxia abolished the steroid hormone-mediated increase in the β1 subunit and BKCa channel current density observed in nonpregnant uterine arteries. Although the activation of protein kinase C inhibited BKCa channel current density in pregnant uterine arteries of normoxic sheep, this effect was ablated in the hypoxic animals. The results demonstrate that selectively targeting BKCa channel β1 subunit plays a critical role in the maladaption of uteroplacental circulation caused by chronic hypoxia, which contributes to the increased incidence of preeclampsia and fetal intrauterine growth restriction associated with gestational hypoxia. PMID:22665123

The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee.

PubMed

Deer, Timothy R; Mekhail, Nagy; Provenzano, David; Pope, Jason; Krames, Elliot; Leong, Michael; Levy, Robert M; Abejon, David; Buchser, Eric; Burton, Allen; Buvanendran, Asokumar; Candido, Kenneth; Caraway, David; Cousins, Michael; DeJongste, Michael; Diwan, Sudhir; Eldabe, Sam; Gatzinsky, Kliment; Foreman, Robert D; Hayek, Salim; Kim, Philip; Kinfe, Thomas; Kloth, David; Kumar, Krishna; Rizvi, Syed; Lad, Shivanand P; Liem, Liong; Linderoth, Bengt; Mackey, Sean; McDowell, Gladstone; McRoberts, Porter; Poree, Lawrence; Prager, Joshua; Raso, Lou; Rauck, Richard; Russo, Marc; Simpson, Brian; Slavin, Konstantin; Staats, Peter; Stanton-Hicks, Michael; Verrills, Paul; Wellington, Joshua; Williams, Kayode; North, Richard

2014-08-01

The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications. The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar. Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medication-related side effects and has enduring effect. Device-related complications are not uncommon; however, the incidence is becoming less frequent as technology progresses and surgical skills improve. Randomized controlled studies support the efficacy of spinal cord stimulation in treating failed back surgery syndrome and complex regional pain syndrome. Similar studies of neurostimulation for peripheral neuropathic pain, postamputation pain, postherpetic neuralgia, and other causes of nerve injury are needed. International guidelines recommend spinal cord stimulation to treat refractory angina; other indications, such as congestive heart failure, are being investigated. Appropriate neurostimulation is safe and effective in some chronic pain conditions. Technological refinements and clinical evidence will continue to expand its use. The NACC seeks to facilitate the efficacy and safety of neurostimulation. © 2014 International Neuromodulation Society.

TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to pro-inflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages1

PubMed Central

Zheng, Shasha; Hedl, Matija; Abraham, Clara

2014-01-01

Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of NOD2, the Crohn’s disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor (PRR) stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl and Mer (TAM) receptors in regulating chronic PRR stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and pro-inflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGFβ-dependent TAM upregulation in human macrophages, which in turn, upregulated SOCS3 expression. Restoring SOCS3 expression under TAM knockdown conditions restored chronic NOD2-mediated pro-inflammatory cytokine downregulation. In contrast to the upregulated pro-inflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, MAFK and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for downregulating pro-inflammatory cytokines under the chronic NOD2 stimulation conditions observed in the intestinal environment. PMID:25567680

Chronic infection and the origin of adaptive immune system.

PubMed

Usharauli, David

2010-08-01

It has been speculated that the rise of the adaptive immune system in jawed vertebrates some 400 million years ago gave them a superior protection to detect and defend against pathogens that became more elusive and/or virulent to the host that had only innate immune system. First, this line of thought implies that adaptive immune system was a new, more sophisticated layer of host defense that operated independently of the innate immune system. Second, the natural consequence of this scenario would be that pathogens would have exercised so strong an evolutionary pressure that eventually no host could have afforded not to have an adaptive immune system. Neither of these arguments is supported by the facts. First, new experimental evidence has firmly established that operation of adaptive immune system is critically dependent on the ability of the innate immune system to detect invader-pathogens and second, the absolute majority of animal kingdom survives just fine with only an innate immune system. Thus, these data raise the dilemma: If innate immune system was sufficient to detect and protect against pathogens, why then did adaptive immune system develop in the first place? In contrast to the innate immune system, the adaptive immune system has one important advantage, precision. By precision I mean the ability of the defense system to detect and remove the target, for example, infected cells, without causing unwanted bystander damage of surrounding tissue. While the target precision per se is not important for short-term immune response, it becomes a critical factor when the immune response is long-lasting, as during chronic infection. In this paper I would like to propose new, "toxic index" hypothesis where I argue that the need to reduce the collateral damage to the tissue during chronic infection(s) was the evolutionary pressure that led to the development of the adaptive immune system. Copyright 2010 Elsevier Ltd. All rights reserved.

Analysis of the Literature on Chronic Cough in Children

PubMed Central

Bergamini, Marcello; Kantar, Ahmad; Cutrera, Renato; Interest Group, Italian Pediatric Cough

2017-01-01

Throughout childhood, various developmental phenomena influence the cough reflex. Among these are the modifications in the anatomy and functions of the respiratory tract and the central and peripheral nervous systems. Moreover, after birth, the immunological response undergoes progressive transformations with the acquisition of immune memory processes. These conditions make infections and airway abnormalities the overwhelming cause of chronic cough in children and infants. In children, chronic cough should be treated on the basis of etiology. The aim of this article is to provide thorough research and analysis of the medical literature published up to 2014 on chronic cough in children as a disease entity, including the epidemiologic, etiologic, diagnostic, prognostic, and therapeutic aspects. Our results demonstrate differences in the definition of chronic cough, the characteristics of diagnostic procedures, study settings, and prevalence of the main causes. However, few studies regarding epidemiology and the quality of life have been reported. Many therapeutic approaches that are considered effective in adults with chronic cough seem to be less efficient in children. Regardless of the setting, whether pediatric or non-pediatric, children with chronic cough should be carefully evaluated using child-specific protocols and algorithms. Awareness of the various pathophysiological conditions associated with chronic cough is vital for making a correct diagnosis and providing appropriate treatment. The prevalence of the different causes of chronic cough depends on various issues. Among these are the population under consideration and its age range, infectious disease control and prevention, the diagnostic procedures employed, disease definition criteria, and the local health system. Clinical guidelines for the management of children with chronic cough should take these components into consideration. Further clinical and basic research studies are still needed for better diagnosis, treatment, and prevention of chronic cough in children. PMID:28553418

Analysis of the Literature on Chronic Cough in Children.

PubMed

Bergamini, Marcello; Kantar, Ahmad; Cutrera, Renato; Interest Group, Italian Pediatric Cough

2017-01-01

Throughout childhood, various developmental phenomena influence the cough reflex. Among these are the modifications in the anatomy and functions of the respiratory tract and the central and peripheral nervous systems. Moreover, after birth, the immunological response undergoes progressive transformations with the acquisition of immune memory processes. These conditions make infections and airway abnormalities the overwhelming cause of chronic cough in children and infants. In children, chronic cough should be treated on the basis of etiology. The aim of this article is to provide thorough research and analysis of the medical literature published up to 2014 on chronic cough in children as a disease entity, including the epidemiologic, etiologic, diagnostic, prognostic, and therapeutic aspects. Our results demonstrate differences in the definition of chronic cough, the characteristics of diagnostic procedures, study settings, and prevalence of the main causes. However, few studies regarding epidemiology and the quality of life have been reported. Many therapeutic approaches that are considered effective in adults with chronic cough seem to be less efficient in children. Regardless of the setting, whether pediatric or non-pediatric, children with chronic cough should be carefully evaluated using child-specific protocols and algorithms. Awareness of the various pathophysiological conditions associated with chronic cough is vital for making a correct diagnosis and providing appropriate treatment. The prevalence of the different causes of chronic cough depends on various issues. Among these are the population under consideration and its age range, infectious disease control and prevention, the diagnostic procedures employed, disease definition criteria, and the local health system. Clinical guidelines for the management of children with chronic cough should take these components into consideration. Further clinical and basic research studies are still needed for better diagnosis, treatment, and prevention of chronic cough in children.

Antimicrobial-impregnated dressing combined with negative-pressure wound therapy increases split-thickness skin graft engraftment: a simple effective technique.

PubMed

Wu, Cheng-Chun; Chew, Khong-Yik; Chen, Chien-Chang; Kuo, Yur-Ren

2015-01-01

Immobilization and adequate surface contact to wounds are critical for skin graft take. Techniques such as the tie-over dressing, cotton bolster, and vacuum-assisted closure are used to address this, but each has its limitations. This study is designed to assess the effect of antimicrobial-impregnated dressing (AMD) combined with negative-pressure wound therapy (NPWT) on skin graft survival. Retrospective case-control study : Patients with chronic or contaminated wounds treated with split-thickness skin graft. A broad spectrum of wounds was included, from causes such as trauma, burns, chronic diabetic ulcers, and infection. Antimicrobial-impregnated dressing, which contains 0.2% polyhexamethylene biguanide, with NPWT MAIN OUTCOME MEASURE:: Success of skin graft : In the AMD group, all skin grafts achieved 100% take without secondary intervention. No infection or graft failure was observed in any patients, and no complications, such as hematoma or seroma formation, were noted, although in the control group partial loss of skin grafts was noted in 3 patients. Infection and inadequate immobilization were thought to be the main reasons. There were no hematoma or seroma formations in the control group. Use of an AMD dressing with NPWT after split-thickness skin grafting can be an effective method to ensure good graft to wound contact and enhances skin graft take in chronic and contaminated wounds.

Increased soluble serum markers caspase-cleaved cytokeratin-18, histones, and ST2 indicate apoptotic turnover and chronic immune response in COPD.

PubMed

Hacker, Stefan; Lambers, Christopher; Pollreisz, Andreas; Hoetzenecker, Konrad; Lichtenauer, Michael; Mangold, Andreas; Niederpold, Tina; Hacker, Andreas; Lang, György; Dworschak, Martin; Vukovich, Thomas; Gerner, Christopher; Klepetko, Walter; Ankersmit, Hendrik Jan

2009-01-01

Chronic obstructive pulmonary disease (COPD) is a worldwide burden and a major cause of death. The disease is accompanied by chronic inflammation and increased cellular turnover that is partly due to an overwhelming induction of apoptosis. In this study, we hypothesized that systemic markers of apoptosis are altered in patients with mild-to-severe COPD. A total number of 64 patients and controls were enrolled in the study. Lung function parameters of all groups (nonsmoker, healthy smoker, COPD GOLD I&II, COPD GOLD III&IV) were evaluated at the time of inclusion. Enzyme-linked immunosorbent assays were used to quantify protein levels in serum samples. Serum contents of apoptotic end-products caspase-cleaved cytokeratin-18 and histone-associated-DNA-fragments were increased in patients with COPD, whereas anti-inflammatory soluble ST2 showed a peak in patients with COPD I&II (P=0.031) compared to healthy smokers. Levels of pro-inflammatory caspase-1/ ICE correlated significantly with the number of pack years (R=0.337; P=0.007). Our results indicate a systemic release of apoptosis-specific proteins as markers for increased cellular turnover accompanied by progression of COPD. Furthermore, soluble ST2 seems to have a critical role in the anti-inflammatory regulatory mechanism at early stages of the disease.

Short-Term Caloric Restriction Suppresses Cardiac Oxidative Stress and Hypertrophy Caused by Chronic Pressure Overload.

PubMed

Kobara, Miyuki; Furumori-Yukiya, Akiko; Kitamura, Miho; Matsumura, Mihoko; Ohigashi, Makoto; Toba, Hiroe; Nakata, Tetsuo

2015-08-01

Caloric restriction (CR) prevents senescent changes, in which reactive oxygen species (ROS) have a critical role. Left ventricular (LV) hypertrophy is a risk factor for cardiovascular diseases. We examined whether CR alters cardiac redox state and hypertrophy from chronic pressure overload. Male c57BL6 mice were subjected to ascending aortic constriction (AAC) with ad libitum caloric intake (AL + AAC group) or 40% restricted caloric intake (CR + AAC group). CR was initiated 2 weeks before AAC and was continued for 4 weeks. Two weeks after constriction, AAC increased LV wall thickness, impaired transmitral flow velocity, and augmented myocyte hypertrophy and fibrosis, in association with enhancement of BNP and collagen III expressions in the AL + AAC group. In the AL + AAC group, oxidative stress in cardiac tissue and mitochondria were enhanced, and NADPH oxidase activity and mitochondrial ROS production were elevated. These changes were significantly attenuated in the CR + AAC group. Additionally, in antioxidant systems, myocardial glutathione peroxidase and superoxide dismutase activities were enhanced in the CR + AAC group. Chronic pressure overload increased cardiac oxidative damage, in association with cardiac hypertrophy and fibrosis. Short-term CR suppressed oxidative stress and improved cardiac function, suggesting that short-term CR could be a useful strategy to prevent pressure overload-induced cardiac injury. Copyright © 2015 Elsevier Inc. All rights reserved.

Choosing a Wound Dressing Based on Common Wound Characteristics

PubMed Central

Dabiri, Ganary; Damstetter, Elizabeth; Phillips, Tania

2016-01-01

Significance: Chronic wounds are a major healthcare burden.The practitioner should have an appropriate understanding of both the etiology of the wound as well as the optimal type of dressings to use. Fundamental wound characteristics may be used to guide the practitioner's choice of dressings. The identification of optimal dressings to use for a particular wound type is an important element in facilitating wound healing. Recent Advances: Researchers have sought to design wound dressings that aim to optimize each stage in the healing process. In addition, dressings have been designed to target and kill infection-causing bacteria, with the incorporation of antimicrobial agents. Critical Issues: Chronic wounds are frequently dynamic in presentation, and the numerous wound dressings available make dressing selection challenging for the practitioner. Choosing the correct dressing decreases time to healing, provides cost-effective care, and improves patient quality of life. Future Directions: Research into the mechanisms of wound healing has enhanced our ability to heal chronic wounds at a faster rate through the use of moisture-retentive dressings. Newer dressings are incorporating the use of nanotechnology by incorporating miniature electrical sensors into the dressing. These dressings are engineered to detect changes in a wound environment and alert the patient or practitioner by altering the color of the dressing or sending a message to a smartphone. Additional investigations are underway that incorporate biologic material such as stem cells into dressings. PMID:26858913

mHealth For Aging China: Opportunities and Challenges

PubMed Central

Sun, Jing; Guo, Yutao; Wang, Xiaoning; Zeng, Qiang

2016-01-01

The aging population with chronic and age-related diseases has become a global issue and exerted heavy burdens on the healthcare system and society. Neurological diseases are the leading chronic diseases in the geriatric population, and stroke is the leading cause of death in China. However, the uneven distribution of caregivers and critical healthcare workforce shortages are major obstacles to improving disease outcome. With the advancement of wearable health devices, cloud computing, mobile technologies and Internet of Things, mobile health (mHealth) is rapidly developing and shows a promising future in the management of chronic diseases. Its advantages include its ability to improve the quality of care, reduce the costs of care, and improve treatment outcomes by transferring in-hospital treatment to patient-centered medical treatment at home. mHealth could also enhance the international cooperation of medical providers in different time zones and the sharing of high-quality medical service resources between developed and developing countries. In this review, we focus on trends in mHealth and its clinical applications for the prevention and treatment of diseases, especially aging-related neurological diseases, and on the opportunities and challenges of mHealth in China. Operating models of mHealth in disease management are proposed; these models may benefit those who work within the mHealth system in developing countries and developed countries. PMID:26816664

[Dysphagia management of acute and long-term critically ill intensive care patients].

PubMed

Zielske, J; Bohne, S; Axer, H; Brunkhorst, F M; Guntinas-Lichius, O

2014-10-01

Dysphagia is a severe complication in critically ill patients and affects more than half the patients in an intensive care unit. Dysphagia also has a strong impact on morbidity and mortality. Risk factors for the development of dysphagia are neurological diseases, age >55-70 years, intubation >7 days and sepsis. With increasing numbers of long-term survivors chronic dysphagia is becoming an increasing problem. There is not much knowledge on the influence of specific diseases, including the direct impact of sepsis on the development of dysphagia. Fiberoptic evaluation of swallowing is a standardized tool for bedside evaluation, helping to plan swallowing training during the acute phase and to decrease the rate of chronic dysphagia. For evaluation of chronic dysphagia even more extensive diagnostic tools as well as several options of stepwise rehabilitation using restitution, compensation and adaption strategies for swallowing exist. Currently it seems that these options are not being sufficiently utilized. In general, there is a need for controlled clinical trials analyzing specific swallowing rehabilitation concepts for former critically ill patients and long-term survivors.

Critical Review of Health Impacts of Wildfire Smoke Exposure.

PubMed

Reid, Colleen E; Brauer, Michael; Johnston, Fay H; Jerrett, Michael; Balmes, John R; Elliott, Catherine T

2016-09-01

Wildfire activity is predicted to increase in many parts of the world due to changes in temperature and precipitation patterns from global climate change. Wildfire smoke contains numerous hazardous air pollutants and many studies have documented population health effects from this exposure. We aimed to assess the evidence of health effects from exposure to wildfire smoke and to identify susceptible populations. We reviewed the scientific literature for studies of wildfire smoke exposure on mortality and on respiratory, cardiovascular, mental, and perinatal health. Within those reviewed papers deemed to have minimal risk of bias, we assessed the coherence and consistency of findings. Consistent evidence documents associations between wildfire smoke exposure and general respiratory health effects, specifically exacerbations of asthma and chronic obstructive pulmonary disease. Growing evidence suggests associations with increased risk of respiratory infections and all-cause mortality. Evidence for cardiovascular effects is mixed, but a few recent studies have reported associations for specific cardiovascular end points. Insufficient research exists to identify specific population subgroups that are more susceptible to wildfire smoke exposure. Consistent evidence from a large number of studies indicates that wildfire smoke exposure is associated with respiratory morbidity with growing evidence supporting an association with all-cause mortality. More research is needed to clarify which causes of mortality may be associated with wildfire smoke, whether cardiovascular outcomes are associated with wildfire smoke, and if certain populations are more susceptible. Reid CE, Brauer M, Johnston FH, Jerrett M, Balmes JR, Elliott CT. 2016. Critical review of health impacts of wildfire smoke exposure. Environ Health Perspect 124:1334-1343; http://dx.doi.org/10.1289/ehp.1409277.

Simultaneous presence of two hematological malignancies: chronic lymphocytic leukemia and myelofibrosis in a patient.

PubMed

Palta, Anshu; Garg, Shailja; Chauhan, Sandeep; Varma, Neelam

2011-03-01

Coexistence of chronic lymphocytic leukemia (CLL) with myelofibrosis is a rare association with only isolated case reports in the literature. We report an unusual case of CLL in which the cause of anemia was coexistent myelofibrosis. In a case of CLL presenting with refractory anemia, besides common causes like autoimmune hemolytic anemia and marrow infiltration, other causes like myelofibrosis should be searched for.

Diarrheal Diseases - Acute and Chronic

MedlinePlus

... Topic / Diarrheal Diseases – Acute and Chronic Diarrheal Diseases – Acute and Chronic Basics Resources Overview Acute diarrhea is ... bulky, greasy or very bad smelling stools. Causes – Acute Diarrhea Most cases of acute, watery diarrhea are ...

Chronic Sinusitis

MedlinePlus

... connected to chronic sinusitis Aspirin sensitivity that causes respiratory symptoms An immune system disorder, such as HIV/AIDS or cystic fibrosis Hay fever or another allergic condition that affects your sinuses Regular exposure to pollutants such as cigarette smoke Complications Chronic ...

Lack of exercise is a major cause of chronic diseases

PubMed Central

Booth, Frank W.; Roberts, Christian K.; Laye, Matthew J.

2014-01-01

Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause vs. treatment; physical activity and inactivity mechanisms differ; gene-environment interaction [including aerobic training adaptations, personalized medicine, and co-twin physical activity]; and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [Accelerated biological aging/premature death, low cardiorespiratory fitness (VO2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, non-alcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, preeclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life. PMID:23798298

Lack of exercise is a major cause of chronic diseases.

PubMed

Booth, Frank W; Roberts, Christian K; Laye, Matthew J

2012-04-01

Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause versus treatment; physical activity and inactivity mechanisms differ; gene-environment interaction (including aerobic training adaptations, personalized medicine, and co-twin physical activity); and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [accelerated biological aging/premature death, low cardiorespiratory fitness (VO2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, nonalcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, pre-eclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life. © 2012 American Physiological Society. Compr Physiol 2:1143-1211, 2012.

Unusual presentation of a familiar pathology: chronic appendicitis.

PubMed

Sierakowski, Kyra; Pattichis, Andrew; Russell, Patrick; Wattchow, David

2016-02-11

We present a case of a man who experienced night sweats, abdominal pain and fever for over 3 months, with incomplete response to broad-spectrum intravenous antibiotics. Although CT imaging was insufficient to identify the cause for his chronic abdominal pain, the abnormality of a 'misty mesentery' was crucial in guiding further investigation. The final diagnosis of chronic appendicitis was made through laparoscopic and pathological examination. This case highlights the utility of a collaborative diagnostic effort between disciplines. Chronic appendicitis can cause lingering abdominal pain. Early recognition and appropriate referral can save patients months and even years of unnecessary suffering. 2016 BMJ Publishing Group Ltd.

Managing patients with chronic cough: challenges and solutions.

PubMed

Perotin, Jeanne-Marie; Launois, Claire; Dewolf, Maxime; Dumazet, Antoine; Dury, Sandra; Lebargy, François; Dormoy, Valérian; Deslee, Gaëtan

2018-01-01

Chronic cough is a common complaint and a frequent cause of medical consultation. Its management can be difficult. We present here an overview of the current guidelines for the management of chronic cough. Different steps are detailed, including the initial research of an obvious etiology and alert signs that should lead to further investigation of underlying condition. The diagnosis of the most frequent causes: asthma, non-asthmatic eosinophilic bronchitis, gastroesophageal reflux disease and upper airway cough syndrome should be considered, assessed and treated accordingly. Recent advances have been made in the comprehension of refractory chronic cough pathophysiology as well as its pharmacologic and non-pharmacologic treatment, especially speech pathology therapy.

[In Process Citation].

PubMed

Scherrer, Beat; Della Chiesa, Andrea; Polska, Elzbieta; Kutten Berger, Johannes J

Inflammation of bone is caused either by bacterial infection or occasionally by physical stimulus. Primary chronic osteomyelitis of mandibular bone is a chronic inflammation of an unknown cause. Pain, swelling, limited mouth opening, regional lymphadenopathy and hypaesthesia are clinical symptoms at initial presentation. Results of biopsy, computed tomography and scintigraphy reveal the diagnosis of a primary chronic osteomyelitis. Its management is long-term antibiotic therapy, hyperbaric oxygen and surgical therapy, even bisphophonate treatement may be a good option. The case report presents a primary progressive chronic osteomyelitis of the manibular bone of a ten year old boy. Clinical and radiological signs are discussed as well as diagnosis, management and follow-up.

Periodontitis in Chronic Heart Failure.

PubMed

Fröhlich, Hanna; Herrmann, Kristina; Franke, Jennifer; Karimi, Alamara; Täger, Tobias; Cebola, Rita; Katus, Hugo A; Zugck, Christian; Frankenstein, Lutz

2016-08-01

Periodontal disease has been associated with an increased risk of cardiovascular events. The purpose of our study was to investigate whether a correlation between periodontitis and chronic heart failure exists, as well as the nature of the underlying cause. We enrolled 71 patients (mean age, 54 ± 13 yr; 56 men) who had stable chronic heart failure; all underwent complete cardiologic and dental evaluations. The periodontal screening index was used to quantify the degree of periodontal disease. We compared the findings to those in the general population with use of data from the 4th German Dental Health Survey. Gingivitis, moderate periodontitis, and severe periodontitis were present in 17 (24%), 17 (24%), and 37 (52%) patients, respectively. Severe periodontitis was more prevalent among chronic heart failure patients than in the general population. In contrast, moderate periodontitis was more prevalent in the general population (P <0.00001). The severity of periodontal disease was not associated with the cause of chronic heart failure or the severity of heart failure symptoms. Six-minute walking distance was the only independent predictor of severe periodontitis. Periodontal disease is highly prevalent in chronic heart failure patients regardless of the cause of heart failure. Prospective trials are warranted to clarify the causal relationship between both diseases.

Noninvasive assessment of liver fibrosis in patients with chronic hepatitis B.

PubMed

Enomoto, Masaru; Morikawa, Hiroyasu; Tamori, Akihiro; Kawada, Norifumi

2014-09-14

Infection with hepatitis B virus is an important health problem worldwide: it affects more than 350 million people and is a leading cause of liver-related morbidity, accounting for 1 million deaths annually. Hepatic fibrosis is a consequence of the accumulation of extracellular matrix components in the liver. An accurate diagnosis of liver fibrosis is essential for the management of chronic liver disease. Liver biopsy has been considered the gold standard for diagnosing disease, grading necroinflammatory activity, and staging fibrosis. However, liver biopsy is unsuitable for repeated evaluations because it is invasive and can cause major complications, including death. Several noninvasive evaluations have been introduced for the assessment of liver fibrosis: serum biomarkers, combined indices or scores, and imaging techniques including transient elastography, acoustic radiation force impulse, real-time tissue elastography, and magnetic resonance elastography. Here, we review the recent progress of noninvasive assessment of liver fibrosis in patients with chronic hepatitis B. Most noninvasive evaluations for liver fibrosis have been validated first in patients with chronic hepatitis C, and later in those with chronic hepatitis B. The establishment of a noninvasive assessment of liver fibrosis is urgently needed to aid in the management of this leading cause of chronic liver disease.

Betel quid, chewing habits and difficult intubation: A case report and critical appraisal of evidence for practice.

PubMed

Narendra, P L; Hegde, Harihar V; Vijaykumar, T K; Nallamilli, Samson

2015-01-01

Betel quid is used by 10-20% of world of population. Oral submucus fibrosis (OSF) is a chronic premalignant disease common in South Asian countries where betel quid is chewed. It is characterized by juxtaepithelial fibrosis of oral cavity and limited mouth opening, which can cause difficult intubation. A recent study in Taiwan has revealed long-term betel nut chewing is not predictor of difficult intubation. We describe two cases of OSF and critically analyze this study and its implications for clinical practice. OSF is now seen in Saudi Arabia and western countries with use of commercial betel quid substitutes. Although betel quid without tobacco is used in Taiwan, available evidence suggests rapid and early development of OSF where commercial chewing products like Pan Masala are used in India. Effects of betel quid may vary depending on the composition of quid and chewing habits. Studies where personal habits are involved must be analyzed carefully for external validity. Even though, Taiwan study is controlled, its validity outside Taiwan is highly questionable. Since OSF can cause unanticipated difficult intubation, thus during preanesthetic assessment, history of betel quid chewing, more importantly use of commercial chewing products is more likely to give clues to severity of OSF and possible difficult intubation. Further controlled trails in populations where commercial chewing products are used is necessary to detect association of chewing habits and difficult intubation.

Relative adrenal insufficiency in mice deficient in 5α-reductase 1

PubMed Central

Livingstone, Dawn E W; Di Rollo, Emma M; Yang, Chenjing; Codrington, Lucy E; Mathews, John A; Kara, Madina; Hughes, Katherine A; Kenyon, Christopher J; Walker, Brian R; Andrew, Ruth

2014-01-01

Patients with critical illness or hepatic failure exhibit impaired cortisol responses to ACTH, a phenomenon known as ‘relative adrenal insufficiency’. A putative mechanism is that elevated bile acids inhibit inactivation of cortisol in liver by 5α-reductases type 1 and type 2 and 5β-reductase, resulting in compensatory downregulation of the hypothalamic–pituitary–adrenal axis and adrenocortical atrophy. To test the hypothesis that impaired glucocorticoid clearance can cause relative adrenal insufficiency, we investigated the consequences of 5α-reductase type 1 deficiency in mice. In adrenalectomised male mice with targeted disruption of 5α-reductase type 1, clearance of corticosterone was lower after acute or chronic (eightfold, P<0.05) administration, compared with WT control mice. In intact 5α-reductase-deficient male mice, although resting plasma corticosterone levels were maintained, corticosterone responses were impaired after ACTH administration (26% lower, P<0.05), handling stress (2.5-fold lower, P<0.05) and restraint stress (43% lower, P<0.05) compared with WT mice. mRNA levels of Nr3c1 (glucocorticoid receptor), Crh and Avp in pituitary or hypothalamus were altered, consistent with enhanced negative feedback. These findings confirm that impaired peripheral clearance of glucocorticoids can cause ‘relative adrenal insufficiency’ in mice, an observation with important implications for patients with critical illness or hepatic failure, and for patients receiving 5α-reductase inhibitors for prostatic disease. PMID:24872577

Just regionalisation: rehabilitating care for people with disabilities and chronic illnesses.

PubMed

Secker, Barbara; Goldenberg, Maya J; Gibson, Barbara E; Wagner, Frank; Parke, Bob; Breslin, Jonathan; Thompson, Alison; Lear, Jonathan R; Singer, Peter A

2006-08-29

Regionalised models of health care delivery have important implications for people with disabilities and chronic illnesses yet the ethical issues surrounding disability and regionalisation have not yet been explored. Although there is ethics-related research into disability and chronic illness, studies of regionalisation experiences, and research directed at improving health systems for these patient populations, to our knowledge these streams of research have not been brought together. Using the Canadian province of Ontario as a case study, we address this gap by examining the ethics of regionalisation and the implications for people with disabilities and chronic illnesses. The critical success factors we provide have broad applicability for guiding and/or evaluating new and existing regionalised health care strategies. Ontario is in the process of implementing fourteen Local Health Integration Networks (LHINs). The implementation of the LHINs provides a rare opportunity to address systematically the unmet diverse care needs of people with disabilities and chronic illnesses. The core of this paper provides a series of composite case vignettes illustrating integration opportunities relevant to these populations, namely: (i) rehabilitation and services for people with disabilities; (ii) chronic illness and cancer care; (iii) senior's health; (iv) community support services; (v) children's health; (vi) health promotion; and (vii) mental health and addiction services. For each vignette, we interpret the governing principles developed by the LHINs - equitable access based on patient need, preserving patient choice, responsiveness to local population health needs, shared accountability and patient-centred care - and describe how they apply. We then offer critical success factors to guide the LHINs in upholding these principles in response to the needs of people with disabilities and chronic illnesses. This paper aims to bridge an important gap in the literature by examining the ethics of a new regionalisation strategy with a focus on the implications for people with disabilities and chronic illnesses across multiple sites of care. While Ontario is used as a case study to contextualize our discussion, the issues we identify, the ethical principles we apply, and the critical success factors we provide have broader applicability for guiding and evaluating the development of - or revisions to - a regionalised health care strategy.

Reductions in the Cardiac Transient Outward K+ Current Ito Caused by Chronic β-Adrenergic Receptor Stimulation Are Partly Rescued by Inhibition of Nuclear Factor κB.

PubMed

Panama, Brian K; Korogyi, Adam S; Aschar-Sobbi, Roozbeh; Oh, Yena; Gray, Charles B B; Gang, Hongying; Brown, Joan Heller; Kirshenbaum, Lorrie A; Backx, Peter H

2016-02-19

The fast transient outward potassium current (Ito,f) plays a critical role in the electrical and contractile properties of the myocardium. Ito,f channels are formed by the co-assembly of the pore-forming α-subunits, Kv4.2 and Kv4.3, together with the accessory β-subunit KChIP2. Reductions of Ito,f are common in the diseased heart, which is also associated with enhanced stimulation of β-adrenergic receptors (β-ARs). We used cultured neonatal rat ventricular myocytes to examine how chronic β-AR stimulation decreases Ito,f. To determine which downstream pathways mediate these Ito,f changes, adenoviral infections were used to inhibit CaMKIIδc, CaMKIIδb, calcineurin, or nuclear factor κB (NF-κB). We observed that chronic β-AR stimulation with isoproterenol (ISO) for 48 h reduced Ito,f along with mRNA expression of all three of its subunits (Kv4.2, Kv4.3, and KChIP2). Inhibiting either CaMKIIδc nor CaMKIIδb did not prevent the ISO-mediated Ito,f reductions, even though CaMKIIδc and CaMKIIδb clearly regulated Ito,f and the mRNA expression of its subunits. Likewise, calcineurin inhibition did not prevent the Ito,f reductions induced by β-AR stimulation despite strongly modulating Ito,f and subunit mRNA expression. In contrast, NF-κB inhibition partly rescued the ISO-mediated Ito,f reductions in association with restoration of KChIP2 mRNA expression. Consistent with these observations, KChIP2 promoter activity was reduced by p65 as well as β-AR stimulation. In conclusion, NF-κB, and not CaMKIIδ or calcineurin, partly mediates the Ito,f reductions induced by chronic β-AR stimulation. Both mRNA and KChIP2 promoter data suggest that the ISO-induced Ito,f reductions are, in part, mediated through reduced KChIP2 transcription caused by NF-κB activation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

State of the science: chronic periodontitis and systemic health.

PubMed

Otomo-Corgel, Joan; Pucher, Jeffery J; Rethman, Michael P; Reynolds, Mark A

2012-09-01

Inflammatory periodontal diseases exhibit an association with multiple systemic conditions. Currently, there is a lack of consensus among experts on the nature of these associations and confusion among health care providers and the public on how to interpret this rapidly growing body of science. This article overviews the current evidence linking periodontal diseases to diabetes, cardiovascular disease, osteoporosis, preterm low birth weight babies, respiratory diseases, and rheumatoid arthritis. Evidence was taken from systematic reviews, clinical trials, and mechanistic studies retrieved in searches of the PubMed electronic database. The available data provide the basis for applied practical clinical recommendations. Evidence is summarized and critically reviewed from systematic reviews, primary clinical trials, and mechanistic studies Surrogate markers for chronic periodontitis, such as tooth loss, show relatively consistent but weak associations with multiple systemic conditions. Despite biological plausibility, shorter-term interventional trials have generally not supported unambiguous cause-and-effect relationships. Nevertheless, the effective treatment of periodontal infections is important to achieve oral health goals, as well as to reduce the systemic risks of chronic local inflammation and bacteremias. Inflammatory periodontal diseases exhibit an association with multiple systemic conditions. With pregnancy as a possible exception, the local and systemic effects of periodontal infections and inflammation are usually exerted for many years, typically among those who are middle-aged or older. It follows that numerous epidemiological associations linking chronic periodontitis to age-associated and biologically complex conditions such as diabetes, cardiovascular disease, osteoporosis, respiratory diseases, rheumatoid arthritis, certain cancers, erectile dysfunction, kidney disease and dementia, have been reported. In the coming years, it seems likely that additional associations will be reported, despite adjustments for known genetic, behavioral and environmental confounders. Determining cause-and-effect mechanisms is more complicated, especially in circumstances where systemic effects may be subtle. Currently, however, there is a lack of consensus among experts on the nature of these associations and confusion among health care providers and the public on how to interpret this rapidly growing body of science. This article overviews the current evidence linking periodontal diseases to diabetes, cardiovascular disease, osteoporosis, preterm/low birth weight babies, respiratory diseases, and rheumatoid arthritis. Copyright © 2012 Elsevier Inc. All rights reserved.

Hypertension from chronic central sodium chloride in mice is mediated by the ouabain-binding site on the Na,K-ATPase α2-isoform

PubMed Central

Dostanic, Iva; Lingrel, Jerry B.; Hou, Xiaohong; Wu, Hengwei

2011-01-01

A chronic increase in the concentration of sodium chloride in the cerebrospinal fluid (CSF) (↑CSF [NaCl]) appears to be critically important for the development of salt-dependent hypertension. In agreement with this concept, increasing CSF [NaCl] chronically by intracerebroventricular (icv) infusion of NaCl-rich artificial CSF (aCSF-HiNaCl) in rats produces hypertension by the same mechanisms (i.e., aldosterone-ouabain pathway in the brain) as that produced by dietary sodium in salt-sensitive strains. We first demonstrate here that icv aCSF-HiNaCl for 10 days also causes hypertension in wild-type (WT) mice. We then used both WT and gene-targeted mice to explore the mechanisms. In WT mice with a ouabain-sensitive Na,K-ATPase α2-isoform (α2S/S), mean arterial pressure rose by ∼25 mmHg within 2 days of starting aCSF-HiNaCl (0.6 nmol Na/min) and remained elevated throughout the study. Ouabain (171 pmol/day icv) increased blood pressure to a similar extent. aCSF-HiNaCl or ouabain given at the same rates subcutaneously instead of intracerebroventricularly had no effect on blood pressure. The pressor response to icv aCSF-HiNaCl was abolished by an anti-ouabain antibody given intracerebroventricularly but not subcutaneously, indicating that it is mediated by an endogenous ouabain-like substance in the brain. We compared the effects of icv aCSF-HiNaCl or icv ouabain on blood pressure in α2S/S versus knockout/knockin mice with a ouabain-resistant endogenous α2-subunit (α2R/R). In α2R/R, there was no pressor response to icv aCSF-HiNaCl in contrast to WT mice. The α2R/R genotype also lacked a pressor response to icv ouabain. These data demonstrate that chronic ↑CSF [NaCl] causes hypertension in mice and that the blood pressure response is mediated by the ouabain-like substance in the brain, specifically by its binding to the α2-isoform of the Na,K-ATPase. PMID:21856907

Promoting normal development and self-efficacy in school-age children managing chronic conditions.

PubMed

Mickley, Kristyn L; Burkhart, Patricia V; Sigler, April N

2013-06-01

Chronic conditions can affect school-age children in more ways than just physically. Normal childhood maturation is critical at this age, yet daily management of chronic symptoms can be challenging. This article describes 4 common childhood chronic illnesses (asthma, seizure disorders, diabetes, and cystic fibrosis), and the impact these conditions have on the developing child. Self-efficacy, the belief that one can effectively perform necessary skills, is essential to self-management of chronic conditions and contributes in a positive way to the child's normal development. Implications for clinical practice and future research are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Invariant natural killer T cells ameliorate murine chronic GVHD by expanding donor regulatory T cells.

PubMed

Du, Jing; Paz, Katelyn; Thangavelu, Govindarajan; Schneidawind, Dominik; Baker, Jeanette; Flynn, Ryan; Duramad, Omar; Feser, Colby; Panoskaltsis-Mortari, Angela; Negrin, Robert S; Blazar, Bruce R

2017-06-08

Chronic graft-versus-host-disease (cGVHD) can cause multiorgan system disease, typically with autoimmune-like features, resulting in high mortality and morbidity caused by treatment limitations. Invariant natural killer T cells (iNKTs), a small population characterized by expression of a semi-invariant T-cell receptor, rapidly produce copious amounts of diverse cytokines on activation that exert potent immune regulatory function. Here, we show that iNKTs are significantly reduced in a cGVHD murine model that recapitulates several aspects of autoimmunity and organ fibrosis observed in patients with cGVHD. Low iNKT infused doses effectively prevented and, importantly, reversed established cGVHD, as did third-party iNKTs. iNKTs suppressed the autoimmune response by reducing the germinal center (GC) reaction, which was associated with an increase in total Tregs and follicular Tregs (Tfr) that control the GC reaction, along with pathogenic antibody production. Treg depletion during iNKT infusions completely abolished iNKT efficacy in treating cGVHD. iNKT cell interleukin 4 production and GC migration were critical to cGVHD reversal. In vivo stimulation of iNKT cells by α-galactosyl-ceramide was effective in both preventing and treating cGVHD. Together, this study demonstrates iNKT deficiency in cGVHD mice and highlights the key role of iNKTs in regulating cGVHD pathogenesis and as a potentially novel prophylactic and therapeutic option for patients with cGVHD. © 2017 by The American Society of Hematology.

Inflammatory Cytokines as Uremic Toxins: "Ni Son Todos Los Que Estan, Ni Estan Todos Los Que Son".

PubMed

Castillo-Rodríguez, Esmeralda; Pizarro-Sánchez, Soledad; Sanz, Ana B; Ramos, Adrian M; Sanchez-Niño, Maria Dolores; Martin-Cleary, Catalina; Fernandez-Fernandez, Beatriz; Ortiz, Alberto

2017-03-23

Chronic kidney disease is among the fastest growing causes of death worldwide. An increased risk of all-cause and cardiovascular death is thought to depend on the accumulation of uremic toxins when glomerular filtration rate falls. In addition, the circulating levels of several markers of inflammation predict mortality in patients with chronic kidney disease. Indeed, a number of cytokines are listed in databases of uremic toxins and uremic retention solutes. They include inflammatory cytokines (IL-1β, IL-18, IL-6, TNFα), chemokines (IL-8), and adipokines (adiponectin, leptin and resistin), as well as anti-inflammatory cytokines (IL-10). We now critically review the cytokines that may be considered uremic toxins. We discuss the rationale to consider them uremic toxins (mechanisms underlying the increased serum levels and evidence supporting their contribution to CKD manifestations), identify gaps in knowledge, discuss potential therapeutic implications to be tested in clinical trials in order to make this knowledge useful for the practicing physician, and identify additional cytokines, cytokine receptors and chemokines that may fulfill the criteria to be considered uremic toxins, such as sIL-6R, sTNFR1, sTNFR2, IL-2, CXCL12, CX3CL1 and others. In addition, we suggest that IL-10, leptin, adiponectin and resistin should not be considered uremic toxins toxins based on insufficient or contradictory evidence of an association with adverse outcomes in humans or preclinical data not consistent with a causal association.

Measuring School Functioning in Students with Chronic Fatigue Syndrome: A Systematic Review

ERIC Educational Resources Information Center

Tollit, Michelle; Politis, Jennifer; Knight, Sarah

2018-01-01

Background: It is often surmised that school functioning is significantly impacted in chronic fatigue syndrome (CFS); however, how this phenomenon manifests itself has rarely been characterized. Methods: This systematic review synthesized and critically appraised methods, constructs, and instruments used to assess school functioning in students…

Chronic Pain and Depression: Does the Evidence Support a Relationship?

ERIC Educational Resources Information Center

Romano, Joan M.; Turner, Judith A.

1985-01-01

A critical evaluation of the relevant literature provides some support for an association between depression and chronic pain. Common conceptual and methodological problems are discussed. Current biological and psychological models of the mechanisms by which the two syndromes may interact are summarized, and suggestions are made for future…

Chronic Q Fever Diagnosis—Consensus Guideline versus Expert Opinion

PubMed Central

Wegdam-Blans, Marjolijn C.A.; Wever, Peter C.; Renders, Nicole H.M.; Delsing, Corine E.; Sprong, Tom; van Kasteren, Marjo E.E.; Bijlmer, Henk; Notermans, Daan; Oosterheert, Jan Jelrik; Stals, Frans S.; Nabuurs-Franssen, Marrigje H.; Bleeker-Rovers, Chantal P.

2015-01-01

Chronic Q fever, caused by Coxiella burnetii, has high mortality and morbidity rates if left untreated. Controversy about the diagnosis of this complex disease has emerged recently. We applied the guideline from the Dutch Q Fever Consensus Group and a set of diagnostic criteria proposed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 2006–2012. Of the patients who had proven cases of chronic Q fever by the Dutch guideline, 46 (30.5%) would not have received a diagnosis by the alternative criteria designed by Raoult, and 14 (4.9%) would have been considered to have possible chronic Q fever. Six patients with proven chronic Q fever died of related causes. Until results from future studies are available, by which current guidelines can be modified, we believe that the Dutch literature-based consensus guideline is more sensitive and easier to use in clinical practice. PMID:26277798

Pathophysiology, Evaluation, and Management of Chronic Watery Diarrhea

PubMed Central

Camilleri, Michael; Sellin, Joseph H.; Barrett, Kim E.

2016-01-01

Chronic watery diarrhea poses a diagnostic and therapeutic challenge and is often a disabling condition for patients. Although acute diarrhea is likely to be caused by infection, the causes of chronic diarrhea (more than 4 weeks in duration) are more elusive. We review on the pathophysiology, diagnosis, and treatment of chronic diarrhea. Drawing on recent insights into the molecular mechanisms of intestinal epithelial transport and barrier function, we discuss how diarrhea can result from a decrease in luminal solute absorption, an increase in secretion, or both, as well as derangements in barrier properties. We also describe the various extra-epithelial factors that activate diarrheal mechanisms. Finally, clinical evaluation and tests used in assessment of patients presenting with chronic diarrhea are reviewed, and an algorithm guiding therapeutic decisions and pharmacotherapy is presented. PMID:27773805

Primary Ciliary Dyskinesia Caused by Homozygous Mutation in DNAL1, Encoding Dynein Light Chain 1

PubMed Central

Mazor, Masha; Alkrinawi, Soliman; Chalifa-Caspi, Vered; Manor, Esther; Sheffield, Val C.; Aviram, Micha; Parvari, Ruti

2011-01-01

In primary ciliary dyskinesia (PCD), genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, randomization of left-right body asymmetry, and, frequently, male infertility. The most frequent defects involve outer and inner dynein arms (ODAs and IDAs) that are large multiprotein complexes responsible for cilia-beat generation and regulation, respectively. Although it has long been suspected that mutations in DNAL1 encoding the ODA light chain1 might cause PCD such mutations were not found. We demonstrate here that a homozygous point mutation in this gene is associated with PCD with absent or markedly shortened ODA. The mutation (NM_031427.3: c.449A>G; p.Asn150Ser) changes the Asn at position150, which is critical for the proper tight turn between the β strand and the α helix of the leucine-rich repeat in the hydrophobic face that connects to the dynein heavy chain. The mutation reduces the stability of the axonemal dynein light chain 1 and damages its interactions with dynein heavy chain and with tubulin. This study adds another important component to understanding the types of mutations that cause PCD and provides clinical information regarding a specific mutation in a gene not yet known to be associated with PCD. PMID:21496787

Evaluation of Occupational and Environmental Factors in the Assessment of Chronic Cough in Adults: A Systematic Review.

PubMed

Tarlo, Susan M; Altman, Kenneth W; French, Cynthia T; Diekemper, Rebecca L; Irwin, Richard S

2016-01-01

Several recent cough guidelines have advised consideration of occupational or environmental causes for chronic cough, but it is unclear how frequently this recommendation has been routinely applied. Therefore, we undertook a systematic review to address this aspect. Cough guidelines and protocols were reviewed to identify recommendations for assessment of occupational and environmental aspects of chronic cough. The systematic search previously used to identify intervention fidelity to the use of protocols for diagnosis and management of chronic cough in adults was used for this review after extension to June 2015. PubMed, Scopus, and the Cochrane Library were searched using the same search terms and inclusion criteria as previously. Papers that met our criteria were then reviewed to identify methods used to assess occupational and environmental aspects of chronic cough and the outcomes of these assessments. Among the 10 general chronic cough guidelines and protocols identified, only the three published since 2006 included details advising detailed occupational and environmental assessments. One additional cough statement focused entirely on occupational cough. Of the 28 cohort studies of patients with chronic cough that specifically noted that they followed guidelines or protocols, none provided details of occupational and environmental assessments. Despite published recommendations, it is not apparent that occupational and environmental causes for chronic cough are addressed in detail during assessments of patients with chronic cough. This leaves open to speculation whether lack of recognition of an occupational cause may delay important preventive measures, put additional workers at risk, and/or be the reason why a chronic cough may remain unexplained. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies

PubMed Central

Finsterwald, Charles; Alberini, Cristina M.

2013-01-01

A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitaryadrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the effects of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the formation of strong long-term memories because the activation of hippocampal GRs after learning is coupled to the recruitment of the growth and pro-survival BDNF/cAMP response element-binding protein (CREB) pathway, which is well-know to be a general mechanism required for long-term memory formation. We will then speculate about how these results may explain the negative effects of traumatic or chronic stress on memory and cognitive functions. PMID:24113652

The causes of skin damage and leg ulceration in chronic venous disease.

PubMed

Smith, Philip Coleridge

2006-09-01

Chronic venous disease with skin changes of the leg is a common condition affecting up to 1 in 20 people in westernized countries. The causes of this problem are not fully understood, although research in recent years has revealed a number of important mechanisms that contribute to the disease process. Patients with chronic venous disease suffer persistently raised pressures in their deep and superficial veins in the lower limb. Leucocytes become "trapped" in the circulation of the leg during periods of venous hyper-tension produced by sitting or standing. Studies of the plasma levels of neutrophil granule enzymes shows that these are increased during periods of venous hypertension, suggesting that this causes activation of the neutrophils. Investigation of the leucocyte surface ligands CD11b and CD62L shows that the more activated neutrophils and monocytes are sequestered during venous hypertension. Measurement of plasma levels of the soluble parts of the endothelial adhesion molecules VCAM, ICAM, and ELAM show that these are all elevated in patients with chronic venous disease compared to controls. Following 30 minutes of venous hypertension produced by standing, these levels are further increased. These data suggest that venous hypertension causes neutrophil and monocyte activation, which in turn causes injury to the endothelium. Chronic injury to the endothelium leads to a chronic inflammatory condition of the skin that we know clinically as lipodermatosclerosis. This is mediated by perivascular inflammatory cells, principally macrophages, in the skin microcirculation. These stimulate fibroblasts in the skin leading to tissue remodeling and laying down of fibrous tissue. Vascular endothelial growth factor stimulates proliferation of capillaries within the skin. Skin in this state has the potential to ulcerate in response to minor injury.

SUBCHRONIC ENDOTOXIN INHALATION CAUSES CHRONIC AIRWAY DISEASE IN ENDOTOXIN-SENSITIVE BUT NOT ENDOTOXIN-RESISTANT MICE

EPA Science Inventory

SUBCHRONIC ENDOTOXIN INHALATION CAUSES CHRONIC AIRWAY DISEASE IN ENDOTOXIN-SENSITIVE BUT NOT ENDOTOXIN-RESISTANT MICE. D. M. Brass, J. D. Savov, *S. H. Gavett, ?C. George, D. A. Schwartz. Duke Univ Medical Center Durham, NC, *U.S. E.P.A. Research Triangle Park, NC, ?Univ of Iowa,...

THE ROLE OF GENETIC SUSCEPTIBILITY IN EXPERIMENTAL INDUCTION CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND PARTICULATE MATTER (PM) HEALTH EFFECTS.

EPA Science Inventory

Human COPD represents the 4th common cause of mortality worldwide and is characterized by presence of chronic bronchitis/inflammation and emphysema. The primary cause is cigarette smoking, as nearly all COPD patients are smokers. However, only about 10% of smokers develop this di...

Conversations About Goals and Values Are Feasible and Acceptable in Long-Term Acute Care Hospitals: A Pilot Study.

PubMed

Lamas, Daniela J; Owens, Robert L; Nace, R Nicholas; Massaro, Anthony F; Pertsch, Nathan J; Moore, Susan T; Bernacki, Rachelle E; Block, Susan D

2017-07-01

The chronically critically ill have survived acute critical illness but require prolonged mechanical ventilation. These patients are frequently transferred from acute care to long-term acute care hospitals (LTACHs) for prolonged recovery, yet many suffer setbacks requiring readmission to acute care. The patient's relatively improved condition while at the LTACH might be an opportunity for communication regarding care goals; however, there have been no prior studies of the feasibility of such conversations in the LTACH. To determine the feasibility, acceptability, and potential usefulness of conversations about serious illness with chronic critical illness patients or their surrogate decision makers after LTACH admission. We adapted an existing conversation guide for use in chronically critically ill (defined by tracheotomy for prolonged ventilation) LTACH patients or their surrogates to explore views about quality of life, understanding of medical conditions, expectations, and planning for setbacks. These conversations were conducted by one interviewer and summarized for the patients' clinicians. We surveyed patients, surrogates, and clinicians to assess acceptability. A total of 70 subjects were approached and 50 (71%) were enrolled, including 30 patients and 20 surrogates. The median duration of the conversation was 14 minutes 45 seconds [IQR 12:46, 19]. The presence of ongoing mechanical ventilation did not lead to longer conversations; in fact, conversations with patients were shorter than those with surrogates. The majority of subjects (81%) described the conversation as worthwhile. The majority of clinicians (73%) reported that the conversation offered a new and significant understanding of the patient's preferences if a setback were to occur. Conversations about serious illness care goals can be accomplished in a relatively short period of time, are acceptable to chronically critically ill patients and their surrogate decision makers in the LTACH, and are perceived as worthwhile by patients, surrogates, and clinicians.

Evidence-based approach for disaster preparedness authorities to inform the contents of repositories for prescription medications for chronic disease management and control.

PubMed

Brown, David W; Young, Stacy L; Engelgau, Michael M; Mensah, George A

2008-01-01

Chronic diseases are major causes of death and disability and often require multiple prescribed medications for treatment and control. Public health emergencies (e.g., disasters due to natural hazards) that disrupt the availability or supply of these medications may exacerbate chronic disease or even cause death. A repository of chronic disease pharmaceuticals and medical supplies organized for rapid response in the event of a public health emergency is desirable. However, there is no science base for determining the contents of such a repository. This study provides the first step in an evidence-based approach to inform the planning, periodic review, and revision of repositories of chronic disease medications. Data from the 2004 National Hospital Ambulatory Medical Care Survey (NHAMCS) were used to examine the prescription medication needs of persons presenting to US hospital emergency departments for chronic disease exacerbations. It was assumed that the typical distribution of cases for an emergency department will reflect the patient population treated in the days after a public health emergency. The estimated numbers of prescribed drugs for chronic conditions that represent the five leading causes of death, the five leading primary diagnoses for physician office visits, and the five leading causes of disease burden assessed by disability-adjusted life years are presented. The 2004 NHAMCS collected data on 36,589 patient visits that were provided by 376 emergency departments. Overall, the five drug classes mentioned most frequently for emergency department visits during 2004 were narcotic analgesics (30.7 million), non-steroidal anti-inflammatory drugs (25.2 million), non-narcotic analgesics (15.2 million), sedatives and hypnotics (10.4 million), and cephalosporins (8.2 million). The drug classes mentioned most frequently for chronic conditions were: (1) for heart disease, antianginal agents/vasodilators (715,000); (2) for cancer, narcotic analgesics (53,000); (3) for stroke, non-narcotic analgesics (138,000); (4) for chronic obstructive pulmonary disease, anti-asthmatics/bronchodilators (3.2 million); and (5) for diabetes, hypoglycemic agents (261,000). Ten medication categories were common across four or more chronic conditions. Persons with chronic diseases have an urgent need for ongoing care and medical support after public health emergencies. These findings provide one evidence-based approach for informing public health preparedness in terms of planning for and review of the prescription medication needs of clinically vulnerable populations with prevalent chronic disease.

Isocyanates and respiratory disease: current status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musk, A.W.; Peters, J.M.; Wegman, D.H.

This paper reviews the known respiratory effects of isocyanates. There is good evidence to indicate that isocyanates: cause chemical bronchitis/pneumonitis; are potent pulmonary sensitizers capable of causing isocyanate asthma; cause nonspecific airways disease, including chronic bronchitis; can induce a general asthmatic state; and can cause hypersensitivity pneumonitis. Similar dose-response relationships are seen for both acute and chronic effects. There are plants operating in which exposures are well controlled and in which no respiratory effects can be detected. Suggestions are provided for preplacement assessment and periodic surveillance for workers exposed to these compounds.114 references.

Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor.

PubMed

Taliaz, Dekel; Loya, Assaf; Gersner, Roman; Haramati, Sharon; Chen, Alon; Zangen, Abraham

2011-03-23

Chronic stress is a trigger for several psychiatric disorders, including depression; however, critical individual differences in resilience to both the behavioral and the neurochemical effects of stress have been reported. A prominent mechanism by which the brain reacts to acute and chronic stress is activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is inhibited by the hippocampus via a polysynaptic circuit. Alterations in secretion of stress hormones and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were implicated in depression and the effects of antidepressant medications. However, the potential role of hippocampal BDNF in behavioral resilience to chronic stress and in the regulation of the HPA axis has not been evaluated. In the present study, Sprague Dawley rats were subjected to 4 weeks of chronic mild stress (CMS) to induce depressive-like behaviors after lentiviral vectors were used to induce localized BDNF overexpression or knockdown in the hippocampus. The behavioral outcome was measured during 3 weeks after the CMS procedure, then plasma samples were taken for measurements of corticosterone levels, and finally hippocampal tissue was taken for BDNF measurements. We found that hippocampal BDNF expression plays a critical role in resilience to chronic stress and that reduction of hippocampal BDNF expression in young, but not adult, rats induces prolonged elevations in corticosterone secretion. The present study describes a mechanism for individual differences in responses to chronic stress and implicates hippocampal BDNF in the development of neural circuits that control adequate stress adaptations.

Haploinsufficiency of the ammonia transporter Rhcg predisposes to chronic acidosis: Rhcg is critical for apical and basolateral ammonia transport in the mouse collecting duct.

PubMed

Bourgeois, Soline; Bounoure, Lisa; Christensen, Erik I; Ramakrishnan, Suresh K; Houillier, Pascal; Devuyst, Olivier; Wagner, Carsten A

2013-02-22

Ammonia secretion by the collecting duct (CD) is critical for acid-base homeostasis and, when defective, causes distal renal tubular acidosis (dRTA). The Rhesus protein RhCG mediates NH(3) transport as evident from cell-free and cellular models as well as from Rhcg-null mice. Here, we investigated in a Rhcg mouse model the metabolic effects of Rhcg haploinsufficiency, the role of Rhcg in basolateral NH(3) transport, and the mechanisms of adaptation to the lack of Rhcg. Both Rhcg(+/+) and Rhcg(+/-) mice were able to handle an acute acid load, whereas Rhcg(-/-) mice developed severe metabolic acidosis with reduced ammonuria and high mortality. However, chronic acid loading revealed that Rhcg(+/-) mice did not fully recover, showing lower blood HCO(3)(-) concentration and more alkaline urine. Microperfusion studies demonstrated that transepithelial NH(3) permeability was reduced by 80 and 40%, respectively, in CDs from Rhcg(-/-) and Rhcg(+/-) mice compared with controls. Basolateral membrane permeability to NH(3) was reduced in CDs from Rhcg(-/-) mice consistent with basolateral Rhcg localization. Rhcg(-/-) responded to acid loading with normal expression of enzymes and transporters involved in proximal tubular ammoniagenesis but reduced abundance of the NKCC2 transporter responsible for medullary accumulation of ammonium. Consequently, tissue ammonium content was decreased. These data demonstrate a role for apical and basolateral Rhcg in transepithelial NH(3) transport and uncover an incomplete dRTA phenotype in Rhcg(+/-) mice. Haploinsufficiency or reduced expression of RhCG may underlie human forms of (in)complete dRTA.

Preterm birth and inflammation-The role of genetic polymorphisms.

PubMed

Holst, Daniela; Garnier, Yves

2008-11-01

Spontaneous preterm labour and preterm births are still the leading cause of perinatal morbidity and mortality in the developed world. Previous efforts to prevent preterm birth have been hampered by a poor understanding of the underlying pathophysiology, inadequate diagnostic tools and generally ineffective therapies. Clinical, epidemiological and experimental studies indicate that genito-urinary tract infections play a critical role in the pathogenesis of preterm birth. Moreover, intrauterine infection increases perinatal mortality and morbidity, such as cerebral palsy and chronic lung disease, significantly. It has recently been suggested that gene-environment interactions play a significant role in determining the risk of preterm birth. Polymorphisms of certain critical genes may be responsible for a harmful inflammatory response in those who possess them. Accordingly, polymorphisms that increase the magnitude or the duration of the inflammatory response were associated with an increased risk of preterm birth. In contrast polymorphisms that decrease the inflammatory response were associated with a lower risk of preterm birth. This article will review the current understanding of pathogenetic pathways in the aetiology of preterm birth.

Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity syndromes.

PubMed

Yunus, Muhammad B

2007-06-01

To discuss fibromyalgia syndrome (FMS) and overlapping conditions, eg, irritable bowel syndrome, headaches, and chronic fatigue syndrome, within the concept of central sensitivity syndromes (CSS). A critical overview of the literature and incorporation of the author's own views. The concept of CSS seems viable. It is based on mutual associations among the CSS conditions as well as the evidence for central sensitization (CS) among several CSS members. However, such evidence is weak or not available in other members at this time, requiring further studies. The biology of CSS is based on neuroendocrine aberrations, including CS, that interact with psychosocial factors to cause a number of symptoms. CSS is an important new concept that embraces the biopsychosocial model of disease. Further critical studies are warranted to fully test this concept. However, it seems to have important significance for new directions for research and patient care involving physician and patient education. Each patient, irrespective of diagnosis, should be treated as an individual considering both the biological and psychosocial contributions to his or her symptoms and suffering.

Should patients with self-inflicted illness receive lower priority in access to healthcare resources? Mapping out the debate.

PubMed

Sharkey, Kerith; Gillam, Lynn

2010-11-01

The distribution of scarce healthcare resources is an increasingly important issue due to factors such as expensive 'high tech' medicine, longer life expectancies and the rising prevalence of chronic illness. Furthermore, in the current healthcare context lifestyle-related factors such as high blood pressure, tobacco use and obesity are believed to contribute significantly to the global burden of disease. As such, this paper focuses on an ongoing debate in the academic literature regarding the role of responsibility for illness in healthcare resource allocation: should patients with self-caused illness receive lower priority in access to healthcare resources? This paper critically describes the lower priority debate's 12 key arguments and maps out their relationships. This analysis reveals that most arguments have been refuted and that the debate has stalled and remains unresolved. In conclusion, we suggest progression could be achieved by inviting multidisciplinary input from a range of stakeholders for the development of evidence-based critical evaluations of existing arguments and the development of novel arguments, including the outstanding rebuttals.

GSDMD is critical for autoinflammatory pathology in a mouse model of Familial Mediterranean Fever.

PubMed

Kanneganti, Apurva; Malireddi, R K Subbarao; Saavedra, Pedro H V; Vande Walle, Lieselotte; Van Gorp, Hanne; Kambara, Hiroto; Tillman, Heather; Vogel, Peter; Luo, Hongbo R; Xavier, Ramnik J; Chi, Hongbo; Lamkanfi, Mohamed

2018-06-04

Pyroptosis is an inflammasome-induced lytic cell death mode, the physiological role of which in chronic inflammatory diseases is unknown. Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide, affecting an estimated 150,000 patients. The disease is caused by missense mutations in Mefv that activate the Pyrin inflammasome, but the pathophysiologic mechanisms driving autoinflammation in FMF are incompletely understood. Here, we show that Clostridium difficile infection of FMF knock-in macrophages that express a chimeric FMF-associated Mefv V726A Pyrin elicited pyroptosis and gasdermin D (GSDMD)-mediated interleukin (IL)-1β secretion. Importantly, in vivo GSDMD deletion abolished spontaneous autoinflammatory disease. GSDMD-deficient FMF knock-in mice were fully protected from the runted growth, anemia, systemic inflammatory cytokine production, neutrophilia, and tissue damage that characterize this autoinflammatory disease model. Overall, this work identifies pyroptosis as a critical mechanism of IL-1β-dependent autoinflammation in FMF and highlights GSDMD inhibition as a potential antiinflammatory strategy in inflammasome-driven diseases. © 2018 Kanneganti et al.

Colonization by Pneumocystis jirovecii and Its Role in Disease

PubMed Central

Norris, Karen A.

2012-01-01

Summary: Although the incidence of Pneumocystis pneumonia (PCP) has decreased since the introduction of combination antiretroviral therapy, it remains an important cause of disease in both HIV-infected and non-HIV-infected immunosuppressed populations. The epidemiology of PCP has shifted over the course of the HIV epidemic both from changes in HIV and PCP treatment and prevention and from changes in critical care medicine. Although less common in non-HIV-infected immunosuppressed patients, PCP is now more frequently seen due to the increasing numbers of organ transplants and development of novel immunotherapies. New diagnostic and treatment modalities are under investigation. The immune response is critical in preventing this disease but also results in lung damage, and future work may offer potential areas for vaccine development or immunomodulatory therapy. Colonization with Pneumocystis is an area of increasing clinical and research interest and may be important in development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss current clinical and research topics in the study of Pneumocystis and highlight areas for future research. PMID:22491773

HIV-1 infection and antiretroviral therapies: risk factors for osteoporosis and bone fracture.

PubMed

Ofotokun, Ighovwerha; Weitzmann, M Neale

2010-12-01

Patients with HIV-1 infection/AIDS are living longer due to the success of highly active antiretroviral therapy (HAART). However, serious metabolic complications including bone loss and fractures are becoming common. Understanding the root causes of bone loss and its potential implications for aging AIDS patients will be critical to the design of effective interventions to stem a tidal wave of fractures in a population chronically exposed to HAART. Paradoxically, bone loss may occur not only due to HIV/AIDS but also as a consequence of HAART. The cause and mechanisms driving these distinct forms of bone loss, however, are complex and controversial. This review examines our current understanding of the underlying causes of HIV-1 and HAART-associated bone loss, and recent findings pertaining to the relevance of the immuno-skeletal interface in this process. It is projected that by 2015 more than half of the HIV/AIDS population in the USA will be over the age of 50 and the synergy between HIV and/or HAART-related bone loss with age-associated bone loss could lead to a significant health threat. Aggressive antiresorptive therapy may be warranted in high-risk patients.

Etiology and mode of presentation of chronic liver diseases in India: A multi centric study.

PubMed

Mukherjee, Partha S; Vishnubhatla, Sreenivas; Amarapurkar, Deepak N; Das, Kausik; Sood, Ajit; Chawla, Yogesh K; Eapen, Chundamannil E; Boddu, Prabhakar; Thomas, Varghese; Varshney, Subodh; Hidangmayum, Diamond Sharma; Bhaumik, Pradip; Thakur, Bhaskar; Acharya, Subrat K; Chowdhury, Abhijit

2017-01-01

There is a paucity of health policy relevant data for chronic liver disease from India, impeding formulation of an interventional strategy to address the issue. A prospective, multicentric study to delineate the etiology and clinical profile of chronic liver disease in India is reported here. A centrally coordinated and monitored web-based data repository was developed (Feb, 2010 to Jan, 2013) and analyzed. Eleven hospitals from different parts of India participated. Data were uploaded into a web based proforma and monitored by a single centre according to a standardized protocol. 1.28% (n = 266621) of all patients (n = 20701383) attending the eleven participating hospitals of India had liver disease. 65807 (24·68%) were diagnosed for the first time (new cases). Of these, 13014 (19·77%, median age 43 years, 73% males) cases of chronic liver disease were finally analyzed. 33.9% presented with decompensated cirrhosis. Alcoholism (34·3% of 4413) was the commonest cause of cirrhosis while Hepatitis B (33·3%) was predominant cause of chronic liver disease in general and non-cirrhotic chronic liver disease (40·8% out of 8163). There was significant interregional differences (hepatitis C in North, hepatitis B in East and South, alcohol in North-east, Non-alcoholic Fatty Liver Disease in West) in the predominant cause of chronic liver disease. Hepatitis B (46·8% of 438 cases) was the commonest cause of hepatocellular Cancer.11·7% had diabetes. Observations of our study will help guide a contextually relevant liver care policy for India and could serve as a framework for similar endeavor in other developing countries as well.

Burden of Chronic Viral Hepatitis and Liver Cirrhosis in Brazil - the Brazilian Global Burden of Disease Study.

PubMed

de Carvalho, Juliana R; Villela-Nogueira, Cristiane A; Perez, Renata M; Portugal, Flavia B; Flor, Luisa S; Campos, Mônica R; Schramm, Joyce M A

Data on epidemiology of liver diseases in Brazil is scarce. This study aimed to estimate the burden of chronic viral hepatitis and liver cirrhosis in the country. The indicator used was disability-adjusted life year (DALY), a sum of years of life lost due to premature mortality (YLL) and years lived with disability (YLD). Liver cirrhosis was analyzed in etiologic categories and cirrhosis of viral origin was considered part of the burden of chronic hepatitis. There were 57,380 DALYs (30.3 per 100,000 inhabitants) attributable to chronic hepatitis B and cirrhosis due to hepatitis B, with 41,262 DALYs in men. Most burden was caused by YLL (47,015 or 24.8/100,000) rather than YLD (10,365 or 5.5/100,000). Chronic hepatitis C and cirrhosis due to hepatitis C were responsible for 207,747 DALYs (109.6/100,000), of which 137,922 were YLL (72.7/100,000) and 69,825 (36.8/100,000) were YLD, with a higher proportion of DALYs in men (73.9%). Cirrhosis due to alcohol or other causes had a total of 536,169 DALYs (1,4% of total DALYs in Brazil), with 418,272 YLL (341,140 in men) and 117,897 YLD (97,965 in men). Highest DALYs' rates occurred at ages 60-69 in chronic hepatitis and at ages 45-59 in cirrhosis due to alcohol or other causes. Chronic viral hepatitis and liver cirrhosis are responsible for a significant burden in Brazil, affecting mainly men and individuals still in their productive years. Most burden is related to non-viral causes of cirrhosis, with a major contribution of alcohol.

Characteristics of critically ill patients in ICUs in mainland China.

PubMed

Du, Bin; An, Youzhong; Kang, Yan; Yu, Xiangyou; Zhao, Mingyan; Ma, Xiaochun; Ai, Yuhang; Xu, Yuan; Wang, Yushan; Qian, Chuanyun; Wu, Dawei; Sun, Renhua; Li, Shusheng; Hu, Zhenjie; Cao, Xiangyuan; Zhou, Fachun; Jiang, Li; Lin, Jiandong; Chen, Erzhen; Qin, Tiehe; He, Zhenyang; Zhou, Lihua

2013-01-01

We sought to describe the demographics, case mix, interventions, and clinical outcome of critically ill patients admitted to ICUs in Mainland China. A 2-month (July 1, 2009, to August 31, 2009) prospective, observational cohort study. Twenty-two ICUs in Mainland China. Adult patients admitted to participating ICUs during the study period with an ICU length of stay >24 hrs. None. Patient characteristics, including demographics, underlying diseases, severity of illness, admission status, complications, intervention and treatment during ICU stay, and clinical outcome were recorded in case report form. The primary outcome measure was all-cause hospital mortality. Independent predictors for hospital mortality were determined with multivariate logistic regression analysis. One thousand two hundred ninety-seven patients met the inclusion criteria for the study, 821 (63.3%) were male, and mean age was 58.5 ± 19.2 yrs. Mean Acute Physiology and Chronic Health Evaluation II score was 18.0 ± 8.1, and mean Sequential Organ Failure Assessment score was 6.5 ± 3.8. One third of the patients were postoperative ICU admissions. Seven hundred sixty-five patients (59.0%) developed infections, followed by severe sepsis or septic shock (484, 37.3%), acute kidney injury (398, 30.7%), and acute lung injury/acute respiratory distress syndrome (351, 27.1%). Mechanical ventilation was used in almost three fourths of the patients, whereas any type of renal replacement therapy was used in 173 patients (13.3%). Hospital mortality was 20.3%. Multivariate logistic regression analysis found that Acute Physiology and Chronic Health Evaluation II score, solid tumor, severe sepsis/septic shock, acute lung injury/acute respiratory distress syndrome, and acute kidney injury were independent risk factors for hospital mortality. Critically ill patients in ICUs in Mainland China exhibited a case mix similar to those of Western countries, although there are significant differences in intensive care unit admission rates and disease severity between Western and Chinese ICUs.

Family functioning in families of first-episode psychosis patients as compared to chronic mentally ill patients and healthy controls.

PubMed

Koutra, Katerina; Triliva, Sofia; Roumeliotaki, Theano; Stefanakis, Zacharias; Basta, Maria; Lionis, Christos; Vgontzas, Alexandros N

2014-11-30

The present study aimed to investigate possible differences in family environment among patients experiencing their First Episode of Psychosis (FEP), chronic patients and controls. Family cohesion and flexibility (FACES-IV) and psychological distress (GHQ-28) were evaluated in families of 50 FEP and 50 chronic patients, as well as 50 controls, whereas expressed emotion (FQ) and family burden (FBS) were assessed in families of FEP and chronic patients. Multivariable linear regression analysis, adjusted for confounders, indicated impaired cohesion and flexibility for families of FEP patients compared to controls, and lower scores for families of chronic patients compared to those of FEP patients. Caregivers of chronic patients scored significantly higher in criticism, and reported higher burden and psychological distress than those of FEP patients. Our findings suggest that unbalanced levels of cohesion and flexibility, high criticism and burden appeared to be the outcome of psychosis and not risk factors triggering the onset of the illness. Furthermore, emotional over-involvement both in terms of positive (i.e. concern) and negative behaviors (i.e. overprotection) is prevalent in Greek families. Psychoeducational interventions from the early stages of the illness should be considered to promote caregivers' awareness regarding the patients' illness, which in turn, may ameliorate dysfunctional family interactions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Is there any Role for Splenectomy in Adulthood Onset Chronic Immun e Thrombocytopenia in the Era of TPO Receptors Agonists? A Critic al Overview.

PubMed

Vibor, Milunovic; Rogulj, Inga Mandac; Ostojic, Slobodanka Kolonic

2017-07-04

Immune thrombocytopenia (ITP) in adulthood is characterized by chronic relapsing course. Despite the efficacious first line treatment (corticosteroid, intravenous immunoglobulin), majority of patients will enter the chronic phase warranting another treatment approach. Until recently, splenectomy performed in ITP chronic phase represented the standard of care with longterm remissions in more than 70% of patients, but it has never been tested in clinical trials. However, with the advances of our understanding of ITP pathophysiology and the shifting focus on megakaryocyte impairment, novel drugs were introduced in the treatment paradigm, mainly trombopoietin receptor agonists (TPO-RAs); romiplostim and eltrombopag. These TPO-RAs were tested in randomized controlled trials resulting in adequate platelet response with few side effects and less need for additional therapy leading to approval of corresponding regulatory agencies and wide acceptance by hematological community, but however TPO-RAs must be taken continuously to maintain the response. With their onset, the rate of splenectomy in chronic ITP has diminished in modern era. The main aim behind conducting this review is to evaluate the pros and cons of splenectomy compared to TPO-RAs treatment in order to provide the critical overview which may help the practicing clinician in managing often challenging cases of chronic ITP. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Causes of Death of Prisoners of War during the Korean War (1950-1953)

PubMed Central

Lee, Myoung-Soon; Kang, Min-Jung

2013-01-01

Purpose This study aimed at analyzing the causes of death of prisoners of war (POWs) during the Korean War (1950-1953) who fought for the Communist side (North Korea and the People's Republic of China). In 1998, the United States Department of Defense released new information about the prisoners including, 7,614 deaths of the POW during the Korean War. The data on the causes of death of the POWs during the Korean War provides valuable information on the both the public health and history of the conflict. Materials and Methods To analyze the causes of death of the POWs, we classified the clinical diagnosis and findings on 7,614 deaths into 22 chapters, as outlined in the International Statistical Classification of Diseases and Related Health Problems-10th Revision (ICD-10). Second, we traced changes in the monthly death totals of POWs as well as deaths caused by common infectious diseases and external causes of death including injury over time from August 1950 to September 1953. Results The most common category of causes of deaths of POWs was infectious disease, 5,013 (65.8%) out of 7,614 deaths, followed by external causes including injury, 817 (10.7%). Overall, tuberculosis and dysentery/diarrhea were the most common causes of death. Deaths caused by acute and chronic infection, or external causes showed different patterns of increases and decline over time during the Korean War. Conclusion The information and data on POWs' deaths during the Korean War reflects the critical impact of the POWs' living conditions and the effect of public health measures implemented in POW camps during the war. PMID:23364985

Neighborhood poverty rate and mortality in patients receiving critical care in the academic medical center setting.

PubMed

Zager, Sam; Mendu, Mallika L; Chang, Domingo; Bazick, Heidi S; Braun, Andrea B; Gibbons, Fiona K; Christopher, Kenneth B

2011-06-01

Poverty is associated with increased risk of chronic illness but its contribution to critical care outcome is not well defined. We performed a multicenter observational study of 38,917 patients, aged ≥ 18 years, who received critical care between 1997 and 2007. The patients were treated in two academic medical centers in Boston, Massachusetts. Data sources included 1990 US census and hospital administrative data. The exposure of interest was neighborhood poverty rate, categorized as < 5%, 5% to 10%, 10% to 20%, 20% to 40% and > 40%. Neighborhood poverty rate is the percentage of residents below the federal poverty line. Census tracts were used as the geographic units of analysis. Logistic regression examined death by days 30, 90, and 365 post-critical care initiation and in-hospital mortality. Adjusted ORs were estimated by multivariable logistic regression models. Sensitivity analysis was performed for 1-year postdischarge mortality among patients discharged to home. Following multivariable adjustment, neighborhood poverty rate was not associated with all-cause 30-day mortality: 5% to 10% OR, 1.05 (95% CI, 0.98-1.14; P = .2); 10% to 20% OR, 0.96 (95% CI, 0.87-1.06; P = .5); 20% to 40% OR, 1.08 (95% CI, 0.96-1.22; P = .2); > 40% OR, 1.20 (95% CI, 0.90-1.60; P = .2); referent in each is < 5%. Similar nonsignificant associations were noted at 90-day and 365-day mortality post-critical care initiation and in-hospital mortality. Among patients discharged to home, neighborhood poverty rate was not associated with 1-year-postdischarge mortality. Our study suggests that there is no relationship between the neighborhood poverty rate and mortality up to 1 year following critical care at academic medical centers.

Nurse practitioner coverage is associated with a decrease in length of stay in a pediatric chronic ventilator dependent unit

PubMed Central

Rowan, Courtney M; Cristea, A Ioana; Hamilton, Jennifer C; Taylor, Nicole M; Nitu, Mara E; Ackerman, Veda L

2016-01-01

AIM: To hypothesize a dedicated critical care nurse practitioner (NP) is associated with a decreased length of stay (LOS) from a pediatric chronic ventilator dependent unit (PCVDU). METHODS: We retrospectively reviewed patients requiring care in the PCVDU from May 2001 through May 2011 comparing the 5 years prior to the 5 years post implementation of the critical care NP in 2005. LOS and room charges were obtained. RESULTS: The average LOS decreased from a median of 55 d [interquartile range (IQR): 9.8-108.3] to a median of 12 (IQR: 4.0-41.0) with the implementation of a dedicated critical care NP (P < 1.0001). Post implementation of a dedicated NP, a savings of 25738049 in room charges was noted over 5 years. CONCLUSION: Our data demonstrates a critical care NP coverage model in a PCVDU is associated with a significantly reduced LOS demonstrating that the NP is an efficient and likely cost-effective addition to a medically comprehensive service. PMID:27170929

The Chronic Illness Initiative: Supporting College Students with Chronic Illness Needs at DePaul University

ERIC Educational Resources Information Center

Royster, Lynn; Marshall, Olena

2008-01-01

College students with chronic illness find it difficult to succeed in traditional degree programs due to disruptions caused by relapses and unpredictable waxing and waning symptoms. College disability offices are often unable to help, both because their standard supports are not appropriate and because students with chronic illness frequently do…

Molecular Pathogenesis of NASH

PubMed Central

Caligiuri, Alessandra; Gentilini, Alessandra; Marra, Fabio

2016-01-01

Nonalcoholic steatohepatitis (NASH) is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression. PMID:27657051

Compartment syndromes

NASA Technical Reports Server (NTRS)

Mubarak, S. J.; Pedowitz, R. A.; Hargens, A. R.

1989-01-01

The compartment syndrome is defined as a condition in which high pressure within a closed fascial space (muscle compartment) reduces capillary blood perfusion below the level necessary for tissue viability'. This condition occurs in acute and chronic (exertional) forms, and may be secondary to a variety of causes. The end-result of an extended period of elevated intramuscular pressure may be the development of irreversible tissue injury and Volkmann's contracture. The goal of treatment of the compartment syndrome is the reduction of intracompartmental pressure thus facilitating reperfusion of ischaemic tissue and this goal may be achieved by decompressive fasciotomy. Controversy exists regarding the critical pressure-time thresholds for surgical decompression and the optimal diagnostic methods of measuring intracompartmental pressures. This paper will update and review some current knowledge regarding the pathophysiology, aetiology, diagnosis, and treatment of the acute compartment syndrome.

Quorum quenching quandary: resistance to antivirulence compounds

PubMed Central

Maeda, Toshinari; García-Contreras, Rodolfo; Pu, Mingming; Sheng, Lili; Garcia, Luis Rene; Tomás, Maria; Wood, Thomas K

2012-01-01

Quorum sensing (QS) is the regulation of gene expression in response to the concentration of small signal molecules, and its inactivation has been suggested to have great potential to attenuate microbial virulence. It is assumed that unlike antimicrobials, inhibition of QS should cause less Darwinian selection pressure for bacterial resistance. Using the opportunistic pathogen Pseudomonas aeruginosa, we demonstrate here that bacterial resistance arises rapidly to the best-characterized compound that inhibits QS (brominated furanone C-30) due to mutations that increase the efflux of C-30. Critically, the C-30-resistant mutant mexR was more pathogenic to Caenorhabditis elegans in the presence of C-30, and the same mutation arises in bacteria responsible for chronic cystic fibrosis infections. Therefore, bacteria may evolve resistance to many new pharmaceuticals thought impervious to resistance. PMID:21918575

Experiences of coexisting with chronic illnesses among elderly women in communities.

PubMed

Chang, Yu-Mei; Tsao, Lee-Ing; Huang, Min-His

2014-01-01

Based on the increasing numbers of women in the aging population, the health of women will become critical in the future. Our purpose in this study was to analyze the experiences of elderly women with chronic illness. Twelve elderly Taiwanese women participated in in-depth interviews. "Using my own power out of the disease shackle" was the core category referring to elderly women who coexist with chronic illnesses. Elderly women should be provided with individually targeted plans for disease management and health maintenance to enable them to participate in health care decisions at the onset of chronic diseases.

Self-Esteem: Issues for Adolescents with Chronic Illnesses and Disabilities. CYDLINE Reviews.

ERIC Educational Resources Information Center

Minnesota Univ., Minneapolis. National Center for Youth with Disabilities.

This annotated bibliography focuses on issues of self-esteem in adolescents with disabilities, which is seen as closely related to development of critical social skills. References have been drawn from the National Center for Youth with Disabilities' National Resource Library, a database about youth with chronic illnesses and disabilities. The…

TOWARDS RELIABLE AND COST-EFFECTIVE OZONE EXPOSURE ASSESSMENT: PARAMETER EVALUATION AND MODEL VALIDATION USING THE HARVARD SOUTHERN CALIFORNIA CHRONIC OZONE EXPOSURE STUDY DATA

EPA Science Inventory

Accurate assessment of chronic human exposure to atmospheric criteria pollutants, such as ozone, is critical for understanding human health risks associated with living in environments with elevated ambient pollutant concentrations. In this study, we analyzed a data set from a...

Budd-Chiari Syndrome Due to Protein C Deficiency: A Rare Disorder to cause Chronic Liver Disease.

PubMed

Begum, Rukshana; Mahtab, Mamun Al; Mamun, Ayub Al; Moben, Ahmed Lutful; Hossain, Sharker Mohammad Shahadat; Das, Dulal Chandra; Malakar, Debraj; Or Rashid, Harun; Roy, Partho Protim; Rahman, Salimur

2016-01-01

The Budd-Chiari syndrome (BCS) is a rare disorder due to chronic liver disease (CLD), which is caused by the obstruction of hepatic venous outflow that can be located at any place from the small hepatic venules up to the entrance of the inferior vena cava (IVC) into the right atrium. Among the causes of BCS, the rarer one is coagulation factor deficiencies. Here, we report a case of BCS associated with deficiency of protein C resulting in thrombus in IVC. The patient was a 50-year-old male, who had been suffering from recurrent abdominal and leg swelling for a long period of 7 years. He was evaluated thoroughly, and other causes of liver cirrhosis were excluded. Begum R, Al Mahtab M, Al Mamun A, Moben AL, Hossain SMS, Das DC, Malakar D, Rashid HO, Roy PP, Rahman S. Budd-Chiari Syndrome Due to Protein C Deficiency: A Rare Disorder to cause Chronic Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(2):194-197.

Periodontitis in Chronic Heart Failure

PubMed Central

Fröhlich, Hanna; Herrmann, Kristina; Franke, Jennifer; Karimi, Alamara; Täger, Tobias; Cebola, Rita; Katus, Hugo A.; Zugck, Christian

2016-01-01

Periodontal disease has been associated with an increased risk of cardiovascular events. The purpose of our study was to investigate whether a correlation between periodontitis and chronic heart failure exists, as well as the nature of the underlying cause. We enrolled 71 patients (mean age, 54 ± 13 yr; 56 men) who had stable chronic heart failure; all underwent complete cardiologic and dental evaluations. The periodontal screening index was used to quantify the degree of periodontal disease. We compared the findings to those in the general population with use of data from the 4th German Dental Health Survey. Gingivitis, moderate periodontitis, and severe periodontitis were present in 17 (24%), 17 (24%), and 37 (52%) patients, respectively. Severe periodontitis was more prevalent among chronic heart failure patients than in the general population. In contrast, moderate periodontitis was more prevalent in the general population (P <0.00001). The severity of periodontal disease was not associated with the cause of chronic heart failure or the severity of heart failure symptoms. Six-minute walking distance was the only independent predictor of severe periodontitis. Periodontal disease is highly prevalent in chronic heart failure patients regardless of the cause of heart failure. Prospective trials are warranted to clarify the causal relationship between both diseases. PMID:27547136

Perinatal White Matter Injury: The Changing Spectrum of Pathology and Emerging Insights into Pathogenetic Mechanisms

ERIC Educational Resources Information Center

Back, Stephen A.

2006-01-01

Perinatal brain injury in survivors of premature birth has a unique and unexplained predilection for periventricular cerebral white matter. Periventricular white-matter injury (PWMI) is now the most common cause of brain injury in preterm infants and the leading cause of chronic neurological morbidity. The spectrum of chronic PWMI includes focal…

Vaccine Candidates against Nontypeable Haemophilus influenzae: a Review

PubMed Central

Behrouzi, Ava; Vaziri, Farzam; Rahimi-Jamnani, Fatemeh; Afrough, Parviz; Rahbar, Mohammad; Satarian, Fereshteh; Siadat, Seyed Davar

2017-01-01

Nonencapsulated, nontypeable Hemophilus influenzae (NTHi) remains an important cause of acute otitis and respiratory diseases in children and adults. NTHi bacteria are one of the major causes of respiratory tract infections, including acute otitis media, cystic fibrosis, and community-acquired pneumonia among children, especially in developing countries. The bacteria can also cause chronic diseases such as chronic bronchitis and chronic obstructive pulmonary disease in the lower respiratory tract of adults. Such bacteria express several outer membrane proteins, some of which have been studied as candidates for vaccine development. Due to the lack of effective vaccines as well as the spread and prevalence of NTHi worldwide, there is an urgent need to design and develop effective vaccine candidates against these strains. PMID:28088130

Self-Care and All-Cause Mortality in Patients With Chronic Heart Failure.

PubMed

Kessing, Dionne; Denollet, Johan; Widdershoven, Jos; Kupper, Nina

2016-03-01

This study examined the association of self-care with all-cause mortality in a cohort of patients with chronic heart failure (HF). Although self-care is crucial to maintain health in patients with chronic HF, studies examining an association with clinical outcomes are scarce. Consecutive patients with chronic HF (n = 559, mean age 66.3 ± 9.5 years, 78% men) completed the 9-item European Heart Failure Self-care Behaviour scale. Our endpoint was all-cause mortality. Associations between self-care and all-cause mortality were assessed with Kaplan-Meier analyses and multivariable Cox regression accounting for standard sociodemographic and clinical covariates, psychological distress, and self-rated health. After a median follow-up of 5.5 ± 2.4 years (range 16 weeks to 9.9 years), 221 deaths (40%) from any cause were recorded. There was no evidence of a mortality benefit in patients high over those low in global self-care (p = 0.71). In post hoc analyses, low self-reported sodium intake was associated with increased mortality (adjusted hazard ratio: 1.47; 95% confidence interval: 1.10 to 1.96; p = 0.01). Other significant predictors of mortality were: male sex, lack of a partner, New York Heart Association functional class III to IV, and increasing comorbid conditions. Global self-care was not associated with long-term mortality whereas low self-reported sodium intake independently predicted increased all-cause mortality beyond parameters of disease severity. Replication of findings is needed as well as studies examining the correspondence of subjectively and objectively measured sodium intake and its effects on long-term prognosis in patients with chronic HF. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Evidence-based hypnotherapy for asthma: a critical review.

PubMed

Brown, Daniel

2007-04-01

Asthma is a chronic disease with intermittent acute exacerbations, characterized by obstructed airways, hyper-responsiveness, and sometimes by chronic airway inflammation. Critically reviewing evidence primarily from controlled outcome studies on hypnosis for asthma shows that hypnosis is possibly efficacious for treatment of symptom severity and illness-related behaviors and is efficacious for managing emotional states that exacerbate airway obstruction. Hypnosis is also possibly efficacious for decreasing airway obstruction and stabilizing airway hyper-responsiveness in some individuals, but there is insufficient evidence that hypnosis affects asthma's inflammatory process. Promising research needs to be replicated with larger samples and better designs with careful attention paid to the types of hypnotic suggestions given. The critical issue is not so much whether it is used but how it is used. Future outcome research must address the relative contribution of expectancies, hypnotizability, hypnotic induction, and specific suggestions.

Activity in the chronically critically ill.

PubMed

Winkelman, Chris; Higgins, Patricia A; Chen, Yea-Jyh Kathy

2005-01-01

Although therapeutic activity prevents functional decline and reduces mortality, little is known about typical levels of activity among intensive care unit (ICU) patients. This report of a preliminary study describes typical therapeutic activity and compares the use of two measures of activity in a small sample of chronically critically ill adults. Type, frequency, and duration of therapeutic activity were measured simultaneously with direct observation and actigraphy. The only consistent activity documented was turning (frequency: 3 turns/8 hours; duration: mean average of 11 minutes). Analysis demonstrated acceptable agreement between the two measures of activity for both frequency and duration of therapeutic but not for type of activity. Congruence between measures for duration of activity was also supported. This study provides information for investigators and practitioners who are interested in measuring or implementing therapeutic activity in selected critically ill adults.

Activity in the Chronically Critically III

PubMed Central

Winkelman, Chris; Higgins, Patricia A.; Kathy Chen, Yea-Jyh

2006-01-01

Although therapeutic activity prevents functional decline and reduces mortality, little is known about typical levels of activity among intensive care unit (ICU) patients. This report of a preliminary study describes typical therapeutic activity and compares the use of two measures of activity in a small sample of chronically critically ill adults. Type, frequency, and duration of therapeutic activity were measured simultaneously with direct observation and actigraphy. The only consistent activity documented was turning (frequency: 3 turns/8 hours; duration: mean average of 11 minutes). Analysis demonstrated acceptable agreement between the two measures of activity for both frequency and duration of therapeutic but not for type of activity. Congruence between measures for duration of activity was also supported. This study provides information for investigators and practitioners who are interested in measuring or implementing therapeutic activity in selected critically ill adults. PMID:16327517

A Critical Appraisal of Extracorporeal Photopheresis as a Treatment Modality for Acute and Chronic Graft-Versus-Host Disease

PubMed Central

Rafei, Hind; A. Kharfan-Dabaja, Mohamed

2017-01-01

Although significant advances have been made in the biologic understanding of graft-versus-host disease (GVHD) and its treatment options, GVHD remains the single most challenging obstacle to the success of allogeneic hematopoietic cell transplantation (HCT) due to high risk of disabling morbidity and mortality. Extracorporeal photopheresis (ECP) has promising effects in controlling steroid-refractory GVHD, both acute and chronic, and it has been studied extensively. Its putative immunomodulatory mechanisms, while not immunosuppressive, position ECP as an attractive treatment strategy for GVHD patients who are already receiving global immunosuppression. However, ECP is relatively underutilized due in part to limited access and time commitment. Here, we review the recent findings on the ECP efficacy in both acute and chronic GVHD, primarily for steroid-refractory status, and we critically appraise its benefits. We also explore salient considerations on the optimal use of ECP in the treatment of refractory GVHD. PMID:29019937

Signal Transduction in the Chronic Leukemias: Implications for Targeted Therapies

PubMed Central

Ahmed, Wesam; Van Etten, Richard A.

2013-01-01

The chronic leukemias, including chronic myeloid leukemia (CML), the Philadelphia-negative myeloproliferative neoplasms (MPNs), and chronic lymphocytic leukemia (CLL), have been characterized extensively for abnormalities of cellular signaling pathways. This effort has led to the elucidation of the central role of dysregulated tyrosine kinase signaling in the chronic myeloid neoplasms and of constitutive B-cell receptor signaling in CLL. This, in turn, has stimulated the development of small molecule inhibitors of these signaling pathways for therapy of chronic leukemia. Although the field is still in its infancy, the clinical results with these agents have ranged from encouraging (CLL) to spectacular (CML). In this review, we summarize recent studies that have helped to define the signaling pathways critical to the pathogenesis of the chronic leukemias. We also discuss correlative studies emerging from clinical trials of drugs targeting these pathways. PMID:23307472

Epidemiology of cough in relation to China

PubMed Central

2013-01-01

Cough is one of the most common complaints for which patients seek medical attention. Misdiagnosis and mistreatment of cough exist commonly in China. The prevalence of acute cough caused by upper airway infection fluctuates between 9% and 64% in the community, for chronic cough, the prevalence >10% in most surveys, ranging from 7.2%-33%. The common causes of chronic cough are upper airway cough syndrome (previously called as post nasal drip syndrome [PNDS]), cough variant asthma (CVA), gastroesophageal reflux related cough (GERD) and eosinophilic bronchitis (EB). There is a regional discrepancy regarding the prevalence of common causes of cough and distribution of gender among China, UK, USA, the most common cause of chronic cough in China are CVA, followed by UACS, EB and atopic cough (AC), the male is almost equal to female in numbers in China. The risk factors for cough includes cold air, smoking, environmental pollutants, noxious substances and allergens, and unreasonable diet habits. PMID:23835047

Taxon-Function Decoupling as an Adaptive Signature of Lake Microbial Metacommunities Under a Chronic Polymetallic Pollution Gradient

PubMed Central

Cheaib, Bachar; Le Boulch, Malo; Mercier, Pierre-Luc; Derome, Nicolas

2018-01-01

Adaptation of microbial communities to anthropogenic stressors can lead to reductions in microbial diversity and disequilibrium of ecosystem services. Such adaptation can change the molecular signatures of communities with differences in taxonomic and functional composition. Understanding the relationship between taxonomic and functional variation remains a critical issue in microbial ecology. Here, we assessed the taxonomic and functional diversity of a lake metacommunity system along a polymetallic pollution gradient caused by 60 years of chronic exposure to acid mine drainage (AMD). Our results highlight three adaptive signatures. First, a signature of taxon—function decoupling was detected in the microbial communities of moderately and highly polluted lakes. Second, parallel shifts in taxonomic composition occurred between polluted and unpolluted lakes. Third, variation in the abundance of functional modules suggested a gradual deterioration of ecosystem services (i.e., photosynthesis) and secondary metabolism in highly polluted lakes. Overall, changes in the abundance of taxa, function, and more importantly the polymetallic resistance genes such as copA, copB, czcA, cadR, cCusA, were correlated with trace metal content (mainly Cadmium) and acidity. Our findings highlight the impact of polymetallic pollution gradient at the lowest trophic levels. PMID:29774016

Gratitude when it is needed most: social functions of gratitude in women with metastatic breast cancer.

PubMed

Algoe, Sara B; Stanton, Annette L

2012-02-01

Theory and evidence suggest that everyday positive emotions may be potent factors in resilience during periods of chronic stress, yet the body of evidence is scant. Even less research focuses on the adaptive functions of specific positive emotions in this critical context. In the current research, 54 women with metastatic breast cancer provided information about their emotional responses to benefits received to test hypotheses regarding the social functions of gratitude. One set of analyses provide support for the hypothesized role of ego-transcendence in feeling gratitude upon receipt of a benefit from another person. As predicted, in a second set of analyses, grateful responding to received benefits predicted an increase in perceived social support over three months only for women low in ambivalence over emotional expression. These findings add to evidence regarding the social causes and consequences of gratitude, supporting a view of gratitude as an other-focused positive emotion that functions to promote high-quality relationships. Discussion focuses on the chronically stressful context as an important testing ground for theory on gratitude and other positive emotions. PsycINFO Database Record (c) 2012 APA, all rights reserved

The search for drug-targetable diagnostic, prognostic and predictive biomarkers in chronic graft-versus-host disease.

PubMed

Ren, Hong-Gang; Adom, Djamilatou; Paczesny, Sophie

2018-05-01

Chronic graft-versus-host disease (cGVHD) continues to be the leading cause of late morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is an increasingly applied curative method for both benign and malignant hematologic disorders. Biomarker identification is crucial for the development of noninvasive and cost-effective cGVHD diagnostic, prognostic, and predictive test for use in clinic. Furthermore, biomarkers may help to gain a better insight on ongoing pathophysiological processes. The recent widespread application of omics technologies including genomics, transcriptomics, proteomics and cytomics provided opportunities to discover novel biomarkers. Areas covered: This review focuses on biomarkers identified through omics that play a critical role in target identification for drug development, and that were verified in at least two independent cohorts. It also summarizes the current status on omics tools used to identify these useful cGVHD targets. We briefly list the biomarkers identified and verified so far. We further address challenges associated to their exploitation and application in the management of cGVHD patients. Finally, insights on biomarkers that are drug targetable and represent potential therapeutic targets are discussed. Expert commentary: We focus on biomarkers that play an essential role in target identification.

Lung transplantation for cystic fibrosis: results, indications, complications, and controversies.

PubMed

Lynch, Joseph P; Sayah, David M; Belperio, John A; Weigt, S Sam

2015-04-01

Survival in patients with cystic fibrosis (CF) has improved dramatically over the past 30 to 40 years, with mean survival now approximately 40 years. Nonetheless, progressive respiratory insufficiency remains the major cause of mortality in CF patients, and lung transplantation (LT) is eventually required. Timing of listing for LT is critical, because up to 25 to 41% of CF patients have died while awaiting LT. Globally, approximately 16.4% of lung transplants are performed in adults with CF. Survival rates for LT recipients with CF are superior to other indications, yet LT is associated with substantial morbidity and mortality (∼50% at 5-year survival rates). Myriad complications of LT include allograft failure (acute or chronic), opportunistic infections, and complications of chronic immunosuppressive medications (including malignancy). Determining which patients are candidates for LT is difficult, and survival benefit remains uncertain. In this review, we discuss when LT should be considered, criteria for identifying candidates, contraindications to LT, results post-LT, and specific complications that may be associated with LT. Infectious complications that may complicate CF (particularly Burkholderia cepacia spp., opportunistic fungi, and nontuberculous mycobacteria) are discussed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Insights into host-pathogen interactions from state-of-the-art animal models of respiratory Pseudomonas aeruginosa infections.

PubMed

Lorenz, Anne; Pawar, Vinay; Häussler, Susanne; Weiss, Siegfried

2016-11-01

Pseudomonas aeruginosa is an important opportunistic pathogen that can cause acute respiratory infections in immunocompetent patients or chronic infections in immunocompromised individuals and in patients with cystic fibrosis. When acquiring the chronic infection state, bacteria are encapsulated within biofilm structures enabling them to withstand diverse environmental assaults, including immune reactions and antimicrobial therapy. Understanding the molecular interactions within the bacteria, as well as with the host or other bacteria, is essential for developing innovative treatment strategies. Such knowledge might be accumulated in vitro. However, it is ultimately necessary to confirm these findings in vivo. In the present Review, we describe state-of-the-art in vivo models that allow studying P. aeruginosa infections in molecular detail. The portrayed mammalian models exclusively focus on respiratory infections. The data obtained by alternative animal models which lack lung tissue, often provide molecular insights that are easily transferable to mammals. Importantly, these surrogate in vivo systems reveal complex molecular interactions of P. aeruginosa with the host. Herein, we also provide a critical assessment of the advantages and disadvantages of such models. © 2016 Federation of European Biochemical Societies.

Taxon-Function Decoupling as an Adaptive Signature of Lake Microbial Metacommunities Under a Chronic Polymetallic Pollution Gradient.

PubMed

Cheaib, Bachar; Le Boulch, Malo; Mercier, Pierre-Luc; Derome, Nicolas

2018-01-01

Adaptation of microbial communities to anthropogenic stressors can lead to reductions in microbial diversity and disequilibrium of ecosystem services. Such adaptation can change the molecular signatures of communities with differences in taxonomic and functional composition. Understanding the relationship between taxonomic and functional variation remains a critical issue in microbial ecology. Here, we assessed the taxonomic and functional diversity of a lake metacommunity system along a polymetallic pollution gradient caused by 60 years of chronic exposure to acid mine drainage (AMD). Our results highlight three adaptive signatures. First, a signature of taxon-function decoupling was detected in the microbial communities of moderately and highly polluted lakes. Second, parallel shifts in taxonomic composition occurred between polluted and unpolluted lakes. Third, variation in the abundance of functional modules suggested a gradual deterioration of ecosystem services (i.e., photosynthesis) and secondary metabolism in highly polluted lakes. Overall, changes in the abundance of taxa, function, and more importantly the polymetallic resistance genes such as copA, copB, czcA, cadR, cCusA , were correlated with trace metal content (mainly Cadmium) and acidity. Our findings highlight the impact of polymetallic pollution gradient at the lowest trophic levels.

Characteristic patterns in the fibrotic lung. Comparing idiopathic pulmonary fibrosis with chronic lung allograft dysfunction.

PubMed

Fernandez, Isis E; Heinzelmann, Katharina; Verleden, Stijn; Eickelberg, Oliver

2015-03-01

Tissue fibrosis, a major cause of death worldwide, leads to significant organ dysfunction in any organ of the human body. In the lung, fibrosis critically impairs gas exchange, tissue oxygenation, and immune function. Idiopathic pulmonary fibrosis (IPF) is the most detrimental and lethal fibrotic disease of the lung, with an estimated median survival of 50% after 3-5 years. Lung transplantation currently remains the only therapeutic alternative for IPF and other end-stage pulmonary disorders. Posttransplant lung function, however, is compromised by short- and long-term complications, most importantly chronic lung allograft dysfunction (CLAD). CLAD affects up to 50% of all transplanted lungs after 5 years, and is characterized by small airway obstruction with pronounced epithelial injury, aberrant wound healing, and subepithelial and interstitial fibrosis. Intriguingly, the mechanisms leading to the fibrotic processes in the engrafted lung exhibit striking similarities to those in IPF; therefore, antifibrotic therapies may contribute to increased graft function and survival in CLAD. In this review, we focus on these common fibrosis-related mechanisms in IPF and CLAD, comparing and contrasting clinical phenotypes, the mechanisms of fibrogenesis, and biomarkers to monitor, predict, or prognosticate disease status.

Compensatory mechanisms in fish populations: Literature reviews: Volume 1, Critical evaluation of case histories of fish populations experiencing chronic exploitation or impact: Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saila, S.B.; Chen, X.; Erzini, K.

1987-05-01

This study includes case histories of certain fish species which are experiencing chronic perturbations and related literature pertaining to compensation processes. ''Compensation'' has been defined as the ability of fish to offset the population reduction caused by natural or man-induced stresses. Certain compensation methods are widely accepted, and include cannibalism, competition, disease, growth and predation, among others. These compensation methods are examined in relation to each fish species included in the study. Stock-recruit relationships and empirical observations of changes in growth and mortality have been the focus of much of the background on compensation. One of the conclusions drawn frommore » this study is that a significant amount of recruitment variability exists and can be attributed to environmental (rather than compensatory) factors. The stock-recruitment problem appears to be the most significant scientific problem related to compensation in the types of fish included in this study. Results of the most recent studies of the American shad support this theory. Life histories, breeding biology and other pertinent data relating to each species included in the study will be found in the appendices.« less

Targeting chronic inflammation in cerebral aneurysms: focusing on NF-kappaB as a putative target of medical therapy.

PubMed

Aoki, Tomohiro; Nishimura, M

2010-03-01

Cerebral aneurysms (CAs) are the main cause of life-threatening subarachnoid hemorrhage. Given its prevalence and endpoint, CA treatment is a public health issue. Effective medical treatment of CAs is lacking because the detailed mechanisms of CA formation are incompletely understood. The aim of this contribution is to review recent articles about CA formation, to suggest the underlying mechanisms of CA formation, and to discuss potential therapeutic targets for treatment. Articles were collected by an internet search of PubMed using the keywords 'intracranial' or 'cerebral aneurysm'. A review of articles about the pathogenesis of CA formation focusing on inflammation. Recent articles demonstrate that inflammation-related-molecule induction and inflammatory cell infiltration in CA walls and the close relationship between inflammatory responses and CA formation. From studies in experimental models, chronic inflammation triggered primarily by NF-kappaB activation in endothelial cells and subsequent macrophage infiltration have critical roles in CA formation. Inhibition of inflammation-related molecules in CA walls results in the decreased incidence of CA formation. Agents with anti-inflammatory activity (particularly anti- NF-kappaB effects) have potential as therapeutic drugs for CAs.

Resveratrol induces human keratinocyte damage via the activation of class III histone deacetylase, Sirt1.

PubMed

Lee, Ju-Hee; Kim, Jin-Shang; Park, Sang-Youel; Lee, You-Jin

2016-01-01

Human skin diseases are various and induce chronic inflammatory disorders, including psoriasis, atopic dermatitis and certain forms of ichthyosis. Psoriasis is a chronic inflammatory skin disease characterized by circumscribed, red, thickened plaques. Regulation of the balance between growth, differentiation and death is critical to keratinocytes; when altered, epidermal keratinocytes undergo hyperproliferation, abnormal differentiation and inflammatory infiltration. In the present study, we focused on the effects of resveratrol, found in red wine and peanuts, on the cell death of keratinocytes. We additionally studied the mechanism of resveratrol on Sirt1, a class III histone deacetylase, and Akt phosphorylation. Resveratrol caused apoptosis and increased Sirt1 expression in human HaCaT keratinocytes, following a decrease in the p62 protein level. Inhibition of Sirt1 by Sirt1 inhibitor restored cell viability and protein levels. Furthermore, we showed that resveratrol-induced Sirt1 blocked Akt phosphorylation. The present results indicated that resveratrol inhibited the Akt pathways by inducing Sirt1, thus leading to cell death. These data suggest that resveratrol-mediated activation of Sirt1 histone deacetylase may be a potential therapeutic target for skin diseases including psoriasis.

Improvement in the management of chronic obstructive pulmonary disease following a clinical educational program: results from a prospective cohort study in the Sicilian general practice setting.

PubMed

Ferrara, Rosarita; Ientile, Valentina; Piccinni, Carlo; Pasqua, Alessandro; Pecchioli, Serena; Fontana, Andrea; Alecci, Umberto; Scoglio, Riccardo; Magliozzo, Francesco; Torrisi, Sebastiano Emanuele; Vancheri, Carlo; Vitulo, Patrizio; Fantaci, Giovanna; Ferrajolo, Carmen; Cazzola, Mario; Cricelli, Claudio; Caputi, Achille Patrizio; Trifirò, Gianluca

2018-03-23

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lungs associated with progressive disability. Although general practitioners (GPs) should play an important role in the COPD management, critical issues have been documented in the primary care setting. The aim of this study was to evaluate the effectiveness of an educational program for the improvement of the COPD management in a Sicilian general practice setting. The effectiveness of the program, was evaluated by comparing 15 quality-of-care indicators developed from data extracted by 33 GPs, at baseline vs. 12 and 24 months, and compared with data from a national primary care database (HSD). Moreover, data on COPD-related and all-cause hospitalizations over time of COPD patients, was measured. Overall, 1,465 patients (3.2%) had a registered diagnosis of COPD at baseline vs. 1,395 (3.0%) and 1,388 (3.0%) over time (vs. 3.0% in HSD). COPD patients with one spirometry registered increased from 59.7% at baseline to 73.0% after 2 years (vs. 64.8% in HSD). Instead, some quality of care indicators where not modified such as proportion of COPD patients treated with ICS in monotherapy that was almost stable during the study period: 9.6% (baseline) vs. 9.9% (after 2 years), vs. 7.7% in HSD. COPD-related and all-cause hospitalizations of patients affected by COPD decreased during the two observation years (from 6.9% vs. 4.0%; from 23.0% vs. 18.9%, respectively). Our study showed that educational program involving specialists, clinical pharmacologists and GPs based on training events and clinical audit may contribute to partly improve both diagnostic and therapeutic management of COPD in primary care setting, despite this effect may vary across GPs and indicators of COPD quality of care.

High fluoride and low calcium levels in drinking water is associated with low bone mass, reduced bone quality and fragility fractures in sheep.

PubMed

Simon, M J K; Beil, F T; Rüther, W; Busse, B; Koehne, T; Steiner, M; Pogoda, P; Ignatius, A; Amling, M; Oheim, R

2014-07-01

Chronic environmental fluoride exposure under calcium stress causes fragility fractures due to osteoporosis and bone quality deterioration, at least in sheep. Proof of skeletal fluorosis, presenting without increased bone density, calls for a review of fracture incidence in areas with fluoridated groundwater, including an analysis of patients with low bone mass. Understanding the skeletal effects of environmental fluoride exposure especially under calcium stress remains an unmet need of critical importance. Therefore, we studied the skeletal phenotype of sheep chronically exposed to highly fluoridated water in the Kalahari Desert, where livestock is known to present with fragility fractures. Dorper ewes from two flocks in Namibia were studied. Chemical analyses of water, blood and urine were executed for both cohorts. Skeletal phenotyping comprised micro-computer tomography (μCT), histological, histomorphometric, biomechanical, quantitative backscattered electron imaging (qBEI) and energy-dispersive X-ray (EDX) analysis. Analysis was performed in direct comparison with undecalcified human iliac crest bone biopsies of patients with fluoride-induced osteopathy. The fluoride content of water, blood and urine was significantly elevated in the Kalahari group compared to the control. Surprisingly, a significant decrease in both cortical and trabecular bones was found in sheep chronically exposed to fluoride. Furthermore, osteoid parameters and the degree and heterogeneity of mineralization were increased. The latter findings are reminiscent of those found in osteoporotic patients with treatment-induced fluorosis. Mechanical testing revealed a significant decrease in the bending strength, concurrent with the clinical observation of fragility fractures in sheep within an area of environmental fluoride exposure. Our data suggest that fluoride exposure with concomitant calcium deficit (i) may aggravate bone loss via reductions in mineralized trabecular and cortical bone mass and (ii) can cause fragility fractures and (iii) that the prevalence of skeletal fluorosis especially due to groundwater exposure should be reviewed in many areas of the world as low bone mass alone does not exclude fluorosis.

Alcohol-Induced Developmental Origins of Adult-Onset Diseases

PubMed Central

Lunde, Emilie R.; Washburn, Shannon E.; Golding, Michael C.; Bake, Shameena; Miranda, Rajesh C.; Ramadoss, Jayanth

2016-01-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems, and is encompassed by the term Fetal Alcohol Spectrum Disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker’s hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult-development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psycho-behavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult-onset of neuro-behavioral deficits, cardiovascular disease, endocrine dysfunction, nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation is a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter-relation are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. PMID:27254466

Alcohol-Induced Developmental Origins of Adult-Onset Diseases.

PubMed

Lunde, Emilie R; Washburn, Shannon E; Golding, Michael C; Bake, Shameena; Miranda, Rajesh C; Ramadoss, Jayanth

2016-07-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. Copyright © 2016 by the Research Society on Alcoholism.

Damage pattern as a function of radiation quality and other factors.

PubMed

Burkart, W; Jung, T; Frasch, G

1999-01-01

An understanding of damage pattern in critical cellular structures such as DNA is an important prerequisite for a mechanistic assessment of primary radiation damage, its possible repair, and the propagation of residual changes in somatic and germ cells as potential contributors to disease or ageing. Important quantitative insights have been made recently on the distribution in time and space of critical lesions from direct and indirect action of ionizing radiation on mammalian cells. When compared to damage from chemicals or from spontaneous degradation, e.g. depurination or base deamination in DNA, the potential of even low-LET radiation to create local hot spots of damage from single particle tracks is of utmost importance. This has important repercussions on inferences from critical biological effects at high dose and dose rate exposure situations to health risks at chronic, low-level exposures as experienced in environmental and controlled occupational settings. About 10,000 DNA lesions per human cell nucleus and day from spontaneous degradation and chemical attack cause no apparent effect, but a dose of 4 Gy translating into a similar number of direct and indirect DNA breaks induces acute lethality. Therefore, single lesions cannot explain the high efficiency of ionizing radiation in the induction of mutation, transformation and loss of proliferative capacity. Clustered damage leading to poorly repairable double-strand breaks or even more complex local DNA degradation, correlates better with fixed damage and critical biological endpoints. A comparison with other physical, chemical and biological agents indicates that ionizing radiation is indeed set apart from these by its unique micro- and nano-dosimetric traits. Only a few other agents such as bleomycin have a similar potential to cause complex damage from single events. However, in view of the multi-stage mechanism of carcinogenesis, it is still an open question whether dose-effect linearity for complex primary DNA damage and resulting fixed critical cellular lesions translate into linearity for radiation-induced cancer. To solve this enigma, a quantitative assessment of all genotoxic and harmful non-genotoxic agents affecting the human body would be needed.

Effect of free radical scavenger, edaravone, for patients with carbon monoxide poisoning.

PubMed

Mori, Kiyofumi; Beppu, Takaaki; Fujisawa, Yutaka; Onodera, Makoto; Ogasawara, Kuniaki; Sasaki, Makoto; Ehara, Shigeru; Sakai, Akio; Endo, Shigeatsu

2015-12-01

Chronic neurological symptoms after carbon monoxide (CO) poisoning are caused by various biological processes in the damaged brain, with free radicals playing roles as mediators in establishing pathological processes leading to chronic neurological symptoms under CO poisoning. This study aimed to clarify the effects of a free radical scavenger, edaravone, in patients with CO poisoning. We retrospectively compared two groups comprising patients treated with hyperbaric oxygenation alone (Group A, n=25) or edaravone in addition to hyperbaric oxygenation (Group B, n=25). Edaravone was administrated intravenously at 30 mg every 12h for 7 days. Patient characteristics, general conditions on admission, and frequency of chronic neurological symptoms were compared between groups. Among patients showing chronic neurological symptoms, cognitive function and daily activity were also compared between groups. No significant differences in characteristics or general conditions on admission were identified between groups. In Group B, no patients presented with marked complications caused by edaravone. Although chronic persisting symptoms were less frequent in Group B (n=1, 0.04%) than in Group A (n=5, 20%), this difference was not significant. In the 11 patients showing chronic symptoms, scores for cognitive function and daily activity in the chronic phase were better in Group B than in Group A, but no significant differences were apparent. The present results suggest that edaravone represents a tolerable and feasible treatment for CO-poisoned patients. Further studies are needed to clarify whether edaravone can favorably influence chronic neurological symptoms caused by CO poisoning. Copyright © 2015 Elsevier B.V. All rights reserved.

Personalized Medicine for Chronic Respiratory Infectious Diseases: Tuberculosis, Nontuberculous Mycobacterial Pulmonary Diseases, and Chronic Pulmonary Aspergillosis.

PubMed

Salzer, Helmut J F; Wassilew, Nasstasja; Köhler, Niklas; Olaru, Ioana D; Günther, Gunar; Herzmann, Christian; Kalsdorf, Barbara; Sanchez-Carballo, Patricia; Terhalle, Elena; Rolling, Thierry; Lange, Christoph; Heyckendorf, Jan

2016-01-01

Chronic respiratory infectious diseases are causing high rates of morbidity and mortality worldwide. Tuberculosis, a major cause of chronic pulmonary infection, is currently responsible for approximately 1.5 million deaths per year. Although important advances in the fight against tuberculosis have been made, the progress towards eradication of this disease is being challenged by the dramatic increase in multidrug-resistant bacilli. Nontuberculous mycobacteria causing pulmonary disease and chronic pulmonary aspergillosis are emerging infectious diseases. In contrast to other infectious diseases, chronic respiratory infections share the trait of having highly variable treatment outcomes despite longstanding antimicrobial therapy. Recent scientific progress indicates that medicine is presently at a transition stage from programmatic to personalized management. We explain current state-of-the-art management concepts of chronic pulmonary infectious diseases as well as the underlying methods for therapeutic decisions and their implications for personalized medicine. Furthermore, we describe promising biomarkers and techniques with the potential to serve future individual treatment concepts in this field of difficult-to-treat patients. These include candidate markers to improve individual risk assessment for disease development, the design of tailor-made drug therapy regimens, and individualized biomarker-guided therapy duration to achieve relapse-free cure. In addition, the use of therapeutic drug monitoring to reach optimal drug dosing with the smallest rate of adverse events as well as candidate agents for future host-directed therapies are described. Taken together, personalized medicine will provide opportunities to substantially improve the management and treatment outcome of difficult-to-treat patients with chronic respiratory infections. © 2016 S. Karger AG, Basel.

Detection and differentiation of coxiella burnetii in biological fluids

DOEpatents

Frazier, Marvin E.; Mallavia, Louis P.; Samuel, James E.; Baca, Oswald G.

1993-01-01

Methods for detecting the presence of Coxiella burnetii in biological samples, as well as a method for differentiating strains of C. burnetii that are capable of causing acute disease from those strains capable of causing chronic disease are disclosed. The methods generally comprise treating cells contained within the biological sample to expose cellular DNA, and hybridizing the cellular DNA with a DNA probe containing DNA sequences that specifically hybridize with C. burnetii DNA of strains associated with the capacity to cause acute or chronic disease.

Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: II. A focus on growth impairment in fish.

PubMed

Groh, Ksenia J; Carvalho, Raquel N; Chipman, James K; Denslow, Nancy D; Halder, Marlies; Murphy, Cheryl A; Roelofs, Dick; Rolaki, Alexandra; Schirmer, Kristin; Watanabe, Karen H

2015-02-01

Adverse outcome pathways (AOPs) organize knowledge on the progression of toxicity through levels of biological organization. By determining the linkages between toxicity events at different levels, AOPs lay the foundation for mechanism-based alternative testing approaches to hazard assessment. Here, we focus on growth impairment in fish to illustrate the initial stages in the process of AOP development for chronic toxicity outcomes. Growth is an apical endpoint commonly assessed in chronic toxicity tests for which a replacement is desirable. Based on several criteria, we identified reduction in food intake to be a suitable key event for initiation of middle-out AOP development. To start exploring the upstream and downstream links of this key event, we developed three AOP case studies, for pyrethroids, selective serotonin reuptake inhibitors (SSRIs) and cadmium. Our analysis showed that the effect of pyrethroids and SSRIs on food intake is strongly linked to growth impairment, while cadmium causes a reduction in growth due to increased metabolic demands rather than changes in food intake. Locomotion impairment by pyrethroids is strongly linked to their effects on food intake and growth, while for SSRIs their direct influence on appetite may play a more important role. We further discuss which alternative tests could be used to inform on the predictive key events identified in the case studies. In conclusion, our work demonstrates how the AOP concept can be used in practice to assess critically the knowledge available for specific chronic toxicity cases and to identify existing knowledge gaps and potential alternative tests. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chronic disease and disability among Iraqi populations displaced in Jordan and Syria.

PubMed

Doocy, Shannon; Sirois, Adam; Tileva, Margarita; Storey, J Douglas; Burnham, Gilbert

2013-01-01

The Iraq conflict resulted in the largest displacement in the Middle East since the Palestinian crisis, and provision of health services to the displaced population presents a critical challenge. The study aimed to provide information on chronic medical conditions and disability to inform humanitarian assistance planning. Nationally representative cross-sectional surveys of Iraqi populations displaced in Jordan and Syria were conducted in late 2008 and early 2009. Clusters of 10 household were randomly selected using probability-based sampling; a total of 1200 and 813 Iraqi households in Jordan and Syria, respectively, were interviewed. The majority of respondents in both countries perceived healthcare as unaffordable but accessible; cost was an important barrier to care. In Jordan, most routine health expenditures were for medications where in Syria, expenses were divided between medical consultations and medication. Chronic disease prevalence among adults was 51.5% (confidence interval (CI): 49.4-53.5) in Syria and 41.0% (CI: 39.4-42.7) in Jordan, most common were hypertension and musculoskeletal problems. Overall disability rates were 7.1% (CI: 6.3-8.0) in Syria and 3.4% (CI: 3.0-3.9) in Jordan. In both countries, the majority of disability was attributed to conflict, prevalence was higher in men than women, and depression was the leading cause of mental health disability. Chronic illnesses, disabilities and psychological health are key challenges for the Iraqi population and the health systems in Jordan and Syria. Continued attention to the development of systems to manage conditions that require secondary and tertiary care is essential, particularly given reported difficulties in accessing care and the anticipated prolonged displacement. Copyright © 2012 John Wiley & Sons, Ltd.

Spinal Cord Injury Causes Brain Inflammation Associated with Cognitive and Affective Changes: Role of Cell Cycle Pathways

PubMed Central

Zhao, Zaorui; Sabirzhanov, Boris; Stoica, Bogdan A.; Kumar, Alok; Luo, Tao; Skovira, Jacob; Faden, Alan I.

2014-01-01

Experimental spinal cord injury (SCI) causes chronic neuropathic pain associated with inflammatory changes in thalamic pain regulatory sites. Our recent studies examining chronic pain mechanisms after rodent SCI showed chronic inflammatory changes not only in thalamus, but also in other regions including hippocampus and cerebral cortex. Because changes appeared similar to those in our rodent TBI models that are associated with neurodegeneration and neurobehavioral dysfunction, we examined effects of mouse SCI on cognition, depressive-like behavior, and brain inflammation. SCI caused spatial and retention memory impairment and depressive-like behavior, as evidenced by poor performance in the Morris water maze, Y-maze, novel objective recognition, step-down passive avoidance, tail suspension, and sucrose preference tests. SCI caused chronic microglial activation in the hippocampus and cerebral cortex, where microglia with hypertrophic morphologies and M1 phenotype predominated. Stereological analyses showed significant neuronal loss in the hippocampus at 12 weeks but not 8 d after injury. Increased cell-cycle-related gene (cyclins A1, A2, D1, E2F1, and PCNA) and protein (cyclin D1 and CDK4) expression were found chronically in hippocampus and cerebral cortex. Systemic administration of the selective cyclin-dependent kinase inhibitor CR8 after SCI significantly reduced cell cycle gene and protein expression, microglial activation and neurodegeneration in the brain, cognitive decline, and depression. These studies indicate that SCI can initiate a chronic brain neurodegenerative response, likely related to delayed, sustained induction of M1-type microglia and related cell cycle activation, which result in cognitive deficits and physiological depression. PMID:25122899

Changing Epidemiology of Mucoralean Fungi: Chronic Cutaneous Infection Caused by Mucor irregularis.

PubMed

Chander, Jagdish; Kaur, Mandeep; Bhalla, Mala; Punia, Rajpal Singh; Singla, Nidhi; Bhola, Kalyani; Alastruey-Izquierdo, Ana; Stchigel, Alberto M; Guarro, Josep

2015-10-01

The fungi pertaining to order Mucorales usually cause an acute form of clinical disease called mucormycosis. A primary chronic presentation in an immunocompetent patient is a rare form of mucormycosis. Mucor irregularis is known for causing chronic cutaneous infections geographically confined to Asia, mainly in China. We describe a case of primary chronic cutaneous mucormycosis caused by M. irregularis from a new geographical niche in India, highlighting changing aspects of its epidemiology. The patient was a farmer with a history of skin lesions over the lower limb for the past 6 years. The biopsy taken from the lesions showed pauci-septate hyphae with right-angle branching on KOH wet mount as well as special fungal stains. On fungal culture, greyish-white cottony mycelial growth of Mucormycetes was obtained. The strain was finally identified as M. irregularis on macro- and microscopic features on 2 % MEA and DNA sequencing. The antifungal susceptibility was done using EUCAST broth microdilution method and was found to be susceptible to commonly used antifungal agents. The patient was started on oral itraconazole and saturated solution of potassium iodide (SSKI). While undergoing treatment for 2 months, he was lost to follow-up, however, after a year when he recently visited the hospital; the disease got completely healed with no new crops of skin lesions. Mucoralean fungi should also be suspected in cases with chronic presentation, in immunocompetent host, as there is emergence of such fungi in new endemic areas, particularly located in Asia. The role of other antifungal agents apart from amphotericin B for the treatment of chronic mucormycosis needs to be explored.

Assessment of driving-related performance in chronic whiplash using an advanced driving simulator.

PubMed

Takasaki, Hiroshi; Treleaven, Julia; Johnston, Venerina; Rakotonirainy, Andry; Haines, Andrew; Jull, Gwendolen

2013-11-01

Driving is often nominated as problematic by individuals with chronic whiplash associated disorders (WAD), yet driving-related performance has not been evaluated objectively. The purpose of this study was to test driving-related performance in persons with chronic WAD against healthy controls of similar age, gender and driving experience to determine if driving-related performance in the WAD group was sufficiently impaired to recommend fitness to drive assessment. Driving-related performance was assessed using an advanced driving simulator during three driving scenarios; freeway, residential and a central business district (CBD). Total driving duration was approximately 15min. Five driving tasks which could cause a collision (critical events) were included in the scenarios. In addition, the effect of divided attention (identify red dots projected onto side or rear view mirrors) was assessed three times in each scenario. Driving performance was measured using the simulator performance index (SPI) which is calculated from 12 measures. z-Scores for all SPI measures were calculated for each WAD subject based on mean values of the control subjects. The z-scores were then averaged for the WAD group. A z-score of ≤-2 indicated a driving failing grade in the simulator. The number of collisions over the five critical events was compared between the WAD and control groups as was reaction time and missed response ratio in identifying the red dots. Seventeen WAD and 26 control subjects commenced the driving assessment. Demographic data were comparable between the groups. All subjects completed the freeway scenario but four withdrew during the residential and eight during the CBD scenario because of motion sickness. All scenarios were completed by 14 WAD and 17 control subjects. Mean z-scores for the SPI over the three scenarios was statistically lower in the WAD group (-0.3±0.3; P<0.05) but the score was not below the cut-off point for safe driving. There were no differences in the reaction time and missed response ratio in divided attention tasks between the groups (All P>0.05). Assessment of driving in an advanced driving simulator for approximately 15min revealed that driving-related performance in chronic WAD was not sufficiently impaired to recommend the need for fitness to drive assessment. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Current alternatives in the surgical treatment of chronic pancreatitis--a review article].

PubMed

Kat'uchová, Jana; Radonak, Jozef

2011-01-01

Chronic pancreatitis is characterized as an inflammatory process affecting the pancreas that causes progressive destruction of the gland and fibrosis, with subsequent endocrine and exocrine insufficiency. The most common cause of chronic pancreatitis is alcohol use in combination with nicotine. Manifestations are persistent or recurrent painful attacks. The only parameter of successful treatment of chronic pancreatitis is a relieve from long-lasting pain and improvement of the quality of life. Surgical treatment options include drainage operations on the pancreas, pancreatic resection or a combination of both. With optimal surgical treatment performed and good patient's compliance, operations for chronic pancreatitis have low number of post-operative complications and relatively good long-term results. The continued consumption of alcohol and drugs bring about worse outcomes, sometimes even a complete failure of therapy. Chronic pancreatitis also has considerable socio-economic consequences. Due to the persisting pain and frequent hospitalization it can lead to long-term disability and early retirement predominantly in young patients.

Chronic Lower Leg Pain in Athletes

PubMed Central

Brewer, Rachel Biber; Gregory, Andrew J. M.

2012-01-01

Context: Chronic lower leg pain in athletes can be a frustrating problem for patients and a difficult diagnosis for clinicians. Myriad approaches have been suggested to evaluate these conditions. With the continued evolution of diagnostic studies, evidence-based guidance for a standard approach is unfortunately sparse. Evidence Acquisition: PubMed was searched from January 1980 to May 2011 to identify publications regarding chronic lower leg pain in athletes (excluding conditions related to the foot), including differential diagnosis, clinical presentation, physical examination, history, diagnostic workup, and treatment. Results: Leg pain in athletes can be caused by many conditions, with the most frequent being medial tibial stress syndrome; chronic exertional compartment syndrome, stress fracture, nerve entrapment, and popliteal artery entrapment syndrome are also considerations. Conservative management is the mainstay of care for the majority of causes of chronic lower leg pain; however, surgical intervention may be necessary. Conclusion: Chronic lower extremity pain in athletes includes a wide differential and can pose diagnostic dilemmas for clinicians. PMID:23016078

How Do Health Policies Affect My Health?: A Performance Task for High School

ERIC Educational Resources Information Center

Wycoff-Horn, Marcie R.; Caravella, Tracy J.

2011-01-01

It is well known that chronic diseases are the most common, costly, and preventable of all health issues in the United States. Chronic diseases continue to be a major health concern. Of the top 10 leading causes of mortality, 7 are identified as chronic. More recently, the prevalence of these chronic conditions has increased among the adolescent…

Acute-On-Chronic Liver Failure: Causes, Clinical Characteristics and Predictors of Mortality.

PubMed

Tasneem, Abbas Ali; Luck, Nasir Hassan

2017-01-01

To determine the causes, characteristics and predictors of mortality in patients with acute-on-chronic liver failure (ACLF). Cross-sectional study. Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, from July 2014 to June 2016. All patients with acute-on-chronic liver disease (ACLD) with ages > 12 were included. Patients with ACLF, as defined by the Asian Pacific Association for the Study of Liver (APASL, 2014) were identified. Predictors of mortality were identified using chi-square or Fisher's exact test. Included in the study were 72 patients with mean age of 36.71 years, 46 (63.9%) being males. Among them, 61 developed ACLF. Commonest causes of chronic liver disease (CLD) were chronic viral hepatitis (37, 51.4%) and autoimmune hepatitis (14, 19.4%). Commonest causes of acute liver injury (ALI) were acute viral hepatitis (24, 33.3%) and drug induced liver injury (DILI) (17, 23.6%). Among those with ACLF, 24 (39.3%) patients died with median survival of 17.1 ±13.5 days. Mortality was significantly associated with Child Turcotte Pugh (CTP) score ≥13 (p=0.010), model for end-stage liver disease (MELD) score ≥30 (p=0.001), age >40 years (p=0.036), organ failures (OF) ≥3 (p <0.0001), portosystemic encephalopathy (PSE) (p <0.0001), renal failure (p <0.0001) and urosepsis (p <0.0001). Acute viral hepatitis and DILI are commonest causes of ACLF. Mortality is high in ACLF patients having OF ≥3, CTP ≥13, MELD ≥30, age >40 years, PSE, renal failure and urosepsis.

TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to proinflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages.

PubMed

Zheng, Shasha; Hedl, Matija; Abraham, Clara

2015-02-15

Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of nucleotide-binding oligomerization domain 2 (NOD2), the Crohn's disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl, and Mer (TAM) receptors in regulating chronic pattern recognition receptor stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and proinflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGF-β-dependent TAM upregulation in human macrophages, which, in turn, upregulated suppressor of cytokine signaling 3 expression. Restoring suppressor of cytokine signaling 3 expression under TAM knockdown conditions restored chronic NOD2-mediated proinflammatory cytokine downregulation. In contrast to the upregulated proinflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, musculoaponeurotic fibrosarcoma oncogene homolog K, and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for downregulating proinflammatory cytokines under the chronic NOD2 stimulation conditions observed in the intestinal environment. Copyright © 2015 by The American Association of Immunologists, Inc.

Lost productive life years caused by chronic conditions in Australians aged 45-64 years, 2010-2030.

PubMed

Schofield, Deborah J; Shrestha, Rupendra N; Cunich, Michelle; Tanton, Robert; Kelly, Simon; Passey, Megan E; Veerman, Lennert J

2015-09-21

To estimate (1) productive life years (PLYs) lost because of chronic conditions in Australians aged 45-64 years from 2010 to 2030, and (2) the impact of this loss on gross domestic product (GDP) over the same period. A microsimulation model, Health&WealthMOD2030, was used to project lost PLYs caused by chronic conditions from 2010 to 2030. The base population consisted of respondents aged 45-64 years to the Australian Bureau of Statistics Survey of Disability, Ageing and Carers 2003 and 2009. The national impact of lost PLYs was assessed with Treasury's GDP equation. Lost PLYs due to chronic disease at 2010, 2015, 2020, 2025 and 2030 (ie, whole life years lost because of chronic disease); the national impact of lost PLYs at the same time points (GDP loss caused by PLYs); the effects of population growth, labour force trends and chronic disease trends on lost PLYs and GDP at each time point. Using Health&WealthMOD2030, we estimated a loss of 347,000 PLYs in 2010; this was projected to increase to 459,000 in 2030 (32.28% increase over 20 years). The leading chronic conditions associated with premature exits from the labour force were back problems, arthritis and mental and behavioural problems. The percentage increase in the number of PLYs lost by those aged 45-64 years was greater than that of population growth for this age group (32.28% v 27.80%). The strongest driver of the increase in lost PLYs was population growth (accounting for 89.18% of the increase), followed by chronic condition trends (8.28%). Our study estimates an increase of 112 000 lost PLYs caused by chronic illness in older workers in Australia between 2010 and 2030, with the most rapid growth projected to occur in men aged 55-59 years and in women aged 60-64 years. The national impact of this lost labour force participation on GDP was estimated to be $37.79 billion in 2010, increasing to $63.73 billion in 2030.

Chronic mild stress influences nerve growth factor through a matrix metalloproteinase-dependent mechanism.

PubMed

Kucharczyk, Mateusz; Kurek, Anna; Detka, Jan; Slusarczyk, Joanna; Papp, Mariusz; Tota, Katarzyna; Basta-Kaim, Agnieszka; Kubera, Marta; Lason, Wladyslaw; Budziszewska, Bogusława

2016-04-01

Stress is generally a beneficial experience that motivates an organism to action to overcome the stressful challenge. In particular situations, when stress becomes chronic might be harmful and devastating. The hypothalamus is a critical coordinator of stress and the metabolic response; therefore, disruptions in this structure may be a significant cause of the hormonal and metabolic disturbances observed in depression. Chronic stress induces adverse changes in the morphology of neural cells that are often associated with a deficiency of neurotrophic factors (NTFs); additionally, many studies indicate that insufficient NTF synthesis may participate in the pathogenesis of depression. The aim of the present study was to determine the expression of the nerve growth factor (NGF) in the hypothalamus of male rats subjected to chronic mild stress (CMS) or to prenatal stress (PS) and to PS in combination with an acute stress event (AS). It has been found that chronic mild stress, but not prenatal stress, acute stress or a combination of PS with AS, decreased the concentration of the mature form of NGF (m-NGF) in the rat hypothalamus. A discrepancy between an increase in the Ngf mRNA and a decrease in the m-NGF levels suggested that chronic mild stress inhibited NGF maturation or enhanced the degradation of this factor. We have shown that NGF degradation in the hypothalamus of rats subjected to chronic mild stress is matrix metalloproteinase-dependent and related to an increase in the active forms of some metalloproteinases (MMP), including MMP2, MMP3, MMP9 and MMP13, while the NGF maturation process does not seem to be changed. We suggested that activated MMP2 and MMP9 potently cleave the mature but not the pro- form of NGF into biologically inactive products, which is the reason for m-NGF decomposition. In turn, the enhanced expression of Ngf in the hypothalamus of these rats is an attempt to overcome the reduced levels of m-NGF. Additionally, the decreased level of m-NGF together with the increased level of pro-NGF can decrease TrkA-mediated neuronal survival signalling and enhance the action of pro-NGF on the p75(NTR) receptor, respectively, to evoke pro-apoptotic signalling. This hypothesis is supported by elevated levels of the caspase-3 mRNA in the hypothalamus of rats subjected to chronic mild stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

Critical Review of Health Impacts of Wildfire Smoke Exposure

PubMed Central

Reid, Colleen E.; Brauer, Michael; Johnston, Fay H.; Jerrett, Michael; Balmes, John R.; Elliott, Catherine T.

2016-01-01

Background: Wildfire activity is predicted to increase in many parts of the world due to changes in temperature and precipitation patterns from global climate change. Wildfire smoke contains numerous hazardous air pollutants and many studies have documented population health effects from this exposure. Objectives: We aimed to assess the evidence of health effects from exposure to wildfire smoke and to identify susceptible populations. Methods: We reviewed the scientific literature for studies of wildfire smoke exposure on mortality and on respiratory, cardiovascular, mental, and perinatal health. Within those reviewed papers deemed to have minimal risk of bias, we assessed the coherence and consistency of findings. Discussion: Consistent evidence documents associations between wildfire smoke exposure and general respiratory health effects, specifically exacerbations of asthma and chronic obstructive pulmonary disease. Growing evidence suggests associations with increased risk of respiratory infections and all-cause mortality. Evidence for cardiovascular effects is mixed, but a few recent studies have reported associations for specific cardiovascular end points. Insufficient research exists to identify specific population subgroups that are more susceptible to wildfire smoke exposure. Conclusions: Consistent evidence from a large number of studies indicates that wildfire smoke exposure is associated with respiratory morbidity with growing evidence supporting an association with all-cause mortality. More research is needed to clarify which causes of mortality may be associated with wildfire smoke, whether cardiovascular outcomes are associated with wildfire smoke, and if certain populations are more susceptible. Citation: Reid CE, Brauer M, Johnston FH, Jerrett M, Balmes JR, Elliott CT. 2016. Critical review of health impacts of wildfire smoke exposure. Environ Health Perspect 124:1334–1343; http://dx.doi.org/10.1289/ehp.1409277 PMID:27082891

Bacterial Prostatitis: Bacterial Virulence, Clinical Outcomes, and New Directions.

PubMed

Krieger, John N; Thumbikat, Praveen

2016-02-01

Four prostatitis syndromes are recognized clinically: acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis/chronic pelvic pain syndrome, and asymptomatic prostatitis. Because Escherichia coli represents the most common cause of bacterial prostatitis, we investigated the importance of bacterial virulence factors and antimicrobial resistance in E. coli strains causing prostatitis and the potential association of these characteristics with clinical outcomes. A structured literature review revealed that we have limited understanding of the virulence-associated characteristics of E. coli causing acute prostatitis. Therefore, we completed a comprehensive microbiological and molecular investigation of a unique strain collection isolated from healthy young men. We also considered new data from an animal model system suggesting certain E. coli might prove important in the etiology of chronic prostatitis/chronic pelvic pain syndrome. Our human data suggest that E. coli needs multiple pathogenicity-associated traits to overcome anatomic and immune responses in healthy young men without urological risk factors. The phylogenetic background and accumulation of an exceptional repertoire of extraintestinal pathogenic virulence-associated genes indicate that these E. coli strains belong to a highly virulent subset of uropathogenic variants. In contrast, antibiotic resistance confers little added advantage to E. coli strains in these healthy outpatients. Our animal model data also suggest that certain pathogenic E. coli may be important in the etiology of chronic prostatitis/chronic pelvic pain syndrome through mechanisms that are dependent on the host genetic background and the virulence of the bacterial strain.

Chronic pancreatitis associated with the p.G208A variant of PRSS1 gene in a European patient.

PubMed

Hegyi, Eszter; Cierna, Iveta; Vavrova, Ludmila; Ilencikova, Denisa; Konecny, Michal; Kovacs, Laszlo

2014-01-10

The major etiologic factor of chronic pancreatitis in adults is excessive alcohol consumption, whereas among children structural anomalies, systemic and metabolic disorders, and genetic factors are prevalent. Mutations in the cationic trypsinogen gene (PRSS1) cause hereditary pancreatitis, while mutations in serine protease inhibitor Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR) and chymotrypsin C (CTRC) genes have been shown to associate with chronic pancreatitis as independent risk factors. We present a case of 13-year-old boy with idiopathic chronic pancreatitis. Given the unexplained attacks of pancreatitis since early childhood and despite the negative family history, molecular-genetic analysis of four pancreatitis susceptibility genes (PRSS1, SPINK1, CTRC and CFTR) was performed. The boy was found to carry the c.623G>C (p.G208A) mutation of the PRSS1 gene and the c.180C>T (p.G60G) mutation of the CTRC gene, both in heterozygous state. These mutations are considered as contributing risk factors for chronic pancreatitis. In children with idiopathic chronic pancreatitis genetic causes should be considered, even in absence of positive family history. To the best of our knowledge, this is the first description of a European patient with chronic pancreatitis associated with the p.G208A mutation of PRSS1 gene. This mutation was previously reported only in Asian subjects and is thought to be a unique genetic cause of pancreatitis in Asia.

Caecal volvulus in a patient with chronic intestinal pseudo-obstruction

PubMed Central

El-Khatib, C

2011-01-01

Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder characterised by recurrent symptoms and signs of intestinal obstruction without an underlying mechanical cause. Caecal volvulus remains a rare cause of intestinal obstruction that often requires operative intervention. We describe the previously unreported case of caecal volvulus occurring in an adult patient with CIPO, together with his subsequent management. PMID:22004621

Obesity, chronic disease, and economic growth: a case for "big picture" prevention.

PubMed

Egger, Garry

2011-01-01

The discovery of a form of chronic, low-grade systemic inflammation ("metaflammation") linked with obesity, but also associated with several lifestyle-related behaviours not necessarily causing obesity, suggests a re-consideration of obesity as a direct cause of chronic disease and a search for the main drivers-or cause of causes. Factors contributing to this are considered here within an environmental context, leading to the conclusion that humans have an immune reaction to aspects of the modern techno-industrial environment, to which they have not fully adapted. It is suggested that economic growth-beyond a point-leads to increases in chronic diseases and climate change and that obesity is a signal of these problems. This is supported by data from Sweden over 200 years, as well as "natural" experiments in disrupted economies like Cuba and Nauru, which have shown a positive health effect with economic downturns. The effect is reflected both in human health and environmental problems such as climate change, thus pointing to the need for greater cross-disciplinary communication and a concept shift in thinking on prevention if economic growth is to continue to benefit human health and well-being.

Epidemiology of chronic obstructive pulmonary disease: health effects of air pollution.

PubMed

Viegi, Giovanni; Maio, Sara; Pistelli, Francesco; Baldacci, Sandra; Carrozzi, Laura

2006-09-01

COPD is one of the leading causes of morbidity and mortality in the industrialized and the developing countries. According to the prediction of the World Health Organization, COPD will become the third leading cause of mortality and the fifth cause of disability in 2020 worldwide. In epidemiology, distinct phenotypic entities converge on the term COPD, so that prevalence and mortality data may be inclusive of chronic bronchitis, emphysema and asthma; moreover, the assessment of prevalence rates may change considerably according to the diagnostic tools used. Thus, a considerable problem is to estimate the real prevalence of COPD in the general population. COPD is determined by the action of a number of various risk factors, among which, the most important is cigarette smoking. However, during the last few decades, evidence from epidemiological studies finding consistent associations between air pollution and various outcomes (respiratory symptoms, reduced lung function, chronic bronchitis and mortality), has suggested that outdoor air pollution is a contributing cause of morbidity and mortality. In conclusion, epidemiological studies suggest that air pollution plays a remarkable role in the exacerbation and in the pathogenesis of chronic respiratory diseases. Thus, respiratory physicians, as well as public health professionals, should advocate for a cleaner environment.

Use of strong opioids for chronic pain in osteoarthritis: an insight into the Latin American reality.

PubMed

Ruiz Iban, Miguel Angel; Benavides, Javier; Forero, Juan Pablo; Bittelman, Sacha; Martinez, Rafael; Mite, Miguel Angel; Diaz Heredia, Jorge; Ulloa, Sergio; Lizárraga Ferrand, Mauro Marcelo

2018-01-01

Osteoarthritis is the most common cause of arthritis and one of the main causes of chronic pain. Although opioids are frequently employed for chronic pain treatment, their usage for osteoarthritis pain remains controversial due to the associated adverse effects. Most guidelines reserve their use for refractory pain in patients with hip and knee osteoarthritis. The situation is even more complex in Latin America, where the prevalence of insufficient pain treatment is high because of the limited availability and use of strong opioids. Areas covered: In this article we review the epidemiology of osteoarthritis, its socioeconomic burden, its impact as a chronic pain cause and the pharmacological treatment options, giving emphasis to the role of strong opioids, their safety and efficacy, especially in Latin American countries, where restrictions regulate their usage. Expert commentary: Usage of strong opioids is safe and effective in the short-term management of osteoarthritis with moderate to severe pain, when other pharmacological treatments are inadequate and surgery is contraindicated, provided their use adheres to existing guidelines. Educational programs for patients and physicians and further research on treating chronic pain with opioids should be implemented to reduce adverse effects and improve care quality.

Detection of sexually transmitted pathogens in patients with chronic prostatitis/chronic pelvic pain: a prospective clinical study.

PubMed

Papeš, Dino; Pasini, Miram; Jerončić, Ana; Vargović, Martina; Kotarski, Viktor; Markotić, Alemka; Škerk, Višnja

2017-05-01

In <10% of patients with prostatitis syndrome, a causative uropathogenic organism can be detected. It has been shown that certain organisms that cause sexually transmitted infections can also cause chronic bacterial prostatitis, which can be hard to diagnose and treat appropriately because prostatic samples obtained by prostatic massage are not routinely tested to detect them. We conducted a clinical study to determine the prevalence of Chlamydia, mycoplasma, and trichomonas infection in 254 patients that were previously diagnosed and treated for chronic prostatitis/chronic pelvic pain syndrome due to negative urethral swab, urine, and prostate samples. Urethral swabs and standard Meares-Stamey four-glass tests were done. Detailed microbiological analysis was conducted to detect the above organisms. Thirty-five (13.8%) patients had positive expressed prostatic secretions/VB3 samples, of which 22 (10.1%) were sexually transmitted organisms that were not detected on previous tests.

Impact of PACAP and PAC1 Receptor Deficiency on the Neurochemical and Behavioral Effects of Acute and Chronic Restraint Stress in Male C57BL/6 Mice

PubMed Central

Mustafa, Tomris; Jiang, Sunny Zhihong; Eiden, Adrian M.; Weihe, Eberhard; Thistlethwaite, Ian; Eiden, Lee E.

2016-01-01

Acute restraint stress (ARS) for 3 hours causes CORT elevation in venous blood, which is accompanied by Fos up-regulation in the paraventricular nucleus (PVN) of male C57BL/6 mice. CORT elevation by ARS is attenuated in PACAP-deficient mice, but unaffected in PAC1-deficient mice. Correspondingly, Fos up-regulation by ARS is greatly attenuated in PACAP-deficient mice, but much less so in PAC1-deficient animals. We noted that both PACAP- and PAC1-deficiency greatly attenuate CORT elevation after ARS when CORT measurements are performed on trunk blood following euthanasia by abrupt cervical separation: this latter observation is of critical importance in assessing the role of PACAP neurotransmission in ARS, based on previous reports in which serum CORT was sampled from trunk blood. Seven days of chronic restraint stress (CRS) induces non-habituating CORT elevation, and weight loss consequent to hypophagia, in wild-type male C57BL/6 mice. Both CORT elevation and weight loss following seven day CRS are severely blunted in PACAP-deficient mice, but only slightly in PAC1 deficient mice. However, longer periods of daily restraint (14–21 days) resulted in sustained weight loss and elevated CORT in wild-type mice, and these effects of long-term chronic stress were attenuated or abolished in both PACAP- and PAC1-deficient mice. We conclude that while a PACAP receptor in addition to PAC1 may mediate some of the PACAP-dependent central effects of acute restraint stress and short-term (<7 days) chronic restraint stress on the HPA axis, the PAC1 receptor plays a prominent role in mediating PACAP-dependent HPA axis activation, and hypophagia, during long-term (>7 days) chronic restraint stress. PMID:25853791

[Assessment of chronic glucose metabolism disorders coexisting with respiratory failure in non-critical ill patients hospitalized with lower respiratory tract infections].

PubMed

Sobocińska, Magdalena Barbara; Loba, Jerzy

2015-01-01

Lungs are the target organ in chronic hyperglycemia, but its large reserves causes a subclinical course of these changes. Given the results of other researchers indicating reduced active surface of gas exchange and pulmonary capillary damage, it can be assumed that diabetes and other hyperglycemic states diminish these reserves and impair effectiveness of respiratory gas exchange during pneumonia. So it is plausible to observe coexistence of glucose metabolism disorders and respiratory failure in patients hospitalized with lower respiratory tract infection. An observational study was conducted on 130 patients hospitalized with bacteriologically confirmed pneumonia. 63 patients suffering from chronic glucose metabolism disorders (A) and 67 randomly selected patients in control group (B) were observed on laboratory and clinical findings. There was no significant difference in prevalence of acute respiratory failure, although in the study group a slightly greater number of patients diagnosed with acute respiratory failure was observed. There was a significantly greater number of patients with previously confirmed chronic respiratory failure using long-term oxygen theraphy in A group (p = 0.029). The B patients with average blood glucose level > 108 mg/dl had significantly lower partial pressure of oxygen (PaO2)(gIc ≤ 108: 58.6 +/- 9.8; glc > 108: 51.7 +/- 11.1; p = 0.042). There was a statistically significant negative correlation of the average blood glucose level and PaO2 in the control group (p = 0.0152) and a significant inverse association between the average blood glucose level and the partial pressure of oxygen in patients without COPD belonging to the control group (p = 0.049). Respiratory failure is frequent in patients hospitalized with pneumonia. In patients without chronic glucose metabolism disorders with blood glucose level rising the oxygen tension decreases The association is stronger in patients without COPD.

Adrenergic Signaling: A Targetable Checkpoint Limiting Development of the Antitumor Immune Response.

PubMed

Qiao, Guanxi; Chen, Minhui; Bucsek, Mark J; Repasky, Elizabeth A; Hylander, Bonnie L

2018-01-01

An immune response must be tightly controlled so that it will be commensurate with the level of response needed to protect the organism without damaging normal tissue. The roles of cytokines and chemokines in orchestrating these processes are well known, but although stress has long been thought to also affect immune responses, the underlying mechanisms were not as well understood. Recently, the role of nerves and, specifically, the sympathetic nervous system, in regulating immune responses is being revealed. Generally, an acute stress response is beneficial but chronic stress is detrimental because it suppresses the activities of effector immune cells while increasing the activities of immunosuppressive cells. In this review, we first discuss the underlying biology of adrenergic signaling in cells of both the innate and adaptive immune system. We then focus on the effects of chronic adrenergic stress in promoting tumor growth, giving examples of effects on tumor cells and immune cells, explaining the methods commonly used to induce stress in preclinical mouse models. We highlight how this relates to our observations that mandated housing conditions impose baseline chronic stress on mouse models, which is sufficient to cause chronic immunosuppression. This problem is not commonly recognized, but it has been shown to impact conclusions of several studies of mouse physiology and mouse models of disease. Moreover, the fact that preclinical mouse models are chronically immunosuppressed has critical ramifications for analysis of any experiments with an immune component. Our group has found that reducing adrenergic stress by housing mice at thermoneutrality or treating mice housed at cooler temperatures with β-blockers reverses immunosuppression and significantly improves responses to checkpoint inhibitor immunotherapy. These observations are clinically relevant because there are numerous retrospective epidemiological studies concluding that cancer patients who were taking β-blockers have better outcomes. Clinical trials testing whether β-blockers can be repurposed to improve the efficacy of traditional and immunotherapies in patients are on the horizon.

Adrenergic Signaling: A Targetable Checkpoint Limiting Development of the Antitumor Immune Response

PubMed Central

Qiao, Guanxi; Chen, Minhui; Bucsek, Mark J.; Repasky, Elizabeth A.; Hylander, Bonnie L.

2018-01-01

An immune response must be tightly controlled so that it will be commensurate with the level of response needed to protect the organism without damaging normal tissue. The roles of cytokines and chemokines in orchestrating these processes are well known, but although stress has long been thought to also affect immune responses, the underlying mechanisms were not as well understood. Recently, the role of nerves and, specifically, the sympathetic nervous system, in regulating immune responses is being revealed. Generally, an acute stress response is beneficial but chronic stress is detrimental because it suppresses the activities of effector immune cells while increasing the activities of immunosuppressive cells. In this review, we first discuss the underlying biology of adrenergic signaling in cells of both the innate and adaptive immune system. We then focus on the effects of chronic adrenergic stress in promoting tumor growth, giving examples of effects on tumor cells and immune cells, explaining the methods commonly used to induce stress in preclinical mouse models. We highlight how this relates to our observations that mandated housing conditions impose baseline chronic stress on mouse models, which is sufficient to cause chronic immunosuppression. This problem is not commonly recognized, but it has been shown to impact conclusions of several studies of mouse physiology and mouse models of disease. Moreover, the fact that preclinical mouse models are chronically immunosuppressed has critical ramifications for analysis of any experiments with an immune component. Our group has found that reducing adrenergic stress by housing mice at thermoneutrality or treating mice housed at cooler temperatures with β-blockers reverses immunosuppression and significantly improves responses to checkpoint inhibitor immunotherapy. These observations are clinically relevant because there are numerous retrospective epidemiological studies concluding that cancer patients who were taking β-blockers have better outcomes. Clinical trials testing whether β-blockers can be repurposed to improve the efficacy of traditional and immunotherapies in patients are on the horizon. PMID:29479349

Evidence for the effectiveness of Alexander Technique lessons in medical and health-related conditions: a systematic review.

PubMed

Woodman, J P; Moore, N R

2012-01-01

Complementary medicine and alternative approaches to chronic and intractable health conditions are increasingly being used, and require critical evaluation. The aim of this review was to systematically evaluate available evidence for the effectiveness and safety of instruction in the Alexander Technique in health-related conditions. PUBMED, EMBASE, PSYCHINFO, ISI Web-of-Knowledge, AMED, CINHAL-plus, Cochrane library and Evidence-based Medicine Reviews were searched to July 2011. Inclusion criteria were prospective studies evaluating Alexander Technique instruction (individual lessons or group delivery) as an intervention for any medical indication/health-related condition. Studies were categorised and data extracted on study population, randomisation method, nature of intervention and control, practitioner characteristics, validity and reliability of outcome measures, completeness of follow-up and statistical analyses.   Of 271 publications identified, 18 were selected: three randomised, controlled trials (RCTs), two controlled non-randomised studies, eight non-controlled studies, four qualitative analyses and one health economic analysis. One well-designed, well-conducted RCT demonstrated that, compared with usual GP care, Alexander Technique lessons led to significant long-term reductions in back pain and incapacity caused by chronic back pain. The results were broadly supported by a smaller, earlier RCT in chronic back pain. The third RCT, a small, well-designed, well-conducted study in individuals with Parkinson's disease, showed a sustained increased ability to carry out everyday activities following Alexander lessons, compared with usual care. The 15 non-RCT studies are also reviewed. Strong evidence exists for the effectiveness of Alexander Technique lessons for chronic back pain and moderate evidence in Parkinson's-associated disability. Preliminary evidence suggests that Alexander Technique lessons may lead to improvements in balance skills in the elderly, in general chronic pain, posture, respiratory function and stuttering, but there is insufficient evidence to support recommendations in these areas. © 2011 Blackwell Publishing Ltd.

The link between chronic kidney disease and cardiovascular disease.

PubMed

Said, Sarmad; Hernandez, German T

2014-07-01

It is well known that patients with chronic kidney disease (CKD) have a strong risk of cardiovascular disease (CVD). However, the excess risk of cardiovascular disease in patients with CKD is only partially explained by the presence of traditional risk factors, such as hypertension and diabetes mellitus. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO and Web of Science has been searched. Chronic kidney disease even in its early stages can cause hypertension and potentiate the risk for cardiovascular disease. However, the practice of intensive blood pressure lowering was criticized in recent systematic reviews. Available evidence is inconclusive but does not prove that a blood pressure target of less than 130/80 mmHg as recommended in the guidelines improves clinical outcomes more than a target of less than 140/90 mmHg in adults with CKD. The association between CKD and CVD has been extensively documented in the literature. Both CKD and CVD share common traditional risk factors, such as smoking, obesity, hypertension, diabetes mellitus, and dyslipidemia. However, cardiovascular disease remains often underdiagnosed und undertreated in patients with CKD. It is imperative that as clinicians, we recognize that patients with CKD are a group at high risk for developing CVD and cardiovascular events. Additional studies devoted to further understand the risk factors for CVD in patients with CKD are necessary to develop and institute preventative and treatment strategies to reduce the high morbidity and mortality in patients with CKD.

The link between chronic kidney disease and cardiovascular disease

PubMed Central

Said, Sarmad; Hernandez, German T.

2014-01-01

Context: It is well known that patients with chronic kidney disease (CKD) have a strong risk of cardiovascular disease (CVD). However, the excess risk of cardiovascular disease in patients with CKD is only partially explained by the presence of traditional risk factors, such as hypertension and diabetes mellitus. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO and Web of Science has been searched. Results: Chronic kidney disease even in its early stages can cause hypertension and potentiate the risk for cardiovascular disease. However, the practice of intensive blood pressure lowering was criticized in recent systematic reviews. Available evidence is inconclusive but does not prove that a blood pressure target of less than 130/80 mmHg as recommended in the guidelines improves clinical outcomes more than a target of less than 140/90 mmHg in adults with CKD. Conclusions: The association between CKD and CVD has been extensively documented in the literature. Both CKD and CVD share common traditional risk factors, such as smoking, obesity, hypertension, diabetes mellitus, and dyslipidemia. However, cardiovascular disease remains often underdiagnosed und undertreated in patients with CKD. It is imperative that as clinicians, we recognize that patients with CKD are a group at high risk for developing CVD and cardiovascular events. Additional studies devoted to further understand the risk factors for CVD in patients with CKD are necessary to develop and institute preventative and treatment strategies to reduce the high morbidity and mortality in patients with CKD. PMID:25093157

Chronic lead exposure induces cochlear oxidative stress and potentiates noise-induced hearing loss.

PubMed

Jamesdaniel, Samson; Rosati, Rita; Westrick, Judy; Ruden, Douglas M

2018-08-01

Acquired hearing loss is caused by complex interactions of multiple environmental risk factors, such as elevated levels of lead and noise, which are prevalent in urban communities. This study delineates the mechanism underlying lead-induced auditory dysfunction and its potential interaction with noise exposure. Young-adult C57BL/6 mice were exposed to: 1) control conditions; 2) 2 mM lead acetate in drinking water for 28 days; 3) 90 dB broadband noise 2 h/day for two weeks; and 4) both lead and noise. Blood lead levels were measured by inductively coupled plasma mass spectrometry analysis (ICP-MS) lead-induced cochlear oxidative stress signaling was assessed using targeted gene arrays, and the hearing thresholds were assessed by recording auditory brainstem responses. Chronic lead exposure downregulated cochlear Sod1, Gpx1, and Gstk1, which encode critical antioxidant enzymes, and upregulated ApoE, Hspa1a, Ercc2, Prnp, Ccl5, and Sqstm1, which are indicative of cellular apoptosis. Isolated exposure to lead or noise induced 8-12 dB and 11-25 dB shifts in hearing thresholds, respectively. Combined exposure induced 18-30 dB shifts, which was significantly higher than that observed with isolated exposures. This study suggests that chronic exposure to lead induces cochlear oxidative stress and potentiates noise-induced hearing impairment, possibly through parallel pathways. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Actions of Bupivacaine, a Widely Used Local Anesthetic, on NMDA Receptor Responses

PubMed Central

Paganelli, Meaghan A.

2015-01-01

NMDA receptors mediate excitatory neurotransmission in brain and spinal cord and play a pivotal role in the neurological disease state of chronic pain, which is caused by central sensitization. Bupivacaine is the indicated local anesthetic in caudal, epidural, and spinal anesthesia and is widely used clinically to manage acute and chronic pain. In addition to blocking Na+ channels, bupivacaine affects the activity of many other channels, including NMDA receptors. Importantly, bupivacaine inhibits NMDA receptor-mediated synaptic transmission in the dorsal horn of the spinal cord, an area critically involved in central sensitization. We used recombinant NMDA receptors expressed in HEK293 cells and found that increasing concentrations of bupivacaine decreased channel open probability in GluN2 subunit- and pH-independent manner by increasing the mean duration of closures and decreasing the mean duration of openings. Using kinetic modeling of one-channel currents, we attributed the observed current decrease to two main mechanisms: a voltage-dependent “foot-in-the-door” pore block and an allosteric gating effect. Further, the inhibition was state-independent because it occurred to the same degree whether the drug was applied before or after glutamate stimulation and was mediated by extracellular and intracellular inhibitory sites, via hydrophilic and hydrophobic pathways. These results predict that clinical doses of bupivacaine would decrease the peak and accelerate the decay of synaptic NMDA receptor currents during normal synaptic transmission. These quantitative predictions inform possible applications of bupivacaine as preventative and therapeutic approaches in chronic pain. PMID:25589775

Altered Redox Balance in the Development of Chronic Hypoxia-induced Pulmonary Hypertension.

PubMed

Jernigan, Nikki L; Resta, Thomas C; Gonzalez Bosc, Laura V

2017-01-01

Normally, the pulmonary circulation is maintained in a low-pressure, low-resistance state with little resting tone. Pulmonary arteries are thin-walled and rely heavily on pulmonary arterial distension and recruitment for reducing pulmonary vascular resistance when cardiac output is elevated. Under pathophysiological conditions, however, active vasoconstriction and vascular remodeling lead to enhanced pulmonary vascular resistance and subsequent pulmonary hypertension (PH). Chronic hypoxia is a critical pathological factor associated with the development of PH resulting from airway obstruction (COPD, sleep apnea), diffusion impairment (interstitial lung disease), developmental lung abnormalities, or high altitude exposure (World Health Organization [WHO]; Group III). The rise in pulmonary vascular resistance increases right heart afterload causing right ventricular hypertrophy that can ultimately lead to right heart failure in patients with chronic lung disease. PH is typically characterized by diminished paracrine release of vasodilators, antimitogenic factors, and antithrombotic factors (e.g., nitric oxide and protacyclin) and enhanced production of vasoconstrictors and mitogenic factors (e.g., reactive oxygen species and endothelin-1) from the endothelium and lung parenchyma. In addition, phenotypic changes to pulmonary arterial smooth muscle cells (PASMC), including alterations in Ca 2+ homeostasis, Ca 2+ sensitivity, and activation of transcription factors are thought to play prominent roles in the development of both vasoconstrictor and arterial remodeling components of hypoxia-associated PH. These changes in PASMC function are briefly reviewed in Sect. 1 and the influence of altered reactive oxygen species homeostasis on PASMC function discussed in Sects. 2-4.

The critical care management of spontaneous intracranial hemorrhage: a contemporary review.

PubMed

de Oliveira Manoel, Airton Leonardo; Goffi, Alberto; Zampieri, Fernando Godinho; Turkel-Parrella, David; Duggal, Abhijit; Marotta, Thomas R; Macdonald, R Loch; Abrahamson, Simon

2016-09-18

Spontaneous intracerebral hemorrhage (ICH), defined as nontraumatic bleeding into the brain parenchyma, is the second most common subtype of stroke, with 5.3 million cases and over 3 million deaths reported worldwide in 2010. Case fatality is extremely high (reaching approximately 60 % at 1 year post event). Only 20 % of patients who survive are independent within 6 months. Factors such as chronic hypertension, cerebral amyloid angiopathy, and anticoagulation are commonly associated with ICH. Chronic arterial hypertension represents the major risk factor for bleeding. The incidence of hypertension-related ICH is decreasing in some regions due to improvements in the treatment of chronic hypertension. Anticoagulant-related ICH (vitamin K antagonists and the newer oral anticoagulant drugs) represents an increasing cause of ICH, currently accounting for more than 15 % of all cases. Although questions regarding the optimal medical and surgical management of ICH still remain, recent clinical trials examining hemostatic therapy, blood pressure control, and hematoma evacuation have advanced our understanding of ICH management. Timely and aggressive management in the acute phase may mitigate secondary brain injury. The initial management should include: initial medical stabilization; rapid, accurate neuroimaging to establish the diagnosis and elucidate an etiology; standardized neurologic assessment to determine baseline severity; prevention of hematoma expansion (blood pressure management and reversal of coagulopathy); consideration of early surgical intervention; and prevention of secondary brain injury. This review aims to provide a clinical approach for the practicing clinician.

Comparison of the influence of two models of mild stress on hippocampal brain-derived neurotrophin factor (BDNF) immunoreactivity in old age rats.

PubMed

Badowska-Szalewska, Ewa; Ludkiewicz, Beata; Krawczyk, Rafał; Melka, Natalia; Moryś, Janusz

2017-01-01

The way hippocampal neurons function during stress in old age (critical times of life) is dependent on brain derived neurotrophin factor (BDNF). This study examined the influence of acute and chronic forced swim (FS) or high-light open field (HL‑OF) stimulation on the density of BDNF immunoreactive (ir) neurons in the hippocampal pyramidal layers of CA1, CA2, CA3 regions and the granular layer of dentate gyrus (DG) in old (postnatal day 720; P720) Wistar Han rats. Our data showed that in comparison with non-stressed rats, acute FS caused a significant increase in the density of BDNF-ir neurons in CA2 and CA3, while acute HL-OF led to an increase in this factor in all hippocampal subfields with the exception of DG. However, the density of BDNF-ir cells remained unchanged after exposure to chronic FS or HL‑OF in the hippocampal regions in relation to the control rats. These results indicate that acute FS or HL-OF proved to be a stressor that induces an increase in the density of BDNF-ir pyramidal neurons, which was probably connected with up-regulation of HPA axis activity and short‑time memory processing of the stressful situation. Moreover, as far as the influence on BDNF-ir cells in hippocampus is concerned, chronic FS or HL-OF was not an aggravating factor for rats in the ontogenetic periods studied.

Catastrophic Health Expenditure of Chronic Diseases: Evidence from Hamadan, Iran

PubMed Central

Rezapour, Aziz; Vahedi, Sajad; Khiavi, Farzad Faraji; Esmaeilzadeh, Firooz; Javan-Noughabi, Javad; Rajabi, Abdolhalim

2017-01-01

Background: Chronic noncommunicable diseases (NCDs) could increase the risk of catastrophic health expenditure (CHE). The present study aims to analyze CHE among households with and without chronic NCDs in Hamedan. Methods: In this cross-sectional study, 780 households’ patients, who were being discharged from hospitals in Hamedan, were selected using a proportional stratified random sampling method. Required data were collected through interview and observation using World Health Organization standard questionnaire. A household with chronic NCDs is defined as the one with ≥1 chronic disease patient. Both descriptive and analytical statistics, as well as different approaches and thresholds, were used to study CHE among households. Results: The households with chronic disease had higher incidence and intensity of CHE in all approaches and threshold. This result was shown through distributive-sensitive measures. The Regression analysis revealed that lower economic status, lower household size, and high utilization of health care were associated with the CHE incidence and intensity in the households with chronic NCDs in Hamedan. Conclusions: There is a high degree of CHE were caused by chronic NCDs. By thoughtful reconsideration in health-care financing, along with addressing relevant socioeconomic factors, the health system of Iran could cope with financial adversities caused by chronic NCDs. PMID:29291041

Arformoterol Oral Inhalation

MedlinePlus

... coughing, and chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of lung diseases, which includes chronic bronchitis and emphysema). Arformoterol is in a class of medications called ...

Salmeterol Oral Inhalation

MedlinePlus

... chest tightness caused by asthma and chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema). It also is used to prevent bronchospasm (breathing ...

Formoterol Oral Inhalation

MedlinePlus

... breath, and breathing difficulties caused by chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema) in adults. Formoterol inhalation powder is also used ...

Clinical stage of infection is critical in the antemortem diagnosis of chronic wasting disease in deer and elk

USDA-ARS?s Scientific Manuscript database

Chronic wasting disease (CWD) is an efficiently transmitted spongiform encephalopathy of cervids (e.g. deer, elk, and moose), and is the only known prion disease affecting both free-ranging wildlife and captive animals. The antemortem detection of CWD and other prion diseases has proven difficult, d...

Early-Years Absenteeism Seen as Critical

ERIC Educational Resources Information Center

Sparks, Sarah D.

2010-01-01

While efforts to reduce chronic absenteeism typically focus on adolescents, experts say that the early grades are the place to start. Statistics show that rates of absenteeism in kindergarten and 1st grade can rival those in high school. An average of one in 10 pupils in grades K-12 nationwide is considered chronically absent, defined as missing…

Development of Alternatives to Chronic Ecotoxicity Tests: Predicting Early-life Stage and Endocrine-mediated Toxicity in Aquatic Vertebrate Species

EPA Science Inventory

In June 2010, the ILSI Health and Environmental Sciences Institute (HESI) with support from sanofi-aventis, NC3Rs, the Humane Society, L’Oreal, and ECVAM, held a workshop aimed at examining critical science needs related to the development of alternatives to chronic fish toxicity...

All-cause and cause-specific mortality among Black and White North Carolina state prisoners, 1995-2005

PubMed Central

Wohl, David A.; Schoenbach, Victor J.

2011-01-01

Purpose We compared mortality rates among state prisoners and other state residents to identify prisoners’ healthcare needs Methods We linked North Carolina prison records with state death records for 1995-2005 to estimate all-cause and cause-specific death rates among Black and White male prisoners aged 20-79 years, and used standardized mortality ratios (SMRs) to compare these observed deaths with the expected number based on death rates among state residents Results The all-cause SMR of Black prisoners was 0.52 (95%CI: 0.48 0.57), with fewer deaths than expected from accidents, homicides, cardiovascular disease and cancer. The all-cause SMR of White prisoners was 1.12 (95%CI: 1.01, 1.25) with fewer deaths than expected for accidents, but more deaths than expected from viral hepatitis, liver disease, cancer, chronic lower respiratory disease, and HIV. Conclusions Mortality of Black prisoners was lower than that of Black state residents for both traumatic and chronic causes of death. Mortality of White prisoners was lower than that of White state residents for accidents, but higher for several chronic causes of death. Future studies should investigate the effect of prisoners’ pre-incarceration and in-prison morbidity, the prison environment, and prison healthcare on prisoners’ patterns of mortality. PMID:21737304

Inefficient procurement processes undermine access to medicines in the Western Cape Province of South Africa.

PubMed

Magadzire, Bvudzai P; Ward, Kim; Leng, Henry M J; Sanders, David

2017-06-30

South Africa (SA) has experienced several stock-outs of life-saving medicines for the treatment of major chronic infectious and non-communicable diseases in the public sector. To identify the causes of stock-outs and to illustrate how they undermine access to medicines (ATM) in the Western Cape Province, SA. This qualitative study was conducted with a sample of over 70 key informants (frontline health workers, sub-structure and provincial health service managers). We employed the critical incident technique to identify significant occurrences in our context, the consequences of which impacted on access to medicines during a defined period. Stock-outs were identified as one such incident, and we explored when, where and why they occurred, in order to inform policy and practice. Medicines procurement is a centralised function in SA. Health service managers unanimously agreed that stock-outs resulted from the following inefficiencies at the central level: (i) delays in awarding of pharmaceutical tenders; (ii) absence of contracts for certain medicines appearing on provincial code lists; and (iii) suppliers' inability to satisfy contractual agreements. The recurrence of stock-outs had implications at multiple levels: (i) health facility operations; (ii) the Chronic Dispensing Unit (CDU), which prepacks medicines for over 300 000 public sector patients; and (iii) community-based medicines distribution systems, which deliver the CDU's prepacked medicines to non-health facilities nearer to patient homes. For instance, stock-outs resulted in omission of certain medicines from CDU parcels that were delivered to health facilities. This increased workload and caused frustration for frontline health workers who were expected to dispense omitted medicines manually. According to frontline health workers, this translated into longer waiting times for patients and associated dissatisfaction. In some instances, patients were asked to return for undispensed medication at a later date, which could potentially affect adherence to treatment and therapeutic outcomes. Stock-outs therefore undermined the intended benefits of ATM strategies. Addressing the procurement challenges, most notably timeous tender awards and supplier performance management, is critical for successful implementation of ATM strategies.

Our paper 20 years later: from acute renal failure to acute kidney injury--the metamorphosis of a syndrome.

PubMed

Druml, Wilfred; Lenz, Kurt; Laggner, Anton N

2015-11-01

More than 20 years ago we reported an analysis of a case series of elderly critically ill patients with acute kidney injury (AKI)--then termed acute renal failure. At that time, AKI was regarded as a "simple" complication, but has since undergone a fundamental change and actually has become one of the central syndromes in the critically ill patient. We have analyzed elderly patients above 65 years of age with an AKI defined as serum creatinine above 3 mg/dl corresponding to modern KDIGO stage 3, most of them requiring renal replacement therapy (RRT). Using an extremely complete data set the diagnosis differentiated the underlying disease entity, the dominant cause of AKI, acute and chronic risk factors (comorbidities). Special aspects such as severity of disease, early AKI at admission versus late AKI, early versus later start of RRT, AKI not treated by RRT in spite of indication for RRT, various measures of short-term and long-term prognosis, renal outcome, patients dying with resolved AKI, and causes of death were evaluated. Crude mortality was 61% which corresponds to modern studies with gross variation among the different subgroups. Age per se was not a determinant of survival either within the group of elderly patients or as compared to younger age groups. Despite an increase in mean age and disease severity during the observation period prognosis improved. A total of 17% of patients developed a chronic kidney disease. Long-term survival as compared to the general population was low. A look back at the last two decades illustrates a remarkable evolution or rather metamorphosis of a syndrome. AKI has evolved as a central syndrome in intensive care patients, a systemic disease process associated with multiple systemic sequels and extra-renal organ injury and exerting a pronounced effect on the course of disease and short- and long-term prognosis not only of the patient but also of the kidney. Moreover, the "non-renal-naïve" elderly patient with multiple comorbidities has become the most frequent ICU patient in industrialized nations.

Increased anal basal pressure in chronic anal fissures may be caused by overreaction of the anal-external sphincter continence reflex.

PubMed

van Meegdenburg, Maxime M; Trzpis, Monika; Heineman, Erik; Broens, Paul M A

2016-09-01

Chronic anal fissure is a painful disorder caused by linear ulcers in the distal anal mucosa. Even though it counts as one of the most common benign anorectal disorders, its precise etiology and pathophysiology remains unclear. Current thinking is that anal fissures are caused by anal trauma and pain, which leads to internal anal sphincter hypertonia. Increased anal basal pressure leads to diminished anodermal blood flow and local ischemia, which delays healing and leads to chronic anal fissure. The current treatment of choice for chronic anal fissure is either lateral internal sphincterotomy or botulinum toxin injections. In contrast to current thinking, we hypothesize that the external, rather than the internal, anal sphincter is responsible for increased anal basal pressure in patients suffering from chronic anal fissure. We think that damage to the anal mucosa leads to hypersensitivity of the contact receptors of the anal-external sphincter continence reflex, resulting in overreaction of the reflex. Overreaction causes spasm of the external anal sphincter. This in turn leads to increased anal basal pressure, diminished anodermal blood flow, and ischemia. Ischemia, finally, prevents the anal fissure from healing. Our hypothesis is supported by two findings. The first concerned a chronic anal fissure patient with increased anal basal pressure (170mmHg) who had undergone lateral sphincterotomy. Directly after the operation, while the submucosal anesthetic was still active, basal anal pressure decreased to 80mmHg. Seven hours after the operation, when the anesthetic had completely worn off, basal anal pressure increased again to 125mmHg, even though the internal anal sphincter could no longer be responsible for the increase. Second, in contrast to previous studies, recent studies demonstrated that botulinum toxin influences external anal sphincter activity and, because it is a striated muscle relaxant, it seems reasonable to presume that it affects the striated external anal sphincter, rather than the smooth internal anal sphincter. If our hypothesis is proved correct, the treatment option of lateral internal sphincterotomy should be abandoned in patients suffering from chronic anal fissures, since it fails to eliminate the cause of high anal basal pressure. Additionally, lateral internal sphincterotomy may cause damage to the anal-external sphincter continence reflex, resulting in fecal incontinence. Instead, higher doses of botulinum toxin should be administered to those patients suffering from chronic anal fissure who appeared unresponsive to lower doses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tendons – time to revisit inflammation

PubMed Central

Rees, Jonathan D; Stride, Matthew; Scott, Alex

2014-01-01

It is currently widely accepted among clinicians that chronic tendinopathy is caused by a degenerative process devoid of inflammation. Current treatment strategies are focused on physical treatments, peritendinous or intratendinous injections of blood or blood products and interruption of painful stimuli. Results have been at best, moderately good and at worst a failure. The evidence for non-infammatory degenerative processes alone as the cause of tendinopathy is surprisingly weak. There is convincing evidence that the inflammatory response is a key component of chronic tendinopathy. Newer anti-inflammatory modalities may provide alternative potential opportunities in treating chronic tendinopathies and should be explored further. PMID:23476034

Two cases of tinea ciliaris with blepharitis due to Microsporum audouinii and Trichophyton verrucosum and review of the literature.

PubMed

Sahin, Gulay Ozel; Dadaci, Zeynep; Ozer, Turkan Toka

2014-09-01

Dermatophytes are rarely taken into account among the causes of blepharitis. In our report, we describe a 69-year-old man and a 40-year-old woman with chronic blepharitis for 10 years and 4 years respectively, in whom we examined the scales and pulled eyelashes on direct microscopy and isolated Microsporum audouinii and Trichophyton verrrucosum in the culture. We emphasise that dermatophytes may play a role in the etiopathogenesis of chronic blepharitis. In chronic, treatment resistance blepharitis fungal infections may be considered as possible cause. © 2014 Blackwell Verlag GmbH.

Chronic systemic pesticide exposure reproduces features of Parkinson's disease.

PubMed

Betarbet, R; Sherer, T B; MacKenzie, G; Garcia-Osuna, M; Panov, A V; Greenamyre, J T

2000-12-01

The cause of Parkinson's disease (PD) is unknown, but epidemiological studies suggest an association with pesticides and other environmental toxins, and biochemical studies implicate a systemic defect in mitochondrial complex I. We report that chronic, systemic inhibition of complex I by the lipophilic pesticide, rotenone, causes highly selective nigrostriatal dopaminergic degeneration that is associated behaviorally with hypokinesia and rigidity. Nigral neurons in rotenone-treated rats accumulate fibrillar cytoplasmic inclusions that contain ubiquitin and alpha-synuclein. These results indicate that chronic exposure to a common pesticide can reproduce the anatomical, neurochemical, behavioral and neuropathological features of PD.

Emerging chronic non-communicable diseases in rural communities of Northern Ethiopia: evidence using population-based verbal autopsy method in Kilite Awlaelo surveillance site.

PubMed

Weldearegawi, Berhe; Ashebir, Yemane; Gebeye, Ejigu; Gebregziabiher, Tesfay; Yohannes, Mekonnen; Mussa, Seid; Berhe, Haftu; Abebe, Zerihun

2013-12-01

In countries where most deaths are outside health institutions and medical certification of death is absent, verbal autopsy (VA) method is used to estimate population level causes of death. VA data were collected by trained lay interviewers for 409 deaths in the surveillance site. Two physicians independently assigned cause of death using the International Classification of Diseases manual. In general, infectious and parasitic diseases accounted for 35.9% of death, external causes 15.9%, diseases of the circulatory system 13.4% and perinatal causes 12.5% of total deaths. Mortalities attributed to maternal causes and malnutrition were low, 0.2 and 1.5%, respectively. Causes of death varied by age category. About 22.1, 12.6 and 8.4% of all deaths of under 5-year-old children were due to bacterial sepsis of the newborn, acute lower respiratory infections such as neonatal pneumonia and prematurity including respiratory distress, respectively. For 5-15-year-old children, accidental drowning and submersion, accounting for 34.4% of all deaths in this age category, and accidental fall, accounting for 18.8%, were leading causes of death. Among 15-49-year-old adults, HIV/AIDS (16.3%) and tuberculosis (12.8%) were commonest causes of death, whereas tuberculosis and cerebrovascular diseases were major killers of those aged 50 years and above. In the rural district, mortality due to chronic non-communicable diseases was very high. The observed magnitude of death from chronic non-communicable disease is unlikely to be unique to this district. Thus, formulation of chronic disease prevention and control strategies is recommended.

Prevalence and causes of work disability among working-age U.S. adults, 2011-2013, NHIS.

PubMed

Theis, Kristina A; Roblin, Douglas W; Helmick, Charles G; Luo, Ruiyan

2018-01-01

Chronic conditions are among the major causes of work disability (WD), which is associated with lower employment, less economic activity, and greater dependence on social programs, while limiting access to the benefits of employment participation. We estimated the overall prevalence of WD among working-age (18-64 years) U.S. adults and the most common causes of WD overall and by sex. Next, we estimated the prevalence and most common causes of WD among adults with 12 common chronic conditions by sex and age. We hypothesized that musculoskeletal conditions would be among the most common causes of WD overall and for individuals with other diagnosed chronic conditions. Data were obtained from years 2011, 2012, and 2013 of the National Health Interview Survey. WD was defined by a "yes" response to one or both of: "Does a physical, mental, or emotional problem NOW keep you from working at a job or business?" and "Are you limited in the kind OR amount of work you can do because of a physical, mental or emotional problem?" Overall, 20.1 million adults (10.4% (95% CI = 10.1-10.8) of the working-age population) reported WD. The top three most commonly reported causes of WD were back/neck problems 30.3% (95% CI = 29.1-31.5), depression/anxiety/emotional problems 21.0% (19.9-22.0), and arthritis/rheumatism 18.6 (17.6-19.6). Musculoskeletal conditions were among the three most common causes of WD overall and by age- and sex-specific respondents across diagnosed chronic conditions. Quantifying the prevalence and causes of work disability by age and sex can help prioritize interventions. Published by Elsevier Inc.

Chronic Pancreatitis.

PubMed

Stram, Michelle; Liu, Shu; Singhi, Aatur D

2016-12-01

Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal ("groove") pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Addressing chronic operational issues at the W. M. Keck Observatory

NASA Astrophysics Data System (ADS)

Nordin, Tom; Matsuda, Richard

2016-07-01

The W. M. Keck Observatory (WMKO) has a good track record at addressing large critical faults which impact observing. Our performance tracking and correcting chronic minor faults has been mixed, yet this class of problems has a significant negative impact on scientific productivity and staff effectiveness. We have taken steps to address this shortcoming. This paper outlines the creation of a program to identify, categorize and rank these chronic operational issues, track them over time, and develop management options for their resolution. The success of the program at identifying these chronic operational issues and the advantages of dedicating observatory resources to this endeavor are presented.

Is exercise an alternative treatment for chronic insomnia?

PubMed Central

Passos, Giselle Soares; Poyares, Dalva Lucia Rollemberg; Santana, Marcos Gonçalves; Tufik, Sergio; de Mello, Marco Túlio

2012-01-01

The purposes of this systematic/critical review are: 1) to identify studies on the effects of exercise on chronic insomnia and sleep complaints in middle-aged and older adults and to compare the results of exercise with those obtained with hypnotic medications and 2) to discuss potential mechanisms by which exercise could promote sleep in insomniac patients. We identified studies from 1983 through 2011 using MEDLINE, SCOPUS and Web of Science. For systematic analyses, only studies assessing the chronic effects of exercise on sleep in people with sleep complaints or chronic insomnia were considered. We used the following keywords when searching for articles: insomnia, sleep, sleep complaints, exercise and physical activity. For a critical review, studies were selected on the effects of exercise and possible mechanisms that may explain the effects of exercise on insomnia. We identified five studies that met our inclusion criteria for systematic review. Exercise training is effective at decreasing sleep complaints and insomnia. Aerobic exercise has been more extensively studied, and its effects are similar to those observed after hypnotic medication use. Mechanisms are proposed to explain the effects of exercise on insomnia. There is additional documented evidence on the antidepressant and anti-anxiety effects of exercise. Exercise is effective to decrease sleep complaints and to treat chronic insomnia. Exercise presented similar results when compared with hypnotics; however, prospective studies comparing the effects of exercise with medical and non-medical treatments are warranted before including exercise as a first-line treatment for chronic insomnia are necessary. PMID:22760906

[Assistenza cardiocircolatoria. (Cardio-circulatory care)].

PubMed

Cogo, P E

2010-06-01

Mortality in pediatric cardiovascular failure is markedly improved with the advent of neonatal and pediatric intensive care and with the implementation of treatment guidelines. In 2002 the American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Shock reported mortality rates of 0%-5% in previously healthy and 10% in chronically ill children with septic shock associated with implementation of "best clinical practices". Early recognition of shock is the key to successful resuscitation in critically ill children. Often, shock results in or co-exists with myo-cardial dysfunction or acute lung injury. Recognition and appropriate management of these insults is crucial for successful outcomes. Resuscitation should be directed to restoration of tissue perfusion and normalization of cardiac and respiratory function. The underlying cause of shock should also be addressed urgently. The physiological response of individual children to shock resuscitation varies and is often unpredictable. Therefore, repeated assessments of vital parameters are needed for taking appropriate decisions. Global indices of tissue oxygen delivery help in targeting therapies more accurately. Isotonic fluids form the cornerstone of treatment and the amount required for resuscitation is based on etiologies and therapeutic response. After resuscitation has been initiated, targeted history and clinical evaluation must be performed to ascertain the cause of shock and management of co-morbidities should be implemented simultaneously. While the management of shock can be protocol based, the treatment needs to be individualized depending on the suspected etiology and therapeutic response particularly for children who suffer from congenital heart disease.

Paclitaxel-Coated Balloons: Review of a Promising Interventional Approach to Preventing Restenosis in Femoropopliteal Arteries

PubMed Central

Teleb, Mohamed; Wardi, Miraie; Gosavi, Sucheta; Said, Sarmad; Mukherjee, Debabrata

2015-01-01

Peripheral arterial disease (PAD), a major cause of morbidity and mortality worldwide, is characterized by intermittent claudication and is associated with chronic diseases such as diabetes and hypertension. The goal of treatment is to address the underlying cause and to modify risk factors. Although medical management is the first-line treatment of PAD, some individuals may have severe symptoms and require revascularization with percutaneous transluminal angioplasty with or without stent placement or surgery. Interventional approaches may, however, be associated with high prevalence of restenosis and subsequent complications such as critical limb ischemia and amputation. Drug-eluting balloons (DEBs) are a new interventional technology with the primary goal of preventing restenosis. We review the clinical trials and studies that assessed the efficacy and safety profile of DEB and will focus on the restenosis rate in femoropopliteal arteries including target lesion revascularization (TLR) and late lumen lesion (LLL) using different modalities of intervention such as stents and DEB. Average data collected from the trials reported included restenosis rate of 25%, 0.3 mm LLL, and 14% reduction in TLR with DEB versus uncoated balloons. Below the knee (BTK) only intervention studies were excluded from this review as endovascular approach is usually reserved for critical limb ischemia for BTK disease. Interventional approach to treat PAD with DEB appears to be a promising technology. Additional larger studies are needed to further define safety, efficacy, and longer term outcome with this novel technology. PMID:27231422

Role of high tibial osteotomy in chronic injuries of posterior cruciate ligament and posterolateral corner.

PubMed

Savarese, Eugenio; Bisicchia, Salvatore; Romeo, Rocco; Amendola, Annunziato

2011-03-01

High tibial osteotomy (HTO) is a surgical procedure used to change the mechanical weight-bearing axis and alter the loads carried through the knee. Conventional indications for HTO are medial compartment osteoarthritis and varus malalignment of the knee causing pain and dysfunction. Traditionally, knee instability associated with varus thrust has been considered a contraindication. However, today the indications include patients with chronic ligament deficiencies and malalignment, because an HTO procedure can change not only the coronal but also the sagittal plane of the knee. The sagittal plane has generally been ignored in HTO literature, but its modification has a significant impact on biomechanics and joint stability. Indeed, decreased posterior tibial slope causes posterior tibia translation and helps the anterior cruciate ligament (ACL)-deficient knee. Vice versa, increased tibial slope causes anterior tibia translation and helps the posterior cruciate ligament (PCL)-deficient knee. A review of literature shows that soft tissue procedures alone are often unsatisfactory for chronic posterior instability if alignment is not corrected. Since limb alignment is the most important factor to consider in lower limb reconstructive surgery, diagnosis and treatment of limb malalignment should not be ignored in management of chronic ligamentous instabilities. This paper reviews the effects of chronic posterior instability and tibial slope alteration on knee and soft tissues, in addition to planning and surgical technique for chronic posterior and posterolateral instability with HTO.

Disability Risks of Chronic Illnesses and Impairments. Disability Statistics Report 2.

ERIC Educational Resources Information Center

LaPlante, Mitchell P.

This report provides results from an investigation of comparative disability risks of specific chronic physical and mental illnesses, diseases, and impairments. National estimates are presented of the risks of chronic health conditions causing disability--including activity limitation, work disability, and need for assistance in basic life…

Fluticasone and Salmeterol Oral Inhalation

MedlinePlus

... coughing, and chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema). The combination of fluticasone and salmeterol (Advair Diskus) ...

Dysregulated LRRK2 Signaling in Response to Endoplasmic Reticulum Stress Leads to Dopaminergic Neuron Degeneration in C. elegans

PubMed Central

Yuan, Yiyuan; Cao, Pengxiu; Smith, Mark A.; Kramp, Kristopher; Huang, Ying; Hisamoto, Naoki; Matsumoto, Kunihiro; Hatzoglou, Maria; Jin, Hui; Feng, Zhaoyang

2011-01-01

Mutation of leucine-rich repeat kinase 2 (LRRK2) is the leading genetic cause of Parkinson's Disease (PD), manifested as age-dependent dopaminergic neurodegeneration, but the underlying molecular mechanisms remain unclear. Multiple roles of LRRK2 may contribute to dopaminergic neurodegeneration. Endoplasmic reticulum (ER) stress has also been linked to PD pathogenesis, but its interactive mechanism with PD genetic factors is largely unknown. Here, we used C. elegans, human neuroblastoma cells and murine cortical neurons to determine the role of LRRK2 in maintaining dopaminergic neuron viability. We found that LRRK2 acts to protect neuroblastoma cells and C. elegans dopaminergic neurons from the toxicity of 6-hydroxydopamine and/or human α-synuclein, possibly through the p38 pathway, by supporting upregulation of GRP78, a key cell survival molecule during ER stress. A pathogenic LRRK2 mutant (G2019S), however, caused chronic p38 activation that led to death of murine neurons and age-related dopaminergic-specific neurodegeneration in nematodes. These observations establish a critical functional link between LRRK2 and ER stress. PMID:21857923

Co-morbidities of COPD in primary care: frequency, relation to COPD, and treatment consequences.

PubMed

van der Molen, Thys

2010-12-01

In the Western world, chronic obstructive pulmonary disease (COPD) is predominantly caused by long-term smoking, which results in pulmonary inflammation that is often associated with systemic inflammation. A number of co-morbid conditions, such as cardiovascular disease, muscle wasting, type 2 diabetes and asthma, may coexist with COPD; these and other co-morbidities not directly related to COPD are major causes of excess morbidity and mortality. This review sets out to explore the most frequent co-morbidities in COPD and their implications for treatment. Review of the literature on co-morbidities of COPD. Co-morbidities are frequent, but often remain undiagnosed in the COPD patient. In order to provide the best possible care for people with COPD, the physician should be aware of all potential co-morbidities that may arise, and the critical role that effective management of these co-morbidities can play in improving patient outcomes. Increased awareness of the potential co-morbidities of COPD, although potentially adding to the general practitioner's work burden, may provide insights into this difficult disease state and possibly improve each individual's prospects for effective management.

Menstrual dysfunction in female athletes. A review for clinicians.

PubMed

Noakes, T D; van Gend, M

1988-03-19

A critical review of factors considered to cause menstrual dysfunction is women athletes with no overt organic cause for the abnormality is presented. Evidence suggests that although regular exercise can produce a specific change in hypothalamic-pituitary function, in particular reduced pulsatile luteinising hormone secretion, this is not associated with amenorrhoea or oligomenorrhoea in the majority of female athletes, most of whom continue to menstruate cyclically. Thus additional factors must be operative. It seems probable that severe menstrual dysfunction occurs in a specific predisposed subset of women athletes who have a particular personality type or body build and are attracted to a lifestyle including regular vigorous exercise. The biochemical basis may be related to hypothalamic, pituitary or even ovarian dysfunction possibly due to elevated levels of anti-reproductive hormones, including beta-endorphins, dopamine, prolactin and catechol oestrogens, induced by exercise; dopamine appears the most likely candidate. Chronic hypo-oestrogenic or eu-oestrogenic amenorrhoea or oligomenorrhoea may not be benign and should probably be treated in order to reduce the risk of osteoporosis or endometrial hyperplasia and adenocarcinoma.

Rapid changes in the serum total protein and globulin levels in complications caused by facultatively pathogenic Gram-negative bacteria.

PubMed

Petrás, G; Kiss, S; Juraszek, J; Merétey, K

1978-01-01

The changes in the levels of total protein and four globulin fractions were followed up throughout the entire course of complications caused by Gram-negative facultative pathogens in 37 acute cases of respiratory insufficiency accompanying different underlying illnesses and in 9 chronic, bedridden patients given artificial ventilation. At the onset of the infectious complications, in the first place in septic shock, the levels of various globulin fractions showed a decrease corresponding to a half-life of 2 to 4 days. Neither the increased catabolism, nor the protein losses by the urine and tracheal secretions offer a sufficient explanation for the escape of globulins of this extent from the plasma. It seems that this is a consequence of the increase in capillary permeability due to the effect of antigen-antibody reactions and that of endotoxin. As a result, in the critical phase of the infectious complications, at the point of culmination, e.g. in septic shock, diminished amount of different globulins is transported to the site of utilization, that is, to the inflammatory area.

Development of acute pancreatitis caused by sodium valproate in a patient with bipolar disorder on hemodialysis for chronic renal failure: a case report.

PubMed

Okayasu, Hiroaki; Shinozaki, Takahiro; Osone, Akira; Ozeki, Yuji; Shimoda, Kazutaka

2014-03-29

Cases of acute pancreatitis caused by sodium valproate (VPA) have been reported by many authors thus far. However, most of these were cases with epilepsy. Chronic renal failure is also regarded as a risk factor for acute pancreatitis. Here, we report a case of acute pancreatitis development due to VPA in a patient with bipolar disorder on hemodialysis for chronic renal failure. The patient was a 52-year-old Japanese male who was diagnosed as bipolar disorder on hemodialysis for renal failure. He was treated with VPA and manic symptoms gradually stabilized. However, the patient complained of severe abdominal pain. Blood amylase was found to be markedly high, and computed tomography revealed pancreatomegaly and an increased amount of peripancreatic fat. Hence, we diagnosed the case as acute pancreatitis caused by VPA. We discontinued oral medication, and he was started on a pancreatic enzyme inhibitor, antibiotics, and transfusion, and he showed improvement. It has been reported that acute pancreatitis induced by VPA is caused by intermediate metabolites of VPA. We consider that patients with renal failure are prone to pancreatitis caused by VPA because of the accumulation of these intermediate metabolites. We need close monitoring for serious adverse effects such as pancreatitis when we prescribe VPA to patients with bipolar disorder on hemodialysis for chronic renal failure, although VPA is safer than other mood stabilizers.

Indications and outcomes for surgical treatment of patients with chronic migraine headaches caused by occipital neuralgia.

PubMed

Ducic, Ivica; Hartmann, Emily C; Larson, Ethan E

2009-05-01

Occipital neuralgia is a headache syndrome characterized by paroxysmal headaches localizing to the posterior scalp. The critical diagnostic feature is symptomatic response to local anesthetic blockade of the greater or lesser occipital nerve. Further characterization is debated in the literature regarding the diagnosis and optimal management of this condition. The authors present the largest reported series of surgical neurolysis of the greater occipital nerve in the management of occipital neuralgia. A retrospective chart review was conducted to identify 206 consecutive patients undergoing neurolysis of the greater or, less commonly, excision of the greater and/or lesser occipital nerves. A detailed description of the procedure is presented, as is the algorithm for patient selection and timing of surgery. Preoperative and postoperative visual analogue pain scores and migraine headache indices were measured. Success was defined as a reduction in pain of 50 percent or greater. Of 206 patients, 190 underwent greater occipital nerve neurolysis (171 bilateral). Twelve patients underwent greater and lesser occipital nerve excision, whereas four underwent lesser occipital nerve excision alone. The authors found that 80.5 percent of patients experienced at least 50 percent pain relief and 43.4 percent of patients experienced complete relief of headache. Mean preoperative pain score was 7.9 +/- 1.4. Mean postoperative pain was 1.9 +/- 1.8. Minimum duration of follow-up was 12 months. There were two minor complications. Neurolysis of the greater occipital nerve appears to provide safe, durable pain relief in the majority of selected patients with chronic headaches caused by occipital neuralgia.

[Cardiac arrest in chronic metabolic alkalosis due to sodium bicarbonate abuse].

PubMed

Niewiński, Grzegorz; Korta, Teresa; Debowska, Małgorzata; Kosiński, Cezary; Kubik, Tomasz; Romanik, Wojciech; Kański, Andrzej

2008-01-01

Moderate metabolic alkalosis has not been considered as a life-threatening situation by many authors, but when it persists and pH increases above 7.65, the situation may become critical. We present a case of a 61-yr-old alcoholic male patient, who had been consuming approximately 200 g of sodium bicarbonate daily for twenty years, due to persisitent heartburn and abdominal pains. The patient was admitted to the ITU after home cardiac arrest and resuscitation. On admission he was unconscious and in respiratory distress, with a GCS of 5. Blood gases revealed that his pH was 7.64, HCO3 44 mmol L(-1), K+ 2.4 mmol L(-1)l, Cl- 44 mmol L(-1), and lactate concentration over 15 mmol L(-1). He was treated with controlled hypercapnia, up to a PaCO2 of 63 mm Hg, sedation, and administration of a large amount of chloride (864 mmol during the first day). The patient regained consciousness after 48 h, was extubated and transferred to the internal medicine department where he died 3 days later. Chronic alkali abuse can lead to various metabolic disturbances, neurologic disturbances and cardiovascular compromise. In the described case, the exact cause of cardiac arrest remained unknown, but may have been caused by alkalosis combined with hypoxia, hypokalemia and poor general condition. The extreme metabolic alkalosis (pH 7.8) could also have been enhanced by the administration of i.v. sodium bicarbonate during resuscitation. The treatment of choice in such cases should consist of vigorous chloride containing fluid resuscitation, ammonium chloride and hemodialysis.

A worldwide experience of the management of battery failures and chronic device retrieval of the Nanostim leadless pacemaker.

PubMed

Lakkireddy, Dhanunjaya; Knops, Reinoud; Atwater, Brett; Neuzil, Petr; Ip, John; Gonzalez, Elkin; Friedman, Paul; Defaye, Pascal; Exner, Derek; Aonuma, Kazutaka; Doshi, Rahul; Sperzel, Johannes; Reddy, Vivek

2017-12-01

The Nanostim leadless pacemaker (LP) met the primary endpoints in an investigational device exemption trial, and was shown to be fully retrievable percutaneously. In October 2016, St Jude Medical issued a worldwide alert of a battery malfunction that caused lost pacing output and LP communication. To report the battery failure mechanism and incidence and the worldwide patient management, including device retrieval experiences. The affected LP battery is a custom lithium-carbon monofluoride cell. These were returned after failure and underwent analysis assessing electronics and battery performance. Data were collected in ongoing clinical studies when LPs were abandoned or retrieved. Of 1423 LPs implanted worldwide, there were 34 battery failures, occurring at 2.9 ± 0.4 years with no instances of associated patient injury. Analysis of returned batteries revealed an increase in battery resistance caused by insufficient electrolyte availability at the cathode/anode interface. A total of 66 of 73 retrieval attempts were successful (90.4%; implant duration range: 0.2-4.0 years). The LP docking button was inaccessible in 6 patients, and the docking button detached from the LP during retrieval in 1 patient. There was 1 case of arteriovenous fistula and another case of the LP docking button migrating into the pulmonary artery. There were also 115 non-LP retrieval patients after the advisory who received an additional pacemaker, with no adverse device-to-device interactions reported. As with standard pacers, LPs can have critical battery failures. Chronic retrieval of LPs is safe and efficacious. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Chronic kidney disease after hematopoietic stem cell transplantation

PubMed Central

Cohen, Eric P; Pais, Priya; Moulder, John E

2010-01-01

Acute and chronic kidney diseases occur after hematopoietic stem cell transplantation. These are caused by the transplant itself, and the complications of transplant. Recent estimates show that near 15% of subjects undergoing HSCT will develop CKD, which is a complication rate that can affect outcome and reduce survival. Investigation of the causes of CKD is needed, as are ways to prevent, mitigate and treat it. PMID:21146127

The duality of health technology in chronic illness: how designers envision our future.

PubMed

Lehoux, Pascale

2008-06-01

This essay critically explores the role of technological innovation in the constitution of chronic states and illness. Drawing on the co-construction of technology and society perspective, it focuses more specifically on the way in which innovation designers envisage the enhancement of the chronically ill and build certain kinds of socio-technical configuration to deal with chronic illness. Using the case of ;intelligent distance patient monitoring' as an illustration, the paper argues that technology creates as much as it solves the problem of chronic illness. Technology is recursively embedded in chronic illness and it generates dual effects: it constrains and sustains users' daily practices. Only by recognizing technology's duality and eventually transcending it will research and policy initiatives be able to deal creatively and responsibly with the design of our future health experiences.

DEP domain-containing mTOR-interacting protein suppresses lipogenesis and ameliorates hepatic steatosis and acute-on-chronic liver injury in alcoholic liver disease.

PubMed

Chen, Hanqing; Shen, Feng; Sherban, Alex; Nocon, Allison; Li, Yu; Wang, Hua; Xu, Ming-Jiang; Rui, Xianliang; Han, Jinyan; Jiang, Bingbing; Lee, Donghwan; Li, Na; Keyhani-Nejad, Farnaz; Fan, Jian-Gao; Liu, Feng; Kamat, Amrita; Musi, Nicolas; Guarente, Leonard; Pacher, Pal; Gao, Bin; Zang, Mengwei

2018-02-19

Alcoholic liver disease (ALD) is characterized by lipid accumulation and liver injury. However, how chronic alcohol consumption causes hepatic lipid accumulation remains elusive. The present study demonstrates that activation of the mechanistic target of rapamycin complex 1 (mTORC1) plays a causal role in alcoholic steatosis, inflammation, and liver injury. Chronic-plus-binge ethanol feeding led to hyperactivation of mTORC1, as evidenced by increased phosphorylation of mTOR and its downstream kinase S6 kinase 1 (S6K1) in hepatocytes. Aberrant activation of mTORC1 was likely attributed to the defects of the DEP domain-containing mTOR-interacting protein (DEPTOR) and the nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 1 (SIRT1) in the liver of chronic-plus-binge ethanol-fed mice and in the liver of patients with ALD. Conversely, adenoviral overexpression of hepatic DEPTOR suppressed mTORC1 signaling and ameliorated alcoholic hepatosteatosis, inflammation, and acute-on-chronic liver injury. Mechanistically, the lipid-lowering effect of hepatic DEPTOR was attributable to decreased proteolytic processing, nuclear translocation, and transcriptional activity of the lipogenic transcription factor sterol regulatory element-binding protein-1 (SREBP-1). DEPTOR-dependent inhibition of mTORC1 also attenuated alcohol-induced cytoplasmic accumulation of the lipogenic regulator lipin 1 and prevented alcohol-mediated inhibition of fatty acid oxidation. Pharmacological intervention with rapamycin alleviated the ability of alcohol to up-regulate lipogenesis, to down-regulate fatty acid oxidation, and to induce steatogenic phenotypes. Chronic-plus-binge ethanol feeding led to activation of SREBP-1 and lipin 1 through S6K1-dependent and independent mechanisms. Furthermore, hepatocyte-specific deletion of SIRT1 disrupted DEPTOR function, enhanced mTORC1 activity, and exacerbated alcoholic fatty liver, inflammation, and liver injury in mice. The dysregulation of SIRT1-DEPTOR-mTORC1 signaling is a critical determinant of ALD pathology; targeting SIRT1 and DEPTOR and selectively inhibiting mTORC1-S6K1 signaling may have therapeutic potential for treating ALD in humans. (Hepatology 2018). © 2018 by the American Association for the Study of Liver Diseases.

Pain in general practice. Pain as a cause of patient-doctor contact.

PubMed

Frølund, F; Frølund, C

1986-05-01

In 1983 26 general practitioners in a Danish provincial town made a week's survey of pain as the main cause of patient-doctor contact during the day time. The population served was 45 000-50 000 persons of all ages. Coexistent pain which was not the cause of actual contact was not recorded. Out of 2 886 contacts of all causes 641 were due to pain (22% or 222/1 000 contacts). Percentages for acute and chronic pain were 61 and 39 respectively. The commonest causes of pain were musculo-skeletal (50%), visceral including cardio-vascular (20%), infectious (15%), and headaches (8%). The overall female: male ratio was 1.5: 1, but with considerable variation within the different pain categories. The ratios for acute and chronic pain were 1.4: 1 and 1.8: 1 respectively. About one hundred contacts were recorded as "problem cases" whose predominant complaints were low back pain, headaches, and visceral pain. Pain--especially chronic pain with a non-malignant cause--is a major problem in general practice. Essentially, pain is a primary health care problem and research in this field should be encouraged.

Persistent post-surgical pain and experimental pain sensitivity in the Tromsø study: comorbid pain matters.

PubMed

Johansen, Aslak; Schirmer, Henrik; Stubhaug, Audun; Nielsen, Christopher S

2014-02-01

In a large survey incorporating medical examination (N=12,981), information on chronic pain and surgery was collected, and sensitivity to different pain modalities was tested. Tolerance to the cold pressor test was analysed with survival statistics for 10,486 individuals, perceived cold pressor pain intensity was calculated for 10,367 individuals, heat pain threshold was assessed for 4,054 individuals, and pressure pain sensitivity for 4,689 individuals. Persistent post-surgical pain, defined by self-report, was associated with lower cold pressor tolerance (sex-adjusted hazard ratio=1.34, 95% confidence interval=1.08-1.66), but not when adjusting for other chronic pain. Other experimental pain modalities did not differentiate between individuals with or without post-surgical pain. Of the individuals with chronic pain (N=3352), 6.2% indicated surgery as a cause, although only 0.5% indicated surgery as the only cause. The associations found between persistent post-surgical pain and cold pressor tolerance is largely explained by the co-existence of chronic pain from other causes. We conclude that most cases of persistent post-surgical pain are coexistent with other chronic pain, and that, in an unselected post-surgical population, persistent post-surgical pain is not significantly associated with pain sensitivity when controlling for comorbid pain from other causes. A low prevalence of self-reported persistent pain from surgery attenuates statistically significant associations. We hypothesize that general chronic pain is associated with central changes in pain processing as expressed by reduced tolerance for the cold pressor test. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Sounding the alarm on chronic kidney disease in farming communities: María Isabel Rodríguez MD. Minister of health, El Salvador. Interview by Conner Gorry.

PubMed

Rodríguez, María Isabel

2013-07-01

In April 2013, a consortium of regional health ministries, nongovernmental organizations, aid agencies, clinical specialists and researchers from diverse sectors convened in San Salvador to discuss the epidemic of chronic kidney disease of unknown or non-traditional causes (CKDu) plaguing agricultural communities in Central America and beyond. The three-day meeting, where presentation of research on the clinical and epidemiological characteristics of CKDu roused significant debate, led the Pan American Health Organization to declare CKDu "a pressing and serious health problem [which] represents a burden for families, communities, health systems and society as a whole."[1] This High-level Meeting on Chronic Kidney Disease of Non-Traditional Causes in Central America (24-26 April) followed several international meetings at which Dr María Isabel Rodríguez, El Salvador's Minister of Health, presented studies on the disease burden in her country, where end-stage renal disease is the leading cause of hospital deaths. She outlined results of original scientific research by Dr Carlos Orantes (first published in MEDICC Review), that described an "elevated prevalence of chronic kidney disease, chronic renal failure and risk factors" among the patients studied, noting that "the most common [form] was chronic kidney disease of unknown cause, associated with neither diabetes nor hypertension."[2] In this interview with MEDICC Review, Dr Rodríguez discussed the gravity of the problem in Salvadoran agricultural communities; the importance of CKDu research in other countries; and the urgent need for intersectoral action and active community participation to confront and control the epidemic.

A dose for the wiser is enough: the alcohol benefits for associative learning in zebrafish.

PubMed

Chacon, Diana M; Luchiari, Ana C

2014-08-04

This study aimed to test seeking behavior caused by alcohol and the drug effects on learning in the zebrafish, Danio rerio. Three treatments were conducted: acute, chronic and withdrawal, using 0.10%, 0.25%, and 1.00% alcohol and control (0.00%) (vol/vol.%). For the drug seeking behavior, we used a place preference paradigm (shuttle box tank) before and after alcohol exposure in acute (single exposure) and chronic (7 days) treatments. We observed a change in the basal preference due to the association with alcohol only for 0.25% and 1.00% doses in both acute and chronic offering, indicating an alcohol-seeking behavior after the drug exposure. For the learning task, two treatments were tested: chronic alcohol exposure (26 days including the learning period) and alcohol withdrawal (15 days of alcohol exposure before the learning period). During the learning period, fish received light stimulus followed by food in a pre-defined area of the tank for 8 consecutive days. The low dose group (0.10%) learned the task by the 3rd day both in chronic and withdrawal treatments. The higher doses (0.25% and 1.00%) caused a learning impairment in the chronic treatment group, while fish from the alcohol withdrawal treatment displayed learning on the final testing day. Therefore, we suggest that high alcohol doses impair learning and cause drug seeking behavior, even after drug exposure cessation, while low doses positively affect learning and do not cause seeking behavior. Given our results we propose that the zebrafish is a promising model for identifying active compounds, antibodies or genes which modulate the alcohol dual effects: learning improvement and reinforcing behavior. Copyright © 2014 Elsevier Inc. All rights reserved.

[Evaluation of the standard application of Delphi in the diagnosis of chronic obstructive pulmonary disease caused by occupational irritant chemicals].

PubMed

Zhao, L; Yan, Y J

2017-11-20

Objective: To investigate the problems encountered in the application of the standard (hereinafter referred to as standard) for the diagnosis of chronic obstructive pulmonary disease caused by occu-pational irritant chemicals, to provide reference for the revision of the new standard, to reduce the number of missed patients in occupational COPD, and to get rid of the working environment of those who suffer from chronic respiratory diseases due to long-term exposure to poisons., slowing the progression of the disease. Methods: Using Delphi (Delphi) Expert research method, after the senior experts to demonstrate, to under-stand the GBZ 237-2011 "occupational irritant chemicals to the diagnosis of chronic obstructive pulmonary dis-ease" standard evaluation of the system encountered problems, to seek expert advice, The problems encoun-tered during the clinical implementation of the standards promulgated in 2011 are presented. Results: Through the Delphi Expert investigation method, it is found that experts agree on the content evaluation and implemen-tation evaluation in the standard, but the operational evaluation of the standard is disputed. According to the clinical experience, the experts believe that the range of occupational irritant gases should be expanded, and the operation of the problem of smoking, seniority determination and occupational contact history should be challenged during the diagnosis. Conclusions: Since the promulgation in 2011 of the criteria for the diagnosis of chronic obstructive pulmonary disease caused by occupational stimulant chemicals, there have been some problems in the implementation process, which have caused many occupationally exposed to irritating gases to suffer from "occupational chronic respiratory Diseases" without a definitive diagnosis.

The evolution of pain management in the critically ill trauma patient: Emerging concepts from the global war on terrorism.

PubMed

Malchow, Randall J; Black, Ian H

2008-07-01

The evolution of military medical care to manage polytrauma, critically ill-wounded warriors from the greater war on terrorism has been accompanied by significant changes in the diagnosis, management, and modulation of acute and chronic trauma-related pain. A paradigm shift in pain management includes early treatment of pain at the point of injury and throughout the continuum of care with a combination of standard and novel therapeutic interventions. These concepts are important for all critical care providers because they translate to most critically ill patients, including those resulting from natural disasters. Previous authors have reported a high incidence of moderate to severe pain and poor analgesia in intensive care units associated with sleep disturbances, tachycardia, pulmonary complications, increased stress response with thromboembolic incidents, and immunosuppression, increased intensive care unit and hospital stays, and needless suffering. Although opioids have traditionally been the cornerstone of acute pain management, they have potential negative effects ranging from sedation, confusion, respiratory depression, nausea, ileus, constipation, tolerance, opioid-induced hyperalgesia as well as potential for immunosuppression. Alternatively, multimodal therapy is increasingly recognized as a critical pain management approach, especially when combined with early nutrition and ambulation, designed to improve functional recovery and decrease chronic pain conditions. Multimodal therapy encompasses a wide range of procedures and medications, including regional analgesia with continuous epidural or peripheral nerve block infusions, judicious opioids, acetaminophen, anti-inflammatory agents, anticonvulsants, ketamine, clonidine, mexiletine, antidepressants, and anxiolytics as options to treat or modulate pain at various sites of action. With a more aggressive acute pain management strategy, the military has decreased acute and chronic pain conditions, which may have application in the civilian sector as well.

Chronic musculoskeletal ankle disorders in Sri Lanka.

PubMed

Weerasekara, Ishanka; Hiller, Claire E

2017-05-25

Musculoskeletal disorders of the lower extremities are commonly affected by chronicity and disability. One of the most commonly affected areas is the ankle. Epidemiological information is limited for chronic musculoskeletal ankle disorders in the general community, particularly in the developing world. This study aimed to determine the prevalence and impact of chronic musculoskeletal ankle disorders in the Sri Lankan community. A cross-sectional stratified random sample of people (n = 1000) aged 18 to 85 years in Sri Lanka was undertaken by questionnaire in the general community setting. Of those questionnaires, 827 participants provided data. Point prevalence for no history of ankle injury or ankle disorders, history of ankle injuries without chronic ankle disorders, and chronic ankle disorders were obtained. Point prevalence of chronic musculoskeletal disorders and causes for chronicity was evaluated. There were 448 (54.2%) participants with no ankle disorders, 164 (19.8%) with a history of ankle injury but no chronic disorders, and 215 (26.0%) with chronic ankle disorders. The major component of chronic ankle disorders was musculoskeletal disorders (n = 113, 13.7% of the total sample), most of which were due to ankle injury (n = 80, 9.7% of the total). Sprains were responsible for 17.7% of the total ankle injuries. Arthritis was the other main cause for chronicity of ankle disorders with 4% of total participants (n = 33). Almost 14% of the Sri Lankan community was affected by chronic musculoskeletal ankle disorders. The majority were due to a previous ankle injury, and arthritis. Most people had to limit or change their physical activity because of the chronic ankle disorder. A very low utility of physiotherapy services was observed.

Primary ciliary dyskinesia caused by homozygous mutation in DNAL1, encoding dynein light chain 1.

PubMed

Mazor, Masha; Alkrinawi, Soliman; Chalifa-Caspi, Vered; Manor, Esther; Sheffield, Val C; Aviram, Micha; Parvari, Ruti

2011-05-13

In primary ciliary dyskinesia (PCD), genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, randomization of left-right body asymmetry, and, frequently, male infertility. The most frequent defects involve outer and inner dynein arms (ODAs and IDAs) that are large multiprotein complexes responsible for cilia-beat generation and regulation, respectively. Although it has long been suspected that mutations in DNAL1 encoding the ODA light chain1 might cause PCD such mutations were not found. We demonstrate here that a homozygous point mutation in this gene is associated with PCD with absent or markedly shortened ODA. The mutation (NM_031427.3: c.449A>G; p.Asn150Ser) changes the Asn at position150, which is critical for the proper tight turn between the β strand and the α helix of the leucine-rich repeat in the hydrophobic face that connects to the dynein heavy chain. The mutation reduces the stability of the axonemal dynein light chain 1 and damages its interactions with dynein heavy chain and with tubulin. This study adds another important component to understanding the types of mutations that cause PCD and provides clinical information regarding a specific mutation in a gene not yet known to be associated with PCD. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Chronic Enhancement of CREB Activity in the Hippocampus Interferes with the Retrieval of Spatial Information

ERIC Educational Resources Information Center

Viosca, Jose; Malleret, Gael; Bourtchouladze, Rusiko; Benito, Eva; Vronskava, Svetlana; Kandel, Eric R.; Barco, Angel

2009-01-01

The activation of cAMP-responsive element-binding protein (CREB)-dependent gene expression is thought to be critical for the formation of different types of long-term memory. To explore the consequences of chronic enhancement of CREB function on spatial memory in mammals, we examined spatial navigation in bitransgenic mice that express in a…

High inorganic phosphate causes DNMT1 phosphorylation and subsequent fibrotic fibroblast activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Xiaoying; Department of Cardiology and Pneumology, Göttingen University Medical Center, Georg August University, Göttingen; Xu, Xingbo

Phosphate is an essential constituent of critical cellular functions including energy metabolism, nucleic acid synthesis and phosphorylation-dependent cell signaling. Increased plasma phosphate levels are an independent risk factor for lowered life-expectancy as well as for heart and kidney failure. Nevertheless, direct cellular effects of elevated phosphate concentrations within the microenvironment are poorly understood and have been largely neglected in favor of phosphor-regulatory hormones. Because interstitial fibrosis is the common determinant of chronic progressive kidney disease, and because fibroblasts are major mediators of fibrogenesis, we here explored the effect of high extracellular phosphate levels on renal fibroblasts. We demonstrate that highmore » inorganic phosphate directly induces fibrotic fibroblast activation associated with increased proliferative activity, increased expression of α-smooth muscle actin and increased synthesis of type I collagen. We further demonstrate that such fibroblast activation is dependent on phosphate influx, aberrant phosphorylation of DNA methyltransferase DNMT1 and aberrant CpG island promoter methylation. In summary, our studies demonstrate that elevated phosphate concentrations induce pro-fibrotic fibroblast activation independent of phospho-regulatory hormones. - Highlights: • We exposed human kidney fibroblasts to media containing 1 mM or 3 mM phosphate. • Increased phosphate influx causes phosphorylation of DNA methyltransferase Dnmt1. • Phosphorylated Dnmt1 causes promoter methylation and transcriptional silencing of RASAL1. • Depletion of RASAL1 causes increased intrinsic Ras-GTP activity and fibroblast activation. • Inorganic phosphate causes fibroblast activation independent of phospho-regulatory hormones.« less

Cigarette smoke condensate induces differential expression and promoter methylation profiles of critical genes involved in lung cancer in NL-20 lung cells in vitro: short-term and chronic exposure.

PubMed

Word, Beverly; Lyn-Cook, Lascelles E; Mwamba, Bibi; Wang, Honggang; Lyn-Cook, Beverly; Hammons, George

2013-01-01

Establishing early diagnostic markers of harm is critical for effective prevention programs and regulation of tobacco products. This study examined effects of cigarette smoke condensate (CSC) on expression and promoter methylation profile of critical genes (DAPK, ECAD, MGMT, and RASSF1A) involved in lung cancer development in different human lung cell lines. NL-20 cells were treated with 0.1-100 μg/ml of CSC for 24 to 72 hrs for short-term exposures. DAPK expression or methylation status was not significantly affected. However, CSC treatment resulted in changes in expression and promoter methylation profile of ECAD, MGMT, and RASSF1A. For chronic studies, cells were exposed to 1 or 10 μg/ml CSC up to 28 days. Cells showed morphological changes associated with transformation and changes in invasion capacities and global methylation status. This study provides critical data suggesting that epigenetic changes could serve as an early biomarker of harm due to exposure to cigarette smoke.

A cross-sectional observational study to assess inhaler technique in Saudi hospitalized patients with asthma and chronic obstructive pulmonary disease

PubMed Central

Ammari, Maha Al; Sultana, Khizra; Yunus, Faisal; Ghobain, Mohammed Al; Halwan, Shatha M. Al

2016-01-01

Objectives: To assess the proportion of critical errors committed while demonstrating the inhaler technique in hospitalized patients diagnosed with asthma and chronic obstructive pulmonary disease (COPD). Methods: This cross-sectional observational study was conducted in 47 asthmatic and COPD patients using inhaler devices. The study took place at King Abdulaziz Medical City, Riyadh, Saudi Arabia between September and December 2013. Two pharmacists independently assessed inhaler technique with a validated checklist. Results: Seventy percent of patients made at least one critical error while demonstrating their inhaler technique, and the mean number of critical errors per patient was 1.6. Most patients used metered dose inhaler (MDI), and 73% of MDI users and 92% of dry powder inhaler users committed at least one critical error. Conclusion: Inhaler technique in hospitalized Saudi patients was inadequate. Health care professionals should understand the importance of reassessing and educating patients on a regular basis for inhaler technique, recommend the use of a spacer when needed, and regularly assess and update their own inhaler technique skills. PMID:27146622

Low Level Laser Therapy for chronic knee joint pain patients.

PubMed

Nakamura, Takashi; Ebihara, Satoru; Ohkuni, Ikuko; Izukura, Hideaki; Harada, Takashi; Ushigome, Nobuyuki; Ohshiro, Toshio; Musha, Yoshiro; Takahashi, Hiroshi; Tsuchiya, Kazuaki; Kubota, Ayako

2014-12-27

Chronic knee joint pain is one of the most frequent complaints which is seen in the outpatient clinic in our medical institute. In previous studies we have reported the benefits of low level laser therapy (LLLT) for chronic pain in the shoulder joints, elbow, hand, finger and the lower back. The present study is a report on the effects of LLLT for chronic knee joint pain. Over the past 5 years, 35 subjects visited the outpatient clinic with complaints of chronic knee joint pain caused by the knee osteoarthritis-induced degenerative meniscal tear. They received low level laser therapy. A 1000 mW semi-conductor laser device was used to deliver 20.1 J/cm(2) per point in continuous wave at 830nm, and four points were irradiated per session (1 treatment) twice a week for 4 weeks. A visual analogue scale (VAS) was used to determine the effects of LLLT for the chronic pain and after the end of the treatment regimen a significant improvement was observed (p<0.001). After treatment, no significant differences were observed in the knee joint range of motion. Discussions with the patients revealed that it was important for them to learn how to avoid postures that would cause them knee pain in everyday life in order to have continuous benefits from the treatment. The present study demonstrated that 830 nm LLLT was an effective form of treatment for chronic knee pain caused by knee osteoarthritis. Patients were advised to undertake training involving gentle flexion and extension of the knee.

Chronic constipation: an evidence-based review.

PubMed

Leung, Lawrence; Riutta, Taylor; Kotecha, Jyoti; Rosser, Walter

2011-01-01

Chronic constipation is a common condition seen in family practice among the elderly and women. There is no consensus regarding its exact definition, and it may be interpreted differently by physicians and patients. Physicians prescribe various treatments, and patients often adopt different over-the-counter remedies. Chronic constipation is either caused by slow colonic transit or pelvic floor dysfunction, and treatment differs accordingly. To update our knowledge of chronic constipation and its etiology and best-evidence treatment, information was synthesized from articles published in PubMed, EMBASE, and Cochrane Database of Systematic Reviews. Levels of evidence and recommendations were made according to the Strength of Recommendation taxonomy. The standard advice of increasing dietary fibers, fluids, and exercise for relieving chronic constipation will only benefit patients with true deficiency. Biofeedback works best for constipation caused by pelvic floor dysfunction. Pharmacological agents increase bulk or water content in the bowel lumen or aim to stimulate bowel movements. Novel classes of compounds have emerged for treating chronic constipation, with promising clinical trial data. Finally, the link between senna abuse and colon cancer remains unsupported. Chronic constipation should be managed according to its etiology and guided by the best evidence-based treatment.

Physical Activity Protects the Human Brain against Metabolic Stress Induced by a Postprandial and Chronic Inflammation.

PubMed

Pruimboom, Leo; Raison, Charles L; Muskiet, Frits A J

2015-01-01

In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often appreciated that chronic inflammation may also promote a sedentary lifestyle, which in turn causes chronic inflammation. Given that even minor increases in chronic inflammation reduce brain volume in otherwise healthy individuals, the bidirectional relationship between inflammation and sedentary behaviour may explain why humans have lost brain volume in the last 30,000 years and also intelligence in the last 30 years. We review evidence that lack of physical activity induces chronic low-grade inflammation and, consequently, an energy conflict between the selfish immune system and the selfish brain. Although the notion that increased physical activity would improve health in the modern world is widespread, here we provide a novel perspective on this truism by providing evidence that recovery of normal human behaviour, such as spontaneous physical activity, would calm proinflammatory activity, thereby allocating more energy to the brain and other organs, and by doing so would improve human health.

Etiology of chronic renal failure in Jenin district, Palestine.

PubMed

Abumwais, Jamal Qasem

2012-01-01

A study was conducted on chronic renal failure patients treated by medications or by hemodialysis at The Martyr Dr. Khalil Sulaiman Hospital in Jenin city, Palestine, from 1/8/2005 to 1/8/2006 to know the underlying etiology of chronic renal failure. The subjects included were 84 patients. The information was obtained from files of the patients. The diagnosis was based on medical history, laboratory tests, X-rays, CT scans, ultrasound and renal biopsies. The results showed that the three most common causes of chronic renal failure in Jenin district were diabetes mellitus (33.32%), hypertension (16.7%), and chronic glomerulonephritis (13.1%). Inherited kidney diseases formed an important percentage (17.85%) and included primary hyperoxaluria (10.71%), Alport's syndrome (5.95%), and adult polycystic kidney disease (1.19%). These results differ from what is found in most developing countries including many Arab countries where the principal causes of chronic renal failure are chronic glomerulonephritis and interstitial nephritis. The high prevalence of inherited kidney diseases in some families (primary hyperoxaluria and Alport's) syndrome may be explained by the very high prevalence of consanguineous marriage especially among cousins in these families.

Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF.

PubMed

Quail, Daniela F; Olson, Oakley C; Bhardwaj, Priya; Walsh, Logan A; Akkari, Leila; Quick, Marsha L; Chen, I-Chun; Wendel, Nils; Ben-Chetrit, Nir; Walker, Jeanne; Holt, Peter R; Dannenberg, Andrew J; Joyce, Johanna A

2017-08-01

Obesity is associated with chronic, low-grade inflammation, which can disrupt homeostasis within tissue microenvironments. Given the correlation between obesity and relative risk of death from cancer, we investigated whether obesity-associated inflammation promotes metastatic progression. We demonstrate that obesity causes lung neutrophilia in otherwise normal mice, which is further exacerbated by the presence of a primary tumour. The increase in lung neutrophils translates to increased breast cancer metastasis to this site, in a GM-CSF- and IL5-dependent manner. Importantly, weight loss is sufficient to reverse this effect, and reduce serum levels of GM-CSF and IL5 in both mouse models and humans. Our data indicate that special consideration of the obese patient population is critical for effective management of cancer progression.

Evolution of Cardiovascular Disease During the Transition to End-Stage Renal Disease.

PubMed

Bansal, Nisha

2017-03-01

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). The rate of death in incident dialysis patients remains high. This has led to interest in the study of the evolution of CVD during the critical transition period from CKD to ESRD. Understanding the natural history and risk factors of clinical and subclinical CVD during this transition may help guide the timing of appropriate CVD therapies to improve outcomes in patients with kidney disease. This review provides an overview of the epidemiology of subclinical and clinical CVD during the transition from CKD to ESRD and discusses clinical trials of CVD therapies to mitigate risk of CVD in CKD and ESRD patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Heat stress and public health: a critical review.

PubMed

Kovats, R Sari; Hajat, Shakoor

2008-01-01

Heat is an environmental and occupational hazard. The prevention of deaths in the community caused by extreme high temperatures (heat waves) is now an issue of public health concern. The risk of heat-related mortality increases with natural aging, but persons with particular social and/or physical vulnerability are also at risk. Important differences in vulnerability exist between populations, depending on climate, culture, infrastructure (housing), and other factors. Public health measures include health promotion and heat wave warning systems, but the effectiveness of acute measures in response to heat waves has not yet been formally evaluated. Climate change will increase the frequency and the intensity of heat waves, and a range of measures, including improvements to housing, management of chronic diseases, and institutional care of the elderly and the vulnerable, will need to be developed to reduce health impacts.

Prevention and treatment of relapse after stem cell transplantation in lymphoid malignancies.

PubMed

Sureda, Anna; Dreger, Peter; Bishop, Michael R; Kroger, Nicolaus; Porter, David L

2018-05-24

Relapse is now the major cause of treatment failure after allogeneic HSCT (alloHSCT). Many novel strategies to address this critical issue are now being developed and tested. At the 3rd International Workshop on Biology, Prevention, and Treatment of Relapse held in Hamburg, Germany in November 2016, international experts presented and discussed recent developments in the field. Some approaches may be applicable to a wide range of patients after transplant, whereas some may be very disease-specific. We present a report from the session dedicated to issues related to prevention and treatment of relapse of lymphoid malignancies after alloHSCT. This session included detailed reviews as well as forward-looking commentaries that focused on Hodgkin lymphoma, chronic lymphocytic leukemia and mantle cell lymphoma, diffuse large cell and follicular lymphoma, and multiple myeloma.

Categorizing food-related illness: Have we got it right?

PubMed

Manning, Louise

2017-06-13

Since the 1950s food safety hazards have been categorized simply as (micro) biological, chemical or physical hazards with no clear differentiation between those that cause acute and chronic harm. Indeed international risk assessment methods, including hazard analysis critical control point (HACCP) use these criteria. However, the spectrum of food related illness continues to grow now encompassing food allergy and intolerance, obesity, type 2 diabetes, stroke, heart disease, cancer as well as food poisoning, foodborne illness and food contamination. Therefore over a half-century later is this the time to redefine the spectrum of what constitutes food related illness? This paper considers whether such "redefinition" of food related intoxicating and infectious agents would provide more targeted policy instruments and lead to better risk assessment and thus mitigation of such risk within the food supply chain.

Bruton's Tyrosine Kinase: From X-Linked Agammaglobulinemia Toward Targeted Therapy for B-Cell Malignancies

PubMed Central

Ponader, Sabine; Burger, Jan A.

2014-01-01

Discovery of Bruton's tyrosine kinase (BTK) mutations as the cause for X-linked agammaglobulinemia was a milestone in understanding the genetic basis of primary immunodeficiencies. Since then, studies have highlighted the critical role of this enzyme in B-cell development and function, and particularly in B-cell receptor signaling. Because its deletion affects mostly B cells, BTK has become an attractive therapeutic target in autoimmune disorders and B-cell malignancies. Ibrutinib (PCI-32765) is the most advanced BTK inhibitor in clinical testing, with ongoing phase III clinical trials in patients with chronic lymphocytic leukemia and mantle-cell lymphoma. In this article, we discuss key discoveries related to BTK and clinically relevant aspects of BTK inhibitors, and we provide an outlook into clinical development and open questions regarding BTK inhibitor therapy. PMID:24778403

Percutaneous Mesocaval Shunt Creation in a Patient with Chronic Portal and Superior Mesenteric Vein Thrombosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bercu, Zachary L., E-mail: zachary.bercu@mountsinai.org; Sheth, Sachin B., E-mail: sachinsheth@gmail.com; Noor, Amir, E-mail: amir.noor@gmail.com

The creation of a transjugular intrahepatic portosystemic shunt (TIPS) is a critical procedure for the treatment of recurrent variceal bleeding and refractory ascites in the setting of portal hypertension. Chronic portal vein thrombosis remains a relative contraindication to conventional TIPS and options are limited in this scenario. Presented is a novel technique for management of refractory ascites in a patient with hepatitis C cirrhosis and chronic portal and superior mesenteric vein thrombosis secondary to schistosomiasis and lupus anticoagulant utilizing fluoroscopically guided percutaneous mesocaval shunt creation.

Effects of chronic iTBS-rTMS and enriched environment on visual cortex early critical period and visual pattern discrimination in dark-reared rats.

PubMed

Castillo-Padilla, Diana V; Funke, Klaus

2016-01-01

Early cortical critical period resembles a state of enhanced neuronal plasticity enabling the establishment of specific neuronal connections during first sensory experience. Visual performance with regard to pattern discrimination is impaired if the cortex is deprived from visual input during the critical period. We wondered how unspecific activation of the visual cortex before closure of the critical period using repetitive transcranial magnetic stimulation (rTMS) could affect the critical period and the visual performance of the experimental animals. Would it cause premature closure of the plastic state and thus worsen experience-dependent visual performance, or would it be able to preserve plasticity? Effects of intermittent theta-burst stimulation (iTBS) were compared with those of an enriched environment (EE) during dark-rearing (DR) from birth. Rats dark-reared in a standard cage showed poor improvement in a visual pattern discrimination task, while rats housed in EE or treated with iTBS showed a performance indistinguishable from rats reared in normal light/dark cycle. The behavioral effects were accompanied by correlated changes in the expression of brain-derived neurotrophic factor (BDNF) and atypical PKC (PKCζ/PKMζ), two factors controlling stabilization of synaptic potentiation. It appears that not only nonvisual sensory activity and exercise but also cortical activation induced by rTMS has the potential to alleviate the effects of DR on cortical development, most likely due to stimulation of BDNF synthesis and release. As we showed previously, iTBS reduced the expression of parvalbumin in inhibitory cortical interneurons, indicating that modulation of the activity of fast-spiking interneurons contributes to the observed effects of iTBS. © 2015 Wiley Periodicals, Inc.

Managing Chronic Pain in People with Learning Disabilities: A Case Study

ERIC Educational Resources Information Center

Lewis, Sarah; Bell, Dorothy; Gillanders, David

2007-01-01

Chronic pain is a prevalent, under-diagnosed problem in the learning disability population. This is in part due to communication problems, unrecognized pain behaviours and the effects of medication. As a consequence, chronic pain often goes untreated and causes ongoing distress. This paper initially describes the main research that has been…

What the Classroom Teacher Needs to Know about Children with Chronic Medical Problems.

ERIC Educational Resources Information Center

Frieman, Barry B.; Settel, Joanne

1994-01-01

Explains the causes and symptoms of four chronic diseases (asthma, diabetes, epilepsy, and sickle cell anemia) that afflict large numbers of children, and discusses specific classroom medical procedures that teachers can use to help children with these diseases. Also provides suggestions for working with parents of chronically ill children and…

Don't Do That! And Other Counseling Strategies for the Chronically Disruptive.

ERIC Educational Resources Information Center

Eyde, Donna R.; Fink, Albert H.

This monograph, designed to aid school counselors in their work with students and classroom teachers, reviews the multiple causes of school disturbance and the varied needs of students labeled chronically disruptive. The distinction between chronic disrupters and students with emotional problems is discussed; related issues of school violence,…

Eating Order: A 13-Week Trust Model Class for Dieting Casualties

ERIC Educational Resources Information Center

Jackson, Elizabeth G.

2008-01-01

Chronic dieting distorts eating behaviors and causes weight escalation. Desperation about losing weight results in pursuit of extreme weight loss measures. Instead of offering yet another diet, nutrition educators can teach chronic dieters (dieting casualties) to develop eating competence. Eating Order, a 13-week class for chronic dieters based on…

[PATHOPHYSIOLOGY OF THE CARDIORENAL SYNDROME].

PubMed

Balint, I; Vučak, J; Bašić-Marković, N; Klarić, D; Šakić, V Amerl

2016-12-01

Cardiorenal syndrome, a complex pathophysiological disorder of both the heart and kidneys, is a condition in which acute or chronic damage to one organ can lead to acute or chronic dysfunction of the other organ. Depending on primary organ dysfunction and disease duration, there are five different types of cardiorenal syndrome. Type 1 cardiorenal syndrome (acute cardiorenal syndrome) is defined as acute kidney injury caused by sudden decrease in heart function. Type 2 cardiorenal syndrome (chronic cardiorenal syndrome) refers to chronic kidney disease linked to chronic heart failure. Type 3 cardiorenal syndrome (acute renocardial syndrome) is caused by acute kidney injury that leads to heart failure. Type 4 cardiorenal syndrome (chronic renocardial syndrome) includes chronic heart failure due to chronic kidney disease. Type 5 cardiorenal syndrome (secondary cardiorenal syndrome) is reversible or irreversible condition marked by simultaneous heart and kidney insufficiency, as a result of multiorgan disease such as sepsis, diabetes mellitus, sarcoidosis, amyloidosis, etc. The pathophysiological patterns of cardiorenal syndrome are extremely complicated. Despite numerous publications, perplexed physiological, biochemical and hormonal disturbances as parts of the main pathogenic mechanisms of cardiorenal syndrome remain obscure. Even though there are guidelines for the treatment of patients with heart failure and chronic kidney disease, similar guidelines for the treatment of cardiorenal syndrome are lacking. In everyday practice, it is crucial to diagnose cardiorenal syndrome and use all diagnostic and therapeutic procedures available to prevent or alleviate kidney and heart failure.

[Influence of smoking and industrial air pollutants on respiratory health of nickel industry workers].

PubMed

Shilov, V V; Siurin, S A

2015-01-01

Studies covered respiratory health of 1530 workers of nickel industry, among which were 796 (52.0%) smokers. Findings are that tobacco smoke combined with nickel industry hazards cause potentized negative effects in respiratory organs, with earlier and more frequent chronic bronchitis. For isolated influence of these factors, chronic bronchitis risk is higher from exposure to tobacco smoke vs. occupational hazards (OR = 2.48; DI 1.49-4.13). Chronic obstructive lung disease development in nickel industry workers is caused by smoking. Industrial air pollutants appeared to have no potentizing effect on COLD formation, as well as on toxic pneumosclerosis formation.

[The state of the art research findings on the relationship between chronic periodontitis and Alzheimer's disease: a review].

PubMed

Qian, X S; Ge, S

2018-04-09

Along with the development of periodontal medicine, there is a growing number of evidence showing that periodontitis could influence systemic health. Periodontitis is a chronic inflammatory disease caused by microbial infection mediated by dental plaque. Periodontal pathogenic microorganisms and its toxic products can disseminate through the blood stream or may cause the host immune response, which may lead to pathological changes of cerebral vessels and brain tissues to establish connection with Alzheimer's disease (AD). AD is a progressive neurodegenerative disease characterized by progressive memory loss, language and cognitive dysfunction. This article reviewed the association between chronic periodontitis and AD.

Lung Metastases from Bile Duct Adenocarcinoma Mimicking Chronic Airway Infection and Causing Diagnostic Difficulty.

PubMed

Sato, Mitsuo; Okachi, Shotaro; Fukihara, Jun; Shimoyama, Yoshie; Wakahara, Keiko; Sakakibara, Toshihiro; Hase, Tetsunari; Onishi, Yasuharu; Ogura, Yasuhiro; Maeda, Osamu; Hasegawa, Yoshinori

2018-05-15

We herein report a case of lung metastases with unusual radiological appearances that mimicked those of chronic airway infection, causing diagnostic difficulty. A 60-year-old woman who underwent liver transplantation from a living donor was incidentally diagnosed with bile duct adenocarcinoma after a histopathological analysis of her explanted liver. Six months later, chest computed tomography (CT) revealed bilateral bronchogenic dissemination that had gradually worsened, suggesting chronic airway infection. A biopsy with bronchoscopy from a mass lesion beyond a segmental bronchus revealed adenocarcinoma identical to that of her bile duct adenocarcinoma, leading to the diagnosis of multiple lung metastases from bile duct adenocarcinoma.

Lung Metastases from Bile Duct Adenocarcinoma Mimicking Chronic Airway Infection and Causing Diagnostic Difficulty

PubMed Central

Sato, Mitsuo; Okachi, Shotaro; Fukihara, Jun; Shimoyama, Yoshie; Wakahara, Keiko; Sakakibara, Toshihiro; Hase, Tetsunari; Onishi, Yasuharu; Ogura, Yasuhiro; Maeda, Osamu; Hasegawa, Yoshinori

2017-01-01

We herein report a case of lung metastases with unusual radiological appearances that mimicked those of chronic airway infection, causing diagnostic difficulty. A 60-year-old woman who underwent liver transplantation from a living donor was incidentally diagnosed with bile duct adenocarcinoma after a histopathological analysis of her explanted liver. Six months later, chest computed tomography (CT) revealed bilateral bronchogenic dissemination that had gradually worsened, suggesting chronic airway infection. A biopsy with bronchoscopy from a mass lesion beyond a segmental bronchus revealed adenocarcinoma identical to that of her bile duct adenocarcinoma, leading to the diagnosis of multiple lung metastases from bile duct adenocarcinoma. PMID:29279503

Mind/body dualism in medicine: The case of chronic pelvic pain without organic pathology: a critical review of the literature.

PubMed

Grace, V M

1998-01-01

Chronic pelvic pain in the absence of organic pathology identifiable in medical terms is considered one of the most perplexing conditions that gynecologists confront. A critical analysis of the medical, psychiatric, and psychological literature on chronic pelvic pain without organic pathology reveals that the dichotomous construct of mind and body underpinning medical research and understanding is a barrier to the successful diagnosis and treatment of this condition, and indeed to the productive engagement of the health professional with the patient. The strict duality of the condition's etiology being understood in either physiological or psychogenic terms has been questioned at times over the last 40 years, but only recently has an "integrative model" been proposed. However, it is argued here that although the development of a multidisciplinary approach is important, only a radical deconstruction of the medical paradigm will truly address the problem and enable a real change in practice.

Severe chronic hepatitis secondary to prolonged use of ecstasy and cocaine.

PubMed

Payancé, Audrey; Scotto, Béatrice; Perarnau, Jean-Marc; de Muret, Anne; Bacq, Yannick

2013-11-01

Severe acute hepatotoxicity is a well known complication following the ingestion of ecstasy (3,4-methylenedioxymethamphetamine [MDMA] ecstasy). Hepatic dysfunction has also been reported after acute cocaine intoxication. However, chronic hepatitis after prolonged use of ecstasy and/or cocaine has rarely been reported. We report the case of a 27-year-old woman hospitalized with edema, ascites and severe liver failure (prothrombin rate 33%), following the use of ecstasy and cocaine over the previous 9 months. Clinical, biological, radiological and pathology findings were recorded at admission and over 8 years' follow-up. Liver biopsy showed architectural distortion caused by bridging fibrosis, proliferation of cholangioles, and lesions of active interface hepatitis. Other causes of acute and chronic liver disease were excluded. Magnetic resonance imaging showed marked liver fibrosis. After withdrawal of both substances clinical examination and liver function tests progressively normalized. Long-term monitoring with magnetic resonance imaging showed progressive regression of fibrosis. Use of ecstasy and cocaine may cause chronic hepatitis leading to marked liver fibrosis, which may regress after withdrawal of both substances. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Analysis of bronchial biopsies in chronic cough.

PubMed

Macedo, Patricia; Zhang, Qingling; Saito, Junpei; Liang, Zhike; Ffolkes, Lorrette; Nicholson, Andrew G; Chung, Kian Fan

2017-06-01

Chronic cough is commonly associated with asthma, gastro-oesophageal reflux disease and postnasal drip, but in a significant proportion, no associated cause can be found. We determined whether examination of bronchial biopsies would be useful in determining the cause associated with chronic cough. 100 consecutive patients referred to a specialist cough clinic underwent a systematic assessment including a fiberoptic bronchoscopy for bronchial biopsies. In 38 patients, treatment of associated causes led to amelioration of cough ('explained') and in 62, there was no association or improvement ('idiopathic'). The latter group had a longer duration of cough, a lower FeNO levels and a more sensitive capsaicin cough response, with an increase in basement membrane thickness with no differences in goblet cell hyperplasia and seromucinous hyperplasia, and in lymphocyte, neutrophil and eosinophil counts. The duration of cough was inversely correlated with the degree of neutrophil infiltration. We conclude that pathological examination of bronchial biopsies is unlikely to be useful in the diagnosis of chronic cough in non-smokers. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hemifacial Pain and Hemisensory Disturbance Referred from Occipital Neuralgia Caused by Pathological Vascular Contact of the Greater Occipital Nerve

PubMed Central

Choi, Jin-gyu

2017-01-01

Here we report a unique case of chronic occipital neuralgia caused by pathological vascular contact of the left greater occipital nerve. After 12 months of left-sided, unremitting occipital neuralgia, a hypesthesia and facial pain developed in the left hemiface. The decompression of the left greater occipital nerve from pathological contacts with the occipital artery resulted in immediate relief for hemifacial sensory change and facial pain, as well as chronic occipital neuralgia. Although referral of pain from the stimulation of occipital and cervical structures innervated by upper cervical nerves to the frontal head of V1 trigeminal distribution has been reported, the development of hemifacial sensory change associated with referred trigeminal pain from chronic occipital neuralgia is extremely rare. Chronic continuous and strong afferent input of occipital neuralgia caused by pathological vascular contact with the greater occipital nerve seemed to be associated with sensitization and hypersensitivity of the second-order neurons in the trigeminocervical complex, a population of neurons in the C2 dorsal horn characterized by receiving convergent input from dural and cervical structures. PMID:28331643

Hemifacial Pain and Hemisensory Disturbance Referred from Occipital Neuralgia Caused by Pathological Vascular Contact of the Greater Occipital Nerve.

PubMed

Son, Byung-Chul; Choi, Jin-Gyu

2017-01-01

Here we report a unique case of chronic occipital neuralgia caused by pathological vascular contact of the left greater occipital nerve. After 12 months of left-sided, unremitting occipital neuralgia, a hypesthesia and facial pain developed in the left hemiface. The decompression of the left greater occipital nerve from pathological contacts with the occipital artery resulted in immediate relief for hemifacial sensory change and facial pain, as well as chronic occipital neuralgia. Although referral of pain from the stimulation of occipital and cervical structures innervated by upper cervical nerves to the frontal head of V1 trigeminal distribution has been reported, the development of hemifacial sensory change associated with referred trigeminal pain from chronic occipital neuralgia is extremely rare. Chronic continuous and strong afferent input of occipital neuralgia caused by pathological vascular contact with the greater occipital nerve seemed to be associated with sensitization and hypersensitivity of the second-order neurons in the trigeminocervical complex, a population of neurons in the C2 dorsal horn characterized by receiving convergent input from dural and cervical structures.

Effects of low-dose acetylsalicylic acid and atherosclerotic vascular diseases on the outcome in patients with severe sepsis or septic shock.

PubMed

Otto, Gordon Philipp; Sossdorf, Maik; Boettel, Janina; Kabisch, Björn; Breuel, Hannes; Winning, Johannes; Lösche, Wolfgang

2013-01-01

Sepsis and its sequelae of multiple organ failure is one of the leading causes of death in the industrial countries. Several studies have shown that patients who are treated with low-dose acetyl salicylic acid (ASA) for secondary prevention of atherothrombosis may have a lower risk to develop organ failure in the case of critical illness. The benefit of ASA is probably due to an inhibition of platelet activation as well as an increase in the formation of anti-inflammatory lipoxin A4. On the other hand, the effect of ASA could be - at least partially - an indirect one, caused by atherosclerotic vascular diseases as the cause of ASA treatment. Atherosclerosis is considered as a moderate systemic inflammation and we hypothesise that this chronic condition could have an impact on the outcome in sepsis. To get more information on the benefit of ASA in critically ill patients and on possible interference with atherosclerotic vascular diseases, we analysed the medical records of 886 septic patients who were admitted to the surgical intensive care unit (ICU) of a university hospital. Logistic regression analysis indicated that patients who were treated during the ICU stay with ASA (100 mg/d) had a significantly lower mortality. Odds ratios (ORs; with 95% confidential intervals) of 0.56 (0.37-0.84) and 0.57 (0.39-0.83) were calculated for ICU and hospital mortality, respectively. In contrast, statin treatment did not have significant effect on mortality. Diagnosis of atherosclerotic vascular diseases according to ICD classification did not influence ICU mortality but lowered hospital mortality (OR = 0.71 (0.52-0.99)). Subgroup analysis provided preliminary evidence that clopidogrel when given as only anti-platelet drug may have a similar benefit as ASA, but the combination of ASA and clopidogrel failed to improve the outcome. The time course of plasma fibrinogen and procalcitonin levels indicate that ASA seems to reduce the activation of haemostasis and increase the resolution of inflammation. It is concluded that prospective interventional studies should be done to test the use of ASA as novel therapeutic approach in critically ill patients.

[CHARACTERISTIC FEATURES OF PRESSURE ULCER INFECTION].

PubMed

Kučišec-Tepeš, N

2016-01-01

Pressure ulcer is a localized injury of the skin and/or adjacent tissue, usually above bone protrusions. It is a result of pressure or pressure combined with shear stress, friction and humidity. With regard to long life and delayed healing, it is a chronic wound. Pressure ulcer appears as a consequence of a combination of micro-embolism, ischemia and myonecrosis. These pathophysiological processes provide an ideal medium for proliferation of microorganisms, predominantly bacteria, and development of infection. Progression in the development of pressure ulcer is a dynamic process manifesting in phases, each of which is characterized by its own physiological-anatomical peculiarities and microbiological status. An open lesion without protective barrier becomes contaminated immediately, and, shortly afterwards, colonized by physiological microflora of the host and microbes from the environment. In the absence of preventive measures, the wound becomes critically colonized and infected. The characteristic of chronic wound/pressure ulcer is that it is colonized, and the infection develops depending on various factors in 5% to 80% of cases. The ability of microbes to cause infection depends on a number of factors, which include the pathogen and the host. The number and quantity of virulent factors, microbes, determines the virulence coefficient, which is responsible for overcoming the host’s immune system and development of infection. In the development of pressure ulcer infection, two essential microbial factors predominate, i.e. the presence of adhesin and association with biofilm. Thus, pressure ulcer infection as a chronic wound is characterized by a polymicrobial and heterogeneous population of microbes, domination of biofilm phenotype as a primary factor of virulence present in 90% of cases, phenotype hypervariability of species, and resistance or tolerance of the etiological agents to all types of biocides. The most significant virulence factor is biofilm. It is a corporative community of microbes with a clear architecture managed by quorum sensing molecules. It is through them that the communication between species takes place, the phenotype and virulence change, and resistance develops at the level of genome. The formation of biofilm takes place in several stages, and the speed is measured in hours. Microorganisms in the biofilm are protected from the action of the host’s immune system and, likewise, they are tolerant or resistant to antibiotics, antiseptics, and stress. Bacteria causing pressure ulcer infection are characterized as opportunistic, but also primarily pathogenic. The dominance and combination of species depend on the duration, localization and stage of pressure ulcer. The predominant etiological agents are Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa and Peptostreptococcus spp. Nowadays, multiple-resistant strains predominate, such as MRSA, Acinetobacter spp. and Pseudomonas spp. A chronic wound such as pressure ulcer is ideal for the development of infection, especially if targeted preventive measures are not applied. The diagnosis of infection is complex and is based on the combination of primary and secondary clinical symptoms, tissue in the wound, status of the wound environment, inflammation markers, and results of microbiological examination of targeted samples – biopsies, which are the gold standard. In reaching the diagnosis of infection, it is crucial to differentiate critical colonization from deep tissue infection, which is based on clinical criteria called NERDS-STONEES. The frequency of pressure ulcer infection is 5% to 80%, and biofilm is present in 90% of cases. Due knowledge of the epidemiology of pressure ulcer and follow up of complications such as infection make the basis for the understanding of chronic wound, efforts to improve necessary care, prevention of development and application of a combination of treatment strategies.

Hemodynamic and tubular changes induced by contrast media.

PubMed

Caiazza, Antonella; Russo, Luigi; Sabbatini, Massimo; Russo, Domenico

2014-01-01

The incidence of acute kidney injury induced by contrast media (CI-AKI) is the third cause of AKI in hospitalized patients. Contrast media cause relevant alterations both in renal hemodynamics and in renal tubular cell function that lead to CI-AKI. The vasoconstriction of intrarenal vasculature is the main hemodynamic change induced by contrast media; the vasoconstriction is accompanied by a cascade of events leading to ischemia and reduction of glomerular filtration rate. Cytotoxicity of contrast media causes apoptosis of tubular cells with consequent formation of casts and worsening of ischemia. There is an interplay between the negative effects of contrast media on renal hemodynamics and on tubular cell function that leads to activation of renin-angiotensin system and increased production of reactive oxygen species (ROS) within the kidney. Production of ROS intensifies cellular hypoxia through endothelial dysfunction and alteration of mechanisms regulating tubular cells transport. The physiochemical characteristics of contrast media play a critical role in the incidence of CI-AKI. Guidelines suggest the use of either isoosmolar or low-osmolar contrast media rather than high-osmolar contrast media particularly in patients at increased risk of CI-AKI. Older age, presence of atherosclerosis, congestive heart failure, chronic renal disease, nephrotoxic drugs, and diuretics may multiply the risk of CI-AKI.

Hemodynamic and Tubular Changes Induced by Contrast Media

PubMed Central

Caiazza, Antonella; Russo, Luigi; Russo, Domenico

2014-01-01

The incidence of acute kidney injury induced by contrast media (CI-AKI) is the third cause of AKI in hospitalized patients. Contrast media cause relevant alterations both in renal hemodynamics and in renal tubular cell function that lead to CI-AKI. The vasoconstriction of intrarenal vasculature is the main hemodynamic change induced by contrast media; the vasoconstriction is accompanied by a cascade of events leading to ischemia and reduction of glomerular filtration rate. Cytotoxicity of contrast media causes apoptosis of tubular cells with consequent formation of casts and worsening of ischemia. There is an interplay between the negative effects of contrast media on renal hemodynamics and on tubular cell function that leads to activation of renin-angiotensin system and increased production of reactive oxygen species (ROS) within the kidney. Production of ROS intensifies cellular hypoxia through endothelial dysfunction and alteration of mechanisms regulating tubular cells transport. The physiochemical characteristics of contrast media play a critical role in the incidence of CI-AKI. Guidelines suggest the use of either isoosmolar or low-osmolar contrast media rather than high-osmolar contrast media particularly in patients at increased risk of CI-AKI. Older age, presence of atherosclerosis, congestive heart failure, chronic renal disease, nephrotoxic drugs, and diuretics may multiply the risk of CI-AKI. PMID:24678510

Chronic Fatigue Syndrome

MedlinePlus

... is possible that two or more triggers might work together to cause the illness. How is chronic fatigue ... your family, and your health care provider should work together to decide on a plan. You should figure ...

Isotretinoin and vitiligo: can chronic cheilitis cause koebnerization?

PubMed

Garner, Michael L; McShane, Diana B; Burkhart, Craig N; Morrell, Dean S

2015-01-01

Vitiligo after trauma through koebnerization is a widely reported phenomenon. Herein we present a case of vitiligo in an area of chronic cheilitis after isotretinoin treatment. © 2015 Wiley Periodicals, Inc.

Retrospective analysis of causes of death in mountain pygmy-possums (Burramys parvus) at Healesville Sanctuary, Victoria, Australia.

PubMed

Scheelings, T F; Dobson, E C

2015-11-01

Identification and characterisation of deaths is important for the veterinary management of both wild and captive animals. It is especially important as a tool for monitoring health and disease within populations of endangered species for which little information on morbidity and mortality is known. Investigations into the causes of death and other important necropsy findings were made in a captive population of the critically endangered mountain pygmy-possum (Burramys parvus). Necropsy records from January 2000-December 2013 were reviewed for all possums that had lived and died at Healesville Sanctuary (n = 48). The average age of death of possums in this population was 4.7 years. The most common histological change in mountain pygmy-possums was varying degrees of chronic progressive kidney disease (n = 17). Of these cases, eight animals (47%) had histological changes suggesting the kidney disease was the likely cause of death. Other causes of death included neoplasia (n = 5), necrotising pancreatitis (n = 4), pneumonia (n = 2), reproductive disease (n = 2) and trauma (n = 2). No cause of death was able to be identified in 33.3% (n = 16) of cases. Hepatic lipidosis (n = 5), pneumonia (n = 2) and degenerative joint disease (n = 2) were the most common comorbidities found. Progressive renal disease, often with secondary metastatic mineralisation, appears to be a significant cause of mortality in captive mountain pygmy-possums and further investigation into its pathophysiology, antemortem diagnosis and treatment is warranted. © 2015 Australian Veterinary Association.

Epidemiology of Group B Streptococcal Disease in the United States: Shifting Paradigms

PubMed Central

Schuchat, Anne

1998-01-01

Since its emergence 25 years ago, group B streptococcus has become recognized as a cause of serious illness in newborns, pregnant women, and adults with chronic medical conditions. Heavy colonization of the genital tract with group B streptococcus also increases the risk that a woman will deliver a preterm low-birthweight infant. Early-onset infections (occurring at <7 days of age) are associated with much lower fatality than when they were first described, and their incidence is finally decreasing as the use of preventive antibiotics during childbirth increases among women at risk. New serotypes of group B streptococcus have emerged as important pathogens in adults and newborns. Clinical and laboratory practices—in obstetrics, pediatrics, and clinical microbiology—have an impact on disease and/or its prevention, and protocols established at the institutional level appear to be critical tools for the reduction of perinatal disease due to group B streptococcus. Since intrapartum antibiotics will prevent at best only a portion of the full burden of group B streptococcal disease, critical developments in vaccine evaluation, including study of polysaccharide-protein conjugate vaccines, offer the potential for enhanced prevention in the relatively near future. PMID:9665980

Interleukin-33 modulates inflammation in endometriosis.

PubMed

Miller, Jessica E; Monsanto, Stephany P; Ahn, Soo Hyun; Khalaj, Kasra; Fazleabas, Asgerally T; Young, Steven L; Lessey, Bruce A; Koti, Madhuri; Tayade, Chandrakant

2017-12-20

Endometriosis is a debilitating condition that is categorized by the abnormal growth of endometrial tissue outside the uterus. Although the pathogenesis of this disease remains unknown, it is well established that endometriosis patients exhibit immune dysfunction. Interleukin (IL)-33 is a danger signal that is a critical regulator of chronic inflammation. Although plasma and peritoneal fluid levels of IL-33 have been associated with deep infiltrating endometriosis, its contribution to the disease pathophysiology is unknown. We investigated the role of IL-33 in the pathology of endometriosis using patient samples, cell lines and a syngeneic mouse model. We found that endometriotic lesions produce significantly higher levels of IL-33 compared to the endometrium of healthy, fertile controls. In vitro stimulation of endometrial epithelial, endothelial and endometriotic epithelial cells with IL-33 led to the production of pro-inflammatory and angiogenic cytokines. In a syngeneic mouse model of endometriosis, IL-33 injections caused systemic inflammation, which manifested as an increase in plasma pro-inflammatory cytokines compared to control mice. Furthermore, endometriotic lesions from IL-33 treated mice were highly vascularized and exhibited increased proliferation. Collectively, we provide convincing evidence that IL-33 perpetuates inflammation, angiogenesis and lesion proliferation, which are critical events in the lesion survival and progression of endometriosis.

Human IL-21 and IL-21R deficiencies: two novel entities of primary immunodeficiency.

PubMed

Kotlarz, Daniel; Ziętara, Natalia; Milner, Joshua D; Klein, Christoph

2014-12-01

This review highlights the recent identification of human interleukin-21 (IL-21) and interleukin-21 receptor (IL-21R) deficiencies as novel entities of primary immunodeficiency. We recently described the first patients with IL-21R deficiency who had cryptosporidial infections associated with chronic cholangitis and liver disease. All IL-21R-deficient patients suffered from recurrent respiratory tract infections. Immunological work-up revealed impaired B cell proliferation and immunoglobulin class-switch, reduced T cell effector functions, and variable natural killer cell dysfunctions. Recently, these findings have been extended by the discovery of one patient with a mutation in the IL21 gene. This patient predominantly manifested with very early onset inflammatory bowel disease and recurrent respiratory infections. Laboratory examination showed reduced circulating B cells and impaired B cell class-switch. Human IL-21 and IL-21R deficiencies cause severe, primary immunodeficiency reminiscent of common variable immunodeficiency. Early diagnosis is critical to prevent life-threatening complications, such as secondary liver failure. In view of the critical role of IL-21 in controlling immune homeostasis, early hematopoietic stem cell transplantation might be considered as therapeutic intervention in affected children.

Chronic Exertional Compartment Syndrome

MedlinePlus

... Sometimes chronic exertional compartment syndrome is mistaken for shin splints, a more common cause of leg pain in ... such as running. If you think you have shin splints but they don't get better with self- ...

Chiari Malformation: Diagnosis

MedlinePlus

... Chronic Fatigue, Lupus, Migraines, Carpal Tunnel Syndrome and ALS (Lou Gehrig’s). These associations cause confusion to the ... Sclerosis Fibromyalgia Chronic Fatigue Lupus Migraines Carpal Tunnel ALS (Lou Gehrig’s) Milhorat’s landmark study of over 300 ...

COPD

MedlinePlus

COPD (chronic obstructive pulmonary disease) makes it hard for you to breathe. The two main types are chronic bronchitis and emphysema. The main cause of COPD is long-term exposure to substances that irritate and damage the lungs. This is ...

Chronic Urticaria: Indian Context—Challenges and Treatment Options

PubMed Central

Khan, Sujoy; Maitra, Anirban; Hissaria, Pravin; Roy, Sitesh; Padukudru Anand, Mahesh; Nag, Nalin; Singh, Harpal

2013-01-01

Urticaria is a common condition that occurs in both children and adults. Most cases have no specific allergic trigger and the aetiology of urticaria remains idiopathic and occasionally spontaneous in nature. Inappropriate advice such as avoidance of foods (milk, egg, prawn, and brinjal) is common place in certain sections of India mostly by nonspecialists that should not be routinely recommended. It is important to look for physical urticarias such as pressure urticaria in chronic cases, which may be present either alone or in combination with other causes. Autoimmune causes for chronic urticaria have been found to play an important role in a significant proportion of patients. Long-acting nonsedating antihistamines at higher than the standard doses is safe and effective. Quality of life is affected adversely in patients with chronic symptomatic urticaria and some may require multidisciplinary management. PMID:24223585