Nicotinamide Riboside and Mitochondrial Biogenesis

ClinicalTrials.gov

2018-03-15

Mitochondrial Diseases; Mitochondrial Myopathies; Progressive External Ophthalmoplegia; Progressive Ophthalmoplegia; Progressive; Ophthalmoplegia, External; Mitochondria DNA Deletion; MELAS; Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes; Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome)

Behavior of medial gastrocnemius motor units during postural reactions to external perturbations after stroke.

PubMed

Pollock, C L; Ivanova, T D; Hunt, M A; Garland, S J

2015-10-01

This study investigated the behavior of medial gastrocnemius (GM) motor units (MU) during external perturbations in standing in people with chronic stroke. GM MUs were recorded in standing while anteriorly-directed perturbations were introduced by applying loads of 1% body mass (BM) at the pelvis every 25-40s until 5% BM was maintained. Joint kinematics, surface electromyography (EMG), and force platform measurements were assessed. Although external loads caused a forward progression of the anterior-posterior centre of pressure (APCOP), people with stroke decreased APCOP velocity and centre of mass (COM) velocity immediately following the highest perturbations, thereby limiting movement velocity in response to perturbations. MU firing rate did not increase with loading but the GM EMG magnitude increased, reflecting MU recruitment. MU inter spike interval (ISI) during the dynamic response was negatively correlated with COM velocity and hip angular velocity. The GM utilized primarily MU recruitment to maintain standing during external perturbations. The lack of MU firing rate modulation occurred with a change in postural central set. However, the relationship of MU firing rate with kinematic variables suggests underlying long-loop responses may be somewhat intact after stroke. People with stroke demonstrate alterations in postural control strategies which may explain MU behavior with external perturbations. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

External validation of type 2 diabetes computer simulation models: definitions, approaches, implications and room for improvement-a protocol for a systematic review.

PubMed

Ogurtsova, Katherine; Heise, Thomas L; Linnenkamp, Ute; Dintsios, Charalabos-Markos; Lhachimi, Stefan K; Icks, Andrea

2017-12-29

Type 2 diabetes mellitus (T2DM), a highly prevalent chronic disease, puts a large burden on individual health and health care systems. Computer simulation models, used to evaluate the clinical and economic effectiveness of various interventions to handle T2DM, have become a well-established tool in diabetes research. Despite the broad consensus about the general importance of validation, especially external validation, as a crucial instrument of assessing and controlling for the quality of these models, there are no systematic reviews comparing such validation of diabetes models. As a result, the main objectives of this systematic review are to identify and appraise the different approaches used for the external validation of existing models covering the development and progression of T2DM. We will perform adapted searches by applying respective search strategies to identify suitable studies from 14 electronic databases. Retrieved study records will be included or excluded based on predefined eligibility criteria as defined in this protocol. Among others, a publication filter will exclude studies published before 1995. We will run abstract and full text screenings and then extract data from all selected studies by filling in a predefined data extraction spreadsheet. We will undertake a descriptive, narrative synthesis of findings to address the study objectives. We will pay special attention to aspects of quality of these models in regard to the external validation based upon ISPOR and ADA recommendations as well as Mount Hood Challenge reports. All critical stages within the screening, data extraction and synthesis processes will be conducted by at least two authors. This protocol adheres to PRISMA and PRISMA-P standards. The proposed systematic review will provide a broad overview of the current practice in the external validation of models with respect to T2DM incidence and progression in humans built on simulation techniques. PROSPERO CRD42017069983 .

Chronic sorrow in caregivers of school age children with sickle cell disease: a grounded theory approach.

PubMed

Northington, L

2000-01-01

Chronic illness affects over 1 million children in the United States annually. One such illness prominent in the African-American population is sickle cell disease (SCD), which affects approximately 1 in 375 African Americans in the United States. This potentially life-threatening disease requires caregivers to carefully monitor and supervise children with SCD. Monitoring and caring for children with SCD places heavy burdens, demands, and responsibilities on these caregivers. The psychological stressors and unpredictable nature of the disease could cause caregivers to experience a variety of emotions, with one being chronic sorrow. The purposes of this study were to examine the process of chronic sorrow in caregivers of school age children with SCD, identify the characteristics of chronic sorrow, and generate a substantive theory of chronic sorrow. The methodology used was grounded theory, and data were generated through two interview sessions, a demographic questionnaire, field notes, and memos. Data analyses were performed following the principles of grounded theory. Data suggested these caregivers move through three overlapping stages: learning about and incorporating SCD into their daily lives; experiencing the sorrow; and doing what one has to do and moving on. The diagnosis was the initial trigger to evoke feelings, including sorrow. As time progressed, other internal and external triggers began to evoke feelings of sorrow that eventually became chronic. A process of repatterning began as caregivers learned to live with the unpredictable consequences of SCD, which produced the feelings of chronic sorrow. Repatterning behaviors enabled caregivers to "do what you have to do and move on."

The Impact of Parents, Child Care Providers, Teachers, and Peers on Early Externalizing Trajectories

PubMed Central

Silver, Rebecca B.; Measelle, Jeffrey R.; Armstrong, Jeffrey M.; Essex, Marilyn J.

2010-01-01

This study utilized growth mixture modeling to examine the impact of parents, child care providers, teachers, and peers on the prediction of distinct developmental patterns of classroom externalizing behavior in elementary school. Among 241 children, three groups were identified. 84.6% of children exhibited consistently low externalizing behavior. The externalizing behavior of the Chronic High group (5.8%) remained elevated throughout elementary school; it increased over time in the Low Increasing group (9.5%). Negative relationships with teachers and peers in the kindergarten classroom increased the odds of having chronically high externalizing behavior. Teacher–child conflict increased the likelihood of a developmental pattern of escalating externalizing behavior. Boys were overrepresented in the behaviorally risky groups, and no sex differences in trajectory types were found. PMID:21094398

Inhibitory effect of chronic oral treatment with fluoxetine on capsaicin-induced external carotid vasodilatation in anaesthetised dogs.

PubMed

Muñoz-Islas, Enriqueta; González-Hernández, Abimael; Lozano-Cuenca, Jair; Ramírez-Rosas, Martha Beatríz; Medina-Santillán, Roberto; Centurión, David; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

2015-10-01

During migraine, capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception. Moreover, 5-HT is involved in the pathophysiology of migraine and depression. Interestingly, some limited lines of evidence suggest that fluoxetine may be effective in migraine prophylaxis, but the underlying mechanisms are uncertain. Hence, this study investigated the canine external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine before and after acute and chronic oral treatment with fluoxetine. Forty-eight vagosympathectomised male mongrel dogs were prepared to measure blood pressure, heart rate and external carotid blood flow. The thyroid artery was cannulated for infusions of agonists. In 16 of these dogs, a spinal cannula was inserted (C1-C3) for infusions of 5-HT. The external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine remained unaffected after intracarotid or i.v. fluoxetine. In contrast, the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine, were inhibited after chronic oral treatment with fluoxetine (300 µg/kg; for 90 days) or intrathecal 5-HT. Chronic oral fluoxetine inhibited capsaicin-induced external carotid vasodilatation, and this inhibition could partly explain its potential prophylactic antimigraine action. © International Headache Society 2015.

Crosstalk between the Unfolded Protein Response and NF-κB-Mediated Inflammation in the Progression of Chronic Kidney Disease

PubMed Central

Cruz, Gaile L.; Dickhout, Jeffrey G.

2015-01-01

The chronic inflammatory response is emerging as an important therapeutic target in progressive chronic kidney disease. A key transcription factor in the induction of chronic inflammation is NF-κB. Recent studies have demonstrated that sustained activation of the unfolded protein response (UPR) can initiate this NF-κB signaling phenomenon and thereby induce chronic kidney disease progression. A key factor influencing chronic kidney disease progression is proteinuria and this condition has now been demonstrated to induce sustained UPR activation. This review details the crosstalk between the UPR and NF-κB pathways as pertinent to chronic kidney disease. We present potential tools to study this phenomenon as well as potential therapeutics that are emerging to regulate the UPR. These therapeutics may prevent inflammation specifically induced in the kidney due to proteinuria-induced sustained UPR activation. PMID:25977931

Natural products with anti-aging potential: Affected targets and molecular mechanisms.

PubMed

Cătană, Cristina-Sorina; Atanasov, Atanas G; Berindan-Neagoe, Ioana

2018-03-27

In recent years, there has been a great deal of attention toward the molecular machinery relevant to age-related progression controlled through the external intervention of polyphenols- an epigenetic-modulating diet. Natural products modulate cellular longevity through histone post-translational modification and can also induce the upregulation of autophagy, thus reducing the level of acetyl coenzyme A (AcCoA). In addition, the effect of caloric restriction (CR) on cancer-related chronic inflammation is of great significance in aging. In line with this, SIRT1 protein levels are expanded in response to calorie restriction mimetics (CRM), in this way acting as autophagy inducers relevant to cancer prevention. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Category III chronic prostatitis/chronic pelvic pain syndrome: insights from the National Institutes of Health Chronic Prostatitis Collaborative Research Network studies.

PubMed

Nickel, J Curtis; Alexander, Richard B; Anderson, Rodney; Berger, Richard; Comiter, Craig V; Datta, Nand S; Fowler, Jackson E; Krieger, John N; Landis, J Richard; Litwin, Mark S; McNaughton-Collins, Mary; O'Leary, Michael P; Pontari, Michel A; Schaeffer, Anthony J; Shoskes, Daniel A; White, Paige; Kusek, John; Nyberg, Leroy

2008-07-01

Chronic prostatitis/chronic pelvic pain syndrome remains an enigmatic medical condition. Creation of the National Institutes of Health-funded Chronic Prostatitis Collaborative Research Network (CPCRN) has stimulated a renewed interest in research on and clinical aspects of chronic prostatitis/chronic pelvic pain syndrome. Landmark publications of the CPCRN document a decade of progress. Insights from these CPCRN studies have improved our management of chronic prostatitis/chronic pelvic pain syndrome and offer hope for continued progress.

Association between Smoking and the Progression of Computed Tomography Findings in Chronic Pancreatitis.

PubMed

Lee, Jeong Woo; Kim, Ho Gak; Lee, Dong Wook; Han, Jimin; Kwon, Hyuk Yong; Seo, Chang Jin; Oh, Ji Hye; Lee, Joo Hyoung; Jung, Jin Tae; Kwon, Joong Goo; Kim, Eun Young

2016-05-23

Smoking and alcohol intake are two wellknown risk factors for chronic pancreatitis. However, there are few studies examining the association between smoking and changes in computed tomography (CT) findings in chronic pancreatitis. The authors evaluated associations between smoking, drinking and the progression of calcification on CT in chronic pancreatitis. In this retrospective study, 59 patients with chronic pancreatitis who had undergone initial and follow-up CT between January 2002 and September 2010 were included. Progression of calcification among CT findings was compared according to the amount of alcohol intake and smoking. The median duration of followup was 51.6 months (range, 17.1 to 112.7 months). At initial CT findings, there was pancreatic calcification in 35 patients (59.3%). In the follow-up CT, progression of calcification was observed in 37 patients (62.7%). Progression of calcification was more common in smokers according to the multivariate analysis (odds ratio [OR], 9.987; p=0.006). The amount of smoking was a significant predictor for progression of calcification in the multivariate analysis (OR, 6.051 in less than 1 pack per day smokers; OR, 36.562 in more than 1 pack per day smokers; p=0.008). Continued smoking accelerates pancreatic calcification, and the amount of smoking is associated with the progression of calcification in chronic pancreatitis.

Long-term dose-response studies of inhaled or injected radionuclides. Biennial report, 1 October 1991--30 September 1993

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

Boecker, B.B.; Muggenburg, B.A.; Miller, S.C.

This report describes the scientific progress in, and current status of, life-span studies of the long-term health risks in Beagle dogs of chronic irradiation from internally deposited radionuclides or from an external source. The reporting period for this document is the 2-year period from October 1, 1991 through September 30, 1993. Studies that were initiated at three different laboratories (Inhalation Toxicology Research Institute, ITRI, University of Utah, and Argonne National Laboratory, ANL) are presented here because they are being completed at ITRI. All living dogs in the Utah-initiated studies were transferred to the ITRI facility for the remainder of theirmore » life-span observations and measurements in September 1987. This report is the fourth in a series of reports dealing with the current status and progress of both the Utah and ITRI studies. Other life-span studies involving dogs exposed to gamma radiation from an external source were initiated and conducted for many years at ANL. In 1991, the decision was made to discontinue the chronic irradiation of the remaining living dogs and to transfer all remaining dogs to ITRI for care, clinical observations, and pathological observations at death or euthanasia. This report provides the current status of these dogs. Status reports on the Utah and ITRI studies comprise most of this report. The ITRI-related section presents brief statements of project objectives, the general procedures used in these studies, and some study-specific features for each of the 19 studies being conducted with either beta- or alpha-emitting radionuclides. Dose- and effect-modifying factors being addressed in these studies include total dose, dose rate, LET, solubility, nonuniformity of dose, species, age, sex, health status, and mode of exposure. Recent additions to experimental protocols for studies in which dogs are still alive involve the collection and analysis of tumor tissues using currently available molecular biology techniques.« less

Oligodendrocytes and Progenitors Become Progressively Depleted within Chronically Demyelinated Lesions

PubMed Central

Mason, Jeffrey L.; Toews, Arrel; Hostettler, Janell D.; Morell, Pierre; Suzuki, Kinuko; Goldman, James E.; Matsushima, Glenn K.

2004-01-01

To understand mechanisms that may underlie the progression of a demyelinated lesion to a chronic state, we have used the cuprizone model of chronic demyelination. In this study, we investigated the fate of oligodendrocytes during the progression of a demyelinating lesion to a chronic state and determined whether transplanted adult oligodendrocyte progenitors could remyelinate the chronically demyelinated axons. Although there is rapid regeneration of the oligodendrocyte population following an acute lesion, most of these newly regenerated cells undergo apoptosis if mice remain on a cuprizone diet. Furthermore, the oligodendrocyte progenitors also become progressively depleted within the lesion, which appears to contribute to the chronic demyelination. Interestingly, even if the mice are returned to a normal diet following 12 weeks of exposure to cuprizone, remyelination and oligodendrocyte regeneration does not occur. However, if adult O4+ progenitors are transplanted into the chronically demyelinated lesion of mice treated with cuprizone for 12 weeks, mature oligodendrocyte regeneration and remyelination occurs after the mice are returned to a normal diet. Thus, the formation of chronically demyelinated lesions induced by cuprizone appears to be the result of oligodendrocyte depletion within the lesion and not due to the inability of the chronically demyelinated axons to be remyelinated. PMID:15111314

Association between Smoking and the Progression of Computed Tomography Findings in Chronic Pancreatitis

PubMed Central

Lee, Jeong Woo; Kim, Ho Gak; Lee, Dong Wook; Han, Jimin; Kwon, Hyuk Yong; Seo, Chang Jin; Oh, Ji Hye; Lee, Joo Hyoung; Jung, Jin Tae; Kwon, Joong Goo; Kim, Eun Young

2016-01-01

Background/Aims Smoking and alcohol intake are two well-known risk factors for chronic pancreatitis. However, there are few studies examining the association between smoking and changes in computed tomography (CT) findings in chronic pancreatitis. The authors evaluated associations between smoking, drinking and the progression of calcification on CT in chronic pancreatitis. Methods In this retrospective study, 59 patients with chronic pancreatitis who had undergone initial and follow-up CT between January 2002 and September 2010 were included. Progression of calcification among CT findings was compared according to the amount of alcohol intake and smoking. Results The median duration of follow-up was 51.6 months (range, 17.1 to 112.7 months). At initial CT findings, there was pancreatic calcification in 35 patients (59.3%). In the follow-up CT, progression of calcification was observed in 37 patients (62.7%). Progression of calcification was more common in smokers according to the multivariate analysis (odds ratio [OR], 9.987; p=0.006). The amount of smoking was a significant predictor for progression of calcification in the multivariate analysis (OR, 6.051 in less than 1 pack per day smokers; OR, 36.562 in more than 1 pack per day smokers; p=0.008). Conclusions Continued smoking accelerates pancreatic calcification, and the amount of smoking is associated with the progression of calcification in chronic pancreatitis. PMID:26601825

Chronic elbow dislocation: a rare complication of tennis elbow surgery. Successful treatment by open reduction and external fixator.

PubMed

Degreef, I; De Smet, L

2007-06-01

A case is presented of chronic dislocation of the elbow after tennis elbow surgery combined with posterior interosseous nerve (PIN) release. An open reduction with repair of the collateral ligaments was performed. Postoperative rehabilitation involved the use of an articulated external fixator and there was a successful outcome. Possible causes of the dislocation are discussed.

[Fatal female genital mutilation in a 10-year-old girl].

PubMed

Sow, A; Diagne, G; Keita, Y; Sow, O; Ndiath, A; Ouattara, A; Sarr, M-L; Sylla, A; Moreira, C

2017-10-01

Female genital mutilation (FGM) comprises all procedures involving partial or total removal of the external genitalia and/or any other procedures affecting the female genitalia, for cultural or religious reasons or for nontherapeutic purposes in general. FGM is responsible for a number of short-, medium-, and long-term complications that can engage the vital and functional prognosis, especially in African countries. We report on a case in a 10-year-old girl who underwent genital mutilation, a traditional type of total excision during the neonatal period. She was followed for urethral meatus stenosis, which then was complicated by obstructive chronic kidney failure and urinary sepsis, whose progression was fatal. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Infective Dermatitis in an Adult Patient With HTLV-1

PubMed Central

Riveros, Rosalba; Medina, Raquel; Morel, Maida

2015-01-01

Abstract: Infective dermatitis is a chronic exudative eczematous eruption presenting in human T-lymphotropic virus type 1 (HTLV-1)–infected people. It presents with relapsing erythematous, scaly, and crusted lesions affecting simultaneously the scalp, external ear, retroauricular area, eyelid, paranasal skin, neck axilla, and groin. Superimposed Staphylococcus and Streptococcus infection are common. It mainly affects children and exceptionally adults, and there are only a few published cases. The authors present the first reported case in Paraguay of an adult patient who had symptoms of human T-lymphotropic virus type 1–associated progressive tropical spastic paraparesis, and 6 years after the onset of the neurological symptoms, the patient developed infective dermatitis lesions on the skin, with frequent exacerbations since then. PMID:26588341

Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytopenia or progressive onset type: results of a prospective study.

PubMed

Kuzmina, Z; Eder, S; Böhm, A; Pernicka, E; Vormittag, L; Kalhs, P; Petkov, V; Stary, G; Nepp, J; Knobler, R; Just, U; Krenn, K; Worel, N; Greinix, H T

2012-04-01

Chronic graft-versus-host disease (GVHD) remains a serious complication after allogeneic hematopoietic stem cell transplantation (HCT). In 2005 the National Institutes of Health (NIH) established new criteria for chronic GVHD based on retrospective data and expert recommendations. We prospectively evaluated the incidence of NIH-defined chronic GVHD and its prognostic impact in 178 consecutive patients. The cumulative incidence of chronic GVHD at 3 years was 64, 48 and 16% for chronic classic GVHD and overlap syndrome. Prior acute GVHD and myeloablative conditioning were significantly associated with increased risk of chronic GVHD. Three-year survival (overall survival (OS)) for late-acute GVHD, chronic classic and overlap chronic GVHD when assigned on day 100 were 69, 83 and 73%. OS was significantly worse for patients with platelet counts below 100 g/l at onset of chronic GVHD (35% versus 86%, P<0.0001) and progressive as compared with de novo and quiescent onset of chronic GVHD (54.5% versus 89.5% versus 84%, P = 0.022 and 0.001). Peak severity of chronic GVHD had no impact on non-relapse mortality (NRM) and OS. Recurrent acute GVHD, platelet counts below 100 g/l at diagnosis of chronic GVHD, progressive onset of chronic GVHD and advanced disease stage prior to HCT were significantly associated with increased NRM. This prospective analysis provides for the first-time data on the incidence rates of NIH-defined chronic GVHD categories and identified risk factors for the occurrence of chronic GVHD. A prognostic value of thrombocytopenia and progressive onset type of chronic GVHD for survival after HCT was observed in NIH-defined chronic GVHD.

Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection.

PubMed

Cho, Junhyeon; Lee, Sang Soo; Choi, Yun Suk; Jeon, Yejoo; Chung, Jung Wha; Baeg, Joo Yeong; Si, Won Keun; Jang, Eun Sun; Kim, Jin-Wook; Jeong, Sook-Hyang

2016-11-14

To clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma (HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus (HCV) infection. This prospective cohort study enrolled 174 patients with chronic HCV infection (chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or more different viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively ( P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response (SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.

A novel mouse model identifies cooperating mutations and therapeutic targets critical for chronic myeloid leukemia progression

PubMed Central

Giotopoulos, George; van der Weyden, Louise; Osaki, Hikari; Rust, Alistair G.; Gallipoli, Paolo; Meduri, Eshwar; Horton, Sarah J.; Chan, Wai-In; Foster, Donna; Prinjha, Rab K.; Pimanda, John E.; Tenen, Daniel G.; Vassiliou, George S.; Koschmieder, Steffen; Adams, David J.

2015-01-01

The introduction of highly selective ABL-tyrosine kinase inhibitors (TKIs) has revolutionized therapy for chronic myeloid leukemia (CML). However, TKIs are only efficacious in the chronic phase of the disease and effective therapies for TKI-refractory CML, or after progression to blast crisis (BC), are lacking. Whereas the chronic phase of CML is dependent on BCR-ABL, additional mutations are required for progression to BC. However, the identity of these mutations and the pathways they affect are poorly understood, hampering our ability to identify therapeutic targets and improve outcomes. Here, we describe a novel mouse model that allows identification of mechanisms of BC progression in an unbiased and tractable manner, using transposon-based insertional mutagenesis on the background of chronic phase CML. Our BC model is the first to faithfully recapitulate the phenotype, cellular and molecular biology of human CML progression. We report a heterogeneous and unique pattern of insertions identifying known and novel candidate genes and demonstrate that these pathways drive disease progression and provide potential targets for novel therapeutic strategies. Our model greatly informs the biology of CML progression and provides a potent resource for the development of candidate therapies to improve the dismal outcomes in this highly aggressive disease. PMID:26304963

Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

PubMed Central

Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

2014-01-01

The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

Psychological characteristics of chronic depression: a longitudinal cohort study.

PubMed

Wiersma, Jenneke E; van Oppen, Patricia; van Schaik, Digna J F; van der Does, A J Willem; Beekman, Aartjan T F; Penninx, Brenda W J H

2011-03-01

Few studies have investigated the importance of psychological characteristics for chronicity of depression. Knowledge about psychological differences between chronically depressed persons and nonchronically depressed persons may help to improve treatment of chronic depression. This is the first study to simultaneously compare in large samples various psychological characteristics between chronically depressed and nonchronically depressed adults. Baseline data were drawn from the Netherlands Study of Depression and Anxiety (NESDA), an ongoing longitudinal cohort study aimed at examining the long-term course of depressive and anxiety disorders in different health care settings and phases of illness. Participants were aged 18 to 65 years at the baseline assessment in 2004-2007 and had a current diagnosis of DSM-IV major depressive disorder (N = 1,002). Chronicity of depression was defined as being depressed for 24 months or more in the past 4 to 5 years. The chronicity criterion was fulfilled by 31% (n = 312). The NEO Five-Factor Inventory measured the 5 personality domains, the Leiden Index of Depression Sensitivity-Revised was used to measure cognitive reactivity (eg, hopelessness, rumination), and the Mastery Scale measured external locus of control. Compared to the nonchronically depressed persons, the chronically depressed persons reported significantly higher levels of neuroticism (OR = 1.81; 95% CI, 1.55-2.12; P < .001), external locus of control (OR = 1.94; 95% CI, 1.66-2.28; P < .001), and the following dimensions of cognitive reactivity: hopelessness (OR = 1.64; 95% CI, 1.43-1.88; P < .001), aggression (OR = 1.29; 95% CI, 1.13-1.48; P < .001), risk aversion (OR = 1.43; 95% CI, 1.24-1.63; P < .001), and rumination (OR = 1.55; 95% CI, 1.34-1.78; P < .001). They had significantly lower levels of extraversion (OR = 0.57; 95% CI, 0.49-0.67; P < .001), agreeableness (OR = 0.85; 95% CI, 0.74-0.97; P = .02), and conscientiousness (OR = 0.77; 95% CI, 0.67-0.88; P < .001). When testing these variables multivariably, the odds of chronic depression were significantly increased among those with low extraversion (OR = 0.73; 95% CI, 0.61-0.88; P = .001), high rumination (OR = 1.24; 95% CI, 1.01-1.53; P = .04), and high external locus of control (OR = 1.48; 95% CI, 1.21-1.80; P < .001). Controlling for severity of depressive symptoms, age at onset, comorbidity with anxiety disorders, medical illnesses, and treatment status did not change these results. Our findings suggest that extraversion, rumination, and external locus of control, but not neuroticism, are differentiating psychological characteristics for chronicity of depression. These findings provide suggestions for more specific interventions, focused on extraversion, rumination, and external locus of control, in the treatment of chronic depression. © Copyright 2011 Physicians Postgraduate Press, Inc.

[Experience in treating patients with chronic obstructive bronchitis with fenspirid].

PubMed

Kirichenko, A A; Shabanova, T M

2002-01-01

To study a clinical effect of fenspirid and its impact on external respiration function in patients with chronic obstructive bronchitis (COB) in the exacerbation phase. 30 COB patients participated in the trial (20 males, 10 females, age 39-80 years). The severity of clinical symptoms (cough, sputum, dyspnea) was studied using special scales. External respiration function was examined by a spirometric system "Tamrac system spiro sense Y2 14". Fenspirid treatment was conducted in a dose 80 mg twice a day for 3 months. Control examinations were made 2 weeks, 1 and 3 months after the treatment start. A 3-month treatment with fenspirid resulted in regression of COB symptoms: cough and sputum ceased, dyspnea decreased. This led to improvement in external respiration function, especially in patients with mixed ventilatory disorders with prevailing restriction. Fenspirid is an effective and well tolerated treatment of chronic obstructive bronchitis.

Uric acid and progression of chronic kidney disease.

PubMed

Weaver, Donald J

2018-06-21

The association between serum uric acid levels and human disease has garnered intense interest over the last decade including chronic kidney disease. Animal studies have provided evidence for a potential mechanistic role of uric acid in promoting progression of chronic kidney disease. Epidemiologic studies have also suggested an association between elevated serum uric acid levels and worsening renal function in the general population as well as in patients with chronic kidney disease. However, there is currently insufficient evidence to recommend the use of uric acid-lowering therapy to delay progression of chronic kidney disease in this patient population. Adequately powered, randomized, placebo-controlled trials are required to more precisely evaluate the risk and benefits of uric acid-lowering therapy in pediatric patients.

An unusual renal manifestation of chronic HBV infection.

PubMed

Aravindan, Ananthakrishnapuram; Yong, Jim; Killingsworth, Murray; Strasser, Simone; Suranyi, Michael

2010-08-01

Hepatitis B viral infection is usually a self-limiting disease in immunocompetent individuals. Chronic infection can be seen in up to 5% of infected patients. Renal manifestations of chronic HBV infection are usually glomerular. We describe here an uncommon presentation of a patient with chronic HBV infection with very high viral load and rapidly progressive renal failure. Renal biopsy showed features of tubulointerstitial nephritis and tubular epithelial inclusion bodies suggestive of HBV infection. Entecavir treatment slowed down the progression of his renal disease. Tubulointerstitial nephritis should be considered as a part of the differential diagnosis in patients with HBV infection. Early antiviral treatment may halt the progression of renal disease.

Mechanisms Explaining the Influence of Subclinical Hypothyroidism on the Onset and Progression of Chronic Heart Failure.

PubMed

Triggiani, Vincenzo; Angelo Giagulli, Vito; De Pergola, Giovanni; Licchelli, Brunella; Guastamacchia, Edoardo; Iacoviello, Massimo

2016-01-01

Subclinical hypothyroidism can be associated with the onset and progression of chronic heart failure. We undertook a careful search of the literature aiming to review the possible pathogenetic mechanisms explaining the influence of subclinical hypothyroidism on the onset and progression of chronic heart failure. Thyroid hormones can influence the expression of genes involved in calcium handling and contractile properties of myocardiocytes. Subclinical hypothyroidism, therefore, can alter both cardiovascular morphology and function leading to changes in myocardiocytes shape and structure, and to alterations of both contractile and relaxing properties, impairing systolic as well as diastolic functions. Furthermore, it can favour dyslipidemia, endothelial dysfunction and diastolic hypertension, favouring atherogenesis and coronary heart disease, possibly evolving into chronic heart failure. Beside an influence on the onset of chronic heart failure, subclinical hypothyroidism can represent a risk factor for its progression, in particular hospitalization and mortality but the mechanisms involved need to be fully elucidated. Subclinical hypothyroidism can be associated with the onset of chronic heart failure, because it can favour two frequent conditions that can evolve in heart failure: coronary heart disease and hypertension; it can also alter both cardiovascular morphology and function leading to heart failure progression in patients already affected through mechanisms still not completely understood.

Category III Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Insights from The National Institutes of Health Chronic Prostatitis Collaborative Research Network Studies

PubMed Central

Nickel, J. Curtis; Alexander, Richard B.; Anderson, Rodney; Berger, Richard; Comiter, Craig V.; Datta, Nand S.; Fowler, Jackson E.; Krieger, John N.; Landis, J. Richard; Litwin, Mark S.; McNaughton-Collins, Mary; O'Leary, Michael P.; Pontari, Michel A.; Schaeffer, Anthony J.; Shoskes, Daniel A.; White, Paige; Kusek, John; Nyberg, Leroy

2010-01-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains an enigmatic medical condition. Creation of the (NIH) Chronic Prostatitis Collaborative Research Network (CPCRN) funded by the National Institutes of Health has stimulated a renewed interest in the research and clinical aspects of CP/CPPS. Landmark publications of the NIH-CPCRN over the last 10 years document a decade of progress. Insights from these CPCRN studies have improved our management of patients diagnosed with CP/CPPS and offer hope for continued progress. PMID:18765132

Chronic Progressive Disseminated Histoplasmosis in a Mexican Cockfighter

PubMed Central

Flores-Franco, René Agustín; Gómez-Díaz, Antonio; de Jesús Fernández-Alonso, Antonio

2015-01-01

We present illustrative images from a Mexican 58-year-old man who had the occupation of cockfighting from childhood and presented with chronic progressive disseminated histoplasmosis with primarily cutaneous manifestations. PMID:25568180

Sensitivity to psychosocial chronic stressors and adolescents' externalizing problems: Combined moderator effects of resting heart rate and parental psychiatric history.

PubMed

Zandstra, Anna Roos E; Ormel, Johan; Dietrich, Andrea; van den Heuvel, Edwin R; Hoekstra, Pieter J; Hartman, Catharina A

2018-04-01

From the literature it is not clear whether low resting heart rate (HR) reflects low or high sensitivity to the detrimental effects of adverse environments on externalizing problems. We studied parental psychiatric history (PH), reflecting general vulnerability, as possible moderator explaining these inconsistencies. Using Linear Mixed Models, we analyzed data from 1914 subjects, obtained in three measurement waves (mean age 11, 13.5, and 16 years) from the TRacking Adolescents' Individual Lives Survey population-based cohort and the parallel clinic-referred cohort. As hypothesized, more chronic stressors predicted more externalizing problems in vulnerable individuals with high resting HR but not in those with low resting HR, suggesting high vs. low sensitivity, respectively, to adverse environmental influences. Low sensitivity to adverse environmental influences in vulnerable individuals exposed to high stressor levels was additionally confirmed by high heart rate variability (Root Mean Squared Successive Difference; RMSSD). In adolescents with low vulnerability, in contrast, the association between chronic stressors and externalizing problems did not substantially differ by resting HR and RMSSD. Future research may demonstrate whether our findings extend to other adverse, or beneficial, influences. Notwithstanding their theoretical interest, the effects were small, only pertained to parent-reported externalizing problems, refer to a small subset of respondents in our sample, and are in need of replication. We conclude that HR and RMSSD are unlikely to be strong moderators of the association between stressors and externalizing problems. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparison of Monolateral External Fixation and Internal Fixation for Skeletal Stabilisation in the Management of Small Tibial Bone Defects following Successful Treatment of Chronic Osteomyelitis.

PubMed

Wang, Yicun; Jiang, Hui; Deng, Zhantao; Jin, Jiewen; Meng, Jia; Wang, Jun; Zhao, Jianning; Sun, Guojing; Qian, Hongbo

2017-01-01

To compare the salvage rate and complication between internal fixation and external fixation in patients with small bone defects caused by chronic infectious osteomyelitis debridement. 125 patients with chronic infectious osteomyelitis of tibia fracture who underwent multiple irrigation, debridement procedure, and local/systemic antibiotics were enrolled. Bone defects, which were less than 4 cm, were treated with bone grafting using either internal fixation or monolateral external fixation. 12-month follow-up was conducted with an interval of 3 months to evaluate union of bone defect. Patients who underwent monolateral external fixation had higher body mass index and fasting blood glucose, longer time since injury, and larger bone defect compared with internal fixation. No significant difference was observed in incidence of complications (23.5% versus 19.3%), surgery time (156 ± 23 minutes versus 162 ± 21 minutes), and time to union (11.1 ± 3.0 months versus 10.9 ± 3.1 months) between external fixation and internal fixation. Internal fixation had no significant influence on the occurrence of postoperation complications after multivariate adjustment when compared with external fixation. Furthermore, patients who underwent internal fixation experienced higher level of daily living scales and lower level of anxiety. It was relatively safe to use internal fixation for stabilization in osteomyelitis patients whose bone defects were less than 4 cm and infection was well controlled.

Comparison of Monolateral External Fixation and Internal Fixation for Skeletal Stabilisation in the Management of Small Tibial Bone Defects following Successful Treatment of Chronic Osteomyelitis

PubMed Central

Wang, Yicun; Jiang, Hui; Deng, Zhantao; Meng, Jia; Wang, Jun

2017-01-01

Background To compare the salvage rate and complication between internal fixation and external fixation in patients with small bone defects caused by chronic infectious osteomyelitis debridement. Methods 125 patients with chronic infectious osteomyelitis of tibia fracture who underwent multiple irrigation, debridement procedure, and local/systemic antibiotics were enrolled. Bone defects, which were less than 4 cm, were treated with bone grafting using either internal fixation or monolateral external fixation. 12-month follow-up was conducted with an interval of 3 months to evaluate union of bone defect. Results Patients who underwent monolateral external fixation had higher body mass index and fasting blood glucose, longer time since injury, and larger bone defect compared with internal fixation. No significant difference was observed in incidence of complications (23.5% versus 19.3%), surgery time (156 ± 23 minutes versus 162 ± 21 minutes), and time to union (11.1 ± 3.0 months versus 10.9 ± 3.1 months) between external fixation and internal fixation. Internal fixation had no significant influence on the occurrence of postoperation complications after multivariate adjustment when compared with external fixation. Furthermore, patients who underwent internal fixation experienced higher level of daily living scales and lower level of anxiety. Conclusions It was relatively safe to use internal fixation for stabilization in osteomyelitis patients whose bone defects were less than 4 cm and infection was well controlled. PMID:29333448

Elevated Endothelial Hypoxia-Inducible Factor-1α Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease.

PubMed

Luo, Renna; Zhang, Weiru; Zhao, Cheng; Zhang, Yujin; Wu, Hongyu; Jin, Jianping; Zhang, Wenzheng; Grenz, Almut; Eltzschig, Holger K; Tao, Lijian; Kellems, Rodney E; Xia, Yang

2015-07-01

Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1α (HIF-1α) is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis, we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1α and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with reverse transcription polymerase chain reaction profiling revealed that elevated endothelial HIF-1α is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1α gene expression was induced by angiotensin II in a nuclear factor-κB-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1α and Nf-κb genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1α gene expression in endothelial cells is detrimental to induce kidney injury, hypertension, and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease. © 2015 American Heart Association, Inc.

Homeostasis 6: nurses as external control agents in rheumatoid arthritis.

PubMed

Clancy, John; McVicar, Andrew; Mooney, Janice

All disorders involve a disturbance of cellular and hence chemical function in the body. Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease that usually attacks synovial joints and surrounding ligaments, muscles and their tendons and blood vessels. This article applies the concept of health professionals operating as external agents of homeostatic control (Clancy and McVicar, 20011a; 2011b) to RA and to the care of affected patients, using a case scenario to illustrate attempts to minimize homeostatic imbalances. After reading the article, nurses should be able to understand: how the principles of homeostatic theory apply to skeletomuscular function, in particular to synovial joint function; the skeletomuscular homeostatic role in movement; and that homeostatic failure of reduced mobility, as in RA, is a result of nature-nurture interaction; that illness arises from a cellular, hence chemical, homeostatic imbalance(s) (Clancy and McVicar, 2011a; 2011b; 2011c; 2011d; 2011e). RA is considered a cellular (B-lymphocyte) hence chemical (autoantibody) imbalance that causes the homeostatic imbalances (inflammatory pain, reduced mobility, reduced activities of daily living) associated with the condition. Health professionals are able at act as external agents of homeostatic control to only a limited extent when caring for people with RA because, as with any progressive disorder, they will only be managing signs and symptoms to improve patients' quality of life.

The wound healing, chronic fibrosis, and cancer progression triad

PubMed Central

Rybinski, Brad; Franco-Barraza, Janusz

2014-01-01

For decades tumors have been recognized as “wounds that do not heal.” Besides the commonalities that tumors and wounded tissues share, the process of wound healing also portrays similar characteristics with chronic fibrosis. In this review, we suggest a tight interrelationship, which is governed as a concurrence of cellular and microenvironmental reactivity among wound healing, chronic fibrosis, and cancer development/progression (i.e., the WHFC triad). It is clear that the same cell types, as well as soluble and matrix elements that drive wound healing (including regeneration) via distinct signaling pathways, also fuel chronic fibrosis and tumor progression. Hence, here we review the relationship between fibrosis and cancer through the lens of wound healing. PMID:24520152

Evaluation of laser photobiomodulation (λ 780 nm) on repair of dental replantation in rats

NASA Astrophysics Data System (ADS)

Bastos de Carvalho, Fabíola; Vasconcelos, Rebeca M.; Santos, Laila; dos Santos Barbosa, Artur F.; Aguiar, Marcio C.; Cangussu, Maria Cristina T.; Pinheiro, Antônio Luiz B.; Pedreira Ramalho, Luciana M.

2014-02-01

Up to date the success of tooth replantation is still limited. The majority of the teeth is lost due to progressive external root resorption. The aim of this study was to assess, histologically, the effect of laser photobiomodulation on repair after tooth replantation. Sixty Wistar Albinus rats had the right upper incisor extracted and then divided into 4 groups: G1 - absence of storage medium; G2 - milk u s e d as storage medium; G3 - milk used as storage medium a n d followed by GaAlAs laser irradiation on dental surfaces and at the entrance of alveolus; G4 - milk used as storage medium associated with laser irradiation as in G3 before and after replantation on the buccal and palatal mucosa every 48 hours for 15 days. The animals were sacrificed at 15, 30 and 60 days after replantation. The results showed that after 15 days G4 exhibit more intense chronic inflammation, with presence of clastic cells and moderate inflammatory root resorption (p<0.05) when compared to G3, which presented absence of those parameters. At day 30 in G1, G2 and G4 mild to moderate chronic inflammation and severe external root resorption were observed. G3 remained with no inflammation and inflammatory root resorption with 30 and 60 days of healing experimental times. The results suggest that laser irradiation on the dental entrance of the dental alveolus prior to tooth replantation has a positive biomodulative effect on the healing process in rats.

Change in trunk muscle activities with prone bridge exercise in patients with chronic low back pain.

PubMed

Kong, Yong-Soo; Park, Seol; Kweon, Mi-Gyong; Park, Ji-Won

2016-01-01

[Purpose] The aim of this study was to determine the effect of three different bridge exercises on internal oblique, external oblique, transverse abdominis, and erector spinae activities. [Subjects and Methods] Forty-five subjects with chronic low back pain participated in this study. The training outcome was evaluated with three different testing methods: supine bridge exercise, supine bridge on Swiss ball exercise, and prone bridge exercise. The activities of the transverse abdominis, internal oblique, external oblique, and erector spinae were measured using surface electromyography. [Results] There were significant differences in the internal oblique, external oblique, and erector spinae according to the three kinds of bridging exercises. The internal oblique, external oblique and transverse abdominis activities were highest in the prone bridge exercise, followed by those in the supine bridge on Swiss ball exercise, and supine bridge exercises. The activity of erector spine was highest in the supine bridge on Swiss ball exercise followed by the supine bridge exercise and prone bridge exercise. [Conclusion] These results suggest that prone bridge exercise is more effective than conventional supine bridge exercise and supine bridge on Swiss ball in increasing trunk muscle activity of chronic low back pain patients.

Chronic progressive lymphoedema in draught horses.

PubMed

de Keyser, K; Janssens, S; Buys, N

2015-05-01

The objective of this review was to summarise and evaluate the current state of knowledge about chronic progressive lymphoedema in draught horses. Clinical signs of this multifactorial disorder are mainly restricted to the lower limbs, comprising progressively deteriorating skin, swelling and deformation. Although typical lesions were first reported at the beginning of the 20th century, chronic progressive lymphoedema was recognised as a specific syndrome only in 2003, and since then research has driven forward. Despite the high prevalence in some breeds and the serious economic impact, the pathogenesis is not fully understood, and the available treatment options remain symptomatic and noncurative. There is a need to improve diagnostic techniques and to develop selection tools. © 2014 EVJ Ltd.

Comparing clinical attachment level and pocket depth for predicting periodontal disease progression in healthy sites of patients with chronic periodontitis using multi-state Markov models

PubMed Central

Mdala, Ibrahimu; Olsen, Ingar; Haffajee, Anne D; Socransky, Sigmund S; Thoresen, Magne; de Blasio, Birgitte Freiesleben

2014-01-01

Aim To understand degeneration of healthy sites and identify factors associated with disease progression in patients with chronic periodontitis. Material and Methods Data on healthy sites from 163 American and Swedish subjects were analysed using two-three-state (health, gingivitis, chronic periodontitis) Markov models based on bleeding on probing (BOP), and either clinical attachment level (CAL) + BOP or pocket depth (PD) + BOP. Results In 2 years, 10% (CAL + BOP) and 3% (PD + BOP) of healthy sites developed chronic periodontitis. On average, healthy sites remained healthy for 32 months before transiting in both models. Most transitions (87–97%) from health were to the gingivitis state. The expected duration of the gingivitis lesion was 4–5 months and sites recovered with a high probability (96–98%). Disease severity as measured by number of sites with CAL/PD > 4 mm at baseline and smoking, were associated with fast progression from health to chronic periodontitis within 6 months as were gingival redness in the PD + BOP model only. With age, the rate of disease progression to gingivitis decreased. Conclusion Transition probabilities for gingivitis and chronic periodontitis were higher with CAL + BOP than with PD + BOP. Smoking and disease severity were significant predictors for fast progression. PMID:24888705

The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH).

PubMed

Gandaglia, Giorgio; Briganti, Alberto; Gontero, Paolo; Mondaini, Nicola; Novara, Giacomo; Salonia, Andrea; Sciarra, Alessandro; Montorsi, Francesco

2013-08-01

Several different stimuli may induce chronic prostatic inflammation, which in turn would lead to tissue damage and continuous wound healing, thus contributing to prostatic enlargement. Patients with chronic inflammation and benign prostatic hyperplasia (BPH) have been shown to have larger prostate volumes, more severe lower urinary tract symptoms (LUTS) and a higher probability of acute urinary retention than their counterparts without inflammation. Chronic inflammation could be a predictor of poor response to BPH medical treatment. Thus, the ability to identify patients with chronic inflammation would be crucial to prevent BPH progression and develop target therapies. Although the histological examination of prostatic tissue remains the only available method to diagnose chronic inflammation, different parameters, such as prostatic calcifications, prostate volume, LUTS severity, storage and prostatitis-like symptoms, poor response to medical therapies and urinary biomarkers, have been shown to be correlated with chronic inflammation. The identification of patients with BPH and chronic inflammation might be crucial in order to develop target therapies to prevent BPH progression. In this context, clinical, imaging and laboratory parameters might be used alone or in combination to identify patients that harbour chronic prostatic inflammation. © 2013 BJU International.

A Bizarre, Unexplained, and Progressive External Rotation of the Shoulder as a Presentation of a Metastatic Deposit in the Rotator Cuff.

PubMed

El-Tawil, Sherif; Prinja, Aditya; Stanton, Jeremy

2015-01-01

We describe the first reported case of a tumour deposit within the rotator cuff presenting as a bizarre, progressive, and fixed external rotation deformity of the shoulder. It is also the first reported case to our knowledge of an oesophageal primary metastasising to the rotator cuff.

78 FR 79304 - Cardiovascular Devices; Reclassification of External Counter-Pulsating Devices for Treatment of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-30

... diabeticorum; Venous diseases, including the following: Prophylaxis of deep vein thrombophlebitis, edema (e.g..., edema (e.g., chronic lymphedema) and/or induration (e.g., stasis dermatitis) associated with chronic...

Progression of initially mild hepatic fibrosis in patients with chronic hepatitis C infection.

PubMed

Williams, M J; Lang-Lenton, M

2011-01-01

A significant number of patients with chronic hepatitis C infection have minimal fibrosis at presentation. Although the short-term outlook for such patients is good, there are limited data available on long-term progression. We assessed the risk of fibrosis progression in 282 patients with chronic hepatitis C with Ishak stage 0 or 1 fibrosis on initial liver biopsy. Progression of fibrosis stage occurred in 118 patients (42%) over a median interval of 52.5 months. Thirteen (5%) progressed to severe (Ishak stage 4 or more) fibrosis. Progression was significantly associated with both age at initial biopsy [odds ratio (OR) for progression of 1.31 per 10 year increase in age] and median alanine transaminase (ALT) levels during follow-up (OR of 1.06 per 10 IU/L increase). There was no significant association with gender, histological inflammatory grade, hepatic steatosis or body mass index. We conclude that hepatitis C with initially mild fibrosis does progress in a substantial proportion of patients and should not be viewed as a benign disease. Early antiviral therapy should be considered in older patients and those with high ALT levels.

Chronic and Proximate Depression among Mothers: Implications for Child Well-Being

ERIC Educational Resources Information Center

Turney, Kristin

2011-01-01

This article uses data from the Fragile Families and Child Well-Being Survey (N = 2,427) to examine the association between the chronicity and timing of maternal depression and child well-being. Maternal depression, particularly chronic depression, is linked to internalizing and externalizing problem behaviors in children, and children have worse…

A Bizarre, Unexplained, and Progressive External Rotation of the Shoulder as a Presentation of a Metastatic Deposit in the Rotator Cuff

PubMed Central

El-Tawil, Sherif; Prinja, Aditya; Stanton, Jeremy

2015-01-01

We describe the first reported case of a tumour deposit within the rotator cuff presenting as a bizarre, progressive, and fixed external rotation deformity of the shoulder. It is also the first reported case to our knowledge of an oesophageal primary metastasising to the rotator cuff. PMID:26543658

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.

Comparing clinical attachment level and pocket depth for predicting periodontal disease progression in healthy sites of patients with chronic periodontitis using multi-state Markov models.

PubMed

Mdala, Ibrahimu; Olsen, Ingar; Haffajee, Anne D; Socransky, Sigmund S; Thoresen, Magne; de Blasio, Birgitte Freiesleben

2014-09-01

To understand degeneration of healthy sites and identify factors associated with disease progression in patients with chronic periodontitis. Data on healthy sites from 163 American and Swedish subjects were analysed using two-three-state (health, gingivitis, chronic periodontitis) Markov models based on bleeding on probing (BOP), and either clinical attachment level (CAL) + BOP or pocket depth (PD) + BOP. In 2 years, 10% (CAL + BOP) and 3% (PD + BOP) of healthy sites developed chronic periodontitis. On average, healthy sites remained healthy for 32 months before transiting in both models. Most transitions (87-97%) from health were to the gingivitis state. The expected duration of the gingivitis lesion was 4-5 months and sites recovered with a high probability (96-98%). Disease severity as measured by number of sites with CAL/PD > 4 mm at baseline and smoking, were associated with fast progression from health to chronic periodontitis within 6 months as were gingival redness in the PD + BOP model only. With age, the rate of disease progression to gingivitis decreased. Transition probabilities for gingivitis and chronic periodontitis were higher with CAL + BOP than with PD + BOP. Smoking and disease severity were significant predictors for fast progression. © 2014 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.

Tuberculosis of the ear, a professional disease?

PubMed

Sens, Patrícia Maria; Almeida, Clemente I R; Valle, Lupércio O do; Costa, Luís H C; Angeli, Miguel L S

2008-01-01

Tuberculosis is a rare cause of chronic suppurative otitis media and mastoiditis; the predisposing factors of this association, however, are not commonly described. There has been an alarming increase in the incidence of tuberculosis in Brazil, including tuberculous otitis media. These patients typically present multiple perforations of the tympanic membrane, an ear discharge, and progressive hearing loss. This diagnosis should be taken into account in patients that do not respond to routine therapy for fungal external otitis or bacterial otitis media. In this retrospective study, the authors describe four cases of patients with tuberculous otitis media. This sample consisted of two physicians, a chemical engineer and an underage child in whose family there were cases of active tuberculosis. Predisposing factors for tuberculous otitis were contact with family members that had tuberculosis, professional contact with patients and exposure to pathogenic microorganisms in airways.

Space Shuttle External Tank Project status

NASA Technical Reports Server (NTRS)

Davis, R. M.

1980-01-01

The External Tank Project is reviewed with emphasis on the DDT&E and production phases and the lightweight tank development. It is noted that the DDT&E phase is progressing well with the structural and ground vibration test article programs complete, the propulsion test article program progressing well, and the component qualification and verification testing 92% complete. New tools and facilities are being brought on line to support the increased build rate for the production phase. The lightweight tank, which will provide additional payload in orbit, is progressing to schedule with first delivery in early 1982.

Rapidly Progressive Maxillary Atelectasis.

PubMed

Elkhatib, Ahmad; McMullen, Kyle; Hachem, Ralph Abi; Carrau, Ricardo L; Mastros, Nicholas

2017-07-01

Report of a patient with rapidly progressive maxillary atelectasis documented by sequential imaging. A 51-year-old man, presented with left periorbital and retro-orbital pain associated with left nasal obstruction. An initial computed tomographic (CT) scan of the paranasal sinuses failed to reveal any significant abnormality. A subsequent CT scan, indicated for recurrence of symptoms 11 months later, showed significant maxillary atelectasis. An uncinectomy, maxillary antrostomy, and anterior ethmoidectomy resulted in a complete resolution of the symptoms. Chronic maxillary atelectasis is most commonly a consequence of chronic rhinosinusitis. All previous reports have indicated a chronic process but lacked documentation of the course of the disease. This report documents a patient of rapidly progressive chronic maxillary atelectasis with CT scans that demonstrate changes in the maxillary sinus (from normal to atelectatic) within 11 months.

[New markers of progression of chronic heart failure in patients with myocardial infarction, type 2 diabetes and obesity].

PubMed

Kravchun, P P; Kadykova, O I; Gabisonia, T N

2015-01-01

Currently identified a large number of biomarkers that are closely linked with the development of chronic heart failure, some of which are clusterin and fractalkine. Accordingly, the purpose of our study was - to evaluate the role of clusterin and fractalkine in progression of chronic heart failure in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. We investigated 71 patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. All patients with postinfarction cardiosclerosis, diabetes and obesity were divided into groups according to the functional class of chronic heart failure (CHF). It was found that an increase the level of fractalkine and reduced clusterin leads due to the development of systolic dysfunction and heart failure progression in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. Fractalkine and clusterin play an important role in progression of the heart failure in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity, and this gives them the right to be considered indicators of the severity of CHF.

Periodontal Pocket Depth, Hyperglycemia, and Progression of Chronic Kidney Disease: A Population-Based Longitudinal Study.

PubMed

Chang, Jia-Feng; Yeh, Jih-Chen; Chiu, Ya-Lin; Liou, Jian-Chiun; Hsiung, Jing-Ru; Tung, Tao-Hsin

2017-01-01

No large epidemiological study has been conducted to investigate the interaction and joint effects of periodontal pocket depth and hyperglycemia on progression of chronic kidney disease in patients with periodontal diseases. Periodontal pocket depth was utilized for the grading severity of periodontal disease in 2831 patients from January 2002 to June 2013. Progression of chronic kidney disease was defined as progression of color intensity in glomerular filtration rate and albuminuria grid of updated Kidney Disease-Improving Global Outcomes guidelines. Multivariable-adjusted hazard ratios (aHR) in various models were presented across different levels of periodontal pocket depth and hemoglobin A1c (HbA1c) in forest plots and 3-dimensional histograms. During 7621 person-years of follow-up, periodontal pocket depth and HbA1C levels were robustly associated with incremental risks for progression of chronic kidney disease (aHR 3.1; 95% confidence interval [CI], 2.0-4.6 for periodontal pocket depth >4.5 mm, and 2.5; 95% CI, 1.1-5.4 for HbA1C >6.5%, respectively). The interaction between periodontal pocket depth and HbA1C on progression of chronic kidney disease was strong (P <.01). Patients with higher periodontal pocket depth (>4.5 mm) and higher HbA1C (>6.5%) had the greatest risk (aHR 4.2; 95% CI, 1.7-6.8) compared with the lowest aHR group (periodontal pocket depth ≤3.8 mm and HbA1C ≤6%). Our study identified combined periodontal pocket depth and HbA1C as a valuable predictor of progression of chronic kidney disease in patients with periodontal diseases. While considering the interaction between periodontal diseases and hyperglycemia, periodontal survey and optimizing glycemic control are warranted to minimize the risk of worsening renal function. Copyright © 2016 Elsevier Inc. All rights reserved.

Cognitive-Linguistic Deficit and Speech Intelligibility in Chronic Progressive Multiple Sclerosis

ERIC Educational Resources Information Center

Mackenzie, Catherine; Green, Jan

2009-01-01

Background: Multiple sclerosis is a disabling neurological disease with varied symptoms, including dysarthria and cognitive and linguistic impairments. Association between dysarthria and cognitive-linguistic deficit has not been explored in clinical multiple sclerosis studies. Aims: In patients with chronic progressive multiple sclerosis, the…

Comparison of external catheters with subcutaneous vascular access ports for chronic vascular access in a porcine model.

PubMed

Chuang, Marc; Orvieto, Marcelo; Laven, Brett; Gerber, Glenn; Wardrip, Craig; Ritch, Chad; Shalhav, Arieh

2005-03-01

We sought to compare the outcomes of two chronic vascular access techniques, the externalized catheter and the subcutaneous vascular access port, in pigs. Female farm pigs (n = 30) underwent placement of a chronic vascular access device in the jugular vein for a research protocol: 18 of the animals underwent placement of a tunneled Hickman catheter (THC), and the remaining 12 animals underwent placement of a subcutaneous vascular access port (VAP) without external components. After placement of the devices, animals underwent serial blood sampling. All animals were given identical antibiotic prophylaxis. VAP access required the use of a restraint sling for Huber needle insertion, whereas THC access required no additional equipment. Animals were euthanatized 1 month after placement of the device. In the VAP group, the port was retrieved, cleaned, and steam-autoclaved for reuse. In the THC group, 13 (72%) animals developed infectious complications, and blood and wound cultures were often polymicrobial. One animal was euthanatized secondary to overwhelming sepsis. In addition, three (17%) animals developed thromboembolic complications. In contrast, no thromboembolic complications were noted in the VAP group, and only one animal developed a transient fever which resolved spontaneously; no septic complications or abscesses developed. Blood draws with no anesthesia were successful in both groups. We conclude that subcutaneous vascular access ports are a safe and efficient method for obtaining reliable chronic vascular access for a 1-month period in pigs. The subcutaneous devices were associated with low morbidity. In contrast, externalized catheters can be associated with considerable morbidity.

Trajectories of child externalizing problems between ages 3 and 10 years: Contributions of children's early effortful control, theory of mind, and parenting experiences.

PubMed

Olson, Sheryl L; Choe, Daniel Ewon; Sameroff, Arnold J

2017-10-01

Preventing problem behavior requires an understanding of earlier factors that are amenable to intervention. The main goals of our prospective longitudinal study were to trace trajectories of child externalizing behavior between ages 3 and 10 years, and to identify patterns of developmentally significant child and parenting risk factors that differentiated pathways of problem behavior. Participants were 218 3-year-old boys and girls who were reassessed following the transition to kindergarten (age 5-6 years) and during the late school-age years (age 10). Mothers contributed ratings of children's externalizing behavior at all three time points. Children's self-regulation abilities and theory of mind were assessed during a laboratory visit, and parenting risk (frequent corporal punishment and low maternal warmth) was assessed using interview-based and questionnaire measures. Four developmental trajectories of externalizing behavior yielded the best balance of parsimony and fit with our longitudinal data and latent class growth analysis. Most young children followed a pathway marked by relatively low levels of symptoms that continued to decrease across the school-age years. Atypical trajectories marked chronically high, increasing, and decreasing levels of externalizing problems across early and middle childhood. Three-year-old children with low levels of effortful control were far more likely to show the chronic pattern of elevated externalizing problems than changing or low patterns. Early parental corporal punishment and maternal warmth, respectively, differentiated preschoolers who showed increasing and decreasing patterns of problem behavior compared to the majority of children. The fact that children's poor effortful regulation skills predicted chronic early onset problems reinforces the need for early childhood screening and intervention services.

What motivates Australian health service users with chronic illness to engage in self-management behaviour?

PubMed

Jowsey, Tanisha; Pearce-Brown, Carmen; Douglas, Kirsty A; Yen, Laurann

2014-04-01

Health policy in Australia emphasizes the role of health service users (HSU) in managing their own care but does not include mechanisms to assist HSUs to do so. To describe motivation towards or away from self-management in a diverse group of older Australians with diabetes, chronic heart failure (CHF) or chronic obstructive pulmonary disease (COPD) and suggest policy interventions to increase patient motivation to manage effectively. Content and thematic analyses of in-depth semi-structured interviews. Participants were asked to describe their experience of having chronic illness, including experiences with health professionals and health services. Secondary analysis was undertaken to expose descriptions of self-management behaviours and their corresponding motivational factors. Health service users with diabetes, COPD and/or CHF (N=52). Participant descriptions exposed internal and external sources of motivation. Internal motivation was most often framed positively in terms of the desire to optimize health, independence and wellness and negatively in terms of avoiding the loss of those attributes. External motivation commonly arose from interactions with family, carers and health professionals. Different motivators appeared to work simultaneously and interactively in individuals, and some motivators seemed to be both positive and negative drivers. Successful management of chronic illness requires recognition that the driving forces behind motivation are interconnected. In particular, the significance of family as an external source of motivation suggests a need for increased investment in the knowledge and skill building of family members who contribute to care. © 2011 John Wiley & Sons Ltd.

Association between organizational capacity and involvement in chronic disease prevention programming among Canadian public health organizations

PubMed Central

Hanusaik, Nancy; Sabiston, Catherine M.; Kishchuk, Natalie; Maximova, Katerina; O’Loughlin, Jennifer

2015-01-01

In the context of the emerging field of public health services and systems research, this study (i) tested a model of the relationships between public health organizational capacity (OC) for chronic disease prevention, its determinants (organizational supports for evaluation, partnership effectiveness) and one possible outcome of OC (involvement in core chronic disease prevention practices) and (ii) examined differences in the nature of these relationships among organizations operating in more and less facilitating external environments. OC was conceptualized as skills and resources/supports for chronic disease prevention programming. Data were from a census of 210 Canadian public health organizations with mandates for chronic disease prevention. The hypothesized relationships were tested using structural equation modeling. Overall, the results supported the model. Organizational supports for evaluation accounted for 33% of the variance in skills. Skills and resources/supports were directly and strongly related to involvement. Organizations operating within facilitating external contexts for chronic disease prevention had more effective partnerships, more resources/supports, stronger skills and greater involvement in core chronic disease prevention practices. Results also suggested that organizations functioning in less facilitating environments may not benefit as expected from partnerships. Empirical testing of this conceptual model helps develop a better understanding of public health OC. PMID:25361958

Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia

NASA Astrophysics Data System (ADS)

Brehme, Marc; Koschmieder, Steffen; Montazeri, Maryam; Copland, Mhairi; Oehler, Vivian G.; Radich, Jerald P.; Brümmendorf, Tim H.; Schuppert, Andreas

2016-04-01

Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34+ similarity as a disease progression marker to patient-derived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients’ disease history within chronic phase (CP) and significantly separates “early” from “late” CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis.

Acupuncture May Be Helpful for Chronic Pain: A Meta-Analysis

MedlinePlus

... health-related information is available. Related Topics NIH Analysis Shows Americans Are In Pain Research Results Research Results by Date This page last modified August 29, 2016 Follow NCCIH: Read our disclaimer about external links Twitter Read our disclaimer about external links Facebook Read ...

The Interplay between inflammation and fibrosis in kidney transplantation.

PubMed

Torres, Irina B; Moreso, Francesc; Sarró, Eduard; Meseguer, Anna; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis.

The Interplay between Inflammation and Fibrosis in Kidney Transplantation

PubMed Central

Torres, Irina B.; Moreso, Francesc; Sarró, Eduard; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis. PMID:24991565

Hypertensive chronic kidney disease in African Americans: Strategies for improving care

PubMed Central

MARTINS, DAVID; AGODOA, LAWRENCE; NORRIS, KEITH C.

2013-01-01

African Americans have a disproportionate burden of chronic kidney disease (CKD), which tends to have an earlier onset and a more rapid progression in this population. Many of the factors responsible for the rapid progression of CKD in African Americans are detectable by screening and are modifiable with prompt therapy. PMID:23027732

[Clinicofunctional condition and quality of life in patients with chronic obstructive pulmonary disease before and after outpatient treatment with fenspiride].

PubMed

Butorov, S I; Butorov, I V; Bodrug, N I; Krushka, S I; Tofan, E F

2008-01-01

To study effects of long-term administration of fenspiride in combination with broncholytic drugs on dynamics of clinical symptoms, external respiration function and quality of life in patients with chronic obstructive pulmonary disease (COPD). A comparative randomized trial of fenspiride used for 6 months in combination with broncholytic drugs enrolled 68 COPD patients. A clinical status, external respiration function were examined. Quality of life was evaluated with WHO questionnaire WHOQOL-100. Addition of fenspiride to combined treatment of COPD attenuates COPD symptoms, normalizes blood biochemistry, improves external respiration function, raises exercise tolerance. Quality of life improved by physical and mental state scales. Fenspiride addition to COPD treatment improves efficacy of the standard treatment and is recommended for treatment of COPD of stage I and II in combination with broncholytic drugs.

Using the Program Sustainability Assessment Tool to Assess and Plan for Sustainability

PubMed Central

Mainor, Avia; Moreland-Russell, Sarah; Maier, Ryan C.; Brossart, Laura; Luke, Douglas A.

2014-01-01

Implementing and growing a public health program that benefits society takes considerable time and effort. To ensure that positive outcomes are maintained over time, program managers and stakeholders should plan and implement activities to build sustainability capacity within their programs. We describe a 3-part sustainability planning process that programs can follow to build their sustainability capacity. First, program staff and stakeholders take the Program Sustainability Assessment Tool to measure their program’s sustainability across 8 domains. Next, managers and stakeholders use results from the assessment to inform and prioritize sustainability action planning. Lastly, staff members implement the plan and keep track of progress toward their sustainability goals. Through this process, staff can more holistically address the internal and external challenges and pressures associated with sustaining a program. We include a case example of a chronic disease program that completed the Program Sustainability Assessment Tool and engaged in program sustainability planning. PMID:24456644

A new mitochondrial point mutation in the transfer RNA(Lys) gene associated with progressive external ophthalmoplegia with impaired respiratory regulation.

PubMed

Wolf, Joachim; Obermaier-Kusser, Bert; Jacobs, Martina; Milles, Cornelia; Mörl, Mario; von Pein, Harald D; Grau, Armin J; Bauer, Matthias F

2012-05-15

We report a novel heteroplasmic point mutation G8299A in the gene for mitochondrial tRNA(Lys) in a patient with progressive external ophthalmoplegia complicated by recurrent respiratory insufficiency. Biochemical analysis of respiratory chain complexes in muscle homogenate showed a combined complex I and IV deficiency. The transition does not represent a known neutral polymorphism and affects a position in the tRNA acceptor stem which is conserved in primates, leading to a destabilization of this functionally important domain. In vitro analysis of an essential maturation step of the tRNA transcript indicates the probable pathogenicity of this mutation. We hypothesize that there is a causal relationship between the novel G8299A transition and progressive external ophthalmoplegia with recurrent respiratory failure due to a depressed respiratory drive. Copyright © 2012 Elsevier B.V. All rights reserved.

Epigenetics of kidney disease.

PubMed

Wanner, Nicola; Bechtel-Walz, Wibke

2017-07-01

DNA methylation and histone modifications determine renal programming and the development and progression of renal disease. The identification of the way in which the renal cell epigenome is altered by environmental modifiers driving the onset and progression of renal diseases has extended our understanding of the pathophysiology of kidney disease progression. In this review, we focus on current knowledge concerning the implications of epigenetic modifications during renal disease from early development to chronic kidney disease progression including renal fibrosis, diabetic nephropathy and the translational potential of identifying new biomarkers and treatments for the prevention and therapy of chronic kidney disease and end-stage kidney disease.

Proteolytic roles of matrix metalloproteinase (MMP)-13 during progression of chronic periodontitis: initial evidence for MMP-13/MMP-9 activation cascade.

PubMed

Hernández Ríos, Marcela; Sorsa, Timo; Obregón, Fabián; Tervahartiala, Taina; Valenzuela, María Antonieta; Pozo, Patricia; Dutzan, Nicolás; Lesaffre, Emmanuel; Molas, Marek; Gamonal, Jorge

2009-12-01

Matrix metalloproteinases (MMP)-13 can initiate bone resorption and activate proMMP-9 in vitro, and both these MMPs have been widely implicated in tissue destruction associated with chronic periodontitis. We studied whether MMP-13 activity and TIMP-1 levels in gingival crevicular fluid (GCF) associated with progression of chronic periodontitis assessed clinically and by measuring carboxy-terminal telopeptide of collagen I (ICTP) levels. We additionally addressed whether MMP-13 could potentiate gelatinase activation in diseased gingival tissue. In this prospective study, GCF samples from subjects undergoing clinical progression of chronic periodontitis and healthy controls were screened for ICTP levels, MMP-13 activity and TIMP-1. Diseased gingival explants were cultured, treated or not with MMP-13 with or without adding CL-82198, a synthetic MMP-13 selective inhibitor, and assayed by gelatin zymography and densitometric analysis. Active sites demonstrated increased ICTP levels and MMP-13 activity (p<0.05) in progression subjects. The MMP-9 activation rate was elevated in MMP-13-treated explants (p<0.05) and MMP-13 inhibitor prevented MMP-9 activation. MMP-13 could be implicated in the degradation of soft and hard supporting tissues and proMMP-9 activation during progression of chronic periodontitis. MMP-13 and -9 can potentially form an activation cascade overcoming the protective TIMP-1 shield, which may become useful for diagnostic aims and a target for drug development.

Relation of Insulin Resistance and Liver Fibrosis Progression in Patients with Chronic Hepatitis C Virus Infection

PubMed Central

Mohamed, Hassan R; Abdel-Azziz, Mohamed Yaqoot; Zalata, Kkaled Refaat; Abdel-Razik, Ahmed M M

2009-01-01

Background: Hepatitis C virus (HCV) infection can predispose to the development of insulin resistance before diabetes occurs. Such a potential link is particularly cogent in light of recent data indicate that diabetes may be associated with increased hepatic fibrosis progression in patients with chronic HCV infection. The aim of the study is to determine the prevalence of insulin resistance in non diabetic patients with chronic hepatitis C and its relation to liver fibrosis. Methods: Thirty eight patients with chronic liver diseases. They subdivided into 2 groups; chronic hepatitis C (CHC) with elevated liver enzymes and CHC with normal liver enzymes. Age and sex matched 12 healthy subjects as control group. All subjects were subjected to Careful history and copmlete examination with stress upon symptoms and signs of chronic liver diseases. Investigations include liver function tests; viral markers (Anti HCV antibodies & PCR for HCV). Serum fasting glucose; serum fasting insulin; homeostasis model assessment (HOMA), liver biopsy and abdominal ultrasound. Results: No correlation between viral load and hepatic fibrosis in HCV infected patients. Liver fibrosis is considerably higher among HCV patients with elevated serum transaminase levels. Insulin resistance is present in HCV infected cases compared with control group and it is positively correlated with liver fibrosis. Conclusion: The present data support the hypothesis that insulin resistance may increase the rate of fibrosis progression in non diabetic patients with chronic HCV. Follow up of hyperinsulinemia by serial measurement of HOMA test in non diabetic HCV infected patients may be a biochemical indicator for progression of liver fibrosis. PMID:21475535

N-acteyl-ß-D-glucosaminidase and kidney injury molecule-1: New predictors for long-term progression of chronic kidney disease in patients with heart failure.

PubMed

Jungbauer, Carsten G; Uecer, Ekrem; Stadler, Stefan; Birner, Christoph; Buchner, Stefan; Maier, Lars S; Luchner, Andreas

2016-06-01

Patients with chronic heart failure (CHF) are often characterized by the cardiorenal syndrome (CRS). The aim of the present study was to assess whether novel markers of kidney injury are able to predict progression of chronic kidney disease (CKD) in patients with CHF. New renal biomarkers, N-acteyl-ß-D-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL), were assessed from urine samples of 149 patients with chronic heart failure. During a 5-year-follow-up, renal function was assessed by creatinine and estimated glomerular filtration rate (eGFR CKD EPI) and was available for 138 patients. Further, data regarding all-cause mortality was obtained. Twenty-six patients (18.8%) developed a progression of CKD during the follow-up period, as defined by decline in eGFR category accompanied by a ≥25% drop in eGFR form baseline. No difference regarding age, sex, body mass index, hypertension, diabetes or EF was present between patients with and without CKD progression (each P = n.s.). At baseline, creatinine concentrations and eGFR were significantly different between both groups (sCr: 1.50 ± 0.67 vs 1.04 ± 0.37, P = < 0.001; eGFR: 47.8 ± 12.3 vs. 77.3 ± 23.5 mL/min per 1.73m(2) , each P < 0.001). In a Kaplan-Meier-analysis, KIM-1 and NAG were significant predictors for CKD progression (both P < 0.05). In Cox regression analysis, NAG > median (OR 3.25,P = 0.013), initial eGFR (OR 0.94, P < 0.001) and diuretic use (OR 3.92, P = 0.001) were independent predictors of CKD progression. Further, KIM-1 and NAG were also independent predictors of a combined endpoint of CKD progression and all-cause mortality by Cox regression analysis (each P < 0.05). The combination of both markers showed additive value regarding both endpoints. NGAL showed no association with CKD progression. During long-term follow-up chronic heart failure patients with CKD show a relevant disease progression. The current study emphasizes a strong association of the tubular biomarkers NAG and KIM-1 with CKD progression in chronic heart failure and suggests their usefulness as cardiorenal markers. © 2015 Asian Pacific Society of Nephrology.

Determining the Optimal Number of Spinal Manipulation Sessions for Chronic Low-Back Pain

MedlinePlus

... health-related information is available. Related Topics NIH Analysis Shows Americans Are In Pain Research Results Research Results by Date This page last modified September 13, 2016 Follow NCCIH: Read our disclaimer about external links Twitter Read our disclaimer about external links Facebook Read ...

Advanced phase chronic myeloid leukaemia (CML) in the tyrosine kinase inhibitor era - a report from the Swedish CML register.

PubMed

Söderlund, Stina; Dahlén, Torsten; Sandin, Fredrik; Olsson-Strömberg, Ulla; Creignou, Maria; Dreimane, Arta; Lübking, Anna; Markevärn, Berit; Själander, Anders; Wadenvik, Hans; Stenke, Leif; Richter, Johan; Höglund, Martin

2017-01-01

The primary goal in management of chronic phase (CP) chronic myeloid leukaemia (CML) is to prevent disease progression to accelerated phase (AP) or blast crisis (BC). We have evaluated progression rates in a decentralised healthcare setting and characterised patients progressing to AP/BC on TKI treatment. Using data from the Swedish CML register, we identified CP-CML patients diagnosed 2007-2011 who progressed to AP/BC within 2 yrs from diagnosis (n = 18) as well as patients diagnosed in advanced phase during 2007-2012 (n = 36) from a total of 544 newly diagnosed CML cases. We evaluated baseline characteristics, progression rates, outcome and adherence to guidelines for monitoring and treatment. The cumulative progression rate at 2 yrs was 4.3%. All 18 progression cases had been treated with imatinib, and six progressed within 6 months. High-risk EUTOS score was associated to a higher risk of progression. Insufficient cytogenetic and/or molecular monitoring was found in 33%. Median survival after transformation during TKI treatment was 1.4 yrs. In those presenting with BC and AP, median survival was 1.6 yrs and not reached, respectively. In this population-based setting, progression rates appear comparable to that reported from clinical trials, with similar dismal patient outcome. Improved adherence to CML guidelines may minimise the risk of disease progression. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia

PubMed Central

Brehme, Marc; Koschmieder, Steffen; Montazeri, Maryam; Copland, Mhairi; Oehler, Vivian G.; Radich, Jerald P.; Brümmendorf, Tim H.; Schuppert, Andreas

2016-01-01

Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34+ similarity as a disease progression marker to patient-derived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients’ disease history within chronic phase (CP) and significantly separates “early” from “late” CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis. PMID:27048866

Susceptibility to chronic inflammation: an update.

PubMed

Nasef, Noha Ahmed; Mehta, Sunali; Ferguson, Lynnette R

2017-03-01

Chronic inflammation is defined by the persistence of inflammatory processes beyond their physiological function, resulting in tissue destruction. Chronic inflammation is implicated in the progression of many chronic diseases and plays a central role in chronic inflammatory and autoimmune disease. As such, this review aims to collate some of the latest research in relation to genetic and environmental susceptibilities to chronic inflammation. In the genetic section, we discuss some of the updates in cytokine research and current treatments that are being developed. We also discuss newly identified canonical and non-canonical genes associated with chronic inflammation. In the environmental section, we highlight some of the latest updates and evidence in relation to the role that infection, diet and stress play in promoting inflammation. The aim of this review is to provide an overview of the latest research to build on our current understanding of chronic inflammation. It highlights the complexity associated with chronic inflammation, as well as provides insights into potential new targets for therapies that could be used to treat chronic inflammation and consequently prevent disease progression.

Chronic exposure to cocaine binging predisposes to an accelerated course of dilated cardiomyopathy in conscious dogs following rapid ventricular pacing.

PubMed

Parikh, Pratik; Nikolaidis, Lazaros A; Stolarski, Carol; Shen, You-Tang; Shannon, Richard P

2005-12-01

Despite extensive study, the extent to which cocaine use predisposes to cardiac injury remains unknown. We hypothesized that chronic cocaine binging would increase susceptibility to a subsequent cardiac insult, even in the absence of demonstrable effects on baseline hemodynamics. We studied progression of dilated cardiomyopathy (DCM) induced by rapid ventricular pacing (240 beats per minute) in five conscious, chronically instrumented dogs, after exposure to repetitive cocaine binging (COC) in the form of four consecutive 1 mg/kg i.v. boluses daily for 8 days, to simulate human cocaine abuse. We compared the results with nine control dogs (CON) undergoing the exact pacing protocol, without prior cocaine exposure. Baseline hemodynamics were not significantly altered by chronic cocaine exposure. Following 2 weeks of pacing, COC dogs exhibited accelerated progression to DCM, depressed plasma nitric oxide levels (CON, 17 +/- 2 microM; COC, 10 +/- 2 microM, p < 0.05), and a significantly greater increase in plasma epinephrine (CON, 33 +/- 6 pg/ml; COC, 104 +/- 24 pg/ml). After only 2 weeks of pacing, COC dogs demonstrated progressive DCM of a magnitude comparable with end-stage pacing-induced DCM. Chronic cocaine binging increases susceptibility to a subsequent myocardial insult and accelerates progression of DCM in conscious dogs following rapid pacing. These data suggest that although chronic cocaine use alone may not affect myocardial function, it predisposes to greater susceptibility to a superimposed insult.

Chronic obstructive pulmonary disease and chronic heart failure: two muscle diseases?

PubMed

Troosters, Thierry; Gosselink, Rik; Decramer, Marc

2004-01-01

Chronic obstructive pulmonary disease and congestive heart failure are two increasingly prevalent chronic diseases. Although care for these patients often is provided by different clinical teams, both disease conditions have much in common. In recent decades, more knowledge about the systemic impact of both diseases has become available, highlighting remarkable similarities in terms of prognostic factors and disease management. Rehabilitation programs deal with the systemic consequences of both diseases. Although clinical research also is conducted by various researchers investigating chronic obstructive pulmonary disease and chronic heart failure, it is worthwhile to compare the progress in relation to these two diseases over recent decades. Such comparison, the purpose of the current review, may help clinicians and scientists to learn about progress made in different, yet related, fields. The current review focuses on the similarities observed in the clinical impact of muscle weakness, the mechanisms of muscle dysfunction, the strategies to improve muscle function, and the effects of exercise training on chronic obstructive pulmonary disease and chronic heart failure.

A comparison of patterns of disease extension in keratosis obturans and external auditory canal cholesteatoma.

PubMed

Shinnabe, Akihiro; Hara, Mariko; Hasegawa, Masayo; Matsuzawa, Shingo; Kanazawa, Hiromi; Yoshida, Naohiro; Iino, Yukiko

2013-01-01

To investigate the different pathways of progression to the middle ear in keratosis obturans (KO) and external auditory canal cholesteatoma (EACC). Retrospective case review. Referral hospital otolaryngology department. Patients with KO or EACC and middle ear disease who underwent surgical management were included. Four ears of 4 patients (mean age, 41.25 yr) were the KO group, and 5 ears of 4 patients (mean age, 49.5 yr) were the EACC group. Intraoperative findings of the middle ear cavity were investigated in KO and EACC groups. In the KO group, 3 patients had a perforated tympanic membrane and cholesteatoma in the tympanic cavity. The other patient had preoperative right facial palsy. Removal of the keratin plug revealed an adherent tympanic membrane. In intraoperative findings, the tympanic segment of the fallopian canal was found to be eroded because of inflammation. No case initially progressed to the mastoid cavity. Four patients had external auditory canal cholesteatoma with middle ear disease. In EACC group, all patients had initial progression to the mastoid cavity. KO tends to progress initially to the tympanic cavity via a diseased tympanic membrane. EACC tends to progress to the mastoid cavity via destruction of the posterior bony canal. This is the first report to investigate differences in pathway of progression to the middle ear cavity in these 2 diseases.

Transperineal sonographic anal sphincter complex evaluation in chronic anal fissures.

PubMed

Bedair, Elsaid M; El Hennawy, Hany M; Moustafa, Ahmed Abdu; Meki, Gad Youssef; Bosat, Bosat Elwany

2014-11-01

The purpose of this study was to assess the role of transperineal sonography in assessment of pathologic changes to the anal sphincter complex in patients with chronic anal fissures. We conducted a prospective case-control study of 100 consecutive patients of any age and both sexes with chronic anal fissures who presented to a colorectal clinic between January 2012 and August 2013 (group A) and 50 healthy volunteers (group B). The most common patterns of radiologic changes to anal sphincters associated with chronic anal fissures were circumferential thickening of the anal sphincter complex in 5 patients (5%), circumferential thickening of the internal anal sphincter in 3 patients (3%), preferential thickening of the internal anal sphincter at the 6-o'clock position in 80 patients (80%) and the 12-o'clock position in 7 patients (7%), preferential thickening of the internal and external anal sphincters in 3 patients (3%), and thinning of the internal anal sphincter in 2 patients (2%). Chronic anal fissures cause differential thickening of both internal and external anal sphincters, with a trend toward increased thickness in relation to the site of the fissure. Routine preoperative transperineal sonography for patients with chronic anal fissures is recommended, and it is mandatory in high-risk patients. © 2014 by the American Institute of Ultrasound in Medicine.

Association between organizational capacity and involvement in chronic disease prevention programming among Canadian public health organizations.

PubMed

Hanusaik, Nancy; Sabiston, Catherine M; Kishchuk, Natalie; Maximova, Katerina; O'Loughlin, Jennifer

2015-04-01

In the context of the emerging field of public health services and systems research, this study (i) tested a model of the relationships between public health organizational capacity (OC) for chronic disease prevention, its determinants (organizational supports for evaluation, partnership effectiveness) and one possible outcome of OC (involvement in core chronic disease prevention practices) and (ii) examined differences in the nature of these relationships among organizations operating in more and less facilitating external environments. OC was conceptualized as skills and resources/supports for chronic disease prevention programming. Data were from a census of 210 Canadian public health organizations with mandates for chronic disease prevention. The hypothesized relationships were tested using structural equation modeling. Overall, the results supported the model. Organizational supports for evaluation accounted for 33% of the variance in skills. Skills and resources/supports were directly and strongly related to involvement. Organizations operating within facilitating external contexts for chronic disease prevention had more effective partnerships, more resources/supports, stronger skills and greater involvement in core chronic disease prevention practices. Results also suggested that organizations functioning in less facilitating environments may not benefit as expected from partnerships. Empirical testing of this conceptual model helps develop a better understanding of public health OC. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Locus of Control and Neuropsychological Performance in Chronic Alcoholics.

ERIC Educational Resources Information Center

Shelton, M. D.; And Others

1982-01-01

Examined correlated neuropsychological performance in male chronic alcoholics and non-alcoholic controls. Results showed external locus of control (LOC-E) scores to predict performance on neuropsychological tests in alcoholics but not in controls. Suggests the LOC-E variables cannot account for the widespread differences between the groups on…

Progressive shoulder-neck exercise on cervical muscle functions in middle-aged and senior patients with chronic neck pain.

PubMed

Lin, I-Hsien; Chang, Kwang-Hwa; Liou, Tsan-Hon; Tsou, Chih-Min; Huang, Yi-Ching

2018-02-01

Although neck pain is a common musculoskeletal disorder, there is no consensus on suitable exercise methods for middle-aged and senior patients with chronic neck pain. Therefore, this study investigated the effectiveness of a 6-week shoulder-neck exercise intervention program on cervical muscle function improvement in patients aged 45 years or older with chronic neck pain. The aim of the present study was to evaluate the effects of progressive shoulder-neck exercise on cervical muscle functions of middle-aged and senior patients with chronic neck pain. A randomized controlled single-blind trial. Rehabilitation department of a hospital. A total of 72 subjects aged ≥45 years with chronic neck pain were randomly allocated to either an experimental group (N.=36; age 57.3±8.74 years) or a control group (N.=36; age 58.15±8.17 years). The control group received only traditional physiotherapy, whereas the experimental group participated in a 6-week shoulder-neck exercise program consisting of cranio-cervical flexion and progressive resistance exercises in addition to receiving traditional physiotherapy. The muscle functions of subjects in both groups were tested before the experiment and also after the intervention program. The pretest and posttest measured the cranio-cervical flexion test (CCFT) and the superficial cervical muscle strength. After the intervention, the experimental group had a 56.48 point improvement in the performance index of the CCFT (P<0.001), a 1.71-kg improvement in superficial neck flexor strength (P<0.001), and a 2.52-kg improvement in superficial neck extensor strength (P<0.001), indicating that in 6-week intervention significantly influenced the improvement of cervical muscle functions. This study confirmed that the 6-week progressive shoulder-neck exercise program can effectively improve cervical muscle function in middle-aged and senior patients with chronic neck pain. Progressive shoulder-neck exercise might provide positive effect on deep and superficial neck muscle strength in patients with chronic neck pain. Therefore, this study may serve as a reference for the clinical rehabilitation of patients with chronic neck pain.

Offspring of Parents with Chronic Pain: A Systematic Review and Meta-Analysis of Pain, Health, Psychological, and Family Outcomes

PubMed Central

Higgins, Kristen S.; Birnie, Kathryn A.; Chambers, Christine T.; Wilson, Anna C.; Caes, Line; Clark, Alexander J.; Lynch, Mary; Stinson, Jennifer; Campbell-Yeo, Marsha

2015-01-01

Offspring of parents with chronic pain may be at risk for poorer outcomes than offspring of healthy parents. The objective of this research was to provide a comprehensive mixed-methods, systematic synthesis of all available research on outcomes in offspring of parents with chronic pain. A systematic search was conducted for published articles in English examining pain, health, psychological, or family outcomes in offspring of parents with chronic pain. Fifty-nine eligible articles were identified (31 population-based, 25 clinical, 3 qualitative), including offspring from birth to adulthood and parents with varying chronic pain diagnoses (e.g., mixed pain samples, arthritis). Meta-analysis was used to synthesize the results from population-based and clinical studies, while meta-ethnography was used to synthesize the results of qualitative studies. Increased pain complaints were found in offspring of mothers and of fathers with chronic pain, and when both parents had chronic pain. Newborns of mothers with chronic pain were more likely to have adverse birth outcomes, including low birthweight, preterm delivery, caesarean section, intensive care admission, and mortality. Offspring of parents with chronic pain had greater externalizing and internalizing problems and poorer social competence and family outcomes. No significant differences were found on teacher-reported externalizing problems. The meta-ethnography identified six key concepts (developing independence, developing compassion, learning about health and coping, missing out, emotional health, and struggles communicating with parents). Across study designs, offspring of parents with chronic pain had poorer outcomes than other offspring, although the meta-ethnography noted some constructive impact of having a parent with chronic pain. PMID:26172553

Increasing methylation of the calcitonin gene during disease progression in sequential samples from CML patients.

PubMed

Mills, K I; Guinn, B A; Walsh, V A; Burnett, A K

1996-09-01

In chronic myeloid leukaemia (CML), disease progression from the initial chronic phase to the acute phase or blast crisis has previously been shown to be correlated with progressive increases in hyper-methylation of the calcitonin gene, located at chromosome 11p15. However, sequential studies of individual patients were not performed in these investigations. We have analysed 44 samples from nine patients with typical Philadelphia chromosome positive CML throughout their disease progression to determine the methylation state of the calcitonin gene at these time points. Densitometry was used to quantitate the ratio of the normal 2.0 kb Hpa II fragments, indicating normal methylation status of the gene, compared to the intensity of the abnormal, hyper-methylated, 2.6-3.1 kb Hpa II fragments. We found a gradual increase in the ratio of methylated:unmethylated calcitonin gene during chronic phase with a dramatic rise at blast crisis. Further, the ratio of the abnormal hypermethylated 3.1 kb fragments to the methylated 2.6 kb fragment resulted in the identification of a clonal expansion of abnormally methylated cells. This expansion of cells with hypermethylation of the calcitonin gene during chronic phase was shown to coincide with the presence of a mutation in the p53 gene. The data presented in this study would suggest that an increased methylation status of the calcitonin gene during disease progression may indicate the expansion of abnormal blast cell populations and subsequent progression to blast crisis.

Disease drivers of aging

PubMed Central

Hodes, Richard J.; Sierra, Felipe; Austad, Steven N.; Epel, Elissa; Neigh, Gretchen N.; Erlandson, Kristine M.; Schafer, Marissa J.; LeBrasseur, Nathan K.; Wiley, Christopher; Campisi, Judith; Sehl, Mary E.; Scalia, Rosario; Eguchi, Satoru; Kasinath, Balakuntalam S.; Halter, Jeffrey B.; Cohen, Harvey Jay; Demark-Wahnefried, Wendy; Ahles, Tim A.; Barzilai, Nir; Hurria, Arti; Hunt, Peter W.

2017-01-01

It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship—the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging. PMID:27943360

[Oxidative stress and antioxitant therapy of chronic periodontitis].

PubMed

Shen, Y X; Guo, S J; Wu, Y F

2016-07-01

Chronic periodontitis is a progressive, infectious inflammation disease, caused by the dysbiosis of oral resident flora, leading to the destruction of periodontium. The onset of pathogenic microorganisms is the etiological factor of periodontitis, while the immuno-inflammatory response affects the progression of the disease. Under chronic periodontitis, oxidative stress occurs when excessive reactive oxygen species are produced and exceed the compensative capacity of the organism. Oxidative stress leads to the destruction of periodontium, in a direct way(damaging the biomolecule) or an indirect way(enhancing the produce of inflammatory cytokine and destructive enzymes). Therefore, as the antagonist of the reactive oxygen species, antioxidants may be helpful to treat the chronic periodontitis. This paper reviewed relevant literatures about the destructive role of excessive reactive oxygen species and protective role of antioxidants in chronic periodontitis.

A case of chronic inflammatory demyelinating polyneuropathy presented with unilateral ptosis.

PubMed

Izadi, Sadegh; Karamimagham, Sina; Poursadeghfard, Maryam

2014-01-01

Chronic Inflammatory Demyelinating Polyneuropathy is an autoimmune disease with progressive and relapsing courses. The main clinical presentations are diffuse deep tendon hyporeflexia or areflexia and symmetric proximal-distal muscles weakness. Myasthenia gravis is also an immune mediated disease with fluctuating ocular and bulbar symptoms and sometimes weakness. Although both myasthenia gravis and chronic inflammatory demyelinating polyneuropathy are immune mediated disorders, clinical presentations are obviously different in the two diseases. Herein, we will report a case of chronic inflammatory demyelinating polyneuropathy who presented with isolated unilateral ptosis. Initially, the patient was managed as ocular type of myasthenia gravis, but after progression to general limb weakness and areflexia, the diagnosis of chronic inflammatory demyelinating polyneuropathy was made. Although unilateral ptosis is a typical feature of myasthenia gravis, it may be seen as the first presentation of chronic inflammatory demyelinating polyneuropathy as well which mimics myasthenia gravis disease.

Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice

PubMed Central

Zhao, Lu; Xu, Jianhua; Liang, Fang; Li, Ao; Zhang, Yong; Sun, Jue

2015-01-01

Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies. PMID:26444281

Spikes in acute workload are associated with increased injury risk in elite cricket fast bowlers.

PubMed

Hulin, Billy T; Gabbett, Tim J; Blanch, Peter; Chapman, Paul; Bailey, David; Orchard, John W

2014-04-01

To determine if the comparison of acute and chronic workload is associated with increased injury risk in elite cricket fast bowlers. Data were collected from 28 fast bowlers who completed a total of 43 individual seasons over a 6-year period. Workloads were estimated by summarising the total number of balls bowled per week (external workload), and by multiplying the session rating of perceived exertion by the session duration (internal workload). One-week data (acute workload), together with 4-week rolling average data (chronic workload), were calculated for external and internal workloads. The size of the acute workload in relation to the chronic workload provided either a negative or positive training-stress balance. A negative training-stress balance was associated with an increased risk of injury in the week after exposure, for internal workload (relative risk (RR)=2.2 (CI 1.91 to 2.53), p=0.009), and external workload (RR=2.1 (CI 1.81 to 2.44), p=0.01). Fast bowlers with an internal workload training-stress balance of greater than 200% had a RR of injury of 4.5 (CI 3.43 to 5.90, p=0.009) compared with those with a training-stress balance between 50% and 99%. Fast bowlers with an external workload training-stress balance of more than 200% had a RR of injury of 3.3 (CI 1.50 to 7.25, p=0.033) in comparison to fast bowlers with an external workload training-stress balance between 50% and 99%. These findings demonstrate that large increases in acute workload are associated with increased injury risk in elite cricket fast bowlers.

Successful neuropsychological rehabilitation in a patient with Cerebellar Cognitive Affective Syndrome.

PubMed

Ruffieux, N; Colombo, F; Gentaz, E; Annoni, J-M; Chouiter, L; Roulin Hefti, S; Ruffieux, A; Bihl, T

2017-01-01

The objective of this case study was to describe the neuropsychological rehabilitation of a 16-year-old patient who presented a Cerebellar Cognitive Affective Syndrome (CCAS) following a bilateral cerebellar hemorrhage. The patient presented severe and diffuse cognitive deficits, massive behavioral disorders, and emotion regulation difficulties. The cognitive rehabilitation was performed in the chronic phase (one year after the onset of the hemorrhage) using a transdisciplinary neurobehavioral approach based on the patient's favorite interest (soccer). A significant behavioral and cognitive improvement was observed. The patient became progressively independent in all activities of daily living and was discharged home. The Functional Independence Measure at discharge was 124/126 (vs. 37/126 at entry). The patient was able to complete his schooling despite the mild cognitive and behavioral sequelae. This first description of the use of neurobehavioral therapy in a case of chronic CCAS suggests that (a) major clinical improvement can occur more than one year after the onset of the CCAS, showing the importance of long-term and intensive neurorehabilitation; and (b) when the cerebellum cannot properly play its regulator role in cognition, neuropsychological intervention through a behavioral and cognitive approach can be of great help by acting as an external modulator to help the patient regain control over himself.

Migraines in Women: Current Evidence for Management of Episodic and Chronic Migraines.

PubMed

Deneris, Angela; Rosati Allen, Peggy; Hart Hayes, Emily; Latendresse, Gwen

2017-05-01

Migraine headache is a disabling brain disorder that affects millions of women in the United States. Many migraine sufferers are undertreated. Both inadequate treatment and overuse of abortive migraine medication can contribute to progression from episodic to chronic migraine disorders. A significant number of migraine headaches or severity of episodic migraine headaches warrants treatment with prophylactic medications for prevention. This clinical update reviews the pathophysiology and diagnosis of migraine headaches in women, discusses the efficacy of abortive and chronic pharmacologic treatment, and examines strategies to prevent progression from episodic migraine to chronic migraine. A discussion of treatment during pregnancy and lactation is included. © 2017 by the American College of Nurse-Midwives.

The Pathology of Chronic Obstructive Pulmonary Disease: Progress in the 20th and 21st Centuries.

PubMed

Berg, Kyra; Wright, Joanne L

2016-12-01

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and is the fourth leading cause of death worldwide. There has been significant progress in the pathologic description and pathophysiologic analysis of COPD in the 20th and 21st centuries. We review the history, progression, and significance of pathologic alterations in COPD, including emphysematous changes, airway alterations, and vascular alterations. We also indicate what pathologic features of COPD the practicing pathologist should be describing in standard surgical and autopsy specimens.

Difference in resource utilization between patients with acute and chronic heart failure from Japanese administrative database.

PubMed

Kuwabara, Kazuaki; Matsuda, Shinya; Anan, Makoto; Fushimi, Kiyohide; Ishikawa, Koichi B; Horiguchi, Hiromasa; Hayashida, Kenshi; Fujimori, Kenji

2010-06-11

Many studies have reported economic evaluation of evolving agents or therapies for patients with heart failure (HF). However, little is known whether the disease progression category (acute or chronic HF) would be considered as a risk adjustment in health service research. This study profiles the difference in resource use or medical care for acute versus chronic HF. This study analyzed 17,912 HF patients treated in 62 academic hospitals and 351 community hospitals. Study variables included demographic variables, comorbid status, physical activity or disease progression at admission, procedures and laboratory tests, type and dose of heart-related medications, length of stay (LOS), and total charges (TC; 1 US$= 100 yen) for acute and chronic HF. The independent contributions of disease progression categories on LOS and TC were identified using multivariate analysis. We identified 9813 chronic and 8099 acute HF patients. Median LOS was 18 days for both chronic and acute HF, whereas TC was US$5731 and US$6447, respectively. Regression analysis revealed that acute HF was associated with a slightly greater TC, whereas performance of procedures was the most prominent factor. As NYHA class was the next most influential factor, class 3 or 4 resulted in longer LOS or greater TC, than did class 1. This study suggests that acute HF increased resource use slightly, whereas use of some practices indicated in critical care was affected more by the procedures performed. Disease progression category should remain an indicator for appropriateness of medical care. Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Addition of vitamin D reverses the decline in GFR following treatment with ACE inhibitors/angiotensin receptor blockers in patients with chronic kidney disease.

PubMed

Soares, Abel Esteves; Maes, Michael; Godeny, Paula; Matsumoto, Andressa Keiko; Barbosa, Décio Sabbatini; da Silva, Taysa Antonia F; Souza, Flávio Henrique M O; Delfino, Vinicius Daher Alvares

2017-12-15

Vitamin D has anti-inflammatory, anti-fibrotic effect, and may block the intrarenal renin-angiotensin system. Adequate vitamin D levels in conjunction with the use of Angiotensin-converting Enzyme Inhibitors/Angiotensin Receptor Blockers may help to slow down chronic kidney disease progression. To study a possible beneficial effect of vitamin D supplementation in chronic kidney disease patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on chronic kidney disease progression we performed a clinical study involving vitamin D supplementation in patients with deficiency of this vitamin. This study was conducted in two chronic kidney disease clinics in the city of Londrina, Brazil, from October 2010 to December 2012. It was involved stage 3 and 4 chronic kidney disease (estimated glomerular filtration rate between 60 and 15mL/min/1.73m 2 ) patients with and without vitamin D deficiency. The patients ingested six-month cholecalciferol 50,000IU oral supplementation to chronic kidney disease patients with vitamin D deficiency. We hypothesize changes in estimated glomerular filtration rate over study period. Our data demonstrate reservation of estimated glomerular filtration with cholecalciferol supplementation to chronic kidney disease patients taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. The combination treatment of angiotensin converting enzyme inhibitors/angiotensin receptor blockers with cholecalciferol prevents the decline in estimated glomerular filtration in patients with chronic kidney disease following treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and may represent a valid approach to reduce renal disease progression in chronic kidney disease patients with vitamin D deficiency. This result needs confirmation in prospective controlled clinical trials. Copyright © 2017. Published by Elsevier Inc.

[Role of smoking in bronchopulmonary disease formation in nickel production workers].

PubMed

Rocheva, I I; Siurin, S A; Nikanov, A N; Panychev

2007-01-01

Questionnaire and external respiration studies in 295 workers engaged into nickel production (including 158 smokers and 137 nonsmokers) revealed that smoking (7.92 +/- 0.63 packs/year in average) causes clinical symptoms of broncho-pulmonary diseases, lower functional parameters, increased risk of acute and chronic respiratory diseases preceding to chronic bronchitis.

The Main Concept Analysis in Cantonese Aphasic Oral Discourse: External Validation and Monitoring Chronic Aphasia

ERIC Educational Resources Information Center

Kong, Anthony Pak-Hin

2011-01-01

Purpose: The 1st aim of this study was to further establish the external validity of the main concept (MC) analysis by examining its relationship with the Cantonese Linguistic Communication Measure (CLCM; Kong, 2006; Kong & Law, 2004)--an established quantitative system for narrative production--and the Cantonese version of the Western Aphasia…

Chronic anal fissure: morphometric analysis of the anal canal at 3.0 Tesla MR imaging.

PubMed

Erden, Ayşe; Peker, Elif; Gençtürk, Zeynep Bıyıklı

2017-02-01

OBJECTıVE: To compare the morphometric data relating to the muscular structures of the anal canal, in patients with chronic anal fissure and in control group, examined at a 3.0 Tesla MR system. Forty-seven consecutive patients with chronic anal fissure and randomly selected 40 patients who had no claims for perianal disease during their life time were included in the study. T2-weighted sagittal, high-resolution (HR) T2-weighted, and contrast-enhanced fat-suppressed T1-weighted oblique axial and oblique coronal images were retrospectively analyzed by two observers in consensus. Thickness of sphincteric muscles, anal canal length, anorectal angle, thickness of anococcygeal ligament, depth of Minor triangle, width between subcutaneous sphincters, vascularity of posterior commissure, visibility of posterosuperior projection of external sphincter, and angle between the distal anal canal and posterosuperior projection of external sphincter (H angle) in patients and in controls were compared and analyzed using t test, Mann-Whitney U test, and Spearman correlation. The patients with chronic anal fissure had longer anal canal (51.50 mm ± 0.91 vs. 44.11 mm ± 0.71; p = 0.000), thicker internal anal sphincter muscle at mid-anal level (4.18 ± 0.15 vs. 3.39 ± 0.07; p = 0.007), and wider space between subcutaneous external sphincters (11.39 ± 0.50 vs. 6.89 ± 0.22; p = 0.000). In patients, there was a positive correlation between H angle and external sphincter thickness at proximal (r = 0.347; p = 0.021), middle (r = 0427; p = 0.000), and distal (r = 0.518; p = 0.000)) levels of the anal canal. CONCLUSıON: 3.0 Tesla MR imaging provides detailed information about the morphometric changes in the anal sphincter muscles in patients with chronic anal fissure.

Progressive trichodysplasia spinulosa in a patient with chronic lymphocytic leukaemia in remission.

PubMed

Lee, Joyce S-S; Frederiksen, Peter; Kossard, Steven

2008-02-01

A 70-year old Caucasian man with chronic lymphocytic leukaemia developed trichodysplasia spinulosa 2 months after ceasing chemotherapy. Histological features characteristic to this condition include dilated and enlarged hair follicles, hyperplastic hair bulbs, hyperplasia of inner root sheath cells with numerous large, eosinophilic, trichohyaline granules, and hypercornification. Although he was in remission for chronic lymphocytic leukaemia, lesions were slowly progressive 15 months after cessation of chemotherapy. We also describe a painless pull-test where spicules can be easily plucked and assessed microscopically for inner root sheath keratinization, or observed with surface microscopy in a clinic setting.

Chronic Inflammatory Demyelinating Polyneuropathy

PubMed Central

Dimachkie, Mazen M.; Barohn, Richard J.

2014-01-01

Opinion statement Chronic Inflammatory polyneuropathies are an important group of neuromuscular disorders that present chronically and progress over more than 8 weeks, being referred to as chronic inflammatory demyelinating polyneuropathy (CIDP). Despite tremendous progress in elucidating disease pathogenesis, the exact triggering event remains unknown. Our knowledge regarding diagnosis and management of CIDP and its variants continues to expand, resulting in improved opportunities for identification and treatment. Most clinical neurologists will be involved in the management of patients with these disorders, and should be familiar with available therapies for CIDP. We review the distinctive clinical, laboratory, and electro-diagnostic features that aid in diagnosis. We emphasize the importance of clinical patterns that define treatment responsiveness and the most appropriate therapies in order to improve prognosis. PMID:23564314

The role of iron in the pathophysiology and treatment of chronic hepatitis C

PubMed Central

Price, Leslie; Kowdley, Kris V

2009-01-01

Increased hepatic iron content may be observed in patients with chronic hepatitis C infection, and may contribute to disease severity. The presence of hemochromatosis gene mutations is associated with increased hepatic iron accumulation and may lead to accelerated disease progression. Hepatic iron depletion has been postulated to decrease the risk of hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C. It is possible that iron depletion stabilizes or improves liver histology and slows disease progression in these individuals. The present article reviews the prevalence and risk factors for hepatic iron overload in chronic hepatitis C, with emphasis on the available data regarding the efficacy of iron depletion in the treatment of this common liver disease. PMID:20011735

Strengthening National Disease Surveillance and Response-Haiti, 2010-2015.

PubMed

Juin, Stanley; Schaad, Nicolas; Lafontant, Donald; Joseph, Gerard A; Barzilay, Ezra; Boncy, Jacques; Barrais, Robert; Louis, Frantz Jean; Jean Charles, Nadia Lapierre; Corvil, Salomon; Barthelemy, Nickolsno; Dismer, Amber; Pierre, Jean Samuel; Archer, Roodly W; Antoine, Mayer; Marston, Barbara; Katz, Mark; Dely, Patrick; Adrien, Paul; Fitter, David L; Lowrance, David; Patel, Roopal

2017-10-01

Haiti's health system has faced many challenges over the years, with competing health priorities in the context of chronic financial and human resource limitations. As a result, the existing notifiable disease surveillance system was unable to provide the most basic epidemiologic data for public health decision-making and action. In the wake of the January 2010 earthquake, the Haitian Ministry of Public Health and Population collaborated with the U.S. Centers for Disease Control and Prevention, the Pan American Health Organization, and other local and international partners to implement a functional national surveillance system. More than 7 years later, it is important to take the opportunity to reflect on progress made on surveillance and response in Haiti, including disease detection, reporting, outbreak investigation, and response. The national epidemiologic surveillance network that started with 51 sites in 2010 has been expanded to 357 sites as of December 2015. Disease outbreaks identified via the surveillance system, or other surveillance approaches, are investigated by epidemiologists trained by the Ministry of Health's Field Epidemiology Training Program. Other related surveillance modules have been developed on the same model and electronic platform, allowing the country to document the impact of interventions, track progress, and monitor health problems. Sustainability remains the greatest challenge since most of the funding for surveillance come from external sources.

Presence of novel compound BCR-ABL mutations in late chronic and advanced phase imatinib sensitive CML patients indicates their possible role in CML progression.

PubMed

Akram, Afia Muhammad; Iqbal, Zafar; Akhtar, Tanveer; Khalid, Ahmed Mukhtar; Sabar, Muhammad Farooq; Qazi, Mahmood Hussain; Aziz, Zeba; Sajid, Nadia; Aleem, Aamer; Rasool, Mahmood; Asif, Muhammad; Aloraibi, Saleh; Aljamaan, Khaled; Iqbal, Mudassar

2017-04-03

BCR-ABL kinase domain (K D ) mutations are well known for causing resistance against tyrosine kinase inhibitors (TKIs) and disease progression in chronic myeloid leukemia (CML). In recent years, compound BCR-ABL mutations have emerged as a new threat to CML patients by causing higher degrees of resistance involving multiple TKIs, including ponatinib. However, there are limited reports about association of compound BCR-ABL mutations with disease progression in imatinib (IM) sensitive CML patients. Therefore, we investigated presence of ABL-K D mutations in chronic phase (n = 41), late chronic phase (n = 33) and accelerated phase (n = 16) imatinib responders. Direct sequencing analysis was used for this purpose. Eleven patients (12.22%) in late-CP CML were detected having total 24 types of point mutations, out of which 8 (72.72%) harbored compound mutated sites. SH2 contact site mutations were dominant in our study cohort, with E355G (3.33%) being the most prevalent. Five patients (45%) all having compound mutated sites, progressed to advanced phases of disease during follow up studies. Two novel silent mutations G208G and E292E/E were detected in combination with other mutants, indicating limited tolerance for BCR-ABL1 kinase domain for missense mutations. However, no patient in early CP of disease manifested mutated ABL-K D . Occurrence of mutations was found associated with elevated platelet count (p = 0.037) and patients of male sex (p = 0.049). The median overall survival and event free survival of CML patients (n = 90) was 6.98 and 5.8 y respectively. The compound missense mutations in BCR-ABL kinase domain responsible to elicit disease progression, drug resistance or disease relapse in CML, can be present in yet Imatinib sensitive patients. Disease progression observed here, emphasizes the need of ABL-K D mutation screening in late chronic phase CML patients for improved clinical management of disease.

[Various pathways leading to the progression of chronic liver diseases].

PubMed

Egresi, Anna; Lengyel, Gabriella; Somogyi, Anikó; Blázovics, Anna; Hagymási, Krisztina

2016-02-21

As the result of various effects (viruses, metabolic diseases, nutritional factors, toxic agents, autoimmune processes) abnormal liver function, liver steatosis and connective tissue remodeling may develop. Progression of this process is complex including various pathways and a number of factors. The authors summarize the factors involved in the progression of chronic liver disease. They describe the role of cells and the produced inflammatory mediators and cytokines, as well as the relationship between the disease and the intestinal flora. They emphasize the role of oxidative stress, mitochondrial dysfunction and cell death in disease progression. Insulin resistance and micro-elements (iron, copper) in relation to liver damage are also discussed, and genetic and epigenetic aspects underlying disease progression are summarized. Discovery of novel treatment options, assessment of the effectiveness of treatment, as well as the success and proper timing of liver transplantation may depend on a better understanding of the process of disease progression.

Chronic pancreatitis.

PubMed

DiMagno, Matthew J; DiMagno, Eugene P

2012-09-01

We review important new clinical observations in chronic pancreatitis reported in 2011. Smoking increases the risk of nongallstone acute pancreatitis and the progression of acute pancreatitis to chronic pancreatitis. Binge drinking during Oktoberfest did not associate with increased hospital admissions for acute pancreatitis. The unfolded protein response is an adaptive mechanism to maintain pancreatic health in response to noxious stimuli such as alcohol. Onset of diabetes mellitus in chronic pancreatitis is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90 000 United States Pharmacopeia units of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared with endoscopic treatment in patients advanced chronic pancreatitis with a dilated main duct ± pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with chronic pancreatitis but approximately 30% of patients have significant side effects. Patients with nongallstone-related acute pancreatitis or chronic pancreatitis of any cause should cease smoking. Results of this year's investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in chronic pancreatitis, and the mechanisms and treatment of neuropathic pain in chronic pancreatitis.

The main concept analysis in cantonese aphasic oral discourse: external validation and monitoring chronic aphasia.

PubMed

Kong, Anthony Pak-Hin

2011-02-01

The 1st aim of this study was to further establish the external validity of the main concept (MC) analysis by examining its relationship with the Cantonese Linguistic Communication Measure (CLCM; Kong, 2006; Kong & Law, 2004)-an established quantitative system for narrative production-and the Cantonese version of the Western Aphasia Battery (CAB; Yiu, 1992). The 2nd purpose of the study was to evaluate how well the MC analysis reflects the stability of discourse production among chronic Cantonese speakers with aphasia. Sixteen participants with aphasia were evaluated on the MC analysis, CAB, and CLCM in the summer of 2008 and were subsequently reassessed in the summer of 2009. They encompassed a range of aphasia severity (with an Aphasia Quotient ranging between 30.2/100 and 94.8/100 at the time of the 1st evaluation). Significant associations were found between the MC measures and the corresponding CLCM indices and CAB performance scores that were relevant to the presence, accuracy, and completeness of content in oral narratives. Moreover, the MC analysis was found to yield comparable scores for chronic speakers on 2 occasions 1 year apart. The present study has further established the external validity of MC analysis in Cantonese. Future investigations involving more speakers with aphasia will allow adequate description of its psychometric properties.

Disease progression of acute pancreatitis in pediatric patients.

PubMed

Hao, Fabao; Guo, Hongjie; Luo, Qianfu; Guo, Chunbao

2016-05-15

Approximately 10% of patients with acute pancreatitis (AP) progress to chronic pancreatitis. Little is known about the factors that affect recurrence of pancreatitis after an initial episode. We retrospectively investigated patients with AP, focusing on their outcomes and the predictors for disease progression. Between July 2003 and June 2015, we retrospectively enrolled first-time AP patients with medical records on disease etiology, severity (according to the Atlanta classifications), and recurrence of AP. Independent predictors of recurrent AP (RAP) and chronic pancreatitis were identified using the logistic regression model. Of the total 159 patients, 45 (28.3%) developed RAP, including two episodes of RAP in 19 patients, and 9 (5.7%) developed chronic pancreatitis. The median duration from the time of AP to the onset of RAP was 5.6 ± 2.3 months. RAP patients were identified as more common among patients with idiopathic first-time AP. The presence of severe ascites, pancreatic necrosis, and systemic complications was independent predictors of RAP in pediatric patients. Experiencing over two RAP episodes was the predictor for developing chronic pancreatitis. No influence of age or number of AP episodes was found on the occurrence of abdominal pain, pain severity, and the prevalence of any pain. Severity of first-time AP and idiopathic first-time AP are related to RAP. Recurrence increases risk for progression to chronic pancreatitis. The risk of recurrence increased with increasing numbers of AP episodes. Copyright © 2016 Elsevier Inc. All rights reserved.

Malaria control in South Sudan, 2006–2013: strategies, progress and challenges

PubMed Central

2013-01-01

Background South Sudan has borne the brunt of years of chronic warfare and probably has the highest malaria burden in sub-Saharan Africa. However, effective malaria control in post-conflict settings is hampered by a multiplicity of challenges. This manuscript reports on the strategies, progress and challenges of malaria control in South Sudan and serves as an example epitome for programmes operating in similar environments and provides a window for leveraging resources. Case description To evaluate progress and challenges of the national malaria control programme an in-depth appraisal was undertaken according to the World Health Organization standard procedures for malaria programme performance review. Methodical analysis of published and unpublished documents on malaria control in South Sudan was conducted. To ensure completeness, findings of internal thematic desk assessments were triangulated in the field and updated by external review teams. Discussion and evaluation South Sudan has strived to make progress in implementing the WHO recommended malaria control interventions as set out in the 2006–2013 National Malaria Strategic Plan. The country has faced enormous programmatic constraints including infrastructure, human and financial resource and a weak health system compounded by an increasing number of refugees, returnees and internally displaced people. The findings present a platform on which to tailor an evidence-based 2014–2018 national malaria strategic plan for the country and a unique opportunity for providing a model for countries in a post-conflict situation. Conclusions The prospects for effective malaria control and elimination are huge in South Sudan. Nevertheless, strengthened coordination, infrastructure and human resource capacity, monitoring and evaluation are required. To achieve all this, allocation of adequate local funding would be critical. PMID:24160336

Association between First Nations ethnicity and progression to kidney failure by presence and severity of albuminuria.

PubMed

Samuel, Susan M; Palacios-Derflingher, Luz; Tonelli, Marcello; Manns, Braden; Crowshoe, Lynden; Ahmed, Sofia B; Jun, Min; Saad, Nathalie; Hemmelgarn, Brenda R

2014-02-04

Despite a low prevalence of chronic kidney disease (estimated glomerular filtration rate [GFR]<60 mL/min per 1.73 m2), First Nations people have high rates of kidney failure requiring chronic dialysis or kidney transplantation. We sought to examine whether the presence and severity of albuminuria contributes to the progression of chronic kidney disease to kidney failure among First Nations people. We identified all adult residents of Alberta (age≥18 yr) for whom an outpatient serum creatinine measurement was available from May 1, 2002, to Mar. 31, 2008. We determined albuminuria using urine dipsticks and categorized results as normal (i.e., no albuminuria), mild, heavy or unmeasured. Our primary outcome was progression to kidney failure (defined as the need for chronic dialysis or kidney transplantation, or a sustained doubling of serum creatinine levels). We calculated rates of progression to kidney failure by First Nations status, by estimated GFR and by albuminuria category. We determined the relative hazard of progression to kidney failure for First Nations compared with non-First Nations participants by level of albuminuria and estimated GFR. Of the 1 816 824 participants we identified, 48 669 (2.7%) were First Nations. First Nations people were less likely to have normal albuminuria compared with non-First Nations people (38.7% v. 56.4%). Rates of progression to kidney failure were consistently 2- to 3-fold higher among First Nations people than among non-First Nations people, across all levels of albuminuria and estimated GFRs. Compared with non-First Nations people, First Nations people with an estimated GFR of 15.0-29.9 mL/min per 1.73 m2 had the highest risk of progression to kidney failure, with similar hazard ratios for those with normal and heavy albuminuria. Albuminuria confers a similar risk of progression to kidney failure for First Nations and non-First Nations people.

Nuclear scanning in necrotizing progressive ''malignant'' external otitis

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

Parisier, S.C.; Lucente, F.E.; Som, P.M.

1982-09-01

The usefulness of radionuclear scanning in the treatment of 18 patients with necrotizing progressive ''malignant'' external otitis is discussed. A Tc 99-m bone scan, a valuable test since results are positive in early cases of osteomyelitis of the temporal bone and base of skull, showed increased uptake in all 18 patients. In 6 patients, Ga-67 citrate scans were obtained at the start of therapy and at 5-6 week intervals thereafter. The serial gallium scans were useful in evaluating the effectiveness of therapy since the uptake decrease with control of infection.

Impact of stress on cancer metastasis

PubMed Central

Moreno-Smith, Myrthala; Lutgendorf, Susan K; Sood, Anil K

2011-01-01

The influence of psychosocial factors on the development and progression of cancer has been a longstanding hypothesis since ancient times. In fact, epidemiological and clinical studies over the past 30 years have provided strong evidence for links between chronic stress, depression and social isolation and cancer progression. By contrast, there is only limited evidence for the role of these behavioral factors in cancer initiation. Recent cellular and molecular studies have identified specific signaling pathways that impact cancer growth and metastasis. This article provides an overview of the relationship between psychosocial factors, specifically chronic stress, and cancer progression. PMID:21142861

Modulation of TGF-beta signaling during progression of chronic liver diseases.

PubMed

Matsuzaki, Koichi

2009-01-01

A large body of work has established roles for epithelial cells as important mediators of progressive fibrosis and carcinogenesis. Transforming growth factor-beta (TGF-beta) and pro-inflammatory cytokines are important inducers of fibro-carcinogenesis. TGF-beta signaling involves phosphorylation of Smad3 at middle linker and/or C-terminal regions. Reversible shifting of Smad3-dependent signaling between tumor-suppression and oncogenesis in hyperactive Ras-expressing epithelial cells indicates that Smad3 phosphorylated at the C-terminal region (pSmad3C) transmits a tumor-suppressive TGF-beta signal, while oncogenic activities such as cell proliferation and invasion are promoted by Smad3 phosphorylated at the linker region (pSmad3L). Notably, pSmad3L-mediated signaling promotes extracellular matrix deposition by activated mesenchymal cells. During progression of chronic liver diseases, hepatic epithelial hepatocytes undergo transition from the tumor-suppressive pSmad3C pathway to the fibrogenic/oncogenic pSmad3L pathway, accelerating liver fibrosis and increasing risk of hepatocellular carcinoma. c-Jun N-terminal kinase activated by pro-inflammatory cytokines is mediating this perturbed hepatocytic TGF-beta signaling. Thus, TGF-beta signaling of hepatocytes affected by chronic inflammation offers a general framework for understanding the molecular mechanisms of human fibro-carcinogenesis during progression of chronic liver diseases.

[The relevance of internal and external participation for patient satisfaction].

PubMed

Zimmermann, L; Michaelis, M; Quaschning, K; Müller, C; Körner, M

2014-08-01

Patient satisfaction is an essential quality and outcome criteria for patient-centered treatment of chronic diseases. For successful implementation of integrated patient-centered care it is important to take the needs and expectations of the patients into consideration in the treatment process and to involve them in decision-making (external participation), as well as establishing patient-centered collaboration within the team and organization (internal participation). This study examines in what respect patient satisfaction can be predicted through parameters that focus on the personal needs of the individual or internal and external participation. To this end we used a multicenter cross-sectional study to collect evaluations from N=329 patients with different chronic diseases in 11 rehabilitation clinics. Patient satisfaction (ZUF-8) served as the criterion, and the predictors were external participation (PEF-FB-9), satisfaction with decision-making (Man-Son-Hing Scale) and internal participation (Internal Participation Scale), socio-demographic factors and rehabilitation status (IRES-24). The data were analyzed statistically using multiple linear regression. A high degree of variance of patient satisfaction could be explained by the parameters applied (Goodness-of-fit: R²corrected=47.3%). The strongest predictors of satisfaction were internal participation (Beta=0.44, p<0.001) and satisfaction with the decision-making (Beta=0.36, p<0.001). The study provides initial indications of the positive effects of internal and external participation. Further studies are necessary to substantiate the connection between internal and external participation and patient satisfaction. © Georg Thieme Verlag KG Stuttgart · New York.

Chronic inflammation-related DNA damage response: a driving force of gastric cardia carcinogenesis

PubMed Central

Guo, Yi; Tian, Dongping; Yun, Hailong; Chen, Donglin; Su, Min

2015-01-01

Gastric cardia cancer (GCC) is a highly aggressive disease associated with chronic inflammation. To investigate the relationship between DNA damage response (DDR) and chronic inflammation, we collected 100 non-tumor gastric cardia specimens of Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. A significantly higher proportion of severe chronic inflammation was found in dysplastic epithelia (80.9%) in comparison with that in non-dysplastic tissues (40.7%) (P<0.001). Immunohistochemical analysis demonstrated that DNA damage response was parallel with the chronic inflammation degrees from normal to severe inflammation (P<0.05). We found that DNA damage response was progressively increased with the progression of precancerous lesions (P<0.05). These findings provide pathological evidence that persistent chronic inflammation-related DNA damage response may be a driving force of gastric cardia carcinogenesis. Based on these findings, DNA damage response in non-malignant tissues may become a promising biomedical marker for predicting malignant transformation in the gastric cardia. PMID:25650663

Chronic inflammation-related DNA damage response: a driving force of gastric cardia carcinogenesis.

PubMed

Lin, Runhua; Xiao, Dejun; Guo, Yi; Tian, Dongping; Yun, Hailong; Chen, Donglin; Su, Min

2015-02-20

Gastric cardia cancer (GCC) is a highly aggressive disease associated with chronic inflammation. To investigate the relationship between DNA damage response (DDR) and chronic inflammation, we collected 100 non-tumor gastric cardia specimens of Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. A significantly higher proportion of severe chronic inflammation was found in dysplastic epithelia (80.9%) in comparison with that in non-dysplastic tissues (40.7%) (P<0.001). Immunohistochemical analysis demonstrated that DNA damage response was parallel with the chronic inflammation degrees from normal to severe inflammation (P<0.05). We found that DNA damage response was progressively increased with the progression of precancerous lesions (P<0.05). These findings provide pathological evidence that persistent chronic inflammation-related DNA damage response may be a driving force of gastric cardia carcinogenesis. Based on these findings, DNA damage response in non-malignant tissues may become a promising biomedical marker for predicting malignant transformation in the gastric cardia.

Chronic Migraine: An Update on Physiology, Imaging, and the Mechanism of Action of Two Available Pharmacologic Therapies.

PubMed

Aurora, Sheena K; Brin, Mitchell F

2017-01-01

Several lines of research support the hypothesis that migraine is a spectrum of illness, with clinical symptoms that vary along a continuum from episodic migraine to chronic migraine. Physiologic changes may result in episodic migraine evolving into chronic migraine over months to years in susceptible individuals. With chronification, headache frequency increases, becoming more disabling and less responsive to therapy. Neurophysiologic and functional imaging research has reported that chronic migraine may be associated with severity-specific metabolic, functional, and structural abnormalities in the brainstem. Without longitudinal studies, it is unclear whether these changes may represent a continuum of individual progression and/or are reversible. Furthermore, chronic migraine is associated with larger impairments in cortical processing of sensory stimuli when compared with episodic migraine, possibly caused by more pronounced cortical hyperexcitability. Progressive changes in nociceptive thresholds and subsequent central sensitization due to recurrent migraine attacks in vulnerable individuals contribute to the chronic migraine state. This may result in changes to baseline neurologic function between headache attacks, evident in both electrophysiological and functional imaging research. Patients experiencing migraine chronification may report increased non-headache pain, fatigue, psychiatric disorders (eg, depression, anxiety), gastrointestinal complaints, and other somatic conditions associated with their long-term experience with migraine pain. Recent research provides a foundation for differentiating episodic and chronic migraine based on neurophysiologic and neuroimaging tools. In this literature review, we consider these findings in the context of models designed to explain the physiology and progression of episodic migraine into chronic migraine, and consider treatment of chronic migraine in susceptible individuals. Advances in pharmacotherapy provide treatment options for chronic migraine. Of the currently available treatment options, only onabotulinumtoxinA and topiramate have received regulatory approval and have demonstrated efficacy in patients with chronic migraine, although the exact mechanisms of action are not fully elucidated. © 2016 The Authors Headache published by Wiley Periodicals, Inc. on behalf of American Headache Society.

[Primary sclerosing cholangitis associated with Sjögren's syndrome, retroperitoneal fibrosis and chronic pancreatitis. Report of a case].

PubMed

Barreda, F; Contardo, C; León, A; Navarrete, J; Figueroa, R; Attanasio, F

1989-01-01

Primary Sclerosing Cholangitis (PSC) is an unusual chronic, cholestatic disease of unknown etiology, more frequently seen in young adults in close relationship with Chronic Ulcerative Colitis. We report the case of a 30 year old woman, coming from the peruvian amazon with PSC associated with Sjögren Syndrome, Chronic Pancreatitis and Retroperitoneal Fibrosis, without colonic involvement. She was treated with external biliary drainage and controlled for 12 months. In this paper, clinical, biochemical, radiological, histological and therapeutic features are reviewed as well as its possible immunologie autoimmune origin.

[Advances in genetics of congenital malformation of external and middle ear].

PubMed

Wang, Dayong; Wang, Qiuju

2013-05-01

Congenital malformation of external and middle ear is a common disease in ENT department, and the incidence of this disease is second only to cleft lip and palate in the whole congenital malformations of the head and face. The external and middle ear malformations may occur separately, or as an important ear symptom of the systemic syndrome. We systematically review and analysis the genetic research progress of congenital malformation of external and middle ear, which would be helpful to understand the mechanism of external and middle ear development, and to provide clues for the further discovery of new virulence genes.

Risk factors for long-term persistence of serum hepatitis B surface antigen following acute hepatitis B virus infection in Japanese adults.

PubMed

Ito, Kiyoaki; Yotsuyanagi, Hiroshi; Yatsuhashi, Hiroshi; Karino, Yoshiyasu; Takikawa, Yasuhiro; Saito, Takafumi; Arase, Yasuji; Imazeki, Fumio; Kurosaki, Masayuki; Umemura, Takeji; Ichida, Takafumi; Toyoda, Hidenori; Yoneda, Masashi; Mita, Eiji; Yamamoto, Kazuhide; Michitaka, Kojiro; Maeshiro, Tatsuji; Tanuma, Junko; Tanaka, Yasuhito; Sugiyama, Masaya; Murata, Kazumoto; Masaki, Naohiko; Mizokami, Masashi

2014-01-01

The proportion of patients who progress to chronicity following acute hepatitis B (AHB) varies widely worldwide. Moreover, the association between viral persistence after AHB and hepatitis B virus (HBV) genotypes in adults remains unclear. A nationwide multicenter study was conducted throughout Japan to evaluate the influence of clinical and virological factors on chronic outcomes in patients with AHB. For comparing factors between AHB patients with viral persistence and those with self-limited infection, 212 AHB patients without human immunodeficiency virus (HIV) coinfection were observed in 38 liver centers until serum hepatitis B surface antigen (HBsAg) disappeared or a minimum of 6 months in cases where HBsAg persisted. The time to disappearance of HBsAg was significantly longer for genotype A patients than that of patients infected with non-A genotypes. When chronicity was defined as the persistence of HBsAg positivity for more than 6 or 12 months, the rate of progression to chronicity was higher in patients with genotype A, although many cases caused by genotype A were prolonged cases of AHB, rather than chronic infection. Multivariate logistic regression analysis revealed only genotype A was independently associated with viral persistence following AHB. A higher peak level of HBV DNA and a lower peak of alanine aminotransferase (ALT) levels were characteristics of AHB caused by genotype A. Treatment with nucleotide analogs (NAs) did not prevent progression to chronic infection following AHB overall. Subanalysis suggested early NA initiation may enhance the viral clearance. Genotype A was an independent risk factor for progression to chronic infection following AHB. Our data will be useful in elucidating the association between viral persistence after AHB, host genetic factors, and treatment with NAs in future studies. © 2013 by the American Association for the Study of Liver Diseases.

Diurnal and nocturnal skin temperature regulation in chronic complex regional pain syndrome.

PubMed

Schilder, Johanna C M; Niehof, Sjoerd P; Marinus, Johan; van Hilten, Jacobus J

2015-03-01

Skin temperature changes due to vasomotor disturbances are important features of complex regional pain syndrome (CRPS). Because this phenomenon has only been studied under controlled conditions, information on daily circadian variability is lacking. Also, studies in chronic CRPS patients with abnormal posturing, in which coldness of the affected extremity is more common, do not exist. We examined the response to external heating as well as circadian temperature changes over several days in the affected legs of 14 chronic CRPS patients with abnormal posturing and 17 controls. Skin temperatures were recorded hourly for 14 days using wireless sensors. Although the patients' affected extremities were significantly colder before external heating, the vasodilatory response was similar in the 2 groups. Additionally, median skin temperature differences between both legs and their variability was larger in patients than in controls during the day, but not during the night. These findings indicate that the mechanisms underlying impaired skin circulation in CRPS during daytime are reversible under certain circumstances. The large variation in skin temperature differences during the day questions the validity of using a single measurement in the diagnosis of CRPS, and our results indicate that only temperature differences >1.0 °C should be considered to reflect vasomotor disturbances. This article shows that chronic CRPS patients have a normal vasodilatory response to external heating and that skin temperature differences between the affected and unaffected lower limbs, which were highly variable during daytime, disappeared during sleep. This indicates that part of the vasomotor regulation in these patients is still functional. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

The gut-kidney axis in chronic renal failure: A new potential target for therapy.

PubMed

Khoury, Tawfik; Tzukert, Keren; Abel, Roy; Abu Rmeileh, Ayman; Levi, Ronen; Ilan, Yaron

2017-07-01

Evidence is accumulating to consider the gut microbiome as a central player in the gut-kidney axis. Microbiome products, such as advanced glycation end products, phenols, and indoles, are absorbed into the circulation but are cleared by normal-functioning kidneys. These products then become toxic and contribute to the uremic load and to the progression of chronic kidney failure. In this review, we discuss the gut-kidney interaction under the state of chronic kidney failure as well as the potential mechanisms by which a change in the gut flora (termed gut dysbiosis) in chronic kidney disease (CKD) exacerbates uremia and leads to further progression of CKD and inflammation. Finally, the potential therapeutic interventions to target the gut microbiome in CKD are discussed. © 2016 International Society for Hemodialysis.

Endothelial activation biomarkers increase after HIV-1 acquisition: plasma vascular cell adhesion molecule-1 predicts disease progression.

PubMed

Graham, Susan M; Rajwans, Nimerta; Jaoko, Walter; Estambale, Benson B A; McClelland, R Scott; Overbaugh, Julie; Liles, W Conrad

2013-07-17

We aimed to determine whether endothelial activation biomarkers increase after HIV-1 acquisition, and whether biomarker levels measured in chronic infection would predict disease progression and death in HIV-1 seroconverters. HIV-1-seronegative Kenyan women were monitored monthly for seroconversion, and followed prospectively after HIV-1 acquisition. Plasma levels of angiopoietin-1 and angiopoietin-2 (ANG-1, ANG-2) and soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were tested in stored samples from pre-infection, acute infection, and two chronic infection time points. We used nonparametric tests to compare biomarkers before and after HIV-1 acquisition, and Cox proportional-hazards regression to analyze associations with disease progression (CD4 < 200 cells/μl, stage IV disease, or antiretroviral therapy initiation) or death. Soluble ICAM-1 and VCAM-1 were elevated relative to baseline in all postinfection periods assessed (P < 0.0001). Soluble E-selectin and the ANG-2:ANG-1 ratio increased in acute infection (P = 0.0001), and ANG-1 decreased in chronic infection (P = 0.0004). Among 228 participants followed over 1028 person-years, 115 experienced disease progression or death. Plasma VCAM-1 levels measured during chronic infection were independently associated with time to HIV progression or death (adjusted hazard ratio 5.36, 95% confidence interval 1.99-14.44 per log10 increase), after adjustment for set point plasma viral load, age at infection, and soluble ICAM-1 levels. HIV-1 acquisition was associated with endothelial activation, with sustained elevations of soluble ICAM-1 and VCAM-1 postinfection. Soluble VCAM-1 may be an informative biomarker for predicting the risk of HIV-1 disease progression, morbidity, and mortality.

Endothelial Activation Biomarkers Increase after HIV-1 Acquisition: Plasma VCAM-1 Predicts Disease Progression

PubMed Central

GRAHAM, Susan M.; RAJWANS, Nimerta; JAOKO, Walter; ESTAMBALE, Benson B.A.; MCCLELLAND, R. Scott; OVERBAUGH, Julie; LILES, W. Conrad

2013-01-01

Objective We aimed to determine whether endothelial activation biomarkers increase after HIV-1 acquisition, and whether biomarker levels measured in chronic infection would predict disease progression and death in HIV-1 seroconverters. Design HIV-1-seronegative Kenyan women were monitored monthly for seroconversion, and followed prospectively after HIV-1 acquisition. Methods Plasma levels of angiopoietins-1 and -2 (ANG-1, ANG-2) and soluble vascular cell adhesion marker-1 (VCAM-1), intercellular adhesion marker-1 (ICAM-1), and E-selectin were tested in stored samples from before infection, acute infection, and at two points during chronic infection. We used non-parametric tests to compare biomarkers before and after HIV-1 acquisition, and Cox proportional-hazards regression to analyze associations with disease progression (CD4 <200 cells/μL, Stage IV disease, or ART initiation) or death. Results Soluble ICAM-1 and VCAM-1 were elevated relative to baseline in all post-infection periods assessed (p<0.0001). Soluble E-selectin and the ANG-2:ANG-1 ratio increased in acute infection (p=0.0001), and ANG-1 decreased in chronic infection (p=0.0004). Among 228 subjects followed over 1,028 person-years, 115 experienced disease progression or death. Plasma VCAM-1 levels measured during chronic infection were independently associated with time to HIV progression or death (aHR 5.36, 95% confidence interval 1.99–14.44 per log10 increase), after adjustment for set point plasma viral load, age at infection, and soluble ICAM-1 levels. Conclusions HIV-1 acquisition was associated with endothelial activation, with sustained elevations of soluble ICAM-1 and VCAM-1 post-infection. Soluble VCAM-1 may be an informative biomarker for predicting the risk of HIV-1 disease progression, morbidity, and mortality. PMID:23807276

Evolution of external genitalia: insights from reptilian development.

PubMed

Gredler, Marissa L; Larkins, Christine E; Leal, Francisca; Lewis, A Kelsey; Herrera, Ana M; Perriton, Claire L; Sanger, Thomas J; Cohn, Martin J

2014-01-01

External genitalia are found in each of the major clades of amniotes. The phallus is an intromittent organ that functions to deliver sperm into the female reproductive tract for internal fertilization. The cellular and molecular genetic mechanisms of external genital development have begun to be elucidated from studies of the mouse genital tubercle, an embryonic appendage adjacent to the cloaca that is the precursor of the penis and clitoris. Progress in this area has improved our understanding of genitourinary malformations, which are among the most common birth defects in humans, and created new opportunities for comparative studies of other taxa. External genitalia evolve rapidly, which has led to a striking diversity of anatomical forms. Within the past year, studies of external genital development in non-mammalian amniotes, including birds, lizards, snakes, alligators, and turtles, have begun to shed light on the molecular and morphogenetic mechanisms underlying the diversification of phallus morphology. Here, we review recent progress in the comparative developmental biology of external genitalia and discuss the implications of this work for understanding external genital evolution. We address the question of the deep homology (shared common ancestry) of genital structures and of developmental mechanisms, and identify new areas of investigation that can be pursued by taking a comparative approach to studying development of the external genitalia. We propose an evolutionary interpretation of hypospadias, a congenital malformation of the urethra, and discuss how investigations of non-mammalian species can provide novel perspectives on human pathologies.

Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia

PubMed Central

Jabbour, Elias J.; Hughes, Timothy P.; Cortés, Jorge E.; Kantarjian, Hagop M.; Hochhaus, Andreas

2014-01-01

Despite vast improvements in treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment. PMID:24050507

Maslow's Hierarchy of Needs and the individual with chronic vestibular dysfunction.

PubMed

Haybach, P J

1994-01-01

Individuals with chronic vestibular dysfunction may have unmet physiological or safety needs on a chronic basis. Their inability to fulfill the basic needs and progress to higher needs can lead to a patient population with many psychosocial problems. Very often such problems are ignored or unrecognized or are misdiagnosed, and treated inappropriately. This disruption in the individual's life can lead to an inability to progress as a human being. Nursing assessment and appropriate interventions should be developed to treat psychosocial problems in this patient population. The nursing profession should serve patients with vestibular dysfunction through direct care, teaching, counseling, support group facilitation, and research into appropriate interventions.

[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.

Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia.

PubMed

Jabbour, Elias J; Hughes, Timothy P; Cortés, Jorge E; Kantarjian, Hagop M; Hochhaus, Andreas

2014-07-01

Despite vast improvements in the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment.

Inflammation, atrophy, and gastric cancer

PubMed Central

Fox, James G.; Wang, Timothy C.

2006-01-01

The association between chronic inflammation and cancer is now well established. This association has recently received renewed interest with the recognition that microbial pathogens can be responsible for the chronic inflammation observed in many cancers, particularly those originating in the gastrointestinal system. A prime example is Helicobacter pylori, which infects 50% of the world’s population and is now known to be responsible for inducing chronic gastric inflammation that progresses to atrophy, metaplasia, dysplasia, and gastric cancer. This Review provides an overview of recent progress in elucidating the bacterial properties responsible for colonization of the stomach, persistence in the stomach, and triggering of inflammation, as well as the host factors that have a role in determining whether gastritis progresses to gastric cancer. We also discuss how the increased understanding of the relationship between inflammation and gastric cancer still leaves many questions unanswered regarding recommendations for prevention and treatment. PMID:17200707

Biofeedback training in chronic constipation.

PubMed Central

Benninga, M A; Büller, H A; Taminiau, J A

1993-01-01

Twenty nine patients, aged 5-16 years, were studied to evaluate whether biofeedback training is effective in treating children with chronic constipation and encopresis; the clinical outcome at six weeks and 12 months was also evaluated. Patients received on average five biofeedback training sessions. The existence of external anal contraction or decreased rectal sensation in 16 (55%) and eight (27%) of the children, respectively was identified on manometry. After biofeedback training, 26 (90%) of the patients learned to relax the external anal sphincter; 18 (63%) normalised rectal sensation. The training resulted in a significant increase in defecation frequency and a significant decrease in encopresis. At six weeks, 16 (55%) of the patients were clinically symptom free. At follow up after 12 months the results were sustained. Only three patients showed a relapse within six months, of whom two were successfully treated with one extra training session. Biofeedback training might be a useful therapeutical approach in children with chronic constipation and encopresis. PMID:8434996

Predictive modeling of addiction lapses in a mobile health application.

PubMed

Chih, Ming-Yuan; Patton, Timothy; McTavish, Fiona M; Isham, Andrew J; Judkins-Fisher, Chris L; Atwood, Amy K; Gustafson, David H

2014-01-01

The chronically relapsing nature of alcoholism leads to substantial personal, family, and societal costs. Addiction-comprehensive health enhancement support system (A-CHESS) is a smartphone application that aims to reduce relapse. To offer targeted support to patients who are at risk of lapses within the coming week, a Bayesian network model to predict such events was constructed using responses on 2,934 weekly surveys (called the Weekly Check-in) from 152 alcohol-dependent individuals who recently completed residential treatment. The Weekly Check-in is a self-monitoring service, provided in A-CHESS, to track patients' recovery progress. The model showed good predictability, with the area under receiver operating characteristic curve of 0.829 in the 10-fold cross-validation and 0.912 in the external validation. The sensitivity/specificity table assists the tradeoff decisions necessary to apply the model in practice. This study moves us closer to the goal of providing lapse prediction so that patients might receive more targeted and timely support. © 2013.

Predictive Modeling of Addiction Lapses in a Mobile Health Application

PubMed Central

Chih, Ming-Yuan; Patton, Timothy; McTavish, Fiona M.; Isham, Andrew; Judkins-Fisher, Chris L.; Atwood, Amy K.; Gustafson, David H.

2013-01-01

The chronically relapsing nature of alcoholism leads to substantial personal, family, and societal costs. Addiction-Comprehensive Health Enhancement Support System (A-CHESS) is a smartphone application that aims to reduce relapse. To offer targeted support to patients who are at risk of lapses within the coming week, a Bayesian network model to predict such events was constructed using responses on 2,934 weekly surveys (called the Weekly Check-in) from 152 alcohol-dependent individuals who recently completed residential treatment. The Weekly Check-in is a self-monitoring service, provided in A-CHESS, to track patients’ recovery progress. The model showed good predictability, with the area under receiver operating characteristic curve of 0.829 in the 10-fold cross-validation and 0.912 in the external validation. The sensitivity/specificity table assists the tradeoff decisions necessary to apply the model in practice. This study moves us closer to the goal of providing lapse prediction so that patients might receive more targeted and timely support. PMID:24035143

Transitioning from Acute to Chronic Pain: An Examination of Different Trajectories of Low-Back Pain.

PubMed

Gatchel, Robert J; Bevers, Kelley; Licciardone, John C; Su, Jianzhong; Du, Ying; Brotto, Marco

2018-05-17

Traditionally, there has been a widely accepted notion that the transition from acute to chronic pain follows a linear trajectory, where an injury leads to acute episodes, subacute stages, and progresses to a chronic pain condition. However, it appears that pain progression is much more complicated and individualized than this original unsupported assumption. It is now becoming apparent that, while this linear progression may occur, it is not the only path that pain, specifically low-back pain, follows. It is clear there is a definite need to evaluate how low-back pain trajectories are classified and, subsequently, how we can more effectively intervene during these progression stages. In order to better understand and manage pain conditions, we must examine the different pain trajectories, and develop a standard by which to use these classifications, so that clinicians can better identify and predict patient-needs and customize treatments for maximum efficacy. The present article examines the most recent trajectory research, and highlights the importance of developing a broader model for patient evaluation.

The Spectrum of Disease in Chronic Traumatic Encephalopathy

ERIC Educational Resources Information Center

McKee, Ann C.; Stein, Thor D.; Nowinski, Christopher J.; Stern, Robert A.; Daneshvar, Daniel H.; Alvarez, Victor E.; Lee, Hyo-Soon; Hall, Garth; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Cormier, Kerry A.; Jacobs, Matthew A.; Martin, Brett R.; Abraham, Carmela R.; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.; Cantu, Robert C.

2013-01-01

Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging…

Chronic inflammatory demyelinating polyneuropathy in two siblings.

PubMed Central

Gabreëls-Festen, A A; Hageman, A T; Gabreëls, F J; Joosten, E M; Renier, W O; Weemaes, C M; ter Laak, H J

1986-01-01

A familial occurrence of chronic inflammatory demyelinating polyneuropathy is reported. The diagnostic problems in distinguishing the progressive form of this disease in childhood from hereditary motor and sensory neuropathy types I and III are discussed. Criteria for a definite diagnosis of chronic inflammatory demyelinating polyneuropathy are proposed. Images PMID:3456424

Fibrosis progression in African Americans and Caucasian Americans with chronic hepatitis C.

PubMed

Terrault, Norah A; Im, Kelly; Boylan, Ross; Bacchetti, Peter; Kleiner, David E; Fontana, Robert J; Hoofnagle, Jay H; Belle, Steven H

2008-12-01

Prior studies suggest the rate of liver fibrosis progression is slower in African Americans (AAs) than Caucasian Americans (CAs) with chronic HCV infection. With a multi-state Markov model, fibrosis progression was evaluated in a well-characterized cohort of 143 AA and 157 CA adults with untreated chronic HCV genotype 1 infection. In subjects with a history of injection drug use, duration of infection was imputed from a fitted risk model rather than assumed to be the reported first year of use. The distribution of Ishak fibrosis stages was 0 (8.7%), 1/2 (55.7%), 3/4 (29.3%), and 5/6 (6.3%) and was similar in AAs and CAs (P = .22). After adjusting for biopsy adequacy, AAs had a 10% lower rate of fibrosis progression than did CAs, but the difference was not statistically significant (hazard ratio, 0.90; 95% confidence interval, 0.72-1.12). The overall 20-year estimates of probabilities of progression from stage 0 to stages 1/2, 3/4, and 5/6 were 59.3%, 28.8%, and 4.7%, respectively. The estimated median time from no fibrosis to cirrhosis was 79 years for the entire cohort and 74 and 83 years for CAs and AAs, respectively. In 3-variable models including race and biopsy adequacy, the factors significantly associated with fibrosis progression were age when infected, steatosis, ALT level, and necroinflammatory score. The rates of fibrosis progression were slow and did not appear to differ substantially between AAs and CAs.

Progressive Chronic Retinal Axonal Loss Following Acute Methanol-Induced Optic Neuropathy: Four-Year Prospective Cohort Study.

PubMed

Nurieva, Olga; Diblik, Pavel; Kuthan, Pavel; Sklenka, Petr; Meliska, Martin; Bydzovsky, Jan; Heissigerova, Jarmila; Urban, Pavel; Kotikova, Katerina; Navratil, Tomas; Komarc, Martin; Seidl, Zdenek; Vaneckova, Manuela; Pelclova, Daniela; Zakharov, Sergey

2018-04-27

To study the dynamics and clinical determinants of chronic retinal nerve fiber layer thickness (RNFL) loss after methanol-induced optic neuropathy. Prospective cohort study. All patients underwent complete ophthalmic evaluation including SD-OCT three times during four years of observation:4.9[±0.6], 25.0[±0.6], and 49.9[±0.5] months after discharge. Eighty-four eyes of 42 survivors of methanol poisoning; mean age (standard deviation) of 45.7[±4.4] years, and 82 eyes of 41 controls; mean age 44.0[±4.2] years. global and temporal RNFL loss. Abnormal RNFL thickness was registered in 13/42(31%) survivors of methanol poisoning and chronic axonal loss in 10/42(24%) patients. Significant decrease of global/temporal RNFL thickness during the observation period was found in the study population compared to the controls (p<0.001). The risk estimate of chronic global RNFL loss for arterial blood pH<7.3 at admission was: 11.65(1.91-71.12;95%CI) after adjusting for age and sex. The patients with chronic axonal degeneration demonstrated progressive visual loss in 7/10 cases. The patients with abnormal RNFL thickness had magnetic resonance signs of brain damage in 10/13 versus 8/29 cases with normal RNFL thickness (p=0.003). Signs of brain hemorrhages were present in 7/13 patients with abnormal RNFL thickness versus 5/29 cases with normal RNFL thickness (p=0.015). Methanol-induced optic neuropathy may lead to chronic retinal axonal loss during the following years. Arterial blood pH on admission is the strongest predictor of chronic RNFL thickness decrease. Chronic retinal neurodegeneration is associated with the progressive loss of visual functions and necrotic brain lesions. Copyright © 2018. Published by Elsevier Inc.

Pathophysiology of chronic pancreatitis.

PubMed

Behrman, Stephen W; Fowler, Eric S

2007-12-01

Although the most common causes of chronic pancreatitis have not changed, it has become clear that a host of modifying biochemical, inflammatory, neural, and genetic deviations allows the disease to progress. Alterations in biochemical composition allow calcific stone formation, whereas various toxins, cytokines, and neuropeptides contribute to the progression of fibrosis and pain production. The basic cellular structure contributing to fibrosis of the pancreas has been elucidated and factors responsible for its activation delineated. Of most importance is the recent recognition of a set of genetic mutations that results in several aberrations of normal pancreatic physiology, which, in conjunction with other inciting insults or by themselves, allow the disease to begin and progress.

Inflammation in Acute and Chronic Pancreatitis

PubMed Central

Habtezion, Aida

2015-01-01

Summary Immune cell contribution to the pathogenesis of acute and chronic pancreatitis is gaining more appreciation and further understanding in immune signaling presents potential therapeutic targets that can alter disease progression. PMID:26107390

Progressive external ophthalmoplegia (PEO) due to a mutation in the C10orf2 (PEO1) gene mimicking a myasthenic crisis.

PubMed

Gonzalez-Moron, Dolores; Bueri, Jose; Kauffman, Marcelo Andres

2013-09-07

We described a case of a patient with autosomal dominant progressive external ophthalmoplegia (PEO) who presented with the acute onset dysphagia, quadriparesis, ptosis and respiratory insufficiency following a cardiac procedure and mimicking a myasthenic crisis. A pathogenic mutation in the C10orf2 (PEO1) gene was confirmed. The unusual presentation of our patient contributes to expand the clinical phenotype of PEO1 mutations and reinforces the need to consider mitochondrial myopathy as differential diagnosis of myasthenia gravis even in the case of acute onset symptoms.

α2-adrenergic blockade mimics the enhancing effect of chronic stress on breast cancer progression

PubMed Central

Lamkin, Donald M.; Sung, Ha Yeon; Yang, Gyu Sik; David, John M.; Ma, Jeffrey C.Y.; Cole, Steve W.; Sloan, Erica K.

2014-01-01

Experimental studies in preclinical mouse models of breast cancer have shown that chronic restraint stress can enhance disease progression by increasing catecholamine levels and subsequent signaling of β-adrenergic receptors. Catecholamines also signal α-adrenergic receptors, and greater α-adrenergic signaling has been shown to promote breast cancer in vitro and in vivo. However, antagonism of α-adrenergic receptors can result in elevated catecholamine levels, which may increase β-adrenergic signaling, because pre-synaptic α2-adrenergic receptors mediate an autoinhibition of sympathetic transmission. Given these findings, we examined the effect of α-adrenergic blockade on breast cancer progression under non-stress and stress conditions (chronic restraint) in an orthotopic mouse model with MDA-MB-231HM cells. Chronic restraint increased primary tumor growth and metastasis to distant tissues as expected, and non-selective α-adrenergic blockade by phentolamine significantly inhibited those effects. However, under non-stress conditions, phentolamine increased primary tumor size and distant metastasis. Sympatho-neural gene expression for catecholamine biosynthesis enzymes was elevated by phentolamine under non-stress conditions, and the non-selective β-blocker propranolol inhibited the effect of phentolamine on breast cancer progression. Selective α2-adrenergic blockade by efaroxan also increased primary tumor size and distant metastasis under non-stress conditions, but selective α1-adrenergic blockade by prazosin did not. These results are consistent with the hypothesis that α2-adrenergic signaling can act through an autoreceptor mechanism to inhibit sympathetic catecholamine release and, thus, modulate established effects of β-adrenergic signaling on tumor progression-relevant biology. PMID:25462899

33 CFR 385.22 - Independent scientific review and external peer review.

Code of Federal Regulations, 2014 CFR

2014-07-01

... external peer review. 385.22 Section 385.22 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES... review panel, convened by a body, such as the National Academy of Sciences, to review the Plan's progress...

33 CFR 385.22 - Independent scientific review and external peer review.

Code of Federal Regulations, 2011 CFR

2011-07-01

... external peer review. 385.22 Section 385.22 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES... review panel, convened by a body, such as the National Academy of Sciences, to review the Plan's progress...

33 CFR 385.22 - Independent scientific review and external peer review.

Code of Federal Regulations, 2012 CFR

2012-07-01

... external peer review. 385.22 Section 385.22 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES... review panel, convened by a body, such as the National Academy of Sciences, to review the Plan's progress...

33 CFR 385.22 - Independent scientific review and external peer review.

Code of Federal Regulations, 2010 CFR

2010-07-01

... external peer review. 385.22 Section 385.22 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES... review panel, convened by a body, such as the National Academy of Sciences, to review the Plan's progress...

33 CFR 385.22 - Independent scientific review and external peer review.

Code of Federal Regulations, 2013 CFR

2013-07-01

... external peer review. 385.22 Section 385.22 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES... review panel, convened by a body, such as the National Academy of Sciences, to review the Plan's progress...

Single severe traumatic brain injury produces progressive pathology with ongoing contralateral white matter damage one year after injury.

PubMed

Pischiutta, Francesca; Micotti, Edoardo; Hay, Jennifer R; Marongiu, Ines; Sammali, Eliana; Tolomeo, Daniele; Vegliante, Gloria; Stocchetti, Nino; Forloni, Gianluigi; De Simoni, Maria-Grazia; Stewart, William; Zanier, Elisa R

2018-02-01

There is increasing recognition that traumatic brain injury (TBI) may initiate long-term neurodegenerative processes, particularly chronic traumatic encephalopathy. However, insight into the mechanisms transforming an initial biomechanical injury into a neurodegenerative process remain elusive, partly as a consequence of the paucity of informative pre-clinical models. This study shows the functional, whole brain imaging and neuropathological consequences at up to one year survival from single severe TBI by controlled cortical impact in mice. TBI mice displayed persistent sensorimotor and cognitive deficits. Longitudinal T2 weighted magnetic resonance imaging (MRI) showed progressive ipsilateral (il) cortical, hippocampal and striatal volume loss, with diffusion tensor imaging demonstrating decreased fractional anisotropy (FA) at up to one year in the il-corpus callosum (CC: -30%) and external capsule (EC: -21%). Parallel neuropathological studies indicated reduction in neuronal density, with evidence of microgliosis and astrogliosis in the il-cortex, with further evidence of microgliosis and astrogliosis in the il-thalamus. One year after TBI there was also a decrease in FA in the contralateral (cl) CC (-17%) and EC (-13%), corresponding to histopathological evidence of white matter loss (cl-CC: -68%; cl-EC: -30%) associated with ongoing microgliosis and astrogliosis. These findings indicate that a single severe TBI induces bilateral, long-term and progressive neuropathology at up to one year after injury. These observations support this model as a suitable platform for exploring the mechanistic link between acute brain injury and late and persistent neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Next-generation sequencing identifies major DNA methylation changes during progression of Ph+ chronic myeloid leukemia

PubMed Central

Heller, G; Topakian, T; Altenberger, C; Cerny-Reiterer, S; Herndlhofer, S; Ziegler, B; Datlinger, P; Byrgazov, K; Bock, C; Mannhalter, C; Hörmann, G; Sperr, W R; Lion, T; Zielinski, C C; Valent, P; Zöchbauer-Müller, S

2016-01-01

Little is known about the impact of DNA methylation on the evolution/progression of Ph+ chronic myeloid leukemia (CML). We investigated the methylome of CML patients in chronic phase (CP-CML), accelerated phase (AP-CML) and blast crisis (BC-CML) as well as in controls by reduced representation bisulfite sequencing. Although only ~600 differentially methylated CpG sites were identified in samples obtained from CP-CML patients compared with controls, ~6500 differentially methylated CpG sites were found in samples from BC-CML patients. In the majority of affected CpG sites, methylation was increased. In CP-CML patients who progressed to AP-CML/BC-CML, we identified up to 897 genes that were methylated at the time of progression but not at the time of diagnosis. Using RNA-sequencing, we observed downregulated expression of many of these genes in BC-CML compared with CP-CML samples. Several of them are well-known tumor-suppressor genes or regulators of cell proliferation, and gene re-expression was observed by the use of epigenetic active drugs. Together, our results demonstrate that CpG site methylation clearly increases during CML progression and that it may provide a useful basis for revealing new targets of therapy in advanced CML. PMID:27211271

Chronic kidney disease among children in Guatemala.

PubMed

Cerón, Alejandro; Fort, Meredith P; Morine, Chris M; Lou-Meda, Randall

2014-12-01

To describe the distribution of pediatric chronic kidney disease (CKD) in Guatemala, estimate incidence and prevalence of pediatric end-stage renal disease (ESRD), and estimate time to progress to ESRD. This study analyzed the registry of the only pediatric nephrology center in Guatemala, from 2004-2013. Incidence and prevalence were calculated for annual periods. Moran's index for spatial autocorrelation was used to determine significance of geographic distribution of incidence. Time to progress to ESRD and associated risk factors were calculated with multivariate Cox regression. Of 1 545 patients from birth to less than 20 years of age, 432 had chronic renal failure (CRF). Prevalence and incidence of ESRD were 4.9 and 4.6 per million age-related population, respectively. Incidence was higher for the Pacific coast and Guatemala City. The cause of CRF was undetermined in 43% of patients. Average time to progress to ESRD was 21.9 months; factors associated with progression were: older age, diagnosis of glomerulopathies, and advanced-stage CKD at consultation. Prevalence and incidence of ESRD in Guatemala are lower than in other countries. This may reflect poor access to diagnosis. Areas with higher incidence and large proportion of CKD of undetermined cause are compatible with other studies from the geographic subregion. Findings on progression to ESRD may reflect delayed referral.

Chronic Nerve Compression Accelerates the Progression of Diabetic Peripheral Neuropathy in a Rat Model: A Study of Gene Expression Profiling.

PubMed

Tu, Yiji; Chen, Zenggan; Hu, Junda; Ding, Zuoyou; Lineaweaver, William C; Dellon, A Lee; Zhang, Feng

2018-04-25

 This article investigates the role of chronic nerve compression in the progression of diabetic peripheral neuropathy (DPN) by gene expression profiling.  Chronic nerve compression was created in streptozotocin (STZ)-induced diabetic rats by wrapping a silicone tube around the sciatic nerve (SCN). Neurological deficits were evaluated using pain threshold test, motor nerve conduction velocity (MNCV), and histopathologic examination. Differentially expressed genes (DGEs) and metabolic processes associated with chronic nerve compression were analyzed.  Significant changes in withdrawal threshold and MNCV were observed in diabetic rats 6 weeks after diabetes induction, and in DPN rats 4 weeks after diabetes induction. Histopathologic examination of the SCN in DPN rats presented typical changes of myelin degeneration in DPN. Function analyses of DEGs demonstrated that biological processes related to inflammatory response, extracellular matrix component, and synaptic transmission were upregulated after diabetes induction, and chronic nerve compression further enhanced those changes. While processes related to lipid and glucose metabolism, response to insulin, and apoptosis regulation were inhibited after diabetes induction, chronic nerve compression further enhanced these inhibitions.  Our study suggests that additional silicone tube wrapping on the SCN of rat with diabetes closely mimics the course and pathologic findings of human DPN. Further studies are needed to verify the effectiveness of this rat model of DPN and elucidate the roles of the individual genes in the progression of DPN. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Answering the call to address chronic pain in military service members and veterans: Progress in improving pain care and restoring health.

PubMed

Schoneboom, Bruce A; Perry, Susan M; Barnhill, William Keith; Giordano, Nicholas A; Wiltse Nicely, Kelly L; Polomano, Rosemary C

2016-01-01

Chronic noncancer pain (CNCP) in military and veteran populations mirrors the experience of chronic pain in America; however, these two populations have unique characteristics and comorbid conditions such as traumatic brain injuries, postconcussive syndrome, posttraumatic stress disorder, and behavioral health disorders that complicate the diagnosis and treatment of chronic pain. Military members and veterans may also be stigmatized about their conditions and experience problems with integration back into healthy lifestyles and society as a whole following deployments and after military service. The military and veteran health care systems have made chronic pain a priority and have made substantial strides in addressing this condition through advances in practice, education, research, and health policy. Despite this progress, significant challenges remain in responding to the wide-spread problem of chronic pain. The purpose of this article is to: (a) examine the state of CNCP in military and veteran populations; (b) discuss progress made in pain practice, education, research, and health policy; and (c) examine research, evidence-based practice guidelines, and expert consensus reports that are foundational to advancing pain care and improving health for military service members and veterans with CNCP. In addition, recommendations are proposed to address this widespread health problem through the expanded use of advanced practice registered nurses, the implementation of models of care, and use of national resources to educate health care providers, support practice, and promote effective pain care. Copyright © 2016 Elsevier Inc. All rights reserved.

[Turpentine baths in rehabilitation of patients with chronic obstructive pulmonary disease].

PubMed

Aĭrapetova, N S; Polikanova, E B; Davydova, O B; Gosn, L D; Kulikova, O V; Ksenofontova, I V; Nikoda, N V; Rassulova, M A; Nitchenko, O V; Siziakova, L A; Doronina, Iu V; Derevnina, N A

2007-01-01

We have investigated effects of turpentine baths with white emultion, yellow solution and mixed on the course of inflammation, immunocompetent system, external respiration function, pulmonary cardiohemodynamics, physical performance in patients with chronic obstructive pulmonary disease. We developed differential indications for each bath variant depending on the features of a clinical picture of the disease, comorbid pathology and revealed contraindications to their administration.

Cold atmospheric plasma for local infection control and subsequent pain reduction in a patient with chronic post-operative ear infection

PubMed Central

Isbary, G; Shimizu, T; Zimmermann, J L; Thomas, H M; Morfill, G E; Stolz, W

2013-01-01

Following surgery of cholesteatoma, a patient developed a chronic infection of the external auditory canal, including extended-spectrum β-lactamase producing Escherichia coli, which caused severe pain. The application of cold atmospheric plasma resulted in a significant reduction in pain and clearance of bacterial carriage, allowing antibiotics and analgesics to be ceased. PMID:25356328

Development and Validation of a Novel Scoring System for Predicting Technical Success of Chronic Total Occlusion Percutaneous Coronary Interventions: The PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) Score.

PubMed

Christopoulos, Georgios; Kandzari, David E; Yeh, Robert W; Jaffer, Farouc A; Karmpaliotis, Dimitri; Wyman, Michael R; Alaswad, Khaldoon; Lombardi, William; Grantham, J Aaron; Moses, Jeffrey; Christakopoulos, Georgios; Tarar, Muhammad Nauman J; Rangan, Bavana V; Lembo, Nicholas; Garcia, Santiago; Cipher, Daisha; Thompson, Craig A; Banerjee, Subhash; Brilakis, Emmanouil S

2016-01-11

This study sought to develop a novel parsimonious score for predicting technical success of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) performed using the hybrid approach. Predicting technical success of CTO PCI can facilitate clinical decision making and procedural planning. We analyzed clinical and angiographic parameters from 781 CTO PCIs included in PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) using a derivation and validation cohort (2:1 sampling ratio). Variables with strong association with technical success in multivariable analysis were assigned 1 point, and a 4-point score was developed from summing all points. The PROGRESS CTO score was subsequently compared with the J-CTO (Multicenter Chronic Total Occlusion Registry in Japan) score in the validation cohort. Technical success was 92.9%. On multivariable analysis, factors associated with technical success included proximal cap ambiguity (beta coefficient [b] = 0.88), moderate/severe tortuosity (b = 1.18), circumflex artery CTO (b = 0.99), and absence of "interventional" collaterals (b = 0.88). The resulting score demonstrated good calibration and discriminatory capacity in the derivation (Hosmer-Lemeshow chi-square = 2.633; p = 0.268, and receiver-operator characteristic [ROC] area = 0.778) and validation (Hosmer-Lemeshow chi-square = 5.333; p = 0.070, and ROC area = 0.720) subset. In the validation cohort, the PROGRESS CTO and J-CTO scores performed similarly in predicting technical success (ROC area 0.720 vs. 0.746, area under the curve difference = 0.026, 95% confidence interval = -0.093 to 0.144). The PROGRESS CTO score is a novel useful tool for estimating technical success in CTO PCI performed using the hybrid approach. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

PubMed

Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

2017-09-01

Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of disability regression was predominantly associated with pre-baseline disability, therapy and relapse activity. Relapse incidence was associated with pretreatment relapse activity, age and relapsing disease course, with the strength of these associations varying among therapies. Accuracy and internal validity (n = 1196) of the resulting predictive models was high (>80%) for relapse incidence during the first year and for disability outcomes, moderate for relapse incidence in Years 2-4 and for the change in the cumulative disease burden, and low for conversion to secondary progressive disease and treatment discontinuation. External validation showed similar results, demonstrating high external validity for disability and relapse outcomes, moderate external validity for cumulative disease burden and low external validity for conversion to secondary progressive disease and treatment discontinuation. We conclude that demographic, clinical and paraclinical information helps predict individual response to disease-modifying therapies at the time of their commencement. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

U.S. Army Medical Research Institute of Infectious Diseases Annual Progress Report, Fiscal Year 1987

DTIC Science & Technology

1987-10-01

The distribution of Q fever is worldwide. About 5% of cases are chronic, involving liver granuloma or cardiac tissue ( endocarditis ). In acute disease...chronic hepatitis and occasionally endocarditis . The acute and chronic forms of the disease are treated with tetracycline. However, chronic... endocarditis disease requires long- term (1 to 2 years) treatment with tetracycline or rifampicin. Chemotherapy -- is successful only after surgery to replace

Validation of an instrument to measure inter-organisational linkages in general practice.

PubMed

Amoroso, Cheryl; Proudfoot, Judith; Bubner, Tanya; Jayasinghe, Upali W; Holton, Christine; Winstanley, Julie; Beilby, Justin; Harris, Mark F

2007-12-03

Linkages between general medical practices and external services are important for high quality chronic disease care. The purpose of this research is to describe the development, evaluation and use of a brief tool that measures the comprehensiveness and quality of a general practice's linkages with external providers for the management of patients with chronic disease. In this study, clinical linkages are defined as the communication, support, and referral arrangements between services for the care and assistance of patients with chronic disease. An interview to measure surgery-level (rather than individual clinician-level) clinical linkages was developed, piloted, reviewed, and evaluated with 97 Australian general practices. Two validated survey instruments were posted to patients, and a survey of locally available services was developed and posted to participating Divisions of General Practice (support organisations). Hypotheses regarding internal validity, association with local services, and patient satisfaction were tested using factor analysis, logistic regression and multilevel regression models. The resulting General Practice Clinical Linkages Interview (GP-CLI) is a nine-item tool with three underlying factors: referral and advice linkages, shared care and care planning linkages, and community access and awareness linkages. Local availability of chronic disease services has no affect on the comprehensiveness of services with which practices link, however, comprehensiveness of clinical linkages has an association with patient assessment of access, receptionist services, and of continuity of care in their general practice. The GP-CLI may be useful to researchers examining comparable health care systems for measuring the comprehensiveness and quality of linkages at a general practice-level with related services, possessing both internal and external validity. The tool can be used with large samples exploring the impact, outcomes, and facilitators of high quality clinical linkages in general practice.

Perchlorate disrupts embryonic androgen synthesis and reproductive development in threespine stickleback without changing whole-body levels of thyroid hormone

PubMed Central

Petersen, Ann M.; Dillon, Danielle; Bernhardt, Richard A.; Torunsky, Roberta; Postlethwait, John H.; von Hippel, Frank A.; Buck, C. Loren; Cresko, William A.

2014-01-01

Perchlorate, an environmental contaminant, disrupts normal functioning of the thyroid. We previously showed that perchlorate disrupts behavior and gonad development, and induces external morphological changes in a vertebrate model organism, the threespine stickleback. Whether perchlorate alters these phenotypes via a thyroid-mediated mechanism, and the extent to which the effects depend on dose, are unknown. To address these questions, we chronically exposed stickleback to control conditions and to three concentrations of perchlorate (10, 30 and 100 ppm) at various developmental stages from fertilization to reproductive maturity. Adults chronically exposed to perchlorate had increased numbers of thyroid follicles and decreased numbers of thyrocytes. Surprisingly, T4 and T3 levels in larval, juvenile, and adult whole fish chronically exposed to perchlorate did not differ from controls, except at the lowest perchlorate dose, suggesting a non-monotonic dose response curve. We found no detectable abnormalities in external phenotype at any dose of perchlorate, indicating that the increased number of thyroid follicles compensated for the disruptive effects of these doses. In contrast to external morphology, gonadal development was altered substantially, with the highest dose of perchlorate causing the largest effects. Perchlorate increased the number both of early stage ovarian follicles in females and of advanced spermatogenic stages in males. Perchlorate also disrupted embryonic androgen levels. We conclude that chronic perchlorate exposure may not result in lasting adult gross morphological changes but can produce lasting modifications to gonads when compensation of T3 and T4 levels occurs by thyroid follicle hyperplasia. Perchlorate may therefore affect vertebrate development via both thyroidal and non-thyroidal mechanisms. PMID:25448260

Chronic inflammation-associated genomic instability paves the way for human esophageal carcinogenesis.

PubMed

Lin, Runhua; Zhang, Chong; Zheng, Jiaxuan; Tian, Dongping; Lei, Zhijin; Chen, Donglin; Xu, Zexin; Su, Min

2016-04-26

Chronic inflammation is associated with increased risk of cancer development, whereas the link between chronic inflammation and esophageal carcinogenesis is still obscure heretofore. This study aimed to investigate the relationship between chronic inflammation and DNA damage, as well as the possible role of DNA damage in esophageal carcinogenic process. Endoscopic esophageal biopsies from 109 individuals from Chaoshan littoral, a high-risk region for esophageal squamous cell carcinoma (ESCC), were examined to evaluate the association between chronic inflammation and histological severity, while additional 204 esophageal non-tumor samples from patients with ESCC were collected. Immunohistochemistry was performed to detect the oxidative DNA damage and DNA double-strand breaks (DSBs). Significantly positive correlation was observed between degree of chronic inflammation and esophageal precursor lesions (rs = 0.37, P < 0.01). Immunohistochemical analysis showed that oxidative DNA damage level was positively correlated with the degree of chronic inflammation (rs = 0.21, P < 0.05). Moreover, the level of oxidative DNA damage positively correlated with histological severity (rs = 0.49, P < 0.01). We found that the extent of DSBs was progressively increased with inflammation degree (P < 0.01) and the progression of precancerous lesions (P < 0.001). Collectively, these findings provide evidence linking chronic inflammation-associated genomic instability with esophageal carcinogenesis and suggest possibilities for early detection and intervention of esophageal carcinogenesis.

Chronic pancreatitis: diagnosis, classification, and new genetic developments.

PubMed

Etemad, B; Whitcomb, D C

2001-02-01

The utilization of recent advances in molecular and genomic technologies and progress in pancreatic imaging techniques provided remarkable insight into genetic, environmental, immunologic, and pathobiological factors leading to chronic pancreatitis. Translation of these advances into clinical practice demands a reassessment of current approaches to diagnosis, classification, and staging. We conclude that an adequate pancreatic biopsy must be the gold standard against which all diagnostic approaches are judged. Although computed tomography remains the initial test of choice for the diagnosis of chronic pancreatitis, the roles of endoscopic retrograde pancreatography, endoscopic ultrasonography, and magnetic resonance imaging are considered. Once chronic pancreatitis is diagnosed, proper classification becomes important. Major predisposing risk factors to chronic pancreatitis may be categorized as either (1) toxic-metabolic, (2) idiopathic, (3) genetic, (4) autoimmune, (5) recurrent and severe acute pancreatitis, or (6) obstructive (TIGAR-O system). After classification, staging of pancreatic function, injury, and fibrosis becomes the next major concern. Further research is needed to determine the clinical and natural history of chronic pancreatitis developing in the context of various risk factors. New methods are needed for early diagnosis of chronic pancreatitis, and new therapies are needed to determine whether interventions will delay or prevent the progression of the irreversible damage characterizing end-stage chronic pancreatitis.

The Complex Interplay between Chronic Inflammation, the Microbiome, and Cancer: Understanding Disease Progression and What We Can Do to Prevent It

PubMed Central

Bording-Jorgensen, Michael; Dijk, Stephanie

2018-01-01

Cancer is a multifaceted condition, in which a senescent cell begins dividing in an irregular manner due to various factors such as DNA damage, growth factors and inflammation. Inflammation is not typically discussed as carcinogenic; however, a significant percentage of cancers arise from chronic microbial infections and damage brought on by chronic inflammation. A hallmark cancer-inducing microbe is Helicobacter pylori and its causation of peptic ulcers and potentially gastric cancer. This review discusses the recent developments in understanding microbes in health and disease and their potential role in the progression of cancer. To date, microbes can be linked to almost every cancer, including colon, pancreatic, gastric, and even prostate. We discuss the known mechanisms by which these microbes can induce cancer growth and development and how inflammatory cells may contribute to cancer progression. We also discuss new treatments that target the chronic inflammatory conditions and their associated cancers, and the impact microbes have on treatment success. Finally, we examine common dietary misconceptions in relation to microbes and cancer and how to avoid getting caught up in the misinterpretation and over inflation of the results. PMID:29558443

Acute and chronic psychological stress as risk factors for cardiovascular disease: Insights gained from epidemiological, clinical and experimental studies.

PubMed

Lagraauw, H Maxime; Kuiper, Johan; Bot, Ilze

2015-11-01

Cardiovascular disease (CVD) remains a leading cause of death worldwide and identification and therapeutic modulation of all its risk factors is necessary to ensure a lower burden on the patient and on society. The physiological response to acute and chronic stress exposure has long been recognized as a potent modulator of immune, endocrine and metabolic pathways, however its direct implications for cardiovascular disease development, progression and as a therapeutic target are not completely understood. More and more attention is given to the bidirectional interaction between psychological and physical health in relation to cardiovascular disease. With atherosclerosis being a chronic disease starting already at an early age the contribution of adverse early life events in affecting adult health risk behavior, health status and disease development is receiving increased attention. In addition, experimental research into the biological pathways involved in stress-induced cardiovascular complications show important roles for metabolic and immunologic maladaptation, resulting in increased disease development and progression. Here we provide a concise overview of human and experimental animal data linking chronic and acute stress to CVD risk and increased progression of the underlying disease atherosclerosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Progression from acute to chronic pancreatitis: prognostic factors, mortality, and natural course.

PubMed

Nøjgaard, Camilla; Becker, Ulrik; Matzen, Peter; Andersen, Jens Rikardt; Holst, Claus; Bendtsen, Flemming

2011-11-01

Knowledge of the natural course of acute pancreatitis (AP) and risk of progression to chronic pancreatitis (CP) is limited. The aims were to describe: (1) the incidence of progression from AP to CP, (2) prognostic factors for progression, and (3) the natural course and mortality of progressive AP. During 1977 to 1982, patients admitted to hospitals in Copenhagen with a diagnosis of AP or CP were included in a prospective cohort and followed up by the Danish registries in 2008. The subcohort analyses comprised 352 AP patients. Progressive AP was found in 85 patients (24.1%) during follow-up; 48.2% developed from alcoholic AP, 47.0% from idiopathic AP, and 4.8% from other causes. The mortality rate for patients with progressive AP was 2.7 times higher than in patients with nonprogressive acute pancreatitis, and 5.3 to 6.5 times higher than in the background population. In Cox regression analyses corrected for age, only smoking was of significance for the progression from AP to CP. Acute pancreatitis can progress to CP, not only from alcoholic but also from nonalcoholic AP. Smoking was the strongest risk factor associated with progression. The mortality rate for these patients was 5 to 6 times the mortality rate in the population.

Salivary pathogen and serum antibody to assess the progression of chronic periodontitis: a 24-mo prospective multicenter cohort study.

PubMed

Morozumi, T; Nakagawa, T; Nomura, Y; Sugaya, T; Kawanami, M; Suzuki, F; Takahashi, K; Abe, Y; Sato, S; Makino-Oi, A; Saito, A; Takano, S; Minabe, M; Nakayama, Y; Ogata, Y; Kobayashi, H; Izumi, Y; Sugano, N; Ito, K; Sekino, S; Numabe, Y; Fukaya, C; Yoshinari, N; Fukuda, M; Noguchi, T; Kono, T; Umeda, M; Fujise, O; Nishimura, F; Yoshimura, A; Hara, Y; Nakamura, T; Noguchi, K; Kakuta, E; Hanada, N; Takashiba, S; Yoshie, H

2016-12-01

A diagnosis of periodontitis progression is presently limited to clinical parameters such as attachment loss and radiographic imaging. The aim of this multicenter study was to monitor disease progression in patients with chronic periodontitis during a 24-mo follow-up program and to evaluate the amount of bacteria in saliva and corresponding IgG titers in serum for determining the diagnostic usefulness of each in indicating disease progression and stability. A total of 163 patients with chronic periodontitis who received trimonthly follow-up care were observed for 24 mo. The clinical parameters and salivary content of Porphyromonas gingivalis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were assessed using the modified Invader PLUS assay, and the corresponding serum IgG titers were measured using ELISA. The changes through 24 mo were analyzed using cut-off values calculated for each factor. One-way ANOVA or Fisher's exact test was used to perform between-group comparison for the data collected. Diagnostic values were calculated using Fisher's exact test. Of the 124 individuals who completed the 24-mo monitoring phase, 62 exhibited periodontitis progression, whereas 62 demonstrated stable disease. Seven patients withdrew because of acute periodontal abscess. The ratio of P. gingivalis to total bacteria and the combination of P. gingivalis counts and IgG titers against P. gingivalis were significantly related to the progression of periodontitis. The combination of P. gingivalis ratio and P. gingivalis IgG titers was significantly associated with the progression of periodontitis (p = 0.001, sensitivity = 0.339, specificity = 0.790). It is suggested that the combination of P. gingivalis ratio in saliva and serum IgG titers against P. gingivalis may be associated with the progression of periodontitis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Progression of recurrent acute and chronic pancreatitis: A short-term follow up study from a southern Indian centre.

PubMed

Kamath, M Ganesh; Pai, C Ganesh; Kamath, Asha

2016-11-01

Little data exist on the progression of recurrent acute (RAP) and chronic pancreatitis (CP) from regions from where the entity of tropical chronic pancreatitis was originally described. The study aimed to follow up patients with RAP and CP seen at a southern Indian centre for progression of disease over time. Prospectively enrolled patients with RAP and CP were followed up, and the alcoholic and idiopathic subgroups were assessed for progression of structural and functional changes in the organ. One hundred and forty patients (RAP = 44; 31.4 %, CP = 96; 68.5 %) were followed up over a median 12.2 (interquartile range 12.0-16.8) months. The cause was alcohol in 31 (22.1 %) and not evident in 109 (77.8 %). The disease progressed from RAP to CP in 7 (15.9 %), 6 (16.2 %) out of 37 in the idiopathic and 1 (14.2 %; p = 1.00) out of 7 in the alcoholic subgroups. Three (42.8 %) and 1 (14.2 %) developed steatorrhea and diabetes mellitus (DM), respectively, and 2 (4.5 %) developed calcification. Established CP progressed in 19 (19.7 %), 1 (1.0 %), 5 (5.2 %), 2 (2.0 %) and 11 (11.4 %) newly developed DM, steatorrhea, calcification and duct dilation during follow up. Among the idiopathic and alcoholic CP, disease progression was seen in 15 (20.8 %) out of 72 and 4 (16.6 %) out of 24 respectively. Idiopathic RAP and CP progressed during the short-term follow up. This is similar to other etiological forms of pancreatitis, as described from elsewhere in the world.

Predictive factors for progression through the difficulty levels of Pilates exercises in patients with low back pain: a secondary analysis of a randomized controlled trial.

PubMed

Franco, Katherinne Ferro Moura; Franco, Yuri Rafael Dos Santos; Oliveira, Naiane Teixeira Bastos de; Padula, Rosimeire Simprini; Cabral, Cristina Maria Nunes

2018-04-17

The progression through the difficulty levels of Pilates exercises is a subjective criterion, that depends on the therapist's experience and ability to identify the best moment to progress to the next level. To identify the factors that interfere in the progression through the difficulty levels of the Pilates exercises in patients with chronic nonspecific low back pain. Data from 139 patients with chronic nonspecific low back pain from a randomized controlled trial were used for statistical analysis using binary logistic regression. The dependent variable was the progression through the difficulty levels, and the independent variables were age, gender, educational level, low back pain duration, pain intensity, general disability, kinesiophobia, previous physical activity, and number of absences. The factors that interfered in the progression through the difficulty levels were previous physical inactivity (odds ratio [OR]=5.14, 95% confidence interval [CI]: 1.53-17.31), low educational level (OR=2.62, 95% CI: 1.12-6.10), more advanced age (OR=0.95, 95% CI: 0.92-0.98) and more absences (OR=0.63, 95% CI: 0.50-0.79). These variables explain 41% of the non-progression through the difficulty level of the exercises. Physical inactivity, low educational level, more advanced age and greater number of absences can be interfering factors in the progression through the difficulty levels of the Pilates exercises in patients with chronic nonspecific low back pain. Copyright © 2018 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

[Persistence of chronic inflammatory responses, role in the development of chronic pancreatitis, obesity and pancreatic cancer].

PubMed

Khristich, T N

2014-11-01

The purpose of the review--to analyze the basic data of the role of chronic low-intensity inflammatory response as general biological process in the development and progression of chronic pancreatitis, obesity, and pancreatic cancer. Highlighted evidence from epidemiological studies showing that chronic pancreatitis and obesity are independent risk factors for pancreatic cancer, regardless of diabetes. Studied role of adipokines as Cytokines regulating of immune inflammatory response. Draws attention to the staging of pancreatic cancer in obesity.

Chronic Δ9-Tetrahydrocannabinol Administration May Not Attenuate Simian Immunodeficiency Virus Disease Progression in Female Rhesus Macaques

PubMed Central

Amedee, Angela M.; Nichols, Whitney A.; LeCapitaine, Nicole J.; Stouwe, Curtis Vande; Birke, Leslie L.; Lacour, Nedra; Winsauer, Peter J.

2014-01-01

Abstract Persons living with HIV/AIDS (PLWHA) frequently use cannabinoids, either recreationally by smoking marijuana or therapeutically (delta-9-tetrahydrocannabinol; Δ9-THC dronabinol). Previously, we demonstrated that chronic Δ9-THC administration decreases early mortality in male simian immunodeficiency virus (SIV)-infected macaques. In this study, we sought to examine whether similar protective effects resulted from chronic cannabinoid administration in SIV-infected female rhesus macaques. Clinical and viral parameters were evaluated in eight female rhesus macaques that received either Δ9-THC (0.18–0.32 mg/kg, intramuscularly, twice daily) or vehicle (VEH) starting 28 days prior to intravenous inoculation with SIVmac251. SIV disease progression was assessed by changes in body weight, mortality, viral levels in plasma and mucosal sites, and lymphocyte subsets. In contrast to our results in male animals, chronic Δ9-THC did not protect SIV-infected female rhesus macaques from early mortality. Markers of SIV disease, including viral load and CD4+/CD8+ ratio, were not altered by Δ9-THC compared to control females; however, females that received chronic Δ9-THC did not gain as much weight as control animals. In addition, Δ9-THC administration increased total CXCR4 expression in both peripheral and duodenal CD4+ and CD8+ T lymphocytes prior to SIV inoculation. Although protection from early mortality was not evident, chronic Δ9-THC did not affect clinical markers of SIV disease progression. The contrasting effects of chronic Δ9-THC in males versus females remain to be explained, but highlight the need for further studies to explore the sex-dependent effects of Δ9-THC and other cannabinoids on the HIV disease course and their implications for virus transmission. PMID:25113915

Acoustic radiation force impulse elastography of the kidneys: is shear wave velocity affected by tissue fibrosis or renal blood flow?

PubMed

Asano, Kenichiro; Ogata, Ai; Tanaka, Keiko; Ide, Yoko; Sankoda, Akiko; Kawakita, Chieko; Nishikawa, Mana; Ohmori, Kazuyoshi; Kinomura, Masaru; Shimada, Noriaki; Fukushima, Masaki

2014-05-01

The aim of this study was to identify the main influencing factor of the shear wave velocity (SWV) of the kidneys measured by acoustic radiation force impulse elastography. The SWV was measured in the kidneys of 14 healthy volunteers and 319 patients with chronic kidney disease. The estimated glomerular filtration rate was calculated by the serum creatinine concentration and age. As an indicator of arteriosclerosis of large vessels, the brachial-ankle pulse wave velocity was measured in 183 patients. Compared to the degree of interobserver and intraobserver deviation, a large variance of SWV values was observed in the kidneys of the patients with chronic kidney disease. Shear wave velocity values in the right and left kidneys of each patient correlated well, with high correlation coefficients (r = 0.580-0.732). The SWV decreased concurrently with a decline in the estimated glomerular filtration rate. A low SWV was obtained in patients with a high brachial-ankle pulse wave velocity. Despite progression of renal fibrosis in the advanced stages of chronic kidney disease, these results were in contrast to findings for chronic liver disease, in which progression of hepatic fibrosis results in an increase in the SWV. Considering that a high brachial-ankle pulse wave velocity represents the progression of arteriosclerosis in the large vessels, the reduction of elasticity succeeding diminution of blood flow was suspected to be the main influencing factor of the SWV in the kidneys. This study indicates that diminution of blood flow may affect SWV values in the kidneys more than the progression of tissue fibrosis. Future studies for reducing data variance are needed for effective use of acoustic radiation force impulse elastography in patients with chronic kidney disease.

A Study of Acute and Chronic Tissue Changes in Surgical and Traumatically-Induced Experimental Models of Knee Joint Injury Using Magnetic Resonance Imaging and Micro-Computed Tomography

PubMed Central

Fischenich, Kristine M.; Pauly, Hannah M.; Button, Keith D.; Fajardo, Ryan S.; DeCamp, Charles E.; Haut, Roger C.; Haut Donahue, Tammy L.

2016-01-01

Objective The objective of this study was to monitor the progression of joint damage in two animal models of knee joint trauma using two non-invasive, clinically available imaging modalities. Methods A 3-T clinical magnet and micro-computed tomography (mCT) was used to document changes immediately following injury (acute) and post-injury (chronic) at time points of 4, 8, or 12 weeks. Joint damage was recorded at dissection and compared to the chronic magnetic resonance imaging (MRI) record. Fifteen Flemish Giant rabbits were subjected to a single tibiofemoral compressive impact (ACLF), and 18 underwent a combination of anterior cruciate ligament (ACL) and meniscal transection (mACLT). Results All ACLF animals experienced ACL rupture, and 13 also experienced acute meniscal damage. All ACLF and mACLT animals showed meniscal and articular cartilage damages at dissection. Meniscal damage was documented as early as 4 weeks and worsened in 87% of the ACLF animals and 71% of the mACLT animals. Acute cartilage damage also developed further and increased in occurrence with time in both models. A progressive decrease in bone quantity and quality was documented in both models. The MRI data closely aligned with dissection notes suggesting this clinical tool may be a non-invasive method for documenting joint damage in lapine models of knee joint trauma. Conclusions The study investigates the acute to chronic progression of meniscal and cartilage damage at various time points, and chronic changes to the underlying bone in two models of posttraumatic osteoarthritis (PTOA), and highlights the dependency of the model on the location, type, and progression of damage over time. PMID:27756698

Evolution of anti-Trypanosoma cruzi antibody production in patients with chronic Chagas disease: Correlation between antibody titers and development of cardiac disease severity

PubMed Central

Georg, Ingebourg; Hasslocher-Moreno, Alejandro Marcel; Xavier, Sergio Salles; de Holanda, Marcelo Teixeira; Bonecini-Almeida, Maria da Gloria

2017-01-01

Chagas disease is one of the most important endemic infections in Latin America affecting around 6–7 million people. About 30–50% of patients develop the cardiac form of the disease, which can lead to severe cardiac dysfunction and death. In this scenario, the identification of immunological markers of disease progression would be a valuable tool for early treatment and reduction of death rates. In this observational study, the production of anti-Trypanosoma cruzi antibodies through a retrospective longitudinal follow-up in chronic Chagas disease patients´ cohort and its correlation with disease progression and heart commitment was evaluated. Strong inverse correlation (ρ = -0.6375, p = 0.0005) between anti-T. cruzi IgG1 titers and left ventricular ejection fraction (LVEF) in chronic Chagas cardiomyopathy (CCC) patients were observed after disease progression. Elevated levels of anti-T. cruzi IgG3 titers were detected in all T. cruzi-infected patients, indicating a lack of correlation of this IgG isotype with disease progression. Furthermore, low levels of anti-T. cruzi IgG2, IgG4, and IgA were detected in all patients through the follow-up. Although without statistical significance anti-T. cruzi IgE tends to be more reactive in patients with the indeterminate form (IND) of the disease (p = 0.0637). As this study was conducted in patients with many years of chronic disease no anti-T. cruzi IgM was detected. Taken together, these results indicate that the levels of anti-T. cruzi IgG1 could be considered to seek for promising biomarkers to predict the severity of chronic Chagas disease cardiomyopathy. PMID:28723905

Informant Discrepancies in Externalizing and Internalizing Symptoms and Adaptive Skills of High-Functioning Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

McDonald, Christin A.; Lopata, Christopher; Donnelly, James P.; Thomeer, Marcus L.; Rodgers, Jonathan D.; Jordan, Allyson K.

2016-01-01

Assessment of clinical symptoms requires information from multiple informants. Discrepancies between informants' ratings can have significant implications in school settings (e.g., access to services, treatment planning, progress monitoring). This study examined parent-teacher discrepancies for ratings of internalizing and externalizing symptoms,…

Meta-Omic Platforms to Assist in the Understanding of NAFLD Gut Microbiota Alterations: Tools and Applications

PubMed Central

Del Chierico, Federica; Gnani, Daniela; Vernocchi, Pamela; Petrucca, Andrea; Alisi, Anna; Dallapiccola, Bruno; Nobili, Valerio; Lorenza, Putignani

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide as a result of the increasing prevalence of obesity, starting from early life stages. It is characterized by a spectrum of liver diseases ranging from simple fatty liver (NAFL) to steatohepatitis (NASH), with a possible progression to fibrosis, thus increasing liver-related morbidity and mortality. NAFLD development is driven by the co-action of several risk factors, including obesity and metabolic syndrome, which may be both genetically induced and diet-related. Recently, particular attention has been paid to the gut-liver axis, which may play a physio-pathological role in the onset and progression of the disease. The gut microbiota is intended to act as a bioreactor that can guarantee autonomous metabolic and immunological functions and that can drive functional strategies within the environment of the body in response to external stimuli. The complexity of the gut microbiota suggests that it behaves as an organ. Therefore, the concept of the gut-liver axis must be complemented with the gut-microbiota-liver network due to the high intricacy of the microbiota components and metabolic activities; these activities form the active diet-driven power plant of the host. Such complexity can only be revealed using systems biology, which can integrate clinical phenomics and gut microbiota data. PMID:24402126

Strengthening National Disease Surveillance and Response—Haiti, 2010–2015

PubMed Central

Juin, Stanley; Schaad, Nicolas; Lafontant, Donald; Joseph, Gerard A.; Barzilay, Ezra; Boncy, Jacques; Barrais, Robert; Louis, Frantz Jean; Jean Charles, Nadia Lapierre; Corvil, Salomon; Barthelemy, Nickolsno; Dismer, Amber; Pierre, Jean Samuel; Archer, Roodly W.; Antoine, Mayer; Marston, Barbara; Katz, Mark; Dely, Patrick; Adrien, Paul; Fitter, David L.; Lowrance, David; Patel, Roopal

2017-01-01

Abstract. Haiti’s health system has faced many challenges over the years, with competing health priorities in the context of chronic financial and human resource limitations. As a result, the existing notifiable disease surveillance system was unable to provide the most basic epidemiologic data for public health decision-making and action. In the wake of the January 2010 earthquake, the Haitian Ministry of Public Health and Population collaborated with the U.S. Centers for Disease Control and Prevention, the Pan American Health Organization, and other local and international partners to implement a functional national surveillance system. More than 7 years later, it is important to take the opportunity to reflect on progress made on surveillance and response in Haiti, including disease detection, reporting, outbreak investigation, and response. The national epidemiologic surveillance network that started with 51 sites in 2010 has been expanded to 357 sites as of December 2015. Disease outbreaks identified via the surveillance system, or other surveillance approaches, are investigated by epidemiologists trained by the Ministry of Health’s Field Epidemiology Training Program. Other related surveillance modules have been developed on the same model and electronic platform, allowing the country to document the impact of interventions, track progress, and monitor health problems. Sustainability remains the greatest challenge since most of the funding for surveillance come from external sources. PMID:29064361

Taking Targets to Task Revisited: How Indicators of Progress on Access to Education can Mislead. CREATE Pathways to Access. Research Monograph No. 54

ERIC Educational Resources Information Center

Lewin, Keith M.

2011-01-01

"Education for All" (EFA) identifies goals and targets and translates these into indicators which are used to evaluate progress and influence flows of external financing. The search for evidence based policy depends on measures of performance that can link cause and effect and that represent real gains in progress towards desired…

Chronic alcohol intake promotes tumor growth in a diethylnitrosamine-induced hepatocarcinogenesis mouse model through increased Wnt/Beta-catenin signaling

USDA-ARS?s Scientific Manuscript database

Ethanol (EtOH) metabolism is involved in both initiating and promoting mechanisms in hepatocellular carcinoma progression in chronic alcoholics. In this study, we developed a mouse model to test the hypothesis that chronic EtOH consumption promotes tumor growth irrespective of EtOH-related initiati...

Malignant transformation of oral lichen planus by a chronic inflammatory process. Use of topical corticosteroids to prevent this progression?

PubMed

Otero-Rey, Eva Maria; Suarez-Alen, Fatima; Peñamaria-Mallon, Manuel; Lopez-Lopez, Jose; Blanco-Carrion, Andres

2014-11-01

Oral lichen planus is a potentially malignant disorder with a capacity, although low, for malignant transformation. Of all the factors related to the process of malignant transformation, it is believed that the chronic inflammatory process plays a key role in the development of oral cancer. This inflammatory process is capable of providing a microenvironment based on different inflammatory cells and molecules that affect cellular growth, proliferation and differentiation. The objectives of our study are: to review the available evidence about the possible relationship between the chronic inflammatory process present in oral lichen planus and its malignant transformation, to discuss the potential therapeutic implications derived from this relationship and to study the role that topical corticosteroids play in the control of oral lichen planus inflammation and its possible progression to malignant transformation. The maintenance of a minimum dose of topical corticosteroids could prevent the inflammatory progression of oral lichen planus to oral cancer.

Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes.

PubMed

Tzoulis, Charalampos; Neckelmann, Gesche; Mørk, Sverre J; Engelsen, Bernt E; Viscomi, Carlo; Moen, Gunnar; Ersland, Lars; Zeviani, Massimo; Bindoff, Laurence A

2010-05-01

Mutations in the catalytic subunit of the mitochondrial DNA-polymerase gamma cause a wide spectrum of clinical disease ranging from infantile hepato-encephalopathy to juvenile/adult-onset spinocerebellar ataxia and late onset progressive external ophthalmoplegia. Several of these syndromes are associated with an encephalopathy that characteristically shows episodes of rapid neurological deterioration and the development of acute cerebral lesions. The purpose of this study was to investigate the nature, distribution and natural evolution of central nervous system lesions in polymerase gamma associated encephalopathy focusing particularly on lesions identified by magnetic resonance imaging. We compared radiological, electrophysiological and pathological findings where available to study potential mechanisms underlying the episodes of exacerbation and acute cerebral lesions. We studied a total of 112 magnetic resonance tomographies and 11 computed tomographies in 32 patients with polymerase gamma-encephalopathy, including multiple serial examinations performed during both the chronic and acute phases of the disease and, in several cases, magnetic resonance spectroscopy and serial diffusion weighted studies. Data from imaging, electroencephalography and post-mortem examination were compared in order to study the underlying disease process. Our findings show that magnetic resonance imaging in polymerase gamma-related encephalopathies has high sensitivity and can identify patterns that are specific for individual syndromes. One form of chronic polymerase gamma-encephalopathy, that is associated with the c.1399G > A and c.2243G > C mutations, is characterized by progressive cerebral and cerebellar atrophy and focal lesions of the thalamus, deep cerebellar structures and medulla oblongata. Acute encephalopathies, both infantile and later onset, show similar pictures with cortical stroke-like lesions occurring during episodes of exacerbation. These lesions can occur both with and without electroencephalographic evidence of concurrent epileptic activity, and have diffusion, spectroscopic and histological profiles strongly suggestive of neuronal energy failure. We suggest therefore that both infantile and later onset polymerase gamma related encephalopathies are part of a continuum.

Effectiveness of home-based cupping massage compared to progressive muscle relaxation in patients with chronic neck pain--a randomized controlled trial.

PubMed

Lauche, Romy; Materdey, Svitlana; Cramer, Holger; Haller, Heidemarie; Stange, Rainer; Dobos, Gustav; Rampp, Thomas

2013-01-01

Chronic neck pain is a major public health problem with very few evidence-based complementary treatment options. This study aimed to test the efficacy of 12 weeks of a partner-delivered home-based cupping massage, compared to the same period of progressive muscle relaxation in patients with chronic non-specific neck pain. Patients were randomly assigned to self-directed cupping massage or progressive muscle relaxation. They were trained and asked to undertake the assigned treatment twice weekly for 12 weeks. Primary outcome measure was the current neck pain intensity (0-100 mm visual analog scale; VAS) after 12 weeks. Secondary outcome measures included pain on motion, affective pain perception, functional disability, psychological distress, wellbeing, health-related quality of life, pressure pain thresholds and adverse events. Sixty one patients (54.1±12.7 years; 73.8%female) were randomized to cupping massage (n = 30) or progressive muscle relaxation (n = 31). After treatment, both groups showed significantly less pain compared to baseline however without significant group differences. Significant effects in favor of cupping massage were only found for wellbeing and pressure pain thresholds. In conclusion, cupping massage is no more effective than progressive muscle relaxation in reducing chronic non-specific neck pain. Both therapies can be easily used at home and can reduce pain to a minimal clinically relevant extent. Cupping massage may however be better than PMR in improving well-being and decreasing pressure pain sensitivity but more studies with larger samples and longer follow-up periods are needed to confirm these results. ClinicalTrials.gov NCT01500330.

Effectiveness of Home-Based Cupping Massage Compared to Progressive Muscle Relaxation in Patients with Chronic Neck Pain—A Randomized Controlled Trial

PubMed Central

Lauche, Romy; Materdey, Svitlana; Cramer, Holger; Haller, Heidemarie; Stange, Rainer; Dobos, Gustav; Rampp, Thomas

2013-01-01

Chronic neck pain is a major public health problem with very few evidence-based complementary treatment options. This study aimed to test the efficacy of 12 weeks of a partner-delivered home-based cupping massage, compared to the same period of progressive muscle relaxation in patients with chronic non-specific neck pain. Patients were randomly assigned to self-directed cupping massage or progressive muscle relaxation. They were trained and asked to undertake the assigned treatment twice weekly for 12 weeks. Primary outcome measure was the current neck pain intensity (0–100 mm visual analog scale; VAS) after 12 weeks. Secondary outcome measures included pain on motion, affective pain perception, functional disability, psychological distress, wellbeing, health-related quality of life, pressure pain thresholds and adverse events. Sixty one patients (54.1±12.7 years; 73.8%female) were randomized to cupping massage (n = 30) or progressive muscle relaxation (n = 31). After treatment, both groups showed significantly less pain compared to baseline however without significant group differences. Significant effects in favor of cupping massage were only found for wellbeing and pressure pain thresholds. In conclusion, cupping massage is no more effective than progressive muscle relaxation in reducing chronic non-specific neck pain. Both therapies can be easily used at home and can reduce pain to a minimal clinically relevant extent. Cupping massage may however be better than PMR in improving well-being and decreasing pressure pain sensitivity but more studies with larger samples and longer follow-up periods are needed to confirm these results. Trial Registration ClinicalTrials.gov NCT01500330 PMID:23762355

The progressive nature of concentration camp syndrome in former prisoners of Nazi concentration camps--Not just history, but the important issue of contemporary medicine.

PubMed

Jabłoński, Robert; Rosińczuk, Joanna; Leszek, Jerzy; Uchmanowicz, Izabella; Panaszek, Bernard

2016-04-01

Constant stress, slave labor, tortures, and starvation all affected the health of concentration camp prisoners, contributing to multimorbidities, increased mortality and accelerated development of chronic illnesses, what we have shown in an earlier publication. The interrelated somatic and psychological symptoms gave rise to concentration camp syndrome (KZ-syndrome), which has many features of PTSD, occurring frequently nowadays. The paper attempts at assessing the influence of concentration camp conditions on functional disorders in each system of the human body, occurring in KZ-syndrome, and at demonstrating the progressive nature of the syndrome. A retrospective assessment of the former prisoners' health after 5 and 30 years following their leaving camps was performed based on medical records and surveys. The materials included 250 former prisoners who underwent medical examination in 1950, i.e. 5 years after leaving the camp, of whom 120 former prisoners survived and were examined and surveyed in 1975, i.e. 30 years after leaving the camp. KZ-syndrome was shown to occur in 58.8% of former prisoners 5 years after leaving the camp, and in 77.5% after 30 years (p < 0.001), which confirms the syndrome's chronic and progressive nature. Pathological sequels of internment in concentration camps, in the form of KZ-syndrome, were observed in most former prisoners. Over time, the number of morbidities and the intensity of symptoms increased, which indicates that the syndrome has a chronic and progressive nature. KZ-syndrome is a multi-organ disorder, with numerous chronic comorbidities exacerbating the progression. Copyright © 2015 Elsevier Ltd. All rights reserved.

External fixation for severe open fractures of the humerus caused by missiles.

PubMed

Zinman, C; Norman, D; Hamoud, K; Reis, N D

1997-10-01

To evaluate the use of external fixation of the humerus after missile injuries. Retrospective. University medical center. Twenty-six soldiers with twenty-six open Gustilo type III fractures. Immediate external fixation. Clinical, functional, social, and rehabilitation criteria were evaluated. Excellent in fourteen patients (61%), good in four (17%), fair in three (13%), and poor in two (9%). All fractures eventually healed. External fixation is the preferred initial treatment for stabilizing severe open missile fractures of the humerus. Its use, together with radical debridement of dead bone, has reduced the incidence of chronic infection and improved the prognosis of vascular repairs. As a result, the rate of morbidity and upper limb amputation has been reduced significantly, compared with our previous experience.

Allopurinol Against Progression of Chronic Kidney Disease.

PubMed

Golmohammadi, Sima; Almasi, Afshin; Manouchehri, M; Omrani, Hamid Reza; Zandkarimi, Mohammad Reza

2017-07-01

Hyperuricemia is common in approximately 50% of patients with kidney failure due to decreased uric acid excretion, and it has been recently known as an independent factor in the progression of renal insufficiency. Allopurinol inhibits the production of uric acid. The aim of this study was to evaluate the effect of allopurinol on chronic kidney disease progression. In a clinical trial, patients with stages 3 and 4 of chronic kidney disease were divided into two groups to receive allopurinol, 100 mg, daily and placebo for 12 months. Patients' kidney function and serum uric acid levels were assessed at baseline and 3, 6, and 12 months after initial administration. Subgroups of patients with severe and mild glomerular filtration rate (GFR) impairment (GFR, 15 mL/min/1.73 m2 to 30 mL/min/1.73 m2 and 30 mL/min/1.73 m2 to 60 mL/min/1.73 m2, respectively), were compared between the groups. Serum uric acid levels decreased significantly during after 12 months of allopurinol administration (P = .004). In patients with severe GFR impairment, serum creatinine levels did not decrease significantly and there was no significant increase in GFR, but in those with mild GFR impairment, serum creatinine levels decreased and GFR increase significantly (P < .001) after administration of allopurinol. These effects were not observed in the control subgroups. Allopurinol may slow down stage 3 chronic kidney disease progression and could be administered with other effective medications for controlling the kidney disease.

Cannabinoid administration attenuates the progression of simian immunodeficiency virus.

PubMed

Molina, Patricia E; Winsauer, Peter; Zhang, Ping; Walker, Edith; Birke, Leslie; Amedee, Angela; Stouwe, Curtis Vande; Troxclair, Dana; McGoey, Robin; Varner, Kurt; Byerley, Lauri; LaMotte, Lynn

2011-06-01

Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), the primary psychoactive component in marijuana, is FDA approved to ameliorate AIDS-associated wasting. Because cannabinoid receptors are expressed on cells of the immune system, chronic Δ(9)-THC use may impact HIV disease progression. We examined the impact of chronic Δ(9)-THC administration (0.32 mg/kg im, 2 × daily), starting 28 days prior to inoculation with simian immunodeficiency virus (SIV(mac251); 100 TCID(50)/ml, iv), on immune and metabolic indicators of disease during the initial 6 month asymptomatic phase of infection in rhesus macaques. SIV(mac251) inoculation resulted in measurable viral load, decreased lymphocyte CD4(+)/CD8(+) ratio, and increased CD8(+) proliferation. Δ(9)-THC treatment of SIV-infected animals produced minor to no effects in these parameters. However, chronic Δ(9)-THC administration decreased early mortality from SIV infection (p = 0.039), and this was associated with attenuation of plasma and CSF viral load and retention of body mass (p = NS). In vitro, Δ(9)-THC (10 μm) decreased SIV (10 TCID(50)) viral replication in MT4-R5 cells. These results indicate that chronic Δ(9)-THC does not increase viral load or aggravate morbidity and may actually ameliorate SIV disease progression. We speculate that reduced levels of SIV, retention of body mass, and attenuation of inflammation are likely mechanisms for Δ(9)-THC-mediated modulation of disease progression that warrant further study.

A small molecule inhibitor of NFκB blocks ER stress and the NLRP3 inflammasome and prevents progression of pancreatitis.

PubMed

Kanak, Mazhar A; Shahbazov, Rauf; Yoshimatsu, Gumpei; Levy, Marlon F; Lawrence, Michael C; Naziruddin, Bashoo

2017-03-01

The underlying molecular mechanism that leads to development of chronic pancreatitis remains elusive. The aim of this study is to understand the downstream inflammatory signaling involved in progression of chronic pancreatitis, and to use withaferin A (WA), a small molecule inhibitor of nuclear factor κB (NFκB), to prevent progression of chronic pancreatitis. Two different protocols were used to induce pancreatitis in mice: standard and stringent administration of cerulein. The severity of pancreatitis was assessed by means of pancreatic histology and serum amylase levels. Immunohistochemistry and flow-cytometric analysis was performed to visualize immune cell infiltration into the pancreas. Real-time PCR and Western blot were used to analyze the downstream signaling mechanism involved in the development of chronic pancreatitis. The severity of cerulein-induced pancreatitis was reduced significantly by WA, used as either preventive or curative treatment. Immune cell infiltration into the pancreas and acinar cell death were efficiently reduced by WA treatment. Expression of proinflammatory and proapoptotic genes regulated by NFκB activation was increased by cerulein treatment, and WA suppressed these genes significantly. Sustained endoplasmic reticulum stress activation by cerulein administration was reduced. NLRP3 inflammasome activation in cerulein-induced pancreatitis was identified, and this was also potently blocked by WA. The human pancreatitis tissue gene signature correlated with the mouse model. Our data provide evidence for the role of NFκB in the pathogenesis of chronic pancreatitis, and strongly suggest that WA could be used as a potential therapeutic drug to alleviate some forms of chronic pancreatitis.

Asthma progression to airway remodeling and bone marrow eosinophil responses in genetically distinct strains of mice.

PubMed

Hogan, Mary Beth; Piktel, Debra; Hubbs, Ann F; McPherson, Leslie E; Landreth, Kenneth S

2008-12-01

Patient factors that cause long-term airway remodeling are largely unidentified. This suggests that genetic differences may determine which asthmatic patients develop airway remodeling. A murine model with repeated allergen exposure leading to peribronchial fibrosis in complement factor 5 (C5)-deficient A/J mice has been used to study asthma progression. No studies have addressed the systemic effects of allergen sensitization or chronic allergen exposure on bone marrow eosinophilopoiesis in this mouse strain. To investigate bone marrow eosinophil responses during acute sensitization and chronic allergen exposure using genetically distinct mouse strains differing in persistent airway reactivity and remodeling. The C5-sufficient BALB/c and C5-deficient A/J mice were repetitively exposed to intranasal ovalbumin for 12 weeks. Subsequently, the mice were evaluated for airway eosinophilia, mucus-containing goblet cells, and peribronchial fibrosis. Both strains of mice were also acutely sensitized to ovalbumin. Bone marrow eosinophil progenitor cells and mature eosinophils were enumerated. BALB/c and A/J mice have similar bone marrow responses after acute allergen exposure, with elevations in bone marrow eosinophil progenitor cell and eosinophil numbers. After chronic allergen exposure, only C5-deficient A/J mice that developed peribronchial fibrosis exhibited bone marrow eosinophilia. BALB/c mice lacked peribronchial fibrosis and extinguished accelerated eosinophil production after long-term allergen challenge. Chronic airway remodeling after repeated allergen exposure in genetically different mice correlated with differences in long-term bone marrow eosinophilopoiesis. Preventing asthma from progressing to chronic airway remodeling with fibrosis may involve identifying genetically determined influences on bone marrow responses to chronic allergen exposure.

The role of renin-angiotensin-aldosterone system genes in the progression of chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study.

PubMed

Kelly, Tanika N; Raj, Dominic; Rahman, Mahboob; Kretzler, Matthias; Kallem, Radhakrishna R; Ricardo, Ana C; Rosas, Sylvia E; Tao, Kaixiang; Xie, Dawei; Hamm, Lotuce Lee; He, Jiang

2015-10-01

We conducted single-marker, gene- and pathway-based analyses to examine the association between renin-angiotensin-aldosterone system (RAAS) variants and chronic kidney disease (CKD) progression among Chronic Renal Insufficiency Cohort study participants. A total of 1523 white and 1490 black subjects were genotyped for 490 single nucleotide polymorphisms (SNPs) in 12 RAAS genes as part of the ITMAT-Broad-CARe array. CKD progression phenotypes included decline in estimated glomerular filtration rate (eGFR) over time and the occurrence of a renal disease event, defined as incident end-stage renal disease or halving of eGFR from baseline. Mixed-effects models were used to examine SNP associations with eGFR decline, while Cox proportional hazards models tested SNP associations with renal events. Gene- and pathway-based analyses were conducted using the truncated product method. All analyses were stratified by race, and a Bonferroni correction was applied to adjust for multiple testing. Among white and black participants, eGFR declined an average of 1.2 and 2.3 mL/min/1.73 m(2)/year, respectively, while renal events occurred in a respective 11.5 and 24.9% of participants. We identified strong gene- and pathway-based associations with CKD progression. The AGT and RENBP genes were consistently associated with risk of renal events in separate analyses of white and black participants (both P < 1.00 × 10(-6)). Driven by the significant gene-based findings, the entire RAAS pathway was also associated with renal events in both groups (both P < 1.00 × 10(-6)). No single-marker associations with CKD progression were observed. The current study provides strong evidence for a role of the RAAS in CKD progression. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The role of renin–angiotensin–aldosterone system genes in the progression of chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study

PubMed Central

Kelly, Tanika N.; Raj, Dominic; Rahman, Mahboob; Kretzler, Matthias; Kallem, Radhakrishna R.; Ricardo, Ana C.; Rosas, Sylvia E.; Tao, Kaixiang; Xie, Dawei; Hamm, Lotuce Lee; He, Jiang; Appel, J.; Feldman, Harold I.; Go, Alan S.; Kusek, John W.; Lash, James P.; Ojo, Akinlolu; Townsend, Raymond R.

2015-01-01

Background We conducted single-marker, gene- and pathway-based analyses to examine the association between renin–angiotensin–aldosterone system (RAAS) variants and chronic kidney disease (CKD) progression among Chronic Renal Insufficiency Cohort study participants. Methods A total of 1523 white and 1490 black subjects were genotyped for 490 single nucleotide polymorphisms (SNPs) in 12 RAAS genes as part of the ITMAT-Broad-CARe array. CKD progression phenotypes included decline in estimated glomerular filtration rate (eGFR) over time and the occurrence of a renal disease event, defined as incident end-stage renal disease or halving of eGFR from baseline. Mixed-effects models were used to examine SNP associations with eGFR decline, while Cox proportional hazards models tested SNP associations with renal events. Gene- and pathway-based analyses were conducted using the truncated product method. All analyses were stratified by race, and a Bonferroni correction was applied to adjust for multiple testing. Results Among white and black participants, eGFR declined an average of 1.2 and 2.3 mL/min/1.73 m2/year, respectively, while renal events occurred in a respective 11.5 and 24.9% of participants. We identified strong gene- and pathway-based associations with CKD progression. The AGT and RENBP genes were consistently associated with risk of renal events in separate analyses of white and black participants (both P < 1.00 × 10−6). Driven by the significant gene-based findings, the entire RAAS pathway was also associated with renal events in both groups (both P < 1.00 × 10−6). No single-marker associations with CKD progression were observed. Conclusions The current study provides strong evidence for a role of the RAAS in CKD progression. PMID:25906781

An assessment of the Pacific Regional Cancer Coalition: outcomes and implications of a regional coalition internal and external assessment.

PubMed

Sy, Angela U; Heckert, Karen A; Buenconsejo-Lum, Lee; Hedson, Johnny; Tamang, Suresh; Palafox, Neal

2011-11-01

The Pacific Regional Cancer Coalition (PRCC) provides regional leadership in the U.S. Affiliated Pacific Islands (USAPI) to implement the Regional Comprehensive Control Plan: 2007-2012, and to evaluate its coalition and partnerships. The Pacific Center of Excellence in the Elimination of Disparities (CEED), aims to reduce cancer disparities and conducts evaluation activities relevant to cancer prevention and control in the USAPI. The PRCC Self (internal) and Partner (external) Assessments were conducted to assess coalition functioning, regional and national partnerships, sustainability, and the role of regionalism for integrating all chronic disease prevention and control in the Pacific. Self-administered questionnaires and key informant telephone interviews with PRCC members (N=20), and representatives from regional and national partner organizations were administered (N=26). Validated multi item measures using 5-point scales on coalition and partnership characteristics were used. Chronbach's alphas and averages for the measures were computed. Internal coalition measures: satisfaction (4.2, SD=0.48) communication (4.0, SD=0.56), respect (4.0, SD=0.60) were rated more highly than external partnership measures: resource sharing (3.5, SD=0.74), regionalism (3.9, SD=0.47), use of findings (3.9, SD=0.50). The PRCC specifically identified its level of "collaboration" with external partners including Pacific CEED. External partners identified its partnership with the PRCC in the "coalition" stage. PRCC members and external partners are satisfied with their partnerships. All groups should continue to focus on building collaboration with partners to reflect a truly regional approach to sustain the commitment, the coalitions and the programming to reduce cancer in the USAPI. PRCC and partners should also work together to integrate all chronic disease prevention and control efforts in the Pacific.

Novel and Experimental Therapies in Chronic Pancreatitis.

PubMed

Jagannath, Soumya; Garg, Pramod Kumar

2017-07-01

Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas. The currently available treatment of CP is aimed at controlling symptoms and managing complications. Unfortunately, no specific treatment is available to halt the progression of the disease process because the pathophysiological perturbations in CP are not well understood. In this review, we discuss various therapeutic targets and investigational agents acting on these targets. Among these, therapies modulating immune cells and those acting on pancreatic stellate cells appear promising and may translate into clinical benefit in near future. However, these experimental therapies are mostly in animal models and they do not recapitulate all aspects of human disease. Still they may be beneficial in developing effective therapeutic modalities to curb inflammation in chronic pancreatitis.

Autophagy and oxidative stress in non-communicable diseases: A matter of the inflammatory state?

PubMed

Peña-Oyarzun, Daniel; Bravo-Sagua, Roberto; Diaz-Vega, Alexis; Aleman, Larissa; Chiong, Mario; Garcia, Lorena; Bambs, Claudia; Troncoso, Rodrigo; Cifuentes, Mariana; Morselli, Eugenia; Ferreccio, Catterina; Quest, Andrew F G; Criollo, Alfredo; Lavandero, Sergio

2018-05-30

Non-communicable diseases (NCDs), also known as chronic diseases, are long-lasting conditions that affect millions of people around the world. Different factors contribute to their genesis and progression; however they share common features, which are critical for the development of novel therapeutic strategies. A persistently altered inflammatory response is typically observed in many NCDs together with redox imbalance. Additionally, dysregulated proteostasis, mainly derived as a consequence of compromised autophagy, is a common feature of several chronic diseases. In this review, we discuss the crosstalk among inflammation, autophagy and oxidative stress, and how they participate in the progression of chronic diseases such as cancer, cardiovascular diseases, obesity and type II diabetes mellitus. Copyright © 2018 Elsevier Inc. All rights reserved.

Parental health literacy and progression of chronic kidney disease in children.

PubMed

Ricardo, Ana C; Pereira, Lynn N; Betoko, Aisha; Goh, Vivien; Amarah, Amatur; Warady, Bradley A; Moxey-Mims, Marva; Furth, Susan; Lash, James P

2018-06-14

Limited health literacy has been associated with adverse outcomes in children. We evaluated this association in the setting of chronic kidney disease (CKD). We assessed the parental health literacy of 367 children enrolled in the Chronic Kidney Disease in Children (CKiD) Study, using the Short Test of Functional Health Literacy (STOFHLA). We evaluated the association between parental health literacy and CKD progression, defined as time to the composite event of renal replacement therapy (RRT, dialysis, or kidney transplant) or 50% decline in estimated glomerular filtration rate (eGFR). Median CKiD participant age was 9.5 years, 63% were male, and 59% non-Hispanic white. Median eGFR at baseline was 63 ml/min/1.73 m 2 , and median urine protein-to-creatinine ratio was 0.22. The median STOFHLA score was 98. Over a median follow-up of 3.7 years, the overall CKD progression rate was 2.8 per 100 person-years. After adjustment for demographic and clinical factors, the relative time to CKD progression was 28% longer per 1 SD increase in STOFHLA score (relative time, 95% CI, 1.28, 1.06-1.53). In this cohort of children with CKD, higher parental health literacy was associated with a nearly 30% longer time to the composite CKD progression outcome.

Disease progression in Chinese chronic hepatitis C patients with persistently normal alanine aminotransaminase levels.

PubMed

Hui, C-K; Zhang, H-Y; Shek, T; Yao, H; Yueng, Y-H; Leung, K-W; Lai, S-T; Lai, J-Y; Leung, N; Lau, G K

2007-06-01

Although chronic hepatitis C virus-infected patients with persistently normal alanine aminotransaminase levels usually have mild liver disease, disease progression can still occur. However, it is uncertain which group of patients is at risk of disease progression. To examine the severity of liver disease on liver biopsy in Chinese patients with persistently normal alanine aminotransaminase levels, and their disease progression over time. Eighty-two patients with persistently normal alanine aminotransaminase levels were followed up longitudinally. The median time of follow-up was 8.1 years. Forty-seven of the 82 patients (57.3%) had a second liver biopsy. At the time of analysis, six of the 82 patients (7.3%) developed decompensated liver cirrhosis. Patients with an initial fibrosis stage F2 or F3 [6/23 (26.1%) vs. 0/59 (0%), P < 0.0001] or inflammatory grade A2 or A3 [5/40 (12.5%) vs. 1/42 (2.4%), P = 0.04] were more likely to develop decompensated liver cirrhosis. On multivariate analysis, initial fibrosis stage F2 or F3 was independently associated with progression to decompensated liver cirrhosis (relative risk 2.3, 95% confidence interval 0.03-2.5, P = 0.02). Chinese chronic hepatitis C virus patients with persistently normal alanine aminotransaminase levels with moderate to severe fibrosis at initial evaluation are more likely to develop decompensated liver cirrhosis.

Urine Trefoil Factors as Prognostic Biomarkers in Chronic Kidney Disease.

PubMed

Yamanari, Toshio; Sugiyama, Hitoshi; Tanaka, Keiko; Morinaga, Hiroshi; Kitagawa, Masashi; Onishi, Akifumi; Ogawa-Akiyama, Ayu; Kano, Yuzuki; Mise, Koki; Ohmoto, Yasukazu; Shikata, Kenichi; Wada, Jun

2018-01-01

Trefoil factor family (TFF) peptides are increased in serum and urine in patients with chronic kidney disease (CKD). However, whether the levels of TFF predict the progression of CKD remains to be elucidated. We determined the TFF levels using peptide-specific ELISA in spot urine samples and performed a prospective cohort study. The association between the levels of urine TFFs and other urine biomarkers as well as the renal prognosis was analyzed in 216 CKD patients (mean age: 53.7 years, 47.7% female, 56.9% with chronic glomerulonephritis, and mean eGFR: 58.5 ml/min/1.73 m 2 ). The urine TFF1 and TFF3 levels significantly increased with the progression of CKD stages, but not the urine TFF2 levels. The TFF1 and TFF3 peptide levels predicted the progression of CKD ≥ stage 3b by ROC analysis (AUC 0.750 and 0.879, resp.); however, TFF3 alone predicted CKD progression in a multivariate logistic regression analysis (odds ratio 3.854, 95% confidence interval 1.316-11.55). The Kaplan-Meier survival curves demonstrated that patients with a higher TFF1 and TFF3 alone, or in combination with macroalbuminuria, had a significantly worse renal prognosis. The data suggested that urine TFF peptides are associated with renal progression and the outcomes in patients with CKD.

Urine Trefoil Factors as Prognostic Biomarkers in Chronic Kidney Disease

PubMed Central

Yamanari, Toshio; Tanaka, Keiko; Morinaga, Hiroshi; Kitagawa, Masashi; Onishi, Akifumi; Ogawa-Akiyama, Ayu; Kano, Yuzuki; Mise, Koki; Ohmoto, Yasukazu; Shikata, Kenichi

2018-01-01

Introduction Trefoil factor family (TFF) peptides are increased in serum and urine in patients with chronic kidney disease (CKD). However, whether the levels of TFF predict the progression of CKD remains to be elucidated. Methods We determined the TFF levels using peptide-specific ELISA in spot urine samples and performed a prospective cohort study. The association between the levels of urine TFFs and other urine biomarkers as well as the renal prognosis was analyzed in 216 CKD patients (mean age: 53.7 years, 47.7% female, 56.9% with chronic glomerulonephritis, and mean eGFR: 58.5 ml/min/1.73 m2). Results The urine TFF1 and TFF3 levels significantly increased with the progression of CKD stages, but not the urine TFF2 levels. The TFF1 and TFF3 peptide levels predicted the progression of CKD ≥ stage 3b by ROC analysis (AUC 0.750 and 0.879, resp.); however, TFF3 alone predicted CKD progression in a multivariate logistic regression analysis (odds ratio 3.854, 95% confidence interval 1.316–11.55). The Kaplan-Meier survival curves demonstrated that patients with a higher TFF1 and TFF3 alone, or in combination with macroalbuminuria, had a significantly worse renal prognosis. Conclusion The data suggested that urine TFF peptides are associated with renal progression and the outcomes in patients with CKD. PMID:29850501

Beneficial and detrimental role of adenosine signaling in diseases and therapy

PubMed Central

Liu, Hong

2015-01-01

Adenosine is a major signaling nucleoside that orchestrates cellular and tissue adaptation under energy depletion and ischemic/hypoxic conditions by activation of four G protein-coupled receptors (GPCR). The regulation and generation of extracellular adenosine in response to stress are critical in tissue protection. Both mouse and human studies reported that extracellular adenosine signaling plays a beneficial role during acute states. However, prolonged excess extracellular adenosine is detrimental and contributes to the development and progression of various chronic diseases. In recent years, substantial progress has been made to understand the role of adenosine signaling in different conditions and to clarify its significance during the course of disease progression in various organs. These efforts have and will identify potential therapeutic possibilities for protection of tissue injury at acute stage by upregulation of adenosine signaling or attenuation of chronic disease progression by downregulation of adenosine signaling. This review is to summarize current progress and the importance of adenosine signaling in different disease stages and its potential therapeutic effects. PMID:26316513

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis

PubMed Central

Farci, Patrizia; Wollenberg, Kurt; Diaz, Giacomo; Engle, Ronald E.; Lai, Maria Eliana; Klenerman, Paul; Purcell, Robert H.; Pybus, Oliver G.; Alter, Harvey J.

2012-01-01

Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unknown. Using serial, prospectively collected samples from cases of transfusion-associated hepatitis C, we identified outcome-specific features that predict long-term disease severity. Slowly progressing disease correlated with an early alanine aminotransferase peak and antibody seroconversion, transient control of viremia, and significant induction of IFN-γ and MIP-1β, all indicative of an effective, albeit insufficient, adaptive immune response. By contrast, rapidly progressive disease correlated with persistent and significant elevations of alanine aminotransferase and the profibrogenic chemokine MCP-1 (CCL-2), greater viral diversity and divergence, and a higher rate of synonymous substitution. This study suggests that the long-term course of chronic hepatitis C is determined early in infection and that disease severity is predicted by the evolutionary dynamics of hepatitis C virus and the level of MCP-1, a chemokine that appears critical to the induction of progressive fibrogenesis and, ultimately, the ominous complications of cirrhosis. PMID:22829669

Risk Factors for Progression of Chronic Kidney Disease

PubMed Central

Staples, Amy; Wong, Craig

2010-01-01

Purpose of Review Provides an overview of the identified risk factors for chronic kidney disease (CKD) progression emphasizing the pediatric population. Recent findings Over the past ten years, there have been significant changes to our understanding and study of pre-terminal kidney failure. Recent refinements in the measurement of glomerular filtration rate (GFR) and GFR estimating equations are important tools for identification and association of risk factors for CKD progression in children. In pediatric CKD, lower level of kidney function at presentation, higher levels of proteinuria, and hypertension are known markers for a more rapid decline in GFR. Anemia and other reported risk factors from the pre-genomic era have need for further study and validation. Genome-wide association studies have identified genetic loci which have provided novel genetic risk factors for CKD progression. Summary With cohort studies of children with CKD becoming mature, they have started to yield important refinements to the assessment of CKD progression. While many of the traditional risk factors for renal progression will certainly be assessed, such cohorts will be important for evaluating novel risk factors identified by genome-wide studies. PMID:20090523

Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis.

PubMed

Farci, Patrizia; Wollenberg, Kurt; Diaz, Giacomo; Engle, Ronald E; Lai, Maria Eliana; Klenerman, Paul; Purcell, Robert H; Pybus, Oliver G; Alter, Harvey J

2012-09-04

Chronic hepatitis C may follow a mild and stable disease course or progress rapidly to cirrhosis and liver-related death. The mechanisms underlying the different rates of disease progression are unknown. Using serial, prospectively collected samples from cases of transfusion-associated hepatitis C, we identified outcome-specific features that predict long-term disease severity. Slowly progressing disease correlated with an early alanine aminotransferase peak and antibody seroconversion, transient control of viremia, and significant induction of IFN-γ and MIP-1β, all indicative of an effective, albeit insufficient, adaptive immune response. By contrast, rapidly progressive disease correlated with persistent and significant elevations of alanine aminotransferase and the profibrogenic chemokine MCP-1 (CCL-2), greater viral diversity and divergence, and a higher rate of synonymous substitution. This study suggests that the long-term course of chronic hepatitis C is determined early in infection and that disease severity is predicted by the evolutionary dynamics of hepatitis C virus and the level of MCP-1, a chemokine that appears critical to the induction of progressive fibrogenesis and, ultimately, the ominous complications of cirrhosis.

The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for malignant glioma

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

Tsao, May N.; Mehta, Minesh P.; Whelan, Timothy J.

2005-09-01

Purpose: To systematically review the evidence for the use of stereotactic radiosurgery or stereotactic fractionated radiation therapy in adult patients with malignant glioma. Methods: Key clinical questions to be addressed in this evidence-based review were identified. Outcomes considered were overall survival, quality of life or symptom control, brain tumor control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2) databases were searched using OVID. In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncologymore » (1997-2004), ASTRO (1997-2004), and the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the literature search were reviewed and tabulated. This process included an assessment of the level of evidence. Results: For patients with newly diagnosed malignant glioma, radiosurgery as boost therapy with conventional external beam radiation was examined in one randomized trial, five prospective cohort studies, and seven retrospective series. There is Level I evidence that the use of radiosurgery boost followed by external beam radiotherapy and carmustine (BCNU) does not confer benefit with respect to overall survival, quality of life, or patterns of failure as compared with external beam radiotherapy and BCNU. There is Level I-III evidence of toxicity associated with radiosurgery boost as compared with external beam radiotherapy alone. The results of the prospective and retrospective studies may be influenced by selection bias. Radiosurgery used as salvage for recurrent or progressive malignant glioma after conventional external beam radiotherapy failure was reported in zero randomized trials, three prospective cohort studies, and five retrospective series. The available data are sparse and insufficient to make absolute recommendations. Stereotactic fractionated radiation therapy has been reported as boost therapy with external beam radiotherapy for patients with newly diagnosed malignant glioma in only three prospective studies. As primary therapy alone without conventional external beam radiotherapy for newly diagnosed malignant glioma patients, stereotactic fractionated radiation therapy has been reported in only one prospective study. There were only three prospective series and two retrospective studies reported for patients with recurrent or progressive malignant glioma. Conclusions: For patients with malignant glioma, there is Level I-III evidence that the use of radiosurgery boost followed by external beam radiotherapy and BCNU does not confer benefit in terms of overall survival, local brain control, or quality of life as compared with external beam radiotherapy and BCNU. The use of radiosurgery boost is associated with increased toxicity. For patients with malignant glioma, there is insufficient evidence regarding the benefits/harms of using radiosurgery at the time progression or recurrence. There is also insufficient evidence regarding the benefits/harms in the use of stereotactic fractionated radiation therapy for patients with newly diagnosed or progressive/recurrent malignant glioma.« less

Diagnosis, treatment, and nursing care of patients with chronic leukemia.

PubMed

Breed, Cheryl D

2003-05-01

To provide an update on the impact of new information about the molecular biology of chronic leukemia and new treatment modalities available to patients. Published articles, books, and research studies. There has been significant progress in the diagnosis and management of chronic myeloid and chronic lymphocytic leukemia. New therapies provide more options for patients and longer treatment periods. With increasing treatment options and longer survival, patients with chronic myelogenous or chronic lymphocytic leukemia need increased education, support, and assistance with symptom management. Nurses caring for these patients must remain knowledgeable about new treatments and their management.

Understanding and treatment of chronic pancreatitis.

PubMed

Drewes, Asbjørn Mohr

2013-11-14

Chronic pancreatitis is characterized by an inflammatory process of the pancreas, which is replaced by fibrosis and progressive destruction. The three major clinical features of chronic pancreatitis are pain, maldigestion, and diabetes. Chronic pancreatitis has a profound impact on social life and employment patterns. In the current issue, different topics highlight experimental models of chronic pancreatitis and bridge findings from recent research to bedside. Although the disease is still difficult to treat the current papers represent useful guidelines on how to approach chronic pancreatitis in the clinical settings with the major aim to improve the patient's suffering and quality of life.

Molecular characterization of chronic-type adult T-cell leukemia/lymphoma.

PubMed

Yoshida, Noriaki; Karube, Kennosuke; Utsunomiya, Atae; Tsukasaki, Kunihiro; Imaizumi, Yoshitaka; Taira, Naoya; Uike, Naokuni; Umino, Akira; Arita, Kotaro; Suguro, Miyuki; Tsuzuki, Shinobu; Kinoshita, Tomohiro; Ohshima, Koichi; Seto, Masao

2014-11-01

Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type-1-induced neoplasm with four clinical subtypes: acute, lymphoma, chronic, and smoldering. Although the chronic type is regarded as indolent ATL, about half of the cases progress to acute-type ATL. The molecular pathogenesis of acute transformation in chronic-type ATL is only partially understood. In an effort to determine the molecular pathogeneses of ATL, and especially the molecular mechanism of acute transformation, oligo-array comparative genomic hybridization and comprehensive gene expression profiling were applied to 27 and 35 cases of chronic and acute type ATL, respectively. The genomic profile of the chronic type was nearly identical to that of acute-type ATL, although more genomic alterations characteristic of acute-type ATL were observed. Among the genomic alterations frequently observed in acute-type ATL, the loss of CDKN2A, which is involved in cell-cycle deregulation, was especially characteristic of acute-type ATL compared with chronic-type ATL. Furthermore, we found that genomic alteration of CD58, which is implicated in escape from the immunosurveillance mechanism, is more frequently observed in acute-type ATL than in the chronic-type. Interestingly, the chronic-type cases with cell-cycle deregulation and disruption of immunosurveillance mechanism were associated with earlier progression to acute-type ATL. These findings suggested that cell-cycle deregulation and the immune escape mechanism play important roles in acute transformation of the chronic type and indicated that these alterations are good predictive markers for chronic-type ATL. ©2014 American Association for Cancer Research.

Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes

PubMed Central

Naesens, Maarten; Khatri, Purvesh; Li, Li; Sigdel, Tara K.; Vitalone, Matthew J.; Chen, Rong; Butte, Atul J.; Salvatierra, Oscar; Sarwal, Minnie M.

2015-01-01

The degree of progressive chronic histological damage is associated with long-term renal allograft survival. In order to identify promising molecular targets for timely intervention, we examined renal allograft protocol and indication biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome microarray expression profiling. In data-driven analysis, we found a highly regulated pattern of adaptive and innate immune gene expression that correlated with established or ongoing histological chronic injury, and also with development of future chronic histological damage, even in histologically pristine kidneys. Hence, histologically unrecognized immunological injury at a molecular level sets the stage for the development of chronic tissue injury, while the same molecular response is accentuated during established and worsening chronic allograft damage. Irrespective of the hypothesized immune or nonimmune trigger for chronic allograft injury, a highly orchestrated regulation of innate and adaptive immune responses was found in the graft at the molecular level. This occurred months before histologic lesions appear, and quantitatively below the diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus, measurement of specific immune gene expression in protocol biopsies may be warranted to predict the development of subsequent chronic injury in histologically quiescent grafts and as a means to titrate immunosuppressive therapy. PMID:21881554

Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes.

PubMed

Naesens, Maarten; Khatri, Purvesh; Li, Li; Sigdel, Tara K; Vitalone, Matthew J; Chen, Rong; Butte, Atul J; Salvatierra, Oscar; Sarwal, Minnie M

2011-12-01

The degree of progressive chronic histological damage is associated with long-term renal allograft survival. In order to identify promising molecular targets for timely intervention, we examined renal allograft protocol and indication biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome microarray expression profiling. In data-driven analysis, we found a highly regulated pattern of adaptive and innate immune gene expression that correlated with established or ongoing histological chronic injury, and also with development of future chronic histological damage, even in histologically pristine kidneys. Hence, histologically unrecognized immunological injury at a molecular level sets the stage for the development of chronic tissue injury, while the same molecular response is accentuated during established and worsening chronic allograft damage. Irrespective of the hypothesized immune or nonimmune trigger for chronic allograft injury, a highly orchestrated regulation of innate and adaptive immune responses was found in the graft at the molecular level. This occurred months before histologic lesions appear, and quantitatively below the diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus, measurement of specific immune gene expression in protocol biopsies may be warranted to predict the development of subsequent chronic injury in histologically quiescent grafts and as a means to titrate immunosuppressive therapy.

Distraction for proximal interphalangeal joint contractures: long-term results.

PubMed

Houshian, Shirzad; Jing, Shan Shan; Kazemian, Gholam Hussein; Emami-Moghaddam-Tehrani, Mohammad

2013-10-01

To report the medium- to long-term outcomes of joint distraction using a unilateral external fixator in the treatment of chronic post-traumatic proximal interphalangaeal (PIP) joint contractures. Between September 2001 and October 2011, 94 consecutive patients (98 PIP joints) with a mean age of 43 years (range, 17-69 y) were treated with external fixation for chronic flexion deformity of the PIP joint from trauma. The average time from injury to surgery was 48 months (range, 6-84 mo), and the duration of joint distraction was 10 days (range, 7-22 d). Patients were followed for a mean period of 54 months (range, 12-72 mo). The average gain in joint flexion was 25° and in joint extension was 40°. The mean improvement in the active range of movement was 67° (range. 30°-90°). There was no loss of motion on the latest follow-up. Patients younger than 40 years fared slightly better than those older than 40 years. Two patients developed swelling, pain, and erythema during treatment, which resolved upon temporarily stopping the distraction process. There were 12 cases of superficial pin-site infections, which were managed conservatively without serious complications or adverse outcome. External fixation is a simple and effective treatment modality for chronic traumatic PIP joint contractures with good predictable medium- to long-term results. Careful patient selection and monitoring are required. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Rehabilitation of Executive Functions in Patients with Chronic Acquired Brain Injury with Goal Management Training, External Cuing, and Emotional Regulation: A Randomized Controlled Trial.

PubMed

Tornås, Sveinung; Løvstad, Marianne; Solbakk, Anne-Kristin; Evans, Jonathan; Endestad, Tor; Hol, Per Kristian; Schanke, Anne-Kristine; Stubberud, Jan

2016-04-01

Executive dysfunction is a common consequence of acquired brain injury (ABI), causing significant disability in daily life. This randomized controlled trial investigated the efficacy of Goal Management Training (GMT) in improving executive functioning in patients with chronic ABI. Seventy patients with a verified ABI and executive dysfunction were randomly allocated to GMT (n=33) or a psycho-educative active control condition, Brain Health Workshop (BHW) (n=37). In addition, all participants received external cueing by text messages. Neuropsychological tests and self-reported questionnaires of executive functioning were administered pre-intervention, immediately after intervention, and at 6 months follow-up. Assessors were blinded to group allocation. Questionnaire measures indicated significant improvement of everyday executive functioning in the GMT group, with effects lasting at least 6 months post-treatment. Both groups improved on the majority of the applied neuropsychological tests. However, improved performance on tests demanding executive attention was most prominent in the GMT group. The results indicate that GMT combined with external cueing is an effective metacognitive strategy training method, ameliorating executive dysfunction in daily life for patients with chronic ABI. The strongest effects were seen on self-report measures of executive functions 6 months post-treatment, suggesting that strategies learned in GMT were applied and consolidated in everyday life after the end of training. Furthermore, these findings show that executive dysfunction can be improved years after the ABI.

[Pathophysiology of hormonal, immune, metabolic changes in acute and chronic pancreatitis. Experimental and clinical studies].

PubMed

Trubitsyna, I E; Chikunova, B Z; Tkachenko, E V; Tsaregorodtseva, T M; Vinokurova, L V; Varvanina, G G

2008-01-01

There is literature review of the acute and chronic pancreatitis experimental models. Patogenetic necrosis mechanisms with fibrosis progress in pancreas were revealed. The stimulation of the proteolytic enzymes synthesis and secretion, that was examined in experiments were compared with clinical examinations. The patients with chronic pancreatitis were investigated in the Central Research Institute of Gastroenterology.

Chronic Diarrhea in Dogs: What Do We Actually Know About It?

PubMed

Westermarck, Elias

2016-06-01

There is a paucity of research based knowledge about chronic diarrhoea in dogs. In the literature no studies can be found that confirms that round worm, whip worm, hook worm or giardia cause chronic diarrhoea in dogs. For this reason, it is questionable to study endoparasites when clarifying the reason for chronic diarrhoea in dogs. No study confirms that clostridium-, campylobacter- or salmonella species cause chronic diarrhoea signs in dogs. There is no research-based information to-date that endoscopy would be helpful in the diagnosis of dogs with chronic diarrhoea or to monitor how the disease progresses. Neither no reliable laboratory test can be recommended to be used in evaluating the seriousness of the disease or to monitor the progress of the disease. There is no evidence based information on what food should be recommended for dogs suffering from diarrhoea. Only a few studies have been published that show how effective antibiotics are in the treatment of diarrhoeal dogs. Many more studies are needed before it is possible to determine how effective corticosteroids are in the treatment of diarrhoea in dogs. Copyright © 2016 Elsevier Inc. All rights reserved.

Animal models for investigating chronic pancreatitis

PubMed Central

2011-01-01

Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed. PMID:22133269

Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions

PubMed Central

Gillen, Kelly M.; Mubarak, Mayyan; Nguyen, Thanh D.; Pitt, David

2018-01-01

Microglia are resident immune cells that fulfill protective and homeostatic functions in the central nervous system (CNS) but may also promote neurotoxicity in the aged brain and in chronic disease. In multiple sclerosis (MS), an autoimmune demyelinating disease of the CNS, microglia and macrophages contribute to the development of white matter lesions through myelin phagocytosis, and possibly to disease progression through diffuse activation throughout myelinated white matter. In this review, we discuss an additional compartment of myeloid cell activation in MS, i.e., the rim and normal adjacent white matter of chronic active lesions. In chronic active lesions, microglia and macrophages may contain high amounts of iron, express markers of proinflammatory polarization, are activated for an extended period of time (years), and drive chronic tissue damage. Iron-positive myeloid cells can be visualized and quantified with quantitative susceptibility mapping (QSM), a magnetic resonance imaging technique. Thus, QSM has potential as an in vivo biomarker for chronic inflammatory activity in established white matter MS lesions. Reducing chronic inflammation associated with iron accumulation using existing or novel MS therapies may impact disease severity and progression. PMID:29515576

A Prospective Outcomes Study of Proton Therapy for Chordomas and Chondrosarcomas of the Spine

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

Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org; Rotondo, Ronny L.; Begosh-Mayne, Dustin

Purpose: To evaluate the effectiveness of definitive or adjuvant external beam proton therapy on survival in patients with chordomas and chondrosarcomas of the spine. Methods and Materials: Between March 2007 and May 2013, 51 patients with a median age of 58 years (range, 22-83 years) with chordoma (n=34) or chondrosarcomas (n=17) of the sacrum (n=21), the cervical spine (n=20), and the thoracolumbar spine (n=10) were treated with external beam proton therapy to a median dose of 70.2 Gy(RBE) [range, 64.2-75.6 Gy(RBE)] at our institution. Distant metastases, overall survival, cause-specific survival, local control, and disease-free survival were calculated. Results: The mean follow-up time was 3.7 yearsmore » (range, 0.3-7.7 years). Across all time points, 25 patients experienced disease recurrence: 18 local recurrences, 6 local and distant recurrences, and 1 distant metastasis. The 4-year rates of overall survival and cause-specific survival were 72%; disease-free survival was 57%, local control was 58%, and freedom from distant metastases was 86%. The median time to local progression was 1.7 years (range, 0.2-6.0 years), and the median time to distant progression was 1.6 years (range, 0.2-6.0 years). The risk factors for local recurrence were age ≤58 years (62% vs 26%; P=.04) and recurrence after prior surgery (29% vs 81%; P=.01). Secondary cancers developed in 2 patients: B-cell lymphoma 5.5 years after treatment and bladder cancer 2 years after treatment. We observed the following toxicities: sacral soft tissue necrosis requiring surgery (n=2), T1 vertebral fracture requiring fusion surgery (n=1), chronic urinary tract infections (n=1), surgery for necrotic bone cyst (n=1), and grade 2 bilateral radiation nephritis (n=1). Conclusion: High-dose proton therapy controls more than half of spinal chordomas and chondrosarcomas and compares favorably with historic photon data. Local progression is the dominant mode of treatment failure and may be reduced by treating patients at the time of initial diagnosis. The impact of age is a novel finding of this study.« less

Relief of mitral leaflet tethering following chronic myocardial infarction by chordal cutting diminishes left ventricular remodeling.

PubMed

Messas, Emmanuel; Bel, Alain; Szymanski, Catherine; Cohen, Iris; Touchot, Bernard; Handschumacher, Mark D; Desnos, Michel; Carpentier, Alain; Menasché, Philippe; Hagège, Albert A; Levine, Robert A

2010-11-01

one of the key targets in treating mitral regurgitation (MR) is reducing the otherwise progressive left ventricular (LV) remodeling that exacerbates MR and conveys adverse prognosis. We have previously demonstrated that severing 2 second-order chordae to the anterior mitral leaflet relieves tethering and ischemic MR acutely. The purpose of this study was to test whether this technique reduces the progression of LV remodeling in the chronic ischemic MR setting. a posterolateral MI was created in 18 sheep by obtuse marginal branch ligation. After chronic remodeling and MR development at 3 months, 6 sheep were randomized to sham surgery (control group) and 12 to second-order chordal cutting (6 each to anterior leaflet [AntL] and bileaflet [BiL] chordal cutting, techniques that are in clinical application). At baseline, chronic infarction (3 months), and follow-up at a mean of 6.6 months post-myocardial infarction (MI) (euthanasia), we measured LV end-diastolic (EDV) and end-systolic volume (ESV), ejection fraction, wall motion score index, and posterior leaflet (PL) restriction angle relative to the annulus by 2D and 3D echocardiography. All measurements were comparable among groups at baseline and chronic MI. At euthanasia, AntL and BiL chordal cutting limited the progressive remodeling seen in controls. LVESV increased relative to chronic MI by 109±8.7% in controls versus 30.5±6.1% with chordal cutting (P<0.01) (LVESV in controls, 82.5±2.6 mL; in AntL, 60.6±5.1 mL; in BiL, 61.8±4.1 mL). LVEDV increased by 63±2.0% in controls versus 26±5.5% and 22±3.4% with chordal cutting (P<0.01). LV ejection fraction and wall motion score index were not significantly different at follow-up among the chordal cutting and control groups. MR progressively increased to moderate in controls but decreased to trace-mild with AntL and BiL chordal cutting (MR vena contracta in controls, 5.9±1.1 mm; in AntL, 2.6±0.1 mm; in BiL, 1.7±0.1 mm; P<0.01). BiL chordal cutting provided greater PL mobility (decreased PL restriction angle to 54.2±5.0° versus 83±3.2° with AntL chordal cutting; P<0.01). reduced leaflet tethering by chordal cutting in the chronic post-MI setting substantially decreases the progression of LV remodeling with sustained reduction of MR over a chronic follow-up. These benefits have the potential to improve clinical outcomes.

Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

PubMed

Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

2017-02-01

Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

Chronic inflammation-associated genomic instability paves the way for human esophageal carcinogenesis

PubMed Central

Tian, Dongping; Lei, Zhijin; Chen, Donglin; Xu, Zexin; Su, Min

2016-01-01

Chronic inflammation is associated with increased risk of cancer development, whereas the link between chronic inflammation and esophageal carcinogenesis is still obscure heretofore. This study aimed to investigate the relationship between chronic inflammation and DNA damage, as well as the possible role of DNA damage in esophageal carcinogenic process. Endoscopic esophageal biopsies from 109 individuals from Chaoshan littoral, a high-risk region for esophageal squamous cell carcinoma (ESCC), were examined to evaluate the association between chronic inflammation and histological severity, while additional 204 esophageal non-tumor samples from patients with ESCC were collected. Immunohistochemistry was performed to detect the oxidative DNA damage and DNA double-strand breaks (DSBs). Significantly positive correlation was observed between degree of chronic inflammation and esophageal precursor lesions (rs = 0.37, P < 0.01). Immunohistochemical analysis showed that oxidative DNA damage level was positively correlated with the degree of chronic inflammation (rs = 0.21, P < 0.05). Moreover, the level of oxidative DNA damage positively correlated with histological severity (rs = 0.49, P < 0.01). We found that the extent of DSBs was progressively increased with inflammation degree (P < 0.01) and the progression of precancerous lesions (P < 0.001). Collectively, these findings provide evidence linking chronic inflammation-associated genomic instability with esophageal carcinogenesis and suggest possibilities for early detection and intervention of esophageal carcinogenesis. PMID:27028857

Role of Antioxidants and Natural Products in Inflammation

PubMed Central

Fard, Masoumeh Tangestani; Tan, Woan Sean; Gothai, Sivapragasam; Kumar, S. Suresh

2016-01-01

Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease. Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases. In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases. In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders. The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases. PMID:27803762

MR-1 blocks the megakaryocytic differentiation and transition of CML from chronic phase to blast crisis through MEK dephosphorylation

PubMed Central

Zhao, W; He, H; Ren, K; Li, B; Zhang, H; Lin, Y; Shao, R-g

2013-01-01

Chronic myelogenous leukemia (CML) evolves from a chronic phase characterized by the Philadelphia chromosome as the sole genetic abnormality and the accumulation of mature cells in peripheral blood into blast crisis, which is characterized by the rapid expansion of myeloid- or lymphoid-differentiation-arrested blast cells. Although ample studies have been conducted on the disease progress mechanisms, the underlying molecular mechanisms of the malignant phenotype transition are still unclear. In this study, we have shown that myofibrillogenesis regulator-1 (MR-1) was overexpressed in blast crisis patients and leukemic cells, but there was little trace expressed in healthy individuals and in most patients in CML chronic phase. MR-1 could inhibit the differentiation of myeloid cells into megakaryocytic lineages and accelerate cell proliferation. The molecular mechanism responsible for these effects was the interaction of MR-1 with MEK, which blocked the MEK/ERK signaling pathway by dephosphorylating MEK. Our results provide compelling and important evidence that MR-1 might act as a diagnostic marker and potential target of CML progression from chronic phase to blast crisis. PMID:23542180

IRIS Toxicological Review of Inorganic Arsenic (Cancer) ...

EPA Pesticide Factsheets

On February 19, 2010, the draft IRIS Toxicological Review of Inorganic Arsenic (Cancer) external review draft document and the charge to external peer reviewers were released for public review and comment. The draft document and the charge to external peer reviewers were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the Toxicological Review of Inorganic Arsenic and the charge to external peer reviewers are posted on this site. This draft IRIS health assessment addresses only cancer human health effects that may result from chronic exposure to this chemical. An assessment of noncancer health effects of inorganic arsenic will be released for external peer review and public comment at a later date.

Bone scanning in severe external otitis

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

Levin, W.J.; Shary, J.H. 3d.; Nichols, L.T.

1986-11-01

Technetium99 Methylene Diphosphate bone scanning has been considered an early valuable tool to diagnose necrotizing progressive malignant external otitis. However, to our knowledge, no formal studies have actually compared bone scans of otherwise young, healthy patients with severe external otitis to scans of patients with clinical presentation of malignant external otitis. Twelve patients with only severe external otitis were studied with Technetium99 Diphosphate and were compared to known cases of malignant otitis. All scans were evaluated by two neuroradiologists with no prior knowledge of the clinical status of the patients. Nine of the 12 patients had positive bone scans withmore » many scans resembling those reported with malignant external otitis. Interestingly, there was no consistent correlation between the severity of clinical presentation and the amount of Technetium uptake. These findings suggest that a positive bone scan alone should not be interpreted as indicative of malignant external otitis.« less

Macrophage Depletion Attenuates Extracellular Matrix Deposition and Ductular Reaction in a Mouse Model of Chronic Cholangiopathies

PubMed Central

Syn, Wing-Kin; Lagaisse, Kimberly; van Hul, Noemi; Heindryckx, Femke; Sowa, Jan-Peter; Peeters, Liesbeth; Van Vlierberghe, Hans; Leclercq, Isabelle A.; Canbay, Ali

2016-01-01

Chronic cholangiopathies, such as primary and secondary sclerosing cholangitis, are progressive disease entities, associated with periportal accumulation of inflammatory cells, encompassing monocytes and macrophages, peribiliary extracellular matrix (ECM) deposition and ductular reaction (DR). This study aimed to elucidate the relevance of macrophages in the progression of chronic cholangiopathies through macrophage depletion in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) mouse model. One group of mice received a single i.p. injection of Clodronate encapsulated liposomes (CLOLipo) at day 7 of a 14 day DDC treatment, while control animals were co-treated with PBSLipo instead. Mice were sacrificed after 7 or respectively 14 days of treatment for immunohistochemical assessment of macrophage recruitment (F4/80), ECM deposition (Sirius Red, Laminin) and DR (CK19). Macrophage depletion during a 14 day DDC treatment resulted in a significant inhibition of ECM deposition. Porto-lobular migration patterns of laminin-rich ECM and ductular structures were significantly attenuated and a progression of DR was effectively inhibited by macrophage depletion. CLOLipo co-treatment resulted in a confined DR to portal regions without amorphous cell clusters. This study suggests that therapeutic options selectively directed towards macrophages might represent a feasible treatment for chronic cholestatic liver diseases. PMID:27618307

[50 years of progress in pathophysiology, diagnosis and treatment of chronic pancreatitis].

PubMed

Lerch, M M; Mayerle, J

2013-04-01

The German Journal of Gastroenterology celebrates its fifties anniversary in 2013. Over half a century original studies, reviews and guidelines covering the topics of acute and chronic pancreatitis as well as pancreatic cancer have assumed a prominent role on its pages. Already in the first edition of the Journal Haemmerli and Hefti have summarized the Zurich experience with chronic pancreatitis and provided a detailed state-of-the-art review for the year 1963. 50 years later the current guidelines of the German Society of Digestive and Metabolic Diseases (DGVS) have been published in the same Journal and allow to summarize the scientific progress over this period. Back then chronic pancreatitis was regarded as a rare disorder (tenfold less common than e. g. acute pancreatitis or pancreatic cancer). This misconception had little to do with actual prevalence but with highly insensitive diagnostic tests, particularly in the area of diagnostic imaging. While pathogenetic factors for chronic pancreatitis, including a possible genetic disposition, were largely known in 1963, our understanding of their cellular mechanisms has very much improved. The greatest progress in diagnostic options was achieved by the introduction of novel imaging techniques such as ultrasound and endoscopic ultrasound, ERCP, CT and MRCP. In terms of therapy the notion that a blockage of pancreatitic secretion is an effective pharmacological option has been abandoned and endoscopic intervention and surgical treatment have been newly developed as alternatives. © Georg Thieme Verlag KG Stuttgart · New York.

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.

Chronic Trypanosoma cruzi infection potentiates adipose tissue macrophage polarization toward an anti-inflammatory M2 phenotype and contributes to diabetes progression in a diet-induced obesity model.

PubMed

Cabalén, María E; Cabral, María F; Sanmarco, Liliana M; Andrada, Marta C; Onofrio, Luisina I; Ponce, Nicolás E; Aoki, María P; Gea, Susana; Cano, Roxana C

2016-03-22

Chronic obesity and Chagas disease (caused by the protozoan Trypanosoma cruzi) represent serious public health concerns. The interrelation between parasite infection, adipose tissue, immune system and metabolism in an obesogenic context, has not been entirely explored. A novel diet-induced obesity model (DIO) was developed in C57BL/6 wild type mice to examine the effect of chronic infection (DIO+I) on metabolic parameters and on obesity-related disorders. Dyslipidemia, hyperleptinemia, and cardiac/hepatic steatosis were strongly developed in DIO mice. Strikingly, although these metabolic alterations were collectively improved by infection, plasmatic apoB100 levels remain significantly increased in DIO+I, suggesting the presence of pro-atherogenic small and dense LDL particles. Moreover, acute insulin resistance followed by chronic hyperglycemia with hypoinsulinemia was found, evidencing an infection-related-diabetes progression. These lipid and glucose metabolic changes seemed to be highly dependent on TLR4 expression since TLR4-/- mice were protected from obesity and its complications. Notably, chronic infection promoted a strong increase in MCP-1 producing macrophages with a M2 (F4/80+CD11c-CD206+) phenotype associated to oxidative stress in visceral adipose tissue of DIO+I mice. Importantly, infection reduced lipid content but intensified inflammatory infiltrates in target tissues. Thus, parasite persistence in an obesogenic environment and the resulting host immunometabolic dysregulation may contribute to diabetes/atherosclerosis progression.

Current and future disease progression of the chronic HCV population in the United States.

PubMed

Zalesak, Martin; Francis, Kevin; Gedeon, Alex; Gillis, John; Hvidsten, Kyle; Kidder, Phyllis; Li, Hong; Martyn, Derek; Orne, Leslie; Smith, Amanda; Kwong, Ann

2013-01-01

Chronic hepatitis C virus (HCV) infection can lead to advanced liver disease (AdvLD), including cirrhosis, decompensated cirrhosis, and liver cancer. The aim of this study was to determine recent historical rates of HCV patient progression to AdvLD and to project AdvLD prevalence through 2015. We first determined total 2008 US chronic HCV prevalence from the National Health and Nutrition Evaluation Surveys. Next, we examined disease progression and associated non-pharmacological costs of diagnosed chronic HCV-infected patients between 2007-2009 in the IMS LifeLink and CMS Medicare claims databases. A projection model was developed to estimate AdvLD population growth through 2015 in patients diagnosed and undiagnosed as of 2008, using the 2007-2009 progression rates to generate a "worst case" projection of the HCV-related AdvLD population (i.e., scenario where HCV treatment is the same in the forecasted period as it was before 2009). We found that the total diagnosed chronic HCV population grew from 983,000 to 1.19 million in 2007-2009, with patients born from 1945-1964 accounting for 75.0% of all patients, 83.7% of AdvLD patients, and 79.2% of costs in 2009, indicating that HCV is primarily a disease of the "baby boomer" population. Non-pharmacological costs grew from $7.22 billion to $8.63 billion, with the majority of growth derived from the 60,000 new patients that developed AdvLD in 2007-2009, 91.5% of whom were born between 1945 and 1964. The projection model estimated the total AdvLD population would grow from 195,000 in 2008 to 601,000 in 2015, with 73.5% of new AdvLD cases from patients undiagnosed as of 2008. AdvLD prevalence in patients diagnosed as of 2008 was projected to grow 6.5% annually to 303,000 patients in 2015. These findings suggest that strategies to diagnose and treat HCV-infected patients are urgently needed to increase the likelihood that progression is interrupted, particularly for patients born from 1945-1964.

Are radiosensitivity data derived from natural field conditions consistent with data from controlled exposures? A case study of Chernobyl wildlife chronically exposed to low dose rates.

PubMed

Garnier-Laplace, J; Geras'kin, S; Della-Vedova, C; Beaugelin-Seiller, K; Hinton, T G; Real, A; Oudalova, A

2013-07-01

The discrepancy between laboratory or controlled conditions ecotoxicity tests and field data on wildlife chronically exposed to ionising radiation is presented for the first time. We reviewed the available chronic radiotoxicity data acquired in contaminated fields and used a statistical methodology to support the comparison with knowledge on inter-species variation of sensitivity to controlled external γ irradiation. We focus on the Chernobyl Exclusion Zone and effects data on terrestrial wildlife reported in the literature corresponding to chronic dose rate exposure situations (from background ~100 nGy/h up to ~10 mGy/h). When needed, we reconstructed the dose rate to organisms and obtained consistent unbiased data sets necessary to establish the dose rate-effect relationship for a number of different species and endpoints. Then, we compared the range of variation of radiosensitivity of species from the Chernobyl-Exclusion Zone with the statistical distribution established for terrestrial species chronically exposed to purely gamma external irradiation (or chronic Species radioSensitivity Distribution - SSD). We found that the best estimate of the median value (HDR50) of the distribution established for field conditions at Chernobyl (about 100 μGy/h) was eight times lower than the one from controlled experiments (about 850 μGy/h), suggesting that organisms in their natural environmental were more sensitive to radiation. This first comparison highlights the lack of mechanistic understanding and the potential confusion coming from sampling strategies in the field. To confirm the apparent higher sensitive of wildlife in the Chernobyl Exclusion Zone, we call for more a robust strategy in field, with adequate design to deal with confounding factors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Publications of the Jet Propulsion Laboratory, 1981

NASA Technical Reports Server (NTRS)

1982-01-01

Over 500 externally distributed technical reports released during 1981 that resulted from scientific and engineering work performed, or managed by Jet Propulsion Laboratory are listed by primary author. Of the total number of entries, 311 are from the bimonthly Deep Space Network Progress Report, and its successor, the Telecommunications and Data Acquisition Progress Report.

Chronic stress accelerates pancreatic cancer growth and invasion: A critical role for beta-adrenergic signaling in the pancreatic microenvironment

PubMed Central

Kim-Fuchs, Corina; Le, Caroline P.; Pimentel, Matthew A.; Shackleford, David; Ferrari, Davide; Angst, Eliane; Hollande, Frédéric; Sloan, Erica K.

2014-01-01

Pancreatic cancer cells intimately interact with a complex microenvironment that influences pancreatic cancer progression. The pancreas is innervated by fibers of the sympathetic nervous system (SNS) and pancreatic cancer cells have receptors for SNS neurotransmitters which suggests that pancreatic cancer may be sensitive to neural signaling. In vitro and non-orthotopic in vivo studies showed that neural signaling modulates tumour cell behavior. However the effect of SNS signaling on tumor progression within the pancreatic microenvironment has not previously been investigated. To address this, we used in vivo optical imaging to non-invasively track growth and dissemination of primary pancreatic cancer using an orthotopic mouse model that replicates the complex interaction between pancreatic tumor cells and their microenvironment. Stress-induced neural activation increased primary tumor growth and tumor cell dissemination to normal adjacent pancreas. These effects were associated with increased expression of invasion genes by tumor cells and pancreatic stromal cells. Pharmacological activation of β-adrenergic signaling induced similar effects to chronic stress, and pharmacological β-blockade reversed the effects of chronic stress on pancreatic cancer progression. These findings indicate that neural β-adrenergic signaling regulates pancreatic cancer progression and suggest β-blockade as a novel strategy to complement existing therapies for pancreatic cancer. PMID:24650449

Meniscal Extrusion Progresses Shortly after the Medial Meniscus Posterior Root Tear.

PubMed

Furumatsu, Takayuki; Kodama, Yuya; Kamatsuki, Yusuke; Hino, Tomohito; Okazaki, Yoshiki; Ozaki, Toshifumi

2017-12-01

Medial meniscus posterior root tears (MMPRT) induce medial meniscus extrusion (MME). However, the time-dependent extent of MME in patients suffering from the MMPRT remains unclear. This study evaluated the extent of MME after painful popping events that occurred at the onset of the MMPRT. Thirty-five patients who had an episode of posteromedial painful popping were investigated. All the patients were diagnosed as having an MMPRT by magnetic resonance imaging (MRI) within 12 months after painful popping. Medial meniscus body width (MMBW), absolute MME, and relative MME (100×absolute MME/MMBW) were assessed among three groups divided according to the time after painful popping events: early period (〈1 month), subacute period (1-3 months), and chronic period (4-12 months). In the early period, absolute and relative MMEs were 3.0 mm and 32.7%, respectively. Absolute MME increased up to 4.2 mm and 5.8 mm during the subacute and chronic periods, respectively. Relative MME also progressed to 49.2% and 60.3% in the subacute and chronic periods, respectively. This study demonstrated that absolute and relative MMEs increased progressively within the short period after the onset of symptomatic MMPRT. Our results suggest that early diagnosis of an MMPRT may be important to prevent progression of MME following the MMPRT.

Targeted therapy of chronic liver diseases with the inhibitors of angiogenesis.

PubMed

Srivastava, Ankita; Shukla, Vanistha; Tiwari, Deepika; Gupta, Jaya; Kumar, Sunil; Kumar, Awanish

2018-05-30

Angiogenesis appears to be intrinsically associated with the progression of chronic liver diseases, which eventually leads to the development of cirrhosis and related complications, including hepatocellular carcinoma. Several studies have suggested that this association is relevant for chronic liver disease (CLD) progression, with angiogenesis. The fact that angiogenesis plays a pivotal role in CLDs gives rise to new opportunities for treating CLDs. Inhibitor of angiogenesis has proved effective for the treatment of patients suffering from CLD. However, it is limited in diagnosis. The last decade has witnessed a plethora of publications which elucidate the potential of angiogenesis inhibitors for the therapy of CLD. The close relationship between the progression of CLDs and angiogenesis emphasizes the need for anti-angiogenic therapy to block/slow down CLD progression. The present review summarizes all these discussions, the results of the related studies carried out to date and the future prospects in this field. We discuss liver angiogenesis in normal and pathophysiologic conditions with a focus on the role and future use of angiogenic factors as second-line treatment of CLD. This review compiles relevant findings and offers opinions that have emerged in last few years relating liver angiogenesis and its treatment using anti-angiogenic factors. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Malignant external otitis: CT evaluation

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

Curtin, H.D.; Wolfe, P.; May, M.

1982-11-01

Malignant external otitis is an aggressive infection caused by Pseudomonas aeruginosa that most often occurs in elderly diabetics. Malignant external otitis often spreads inferiorly from the external canal to involve the subtemporal area and progresses medially towards the petrous apex leading to multiple cranial nerve palsies. The computed tomographic (CT) findings in malignant external otitis include obliteration of the normal fat planes in the subtemporal area as well as patchy destruction of the bony cortex of the mastoid. The point of exit of the various cranial nerves can be identified on CT scans, and the extent of the inflammatory massmore » correlates well with the clinical findings. Four cases of malignant external otitis are presented. In each case CT provided a good demonstration of involvement of the soft tissues at the base of the skull.« less

Mortality among workers with chronic radiation sickness

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

Shilnikova, N.S.; Koshurnikova, N.A.; Bolotnikova, M.G.

1996-07-01

This study is based on a registry containing medical and dosimetric data of the employees who began working at different plants of the Mayak nuclear complex between 1948 and 1958 who developed chronic radiation sickness. Mayak is the first nuclear weapons plutonium production enterprise built in Russia and includes nuclear reactors, a radiochemical plant for plutonium separation, and a plutonium production enterprise built in Russia and includes nuclear reactors, a radiochemical plant for plutonium separation, and a plutonium production plant.Workers whose employment began between 1948 and 1958 exhibited a 6-28% incidence of chronic radiation sickness at the different facilities. Theremore » were no cases of chronic radiation sickness among those who began working after 1958. Data on doses of external whole-body gamma-irradiation and mortality in workers with chronic radiation sickness are presented. 6 refs., 5 tabs.« less

Curcumin, inflammation, and chronic diseases: how are they linked?

PubMed

He, Yan; Yue, Yuan; Zheng, Xi; Zhang, Kun; Chen, Shaohua; Du, Zhiyun

2015-05-20

It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.

Novel sila-amide derivatives of N-acetylcysteine protects platelets from oxidative stress-induced apoptosis.

PubMed

Paul, Manoj; Thushara, Ram M; Jagadish, Swamy; Zakai, Uzma I; West, Robert; Kemparaju, Kempaiah; Girish, Kesturu S

2017-02-01

Oxidative stress-induced platelet apoptosis is one among the many causes for the development and progression of many disorders like cardiovascular diseases, arthritis, Alzheimer's disease and many chronic inflammatory responses. Many studies have demonstrated the less optimal effect of N-acetyl cysteine (NAC) in oxidative stress-induced cellular damage. This could be due to its less lipophilicity which makes it difficult to enter the cellular membrane. Therefore in the present study, lipophilic sila-amide derivatives (6a and 6b) synthesized through the reaction of NAC with 3-Aminopropyltrimethylsilane and aminomethyltrimethylsilane were used to determine their protective property against oxidative stress-induced platelet apoptosis. At a concentration of 10 µM, compound 6a and 6b were able to significantly inhibit Rotenone/H 2 O 2 induced platelet apoptotic markers like reactive oxygen species, intracellular calcium level, mitochondrial membrane potential, cytochrome c release from mitochondrial to the cytosol, caspase-9 and -3 activity and phosphatidylserine externalization. Therefore, the compounds can be extrapolated as therapeutic agents to protect platelets from oxidative stress-induced platelet apoptosis and its associated complications.

Effectiveness of Ayurvedic Massage (Sahacharadi Taila) in Patients with Chronic Low Back Pain: A Randomized Controlled Trial.

PubMed

Kumar, Syal; Rampp, Thomas; Kessler, Christian; Jeitler, Michael; Dobos, Gustav J; Lüdtke, Rainer; Meier, Larissa; Michalsen, Andreas

2017-02-01

Ayurveda is one of the oldest comprehensive healthcare systems worldwide. Ayurvedic massage and physical therapy are frequently used to treat patients with chronic pain syndromes and disorders of the musculoskeletal system. This study aimed to evaluate the effectiveness of Ayurvedic massage in nonspecific chronic low back pain by means of a randomized clinical trial. Sixty-four patients (mean age, 54.8 years; 49 women and 15 men) with chronic low back pain who scored >40 mm on a 100-mm visual analogue scale (VAS) were randomly assigned to a 2-week massage group with 6 hours of Ayurvedic massage and external treatment (n = 32) or to a 2-week local thermal therapy group (n = 32). The study observation period was 4 weeks, consisting of a 2-week intervention phase followed by a 2-week follow-up phase. Primary outcome measure was the change of mean pain (VAS) from baseline to week 4. Secondary outcomes included pain-related bothersomeness, the Roland Disability Questionnaire, quality of life (Medical Outcomes Study 36-Item Short Form), the Hanover Functional Ability Questionnaire for measuring back pain-related disability, and psychological outcomes. Outcomes were assessed at baseline and after 2 and 4 weeks. Mean back pain (primary outcome) at week 2 was significantly reduced from 53.4 ± 18.5 to 21.6 ± 18.2 in the massage group and from 55.3 ± 12.9 to 41.8 ± 19.8 in the standard thermal therapy group (mean group difference, -18.7; 95% confidence interval, -28.7 to -8.7; p < 0.001). While beneficial effects on pain-related bothersomeness and psychological well-being were also apparent, the Ayurvedic intervention did not improve function or disability in the short-term observation period. Both programs were safe and well tolerated. Ayurvedic external treatment is effective for pain-relief in chronic low back pain in the short term. Further studies with longer observation periods are needed to evaluate the long-term effects of the Ayurvedic external treatment approach on function and disability.

Clinical applications of squamous cell carcinoma antigen-immunoglobulins M to monitor chronic hepatitis C

PubMed Central

Martini, Andrea; Gallotta, Andrea; Pontisso, Patrizia; Fassina, Giorgio

2015-01-01

Hepatitis C virus (HCV) is the main cause of chronic liver disease and cirrhosis in Western countries. Over time, the majority of cirrhotic patients develop hepatocellular carcinoma (HCC), one of the most common fatal cancers worldwide - fourth for incidence rate. A high public health priority need is the development of biomarkers to screen for liver disease progression and for early diagnosis of HCC development, particularly in the high risk population represented by HCV-positive patients with cirrhosis. Several studies have shown that serological determination of a novel biomarker, squamous cell carcinoma antigen-immunoglobulins M (SCCA-IgM), might be useful to identify patients with progressive liver disease. In the initial part of this review we summarize the main clinical studies that have investigated this new circulating biomarker on HCV-infected patients, providing evidence that in chronic hepatitis C SCCA-IgM may be used to monitor progression of liver disease, and also to assess the virological response to antiviral treatment. In the last part of this review we address other, not less important, clinical applications of this biomarker in hepatology. PMID:26689503

Meditation as a Therapeutic Intervention for Adults at Risk for Alzheimer’s Disease – Potential Benefits and Underlying Mechanisms

PubMed Central

Innes, Kim E.; Selfe, Terry Kit

2014-01-01

Alzheimer’s disease (AD) is a chronic, progressive, brain disorder that affects at least 5.3 million Americans at an estimated cost of $148 billion, figures that are expected to rise steeply in coming years. Despite decades of research, there is still no cure for AD, and effective therapies for preventing or slowing progression of cognitive decline in at-risk populations remain elusive. Although the etiology of AD remains uncertain, chronic stress, sleep deficits, and mood disturbance, conditions common in those with cognitive impairment, have been prospectively linked to the development and progression of both chronic illness and memory loss and are significant predictors of AD. Therapies such as meditation that specifically target these risk factors may thus hold promise for slowing and possibly preventing cognitive decline in those at risk. In this study, we briefly review the existing evidence regarding the potential utility of meditation as a therapeutic intervention for those with and at risk for AD, discuss possible mechanisms underlying the observed benefits of meditation, and outline directions for future research. PMID:24795656

ROLE OF THE RENAL MICROCIRCULATION IN PROGRESSION OF CHRONIC KIDNEY INJURY IN OBESITY

PubMed Central

Chade, Alejandro R.; Hall, John E.

2016-01-01

Background Obesity is largely responsible for the growing incidence and prevalence of diabetes, cardiovascular, and renal disease. Current strategies to prevent and treat obesity and its consequences have been insufficient to reverse the ongoing trends. Lifestyle modification or pharmacological therapies often produce modest weight loss which is not sustained and recurrence of obesity is frequently observed, leading to progression of target organ damage in many obese subjects. Therefore, research efforts have focused not only on the factors that regulate energy balance, but also on understanding mechanisms of target organ injury in obesity. Summary and Key message Microvascular disease plays a pivotal role in progressive kidney injury from different etiologies such as hypertension, diabetes, and atherosclerosis, which are all important consequences of chronic obesity. The microvascular networks are anatomical units that are closely adapted to specific functions of nutrition and removal of waste in every organ. Damage of the small vessels in several tissues and organs has been reported in obesity and may increase cardio-renal risk. However, the mechanisms by which obesity and its attendant cardiovascular and metabolic consequences interact to cause renal microvascular injury and chronic kidney disease are still unclear, although substantial progress has been made in recent years. This review addresses potential mechanisms and consequences of obesity-induced renal microvascular injury as well as current treatments that may provide protection of the renal microcirculation and slow progressive kidney injury in obesity. PMID:27771702

Chronic Disease and Perceived Developmental Progression in Adolescence.

ERIC Educational Resources Information Center

Seiffge-Krenke, Inge

1998-01-01

Examined whether chronic illness causes delays in adolescents' perceived developmental status, using annually-completed questionnaires from insulin-dependent and healthy adolescents. Found that, in first year of study, diabetic adolescents reported delays in physical maturity and an independent lifestyle compared with healthy peers. Overall…

Molecular genetics of chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia.

PubMed

Li, Bing; Gale, Robert Peter; Xiao, Zhijian

2014-12-12

According to the 2008 World Health Organization classification, chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia are rare diseases. The remarkable progress in our understanding of the molecular genetics of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms has made it clear that there are some specific genetic abnormalities in these 3 rare diseases. At the same time, there is considerable overlap among these disorders at the molecular level. The various combinations of genetic abnormalities indicate a multi-step pathogenesis, which likely contributes to the marked clinical heterogeneity of these disorders. This review focuses on the current knowledge and challenges related to the molecular pathogenesis of chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia and relationships between molecular findings, clinical features and prognosis.

Surgical and endoscopic treatment of pain in chronic pancreatitis: a multidisciplinary update.

PubMed

Issa, Y; van Santvoort, H C; van Goor, H; Cahen, D L; Bruno, M J; Boermeester, M A

2013-01-01

Chronic pancreatitis is an inflammatory disease of the pancreas with abdominal pain as the most prominent symptom. Adequate treatment of patients with chronic pancreatitis remains a major challenge, mainly because of the lack of evidence-based treatment protocols. The primary goal of treatment is to achieve long-term pain relief, control of the complications associated with the disease, and to restore the quality of life. Currently, a conservative step-up approach is often used for the treatment of pain; progression to severe and intractable pain is considered necessary before invasive treatment is considered. Recent studies, however, suggest that surgical intervention should not be considered only as last-resort treatment, since it can mitigate disease progression, achieve excellent pain control, and preserve pancreatic function. In this review, we present a state-of-the art overview of endoscopic and surgical treatment options for patients with painful chronic pancreatitis, and elaborate on the timing of surgery. Copyright © 2013 S. Karger AG, Basel.

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.

High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients

PubMed Central

2013-01-01

Background Metabolic acidosis leads to chronic kidney disease (CKD) progression. The guidelines recommend a lower limit of serum bicarbonate level, but no upper limit. For serum bicarbonate level to be clinically useful as a therapeutic target marker, it is necessary to investigate the target serum bicarbonate level within the normal range to prevent CKD progression. Methods One hundred and thirteen elderly CKD patients, whose serum bicarbonate level was controlled within the normal range, were enrolled in this retrospective cohort study in Ibaraki, Japan. Outcome was defined as a decrease of 25% or more in estimated glomerular filtration rate (eGFR) or starting dialysis. We used Cox proportional hazard models adjusted for patients’ characteristics to examine the association between serum bicarbonate level and the outcome. Results Female patients were 36.3%: average age (SD), 70.4 (6.6) years; eGFR, 25.7 (13.6) ml/min/1.73 m2; serum bicarbonate level, 27.4 (3.2) mEq/l. Patients with the lowest quartile of serum bicarbonate levels [23.4 (1.8) mEq/l] showed a high risk of CKD progression compared with patients with high serum bicarbonate levels [28.8 (2.3) mEq/l]: adjusted hazard ratio (HR), 3.511 (95% CI, 1.342-9.186). A 1 mEq/l increase in serum bicarbonate level was associated with a low risk of CKD progression: adjusted HR, 0.791 [95% confidence interval (CI), 0.684-0.914]. Conclusions In elderly CKD patients, our findings suggest that serum bicarbonate level is independently associated with CKD progression, and that a high serum bicarbonate level is associated with a low risk of CKD progression. A high target serum bicarbonate level within the normal range may be effective for preventing CKD progression. PMID:23298330

Circadian rhythms, time-restricted feeding, and healthy aging.

PubMed

Manoogian, Emily N C; Panda, Satchidananda

2017-10-01

Circadian rhythms optimize physiology and health by temporally coordinating cellular function, tissue function, and behavior. These endogenous rhythms dampen with age and thus compromise temporal coordination. Feeding-fasting patterns are an external cue that profoundly influence the robustness of daily biological rhythms. Erratic eating patterns can disrupt the temporal coordination of metabolism and physiology leading to chronic diseases that are also characteristic of aging. However, sustaining a robust feeding-fasting cycle, even without altering nutrition quality or quantity, can prevent or reverse these chronic diseases in experimental models. In humans, epidemiological studies have shown erratic eating patterns increase the risk of disease, whereas sustained feeding-fasting cycles, or prolonged overnight fasting, is correlated with protection from breast cancer. Therefore, optimizing the timing of external cues with defined eating patterns can sustain a robust circadian clock, which may prevent disease and improve prognosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Obesity and heart failure as a mediator of the cerebrorenal interaction.

PubMed

Jindal, Ankur; Whaley-Connell, Adam; Sowers, James R

2013-01-01

The obesity epidemic is contributing substantially to the burden of cardiovascular disease including heart disease and congestive heart failure, in the United States and the rest of the world. Overnutrition as a driver of obesity, promotes alterations in fatty acid, lipid, and glucose metabolism that influence myocardial function and progression of heart failure from diastolic to systolic failure. The association of progressive heart failure and progressive chronic kidney disease is well documented and often referred to as the cardiorenal syndrome, as well as a prognosticator for cerebrovascular disease (e.g. stroke). Whether the relationship between obesity, heart disease/failure and risk for chronic kidney disease and stroke is direct or a confluence of risk factors is poorly understood. Copyright © 2013 S. Karger AG, Basel.

Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia.

PubMed

Seymour, John F; Kipps, Thomas J; Eichhorst, Barbara; Hillmen, Peter; D'Rozario, James; Assouline, Sarit; Owen, Carolyn; Gerecitano, John; Robak, Tadeusz; De la Serna, Javier; Jaeger, Ulrich; Cartron, Guillaume; Montillo, Marco; Humerickhouse, Rod; Punnoose, Elizabeth A; Li, Yan; Boyer, Michelle; Humphrey, Kathryn; Mobasher, Mehrdad; Kater, Arnon P

2018-03-22

Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. In this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab for the first 6 months (venetoclax-rituximab group) or bendamustine plus rituximab for 6 months (bendamustine-rituximab group). The trial design did not include crossover to venetoclax plus rituximab for patients in the bendamustine-rituximab group in whom progression occurred. The primary end point was investigator-assessed progression-free survival. After a median follow-up period of 23.8 months, the rate of investigator-assessed progression-free survival was significantly higher in the venetoclax-rituximab group (32 events of progression or death in 194 patients) than in the bendamustine-rituximab group (114 events in 195 patients); the 2-year rates of progression-free survival were 84.9% and 36.3%, respectively (hazard ratio for progression or death, 0.17; 95% confidence interval [CI], 0.11 to 0.25; P<0.001 by the stratified log-rank test). The benefit was maintained across all clinical and biologic subgroups, including the subgroup of patients with chromosome 17p deletion; the 2-year rate of progression-free survival among patients with chromosome 17p deletion was 81.5% in the venetoclax-rituximab group versus 27.8% in the bendamustine-rituximab group (hazard ratio, 0.13; 95% CI, 0.05 to 0.29), and the 2-year rate among those without chromosome 17p deletion was 85.9% versus 41.0% (hazard ratio, 0.19; 95% CI, 0.12 to 0.32). The benefit of venetoclax plus rituximab over bendamustine plus rituximab was confirmed by an independent review committee assessment of progression-free survival and other secondary efficacy end points. The rate of grade 3 or 4 neutropenia was higher in the venetoclax-rituximab group than in the bendamustine-rituximab group, but the rates of grade 3 or 4 febrile neutropenia and infections or infestations were lower with venetoclax than with bendamustine. The rate of grade 3 or 4 tumor lysis syndrome in the venetoclax-rituximab group was 3.1% (6 of 194 patients). Among patients with relapsed or refractory chronic lymphocytic leukemia, venetoclax plus rituximab resulted in significantly higher rates of progression-free survival than bendamustine plus rituximab. (Funded by Genentech and AbbVie; ClinicalTrials.gov number, NCT02005471 .).

Long-term outcomes of external femoral derotation osteotomies in children with cerebral palsy.

PubMed

Õunpuu, Sylvia; Solomito, Matthew; Bell, Katharine; Pierz, Kristan

2017-07-01

External femoral derotation osteotomy (FDO) is an orthopaedic intervention to correct increased femoral anteversion and associated excessive internal hip rotation and internal foot progression during gait in children with cerebral palsy. The resulting functional issues may include clearance problems and hip abductor lever-arm dysfunction. The purpose of this study was to evaluate long-term gait outcomes of FDO. Twenty ambulatory patients (27 sides) with cerebral palsy who underwent pre-operative (P0) and a one year post-operative (P1) gait analysis as part of the standard of care had a second post-operative analysis (P2) approximately 11 years post-surgical intervention. Mean hip rotation in stance showed statistically significant decreases in internal rotation at P1 post-surgical intervention that were maintained long-term (mean hip rotation P0: 21±9, P1: 0±9 and P2: 6±12 degrees internal). Similar results were seen with mean foot progression (P0: 9±16 degrees internal, P1: 14±13 degrees external, P2: 13±16 degrees external). However, 2/27 sides (9%) showed a recurrence of internal hip rotation of >15° at the 11year follow-up. The reasons for this recurrence could include age, surgical location and ongoing disease process all of which need to be further examined. We conclude that FDO can show long-term kinematic and functional benefits when performed in the prepubescent child with cerebral palsy in comparison to the natural progression of of hip rotation in cerebral palsy. Copyright © 2017 Elsevier B.V. All rights reserved.

Natural history of hepatitis C.

PubMed

Westbrook, Rachel H; Dusheiko, Geoffrey

2014-11-01

There has long been evidence that hepatitis C can lead to persistent infection in a high proportion of infected individuals, and can progress to chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC). The transition from acute to chronic hepatitis C is usually sub-clinical. Accurate studies of the time course for clearance of acute hepatitis C are difficult to carry out because of the silent onset of the acute disease. The likelihood of spontaneous HCV resolution is associated with several genetic factors, including IL28B inheritance and the DQB1*0301 allele of the major histocompatibility complex class II. Most data suggest that resolution in the acute phase without progression to chronic disease is not accompanied by significant disease, but minor histological lesions have been observed in anti-HCV positive, HCV RNA negative individuals. The risk of reinfection remains a possibility after clearance of acute hepatitis C. High rates of sexually-transmitted infection are being reported in HIV positive men who have sex with men (MSM). Chronic infection with HCV is the leading cause of end-stage liver disease, hepatocellular carcinoma (HCC) and liver related death in the Western world. The natural history of the chronic disease remains incompletely defined. It is generally a slowly progressive disease characterized by persistent hepatic inflammation, leading to the development of cirrhosis in approximately 10-20% of patients over 20-30 years of HCV infection. However, the published data indicate varying progression rates to cirrhosis. Overall, once cirrhosis has developed there is a 1-5% annual risk of HCC and a 3-6% annual risk of hepatic decompensation. Following an episode of decompensation the risk of death in the following year is between 15% and 20%. The high number of chronically infected individuals, the burden of disease, and the absence of a vaccine indicates that treatment will form part of the disease control but the impact, effectiveness and outcomes of treatment in various groups remain uncertain. Several studies and meta-analysis have concluded that eradication of HCV with antiviral therapy reduces the risk of HCC in patients with chronic hepatitis C, independent of fibrosis stage, but the risk is not eliminated. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Predicting Disease Progression in Scleroderma with Skin and Blood Biomarkers

DTIC Science & Technology

2014-10-01

AWARD NUMBER: W81XWH-13-1-0452 TITLE: Predicting Disease Progression in Scleroderma with Skin...Annual 3. DATES COVERED 23Sep 2013 – 22 Sep 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Predicting Disease Progression in...Scleroderma (Systemic Sclerosis, SSc) is a chronic, incurable autoimmune disease associated with high morbidity and mortality primarily due to SSc-lung

Proactive and Early Aggressive Wound Management: A Shift in Strategy Developed by a Consensus Panel Examining the Current Science, Prevention, and Management of Acute and Chronic Wounds.

PubMed

Bohn, Gregory A; Schultz, Gregory S; Liden, Brock A; Desvigne, Michael N; Lullove, Eric J; Zilberman, Igor; Regan, Mary B; Ostler, Marta; Edwards, Karen; Arvanitis, Georgia M; Hartman, Jodi F

2017-11-01

Normal wound healing is accomplished through a series of well-coordinated, progressive events with overlapping phases. Chronic wounds are described as not progressing to healing or not being responsive to management in a timely manner. A consensus panel of multidisciplinary wound care professionals was assembled to (1) educate wound care practitioners by identifying key principles of the basic science of chronic wound pathophysiology, highlighting the impact of metalloproteinases and biofilms, as well as the role of the extracellular matrix; and (2) equip practitioners with a systematic strategy for the prevention and healing of acute injuries and chronic wounds based upon scientific evidence and the panel members' expertise. An algorithm is presented that represents a shift in strategy to proactive and early aggressive wound management. With proactive management, adjunct therapies are applied preemptively to acute injuries to reduce wound duration and risk of chronicity. For existing chronic wounds, early aggressive wound management is employed to break the pathophysiology cycle and drive wounds toward healing. Reducing bioburden through debridement and bioburden management and using collagen dressings to balance protease activity prior to the use of advanced modalities may enhance their effectiveness. This early aggressive wound management strategy is recommended for patients at high risk for chronic wound development at a minimum. In their own practices, the panel members apply this systematic strategy for all patients presenting with acute injuries or chronic wounds.

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia.

PubMed

Horga, Alejandro; Pitceathly, Robert D S; Blake, Julian C; Woodward, Catherine E; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E; Plant, Gordon T; Houlden, Henry; Sweeney, Mary G; Hanna, Michael G; Reilly, Mary M

2014-12-01

Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P<0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P=0.002; odds ratio 8.43, 95% confidence interval 2.24-31.76). Multinomial logistic regression analysis identified peripheral neuropathy, family history and hearing loss as significant predictors of the genotype, and the same three variables showed the highest performance in genotype classification in a decision tree analysis. Of these variables, peripheral neuropathy had the highest specificity (91%), negative predictive value (83%) and positive likelihood ratio (5.87) for the diagnosis of a nuclear DNA defect. These results indicate that peripheral neuropathy is a rare finding in patients with single mitochondrial DNA deletions but that it is highly predictive of an underlying nuclear DNA defect. This observation may facilitate the development of diagnostic algorithms. We suggest that nuclear gene testing may enable a more rapid diagnosis and avoid muscle biopsy in patients with progressive external ophthalmoplegia and peripheral neuropathy. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia

PubMed Central

Pitceathly, Robert D. S.; Blake, Julian C.; Woodward, Catherine E.; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E.; Plant, Gordon T.; Houlden, Henry; Sweeney, Mary G.; Hanna, Michael G.; Reilly, Mary M.

2014-01-01

Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P < 0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P = 0.002; odds ratio 8.43, 95% confidence interval 2.24–31.76). Multinomial logistic regression analysis identified peripheral neuropathy, family history and hearing loss as significant predictors of the genotype, and the same three variables showed the highest performance in genotype classification in a decision tree analysis. Of these variables, peripheral neuropathy had the highest specificity (91%), negative predictive value (83%) and positive likelihood ratio (5.87) for the diagnosis of a nuclear DNA defect. These results indicate that peripheral neuropathy is a rare finding in patients with single mitochondrial DNA deletions but that it is highly predictive of an underlying nuclear DNA defect. This observation may facilitate the development of diagnostic algorithms. We suggest that nuclear gene testing may enable a more rapid diagnosis and avoid muscle biopsy in patients with progressive external ophthalmoplegia and peripheral neuropathy. PMID:25281868

Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease

PubMed Central

Germi, Raphaëlle; Bernard, Corinne; Garcia-Montojo, Marta; Deluen, Cécile; Farinelli, Laurent; Faucard, Raphaël; Veas, Francisco; Stefas, Ilias; Fabriek, Babs O; Van-Horssen, Jack; Van-der-Valk, Paul; Gerdil, Claire; Mancuso, Roberta; Saresella, Marina; Clerici, Mario; Marcel, Sébastien; Creange, Alain; Cavaretta, Rosella; Caputo, Domenico; Arru, Giannina; Morand, Patrice; Lang, Alois B; Sotgiu, Stefano; Ruprecht, Klemens; Rieckmann, Peter; Villoslada, Pablo; Chofflon, Michel; Boucraut, Jose; Pelletier, Jean; Hartung, Hans-Peter

2012-01-01

Background: The envelope protein from multiple sclerosis (MS) associated retroviral element (MSRV), a member of the Human Endogenous Retroviral family ‘W’ (HERV-W), induces dysimmunity and inflammation. Objective: The objective of this study was to confirm and specify the association between HERV-W/MSRV envelope (Env) expression and MS. Methods: 103 MS, 199 healthy controls (HC) and controls with other neurological diseases (28), chronic infections (30) or autoimmunity (30) were analysed with an immunoassay detecting Env in serum. Env RNA or DNA copy numbers in peripheral blood mononuclear cells (PBMC) were determined by a quantitative polymerase chain reaction (PCR). Env was detected by immunohistology in the brains of patients with MS with three specific monoclonals. Results: Env antigen was detected in a serum of 73% of patients with MS with similar prevalence in all clinical forms, and not in chronic infection, systemic lupus, most other neurological diseases and healthy donors (p<0.01). Cases with chronic inflammatory demyelinating polyneuropathy (5/8) and rare HC (4/103) were positive. RNA expression in PBMC and DNA copy numbers were significantly elevated in patients with MS versus HC (p<0.001). In patients with MS, DNA copy numbers were significantly increased in chronic progressive MS (secondary progressive MS vs relapsing–remitting MS (RRMS) p<0.001; primary progressive MS vs RRMS –<0.02). Env protein was evidenced in macrophages within MS brain lesions with particular concentrations around vascular elements. Conclusion: The association between MS disease and the MSRV-type HERV-W element now appears quite strong, as evidenced ex-vivo from serum and PBMC with post-mortem confirmation in brain lesions. Chronic progressive MS, RRMS and clinically isolated syndrome show different ELISA (Enzyme-Linked Immunosorbent Assay) and/or PCR profiles suggestive of an increase with disease evolution, and amplicon sequencing confirms the association with particular HERV-W elements. PMID:22457345

Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease

PubMed Central

Appel, Lawrence J.; Wright, Jackson T.; Greene, Tom; Agodoa, Lawrence Y.; Astor, Brad C.; Bakris, George L.; Cleveland, William H.; Charleston, Jeanne; Contreras, Gabriel; Faulkner, Marquetta L.; Gabbai, Francis B.; Gassman, Jennifer J.; Hebert, Lee A.; Jamerson, Kenneth A.; Kopple, Joel D.; Kusek, John W.; Lash, James P.; Lea, Janice P.; Lewis, Julia B.; Lipkowitz, Michael S.; Massry, Shaul G.; Miller, Edgar R.; Norris, Keith; Phillips, Robert A.; Pogue, Velvie A.; Randall, Otelio S.; Rostand, Stephen G.; Smogorzewski, Miroslaw J.; Toto, Robert D.; Wang, Xuelei

2013-01-01

BACKGROUND In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. METHODS We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. RESULTS During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P = 0.27). However, the effects differed according to the baseline level of proteinuria (P = 0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P = 0.01). CONCLUSIONS In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.) PMID:20818902

Beta-adrenergic signaling promotes tumor angiogenesis and prostate cancer progression through HDAC2-mediated suppression of thrombospondin-1.

PubMed

Hulsurkar, M; Li, Z; Zhang, Y; Li, X; Zheng, D; Li, W

2017-03-01

Chronic behavioral stress and beta-adrenergic signaling have been shown to promote cancer progression, whose underlying mechanisms are largely unclear, especially the involvement of epigenetic regulation. Histone deacetylase-2 (HDAC2), an epigenetic regulator, is critical for stress-induced cardiac hypertrophy. It is unknown whether it is necessary for beta-adrenergic signaling-promoted cancer progression. Using xenograft models, we showed that chronic behavioral stress and beta-adrenergic signaling promote angiogenesis and prostate cancer progression. HDAC2 was induced by beta-adrenergic signaling in vitro and in mouse xenografts. We next uncovered that HDAC2 is a direct target of cAMP response element-binding protein (CREB) that is activated by beta-adrenergic signaling. Notably, HDAC2 is necessary for beta-adrenergic signaling to induce angiogenesis. We further demonstrated that, upon CREB activation, HDAC2 represses thrombospondin-1 (TSP1), a potent angiogenesis inhibitor, through epigenetic regulation. Together, these data establish a novel pathway that HDAC2 and TSP1 act downstream of CREB activation in beta-adrenergic signaling to promote cancer progression.

[Prevention of pressure ulcer (bedsore)].

PubMed

Sedmak, Dijana; Vrhovec, Marina; Huljev, Dubravko

2013-10-01

Although progress in many fields of science, medicine and technology is evident, we are still witnessing the appearance of bedsores and its consequences. However, in the last fifty years there has been considerable progress in the understanding of its causes, prevention and treatment. Prevention and treatment of pressure ulcers are complicated by the many misconceptions. However, with due knowledge of the process of healing of acute and chronic wounds and of the pathophysiological processes, in many cases chronic wounds, like pressure ulcers, can now be prevented and cured, and thus reduce the cost of treatment, as well as the mortality rate.

The role and challenges of the food industry in addressing chronic disease

PubMed Central

2010-01-01

Summary Increasingly, food companies play an important role in stemming the rising burden of nutrition-related chronic diseases. Concrete actions taken by these companies include global public commitments to address food reformulation, consumer information, responsible marketing, promotion of healthy lifestyles, and public-private partnerships. These actions are reviewed together with eleven specific PepsiCo goals and commitments that address products, the marketplace, and communities at large. Interim progress on these goals and commitments are discussed as well as constraints hampering faster progress. Further disease prevention depends on increasing implementation of private-public initiatives. PMID:20509876

Staphylococcus aureus Biofilms Decrease Osteoblast Viability, Inhibits Osteogenic Differentiation, and Increases Bone Resorption in vitro

DTIC Science & Technology

2013-06-01

severe and often debilitating disease characterized by inflammatory destruction of bone. Despite treatment, chronic infection often develops which is...biofilms may contribute to bone loss during chronic osteomyelitis simultaneously by: (1) reducing osteoblast viability and osteogenic potential thereby...accounting for more than half of all cases [1]. Despite treatment and surgical intervention up to 30% of osteomyelitis cases progress into a chronic

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma

PubMed Central

Nickerson, John M.; Gao, Feng-juan; Sun, Zhongmou; Chen, Xin-ya; Zhang, Shu-jie; Gao, Feng; Chen, Jun-yi; Luo, Yi; Wang, Yan; Sun, Xing-huai

2015-01-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. PMID:25478814

OpenMDAO Framework Status

NASA Technical Reports Server (NTRS)

Naiman, Cynthia Gutierrez

2010-01-01

Advancing and exploring the science of Multidisciplinary Analysis & Optimization (MDAO) capabilities are high-level goals in the Fundamental Aeronautics Program s Subsonic Fixed Wing (SFW) project. The OpenMDAO team has made significant progress toward completing the Alpha OpenMDAO deliverable due in September 2010. Included in the presentation are: details of progress on developing the OpenMDAO framework, example usage of OpenMDAO, technology transfer plans, near term plans, progress toward establishing partnerships with external parties, and discussion of additional potential collaborations.

The Risk Factors That Predict Chronic Hypertension After Delivery in Women With a History of Hypertensive Disorders of Pregnancy

PubMed Central

Hwang, Ji-won; Park, Sung-Ji; Oh, Soo-young; Chang, Sung-A.; Lee, Sang-Chol; Park, Seung Woo; Kim, Duk-Kyung

2015-01-01

Abstract Hypertensive disorders of pregnancy (HDP) is one of the most important lethal complications in pregnant mothers. It is also associated with the subsequent development of chronic hypertension. The objective of this study was to identify the clinical risk factors of postpartum chronic hypertension in women diagnosed with HDP. Six hundred patients as HDP, who diagnosed and followed-up at least 6 month after delivery, were included in the study. We divided the included subjects in 2 groups based on the development of postpartum chronic hypertension: presenting with the chronic hypertension, “case group” (n = 41) and without chronic hypertension, “control group” (n = 559). Clinical and demographic factors were evaluated. By multiple regression analysis, early onset hypertension with end-organ dysfunction, smoking, higher prepregnancy body mass index (BMI), and comorbidities, systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APLS), were associated with progression to chronic hypertension in the postpartum period. The value of area under the curves (AUC) for the 5 models, that generated to combine the significant factors, increased from 0.645 to 0.831, which indicated improved prediction of progression to the chronic hypertension. Additional multivariate analysis revealed significant specific risk factors. This retrospective single hospital-based study demonstrated that the clinical risk factors, that is early onset hypertension with end-organ dysfunction, smoking, and higher prepregnancy BMI, were significant independent predictors of chronic hypertension in women after delivery. Identification of risk factors allowed us to narrow the subject field for monitoring and managing high blood pressure in the postpartum period. PMID:26496291

Near-infrared spectroscopy for monitoring of tissue oxygenation of exercising skeletal muscle in a chronic compartment syndrome model

NASA Technical Reports Server (NTRS)

Breit, G. A.; Gross, J. H.; Watenpaugh, D. E.; Chance, B.; Hargens, A. R.

1997-01-01

Variations in the levels of muscle hemoglobin and of myoglobin oxygen saturation can be detected non-invasively with near-infrared spectroscopy. This technique could be applied to the diagnosis of chronic compartment syndrome, in which invasive testing has shown increased intramuscular pressure associated with ischemia and pain during exercise. We simulated chronic compartment syndrome in ten healthy subjects (seven men and three women) by applying external compression, through a wide inflatable cuff, to increase the intramuscular pressure in the anterior compartment of the leg. The tissue oxygenation of the tibialis anterior muscle was measured with near-infrared spectroscopy during gradual inflation of the cuff to a pressure of forty millimeters of mercury (5.33 kilopascals) during fourteen minutes of cyclic isokinetic dorsiflexion and plantar flexion of the ankle. The subjects exercised with and without external compression. The data on tissue oxygenation for each subject then were normalized to a scale of 100 per cent (the baseline value, or the value at rest) to 0 per cent (the physiological minimum, or the level of oxygenation achieved by exercise to exhaustion during arterial occlusion of the lower extremity). With external compression, tissue oxygenation declined at a rate of 1.4 +/- 0.3 per cent per minute (mean and standard error) during exercise. After an initial decrease at the onset, tissue oxygenation did not decline during exercise without compression. The recovery of tissue oxygenation after exercise was twice as slow with compression (2.5 +/- 0.6 minutes) than it was without the use of compression (1.3 +/- 0.2 minutes).

The spectrum of disease in chronic traumatic encephalopathy.

PubMed

McKee, Ann C; Stern, Robert A; Nowinski, Christopher J; Stein, Thor D; Alvarez, Victor E; Daneshvar, Daniel H; Lee, Hyo-Soon; Wojtowicz, Sydney M; Hall, Garth; Baugh, Christine M; Riley, David O; Kubilus, Caroline A; Cormier, Kerry A; Jacobs, Matthew A; Martin, Brett R; Abraham, Carmela R; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L; Budson, Andrew E; Goldstein, Lee E; Kowall, Neil W; Cantu, Robert C

2013-01-01

Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I-IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I-III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy was the sole diagnosis in 43 cases (63%); eight were also diagnosed with motor neuron disease (12%), seven with Alzheimer's disease (11%), 11 with Lewy body disease (16%) and four with frontotemporal lobar degeneration (6%). There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in chronic traumatic encephalopathy that occurs in conjunction with widespread axonal disruption and loss. The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein.

The spectrum of disease in chronic traumatic encephalopathy

PubMed Central

McKee, Ann C.; Stein, Thor D.; Nowinski, Christopher J.; Stern, Robert A.; Daneshvar, Daniel H.; Alvarez, Victor E.; Lee, Hyo-Soon; Hall, Garth; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Cormier, Kerry A.; Jacobs, Matthew A.; Martin, Brett R.; Abraham, Carmela R.; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.; Cantu, Robert C.

2013-01-01

Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I–IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I–III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy was the sole diagnosis in 43 cases (63%); eight were also diagnosed with motor neuron disease (12%), seven with Alzheimer’s disease (11%), 11 with Lewy body disease (16%) and four with frontotemporal lobar degeneration (6%). There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in chronic traumatic encephalopathy that occurs in conjunction with widespread axonal disruption and loss. The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein. PMID:23208308

Unfinished Agendas: New and Continuing Gender Challenges in Higher Education

ERIC Educational Resources Information Center

Glazer-Raymo, Judith, Ed.

2008-01-01

This revealing volume examines the current role and status of women in higher education--and suggests a direction for the future. Judith Glazer-Raymo and other distinguished scholars and administrators assess the progress of women in academe using three lenses: the feminist agenda as a work in progress, growing internal and external challenges to…

The Enhanced liver fibrosis score is associated with clinical outcomes and disease progression in patients with chronic liver disease.

PubMed

Irvine, Katharine M; Wockner, Leesa F; Shanker, Mihir; Fagan, Kevin J; Horsfall, Leigh U; Fletcher, Linda M; Ungerer, Jacobus P J; Pretorius, Carel J; Miller, Gregory C; Clouston, Andrew D; Lampe, Guy; Powell, Elizabeth E

2016-03-01

Current tools for risk stratification of chronic liver disease subjects are limited. We aimed to determine whether the serum-based ELF (Enhanced Liver Fibrosis) test predicted liver-related clinical outcomes, or progression to advanced liver disease, and to compare the performance of ELF to liver biopsy and non-invasive algorithms. Three hundred patients with ELF scores assayed at the time of liver biopsy were followed up (median 6.1 years) for liver-related clinical outcomes (n = 16) and clear evidence of progression to advanced fibrosis (n = 18), by review of medical records and clinical data. Fourteen of 73 (19.2%) patients with ELF score indicative of advanced fibrosis (≥9.8, the manufacturer's cut-off) had a liver-related clinical outcome, compared to only two of 227 (<1%) patients with ELF score <9.8. In contrast, the simple scores APRI and FIB-4 would only have predicted subsequent decompensation in six and four patients respectively. A unit increase in ELF score was associated with a 2.53-fold increased risk of a liver-related event (adjusted for age and stage of fibrosis). In patients without advanced fibrosis on biopsy at recruitment, 55% (10/18) with an ELF score ≥9.8 showed clear evidence of progression to advanced fibrosis (after an average 6 years), whereas only 3.5% of those with an ELF score <9.8 (8/207) progressed (average 14 years). In these subjects, a unit increase in ELF score was associated with a 4.34-fold increased risk of progression. The ELF score is a valuable tool for risk stratification of patients with chronic liver disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery.

PubMed

Mizuguchi, K Annette; Huang, Chuan-Chin; Shempp, Ian; Wang, Justin; Shekar, Prem; Frendl, Gyorgy

2018-06-01

The study objective was to identify patients who are likely to develop progressive kidney dysfunction (acute kidney disease) before their hospital discharge after cardiac surgery, allowing targeted monitoring of kidney function in this at-risk group with periodic serum creatinine measurements. Risks of progression to acute kidney disease (a state in between acute kidney injury and chronic kidney disease) were modeled from acute kidney injury stages (Kidney Disease: Improving Global Outcomes) in patients undergoing cardiac surgery. A modified Poisson regression with robust error variance was used to evaluate the association between acute kidney injury stages and the development of acute kidney disease (defined as doubling of creatinine 2-4 weeks after surgery) in this observational study. Acute kidney disease occurred in 4.4% of patients with no preexisting kidney disease and 4.8% of patients with preexisting chronic kidney disease. Acute kidney injury predicted development of acute kidney disease in a graded manner in which higher stages of acute kidney injury predicted higher relative risk of progressive kidney disease (area under the receiver operator characteristic curve = 0.82). This correlation persisted regardless of baseline kidney function (P < .001). Of note, development of acute kidney disease was associated with higher mortality and need for renal replacement therapy. The degree of acute kidney injury can identify patients who will have a higher risk of progression to acute kidney disease. These patients may benefit from close follow-up of renal function because they are at risk of progressing to chronic kidney disease or end-stage renal disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

The effects of AST-120 on chronic kidney disease progression in the United States of America: a post hoc subgroup analysis of randomized controlled trials.

PubMed

Schulman, Gerald; Berl, Tomas; Beck, Gerald J; Remuzzi, Giuseppe; Ritz, Eberhard; Shimizu, Miho; Shobu, Yuko; Kikuchi, Mami

2016-09-30

The orally administered spherical carbon adsorbent AST-120 is used on-label in Asian countries to slow renal disease progression in patients with progressive chronic kidney disease (CKD). Recently, two multinational, randomized, double-blind, placebo-controlled, phase 3 trials (Evaluating Prevention of Progression in Chronic Kidney Disease [EPPIC] trials) examined AST-120's efficacy in slowing CKD progression. This study assessed the efficacy of AST-120 in the subgroup of patients from the United States of America (USA) in the EPPIC trials. In the EPPIC trials, 2035 patients with moderate to severe CKD were studied, of which 583 were from the USA. The patients were randomly assigned to two groups of equal size that were treated with AST-120 or placebo (9 g/day). The primary end point was a composite of dialysis initiation, kidney transplantation, or serum creatinine doubling. The Kaplan-Meier curve for the time to achieve the primary end point in the placebo-treated patients from the USA was similar to that projected before the study. The per protocol subgroup analysis of the population from the USA which included patients with compliance rates of ≥67 % revealed a significant difference between the treatment groups in the time to achieve the primary end point (Hazard Ratio, 0.74; 95 % Confidence Interval, 0.56-0.97). This post hoc subgroup analysis of EPPIC study data suggests that treatment with AST-120 might delay the time to primary end point in CKD patients from the USA. A further randomized controlled trial in progressive CKD patients in the USA is necessary to confirm the beneficial effect of adding AST-120 to standard therapy regimens. ClinicalTrials.gov NCT00500682 ; NCT00501046 .

C3 glomerulonephritis and dense deposit disease share a similar disease course in a large United States cohort of patients with C3 glomerulopathy.

PubMed

Bomback, Andrew S; Santoriello, Dominick; Avasare, Rupali S; Regunathan-Shenk, Renu; Canetta, Pietro A; Ahn, Wooin; Radhakrishnan, Jai; Marasa, Maddalena; Rosenstiel, Paul E; Herlitz, Leal C; Markowitz, Glen S; D'Agati, Vivette D; Appel, Gerald B

2018-04-01

C3 glomerulonephritis (C3GN) and dense deposit disease comprise the two classes of C3 glomerulopathy. Studies from Europe and Asia have aided our understanding of this recently defined disorder, but whether these data apply to a diverse United States patient population remains unclear. We, therefore, reviewed clinical and histopathological data, including generation of a C3 Glomerulopathy Histologic Index to score biopsy activity and chronicity, to determine predictors of progression to end-stage renal disease (ESRD) and advanced chronic kidney disease (CKD) in 111 patients (approximately 35% non-white) with C3 glomerulopathy: 87 with C3GN and 24 with dense deposit disease. Complement-associated gene variants and autoantibodies were detected in 24% and 35% of screened patients, respectively. Our C3 Glomerulopathy Histologic Index denoted higher activity in patients with C3GN and higher chronicity in patients with dense deposit disease. Over an average of 72 months of follow-up, remission occurred in 38% of patients with C3GN and 25% of patients with dense deposit disease. Progression to late-stage CKD and ESRD was common, with no differences between C3GN (39%) and dense deposit disease (42%). In multivariable models, the strongest predictors for progression were estimated glomerular filtration rate at diagnosis (clinical variables model) and tubular atrophy/interstitial fibrosis (histopathology variables model). Using our C3 Glomerulopathy Histologic Index, both total activity and total chronicity scores emerged as the strongest predictors of progression. Thus, in a large, diverse American cohort of patients with C3 glomerulopathy, there is a high rate of progression to CKD and ESRD with no differences between C3GN and dense deposit disease. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

IRIS Toxicological Review of Dichloromethane (Methylene ...

EPA Pesticide Factsheets

On March 31, 2010, the draft IRIS Toxicological Review of Dichloromethane (Methylene Chloride) external review draft document and the charge to external peer reviewers were released for public review and comment. The draft document and the charge to external peer reviewers were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the Toxicological Review of Dichloromethane (Methylene Chloride) and the charge to external peer reviewers are posted on this site. The draft Toxicological Review of Dichloromethane provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to dichloromethane.

Physiological work performance in chronic low back disability: effects of a progressive activity program.

PubMed

Thomas, L K; Hislop, H J; Waters, R L

1980-04-01

Fifteen patients were tested before and after treatment in a multifaceted inpatient program for chronic low back pain to determine if a gradually progressive activity program affected gait performance and physiological capacity. Before treatment, all patients demonstrated decreased physiological conditioning by higher-than-expected values for oxygen consumption and heart rate and by lower-than-normal gait velocity, stride length, and cadence. After treatment, an increase in mean walking velocity of 19 meters/minute reflected parallel gains in cadence and stride length. Improved mechanical performance resulted in improved "energetics." Energy spent per unit of distance walked decreased by 18 percent after treatment, providing a useful measure of increased physiological efficiency. Results indicated that patients with chronic low back disability can derive significant conditioning effects from an exercise program based on general function.

[CHRONIC RENAL FAILURE AND PREGNANCY--A CASE REPORT].

PubMed

Amaliev, G M; Uchikova, E; Malinova, M

2015-01-01

Pregnancy in women with chronic renal failure is a complex therapeutic problem requiring a multidisciplinary approach. It is associated with a higher risk of many perinatal complications. The most common abnormalities are related to: progression of renal failure, development of preeclampsia development of nephrotic syndrome, anemic syndrome, IUGR and fetal death. The prognosis depends on the values of serum creatinine prior to pregnancy, the degree of deterioration of renal function, development of additional obstetric complications and the specific etiological reasons that have led to the occurrence of renal failure. Determining the optimum time for authorization birth depends on the condition of the mother, the condition of the fetus and the rate of progression of renal failure, and the deadline the pregnancy should be terminated is 35 weeks. We present a case of a patient with chronic renal failure, with favorable perinatal outcome.

[Elucidating the molecular mechanism of prostate cancer progression under chronic hypoxia and development of the novel therapeutic approach].

PubMed

Nomura, Takeo; Yamasaki, Mutsushi; Mimata, Hiromitsu

2014-12-01

Cancer cells encounter a hypoxic microenvironment during tumor growth and progression. In addition, androgen-deprivation therapy against prostate cancer can develop secondary to a hypoxic condition caused by drastic blood supply reduction because androgen drives angiogenic inducers including vascular endothelial growth factor (VEGF) and inhibits angiogenesis inhibitor prostatic pigment epithelium-derived factor (PEDF). Extreme hypoxic conditions are not suitable for cancer survival, however, cancer cells soon adapt to a hypoxic environment and survive. We established a prostate cancer cell line cultured under chronic hypoxia and analyzed a castration-resistant phenotype. Here, the Vav3 was identified as a key oncogenic molecule associated with castration-resistance under chronic hypoxia. We analyzed the functions of Vav3 and Vav3-mediated signaling to establish a novel therapeutic target for castration-resistant prostate cancer.

An Adaptive Security Construct: Insurgency in Sudan

DTIC Science & Technology

2007-12-01

and “External Actors” existing as both foundational and supporting relatives. The “ Legs ” between cornerpoints, in addition to defining the tactical...directly. In a simplified mirror-image, the same progression of legs underlies each side’s connection with international or non-governmental external...Technologies ( DTI ), March 21, 2007). 45 Ghazal, Lakes, and Warab), and Upper Nile (Junqali, Wahdah, and Upper Nile).94 Allegations of corruption persist

Photographic guide of selected external defect indicators and associated internal defects in yellow birch

Treesearch

Everette D. Rast; John A. Beaton; David L. Sonderman

1991-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for yellow birch. Eleven types of external...

Photographic guide of selected external defect indicators and associated internal defects in sugar maple

Treesearch

Everette D. Rast; John A. Beaton; David L. Sonderman

1991-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for sugar maple. Eleven types of external...

Photographic guide of selected external defect indicators and associated internal defects in yellow-poplar

Treesearch

Everette D. Rast; John A. Beaton; David L. Sonderman

1991-01-01

To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for yellow-poplar. Twelve types of external...

The Variable Polarity Plasma Arc Welding Process: Its Application to the Space Shuttle External Tank

NASA Technical Reports Server (NTRS)

Nunes, A. C., Jr.; Bayless, E. O., Jr.; Wilson, W. A.

1984-01-01

This report describes progress in the implementation of the Variable Polarity Plasma Arc Welding (VPPAW) process at the External Tank (ET) assembly facility. Design allowable data has been developed for thicknesses up to 1.00 in. More than 24,000 in. of welding on liquid oxygen and liquid hydrogen cylinders has been made without an internal defect.

An overview of a cohort of South African patients with mitochondrial disorders.

PubMed

Smuts, Izelle; Louw, Roan; du Toit, Hanli; Klopper, Brenda; Mienie, Lodewyk J; van der Westhuizen, Francois H

2010-12-01

Mitochondrial disorders are frequently encountered inherited diseases characterized by unexplained multisystem involvement with a chronic, intermittent, or progressive nature. The objective of this paper is to describe the profile of patients with mitochondrial disorders in South Africa. Patients with possible mitochondrial disorders were accessed over 10 years. Analyses for respiratory chain and pyruvate dehydrogenase complex enzymes were performed on muscle. A diagnosis of a mitochondrial disorder was accepted only if an enzyme activity was deficient. Sixty-three patients were diagnosed with a mitochondrial disorder, including 40 African, 20 Caucasian, one mixed ancestry, and two Indian patients. The most important findings were the difference between African patients and other ethnicities: respiratory chain enzyme complexes CI+III or CII+III deficiencies were found in 52.5% of African patients, being of statistical significance (p value = 0.0061). They also presented predominantly with myopathy (p value = 0.0018); the male:female ratio was 1:1.2. Twenty-five (62.5%) African patients presented with varying degrees of a myopathy accompanied by a myopathic face, high palate, and scoliosis. Fourteen of these 25 also had ptosis and/or progressive external ophthalmoplegia. No patients of other ethnicities presented with this specific myopathic phenotype. Caucasian patients (16/20) presented predominantly with central nervous system involvement. Of the South African pediatric neurology patients, Africans are more likely to present with myopathy and CII+III deficiency, and Caucasian patients are more likely to present with encephalopathy or encephalomyopathy.

Hemoglobin induced lung vascular oxidation, inflammation, and remodeling contributes to the progression of hypoxic pulmonary hypertension and is attenuated in rats with repeat dose haptoglobin administration

PubMed Central

Baek, Jin Hyen; Hassell, Kathryn; Nuss, Rachelle; Eigenberger, Paul; Lisk, Christina; Loomis, Zoe; Maltzahn, Joanne; Stenmark, Kurt R; Nozik-Grayck, Eva

2015-01-01

Objective Haptoglobin (Hp) is an approved treatment in Japan with indications for trauma, burns and massive transfusion related hemolysis. Additional case reports suggest uses in other acute hemolytic events that lead to acute kidney injury. However, Hp's protective effects on the pulmonary vasculature have not been evaluated within the context of mitigating the consequences of chronic hemoglobin (Hb) exposure in the progression of pulmonary hypertension (PH) secondary to hemolytic diseases. This study was performed to assess the utility of chronic Hp therapy in a preclinical model of Hb and hypoxia mediated PH. Approach and results Rats were simultaneously exposed to chronic Hb-infusion (35 mg per day) and hypobaric hypoxia for five weeks in the presence or absence of Hp treatment (90 mg/kg twice a week). Hp inhibited the Hb plus hypoxia-mediated non-heme iron accumulation in lung and heart tissue, pulmonary vascular inflammation and resistance, and right ventricular hypertrophy, which suggest a positive impact on impeding the progression of PH. In addition, Hp therapy was associated with a reduction in critical mediators of PH, including lung adventitial macrophage population and endothelial ICAM-1 expression. Conclusions By preventing Hb-mediated pathology, Hp infusions: (1) demonstrate a critical role for Hb in vascular remodeling associated with hypoxia; and (2) suggest a novel therapy for chronic hemolysis associated PH. PMID:25656991

Hemoglobin-induced lung vascular oxidation, inflammation, and remodeling contribute to the progression of hypoxic pulmonary hypertension and is attenuated in rats with repeated-dose haptoglobin administration.

PubMed

Irwin, David C; Baek, Jin Hyen; Hassell, Kathryn; Nuss, Rachelle; Eigenberger, Paul; Lisk, Christina; Loomis, Zoe; Maltzahn, Joanne; Stenmark, Kurt R; Nozik-Grayck, Eva; Buehler, Paul W

2015-05-01

Haptoglobin (Hp) is an approved treatment in Japan for trauma, burns, and massive transfusion-related hemolysis. Additional case reports suggest uses in other acute hemolytic events that lead to acute kidney injury. However, Hp's protective effects on the pulmonary vasculature have not been evaluated within the context of mitigating the consequences of chronic hemoglobin (Hb) exposure in the progression of pulmonary hypertension (PH) secondary to hemolytic diseases. This study was performed to assess the utility of chronic Hp therapy in a preclinical model of Hb and hypoxia-mediated PH. Rats were simultaneously exposed to chronic Hb infusion (35 mg per day) and hypobaric hypoxia for 5 weeks in the presence or absence of Hp treatment (90 mg/kg twice a week). Hp inhibited the Hb plus hypoxia-mediated nonheme iron accumulation in lung and heart tissue, pulmonary vascular inflammation and resistance, and right-ventricular hypertrophy, which suggests a positive impact on impeding the progression of PH. In addition, Hp therapy was associated with a reduction in critical mediators of PH, including lung adventitial macrophage population and endothelial ICAM-1 expression. By preventing Hb-mediated pathology, Hp infusions: (1) demonstrate a critical role for Hb in vascular remodeling associated with hypoxia and (2) suggest a novel therapy for chronic hemolysis-associated PH. Copyright © 2015 Elsevier Inc. All rights reserved.

Chinese herbal medicine Shenqi Detoxification Granule inhibits fibrosis in adenine induced chronic renal failure rats.

PubMed

Peng, Min; Cai, Pingping; Ma, Hongbo; Meng, Hongyan; Xu, Yuan; Zhang, Xiaoyi; Si, Guomin

2014-01-01

Progressive fibrosis accompanies all chronic renal disease, connective tissue growth factor (CTGF,) and platelet-derived growth factor-B, (PDGF-B,) play important roles in extra-cellular matrix abnormal accumulation, while endothelin-1 (ET-1) nitric oxide (NO,) are related to endothelial dysfunction, which mediates the progression of renal fibrosis. Shenqi Detoxification Granule (SDG), a traditional Chinese herbal formula, has been used for treatment of chronic renal failure in clinic for many years. In order to evaluate the efficacy, and explore the mechanism of SDG to inhibit the progression of renal fibrosis, study was carried out using the adenine-induced Wister rats as the CRF model, and losartan as postive control drug. Levels of serum creatinine [Scr], and blood urea nitrogen (BUN), albumin (ALB), 24hrs, urine protein (24hUP), triacylglycerol (TG), and cholesterol (CHO), together with ET-1, and NO were detected. Pathological changes of renal tissues were observed by HE, staining. In addition, CTGF and PDGF-B expression were analyzed by immuno-histo-chemistry. The results indicated that SDG can effectively reduce Scr, BUN, 24hUP, TG, and CHO levels, increase ALB levels, inhibit renal tissue damage in CRF rats, and the mechanism maybe reduce PDGF-B, CTGF expression and ET-1/NO. Shenqi Detoxification Granule is a beneficial treatment for chronic renal failure.

Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis.

PubMed

Humphreys, Benjamin D; Xu, Fengfeng; Sabbisetti, Venkata; Grgic, Ivica; Movahedi Naini, Said; Wang, Ningning; Chen, Guochun; Xiao, Sheng; Patel, Dhruti; Henderson, Joel M; Ichimura, Takaharu; Mou, Shan; Soeung, Savuth; McMahon, Andrew P; Kuchroo, Vijay K; Bonventre, Joseph V

2013-09-01

Acute kidney injury predisposes patients to the development of both chronic kidney disease and end-stage renal failure, but the molecular details underlying this important clinical association remain obscure. We report that kidney injury molecule-1 (KIM-1), an epithelial phosphatidylserine receptor expressed transiently after acute injury and chronically in fibrotic renal disease, promotes kidney fibrosis. Conditional expression of KIM-1 in renal epithelial cells (Kim1(RECtg)) in the absence of an injury stimulus resulted in focal epithelial vacuolization at birth, but otherwise normal tubule histology and kidney function. By 4 weeks of age, Kim1(RECtg) mice developed spontaneous and progressive interstitial kidney inflammation with fibrosis, leading to renal failure with anemia, proteinuria, hyperphosphatemia, hypertension, cardiac hypertrophy, and death, analogous to progressive kidney disease in humans. Kim1(RECtg) kidneys had elevated expression of proinflammatory monocyte chemotactic protein-1 (MCP-1) at early time points. Heterologous expression of KIM-1 in an immortalized proximal tubule cell line triggered MCP-1 secretion and increased MCP-1-dependent macrophage chemotaxis. In mice expressing a mutant, truncated KIM-1 polypeptide, experimental kidney fibrosis was ameliorated with reduced levels of MCP-1, consistent with a profibrotic role for native KIM-1. Thus, sustained KIM-1 expression promotes kidney fibrosis and provides a link between acute and recurrent injury with progressive chronic kidney disease.

DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.

PubMed

Larkin, Benjamin P; Glastras, Sarah J; Chen, Hui; Pollock, Carol A; Saad, Sonia

2018-04-24

Chronic kidney disease (CKD) is a global epidemic, and its major risk factors include obesity and type 2 diabetes. Obesity not only promotes metabolic dysregulation and the development of diabetic kidney disease but also may independently lead to CKD by a variety of mechanisms, including endocrine and metabolic dysfunction, inflammation, oxidative stress, altered renal hemodynamics, and lipotoxicity. Deleterious renal effects of obesity can also be transmitted from one generation to the next, and it is increasingly recognized that offspring of obese mothers are predisposed to CKD. Epigenetic modifications are changes that regulate gene expression without altering the DNA sequence. Of these, DNA methylation is the most studied. Epigenetic imprints, particularly DNA methylation, are laid down during critical periods of fetal development, and they may provide a mechanism by which maternal-fetal transmission of chronic disease occurs. Our current review explores the evidence for the role of DNA methylation in the development of CKD, diabetic kidney disease, diabetes, and obesity. DNA methylation has been implicated in renal fibrosis-the final pathophysiologic pathway in the development of end-stage kidney disease-which supports the notion that demethylating agents may play a potential therapeutic role in preventing development and progression of CKD.-Larkin, B. P., Glastras, S. J., Chen, H., Pollock, C. A., Saad, S. DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.

Chronic Inflammation-Related HPV: A Driving Force Speeds Oropharyngeal Carcinogenesis

PubMed Central

Liu, Xin; Ma, Xiangrui; Lei, Zhengge; Feng, Hao; Wang, Shasha; Cen, Xiao; Gao, Shiyu; Jiang, Yaping; Jiang, Jian; Chen, Qianming; Tang, Yajie; Tang, Yaling; Liang, Xinhua

2015-01-01

Oropharyngeal squamous cell carcinoma (OPSCC) has been known to be a highly aggressive disease associated with human papilloma virus (HPV) infection. To investigate the relationship between HPV and chronic inflammation in oropharyngeal carcinogenesis, we collected 140 oral mucous fresh specimens including 50 OPSCC patients, 50 cancer in situ, 30 precancerous lesions, and 10 normal oral mucous. Our data demonstrated that there was a significantly higher proportion of severe chronic inflammation in dysplastic epithelia in comparison with that in normal tissues (P<0.001). The positive rate of HPV 16 was parallel with the chronic inflammation degrees from mild to severe inflammation (P<0.05). The positive rate of HPV 16 was progressively improved with the malignant progression of oral mucous (P<0.05). In addition, CD11b+ LIN- HLA-DR-CD33+ MDSCs were a critical cell population that mediates inflammation response and immune suppression in HPV-positive OPSCC. These indicated that persistent chronic inflammation-related HPV infection might drive oropharyngeal carcinogenesis and MDSCs might pay an important role during this process. Thus, a combination of HPV infection and inflammation expression might become a helpful biomedical marker to predict oropharyngeal carcinogenesis. PMID:26193368

Chronic Inflammation-Related HPV: A Driving Force Speeds Oropharyngeal Carcinogenesis.

PubMed

Liu, Xin; Ma, Xiangrui; Lei, Zhengge; Feng, Hao; Wang, Shasha; Cen, Xiao; Gao, Shiyu; Jiang, Yaping; Jiang, Jian; Chen, Qianming; Tang, Yajie; Tang, Yaling; Liang, Xinhua

2015-01-01

Oropharyngeal squamous cell carcinoma (OPSCC) has been known to be a highly aggressive disease associated with human papilloma virus (HPV) infection. To investigate the relationship between HPV and chronic inflammation in oropharyngeal carcinogenesis, we collected 140 oral mucous fresh specimens including 50 OPSCC patients, 50 cancer in situ, 30 precancerous lesions, and 10 normal oral mucous. Our data demonstrated that there was a significantly higher proportion of severe chronic inflammation in dysplastic epithelia in comparison with that in normal tissues (P<0.001). The positive rate of HPV 16 was parallel with the chronic inflammation degrees from mild to severe inflammation (P<0.05). The positive rate of HPV 16 was progressively improved with the malignant progression of oral mucous (P<0.05). In addition, CD11b+ LIN- HLA-DR-CD33+ MDSCs were a critical cell population that mediates inflammation response and immune suppression in HPV-positive OPSCC. These indicated that persistent chronic inflammation-related HPV infection might drive oropharyngeal carcinogenesis and MDSCs might pay an important role during this process. Thus, a combination of HPV infection and inflammation expression might become a helpful biomedical marker to predict oropharyngeal carcinogenesis.

Addressing Chronic Disease Within Supportive Housing Programs

PubMed Central

Henwood, Benjamin F.; Stanhope, Victoria; Brawer, Rickie; Weinstein, Lara Carson; Lawson, James; Stwords, Edward; Crossan, Cornelius

2015-01-01

Background Tenants of supportive housing have a high burden of chronic health conditions. Objectives To examine the feasibility of developing a tenant-involved health promotion initiative within a “housing first” agency using a community-based participatory research (CBPR) framework. Methods Qualitative analyses of nine research capacity-building group meetings and fifteen individual pre- and post-interviews with those who completed a chronic disease self-management program, resulting in the development of several themes. Results Tenants of supportive housing successfully partnered with health care providers to implement a chronic disease self-management program, noting that “health care becomes ‘relevant’ with housing.” Conclusions Supportive housing organizations are well-situated to implement health promotion initiatives. Such publicly subsidized housing that is accompanied by comprehensive supports must also include self-management training to help people overcome both internal and external barriers to addressing chronic health needs. PMID:23543023

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...

Transcriptional profiling of ileocecal valve of Holstein dairy cows infected with mycobacterium avium subsp. paratuberculosis

USDA-ARS?s Scientific Manuscript database

Johne’s disease is a chronic infection of the small intestine caused by Mycobacterium avium subspecies paratuberculosis (MAP), an intracellular bacterium. The events of pathogen survival within the host cell(s), chronic inflammation and the progression from asymptomatic subclinical stage to an advan...

Break dance hip: chronic avulsion of the anterior superior iliac spine.

PubMed

Winkler, A R; Barnes, J C; Ogden, J A

1987-01-01

A case of chronic, progressive avulsion of the anterior superior iliac spine leading to the formation of a long, attenuated spur of bone in an 18-year-old black male break dancer is described. The mechanism of formation appeared to be repetitive avulsion from break dancing.

Rehabilitation of the Ankle after Acute Sprain or Chronic Instability.

ERIC Educational Resources Information Center

Mattacola, Carl G.; Dwyer, Maureen K.

2002-01-01

Outlines rehabilitation concepts applicable to acute and chronic ankle injury, providing evidence for current techniques used in ankle rehabilitation and describing a functional rehabilitation program that progresses from basic to advanced, while taking into account empirical data from the literature and clinical practice. The article notes that…

76 FR 57024 - Notice of Teleconference of the Chronic Hazard Advisory Panel on Phthalates and Phthalate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-15

... Product Safety Improvement Act of 2008 (CPSIA) (Pub. L. 110- 314). The CHAP will discuss its progress... CONSUMER PRODUCT SAFETY COMMISSION Notice of Teleconference of the Chronic Hazard Advisory Panel on Phthalates and Phthalate Substitutes AGENCY: Consumer Product Safety Commission. ACTION: Notice of...

Risk factors associated with disease progression and mortality in chronic kidney disease of uncertain etiology: a cohort study in Medawachchiya, Sri Lanka.

PubMed

Senevirathna, Lalantha; Abeysekera, Tilak; Nanayakkara, Shanika; Chandrajith, Rohana; Ratnatunga, Neelakanthi; Harada, Kouji H; Hitomi, Toshiaki; Komiya, Toshiyuki; Muso, Eri; Koizumi, Akio

2012-05-01

The alarming rise in the prevalence of chronic kidney disease of uncertain etiology (CKDu) among the low socioeconomic farming community in the North Central Province of Sri Lanka has been recognized as an emerging public health issue in the country. This study sought to determine the possible factors associated with the progression and mortality of CKDu. The study utilized a single-center cohort registered in 2003 and followed up until 2009 in a regional clinic in the endemic region, and used a Cox proportional hazards model. We repeatedly found an association between disease progression and hypertension. Men were at higher risk of CKDu than women. A significant proportion of the patients in this cohort were underweight, which emphasized the need for future studies on the nutritional status of these patients. Compared with findings in western countries and other regions of Asia, we identified hypertension as a major risk factor for progression of CKDu in this cohort.

Hormones and arterial stiffness in patients with chronic kidney disease.

PubMed

Gungor, Ozkan; Kircelli, Fatih; Voroneanu, Luminita; Covic, Adrian; Ok, Ercan

2013-01-01

Cardiovascular disease constitutes the major cause of mortality in patients with chronic kidney disease. Arterial stiffness is an important contributor to the occurrence and progression of cardiovascular disease. Various risk factors, including altered hormone levels, have been suggested to be associated with arterial stiffness. Based on the background that chronic kidney disease predisposes individuals to a wide range of hormonal changes, we herein review the available data on the association between arterial stiffness and hormones in patients with chronic kidney disease and summarize the data for the general population.

Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha.

PubMed

Hirotani, Makoto; Nakano, Hitoshi; Ura, Shigehisa; Yoshida, Kazuto; Niino, Masaaki; Yabe, Ichiro; Sasaki, Hidenao

2009-01-01

Interferon-alpha (IFN-alpha), though widely used for the treatment of chronic viral hepatitis, may be associated with the occurrence of autoimmune disorders. In this case report, a patient with chronic hepatitis C virus infection had chronic inflammatory demyelinating polyneuropathy (CIDP) after the initiation of IFN-alpha therapy. The neurological symptoms of this patient continued to progress even though the treatment with IFN-alpha had been withdrawn; the symptoms improved dramatically following treatment with intravenous immunoglobulin. This case may therefore provide an important clue to understand the immune mechanism of CIDP and IFN-alpha.

Massive localized lymphedema of the male external genitalia: a clinicopathologic study of 6 cases.

PubMed

Lee, Stephen; Han, Jeong S; Ross, Hillary M; Epstein, Jonathan I

2013-02-01

Massive localized lymphedema is a reactive pseudotumor strongly associated with obesity. The tumor most commonly presents as pendulous masses in the lower limbs with only 3 reported cases involving external male genitalia. In this study, we report an additional 6 cases localized to the external male genitalia. The cases were retrospectively identified from the surgical pathology database of the Johns Hopkins Hospital. All 6 patients were obese (5 presented with diffuse scrotal edema and 1 with a penile mass). In all cases, the clinical impression was of a benign chronic process developing over 3 months to 1 year. All 3 cases from outside institutions were referred with benign pathologic diagnoses. The lesions ranged in size from 4 to 55 cm. Microscopically, all cases exhibited stromal fibrosis and edema, multinucleated stromal cells, perivascular chronic inflammation, and lymphangiectasia. Entrapped fat was a minor feature and seen in only 3 cases. Variable hyperplasia and hypertrophy of dartos muscle were noted in 6 lesions. Three cases showed prominent microvascular proliferation around the edge of individual dartos muscle bundles. In summary, diagnosis of massive localized lymphedema requires appropriate correlation between clinical and microscopic findings. Lesions in the male external genitalia share many microscopic findings with massive localized lymphedema at other sites, although entrapped adipose tissue is not prominent. Additional, although not specific, findings include variably hyperplastic and hypertrophic dartos muscle and capillary neoangiogenesis at the interface between smooth muscle bundles and stroma. Copyright © 2013 Elsevier Inc. All rights reserved.

Leukemia risk associated with chronic external exposure to ionizing radiation in a French cohort of nuclear workers.

PubMed

Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

2012-11-01

Leukemia is one of the earliest cancer effects observed after acute exposure to relatively high doses of ionizing radiation. Leukemia mortality after external exposure at low doses and low-dose rates has been investigated at the French Atomic Energy Commission (CEA) and Nuclear Fuel Company (AREVA NC) after an additional follow-up of 10 years. The cohort included radiation-monitored workers employed for at least one year during 1950-1994 at CEA or AREVA NC and followed during 1968-2004. Association between external exposure and leukemia mortality was estimated with excess relative risk (ERR) models and time-dependent modifying factors were investigated with time windows. The cohort included 36,769 workers, followed for an average of 28 years, among whom 73 leukemia deaths occurred. Among the workers with a positive recorded dose, the mean cumulative external dose was 21.7 mSv. Results under a 2-year lag assumption suggested that the risk of leukemia (except chronic lymphatic leukemia) increased significantly by 8% per 10 mSv. The magnitude of the association for myeloid leukemia was larger. The higher ERR/Sv for doses received 2-14 years earlier suggest that time since exposure modifies the effect. The ERR/Sv also appeared higher for doses received at exposure rates ≥20 mSv per year. These results are consistent with those found in other studies of nuclear workers. However, confidence intervals are still wide. Further analyses should be conducted in pooled cohorts of nuclear workers.

The effect of preexisting respiratory co-morbidities on burn outcomes☆

PubMed Central

Knowlin, Laquanda T.; Stanford, Lindsay B.; Cairns, Bruce A.; Charles, Anthony G.

2018-01-01

Introduction Burns cause physiologic changes in multiple organ systems in the body. Burn mortality is usually attributable to pulmonary complications, which can occur in up to 41% of patients admitted to the hospital after burn. Patients with preexisting comorbidities such as chronic lung diseases may be more susceptible. We therefore sought to examine the impact of preexisting respiratory disease on burn outcomes. Methods A retrospective analysis of patients admitted to a regional burn center from 2002–2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, smoker status, length of hospital stay, and days of mechanical ventilation. Bivariate analysis was performed and Cox regression modeling using significant variables was utilized to estimate hazard of progression to mechanical ventilation and mortality. Results There were a total of 7640 patients over the study period. Overall survival rate was 96%. 8% (n=672) had a preexisting respiratory disease. Chronic lung disease patients had a higher mortality rate (7%) compared to those without lung disease (4%, p<0.01). The adjusted Cox regression model to estimate the hazard of progression to mechanical ventilation in patients with respiratory disease was 21% higher compared to those without respiratory disease (HR=1.21, 95% CI=1.01–1.44). The hazard of progression to mortality is 56% higher (HR=1.56, 95% CI=1.10–2.19) for patients with pre-existing respiratory disease compared to those without respiratory disease after controlling for patient demographics and injury characteristics. Conclusion Preexisting chronic respiratory disease significantly increases the hazard of progression to mechanical ventilation and mortality in patients following burn. Given the increasing number of Americans with chronic respiratory diseases, there will likely be a greater number of individuals at risk for worse outcomes following burn. PMID:28341260

The effect of preexisting respiratory co-morbidities on burn outcomes.

PubMed

Knowlin, Laquanda T; Stanford, Lindsay B; Cairns, Bruce A; Charles, Anthony G

2017-03-01

Burns cause physiologic changes in multiple organ systems in the body. Burn mortality is usually attributable to pulmonary complications, which can occur in up to 41% of patients admitted to the hospital after burn. Patients with preexisting comorbidities such as chronic lung diseases may be more susceptible. We therefore sought to examine the impact of preexisting respiratory disease on burn outcomes. A retrospective analysis of patients admitted to a regional burn center from 2002-2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, smoker status, length of hospital stay, and days of mechanical ventilation. Bivariate analysis was performed and Cox regression modeling using significant variables was utilized to estimate hazard of progression to mechanical ventilation and mortality. There were a total of 7640 patients over the study period. Overall survival rate was 96%. 8% (n=672) had a preexisting respiratory disease. Chronic lung disease patients had a higher mortality rate (7%) compared to those without lung disease (4%, p<0.01). The adjusted Cox regression model to estimate the hazard of progression to mechanical ventilation in patients with respiratory disease was 21% higher compared to those without respiratory disease (HR=1.21, 95% CI=1.01-1.44). The hazard of progression to mortality is 56% higher (HR=1.56, 95% CI=1.10-2.19) for patients with pre-existing respiratory disease compared to those without respiratory disease after controlling for patient demographics and injury characteristics. Preexisting chronic respiratory disease significantly increases the hazard of progression to mechanical ventilation and mortality in patients following burn. Given the increasing number of Americans with chronic respiratory diseases, there will likely be a greater number of individuals at risk for worse outcomes following burn. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

"Here we're all in the same boat"--a qualitative study of group based rehabilitation for sick-listed citizens with chronic pain.

PubMed

Andersen, Lotte Nygaard; Kohberg, Maria; Herborg, Lene Gram; Søgaard, Karen; Roessler, Kirsten Kaya

2014-08-01

Musculoskeletal pain impacts upon everyday life. A degree of chronicity may pose an increased risk of sickness absence. One of two rehabilitative interventions, "Tailored Physical Activity" or "Chronic Pain Self-Management Program", was offered to sick-listed citizens who experienced pain. The objectives of this paper were to: (1) Assess what factors are experienced as problematic for sick-listed citizens in everyday life with chronic pain, and (2) Evaluate the significance of two distinct rehabilitative interventions on the future everyday lives of sick-listed citizens. Seven semi-structured interviews with sick-listed citizens were analyzed using a phenomenological-hermeneutical approach. Results were discussed by applying the theoretical framework of Antonovsky's salutogenetic model and Yaloms principles for group psychology. The potential for development of citizen's coping is evaluated based on Roessler's notion of progression. The analysis revealed four main themes: (1) Living with pain and unemployment; (2) "Putting my foot down" and "asking for help"; (3) Significance of the group, including instructors, and; (4) Aspects significant to progression. Unemployment is a major life event that promotes stress and can be accompanied by problems related to depressed mood, acceptance of the life situation, feelings of not being useful, feelings of losing control and identity conflicts. Group characteristics that gave a significant basis for progression in the self-management program are both emotional and instrumental, while the physical training program offers a "here-and-now"-experience and motivation to participate. This study indicates that the self-management program could potentially improve coping while the physical activity program revealed one example of a means of progression. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Therapeutic Exercise Training to Reduce Chronic Headache in Working Women: Design of a Randomized Controlled Trial.

PubMed

Rinne, Marjo; Garam, Sanna; Häkkinen, Arja; Ylinen, Jari; Kukkonen-Harjula, Katriina; Nikander, Riku

2016-05-01

Cervicogenic headache and migraine are common causes of visits to physicians and physical therapists. Few randomized trials utilizing active physical therapy and progressive therapeutic exercise have been previously published. The existing evidence on active treatment methods supports a moderate effect on cervicogenic headache. The aim of this study is to investigate whether a progressive, group-based therapeutic exercise program decreases the intensity and frequency of chronic headache among women compared with a control group receiving a sham dose of transcutaneous electrical nerve stimulation (TENS) and stretching exercises. A randomized controlled trial with 6-month intervention and follow-up was developed. The participants were randomly assigned to either a treatment group or a control group. The study is being conducted at 2 study centers. The participants are women aged 18 to 60 years with chronic cervicogenic headache or migraine. The treatment group's exercise program consisted of 6 progressive therapeutic exercise modules, including proprioceptive low-load progressive craniocervical and cervical exercises and high-load exercises for the neck muscles. The participants in the control group received 6 individually performed sham TENS treatment sessions. The primary outcome is the intensity of headache. The secondary outcomes are changes in frequency and duration of headache, neck muscle strength, neck and shoulder flexibility, impact of headache on daily life, neck disability, fear-avoidance beliefs, work ability, and quality of life. Between-group differences will be analyzed separately at 6, 12, and 24 months with generalized linear mixed models. In the case of count data (eg, frequency of headache), Poisson or negative binomial regression will be used. The therapists are not blinded. The effects of specific therapeutic exercises on frequency, intensity, and duration of chronic headache and migraine will be reported. © 2016 American Physical Therapy Association.

Host virus and pneumococcus-specific immune responses in high-count monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia: implications for disease progression

PubMed Central

Criado, Ignacio; Muñoz-Criado, Santiago; Rodríguez-Caballero, Arancha; Nieto, Wendy G.; Romero, Alfonso; Fernández-Navarro, Paulino; Alcoceba, Miguel; Contreras, Teresa; González, Marcos; Orfao, Alberto; Almeida, Julia

2017-01-01

Patients diagnosed with chronic lymphocytic leukemia (CLL) display a high incidence of infections due to an associated immunodeficiency that includes hypogammaglobulinemia. A higher risk of infections has also been recently reported for high-count monoclonal B-cell lymphocytosis, while no information is available in low-count monoclonal B-cell lymphocytosis. Here, we evaluated the status of the humoral immune system in patients with chronic lymphocytic leukemia (n=58), as well as in low- (n=71) and high- (n=29) count monoclonal B-cell lymphocytosis versus healthy donors (n=91). Total free plasma immunoglobulin titers and specific levels of antibodies against cytomegalovirus, Epstein-Barr virus, influenza and S.pneumoniae were measured by nephelometry and ELISA-based techniques, respectively. Overall, our results show that both CLL and high-count monoclonal B-cell lymphocytosis patients, but not low-count monoclonal B-cell lymphocytosis subjects, present with relatively high levels of antibodies specific for the latent viruses investigated, associated with progressively lower levels of S.pneumoniae-specific immunoglobulins. These findings probably reflect asymptomatic chronic reactivation of humoral immune responses against host viruses associated with expanded virus-specific antibody levels and progressively decreased protection against other micro-organisms, denoting a severe humoral immunodeficiency state not reflected by the overall plasma immunoglobulin levels. Alternatively, these results could reflect a potential role of ubiquitous viruses in the pathogenesis of the disease. Further analyses are necessary to establish the relevance of such asymptomatic humoral immune responses against host viruses in the expansion of the tumor B-cell clone and progression from monoclonal B-cell lymphocytosis to CLL. PMID:28385786

Mycophenolate mofetil combined with systemic corticosteroids prevents progression to chronic recurrent inflammation and development of 'sunset glow fundus' in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease.

PubMed

Abu El-Asrar, Ahmed M; Dosari, Mona; Hemachandran, Suhail; Gikandi, Priscilla W; Al-Muammar, Abdulrahman

2017-02-01

To evaluate the effectiveness and safety of mycophenolate mofetil (MMF) as first-line therapy combined with systemic corticosteroids in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease. This prospective study included 38 patients (76 eyes). The main outcome measures were final visual acuity, corticosteroid-sparing effect, progression to chronic recurrent granulomatous uveitis and development of complications, particularly 'sunset glow fundus'. The mean follow-up period was 37.0 ± 29.3 (range 9-120 months). Visual acuity of 20/20 was achieved by 93.4% of the eyes. Corticosteroid-sparing effect was achieved in all patients. The mean interval between starting treatment and tapering to 10 mg or less daily was 3.8 ± 1.3 months (range 3-7 months). Twenty-two patients (57.9%) discontinued treatment without relapse of inflammation. The mean time observed off of treatment was 28.1 ± 19.6 months (range 1-60 months). None of the eyes progressed to chronic recurrent granulomatous uveitis. The ocular complications encountered were glaucoma in two eyes (2.6%) and cataract in five eyes (6.6%). None of the eyes developed 'sunset glow fundus', and none of the patients developed any systemic adverse events associated with the treatment. Use of MMF as first-line therapy combined with systemic corticosteroids in patients with initial-onset acute VKH disease prevents progression to chronic recurrent granulomatous inflammation and development of 'sunset glow fundus'. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

[Tuberculous chronic otitis media. A clinical case].

PubMed

Pérez Fernández, C A; Armengot Canceller, M; Campos Catalá, A; Abril, V; Calabuig Crespo, M C; Basterra Alegría, J

2000-01-01

Tuberculous otitis media is a rare cause of chronic suppurative infection of the middle ear and mastoid. Patients typically have chronic tympanic membrane perforation and ear discharge associated with progressive, profound hearing loss, and resistance to antibiotic treatment. Diagnosis is often delayed by a low clinical suspicion, thus leading to complications such as irreversible hearing loss and facial nerve paralysis. Histological examination of a biopsy specimen reveals tuberculous changes. The disease is treated with antituberculosis agents.

Normalization behaviours of rural fathers living with chronically-ill children: an Australian experience.

PubMed

Peck, Blake; Lillibridge, Jennifer

2005-03-01

This article reports findings from a larger qualitative study conducted to gain insight into the experience of fathers living with their chronically-ill children in rural Victoria, Australia. Data were collected via unstructured interviews with four fathers. The findings presented in this article explore the phenomena of normalization for fathers within the chronic illness experience. Fathers described normalizing the experience of living with their chronically-ill child as involving a combination of various coping strategies and behaviours including: (1) accepting the child's condition, (2) changing expectations, (3) focusing energies on a day-to-day basis, (4) minimizing knowledge-seeking behaviours, and (5) engaging in external distraction activities. Findings highlight the complex and unique normalization strategies these men utilized and contribute to knowledge and understanding of the complex nature of raising a chronically-ill child in rural Australia and provide a sound basis upon which to guide an ongoing and holistic assessment of fathers with chronically-ill children.

Probing Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Immune Response in the Progression of Chronic Obstructive Pulmonary Disease Using Multiscale Network Modeling

PubMed Central

Pan, Zhichao; Yu, Haishan; Liao, Jie-Lou

2016-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD. Yet, only a relatively small percentage of smokers develop the disease, showing that disease susceptibility varies significantly among smokers. As smoking cessation can prevent the disease in some smokers, quitting smoking cannot halt the progression of COPD in others. Despite extensive research efforts, cellular and molecular mechanisms of COPD remain elusive. In particular, the disease susceptibility and smoking cessation effects are poorly understood. To address these issues in this work, we develop a multiscale network model that consists of nodes, which represent molecular mediators, immune cells and lung tissues, and edges describing the interactions between the nodes. Our model study identifies several positive feedback loops and network elements playing a determinant role in the CS-induced immune response and COPD progression. The results are in agreement with clinic and laboratory measurements, offering novel insight into the cellular and molecular mechanisms of COPD. The study in this work also provides a rationale for targeted therapy and personalized medicine for the disease in future. PMID:27669518

Fear of progression in chronic diseases: psychometric properties of the Fear of Progression Questionnaire.

PubMed

Herschbach, Peter; Berg, Petra; Dankert, Andrea; Duran, Gabriele; Engst-Hastreiter, Ursula; Waadt, Sabine; Keller, Monika; Ukat, Robert; Henrich, Gerhard

2005-06-01

The aim of this study was the development and psychometric testing of a new psychological questionnaire to measure the fear of progression (FoP) in chronically ill patients (cancer, diabetes mellitus and rheumatic diseases). The Fear of Progression Questionnaire (FoP-Q) was developed in four phases: (1) generation of items (65 interviews); (2) reduction of items--the initial version of the questionnaire (87 items) was presented to 411 patients, to construct subscales and test the reliability; (3) testing the convergent and discriminative validity of the reduced test version (43 items) within a new sample (n=439); (4) translation--German to English. The scale comprised five factors (Cronbach's alpha >.70): affective reactions (13 items), partnership/family (7), occupation (7), loss of autonomy (7) and coping with anxiety (9). The test-retest reliability coefficients varied between .77 and .94. There was only a medium relationship to traditional anxiety scales. This is an indication of the independence of the FoP. Significant relationships between the FoP-Q and the patient's illness behaviour indicate discriminative validity. The FoP-Q is a new and unique questionnaire developed for the chronically ill. A major problem and source of stress for this patient group has been measuring both specifically and economically the FoP of an illness. The FoP-Q was designed to resolve this problem, fulfill this need and reduce this stress.

Gene expression patterns in the progression of canine copper-associated chronic hepatitis

PubMed Central

Dirksen, Karen; Spee, Bart; Penning, Louis C.; van den Ingh, Ted S. G. A. M.; Burgener, Iwan A.; Watson, Adrian L.; Groot Koerkamp, Marian; Rothuizen, Jan

2017-01-01

Copper is an essential trace element, but can become toxic when present in abundance. The severe effects of copper-metabolism imbalance are illustrated by the inherited disorders Wilson disease and Menkes disease. The Labrador retriever dog breed is a novel non-rodent model for copper-storage disorders carrying mutations in genes known to be involved in copper transport. Besides disease initiation and progression of copper accumulation, the molecular mechanisms and pathways involved in progression towards copper-associated chronic hepatitis still remain unclear. Using expression levels of targeted candidate genes as well as transcriptome micro-arrays in liver tissue of Labrador retrievers in different stages of copper-associated hepatitis, pathways involved in progression of the disease were studied. At the initial phase of increased hepatic copper levels, transcriptomic alterations in livers mainly revealed enrichment for cell adhesion, developmental, inflammatory, and cytoskeleton pathways. Upregulation of targeted MT1A and COMMD1 mRNA shows the liver’s first response to rising intrahepatic copper concentrations. In livers with copper-associated hepatitis mainly an activation of inflammatory pathways is detected. Once the hepatitis is in the chronic stage, transcriptional differences are found in cell adhesion adaptations and cytoskeleton remodelling. In view of the high similarities in copper-associated hepatopathies between men and dog extrapolation of these dog data into human biomedicine seems feasible. PMID:28459846

Functional magnetic resonance imaging in chronic ischaemic stroke.

PubMed

Lake, Evelyn M R; Bazzigaluppi, Paolo; Stefanovic, Bojana

2016-10-05

Ischaemic stroke is the leading cause of adult disability worldwide. Effective rehabilitation is hindered by uncertainty surrounding the underlying mechanisms that govern long-term ischaemic injury progression. Despite its potential as a sensitive non-invasive in vivo marker of brain function that may aid in the development of new treatments, blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has found limited application in the clinical research on chronic stage stroke progression. Stroke affects each of the physiological parameters underlying the BOLD contrast, markedly complicating the interpretation of BOLD fMRI data. This review summarizes current progress on application of BOLD fMRI in the chronic stage of ischaemic injury progression and discusses means by which more information may be gained from such BOLD fMRI measurements. Concomitant measurements of vascular reactivity, neuronal activity and metabolism in preclinical models of stroke are reviewed along with illustrative examples of post-ischaemic evolution in neuronal, glial and vascular function. The realization of the BOLD fMRI potential to propel stroke research is predicated on the carefully designed preclinical research establishing an ischaemia-specific quantitative model of BOLD signal contrast to provide the framework for interpretation of fMRI findings in clinical populations.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. © 2016 The Author(s).

Cancer Systems Biology Consortium | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

Cancer is a complex disease system involving multiple molecular, genetic, and cellular events. From its early initiation through progression and metastasis, cancer can adapt and evolve as a result of both internal and external signals. These properties make cancer difficult to predict, prevent, and treat. There has been significant progress in characterizing the genetics of cancer, as well as the downstream effects on the molecular and cellular pathways that are critical for the initiation and progression of cancer.

[Chronic inflammatory demyelinating polyradiculoneuropathy in childhood: outcomes after methylprednisolone pulse therapy].

PubMed

Rafai, M A; Moutaouakil, F; El Otmani, H; Fadel, H; Boulaajaj, F Z; El Moutawakil, B; Gam, I; Slassi, I

2006-06-01

Chronic inflammatory demyelinating polyneuropathy (CIDP) in children is relatively rare and treatment is based primarily on intravenous immunoglobulins or oral corticosteroids. Boluses of methylprednisolone (MP) are a seldom used alternative. We report the case of an 8-year-old child, first presented at the age of 3 years, with recurring episodes of functional impotence of both lower limbs and walking impairment, partially reversible without treatment. Clinical, progressive, and electrophysiological data and the analysis of the cerebrospinal fluid were compatible with CIDP. MP boluses were administered: after a total eight monthly boluses, very satisfactory progression on the clinical and electrophysiological fronts was noted after 24 months. Childhood CIDP presents clinical, electrophysiological, progressive, and prognostic particularities, they recur readily and the outcome is good. Boluses of methylprednisolone are an alternative to the treatment of these neuropathies in childhood.

Rationale for treating hepatitis C virus infection in patients with mild to moderate chronic kidney disease.

PubMed

Ridruejo, Ezequiel; Mendizabal, Manuel; Silva, Marcelo O

2018-04-01

Hepatitis C virus infection (HCV) is highly prevalent in patients with chronic kidney disease (CKD) and kidney transplant recipients. Little information exists on treatment in patients with CKD stages 2 to 3, where CKD progression might be slowed by HCV treatment. These patients are not considered a high priority for HCV treatment in most international guidelines. Although some recently published guidelines propose universal treatment, others are still recommending it only in high priority groups. In this review, we evaluate current evidence of HCV infection impact on CKD progression, on cardiovascular and metabolic risk, and the benefits of HCV infection treatment to improve cardiovascular and metabolic outcomes. We made special focus on the benefits of HCV infection treatment in patients with stages 2 to 3 CKD to avoid CKD progression. © 2018 International Society for Hemodialysis.

ACE and SGLT2 inhibitors: the future for non-diabetic and diabetic proteinuric renal disease.

PubMed

Perico, Norberto; Ruggenenti, Piero; Remuzzi, Giuseppe

2017-04-01

Most chronic nephropathies progress relentlessly to end-stage kidney disease. Research in animals and humans has helped our understanding of the mechanisms of chronic kidney disease progression. Current therapeutic strategies to prevent or revert renal disease progression focus on reduction of urinary protein excretion and blood pressure control. Blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors and/or angiotensin II type 1 receptor blockers is the most effective treatment to achieve these purposes in non-diabetic and diabetic proteinuric renal diseases. For those individuals in which nephroprotection by RAS blockade is only partial, sodium-glucose linked cotransporter-2 (SGLT2) inhibitors could be a promising new class of drugs to provide further renoprotective benefit when added on to RAS blockers. Copyright © 2017 Elsevier Ltd. All rights reserved.

[The impact of psychological variables on the presentation and progress of asthma and patient's cognitive functions].

PubMed

Talarowska, Monika; Florkowski, Antoni; Gałecki, Piotr; Szemraj, Janusz; Zboralski, Krzysztof; Pietras, Tadeusz; Górski, Paweł

2009-01-01

Chronic respiratory system diseases become serious public health problem all over the world. The most prevalent are obstructive diseases (asthma and COPD). The prevalence of asthma is still high and concern patients representing wide range of age and socio-economic status. Despite progress in diagnostic and therapeutic options several studies showed that asthma has an impact on health-related quality of life and patients' coping. Asthma as chronic condition results in limitations of patients activity and social relations. Thus psychosocial variables, which may have an impact on asthma symptoms presentation and disease progress, should be considered. There are only few reports concerning cognitive functions in asthma. The aim of the study was to assess the potential impact of psychosocial factors on asthma symptoms presentation, and cognitive function in asthma patients.

Stay Focused! The Effects of Internal and External Focus of Attention on Movement Automaticity in Patients with Stroke

PubMed Central

Kal, E. C.; van der Kamp, J.; Houdijk, H.; Groet, E.; van Bennekom, C. A. M.; Scherder, E. J. A.

2015-01-01

Dual-task performance is often impaired after stroke. This may be resolved by enhancing patients’ automaticity of movement. This study sets out to test the constrained action hypothesis, which holds that automaticity of movement is enhanced by triggering an external focus (on movement effects), rather than an internal focus (on movement execution). Thirty-nine individuals with chronic, unilateral stroke performed a one-leg-stepping task with both legs in single- and dual-task conditions. Attentional focus was manipulated with instructions. Motor performance (movement speed), movement automaticity (fluency of movement), and dual-task performance (dual-task costs) were assessed. The effects of focus on movement speed, single- and dual-task movement fluency, and dual-task costs were analysed with generalized estimating equations. Results showed that, overall, single-task performance was unaffected by focus (p = .341). Regarding movement fluency, no main effects of focus were found in single- or dual-task conditions (p’s ≥ .13). However, focus by leg interactions suggested that an external focus reduced movement fluency of the paretic leg compared to an internal focus (single-task conditions: p = .068; dual-task conditions: p = .084). An external focus also tended to result in inferior dual-task performance (β = -2.38, p = .065). Finally, a near-significant interaction (β = 2.36, p = .055) suggested that dual-task performance was more constrained by patients’ attentional capacity in external focus conditions. We conclude that, compared to an internal focus, an external focus did not result in more automated movements in chronic stroke patients. Contrary to expectations, trends were found for enhanced automaticity with an internal focus. These findings might be due to patients’ strong preference to use an internal focus in daily life. Future work needs to establish the more permanent effects of learning with different attentional foci on re-automating motor control after stroke. PMID:26317437

An Assessment of the Pacific Regional Cancer Coalition: Outcomes and Implications of a Regional Coalition Internal and External Assessment

PubMed Central

Heckert, Karen A; Buenconsejo-Lum, Lee; Hedson, Johnny; Tamang, Suresh; Palafox, Neal

2011-01-01

Significance The Pacific Regional Cancer Coalition Signifi(PRCC) provides regional leadership in the US Affiliated Pacific Islands (USAPI) to implement the Regional Comprehensive Control Plan: 2007–2012, and to evaluate its coalition and partnerships. The Pacific Center of Excellence in the Elimination of Disparities (CEED), aims to reduce cancer disparities and conducts evaluation activities relevant to cancer prevention and control in the USAPI. Purpose The PRCC Self (internal) and Partner (external) Assessments were conducted to assess coalition functioning, regional and national partnerships, sustainability, and the role of regionalism for integrating all chronic disease prevention and control in the Pacific. Methods Self-administered questionnaires and key informant telephone interviews with PRCC members (N=20), and representatives from regional and national partner organizations were administered (N=26). Validated multi item measures using 5-point scales on coalition and partnership characteristics were used. Chronbach's alphas and averages for the measures were computed. Results Internal coalition measures: satisfaction (4.2, SD=0.48) communication (4.0, SD=0.56), respect (4.0, SD=0.60) were rated more highly than external partnership measures: resource sharing (3.5, SD=0.74), regionalism (3.9, SD=0.47), use of findings (3.9, SD=0.50). The PRCC specifically identified its level of “collaboration” with external partners including Pacific CEED. External partners identified its partnership with the PRCC in the “coalition” stage. Principal Conclusions PRCC members and external partners are satisfied with their partnerships. All groups should continue to focus on building collaboration with partners to reflect a truly regional approach to sustain the commitment, the coalitions and the programming to reduce cancer in the USAPI. PRCC and partners should also work together to integrate all chronic disease prevention and control efforts in the Pacific. PMID:22235160

Factors That Affect Disease Progression After First Attack of Acute Pancreatitis.

PubMed

Bertilsson, Sara; Swärd, Per; Kalaitzakis, Evangelos

2015-09-01

Little is known about recurrence of pancreatitis after an initial episode, and little is known about how the disease progresses or what factors affect progression. We performed a population-based study of patients with acute pancreatitis (AP) to determine their outcomes and associated factors. We performed a retrospective study of patients with first-time AP from 2003 through 2012 in a well-defined area of Sweden. Data were collected from medical records on disease etiology, severity (according to the Atlanta classification), recurrence of AP, subsequent chronic pancreatitis, and mortality. Patients were followed up for a median time of 4.6 years, until death or the end of 2013. We identified 1457 patients with first-time AP (48% biliary disease, 17% alcohol-associated, 9.9% severe); 23% of patients had 1 or more recurrences. Risk for recurrence was significantly higher among smokers (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.03-1.95; P = .03), patients with alcohol-associated AP (HR, 1.58; 95% CI, 1.25-2.23; P < .01), after organ failure (HR, 1.46; 95% CI 1.05-2.03; P = .02), and in patients with systemic complications (HR, 1.88; 95% CI, 1.27-2.79; P < .01) or local complications (HR, 1.66; 95% CI, 1.22-2.27; P < .01). AP of all etiologies progressed to chronic pancreatitis, although alcohol-associated AP progressed most frequently (2.8/100 patient-years). Patients with recurrent AP were at the highest risk for chronic pancreatitis (HR, 6.74; 95% CI, 4.02-11.3; P < .01), followed by alcohol-associated AP (HR, 3.10; 95% CI, 2.05-5.87; P < .01), smoking (HR, 2.26; 95% CI, 1.12-4.58; P = .02), systemic complications (HR, 1.37; 95% CI, 1.06-4.62; P = .03), and peripancreatic necrosis (HR, 2.74; 95% CI, 1.7-4.43; P < .01). In-hospital mortality was 2.8%, and independently associated only with organ failure (odds ratio, 71.17; 95% CI, 21.14-239.60; P < .01). Fifty-three percent of patients who died during disease recurrence had biliary AP; a higher percentage of these patients died upon first recurrence (5.9%) than upon first attack of AP (2%; P = .01). The severity of first-time AP, smoking, and alcohol abuse are related to recurrence and subsequent chronic pancreatitis. Recurrence increases the risk for progression to chronic pancreatitis. Most patients who die upon disease recurrence have biliary AP. Copyright © 2015. Published by Elsevier Inc.

Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism

PubMed Central

Vujkovic-Cvijin, Ivan; Dunham, Richard M.; Iwai, Shoko; Maher, M. Cyrus; Albright, Rebecca G.; Broadhurst, Mara J.; Hernandez, Ryan D.; Lederman, Michael M.; Huang, Yong; Somsouk, Ma; Deeks, Steven G.; Hunt, Peter W.; Lynch, Susan V.; McCune, Joseph M.

2014-01-01

Progressive HIV infection is characterized by dysregulation of the intestinal immune barrier, translocation of immunostimulatory microbial products, and chronic systemic inflammation that is thought to drive progression of disease to AIDS. Elements of this pathologic process persist despite viral suppression during highly active antiretroviral therapy (HAART) and drivers of these phenomena remain poorly understood. Disrupted intestinal immunity can precipitate dysbiosis that induces chronic inflammation in the mucosa and periphery of mice. However, putative microbial drivers of HIV-associated immunopathology versus recovery have not been identified in humans. Using high-resolution bacterial community profiling, we identified a dysbiotic mucosal-adherent community enriched in Proteobacteria and depleted of Bacteroidia members that was associated with markers of mucosal immune disruption, T cell activation, and chronic inflammation in HIV-infected subjects. Furthermore, this dysbiosis was evident among HIV-infected subjects undergoing HAART, and the extent of dysbiosis correlated with activity of the kynurenine pathway of tryptophan metabolism and plasma concentrations of the inflammatory cytokine interleukin-6 (IL-6), two established markers of disease progression. Gut-resident bacteria with capacity to metabolize tryptophan through the kynurenine pathway were found to be enriched in HIV-infected subjects, strongly correlated with kynurenine levels in HIV-infected subjects, and capable of kynurenine production in vitro. These observations demonstrate a link between mucosal-adherent colonic bacteria and immunopathogenesis during progressive HIV infection, which is apparent even in the setting of viral suppression during HAART. This link suggests that gut-resident microbial populations may influence intestinal homeostasis during HIV disease. PMID:23843452

Basal values and changes of liver stiffness predict the risk of disease progression in compensated advanced chronic liver disease.

PubMed

Pons, Mònica; Simón-Talero, Macarena; Millán, Laura; Ventura-Cots, Meritxell; Santos, Begoña; Augustin, Salvador; Genescà, Joan

2016-10-01

Transient elastography has been proposed as a tool to predict the risk of decompensation in patients with chronic liver disease. We aimed to identify risk groups of disease progression, using a combination of baseline liver stiffness measurement (LSM) and its change over time (delta-LSM) in patients with compensated advanced chronic liver disease (cACLD). Ninety-four patients with baseline LSM ≥10kPa, Child-Pugh score 5 and without previous decompensation were included. A second LSM was performed during follow-up and data on liver function and liver-related events were collected. The primary endpoint was a composite that included death, liver decompensation and impairment in at least 1 point in Child-Pugh score. After a median follow-up of 43.6 months, 15% of patients presented the primary endpoint. Multivariate analysis identified baseline LSM (OR 1.12, P=0.002) and delta-LSM (OR 1.02, P=0.048) as independent predictors of the primary endpoint. A high risk group represented by patients with baseline LSM ≥21kPa and delta-LSM ≥10% (risk of progression 47.1%, 95% CI: 23-71%) was identified, while patients with LSM <21kPa and delta-LSM <10% presented zero risk of progression (P=0.03). Simple classification rules using baseline LSM and delta-LSM identify cACLD patients at low or high risk of disease progression. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Investigation of the effects of external current systems on the MAGSAT data utilizing grid cell modeling techniques

NASA Technical Reports Server (NTRS)

Klumpar, D. M. (Principal Investigator)

1982-01-01

Progress made in reducing MAGSAT data and displaying magnetic field perturbations caused primarily by external currents is reported. A periodic and repeatable perturbation pattern is described that arises from external current effects but appears as unique signatures associated with upper middle latitudes on the Earth's surface. Initial testing of the modeling procedure that was developed to compute the magnetic fields at satellite orbit due to current distributions in the ionosphere and magnetosphere is also discussed. The modeling technique utilizes a linear current element representation of the large scale space current system.

Center for Information Services Fourth Quarterly Progress Report, Phase IIB; Detailed Design and Prototype Development, 1 October 1971 to 31 December 1971.

ERIC Educational Resources Information Center

Kehl, W. B.; And Others

The administrative activity, including organization, staff, budget and external contacts, and the technical progress of IPS development, experimental service, workshops, documentation and related activities of the Center for Information Services (at the University of California, Los Angeles) are reported upon in this document. Pages 9 and 10 may…

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.

Compartmental and temporal dynamics of chronic inflammation and airway remodelling in a chronic asthma mouse model.

PubMed

Alrifai, Mohammed; Marsh, Leigh M; Dicke, Tanja; Kılıç, Ayse; Conrad, Melanie L; Renz, Harald; Garn, Holger

2014-01-01

Allergic asthma is associated with chronic airway inflammation and progressive airway remodelling. However, the dynamics of the development of these features and their spontaneous and pharmacological reversibility are still poorly understood. We have therefore investigated the dynamics of airway remodelling and repair in an experimental asthma model and studied how pharmacological intervention affects these processes. Using BALB/c mice, the kinetics of chronic asthma progression and resolution were characterised in absence and presence of inhaled corticosteroid (ICS) treatment. Airway inflammation and remodelling was assessed by the analysis of bronchoalveolar and peribronichal inflammatory cell infiltrate, goblet cell hyperplasia, collagen deposition and smooth muscle thickening. Chronic allergen exposure resulted in early (goblet cell hyperplasia) and late remodelling (collagen deposition and smooth muscle thickening). After four weeks of allergen cessation eosinophilic inflammation, goblet cell hyperplasia and collagen deposition were resolved, full resolution of lymphocyte inflammation and smooth muscle thickening was only observed after eight weeks. ICS therapy when started before the full establishment of chronic asthma reduced the development of lung inflammation, decreased goblet cell hyperplasia and collagen deposition, but did not affect smooth muscle thickening. These effects of ICS on airway remodelling were maintained for a further four weeks even when therapy was discontinued. Utilising a chronic model of experimental asthma we have shown that repeated allergen exposure induces reversible airway remodelling and inflammation in mice. Therapeutic intervention with ICS was partially effective in inhibiting the transition from acute to chronic asthma by reducing airway inflammation and remodelling but was ineffective in preventing smooth muscle hypertrophy.

L-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study

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

Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna

Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of L-boronophenylalanine-fructose (L-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of L-BPA-F, eithermore » 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated L-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of L-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an L-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.« less

[A case of mixed connective tissue disease positive for proteinase 3 antineutrophil cytoplasmic antibody in a patient with slowly progressive type 1 diabetes mellitus and chronic thyroiditis].

PubMed

Michitsuji, Tohru; Horai, Yoshiro; Sako, Ayaka; Asano, Taro; Iwanaga, Nozomi; Izumi, Yasumori; Kawakami, Atsushi

2017-01-01

  A female in her sixties with slowly progressive type 1 diabetes mellitus (SPT1DM) and chronic thyroiditis was referred to our rheumatology department with swelling in her fingers. A prominent atherosclerotic lesion was revealed upon brain magnetic resonance imaging, and she was found to have mixed connective tissue disease (MCTD) positive for proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA). This rare case of MCTD accompanying SPT1DM and PR3-ANCA suggested that a synergy between MCTD and PR3-ANCA triggers atherosclerosis.

The crosstalk of gut microbiota and chronic kidney disease: role of inflammation, proteinuria, hypertension, and diabetes mellitus.

PubMed

Kanbay, Mehmet; Onal, Emine M; Afsar, Baris; Dagel, Tuncay; Yerlikaya, Aslihan; Covic, Adrian; Vaziri, Nosratola D

2018-05-04

Chronic kidney disease (CKD) has been shown to result in profound changes in the composition and functions of the gut microbial flora which by disrupting intestinal epithelial barrier and generating toxic by-products contributes to systemic inflammation and the associated complications. On the other hand, emerging evidence points to the role of the gut microbiota in the development and progression of CKD by provoking inflammation, proteinuria, hypertension, and diabetes. These observations demonstrate the causal interconnection between the gut microbial dysbiosis and CKD. The gut microbiota closely interacts with the inflammatory, renal, cardiovascular, and endocrine systems via metabolic, humoral, and neural signaling pathways, events which can lead to chronic systemic inflammation, proteinuria, hypertension, diabetes, and kidney disease. Given the established role of the gut microbiota in the development and progression of CKD and its complications, favorable modification of the composition and function of the gut microbiome represents an appealing therapeutic target for prevention and treatment of CKD. This review provides an overview of the role of the gut microbial dysbiosis in the pathogenesis of the common causes of CKD including hypertension, diabetes, and proteinuria as well as progression of CKD.

Mind body therapies in rehabilitation of patients with rheumatic diseases.

PubMed

Del Rosso, Angela; Maddali-Bongi, Susanna

2016-02-01

Mind body therapies (MBT) share a global approach involving both mental and physical dimensions, and focus on relationship between brain, mind, body and behavior and their effects on health and disease. MBT include concentration based therapies and movement based therapies, comprising traditional Oriental practices and somatic techniques. The greatest part of rheumatic diseases have a chronic course, leading to progressive damages at musculoskeletal system and causing physical problems, psychological and social concerns. Thus, rheumatic patients need to be treated with a multidisciplinary approach integrating pharmacological therapies and rehabilitation techniques, that not should only aim to reduce the progression of damages at musculoskeletal system. Thus, MBT, using an overall approach, could be useful in taking care of the overall health of the patients with chronic rheumatic diseases. This review will deal with different MBT and with their effects in the most common chronic rheumatic diseases (Rheumatoid Arthritis, Ankylosing Spondylitis, Fibromyalgia Syndrome). Copyright © 2015. Published by Elsevier Ltd.

Clinical Manifestations and the Natural History of HIV Infection in Adults

PubMed Central

Piot, Peter; Colebunders, Robert

1987-01-01

The clinical expression of infection with the human immunodeficiency virus (HIV) appears increasingly complex. It includes manifestations due to opportunistic diseases, as well as illness directly caused by HIV itself. Neurologic disease may include involvement of the brain, spinal cord and peripheral nerves and is probably directly caused by HIV, as is lymphocytic interstitial pneumonia. The etiology of the chronic diarrhea and a papular pruritic skin eruption associated with HIV infection is unclear. Between 2% and 8% of HIV-infected persons progress to the acquired immunodeficiency syndrome (AIDS) per year, with no apparent decrease in the rate of disease progression over time. A chronically activated state secondary to chronic microbial antigenic exposure may increase both the susceptibility to HIV infection and development of disease. Increased HIV gene expression, followed by persistent antigenemia, appear to be triggering factors in clinical deterioration. The role, if any, of environmental and/or genetic cofactors remains unclear. Images PMID:3433753

Indian chronic kidney disease study: Design and methods.

PubMed

Kumar, Vivek; Yadav, Ashok Kumar; Gang, Sishir; John, Oommen; Modi, Gopesh K; Ojha, Jai Prakash; Pandey, Rajendra; Parameswaran, Sreejith; Prasad, Narayan; Sahay, Manisha; Varughese, Santosh; Baid-Agarwal, Seema; Jha, Vivekanand

2017-04-01

The rate and factors that influence progression of chronic kidney disease (CKD) in developing countries like India are unknown. A pan-country prospective, observational cohort study is needed to address these knowledge gaps. The Indian Chronic Kidney Disease (ICKD) study will be a cohort study of approximately 5000 patients with mild to moderate CKD presenting to centres that represent different geographical regions in India. Time to 50% decline in baseline estimated glomerular filtration rate, need of renal replacement therapy or any new cardiovascular disease (CVD) event or death from CVD are the primary end points. This study will provide the opportunity to determine risk factors for CKD progression and development of CVD in Indian subjects and perform international comparisons to determine ethnic and geographical differences. A bio-repository will provide a chance to discover biomarkers and explore genetic risk factors. © 2016 Asian Pacific Society of Nephrology.

Sirtuin 1 and aging theory for chronic obstructive pulmonary disease.

PubMed

Conti, V; Corbi, G; Manzo, V; Pelaia, G; Filippelli, A; Vatrella, A

2015-01-01

Chronic Obstructive Pulmonary disease (COPD) is an inflammatory syndrome that represents an increasing health problem, especially in the elderly population. Drug therapies are symptomatic and inadequate to contrast disease progression and mortality. Thus, there is an urgent need to clarify the molecular mechanisms responsible for this condition in order to identify new biomarkers and therapeutic targets. Processes including oxidant/antioxidant, protease/antiprotease, and proliferative/antiproliferative balance and control of inflammatory response become dysfunctional during aging as well as in COPD. Recently it was suggested that Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to oxidative stress and chronic inflammation, is implicated in both development and progression of COPD. The present review focuses on the involvement of SIRT1 in the regulation of redox state, inflammation, and premature senescence, all crucial characteristics of COPD phenotypes. Recent evidence corroborating the statement of the "aging theory for COPD" was also discussed.

[Effectiveness of fenspiride in patients with chronic obstructive bronchitis].

PubMed

Shorokhova, T D; Medvedeva, I V; Lapik, S V; Solov'eva, O G; Gracheva, E Iu; Iusupova, R S

2001-01-01

Patients with chronic obstructive pulmonary disease of moderate severity were investigated for two months for assessment of fenspiride activity. Examination of the patients (age 42.6 +/- 5.3) took place before and after fenspiride therapy. In comparison to the control group, fenspiride patients showed improvement of external respiration function: FEV 1, FVC, FEF 50-75, PEF increased. Dienic conjugates, malonic dialdehyde levels decreased, alpha-tocopherol in platelet membranes rose, functional activity of platelets fell. Side effects were rare and not serious. It is concluded that fenspiride has an antiinflammatory effect, reduces bronchoconstriction and depresses platelet aggregation, is well tolerated. Fenspiride is an effective drug for the treatment of moderate chronic obstructive bronchitis.

Treatment of Recurrent Eczematous External Otitis with Honey Eardrops: A Proof-of-Concept Study.

PubMed

Henatsch, Darius; Nabuurs, Cindy H; van de Goor, Rens M; Wolffs, Petra F; Stokroos, Robert J

2017-10-01

Eczematous external otitis is a chronic inflammatory disease and often difficult to treat. Our objective was to investigate the clinical effect and in vitro antibacterial potential of medical honey eardrops as treatment of eczematous external otitis. In a prospective study, 15 patients diagnosed with recurrent eczematous external otitis were treated with medical honey eardrops for 2 weeks. The following clinical outcomes were evaluated: visual analog scale of ear complaints, score of eczema, and eradication of bacterial infection. Furthermore, the antibacterial effect of honey eardrops against different bacterial strains was tested in vitro. Treatment resulted in less discomfort and itching and decreased signs of eczema, with high patient satisfaction and without adverse reactions. Honey eardrops showed a strong in vitro inhibitory activity against all tested strains but did not eradicate Staphylococcus aureus infection in vivo. The results of this preliminary study indicate a possible role of honey eardrops in eczematous ear disease.

Evidence for the presence of an autoimmune component to the chronic muscle wasting disease characteristic of calves infected with Aarcocystis cruzi

USDA-ARS?s Scientific Manuscript database

Infection with Sarcocystis spp. often resolves in a progressive decline in muscle integrity. The underlying cause for this has remained undetermined. Previously, we described the presence of proinflammatory muscle protein nitration (PMPN) in calves (ScI) chronically infected with Sarcocystis cruzi. ...

Dietary vitamin K and therapeutic warfarin alter susceptibility to vascular calcification in experimental chronic kidney disease

USDA-ARS?s Scientific Manuscript database

The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease (CVD), with vascular calcification (VC) being a key modifier of disease progression. A local regulator of vascular calcification is vitamin K. This gamma-glutamyl carboxylase substrate is an essential ...

Cytogenetic damage analysis in mice chronically exposed to low-dose internal tritium beta-particle radiation.

PubMed

Roch-Lefèvre, Sandrine; Grégoire, Eric; Martin-Bodiot, Cécile; Flegal, Matthew; Fréneau, Amélie; Blimkie, Melinda; Bannister, Laura; Wyatt, Heather; Barquinero, Joan-Francesc; Roy, Laurence; Benadjaoud, Mohamed; Priest, Nick; Jourdain, Jean-René; Klokov, Dmitry

2018-06-08

The aim of this study was to carry out a comprehensive examination of potential genotoxic effects of low doses of tritium delivered chronically to mice and to compare these effects to the ones resulting from equivalent doses of gamma-irradiation. Mice were chronically exposed for one or eight months to either tritiated water (HTO) or organically bound tritium (OBT) in drinking water at concentrations of 10 kBq/L, 1 MBq/L or 20 MBq/L. Dose rates of internal β-particle resulting from such tritium treatments were calculated and matching external gamma-exposures were carried out. We measured cytogenetic damage in bone marrow and in peripheral blood lymphocytes (PBLs) and the cumulative tritium doses (0.009 - 181 mGy) were used to evaluate the dose-response of OBT in PBLs, as well as its relative biological effectiveness (RBE). Neither tritium, nor gamma exposures produced genotoxic effects in bone marrow. However, significant increases in chromosome damage rates in PBLs were found as a result of chronic OBT exposures at 1 and 20 M Bq/L, but not at 10 kBq/L. When compared to an external acute gamma-exposure ex vivo , the RBE of OBT for chromosome aberrations induction was evaluated to be significantly higher than 1 at cumulative tritium doses below 10 mGy. Although found non-existent at 10 kBq/L (the WHO limit), the genotoxic potential of low doses of tritium (>10 kBq/L), mainly OBT, may be higher than currently assumed.

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.

Chronic headache and potentially modifiable risk factors: screening and behavioral management of sleep disorders.

PubMed

Rains, Jeanetta C

2008-01-01

Sleep-related variables have been identified among risk factors for frequent and severe headache conditions. It has been postulated that migraine, chronic daily headache, and perhaps other forms of chronic headache are progressive disorders. Thus, sleep and other modifiable risk factors may be clinical targets for prevention of headache progression or chronification. The present paper is part of the special series of papers entitled "Chronification of Headache" describing the empirical evidence, future research directions, proposed mechanisms, and risk factors implicated in headache chronification as well as several papers addressing individual risk factors (ie, sleep disorders, medication overuse, psychiatric disorders, stress, obesity). Understanding the link between risk factors and headache may yield novel preventative and therapeutic approaches in the management of headache. The present paper in the special series reviews epidemiological research as a means of quantifying the relationship between chronic headache and sleep disorders (sleep-disordered breathing, insomnia, circadian rhythm disorders, parasomnias) discusses screening for early detection and treatment of more severe and prevalent sleep disorders, and discusses fundamental sleep regulation strategies aimed at headache prevention for at-risk individuals.

Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages

PubMed Central

Stout, Robert D.; Watkins, Stephanie K.; Suttles, Jill

2009-01-01

The extent to which the functional heterogeneity of Mϕs is dependent on the differentiation of functional sublineages remains unresolved. One alternative hypothesis proposes that Mϕs are functionally plastic cells, which are capable of altering their functional activities progressively in response to progressively changing signaling molecules generated in their microenvironment. This “functional plasticity” hypothesis predicts that the functionally polarized Mϕs in chronic pathologies do not represent Mϕ sublineages but rather, are mutable phenotypes sustained by chronic signaling from the pathological environment. Solid TAMϕs are chronically polarized to provide activities that support tumor growth and metastasis and suppress adaptive immune responses. In support of the functional plasticity hypothesis, administration of slow-release microsphere-encapsulated IL-12 successfully reprogrammed TAMϕs in situ, reducing Mϕ support of tumor growth and metastasis and enhancing Mϕ proimmunogenic activities. Increased knowledge of how Mϕ function is regulated and how polarized Mϕs can be reprogrammed in situ will increase our ability to control Mϕ function in a variety of pathological states, including cancer and chronic inflammatory disease. PMID:19605698

Recent Progress in Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia.

PubMed

Dao, Kim-Hien T; Tyner, Jeffrey W; Gotlib, Jason

2017-10-01

We reviewed recent diagnostic and therapeutic progress in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). We summarized recent genetic data that may guide future efforts towards implementing risk-adapted therapy based on mutational profile and improving disease control and survival of affected patients. Recent genetic data in CNL and aCML prompted modifications to the World Health Organization (WHO) diagnostic criteria, which have improved our understanding of how CNL and aCML are different diseases despite sharing common findings of peripheral granulocytosis and marrow myeloid hyperplasia. The overlap of recurrently mutated genes between aCML and CMML support considering CSF3R-T618I mutated cases as a distinct entity, either as CNL or CNL with dysplasia. Ongoing preclinical and clinical studies will help to further inform the therapeutic approach to these diseases. Our understanding of CNL and aCML has greatly advanced over the last few years. This will improve clarity for the diagnosis of these diseases, provide a strategy for risk stratification, and guide risk-adapted therapy.

Chronic Chagas cardiomyopathy: a review of the main pathogenic mechanisms and the efficacy of aetiological treatment following the BENznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial.

PubMed

Rassi, Anis; Marin, José Antonio; Rassi, Anis

2017-03-01

Chagas cardiomyopathy is the most frequent and most severe manifestation of chronic Chagas disease, and is one of the leading causes of morbidity and death in Latin America. Although the pathogenesis of Chagas cardiomyopathy is incompletely understood, it may involve several mechanisms, including parasite-dependent myocardial damage, immune-mediated myocardial injury (induced by the parasite itself and by self-antigens), and microvascular and neurogenic disturbances. In the past three decades, a consensus has emerged that parasite persistence is crucial to the development and progression of Chagas cardiomyopathy. In this context, antiparasitic treatment in the chronic phase of Chagas disease could prevent complications related to the disease. However, according to the results of the BENEFIT trial, benznidazole seems to have no benefit for arresting disease progression in patients with chronic Chagas cardiomyopathy. In this review, we give an update on the main pathogenic mechanisms of Chagas disease, and re-examine and discuss the results of the BENEFIT trial, together with its limitations and implications.

Antagonism of scavenger receptor CD36 by 5A peptide prevents chronic kidney disease progression in mice independent of blood pressure regulation

PubMed Central

Souza, Ana Carolina P.; Bocharov, Alexander V.; Baranova, Irina; Vishnyakova, Tatyana; Huang, Yuning G.; Wilkins, Kenneth J.; Hu, Xuzhen; Street, Jonathan M.; Alvarez-Prats, Alejandro; Mullick, Adam E.; Patterson, Amy P.; Remaley, Alan; Eggerman, Thomas L.; Yuen, Peter S.T.; Star, Robert A.

2016-01-01

Scavenger receptor CD36 participates in lipid metabolism and inflammatory pathways important for cardiovascular disease and chronic kidney disease (CKD). Few pharmacological agents are available to slow the progression of CKD. However, apolipoprotein AI-mimetic peptide 5A antagonizes CD36 in vitro. To test the efficacy of 5A, and to test the role of CD36 during CKD, we compared wild type to CD36 knockout mice and wild type mice treated with 5A, in a progressive CKD model that resembles human disease. Knockout and 5A-treated wild type mice were protected from CKD progression without changes in blood pressure and had reductions in cardiovascular risk surrogate markers that are associated with CKD. Treatment with 5A did not further protect CD36 knockout mice from CKD progression, implicating CD36 as its main site of action. In a separate model of kidney fibrosis, 5A-treated wild type mice had less macrophage infiltration and interstitial fibrosis. Peptide 5A exerted anti-inflammatory effects in the kidney and decreases renal expression of inflammasome genes. Thus, CD36 is a new therapeutic target for CKD and its associated cardiovascular risk factors. Peptide 5A may be a promising new agent to slow CKD progression. PMID:26994575

Indagation of serum and salivary reactive oxygen metabolite and cortisol levels in chronic periodontitis and stress-induced chronic periodontitis patients.

PubMed

Sudhakar, Uma; Thyagarajan, Ramakrishnan; Jeyapal, Bhagyameena; Jagadeesh, Sushuruthi; Jayakumar, Parvathee

2017-01-01

Periodontal disease is not a conventional bacterial infection but is an inflammatory disease initiated by immune response against a group of microorganisms in susceptible hosts. There are many intriguing researches that unfold the secrets of chronic periodontitis. The current researches in chronic periodontitis are directed toward an approach that respects the scientific relationship between the various risk factors, the genetic factors, and the progression of the disease. This study aims to evaluate the cortisol and reactive oxygen metabolites (ROM) concentration in serum and to find out their association in periodontal health and disease. In this study, totally thirty patients have been taken and divided into two groups of chronic periodontitis (Group I) and stress-induced chronic periodontitis (Group II) and evaluated the correlation between the ROM and cortisol levels in them. This is the first study, where both the levels of ROM and cortisol are checked in the serum and saliva. The analysis is done to check the association between them. The data were statistically analyzed using software program (SPSSV 16), Pearson correlation, and paired t -test. Comparison of the mean ROM levels in Group I and Group II showed that mean ROM level in Group II is highly significant than Group I. Our study suggests that stress can have a role in the progression of periodontal disease by increasing the cortisol and ROM levels.

Chronic pancreatitis.

PubMed

Kleeff, Jorg; Whitcomb, David C; Shimosegawa, Tooru; Esposito, Irene; Lerch, Markus M; Gress, Thomas; Mayerle, Julia; Drewes, Asbjørn Mohr; Rebours, Vinciane; Akisik, Fatih; Muñoz, J Enrique Domínguez; Neoptolemos, John P

2017-09-07

Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma.

PubMed

Wu, Ji-Hong; Zhang, Sheng-Hai; Nickerson, John M; Gao, Feng-Juan; Sun, Zhongmou; Chen, Xin-Ya; Zhang, Shu-Jie; Gao, Feng; Chen, Jun-Yi; Luo, Yi; Wang, Yan; Sun, Xing-Huai

2015-02-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Using Baseline Data to Predict Chronic PTSD 48-months After Mothers Report Intimate Partner Violence: Outcomes for Mothers and the Intergenerational Impact on Child Behavioral Functioning.

PubMed

Maddoux, John; McFarlane, Judith; Symes, Lene; Fredland, Nina; Feder, Gene

2018-06-01

Worldwide one in three women report intimate partner violence. Many of these women report long term mental health problems, especially PTSD, which is associated with negative problem solving, isolation, somatization, depression, and anxiety. Children are impacted by their exposure to domestic violence and experience internal (i.e., depression, anxiety) and external (i.e., hostility, delinquency) behavioral clinical problems. To predict which women will experience chronic PTSD symptoms, a PTSD predictor tool was developed and applied to PTSD symptom scores four years after 300 mothers with children (age 18 months to 16 years) received assistance for the violence. At four years, 266 (89%) of the 300 mother child dyads were retained. Of those, 245 met inclusion criteria for this study and 53% had scores above the clinical threshold for PTSD. The predictor tool performed well. There was a significant association, χ 2 (4) = 11.83, p = .019, Cramer's V = 0.229, between mothers predicted at low/some risk for chronic PTSD and scoring below the cut-off score for diagnostic PTSD symptoms at four years. Mothers predicted to be at extreme risk for chronic PTSD reported PTSD symptoms at or above the diagnostic level at 48 months. Children whose mothers had PTSD were at greater risk for Borderline/Clinical range behavioral problems compared to children whose mothers did not have PTSD. Relative risk values ranged from 2.07 (Externalizing) to 2.30 (Internalizing). When appropriate interventions are available, the PTSD predictor tool can assist with triage and guided referral of women at risk for chronic PTSD. Copyright © 2018. Published by Elsevier Inc.

[Research on the application of "H shaped" single-tube double-lumen drainage tube in the treatment of chronic subdural hematoma].

PubMed

Sun, T; Jiang, Z Q; Zhang, S J; Lou, F Y; Zhang, T; Han, Y; Zheng, X L

2016-04-05

To explore the effect of chronic subdural hematoma external drainage surgery using self-made "H shaped" flush type single-tube double-lumen drainage tube. There were 56 cases chosen from the First Affiliated Hospital of Bengbu Medical College between Jan 2013 and Aug 2015. These patients with unilateral chronic subdural hematoma requiring surgery to place drilling external drainage catheter were randomly divided into group A (21 cases, using self-made single-tube double lumen "H shaped" drainage tube) and group B (35 cases, traditional silicone drainage tube), then the residual liquid volume after drainage on the first day, the days that the tube stay in body and the residual fluid volume after removing the tube were compared between the two groups. The residual liquid volume after drainage on the first day in group A was (23±15)ml, in group B was (31±15)ml. The days that the tube stay in body in group A was (2.7±1.0)d, in group B was (3.3±1.1)d, the two groups had statistical differences (P<0.05). The residual fluid volume after removing the tube in group A was (13±7) ml, in group B was (16±8)ml, but the data in these two groups had no significantly statistical differences (P>0.05). The effect of self-made "H shaped" flush type single-tube double-lumen drainage tube in the drainage of chronic subdural hematoma drainage is good, with short tube stay in the body; therefore, it is a safe and effective way to treat chronic subdural hematoma, and is worthy of clinical application.

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.

Inspiratory muscle training in patients with chronic obstructive pulmonary disease: structural adaptation and physiologic outcomes.

PubMed

Ramirez-Sarmiento, Alba; Orozco-Levi, Mauricio; Guell, Rosa; Barreiro, Esther; Hernandez, Nuria; Mota, Susana; Sangenis, Merce; Broquetas, Joan M; Casan, Pere; Gea, Joaquim

2002-12-01

The present study was aimed at evaluating the effects of a specific inspiratory muscle training protocol on the structure of inspiratory muscles in patients with chronic obstructive pulmonary disease. Fourteen patients (males, FEV1, 24 +/- 7% predicted) were randomized to either inspiratory muscle or sham training groups. Supervised breathing using a threshold inspiratory device was performed 30 minutes per day, five times a week, for 5 consecutive weeks. The inspiratory training group was subjected to inspiratory loading equivalent to 40 to 50% of their maximal inspiratory pressure. Biopsies from external intercostal muscles and vastus lateralis (control muscle) were taken before and after the training period. Muscle samples were processed for morphometric analyses using monoclonal antibodies against myosin heavy chain isoforms I and II. Increases in both the strength and endurance of the inspiratory muscles were observed in the inspiratory training group. This improvement was associated with increases in the proportion of type I fibers (by approximately 38%, p < 0.05) and in the size of type II fibers (by approximately 21%, p < 0.05) in the external intercostal muscles. No changes were observed in the control muscle. The study demonstrates that inspiratory training induces a specific functional improvement of the inspiratory muscles and adaptive changes in the structure of external intercostal muscles.

Reversible phospho-Smad3 signalling between tumour suppression and fibrocarcinogenesis in chronic hepatitis B infection.

PubMed

Deng, Y-R; Yoshida, K; Jin, Q L; Murata, M; Yamaguchi, T; Tsuneyama, K; Moritoki, Y; Niu, J Q; Matsuzaki, K; Lian, Z-X

2014-04-01

Transforming growth factor (TGF)-β, type I receptor (TβRI) and c-Jun N-terminal kinases (JNK) phosphorylate Smad3 differentially to create 2 isoforms phosphorylated (p) at the COOH-terminus (C) or at the linker region (L) and regulate hepatocytic fibrocarcinogenesis. This study aimed to compare the differences between how hepatitis B virus (HBV) infection affected hepatocytic Smad3 phosphorylated isoforms before and after anti-viral therapy. To clarify the relationship between Smad3 phosphorylation and liver disease progression, we studied 10 random patients in each stage of HBV-related fibrotic liver disease (F1-4) and also 10 patients with HBV-associated HCC. To examine changes in phosphorylated Smad3 signalling before and after anti-HBV therapies, we chose 27 patients with chronic hepatitis B who underwent baseline and follow-up biopsies at 52 weeks from the start of nucleoside analogue treatments (Lamivudine 100 mg daily or Telbivudine 600 mg daily). Fibrosis stage, inflammatory activity and phosphorylated Smad3 positivity in the paired biopsy samples were compared. Hepatocytic pSmad3C signalling shifted to fibrocarcinogenic pSmad3L signalling as the livers progressed from chronic hepatitis B infection to HCC. After nucleoside analogue treatment, serum alanine aminotransferase (ALT) and HBV-DNA levels in 27 patients with HBV-related chronic liver diseases were decreased dramatically. Decrease in HBV-DNA restored pSmad3C signalling in hepatocytes, while eliminating prior fibrocarcinogenic pSmad3L signalling. Oral nucleoside analogue therapies can suppress fibrosis and reduce HCC incidence by successfully reversing phosphorylated Smad3 signalling; even liver disease progressed to cirrhosis in chronic hepatitis B patients. © 2013 British Society for Immunology.

Endothelin-A receptor blockade slows the progression of renal injury in experimental renovascular disease.

PubMed

Kelsen, Silvia; Hall, John E; Chade, Alejandro R

2011-07-01

Endothelin (ET)-1, a potent renal vasoconstrictor with mitogenic properties, is upregulated by ischemia and has been shown to induce renal injury via the ET-A receptor. The potential role of ET-A blockade in chronic renovascular disease (RVD) has not, to our knowledge, been previously reported. We hypothesized that chronic ET-A receptor blockade would preserve renal hemodynamics and slow the progression of injury of the stenotic kidney in experimental RVD. Renal artery stenosis, a major cause of chronic RVD, was induced in 14 pigs and observed for 6 wk. In half of the pigs, chronic ET-A blockade was initiated (RVD+ET-A, 0.75 mg·kg(-1)·day(-1)) at the onset of RVD. Single-kidney renal blood flow, glomerular filtration rate, and perfusion were quantified in vivo after 6 wk using multidetector computer tomography. Renal microvascular density was quantified ex vivo using three-dimensional microcomputer tomography, and growth factors, inflammation, apoptosis, and fibrosis were determined in renal tissue. The degree of stenosis and increase in blood pressure were similar in RVD and RVD+ET-A pigs. Renal hemodynamics, function, and microvascular density were decreased in the stenotic kidney but preserved by ET-A blockade, accompanied by increased renal expression of vascular endothelial growth factor, hepatocyte growth factor, and downstream mediators such as phosphorilated-Akt, angiopoietins, and endothelial nitric oxide synthase. ET-A blockade also reduced renal apoptosis, inflammation, and glomerulosclerosis. This study shows that ET-A blockade slows the progression of renal injury in experimental RVD and preserves renal hemodynamics, function, and microvascular density in the stenotic kidney. These results support a role for ET-1/ET-A as a potential therapeutic target in chronic RVD.

Endothelin-A receptor blockade slows the progression of renal injury in experimental renovascular disease

PubMed Central

Kelsen, Silvia; Hall, John E.

2011-01-01

Endothelin (ET)-1, a potent renal vasoconstrictor with mitogenic properties, is upregulated by ischemia and has been shown to induce renal injury via the ET-A receptor. The potential role of ET-A blockade in chronic renovascular disease (RVD) has not, to our knowledge, been previously reported. We hypothesized that chronic ET-A receptor blockade would preserve renal hemodynamics and slow the progression of injury of the stenotic kidney in experimental RVD. Renal artery stenosis, a major cause of chronic RVD, was induced in 14 pigs and observed for 6 wk. In half of the pigs, chronic ET-A blockade was initiated (RVD+ET-A, 0.75 mg·kg−1·day−1) at the onset of RVD. Single-kidney renal blood flow, glomerular filtration rate, and perfusion were quantified in vivo after 6 wk using multidetector computer tomography. Renal microvascular density was quantified ex vivo using three-dimensional microcomputer tomography, and growth factors, inflammation, apoptosis, and fibrosis were determined in renal tissue. The degree of stenosis and increase in blood pressure were similar in RVD and RVD+ET-A pigs. Renal hemodynamics, function, and microvascular density were decreased in the stenotic kidney but preserved by ET-A blockade, accompanied by increased renal expression of vascular endothelial growth factor, hepatocyte growth factor, and downstream mediators such as phosphorilated-Akt, angiopoietins, and endothelial nitric oxide synthase. ET-A blockade also reduced renal apoptosis, inflammation, and glomerulosclerosis. This study shows that ET-A blockade slows the progression of renal injury in experimental RVD and preserves renal hemodynamics, function, and microvascular density in the stenotic kidney. These results support a role for ET-1/ET-A as a potential therapeutic target in chronic RVD. PMID:21478482

Dietary Metabolites and Chronic Kidney Disease.

PubMed

Hasegawa, Sho; Jao, Tzu-Ming; Inagi, Reiko

2017-04-04

Dietary contents and their metabolites are closely related to chronic kidney disease (CKD) progression. Advanced glycated end products (AGEs) are a type of uremic toxin produced by glycation. AGE accumulation is not only the result of elevated glucose levels or reduced renal clearance capacity, but it also promotes CKD progression. Indoxyl sulfate, another uremic toxin derived from amino acid metabolism, accumulates as CKD progresses and induces tubulointerstitial fibrosis and glomerular sclerosis. Specific types of amino acids (d-serine) or fatty acids (palmitate) are reported to be closely associated with CKD progression. Promising therapeutic targets associated with nutrition include uremic toxin absorbents and inhibitors of AGEs or the receptor for AGEs (RAGE). Probiotics and prebiotics maintain gut flora balance and also prevent CKD progression by enhancing gut barriers and reducing uremic toxin formation. Nrf2 signaling not only ameliorates oxidative stress but also reduces elevated AGE levels. Bardoxolone methyl, an Nrf2 activator and NF-κB suppressor, has been tested as a therapeutic agent, but the phase 3 clinical trial was terminated owing to the high rate of cardiovascular events. However, a phase 2 trial has been initiated in Japan, and the preliminary analysis reveals promising results without an increase in cardiovascular events.

Dietary Metabolites and Chronic Kidney Disease

PubMed Central

Hasegawa, Sho; Jao, Tzu-Ming; Inagi, Reiko

2017-01-01

Dietary contents and their metabolites are closely related to chronic kidney disease (CKD) progression. Advanced glycated end products (AGEs) are a type of uremic toxin produced by glycation. AGE accumulation is not only the result of elevated glucose levels or reduced renal clearance capacity, but it also promotes CKD progression. Indoxyl sulfate, another uremic toxin derived from amino acid metabolism, accumulates as CKD progresses and induces tubulointerstitial fibrosis and glomerular sclerosis. Specific types of amino acids (d-serine) or fatty acids (palmitate) are reported to be closely associated with CKD progression. Promising therapeutic targets associated with nutrition include uremic toxin absorbents and inhibitors of AGEs or the receptor for AGEs (RAGE). Probiotics and prebiotics maintain gut flora balance and also prevent CKD progression by enhancing gut barriers and reducing uremic toxin formation. Nrf2 signaling not only ameliorates oxidative stress but also reduces elevated AGE levels. Bardoxolone methyl, an Nrf2 activator and NF-κB suppressor, has been tested as a therapeutic agent, but the phase 3 clinical trial was terminated owing to the high rate of cardiovascular events. However, a phase 2 trial has been initiated in Japan, and the preliminary analysis reveals promising results without an increase in cardiovascular events. PMID:28375181

Cumulative adversity in childhood and emergent risk factors for long-term health.

PubMed

Slopen, Natalie; Koenen, Karestan C; Kubzansky, Laura D

2014-03-01

To examine whether and when effects of cumulative adversity in the first 7 years of life are evident in relation to 3 childhood markers of risk for poor adult physical health. The study data are from an English birth cohort. Parental reports of 8 social risk factors were obtained during the child's first 7 years, and scores were created to reflect cumulative adversity at 4 developmental periods. At age 7 and 11 years, weight, height, and blood pressure (BP) were measured by clinic staff, and caregivers reported behavior problems. Linear regression was used to estimate associations of cumulative adversity with each outcome (n = 4361) and changes in these outcomes between 7 and 11 years (n = 3348). At age 7 years, mean adversity and chronic exposure to high adversity were associated with elevated body mass index (BMI) and internalizing and externalizing symptoms (P < .05), but not elevated BP. Adversity in all developmental periods was associated with elevated numbers of internalizing and externalizing symptoms (P < .0001), but associations were less robust for BMI. Adversity did not predict change in BMI or BP between age 7 and 11 years, however, it predicted increases in internalizing and externalizing symptoms (P < .0001). Cumulative adversity was associated with BMI and behavior problems at age 7 years, and our data indicate that timing and chronicity of exposure to adversity differentially influence diverse indicators of long-term health risk commonly measured in childhood. This research suggests the hypothesis that interventions to address adversity could reduce the development of multiple chronic disease risk factors and limit their effects on health. Copyright © 2014 Mosby, Inc. All rights reserved.

‘Elastic band strategy’: women's lived experiences of coping with domestic violence in rural Indonesia

PubMed Central

Hayati, Elli Nur; Eriksson, Malin; Hakimi, Mohammad; Högberg, Ulf; Emmelin, Maria

2013-01-01

Background Experiencing domestic violence is considered a chronic and stressful life event. A theoretical framework of coping strategies can be used to understand how women deal with domestic violence. Traditional values strongly influenced by religious teachings that interpret men as the leaders of women play an important role in the lives of Javanese women, where women are obliged to obey their husbands. Little is known about how sociocultural and psychosocial contexts influence the ways in which women cope with domestic violence. Objective Our study aimed to deepen our understanding of how rural Javanese women cope with domestic violence. Our objective was to explore how the sociocultural context influences coping dynamics of women survivors of domestic violence in rural Purworejo. Design A phenomenological approach was used to transform lived experiences into textual expressions of the coping dynamics of women survivors of domestic violence. Results Experiencing chronic violence ruined the women's personal lives because of the associated physical, mental, psychosocial, and financial impairments. These chronic stressors led women to access external and internal resources to form coping strategies. Both external and internal factors prompted conflicting impulses to seek support, that is, to escape versus remain in the relationship. This strong tension led to a coping strategy that implied a long-term process of moving between actively opposing the violence and surrendering or tolerating the situation, resembling an elastic band that stretches in and out. Conclusions Women survivors in Purworejo face a lack of institutional support and tend to have traditional beliefs that hamper their potential to stop the abuse. Although the women in this study were educated and economically independent, they still had difficulty mobilizing internal and external support to end the abuse, partly due to internalized gender norms. PMID:23336615

Neurocognitive performance and physical function do not change with physical-cognitive-mindfulness training in female laboratory technicians with chronic musculoskeletal pain

PubMed Central

Jay, Kenneth; Brandt, Mikkel; Schraefel, mc; Jakobsen, Markus Due; Sundstrup, Emil; Sjøgaard, Gisela; Vinstrup, Jonas; Andersen, Lars L.

2016-01-01

Abstract Background: Cognitive and physical performance can be negatively affected by chronic pain. This study evaluates the effect of combined physical-, cognitive-, and mindfulness training (PCMT) on cognitive and physical performance. Methods: From a large pharmaceutical company in Denmark we randomly allocated 112 female laboratory technicians with chronic upper limb pain to group-based PCMT at the worksite or a reference group for 10 weeks. Neurocognitive performance was measured by the computerized central nervous system vital signs neurocognitive assessment battery. Physical function was assessed in terms of shoulder external rotation strength and rate of force development in a custom-made dynamometer setup. Results: No between-group differences (least square means [95% confidence interval]) from baseline to follow-up could be detected in any of the neurocognitive domains as measured by the central nervous system vital signs neurocognitive assessment battery, for example, Psychomotoer Speed 1.9 (−1.0 to 4.7), Reaction Time −4.0 (−19.5 to 11.6), Complex Attention −0.3 (−1.9 to 1.4), and Executive Function −0.2 (−3.5 to 3.0). Similarly, we found no change in maximal voluntary isometric strength −0.63 (−4.8 to 3.6), or rate of force development 14.8 (−12.6 to 42.2) of the shoulder external rotators. Finally, test–retest reliability of maximal voluntary contraction and rate of force development shoulder external rotation showed high reliability at 0 to 30 ms, 0 to 50 ms, 0 to 100 ms, and 0 to 200 ms with ICCs at 0.95, 0.92, 0.93, 0.92, and 0.91, respectively. Conclusion: Ten weeks of PCMT did not improve neurocognitive or physical performance. PMID:27977585

[Latex ligation in treatment of chronic hemorrhoids].

PubMed

Ektov, V N; Somov, K A

2015-01-01

We analyzed the results of treatment of 432 patients with chronic hemorrhoids using different variants of latex ligation. New technique including ligation of mucosa and submucosa of low-ampullar rectum providing ligation of hemorrhoidalvessels, lifting and recto-anal repair is developed and suggested. This method is advisable to use in case of chronic internal hemorrhoids stages I and II. The authors recommend simultaneous combined ligation of mucosa of low-ampullar rectum and internal hemorrhoids for stages III and IV. Different variants of latex ligation with external hemorrhoids excision were used in 103 patients. Pointed variants of latex ligation preserve important advantages including mini-invasiveness, simplicity and wide availability, low cost. Good remote results were obtained after these procedures in 87.3% of observations. Suggested tactics extends use of latex ligation and increases its effectiveness in treatment of different stages and forms of chronic hemorrhoids.

Does low-dose prolonged steroid therapy affect the natural history of chronic hepatitis C?

PubMed

Romero Gutiérrez, Marta; del Campo Terrón, Santos; Moreno Zamora, Ana; Sánchez Ruano, Juan José; Artaza Varasa, Tomás; Bárcena Marugán, Rafael

2014-05-01

Chronic hepatitis C patients may require steroids due to other comorbidities. However, there is not enough information to consider steroids as beneficial or harmful drugs on natural history of chronic hepatitis C. The aim of the present study was to examine the effect of low-dose prolonged therapy with corticosteroids with or without azathioprine on these study patients. A retrospective-prospective observational study was established. Twenty-eight patients with chronic hepatitis C and treated with corticosteroids at low-dose (≤30 mg/day) with or without azathioprine for more than 6 months were included. AST, ALT, HCV RNA, and liver fibrosis were determined, and results were compared with a control group of non-treated chronic hepatitis C patients. The mean age was 47 ± 10 years. The male proportion was 43%. The mean dose of prednisone was 9 ± 5 mg/day (range: 2.5-30 mg/day). The mean treatment time was 76 ± 80 months (range: 7-349 months). Thirty six percent received concomitant azathioprine. Transaminases decreased significantly only within the first 3 months of treatment, with non-significant changes thereafter. Corticosteroids led to a non-significant increase in HCV RNA. Knodell Histology Activity Index decreased (from 8.5 ± 3.7 to 4.7 ± 1.7; P = 0.1). Fibrosis progression per year (final fibrosis stage-initial fibrosis stage/time between explorations, in years), was lower in treated cases than in control group (0.054 ± 0.25 units vs. 0.196 ± 0.6 units, P = 0.26). In conclusion, corticosteroid treatment caused a significant initial decrease in transaminases, non-significant changes in HCV RNA, and a trend to a slower fibrosis progression in comparison to a control group. Therefore, corticosteroids did not accelerate progression of chronic hepatitis C. © 2014 Wiley Periodicals, Inc.

Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group

PubMed Central

Winqvist, Maria; Asklid, Anna; Andersson, PO; Karlsson, Karin; Karlsson, Claes; Lauri, Birgitta; Lundin, Jeanette; Mattsson, Mattias; Norin, Stefan; Sandstedt, Anna; Hansson, Lotta; Österborg, Anders

2016-01-01

Ibrutinib, a Bruton’s tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine health-care are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy ≥10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression-free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richter’s transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia. PMID:27198718

Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group.

PubMed

Winqvist, Maria; Asklid, Anna; Andersson, P O; Karlsson, Karin; Karlsson, Claes; Lauri, Birgitta; Lundin, Jeanette; Mattsson, Mattias; Norin, Stefan; Sandstedt, Anna; Hansson, Lotta; Österborg, Anders

2016-12-01

Ibrutinib, a Bruton's tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine health-care are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy ≥10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression-free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richter's transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia. Copyright© Ferrata Storti Foundation.

Adult advanced chronic lymphocytic leukemia: computational analysis of whole-body CT documents a bone structure alteration.

PubMed

Fiz, Francesco; Marini, Cecilia; Piva, Roberta; Miglino, Maurizio; Massollo, Michela; Bongioanni, Francesca; Morbelli, Silvia; Bottoni, Gianluca; Campi, Cristina; Bacigalupo, Andrea; Bruzzi, Paolo; Frassoni, Francesco; Piana, Michele; Sambuceti, Gianmario

2014-06-01

To assess the presence of alteration of bone structure and bone marrow metabolism in adult patients who were suspected of having advanced chronic lymphocytic leukemia (ACLL) by using a computational prognostic model that was based on computational analysis of positron emission tomography (PET)/computed tomography (CT) images. In this retrospective study, all patients signed written informed consent as a requisite to undergo PET/CT examination. However, due to its observational nature, approval from the ethical committee was not deemed necessary. Twenty-two previously untreated chronic lymphocytic leukemia patients underwent PET/CT for disease progression. PET/CT images were analyzed by using dedicated software, capable of recognizing an external 2-pixel bone ring whose Hounsfield coefficient served as cutoff to recognize trabecular and compact bone. PET/CT data from 22 age- and sex-matched control subjects were used as comparison. All data are reported as means ± standard deviations. The Student t test, log-rank, or Cox proportional hazards model were used as appropriate, considering a difference with a P value of less than .05 as significant. Trabecular bone was expanded in ACLL patients and occupied a larger fraction of the skeleton with respect to control subjects (mean, 39% ± 5 [standard deviation] vs 31% ± 7; ie, 32 of 81 mL/kg of ideal body weight vs 27 of 86 mL/kg of ideal body weight, respectively; P < .001). After stratification according to median value, patients with a ratio of trabecular to skeletal bone volume of more than 37.3% showed an actuarial 2-year survival of 18%, compared with 82% for those with a ratio of less than 37.3% (P < .001), independent from age, sex, biological markers, and disease duration. These data suggest that computational assessment of skeletal alterations might represent a new window for prediction of the clinical course of the disease.

Prospective Phase I-II Trial of Helical Tomotherapy With or Without Chemotherapy for Postoperative Cervical Cancer Patients

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

Schwarz, Julie K., E-mail: jschwarz@radonc.wustl.edu; Department of Cell Biology and Physiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO

2011-12-01

Purpose: To investigate, in a prospective trial, the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy (RT) delivered using helical tomotherapy, with or without the administration of concurrent chemotherapy. Patients and Methods: A total of 24 evaluable patients entered the study between March 2006 and August 2009. The indications for postoperative RT were tumor size, lymphovascular space invasion, and the depth of cervical stromal invasion in 15 patients; 9 patients underwent postoperative RT because of surgically positive lymph nodes. All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy.more » Treatment consisted of concurrent weekly platinum in 17, sequential carboplatin/Taxol in 1, and RT alone in 6. The patients were monitored for acute and chronic toxicity using the Common Toxicity Criteria, version 3.0. Results: The median follow-up was 24 months (range, 4-49). At the last follow-up visit, 23 patients were alive and disease free. Of the 24 patients, 12 (50%) experienced acute Grade 3 gastrointestinal toxicity (anorexia in 5, diarrhea in 4, and nausea in 3). One patient developed acute Grade 4 genitourinary toxicity (vesicovaginal fistula). For patients treated with concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 71% and 24%, respectively. For patients treated without concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 29% and 14%, respectively. Two long-term toxicities occurred (vesicovaginal fistula at 25 months and small bowel obstruction at 30 months). The overall and progression-free survival rate at 3 years for all patients was 100% and 89%, respectively. Conclusion: The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or without chemotherapy is feasible, with acceptable acute and chronic toxicity.« less

Effect of taping on foot kinematics in persons with chronic ankle instability.

PubMed

Deschamps, Kevin; Dingenen, Bart; Pans, Femke; Van Bavel, Isabelle; Matricali, Giovanni Arnoldo; Staes, Filip

2016-07-01

To investigate differences in rigid-foot and multi-segmental foot kinematics between healthy (control) and chronic ankle instability (CAI) participants during running and to evaluate the effect of low-Dye (LD) and high-Dye (HD) taping on foot kinematics of CAI subjects. Cross-sectional, comparative study. Kinematic data of 12 controls and 15 CAI participants were collected by a 3D motion analysis system during running. CAI participants performed barefoot (CAI_BF) running trials as well as trials with taping. A rigid Plug-in gait Model and the Rizzoli 3D Multi-Segment Foot Model were used. Groups were compared using one-dimensional statistical parametric mapping. An increased inversion, a decreased dorsiflexion between the foot and tibia and a decreased external foot progression angle were found during terminal swing and early stance in the CAI_BF group. With respect to the taped conditions, post-hoc SPM{t} calculations highlighted a more dorsiflexed rearfoot (38-46% running cycle) in the CAI_HD compared to the CAI_LD, and a more inverted Mid-Met angle (6-24% running cycle) in the CAI_LD compared to the CAI_BF condition. This study revealed significant differences in rigid foot and multi-segmental foot kinematics between all groups. As high-dye taping embraces shank-rearfoot and forefoot, it seems to have better therapeutic features with respect to low-dye taping as the latter created a more inverted forefoot which may not be recommended in this population. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Immunosuppression associated with chronic inflammation in the tumor microenvironment

PubMed Central

Wang, Dingzhi; DuBois, Raymond N.

2015-01-01

Chronic inflammation contributes to cancer development via multiple mechanisms. One potential mechanism is that chronic inflammation can generate an immunosuppressive microenvironment that allows advantages for tumor formation and progression. The immunosuppressive environment in certain chronic inflammatory diseases and solid cancers is characterized by accumulation of proinflammatory mediators, infiltration of immune suppressor cells and activation of immune checkpoint pathways in effector T cells. In this review, we highlight recent advances in our understanding of how immunosuppression contributes to cancer and how proinflammatory mediators induce the immunosuppressive microenvironment via induction of immunosuppressive cells and activation of immune checkpoint pathways. PMID:26354776

Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Cardiovascular Links

PubMed Central

Laratta, Cheryl R.; van Eeden, Stephan

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease resulting from exposure to cigarette smoke, noxious gases, particulate matter, and air pollutants. COPD is exacerbated by acute inflammatory insults such as lung infections (viral and bacterial) and air pollutants which further accelerate the steady decline in lung function. The chronic inflammatory process in the lung contributes to the extrapulmonary manifestations of COPD which are predominantly cardiovascular in nature. Here we review the significant burden of cardiovascular disease in COPD and discuss the clinical and pathological links between acute exacerbations of COPD and cardiovascular disease. PMID:24724085

Distal acquired demyelinating symmetric polyneuropathy progressing to classic chronic inflammatory demyelinating polyneuropathy and response to fludarabine and cyclophosphamide.

PubMed

Leitch, Megan M; Sherman, William H; Brannagan, Thomas H

2013-02-01

Distal acquired demyelinating symmetric polyneuropathy (DADS) is proposed as a distinct entity from classic chronic inflammatory demyelinating polyneuropathy (CIDP). We report a 58-year-old woman with DADS that progressed to a severe case of classic CIDP. She had distal numbness and paresthesias, minimal distal weakness and impaired vibratory sensation. She had anti-MAG antibodies, negative Western blot, and lacked a monoclonal gammopathy. There were prolonged distal motor latencies. She remained stable for 6 years until developing proximal and distal weakness. Nerve conduction studies showed multiple conduction blocks. She developed quadriparesis despite first-line treatment for CIDP. She was started on cyclophosphamide and fludarabine. Twenty-five months after receiving chemotherapy, she had only mild signs of neuropathy off all immunotherapy. DADS may progress to classic CIDP and is unlikely to be a separate disorder. Fludarabine and cyclophosphamide may be effective for refractory CIDP. Copyright © 2012 Wiley Periodicals, Inc.

Progression of tau pathology within cholinergic nucleus basalis neurons in chronic traumatic encephalopathy: A Chronic Effects of Neurotrauma Consortium Study

PubMed Central

Mufson, Elliott J.; Perez, Sylvia E.; Nadeem, Muhammad; Mahady, Laura; Kanaan, Nicholas M.; Abrahamson, Eric E.; Ikonomovic, Milos D.; Crawford, Fiona; Alvarez, Victor; Stein, Thor; McKee, Ann C.

2017-01-01

Objective To test the hypothesis that the nucleus basalis of Meynert (nbM), a cholinergic basal forebrain (CBF) cortical projection system, develops neurofibrillary tangles (NFTs) during the progressive pathological stages of chronic traumatic encephalopathy (CTE) in the brain of athletes. Method To characterize NFT pathology we used tau- antibodies marking early, intermediate, and late stages of NFT development in cholinergic basal forebrain tissue obtained at autopsy from eighteen former athletes and veterans with a history of repetitive mild traumatic brain injury (TBI). Results We found evidence that cholinergic nbM neurons develop intracellular tau-immunoreactive changes progressively across the pathological stages of CTE. In particular, there was an increase in pretangle (phosphorylated pS422) and oligomeric (TOC1 and TNT1) forms of tau in stage IV compared to stage II CTE cases. The nbM neurons also displayed pathologic TDP-43 inclusions and diffuse extracellular and vascular amyloid-β (Aβ) deposits in CTE. A higher percent of pS422/p75NTR, pS422 and TNT1 labeled neurons were significantly correlated with age at symptom onset, interval between symptom onset and death and age at death. Conclusion The development of NFTs within the nbM neurons could contribute to the basal forebrain cortical cholinergic disconnection in CTE. Further studies are needed to determine the mechanism driving NFT formation in the nbM neurons and its relation to chronic cognitive dysfunction in CTE. PMID:27834536

Lack of clinical and histological progression of chronic hepatitis C in individuals with true persistently normal ALT: the result of a 17-year follow-up.

PubMed

Nunnari, G; Pinzone, M R; Cacopardo, B

2013-04-01

Thirty to 40% of patients with chronic hepatitis C have persistently normal alanine aminotransferase (PNALT). Even though traditionally considered as healthy people, most PNALT carriers actually have some degree of clinical progression and histological liver damage. We evaluated the clinical and histological outcome of a 17-year follow-up on a cohort of patients with chronic HCV infection and PNALT. Between 1994 and 2011, 70 PNALTs and 55 Hyper-alanine aminotransferase (ALT) subjects underwent a clinical, biochemical, virological and histological follow-up. At the end of the follow-up, all patients were alive. In the PNALT group, none of the patients developed hepatic decompensation, while 14.5% of Hyper-ALTs were diagnosed as affected by decompensated cirrhosis. No significant variation of the Metavir grading and staging scores was observed among PNALTs by comparing pre- and post-follow-up liver specimens. On the contrary, a significant increase in both Metavir grading and staging scores was noticed within the Hyper-ALT group. Finally, the analysis of IL28B single-nucleotide polymorphism rs12979860 revealed no difference between Hyper-ALTs and PNALTs in terms of frequency of C/C genotype. In conclusion, progression of chronic hepatitis C among PNALTs is slow or even absent, because at the end of the 17-year follow-up histological and clinical parameters had not worsened significantly. © 2012 Blackwell Publishing Ltd.

Chronic mild stress facilitates melanoma tumor growth in mouse lines selected for high and low stress-induced analgesia.

PubMed

Ragan, Agnieszka R; Lesniak, Anna; Bochynska-Czyz, Marta; Kosson, Anna; Szymanska, Hanna; Pysniak, Kazimiera; Gajewska, Marta; Lipkowski, Andrzej W; Sacharczuk, Mariusz

2013-09-01

Both chronic stress conditions and hyperergic reaction to environmental stress are known to enhance cancer susceptibility. We described two mouse lines that displayed high (HA) and low (LA) swim stress-induced analgesia (SSIA) to investigate the relationship between inherited differences in sensitivity to stress and proneness to an increased growth rate of subcutaneously inoculated melanoma. These lines display several genetic and physiological differences, among which distinct sensitivity to mutagens and susceptibility to cancer are especially noticeable. High analgesic mice display high proneness both to stress and a rapid local spread of B16F0 melanoma. However, stress-resistant LA mice do not develop melanoma tumors after inoculation, or if so, tumors regress spontaneously. We found that the chronic mild stress (CMS) procedure leads to enhanced interlinear differences in melanoma susceptibility. Tumors developed faster in stress conditions in both lines. However, LA mice still displayed a tendency for spontaneous regression, and 50% of LA mice did not develop a tumor, even under stressed conditions. Moreover, we showed that chronic stress, but not tumor progression, induces depressive behavior, which may be an important clue in cancer therapy. Our results clearly indicate how the interaction between genetic susceptibility to stress and environmental stress determine the risk and progression of melanoma. To our knowledge, HA/LA mouse lines are the first animal models of distinct melanoma progression mediated by inherited differences in stress reactivity.

Acute kidney injury after non-cardiovascular surgery: risk factors and impact on development of chronic kidney disease and long-term mortality.

PubMed

Pourafkari, Leili; Arora, Pradeep; Porhomayon, Jahan; Dosluoglu, Hasan H; Arora, Preksha; Nader, Nader D

2018-05-03

To identify factors associated with acute kidney injury (AKI) and its progression to chronic kidney disease (CKD) in a non-cardiac/non-vascular surgery setting. This study examined the Veterans Affairs Surgical Quality database for surgical entries between 2000-2014. Demographics, comorbidities, laboratory findings and hospital outcomes were assessed. The primary end-point was the occurrence of AKI, defined as an increase of ≥0.3 mg/dL, 48 h post-operatively. Major adverse cardiac event (MACE) was defined as the composite first occurrence of myocardial infarction, cardiac arrest, and death in 30 days (secondary end-point) and was compared between two groups. Rates of progression to CKD in 1 year and long-term survival were examined. Occurrence of AKI 48 h post-operatively. AKI was documented in 8.5% of patients. Age, diabetes, and chronic obstructive pulmonary disease, chronic kidney disease, platelet count, serum albumin level, and duration of surgery were identified as independent predictors of AKI. In total, 6.4% patients developed MACE, which was more frequent in patients with AKI (p < .001). Age and pre-operative hematocrit <30% were independent predictors of progression to CKD. Pre-operative hematocrit with a cut-off value of 30% was the only modifiable factor to predict the long-term survival. Development of AKI is associated with increased odds of various post-operative complications and long-term renal insufficiency and mortality.

Anthropometric evaluation of pediatric patients with nonprogressive chronic encephalopathy according to different methods of classification☆

PubMed Central

Teixeira, Jéssica Socas; Gomes, Mirian Martins

2014-01-01

Objective: To perform anthropometric assessment of patients with quadriplegic, chronic non-progressive encephalopathy, comparing two distinct references of nutritional classification and to compare the estimated height to the length measured by stadiometer. Method: Cross-sectional study including 0-3-year children with quadriplegic chronic non-progressive encephalopathy in secondary public hospital. Length, weight, arm circumference, triceps skinfold and knee height were measured. The arm muscle circumference and estimated height were calculated. The following relations were evaluated: weight-for-age, length-for-age and weight-for-length, using as reference the charts of the World Health Organization (WHO) and those proposed by Krick et al. Results: Fourteen children with a mean age of 21 months were evaluated. Assessment of anthropometric indicators showed significant difference between the two classification methods to assess nutritional indicators length/age (p=0.014), weight/age (p=0.014) and weight/length (p=0.001). There was significant correlation between measured length and estimated height (r=0.796, p=0.001). Evaluation of arm circumference and triceps skinfold showed that most patients presented some degree of malnutrition. According to arm muscle circumference, most were eutrophic. Conclusions: Specific curves for children with chronic non-progressive encephalopathy appear to underestimate malnutrition when one takes into account indicators involving weight. Curves developed for healthy children can be a good option for clinical practice and weight-for-length indicator and body composition measurements should be considered as complementary tools. PMID:25479849

Use of the NBME Comprehensive Basic Science Examination as a Progress Test in the Preclerkship Curriculum of a New Medical School

ERIC Educational Resources Information Center

Johnson, Teresa R.; Khalil, Mohammed K.; Peppler, Richard D.; Davey, Diane D.; Kibble, Jonathan D.

2014-01-01

In the present study, we describe the innovative use of the National Board of Medical Examiners (NBME) Comprehensive Basic Science Examination (CBSE) as a progress test during the preclerkship medical curriculum. The main aim of this study was to provide external validation of internally developed multiple-choice assessments in a new medical…

Coaching Doctoral Students--A Means to Enhance Progress and Support Self-Organisation in Doctoral Education

ERIC Educational Resources Information Center

Godskesen, Mirjam; Kobayashi, Sofie

2016-01-01

In this paper we focus on individual coaching carried out by an external coach as a new pedagogical element that can impact doctoral students' sense of progress in doctoral education. The study used a mixed-methods approach in that we draw on quantitative and qualitative data from the evaluation of a project on coaching doctoral students. We…

Progression of chronic periodontitis can be predicted by the levels of Porphyromonas gingivalis and Treponema denticola in subgingival plaque.

PubMed

Byrne, S J; Dashper, S G; Darby, I B; Adams, G G; Hoffmann, B; Reynolds, E C

2009-12-01

Chronic periodontitis is an inflammatory disease of the supporting tissues of the teeth associated with bacteria. Diagnosis is achieved retrospectively by clinical observation of attachment loss. Predicting disease progression would allow for targeted preventive therapy. The aim of this study was to monitor disease progression in patients on a maintenance program and determine the levels of specific bacteria in subgingival plaque samples and then examine the ability of the clinical parameters of disease and levels of specific bacteria in the plaque samples to predict disease progression. During a 12-month longitudinal study of 41 subjects, 25 sites in 21 subjects experienced disease progression indicated by at least 2 mm of clinical attachment loss. Real-time polymerase chain reaction was used to determine the levels of Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in subgingival plaque samples. No clinical parameters were able to predict periodontal disease progression. In sites undergoing imminent periodontal disease progression within the next 3 months, significant partial correlations were found between P. gingivalis and T. forsythia (r = 0.55, P < 0.001) and T. denticola and T. forsythia (r = 0.43, P = 0.04). The odds of a site undergoing imminent periodontal disease progression increased with increasing levels of P. gingivalis and T. denticola. Monitoring the proportions of P. gingivalis and T. denticola in subgingival plaque has the potential to help identify sites at significant risk for progression of periodontitis, which would assist in the targeted treatment of disease.

Chronic monitoring of lower urinary tract activity via a sacral dorsal root ganglia interface

NASA Astrophysics Data System (ADS)

Khurram, Abeer; Ross, Shani E.; Sperry, Zachariah J.; Ouyang, Aileen; Stephan, Christopher; Jiman, Ahmad A.; Bruns, Tim M.

2017-06-01

Objective. Our goal is to develop an interface that integrates chronic monitoring of lower urinary tract (LUT) activity with stimulation of peripheral pathways. Approach. Penetrating microelectrodes were implanted in sacral dorsal root ganglia (DRG) of adult male felines. Peripheral electrodes were placed on or in the pudendal nerve, bladder neck and near the external urethral sphincter. Supra-pubic bladder catheters were implanted for saline infusion and pressure monitoring. Electrode and catheter leads were enclosed in an external housing on the back. Neural signals from microelectrodes and bladder pressure of sedated or awake-behaving felines were recorded under various test conditions in weekly sessions. Electrodes were also stimulated to drive activity. Main results. LUT single- and multi-unit activity was recorded for 4-11 weeks in four felines. As many as 18 unique bladder pressure single-units were identified in each experiment. Some channels consistently recorded bladder afferent activity for up to 41 d, and we tracked individual single-units for up to 23 d continuously. Distension-evoked and stimulation-driven (DRG and pudendal) bladder emptying was observed, during which LUT sensory activity was recorded. Significance. This chronic implant animal model allows for behavioral studies of LUT neurophysiology and will allow for continued development of a closed-loop neuroprosthesis for bladder control.

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.

Course of alcoholic chronic pancreatitis: a prospective clinicomorphological long-term study.

PubMed

Ammann, R W; Heitz, P U; Klöppel, G

1996-07-01

The pathogenesis of alcoholic chronic pancreatitis and its relationship to alcoholic acute pancreatitis are debated. According to our recent clinical long-term study, alcoholic chronic pancreatitis seems to evolve from severe acute pancreatits. The aim of this study was to correlate clinical findings to the pancreatic histopathology at early and advanced stages of the disease. Morphological changes (pseudocysts, autodigestive necrosis, calcification, and perilobular and intralobular fibrosis) were recorded in 37 surgical and 46 postmortem pancreas specimens of 73 patients from our long-term series, who progressed from clinically acute to chronic pancreatitis (mean follow-up, 12 years). Pancreatic function was monitored at yearly intervals. Surgical interventions were performed at a mean of 4.1 years from onset. Histologically, focal necrosis (49%) and mild perilobular fibrosis (54%) predominated, Pseudocysts (n = 41, mostly postnecrotic) occurred in 88% within 6 years from onset. Autopsy specimens were obtained at a mean of 12 years. These pancreata often showed severe perilobular and intralobular fibrosis (85%) and calcifications (74%), but rarely necrosis (4%). Fibrosis correlated with progressive pancreatic dysfunction (P < 0.001), particularly in the 10 patients with two histological assessments (mean interval between biopsy and autopsy, 8 years). The data support an evolution from severe alcoholic acute pancreatitis to chronic pancreatitis.

Risk of Pancreatic Cancer After a Primary Episode of Acute Pancreatitis.

PubMed

Rijkers, Anton P; Bakker, Olaf J; Ahmed Ali, Usama; Hagenaars, Julia C J P; van Santvoort, Hjalmar C; Besselink, Marc G; Bollen, Thomas L; van Eijck, Casper H

2017-09-01

Acute pancreatitis may be the first manifestation of pancreatic cancer. The aim of this study was to assess the risk of pancreatic cancer after a first episode of acute pancreatitis. Between March 2004 and March 2007, all consecutive patients with a first episode of acute pancreatitis were prospectively registered. Follow-up was based on hospital records audit, radiological imaging, and patient questionnaires. Outcome was stratified based on the development of chronic pancreatitis. We included 731 patients. The median follow-up time was 55 months. Progression to chronic pancreatitis was diagnosed in 51 patients (7.0%). In this group, the incidence rate per 1000 person-years for developing pancreatic cancer was 9.0 (95% confidence interval, 2.3-35.7). In the group of 680 patients who did not develop chronic pancreatitis, the incidence rate per 1000 person-years for developing pancreatic cancer in this group was 1.1 (95% confidence interval, 0.3-3.3). Hence, the rate ratio of pancreatic cancer was almost 9 times higher in patients who developed chronic pancreatitis compared with those who did not (P = 0.049). Although a first episode of acute pancreatitis may be related to pancreatic cancer, this risk is mainly present in patients who progress to chronic pancreatitis.

From Ideas to Efficacy: The ORBIT Model for Developing Behavioral Treatments for Chronic Diseases

PubMed Central

Czajkowski, Susan M.; Powell, Lynda H.; Adler, Nancy; Naar-King, Sylvie; Reynolds, Kim D.; Hunter, Christine M.; Laraia, Barbara; Olster, Deborah H.; Perna, Frank M.; Peterson, Janey C.; Epel, Elissa; Boyington, Josephine E.; Charlson, Mary E.

2015-01-01

Objective Given the critical role of behavior in preventing and treating chronic diseases, it is important to accelerate the development of behavioral treatments that can improve chronic disease prevention and outcomes. Findings from basic behavioral and social science research hold great promise for addressing behaviorally-based clinical health problems, yet there is currently no established pathway for translating fundamental behavioral science discoveries into health-related treatments ready for Phase III efficacy testing. This article provides a systematic framework for guiding efforts to translate basic behavioral science findings into behavioral treatments for preventing and treating chronic illness. Methods The ORBIT model for behavioral treatment development is described as involving a flexible and progressive process, pre-specified clinically significant milestones for forward movement, and return to earlier stages for refinement and optimization. Results This article presents the background and rationale for the ORBIT model, a summary of key questions for each phase, a selection of study designs and methodologies well-suited to answering these questions, and pre-specified milestones for forward or backward movement across phases. Conclusions The ORBIT model provides a progressive, clinically-relevant approach to increasing the number of evidence-based behavioral treatments available to prevent and treat chronic diseases. PMID:25642841

Prevention and treatment of cancer targeting chronic inflammation: research progress, potential agents, clinical studies and mechanisms.

PubMed

Zhang, Yong; Kong, Weijia; Jiang, Jiandong

2017-06-01

Numerous experimental and clinical studies indicate that chronic inflammation is closely related to the initiation, progression, and spread of cancer, in which proinflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α), and transcription factors, such as nuclear factor-κB (NF-κB), and signal transducer and activator of transcription 3 (STAT3), play pivotal roles. Stimulated by proinflammatory cytokines, NF-κB and STAT3 can modulate the expression of target genes, most of which are oncogenic ones, and promote the survival, proliferation, invasion, and metastasis of cancer cells. Now it is generally accepted that inflammation-related molecules and pathways are useful targets for the prevention and treatment of cancer. In this review, we summarize the relationship between chronic inflammation and cancer and describe some potentially useful agents including aspirin, meformin, statins, and some natural products (green tea catechins, andrographolide, curcumin) for their cancer prevention and treatment activities targeting chronic inflammation. The results of typical clinical studies are included, and the influences of these agents on the proinflammatory cytokines and inflammation-related pathways are discussed. Data from the present review support that agents targeting chronic inflammation may have a broad application prospect for the prevention and treatment of cancer in the future.

APOL1 risk variants, race, and progression of chronic kidney disease.

PubMed

Parsa, Afshin; Kao, W H Linda; Xie, Dawei; Astor, Brad C; Li, Man; Hsu, Chi-yuan; Feldman, Harold I; Parekh, Rulan S; Kusek, John W; Greene, Tom H; Fink, Jeffrey C; Anderson, Amanda H; Choi, Michael J; Wright, Jackson T; Lash, James P; Freedman, Barry I; Ojo, Akinlolu; Winkler, Cheryl A; Raj, Dominic S; Kopp, Jeffrey B; He, Jiang; Jensvold, Nancy G; Tao, Kaixiang; Lipkowitz, Michael S; Appel, Lawrence J

2013-12-05

Among patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients. In two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline. In the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons). Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

APOL1 Risk Variants, Race, and Progression of Chronic Kidney Disease

PubMed Central

Parsa, Afshin; Kao, W.H. Linda; Xie, Dawei; Astor, Brad C.; Li, Man; Hsu, Chi-yuan; Feldman, Harold I.; Parekh, Rulan S.; Kusek, John W.; Greene, Tom H.; Fink, Jeffrey C.; Anderson, Amanda H.; Choi, Michael J.; Wright, Jackson T.; Lash, James P.; Freedman, Barry I.; Ojo, Akinlolu; Winkler, Cheryl A.; Raj, Dominic S.; Kopp, Jeffrey B.; He, Jiang; Jensvold, Nancy G.; Tao, Kaixiang; Lipkowitz, Michael S.; Appel, Lawrence J.

2014-01-01

BACKGROUND Among patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients. METHODS In two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline. RESULTS In the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons). CONCLUSIONS Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.) PMID:24206458

Improvement of fatigue resistance for multilayer lead zirconate titanate (PZT)-based ceramic actuators by external mechanical loads

NASA Astrophysics Data System (ADS)

Yang, Gang; Yue, Zhenxing; Ji, Ye; Chu, Xiangcheng; Li, Longtu

2008-12-01

The influence of external compressive loads, applied along a direction perpendicular to polarization, on fatigue behaviors of multilayer lead zirconate titanate (PZT)-based ceramic actuators was investigated. Under no external mechanical load, a normal fatigue behavior was observed, demonstrating that both switching polarization (Pswitching) and remnant polarization (Pr) progressively decreased with increasing switching cycles due to domain pinning by charge point defects. However, an anomalous enhancement in both switching and remnant polarizations was observed upon application of the external compressive loads. After 5×106 cycles of polarization switching, Pswitching and Pr increase by about 13% and 6% at 40 MPa, respectively, while Pswitching and Pr increase by about 11% and 21% at 60 MPa, respectively. The improvement of fatigue resistance can be attributed to non-180° domain switching and suppression of microcracking, triggered by external mechanical loads.

Effects of reinforcement on children's academic behavior as a function of self-determined and externally imposed contingencies1

PubMed Central

Felixbrod, Jeffrey J.; O'Leary, K. Daniel

1973-01-01

This experiment was designed to compare the effects of contingent reinforcement under conditions of self-determined and externally imposed performance standards. A major purpose was to examine the maintenance of self-imposed performance standards over time. Children in one contingent reinforcement condition self-determined their academic performance standards. The same performance standards were externally imposed upon children in a second contingent reinforcement condition who were yoked to subjects in the first condition. Children in a no-reinforcement control condition performed in the absence of external reward. Behavioral productivity of the self-determination condition was greater than that of the no-reinforcement condition. Further, no attenuation of the efficacy of contingent reinforcement occurred when performance standards were self-determined rather than externally imposed. Over six sessions, children became progressively more lenient in their self-imposed performance demands in the absence of social surveillance. PMID:16795405

Sunitinib in Treating Patients With Idiopathic Myelofibrosis

ClinicalTrials.gov

2014-05-12

Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Primary Myelofibrosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Hairy Cell Leukemia

Pharmaceutical Approval Update.

PubMed

Kaufman, Michele B

2016-08-01

Venetoclax (Venclexta) for chronic lymphocytic leukemia; riboflavin 5'-phosphate solutions (Photrexa Viscous and Photrexa) for progressive keratoconus; and pimavanserin (Nuplazid) for Parkinson's disease psychosis.

[Efficacy of nebulizer therapy with acetylcystein in outpatients with chronic obstructive lung disease].

PubMed

Stepanishcheva, L A; Ignatova, G L; Blinova, E V

2005-01-01

Chronic obstructive lung disease (COLD) is a widespread illness with constantly growing mortality. Mucolytic therapy plays a significant role in treatment of patients with COLD. The paper contains the results of nebulization with acetyl-cystein as part of rehabilitation program in outpatients with stable clinical course of I-II stage of COLD. The results demonstrated significant clinical improvement, as well as positive changes in external respiration parameters (1 sforced expiratory volume), increase of physical activity tolerance, and disappearance of acute inflammation phase reactants in saliva.

The Management of Chronic Disease: a Study of Employee Morbidity and Mortality at the NASA, Goddard Space Flight Center, 1966 - 1971

NASA Technical Reports Server (NTRS)

Villafana, C.; Mockbee, J.

1971-01-01

Several approaches to studying chronic disease patterns in the employee population at Goddard Space Flight Center from 1966 to 1970 are presented. Attempts were made to summarize preliminary data for 1971 and relate this data to specific programs and events which may have had some causative influence. Investigative data for the study cover records of periodic and return to work examinations, injury and illness visit reports, mortality data, and health trends with and without external influences.

Effects of progressive backward body weight suppoted treadmill training on gait ability in chronic stroke patients: A randomized controlled trial.

PubMed

Kim, Kyung Hun; Lee, Kyoung Bo; Bae, Young-Hyeon; Fong, Shirley S M; Lee, Suk Min

2017-10-23

A stroke patient with hemiplegic gait is generally described as being slow and asymmetric. Body weight-supported treadmill training and backward gait training are recent additions to therapeutic gait trainings that may help improve gait in stroke patient with hemiplegic gait. Therefore, we examined the effect of progressive backward body weight-supported treadmill training on gait in chronic stroke patients with hemiplegic gait. Thirty subjects were divided to the experimental and control groups. The experimental group consisted of 15 patients and underwent progressive backward body weight-supported treadmill training. The control group consisted of 15 patients and underwent general treadmill gait training five times per week, for a total of four weeks. The OptoGait was used to analyze gait kinematics, and the dynamic gait index (DGI) and results of the 6-minute walk test were used as the clinical evaluation indicators. A follow-up test was carried out four weeks later to examine persistence of exercise effects. The experimental group showed statistically significant results in all dependent variables week four compared to the control group. However, until the eighth week, only the dependent variables, of affected step length (ASL), stride length (SL), and DGI differed significantly between the two groups. This study verified that progressive bodyweight-supported treadmill training had a positive influence on the temporospatial characteristics of gait and clinical gait evaluation index in chronic stroke patients.

Disease-related mortality exceeds treatment-related mortality in patients with chronic myeloid leukemia on second-line or later therapy.

PubMed

Pearson, Edward; McGarry, Lisa; Gala, Smeet; Nieset, Christopher; Nanavaty, Merena; Mwamburi, Mkaya; Levy, Yair

2016-04-01

Treatment of newly-diagnosed patients with chronic-phase chronic myeloid leukemia (CP-CML) with tyrosine kinase inhibitors (TKIs) results in near-normal life expectancy. However, CP-CML patients resistant to initial TKIs face a poorer prognosis and significantly higher CML-related mortality. We conducted a systematic literature review to evaluate the specific causes of deaths (diseases progression versus drug-related) in CP-CML patients receiving second- or third-line therapy. We identified eight studies based on our criteria that reported causes of death. Overall, 5% of second-line and 10% of third-line patients died during the study follow-up period. For second-line, (7 studies, n=1926), mortality was attributed to disease progression for 41% of deaths, 2% to treatment-related causes, 3% were treatment-unrelated, and 50% were unspecified adverse events (AEs), not likely related to study drug. In third-line, (2 studies, n=144), 71% deaths were attributed to disease progression, 7% treatment-related AEs, 14% treatment-unrelated and 7% unspecified AEs. Annual death rates for second- and third-line therapy were significantly higher than for general population in similar age group. Our findings suggest death attributed to disease progression is approximately 10 times that due to treatment-related AEs in patients with CP-CML receiving second- or third-line therapy. Therefore, the potential benefits of effective treatment for these patients with the currently available TKIs outweigh the risks of treatment-induced AEs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Higher Ratio of Serum Alpha-Fetoprotein Could Predict Outcomes in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma and Normal Alanine Aminotransferase

PubMed Central

Park, Joong-Won

2016-01-01

Background The role of serum alpha-fetoprotein (AFP) levels in the surveillance and diagnosis of hepatocellular carcinoma (HCC) is controversial. The aim of this study was to investigate the value of serially measured serum AFP levels in HCC progression or recurrence after initial treatment. Methods A total of 722 consecutive patients newly diagnosed with HCC and treated at the National Cancer Center, Korea, between January 2004 and December 2009 were enrolled. The AFP ratios between 4–8 weeks post-treatment and those at the time of HCC progression or recurrence were obtained. Multivariate logistic regression analysis was performed to correlate the post-treatment AFP ratios with the presence of HCC progression or recurrence. Results The etiology of HCC was related to chronic hepatitis B virus (HBV) infection in 562 patients (77.8%), chronic hepatitis C virus (HCV) infection in 74 (10.2%), and non-viral cause in 86 (11.9%). There was a significant decrease in serum AFP levels from the baseline to 4 to 8 weeks after treatment (median AFP, 319.6 ng/mL vs. 49.6 ng/mL; p< 0.001). Multivariate analysis showed that an AFP ratio > 1.0 was an independently associated with HCC progression or recurrence. Among the different causes of HCC analyzed, this association was significant only for HCC related to chronic hepatitis B (p< 0.001) and non-viral causes (p<0.05), and limited only to patients who had normal alanine aminotransferase (ALT) levels. Conclusion Serial measurements of serum AFP ratios could be helpful in detecting progression or recurrence in treated patients with HBV-HCC and normal ALT. PMID:27304617

Thrombospondin-1 deficiency causes a shift from fibroproliferative to inflammatory kidney disease and delays onset of renal failure.

PubMed

Zeisberg, Michael; Tampe, Björn; LeBleu, Valerie; Tampe, Desiree; Zeisberg, Elisabeth M; Kalluri, Raghu

2014-10-01

Thrombospondin-1 (TSP1) is a multifunctional matricellular protein known to promote progression of chronic kidney disease. To gain insight into the underlying mechanisms through which TSP1 accelerates chronic kidney disease, we compared disease progression in Col4a3 knockout (KO) mice, which develop spontaneous kidney failure, with that of Col4a3;Tsp1 double-knockout (DKO) mice. Decline of excretory renal function was significantly delayed in the absence of TSP1. Although Col4a3;Tsp1 DKO mice did progress toward end-stage renal failure, their kidneys exhibited distinct histopathological lesions, compared with creatinine level-matched Col4a3 KO mice. Although kidneys of both Col4a3 KO and Col4a3;Tsp1 DKO mice exhibited a widened tubulointerstitium, predominant lesions in Col4a3 KO kidneys were collagen deposition and fibroblast accumulation, whereas in Col4a3;Tsp1 DKO kidney inflammation was predominant, with less collagen deposition. Altered disease progression correlated with impaired activation of transforming growth factor-β1 (TGF-β1) in vivo and in vitro in the absence of TSP1. In summary, our findings suggest that TSP1 contributes to progression of chronic kidney disease by catalyzing activation of latent TGF-β1, resulting in promotion of a fibroproliferative response over an inflammatory response. Furthermore, the findings suggest that fibroproliferative and inflammatory lesions are independent entities, both of which contribute to decline of renal function. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Neurocognitive Outcomes in Children with Chronic Kidney Disease: Current Findings and Contemporary Endeavors

ERIC Educational Resources Information Center

Gerson, Arlene C.; Butler, Robert; Moxey-Mims, Marva; Wentz, Alicia; Shinnar, Shlomo; Lande, Marc B.; Mendley, Susan R.; Warady, Bradley A.; Furth, Susan L.; Hooper, Stephen R.

2006-01-01

Given the rise in chronic kidney disease (CKD) in both children and adults, CKD has recently been targeted as a public health priority. Childhood onset kidney disease is generally a noncurable and progressive condition that leads to kidney failure by early adulthood. Fortunately, improved identification of kidney problems allows for early…

Crusted scabies in a patient with chronic graft-versus-host disease.

PubMed

Magee, K L; Hebert, A A; Rapini, R P

1991-11-01

We describe a 20-year-old man with chronic graft-versus-host disease and progressive cutaneous changes. His skin became more lichenified despite therapy with azathioprine, prednisone, and cyclosporine. Although it was initially thought that lichenoid graft-versus-host disease had developed, it was subsequently discovered that the patient had crusted (Norwegian) scabies.

The antioxidant n-acetylcysteine reduced necrosis, but exacerbated liver fibrosis induced by chronic alcohol in rats fed via total enteral nutrition

USDA-ARS?s Scientific Manuscript database

Despite many years of research, the molecular mechanisms underlying progression of alcoholic liver injury from simple steatosis through steatohepatitis and fibrosis remain in dispute. In the current study male Sprague-Dawley rats (350 g) were chronically fed a high unsaturated fat diet for 120 d usi...

Diagnosis of chronic active hepatitis in a miniature schnauzer.

PubMed

Hendrix, Alana D

2004-09-01

A 12-year-old male castrated miniature schnauzer was presented with a history of abdominal distension. Serum biochemical analysis and abdominal ultrasonography indicated hepatic disease. A wedge biopsy provided a diagnosis of chronic active hepatitis. A therapeutic regime was initiated to improve the quality of life and slow the progression of this disease is described.

Diagnosis of chronic active hepatitis in a miniature schnauzer

PubMed Central

2004-01-01

Abstract A 12-year-old male castrated miniature schnauzer was presented with a history of abdominal distension. Serum biochemical analysis and abdominal ultrasonography indicated hepatic disease. A wedge biopsy provided a diagnosis of chronic active hepatitis. A therapeutic regime was initiated to improve the quality of life and slow the progression of this disease is described. PMID:15510687

Diagnosis of Late Stage, Early Onset, Small Fiber Polyneuropathy

DTIC Science & Technology

2016-10-01

progress. 15. SUBJECT TERMS Neuropathy , Gulf War Illness, chronic widespread pain, chronic multisymptom illness, small- fiber polyneuropathy, case...life or express it in response to environmental triggers encountered by warfighters, such as neurotoxic exposures. 2. KEYWORDS: Neuropathy , Gulf...objective evidence of neuropathy (abnormal skin biopsy or autonomic function test) were analyzed. Preliminary results indicate that SFPN patients

Fragmented Foundations: Education and Chronic Crisis in the Occupied Palestinian Territory

ERIC Educational Resources Information Center

Nicolai, Susan

2007-01-01

This study explores the setting up and development of the first Palestinian-led education system, from 1994 to 2005. Given the context of chronic crisis, and the immensity of the endeavour, the Palestinians have made substantial progress in a relatively short time. However, the Palestinian education story does not end here. The author looks at…

High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease

USDA-ARS?s Scientific Manuscript database

Inflammation is a major mediator of CKD progression and is partly driven by altered gut microbiome and intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting in dominance of urease-possessing bacteria; disruption of epithelial barrier by urea-derived ammoni...

A resistant starch fiber diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease (CKD)

USDA-ARS?s Scientific Manuscript database

Inflammation is a constant feature and a major mediator of CKD progression. It is, in part, driven by altered gut microbiome and disruption of intestinal epithelial barrier, events which are primarily caused by: 1- urea influx in the intestine resulting in dominance of urease-possessing bacteria; 2-...

Chronic Family Economic Hardship, Family Processes and Progression of Mental and Physical Health Symptoms in Adolescence

ERIC Educational Resources Information Center

Lee, Tae Kyoung; Wickrama, K. A. S.; Simons, Leslie Gordon

2013-01-01

Research has documented the relationship between family stressors such as family economic hardship and marital conflict and adolescents' mental health symptoms, especially depressive symptoms. Few studies, however, have examined the processes whereby supportive parenting lessens this effect and the progression of mental health and physical health…

Exploration of Anaemia as a Progression Factor in African Americans with Cardiovascular Disease

USDA-ARS?s Scientific Manuscript database

Despite the higher incidence of end stage renal disease (ESRD) among African Americans, whites in the United States population have a higher prevalence of chronic kidney disease. This may be due, in part, to a faster rate of progression to ESRD among African Americans with kidney disease. Anemia i...

Endogenous Antiangiogenic Factors in Chronic Kidney Disease: Potential Biomarkers of Progression.

PubMed

Tanabe, Katsuyuki; Sato, Yasufumi; Wada, Jun

2018-06-24

Chronic kidney disease (CKD) is a major global health problem. Unless intensive intervention is initiated, some patients can rapidly progress to end-stage kidney disease. However, it is often difficult to predict renal outcomes using conventional laboratory tests in individuals with CKD. Therefore, many researchers have been searching for novel biomarkers to predict the progression of CKD. Angiogenesis is involved in physiological and pathological processes in the kidney and is regulated by the balance between a proangiogenic factor, vascular endothelial growth factor (VEGF)-A, and various endogenous antiangiogenic factors. In recent reports using genetically engineered mice, the roles of these antiangiogenic factors in the pathogenesis of kidney disease have become increasingly clear. In addition, recent clinical studies have demonstrated associations between circulating levels of antiangiogenic factors and renal dysfunction in CKD patients. In this review, we summarize recent advances in the study of representative endogenous antiangiogenic factors, including soluble fms-related tyrosine kinase 1, soluble endoglin, pigment epithelium-derived factor, VEGF-A 165 b, endostatin, and vasohibin-1, in associations with kidney diseases and discuss their predictive potentials as biomarkers of progression of CKD.

Military-related traumatic brain injury and neurodegeneration

PubMed Central

McKee, Ann C.; Robinson, Meghan E.

2014-01-01

Mild traumatic brain injury (mTBI) includes concussion, subconcussion, and most exposures to explosive blast from improvised explosive devices. mTBI is the most common traumatic brain injury affecting military personnel; however, it is the most difficult to diagnose and the least well understood. It is also recognized that some mTBIs have persistent, and sometimes progressive, long-term debilitating effects. Increasing evidence suggests that a single traumatic brain injury can produce long-term gray and white matter atrophy, precipitate or accelerate age-related neurodegeneration, and increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease. In addition, repetitive mTBIs can provoke the development of a tauopathy, chronic traumatic encephalopathy. We found early changes of chronic traumatic encephalopathy in four young veterans of the Iraq and Afghanistan conflict who were exposed to explosive blast and in another young veteran who was repetitively concussed. Four of the five veterans with early-stage chronic traumatic encephalopathy were also diagnosed with posttraumatic stress disorder. Advanced chronic traumatic encephalopathy has been found in veterans who experienced repetitive neurotrauma while in service and in others who were accomplished athletes. 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 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 has clinical and pathological features that overlap with postconcussion syndrome and posttraumatic stress disorder, suggesting that the three disorders might share some biological underpinnings. PMID:24924675

Military-related traumatic brain injury and neurodegeneration.

PubMed

McKee, Ann C; Robinson, Meghan E

2014-06-01

Mild traumatic brain injury (mTBI) includes concussion, subconcussion, and most exposures to explosive blast from improvised explosive devices. mTBI is the most common traumatic brain injury affecting military personnel; however, it is the most difficult to diagnose and the least well understood. It is also recognized that some mTBIs have persistent, and sometimes progressive, long-term debilitating effects. Increasing evidence suggests that a single traumatic brain injury can produce long-term gray and white matter atrophy, precipitate or accelerate age-related neurodegeneration, and increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease. In addition, repetitive mTBIs can provoke the development of a tauopathy, chronic traumatic encephalopathy. We found early changes of chronic traumatic encephalopathy in four young veterans of the Iraq and Afghanistan conflict who were exposed to explosive blast and in another young veteran who was repetitively concussed. Four of the five veterans with early-stage chronic traumatic encephalopathy were also diagnosed with posttraumatic stress disorder. Advanced chronic traumatic encephalopathy has been found in veterans who experienced repetitive neurotrauma while in service and in others who were accomplished athletes. 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 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 has clinical and pathological features that overlap with postconcussion syndrome and posttraumatic stress disorder, suggesting that the three disorders might share some biological underpinnings. Copyright © 2014. Published by Elsevier Inc.

Transition theory and its relevance to patients with chronic wounds.

PubMed

Neil, J A; Barrell, L M

1998-01-01

A wound, in the broadest sense, is a disruption of normal anatomic structure and function. Acute wounds progress through a timely and orderly sequence of repair that leads to the restoration of functional integrity. In chronic wounds, this timely and orderly sequence goes awry. As a result, people with chronic wounds often face not only physiological difficulties but emotional ones as well. The study of body image and its damage as a result of a chronic wound fits well with Selder's transition theory. This article describes interviews with seven patients with chronic wounds. The themes that emerged from those interviews were compared with Selder's theory to describe patients' experience with chronic wounds as a transition process that can be identified and better understood by healthcare providers.

13-cis Retinoic Acid Inhibits Development and Progression of Chronic Allograft Nephropathy

PubMed Central

Adams, Judith; Kiss, Eva; Arroyo, Ana B.V.; Bonrouhi, Mahnaz; Sun, Qiang; Li, Zhen; Gretz, Norbert; Schnitger, Anna; Zouboulis, Christos C.; Wiesel, Manfred; Wagner, Jürgen; Nelson, Peter J.; Gröne, Hermann-Josef

2005-01-01

Chronic allograft nephropathy is characterized by chronic inflammation and fibrosis. Because retinoids exhibit anti-proliferative, anti-inflammatory, and anti-fibrotic functions, the effects of low and high doses of 13-cis-retinoic acid (13cRA) were studied in a chronic Fisher344→Lewis transplantation model. In 13cRA animals, independent of dose (2 or 20 mg/kg body weight/day) and start (0 or 14 days after transplantation) of 13cRA administration, serum creatinine was significantly lower and chronic rejection damage was dramatically reduced, including subendothelial fibrosis of preglomerular vessels and chronic tubulointerstitial damage. The number of infiltrating mononuclear cells and their proliferative activity were significantly diminished. The mRNA expression of chemokines (MCP-1/CCL2, MIP-1α/CCL3, IP-10/CXCL10, RANTES/CCL5) and proteins associated with fibrosis (plasminogen activator inhibitor-1, transforming growth factor-β1, and collagens I and III) were strikingly lower in treated allografts. In vitro, activated peritoneal macrophages of 13cRA-treated rats showed a pronounced decrease in protein secretion of inflammatory cytokines (eg, tumor necrosis factor-α, interleukin-6). The suppression of the proinflammatory chemokine RANTES/CCL5 × 13cRA in fibroblasts could be mapped to a promoter module comprising IRF-1 and nuclear factor-κB binding elements, but direct binding of retinoid receptors to promoter elements could be excluded. In summary, 13cRA acted as a potent immunosuppressive and anti-fibrotic agent able to prevent and inhibit progression of chronic allograft nephropathy. PMID:15972972

[Possibilities of differentiation of antinuclear antibodies].

PubMed

Müller, W; Rosenthal, M; Stojan, B

1975-10-15

Antinuclear antibodies can give diagnostic informations according to their titre values, the belonging to different classes of immune globulins and on the basis of different patterns of immunofluorescence connection. The determination of granulocyte-specific antibodies which frequently appear in progressive chronic polyarthritis further contributes to the differential-diagnostic classification of diseases of the connective tissue. An antibody against extractable nuclear antigen is specific for the so-called mixed connective tissue disease, an antimitochondrial antibody for the pseudo-LE-syndrome. Moreover, the own examinations resulted in a particularly high and frequent ability of complement fixation of the antinuclear factors in systematic lupus erythematosus and sclerodermy. In contrast to this in the progressive chronic polyarthritis the complement fixation was clearly more insignificant.

A case control study on the structural equation model of the mechanism of coagulation and fibrinolysis imbalance in chronic schistosomiasis.

PubMed

Le, Aiping; Zhang, Lunli; Liu, Wei; Li, Xiaopeng; Ren, Jianwei; Ning, An

2017-02-01

A structural equation model was used for verification with chronic schistosomiasis to investigate the coagulation-anticoagulation system imbalance and to deduce the mechanism of D-dimer (D-D) level elevation in patients with advanced schistosome hepatic disease. We detected the plasma levels of tissue-type fiber plasminogen activator (tPA), urokinase type plasminogen activator (uPA), plasmin-antiplasmin complex (PAP), plasminogen (PLG), antithrombin (AT), plasminogen activator inhibitor 1 (PAI1), D-D, factor VIII: C (FVIII:C), antithrombin-III (AT-III), PLG, protein S (PS), and protein C (PC) in the healthy people as control (69), patients with chronic schistosomiasis (150) or advanced chronic schistosomiasis (90). FVIII, PAP, D-D, tPA, and uPA plasma levels were significantly higher in the chronic group than in the control group and were also significantly higher in the advanced group. However, AT-III, PC, PS, AT, PLG, and PAI1 plasma levels in the advanced and chronic groups were significantly lower than those in the control group. With progression of disease in patients with schistosomiasis japonica, a hypercoagulable state is induced by the coagulation-anticoagulation imbalance, eventually leading to patients with high levels of D-D. Furthermore, we established a structural equation model path of a "chronic schistosomiasis disease stage-(coagulation-anticoagulation-fibrinolysis)-D-D." By using analysis of moment structures (AMOS), it was shown that the chronic schistosomiasis stage was positively related to factor VIII and had negative correlation with AT-III; a good positive correlation with PAP, tPA, and uPA; and a good negative correlation with PLG and PAI1. In addition, our results show that the path coefficient of anticoagulation-fibrinolysis system to the chronic stage of schistosomiasis or D-D levels was significantly higher than that of the coagulation system. In conclusion, the coagulation and fibrinolysis imbalance in patients with chronic schistosomiasis, especially with advanced schistosomiasis, is due to the progression of disease stages.

Is a Responsive Default Mode Network Required for Successful Working Memory Task Performance?

PubMed Central

Čeko, Marta; Gracely, John L.; Fitzcharles, Mary-Ann; Seminowicz, David A.; Schweinhardt, Petra

2015-01-01

In studies of cognitive processing using tasks with externally directed attention, regions showing increased (external-task-positive) and decreased or “negative” [default-mode network (DMN)] fMRI responses during task performance are dynamically responsive to increasing task difficulty. Responsiveness (modulation of fMRI signal by increasing load) has been linked directly to successful cognitive task performance in external-task-positive regions but not in DMN regions. To investigate whether a responsive DMN is required for successful cognitive performance, we compared healthy human subjects (n = 23) with individuals shown to have decreased DMN engagement (chronic pain patients, n = 28). Subjects performed a multilevel working-memory task (N-back) during fMRI. If a responsive DMN is required for successful performance, patients having reduced DMN responsiveness should show worsened performance; if performance is not reduced, their brains should show compensatory activation in external-task-positive regions or elsewhere. All subjects showed decreased accuracy and increased reaction times with increasing task level, with no significant group differences on either measure at any level. Patients had significantly reduced negative fMRI response (deactivation) of DMN regions (posterior cingulate/precuneus, medial prefrontal cortex). Controls showed expected modulation of DMN deactivation with increasing task difficulty. Patients showed significantly reduced modulation of DMN deactivation by task difficulty, despite their successful task performance. We found no evidence of compensatory neural recruitment in external-task-positive regions or elsewhere. Individual responsiveness of the external-task-positive ventrolateral prefrontal cortex, but not of DMN regions, correlated with task accuracy. These findings suggest that a responsive DMN may not be required for successful cognitive performance; a responsive external-task-positive network may be sufficient. SIGNIFICANCE STATEMENT We studied the relationship between responsiveness of the brain to increasing task demand and successful cognitive performance, using chronic pain patients as a probe. fMRI working memory studies show that two main cognitive networks [“external-task positive” and “default-mode network” (DMN)] are responsive to increasing task difficulty. The responsiveness of both of these brain networks is suggested to be required for successful task performance. The responsiveness of external-task-positive regions has been linked directly to successful cognitive task performance, as we also show here. However, pain patients show decreased engagement and responsiveness of the DMN but can perform a working memory task as well as healthy subjects, without demonstrable compensatory neural recruitment. Therefore, a responsive DMN might not be needed for successful cognitive performance. PMID:26290236

Is a Responsive Default Mode Network Required for Successful Working Memory Task Performance?

PubMed

Čeko, Marta; Gracely, John L; Fitzcharles, Mary-Ann; Seminowicz, David A; Schweinhardt, Petra; Bushnell, M Catherine

2015-08-19

In studies of cognitive processing using tasks with externally directed attention, regions showing increased (external-task-positive) and decreased or "negative" [default-mode network (DMN)] fMRI responses during task performance are dynamically responsive to increasing task difficulty. Responsiveness (modulation of fMRI signal by increasing load) has been linked directly to successful cognitive task performance in external-task-positive regions but not in DMN regions. To investigate whether a responsive DMN is required for successful cognitive performance, we compared healthy human subjects (n = 23) with individuals shown to have decreased DMN engagement (chronic pain patients, n = 28). Subjects performed a multilevel working-memory task (N-back) during fMRI. If a responsive DMN is required for successful performance, patients having reduced DMN responsiveness should show worsened performance; if performance is not reduced, their brains should show compensatory activation in external-task-positive regions or elsewhere. All subjects showed decreased accuracy and increased reaction times with increasing task level, with no significant group differences on either measure at any level. Patients had significantly reduced negative fMRI response (deactivation) of DMN regions (posterior cingulate/precuneus, medial prefrontal cortex). Controls showed expected modulation of DMN deactivation with increasing task difficulty. Patients showed significantly reduced modulation of DMN deactivation by task difficulty, despite their successful task performance. We found no evidence of compensatory neural recruitment in external-task-positive regions or elsewhere. Individual responsiveness of the external-task-positive ventrolateral prefrontal cortex, but not of DMN regions, correlated with task accuracy. These findings suggest that a responsive DMN may not be required for successful cognitive performance; a responsive external-task-positive network may be sufficient. We studied the relationship between responsiveness of the brain to increasing task demand and successful cognitive performance, using chronic pain patients as a probe. fMRI working memory studies show that two main cognitive networks ["external-task positive" and "default-mode network" (DMN)] are responsive to increasing task difficulty. The responsiveness of both of these brain networks is suggested to be required for successful task performance. The responsiveness of external-task-positive regions has been linked directly to successful cognitive task performance, as we also show here. However, pain patients show decreased engagement and responsiveness of the DMN but can perform a working memory task as well as healthy subjects, without demonstrable compensatory neural recruitment. Therefore, a responsive DMN might not be needed for successful cognitive performance. Copyright © 2015 the authors 0270-6474/15/3511596-11$15.00/0.

A Case for a Collaborative Classroom

ERIC Educational Resources Information Center

Osterholt, Dorothy A.; Barratt, Katherine

2011-01-01

Students making the transition into college typically come face to face with increased independence and decreased external structure. This may be especially problematic for students with learning disabilities who may be less capable of managing in times of change than others. The outcome is often chronic procrastination, absenteeism, and…

Body Mass Index in Mild Cognitive Impairment According to Age, Sex, Cognitive Intervention, and Hypertension and Risk of Progression to Alzheimer's Disease.

PubMed

Joo, Soo Hyun; Yun, Se Hee; Kang, Dong Woo; Hahn, Chang Tae; Lim, Hyun Kook; Lee, Chang Uk

2018-01-01

Introduction: Mild cognitive impairment (MCI) is a prodromal stage of dementia. The association of body mass index (BMI) and progression to Alzheimer's disease (AD) in MCI subjects according to age, sex, and cognitive intervention remains unknown. We investigated the relationship between BMI and the risk of progression to AD in subjects with MCI, as well as the effect of BMI on progression to AD depending on age, sex, cognitive intervention, and chronic diseases. Methods: Three hundred and eighty-eight MCI subjects were followed for 36.3 ± 18.4 months, prospectively. They underwent neuropsychological testing more than twice during the follow-up period. The MCI subjects were categorized into underweight, normal weight, overweight, and obese subgroups. The associations between baseline BMI and progression to AD over the follow-up period were estimated using Cox proportional hazard regression models. Data were analyzed after stratification by age, sex, cognitive intervention, and chronic diseases. Results: After adjustment for the covariates, the underweight MCI group had a higher risk of progression to AD [hazard ratio (HR): 2.38, 95% confidence interval (CI): 1.17-4.82] relative to the normal weight group. After stratifying by age, sex, cognitive intervention, and chronic diseases, this effect remained significant among females (HR: 3.15, 95% CI: 1.40-7.10), the older elderly ≥75 years old (HR: 3.52, 95% CI: 1.42-8.72), the non-intervention group (HR: 3.06, 95%CI: 1.18-7.91), and the hypertensive group (HR: 4.71, 95% CI: 1.17-18.99). Conclusion: These data indicate that underweight could be a useful marker for identifying individuals at increased risk for AD in MCI subjects. This association is even stronger in females, older elderly subjects, the non-cognitive intervention group, and the hypertensive group.

[Jejunal myenteric denervation induced by benzalkonium chloride].

PubMed

Ramalho, F S; Santos, G C; Ramalho, L N; Kajiwara, J K; Zucoloto, S

1994-01-01

The effects of benzalkonium chloride (BAC) on the number of myenteric neurons, muscle thickness and external perimeter after acute (until 10 days after BAC application) and chronic (30 and 60 days after BAC application) denervation of the proximal jejunum were determined in rats. There was a significant reduction in the number of myenteric neurons of all segments treated with BAC. The extent of denervation varied along the time, and it was reduced in the denervated segments of the chronic group in comparison with the acute group. This may be due to the neuroplasticity phenomenon appearing during the chronic phase. Myenteric denervation increased the thickness of the propria muscle layer, especially in the longitudinal muscle layer, suggesting a higher sensitivity of this layer to myenteric denervation.

Modifiable risk factors for migraine progression.

PubMed

Bigal, Marcelo E; Lipton, Richard B

2006-10-01

Migraine is a chronic-recurrent disorder that progresses in some individuals. Transformed migraine is the result of this progression. Since migraine does not progress in most patients, identifying the risk factors for progression has emerged as a very important public health priority. If risk factors can be identified, that might provide a foundation for more aggressive preventive intervention. Risk factors for progression may be divided into non-remediable (gender, age, race) and remediable categories. In this paper, we focus on several already identified remediable risk factors, including frequency of migraine attacks, obesity, acute medication overuse, caffeine overuse, stressful life events, depression, and sleep disorders. We present the evidence for each risk factor and discuss possible interventions to address them.

IRIS Toxicological Review of Trichloroacetic Acid (TCA) ...

EPA Pesticide Factsheets

On September 24, 2009, the Toxicological Review of Trichloroacetic Acid (TCA) and the charge to external peer reviewers were released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the IRIS Toxicological Review of Trichloroacetic Acid and the charge to external peer reviewers are posted on this site. The draft Toxicological Review of Trichloroacetic Acid provides scientific support and rationale for the hazard identification and dose-response assessment pertaining to chronic exposure to trichloroacetic acid.

IRIS Toxicological Review of Formaldehyde (Interagency ...

EPA Pesticide Factsheets

On June 2, 2010, the Toxicological Review of Formaldehyde and the charge to external peer reviewers were released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the IRIS Toxicological Review of Formaldehyde and the charge to external peer reviewers are posted on this site. The draft Toxicological Review of Formaldehyde-Inhalation Assessment provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic inhalation exposure to formaldehyde.

IRIS Toxicological Review of Urea (Interagency Science ...

EPA Pesticide Factsheets

On September 28, 2010, the Toxicological Review of Urea and the charge to external peer reviewers were released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the IRIS Toxicological Review of Urea and the charge to external peer reviewers are posted on this site. The draft Toxicological Review of Urea provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to Urea.

Gait patterns in hemiplegic patients with equinus foot deformity.

PubMed

Manca, M; Ferraresi, G; Cosma, M; Cavazzuti, L; Morelli, M; Benedetti, M G

2014-01-01

Equinus deformity of the foot is a common feature of hemiplegia, which impairs the gait pattern of patients. The aim of the present study was to explore the role of ankle-foot deformity in gait impairment. A hierarchical cluster analysis was used to classify the gait patterns of 49 chronic hemiplegic patients with equinus deformity of the foot, based on temporal-distance parameters and joint kinematic measures obtained by an innovative protocol for motion assessment in the sagittal, frontal, and transverse planes, synthesized by parametrical analysis. Cluster analysis identified five subgroups of patients with homogenous levels of dysfunction during gait. Specific joint kinematic abnormalities were found, according to the speed of progression in each cluster. Patients with faster walking were those with less ankle-foot complex impairment or with reduced range of motion of ankle-foot complex, that is with a stiff ankle-foot complex. Slow walking was typical of patients with ankle-foot complex instability (i.e., larger motion in all the planes), severe equinus and hip internal rotation pattern, and patients with hip external rotation pattern. Clustering of gait patterns in these patients is helpful for a better understanding of dysfunction during gait and delivering more targeted treatment.

Modified L'Episcopo tendon transfers for irreparable rotator cuff tears: 5-year follow-up.

PubMed

Gerhardt, Christian; Lehmann, Lars; Lichtenberg, Sven; Magosch, Peter; Habermeyer, Peter

2010-06-01

Patients with posterosuperior cuff tears lose functional external rotation of the shoulder. Latissimus dorsi and teres major transfer is performed to restore external rotation. Twenty patients with a mean age was 55.8 +/- 6 years underwent this procedure and were examined at averages of 24.7 (n = 17) and 70.6 (n = 13) months. Two patients did not improve presumably because of failure of the transfer. The Constant and Murley score increased from 55.6 to 90.4 after 2 years and to 87.9 after 5 years. The mean active flexion increased from 119.4 degrees to 169.3 degrees and reached 170 degrees after 5 years, and mean external rotation increased from 12 degrees to 35 degrees , finally reaching 23 degrees . The grade of cuff arthritis progressed from initially Grade 1 in 17% and Grade 2 in 28% to Grade 2 in 8%, Grade 3 in 69%, and Grade 4 in 15% at final followup. The acromiohumeral distance increased from 4.5 mm to 6 mm and decreased to 3.8 mm after 5 years. Electromyographic analysis showed activity during isometric internal and external rotation in the transferred muscle in all patients. The L'Episcopo procedure can restore shoulder function, but cuff arthropathy may progress. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Pilot-in-the-Loop CFD Method Development

DTIC Science & Technology

2016-02-01

Contract # N00014-14-C-0020 Pilot-in-the-Loop CFD Method Development Progress Report (CDRL A001) Progress Report for Period: October 21...of the aircraft from the rest of its external environment. For example, ship airwake are calculated using CFD solutions without the presence of the...approaches with the goal of real time, fully coupled CFD for virtual dynamic interface modeling & simulation. Penn State is supporting the project

Pilot-in-the Loop CFD Method Development

DTIC Science & Technology

2016-04-27

Contract # N00014-14-C-0020 Pilot-in-the-Loop CFD Method Development Progress Report (CDRL A001) Progress Report for Period: January 21...aerodynamics of the aircraft from the rest of its external environment. For example, ship airwake are calculated using CFD solutions without the presence of...hardware approaches with the goal of real time, fully coupled CFD for virtual dynamic interface modeling & simulation. Penn State is supporting the project

Biobehavioral pain profile in individuals with chronic spine pain.

PubMed

Matteliano, Deborah; Scherer, Yvonne Krall; Chang, Yu-Ping

2014-03-01

Pain in the spine is the most frequently described pain problem in primary care, afflicting at least 54 million Americans. When spinal pain becomes chronic, the prognosis for recovery is poor, often leading to disability and reduced quality of life. Clinical treatment is inadequate, often focusing on physical pathology alone. To improve treatment outcomes for chronic pain as recommended by current guidelines, the Biobehavioral Pain Profile (BPP), which includes six pain response subscales, was developed to guide cognitive behavioral therapy (CBT). The purpose of this study was to describe the BPP in 100 individuals with chronic spine pain and examine the associations between the BPP and important clinical outcomes, including chronic pain, disability, and quality of life. Participants reported a high level of pain, a low quality of life, and a high level of disability despite receiving treatment with opioids. Scores on BPP subscales including evaluating loss of control, past and current experience, physiologic responsivity, and thoughts of disease progression were elevated, indicating a need for CBT. Five of the six BPP subscales had a significant association with quality of life, chronic pain, and disability with the thought of disease progression being a strong factor for most of the clinical outcome variables. By identifying BPP, clinicians can provide appropriate treatments to improve individuals' quality of life and prevent further disability. Further study using the BPP to guide CBT is needed. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Indagation of serum and salivary reactive oxygen metabolite and cortisol levels in chronic periodontitis and stress-induced chronic periodontitis patients

PubMed Central

Sudhakar, Uma; Thyagarajan, Ramakrishnan; Jeyapal, Bhagyameena; Jagadeesh, Sushuruthi; Jayakumar, Parvathee

2017-01-01

Background: Periodontal disease is not a conventional bacterial infection but is an inflammatory disease initiated by immune response against a group of microorganisms in susceptible hosts. There are many intriguing researches that unfold the secrets of chronic periodontitis. The current researches in chronic periodontitis are directed toward an approach that respects the scientific relationship between the various risk factors, the genetic factors, and the progression of the disease. Aim: This study aims to evaluate the cortisol and reactive oxygen metabolites (ROM) concentration in serum and to find out their association in periodontal health and disease. Materials and Methods: In this study, totally thirty patients have been taken and divided into two groups of chronic periodontitis (Group I) and stress-induced chronic periodontitis (Group II) and evaluated the correlation between the ROM and cortisol levels in them. This is the first study, where both the levels of ROM and cortisol are checked in the serum and saliva. The analysis is done to check the association between them. Statistical Analysis: The data were statistically analyzed using software program (SPSSV 16), Pearson correlation, and paired t-test. Results: Comparison of the mean ROM levels in Group I and Group II showed that mean ROM level in Group II is highly significant than Group I. Conclusion: Our study suggests that stress can have a role in the progression of periodontal disease by increasing the cortisol and ROM levels. PMID:29491582

Lifestyle modification and progressive renal failure.

PubMed

Ritz, Eberhard; Schwenger, Vedat

2005-08-01

There is increasing evidence that lifestyle factors impact on the risk of developing chronic kidney disease (CKD) and the risk of progression of CKD. Equally important is the consideration that patients with CKD are more likely to die from cardiovascular disease than to reach the stage of end-stage renal failure. It is advantageous that manoeuvres that interfere with progression at the same time also reduce the risk of cardiovascular events. Lifestyle factors that aggravate progression include, among others, smoking, obesity and dietary salt intake. Alcohol consumption, according to some preliminary information, has a bimodal relationship to cardiovascular risk and progression, with moderate consumption being protective.

Wii Fit balance training or progressive balance training in patients with chronic stroke: a randomised controlled trial.

PubMed

Yatar, Gozde Iyigun; Yildirim, Sibel Aksu

2015-04-01

[Purpose] The aim of this study was to compare the effects of Wii Fit balance training (WBT) and progressive balance training (PBT) approaches on balance functions, balance confidence, and activities of daily living in chronic stroke patients. [Subjects] A total of 30 patients were randomized into the WBT (n=15) and PBT (n=15) groups. [Methods] All of the subjects received exercise training based on a neurodevelopemental approach in addition to either Wii Fit or progressive balance training for total of 1 hour a day, 3 days per week for 4 weeks. Primary measurements were static balance function measured with a Wii Balance Board and dynamic balance function assessed with the Berg Balance Scale, Timed Up and Go test, Dynamic Gait Index, and Functional Reach Test. Secondary measures were balance confidence assessed with the Activities-specific Balance Confidence scale and activities of daily living evaluated with the Frenchay Activity Index. [Results] There was not remarkable difference between the two treatments in dynamic balance functions, balance confidence, and activities of daily living. [Conclusion] Although both of the approaches were found to be effective in improving the balance functions, balance confidence, and activities of daily living, neither of them were more preferable than the other for the treatment of balance in patients with chronic stroke.

Demonstration of human T-cell lymphotropic virus type I (HTLV-I) from an HTLV-I seronegative south Indian patient with chronic, progressive spastic paraparesis.

PubMed

Nishimura, M; Mingioli, E; McFarlin, D E; Jacobson, S

1993-12-01

Here we describe a human T-cell lymphotropic virus type I (HTLV-I) seronegative patient from South India with a chronic, progressive spastic paraparesis from which HTLV-I has been isolated from peripheral blood lymphocytes. HTLV-I pol and tax viral sequences were detected in DNA from fresh peripheral blood lymphocytes (PBL) by polymerase chain reaction (PCR) and liquid hybridization techniques. Southern blot analysis of the PCR products demonstrated a low copy number of HTLV-I at the level of one viral copy per 10,000 fresh PBL. A long-term CD4+ T-cell line was established from PBL of this patient using recombinant interleukin-2, OKT3, and feeder cells. DNA from these cultured lines was amplified and portions of the HTLV-I long terminal repeat (U3), pol, env, and tax regions were sequenced (a total of 1,115 bp). The sequence data showed that the HTLV-I associated with this patient was 98.8% homologous to prototype HTLV-I. Southern blot analysis also confirmed the presence of full-length HTLV-I. These results indicate that HTLV-I can be demonstrated in an HTLV-I seronegative patient from South India with a chronic progressive neurological disorder.

Loss of DNAM-1 contributes to CD8+ T cell exhaustion in chronic HIV-1 infection

PubMed Central

Cella, Marina; Presti, Rachel; Vermi, William; Lavender, Kerry; Turnbull, Emma; Ochsenbauer-Jambor, Christina; Kappes, John C.; Ferrari, Guido; Kessels, Lisa; Williams, Ian; McMichael, Andrew J.; Haynes, Barton F.; Borrow, Persephone; Colonna, Marco

2011-01-01

Summary The hallmark of chronic viral infections is a progressive exhaustion of antigen specific CD8+ T cells that leads to persisting viral replication. It is generally believed that exhaustion is a consequence of the accumulation of multiple inhibitory receptors on CD8+ T cells that makes them dysfunctional. Here we show that during human chronic HIV-1 infection a CD8+ T cell positive costimulatory pathway mediated by DNAM-1 is also disrupted. Thus, DNAM-1 downregulation on CD8+ T cells aggravates the impairment of CTL effector function in chronic HIV-1 infection. PMID:20201043

Pyrexia-associated Relapse in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Case Report.

PubMed

Ueda, Jun; Yoshimura, Hajime; Kohara, Nobuo

2018-04-27

Chronic inflammatory demyelinating polyradiculoneuropathy is a relapsing-remitting or chronic progressive demyelinating polyradiculoneuropathy. We report the case of a patient with chronic inflammatory demyelinating polyradiculoneuropathy who experienced relapses on four occasions after experiencing pyrexia and flu-like symptoms. Our patient showed characteristic features, such as relapse after pyrexia and flu-like symptoms, remission after pyretolysis without treatment, and the absence of remarkable improvement in a nerve conduction study in the remission phase. The serum level of tumor necrosis factor-α was elevated in the relapse phase and reduced in the remission phase; thus, the induction of cytokine release by viral infection might have caused the relapses.

Chronic Central Serous Chorioretinopathy in a Patient with Pigment Dispersion Syndrome: A Possible Correlation.

PubMed

Kourkoutas, Dimitrios; Tsakonas, George; Karamaounas, Aristotelis; Karamaounas, Nikolaos

2017-01-01

Chronic central serous chorioretinopathy (CSCR) is a progressive chorioretinopathy with widespread atrophic RPE abnormalities and serous retinal detachments (SRDs) present for 6 months or longer. We report a case of CSCR in a 38-year-old patient with Pigment Dispersion Syndrome (PDS). In the presented case of CSCR, the chronic course of the disease may in part be associated with an underlying generalized degenerative dysfunction of the pigmented cells of the eye on grounds of PDS. We suggest that a chronic course of disease may be suspected in the setting of CSCR with concurrent RPE pathology, such as what is found in PDS.

[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.

Coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma with antecedent chronic lymphocytic leukemia: a case report and review of the literature.

PubMed

Abuelgasim, Khadega A; Rehan, Hinna; Alsubaie, Maha; Al Atwi, Nasser; Al Balwi, Mohammed; Alshieban, Saeed; Almughairi, Areej

2018-03-11

Chronic lymphocytic leukemia and chronic myeloid leukemia are the most common types of adult leukemia. However, it is rare for the same patient to suffer from both. Richter's transformation to diffuse large B-cell lymphoma is frequently observed in chronic lymphocytic leukemia. Purine analog therapy and the presence of trisomy 12, and CCND1 gene rearrangement have been linked to increased risk of Richter's transformation. The coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma in the same patient is extremely rare, with only nine reported cases. Here, we describe the first reported case of concurrent chronic myeloid leukemia and diffuse large B-cell lymphoma in a background of chronic lymphocytic leukemia. A 60-year-old Saudi man known to have diabetes, hypertension, and chronic active hepatitis B was diagnosed as having Rai stage II chronic lymphocytic leukemia, with trisomy 12 and rearrangement of the CCND1 gene in December 2012. He required no therapy until January 2016 when he developed significant anemia, thrombocytopenia, and constitutional symptoms. He received six cycles of fludarabine, cyclophosphamide, and rituximab, after which he achieved complete remission. One month later, he presented with progressive leukocytosis (mostly neutrophilia) and splenomegaly. Fluorescence in situ hybridization from bone marrow aspirate was positive for translocation (9;22) and reverse transcription polymerase chain reaction detected BCR-ABL fusion gene consistent with chronic myeloid leukemia. He had no morphologic or immunophenotypic evidence of chronic lymphocytic leukemia at the time. Imatinib, a first-line tyrosine kinase inhibitor, was started. Eight months later, a screening imaging revealed new liver lesions, which were confirmed to be diffuse large B-cell lymphoma. In chronic lymphocytic leukemia, progressive leukocytosis and splenomegaly caused by emerging chronic myeloid leukemia can be easily overlooked. It is unlikely that chronic myeloid leukemia arose as a result of clonal evolution secondary to fludarabine treatment given the very short interval after receiving fludarabine. It is also unlikely that imatinib contributed to the development of diffuse large B-cell lymphoma; rather, diffuse large B-cell lymphoma arose as a result of Richter's transformation. Fludarabine, trisomy 12, and CCND1 gene rearrangement might have increased the risk of Richter's transformation in this patient.

[Complete necrosis of the penis and testes by strangulation in a psychotic patient].

PubMed

Bart, S; Culty, T; Pizzoferrato, A-C; Thibault, F; Girault, N; Chartier-Kastler, E; Richard, F

2008-07-01

Complete necrosis of the penis and scrotum due to strangulation of the external genitalia is unusually encountered in urologic emergencies. Urological conservative management is recommended. Delayed presentation is a major source of complications. We report the case of a psychotic patient, who was transferred from the emergency department in a context of complete necrosis of the external genitalia. This patient's history included chronic psychotic disorder and positive HIV serology, but he refused to take either neuroleptic or antiretroviral therapy. Complete amputation of the penis and bilateral orchidectomy were performed. We report the first six months of medical management.

Mobile technologies and the holistic management of chronic diseases.

PubMed

Mirza, Farhaan; Norris, Tony; Stockdale, Rosemary

2008-12-01

Ageing populations and unhealthy lifestyles have led to some chronic conditions such as diabetes and heart disease reaching epidemic proportions in many developed nations. This paper explores the potential of mobile technologies to improve this situation. The pervasive nature of these technologies can contribute holistically across the whole spectrum of chronic care ranging from public information access and awareness, through monitoring and treatment of chronic disease, to support for patient carers. A related study to determine the perceptions of healthcare providers to m-health confirmed the view that attitudes were likely to be more important barriers to progress than technology. A key finding concerned the importance of seamless and integrated m-health processes across the spectrum of chronic disease management.

The Experience of Care-Giving for a Person with Parkinson's Disease

ERIC Educational Resources Information Center

Bogard, Connie Lynn

2010-01-01

As the population continues to become more aged and at risk for chronic illness, there will be a growing need for caregivers. Caregivers to persons with Parkinson's disease (PD) face the challenge of providing care over many years due to the chronic progressive nature of this neurological disorder. The purpose of this study was to understand and…

Mineralocorticoid receptor blockade—a novel approach to fight hyperkalaemia in chronic kidney disease

PubMed Central

Ritz, E.; Pitt, B.

2013-01-01

Hyperkalaemia continues to be a major hazard of mineralocorticoid receptor blockade in an effort to retard the progression of chronic kidney disease (CKD). In cardiac patients on mineralocorticoid receptor blockade, RLY-5016 which captures K+ in the colon has been effective in reducing the risk of hyperkalaemia. This compound might be useful in CKD as well. PMID:26120440

Roles, Responsibilities, and Relationships among Older Husbands Caring for Wives with Progressive Dementia and Other Chronic Conditions

ERIC Educational Resources Information Center

Sanders, Sara; Power, James

2009-01-01

Men are playing greater roles in the provision of care for older adults with chronic health conditions. Husbands, in particular, encounter many role transformations as they witness their wives grow in levels of dependence as a result of their illnesses. This qualitative study examines the changes that occurred in the roles, responsibilities, and…

The Decision to Terminate One's Life: Psychoanalytic Thoughts on Suicide.

ERIC Educational Resources Information Center

Rangell, Leo

1988-01-01

Examination of immediate psychoanalytic surround of decision to commit suicide finds range of motivations circumscribed. Often suicide is external aggression turned against oneself. Loss of love, or hopelessness resulting from chronic or acute lowering of self-regard, allows aggression to dominate one's libido. Manic excitement, immortality…

COX-derived prostanoid pathways in gastrointestinal cancer development and progression: novel targets for prevention and intervention.

PubMed

Cathcart, Mary-Clare; O'Byrne, Kenneth J; Reynolds, John V; O'Sullivan, Jacintha; Pidgeon, Graham P

2012-01-01

Arachidonic acid metabolism through cyclooxygenase (COX) pathways leads to the generation of biologically active eicosanoids. Eicosanoid expression levels vary during development and progression of gastrointestinal (GI) malignancies. COX-2 is the major COX-isoform responsible for G.I. cancer development/progression. COX-2 expression increases during progression from a normal to cancerous state. Evidence from observational studies has demonstrated that chronic NSAID use reduces the risk of cancer development, while both incidence and risk of death due to G.I. cancers were significantly reduced by daily aspirin intake. A number of randomized controlled trials (APC trial, Prevention of Sporadic Adenomatous Polyps trial, APPROVe trial) have also shown a significant protective effect in patients receiving selective COX-2 inhibitors. However, chronic use of selective COX-2 inhibitors at high doses was associated with increased cardiovascular risk, while NSAIDs have also been associated with increased risk. More recently, downstream effectors of COX-signaling have been investigated in cancer development/progression. PGE(2), which binds to both EP and PPAR receptors, is the major prostanoid implicated in the carcinogenesis of G.I. cancers. The role of TXA(2) in G.I. cancers has also been examined, although further studies are required to uncover its role in carcinogenesis. Other prostanoids investigated include PGD(2) and its metabolite 15d-PGJ2, PGF(1α) and PGI(2). Targeting these prostanoids in G.I. cancers has the promise of avoiding cardiovascular toxicity associated with chronic selective COX-2 inhibition, while maintaining anti-tumor reactivity. A progressive sequence from normal to pre-malignant to a malignant state has been identified in G.I. cancers. In this review, we will discuss the role of the COX-derived prostanoids in G.I. cancer development and progression. Targeting these downstream prostanoids for chemoprevention and/or treatment of G.I. cancers will also be discussed. Finally, we will highlight the latest pre-clinical technologies as well as avenues for future investigation in this highly topical research field. Copyright © 2011 Elsevier B.V. All rights reserved.

S100-A9 protein in exosomes from chronic lymphocytic leukemia cells promotes NF-κB activity during disease progression.

PubMed

Prieto, Daniel; Sotelo, Natalia; Seija, Noé; Sernbo, Sandra; Abreu, Cecilia; Durán, Rosario; Gil, Magdalena; Sicco, Estefanía; Irigoin, Victoria; Oliver, Carolina; Landoni, Ana Inés; Gabus, Raúl; Dighiero, Guillermo; Oppezzo, Pablo

2017-08-10

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by accumulation of clonal B lymphocytes, resulting from a complex balance between cell proliferation and apoptotic death. Continuous crosstalk between cancer cells and local/distant host environment is required for effective tumor growth. Among the main actors of this dynamic interplay between tumoral cells and their microenvironment are the nano-sized vesicles called exosomes. Emerging evidence indicates that secretion, composition, and functional capacity of exosomes are altered as tumors progress to an aggressive phenotype. In CLL, no data exist exploring the specific changes in the proteomic profile of plasma-derived exosomes from patients during disease evolution. We hereby report for the first time different proteomic profiles of plasma exosomes, both between indolent and progressive CLLs as well as within the individual patients at the onset of disease and during its progression. Next, we focus on the changes of the exosome protein cargoes, which are found exclusively in patients with progressive CLL after disease progression. The alterations in the proteomic cargoes underline different networks specific for leukemia progression related to inflammation, oxidative stress, and NF-κB and phosphatidylinositol 3-kinase/AKT pathway activation. Finally, our results suggest a preponderant role for the protein S100-A9 as an activator of the NFκB pathway during CLL progression and suggest that the leukemic clone can generate an autoactivation loop through S100-A9 expression, NF-κB activation, and exosome secretion. Collectively, our data propose a new pathway for NF-κB activation in CLL and highlight the importance of exosomes as extracellular mediators promoting tumor progression in CLL. © 2017 by The American Society of Hematology.

Multisystem involvement of alveolar echinococcosis in a child.

PubMed

Kantarci, Mecit; Bayraktutan, Ummugulsum; Pirimoglu, Berhan; Ogul, Hayri; Oral, Akgun; Eren, Suat; Gundogdu, Betul

2014-11-13

Alveolar echinococcosis (AE) is a chronic progressive infestation inducing a slowly progressing, life-threatening tumor-like growth in the liver. It may spread to other organs by regional extension or hematogenous or lymphatic metastasis. Herein, we report a fifteen-year-old patient diagnosed with AE of the liver and simultaneous lung and brain metastasis with a literature review.

Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity

PubMed Central

Henao-Mejia, Jorge; Elinav, Eran; Jin, Cheng-Cheng; Hao, Liming; Mehal, Wajahat Z.; Strowig, Till; Thaiss, Christoph A.; Kau, Andrew L.; Eisenbarth, Stephanie C.; Jurczak, Michael J.; Camporez, Joao-Paulo; Shulman, Gerald I.; Gordon, Jeffrey I.; Hoffman, Hal M.; Flavell, Richard A.

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty percent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different animal models reveal that inflammasome deficiency-associated changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic TNF-α expression that drives NASH progression. Furthermore, co-housing of inflammasome-deficient animals to wild type mice results in exacerbation of hepatic steatosis, glucose intolerance, and obesity. Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders. PMID:22297845

Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development.

PubMed

Andersen, Morten; Sajid, Zamra; Pedersen, Rasmus K; Gudmand-Hoeyer, Johanne; Ellervik, Christina; Skov, Vibe; Kjær, Lasse; Pallisgaard, Niels; Kruse, Torben A; Thomassen, Mads; Troelsen, Jesper; Hasselbalch, Hans Carl; Ottesen, Johnny T

2017-01-01

The chronic Philadelphia-negative myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms which ultimately may transform to acute myelogenous leukemia. Most recently, chronic inflammation has been described as an important factor for the development and progression of MPNs in the biological continuum from early cancer stage to the advanced myelofibrosis stage, the MPNs being described as "A Human Inflammation Model for Cancer Development". This novel concept has been built upon clinical, experimental, genomic, immunological and not least epidemiological studies. Only a few studies have described the development of MPNs by mathematical models, and none have addressed the role of inflammation for clonal evolution and disease progression. Herein, we aim at using mathematical modelling to substantiate the concept of chronic inflammation as an important trigger and driver of MPNs.The basics of the model describe the proliferation from stem cells to mature cells including mutations of healthy stem cells to become malignant stem cells. We include a simple inflammatory coupling coping with cell death and affecting the basic model beneath. First, we describe the system without feedbacks or regulatory interactions. Next, we introduce inflammatory feedback into the system. Finally, we include other feedbacks and regulatory interactions forming the inflammatory-MPN model. Using mathematical modeling, we add further proof to the concept that chronic inflammation may be both a trigger of clonal evolution and an important driving force for MPN disease progression. Our findings support intervention at the earliest stage of cancer development to target the malignant clone and dampen concomitant inflammation.

IMATINIB 800MG DAILY INDUCES DEEPER MOLECULAR RESPONSES THAN IMATINIB 400MG DAILY: RESULTS OF SWOG S0325, AN INTERGROUP RANDOMIZED PHASE II TRIAL IN NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOID LEUKAEMIA

PubMed Central

Deininger, Michael W.; Kopecky, Kenneth J.; Radich, Jerald P.; Kamel-Reid, Suzanne; Stock, Wendy; Paietta, Elisabeth; Emanuel, Peter D.; Tallman, Martin; Wadleigh, Martha; Larson, Richard A.; Lipton, Jeffrey H.; Slovak, Marilyn L.; Appelbaum, Frederick R.; Druker, Brian J.

2014-01-01

The standard dose of imatinib for newly diagnosed patients with chronic phase chronic myeloid leukemia (CP-CML) is 400mg daily (IM400), but the optimal dose is unknown. This randomized phase II study compared the rates of molecular, haematologic and cytogenetic response to IM400 vs. imatinib 400mg twice daily (IM800) in 153 adult patients with CP-CML. Dose adjustments for toxicity were flexible to maximize retention on study. Molecular response (MR) at 12 months was deeper in the IM800 arm (4-log reduction of BCR-ABL1 mRNA: 25% vs. 10% of patients, P=0.038; 3-log reduction: 53% vs. 35%, P=0.049). During the first 12 months BCR-ABL1 levels in the IM800 arm were an average 2.9-fold lower than in the IM400 arm (P=0.010). Complete haematologic response was similar, but complete cytogenetic response was higher with IM800 (85% vs. 67%, P=0.040). Grade 3–4 toxicities were more common for IM800 (58% vs. 31%, P=0.0007), and were most commonly haematologic. Few patients have relapsed, progressed or died, but progression-free (P=0.048) and relapse-free (P=0.031) survival were superior for IM800. In newly diagnosed CP-CML patients, IM800 induced deeper molecular responses than IM400, with a trend for improved progression-free and overall survival, but was associated with more severe toxicity. PMID:24383843

[The effect of low-protein diet supplemented with ketoacids in patients with chronic renal failure].

PubMed

Molnár, Márta; Szekeresné Izsák, Margit; Nagy, Judit; Figler, Mária

2009-02-01

It is known that dietary protein restriction slows the progression of chronic renal disease. If daily protein intake is less than 0.5-0.6 g/kgbw, the diet has to be supplemented with essential aminoacids/ketoacids. In this study the authors evaluate the long-term effect of low-protein diet supplemented with ketoacids on the progression of chronic renal failure, calcium and phosphorus metabolism, nutritional status, the compliance of patients and the permanent dietary education for the compliance. 51 predialysis patients have been treated with ketoacids supplemented low-protein diet during 12-57 months (mean treatment period: 26 months). Serum creatinine raised from 349.72+/-78.04 micromol/l to 460.66+/-206.66 micromol/l (27 micromol/l/year or 2.3 micromol/l/month), glomerular filtration rate (GFR) decreased from 21.52+/-7.84 ml/min to 18.22+/-7.76 ml/min (0.83 ml/min/year or 0.07 ml/min/month). The slope of 1/serum creatinine versus time was 0.0018 by linear regression analysis. Serum parathormon decreased significantly, but serum calcium and phosphorus did not change. Nutritional status of patients did not change significantly during the follow-up period. Protein intake decreased significantly and remained at this lower level during the treatment period. According to results: low-protein diet supplemented with ketoacids was effective in slowing progression of chronic renal failure, decreased PTH, did not change nutritional status. With permanently and good education it was possible to keep patients on low-protein diet for a long period.

N-methyl-D-aspartate receptor antagonist effects on prefrontal cortical connectivity better model early than chronic schizophrenia.

PubMed

Anticevic, Alan; Corlett, Philip R; Cole, Michael W; Savic, Aleksandar; Gancsos, Mark; Tang, Yanqing; Repovs, Grega; Murray, John D; Driesen, Naomi R; Morgan, Peter T; Xu, Ke; Wang, Fei; Krystal, John H

2015-03-15

Prefrontal cortex (PFC) function contributes to schizophrenia onset and progression. However, little is known about neural mechanisms behind PFC functional alterations along illness stages. Recent pharmacologic studies indicate that glutamate dysfunction may produce increased functional connectivity. However, pharmacologic models of schizophrenia overlook effects of illness progression on PFC function. This study compared N-methyl-D-aspartate glutamate receptor (NMDAR) antagonist effects in healthy volunteers with stages of schizophrenia with respect to PFC functional connectivity. First, we tested ketamine effects on PFC functional connectivity in healthy volunteers in a data-driven way (n = 19). Next, we compared healthy subjects (n = 96) with three clinical groups: individuals at high risk for schizophrenia (n = 21), people early in their course of schizophrenia (EC-SCZ) (n = 28), and patients with chronic illness (n = 20). Across independent analyses, we used data-driven global brain connectivity techniques restricted to PFC to identify functional dysconnectivity. Results revealed robust PFC hyperconnectivity in healthy volunteers administered ketamine (Cohen's d = 1.46), resembling individuals at high risk for schizophrenia and EC-SCZ. Hyperconnectivity was not found in patients with chronic illness relative to EC-SCZ patients. Results provide the first evidence that ketamine effects on PFC functional connectivity resemble early course but not chronic schizophrenia. Results suggest an illness phase-specific relevance of NMDAR antagonist administration for prefrontal dysconnectivity associated with schizophrenia. This finding has implications for the neurobiology of illness progression and for the widespread use of NMDAR antagonists in the development of therapeutics for schizophrenia. Copyright © 2015. Published by Elsevier Inc.

Vegetarian Diet in Chronic Kidney Disease—A Friend or Foe

PubMed Central

Gluba-Brzózka, Anna; Franczyk, Beata; Rysz, Jacek

2017-01-01

Healthy diet is highly important, especially in patients with chronic kidney disease (CKD). Proper nutrition provides the energy to perform everyday activities, prevents infection, builds muscle, and helps to prevent kidney disease from getting worse. However, what does a proper diet mean for a CKD patient? Nutrition requirements differ depending on the level of kidney function and the presence of co-morbid conditions, including hypertension, diabetes, and cardiovascular disease. The diet of CKD patients should help to slow the rate of progression of kidney failure, reduce uremic toxicity, decrease proteinuria, maintain good nutritional status, and lower the risk of kidney disease-related secondary complications (cardiovascular disease, bone disease, and hypertension). It has been suggested that plant proteins may exert beneficial effects on blood pressure, proteinuria, and glomerular filtration rate, as well as results in milder renal tissue damage when compared to animal proteins. The National Kidney Foundation recommends vegetarianism, or part-time vegetarian diet as being beneficial to CKD patients. Their recommendations are supported by the results of studies demonstrating that a plant-based diet may hamper the development or progression of some complications of chronic kidney disease, such as heart disease, protein loss in urine, and the progression of kidney damage. However, there are sparse reports suggesting that a vegan diet is not appropriate for CKD patients and those undergoing dialysis due to the difficulty in consuming enough protein and in maintaining proper potassium and phosphorus levels. Therefore, this review will focus on the problem as to whether vegetarian diet and its modifications are suitable for chronic kidney disease patients. PMID:28394274

Vegetarian Diet in Chronic Kidney Disease-A Friend or Foe.

PubMed

Gluba-Brzózka, Anna; Franczyk, Beata; Rysz, Jacek

2017-04-10

Healthy diet is highly important, especially in patients with chronic kidney disease (CKD). Proper nutrition provides the energy to perform everyday activities, prevents infection, builds muscle, and helps to prevent kidney disease from getting worse. However, what does a proper diet mean for a CKD patient? Nutrition requirements differ depending on the level of kidney function and the presence of co-morbid conditions, including hypertension, diabetes, and cardiovascular disease. The diet of CKD patients should help to slow the rate of progression of kidney failure, reduce uremic toxicity, decrease proteinuria, maintain good nutritional status, and lower the risk of kidney disease-related secondary complications (cardiovascular disease, bone disease, and hypertension). It has been suggested that plant proteins may exert beneficial effects on blood pressure, proteinuria, and glomerular filtration rate, as well as results in milder renal tissue damage when compared to animal proteins. The National Kidney Foundation recommends vegetarianism, or part-time vegetarian diet as being beneficial to CKD patients. Their recommendations are supported by the results of studies demonstrating that a plant-based diet may hamper the development or progression of some complications of chronic kidney disease, such as heart disease, protein loss in urine, and the progression of kidney damage. However, there are sparse reports suggesting that a vegan diet is not appropriate for CKD patients and those undergoing dialysis due to the difficulty in consuming enough protein and in maintaining proper potassium and phosphorus levels. Therefore, this review will focus on the problem as to whether vegetarian diet and its modifications are suitable for chronic kidney disease patients.

Hypoxia, hypoxia-inducible factors and fibrogenesis in chronic liver diseases.

PubMed

Cannito, Stefania; Paternostro, Claudia; Busletta, Chiara; Bocca, Claudia; Colombatto, Sebastiano; Miglietta, Antonella; Novo, Erica; Parola, Maurizio

2014-01-01

Fibrogenic progression of chronic liver diseases (CLDs) towards the end-point of cirrhosis is currently regarded, whatever the aetiology, as a dynamic and highly integrated cellular response to chronic liver injury. Liver fibrogenesis (i.e., the process) is sustained by hepatic populations of highly proliferative, pro-fibrogenic and contractile myofibroblast-like cells (MFs) that mainly originate from hepatic stellate cells (HSC) or, to a less extent, from portal fibroblasts or bone marrow-derived cells. As is well known, liver fibrosis (i.e., the result) is accompanied by perpetuation of liver injury, chronic hepatitis and persisting activation of tissue repair mechanisms, leading eventually to excess deposition of extracellular matrix (ECM) components. In this scenario, hypoxic areas represent a very common and major feature of fibrotic and cirrhotic liver during the progression of CLDs. Cells exposed to hypoxia respond by means of heterodimeric hypoxia-inducible factors (HIFs) that translocate into the nucleus and binds to a specific core sequence defined hypoxia-responsive element (HRE), present in the promoter on several genes which are considered as hypoxia-regulated target genes. HIFs transcription factors can activate a complex genetic program designed to sustain several changes necessary to efficiently counteract the decrease in oxygen tension. Accordingly, hypoxia, through up-regulation of angiogenesis, is currently believed to significantly contribute to fibrogenic progression of CLDs, mostly by affecting the pro-fibrogenic and pro-angiogenic behaviour of hepatic MFs. In addition, experimental and clinical evidence generated in the last decade also indicates that angiogenesis and fibrogenesis in CLDs may also be sustained by HIF-dependent but hypoxia-independent mediators.

Cell cycle arrest and the evolution of chronic kidney disease from acute kidney injury.

PubMed

Canaud, Guillaume; Bonventre, Joseph V

2015-04-01

For several decades, acute kidney injury (AKI) was generally considered a reversible process leading to complete kidney recovery if the individual survived the acute illness. Recent evidence from epidemiologic studies and animal models, however, have highlighted that AKI can lead to the development of fibrosis and facilitate the progression of chronic renal failure. When kidney injury is mild and baseline function is normal, the repair process can be adaptive with few long-term consequences. When the injury is more severe, repeated, or to a kidney with underlying disease, the repair can be maladaptive and epithelial cell cycle arrest may play an important role in the development of fibrosis. Indeed, during the maladaptive repair after a renal insult, many tubular cells that are undergoing cell division spend a prolonged period in the G2/M phase of the cell cycle. These tubular cells recruit intracellular pathways leading to the synthesis and the secretion of profibrotic factors, which then act in a paracrine fashion on interstitial pericytes/fibroblasts to accelerate proliferation of these cells and production of interstitial matrix. Thus, the tubule cells assume a senescent secretory phenotype. Characteristic features of these cells may represent new biomarkers of fibrosis progression and the G2/M-arrested cells may represent a new therapeutic target to prevent, delay or arrest progression of chronic kidney disease. Here, we summarize recent advances in our understanding of the biology of the cell cycle and how cell cycle arrest links AKI to chronic kidney disease. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Lung disease and coal mining: what pulmonologists need to know.

PubMed

Go, Leonard H T; Krefft, Silpa D; Cohen, Robert A; Rose, Cecile S

2016-03-01

Coal mine workers are at risk for a range of chronic respiratory diseases including coal workers' pneumoconiosis, diffuse dust-related fibrosis, and chronic obstructive pulmonary disease. The purpose of this review is to describe coal mining processes and associated exposures to inform the diagnostic evaluation of miners with respiratory symptoms. Although rates of coal workers' pneumoconiosis declined after regulations were enacted in the 1970s, more recent data shows a reversal in this downward trend. Rapidly progressive pneumoconiosis with progressive massive fibrosis (complicated coal workers' pneumoconiosis) is being observed with increased frequency in United States coal miners, with histologic findings of silicosis and mixed-dust pneumoconiosis. There is increasing evidence of decline in lung function in individuals with pneumoconiosis. Multiple recent cohort studies suggest increased risk of lung cancer in coal miners. A detailed understanding of coal mining methods and processes allows clinicians to better evaluate and confirm chronic lung diseases caused by inhalational hazards in the mine atmosphere.

Hypovitaminosis D, neighborhood poverty, and progression of chronic kidney disease in disadvantaged populations.

PubMed

Mehrotra, R; Norris, K

2010-11-01

In the United States, there are significant racial disparities in the incidence and prevalence of end-stage renal disease. The disparities are greatest for the Blacks and the magnitude of disparity is significantly greater than is evident from the incidence and prevalence data of end-stage renal disease - early stage chronic kidney disease is less common in Blacks and during that stage, mortality rate is significantly higher for that racial group. Recent studies have identified a genetic predisposition for non-diabetic renal disease among Blacks. However, genetic factors explain only part of the higher risk and the racial disparities are a result of a complex interplay of biology and sociology. Herein we focus on two factors and their role in explaining the higher risk for progression of chronic kidney disease among Blacks - one biologic (vitamin D deficiency) and one sociologic (neighborhood poverty). A greater Understanding of these factors is important in order to reduce the racial disparities in the United States.

Synopsis on the linkage of Alzheimer's and Parkinson's disease with chronic diseases.

PubMed

Jabir, Nasimudeen R; Firoz, Chelapram K; Baeesa, Saleh S; Ashraf, Ghulam Md; Akhtar, Suhail; Kamal, Warda; Kamal, Mohammad A; Tabrez, Shams

2015-01-01

Neurodegeneration is the progressive loss of neuronal structure and function, which ultimately leads to neurological disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis, and Huntington's disease. Even after the recent significant advances in neurobiology, the above-mentioned disorders continue to haunt the global population. Several studies have suggested the role of specific environmental and genetic risk factors associated with these disorders. However, the exact mechanism associated with the progression of these disorders still needs to be elucidated. In the recent years, sophisticated research has revealed interesting association of prominent neurodegenerative disorders such as AD and PD with chronic diseases such as cancer, diabetes, and cardiovascular diseases. Several common molecular mechanisms such as generation of free radicals, oxidative DNA damage, aberrations in mitochondrial DNA, and dysregulation of apoptosis have been highlighted as possible points of connection. The present review summarizes the possible mechanism of coexistence of AD and PD with other chronic diseases. © 2014 John Wiley & Sons Ltd.

Vascular calcification: When should we interfere in chronic kidney disease patients and how?

PubMed Central

Sharaf El Din, Usama Abdel Azim; Salem, Mona Mansour; Abdulazim, Dina Ossama

2016-01-01

Chronic kidney disease (CKD) patients are endangered with the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the fatalities. Cardiovascular calcifications affect most of the CKD patients. Most of this calcification is related to disturbed renal phosphate handling. Fibroblast growth factor 23 and klotho deficiency were incriminated in the pathogenesis of vascular calcification through different mechanisms including their effects on endothelium and arterial wall smooth muscle cells. In addition, deficient klotho gene expression, a constant feature of CKD, promotes vascular pathology and shares in progression of the CKD. The role of gut in the etio-pathogenesis of systemic inflammation and vascular calcification is a newly discovered mechanism. This review will cover the medical history, prevalence, pathogenesis, clinical relevance, different tools used to diagnose, the ideal timing to prevent or to withhold the progression of vascular calcification and the different medications and medical procedures that can help to prolong the survival of CKD patients. PMID:27648404

Clinical assessment and treatment of diabetes in patients with chronic kidney disease.

PubMed

Carretero Gómez, J; Arévalo Lorido, J C

2018-04-21

Diabetes mellitus type 2 is the main cause of chronic kidney disease. Patients with this disease have higher morbidity and mortality and risk of hypoglycaemia than those without this disease. In 2010, type 2 diabetes was the reason for starting renal replacement therapy in 24.7% of patients. The prevalence of microalbuminuria, proteinuria and a reduced glomerular filtration rate is 36%, 8% and 22%, respectively. The presence of albuminuria is a predictor of chronic kidney disease. Diabetic kidney disease, previously known as diabetic nephropathy, refers to kidney disease caused by diabetes. Renal hyperfiltration is a marker of intraglomerular hypertension and a risk factor for onset and progression. The new antidiabetic drugs, mainly dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter inhibitors and glucagon-like peptide-1 agonists, have been shown to prevent or slow the progression of kidney disease. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Molecular basis of alcoholism.

PubMed

Most, Dana; Ferguson, Laura; Harris, R Adron

2014-01-01

Acute alcohol intoxication causes cellular changes in the brain that last for hours, while chronic alcohol use induces widespread neuroadaptations in the nervous system that can last a lifetime. Chronic alcohol use and the progression into dependence involve the remodeling of synapses caused by changes in gene expression produced by alcohol. The progression of alcohol use, abuse, and dependence can be divided into stages, which include intoxication, withdrawal, and craving. Each stage is associated with specific changes in gene expression, cellular function, brain circuits, and ultimately behavior. What are the molecular mechanisms underlying the transition from recreational use (acute) to dependence (chronic)? What cellular adaptations result in drug memory retention, leading to the persistence of addictive behaviors, even after prolonged drug abstinence? Research into the neurobiology of alcoholism aims to answer these questions. This chapter will describe the molecular adaptations caused by alcohol use and dependence, and will outline key neurochemical participants in alcoholism at the molecular level, which are also potential targets for therapy. © 2014 Elsevier B.V. All rights reserved.

Efficacy of a novel swallowing exercise program for chronic dysphagia in long-term head and neck cancer survivors.

PubMed

Kraaijenga, Sophie A C; Molen, Lisette van der; Stuiver, Martijn M; Takes, Robert P; Al-Mamgani, Abrahim; Brekel, Michiel W M van den; Hilgers, Frans J M

2017-10-01

The efficacy of rehabilitative exercises for chronic dysphagia treatment in head and neck cancer survivors has not been studied extensively and is ambiguous. A prospective clinical phase II study using an intensive strength training program was carried out in 17 head and neck cancer survivors with chronic dysphagia. Both swallow and nonswallow exercises were performed for 6-8 weeks with a newly developed tool allowing for progressive muscle overload, including chin tuck, jaw opening, and effortful swallow exercises. Outcome parameters were feasibility, compliance, and parameters for effect. Feasibility in terms of the program completion rate was 88%. Compliance with the exercises was 97%. After the training period, chin tuck, jaw opening, and anterior tongue strength had substantially improved. All but 1 patient reported to benefit from the exercises. Feasibility and compliance were high. Some objective and subjective effects of progressive load on muscle strength and swallowing function could be demonstrated. © 2017 Wiley Periodicals, Inc.

A Comparison of Self-Hypnosis Versus Progressive Muscle Relaxation in Patients With Multiple Sclerosis and Chronic Pain1

PubMed Central

Jensen, Mark P.; Barber, Joseph; Romano, Joan M.; Molton, Ivan R.; Raichle, Katherine A.; Osborne, Travis L.; Engel, Joyce M.; Stoelb, Brenda L.; Kraft, George H.; Patterson, David R.

2009-01-01

Twenty-two patients with multiple sclerosis (MS) and chronic pain we recruited into a quasi-experimental trial comparing the effects of self-hypnosis training (HYP) with progressive muscle relaxation (PMR) on pain intensity and pain interference; 8 received HYP and the remaining 14 participants were randomly assigned to receive either HYP or PMR. HYP-condition participants reported significantly greater pre- to postsession as well as pre- to posttreatment decreases in pain and pain interference than PMR-condition participants, and gains were maintained at 3-month follow-up. Most of the participants in both conditions reported that they continued to use the skills they learned in treatment and experienced pain relief when they did so. General hypnotizability was not significantly related to treatment outcome, but treatment-outcome expectancy assessed before and after the first session was. The results support the efficacy of self-hypnosis training for the management of chronic pain in persons with MS. PMID:19234967

Resveratrol Improved the Progression of Chronic Prostatitis via the Downregulation of c-kit/SCF by Activating Sirt1.

PubMed

He, Yi; Zeng, Huizhi; Yu, Yang; Zhang, Jiashu; Zeng, Xiaona; Gong, Fengtao; Duan, Xingping; Liu, Qi; Yang, Bo

2017-07-19

The regulation mechanism of inflammation inducing prostate carcinogenesis remains largely unknown. Therefore, we investigated the role of the c-kit/SCF pathway, which has been associated with the control of prostate carcinogenesis, in chronic prostatitis (CP) rats and evaluated the anti-prostatitis effect of resveratrol. We performed hemolysin and eosin staining to evaluate the histopathological changes in prostates. Multiple approaches evaluated the expression levels of c-kit, stem cell factor (SCF), Sirt1, and carcinogenesis-associated proteins. The CP group exhibited severe diffuse chronic inflammation. Meanwhile, the prostate cells appeared atypia; the activity of c-kit/SCF was upregulated, and carcinogenesis-associated proteins are dysregulated significantly in CP rats. Resveratrol treatment significantly improved these factors by Sirt1 activation. In summary, CP could further cause prostate carcinogenesis, which may be associated with activated c-kit/SCF signaling. Resveratrol treatment could improve the progression of CP via the downregulation of c-kit/SCF by activating Sirt1.

[Influence of cryoglobulinemic syndrome and insulin resistance on the progression of liver cirrhosis in patients with chronic hepatitis C].

PubMed

Kondratiuk, L O; Bezrodna, O V; Kuliesh, O V

2014-01-01

The article presents the results of analysis of the frequency of detection of cryoglobulinemic syndrome (CGS) and insulin resistance (IR) in patients with HCV-associated liver cirrhosis (LC) depending on its stage. There were also evaluated clinical and laboratory features of the disease. The study involved 72 patients with chronic hepatitis C who were divided into 3 main groups according to the presence of LC. The I group included 32 patients with chronic hepatitis C without LC. The II group consisted of 19 patients with compensated HCV-associated LC and III group included 21 patients with decompensated LC. It was shown that terminal stages of the LC (class B-C by Child-Pugh) are characterized by more frequent presence of IR and CGS with more severe clinical picture, which may be caused not only by the influence of the hepatitis C virus (HCV), but also by the progression of LC.

Solid cancer mortality associated with chronic external radiation exposure at the French atomic energy commission and nuclear fuel company.

PubMed

Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

2011-07-01

Studies of nuclear workers make it possible to directly quantify the risks associated with ionizing radiation exposure at low doses and low dose rates. Studies of the CEA (Commissariat à l'Energie Atomique) and AREVA Nuclear Cycle (AREVA NC) cohort, currently the most informative such group in France, describe the long-term risk to nuclear workers associated with external exposure. Our aim is to assess the risk of mortality from solid cancers among CEA and AREVA NC nuclear workers and its association with external radiation exposure. Standardized mortality ratios (SMRs) were calculated and internal Poisson regressions were conducted, controlling for the main confounding factors [sex, attained age, calendar period, company and socioeconomic status (SES)]. During the period 1968-2004, there were 2,035 solid cancers among the 36,769 CEA-AREVA NC workers. Cumulative external radiation exposure was assessed for the period 1950-2004, and the mean cumulative dose was 12.1 mSv. Mortality rates for all causes and all solid cancers were both significantly lower in this cohort than in the general population. A significant excess of deaths from pleural cancer, not associated with cumulative external dose, was observed, probably due to past asbestos exposure. We observed a significant excess of melanoma, also unassociated with dose. Although cumulative external dose was not associated with mortality from all solid cancers, the central estimated excess relative risk (ERR) per Sv of 0.46 for solid cancer mortality was higher than the 0.26 calculated for male Hiroshima and Nagasaki A-bomb survivors 50 years or older and exposed at the age of 30 years or older. The modification of our results after stratification for SES demonstrates the importance of this characteristic in occupational studies, because it makes it possible to take class-based lifestyle differences into account, at least partly. These results show the great potential of a further joint international study of nuclear workers, which should improve knowledge about the risks associated with chronic low doses and provide useful risk estimates for radiation protection.

Feedback and Feedforward Control During Walking in Individuals With Chronic Ankle Instability.

PubMed

Yen, Sheng-Che; Corkery, Marie B; Donohoe, Amy; Grogan, Maddison; Wu, Yi-Ning

2016-09-01

Study Design Controlled laboratory study. Background Recurrent ankle sprains associated with chronic ankle instability (CAI) occur not only in challenging sports but also in daily walking. Understanding whether and how CAI alters feedback and feedforward controls during walking may be important for developing interventions for CAI prevention or treatment. Objective To understand whether CAI is associated with changes in feedback and feedforward control when individuals with CAI are subjected to experimental perturbation during walking. Methods Twelve subjects with CAI and 12 control subjects walked on a treadmill while adapting to external loading that generated inversion perturbation at the ankle joint. Ankle kinematics around heel contact during and after the adaptation were compared between the 2 groups. Results Both healthy and CAI groups showed an increase in eversion around heel contact in early adaptation to the external loading. However, the CAI group adapted back toward the baseline, while the healthy controls showed further increase in eversion in late adaptation. When the external loading was removed in the postadaptation period, healthy controls showed an aftereffect consisting of an increase in eversion around heel contact, but the CAI group showed no aftereffect. Conclusion The results provide preliminary evidence that CAI may alter individuals' feedback and feedforward control during walking. J Orthop Sports Phys Ther 2016;46(9):775-783. Epub 5 Aug 2016. doi:10.2519/jospt.2016.6403.

Academic Pancreas Centers of Excellence: Guidance from a multidisciplinary chronic pancreatitis working group at PancreasFest

PubMed Central

Sheth, Sunil G.; Conwell, Darwin L.; Whitcomb, David C.; Alsante, Matthew; Anderson, Michelle A.; Barkin, Jamie; Brand, Randall; Cote, Gregory A.; Freedman, Steven D.; Gelrud, Andres; Gorelick, Fred; Lee, Linda S.; Morgan, Katherine; Pandol, Stephen; Singh, Vikesh K.; Yadav, Dhiraj; Mel Wilcox, C.; Hart, Phil A.

2017-01-01

Chronic pancreatitis (CP) is a progressive inflammatory disease, which leads to loss of pancreatic function and other disease-related morbidities. A group of academic physicians and scientists developed comprehensive guidance statements regarding the management of CP that include its epidemiology, diagnosis, medical treatment, surgical treatment, and screening. The statements were developed through literature review, deliberation, and consensus opinion. These statements were ultimately used to develop a conceptual framework for the multidisciplinary management of chronic pancreatitis referred to as an academic pancreas center of excellence (APCOE). PMID:28268158

Serial protocol biopsies to quantify the progression of chronic transplant nephropathy in stable renal allografts.

PubMed

Moreso, F; Lopez, M; Vallejos, A; Giordani, C; Riera, L; Fulladosa, X; Hueso, M; Alsina, J; Grinyó, J M; Serón, D

2001-05-01

To evaluate the utility of intimal thickness and interstitial width as a primary efficacy variable in the design of clinical trials aimed to modify the natural history of chronic allograft nephropathy. A donor and a 4-month protocol biopsy were evaluated in 40 stable grafts according to the Banff schema. In 27 patients, a second protocol biopsy was done at 1 yr. Arterial intimal volume fraction (Vvintima/artery) and cortical interstitial volume fraction (Vvinterstitium/cortex) were estimated with a point counting technique. Chronic Banff scores increased during follow-up, while acute scores reached its peak at 4 months. Vvintima/artery and Vvinterstitium/cortex significantly increased at 4 months, but not at 1 yr. Vvintima/artery at 4 months correlated with donor Vvintima/artery (r = 0.57, p < 0.001), histocompatibility (r = 0.38, p = 0.01) and serum cholesterol (r = 0.31, p = 0.047). Vvinterstitium/cortex at 4 months correlated with recipient body surface area (r = 0.44, p = 0.004) and delayed graft function (p = 0.016). Power calculations showed that Vvintima/artery and Vvinterstitium/cortex allow an important reduction in minimum sample size of a hypothetical trial aimed to prevent chronic allograft nephropathy. Intimal thickening and interstitial widening progresses rapidly during the first 4 months after transplantation and slowly thereafter. These parameters can be considered as a primary efficacy variable in trials aimed to prevent chronic allograft nephropathy.

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

G.Y. Fu; L.P. Ku; M.H. Redi

A key issue for compact stellarators is the stability of beta-limiting MHD modes, such as external kink modes driven by bootstrap current and pressure gradient. We report here recent progress in MHD stability studies for low-aspect-ratio Quasi-Axisymmetric Stellarators (QAS) and Quasi-Omnigeneous Stellarators (QOS). We find that the N = 0 periodicity-preserving vertical mode is significantly more stable in stellarators than in tokamaks because of the externally generated rotational transform. It is shown that both low-n external kink modes and high-n ballooning modes can be stabilized at high beta by appropriate 3D shaping without a conducting wall. The stabilization mechanism formore » external kink modes in QAS appears to be an enhancement of local magnetic shear due to 3D shaping. The stabilization of ballooning mode in QOS is related to a shortening of the normal curvature connection length.« less

Evolution of ferromagnetism in charge ordered manganite: An effect of external pressure

NASA Astrophysics Data System (ADS)

Dash, S.; Pradhan, M. K.; Rao, T. Lakshmana

2018-05-01

Detailed magnetic measurements of the Pr0.75Na0.25MnO3 polycrystalline sample have been carried out under external hydrostatic pressure upto 10kbar. Pressure strongly suppresses the first order magnetic transition, while thermal hysteresis narrows down progressively and then disappears with increase in pressure. The significant enhancement of the field cooled magnetization value at different pressures is due to the antiferromagnetic to ferromagnetic transformation, while ruling out any contribution from the domain alignment within the ferromagnetic phase.

Primary Synovial Sarcoma of External Auditory Canal: A Case Report.

PubMed

Devi, Aarani; Jayakumar, Krishnannair L L

2017-07-20

Synovial sarcoma is a rare malignant tumor of mesenchymal origin. Primary synovial sarcoma of the ear is extremely rare and to date only two cases have been published in English medical literature. Though the tumor is reported to have an aggressive nature, early diagnosis and treatment may improve the outcome. Here, we report a rare case of synovial sarcoma of the external auditory canal in an 18-year-old male who was managed by chemotherapy and referred for palliation due to tumor progression.

High Contrast Internal and External Coronagraph Masks Produced by Various Techniques

NASA Technical Reports Server (NTRS)

Balasubramanian, Kunjithapatha; Wilson, Daniel; White, Victor; Muller, Richard; Dickie, Matthew; Yee, Karl; Ruiz, Ronald; Shaklan, Stuart; Cady, Eric; Kern, Brian;

A theoretical analysis and finite element simulation of fixator-bone system stiffness on healing progression.

PubMed

Li, Jianfeng; Zhao, Xia; Hu, Xiaojie; Tao, Chunjing; Ji, Run

2018-03-01

The unilateral external fixator has become a quick and easy application for fracture stabilization of the extremities; the main value for evaluation of mechanical stability of the external fixator is stiffness. The stiffness property of the external fixator affects the local biomechanical environment of fractured bone. In this study, a theoretical model with changing Young's modulus of the callus is established by using the Castigliano's theory, investigating compression stiffness, torsional stiffness and bending stiffness of the fixator-bone system during the healing process. The effects of pin deviation angle on three stiffness methods are also investigated. In addition, finite element simulation is discussed regarding the stress distribution between the fixator and bone. The results reveal the three stiffness evaluation methods are similar for the fixator-bone system. Finite element simulation shows that with increased healing time, the transmission of the load between the fixator and bone are different. In addition, the finite element analyses verify the conclusions obtained from the theoretical model. This work helps orthopedic doctors to monitor the progression of fracture healing and determine the appropriate time for removal of a fixation device and provide important theoretical methodology.

Extended Mortality and Chronic Kidney Disease After Septic Acute Kidney Injury.

PubMed

Chua, Horng-Ruey; Wong, Weng-Kin; Ong, Venetia Huiling; Agrawal, Dipika; Vathsala, Anantharaman; Tay, Hui-Ming; Mukhopadhyay, Amartya

2018-01-01

To evaluate 1-year mortality in patients with septic acute kidney injury (AKI) and to determine association between initial AKI recovery patterns ( reversal within 5 days, beyond 5 days but recovery, or nonrecovery) and chronic kidney disease (CKD) progression. Prospective observational study, with retrospective evaluation of initial nonconsenters, of critically ill patients with septic AKI. We studied 207 patients (age, mean [SD]: 64 [16] years, 39% males), of which 56 (27%), 18 (9%), and 9 (4%) died in intensive care unit (ICU), post-ICU in hospital, and posthospitalization, respectively. Infections (including pneumonia) and major adverse cardiac events accounted for 64% and 12% of deaths, respectively. Factors independently associated with 1-year mortality include older age, ischemic heart disease, higher Simplified Acute Physiology Score II, central nervous system or musculoskeletal primary infections, higher daily fluid balance (FB), and frusemide administration during ICU stay (all P < .05). Among 63 patients receiving renal replacement therapy (RRT), hospital mortality was higher with cumulative median FB >8 L versus ≤8 L at RRT initiation (57% vs 24%; P = .009); there was trend for less ICU- and RRT-free days at day 28 in patients with higher FB pre-RRT ( P = NS). Chronic kidney disease progression over 1 year developed in 21%, 30%, and 79% of 105 initial survivors with AKI reversal, recovery, and nonrecovery, respectively ( P < .001). Acute kidney injury nonrecovery during hospitalization independently predicted CKD progression ( P = .001). Patients with septic AKI had 40% 1-year mortality, mainly associated with infections. High FB and frusemide administration were modifiable risk factors. Risk of CKD progression is high especially with initial AKI nonrecovery.

Understanding the major risk factors in the beginning and the progression of rheumatoid arthritis: current scenario and future prospects.

PubMed

Verma, Mahendra Kumar; Sobha, Kota

2015-09-01

Rheumatoid arthritis (RA), a chronic progressive inflammatory autoimmune disorder characterized by chronic pain and swelling primarily, affects the peripheral joints. RA had attained global concern in the last few decades, affecting more than 1.5 % of the world's population with higher female percentage than male. In the advanced stage, the disease is associated with the destruction of cartilage and bone along with a variety of systemic manifestations leading to functional disability. Inadequate early/preliminary diagnosis and non-specific therapeutics are the major challenges in the management of RA. Till date, the exact cause(s) of the disease remain(s) obscure, and several genetic, hormonal, and environmental factors are associated with the beginning and the progression of the disease. Rheumatoid factor is the only clinically approved bio-marker for the diagnosis, and RA is not restricted to bones, but also affects several vital organs in the advanced stages. Genome-wide association studies have explored novel genetic loci underlying common autoimmune diseases including RA. Recent discoveries of risk alleles have made it possible to define genetic risk profiles of patients with RA. The conventional non-steroidal anti-inflammatory drugs and steroidal drugs are still the choice for the treatment of RA under acute and chronic pathological conditions respectively. However, disease-modifying anti-rheumatic drugs have shown remarkable success in the last decade. The present review provides a comprehensive understanding of the major risk factors and the molecular biology involved in the initiation and the progression of RA with a note on the recent trends in RA therapy.

A Perspective on the Maillard Reaction and the Analysis of Protein Glycation by Mass Spectrometry: Probing the Pathogenesis of Chronic Disease

PubMed Central

Zhang, Qibin; Ames, Jennifer M.; Smith, Richard D.; Baynes, John W.; Metz, Thomas O.

2009-01-01

The Maillard reaction, starting from the glycation of protein and progressing to the formation of advanced glycation end-products (AGEs), is implicated in the development of complications of diabetes mellitus, as well as in the pathogenesis of cardiovascular, renal, and neurodegenerative diseases. In this perspective review, we provide an overview on the relevance of the Maillard reaction in the pathogenesis of chronic disease and discuss traditional approaches and recent developments in the analysis of glycated proteins by mass spectrometry. We propose that proteomics approaches, particularly bottom-up proteomics, will play a significant role in analyses of clinical samples leading to the identification of new markers of disease development and progression. PMID:19093874

A perspective on the Maillard reaction and the analysis of protein glycation by mass spectrometry: probing the pathogenesis of chronic disease.

PubMed

Zhang, Qibin; Ames, Jennifer M; Smith, Richard D; Baynes, John W; Metz, Thomas O

2009-02-01

The Maillard reaction, starting from the glycation of protein and progressing to the formation of advanced glycation end-products (AGEs), is implicated in the development of complications of diabetes mellitus, as well as in the pathogenesis of cardiovascular, renal, and neurodegenerative diseases. In this perspective review, we provide an overview on the relevance of the Maillard reaction in the pathogenesis of chronic disease and discuss traditional approaches and recent developments in the analysis of glycated proteins by mass spectrometry. We propose that proteomics approaches, particularly bottom-up proteomics, will play a significant role in analyses of clinical samples leading to the identification of new markers of disease development and progression.

The effect of physical and psychosocial occupational factors on the chronicity of low back pain in the workers of Iranian metal industry: a cohort study.

PubMed

Aghilinejad, Mashallah; Tavakolifard, Negah; Mortazavi, Sayed Aliakbar; Kabir Mokamelkhah, Elahe; Sotudehmanesh, Akbar; Mortazavi, Seyed Alireza

2015-01-01

Low back pain (LBP) is one of the most common problems among the workers of different industries. The role of occupational factors in causing the LBP has been indicated previously. LBP has great socio-economic costs and most of its costs are related to the chronic LBP. The aim of this study was to identify the occupational risk factors that are related to the progression of the LBP from acute to chronic phase. This cohort study has been conducted on 185 workers with acute LBP. Information related to their occupational exposure at baseline has been measured with a valid questionnaire using the self-report approach. Patients follow up was done monthly for three months after the start of the pain. Those workers whose occupational exposure had not changed during the follow up were divided into two groups of chronic LBP (n = 49) and cured (n = 136) according to the duration of the pain period (more or less than 3 months), and their job exposures were compared. Among the physical and psychosocial risk factors, social support (OR= 0.466, CI= 0.231- 0.940) and job satisfaction (OR= 0.455, CI= 0.232-0.891), and lifting weights more than 15kg (OR=2.482, CI= 1.274-4.834) indicated a significant relationship with the chronicity of the LBP. After putting the variables into the regression model, only lifting>15kg remained statistically significant. According to the observed relationship between these occupational risk factors (social support, job satisfaction, lifting>15kg) and the chronicity of the LBP, there is hope that eliminating these factors in the workers with acute LBP will prevent its progression to the chronic phase.

Beneficial effects of benzodiazepine diazepam on chronic stress-induced impairment of hippocampal structural plasticity and depression-like behavior in mice.

PubMed

Zhao, Yunan; Wang, Zhongli; Dai, Jianguo; Chen, Lin; Huang, Yufang; Zhan, Zhen

2012-03-17

Whether benzodiazepines (BZDs) have beneficial effects on the progress of chronic stress-induced impairment of hippocampal structural plasticity and major depression is uncertain. The present study designed four preclinical experiments to determine the effects of BZDs using chronic unpredictable stress model. In Experiment 1, several time course studies on behavior and hippocampus response to stress were conducted using the forced swim and tail suspension tests (FST and TST) as well as hippocampal structural plasticity markers. Chronic stress induced depression-like behavior in the FST and TST as well as decreased hippocampal structural plasticity that returned to normal within 3 wk. In Experiment 2, mice received p.o. administration of three diazepam dosages prior to each variate stress session for 4 wk. This treatment significantly antagonized the elevation of stress-induced corticosterone levels. Only low- (0.5mg/kg) and medium-dose (1mg/kg) diazepam blocked the detrimental effects of chronic stress. In Experiment 3, after 7 wk of stress sessions, daily p.o. diazepam administration during 1 wk recovery phase dose-dependently accelerated the recovery of stressed mice. In Experiment 4, 1 wk diazepam administration to control mice enhanced significantly hippocampal structural plasticity and induced an antidepressant-like behavioral effect, whereas 4 wk diazepam administration produced opposite effects. Hence, diazepam can slow the progress of chronic stress-induced detrimental consequences by normalizing glucocorticoid hormones. Considering the adverse effect of long-term diazepam administration on hippocampal plasticity, the preventive effects of diazepam may depend on the proper dose. Short-term diazepam treatment enhances hippocampal structural plasticity and is beneficial to recovery following chronic stress. Copyright © 2011 Elsevier B.V. All rights reserved.

Evidence-based clinical practice guidelines for chronic pancreatitis 2015.

PubMed

Ito, Tetsuhide; Ishiguro, Hiroshi; Ohara, Hirotaka; Kamisawa, Terumi; Sakagami, Junichi; Sata, Naohiro; Takeyama, Yoshifumi; Hirota, Morihisa; Miyakawa, Hiroyuki; Igarashi, Hisato; Lee, Lingaku; Fujiyama, Takashi; Hijioka, Masayuki; Ueda, Keijiro; Tachibana, Yuichi; Sogame, Yoshio; Yasuda, Hiroaki; Kato, Ryusuke; Kataoka, Keisho; Shiratori, Keiko; Sugiyama, Masanori; Okazaki, Kazuichi; Kawa, Shigeyuki; Tando, Yusuke; Kinoshita, Yoshikazu; Watanabe, Mamoru; Shimosegawa, Tooru

2016-02-01

Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.

Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial.

PubMed

Bakris, George L; Sarafidis, Pantelis A; Weir, Matthew R; Dahlöf, Björn; Pitt, Bertram; Jamerson, Kenneth; Velazquez, Eric J; Staikos-Byrne, Linda; Kelly, Roxzana Y; Shi, Victor; Chiang, Yann-Tong; Weber, Michael A

2010-04-03

The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality. We assessed the effects of these drug combinations on progression of chronic kidney disease. ACCOMPLISH was a double-blind, randomised trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 mL/min/1.73 m(2) or need for dialysis). Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00170950. The trial was terminated early (mean follow-up 2.9 years [SD 0.4]) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide. At trial completion, vital status was not known for 143 (1%) patients who were lost to follow-up (benazepril plus amlodipine, n=70; benazepril plus hydrochlorothiazide, n=73). All randomised patients were included in the ITT analysis. There were 113 (2.0%) events of chronic kidney disease progression in the benazepril plus amlodipine group compared with 215 (3.7%) in the benazepril plus hydrochlorothiazide group (HR 0.52, 0.41-0.65, p<0.0001). The most frequent adverse event in patients with chronic kidney disease was peripheral oedema (benazepril plus amlodipine, 189 of 561, 33.7%; benazepril plus hydrochlorothiazide, 85 of 532, 16.0%). In patients with chronic kidney disease, angio-oedema was more frequent in the benazepril plus amlodipine group than in the benazepril plus hydrochlorothiazide group. In patients without chronic kidney disease, dizziness, hypokalaemia, and hypotension were more frequent in the benazepril plus hydrochlorothiazide group than in the benazepril plus amlodipine group. Initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy to a greater extent. Novartis. Copyright 2010 Elsevier Ltd. All rights reserved.

Feeling powerless: Locus of control as a potential target for supportive care interventions to increase quality of life and decrease anxiety in ovarian cancer patients.

PubMed

Brown, Alaina J; Sun, Charlotte C; Urbauer, Diana L; Bodurka, Diane C; Thaker, Premal H; Ramondetta, Lois M

2015-08-01

To evaluate if an individual's locus of control (LOC) predicts various quality of life (QOL) and mental well-being measures. To identify targets that might enhance the overall spiritual well-being and QOL of ovarian cancer patients. Multi-site analysis of women with newly diagnosed stages II-IV ovarian, primary peritoneal or fallopian tube cancer. Patients completed the following surveys: Locus of Control Scale (LOC), Functional Assessment of Chronic Illness Therapy-Ovarian (FACT-O), Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp), Edmonton Symptom Assessment score (ESAS), Hospital Anxiety Depression Scale (HADS), Templer's Death Anxiety Scale (DAS), and Herth Hope Index (HHI). Regression models were created to examine the effect of LOC upon QOL, symptoms, and other measures of mental well-being. These models adjusted for the effect of site of care, race, and partnership status as potential confounders. This study enrolled 104 patients from three separate treatment facilities. After adjusting for site, race and partnership status, higher levels of external LOC predicted decreased QOL (FACT-O) (p<0.05). Higher levels of external LOC also correlated with increased death anxiety and general anxiety (p≤0.05). Additionally, higher levels of external LOC predicted decreased hope (HHI) (p≤0.01). Ovarian cancer patients with a high external LOC may be at risk for decreased QOL at the time of their cancer diagnosis. They may also experience higher levels of anxiety and decreased feelings of hope. Identification of these women and interventions designed to increase a woman's sense of control over her situation may improve QOL and overall mental well-being. Copyright © 2015. Published by Elsevier Inc.

The role of external drains and peritoneal conduits in the treatment of recurrent chronic subdural hematoma.

PubMed

Santarius, Thomas; Qureshi, Hammad U; Sivakumaran, Ram; Kirkpatrick, Peter J; Kirollos, Ramez W; Hutchinson, Peter J

2010-06-01

A considerable body of evidence supporting the use of external drainage after evacuation of primary chronic subdural hematoma (CSDH) exists in the literature. However, no systematic study of the value of postoperative drainage in the treatment of recurrent CSDH has been published. The aim of the study was to investigate external drains and subdural-to-peritoneal conduit in the treatment of recurrent CSDH. A retrospective review of cases of CSDH treated in our institution between October 2002 and October 2006 was conducted. During the study period, 408 patients had burr hole evacuation. Sixty-four patients (15.9%) had treatment for recurrence. One patient had craniotomy, and the remaining 63 had another burr hole evacuation: 36 without placement of a drain (BHO), 14 with external drainage (SED), and 13 with placement of subdural-peritoneal catheter (SPC). Fifteen patients (24%) developed a secondary recurrence requiring a third drainage procedure. Postoperative drainage (SED or SPC) was associated with a significantly lower secondary recurrence rate when compared to BHO: 3/27 (11%) versus 12/36 (33%) (χ(2), P=.040). There was no significant difference in recurrence rates between SED and SPC. Postoperative complications included acute subdural hematoma (2), subdural empyema (2), brain edema (2), pneumonia (3), and in-hospital death (2). None of the complications was associated with the use of a specific technique. The results indicate that, as in the treatment of primary CSDHs, the use of drain (SED or SPC) with burr hole evacuation is safe and is associated with lower recurrence rate. Further investigation is needed to clarify the indications of currently available surgical techniques in the treatment of recurrent CSDH. Copyright © 2010 Elsevier Inc. All rights reserved.

Radiation Risks of Leukemia, Lymphoma and Multiple Myeloma Incidence in the Mayak Cohort: 1948–2004

PubMed Central

Kuznetsova, Irina S.; Labutina, Elena V.; Hunter, Nezahat

2016-01-01

Incidence of all types of lymphatic and hematopoietic cancers, including Hodgkin’s lymphoma, non-Hodgkin's lymphoma, multiple myeloma, acute and chronic myeloid leukemia (AML and CML respectively), chronic lymphocytic leukemia (CLL) and other forms of leukemia have been studied in a cohort of 22,373 workers employed at the Mayak Production Association (PA) main facilities during 536,126 person-years of follow-up from the start of employment between 1948 and 1982 to the end of 2004. Risk assessment was performed for both external gamma-radiation and internal alpha-exposure of red bone marrow due to incorporated Pu-239 using Mayak Workers Dosimetry System 2008 taking into account non-radiation factors. The incidence of leukemia excluding CLL showed a non-linear dose response relationship for external gamma exposure with exponential effect modifiers based on time since exposure and age at exposure. Among the major subtypes of leukemia, the excess risk of AML was the highest within the first 2–5 years of external exposure (ERR per Gy: 38.40; 90% CI: 13.92–121.4) and decreased substantially thereafter, but the risks remained statistically significant (ERR per Gy: 2.63; 90% CI: 0.07–12.55). In comparison, excess CML first occurred 5 years after exposure and decreased about 10 years after exposure, although the association was not statistically significant (ERR per Gy: 1.39; 90% CI: -0.22–7.32). The study found no evidence of an association between leukemia and occupational exposure to internal plutonium ERR per Gy 2.13; 90% CI: <0–9.45). There was also no indication of any relationship with either external gamma or internal plutonium radiation exposure for either incidence of Hodgkin or non-Hodgkin lymphoma or multiple myeloma. PMID:27631102

Upregulation of Oxidative Stress Related Genes in a Chronic Kidney Disease Attributed to Specific Geographical Locations of Sri Lanka

PubMed Central

Sayanthooran, Saravanabavan; Gunerathne, Lishanthe; Abeysekera, Tilak D. J.; Sooriyapathirana, Suneth S.

2016-01-01

Objective. To infer the influence of internal and external oxidative stress in chronic kidney disease patients of unknown etiology (CKDu) in Sri Lanka, by analyzing expression of genes related directly or indirectly to oxidative stress: glutamate-cysteine ligase catalytic subunit (GCLC), glutathione S-transferase mu 1 (GSTM1), glucose-6-phosphate dehydrogenase (G6PD), fibroblast growth factor-23 (FGF23), and NLR family pyrin domain containing 3 (NLRP3). Methods. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was carried out for the selected populations: CKDu patients (n = 43), chronic kidney disease patients (CKD; n = 14), healthy individuals from a CKDu endemic area (GHI; n = 9), and nonendemic area (KHI; n = 16). Fold changes were quantified relative to KHI. Results. GCLC had greater than threefold upregulation in all three study groups, with a maximum of 7.27-fold upregulation in GHI (p = 0.000). GSTM1 was not expressed in 25.6% of CKDu and 42.9% of CKD patients, but CKDu patients expressing GSTM1 showed upregulation of 2.60-fold (p < 0.05). Upregulation of FGF23 and NLRP3 genes in CKD and CKDu was observed (p < 0.01), with greater fold changes in CKD. Conclusion. Results suggest higher influence of external sources of oxidative stress in CKDu, possibly owing to environmental conditions. PMID:27975059

Upregulation of Oxidative Stress Related Genes in a Chronic Kidney Disease Attributed to Specific Geographical Locations of Sri Lanka.

PubMed

Sayanthooran, Saravanabavan; Magana-Arachchi, Dhammika N; Gunerathne, Lishanthe; Abeysekera, Tilak D J; Sooriyapathirana, Suneth S

2016-01-01

Objective. To infer the influence of internal and external oxidative stress in chronic kidney disease patients of unknown etiology (CKDu) in Sri Lanka, by analyzing expression of genes related directly or indirectly to oxidative stress: glutamate-cysteine ligase catalytic subunit (GCLC), glutathione S-transferase mu 1 (GSTM1), glucose-6-phosphate dehydrogenase (G6PD), fibroblast growth factor-23 (FGF23), and NLR family pyrin domain containing 3 (NLRP3). Methods. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was carried out for the selected populations: CKDu patients ( n = 43), chronic kidney disease patients (CKD; n = 14), healthy individuals from a CKDu endemic area (GHI; n = 9), and nonendemic area (KHI; n = 16). Fold changes were quantified relative to KHI. Results. GCLC had greater than threefold upregulation in all three study groups, with a maximum of 7.27-fold upregulation in GHI ( p = 0.000). GSTM1 was not expressed in 25.6% of CKDu and 42.9% of CKD patients, but CKDu patients expressing GSTM1 showed upregulation of 2.60-fold ( p < 0.05). Upregulation of FGF23 and NLRP3 genes in CKD and CKDu was observed ( p < 0.01), with greater fold changes in CKD. Conclusion. Results suggest higher influence of external sources of oxidative stress in CKDu, possibly owing to environmental conditions.

Comparing fixed-amount and progressive-amount DRO Schedules for tic suppression in youth with chronic tic disorders.

PubMed

Capriotti, Matthew R; Turkel, Jennifer E; Johnson, Rachel A; Espil, Flint M; Woods, Douglas W

2017-01-01

Chronic tic disorders (CTDs) involve motor and/or vocal tics that often cause substantial distress and impairment. Differential reinforcement of other behavior (DRO) schedules of reinforcement produce robust, but incomplete, reductions in tic frequency in youth with CTDs; however, a more robust reduction may be needed to affect durable clinical change. Standard, fixed-amount DRO schedules have not commonly yielded such reductions, so we evaluated a novel, progressive-amount DRO schedule, based on its ability to facilitate sustained abstinence from functionally similar behaviors. Five youth with CTDs were exposed to periods of baseline, fixed-amount DRO (DRO-F), and progressive-amount DRO (DRO-P). Both DRO schedules produced decreases in tic rate and increases in intertic interval duration, but no systematic differences were seen between the two schedules on any dimension of tic occurrence. The DRO-F schedule was generally preferred to the DRO-P schedule. Possible procedural improvements and other future directions are discussed. © 2016 Society for the Experimental Analysis of Behavior.

Discovery of somatic mutations in the progression of chronic myeloid leukemia by whole-exome sequencing.

PubMed

Huang, Y; Zheng, J; Hu, J D; Wu, Y A; Zheng, X Y; Liu, T B; Chen, F L

2014-02-19

We performed whole-exome sequencing in samples representing accelerated phase (AP) and blastic crisis (BC) in a subject with chronic myeloid leukemia (CML). A total of 12.74 Gb clean data were generated, achieving a mean depth coverage of 64.45 and 69.53 for AP and BC samples, respectively, of the target region. A total of 148 somatic variants were detected, including 76 insertions and deletions (indels), 64 single-nucleotide variations (SNV), and 8 structural variations (SV). On the basis of annotation and functional prediction analysis, we identified 3 SNVs and 6 SVs that showed a potential association with CML progression. Among the genes that harbor the identified variants, GATA2 has previously been reported to play important roles in the progression from AP to BC in CML. Identification of these genes will allow us to gain a better understanding of the pathological mechanism of CML and represents a critical advance toward new molecular diagnostic tests for the development of potential therapies for CML.