Science.gov

Sample records for affect disease severity

  1. Sever's Disease

    MedlinePlus

    ... good flexibility while your child is growing. The stretching exercises pictured in the treatment section can lower ... your child has already recovered from Sever's disease, stretching and putting ice on the heel after activity ...

  2. National Institutes of Health chronic graft-versus-host disease staging in severely affected patients: organ and global scoring correlate with established indicators of disease severity and prognosis.

    PubMed

    Baird, Kristin; Steinberg, Seth M; Grkovic, Lana; Pulanic, Drazen; Cowen, Edward W; Mitchell, Sandra A; Williams, Kirsten M; Datiles, Manuel B; Bishop, Rachel; Bassim, Carol W; Mays, Jacqueline W; Edwards, Dean; Cole, Kristen; Avila, Daniele N; Taylor, Tiffany; Urban, Amanda; Joe, Galen O; Comis, Leora E; Berger, Ann; Stratton, Pamela; Zhang, Dan; Shelhamer, James H; Gea-Banacloche, Juan C; Sportes, Claude; Fowler, Daniel H; Gress, Ronald E; Pavletic, Steven Z

    2013-04-01

    Between 2004 and 2010, 189 adult patients were enrolled on the National Cancer Institute's cross-sectional chronic graft-versus-host disease (cGVHD) natural history study. Patients were evaluated by multiple disease scales and outcome measures, including the 2005 National Institutes of Health (NIH) Consensus Project cGVHD severity scores. The purpose of this study was to assess the validity of the NIH scoring variables as determinants of disease severity in severely affected patients in efforts to standardize clinician evaluation and staging of cGVHD. Out of 189 patients enrolled, 125 met the criteria for severe cGVHD on the NIH global score, 62 of whom had moderate disease, with a median of 4 (range, 1-8) involved organs. Clinician-assigned average NIH organ score and the corresponding organ scores assigned by subspecialists were highly correlated (r = 0.64). NIH global severity scores showed significant associations with nearly all functional and quality of life outcome measures, including the Lee Symptom Scale, Short Form-36 Physical Component Scale, 2-minute walk, grip strength, range of motion, and Human Activity Profile. Joint/fascia, skin, and lung involvement affected function and quality of life most significantly and showed the greatest correlation with outcome measures. The final Cox model with factors jointly predictive for survival included the time from cGVHD diagnosis (>49 versus ≤49 months, hazard ratio [HR] = 0.23; P = .0011), absolute eosinophil count at the time of NIH evaluation (0-0.5 versus >0.5 cells/μL, HR = 3.95; P = .0006), and NIH lung score (3 versus 0-2, HR = 11.02; P < .0001). These results demonstrate that NIH organs and global severity scores are reliable measures of cGVHD disease burden. The strong association with subspecialist evaluation suggests that NIH organ and global severity scores are appropriate for clinical and research assessments, and may serve as a surrogate for more complex subspecialist examinations. In this

  3. The type of dietary fat affects the severity of autoimmune disease in NZB/NZW mice.

    PubMed Central

    Alexander, N. J.; Smythe, N. L.; Jokinen, M. P.

    1987-01-01

    The type of dietary fat dramatically affects the onset of autoimmune disease in lupus-prone female New Zealand Black/New Zealand White F1 (B/W) mice. Disease development was strikingly slowed in mice fed a diet containing quantities of omega-3 fatty acids (fish oil, FO). By 10 months of age, 94% of the FO mice were still living, whereas all the mice fed a saturated fat diet (lard,L) were dead. Those mice fed a corn oil (CO) diet were intermediate with 35% alive at the 10-month time evaluation. Long after the L and CO groups had succumbed to glomerulonephritis, the FO group had negligible proteinuria. Both B and T cell function, particularly antibody production and resultant circulating immune complex (CIC) levels, were modified by the type of dietary fat. FO mice exhibited lower levels of anti-ds-DNA and lower levels of CICs than L or CO mice. B/W antibody response to a T-independent antigen (DNP-dextran) was enhanced at 8 months of age in FO mice, whereas it was suppressed in L mice. T-dependent (sheep red blood cell) responses at that time period were reduced in all the diet groups, a reflection of the reduced numbers of accessory T cells as determined by FACS analysis. The natural killer (NK) response to YAC-1 cells decreased in the L group from 5 to 9 months of age but remained unchanged in the CO and FO groups. Severe glomerulonephritis was the most common histopathologic finding in the L and CO groups. Arteritis was found in the spleens of nearly all the L and CO mice. Arteritis of the heart, colon and intestine, stomach, kidney, and liver were also seen principally in the L mice. In contrast, most FO mice had minimal to mild glomerulonephritis and no or minimal arteritis in the spleen. It is likely omega-3 fatty acids of fish oil reduce immune-complex-induced glomerulonephritis through production of prostaglandin metabolites with attenuated activity and/or through altering cell membrane structure and fluidity, which may, in turn, affect the responsiveness of

  4. Interacting disturbances: wildfire severity affected by stage of forest disease invasion.

    PubMed

    Metz, Margaret R; Frangioso, Kerri M; Meentemeyer, Ross K; Rizzo, David M

    2011-03-01

    Sudden oak death (SOD) is an emerging forest disease causing extensive tree mortality in coastal California forests. Recent California wildfires provided an opportunity to test a major assumption underlying discussions of SOD and land management: SOD mortality will increase fire severity. We examined prefire fuels from host species in a forest monitoring plot network in Big Sur, California (USA), to understand the interactions between disease-caused mortality and wildfire severity during the 2008 Basin Complex wildfire. Detailed measurements of standing dead woody stems and downed woody debris 1-2 years prior to the Basin fire provided a rare picture of the increased fuels attributable to SOD mortality. Despite great differences in host fuel abundance, we found no significant difference in burn severity between infested and uninfested plots. Instead, the relationship between SOD and fire reflected the changing nature of the disease impacts over time. Increased SOD mortality contributed to overstory burn severity only in areas where the pathogen had recently invaded. Where longer-term disease establishment allowed dead material to fall and accumulate, increasing log volumes led to increased substrate burn severity. These patterns help inform forest management decisions regarding fire, both in Big Sur and in other areas of California as the pathogen continues to expand throughout coastal forests.

  5. Disease severity of organic rice as affected by host resistance, fertility and tillage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several studies were conducted to determine the effect of fertilizer inputs and tillage methods on disease incidence in an organic rice production system. The results of these studies suggest that organically produced rice is more vulnerable to infection of narrow brown leaf spot and brown spot. Thi...

  6. Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

    SciTech Connect

    Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; Conway, Jessica M.; Crespo, Gonzalo; Navasa, Miquel; D’Amato, Massimo; Ferenci, Peter; Cotler, Scott J.; Forns, Xavier; Perelson, Alan S.; Dahari, Harel

    2014-06-10

    HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to εmax) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). A biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver diseasemax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.

  7. Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

    DOE PAGES

    Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; ...

    2014-06-10

    HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to εmax) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). Amore » biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver disease (εmax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.« less

  8. Dementia severity and Lewy bodies affect circadian rhythms in Alzheimer disease.

    PubMed

    Harper, David G; Stopa, Edward G; McKee, Ann C; Satlin, Andrew; Fish, David; Volicer, Ladislav

    2004-07-01

    Sleep disturbance is a symptom shared by all neurodegenerative, dementing illnesses, such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), and its presence frequently precipitates decisions to seek institutional care for patients. Although the sleep disturbances of AD and DLB are qualitatively similar, they appear to be more prominent in patients with DLB. Disturbance of the circadian rhythm has been noted and is a potential factor underlying the nocturnal sleep fragmentation and daytime sleepiness observed in these patients. We studied the circadian variation of core-body temperature and motor activity in a total of 32 institutionalized patients with probable AD by NINCDS-ADRDA criteria, 9 of whom also met pathologic criteria for DLB. Eight, healthy, elderly male controls were studied on a clinical research unit designed to simulate the hospital environment where the dementia patients were studied. Circadian variables generally had greater deviations from normal associated with increasing AD pathology, as measured by postmortem-determined Braak stage, supporting the hypothesis that central changes mediate circadian disturbances in AD and DLB. Patients with a postmortem diagnosis of DLB manifested greater disturbances of locomotor activity circadian rhythms than patients with AD, possibly reflecting the greater sleep disturbances seen in this population, but the differences from normal in the circadian rhythms of the AD and DLB patients were qualitatively similar.

  9. Time of Initiating Enzyme Replacement Therapy Affects Immune Abnormalities and Disease Severity in Patients with Gaucher Disease

    PubMed Central

    Ioanou, Chidima; Plassmeyer, Matthew; Ryherd, Mark; Kozhaya, Lina; Austin, Lauren; Abidoglu, Cem; Unutmaz, Derya; Alpan, Oral; Goker-Alpan, Ozlem

    2016-01-01

    Gaucher disease (GD) patients often present with abnormalities in immune response that may be the result of alterations in cellular and/or humoral immunity. However, how the treatment and clinical features of patients impact the perturbation of their immunological status remains unclear. To address this, we assessed the immune profile of 26 GD patients who were part of an enzyme replacement therapy (ERT) study. Patients were evaluated clinically for onset of GD symptoms, duration of therapy and validated outcome measures for ERT. According to DS3 disease severity scoring system criteria, they were assigned to have mild, moderate or severe GD. Flow cytometry based immunophenotyping was performed to analyze subsets of T, B, NK, NKT and dendritic cells. GD patients showed multiple types of immune abnormalities associated to T and B lymphocytes with respect to their subpopulations as well as memory and activation markers. Skewing of CD4 and CD8 T cell numbers resulting in lower CD4/CD8 ratio and an increase in overall T cell activation were observed. A decrease in the overall B cells and an increase in NK and NKT cells were noted in the GD patients compared to controls. These immune alterations do not correlate with GD clinical type or level of biomarkers. However, subjects with persistent immune alterations, especially in B cells and DCs correlate with longer delay in initiation of ERT (ΔTX). Thus, while ERT may reverse some of these immune abnormalities, the immune cell alterations become persistent if therapy is further delayed. These findings have important implications in understanding the immune disruptions before and after treatment of GD patients. PMID:27942037

  10. Disease severity in K/BxN serum transfer-induced arthritis is not affected by IL-33 deficiency

    PubMed Central

    2013-01-01

    Introduction Interleukin (IL)-33 is a cytokine of the IL-1 family, which signals through the ST2 receptor. Previous work suggested implication of the IL-33/ST2 axis in the pathogenesis of human and mouse arthritis. Here, we directly investigated the role of endogenous IL-33 in K/BxN serum transfer-induced arthritis by using IL-33 knockout (KO) mice. Methods Arthritis was induced by injection of complete K/BxN serum or purified IgG. Disease severity was monitored by clinical and histological scoring. Results K/BxN serum transfer induced pronounced arthritis with similar incidence and severity in IL-33 KO and wild-type (WT) mice. In contrast, disease development was significantly reduced in ST2 KO mice. IL-33 expression in synovial tissue was comparable in arthritic WT and ST2 KO mice, and absent in IL-33 KO mice. Transfer of purified arthritogenic IgG instead of complete K/BxN serum also resulted in similar arthritis severity in IL-33 KO and WT mice, excluding a contribution of IL-33 contained in the serum of donor mice to explain this result. We investigated additional potential confounding factors, including purity of genetic background, but the mechanisms underlying reduced arthritis in ST2 KO mice remained unclear. Conclusions The data obtained with IL-33 KO mice indicate that endogenous IL-33 is not required for the development of joint inflammation in K/BxN serum transfer-induced arthritis. On the contrary, arthritis severity was reduced in ST2 KO mice. This observation might relate to IL-33 independent effects of ST2, and/or reveal the existence of confounding variables affecting the severity of joint inflammation in these KO strains. PMID:23324173

  11. Selective mass treatment with ivermectin to control intestinal helminthiases and parasitic skin diseases in a severely affected population.

    PubMed Central

    Heukelbach, Jörg; Winter, Benedikt; Wilcke, Thomas; Muehlen, Marion; Albrecht, Stephan; de Oliveira, Fabíola Araújo Sales; Kerr-Pontes, Lígia Regina Sansigolo; Liesenfeld, Oliver; Feldmeier, Hermann

    2004-01-01

    OBJECTIVE: To assess the short-term and long-term impact of selective mass treatment with ivermectin on the prevalence of intestinal helminthiases and parasitic skin diseases in an economically depressed community in north-east Brazil. METHODS: An intervention was carried out in a traditional fishing village in north-east Brazil where the population of 605 is heavily affected by ectoparasites and enteroparasites. The prevalence of intestinal helminths was determined by serial stool examination and the prevalence of parasitic skin diseases by clinical inspection. A total of 525 people out of a target population of 576 were treated at baseline. The majority of these were treated with ivermectin (200 microg/kg with a second dose given after 10 days). If ivermectin was contraindicated, participants were treated with albendazole or mebendazole for intestinal helminths or with topical deltamethrin for ectoparasites. Follow-up examinations were performed at 1 month and 9 months after treatment. FINDINGS: Prevalence rates of intestinal helminthiases before treatment and at 1 month and 9 months after mass treatment were: hookworm disease 28.5%, 16.4% and 7.7%; ascariasis 17.1%, 0.4% and 7.2%; trichuriasis 16.5%, 3.4% and 9.4%; strongyloidiasis 11.0%, 0.6% and 0.7%; and hymenolepiasis 0.6%; 0.4% and 0.5%, respectively. Prevalence rates of parasitic skin diseases before treatment and 1 month and 9 months after mass treatment were: active pediculosis 16.1%, 1.0% and 10.3%; scabies 3.8%, 1.0% and 1.5%; cutaneous larva migrans 0.7%, 0% and 0%; tungiasis 51.3%, 52.1% and 31.2%, respectively. Adverse events occurred in 9.4% of treatments. They were all of mild to moderate severity and were transient. CONCLUSION: Mass treatment with ivermectin was an effective and safe means of reducing the prevalence of most of the parasitic diseases prevalent in a poor community in north-east Brazil. The effects of treatment lasted for a prolonged period of time. PMID:15375445

  12. Subtle changes in bone mineralization density distribution in most severely affected patients with chronic obstructive pulmonary disease.

    PubMed

    Misof, B M; Roschger, P; Jorgetti, V; Klaushofer, K; Borba, V Z C; Boguszewski, C L; Cohen, A; Shane, E; Zhou, H; Dempster, D W; Moreira, C A

    2015-10-01

    Chronic obstructive pulmonary disease (COPD) is associated with low aBMD as measured by DXA and altered microstructure as assessed by bone histomorphometry and microcomputed tomography. Knowledge of bone matrix mineralization is lacking in COPD. Using quantitative backscatter electron imaging (qBEI), we assessed cancellous (Cn.) and cortical (Ct.) bone mineralization density distribution (BMDD) in 19 postmenopausal women (62.1 ± 7.3 years of age) with COPD. Eight had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. The BMDD outcomes from the patients were compared with healthy reference data and were correlated with previous clinical and histomorphometric findings. In general, the BMDD outcomes for the patients were not significantly different from the reference data. Neither the subgroups of with or without fragility fractures or of who did or did not receive inhaled glucocorticoid treatment, showed differences in BMDD. However, subgroup comparison according to severity revealed 10% decreased cancellous mineralization heterogeneity (Cn.CaWidth) for the most severely affected compared with less affected patients (p=0.042) and compared with healthy premenopausal controls (p=0.021). BMDD parameters were highly correlated with histomorphometric cancellous bone volume (BV/TV) and formation indices: mean degree of mineralization (Cn.CaMean) versus BV/TV (r=0.58, p=0.009), and Cn.CaMean and Ct.CaMean versus bone formation rate (BFR/BS) (r=-0.71, p<0.001). In particular, those with lower BV/TV (<50th percentile) had significantly lower Cn.CaMean (p=0.037) and higher Cn.CaLow (p=0.020) compared with those with higher (>50th percentile) BV/TV. The normality in most of the BMDD parameters and bone formation rates as well as the significant correlations between them suggests unaffected mineralization processes in COPD. Our findings also indicate no significant negative effect of treatment with inhaled glucocorticoids on the bone

  13. Identification of Genetic Loci Affecting the Severity of Symptoms of Hirschsprung Disease in Rats Carrying Ednrbsl Mutations by Quantitative Trait Locus Analysis

    PubMed Central

    Torigoe, Daisuke; Lei, Chuzhao; Lan, Xianyong; Chen, Hong; Sasaki, Nobuya; Wang, Jinxi; Agui, Takashi

    2015-01-01

    Hirschsprung’s disease (HSCR) is a congenital disease in neonates characterized by the absence of the enteric ganglia in a variable length of the distal colon. This disease results from multiple genetic interactions that modulate the ability of enteric neural crest cells to populate developing gut. We previously reported that three rat strains with different backgrounds (susceptible AGH-Ednrbsl/sl, resistant F344-Ednrbsl/sl, and LEH-Ednrbsl/sl) but the same null mutation of Ednrb show varying severity degrees of aganglionosis. This finding suggests that strain-specific genetic factors affect the severity of HSCR. Consistent with this finding, a quantitative trait locus (QTL) for the severity of HSCR on chromosome (Chr) 2 was identified using an F2 intercross between AGH and F344 strains. In the present study, we performed QTL analysis using an F2 intercross between the susceptible AGH and resistant LEH strains to identify the modifier/resistant loci for HSCR in Ednrb-deficient rats. A significant locus affecting the severity of HSCR was also detected within the Chr 2 region. These findings strongly suggest that a modifier gene of aganglionosis exists on Chr 2. In addition, two potentially causative SNPs (or mutations) were detected upstream of a known HSCR susceptibility gene, Gdnf. These SNPs were possibly responsible for the varied length of gut affected by aganglionosis. PMID:25790447

  14. Limited fungicide applications affect foliar and fruit disease severity and phytochemical content of muscadine grape (Vitis rotundifolia Michx.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Berry rot diseases cause significant reductions in yield and quality of muscadine grapes, but these losses may be reduced significantly by fungicide applications. Four studies were conducted to explore the relationship between yield, disease control, berry quality, and phytochemical content followin...

  15. Plant disease severity assessment - How rater bias, assessment method and experimental design affect hypothesis testing and resource use efficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The impact of rater bias and assessment method on hypothesis testing was studied for different experimental designs for plant disease assessment using balanced and unbalanced data sets. Data sets with the same number of replicate estimates for each of two treatments are termed ‘balanced’, and those ...

  16. Disease severity declines over time after a wild boar population has been affected by classical swine fever--legend or actual epidemiological process?

    PubMed

    Lange, M; Kramer-Schadt, S; Blome, S; Beer, M; Thulke, H-H

    2012-09-15

    Classical swine fever (CSF) is a severe multi-systemic disease that can affect both domestic pigs and wild boar. Past outbreaks in European wild boar involved high-virulent CSF virus (CSFV) strains and were mostly self-limiting. In these cases, morbidity and mortality rates were high in the affected regions. In contrast, endemic infections have been observed in several European wild boar populations in recent decades. Morbidity and mortality rates were much lower despite the fact that outbreaks were still detected via diseased or fallen animals. The virus strains involved were mostly classified as genotype 2.3 strains of moderate virulence causing age-dependent disease outcomes. The mechanisms leading to the establishment and perpetuation of endemicity are still not fully understood, but the factor "moderate virulence" seems to be of considerable importance. In this study, we aim to clarify whether the perception of declined 'CSF severity' could hypothetically reflect the adaptation of an initially high-virulent virus or whether this might be better explained as a misinterpretation of observations. A mechanistic eco-epidemiological model was employed to follow up a highly virulent strain of CSFV introduced into large connected wild boar populations. In the model, the virulence of the CSF virus is represented by case mortality and life expectancy after lethal infection. Allowing for small stochastic variation, these two characteristics of the virus are passed on with every new simulated infection that occurs. Model analysis revealed a decrease from high to moderate case mortality within a few years of simulated perpetuation of the virus. The resulting mortality corresponded to the level where the population average of the infectious period and the basic reproduction number of the disease were maximal. This shift in virulence was sufficient to prolong virus circulation considerably beyond the epidemic phase of the simulated outbreaks. Alternative mechanistic

  17. [Severe kyphosis and esophagus hiatal hernia affected in the levodopa absorption of a patient with Parkinson's disease].

    PubMed

    Chihara, Norio; Yamamoto, Toshiyuki; Lin, Youwei; Tsukamoto, Tadashi; Ogawa, Masafumi; Murata, Miho

    2009-08-01

    An 82 year-old woman with Parkinson's disease complained of a tendency to fall. She has had an extensive kyphosis since she was 66 years old. Over the last 6 months, she has repeatedly fallen. Even though she took anti-parkisonian drugs, she had also developed camptocormia. Her plasma levodopa concentration was analyzed for 4 hrs after administrating an oral dose of levodopa (200 mg) plus carbidopa (20 mg) at the time of fasting. The change in the plasma levodopa concentration showed bimodal peaks. The physical symptoms depended on the plasma concentration and improved twice. Esophageal tortuosity and esophageal hiatal hernia were detected by esophagography and upper gastric endoscopy. Such physical symptoms were speculated to have been caused by the transit disturbance of the drug in the gastrointestinal duct. During a second analysis of the plasma levodopa concentration, the patient was instructed to keep extending her back after consuming the same dose of drugs but with a greater amount of water than in the first analysis. A single and a higher peak were observed for the plasma levodopa concentration, and the physical symptoms, including camptocormia and parkinsonism, were improved. Hunched posture could influence the absorption of antiparkinsonian drugs.

  18. Confounding Factors Affecting the National Institutes of Health (NIH) Chronic Graft-Versus-Host Disease Organ-Specific Score and Global Severity

    PubMed Central

    Aki, Sahika Zeynep; Inamoto, Yoshihiro; Carpenter, Paul A.; Storer, Barry E.; Sandmaier, Brenda M.; Lee, Stephanie J.; Martin, Paul J.; Flowers, Mary E.D.

    2016-01-01

    The 2005 NIH chronic graft-versus-host disease (cGVHD) organ severity is based on the assessment of current status regardless of whether abnormalities are due to GVHD. The score assignment does not require knowledge of past manifestations, attribution, or whether cGVHD is still active. The aim of this study is to describe confounding factors affecting organ scores in patients with cGVHD. The study included 189 consecutive cGVHD patients evaluated at our center in 2013. Providers completed the NIH 0–3 organ-specific scoring evaluation with two questions added for each organ to identify abnormalities that were 1) not attributed to cGVHD, or 2) attributed to cGVHD plus other causes. Abnormalities attributed to causes other than GVHD were recorded. Eighty (14%) abnormalities were not attributed to cGVHD in at least one organ, and 41 (7%) abnormalities were attributed to cGVHD plus other causes in at least one organ. A total of 436 (78%) abnormalities were attributed only to cGVHD. Abnormalities not attributed to cGVHD were observed most frequently in the lung, gastrointestinal tract and skin. Most common abnormalities included pre-transplant condition, sequelae from GVHD, deconditioning, infections and medications. Our results support the the 2014 NIH consensus recommendation to consider attribution when scoring organ abnormalities. PMID:27214071

  19. Severe scurvy: an underestimated disease.

    PubMed

    Levavasseur, M; Becquart, C; Pape, E; Pigeyre, M; Rousseaux, J; Staumont-Sallé, D; Delaporte, E

    2015-09-01

    Scurvy is one of the oldest diseases in human history. Nowadays, although scurvy tends to become a forgotten disease in developed country, rare cases still occur, especially in people undergoing extreme diet, old people or children with poor diet and patients with malabsorption. We describe three cases of scurvy. The first case is a patient diagnosed with Crohn's disease, the second one is in a context of anorexia nervosa and drug addiction, and the third case is in a context of social isolation. Early recognition of scurvy can be difficult because symptoms may appear nonspecific and can mimic more common conditions. In any patient with spontaneous hematoma and purpura, in the context of nutritional disorder, scurvy should be systematically considered. As this disease can lead to severe complications, such as bone pain, heart failure or gastrointestinal symptoms, nothing should delay vitamin C supplementation, which is a simple and rapidly effective treatment.

  20. Neonicotinoid pesticides severely affect honey bee queens.

    PubMed

    Williams, Geoffrey R; Troxler, Aline; Retschnig, Gina; Roth, Kaspar; Yañez, Orlando; Shutler, Dave; Neumann, Peter; Gauthier, Laurent

    2015-10-13

    Queen health is crucial to colony survival of social bees. Recently, queen failure has been proposed to be a major driver of managed honey bee colony losses, yet few data exist concerning effects of environmental stressors on queens. Here we demonstrate for the first time that exposure to field-realistic concentrations of neonicotinoid pesticides during development can severely affect queens of western honey bees (Apis mellifera). In pesticide-exposed queens, reproductive anatomy (ovaries) and physiology (spermathecal-stored sperm quality and quantity), rather than flight behaviour, were compromised and likely corresponded to reduced queen success (alive and producing worker offspring). This study highlights the detriments of neonicotinoids to queens of environmentally and economically important social bees, and further strengthens the need for stringent risk assessments to safeguard biodiversity and ecosystem services that are vulnerable to these substances.

  1. Neonicotinoid pesticides severely affect honey bee queens

    PubMed Central

    Williams, Geoffrey R.; Troxler, Aline; Retschnig, Gina; Roth, Kaspar; Yañez, Orlando; Shutler, Dave; Neumann, Peter; Gauthier, Laurent

    2015-01-01

    Queen health is crucial to colony survival of social bees. Recently, queen failure has been proposed to be a major driver of managed honey bee colony losses, yet few data exist concerning effects of environmental stressors on queens. Here we demonstrate for the first time that exposure to field-realistic concentrations of neonicotinoid pesticides during development can severely affect queens of western honey bees (Apis mellifera). In pesticide-exposed queens, reproductive anatomy (ovaries) and physiology (spermathecal-stored sperm quality and quantity), rather than flight behaviour, were compromised and likely corresponded to reduced queen success (alive and producing worker offspring). This study highlights the detriments of neonicotinoids to queens of environmentally and economically important social bees, and further strengthens the need for stringent risk assessments to safeguard biodiversity and ecosystem services that are vulnerable to these substances. PMID:26459072

  2. Smoking and periodontal disease severity.

    PubMed

    Martinez-Canut, P; Lorca, A; Magán, R

    1995-10-01

    This study was performed to assess the influence of smoking on periodontal disease severity. Data concerning periodontal status and smoking habits were collected from 889 periodontal patients: 340 male and 549 female, 21 to 76 years of age, 47.4% being non smokers and 52.6% smokers. Periodontal parameters, recorded by the same examiner (PMC), were: gingival recession (GR), Pocket depth (PD), Probing attachment level (PAL), and mobility (M). The influence of age, sex and tobacco consumption on these periodontal parameters was statistically evaluated using an analysis of variance (ANOVA) with covariates. A non-linear effect model was also fitted by taking the natural logarithms of the response variables (GR, PD, PAL) closer to biomedical phenomena. Mobility was analyzed by a chi2-test. The effect of smoking on periodontitis showed no association with age or with sex. Smoking, age and sex were shown to be statistically significant for periodontitis, by performing both univariate (t-test for equal means) and multivariate tests. p-values for smoking and periodontitis were: GR (p=0.000), PD (p=0.000), PAL (p=0.000) and M (P=0.015). Smoking one cigarette per day, up to 10, and up to 20, increased PAL by 0.5%, 5% and 10%, respectively. The impact of tobacco is comparable to the impact resulting from the factor of age in this sample, increasing PAL by 0.7% for each year of life. Comparison between smokers of less than 10 cigarettes per day (PAL mean 3.72 mm +/-0.86) and non-smokers (PAL mean 3.84 +/- 0.89) showed no differences in PAL (p=0.216), while comparison for smokers from 11 to 20 cigarettes (PAL mean 4.36 +/- 1.23) and for more than 20 cigarettes (PAL mean 4.50 +/- 1.04) demonstrated significant differences (p=0.000). These findings suggest that: (1) tobacco increases periodontal disease severity; (2) this effect is clinically evident above consumption of a certain quantity of tobacco.

  3. Radiosensitive Severe Combined Immunodeficiency Disease

    PubMed Central

    Dvorak, Christopher C.; Cowan, Morton J.

    2009-01-01

    Synopsis Inherited defects in components of the non-homologous end joining DNA repair mechanism produce a T-B-NK+ severe combined immunodeficiency disease (SCID) characterized by heightened sensitivity to ionizing radiation. Patients with the radiosensitive form of SCID may also have increased short- and long-term sensitivity to the alkylator-based chemotherapy regimens traditionally utilized for conditioning prior to allogeneic hematopoietic cell transplantation (HCT). Known etiologies of radiosensitive SCID include deficiencies of Artemis, DNA Ligase IV, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and Cernunnos-XLF, all of which have been treated with HCT. Because of their sensitivity to certain forms of chemotherapy, the approach to donor selection and type of conditioning regimen utilized for a radiosensitive SCID patient requires careful consideration. Significantly more research needs to be done in order to determine the long-term outcomes of radiosensitive SCID patients following HCT, as well as to discover novel non-toxic approaches to HCT that might benefit those with intrinsic radio- and chemo-sensitivity, as well as potentially all patients undergoing an HCT. PMID:20113890

  4. Parthenium Dermatitis Severity Score to Assess Clinical Severity of Disease

    PubMed Central

    Verma, Kaushal K; Bansal, Arika; Bhari, Neetu; Sethuraman, Gomathy

    2017-01-01

    Background: Parthenium dermatitis is the most common type of airborne contact dermatitis in India. It is a chronic disease of a remitting and relapsing course with significant morbidity and distress, but there is no scoring system to assess its severity. Aim: To design a scoring system for the assessment of clinical severity of disease in Parthenium dermatitis and to use this scoring system in various studies to determine its sensitivity, specificity, and reproducibility. Methods and Results: In our first few studies on Parthenium dermatitis, we designed and used a basic clinical severity scoring system based on itching, morphology of the lesions, and areas involved. However, in subsequent studies, we modified it to the present scoring system as Parthenium dermatitis severity score (PDSS). Our studies showed the high sensitivity of PDSS in characterization of the disease severity at the given point of time, as well as to determine the efficacy of a prescribed treatment modality which was reliable and reproducible. Conclusion: Thus, PDSS may be used by clinicians for appropriate scoring of the clinical severity of Parthenium dermatitis and in monitoring the disease response to therapy. PMID:28216730

  5. Knock-down of pantothenate kinase 2 severely affects the development of the nervous and vascular system in zebrafish, providing new insights into PKAN disease.

    PubMed

    Zizioli, Daniela; Tiso, Natascia; Guglielmi, Adele; Saraceno, Claudia; Busolin, Giorgia; Giuliani, Roberta; Khatri, Deepak; Monti, Eugenio; Borsani, Giuseppe; Argenton, Francesco; Finazzi, Dario

    2016-01-01

    Pantothenate Kinase Associated Neurodegeneration (PKAN) is an autosomal recessive disorder with mutations in the pantothenate kinase 2 gene (PANK2), encoding an essential enzyme for Coenzyme A (CoA) biosynthesis. The molecular connection between defects in this enzyme and the neurodegenerative phenotype observed in PKAN patients is still poorly understood. We exploited the zebrafish model to study the role played by the pank2 gene during embryonic development and get new insight into PKAN pathogenesis. The zebrafish orthologue of hPANK2 lies on chromosome 13, is a maternal gene expressed in all development stages and, in adult animals, is highly abundant in CNS, dorsal aorta and caudal vein. The injection of a splice-inhibiting morpholino induced a clear phenotype with perturbed brain morphology and hydrocephalus; edema was present in the heart region and caudal plexus, where hemorrhages with reduction of blood circulation velocity were detected. We characterized the CNS phenotype by studying the expression pattern of wnt1 and neurog1 neural markers and by use of the Tg(neurod:EGFP/sox10:dsRed) transgenic line. The results evidenced that downregulation of pank2 severely impairs neuronal development, particularly in the anterior part of CNS (telencephalon). Whole-mount in situ hybridization analysis of the endothelial markers cadherin-5 and fli1a, and use of Tg(fli1a:EGFP/gata1a:dsRed) transgenic line, confirmed the essential role of pank2 in the formation of the vascular system. The specificity of the morpholino-induced phenotype was proved by the restoration of a normal development in a high percentage of embryos co-injected with pank2 mRNA. Also, addition of pantethine or CoA, but not of vitamin B5, to pank2 morpholino-injected embryos rescued the phenotype with high efficiency. The zebrafish model indicates the relevance of pank2 activity and CoA homeostasis for normal neuronal development and functioning and provides evidence of an unsuspected role for this

  6. Knock-down of pantothenate kinase 2 severely affects the development of the nervous and vascular system in zebrafish, providing new insights into PKAN disease

    PubMed Central

    Zizioli, Daniela; Tiso, Natascia; Guglielmi, Adele; Saraceno, Claudia; Busolin, Giorgia; Giuliani, Roberta; Khatri, Deepak; Monti, Eugenio; Borsani, Giuseppe; Argenton, Francesco; Finazzi, Dario

    2016-01-01

    Pantothenate Kinase Associated Neurodegeneration (PKAN) is an autosomal recessive disorder with mutations in the pantothenate kinase 2 gene (PANK2), encoding an essential enzyme for Coenzyme A (CoA) biosynthesis. The molecular connection between defects in this enzyme and the neurodegenerative phenotype observed in PKAN patients is still poorly understood. We exploited the zebrafish model to study the role played by the pank2 gene during embryonic development and get new insight into PKAN pathogenesis. The zebrafish orthologue of hPANK2 lies on chromosome 13, is a maternal gene expressed in all development stages and, in adult animals, is highly abundant in CNS, dorsal aorta and caudal vein. The injection of a splice-inhibiting morpholino induced a clear phenotype with perturbed brain morphology and hydrocephalus; edema was present in the heart region and caudal plexus, where hemorrhages with reduction of blood circulation velocity were detected. We characterized the CNS phenotype by studying the expression pattern of wnt1 and neurog1 neural markers and by use of the Tg(neurod:EGFP/sox10:dsRed) transgenic line. The results evidenced that downregulation of pank2 severely impairs neuronal development, particularly in the anterior part of CNS (telencephalon). Whole-mount in situ hybridization analysis of the endothelial markers cadherin-5 and fli1a, and use of Tg(fli1a:EGFP/gata1a:dsRed) transgenic line, confirmed the essential role of pank2 in the formation of the vascular system. The specificity of the morpholino-induced phenotype was proved by the restoration of a normal development in a high percentage of embryos co-injected with pank2 mRNA. Also, addition of pantethine or CoA, but not of vitamin B5, to pank2 morpholino-injected embryos rescued the phenotype with high efficiency. The zebrafish model indicates the relevance of pank2 activity and CoA homeostasis for normal neuronal development and functioning and provides evidence of an unsuspected role for this

  7. [Measurement of disease severity in dermatology].

    PubMed

    Deckert, S; Apfelbacher, C; Schmitt, J

    2015-09-01

    In order to determine the appropriate therapy for dermatological diseases, numerous measurement instruments are available to measure disease severity. Due to the lack of laboratory parameters for some dermatological diseases to objectify the disease severity (e.g., atopic dermatitis, psoriasis), questionnaires are used. Laboratory as well as questionnaire-based measurements should be reliable, valid, and sensitive to change. In addition, measurement instruments should be feasible. Classifications of disease severity which are based on inadequate measurement properties result in incorrect clinical decisions and limit evidence-based healthcare. Therefore, systematically developed and evidence-based recommendations for the use of individual measurement instruments should be taken into consideration.

  8. [Vitamin K2 influences several diseases].

    PubMed

    Hey, Henrik; Brasen, Claus Lohman

    2015-08-03

    In this paper we discuss the evidence of vitamin K2 deficiency which is a factor in several chronic diseases like diabetes, osteoporosis, cancer, inflammatory and cardiovascular diseases. This deficiency is very common in the mentioned diseases although it is rarely treated by clinicians. Randomized clinical trials have shown that patients with osteoporosis, cardiovascular diseases and cancer can benefit from vitamin K2 supplement. Further studies are needed to ascertain the effect of vitamin K2 supplement in patients with diabetes and inflammatory bowel diseases.

  9. Severe Spinal Injury in Hirayama Disease

    PubMed Central

    Quarracino, Cecilia; Aguirre, Florencia; Rugilo, Carlos A.; Negri, Luciana De

    2015-01-01

    Hirayama disease is a rare neurological disorder characterized by an insidious progressive subacute unilateral or bilateral weakness of the hands and forearm muscles leading to a painless amyotrophy. The disease primarily affects young men in the second to third decades of life. It has always been described as a second motor neuron disease, thus sparing the pyramidal and sensitive pathways. It usually has a slow progression course of 3 to 5 years followed by stabilization. Since its initial description by Keyzo Hirayama in 1959, most cases have been reported in Asia, particularly Japan and India, although the disease reportedly has worldwide distribution. PMID:26435801

  10. Heart Disease Affects Women of All Ages

    MedlinePlus

    ... Home Current Issue Past Issues Heart Disease Affects Women of All Ages Past Issues / Winter 2007 Table ... of this page please turn Javascript on. Young Women: Lifestyle-related factors that increase heart disease risk ...

  11. Hedging – does it affect the severity of pecan scab?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pecan scab, caused by the plant pathogenic fungus Fusicladium effusum, is the major disease of pecan in Georgia and elsewhere in the region. There are several reasons for hedging, and some issues may arise as a result of the hedging management practice. One of those issues might be increased disease...

  12. Does breast-feeding affect severity of familial Mediterranean fever?

    PubMed

    Makay, Balahan; Unsal, Erbil

    2009-12-01

    Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease, which is caused by an inborn error in innate immune system. It was shown that disease severity of patients of the same ethnic origin differed according to different country of residence, suggesting an influence of environment on phenotype of FMF. Different microbial milieus of the countries were accused. Breast-feeding has an important role on innate immunity and protects the infant from infections. The aim of this study is to investigate whether being breast-fed and duration of breast-feeding has an impact on disease severity of FMF. The mothers of patients were asked to fill a questionnaire about the feeding type in infancy. Mode of delivery, gestational age, and age at onset of FMF symptoms were also asked. The disease severity score of each patient was calculated according to the scoring system suggested by Pras et al. (Am J Med Genet 75:216-219, 1998). MEFV mutations were noted. The mothers of 81 FMF patients completed the questionnaire. Fifteen patients (18.5%) had mild, 49 (60.5%) had moderate, and 17 (21%) had severe disease. All the patients except four were breast-fed for some period. The duration of breast-feeding was similar between three severity groups. Time to introduce cow's milk and complementary foods also did not differ between groups. Longer duration of breast-feeding did not delay the onset of FMF symptoms. Mode of delivery and gestational age had no effect on disease severity. Patients homozygous for M694V had higher severity scores. This preliminary study suggests that breast-feeding is not an exogenous factor having an influence on phenotype of FMF. M694V genotype seems to cause more severe disease.

  13. Affective cycling in thyroid disease

    SciTech Connect

    Tapp, A.

    1988-05-01

    Depression in an elderly man with primary recurrent unipolar depression responded to radioactive iodine treatment of a thyrotoxic nodule, without the addition of psychotropic medications. Two months later, manic symptoms developed concomitant with the termination of the hyperthyroid state secondary to the radioactive iodine treatment. Clinical implications of these findings in relation to the possible mechanism of action of thyroid hormones on affective cycling are discussed.

  14. Elucidating novel disease mechanisms in severe asthma

    PubMed Central

    Kim, Richard Y; Rae, Brittany; Neal, Rachel; Donovan, Chantal; Pinkerton, James; Balachandran, Lohis; Starkey, Malcolm R; Knight, Darryl A; Horvat, Jay C; Hansbro, Philip M

    2016-01-01

    Corticosteroids are broadly active and potent anti-inflammatory agents that, despite the introduction of biologics, remain as the mainstay therapy for many chronic inflammatory diseases, including inflammatory bowel diseases, nephrotic syndrome, rheumatoid arthritis, chronic obstructive pulmonary disease and asthma. Significantly, there are cohorts of these patients with poor sensitivity to steroid treatment even with high doses, which can lead to many iatrogenic side effects. The dose-limiting toxicity of corticosteroids, and the lack of effective therapeutic alternatives, leads to substantial excess morbidity and healthcare expenditure. We have developed novel murine models of respiratory infection-induced, severe, steroid-resistant asthma that recapitulate the hallmark features of the human disease. These models can be used to elucidate novel disease mechanisms and identify new therapeutic targets in severe asthma. Hypothesis-driven studies can elucidate the roles of specific factors and pathways. Alternatively, 'Omics approaches can be used to rapidly generate new targets. Similar approaches can be used in other diseases. PMID:27525064

  15. Traumatic Brain Injury Severity Affects Neurogenesis in Adult Mouse Hippocampus.

    PubMed

    Wang, Xiaoting; Gao, Xiang; Michalski, Stephanie; Zhao, Shu; Chen, Jinhui

    2016-04-15

    Traumatic brain injury (TBI) has been proven to enhance neural stem cell (NSC) proliferation in the hippocampal dentate gyrus. However, various groups have reported contradictory results on whether TBI increases neurogenesis, partially due to a wide range in the severities of injuries seen with different TBI models. To address whether the severity of TBI affects neurogenesis in the injured brain, we assessed neurogenesis in mouse brains receiving different severities of controlled cortical impact (CCI) with the same injury device. The mice were subjected to mild, moderate, or severe TBI by a CCI device. The effects of TBI severity on neurogenesis were evaluated at three stages: NSC proliferation, immature neurons, and newly-generated mature neurons. The results showed that mild TBI did not affect neurogenesis at any of the three stages. Moderate TBI promoted NSC proliferation without increasing neurogenesis. Severe TBI increased neurogenesis at all three stages. Our data suggest that the severity of injury affects adult neurogenesis in the hippocampus, and thus it may partially explain the inconsistent results of different groups regarding neurogenesis following TBI. Further understanding the mechanism of TBI-induced neurogenesis may provide a potential approach for using endogenous NSCs to protect against neuronal loss after trauma.

  16. Resveratrol: A Focus on Several Neurodegenerative Diseases

    PubMed Central

    Tellone, Ester; Galtieri, Antonio; Russo, Annamaria; Giardina, Bruno; Ficarra, Silvana

    2015-01-01

    Molecules of the plant world are proving their effectiveness in countering, slowing down, and regressing many diseases. The resveratrol for its intrinsic properties related to its stilbene structure has been proven to be a universal panacea, especially for a wide range of neurodegenerative diseases. This paper evaluates (in vivo and in vitro) the various molecular targets of this peculiar polyphenol and its ability to effectively counter several neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases and amyotrophic lateral sclerosis. What emerges is that, in the deep heterogeneity of the pathologies evaluated, resveratrol through a convergence on the protein targets is able to give therapeutic responses in neuronal cells deeply diversified not only in morphological structure but especially in their function performed in the anatomical district to which they belong. PMID:26180587

  17. Development and validation of an endoscopic index of the severity for Crohn's disease: a prospective multicentre study. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires du Tube Digestif (GETAID).

    PubMed Central

    Mary, J Y; Modigliani, R

    1989-01-01

    The aim of this study was to develop and validate an endoscopic index for assessing the severity of Crohn's disease. Endoscopic findings were prospectively collected by a multicentre group in 75 patients with Crohn's colitis according to a previously validated procedure. The presence of nine preselected lesions was recorded in the following segments (1) rectum, (2) sigmoid and left colon, (3) transverse colon, (4) right colon, and (5) ileum. In addition the extent of the diseased and ulcerated areas were estimated in each segment. These segmental data were recorded on a standard form, together with the endoscopist's global estimate of lesion severity. A stepwise multiple regression was used to derive an index which was correlated with the endoscopist's global evaluation of lesion severity. Four mucosal lesions: deep and superficial ulcerations, ulcerated and non-ulcerated stenosis, and both estimates of extent involved were selected and weighted to obtain a Crohn's Disease Endoscopic Index of Severity which correlated with the endoscopist's global appraisal of lesion severity (r = 0.83). This index was then prospectively shown to be valid in a further series of 113 colonoscopies (r = 0.81). The index was calculated in 54 patients with active Crohn's disease, before and at the end of a course of corticosteroids: index variations correctly reflected changes in colitis severity as evaluated by the endoscopists (r = 0.72). For endoscopists familiar with the data collection procedure, this Crohn's Disease Endoscopic Index of Severity should be of value in the follow up of patients, especially in clinical trials. PMID:2668130

  18. Ticks and Tickborne Diseases Affecting Military Personnel

    DTIC Science & Technology

    1989-09-01

    by disease transmission. Various bacteria , rickettsiae , viruses, and protozoans are transmitted to people via tick bites (see Chapter 4). Relatively...Ticks may harbor and transmit to people various disease agents such as protozoa, viruses, bacteria , rickettsiae , and toxins. Several factors are...Natural history. The causative agent of RMSF, Rickettsia rickettsii , is transmitted to man by several species of ticks. In the U.S., 2 of the most

  19. Does severity of dermatochalasis in aging affect corneal biomechanical properties?

    PubMed Central

    Atalay, Kurşat; Gurez, Ceren; Kirgiz, Ahmet; Serefoglu Cabuk, Kubra

    2016-01-01

    Purpose The aim of this study was to investigate the possibility of a relationship between corneal biomechanical properties and different grades of dermatochalasis. Patients and methods Patients were assigned to four groups according to the severity of their dermatochalasis: normal (Group 1), mild (Group 2), moderate (Group 3), and severe (Group 4). An Ocular Response Analyzer device was used to measure corneal hysteresis (CH), corneal resistance factor (CRF), and corneal-compensated intraocular pressure (IOPcc). Results We found no significant differences in the mean values of the CH, CRF, and IOPcc of all groups (P=0.75, P=0.93, and P=0.11, respectively). However, CH and IOPcc were negatively correlated in Group 1, Group 2, and Group 3 patients (P=0.013, r=−0.49; P=0.015, r=−0.52; and P=0.011, r=−0.47, respectively), but this correlation was not apparent in the Group 4 patients (P=0.57, r=0.12). CRF and IOPcc were correlated, but only in Group 4 (P=0.001, r=0.66). Conclusion Severe dermatochalasis was associated with altered corneal biomechanical properties. Some of the important visual consequences of dermatochalasis and related diseases (such as floppy eyelid syndrome) can be understood by considering corneal biomechanical alterations. PMID:27274214

  20. [New therapies for children affected by bone diseases].

    PubMed

    Ballhausen, Diana; Dépraz, Nuria Garcia; Kern, Ilse; Unger, Sheila; Bonafé, Luisa

    2012-02-22

    Considerable progress has been achieved in recent years in treating children affected by bone diseases. Advances in the understanding of the molecular pathophysiology of genetic bone diseases have led to the development of enzyme replacement therapies for various lysosomal storage diseases, following the breakthrough initiated in treating Gaucher disease. Clinical studies are underway with tailored molecules correcting bone fragility and alleviating chronic bone pain and other manifestations of hypophosphatasia, or promoting growth of long bones in achondroplasia patients. We further report our very encouraging experience with intravenous bisphosphonate treatment in children suffering from secondary osteopenia and the high prevalence of calcium and vitamin D deficits in these severely disabled children.

  1. Darier's disease misdiagnosed as severe seborrheic dermatitis.

    PubMed

    Schwartz, Jessica L; Clinton, Tony S

    2011-12-01

    Darier's disease is a rare autosomal disorder resulting in characteristic findings of the skin, nails, and mucous membranes. Darier's disease is commonly misdiagnosed as seborrheic dermatitis or eczema. We present the case of a young adult active duty Air Force member with 5 years of skin complaints. The 23-year-old patient had been treated for seborrheic dermatitis and eczema with a variety of oral and topical treatments, which did not result in improvement of his symptoms. Upon referral to dermatology, the dermatologist noted skin, nail, and mucous membrane findings consistent with Darier's disease. A skin biopsy histologically confirmed the presence of Darier's disease and treatment was started. Although the course of the disease cannot be stopped, the patient's symptoms did reduce with the appropriate treatment. This case highlights the importance of revisiting the original diagnosis when conventional treatment fails to improve the disease course.

  2. Heritability of Lung Disease Severity in Cystic Fibrosis

    PubMed Central

    Vanscoy, Lori L.; Blackman, Scott M.; Collaco, Joseph M.; Bowers, Amanda; Lai, Teresa; Naughton, Kathleen; Algire, Marilyn; McWilliams, Rita; Beck, Suzanne; Hoover-Fong, Julie; Hamosh, Ada; Cutler, Dave; Cutting, Garry R.

    2007-01-01

    Rationale: Obstructive lung disease, the major cause of mortality in cystic fibrosis (CF), is poorly correlated with mutations in the disease-causing gene, indicating that other factors determine severity of lung disease. Objectives: To quantify the contribution of modifier genes to variation in CF lung disease severity. Methods: Pulmonary function data from patients with CF living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of FEV1 within the last year was used for cross-sectional analysis. FEV1 measures collected over at least 4 years were used for longitudinal analysis. Genetic contribution to disease variation (i.e., heritability) was estimated in two ways: by comparing similarity of lung function in monozygous (MZ) twins (∼ 100% gene sharing) with that of dizygous (DZ) twins/siblings (∼ 50% gene sharing), and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. Measurements and Main Results: Forty-seven MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (of a total of 526 patients) with CF were studied. Correlations for all measures of lung function for MZ twins (0.82–0.91, p < 0.0001) were higher than for DZ twins and siblings (0.50–0.64, p < 0.001). Heritability estimates from both methods were consistent for each measure of lung function and ranged from 0.54 to 1.0. Heritability estimates generally increased after adjustment for differences in nutritional status (measured as body mass index z-score). Conclusions: Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype. PMID:17332481

  3. Ethnic Differences in Presentation and Severity of Alcoholic Liver Disease

    PubMed Central

    Durbin-Johnson, Blythe; Halsted, Charles H.; Medici, Valentina

    2015-01-01

    Background The frequency of alcoholic liver disease (ALD), including alcoholic steatosis, hepatitis and cirrhosis, varies significantly by ethnicity. Methods With the goal to assess the role of ethnicity in determining the age of onset and severity of ALD and to compare the risk factors for its progression among ethnic groups, we conducted a retrospective chart review of all patients with ALD who were admitted or were followed as outpatients at University of California Davis Medical Center between 2002 and 2010. After excluding HBsAg and HIV positive subjects, we reviewed the charts of 791 ALD patients including 130 with alcoholic fatty liver, 154 with alcoholic hepatitis, and 507 with alcoholic cirrhosis. Results When controlling for all variables in the model, Hispanic patients presented at significantly 4-10 years younger ages than White/Caucasian patients, in each of the three disease severity categories and the results were confirmed after excluding HCV Ab/RNA positive subjects. There were more obese Hispanic patients than White/Caucasian patients, whereas the proportion of patients with hepatitis C was significantly greater in African/American subjects with alcoholic hepatitis and the proportion of patients with diabetes mellitus was significantly lower in White/Caucasian subjects than in Hispanic subjects with cirrhosis. The proportion of subjects with severe alcoholic hepatitis was similar in Hispanic and White/Caucasian patients, but lower in African/American subjects. Conclusion Ethnicity is a major factor affecting the age and severity of presentation of different subtypes of ALD. PMID:25702770

  4. Rosai-Dorfman disease affecting the maxilla

    PubMed Central

    Miniello, Thaís Gimenez; Araujo, Juliane Piragine; Sugaya, Norberto Nobuo; Elias, Fernando Melhem; de Almeida, Oslei Paes

    2016-01-01

    Rosai-Dorfman disease (RDD), formerly called sinus histiocytosis with massive lymphadenopathy, is a non-neoplastic proliferative histiocytic disorder with behavior ranging from highly aggressive to spontaneous remission. Although the lymph nodes are more commonly involved, any organ can be affected. This study aimed to describe the features and the follow-up of a case of extranodal RDD. Our patient was a 39-year-old woman who was referred with an 11-month history of pain in the right maxilla. On clinical examination, some upper right teeth presented full mobility with normal appearance of the surrounding gingiva. Radiographic exams showed an extensive bone reabsorption and maxillary sinus filled with homogeneous tissue, which sometimes showed polypoid formation. An incisional biopsy demonstrated a diffuse inflammatory infiltrate rich in foamy histiocytes displaying lymphocytes emperipolesis. Immunohistochemistry showed positivity for CD68 and S-100, and negativity for CD3, CD20, and CD30. Such features were consistent with the RDD diagnosis. The patient was referred to a hematologist and corticotherapy was administrated for 6 months. RDD is an uncommon disease that rarely affects the maxilla. In the present case, the treatment was conservative, and the patient is currently asymptomatic after 5 years of follow-up. PMID:28210574

  5. Functional capacity of Brazilian patients with Parkinson's disease (PD): relationship between clinical characteristics and disease severity.

    PubMed

    Barbieri, Fabio A; Rinaldi, Natalia M; Santos, Paulo Cezar R; Lirani-Silva, Ellen; Vitório, Rodrigo; Teixeira-Arroyo, Cláudia; Stella, Florindo; Gobbi, Lilian Teresa B

    2012-01-01

    The present study had three objectives: (a) to characterize the functional capacity of patients with PD, (b) to assess the relationship between the physical fitness components of functional capacity with clinical characteristics and disease severity, and (c) to compare the physical fitness components of functional capacity with clinical characteristics according to disease severity. The study included 54 patients with idiopathic PD who were distributed into two groups according to PD severity: unilateral group (n=35); and bilateral group (n=19). All patients underwent psychiatric assessment by means of the Hoehn and Yahr (HY) staging of PD, the Unified Parkinson's Disease Rating Scale (UPDRS), the Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively), and The Mini-Mental State Examination (MMSE). The physical fitness components of functional capacity were evaluated over a 2-day period, using recommendations by the American Alliance for Health, Physical Education, Recreation and Dance, and the Berg Balance Scale (BBS). Pearson correlation coefficients and multiple regressions were calculated to test the correlation between functional capacity and clinical characteristics, and to predict clinical scores from physical performance, respectively. Clinical variables and physical component data were compared between groups using analysis of variance to determine the effects of disease severity. Patients with advanced disease showed low levels of functional capacity. Interestingly, patients with good functional capacity in one of the physical fitness components also showed good capacities in the other components. Disease severity is a major factor affecting functional capacity and clinical characteristics. Medical providers should take disease severity into consideration when prescribing physical activity for PD patients, since the relationship between functional capacity and clinical characteristics is dependent on disease severity.

  6. Severe Primary Raynaud's Disease Treated with Rituximab

    PubMed Central

    Almoallim, Hani

    2016-01-01

    Raynaud's phenomenon refers to reversible spasms of the peripheral arterioles that can be primary Raynaud's phenomenon (PRP) or secondary Raynaud's phenomenon (SRP) to underlying connective tissue disease, both of which are characterized by a triphasic color response triggered by cold exposure or stress. PRP is typically a benign disease, whereas SRP may progress into digital ulcers and/or gangrene. Here, we report a case of a 55-year-old female diagnosed with PRP 7 years ago. Treatment with first-line agents, including calcium channel blocker, aspirin, and phosphodiesterase inhibitor, did not control her symptoms, which progressed to digital ulceration and gangrene. There were no symptoms of underlying autoimmune disease or malignancy, and autoimmune, serology, and immunology test results were normal; a biopsy of her left little finger was negative for vasculitis. Development to critical digital ischemia necessitated treatment with intravenous iloprost and heparin infusion followed by angioplasty, which led to a partial improvement. Due to persistent symptoms, rituximab therapy was initiated and two cycles induced a complete resolution of symptoms. PMID:27651971

  7. Severe Primary Raynaud's Disease Treated with Rituximab.

    PubMed

    Shabrawishi, Mohammed; Albeity, Abdurahman; Almoallim, Hani

    2016-01-01

    Raynaud's phenomenon refers to reversible spasms of the peripheral arterioles that can be primary Raynaud's phenomenon (PRP) or secondary Raynaud's phenomenon (SRP) to underlying connective tissue disease, both of which are characterized by a triphasic color response triggered by cold exposure or stress. PRP is typically a benign disease, whereas SRP may progress into digital ulcers and/or gangrene. Here, we report a case of a 55-year-old female diagnosed with PRP 7 years ago. Treatment with first-line agents, including calcium channel blocker, aspirin, and phosphodiesterase inhibitor, did not control her symptoms, which progressed to digital ulceration and gangrene. There were no symptoms of underlying autoimmune disease or malignancy, and autoimmune, serology, and immunology test results were normal; a biopsy of her left little finger was negative for vasculitis. Development to critical digital ischemia necessitated treatment with intravenous iloprost and heparin infusion followed by angioplasty, which led to a partial improvement. Due to persistent symptoms, rituximab therapy was initiated and two cycles induced a complete resolution of symptoms.

  8. Celiac disease presenting as severe osteopenia.

    PubMed

    Mulder, Christopher J; Cardile, Anthony P; Dickert, Judith

    2011-11-01

    The authors describe a unique presentation of celiac disease as multiple non-traumatic fractures in a young male without gastrointestinal complaints. A 29-year-old man presented with back pain and was found to have a non-traumatic compression fracture of the lumbar and thoracic spine on plain X-ray. Dual-energy x-ray absorptiometry (DXA) confirmed osteoporosis at the L3/L4 vertebral bodies. Parathyroid hormone (PTH), calcium, and vitamin D levels were normal. He had no gastrointestinal complaints, but serologic studies were positive to include an elevated gliadin IgA Ab, gliadin IgG Ab, and an elevated tissue transglutaminase IgA Ab. He was treated with a gluten-free diet, calcium, and vitamin D supplementation as well as teriparatide. Follow up bone density showed improvement and has no further fractures to date. Primary care physicians, gastroenterologists, and endocrinologists must have a high index of clinical suspicion for celiac disease in any patient who presents with low bone density regardless of the serum 25-OH vitamin D levels or presence of gastrointestinal complaints.

  9. Cerebellar cognitive affective syndrome presented as severe borderline personality disorder.

    PubMed

    Pesic, Danilo; Peljto, Amir; Lukic, Biljana; Milovanovic, Maja; Svetozarevic, Snezana; Lecic Tosevski, Dusica

    2014-01-01

    An increasing number of findings confirm the significance of cerebellum in affecting regulation and early learning. Most consistent findings refer to association of congenital vermis anomalies with deficits in nonmotor functions of cerebellum. In this paper we presented a young woman who was treated since sixteen years of age for polysubstance abuse, affective instability, and self-harming who was later diagnosed with borderline personality disorder. Since the neurological and neuropsychological reports pointed to signs of cerebellar dysfunction and dysexecutive syndrome, we performed magnetic resonance imaging of brain which demonstrated partially developed vermis and rhombencephalosynapsis. These findings match the description of cerebellar cognitive affective syndrome and show an overlap with clinical manifestations of borderline personality disorder.

  10. Severe preeclampsia: anesthetic implications of the disease and its management.

    PubMed

    Turner, Judi A

    2009-01-01

    Preeclampsia is a significant, multifactorial, multiorgan disease affecting 6%-8% of all pregnancies in the United States and is the third leading cause of maternal mortality. As such, it is incumbent upon any anesthesia provider involved in obstetric cases to be familiar with the varied manifestations of the disease, management goals from an obstetric standpoint, and the implications for provision of anesthesia in this patient group. Despite improvements in the diagnosis and management of preeclampsia, severe complications can occur in both the mother and the fetus. A systematic approach to the anesthetic evaluation is therefore necessary to reduce morbidity and mortality and to improve outcomes. The potential pitfalls of general anesthesia, including failed intubation, in these complicated patients make regional anesthesia the preferred choice in many cases. Recent studies have shown that spinal anesthesia is often appropriate for preeclamptic patients, even in severe cases. Nevertheless, it is important to be aware of the potential contraindications to neuraxial anesthesia and to prepare for the possibility of encountering a difficult airway.

  11. Food microstructure affects the bioavailability of several nutrients.

    PubMed

    Parada, J; Aguilera, J M

    2007-03-01

    There is an increased interest in the role that some nutrients may play in preventing or ameliorating the effect of major diseases (for example, some types of cancer, cardiovascular diseases, eye disorders, among others). In this respect, the bioavailability or the proportion of an ingested nutrient that is made available (that is, delivered to the bloodstream) for its intended mode of action is more relevant than the total amount present in the original food. Disruption of the natural matrix or the microstructure created during processing may influence the release, transformation, and subsequent absorption of some nutrients in the digestive tract. Alternatively, extracts of bioactive molecules (for example, nutraceuticals) and beneficial microorganisms may be protected during their transit in the digestive system to the absorption sites by encapsulation in designed matrices. This review summarizes relevant in vivo and in vitro methods used to assess the bioavailability of some nutrients (mostly phytochemicals), types of microstructural changes imparted by processing and during food ingestion that are relevant in matrix-nutrient interactions, and their effect on the bioavailability of selected nutrients.

  12. Parkinson's Disease Severity and Use of Dopaminergic Medications

    PubMed Central

    Fang, John Y.; Pérez, Adriana; Christine, Chadwick W.; Leehey, Maureen; Aminoff, Michael J.; Boyd, James T.; Morgan, John C.; Dhall, Rohit; Nicholas, Anthony P; Bodis-Wollner, Ivan; Zweig, Richard M.; Goudreau, John L.

    2015-01-01

    Background The effects of dopaminergic therapy in Parkinson's disease (PD) can vary depending on the class of medication selected. Objective The aim of this post hoc study was to determine if the class of dopaminergic therapy correlated with disease severity in persons with early, treated PD. Methods A non-parametric global statistical test (GST) was used to assess the status of participants treated with dopamine agonist (DA) monotherapy, levodopa (LD) monotherapy or combined LD and DA therapy on multiple PD outcomes encompassing motor, cognitive, psychiatric and autonomic function, as well as disability and quality of life. Results The outcomes measured at the beginning of the study showed lower disease burden for participants on initial DA monotherapy compared to those taking combined LD and DA therapy after controlling for age, education, taking cogmeds and amantadine. Conclusion This observation suggests that clinicians treating early PD patients favor combined LD and DA therapy in patients with more disabling features over DA monotherapy. As such, studies of PD progression in treated PD patients may be affected by the class of symptomatic dopaminergic therapy. PMID:25541182

  13. Graft-versus-host disease affecting oral cavity. A review.

    PubMed

    Margaix-Muñoz, Maria; Bagán, José V; Jiménez, Yolanda; Sarrión, María-Gracia; Poveda-Roda, Rafael

    2015-02-01

    Graft versus host disease (GVHD) is one of the most frequent and serious complications of hematopoietic stem cell transplantation, and is regarded as the leading cause of late mortality unrelated to the underlying malignant disease. GVHD is an autoimmune and alloimmune disorder that usually affects multiple organs and tissues, and exhibits a variable clinical course. It can manifest in either acute or chronic form. The acute presentation of GVHD is potentially fatal and typically affects the skin, gastrointestinal tract and liver. The chronic form is characterized by the involvement of a number of organs, including the oral cavity. Indeed, the oral cavity may be the only affected location in chronic GVHD. The clinical manifestations of chronic oral GVHD comprise lichenoid lesions, hyperkeratotic plaques and limited oral aperture secondary to sclerosis. The oral condition is usually mild, though moderate to severe erosive and ulcerated lesions may also be seen. The diagnosis is established from the clinical characteristics, though confirmation through biopsy study is sometimes needed. Local corticosteroids are the treatment of choice, offering overall response rates of close to 50%. Extracorporeal photopheresis and systemic corticosteroids in turn constitute second line treatment. Oral chronic GVHD is not considered a determinant factor for patient survival, which is close to 52% five years after diagnosis of the condition. Key words:Chronic graft-versus-host disease, oral chronic graft-versus-host disease, pathogenics, management, survival.

  14. Treatment of affective disorders in cardiac disease.

    PubMed

    Mavrides, Nicole; Nemeroff, Charles B

    2015-06-01

    Patients with cardiovascular disease (CVD) commonly have syndromal major depression, and depression has been associated with an increased risk of morbidity and mortality. Prevalence of depression is between 17% and 47% in CVD patients. Pharmacologic and psychotherapeutic interventions have long been studied, and in general are safe and somewhat efficacious in decreasing depressive symptoms in patients with CVD. The impact on cardiac outcomes remains unclear. The evidence from randomized controlled clinical trials indicates that antidepressants, especially selective serotonin uptake inhibitors, are overwhelmingly safe, and likely to be effective in the treatment of depression in patients with CVD. This review describes the prevalence of depression in patients with CVD, the physiological links between depression and CVD, the treatment options for affective disorders, and the clinical trials that demonstrate efficacy and safety of antidepressant medications and psychotherapy in this patient population. Great progress has been made in understanding potential mediators between major depressive disorder and CVD--both health behaviors and shared biological risks such as inflammation.

  15. Treatment of affective disorders in cardiac disease

    PubMed Central

    Mavrides, Nicole; Nemeroff, Charles B.

    2015-01-01

    Patients with cardiovascular disease (CVD) commonly have syndromal major depression, and depression has been associated with an increased risk of morbidity and mortality. Prevalence of depression is between 17% and 47% in CVD patients. Pharmacologic and psychotherapeutic interventions have long been studied, and in general are safe and somewhat efficacious in decreasing depressive symptoms in patients with CVD. The impact on cardiac outcomes remains unclear. The evidence from randomized controlled clinical trials indicates that antidepressants, especially selective serotonin uptake inhibitors, are overwhelmingly safe, and likely to be effective in the treatment of depression in patients with CVD. This review describes the prevalence of depression in patients with CVD, the physiological links between depression and CVD, the treatment options for affective disorders, and the clinical trials that demonstrate efficacy and safety of antidepressant medications and psychotherapy in this patient population. Great progress has been made in understanding potential mediators between major depressive disorder and CVD—both health behaviors and shared biological risks such as inflammation. PMID:26246788

  16. Parameters affecting of Akkuyu's safety assessment for severe core damages

    NASA Astrophysics Data System (ADS)

    Kavun, Yusuf; Karasulu, Muzaffer

    2015-07-01

    We have looked at all past core meltdowns (Three Mile Island, Chernobyl and Fukushima incidents) and postulated the fourth one might be taking place in the future most probably in a newly built reactors anywhere of the earth in any type of NPP. The probability of this observation is high considering the nature of the machine and human interaction. Operation experience is a very significant parameter as well as the safety culture of the host nation. The concerns is not just a lack of experience with industry with the new comers, but also the infrastructure and established institutions who will be dealing with the Emergencies. Lack of trained and educated Emergency Response Organizations (ERO) is a major concern. The culture on simple fire drills even makes the difference when a severe condition occurs in the industry. The study assumes the fourth event will be taking place at the Akkuyu NGS and works backwards as required by the "what went wrong " scenarios and comes up with interesting results. The differences studied in depth to determine the impact to the severe accidents. The all four design have now core catchers. We have looked at the operator errors'like in TMI); Operator errors combined with design deficiencies(like in Chernobyl) and natural disasters( like in Fukushima) and found operator errors to be more probable event on the Akkuyu's postulated next incident. With respect to experiences of the operators we do not have any data except for long and successful operating history of the Soviet design reactors up until the Chernobyl incident. Since the Akkuyu will be built, own and operated by the Russians we have found no alarming concerns at the moment. At the moment, there is no body be able to operate those units in Turkey. Turkey is planning to build the required manpower during the transition period. The resolution of the observed parameters lies to work and educate, train of the host nation and exercise together.

  17. Local variability in respiratory syncytial virus disease severity

    PubMed Central

    Brandenburg, A.; Jeannet, P.; Steensel-Moll, H.; Ott, A.; Rothbarth, P.; Wunderli, W.; Suter, S.; Neijens, H.; Osterhaus, A.; Siegrist, C.

    1997-01-01

    

 Respiratory syncytial virus (RSV) lower respiratory tract infections are considered to be a serious disease in centres such as the Sophia Children's Hospital (Rotterdam, the Netherlands), but as more benign infections in others such as the Geneva Children's Hospital (Switzerland). To assess the clinical severity of RSV infections at the two sites, 151 infants primarily admitted with a virologically confirmed RSV infection were studied prospectively (1994-5) and retrospectively (1993-4) (55 infants in Geneva and 96 in Rotterdam). Parameters of RSV morbidity which were more severe in Rotterdam during the two winter seasons were apnoea (1.8 v 23.9%), the rate of admission to the intensive care unit (3.6 v 28.1%), mechanical ventilation (0 v 7.3%), and length of stay in hospital (6.8 v 9.1 days). In Geneva higher respiratory rates (59.2 v 51.2), more wheezing (65.5 v 28.8%), and more retractions (81.8 v 63.3%) were recorded. Fewer infants younger than 4 months (54.9 v 68.7%), but more breast fed infants (94.1 v 38.5%), were admitted in Geneva, although the morbidity parameters remained different after correction for these two variables in multivariate analyses. Thus unidentified local factors influence the pattern and severity of RSV infection and may affect the results of multicentre prophylactic and therapeutic studies.

 PMID:9487963

  18. A comparison of different category scales for estimating disease severity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant pathologists most often obtain quantitative information on disease severity using visual assessments. Category scales are widely used for assessing disease severity, including for screening germplasm. The most widely used category scale is the Horsfall-Barratt (H-B) scale, but reports show tha...

  19. The presence or severity of pulmonary hypertension does not affect outcomes for single-lung transplantation.

    PubMed

    Julliard, Walker A; Meyer, Keith C; De Oliveira, Nilto C; Osaki, Satoru; Cornwell, Richard C; Sonetti, David A; Maloney, James D

    2016-05-01

    Advanced lung disease (ALD) that requires lung transplantation (LTX) is frequently associated with pulmonary hypertension (PH). Whether the presence of PH significantly affects the outcomes following single-lung transplantation (SLT) remains controversial. Therefore, we retrospectively examined the outcomes of 279 consecutive SLT recipients transplanted at our centre, and the patients were split into four groups based on their mean pulmonary artery pressure values. Outcomes, including long-term survival and primary graft dysfunction, did not differ significantly for patients with versus without PH, even when PH was severe. We suggest that SLT can be performed safely in patients with ALD-associated PH.

  20. Mitochondrial Haplogroups Affect Severity But Not Prevalence of Diabetic Retinopathy

    PubMed Central

    Bregman, Jana A.; Herren, David J.; Estopinal, Christopher B.; Chocron, Isaac M.; Harlow, Paula A.; Warden, Cassandra; Brantley, Milam A.; Samuels, David C.

    2017-01-01

    Purpose We previously reported European mitochondrial haplogroup H to be a risk factor for and haplogroup UK to be protective against proliferative diabetic retinopathy (PDR) among Caucasian patients with diabetic retinopathy (DR). The purpose of this study was to determine whether these haplogroups are also associated with the risk of having DR among Caucasian patients with diabetes. Methods Deidentified medical records for 637 Caucasian patients with diabetes (223 with DR) were obtained from BioVU, Vanderbilt University's electronic, deidentified DNA databank. An additional 197 Caucasian patients with diabetes (98 with DR) were enrolled from the Vanderbilt Eye Institute (VEI). We tested for an association between European mitochondrial haplogroups and DR status. Results The percentage of diabetes patients with DR did not differ across the haplogroups (P = 0.32). The percentage of patients with nonproliferative DR (NPDR; P = 0.0084) and with PDR (P = 0.027) significantly differed across the haplogroups. In logistic regressions adjusting for sex, age, diabetes type, duration of diabetes, and hemoglobin A1c, neither haplogroup H nor haplogroup UK had a significant effect on DR compared with diabetic controls. Haplogroup UK was a significant risk factor (OR = 1.72 [1.13–2.59], P = 0.010) for NPDR compared with diabetic controls in the unadjusted analysis, but not in the adjusted analysis (OR = 1.29 [0.79–2.10], P = 0.20). Conclusions Mitochondrial haplogroups H and UK were associated with severity, but not presence, of DR. These data argue that the effect of these haplogroups is related to ischemia and neovascularization, the defining features of PDR. PMID:28245487

  1. Management of severe rheumatological disease in the burn center.

    PubMed

    Reddy, Preetham; Ahrenholz, David H; Mohr, William J; Gertner, Elie

    2012-01-01

    In recent years, Burn Center has evolved to become a "wound intensive care unit" treating disease processes other than those due to thermal injury. Recent data have shown that more than 16% of admissions to Burn Centers are for nonburn injuries, particularly severe dermatologic diseases. The role of the Burn Center has been expanded to include treatment of patients with severe cutaneous manifestations of rheumatologic diseases. This approach has not been described before. All collagen vascular disease admissions to the Burn Center from 2005 to 2010 have been reviewed. There were 16 admissions where intensive wound management was a major component of the disease management. Disease processes included systemic lupus erythematosus, progressive systemic sclerosis, Raynaud's phenomenon, antiphospholipid syndrome, and dermatomyositis, among others. The authors describe five of these cases in detail. Comanagement of these patients by the Rheumatology and Burn services led to outstanding, successful outcomes. Collagen vascular diseases represent another area where the Burn Center may be the appropriate site for therapy.

  2. The ties that bind: perceived social support, stress, and IBS in severely affected patients

    PubMed Central

    LACKNER, J. M.; BRASEL, A. M.; QUIGLEY, B M.; KEEFER, L.; KRASNER, S. S.; POWELL, C.; KATZ, L. A.; SITRIN, M. D.

    2016-01-01

    Background This study assessed the association between social support and the severity of irritable bowel syndrome (IBS) symptoms in a sample of severely affected IBS patients recruited to an NIH-funded clinical trial. In addition, we examined if the effects of social support on IBS pain are mediated through the effects on stress. Methods Subjects were 105 Rome II diagnosed IBS patients (F = 85%) who completed seven questionnaires which were collected as part of a pretreatment baseline assessment. Key Results Partial correlations were conducted to clarify the relationships between social support and clinically relevant variables with baseline levels of psychopathology, holding constant number of comorbid medical diseases, age, gender, marital status, ethnicity, and education. Analyses indicated that social support was inversely related to IBS symptom severity. Social support was positively related with less severe pain. A similar pattern of data was found for perceived stress but not quality of life impairment. Regression analyses examined if the effects of social support on pain are mediated by stress. The effects of social support on bodily pain were mediated by stress such that the greater the social support the less stress and the less pain. This effect did not hold for symptom severity, quality of life, or psychological distress. Conclusions & Inferences This study links the perceived adequacy of social support to the global severity of symptoms of IBS and its cardinal symptom (pain). It also suggests that the mechanism by which social support alleviates pain is through a reduction in stress levels. PMID:20465594

  3. Remission of severe aphthous stomatitis of celiac disease with etanercept

    PubMed Central

    2013-01-01

    Celiac disease is a common autoimmune disease triggered by gluten-containing foods (wheat, barley and rye) in genetically predisposed individuals. We present a patient with celiac disease complicated by severe aphthous stomatitis resulting in impairing swallowing, chewing and speaking. This led to weight loss, psychosocial problems as well as inability to perform her work. A variety of topical and systemic medications used resulted in either no improvement or only partial alleviation of the patient’s symptoms. After informed consent, etanercept was initiated and resulted in complete remission of aphthous stomatitis, decrease in arthralgia and fatigue and considerable improvement in her quality of life. The use of newer biological agents for selected and severe manifestations of celiac disease may lead to improved morbidity in these patients, but more studies are needed to determine long-term efficacy as well as safety of these drugs in the mucosal and/or systemic complications of this disease. PMID:24365222

  4. Incubation Period Duration and Severity of Clinical Disease Following Severe Acute Respiratory Syndrome Coronavirus Infection

    PubMed Central

    Virlogeux, Victor; Fang, Vicky J.; Wu, Joseph T.; Ho, Lai-Ming; Malik Peiris, J. S.; Leung, Gabriel M.; Cowling, Benjamin J.

    2016-01-01

    Background Few previous studies have investigated the association between the severity of an infectious disease and the length of incubation period. Methods We estimated the association between the length of the incubation period and the severity of infection with the severe acute respiratory syndrome (SARS) coronavirus, using data from the epidemic in 2003 in Hong Kong. Results We estimated the incubation period of SARS based on a subset of patients with available data on exposure periods and a separate subset of patients in a putative common source outbreak, and we found significant associations between shorter incubation period and greater severity in both groups after adjusting for potential confounders. Conclusions Our findings suggest that patients with a shorter incubation period proceeded to have more severe disease. Further studies are needed to investigate potential biological mechanisms for this association. PMID:26133021

  5. Performance of 'Valencia' Orange (Citrus sinensis [L.] Osbeck) on 17 rootstocks in a trial severely affected by huanglongbing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Valencia orange (Citrus sinensis L. Osbeck) was grown on 17 rootstocks through seven years of age and the first four harvest seasons in a central Florida field trial severely affected by huanglongbing (HLB) disease. All trees in the trial had huanglongbing symptoms and were shown by Polymerase chain...

  6. The Prevalence of Diabetes Mellitus in COPD Patients with Severe and Very Severe Stage of the Disease

    PubMed Central

    Stojkovikj, Jagoda; Zafirova-Ivanovska, Beti; Kaeva, Biserka; Anastasova, Sasha; Angelovska, Irena; Jovanovski, Smiljko; Stojkovikj, Dragana

    2016-01-01

    AIM: The aim of the study was to investigate the prevalence of diabetes mellitus in privies diagnosed chronic obstructive pulmonary disease (COPD) patients with severe and very severe disease, which ware stable. METHODS: We investigated 100 subjects, all of them smokers, with smoking status >10 years. They were stratified in two groups. It was clinical, randomized, cross sectional study. Besides demographic parameters, functional parameters, BMI, cholesterol, LDL and HDL, and the level of blood sugar was measured. RESULTS: The prevalence of diabetes mellitus in our survey in total number of COPD patients with severe and very severe stage was 21%. In the very severe group were recorded significantly higher average values of glycaemia compared with severe group (7.67 ± 3.7 vs. 5.62 ± 0.9, p = 0.018). In the group with severe COPD, it was not confirmed any factor with significant predictive effect on the values of glycaemia. As independent significant factors that affect blood glucose in a group of very severe COPD were confirmed cholesterol (p <0.0001) and HDL (p = 0.018). CONCLUSION: These results suggest that the presence of the COPD in patients itself is a factor that results in the clinical presentation of diabetes mellitus Type 2. PMID:27335596

  7. Severe exacerbation of Crohn's disease during sunitinib treatment.

    PubMed

    Boers-Sonderen, Marye J; Mulder, Sasja F; Nagtegaal, Iris D; Jacobs, Joannes F M; Wanten, Geert J; Hoentjen, Frank; van Herpen, Carla M

    2014-02-01

    Sunitinib is a multiple tyrosine kinase inhibitor of the vascular endothelial growth factor and platelet-derived growth factor pathway and inhibits angiogenesis, cell proliferation, and tumor cell invasion, and stimulates apoptosis. Treatment with sunitinib in first-line metastatic renal cell carcinoma improves progression-free survival and overall survival compared with interferon-α. Crohn's disease is characterized by chronic immune-mediated intestinal inflammation. Although the exact pathogenesis of Crohn's disease remains unknown, the involvement of angiogenesis is acknowledged. It is unknown whether sunitinib interferes with the natural course of Crohn's disease. We describe a patient with metastatic renal cell carcinoma and a history of Crohn's disease who was treated with sunitinib and developed a severe exacerbation of Crohn's disease. After rechallenge with sunitinib, a second exacerbation occurred. We therefore conclude that angiogenesis inhibitors should be administered with care in patients with a history of Crohn's disease.

  8. Atypical pestivirus and severe respiratory disease in calves, Europe.

    PubMed

    Decaro, Nicola; Lucente, Maria Stella; Mari, Viviana; Cirone, Francesco; Cordioli, Paolo; Camero, Michele; Sciarretta, Rossana; Losurdo, Michele; Lorusso, Eleonora; Buonavoglia, Canio

    2011-08-01

    In 2010, a HoBi-like pestivirus was isolated from clinically affected calves in Italy. This European virus reproduced a milder form of disease under experimental conditions and was genetically related to previously reported HoBi-like strains. Isolation of this novel virus from a clinical outbreak may have implications for cattle health and prophylactic programs.

  9. Curative treatment for severe sickle cell disease: allogeneic transplantation.

    PubMed

    Oshrine, Benjamin; Talano, Julie-An

    2015-04-01

    Sickle cell disease is an inherited hematologic disorder that in its severe form can result in substantial morbidity and early mortality. Patients with this disorder can suffer from severe pain, lung disease, and strokes, resulting in chronic debilitating conditions, end organ dysfunction, and organ failure. The health care costs of caring for these chronically ill patients are substantial. Allogeneic transplantation is a modality that has the potential to cure these patients. To date, matched sibling donor transplantation is widely accepted as a standard of care for pediatric patients. Utilizing alternative donors for transplant is still under investigation, as is transplant for adult patients with sickle cell disease. This review focuses on the most recent data for hematopoietic cell transplantation for patients with sickle cell disease.

  10. Manifestation of severe coronary heart disease after anabolic drug abuse.

    PubMed

    Mewis, C; Spyridopoulos, I; Kühlkamp, V; Seipel, L

    1996-02-01

    Anabolic steroids are frequently abused, thus increasing the risk of cardiovascular disease, despite the known unfavorable influence on lipid profiles. We report on a young bodybuilder who presented with ventricular tachycardia as the first manifestation of severe underlying coronary heart disease. Coronary angiogram revealed severe stenotic lesions in the right coronary artery and the left descending coronary artery, and hypokinetic regions corresponded to posterolateral and anterior myocardial infarctions. This young patient had a history without any coronary risk factors, but with a 2-year abuse of the anabolic steroid stanazolol. No report published so far has shown possible atherogenic consequences of long-term abuse of stanazolol.

  11. Compartmentalized immune response reflects clinical severity of beryllium disease.

    PubMed

    Newman, L S; Bobka, C; Schumacher, B; Daniloff, E; Zhen, B; Mroz, M M; King, T E

    1994-07-01

    Although beryllium disease has been associated with a bronchoalveolar lavage (BAL) lymphocytosis and T cell-mediated immune response, we do not know if either the BAL cellular profile or the compartmentalized pulmonary response to the antigen reflect the severity of the disease. We studied 110 subjects divided into three groups of subjects: beryllium disease patients (n = 55), beryllium-sensitized patients without disease (n = 8), and control subjects (n = 47). Evaluation included completion of a respiratory symptom questionnaire, clinical examination, chest radiograph, spirometry, body plethysmographic lung volumes, and diffusing capacity (DLCO). In the patient groups, we performed maximal exercise testing with an indwelling arterial line. In addition, we examined BAL and performed blood and BAL beryllium lymphocyte transformation tests (BeLT) as measures of the beryllium-specific T cell-mediated response in these two compartments. In beryllium disease patients we correlated the BAL cellular constituents with clinical parameters indicative of disease severity. Beryllium disease patients exhibited elevated numbers of white cells and lymphocytes in BAL compared with both other groups; however, this lymphocytic alveolitis was significantly obscured in smokers. The BAL cellular constituents correlated with BAL BeLT but not with the blood BeLT. BAL cellular constituents also correlated with the radiographic profusion of small opacities, FEV1/FVC, DLCO, maximal achievable work load, VO2max, and measures of gas exchange at rest and at maximum exercise. We conclude that the lymphocyte-predominant pulmonary inflammatory response in beryllium disease is related to the magnitude of the localized response to antigen and that BAL cellularity, differential cell count, and BeLT reflect beryllium disease clinical severity.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. [A case of complex Crohn's disease with severe complication].

    PubMed

    Tian, Li; Tang, Anliu; Liu, Fen; Guo, Qin; Wang, Xiaoyan; Shen, Shourong

    2016-04-01

    Crohn's disease (CD) is a nonspecific chronic intestinal inflammatory disease with unknown etiology. The course of CD is persistent and recurrent. In the progress, CD can come with many complications such as obstruction, fistula formation, perforation, and hemorrhage. The early diagnosis, treatment, and the time of the surgery for CD pose a big controversy and challenge. There was a female patient diagnosed as Crohn's disease with severe complication in department of Gastroenterology of the Third Xiangya Hospital, Central South University.  We reported the diagnosis and treatment on this patient. The choice for the medicine and surgury was discussed.

  13. [Severe interstitial lung disease from pathologic gastroesophageal reflux in children].

    PubMed

    Ahrens, P; Weimer, B; Hofmann, D

    1999-07-01

    Interstitial lung diseases comprise a heterogeneous group of pulmonary conditions that cause restrictive lung disease of poor prognosis, especially if growth failure, pulmonary hypertension and fibrosis appears. We report on the case of a girl of 11 years of age who suffered from severe nonallergic asthma in early childhood and who developed severe interstitial pulmonary disease caused by gastro-oesophageal reflux at the age of 8 years. This diagnosis was established by lung biopsy, bronchoalveolar lavage and a high amount of lipid-laden alveolar macrophages, 2-level pH measurement and oesophageal biopsy. Because therapy with oral and inhaled steroids failed and Omeprazol showed benificial effects, hemifundoplication according to THAL was performed. At present the lung function is clearly normal and there is no need of any medicaments. Following the history, we can assume the pathological gastro-oesophageal reflux to be the cause of the disease. It is important to state that there were no typical symptoms at any time pointing to gastro-oesophageal reflux disease. The development of pulmonary disease by pathological reflux is very often caused by "silent aspiration". Very typically there are no symptoms such as vomiting, heartburn and pain but only signs of chronic lung disease.

  14. Prevalence of celiac disease in patients with severe food allergy.

    PubMed

    Pillon, R; Ziberna, F; Badina, L; Ventura, A; Longo, G; Quaglia, S; De Leo, L; Vatta, S; Martelossi, S; Patano, G; Not, T; Berti, I

    2015-10-01

    The association between food allergy and celiac disease (CD) is still to be clarified. We screened for CD 319 patients with severe food allergy (IgE > 85 kU/l against food proteins and a history of severe allergic reactions) who underwent specific food oral immunotherapy (OIT), together with 128 children with mild allergy who recovered without OIT, and compared the prevalence data with our historical data regarding healthy schoolchildren. Sixteen patients (5%) with severe allergy and one (0.8%) with mild allergy tested positive for both genetic and serological CD markers, while the prevalence among the schoolchildren was 1%. Intestinal biopsies were obtained in 13/16 patients with severe allergy and in the one with mild allergy, confirming the diagnosis of CD. Sufferers from severe food allergy seem to be at a fivefold increased risk of CD. Our findings suggest that routine screening for CD should be recommended in patients with severe food allergy.

  15. Metabolomic signatures associated with disease severity in multiple sclerosis

    PubMed Central

    Alonso, Cristina; Agirrezabal, Ion; Kotelnikova, Ekaterina; Zubizarreta, Irati; Pulido-Valdeolivas, Irene; Saiz, Albert; Comabella, Manuel; Montalban, Xavier; Villar, Luisa; Alvarez-Cermeño, Jose Carlos; Fernández, Oscar; Alvarez-Lafuente, Roberto; Arroyo, Rafael; Castro, Azucena

    2017-01-01

    Objective: To identify differences in the metabolomic profile in the serum of patients with multiple sclerosis (MS) compared to controls and to identify biomarkers of disease severity. Methods: We studied 2 cohorts of patients with MS: a retrospective longitudinal cohort of 238 patients and 74 controls and a prospective cohort of 61 patients and 41 controls with serial serum samples. Patients were stratified into active or stable disease based on 2 years of prospective assessment accounting for presence of clinical relapses or changes in disability measured with the Expanded Disability Status Scale (EDSS). Metabolomic profiling (lipids and amino acids) was performed by ultra-high-performance liquid chromatography coupled to mass spectrometry in serum samples. Data analysis was performed using parametric methods, principal component analysis, and partial least square discriminant analysis for assessing the differences between cases and controls and for subgroups based on disease severity. Results: We identified metabolomics signatures with high accuracy for classifying patients vs controls as well as for classifying patients with medium to high disability (EDSS >3.0). Among them, sphingomyelin and lysophosphatidylethanolamine were the metabolites that showed a more robust pattern in the time series analysis for discriminating between patients and controls. Moreover, levels of hydrocortisone, glutamic acid, tryptophan, eicosapentaenoic acid, 13S-hydroxyoctadecadienoic acid, lysophosphatidylcholines, and lysophosphatidylethanolamines were associated with more severe disease (non-relapse-free or increase in EDSS). Conclusions: We identified metabolomic signatures composed of hormones, lipids, and amino acids associated with MS and with a more severe course. PMID:28180139

  16. Antibody Response and Disease Severity in Healthcare Worker MERS Survivors

    PubMed Central

    Khalid, Imran; Ahmed, Waleed A.; Dada, Ashraf M.; Bayumi, Daniyah T.; Malic, Laut S.; Althawadi, Sahar; Ignacio, Kim; Alsalmi, Hanadi S.; Al-Abdely, Hail M.; Wali, Ghassan Y.; Qushmaq, Ismael A.; Alraddadi, Basem M.; Perlman, Stanley

    2016-01-01

    We studied antibody response in 9 healthcare workers in Jeddah, Saudi Arabia, who survived Middle East respiratory syndrome, by using serial ELISA and indirect immunofluorescence assay testing. Among patients who had experienced severe pneumonia, antibody was detected for >18 months after infection. Antibody longevity was more variable in patients who had experienced milder disease. PMID:27192543

  17. Linguistic Correlates of Asymmetric Motor Symptom Severity in Parkinson's Disease

    ERIC Educational Resources Information Center

    Holtgraves, Thomas; McNamara, Patrick; Cappaert, Kevin; Durso, Raymond

    2010-01-01

    Asymmetric motor severity is common in Parkinson's Disease (PD) and provides a method for examining the neurobiologic mechanisms underlying cognitive and linguistic deficits associated with the disorder. In the present research, PD participants (N = 31) were assessed in terms of the asymmetry of their motor symptoms. Interviews with the…

  18. Influence of the Circadian System on Disease Severity

    PubMed Central

    Litinski, Mikhail; Scheer, Frank AJL; Shea, Steven A

    2009-01-01

    Synopsis The severity of many diseases varies across the day and night. For example, adverse cardiovascular incidents peak in the morning, asthma is often worse at night and temporal lobe epileptic seizures are most prevalent in the afternoon. These patterns may be due to the day/night rhythm in environment and behavior, and/or endogenous circadian rhythms in physiology. Furthermore, chronic misalignment between the endogenous circadian timing system and the behavioral cycles could be a cause of increased risk of diabetes, obesity, cardiovascular disease and certain cancers in shift workers. Here we describe the magnitude, relevance and potential biological basis of such daily changes in disease severity and of circadian/behavioral misalignment, and present how these insights may help in the development of appropriate chronotherapy. PMID:20161149

  19. Severe hoof disease in free-ranging Roosevelt elk (Cervus elaphus roosevelti) in southwestern Washington, USA.

    PubMed

    Han, Sushan; Mansfield, Kristin G

    2014-04-01

    Reports of free-ranging Roosevelt elk (Cervus elaphus roosevelti) with abnormal hooves and lameness increased significantly in southwestern Washington, USA, during winter 2008. In March 2009 we examined five severely affected elk with clinical lameness from this region to characterize hoof lesions, examine the general health of affected elk, and potentially identify etiologies causing hoof disease. Three clinically normal elk from an adjacent but unaffected region were also collected as normal controls. Grossly, affected elk had deformed hooves that were asymmetrical, markedly elongated, and curved or broken, as well as hooves with sloughed horn. Most affected elk had severe sole ulcers with extensive laminar necrosis and pedal osteomyelitis. Histopathology of normal and abnormal hooves identified acute and chronic laminitis in all affected elk and one control elk. Hepatic copper and selenium levels in all affected and control elk were also deficient, and hoof keratin copper levels were low. No significant underlying systemic or musculoskeletal disease was detected in the affected elk, and attempts to isolate bacterial and viral pathogens were unsuccessful. A primary cause of hoof deformity was not definitively identified in this chronically affected group. Studies to identify infectious hoof disease and to characterize acute and subacute lesions are underway.

  20. Growth Differentiation Factor 15 Predicts Chronic Liver Disease Severity

    PubMed Central

    Lee, Eaum Seok; Kim, Seok Hyun; Kim, Hyun Jin; Kim, Kyung Hee; Lee, Byung Seok; Ku, Bon Jeong

    2017-01-01

    Background/Aims Growth differentiation factor 15 (GDF-15) belongs to the transforming growth factor-β superfamily. GDF-15 is emerging as a biomarker for several diseases. The aim of this study was to determine the clinical performances of GDF-15 for the prediction of liver fibrosis and severity in chronic liver disease. Methods The serum GDF-15 levels were examined via enzyme immunoassay in 145 patients with chronic liver disease and 101 healthy individuals. The patients with chronic liver disease consisted of 54 patients with chronic hepatitis, 44 patients with compensated liver cirrhosis, and 47 patients with decompensated liver cirrhosis. Results Of the patients with chronic liver diseases, the decompensated liver cirrhosis patients had an increased serum GDF-15 (3,483 ng/L) level compared with the patients with compensated liver cirrhosis (1,861 ng/L) and chronic hepatitis (1,232 ng/L). The overall diagnostic accuracies of GDF-15, as determined by the area under the receiver operating characteristic curves, were as follows: chronic hepatitis=0.656 (>574 ng/L, sensitivity, 53.7%; specificity, 79.2%), compensated liver cirrhosis=0.886 (>760 ng/L, sensitivity, 75.6%; specificity, 92.1%), and decompensated liver cirrhosis=0.984 (>869 ng/L, sensitivity, 97.9%; specificity, 94.1%). Conclusions This investigation represents the first study to demonstrate the availability of GDF-15 in chronic liver disease. GDF-15 comprised a useful biomarker for the prediction of liver fibrosis and severity in chronic liver disease. PMID:27728964

  1. Fibrillin levels in a severely affected Marfan syndrome patient with a null allele

    SciTech Connect

    Boxer, M.; Withers, A.P.; Al-Ghaban, Z. |

    1994-09-01

    Marfan syndrome is an autosomal dominantly inherited connective tissue disorder characterized by defects in the cardiovascular, skeletal and ocular systems. A patient was first examined in 1992 having survived an acute sortic dissection with subsequent composite repair and insertion of a prosthetic aortic valve. Clinical examination revealed arachnodactyly, narrow, high arched palate with dental crowding, an arm span exceeding her height by 10.5 cm, joint laxity and bilateral lens subluxation. Analysis of the family showed affected members in three generations and the fibrillin gene, FBN1, was shown to segregate with the disease when using polymorphic markers including an RsaI polymorphism in the 3{prime}-untranslated region of the gene. Analysis of patient mRNA for this RsaI polymorphism by RT-PCR (reverse transcriptase-PCR) amplification and restriction enzyme digestion of the PCR products showed that the copy of the gene segregating with the disease was not transcribed. No low level expression of this allele was observed despite RT-PCR amplification incorporating radioactively labelled dCTP, thus revealing a null allele phenotype. Western blotting analysis of fibrillin secreted by the patient`s dermal fibroblasts using fibrillin-specific antibodies showed only normal sized fibrillin protein. However, immunohistochemical studies of the patient`s tissue and fibroblasts showed markedly lowered levels in staining of microfibrillar structures compared with age-matched controls. This low level of expression of the protein affected in Marfan syndrome in a patient with such severe clinical manifestations is surprising since current understanding would suggest that this molecular phenotype should lead to a mild clinical disorder.

  2. Relation between Severity of Chronic Illness and Adjustment in Children and Adolescents with Sickle Cell Disease.

    ERIC Educational Resources Information Center

    Hurtig, Anita Landau; And Others

    1989-01-01

    The study with 70 children and adolescents with sickle cell disease did not support the hypothesis that illness severity (measured by frequency of hospitalization) would affect adjustment (measured by IQ, self-esteem, social and personal adjustment, behavioral problems, school performance, and peer relations). (Author/DB)

  3. Severe vascular complications in patients affected by systemic sclerosis cyclically treated with iloprost.

    PubMed

    Caramaschi, Paola; Dalla Gassa, Alessandra; Prati, Daniele; Barausse, Giovanni; Tinazzi, Ilaria; Ravagnani, Viviana; Confente, Silvia; Biasi, Domenico

    2012-07-01

    The objective of this study was to evaluate the incidence of the most severe vascular complications, such as pulmonary arterial hypertension, scleroderma renal crisis, and digital necrosis requiring amputation, in a monocentric group of systemic sclerosis (SSc) patients cyclically treated with intravenous iloprost. We reviewed the record-charts of 115 patients affected by SSc (18 men and 97 women, mean age 58.9.1 ± 14.2 years) regularly receiving iloprost for at least 3 years; the mean duration of the treatment was 98.8 ± 37.5 months (a total of 946.8 years of therapy). Demographic and clinical features were recorded. None of the patients died of SSc-associated vascular complications. After iloprost administration digital gangrene requiring amputation developed in 2 patients who had concomitant peripheral arterial disease (a total of 3 episodes; annual incidence of 0.31 for 100 years of iloprost therapy). Four patients were diagnosed with pulmonary arterial hypertension during iloprost treatment (annual incidence of 0.42 for 100 years of drug therapy); in none of the cases did the complication show a progressive course. No cases of scleroderma renal crisis were observed. With the limits of an observational study and in the absence of a control group, our experience suggests that prolonged cyclic iloprost therapy may limit the incidence/progression of severe digital and visceral SSc-vasculopathy.

  4. Detection of Severe Respiratory Disease Epidemic Outbreaks by CUSUM-Based Overcrowd-Severe-Respiratory-Disease-Index Model

    PubMed Central

    Castañón-González, Jorge Alberto; Macías, Alejandro E.; Samaniego, José Lino; Buhse, Thomas; Villanueva-Martínez, Sebastián

    2013-01-01

    A severe respiratory disease epidemic outbreak correlates with a high demand of specific supplies and specialized personnel to hold it back in a wide region or set of regions; these supplies would be beds, storage areas, hemodynamic monitors, and mechanical ventilators, as well as physicians, respiratory technicians, and specialized nurses. We describe an online cumulative sum based model named Overcrowd-Severe-Respiratory-Disease-Index based on the Modified Overcrowd Index that simultaneously monitors and informs the demand of those supplies and personnel in a healthcare network generating early warnings of severe respiratory disease epidemic outbreaks through the interpretation of such variables. A post hoc historical archive is generated, helping physicians in charge to improve the transit and future allocation of supplies in the entire hospital network during the outbreak. The model was thoroughly verified in a virtual scenario, generating multiple epidemic outbreaks in a 6-year span for a 13-hospital network. When it was superimposed over the H1N1 influenza outbreak census (2008–2010) taken by the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City, it showed that it is an effective algorithm to notify early warnings of severe respiratory disease epidemic outbreaks with a minimal rate of false alerts. PMID:24069063

  5. Detection of severe respiratory disease epidemic outbreaks by CUSUM-based overcrowd-severe-respiratory-disease-index model.

    PubMed

    Polanco, Carlos; Castañón-González, Jorge Alberto; Macías, Alejandro E; Samaniego, José Lino; Buhse, Thomas; Villanueva-Martínez, Sebastián

    2013-01-01

    A severe respiratory disease epidemic outbreak correlates with a high demand of specific supplies and specialized personnel to hold it back in a wide region or set of regions; these supplies would be beds, storage areas, hemodynamic monitors, and mechanical ventilators, as well as physicians, respiratory technicians, and specialized nurses. We describe an online cumulative sum based model named Overcrowd-Severe-Respiratory-Disease-Index based on the Modified Overcrowd Index that simultaneously monitors and informs the demand of those supplies and personnel in a healthcare network generating early warnings of severe respiratory disease epidemic outbreaks through the interpretation of such variables. A post hoc historical archive is generated, helping physicians in charge to improve the transit and future allocation of supplies in the entire hospital network during the outbreak. The model was thoroughly verified in a virtual scenario, generating multiple epidemic outbreaks in a 6-year span for a 13-hospital network. When it was superimposed over the H1N1 influenza outbreak census (2008-2010) taken by the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City, it showed that it is an effective algorithm to notify early warnings of severe respiratory disease epidemic outbreaks with a minimal rate of false alerts.

  6. Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis

    PubMed Central

    Grandgirard, Denis; Valente, Luca G.; Täuber, Martin G.; Leib, Stephen L.

    2016-01-01

    Streptococcus pneumoniae bacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement. PMID:27009189

  7. The Level of Cholesterol in COPD Patients with Severe and Very Severe Stage of the Disease

    PubMed Central

    Zafirova-Ivanovska, Beti; Stojkovikj, Jagoda; Dokikj, Dejan; Anastasova, Sasha; Debresliovska, Angela; Zejnel, Sead; Stojkovikj, Dragana

    2016-01-01

    BACKGROUND: High blood cholesterol is part of metabolic syndrome and can be caused by medical conditions or bad dietary habits. AIM: The aim of the study was to investigate the prevalence of hypercholesterolemia in privies diagnosed patients with the severe and very severe stage of COPD, which were stable. MATERIAL AND METHODS: We investigated 100 subjects, all of them smokers, with smoking status >10 years, stratified into two groups: with severe and very severe stage of the disease. It was clinical, randomized, cross-sectional study. Besides demographic parameters and functional parameters, body mass index, cholesterol, LDL, and HDL were investigated. RESULTS: In the group of patients with very severe COPD were recorded significantly higher average values of cholesterol (6.16 ± 1.5 vs. 5.61 ± 1.1, p = 0.039). As independent significant factors influencing cholesterol in the group with a very severe COPD were confirmed the age of the patients (p = 0.005), LDL (p = 0.004) and HDL (p = 0.002). In the group with severe COPD, only LDL was confirmed as an independent significant factor that has an impact on cholesterol (p < 0.0001). CONCLUSION: The results of our survey demonstrated a high level of blood cholesterol and LDL, and low level of blood HDL in both investigated group’s patients with COPD. PMID:27335600

  8. Longitudinal epitope mapping in MuSK myasthenia gravis: implications for disease severity.

    PubMed

    Huijbers, Maartje G; Vink, Anna-Fleur D; Niks, Erik H; Westhuis, Ruben H; van Zwet, Erik W; de Meel, Robert H; Rojas-García, Ricardo; Díaz-Manera, Jordi; Kuks, Jan B; Klooster, Rinse; Straasheijm, Kirsten; Evoli, Amelia; Illa, Isabel; van der Maarel, Silvère M; Verschuuren, Jan J

    2016-02-15

    Muscle weakness in MuSK myasthenia gravis (MG) is caused predominantly by IgG4 antibodies which block MuSK signalling and destabilize neuromuscular junctions. We determined whether the binding pattern of MuSK IgG4 antibodies change throughout the disease course ("epitope spreading"), and affect disease severity or treatment responsiveness. We mapped the MuSK epitopes of 255 longitudinal serum samples of 53 unique MuSK MG patients from three independent cohorts with ELISA. Antibodies against the MuSK Iglike-1 domain determine disease severity. Epitope spreading outside this domain did not contribute to disease severity nor to pyridostigmine responsiveness. This provides a rationale for epitope specific treatment strategies.

  9. CT Metrics of Airway Disease and Emphysema in Severe COPD

    PubMed Central

    Kim, Woo Jin; Silverman, Edwin K.; Hoffman, Eric; Criner, Gerard J.; Mosenifar, Zab; Sciurba, Frank C.; Make, Barry J.; Carey, Vincent; Estépar, Raúl San José; Diaz, Alejandro; Reilly, John J.; Martinez, Fernando J.; Washko, George R.

    2009-01-01

    Background: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV1 and percent predicted value of FEV1 with CT scan measures of emphysema and airway disease. Results: In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r = −0.28, p = 0.0001) and SRWA (r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV1% predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV1% predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions: Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema. PMID:19411295

  10. Noninvasive Measures of Liver Fibrosis and Severity of Liver Disease

    PubMed Central

    Lucero, Catherine; Brown, Robert S.

    2016-01-01

    Determining the degree of fibrosis is an important step in the assessment of disease severity in patients with chronic liver disease. Liver biopsy has been the gold standard for estimating the extent of inflammation and fibrosis, although the procedure has limitations such as sampling error and variability. Noninvasive testing has been shown to be equally predictive in ruling out fibrosis or ruling in advanced fibrosis. Serum biomarkers and imaging-based tests have more limited predictive ability when classifying intermediate stages, but these tools can help identify which patients should receive antiviral treatment sooner and require ongoing cancer surveillance without the need for biopsy. Using a combination of serum markers and imaging tests may also be helpful in providing functional assessment of portal hypertension in patients with chronic liver disease. PMID:27330502

  11. Markers of endothelial cell activation and immune activation are increased in patients with severe leptospirosis and associated with disease severity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: Previous studies concluded that haemorrhage is one of the most accurate prognostic factors of mortality in leptospirosis. Therefore, endothelial cell activation was investigated in relation to disease severity in severe leptospirosis. Methods: Prospective cohort study of severe leptospi...

  12. Parenting Stress Related to Behavioral Problems and Disease Severity in Children with Problematic Severe Asthma.

    PubMed

    Verkleij, Marieke; van de Griendt, Erik-Jonas; Colland, Vivian; van Loey, Nancy; Beelen, Anita; Geenen, Rinie

    2015-09-01

    Our study examined parenting stress and its association with behavioral problems and disease severity in children with problematic severe asthma. Research participants were 93 children (mean age 13.4 ± 2.7 years) and their parents (86 mothers, 59 fathers). As compared to reference groups analyzed in previous research, scores on the Parenting Stress Index in mothers and fathers of the children with problematic severe asthma were low. Higher parenting stress was associated with higher levels of internalizing and externalizing behavioral problems in children (Child Behavior Checklist). Higher parenting stress in mothers was also associated with higher airway inflammation (FeNO). Thus, although parenting stress was suggested to be low in this group, higher parenting stress, especially in the mother, is associated with more airway inflammation and greater child behavioral problems. This indicates the importance of focusing care in this group on all possible sources of problems, i.e., disease exacerbations and behavioral problems in the child as well as parenting stress.

  13. Affective behavior during mother-daughter conflict and borderline personality disorder severity across adolescence.

    PubMed

    Whalen, Diana J; Scott, Lori N; Jakubowski, Karen P; McMakin, Dana L; Hipwell, Alison E; Silk, Jennifer S; Stepp, Stephanie D

    2014-01-01

    Developmental theories of borderline personality disorder (BPD) posit that transactions between child characteristics and adverse environments, especially those in the context of the parent-child relationship, shape and maintain symptoms of the disorder over time. However, very little empirical work has investigated the role of parenting and parent-child transactions that may predict BPD severity over time. We examined maternal and dyadic affective behaviors during a mother-adolescent conflict discussion task as predictors of the course of BPD severity scores across 3 years in a diverse, at-risk sample of girls (N = 74) oversampled for affective instability and their biological mothers. Adolescent girls completed a structured conflict discussion task with their mothers at age 16. Girls' self-reported BPD severity scores were assessed annually from ages 15 to 17. Mother-adolescent interactions were coded using a global rating system of maternal and dyadic affective behaviors. Results from multilevel linear mixed models indicated that positive maternal affective behavior (i.e., supportive/validating behavior, communication skills, autonomy-promoting behavior, and positive affect) and positive dyadic affective behaviors (i.e., satisfaction and positive escalation) were associated with decreases in girls' BPD severity scores over time. Dyadic negative escalation was associated with higher overall levels of BPD severity scores, but negative maternal affective behavior (i.e., negative affect, dominance, conflict, and denial) was not. These findings suggest that the mother-daughter context is an important protective factor in shaping the course of BPD severity scores during adolescence and may be valuable in assessment, intervention, and prevention efforts.

  14. The effects of adapted tango on spatial cognition and disease severity in Parkinson's disease.

    PubMed

    McKee, Kathleen E; Hackney, Madeleine E

    2013-01-01

    The authors determined effects of community-based adapted tango on spatial cognition and disease severity in Parkinson's disease (PD) while controlling for the effects of social interaction. Thirty-three individuals with mild-to-moderate PD (stage I-III) were assigned to twenty 90-min tango (n = 24) or education (n = 9) lessons over 12 weeks. Disease severity, spatial cognition, balance, and fall incidence were evaluated pre-, post-, and 10-12 weeks postintervention. The authors evaluated differences using t tests and analyses of variance. Twenty-three tango and 8 education participants finished. Tango participants improved on disease severity (p = .008), and spatial cognition (p = .021) compared with education participants. Tango participants also improved in balance (p = .038), and executive function (p = .012). Gains were maintained 10-12 weeks postintervention. Multimodal exercise with structured syllabi may improve disease severity and spatial cognition in PD.

  15. Hematopoietic stem cell transplantation for severe combined immunodeficiency diseases.

    PubMed

    Cowan, Morton J; Neven, Benedicte; Cavazanna-Calvo, M; Fischer, A; Puck, Jennifer

    2008-01-01

    Hematopoietic stem cell transplantation (HSCT) is the only curative option for most children with severe combined immunodeficiency disease (SCID). Survival for SCID following HSCT has significantly improved over the past several decades, and ranges from 70% to 95% depending on the clinical condition of the child at the time of transplant, the availability of an HLA-matched sibling donor, and the SCID genotype/phenotype. In this article we will review the types of SCID and discuss the critical HSCT issues that confront us today, including the optimal source of donor cells when an HLA-matched sibling is not available, as well as the pros and cons of using conditioning therapy pretransplant. As SCID children have been followed for several decades, it is becoming apparent that long-term outcome and durable T and B cell immune reconstitution are quite variable depending on the initial treatment and source of donor cells. Finally, the development of methods to improve the early diagnosis of SCID along with designing prospective trials to evaluate the best approaches to curing these diseases with minimal toxicity are critical to improving outcomes for children with SCID.

  16. Relationship of Inflammatory Biomarkers with Severity of Peripheral Arterial Disease

    PubMed Central

    Toyofuku, Takahiro; Inoue, Yoshinori

    2016-01-01

    Objective. The pentraxin family, including high-sensitivity C-reactive protein (hs-CRP), serum amyloid P (SAP), and pentraxin 3 (PTX3), has been identified as playing a key role in inflammatory reactions such as in atherosclerosis and cardiovascular disease. In this study, we examined the relationship between peripheral arterial disease (PAD) and serum levels of pentraxins. Methods. This study was undertaken via a retrospective review of PAD patients with surgical intervention for lesions of the common femoral artery. We evaluated the preoperative patient conditions, hemodynamic status, such as ankle brachial index (ABI), and clinical ischemic conditions according to Rutherford classification. Preoperatively, we collected blood samples for determining the serum levels of hs-CRP, SAP, and PTX3. Results. Twelve PAD patients with common femoral arterial lesions were treated and examined. The hemodynamic severity of PAD was not negatively correlated with hs-CRP, SAP, or PTX3. The clinical severity evaluated by Rutherford classification was significantly positively correlated with the serum level of PTX3 (p = 0.019). Conclusion. We demonstrated that PTX3 might be a better marker of PAD than hs-CRP and SAP. Furthermore, PTX3 might be a prognostic marker to evaluate the severity of PAD. PMID:27559483

  17. Abnormalities of proximal femoral growth after severe Perthes' disease.

    PubMed

    Sponseller, P D; Desai, S S; Millis, M B

    1989-08-01

    We studied the pattern of proximal femoral growth after severe Perthes' disease (Catterall grade III or IV) by retrospective analysis of serial radiographs in 52 hips (46 patients). Our aim was to determine the relationship between proximal femoral growth abnormalities and metaphyseal cysts, epiphyseal extrusion, physeal narrowing, and extensive epiphyseal necrosis. The average follow-up after treatment was 9.8 years (range 4 to 16 years), and 37 of the hips were followed to skeletal maturity. Slowing of proximal femoral growth was common: symmetrical abnormality was seen in 26 hips and asymmetrical abnormality in nine. However, definite premature closure of the proximal femoral physis was seen in only three hips. Abnormality seemed to be due to altered growth velocity rather than to bar formation in most cases. Metaphyseal cysts, epiphyseal extrusion and physeal narrowing during the active stage of the disease, alone or in combination, were found to be neither sensitive nor specific predictors of the subsequent growth pattern.

  18. Bats as reservoirs of severe emerging infectious diseases.

    PubMed

    Han, Hui-Ju; Wen, Hong-ling; Zhou, Chuan-Min; Chen, Fang-Fang; Luo, Li-Mei; Liu, Jian-wei; Yu, Xue-Jie

    2015-07-02

    In recent years severe infectious diseases have been constantly emerging, causing panic in the world. Now we know that many of these terrible diseases are caused by viruses originated from bats (Table 1), such as Ebola virus, Marburg, SARS coronavirus (SARS-CoV), MERS coronavirus (MERS-CoV), Nipah virus (NiV) and Hendra virus (HeV). These viruses have co-evolved with bats due to bats' special social, biological and immunological features. Although bats are not in close contact with humans, spillover of viruses from bats to intermediate animal hosts, such as horses, pigs, civets, or non-human primates, is thought to be the most likely mode to cause human infection. Humans may also become infected with viruses through aerosol by intruding into bat roosting caves or via direct contact with bats, such as catching bats or been bitten by bats.

  19. Celiac disease unmasked by acute severe iron deficiency anemia

    PubMed Central

    Meseeha, Marcelle G.; Attia, Maximos N.; Kolade, Victor O.

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  20. Severe hyponatraemia secondary to desmopressin therapy in von Willebrand's disease.

    PubMed

    Bertholini, D M; Butler, C S

    2000-04-01

    A 42-year-old female with von Willebrand's disease was managed with desmopressin and tranexamic acid to aid haemostasis following a vaginal hysterectomy. Severe acute hyponatraemia (134 to 108 mmol/l) developed over two days, culminating in a generalized tonic-clonic seizure and cerebral oedema. Fluid restriction, cessation of desmopressin and hypertonic saline administration led to a full recovery. Desmopressin is known to reduce free water elimination and produce hyponatraemia, but its extent and rate of development in this patient was surprising. Close monitoring of serum sodium and fluid balance is recommended in these patients.

  1. How does smoking affect olfaction in Parkinson's disease?

    PubMed

    Moccia, Marcello; Picillo, Marina; Erro, Roberto; Vitale, Carmine; Amboni, Marianna; Palladino, Raffaele; Cioffi, Dante Luigi; Barone, Paolo; Pellecchia, Maria Teresa

    2014-05-15

    Smoke-induced upper airway damage and Parkinson's disease (PD) can be considered independent risk factors for smell impairment. Interestingly, cigarette smoking has been strongly associated with reduced risk of PD and, therefore, has been suggested to have neuroprotective effects. Our pilot study aimed to evaluate the relationship between smoking and olfaction in PD patients and matched controls. Sixty-eight PD patients and 61 healthy controls were categorized in relation to PD diagnosis and current smoking status, and evaluated by means of the Italian version of the University of Pennsylvania 40-item Smell Identification Test (UPSIT-40). ANOVA analysis with post-hoc Bonferroni correction showed that non-smoker controls presented a higher UPSIT-40 total score than smoker controls (p<0.001), non-smoker PD patients (p<0.001) and smoker PD patients (p<0.001). In this view, smoking seems to affect olfaction in controls but not in PD patients, and no significant differences were found when comparing smoker controls, smoker PD patients and non-smoker PD patients. Several epidemiological studies showed a negative effect of smoking on olfaction in the general population. Otherwise the sense of smell is similar in smoker and non-smoker PD patients. These results suggest that PD and smoking are not independent risk factors for impairment of sense of smell, but they might variably interact.

  2. A Review of Factors Affecting Vaccine Preventable Disease in Japan

    PubMed Central

    Ching, Michael SL

    2014-01-01

    Japan is well known as a country with a strong health record. However its incidence rates of vaccine preventable diseases (VPD) such as hepatitis B, measles, mumps, rubella, and varicella remain higher than other developed countries. This article reviews the factors that contribute to the high rates of VPD in Japan. These include historical and political factors that delayed the introduction of several important vaccines until recently. Access has also been affected by vaccines being divided into government-funded “routine” (eg, polio, pertussis) and self-pay “voluntary” groups (eg, hepatitis A and B). Routine vaccines have higher rates of administration than voluntary vaccines. Administration factors include differences in well child care schedules, the approach to simultaneous vaccination, vaccination contraindication due to fever, and vaccination spacing. Parental factors include low intention to fully vaccinate their children and misperceptions about side effects and efficacy. There are also provider knowledge gaps regarding indications, adverse effects, interval, and simultaneous vaccination. These multifactorial issues combine to produce lower population immunization rates and a higher incidence of VPD than other developed countries. This article will provide insight into the current situation of Japanese vaccinations, the issues to be addressed and suggestions for public health promotion. PMID:25628969

  3. Emphysematous pyelonephritis: the impact of urolithiasis on disease severity

    PubMed Central

    Myers, Frank; Chi, Thomas; Bagga, Herman S.; Taylor, Andrew G.; Stoller, Marshall L.

    2016-01-01

    Background Emphysematous pyelonephritis is a severe infection of the kidney associated with formation of gas in the renal parenchyma and/or collecting system. The purpose of this study was to evaluate outcomes of patients with emphysematous pyelonephritis in a contemporary cohort and to evaluate the impact of urolithiasis on disease severity. Methods A search of all imaging reports at University of California San Francisco (UCSF) for the term “emphysematous pyelonephritis” was undertaken from 2003–2014. Patients were included if there was clinical evidence of infection, no recent urologic instrumentation, and computerized tomography (CT) demonstrating gas in the renal parenchyma or collecting system. Clinical and laboratory variables were obtained from medical records. Results A total of 14 cases were identified. The majority of patients (57%) had gas confined to the collecting system. Three patients (21%) had gas in the renal parenchyma and 3 patients (21%) had gas extending into perirenal tissues. A total of 8 patients (57%) had concomitant urolithiasis. Seven patients (50%) were managed with antibiotic therapy alone while 6 patients (43%) required percutaneous drainage. No patients required immediate nephrectomy. There were no deaths. Patients with urolithiasis had less severe emphysematous pyelonephritis than patients without urolithiasis (P<0.05). Conclusions The majority of patients in this study had gas contained within the collecting system and were treated successfully with antibiotics alone. Percutaneous drainage was successfully utilized in patients with more advanced disease. No patients required emergent nephrectomy. Emphysematous pyelonephritis in patients with urolithiasis was less severe than in patients without urolithiasis. PMID:27785435

  4. Allergies and Disease Severity in Childhood Narcolepsy: Preliminary Findings

    PubMed Central

    Aydinoz, Secil; Huang, Yu-Shu; Gozal, David; Inocente, Clara O.; Franco, Patricia; Kheirandish-Gozal, Leila

    2015-01-01

    Introduction: Narcolepsy frequently begins in childhood, and is characterized by excessive daytime sleepiness, with the presence of cataplexy reflecting a more severe phenotype. Narcolepsy may result from genetic predisposition involving deregulation of immune pathways, particularly involving T helper 2 cells (Th2). Increased activation of Th2 cells is usually manifested as allergic conditions such as rhinitis, atopic dermatitis, and asthma. We hypothesized that the presence of allergic conditions indicative of increased Th2 balance may dampen the severity of the phenotype in children with narcolepsy. Methods: A retrospective chart review of childhood narcolepsy patients was conducted at three major pediatric sleep centers. Patients were divided into those with narcolepsy without cataplexy (NC−) and narcolepsy with cataplexy (NC+). Demographics, polysomnographic and multiple sleep latency test data, and extraction of information on the presence of allergic diseases such allergic rhinitis, atopic dermatitis, and asthma was performed. Results: There were 468 children identified, with 193 children in NC− group and 275 patients in the NC+ group. Overall, NC+ children were significantly younger, had higher body mass index, and had shorter mean sleep latencies and increased sleep onset rapid eye movement events. The frequency of allergic conditions, particularly asthma and allergic rhinitis, was markedly lower in NC+ (58/275) compared to NC− patients (94/193; P < 0.0001). Conclusion: Involvement of the immune system plays an important role in the pathophysiology of narcolepsy. Current findings further suggest that an increased shift toward T helper 2 cells, as indicated by the presence of allergic conditions, may modulate the severity of the phenotype in childhood narcolepsy, and reduce the prevalence of cataplexy in these patients. Citation: Aydinoz S, Huang YS, Gozal D, Inocente CO, Franco P, Kheirandish-Gozal L. Allergies and disease severity in childhood

  5. The association between periodontal disease parameters and severity of atherosclerosis

    PubMed Central

    Ketabi, Mohammad; Meybodi, Fatemeh Rashidi; Asgari, Mohammad Reza

    2016-01-01

    Background: Atherosclerosis is the most common cause for heart attack and stroke. In the last decade, several epidemiological studies have found an association between periodontal infection and atherosclerosis. The aim of this research was to determine the possible association between chronic periodontal disease and severity of atherosclerosis. Materials and Methods: Eighty-two subjects that were referred to Chamran Heart Hospital in Isfahan for angiography were involved in this study. Fifty-nine subjects had coronary artery obstruction (CAO) and 23 showed no obstruction after angiography. The severity of CAO was assessed. Periodontal parameters including pocket depth (PD), gingival recession (R), clinical attachment level (CAL), and bleeding on probing (BOP) of all subjects were recorded. The decayed-missing-filled (DMF) index of all subjects was also measured. For statistical analysis, Pearson correlation test, Chi-square, and independent t-test were used. Results: There were significant positive correlation between variables R, PD, CAL, decayed (D), missing (M), DMF, BOP, and degree of CAO. However, there were no significant differences between filling variable degree of CAO (left anterior descending, left circumflex, and right coronary artery). Independent t-test showed that the mean of variables R, PD, AL, D, M, and DMF in patients with obstructed arteries were significantly higher than subjects without CAO. But there were no significant differences between variable F in two groups. Conclusion: The results of this cross-section analytical study showed an association between periodontal disease and dental parameters with the severity of CAO measured by angiography. However, this association must not interpret as a cause and effect relationship. PMID:27274346

  6. Environmental determinants of severity in sickle cell disease

    PubMed Central

    Tewari, Sanjay; Brousse, Valentine; Piel, Frédéric B.; Menzel, Stephan; Rees, David C.

    2015-01-01

    Sickle cell disease causes acute and chronic illness, and median life expectancy is reduced by at least 30 years in all countries, with greater reductions in low-income countries. There is a wide spectrum of severity, with some patients having no symptoms and others suffering frequent, life-changing complications. Much of this variability is unexplained, despite increasingly sophisticated genetic studies. Environmental factors, including climate, air quality, socio-economics, exercise and infection, are likely to be important, as demonstrated by the stark differences in outcomes between patients in Africa and USA/Europe. The effects of weather vary with geography, although most studies show that exposure to cold or wind increases hospital attendance with acute pain. Most of the different air pollutants are closely intercorrelated, and increasing overall levels seem to correlate with increased hospital attendance, although higher concentrations of atmospheric carbon monoxide may offer some benefit for patients with sickle cell disease. Exercise causes some adverse physiological changes, although this may be off-set by improvements in cardiovascular health. Most sickle cell disease patients live in low-income countries and socioeconomic factors are undoubtedly important, but little studied beyond documenting that sickle cell disease is associated with decreases in some measures of social status. Infections cause many of the differences in outcomes seen across the world, but again these effects are relatively poorly understood. All the above factors are likely to account for much of the pathology and variability of sickle cell disease, and large prospective studies are needed to understand these effects better. PMID:26341524

  7. Environmental determinants of severity in sickle cell disease.

    PubMed

    Tewari, Sanjay; Brousse, Valentine; Piel, Frédéric B; Menzel, Stephan; Rees, David C

    2015-09-01

    Sickle cell disease causes acute and chronic illness, and median life expectancy is reduced by at least 30 years in all countries, with greater reductions in low-income countries. There is a wide spectrum of severity, with some patients having no symptoms and others suffering frequent, life-changing complications. Much of this variability is unexplained, despite increasingly sophisticated genetic studies. Environmental factors, including climate, air quality, socio-economics, exercise and infection, are likely to be important, as demonstrated by the stark differences in outcomes between patients in Africa and USA/Europe. The effects of weather vary with geography, although most studies show that exposure to cold or wind increases hospital attendance with acute pain. Most of the different air pollutants are closely intercorrelated, and increasing overall levels seem to correlate with increased hospital attendance, although higher concentrations of atmospheric carbon monoxide may offer some benefit for patients with sickle cell disease. Exercise causes some adverse physiological changes, although this may be off-set by improvements in cardiovascular health. Most sickle cell disease patients live in low-income countries and socioeconomic factors are undoubtedly important, but little studied beyond documenting that sickle cell disease is associated with decreases in some measures of social status. Infections cause many of the differences in outcomes seen across the world, but again these effects are relatively poorly understood. All the above factors are likely to account for much of the pathology and variability of sickle cell disease, and large prospective studies are needed to understand these effects better.

  8. Vertebral degenerative disc disease severity evaluation using random forest classification

    NASA Astrophysics Data System (ADS)

    Munoz, Hector E.; Yao, Jianhua; Burns, Joseph E.; Pham, Yasuyuki; Stieger, James; Summers, Ronald M.

    2014-03-01

    Degenerative disc disease (DDD) develops in the spine as vertebral discs degenerate and osseous excrescences or outgrowths naturally form to restabilize unstable segments of the spine. These osseous excrescences, or osteophytes, may progress or stabilize in size as the spine reaches a new equilibrium point. We have previously created a CAD system that detects DDD. This paper presents a new system to determine the severity of DDD of individual vertebral levels. This will be useful to monitor the progress of developing DDD, as rapid growth may indicate that there is a greater stabilization problem that should be addressed. The existing DDD CAD system extracts the spine from CT images and segments the cortical shell of individual levels with a dual-surface model. The cortical shell is unwrapped, and is analyzed to detect the hyperdense regions of DDD. Three radiologists scored the severity of DDD of each disc space of 46 CT scans. Radiologists' scores and features generated from CAD detections were used to train a random forest classifier. The classifier then assessed the severity of DDD at each vertebral disc level. The agreement between the computer severity score and the average radiologist's score had a quadratic weighted Cohen's kappa of 0.64.

  9. Ocular signs correlate well with disease severity and genotype in Fabry disease.

    PubMed

    Pitz, Susanne; Kalkum, Gisela; Arash, Laila; Karabul, Nesrin; Sodi, Andrea; Larroque, Sylvain; Beck, Michael; Gal, Andreas

    2015-01-01

    Ocular signs in Fabry disease have generally been regarded to be primarily of diagnostic value. We explored whether ocular findings, alone or in particular in combination with the α-galactosidase A gene mutation, have predictive value for disease severity. Data from the Fabry Outcome Survey (FOS), a large, global database sponsored by Shire, were selected for adult patients who had undergone ophthalmological examination. Three ocular signs were assessed: cornea verticillata, tortuous conjunctival and/or retinal vessels, and cataract. Fabry disease severity was measured using FOS Mainz Severity Score Index and modifications thereof. Ophthalmological data were available for 1203 (699 female, 504 male) adult patients with eye findings characteristic of Fabry disease in 55.1%. Cornea verticillata had a similar distribution in women (51.1%) and men (50.8%), whereas tortuous vessels and Fabry cataract were somewhat more frequent in men than in women. Patients with cornea verticillata, selected as the principal ocular sign for this study, had more severe disease (median score, 20.0) versus those without ocular signs (11.0; P<0.001). This finding could be confirmed by applying age adjusted severity scores. Moreover, the prevalence of cornea verticillata was significantly higher in patients with null (male, 76.9%; female, 64.5%) and missense (male, 79.2%; female, 67.4%) mutations versus mild missense (male, 17.1%; female, 23.1%) and the p.N215S (male, 15.0%; female, 15.6%) mutations (P<0.01). Our analyses show a correlation between the prevalence of ocular changes in Fabry disease and disease severity. Consequently, information on ocular findings and α-galactosidase A gene mutation may help assess the risk for more severe Fabry disease. These observed findings are of notable clinical importance, as Fabry disease is characterized by high clinical course variability and only weak genotype-phenotype correlation at the individual patient level. Further confirmatory studies

  10. B10 Cell Frequencies and Suppressive Capacity in Myasthenia Gravis Are Associated with Disease Severity

    PubMed Central

    Yi, John S.; Russo, Melissa A.; Massey, Janice M.; Juel, Vern; Hobson-Webb, Lisa D.; Gable, Karissa; Raja, Shruti M.; Balderson, Kristina; Weinhold, Kent J.; Guptill, Jeffrey T.

    2017-01-01

    Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated disease. The mechanisms for loss of self-tolerance in this disease are not well understood, and recently described regulatory B cell (Breg) subsets have not been thoroughly investigated. B10 cells are a subset of Bregs identified by the production of the immunosuppressive cytokine, interleukin-10 (IL-10). B10 cells are known to strongly inhibit B- and T-cell inflammatory responses in animal models and are implicated in human autoimmunity. In this study, we examined quantitative and qualitative aspects of B10 cells in acetylcholine receptor autoantibody positive MG (AChR-MG) patients and healthy controls. We observed reduced B10 cell frequencies in AChR-MG patients, which inversely correlated with disease severity. Disease severity also affected the function of B10 cells, as B10 cells in the moderate/severe group of MG patients were less effective in suppressing CD4 T-cell proliferation. These results suggest that B10 cell frequencies may be a useful biomarker of disease severity, and therapeutics designed to restore B10 cell frequencies could hold promise as a treatment for this disease through restoration of self-tolerance. PMID:28239367

  11. Oral Medication Adherence and Disease Severity in Pediatric Inflammatory Bowel Disease

    PubMed Central

    Hommel, Kevin A.; Denson, Lee A.; Baldassano, Robert N.

    2011-01-01

    Objective The purpose of this study was to examine the relationship of oral medication adherence and perceived adherence barriers with disease severity in a sample of adolescents with IBD. Methods Participants included 62 adolescents, aged 13–17 years, diagnosed with IBD and their parents. Measures of parent- and patient-rated oral medication adherence and related barriers, behavioral and emotional functioning per parent- and self-report, and disease severity per physician reported medical chart data were obtained. Results Fifteen percent of the sample reported clinically elevated depressive symptoms and 24% reported clinically elevated internalizing behavioral problems. Number of reported adherence barriers was 2.6 ± 1.5, and no participants reported zero barriers. Parental ratings of medication adherence (t = −2.11, p < .05) and perceived barriers to adherence (t = 2.05, p < .05) significantly predicted disease severity after statistically controlling for the contributions of behavioral and disease parameters to disease severity. Conclusions Results suggest that oral medication adherence and perceived adherence barriers are significantly related to disease severity in adolescents with IBD. These patients also may be at risk for increased behavioral and emotional problems which may impact health outcomes as well. Clinicians should make particular efforts to attend to medication adherence issues with their patients. Working with patients and families to develop solutions for eliminating adherence barriers might result in better disease outcomes. PMID:21304318

  12. Switching between Abstract Rules Reflects Disease Severity but Not Dopaminergic Status in Parkinson's Disease

    ERIC Educational Resources Information Center

    Kehagia, Angie A.; Cools, Roshan; Barker, Roger A.; Robbins, Trevor W.

    2009-01-01

    This study sought to disambiguate the impact of Parkinson's disease (PD) on cognitive control as indexed by task set switching, by addressing discrepancies in the literature pertaining to disease severity and paradigm heterogeneity. A task set is governed by a rule that determines how relevant stimuli (stimulus set) map onto specific responses…

  13. Latin America: native populations affected by early onset periodontal disease.

    PubMed

    Nowzari, Hessam; Botero, Javier Enrique

    2011-06-01

    Millions of individuals are affected by early onset periodontal disease in Latin America, a continent that includes more than 20 countries. The decision-makers claim that the disease is not commonly encountered. In 2009, 280,919 authorized immigrants were registered in the United States versus 5,460,000 unauthorized (2,600,000 in California). The objective of the present article is to raise awareness about the high prevalence of the disease among Latin Americans and the good prognosis of preventive measures associated with minimal financial cost.

  14. Memantine effects on behaviour in moderately severe to severe Alzheimer's disease: a post-marketing surveillance study.

    PubMed

    Clerici, Francesca; Vanacore, Nicola; Elia, Antonietta; Spila-Alegiani, Stefania; Pomati, Simone; Da Cas, Roberto; Raschetti, Roberto; Mariani, Claudio

    2012-02-01

    The aim of this study is to evaluate memantine effectiveness on behavioural and psychological symptoms of dementia (BPSD) in clinical practice and to identify variables that may predict the therapy effects. The effects of memantine on behaviour were analysed in the database of a post-marketing surveillance study promoted by the Lombardy Region Health Office and involving 43 Alzheimer's disease (AD) Units. From July to December 2005, 399 moderately severe-to-severe AD patients free of cholinergic medications were enrolled, treated with memantine and followed-up for 6 months. BPSD were assessed in a subgroup of 297 patients [mean age 77 ± 8 years; 73% females; mean neuropsychiatric inventory (NPI) score 28 ± 24] for whom the 12-item NPI subscores at baseline, and at 3 and 6 months were available. The 12 BPSD were clustered as follows: affect, physical behaviour, psychosis and hypomania. The main outcome measure was the proportion of individual cluster responders at 6 months of therapy. The proportion of individual cluster responders was 30% affect, 24% physical behaviour, 29% psychosis, 27% hypomania. Patients taking 20 mg memantine daily during the study period had a statistically significant higher probability to experience behavioural improvement than those who discontinued treatment or did not complete memantine titration (affect OR 9.0; 95% CI 3.8-21.6; physical behaviour OR 17.8; 95% CI 5.9-53.6; psychosis OR 23.6; 95% CI 5.1-110.8). The logistic regression analysis was not applicable to the hypomania subsyndrome because of the low cluster prevalence. The standard 20 mg daily memantine treatment regimen was found to be associated with a modest 6-month behavioural improvement in the affect, physical behaviour and psychosis domains in 24-30% of patients.

  15. Multiplicity of Infection and Disease Severity in Plasmodium vivax

    PubMed Central

    Pacheco, M. Andreína; Lopez-Perez, Mary; Vallejo, Andrés F.; Herrera, Sócrates; Arévalo-Herrera, Myriam; Escalante, Ananias A.

    2016-01-01

    Background Multiplicity of infection (MOI) refers to the average number of distinct parasite genotypes concurrently infecting a patient. Although several studies have reported on MOI and the frequency of multiclonal infections in Plasmodium falciparum, there is limited data on Plasmodium vivax. Here, MOI and the frequency of multiclonal infections were studied in areas from South America where P. vivax and P. falciparum can be compared. Methodology/Principal Findings As part of a passive surveillance study, 1,328 positive malaria patients were recruited between 2011 and 2013 in low transmission areas from Colombia. Of those, there were only 38 P. vivax and 24 P. falciparum clinically complicated cases scattered throughout the time of the study. Samples from uncomplicated cases were matched in time and location with the complicated cases in order to compare the circulating genotypes for these two categories. A total of 92 P. vivax and 57 P. falciparum uncomplicated cases were randomly subsampled. All samples were genotyped by using neutral microsatellites. Plasmodium vivax showed more multiclonal infections (47.7%) than P. falciparum (14.8%). Population genetics and haplotype network analyses did not detect differences in the circulating genotypes between complicated and uncomplicated cases in each parasite. However, a Fisher exact test yielded a significant association between having multiclonal P. vivax infections and complicated malaria. No association was found for P. falciparum infections. Conclusion The association between multiclonal infections and disease severity in P. vivax is consistent with previous observations made in rodent malaria. The contrasting pattern between P. vivax and P. falciparum could be explained, at least in part, by the fact that P. vivax infections have lineages that were more distantly related among them than in the case of the P. falciparum multiclonal infections. Future research should address the possible role that acquired

  16. Hyponatraemia: more than just a marker of disease severity?

    PubMed

    Schrier, Robert W; Sharma, Shailendra; Shchekochikhin, Dmitry

    2013-01-01

    Hyponatraemia--the most common serum electrolyte disorder--has also emerged as an important marker of the severity and prognosis of important diseases such as heart failure and cirrhosis. Acute hyponatraemia can cause severe encephalopathy, but the rapid correction of chronic hyponatraemia can also profoundly impair brain function and even cause death. With the expanding elderly population and the increased prevalence of hyponatraemia in this segment of society, prospective studies are needed to examine whether correcting hyponatraemia in the elderly will diminish cognitive impairment, improve balance and reduce the incidence of falls and fractures. Given that polypharmacy is also common in the elderly population, the various medications that may stimulate arginine vasopressin release and/or enhance the hormone's action to increase water absorption must also be taken into consideration. Whether hyponatraemia in a patient with cancer is merely a marker of poor prognosis or whether its presence may alter the patient's quality of life remains to be examined. In any case, hyponatraemia can no longer be considered as just a biochemical bystander in the ill patient. A systematic diagnostic approach is necessary to determine the specific aetiology of a patient's hyponatraemia. Therapy must then be dictated not only by recognized reversible causes such as advanced hypothyroidism, adrenal insufficiency, diuretics or other medicines, but also by whether the hyponatraemia occurred acutely or chronically. Information is emerging that the vast majority of cases of hyponatraemia are caused by the nonosmotic release of arginine vasopressin. Now that vasopressin V2-receptor blockers are available, a new era of clinical investigation is necessary to examine whether hyponatraemia is just a marker of severe disease or whether correction of hyponatraemia could improve a patient's quality of life. Such an approach must involve prospective randomized studies in different groups of

  17. An outbreak in 1965 of severe respiratory illness caused by the Legionnaires' disease bacterium.

    PubMed

    Thacker, S B; Bennett, J V; Tsai, T F; Fraser, D W; McDade, J E; Shepard, C C; Williams, K H; Stuart, W H; Dull, H B; Eickhoff, T C

    1978-10-01

    In January 1977 an unsolved outbreak of infection at St. Elizabeth's Hospital (Washington, D.C.) that occurred in 1965 was linked with Legionnaires' disease. The link was made by fluorescent antibody testing with the bacterium isolated from tissues of persons with Legionnaires' disease in the 1976 outbreak in Philadelphia. In July and August 1965, an epidemic of severe respiratory disease characterized by abrupt onset of high fever, weakness, malaise, and nonproductive cough, frequently accompanied by radiographic evidence of pneumonia, affected at least 81 patients at St. Elizabeth's Hospital, a general psychiatric hospital. Fourteen (17%) of the affected patients died. Intensive epidemiologic and laboratory investigations in 1965 did not determine the etiology. The etiologic organism may have become airborne from sites of soil excavation.

  18. The Role of Celiac Disease in Severity of Liver Disorders and Effect of a Gluten Free Diet on Diseases Improvement

    PubMed Central

    Rostami-Nejad, Mohammad; Haldane, Thea; AlDulaimi, David; Alavian, Seyed Moayed; Zali, Mohammad Reza; Rostami, Kamran

    2013-01-01

    Context Celiac disease (CD) is defined as a permanent intolerance to ingested gluten. The intolerance to gluten results in immune-mediated damage of small intestine mucosa manifested by villous atrophy and crypt hyperplasia. These abnormalities resolve with initiationa gluten-free diet. Evidence Acquisition PubMed, Ovid, and Google were searched for full text articles published between 1963 and 2012. The associated keywords were used, and papers described particularly the impact of celiac disease on severity of liver disorder were identified. Results Recently evidence has emerged revealingthat celiac disease not only is associated with small intestine abnormalities and malabsorption, but is also a multisystem disorder affecting other systems outside gastrointestinal tract, including musculo-skeletal, cardiovascular and nervous systems. Some correlations have been assumed between celiac and liver diseases. In particular, celiac disease is associated with changes in liver biochemistry and linked to alter the prognosis of other disorders. This review will concentrate on the effect of celiac disease and gluten-free diets on the severity of liver disorders. Conclusions Although GFD effect on the progression of CD associated liver diseases is not well defined, it seems that GFD improves liver function tests in patients with a hypertransaminasemia. PMID:24348636

  19. The Implementation of Best Education Practices for a Student Severely Affected by Autism

    ERIC Educational Resources Information Center

    Breitenbach, Marlene M.; Armstrong, Vickie L.; Bryson, Susan E.

    2013-01-01

    In this article, we describe an inclusive educational programme for a young boy severely affected by autism. The programme is exemplary not only academically, but also in terms of what children need socially and emotionally. It represents best practices in action. Given the wide agreement about what constitutes best education practices, but the…

  20. Standardizing ADOS Domain Scores: Separating Severity of Social Affect and Restricted and Repetitive Behaviors

    ERIC Educational Resources Information Center

    Hus, Vanessa; Gotham, Katherine; Lord, Catherine

    2014-01-01

    Standardized Autism Diagnostic Observation Schedule (ADOS) scores provide a measure of autism severity that is less influenced by child characteristics than raw totals (Gotham et al. in "Journal of Autism and Developmental Disorders," 39(5), 693-705 2009). However, these scores combine symptoms from the Social Affect (SA) and Restricted…

  1. Genetic Influences on Cystic Fibrosis Lung Disease Severity

    PubMed Central

    Weiler, Colleen A.; Drumm, Mitchell L.

    2013-01-01

    Understanding the causes of variation in clinical manifestations of disease should allow for design of new or improved therapeutic strategies to treat the disease. If variation is caused by genetic differences between individuals, identifying the genes involved should present therapeutic targets, either in the proteins encoded by those genes or the pathways in which they function. The technology to identify and genotype the millions of variants present in the human genome has evolved rapidly over the past two decades. Originally only a small number of polymorphisms in a small number of subjects could be studied realistically, but speed and scope have increased nearly as dramatically as cost has decreased, making it feasible to determine genotypes of hundreds of thousands of polymorphisms in thousands of subjects. The use of such genetic technology has been applied to cystic fibrosis (CF) to identify genetic variation that alters the outcome of this single gene disorder. Candidate gene strategies to identify these variants, referred to as “modifier genes,” has yielded several genes that act in pathways known to be important in CF and for these the clinical implications are relatively clear. More recently, whole-genome surveys that probe hundreds of thousands of variants have been carried out and have identified genes and chromosomal regions for which a role in CF is not at all clear. Identification of these genes is exciting, as it provides the possibility for new areas of therapeutic development. PMID:23630497

  2. Predictors of disease severity in patients admitted to a cholera treatment center in urban Haiti.

    PubMed

    Valcin, Claude-Lyne; Severe, Karine; Riche, Claudia T; Anglade, Benedict S; Moise, Colette Guiteau; Woodworth, Michael; Charles, Macarthur; Li, Zhongze; Joseph, Patrice; Pape, Jean W; Wright, Peter F

    2013-10-01

    Cholera, previously unrecognized in Haiti, spread through the country in the fall of 2010. An analysis was performed to understand the epidemiological characteristics, clinical management, and risk factors for disease severity in a population seen at the GHESKIO Cholera Treatment Center in Port-au-Prince. A comprehensive review of the medical records of patients admitted during the period of October 28, 2010-July 10, 2011 was conducted. Disease severity on admission was directly correlated with older age, more prolonged length of stay, and presentation during the two epidemic waves seen in the observation period. Although there was a high seroprevalence of human immunodeficiency virus (HIV), severity of cholera was not greater with HIV infection. This study documents the correlation of cholera waves with rainfall and its reduction in settings with improved sanitary conditions and potable water when newly introduced cholera affects all ages equally so that interventions must be directed throughout the population.

  3. Identification of mutations in Colombian patients affected with Fabry disease.

    PubMed

    Uribe, Alfredo; Mateus, Heidi Eliana; Prieto, Juan Carlos; Palacios, Maria Fernanda; Ospina, Sandra Yaneth; Pasqualim, Gabriela; da Silveira Matte, Ursula; Giugliani, Roberto

    2015-12-15

    Fabry Disease (FD) is an X-linked inborn error of glycosphingolipid catabolism, caused by a deficiency of the lisosomal α-galactosidase A (AGAL). The disorder leads to a vascular disease secondary to the involvement of kidney, heart and the central nervous system. The mutation analysis is a valuable tool for diagnosis and genetic counseling. Although more than 600 mutations have been identified, most mutations are private. Our objective was to describe the analysis of nine Colombian patients with Fabry disease by automated sequencing of the seven exons of the GLA gene. Two novel mutations were identified in two patients affected with the classical subtype of FD, in addition to other 6 mutations previously reported. The present study confirms the heterogeneity of mutations in Fabry disease and the importance of molecular analysis for genetic counseling, female heterozygotes detection as well as therapeutic decisions.

  4. Orthodontic approach for patients with severe periodontal disease.

    PubMed

    Arun, Tülin; Sayinsu, Korkmaz; Nalbantgil, Didem

    2005-01-01

    Although comprehensive orthodontic treatment cannot preclude the possibility of periodontal disease developing later, it can be a useful part of the overall treatment plan for a patient who already has periodontal involvement. A careful clinical examination must determine the patient's dental health status, including any existing destruction or deficiencies of the teeth and their support, as well as the patient's ability to achieve and maintain good overall oral hygiene. Two major criteria should be considered in the treatment of these patients: (1) the patient should be seen frequently for periodontal maintenance and (2) minimal orthodontic forces should be applied. Segmented archwires could be used for the treatment mechanics. After treatment, splinting of the teeth is necessary both short- and long-term. With this orthodontic approach, both dental esthetics and function improve and can be maintained. A male patient, 50 years of age, with severe periodontal involvement was referred to the authors' clinic, from the periodontal department, for treatment. The mandibular incisors were intruded by using segmental archwires. At the end of treatment, permanent retention was required due to the severe bone loss.

  5. Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring.

    PubMed

    de Pagter, Mirjam S; van Roosmalen, Markus J; Baas, Annette F; Renkens, Ivo; Duran, Karen J; van Binsbergen, Ellen; Tavakoli-Yaraki, Masoumeh; Hochstenbach, Ron; van der Veken, Lars T; Cuppen, Edwin; Kloosterman, Wigard P

    2015-04-02

    Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across three to five chromosomes. Two mothers did not show any phenotypic abnormalities, although 3-13 protein-coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy-number changes in two children. This resulted in gene-dosage changes, which are probably responsible for the severe congenital phenotypes of these two children. In contrast, the third child, who has a severe congenital disease, harbored all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy-number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein-coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals affects reproduction and is expected to substantially increase the risk of miscarriages, abortions, and severe congenital disease.

  6. Differential phenolic production in leaves of Vitis vinifera cv. Alvarinho affected with esca disease.

    PubMed

    Lima, Marta R M; Felgueiras, Mafalda L; Cunha, Ana; Chicau, Gisela; Ferreres, Federico; Dias, Alberto C P

    2017-03-01

    Esca is a destructive disease of complex etiology affecting grapevines worldwide. A major constraint to the study and control of esca is that the disease is not diagnosed until external leaf and/or fruit symptoms are visible; however external symptoms usually appear several years after infection onset. We studied the phenolic content of V. vinifera cv. Alvarinho leaves using high performance liquid chromatography-diode array detection-mass spectrometry (HPLC-DAD-MS)/LC-MS. Leaves from affected cordons with and without visible symptoms (diseased and apparently healthy leaves, respectively) and leaves from asymptomatic cordons (healthy leaves) were analyzed. Application of principal components analysis (PCA) to HPLC data showed a clear separation between diseased, apparently healthy, and healthy leaves, with the apparently healthy leaves clustered in a medial position. Several compounds were highly correlated with diseased leaves indicating a differential phenolic production due to esca disease in V. vinifera cv. Alvarinho leaves. Total phenolic production was shown to significantly increase in diseased leaves, compared to healthy leaves, with apparently healthy leaves containing a medial amount. Trans-caffeoyltartaric acid, trans-coumaroyl-tartaric acid, quercetin-3-O-glucoside, quercetin-3-O-galactoside, kaempferol-3-glucoside and myricetin were identified among the compounds associated with disease and their content shown to change similarly to total phenolic production. This study shows that it is possible to discriminate between diseased, healthy and apparently healthy leaves by applying PCA to HPLC data.

  7. Association between thyroid autoimmunity and fibromyalgic disease severity.

    PubMed

    Bazzichi, Laura; Rossi, Alessandra; Giuliano, Tiziana; De Feo, Francesca; Giacomelli, Camillo; Consensi, Arianna; Ciapparelli, Antonio; Consoli, Giorgio; Dell'osso, Liliana; Bombardieri, Stefano

    2007-12-01

    Our objectives were to investigate thyroid abnormalities and autoimmunity in 120 patients affected by fibromyalgia (FM) and to study their relationships with clinical data and symptoms. Thyroid assessment by means of antithyroglobulin antibodies, antithyroid peroxidase antibodies, free triiodo-thyronine, free thyroxine, and thyroid stimulating hormone analyses was carried out. The clinical parameters "Fibromyalgia Impact Questionnaire", pain, tender points, fatigue, and other symptoms, and the presence of depression or anxiety disorders were evaluated. The basal thyroid hormone levels of FM patients were in the normal range, while 41% of the patients had at least one thyroid antibody. Patients with thyroid autoimmunity showed a higher percentage of dry eyes, burning, or pain with urination, allodynia, blurred vision, and sore throat. Correlations found between thyroid autoimmunity and age or with the presence of depression or anxiety disorders were not significant. However, in the cohort of post-menopausal patients, the frequency of thyroid autoimmunity was higher with respect to pre-menopausal patients. In conclusion, autoimmune thyroiditis is present in an elevated percentage of FM patients, and it has been associated with the presence of typical symptoms of the disease.

  8. Establishment of clonal myogenic cell lines from severely affected dystrophic muscles - CDK4 maintains the myogenic population

    PubMed Central

    2011-01-01

    Background A hallmark of muscular dystrophies is the replacement of muscle by connective tissue. Muscle biopsies from patients severely affected with facioscapulohumeral muscular dystrophy (FSHD) may contain few myogenic cells. Because the chromosomal contraction at 4q35 linked to FSHD is thought to cause a defect within myogenic cells, it is important to study this particular cell type, rather than the fibroblasts and adipocytes of the endomysial fibrosis, to understand the mechanism leading to myopathy. Results We present a protocol to establish clonal myogenic cell lines from even severely dystrophic muscle that has been replaced mostly by fat, using overexpression of CDK4 and the catalytic component of telomerase (human telomerase reverse transcriptase; hTERT), and a subsequent cloning step. hTERT is necessary to compensate for telomere loss during in vitro cultivation, while CDK4 prevents a telomere-independent growth arrest affecting CD56+ myogenic cells, but not their CD56- counterpart, in vitro. Conclusions These immortal cell lines are valuable tools to reproducibly study the effect of the FSHD mutation within myoblasts isolated from muscles that have been severely affected by the disease, without the confounding influence of variable amounts of contaminating connective-tissue cells. PMID:21798090

  9. Respiratory rehabilitation in severe restrictive lung disease secondary to tuberculosis.

    PubMed

    Yang, G F; Alba, A; Lee, M

    1984-09-01

    There is a need for portable and less expensive devices for patients with chronic respiratory insufficiency. The case of a 44-year-old Hispanic woman is illustrative. The patient had severe restrictive lung disease secondary to right phrenic nerve crush/pneumoperitoneum and left pneumonectomy/decortication for bilateral lower lobe tuberculosis. In 1969, 12 years after her last operation, she developed dyspnea, coryza, and somnolence. She was hospitalized with a PaO2 of 30mmHg; PaCO2 of 77mmHg and a pH of 7.28. Pulmonary function tests showed alveolar hypoventilation and her resting ventilation was between 2.26 to 3.74L/min. Her vital capacity was 1130cc (37% of predicted value) and maximum breathing capacity was 36L/min (44% of predicted value). From 1969, she used a poncho (wraparound) ventilator for her long-term respiratory care and modified the poncho suit to meet her personal needs. In 1971, she discovered that a mouth intermittent positive pressure ventilation (MIPPV) method, often used by patients with neuromuscular disorders, was easier to apply. Since then, she has continued to use a Bantam Respirator with MIPPV and a lipguard/mouthpiece during the night, and the respirator with a mouthpiece for a few hours during the days. However, when she has an upper respiratory infection or feels tired, she finds that she needs the greater rest and comfort that the poncho provides. With the assistance of these two respiratory devices, she has been able to complete her education, marry, and lead a fulfilling life in the community. This patient is considered the first person with severe lung pathology to utilize MIPPV for sleep.

  10. SLC44A2 single nucleotide polymorphisms, isoforms, and expression: Association with severity of Meniere's disease?

    PubMed

    Nair, Thankam S; Kommareddi, Pavan K; Galano, Maria M; Miller, Danielle M; Kakaraparthi, Bala Naveen; Telian, Steven A; Arts, H Alex; El-Kashlan, Hussam; Kilijanczyk, Alyse; Lassig, Amy Anne D; Graham, Martin P; Fisher, Susan G; Stoll, Stefan W; Nair, Rajan P; Elder, James T; Carey, Thomas E

    2016-12-01

    SLC44A2 was discovered as the target of an antibody that causes hearing loss. Knockout mice develop age related hearing loss, loss of sensory cells and spiral ganglion neurons. SLC44A2 has polymorphic sites implicated in human disease. Transfusion related acute lung injury (TRALI) is linked to rs2288904 and genome wide association studies link rs2288904 and rs9797861 to venous thromboembolism (VTE), coronary artery disease and stroke. Here we report linkage disequilibrium of rs2288904 with rs3087969 and the association of these SLC44A2 SNPs with Meniere's disease severity. Tissue-specific isoform expression differences suggest that the N-terminal domain is linked to different functions in different cell types. Heterozygosity at rs2288904 CGA/CAA and rs3087969 GAT/GAC showed a trend for association with intractable Meniere's disease compared to less severe disease and to controls. The association of SLC44A2 SNPs with VTE suggests that thrombi affecting cochlear vessels could be a factor in Meniere's disease.

  11. Kawasaki disease shock syndrome: a rare and severe complication of Kawasaki disease.

    PubMed

    Çakan, Mustafa; Gemici, Hakan; Aktay-Ayaz, Nuray; Keskindemirci, Gonca; Bornaun, Helen; İkizoğlu, Tarkan; Çeliker, Alpay

    2016-01-01

    Kawasaki disease is an acute systemic vasculitis that occurs most commonly in young children. It affects medium-sized muscular arteries and the coronary arteries are the predominant site of involvement. Morbidity and mortality is generally due to coronary artery aneurysms that develop during the chronic phase. Although it is well known that Kawasaki disease can cause myocarditis, tachycardia and heart failure during acute stage, Kawasaki disease shock syndrome has been recently described. It is characterized by hypotension, signs and symptoms of poor perfusion and a shock-like state. Herein we describe two cases of Kawasaki disease shock syndrome that were treated in the pediatric intensive care unit and followed a course without morbidity or mortality.

  12. Ribonucleoprotein assembly defects correlate with spinal muscular atrophy severity and preferentially affect a subset of spliceosomal snRNPs.

    PubMed

    Gabanella, Francesca; Butchbach, Matthew E R; Saieva, Luciano; Carissimi, Claudia; Burghes, Arthur H M; Pellizzoni, Livio

    2007-09-26

    Spinal muscular atrophy (SMA) is a motor neuron disease caused by reduced levels of the survival motor neuron (SMN) protein. SMN together with Gemins2-8 and unrip proteins form a macromolecular complex that functions in the assembly of small nuclear ribonucleoproteins (snRNPs) of both the major and the minor splicing pathways. It is not known whether the levels of spliceosomal snRNPs are decreased in SMA. Here we analyzed the consequence of SMN deficiency on snRNP metabolism in the spinal cord of mouse models of SMA with differing phenotypic severities. We demonstrate that the expression of a subset of Gemin proteins and snRNP assembly activity are dramatically reduced in the spinal cord of severe SMA mice. Comparative analysis of different tissues highlights a similar decrease in SMN levels and a strong impairment of snRNP assembly in tissues of severe SMA mice, although the defect appears smaller in kidney than in neural tissue. We further show that the extent of reduction in both Gemin proteins expression and snRNP assembly activity in the spinal cord of SMA mice correlates with disease severity. Remarkably, defective SMN complex function in snRNP assembly causes a significant decrease in the levels of a subset of snRNPs and preferentially affects the accumulation of U11 snRNP--a component of the minor spliceosome--in tissues of severe SMA mice. Thus, impairment of a ubiquitous function of SMN changes the snRNP profile of SMA tissues by unevenly altering the normal proportion of endogenous snRNPs. These findings are consistent with the hypothesis that SMN deficiency affects the splicing machinery and in particular the minor splicing pathway of a rare class of introns in SMA.

  13. Chlorotic curly stunt: a severe begomovirus disease of bottle gourd in northern India.

    PubMed

    Sohrab, S S; Mandal, B; Ali, A; Varma, A

    2010-06-01

    Bottle gourd (Lagenaria siceraria) an important vegetable crop in India was observed to be affected by a chlorotic curly stunt disease (CCSD) during 2003-2006 in the vegetable growing areas of Delhi and adjoining state of Haryana. The affected plants are severely stunted and bear very small chlorotic and mildly curled leaves. Incidence of the disease varied from 4.7 to 36%. The disease could be easily transmitted by whitefly, Bemisia tabaci but not by sap. The causal virus was found to be a Begomovirus on the basis of whitefly transmission and sequence identity of putative coat protein (CP) and replication initiator protein (Rep) genes. The virus was transmitted to Cucumis sativus, Luffa acutangula, L. cylndrica, Lycopersicon esculentum, Nicotiana tabacum and Praecitrullus fistulosus but not to Citrullus lunatus, Cucumis melo, Cucurbita moschata and Vigna unguiculata. The N-terminal 60 amino acids of CP of the virus had 100% sequence identity with all the isolates of Tomato leaf curl New Delhi virus (ToLCNDV) and two isolates of Squash leaf curl China virus (SLCCV). The full length amino acid sequence of the CP and Rep genes had 100% similarity with ToLCNDV-Svr and -Luffa isolates. The phylogenetic analysis showed that the virus associated with CCSD of bottle gourd belongs to ToLCNDV cluster of the begomoviruses. This is the first record of emergence of a Begomovirus associated severe disease in bottle gourd in India.

  14. The temporal patterns of disease severity and prevalence in schistosomiasis

    SciTech Connect

    Ciddio, Manuela; Gatto, Marino Casagrandi, Renato

    2015-03-15

    Schistosomiasis is one of the most widespread public health problems in the world. In this work, we introduce an eco-epidemiological model for its transmission and dynamics with the purpose of explaining both intra- and inter-annual fluctuations of disease severity and prevalence. The model takes the form of a system of nonlinear differential equations that incorporate biological complexity associated with schistosome's life cycle, including a prepatent period in snails (i.e., the time between initial infection and onset of infectiousness). Nonlinear analysis is used to explore the parametric conditions that produce different temporal patterns (stationary, endemic, periodic, and chaotic). For the time-invariant model, we identify a transcritical and a Hopf bifurcation in the space of the human and snail infection parameters. The first corresponds to the occurrence of an endemic equilibrium, while the latter marks the transition to interannual periodic oscillations. We then investigate a more realistic time-varying model in which fertility of the intermediate host population is assumed to seasonally vary. We show that seasonality can give rise to a cascade of period-doubling bifurcations leading to chaos for larger, though realistic, values of the amplitude of the seasonal variation of fertility.

  15. The temporal patterns of disease severity and prevalence in schistosomiasis

    NASA Astrophysics Data System (ADS)

    Ciddio, Manuela; Mari, Lorenzo; Gatto, Marino; Rinaldo, Andrea; Casagrandi, Renato

    2015-03-01

    Schistosomiasis is one of the most widespread public health problems in the world. In this work, we introduce an eco-epidemiological model for its transmission and dynamics with the purpose of explaining both intra- and inter-annual fluctuations of disease severity and prevalence. The model takes the form of a system of nonlinear differential equations that incorporate biological complexity associated with schistosome's life cycle, including a prepatent period in snails (i.e., the time between initial infection and onset of infectiousness). Nonlinear analysis is used to explore the parametric conditions that produce different temporal patterns (stationary, endemic, periodic, and chaotic). For the time-invariant model, we identify a transcritical and a Hopf bifurcation in the space of the human and snail infection parameters. The first corresponds to the occurrence of an endemic equilibrium, while the latter marks the transition to interannual periodic oscillations. We then investigate a more realistic time-varying model in which fertility of the intermediate host population is assumed to seasonally vary. We show that seasonality can give rise to a cascade of period-doubling bifurcations leading to chaos for larger, though realistic, values of the amplitude of the seasonal variation of fertility.

  16. Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder.

    PubMed

    Mc Mahon, Brenda; Andersen, Sofie B; Madsen, Martin K; Hjordt, Liv V; Hageman, Ida; Dam, Henrik; Svarer, Claus; da Cunha-Bang, Sofi; Baaré, William; Madsen, Jacob; Hasholt, Lis; Holst, Klaus; Frokjaer, Vibe G; Knudsen, Gitte M

    2016-05-01

    Cross-sectional neuroimaging studies in non-depressed individuals have demonstrated an inverse relationship between daylight minutes and cerebral serotonin transporter; this relationship is modified by serotonin-transporter-linked polymorphic region short allele carrier status. We here present data from the first longitudinal investigation of seasonal serotonin transporter fluctuations in both patients with seasonal affective disorder and in healthy individuals. Eighty (11)C-DASB positron emission tomography scans were conducted to quantify cerebral serotonin transporter binding; 23 healthy controls with low seasonality scores and 17 patients diagnosed with seasonal affective disorder were scanned in both summer and winter to investigate differences in cerebral serotonin transporter binding across groups and across seasons. The two groups had similar cerebral serotonin transporter binding in the summer but in their symptomatic phase during winter, patients with seasonal affective disorder had higher serotonin transporter than the healthy control subjects (P = 0.01). Compared to the healthy controls, patients with seasonal affective disorder changed their serotonin transporter significantly less between summer and winter (P < 0.001). Further, the change in serotonin transporter was sex- (P = 0.02) and genotype- (P = 0.04) dependent. In the patients with seasonal affective disorder, the seasonal change in serotonin transporter binding was positively associated with change in depressive symptom severity, as indexed by Hamilton Rating Scale for Depression - Seasonal Affective Disorder version scores (P = 0.01). Our findings suggest that the development of depressive symptoms in winter is associated with a failure to downregulate serotonin transporter levels appropriately during exposure to the environmental stress of winter, especially in individuals with high predisposition to affective disorders.media-1vid110.1093/brain/aww043_video_abstractaww043_video_abstract.

  17. The reproduction in women affected by cooley disease

    PubMed Central

    Pafumi, Carlo; Leanza, Vito; Coco, Luana; Vizzini, Stefania; Ciotta, Lilliana; Messina, Alessandra; Leanza, Gianluca; Zarbo, Giuseppe; D'Agati, Alfio; Palumbo, Marco Antonio; Iemmola, Alessandra; Gulino, Ferdinando Antonio; Teodoro, Maria Cristina; Attard, Matthew; Plesca, Alina Cristina; Soares, Catarina; Kouloubis, Nina; Chammas, Mayada

    2011-01-01

    The health background management and outcomes of 5 pregnancies in 4 women affected by Cooley Disease, from Paediatric Institute of Catania University, are described, considering the preconceptual guidances and cares for such patients. These patients were selected among a group of 100 thalassemic women divided into three subgroups, according to their first and successive menstruation characteristics: i) patients with primitive amenorrhoea, ii) patients with secondary amenorrhoea and iii) patients with normal menstruation. Only one woman, affected by primitive amenorrhoea, needed the induction of ovulation. A precise and detailed pre-pregnancy assessment was effected before each conception. This was constituted by a series of essays, including checks for diabetes and hypothyroidism, for B and C hepatitis and for blood group antibodies. Moreover were evaluated: cardiac function, rubella immunity and transaminases. Other pregnancy monitoring, and cares during labour and delivery were effected according to usual obstetrics practice. All the women were in labour when she were 38 week pregnant, and the outcome were five healthy babies born at term, weighting between 2600 and 3200gs. The only complication was the Caesarean section. The improvements of current treatments, especially in the management of iron deposits, the prolongation of survival rate, will result in a continuous increase of pregnancies in thalassemic women. Pregnancy is now a real possibility for women affected by such disease. We are furthermore studying the possibility to collect the fetus' umbilical cord blood, after the delivery, to attempt eterologus transplantation to his mother trying to get a complete marrow reconstitution. PMID:22184526

  18. Ten factors that affect the severity of environmental impacts of visitors in protected areas.

    PubMed

    Pickering, Catherine Marina

    2010-02-01

    Protected areas represent the major method for conserving biodiversity. However, visitor use can threaten their conservation value. Based on a review of recent research, I have categorized factors that affect the severity of environmental impacts of visitor use. These factors need to be considered or evaluated when assessing visitor use of sites in protected areas. They are: (i) the conservation value of the site, (ii) its resistance to use, (iii) its recovery from use, (iv) its susceptibility to erosion, (v) the severity of direct impacts associated with specific activities, (vi) the severity of indirect impacts, (vii) the amount of use, (viii) the social and (ix) ecological dimensions to the timing of use, and (x) the total area affected. Although the factors may not be of equal importance or necessarily assessed on an equal scale, they allow people to make more informed assessments of potential impacts, assist in identifying where monitoring may be required, and indicate where additional site- or activity-specific research may be appropriate.

  19. The facioscapulohumeral muscular dystrophy (FSHD1) gene affects males more severely and more frequently than females.

    PubMed

    Zatz, M; Marie, S K; Cerqueira, A; Vainzof, M; Pavanello, R C; Passos-Bueno, M R

    1998-05-01

    We investigated 52 families of patients with facioscapulohumeral muscular dystrophy (FSHD1), including 172 patients (104 males and 68 females). Among 273 DNA samples which were analyzed with probe p13E-11, 131 (67 males and 64 females) were shown to carry an EcoRI fragment smaller than 35 kb; 114 among them were examined clinically and neurologically. Results of the present investigation showed that: a) there is no molecular evidence for autosomal or X-linked recessive inheritance of FSHD1; b) an excess of affected males, which is explained by a significantly greater proportion of females than males among asymptomatic cases and a significantly greater proportion of affected sons than daughters observed in the offspring of asymptomatic mothers; c) the penetrance of the FSHD1 gene until age 30 was estimated as 83% for both sexes but was significantly greater for males (95%) than for females (69%); d) new mutations occur significantly more frequently in females than males among somatic/germinal mosaic cases; and e) severely affected cases originated more often through new mutations or were transmitted through maternal than through paternal lines including somatic/germinal mothers. These observations have important implications for understanding the molecular mechanisms responsible for FSHD1 and for genetic and prognostic counseling according to the gender of the affected patient.

  20. Saccadic Eye Movement Characteristics in Adult Niemann-Pick Type C Disease: Relationships with Disease Severity and Brain Structural Measures

    PubMed Central

    Abel, Larry A.; Bowman, Elizabeth A.; Velakoulis, Dennis; Fahey, Michael C.; Desmond, Patricia; Macfarlane, Matthew D.; Looi, Jeffrey Chee Leong; Adamson, Christopher L.; Walterfang, Mark

    2012-01-01

    Niemann-Pick Type C disease (NPC) is a rare genetic disorder of lipid metabolism. A parameter related to horizontal saccadic peak velocity was one of the primary outcome measures in the clinical trial assessing miglustat as a treatment for NPC. Neuropathology is widespread in NPC, however, and could be expected to affect other saccadic parameters. We compared horizontal saccadic velocity, latency, gain, antisaccade error percentage and self-paced saccade generation in 9 adult NPC patients to data from 10 age-matched controls. These saccadic measures were correlated with appropriate MRI-derived brain structural measures (e.g., dorsolateral prefrontal cortex, frontal eye fields, supplemental eye fields, parietal eye fields, pons, midbrain and cerebellar vermis) and with measures of disease severity and duration. The best discriminators between groups were reflexive saccade gain and the two volitional saccade measures. Gain was also the strongest correlate with disease severity and duration. Most of the saccadic measures showed strongly significant correlations with neurophysiologically appropriate brain regions. While our patient sample is small, the apparent specificity of these relationships suggests that as new diagnostic methods and treatments become available for NPC, a broader range of saccadic measures may be useful tools for the assessment of disease progression and treatment efficacy. PMID:23226429

  1. Disseminated Bacillus Calmette Guerin Disease in a Twin Infant with Severe Combined Immunodeficiency Disease

    PubMed Central

    Mittal, Hema; Faridi, MMA; Kumar, Pankaj; Aggarwal, Anju

    2014-01-01

    Fatal-disseminated Bacillus Calmette Guerin (BCG) disease is well known in infants with severe combined immunodeficiency after BCG vaccination. We report a 7 month male infant delivered as a product of in vitro fertilization and twin gestation that presented with fever, cough and multiple nodular skin lesions. A biopsy of skin lesions revealed the presence of acid fast bacilli. Mycobacterium bovis infection was confirmed by polymerase chain reaction (PCR) and molecular studies. Immunological profile confirmed the diagnosis of severe combined immunodeficiency. Only few reports of similar case exist in the literature. PMID:25191057

  2. [McArdle disease or glycogen storage disease type v: Should it affect anaesthetic management?].

    PubMed

    Ayerza-Casas, V; Ferreira-Laso, L; Alloza-Fortun, M C; Fraile-Jimenez, A E

    2015-02-01

    McArdle disease is a metabolic myopathy that can may lead to severe perioperative problems. A case is reported of a woman with a history of McArdle disease, who was scheduled for a mastectomy. An understanding of the physiology and pathology, and the application of appropriate preventive measures can avoid complications. A overview of the complications and the management are described.

  3. Lack of Association between Selenium Status and Disease Severity and Activity in Patients with Graves' Ophthalmopathy

    PubMed Central

    Dehina, Nora; Hofmann, Peter Josef; Behrends, Thomas; Eckstein, Anja; Schomburg, Lutz

    2016-01-01

    Background Selenium (Se) is of importance for regular functioning of the immune system and thyroid gland, and may have a health effect in mild Graves' ophthalmopathy (GO). Objective As the Se status declines in inflammation, we analyzed whether GO activity or severity affects the Se status of patients. Methods Serum Se and selenoprotein P (SePP) concentrations were retrospectively determined in 84 consecutive GO patients before treatment and compared to their clinical activity score (CAS) and severity of eye changes (NOSPECS) status, and to the concentrations of autoantibodies targeting the TSH receptor (TRAK) or the IGF1 receptor (IGF1R-aAB). Results Serum Se and SePP were linearly associated, indicating a suboptimal Se status of our patients. In comparison to data from other European cohorts, the majority of GO patients had a relatively poor Se status ([Se] ± SD; 70.0 ± 23.8 µg/l), below the threshold needed for full expression of selenoproteins. TRAK were inversely associated with Se concentrations, while IGF1R-aAB titers were not associated with Se. Neither Se nor SePP concentrations differed between GO patients with severe versus mild or active versus inactive disease, or showed significant associations with the CAS or NOSPECS values. Conclusion GO patients are at risk of a low Se status, yet disease severity or activity does not seem to affect Se or SePP concentrations directly. However, as the retrospective nature of the analysis does not allow conclusions on a potential causative role of Se on Graves' disease or GO risk, these results neither support nor discourage adjuvant Se supplementation attempts. PMID:27099840

  4. Maple Bark Biochar Affects Rhizoctonia solani Metabolism and Increases Damping-Off Severity.

    PubMed

    Copley, Tanya R; Aliferis, Konstantinos A; Jabaji, Suha

    2015-10-01

    Many studies have investigated the effect of biochar on plant yield, nutrient uptake, and soil microbial populations; however, little work has been done on its effect on soilborne plant diseases. To determine the effect of maple bark biochar on Rhizoctonia damping-off, 11 plant species were grown in a soilless potting substrate amended with different concentrations of biochar and inoculated or not with Rhizoctonia solani anastomosis group 4. Additionally, the effect of biochar amendment on R. solani growth and metabolism in vitro was evaluated. Increasing concentrations of maple bark biochar increased Rhizoctonia damping-off of all 11 plant species. Using multivariate analyses, we observed positive correlations between biochar amendments, disease severity and incidence, abundance of culturable bacterial communities, and physicochemical parameters. Additionally, biochar amendment significantly increased R. solani growth and hyphal extension in vitro, and altered its primary metabolism, notably the mannitol and tricarboxylic acid cycles and the glycolysis pathway. One or several organic compounds present in the biochar, as identified by gas chromatography-mass spectrometry analysis, may be metabolized by R. solani. Taken together, these results indicate that future studies on biochar should focus on the effect of its use as an amendment on soilborne plant pathogens before applying it to soils.

  5. [Severe behavioral changes in a patient with Fahr's disease].

    PubMed

    Kümmer, Arthur; de Castro, Maila; Caramelli, Paulo; Cardoso, Francisco; Teixeira, Antônio Lúcio

    2006-09-01

    We report on a case of a 40 year-old man with Fahrs disease, defined by idiopathic bilateral basal ganglia calcification, who developed depressive disorder, motor and phonic tics, stereotyped behaviors such as punding and personality changes with significant social and familiar implications. We discuss about the psychopathology of Fahrs disease and the relevance of the basal ganglia in the determination of humans behavior.

  6. Asymmetric dimethylarginine but not osteoprotegerin correlates with disease severity in patients with moderate-to-severe psoriasis undergoing anti-tumor necrosis factor-α therapy.

    PubMed

    Pina, Trinitario; Genre, Fernanda; Lopez-Mejias, Raquel; Armesto, Susana; Ubilla, Begoña; Mijares, Veronica; Dierssen-Sotos, Trinidad; Corrales, Alfonso; Gonzalez-Lopez, Marcos A; Gonzalez-Vela, Maria C; Blanco, Ricardo; Hernández, Jose L; Llorca, Javier; Gonzalez-Gay, Miguel A

    2016-04-01

    Patients with psoriasis, in particular those with severe disease, have an increased risk of cardiovascular (CV) events compared with the general population. The aim of the present study is to determine whether correlation between asymmetric dimethylarginine (ADMA) and osteoprotegerin (OPG), two biomarkers associated with CV disease, and disease severity may exist in patients with moderate-to-severe psoriasis. We also aimed to establish if baseline serum levels of these two biomarkers could correlate with the degree of change in the clinical parameters of disease severity following the use of anti-tumor necrosis factor (TNF)-α therapy in these patients. This was a prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α-adalimumab. Patients with kidney disease, hypertension or body mass index of 35 kg/m(2) or more were excluded. Metabolic and clinical evaluation was performed immediately prior to the onset of treatment and at month 6. Twenty-nine patients were assessed. Unlike OPG, a significant positive correlation between ADMA and resistin serum levels was found at the onset of adalimumab and also after 6 months of biologic therapy. We also observed a positive correlation between the percent of body surface area affected (BSA) and ADMA levels obtained before the onset of adalimumab and a negative correlation between baseline ADMA levels and a 6-month BSA change compared with baseline results. In patients with moderate-to-severe psoriasis, ADMA levels correlate with clinical markers of disease severity.

  7. A Weighty Matter: Heaviness Influences the Evaluation of Disease Severity, Drug Effectiveness, and Side Effects

    PubMed Central

    Kaspar, Kai

    2013-01-01

    Peoples' perception of diseases and pharmaceutical drugs is a critical issue in health research. Beliefs about disease severity influence the compliance with recommendations for convalescence and the motivation to perform proper health-behavior. The estimated effectiveness of drugs and severity of side effects influence medication adherence and contribute to placebo effects. The present paper closes the gap between these effects and the concept of embodied cognition from a metaphor-enriched perspective. In five studies, we demonstrate that the bodily sensation of weight influences our evaluations of diseases and drugs. The experience of heaviness enhanced the estimated seriousness of diseases and the estimated effectiveness of drugs. The perceived seriousness of drug side effects was also affected by weight but only when drug effectiveness was not attended to. Moreover, the incidental sensation of weight shows a novel effect when evaluating weight-related drugs. The results are in line with the idea of embodied metaphors and reveal important boundary conditions which contribute to a better understanding of the underlying mechanisms. PMID:24244302

  8. Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis.

    PubMed

    Monin, Leticia; Griffiths, Kristin L; Lam, Wing Y; Gopal, Radha; Kang, Dongwan D; Ahmed, Mushtaq; Rajamanickam, Anuradha; Cruz-Lagunas, Alfredo; Zúñiga, Joaquín; Babu, Subash; Kolls, Jay K; Mitreva, Makedonka; Rosa, Bruce A; Ramos-Payan, Rosalio; Morrison, Thomas E; Murray, Peter J; Rangel-Moreno, Javier; Pearce, Edward J; Khader, Shabaana A

    2015-12-01

    Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1-expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1-expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB.

  9. Short-term efficacy of topical capsaicin therapy in severely affected fibromyalgia patients.

    PubMed

    Casanueva, Benigno; Rodero, Baltasar; Quintial, Covadonga; Llorca, Javier; González-Gay, Miguel A

    2013-10-01

    The purpose of this study was to evaluate the short-term efficacy of topical capsaicin treatment in patients severely affected by fibromyalgia. One hundred and thirty fibromyalgia patients were randomly divided into two groups. The control group, 56 women and 4 men who continued their medical treatment, and the capsaicin group, 70 women who apart from continuing their medical treatment, also underwent topical capsaicin 0.075 % 3 times daily for 6 weeks. At the beginning of the program, there were no significant differences between the two groups in any of the analyzed parameters. At the end of the treatment, there were significant improvements in the capsaicin group in the myalgic score (5.21 vs 3.8, p = 0.02) and global subjective improvement (22.8 vs 5 %, p = 0.001). Six weeks after the end of the treatment, the experimental group showed significant differences in Visual Analogue Scale of depression (5.63 vs 7.35, p = 0.02), Fibromyalgia Impact Questionnaire (67.89 vs 77.7, p = 0.02), role limitations due to emotional problems (36.17 vs 17.2, p = 0.05), Fatigue Severity Scale (6.2 vs 6.6, p = 0.04), myalgic score (3.94 vs 2.66, p = 0.02) and pressure pain threshold (79.25 vs 56.71, p = 0.004). In conclusion, patients severely affected by fibromyalgia can obtain short-term improvements following topical capsaicin 0.075 % treatment three times daily for 6 weeks.

  10. How Do Severe Constraints Affect the Search Ability of Multiobjective Evolutionary Algorithms in Water Resources?

    NASA Astrophysics Data System (ADS)

    Clarkin, T. J.; Kasprzyk, J. R.; Raseman, W. J.; Herman, J. D.

    2015-12-01

    This study contributes a diagnostic assessment of multiobjective evolutionary algorithm (MOEA) search on a set of water resources problem formulations with different configurations of constraints. Unlike constraints in classical optimization modeling, constraints within MOEA simulation-optimization represent limits on acceptable performance that delineate whether solutions within the search problem are feasible. Constraints are relevant because of the emergent pressures on water resources systems: increasing public awareness of their sustainability, coupled with regulatory pressures on water management agencies. In this study, we test several state-of-the-art MOEAs that utilize restricted tournament selection for constraint handling on varying configurations of water resources planning problems. For example, a problem that has no constraints on performance levels will be compared with a problem with several severe constraints, and a problem with constraints that have less severe values on the constraint thresholds. One such problem, Lower Rio Grande Valley (LRGV) portfolio planning, has been solved with a suite of constraints that ensure high reliability, low cost variability, and acceptable performance in a single year severe drought. But to date, it is unclear whether or not the constraints are negatively affecting MOEAs' ability to solve the problem effectively. Two categories of results are explored. The first category uses control maps of algorithm performance to determine if the algorithm's performance is sensitive to user-defined parameters. The second category uses run-time performance metrics to determine the time required for the algorithm to reach sufficient levels of convergence and diversity on the solution sets. Our work exploring the effect of constraints will better enable practitioners to define MOEA problem formulations for real-world systems, especially when stakeholders are concerned with achieving fixed levels of performance according to one or

  11. Unpicking the Semantic Impairment in Alzheimer’s Disease: Qualitative Changes with Disease Severity

    PubMed Central

    Corbett, Faye; Jefferies, Elizabeth; Burns, Alistair; Ralph, Matthew A. Lambon

    2012-01-01

    Despite a vast literature examining semantic impairment in Alzheimer's disease (AD), consensus regarding the nature of the deficit remains elusive. We re-considered this issue in the context of a framework that assumes semantic cognition can break down in two ways: (1) core semantic representations can degrade or (2) cognitive control mechanisms can become impaired [1]. We hypothesised and confirmed that the nature of semantic impairment in AD changes with disease severity. Patients at mild or severe stages of the disorder exhibited impairment across various semantic tasks but the nature of those deficits differed qualitatively for the two groups. Commensurate with early dysfunction of the cognitive control, temporoparietal-frontal-cingulate network, characteristics of deregulated semantic cognition were exhibited by the mild AD cases. In contrast, the severe AD group reproduced features of additional degradation of core semantic representations. These results suggest that spread of pathology into lateral anterior temporal lobes in later stage AD produces degradation of semantic representations, exacerbating the already deregulated system. Moreover, the dual nature of severe patients’ impairment was highlighted by disproportionately poor performance on tasks placing high demand on both conceptual knowledge and control processes–e.g., category fluency. PMID:22207420

  12. Unpicking the semantic impairment in Alzheimer's disease: qualitative changes with disease severity.

    PubMed

    Corbett, Faye; Jefferies, Elizabeth; Burns, Alistair; Ralph, Matthew A Lambon

    2012-01-01

    Despite a vast literature examining semantic impairment in Alzheimer's disease (AD), consensus regarding the nature of the deficit remains elusive. We re-considered this issue in the context of a framework that assumes semantic cognition can break down in two ways: (1) core semantic representations can degrade or (2) cognitive control mechanisms can become impaired. We hypothesised and confirmed that the nature of semantic impairment in AD changes with disease severity. Patients at mild or severe stages of the disorder exhibited impairment across various semantic tasks but the nature of those deficits differed qualitatively for the two groups. Commensurate with early dysfunction of the cognitive control, temporoparietal-frontal-cingulate network, characteristics of deregulated semantic cognition were exhibited by the mild AD cases. In contrast, the severe AD group reproduced features of additional degradation of core semantic representations. These results suggest that spread of pathology into lateral anterior temporal lobes in later stage AD produces degradation of semantic representations, exacerbating the already deregulated system. Moreover, the dual nature of severe patients' impairment was highlighted by disproportionately poor performance on tasks placing high demand on both conceptual knowledge and control processes--e.g., category fluency.

  13. Oral necrotizing microvasculitis in a patient affected by Kawasaki disease.

    PubMed

    Scardina, Giuseppe Alessandro; Fucà, Gerlandina; Carini, Francesco; Valenza, Vincenzo; Spicola, Michele; Procaccianti, Paolo; Messina, Pietro; Maresi, Emiliano

    2007-12-01

    Kawasaki disease (KD) was first described in 1967 by Kawasaki, who defined it as "mucocutaneous lymph node syndrome". KD is an acute systemic vasculitis, which mainly involves medium calibre arteries; its origin is unknown, and it is observed in children under the age of 5, especially in their third year. The principal presentations of KD include fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Within KD, oral mucositis - represented by diffuse mucous membrane erythema, lip and tongue reddening and lingual papillae hypertrophy with subsequent development of strawberry tongue - can occur both in the acute stage of the disease (0-9 days), and in the convalescence stage (>25 days) as a consequence of the pharmacological treatment. KD vascular lesions are defined as systemic vasculitis instead of systemic arteritis. This study analyzed the anatomical-pathological substrata of oral mucositis in a baby affected by Kawasaki disease and suddenly deceased for cardiac tamponade caused by coronary aneurysm rupture (sudden cardiac death of a mechanical type).

  14. Identification of Patients Affected by Mitral Valve Prolapse with Severe Regurgitation: A Multivariable Regression Model

    PubMed Central

    Songia, Paola; Chiesa, Mattia; Alamanni, Francesco; Tremoli, Elena

    2017-01-01

    Background. Mitral valve prolapse (MVP) is the most common cause of severe mitral regurgitation. Besides echocardiography, up to now there are no reliable biomarkers available for the identification of this pathology. We aim to generate a predictive model, based on circulating biomarkers, able to identify MVP patients with the highest accuracy. Methods. We analysed 43 patients who underwent mitral valve repair due to MVP and compared to 29 matched controls. We assessed the oxidative stress status measuring the oxidized and the reduced form of glutathione by liquid chromatography-tandem mass spectrometry method. Osteoprotegerin (OPG) plasma levels were measured by an enzyme-linked immunosorbent assay. The combination of these biochemical variables was used to implement several logistic regression models. Results. Oxidative stress levels and OPG concentrations were significantly higher in patients compared to control subjects (0.116 ± 0.007 versus 0.053 ± 0.013 and 1748 ± 100.2 versus 1109 ± 45.3 pg/mL, respectively; p < 0.0001). The best regression model was able to correctly classify 62 samples out of 72 with accuracy in terms of area under the curve of 0.92. Conclusions. To the best of our knowledge, this is the first study to show a strong association between OPG and oxidative stress status in patients affected by MVP with severe regurgitation. PMID:28261377

  15. Effect of severity disease on the pharmacokinetics of cefuroxime in children with multiple organ system failure.

    PubMed

    Olguín, Hugo Juárez; Asseff, Ismael Lares; Vieyra, Angélica Camacho; Pérez, Adrián Guillé; Saldaña, Napoleón González; Quesada, Argelia Camarillo; Guillé, Gabriela Pérez

    2008-02-01

    The aim of the present study was to investigate if the severity of illness affected the pharmacokinetics of cefuroxime in 11 children diagnosed with multiple organ system failure. The patients were assigned to a severely ill group (group 1), a very severely ill group (group 2), or a control group (group 0). Blood samples were taken and cefuroxime concentrations were measured in plasma by HPLC after the first intravenous infusion of 100 mg of cefuroxime per kg of body weight. The pharmacokinetic profile of cefuroxime exhibited both one and two compartmental distribution. Statistically significant differences between the pharmacokinetic parameters of the severe (group 1) and the very severe patients (group 2) were found, and significant differences (p<0.05) in the pharmacokinetic parameters between groups 1 and 2 vs. the control group were observed for most of the parameters analyzed. However, there was no statistical difference in clearance between group 1 and the control group. The data indicate that the pharmacokinetic differences determined by severity of disease are useful for establishing an individualized regimen dosage in children with multiple organ system failure.

  16. Severe sickle cell disease--pathophysiology and therapy.

    PubMed

    Buchanan, George; Vichinsky, Elliott; Krishnamurti, Lakshmanan; Shenoy, Shalini

    2010-01-01

    Over 70,000 people live with sickle cell disease (SCD) in the United States and multitudes worldwide. About 2000 afflicted babies are born in this country each year. In African countries such as Nigeria, over 100,000 babies are born with the disease each year. Great strides have been made in the conservative management of SCD. However, the medical and psychosocial cost of supporting patients with this chronic illness is enormous and spans a lifetime. Hematopoietic stem cell transplantation (HSCT) can abrogate SCD manifestations, and is the best option for cure today. Yet, this treatment modality is underutilized as less than 500 transplants are reported in the Center for International Blood and Marrow Transplant Research (CIBMTR) database because of its significant risk of morbidity and mortality. There is growing understanding of the pathophysiology of the disease, and this, coupled with advances in transplantation and new approaches to therapy, continue to improve care of patients with SCD both in children and during adulthood. Continuing investigation seeks to predict the course of the disease and to determine timing and modality of therapy in order to optimize outcomes.

  17. Severe dry winter affects plant phenology and carbon balance of a cork oak woodland understorey

    NASA Astrophysics Data System (ADS)

    Correia, A. C.; Costa-e-Silva, F.; Dubbert, M.; Piayda, A.; Pereira, J. S.

    2016-10-01

    Mediterranean climates are prone to a great variation in yearly precipitation. The effects on ecosystem will depend on the severity and timing of droughts. In this study we questioned how an extreme dry winter affects the carbon flux in the understorey of a cork oak woodland? What is the seasonal contribution of understorey vegetation to ecosystem productivity? We used closed-system portable chambers to measure CO2 exchange of the dominant shrub species (Cistus salviifolius, Cistus crispus and Ulex airensis), of the herbaceous layer and on bare soil in a cork oak woodland in central Portugal during the dry winter year of 2012. Shoot growth, leaf shedding, flower and fruit setting, above and belowground plant biomass were measured as well as seasonal leaf water potential. Eddy-covariance and micrometeorological data together with CO2 exchange measurements were used to access the understorey species contribution to ecosystem gross primary productivity (GPP). The herbaceous layer productivity was severely affected by the dry winter, with half of the yearly maximum aboveground biomass in comparison with the 6 years site average. The semi-deciduous and evergreen shrubs showed desynchronized phenophases and lagged carbon uptake maxima. Whereas shallow-root shrubs exhibited opportunistic characteristics in exploiting the understorey light and water resources, deep rooted shrubs showed better water status but considerably lower assimilation rates. The contribution of understorey vegetation to ecosystem GPP was lower during summer with 14% and maximum during late spring, concomitantly with the lowest tree productivity due to tree canopy renewal. The herbaceous vegetation contribution to ecosystem GPP never exceeded 6% during this dry year stressing its sensitivity to winter and spring precipitation. Although shrubs are more resilient to precipitation variability when compared with the herbaceous vegetation, the contribution of the understorey vegetation to ecosystem GPP can

  18. Total colonic aganglionosis and imperforate anus in a severely affected infant with Pallister-Hall syndrome.

    PubMed

    Li, Mindy H; Eberhard, Moriah; Mudd, Pamela; Javia, Luv; Zimmerman, Robert; Khalek, Nahla; Zackai, Elaine H

    2015-03-01

    Pallister-Hall syndrome is a complex malformation syndrome characterized by a wide range of anomalies including hypothalamic hamartoma, polydactyly, bifid epiglottis, and genitourinary abnormalities. It is usually caused by truncating frameshift/nonsense and splicing mutations in the middle third of GLI3. The clinical course ranges from mild to lethal in the neonatal period. We present the first patient with Pallister-Hall syndrome reported with total colonic aganglionosis, a rare form of Hirschsprung disease with poor long-term outcome. The patient also had an imperforate anus, which is the third individual with Pallister-Hall syndrome reported with both Hirschsprung disease and an imperforate anus. Molecular testing via amniocentesis showed an apparently de novo novel nonsense mutation c.2641 C>T (p.Gln881*). His overall medical course was difficult and was complicated by respiratory failure and pan-hypopituitarism. Invasive care was ultimately withdrawn, and the patient expired at three months of age. This patient's phenotype was complex with unusual gastrointestinal features ultimately leading to a unfavorable prognosis and outcome, highlighting the range of clinical severity in patients with Pallister-Hall syndrome.

  19. [The White man's burden - a case study caught between bipolar affective disorder and Huntington's disease].

    PubMed

    Nowidi, K; Kunisch, R; Bouna-Pyrrou, P; Meißner, D; Hennig-Fast, K; Weindl, A; Förster, S; Neuhann, T M; Falkai, P; Berger, M; Musil, R

    2013-06-01

    We report upon a case of a 55 year old patient with a bipolar affective disorder, presenting herself with a depressive symptomatology in addition to a severe motor perturbation. The main emphasis upon admittance was perfecting and improving her latest medication. Four weeks prior to her stay at our clinic a thorough neurological examination had taken place in terms of an invalidity pension trial which did not result in any diagnostic findings. Therefore a neurological disease seemed at first highly unlikely. Even though the prior testing was negative, the ensuing neurological examination at our clinic resulted in movement disorders very much indicative of Huntington's Disease. A detailed investigation in regards to the particular family history of the patient was positive for Huntington's Disease. However, whether the patient's mother had also been a genetic carrier of Huntington's Disease was still unknown at the time the patient was admitted to our clinic. It was nevertheless discovered that her mother had also suffered from a bipolar affective disorder. A genetic testing that followed the neurological examination of the patient proved positive for Huntington's Disease. Neuro-imaging resulted in a bicaudate-index of 2.4 (the critical value is 1.8). In a clinical psychological test battery the ensuing results were highly uncommon for patients with solely a bipolar affective disorder people. Under the medical regimen of Quetiapine, Citalopram and Tiaprid the patient's mood could be stabilized and there was some improvement of her motor pertubation.

  20. Obesity as a Risk and Severity Factor in Rheumatic Diseases (Autoimmune Chronic Inflammatory Diseases)

    PubMed Central

    Gremese, Elisa; Tolusso, Barbara; Gigante, Maria Rita; Ferraccioli, Gianfranco

    2014-01-01

    The growing body of evidence recognizing the adipose tissue (AT) as an active endocrine organ secreting bioactive mediators involved in metabolic and inflammatory disorders, together with the global epidemic of overweight and obesity, rise obesity as a hot topic of current research. The chronic state of low-grade inflammation present in the obese condition and the multiple pleiotropic effects of adipokines on the immune system has been implicated in the pathogenesis of several inflammatory conditions including rheumatic autoimmune and inflammatory diseases. We will discuss the main relevant evidences on the role of the AT on immune and inflammatory networks and the more recent evidences regarding the effects of obesity on the incidence and outcomes of the major autoimmune chronic inflammatory diseases. PMID:25426122

  1. The Surgical Treatment of Severe Endometriosis Positively Affects the Chance of Natural or Assisted Pregnancy Postoperatively

    PubMed Central

    Nesbitt-Hawes, Erin M.; Campbell, Neil; Maley, Peta E.; Won, Haryun; Hooshmand, Dona; Henry, Amanda; Ledger, William; Abbott, Jason A.

    2015-01-01

    Objective. To report reproductive outcomes following laparoscopic surgical excision of histologically confirmed r-ASRM stage III-IV endometriosis. Study Design. A retrospective cohort study was performed at the Royal Hospital for Women, a university teaching hospital, Sydney, Australia. Women who had fertility-preserving laparoscopic excision of stage III-IV endometriosis from 1997 to 2009 were contacted regarding reproductive outcomes. Results. In the study period, 355 women underwent surgery for stage III-IV endometriosis. Follow-up data are available for 253/355 (71%) women. Postoperatively, 142/253 (56%) women attempted to conceive with a conception rate of 104/142 (73%). Confidence intervals for pregnancy for women who were attempting conception (including the nonresponders) range from 104/262 (40%) to 224/262 (85%). Median time to conception was 12 months. No positive prognostic factors for pregnancy were identified on regression analyses. Conclusions. These data provide information to women with suspected severe disease preoperatively concerning their likely postoperative fertility outcomes. Ours is a population with severe endometriosis, rather than an infertile population with endometriosis, so caution needs to be applied when applying these data to women with fertility issues alone. PMID:26247022

  2. The ABC’s of Trait Anger, Psychological Distress, and Disease Severity in HIV

    PubMed Central

    McIntosh, Roger C.; Hurwitz, Barry E.; Antoni, Michael; Gonzalez, Alex; Seay, Julia; Schneiderman, Neil

    2015-01-01

    Background Trait anger consists of affective, behavioral, and cognitive (ABC) dimensions and may increase vulnerability for interpersonal conflict, diminished social support, and greater psychological distress. The concurrent influence anger and psychosocial dysfunction on HIV disease severity is unknown. Purpose Examine plausible psychosocial avenues (e.g. coping, social support, psychological distress) whereby trait anger may indirectly influence HIV disease status. Methods 377 HIV seropositive adults, aged 18–55 years (58% AIDS-defined) completed a battery of psychosocial surveys and provided a fasting blood sample for HIV-1 viral load and T-lymphocyte count assay. Results A second-order factor model confirmed higher levels of the multidimensional anger trait was directly associated with elevated psychological distress and avoidant coping (p<.001) and indirectly associated with greater HIV disease severity (p<.01) (CFI=.90, RMSEA=.06, SRMR=.06). Conclusion The model supports ABC components of anger may negatively influence immune function through various psychosocial mechanisms; however longitudinal study is needed to elucidate these effects. PMID:25385204

  3. Range and severity of a plant disease increased by global warming.

    PubMed

    Evans, Neal; Baierl, Andreas; Semenov, Mikhail A; Gladders, Peter; Fitt, Bruce D L

    2008-05-06

    Climate change affects plants in natural and agricultural ecosystems throughout the world but little work has been done on the effects of climate change on plant disease epidemics. To illustrate such effects, a weather-based disease forecasting model was combined with a climate change model predicting UK temperature and rainfall under high- and low-carbon emissions for the 2020s and 2050s. Multi-site data collected over a 15-year period were used to develop and validate a weather-based model forecasting severity of phoma stem canker epidemics on oilseed rape across the UK. This was combined with climate change scenarios to predict that epidemics will not only increase in severity but also spread northwards by the 2020s. These results provide a stimulus to develop models to predict the effects of climate change on other plant diseases, especially in delicately balanced agricultural or natural ecosystems. Such predictions can be used to guide policy and practice in adapting to effects of climate change on food security and wildlife.

  4. Correlation between BMI and PASI in patients affected by moderate to severe psoriasis undergoing biological therapy.

    PubMed

    Bardazzi, F; Balestri, R; Baldi, E; Antonucci, A; De Tommaso, S; Patrizi, A

    2010-01-01

    Obesity is common in psoriatic patients, and it has been shown to be important for many aspects of the condition. In particular, low-calorie diets can improve the symptoms and response to treatment in pustular psoriasis. The present study investigates the influence of body-weight alteration on the disease's clinical manifestations in moderate to severe psoriasis patients treated with biological drugs. Finally, the influence of a caloric restriction was assessed. This observational transversal study enrolled 33 patients attending our Severe Psoriasis Outpatient Clinic, who were treated with biological drugs. Body Mass Index (BMI) was used as a diagnostic indicator of being overweight and of obesity. Waist circumference was also measured. Body weight and Psoriasis Area Severity Index (PASI) index were measured at follow-up visits at 4 and 8 months. Nonparametric test of Mann-Whitney was used to detect the differences between patient groups. Fisher's exact test was performed to evaluate the different results depending on the therapeutic changes of BMI. There was a strong prevalence of overweight-obese individuals in the group with a mean BMI of 30.59 +/- 6.94. Waist circumference was also above normal in the majority of the patients. Obese patients had a PASI index higher than the average of the whole group (25.03 +/- 12.43), with grade III obese patients having an average PASI of 44 +/- 3.37. At the first and second follow-ups, patients who put on weight did not achieve PASI 50; patients who had a stable weight presented variable response to treatment, while patients who decreased their weight achieved PASI 90 or PASI 75 even when not responding at the first. Further studies are needed to understand if the poor response observed in heavier patients is due to biological drugs pharmacokinetics or because therapy should be BMI based rather than administered in fixed doses, posing then an ethical consideration.

  5. Misfolding of vWF to Pathologically Disordered Conformations Impacts the Severity of von Willebrand Disease

    PubMed Central

    Tischer, Alexander; Madde, Pranathi; Moon-Tasson, Laurie; Auton, Matthew

    2014-01-01

    The primary hemostatic von Willebrand factor (vWF) functions to sequester platelets from rheological blood flow and mediates their adhesion to damaged subendothelium at sites of vascular injury. We have surveyed the effect of 16 disease-causing mutations identified in patients diagnosed with the bleeding diathesis disorder, von Willebrand disease (vWD), on the structure and rheology of vWF A1 domain adhesiveness to the platelet GPIbα receptor. These mutations have a dynamic phenotypical range of bleeding from lack of platelet adhesion to severe thrombocytopenia. Using new rheological tools in combination with classical thermodynamic, biophysical, and spectroscopic metrics, we establish a high propensity of the A1 domain to misfold to pathological molten globule conformations that differentially alter the strength of platelet adhesion under shear flow. Rheodynamic analysis establishes a quantitative rank order between shear-rate-dependent platelet-translocation pause times that linearly correlate with clinically reported measures of patient platelet counts and the severity of thrombocytopenia. These results suggest that specific secondary structure elements remaining in these pathological conformations of the A1 domain regulate GPIbα binding and the strength of vWF-platelet interactions, which affects the vWD functional phenotype and the severity of thrombocytopenia. PMID:25185554

  6. Mapping burn severity in a disease-impacted forest landscape using Landsat and MASTER imagery

    NASA Astrophysics Data System (ADS)

    Chen, Gang; Metz, Margaret R.; Rizzo, David M.; Meentemeyer, Ross K.

    2015-08-01

    Global environmental change has increased forest vulnerability to the occurrence of interacting disturbances, including wildfires and invasive diseases. Mapping post-fire burn severity in a disease-affected forest often faces challenges because burned and infested trees may exhibit a high similarity in spectral reflectance. In this study, we combined (pre- and post-fire) Landsat imagery and (post-fire) high-spectral resolution airborne MASTER data [MODIS (moderate resolution imaging spectroradiometer)/ASTER (advanced spaceborne thermal emission and reflection radiometer)] to map burn severity in a California coastal forest environment, where a non-native forest disease sudden oak death (SOD) was causing substantial tree mortality. Results showed that the use of Landsat plus MASTER bundle performed better than using the individual sensors in most of the evaluated forest strata from ground to canopy layers (i.e., substrate, shrubs, intermediate-sized trees, dominant trees and average), with the best model performance achieved at the dominant tree layer. The mid to thermal infrared spectral bands (3.0-12.5 μm) from MASTER were found to augment Landsat's visible to shortwave infrared bands in burn severity assessment. We also found that infested and uninfested forests similarly experienced moderate to high degrees of burns where CBI (composite burn index) values were higher than 1. However, differences occurred in the regions with low burn severity (CBI values lower than 1), where uninfested stands revealed a much lower burn effect than that in infested stands, possibly due to their higher resilience to small fire disturbances as a result of higher leaf water content.

  7. Detection of enteric pathogens in Turkey flocks affected with severe enteritis, in Brazil.

    PubMed

    Moura-Alvarez, Joelma; Nuñez, Luis F N; Astolfi-Ferreira, Claudete S; Knöbl, Terezinha; Chacón, Jorge L; Moreno, Andrea M; Jones, Richard C; Ferreira, Antonio J Piantino

    2014-08-01

    Twenty-two flocks of turkeys affected by enteric problems, with ages between 10 and 104 days and located in the Southern region of Brazil, were surveyed for turkey by PCR for turkey astrovirus type 2 (TAstV-2), turkey coronavirus (TCoV), hemorrhagic enteritis virus (HEV), rotavirus, reovirus, Salmonella spp., and Lawsonia intracellularis (Li) infections. Eleven profiles of pathogen combination were observed. The most frequently encountered pathogen combinations were TCoV-Li, followed by TCoV-TAstV-2-Li, TCoV-TastV-2. Only TCoV was detected as the sole pathogen in three flocks. Eight and 19 flocks of the 22 were positive for TAstV-2 and TCoV, respectively. Six were positive for Salmonella spp. and L. intracellularis was detected in 12 turkey flocks. Reovirus and HEV were not detected in this survey. These results throw new light on the multiple etiology of enteritis in turkeys. The implications of these findings and their correlation with the clinical signs are comprehensively discussed, illustrating the complexity of the enteric diseases.

  8. Comparison of disease-severity measures within severe and very severe COPD patients: results from a nationally representative chart review and patient survey

    PubMed Central

    Solem, Caitlyn T; Sun, Shawn X; Liu, Sizhu; Macahilig, Cynthia; Katyal, Monica; Gao, Xin; Shorr, Andrew F

    2014-01-01

    Objective This study aimed to compare spirometry- and risk + symptom-based classification systems to physician-based severity assessment and find which system is most predictive of patient-reported health status, as measured by the St George’s Respiratory Questionnaire for COPD (chronic obstructive pulmonary disease; SGRQ-C). Materials and methods In this chart review/patient survey, 99 physicians recruited patients with physician-assessed severe or very severe COPD who had recently experienced a moderate or severe exacerbation. A cross-tabulation was undertaken comparing physician report, spirometry (mild/moderate, forced expiratory volume in 1 second [FEV1] ≥50%; severe, 30% ≤ FEV1 <50%; very severe, FEV1 <30% predicted), and risk + symptom-based (A, low risk/fewer symptoms; B, low risk/more symptoms; C, high risk/fewer symptoms; D, high risk/more symptoms) severity systems. Analysis of covariance models were run for SGRQ-C, varying COPD-severity systems. Results Of 244 patients, 58.6% were severe and 34.8% very severe by physician report, 70% had FEV1 ≤50% at their most recent visit, and 86% fell into quadrant D. Spirometry and physician report had 57.4% agreement, with physicians often indicating higher severity. Physician report and risk + symptom agreement was high (81.2% severe/very severe and D). Physician-reported severity, risk + symptoms, exacerbations in the previous year, and symptoms were significant SGRQ-C predictors, while spirometry was not. Conclusion For recently exacerbating severe or very severe COPD patients, risk + symptoms more closely aligned with physician-reported severity and SGRQ-C versus spirometry. PMID:25284999

  9. Factors that affect substance users’ suicidal behavior: a view from the Addiction Severity Index in Korea

    PubMed Central

    2013-01-01

    Background In South Korea, it has not been easy to negotiate studies that target drug users who are being punished by law, and accordingly, no study on suicidal ideation among substance users has been accomplished yet. In this study, the factors that affect substance users’ suicidal ideation were confirmed. Methods It was based on the data collected from 'The 2009 Study on Substance-Dependent Individuals in Korea’ , which was conducted by The Catholic University of Korea in 2010 as a project sponsored by the Ministry of Health and Welfare of Korea. This study targeted 523 former hospital inpatients, prison inmates, and persons under protective supervision who had used substances such as psychotropic drugs, marijuana, and narcotic agents, and were in the recovery stage at various treatment/rehabilitation centers. Student’s t and chi-square tests were used, and multivariate analysis was performed to examine the strength of the relationships between suicide ideation and various factors. Results According to this study, 41% of these substance users planned suicide with suicidal ideation. Suicidal ideation was confirmed as associated with an unsatisfactory domestic environment, insufficient and unsatisfactory spare time experiences with others, emotional abuse, severe depression, and trouble with controlling violent behavior. Of the substance users who had planned to commit suicide, 56% attempted suicide. Their suicide attempts were shown to have been associated with insufficient protective supervision and the experiences of physical abuse, trouble with controlling violent behavior, and doctors’ prescriptions due to psychological or emotional problems. Conclusion Based on this analysis of the factors that affect suicidal behavior, preventive measures and strategies for substance user were suggested in this study. PMID:24220264

  10. Sediment size distribution and composition in a reservoir affected by severe water level fluctuations.

    PubMed

    López, Pilar; López-Tarazón, José A; Casas-Ruiz, Joan P; Pompeo, Marcelo; Ordoñez, Jaime; Muñoz, Isabel

    2016-01-01

    The reservoir sediments are important sinks for organic carbon (OC), the OC burial being dependent on two opposite processes, deposition and mineralization. Hence factors such as severe water level fluctuations are expected to influence the rate of OC accumulation as they may affect both deposition and mineralization. The Barasona Reservoir has been historically threatened by siltation, whilst the use of water for irrigation involves a drastic decrease of the water level. In this context, we have studied the physical and chemical characteristics (grain size, major and minor elemental compositions, organic and inorganic carbon, and nitrogen) of the recent sediments of the Barasona Reservoir and the relationships among them in order to: a) elucidate the main processes governing OC accumulation, b) evaluate the rate of OC mineralization and c) approach the effect of drought on the sediment characteristics in this system. Our results indicated that Barasona sediments were dominated by fine silts (>60%) and clays (>20%), the mean particle size decreasing from tail to dam. Desiccation increased particle sorting and size distribution became bimodal, but no effect on average size was observed. Attending to the composition, Barasona sediments were very homogeneous with low concentrations of nitrogen (TN) and phosphorus (<1.2 g kg(-1) dw and <0.6 g kg(-1) dw, respectively) and high concentration of OC (≈36 g kg(-1) dw). TN was negatively related to dry weight. Sediment mixing due to drastic changes in water level may have favoured the observed homogeneity of Barasona sediments affecting carbon, major ions and grain size. The high amount of OC deposited in Barasona sediment suggested that the adsorption of OC onto fine particles was more important than in boreal lakes. The rate of oxygen consumption by wet sediment ranged from 2.26 to 3.15 mg O2 m(-2) day(-1), values close to those compiled for Mediterranean running waters.

  11. Dependence as a unifying construct in defining Alzheimer's disease severity.

    PubMed

    McLaughlin, Trent; Feldman, Howard; Fillit, Howard; Sano, Mary; Schmitt, Frederick; Aisen, Paul; Leibman, Christopher; Mucha, Lisa; Ryan, J Michael; Sullivan, Sean D; Spackman, D Eldon; Neumann, Peter J; Cohen, Joshua; Stern, Yaakov

    2010-11-01

    This article reviews measures of Alzheimer's disease (AD) progression in relation to patient dependence and offers a unifying conceptual framework for dependence in AD. Clinicians typically characterize AD by symptomatic impairments in three domains: cognition, function, and behavior. From a patient's perspective, changes in these domains, individually and in concert, ultimately lead to increased dependence and loss of autonomy. Examples of dependence in AD range from a need for reminders (early AD) to requiring safety supervision and assistance with basic functions (late AD). Published literature has focused on the clinical domains as somewhat separate constructs and has given limited attention to the concept of patient dependence as a descriptor of AD progression. This article presents the concept of dependence on others for care needs as a potential method for translating the effect of changes in cognition, function, and behavior into a more holistic, transparent description of AD progression.

  12. [Antidepressive pharmacotherapy. In slight and severe disease, young and old].

    PubMed

    Baghai, T C; Volz, H P; Möller, H J

    2009-02-01

    During the past decade a variety of promising new compounds launched onto the market not only enhancing serotonergic and noradrenergic neurotransmission, but also influencing the dopamine and the melatonergic receptor system. In spite of misleading discussions both in the specialized and in the lay press the clinical effectiveness of antidepressants still is indisputable. The main advantages of the newer drugs are the broadening of the spectrum treatments and a far better tolerability profile in comparison to older compounds. Predominantly depression of medium to high severity should be treated pharmacologically. Especially severe depression seems to respond better to dually acting antidepressants. In children effectiveness of Omega3-fatty acids has been shown, in adolescents SSRI treatment was efficacious. Older patients respond to all antidepressant mechanisms, but more selective substances should be preferred due to a better tolerability. The study of new treatment options is of major importance to provide better strategies for the clinical management of depression in the future, and is thus also of great socio-economic importance.

  13. Rotational stiffness of American football shoes affects ankle biomechanics and injury severity.

    PubMed

    Button, Keith D; Braman, Jerrod E; Davison, Mark A; Wei, Feng; Schaeffer, Maureen C; Haut, Roger C

    2015-06-01

    While previous studies have investigated the effect of shoe-surface interaction on injury risk, few studies have examined the effect of rotational stiffness of the shoe. The hypothesis of the current study was that ankles externally rotated to failure in shoes with low rotational stiffness would allow more talus eversion than those in shoes with a higher rotational stiffness, resulting in less severe injury. Twelve (six pairs) cadaver lower extremities were externally rotated to gross failure while positioned in 20 deg of pre-eversion and 20 deg of predorsiflexion by fixing the distal end of the foot, axially loading the proximal tibia, and internally rotating the tibia. One ankle in each pair was constrained by an American football shoe with a stiff upper, while the other was constrained by an American football shoe with a flexible upper. Experimental bone motions were input into specimen-specific computational models to examine levels of ligament elongation to help understand mechanisms of ankle joint failure. Ankles in flexible shoes allowed 6.7±2.4 deg of talus eversion during rotation, significantly greater than the 1.7±1.0 deg for ankles in stiff shoes (p = 0.01). The significantly greater eversion in flexible shoes was potentially due to a more natural response of the ankle during rotation, possibly affecting the injuries that were produced. All ankles failed by either medial ankle injury or syndesmotic injury, or a combination of both. Complex (more than one ligament or bone) injuries were noted in 4 of 6 ankles in stiff shoes and 1 of 6 ankles in flexible shoes. Ligament elongations from the computational model validated the experimental injury data. The current study suggested flexibility (or rotational stiffness) of the shoe may play an important role in both the severity of ankle injuries for athletes.

  14. Estimation of plant disease severity visually, by digital photography and image analysis, and by hyperspectral imaging

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reliable, precise and accurate estimates of disease severity are important for predicting yield loss, monitoring and forecasting epidemics, for assessing crop germplasm for disease resistance, and for understanding fundamental biological processes including co-evolution. In some situations poor qual...

  15. Levodopa changes the severity of freezing in Parkinson's disease.

    PubMed

    Fietzek, Urban M; Zwosta, Jens; Schroeteler, Frauke E; Ziegler, Kerstin; Ceballos-Baumann, Andres O

    2013-10-01

    Oral levodopa has been proposed to be one of the more effective medications to alleviate freezing of gait, but there is limited data on its efficacy. We evaluated the gait phenomenology of 20 Parkinson's disease patients with freezing of gait before and 60 min after a standardized levodopa dose using a rating scale based on the assumption that festination and akinetic freezing share a common pathophysiology. Levodopa abolished festination and freezing in 20% of patients (p < 0.0001), and reduced the freezing sum score from a median of 15 (IQR 6.75-27.5) to 3.5 (1-11.25), p < 0.001) in all but one of the remainder. Pre-dose ratings correlated with post-dose ratings, in that those patients with lower pre-dose item-scores also showed lower post-dose outcome scores. Levodopa's effect on both festination and akinetic freezing was linear, thereby supporting the concept that festination and freezing are variants on a continuity of episodic gait disorders in PD.

  16. Minireview: Clinical severity in sickle cell disease: the challenges of definition and prognostication

    PubMed Central

    2016-01-01

    Sickle cell disease (SCD) is a monogenic, yet highly phenotypically variable disease with multisystem pathology. This manuscript provides an overview of many of the known determinants, modifiers, and correlates of disease severity in SCD. Despite this wealth of data, modeling the variable and multisystem pathology of SCD continues to be difficult. The current status of prediction of specific adverse outcomes and global disease severity in SCD is also reviewed, highlighting recent successes and ongoing challenges. PMID:27013545

  17. Severity of Demyelinating and Axonal Neuropathy Mouse Models Is Modified by Genes Affecting Structure and Function of Peripheral Nodes.

    PubMed

    Morelli, Kathryn H; Seburn, Kevin L; Schroeder, David G; Spaulding, Emily L; Dionne, Loiuse A; Cox, Gregory A; Burgess, Robert W

    2017-03-28

    Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of inherited polyneuropathies. Mutations in 80 genetic loci can cause forms of CMT, resulting in demyelination and axonal dysfunction. The clinical presentation, including sensory deficits, distal muscle weakness, and atrophy, can vary greatly in severity and progression. Here, we used mouse models of CMT to demonstrate genetic interactions that result in a more severe neuropathy phenotype. The cell adhesion molecule Nrcam and the Na(+) channel Scn8a (NaV1.6) are important components of nodes. Homozygous Nrcam and heterozygous Scn8a mutations synergized with both an Sh3tc2 mutation, modeling recessive demyelinating Charcot-Marie-Tooth type 4C, and mutations in Gars, modeling dominant axonal Charcot-Marie-Tooth type 2D. We conclude that genetic variants perturbing the structure and function of nodes interact with mutations affecting the cable properties of axons by thinning myelin or reducing axon diameter. Therefore, genes integral to peripheral nodes are candidate modifiers of peripheral neuropathy.

  18. The relationship between infecting dose and severity of disease in reported outbreaks of Salmonella infections.

    PubMed Central

    Glynn, J. R.; Bradley, D. J.

    1992-01-01

    The relationship between size of the infecting dose and severity of the resulting disease has been investigated for salmonella infections by reanalysis of data within epidemics for 32 outbreaks, and comparing data between outbreaks for 68 typhoid epidemics and 49 food-poisoning outbreaks due to salmonellas. Attack rate, incubation period, amount of infected food consumed and type of vehicle are used as proxy measures of infecting dose, while case fatality rates for typhoid and case hospitalization rates for food poisoning salmonellas were used to assess severity. Limitations of the data are discussed. Both unweighted and logit analysis models are used. There is no evidence for a dose-severity relationship for Salmonella typhi, but evidence of a correlation between dose and severity is available from within-epidemic or between-epidemic analysis, or both, for Salmonella typhimurium, S. enteritidis, S. infantis, S. newport, and S. thompson. The presence of such a relationship affects the way in which control interventions should be assessed. PMID:1468522

  19. Subthalamic nucleus stimulation affects incentive salience attribution in Parkinson's disease.

    PubMed

    Serranová, Tereza; Jech, Robert; Dušek, Petr; Sieger, Tomáš; Růžička, Filip; Urgošík, Dušan; Růžička, Evžen

    2011-10-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can induce nonmotor side effects such as behavioral and mood disturbances or body weight gain in Parkinson's disease (PD) patients. We hypothesized that some of these problems could be related to an altered attribution of incentive salience (ie, emotional relevance) to rewarding and aversive stimuli. Twenty PD patients (all men; mean age ± SD, 58.3 ± 6 years) in bilateral STN DBS switched ON and OFF conditions and 18 matched controls rated pictures selected from the International Affective Picture System according to emotional valence (unpleasantness/pleasantness) and arousal on 2 independent visual scales ranging from 1 to 9. Eighty-four pictures depicting primary rewarding (erotica and food) and aversive fearful (victims and threat) and neutral stimuli were selected for this study. In the STN DBS ON condition, the PD patients attributed lower valence scores to the aversive pictures compared with the OFF condition (P < .01) and compared with controls (P < .01). The difference between the OFF condition and controls was less pronounced (P < .05). Furthermore, postoperative weight gain correlated with arousal ratings from the food pictures in the STN DBS ON condition (P < .05 compensated for OFF condition). Our results suggest that STN DBS increases activation of the aversive motivational system so that more relevance is attributed to aversive fearful stimuli. In addition, STN DBS-related sensitivity to food reward stimuli cues might drive DBS-treated patients to higher food intake and subsequent weight gain.

  20. Screening-detected rheumatic heart disease can progress to severe disease

    PubMed Central

    Wheaton, Gavin R; Mataika, Reapi L; Kado, Joseph H; Colquhoun, Samantha M; Remenyi, Bo; Steer, Andrew C

    2016-01-01

    Objectives Echocardiography is a sensitive test for rheumatic heart disease (RHD) screening; however the natural history of RHD detected on screening has not been established. We aimed to evaluate the progression of screening-detected RHD in Fiji. Methods All young people previously diagnosed with RHD through screening, with echocardiograms available for review, were eligible. All baseline echocardiograms were reported again. Participants underwent follow-up echocardiography. A paediatric cardiologist determined the diagnosis using the World Heart Federation criteria and assessed the severity of regurgitation and stenosis. Results Ninety-eight participants were recruited (mean age, 17 years; median duration of follow-up, 7.5 years). Two other children had died from severe RHD. Fourteen of 20 (70%) definite RHD cases persisted or progressed, including four (20%) requiring valve surgery. Four (20%) definite RHD cases improved to borderline RHD and two (10%) to normal. Four of 17 (24%) borderline cases progressed to definite RHD (moderate: 2; severe: 2) and two (12%) improved to normal. Four of the 55 cases reclassified as normal at baseline progressed to borderline RHD. Cases with a follow-up interval >5 years were more likely to improve (37% vs 6%, p=0.03). Conclusions The natural history of screening-detected RHD is not benign. Most definite RHD cases persist and others may require surgery or succumb. Progression of borderline cases to severe RHD demonstrates the need for monitoring and individualised consideration of prophylaxis. Robust health system structures are needed for follow-up and delivery of secondary prophylaxis if RHD screening is to be scaled up. PMID:27933106

  1. How glyphosate affects plant disease development: it is more than enhanced susceptibility.

    PubMed

    Hammerschmidt, Ray

    2017-01-09

    Glyphosate has been shown to affect the development of plant disease in several ways. Plants utilize phenolic and other shikimic acid pathway-derived compounds as part of their defense against pathogens, and glyphosate inhibits the biosynthesis of these compounds via its mode of action. Several studies have shown a correlation between enhanced disease and suppression of phenolic compound production after glyphosate. Glyphosate-resistant crop plants have also been studied for changes in resistance as a result of carrying the glyphosate resistance trait. The evidence indicates that neither the resistance trait nor application of glyphosate to glyphosate-resistant plants increases susceptibility to disease. The only exceptions to this are cases where glyphosate has been shown to reduce rust diseases on glyphosate-resistant crops, supporting a fungicidal role for this chemical. Finally, glyphosate treatment of weeds or volunteer crops can cause a temporary increase in soil-borne pathogens that may result in disease development if crops are planted too soon after glyphosate application. © 2017 Society of Chemical Industry.

  2. Interstudy heterogeneity of definitions of diastolic dysfunction severely affects reported prevalence

    PubMed Central

    Selmeryd, Jonas; Henriksen, Egil; Leppert, Jerzy; Hedberg, Pär

    2016-01-01

    Aims The aim of this article is to examine how the European Association of Cardiovascular Imaging (EACVI) and the American Society of Echocardiography (ASE) recommendations on the classification of diastolic dysfunction (DDF) are interpreted in the scientific community and to explore how variations in the DDF definition affect the reported prevalence. Methods and results A systematic review of studies citing the EACVI/ASE consensus document ‘Recommendations for the evaluation of left ventricular diastolic function by echocardiography’ was performed. The definition of DDF used in each study was recorded. Subsequently, several possible interpretations of the EACVI/ASE classification scheme were used to obtain DDF prevalence in a community-based sample (n = 714). In the systematic review, 60 studies were included. In 13 studies, no specification of DDF definition was presented, a one-level classification tree was used in 13, a two-level classification tree in 18, and in the remaining 16 studies, a DDF definition was presented but no grading of DDF was performed. In 17 studies, the DDF definition relied solely on early diastolic tissue velocity and/or left atrial size. In eight of these studies, a single parameter was used, in two studies the logical operator AND was used to combine two or more parameters, and the remaining seven studies used the logical operator OR. The resulting prevalence of DDF in the community-based sample varied from 12 to 84%, depending on the DDF definition used. Conclusion A substantial heterogeneity of definitions of DDF was evident among the studies reviewed, and the different definitions had a substantial impact on the reported prevalence of DDF. PMID:26374880

  3. Effect of Mycoplasma hyopneumoniae colonization at weaning on disease severity in growing pigs.

    PubMed

    Fano, Eduardo; Pijoan, Carlos; Dee, Scott; Deen, John

    2007-07-01

    To determine whether Mycoplasma hyopneumoniae colonization at weaning in off-site weaning systems is associated with the severity of respiratory disease due to this agent in growing pigs, we studied 20 groups, each group representing a different week in production, in sow herds at 3 farms of 3000 sows each that had a prevalence of M. hyopneumoniae colonization at weaning higher than 5%. The calculated sample size for assessment at weaning was 39 piglets for each group under study; 39 litters were randomly selected, and 1 piglet was randomly selected from each litter for testing and ear-tagged. In total, 780 piglets were tested. The presence of M. hyopneumoniae in nasal swabs at weaning was established by nested polymerase chain reaction (PCR). All groups were followed until slaughter, at which time blood samples were collected from each ear-tagged pig to test for M. hyopneumoniae antibodies, bronchial swabs were collected for detection of M. hyopneumoniae DNA by nested PCR, and the lung lesion score and percentage of affected lungs in the same animals were calculated. Correlation analyses showed a positive correlation between colonization at weaning and all 4 dependent variables indicating infection at slaughter: average lung lesion score, percentage of affected lungs, presence of M. hyopneumoniae on the bronchial epithelium, and seroconversion. This study provides evidence that severity of the disease can be predicted by the prevalence at weaning in segregated systems. Therefore, strategies focused on reducing colonization at weaning seem to be important elements in the global control of M. hyopneumoniae in segregated production systems.

  4. Demography, disease and the devil: life-history changes in a disease-affected population of Tasmanian devils (Sarcophilus harrisii).

    PubMed

    Lachish, Shelly; McCallum, Hamish; Jones, Menna

    2009-03-01

    1. Examining the demographic responses of populations to disease epidemics and the nature of compensatory responses to perturbation from epidemics is critical to our understanding of the processes affecting population dynamics and our ability to conserve threatened species. Such knowledge is currently available for few systems. 2. We examined changes to the demography and life-history traits of a population of Tasmanian devils (Sarcophilus harrisii) following the arrival of a debilitating infectious disease, devil facial tumour disease (DFTD), and investigated the population's ability to compensate for the severe population perturbation caused by this epizootic. 3. There was a significant change to the age structure following the arrival of DFTD to the Freycinet Peninsula. This shift to a younger population was caused by the loss of older individuals from the population as a direct consequence of DFTD-driven declines in adult survival rates. 4. Offspring sex ratios of disease mothers were more female biased than those of healthy mothers, indicating that devils may facultatively adjust offspring sex ratios in response to disease-induced changes in maternal condition. 5. We detected evidence of reproductive compensation in response to disease impacts via a reduction in the age of sexual maturity of females (an increase in precocial breeding) over time. 6. The strength of this compensatory response appeared to be limited by factors that constrain the ability of individuals to reach a critical size for sexual maturity in their first year, because of the time limit dictated by the annual breeding season. 7. The ongoing devastating impacts of this disease for adult survival and the apparent reliance of precocial breeding on rapid early growth provide the opportunity for evolution to favour of this new life-history pattern, highlighting the potential for novel infectious diseases to be strong selective forces on life-history evolution.

  5. Behavioral activation and inhibition, negative affect, and gambling severity in a sample of young adult college students.

    PubMed

    Atkinson, John; Sharp, Carla; Schmitz, Joy; Yaroslavsky, Ilya

    2012-09-01

    The prevalence of pathological gambling among college students is increasing. Few studies have directly examined the relation between reward processing and gambling severity while concurrently examining the effects of co-occurring negative affect in this at risk population. This study used Structural Equation Modeling (SEM) techniques to analyze results from an online survey of 352 female and 96 male students age 18-25. Participants completed measures of past year gambling behavior and severity of gambling problems using the Canadian Problem Gambling Index and the Problem Gambling Severity Index. Negative affect and reward processing were measured by the 21-item version of the Depression, Anxiety, and Stress Scales and the Behavioral Inhibition System and Behavioral Activation System (BIS/BAS) scales, respectively. Thirty-five percent of participants reported gambling in the previous 12 months, and 11% had gambling severity scores indicative of "moderate-risk" or "problem gambling." Gambling severity was associated with negative affect. Negative affect, in turn, was correlated with the unitary BIS scale and inversely associated with the BAS reward responsiveness scale. Reward responsiveness was also inversely associated with gambling severity. In the SEM models, the association between reward responsiveness and gambling severity was mediated by negative affect among males but not among females. Potential explanations for these findings and their implications for addressing problem gambling are discussed.

  6. Transient lactose malabsorption in patients affected by symptomatic uncomplicated diverticular disease of the colon.

    PubMed

    Tursi, Antonio; Brandimarte, Giovanni; Giorgetti, Gian Marco; Elisei, Walter

    2006-03-01

    Lactose malabsorption (LM) may be secondary to several small bowel diseases, and small intestinal overgrowth (SIBO) may be one of them. We looked for a correlation between symptomatic diverticular disease of the colon and LM and assessed whether this correlation may be related to SIBO. Ninety consecutive patients (pts; 39 males, 51 females; mean age, 67.2 years; range, 32-91 years) affected by symptomatic uncomplicated diverticular disease of the colon were evaluated to assess orocecal transit time (OCTT), SIBO, and LM by lactulose and lactose H2 breath test (H2-BT) at entry and after 8 weeks of treatment. OCTT was delayed in 67 of 90 pts (74.44%). Fifty-three of 90 pts (58.88%) showed SIBO, and OCTT was normal in 23 of 90 pts (25.56%). LM was diagnosed in 59 of 90 pts (65.55%): 49 of 59 (71.74%) were simultaneously affected by SIBO and delayed OCTT (and thus 49 of 53 pts [92.45%] with delayed OCTT and SIBO were affected by LM); 3 of 59 pts (5.09%) showed only delayed OCTT; 7 of 59 pts (11.86%) did not show either SIBO or delayed OCTT. The association of LM and SIBO was statistically significant (P < 0.001). Seventy-nine of 86 pts (91.86%) showed normal OCTT, while OCTT remained prolonged but shorter in the remaining 7 pts (8.14%). SIBO was eradicated in all pts completing the study, while a new lactulose H2-BT showed persistence of SIBO in one pt with recurrence of symptomatic diverticular disease. Forty-seven of 59 pts (79.66%) had a normal lactose H2-BT (P < 0.002), while 12 of 59 pts (20.34%) showed persistence of LM. LM disappeared in 46 of 49 pts (93.88%) concurrently with normalization of OCTT and eradication of SIBO (P < 0.002); it also disappeared in 1 of 3 pts (33.33%) previously affected by delayed OCTT (without SIBO) and LM concurrently with normalization of OCTT. On the contrary, it persisted in all pts with normal OCTT and absence of SIBO. Moreover, it persisted also in the pt with recurrence of symptomatic diverticular disease and persistence of SIBO

  7. How many standard area diagram sets are needed for accurate disease severity assessment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Standard area diagram sets (SADs) are widely used in plant pathology: a rater estimates disease severity by comparing an unknown sample to actual severities in the SADs and interpolates an estimate as accurately as possible (although some SADs have been developed for categorizing disease too). Most ...

  8. An Acoustic Study of the Relationships among Neurologic Disease, Dysarthria Type, and Severity of Dysarthria

    ERIC Educational Resources Information Center

    Kim, Yunjung; Kent, Raymond D.; Weismer, Gary

    2011-01-01

    Purpose: This study examined acoustic predictors of speech intelligibility in speakers with several types of dysarthria secondary to different diseases and conducted classification analysis solely by acoustic measures according to 3 variables (disease, speech severity, and dysarthria type). Method: Speech recordings from 107 speakers with…

  9. Oral impacts affecting daily performance in a low dental disease Thai population.

    PubMed

    Adulyanon, S; Vourapukjaru, J; Sheiham, A

    1996-12-01

    The aim of the study was to measure incidence of oral impacts on daily performances and their related features in a low dental disease population. 501 people aged 35-44 years in 16 rural villages in Ban Phang district, Khon Kaen, Thailand, were interviewed about oral impacts on nine physical, psychological and social aspects of performance during the past 6 months, and then had an oral examination. The clinical and behavioural data showed that the sample had low caries (DMFT = 2.7) and a low utilization of dental services. 73.6% of all subjects had at least one daily performance affected by an oral impact. The highest incidence of performances affected were Eating (49.7%), Emotional stability (46.5%) and Smiling (26.1%). Eating, Emotional stability and Cleaning teeth performances had a high frequency or long duration of impacts, but a low severity. The low frequency performances; Physical activities, Major role activity and Sleeping were rated as high severity. Pain and discomfort were mainly perceived as the causes of impacts (40.1%) for almost every performance except Smiling. Toothache was the major causal oral condition (32.7%) of almost all aspects of performance. It was concluded that this low caries people have as high an incidence of oral impacts as industrialized, high dental disease populations. Frequency and severity presented the paradoxical effect on different performances and should both be taken into account for overall estimation of impacts.

  10. Age-dependent effect of myostatin blockade on disease severity in a murine model of limb-girdle muscular dystrophy.

    PubMed

    Parsons, Stephanie A; Millay, Douglas P; Sargent, Michelle A; McNally, Elizabeth M; Molkentin, Jeffery D

    2006-06-01

    Myostatin (MSTN) is a muscle-specific secreted peptide that functions to limit muscle growth through an autocrine regulatory feedback loop. Loss of MSTN activity in cattle, mice, and humans leads to a profound phenotype of muscle overgrowth, associated with more and larger fibers and enhanced regenerative capacity. Deletion of MSTN in the mdx mouse model of Duchenne muscular dystrophy enhances muscle mass and reduces disease severity. In contrast, loss of MSTN activity in the dyW/dyW mouse model of laminin-deficient congenital muscular dystrophy, a much more severe and lethal disease model, does not improve all aspects of muscle pathology. Here we examined disease severity associated with myostatin (mstn-/-) deletion in mice nullizygous for delta-sarcoglycan (scgd-/-), a model of limb-girdle muscular dystrophy. Early loss of MSTN activity achieved either by monoclonal antibody administration or by gene deletion each improved muscle mass, regeneration, and reduced fibrosis in scgd-/- mice. However, antibody-mediated inhibition of MSTN in late-stage dystrophic scgd-/- mice did not improve disease. These findings suggest that MSTN inhibition may benefit muscular dystrophy when instituted early or if disease is relatively mild but that MSTN inhibition in severely affected or late-stage disease may be ineffective.

  11. Predicting acute affective symptoms after deep brain stimulation surgery in Parkinson's disease.

    PubMed

    Schneider, Frank; Reske, Martina; Finkelmeyer, Andreas; Wojtecki, Lars; Timmermann, Lars; Brosig, Timo; Backes, Volker; Amir-Manavi, Atoosa; Sturm, Volker; Habel, Ute; Schnitzler, Alfons

    2010-01-01

    The current study aimed to investigate predictive markers for acute symptoms of depression and mania following deep brain stimulation (DBS) surgery of the subthalamic nucleus for the treatment of motor symptoms in Parkinson's disease (PD). Fourteen patients with PD (7 males) were included in a prospective longitudinal study. Neuropsychological tests, psychopathology scales and tests of motor functions were administered at several time points prior to and after neurosurgery. Pre-existing psychopathological and motor symptoms predicted postoperative affective side effects of DBS surgery. As these can easily be assessed, they should be considered along with other selection criteria for DBS surgery.

  12. Discussion on calculation of disease severity index values from scales with unequal intervals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    When estimating severity of disease, a disease interval (or category) scale comprises a number of categories of known numeric values – with plant disease this is generally the percent area with symptoms (e.g., the Horsfall-Barratt (H-B) scale). Studies in plant pathology and plant breeding often use...

  13. Should we screen children with severe acute malnutrition for celiac disease?

    PubMed

    Kumar, Praveen; Mishra, Kirtisudha; Singh, Preeti; Rai, Kiran

    2012-04-01

    The clinical features of severe acute malnutrition (SAM) often overlap with the common manifestations of celiac disease. In this observational pilot study, 76 children fulfilling the case definition of SAM were investigated for celiac disease, tuberculosis and HIV. Celiac disease was diagnosed in 13.1% of SAM children while tuberculosis and HIV were diagnosed in 9.3% and 4%, respectively.

  14. Molecular Epidemiology and Disease Severity of Human Respiratory Syncytial Virus in Vietnam

    PubMed Central

    Tran, Dinh Nguyen; Pham, Thi Minh Hong; Ha, Manh Tuan; Tran, Thi Thu Loan; Dang, Thi Kim Huyen; Yoshida, Lay-Myint; Okitsu, Shoko; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

    2013-01-01

    Respiratory syncytial virus (RSV) is a major cause of acute respiratory infections (ARIs) in children worldwide and can cause high mortality, especially in developing countries. However, information on the clinical and molecular characteristics of RSV infection in developing countries is limited. From April 2010 to May 2011, 1,082 nasopharyngeal swabs were collected from children with ARI admitted to the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for RSV and genotyped by reverse transcription-PCR and sequencing. Demographic and clinical data was also recorded. RSV was found in 23.8% (257/1,082) of samples. RSV A was the dominant subgroup, accounting for 91.4% (235/257), followed by RSV B, 5.1% (13/257), and 9 cases (3.5%) were mixed infection of these subgroups. The phylogenetic analysis revealed that all group A strains belonged to the GA2 genotype. All group B strains belonged to the recently identified BA genotype, and further clustered into 2 recently described subgenotypes BA9 and BA10. One GA2 genotype strain had a premature stop codon which shortened the G protein length. RSV infection was significantly associated with younger age and higher severity score than those without. Co-infection with other viruses did not affect disease severity. RSV A caused more severe disease than RSV B. The results from this study will not only contribute to the growing database on the molecular diversity of RSV circulating worldwide but may be also useful in clinical management and vaccine development. PMID:23349659

  15. Sever's Disease

    MedlinePlus

    ... puts constant pressure on the heel. Poor-fitting shoes can contribute to the condition by not providing ... is to make sure that kids wear proper shoes. Good quality, well-fitting shoes with shock-absorbent ( ...

  16. Sever's Disease

    MedlinePlus

    ... results from physical activities and sports that involve running and jumping, especially those that take place on ... cause pain until all symptoms are gone, especially running barefoot or on hard surfaces because hard impact ...

  17. Spatial prediction of wheat Septoria leaf blotch (Septoria tritici) disease severity in central Ethiopia

    USGS Publications Warehouse

    Wakie, Tewodros; Kumar, Sunil; Senay, Gabriel; Takele, Abera; Lencho, Alemu

    2016-01-01

    A number of studies have reported the presence of wheat septoria leaf blotch (Septoria tritici; SLB) disease in Ethiopia. However, the environmental factors associated with SLB disease, and areas under risk of SLB disease, have not been studied. Here, we tested the hypothesis that environmental variables can adequately explain observed SLB disease severity levels in West Shewa, Central Ethiopia. Specifically, we identified 50 environmental variables and assessed their relationships with SLB disease severity. Geographically referenced disease severity data were obtained from the field, and linear regression and Boosted Regression Trees (BRT) modeling approaches were used for developing spatial models. Moderate-resolution imaging spectroradiometer (MODIS) derived vegetation indices and land surface temperature (LST) variables highly influenced SLB model predictions. Soil and topographic variables did not sufficiently explain observed SLB disease severity variation in this study. Our results show that wheat growing areas in Central Ethiopia, including highly productive districts, are at risk of SLB disease. The study demonstrates the integration of field data with modeling approaches such as BRT for predicting the spatial patterns of severity of a pathogenic wheat disease in Central Ethiopia. Our results can aid Ethiopia's wheat disease monitoring efforts, while our methods can be replicated for testing related hypotheses elsewhere.

  18. Anger, Anxiety, and Depression as Risk Factors for Cardiovascular Disease: The Problems and Implications of Overlapping Affective Dispositions

    ERIC Educational Resources Information Center

    Sul, Jerry; Bunde, James

    2005-01-01

    Several recent reviews (e.g., L. C. Gallo & K. Matthews, 2003; A. Rozanski, J. A. Blumenthal, & J. Kaplan, 1999; R. Rugulies, 2002) have identified 3 affective dispositions--depression, anxiety, and anger-hostility--as putative risk factors for coronary heart disease. There are, however, mixed and negative results. Following a critical summary of…

  19. Brain dopamine-serotonin vesicular transport disease presenting as a severe infantile hypotonic parkinsonian disorder.

    PubMed

    Jacobsen, Jessie C; Wilson, Callum; Cunningham, Vicki; Glamuzina, Emma; Prosser, Debra O; Love, Donald R; Burgess, Trent; Taylor, Juliet; Swan, Brendan; Hill, Rosamund; Robertson, Stephen P; Snell, Russell G; Lehnert, Klaus

    2016-03-01

    Two male siblings from a consanguineous union presented in early infancy with marked truncal hypotonia, a general paucity of movement, extrapyramidal signs and cognitive delay. By mid-childhood they had made little developmental progress and remained severely hypotonic and bradykinetic. They developed epilepsy and had problems with autonomic dysfunction and oculogyric crises. They had a number of orthopaedic problems secondary to their hypotonia. Cerebrospinal fluid (CSF) neurotransmitters were initially normal, apart from mildly elevated 5-hydroxyindolacetic acid, and the children did not respond favourably to a trial of levodopa-carbidopa. The youngest died from respiratory complications at 10 years of age. Repeat CSF neurotransmitters in the older sibling at eight years of age showed slightly low homovanillic acid and 5-hydroxyindoleacetic acid levels. Whole-exome sequencing revealed a novel mutation homozygous in both children in the monoamine transporter gene SLC18A2 (p.Pro237His), resulting in brain dopamine-serotonin vesicular transport disease. This is the second family to be described with a mutation in this gene. Treatment with the dopamine agonist pramipexole in the surviving child resulted in mild improvements in alertness, communication, and eye movements. This case supports the identification of the causal mutation in the original case, expands the clinical phenotype of brain dopamine-serotonin vesicular transport disease and confirms that pramipexole treatment may lead to symptomatic improvement in affected individuals.

  20. Pantomime and Imitation of Limb Gestures in Relation to the Severity of Alzheimer's Disease

    ERIC Educational Resources Information Center

    Parakh, Rupa; Roy, Eric; Koo, Ean; Black, Sandra

    2004-01-01

    The present study was designed to investigate the relationship between performance of limb gestures and the severity of Alzheimer's disease (AD). Apraxia tends to occur at later stages of AD, and the severity of apraxia has been shown to vary with the severity of AD dementia. Participants were 19 mild (including 9 with no cognitive impairment and…

  1. Severe respiratory syncytial virus (RSV) infection in infants with neuromuscular diseases and immune deficiency syndromes.

    PubMed

    Resch, Bernhard; Manzoni, Paolo; Lanari, Marcello

    2009-09-01

    Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infection (LRTI) in infants and children. There is growing evidence of severe RSV disease in infants with neuromuscular diseases and immune deficiency syndromes. Factors predisposing to a more severe course of RSV disease in neuromuscular diseases include the impaired ability to clear secretions from the airways due to ineffective cough, respiratory muscle weakness, high prevalence of gastro-oesophageal reflux and swallowing dysfunction which leads to aspiration. Similarly, pulmonary disease is a common presenting feature and complication of T-cell immunodeficiency. Infants with severe congenital and acquired immune deficiency syndromes may demonstrate prolonged viral shedding in RSV LRTI and are reported to have increased morbidity and mortality associated with RSV infection. Although not indicated in most guideline statements, palivizumab prophylaxis for these uncommon underlying conditions is under consideration by clinicians. Prospective studies are needed to determine the burden of RSV disease in these children.

  2. Saposin C coupled lipid nanovesicles specifically target arthritic mouse joints for optical imaging of disease severity.

    PubMed

    Qi, Xiaoyang; Flick, Matthew J; Frederick, Malinda; Chu, Zhengtao; Mason, Rachel; DeLay, Monica; Thornton, Sherry

    2012-01-01

    Rheumatoid arthritis is a chronic inflammatory disease affecting approximately 1% of the population and is characterized by cartilage and bone destruction ultimately leading to loss of joint function. Early detection and intervention of disease provides the best hope for successful treatment and preservation of joint mobility and function. Reliable and non-invasive techniques that accurately measure arthritic disease onset and progression are lacking. We recently developed a novel agent, SapC-DOPS, which is composed of the membrane-associated lysosomal protein saposin C (SapC) incorporated into 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) lipid nanovesicles. SapC-DOPS has a high fusogenic affinity for phosphatidylserine-enriched microdomains on surfaces of target cell membranes. Incorporation of a far-red fluorophore, CellVue Maroon (CVM), into the nanovesicles allows for in vivo non-invasive visualization of the agent in targeted tissue. Given that phosphatidylserine is present only on the inner leaflet of healthy plasma membranes but is "flipped" to the outer leaflet upon cell damage, we hypothesized that SapC-DOPS would target tissue damage associated with inflammatory arthritis due to local surface-exposure of phosphatidylserine. Optical imaging with SapC-DOPS-CVM in two distinct models of arthritis, serum-transfer arthritis (e.g., K/BxN) and collagen-induced arthritis (CIA) revealed robust SapC-DOPS-CVM specific localization to arthritic paws and joints in live animals. Importantly, intensity of localized fluorescent signal correlated with macroscopic arthritic disease severity and increased with disease progression. Flow cytometry of cells extracted from arthritic joints demonstrated that SapC-DOPS-CVM localized to an average of 7-8% of total joint cells and primarily to CD11b+Gr-1+ cells. Results from the current studies strongly support the application of SapC-DOPS-CVM for advanced clinical and research applications including: detecting early arthritis

  3. Severity of chronic experimental Chagas' heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease

    PubMed Central

    Pereira, Isabela Resende; Vilar-Pereira, Glaucia; da Silva, Andrea Alice; Lannes-Vieira, Joseli

    2014-01-01

    Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi, 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish experimental models that mimic a range of parasitological, pathological and cardiac alterations described in patients with chronic Chagas’ heart disease and evaluate whether heart disease severity was associated with increased TNF and NO levels in the serum. Our results show that C3H/He mice chronically infected with the Colombian T. cruzi strain have more severe cardiac parasitism and inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and fibronectin deposition in the heart tissue, increased levels of creatine kinase cardiac MB isoenzyme activity in the serum and more severe electrical abnormalities were observed in T. cruzi-infected C3H/He mice compared to C57BL/6 mice. Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe and mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF and NO levels in the serum. Therefore, these models are appropriate for studying the pathophysiology and biomarkers of CCC progression, as well as for testing therapeutic agents for patients with Chagas’ heart disease. PMID:24937048

  4. Infectious diseases affect marine fisheries and aquaculture economics

    USGS Publications Warehouse

    Lafferty, Kevin D.; Harvell, C. Drew; Conrad, Jon M.; Friedman, Carolyn S.; Kent, Michael L.; Kuris, Armand M.; Powell, Eric N.; Rondeau, Daniel; Saksida, Sonja M.

    2015-01-01

    Seafood is a growing part of the economy, but its economic value is diminished by marine diseases. Infectious diseases are common in the ocean, and here we tabulate 67 examples that can reduce commercial species' growth and survivorship or decrease seafood quality. These impacts seem most problematic in the stressful and crowded conditions of aquaculture, which increasingly dominates seafood production as wild fishery production plateaus. For instance, marine diseases of farmed oysters, shrimp, abalone, and various fishes, particularly Atlantic salmon, cost billions of dollars each year. In comparison, it is often difficult to accurately estimate disease impacts on wild populations, especially those of pelagic and subtidal species. Farmed species often receive infectious diseases from wild species and can, in turn, export infectious agents to wild species. However, the impact of disease export on wild fisheries is controversial because there are few quantitative data demonstrating that wild species near farms suffer more from infectious diseases than those in other areas. The movement of exotic infectious agents to new areas continues to be the greatest concern.

  5. Infectious Diseases Affect Marine Fisheries and Aquaculture Economics

    NASA Astrophysics Data System (ADS)

    Lafferty, Kevin D.; Harvell, C. Drew; Conrad, Jon M.; Friedman, Carolyn S.; Kent, Michael L.; Kuris, Armand M.; Powell, Eric N.; Rondeau, Daniel; Saksida, Sonja M.

    2015-01-01

    Seafood is a growing part of the economy, but its economic value is diminished by marine diseases. Infectious diseases are common in the ocean, and here we tabulate 67 examples that can reduce commercial species' growth and survivorship or decrease seafood quality. These impacts seem most problematic in the stressful and crowded conditions of aquaculture, which increasingly dominates seafood production as wild fishery production plateaus. For instance, marine diseases of farmed oysters, shrimp, abalone, and various fishes, particularly Atlantic salmon, cost billions of dollars each year. In comparison, it is often difficult to accurately estimate disease impacts on wild populations, especially those of pelagic and subtidal species. Farmed species often receive infectious diseases from wild species and can, in turn, export infectious agents to wild species. However, the impact of disease export on wild fisheries is controversial because there are few quantitative data demonstrating that wild species near farms suffer more from infectious diseases than those in other areas. The movement of exotic infectious agents to new areas continues to be the greatest concern.

  6. Infectious diseases affect marine fisheries and aquaculture economics.

    PubMed

    Lafferty, Kevin D; Harvell, C Drew; Conrad, Jon M; Friedman, Carolyn S; Kent, Michael L; Kuris, Armand M; Powell, Eric N; Rondeau, Daniel; Saksida, Sonja M

    2015-01-01

    Seafood is a growing part of the economy, but its economic value is diminished by marine diseases. Infectious diseases are common in the ocean, and here we tabulate 67 examples that can reduce commercial species' growth and survivorship or decrease seafood quality. These impacts seem most problematic in the stressful and crowded conditions of aquaculture, which increasingly dominates seafood production as wild fishery production plateaus. For instance, marine diseases of farmed oysters, shrimp, abalone, and various fishes, particularly Atlantic salmon, cost billions of dollars each year. In comparison, it is often difficult to accurately estimate disease impacts on wild populations, especially those of pelagic and subtidal species. Farmed species often receive infectious diseases from wild species and can, in turn, export infectious agents to wild species. However, the impact of disease export on wild fisheries is controversial because there are few quantitative data demonstrating that wild species near farms suffer more from infectious diseases than those in other areas. The movement of exotic infectious agents to new areas continues to be the greatest concern.

  7. How will climate change affect wildland fire severity in the western US?

    NASA Astrophysics Data System (ADS)

    Parks, Sean A.; Miller, Carol; Abatzoglou, John T.; Holsinger, Lisa M.; Parisien, Marc-André; Dobrowski, Solomon Z.

    2016-03-01

    Fire regime characteristics in North America are expected to change over the next several decades as a result of anthropogenic climate change. Although some fire regime characteristics (e.g., area burned and fire season length) are relatively well-studied in the context of a changing climate, fire severity has received less attention. In this study, we used observed data from 1984 to 2012 for the western United States (US) to build a statistical model of fire severity as a function of climate. We then applied this model to several (n = 20) climate change projections representing mid-century (2040-2069) conditions under the RCP 8.5 scenario. Model predictions suggest widespread reduction in fire severity for large portions of the western US. However, our model implicitly incorporates climate-induced changes in vegetation type, fuel load, and fire frequency. As such, our predictions are best interpreted as a potential reduction in fire severity, a potential that may not be realized due human-induced disequilibrium between plant communities and climate. Consequently, to realize the reductions in fire severity predicted in this study, land managers in the western US could facilitate the transition of plant communities towards a state of equilibrium with the emerging climate through means such as active restoration treatments (e.g., mechanical thinning and prescribed fire) and passive restoration strategies like managed natural fire (under suitable weather conditions). Resisting changes in vegetation composition and fuel load via activities such as aggressive fire suppression will amplify disequilibrium conditions and will likely result in increased fire severity in future decades because fuel loads will increase as the climate warms and fire danger becomes more extreme. The results of our study provide insights to the pros and cons of resisting or facilitating change in vegetation composition and fuel load in the context of a changing climate.

  8. FACTORS AFFECTING SUSCEPTIBILITY OF THE CORAL MONTASTRAEA FAVEOLATE TO BLACK-BAND DISEASE

    EPA Science Inventory

    Black-band disease affects many species of tropical reef-building corals, but it is unclear what factors contribute to the disease-susceptibility of individual corals or how the disease is transmitted between colonies. Studies have suggested that the ability of black-band disease...

  9. Lack of Evidence of Increased West Nile Virus Disease Severity in the United States in 2012

    PubMed Central

    Lindsey, Nicole P.; Staples, J. Erin; Delorey, Mark J.; Fischer, Marc

    2014-01-01

    In the United States, West Nile virus (WNV) causes annual seasonal outbreaks that fluctuate in size and scope. There was a large multistate outbreak of WNV in 2012, with more human disease cases reported nationally than any year since 2003. We evaluated national surveillance data to determine if the higher number of WNV cases reported in 2012 was associated with changes in the epidemiology or severity of disease compared with 2004–2011. Despite an increased incidence of neuroinvasive disease in 2012, national surveillance data showed no evidence of changes in epidemiology or increased disease severity compared with the previous 8 years. PMID:24218412

  10. Effect of Endurance Cardiovascular Training Intensity on Erectile Dysfunction Severity in Men With Ischemic Heart Disease.

    PubMed

    Kalka, Dariusz; Domagala, Zygmunt A; Kowalewski, Piotr; Rusiecki, Leslaw; Koleda, Piotr; Marciniak, Wojciech; Dworak, Jacek; Adamus, Jerzy; Wojcieszczyk, Joanna; Pyke, Edel; Pilecki, Witold

    2015-09-01

    The protective effect of physical activity on arteries is not limited to coronary vessels, but extends to the whole arterial system, including arteries, in which endothelial dysfunction and atherosclerotic changes are one of the key factors affecting erectile dysfunction development. The objective of this study was to report whether the endurance training intensity and training-induced chronotropic response are linked with a change in erectile dysfunction intensity in men with ischemic heart disease. A total of 150 men treated for ischemic heart disease, who suffered from erectile dysfunction, were analyzed. The study group consisted of 115 patients who were subjected to a cardiac rehabilitation program. The control group consisted of 35 patients who were not subjected to any cardiac rehabilitation. An IIEF-5 (International Index of Erectile Function) questionnaire was used for determining erectile dysfunction before and after cardiac rehabilitation. Cardiac training intensity was objectified by parameters describing work of endurance training. The mean initial intensity of erectile dysfunction in the study group was 12.46 ± 6.01 (95% confidence interval [CI] = 11.35-13.57). Final erectile dysfunction intensity (EDI) assessed after the cardiac rehabilitation program in the study group was 14.35 ± 6.88 (95% CI = 13.08-15.62), and it was statistically significantly greater from initial EDI. Mean final training work was statistically significantly greater than mean initial training work. From among the parameters describing training work, none were related significantly to reduction of EDI. In conclusion, cardiac rehabilitation program-induced improvement in erection severity is not correlated with endurance training intensity. Chronotropic response during exercise may be used for initial assessment of change in cardiac rehabilitation program-induced erection severity.

  11. Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians.

    PubMed

    Clemens, E Bridie; Grant, Emma J; Wang, Zhongfang; Gras, Stephanie; Tipping, Peta; Rossjohn, Jamie; Miller, Adrian; Tong, Steven Y C; Kedzierska, Katherine

    2016-04-01

    Indigenous populations, including Indigenous Australians, are highly susceptible to severe influenza disease and the underlying mechanisms are unknown. We studied immune and genetic factors that could predicate severe influenza disease in Indigenous Australians enrolled in the LIFT study: looking into influenza T-cell immunity. To examine CD8(+) T-cell immunity, we characterised human leukocyte antigen (HLA) profiles. HLA typing confirmed previous studies showing predominant usage of HLA-A*02:01, 11:01, 24:02, 34:01 and HLA-B*13:01, 15:21, 40:01/02, 56:01/02 in Indigenous Australians. We identified two new HLA alleles (HLA-A*02:new and HLA-B*56:new). Modelling suggests that variations within HLA-A*02:new (but not HLA-B56:new) could affect peptide binding. There is a relative lack of known influenza epitopes for the majority of these HLAs, with the exception of a universal HLA-A*02:01-M158 epitope and proposed epitopes presented by HLA-A*11:01/HLA-A*24:02. To dissect universal CD8(+) T-cell responses, we analysed the magnitude, function and T-cell receptor (TCR) clonality of HLA-A*02:01-M158(+)CD8(+) T cells. We found comparable IFN-γ, TNF and CD107a and TCRαβ characteristics in Indigenous and non-Indigenous Australians, suggesting that the ~15% of Indigenous people that express HLA-A*02:01 have universal influenza-specific CD8(+) T-cell immunity. Furthermore, the frequency of an influenza host risk factor, IFITM3-C/C, was comparable between Indigenous Australians and Europeans, suggesting that expression of this allele does not explain increased disease severity at a population level. Our study indicates a need to identify novel influenza-specific CD8(+) T-cell epitopes restricted by HLA-A and HLA-B alleles prevalent in Indigenous populations for the rational design of universal T-cell vaccines.

  12. Prevalence of comorbidities according to predominant phenotype and severity of chronic obstructive pulmonary disease

    PubMed Central

    Camiciottoli, Gianna; Bigazzi, Francesca; Magni, Chiara; Bonti, Viola; Diciotti, Stefano; Bartolucci, Maurizio; Mascalchi, Mario; Pistolesi, Massimo

    2016-01-01

    Background In addition to lung involvement, several other diseases and syndromes coexist in patients with chronic obstructive pulmonary disease (COPD). Our purpose was to investigate the prevalence of idiopathic arterial hypertension (IAH), ischemic heart disease, heart failure, peripheral vascular disease (PVD), diabetes, osteoporosis, and anxious depressive syndrome in a clinical setting of COPD outpatients whose phenotypes (predominant airway disease and predominant emphysema) and severity (mild and severe diseases) were determined by clinical and functional parameters. Methods A total of 412 outpatients with COPD were assigned either a predominant airway disease or a predominant emphysema phenotype of mild or severe degree according to predictive models based on pulmonary functions (forced expiratory volume in 1 second/vital capacity; total lung capacity %; functional residual capacity %; and diffusing capacity of lung for carbon monoxide %) and sputum characteristics. Comorbidities were assessed by objective medical records. Results Eighty-four percent of patients suffered from at least one comorbidity and 75% from at least one cardiovascular comorbidity, with IAH and PVD being the most prevalent ones (62% and 28%, respectively). IAH prevailed significantly in predominant airway disease, osteoporosis prevailed significantly in predominant emphysema, and ischemic heart disease and PVD prevailed in mild COPD. All cardiovascular comorbidities prevailed significantly in predominant airway phenotype of COPD and mild COPD severity. Conclusion Specific comorbidities prevail in different phenotypes of COPD; this fact may be relevant to identify patients at risk for specific, phenotype-related comorbidities. The highest prevalence of comorbidities in patients with mild disease indicates that these patients should be investigated for coexisting diseases or syndromes even in the less severe, pauci-symptomatic stages of COPD. The simple method employed to phenotype and

  13. Alzheimer’s Disease: Diagnosis and Treatment Across the Spectrum of Disease Severity

    PubMed Central

    Neugroschl, Judith; Wang, Sophia

    2012-01-01

    Alzheimer’s disease exists along a spectrum, from early memory changes to functional dependence and death. Using a case illustration, we review the evaluation and diagnosis of mild cognitive impairment and the diagnosis and management of Alzheimer’s disease at each stage, including the management of both cognitive and behavioral/psychiatric aspects of the disease and end-stage and end-of-life care. PMID:21748748

  14. Severe pulmonary hypertension in lung disease: phenotypes and response to treatment.

    PubMed

    Brewis, Melanie J; Church, Alistair C; Johnson, Martin K; Peacock, Andrew J

    2015-11-01

    Pulmonary hypertension (PH) due to lung disease (World Health Organization (WHO) group 3) is common, but severe PH, arbitrarily defined as mean pulmonary artery pressure ≥35 mmHg is reported in only a small proportion. Whether these should be treated as patients in WHO group 1 (i.e. pulmonary arterial hypertension) with PH-targeted therapies is unknown. We compared the phenotypic characteristics and outcomes of 118 incident patients with severe PH and lung disease with 74 idiopathic pulmonary arterial hypertension (IPAH) patients, all treated with pulmonary vasodilators. Lung disease patients were older, more hypoxaemic, and had lower gas transfer, worse New York Heart Association functional class and lower 6-min walking distance (6MWD) than IPAH patients. Poorer survival in those with lung disease was driven by the interstitial lung disease (ILD) cohort. In contrast to IPAH, where significant improvements in 6MWD and N-terminal pro-brain natruiretic peptide (NT-proBNP) occurred, PH therapy in severe PH lung disease did not lead to improvement in 6MWD or functional class, but neither was deterioration seen. NT-proBNP decreased from 2200 to 1596 pg·mL(-1) (p=0.015). Response varied by lung disease phenotype, with poorer outcomes in patients with ILD and emphysema with preserved forced expiratory volume in 1 s. Further study is required to investigate whether vasodilator therapy may delay disease progression in severe PH with lung disease.

  15. How the magnitude of clinical severity and recurrence risk affects reproductive decisions in adult males with different forms of progressive muscular dystrophy.

    PubMed Central

    Eggers, S; Zatz, M

    1998-01-01

    The reproductive history of 177 male patients affected with Becker (BMD) (n=69), limb-girdle (LGMD) (n=54), and facioscapulohumeral (FSHMD) (n=54) muscular dystrophy (MD) was analysed according to severity of the disease (BMD>LGMD>FSHMD) and magnitude of recurrence risk (RR) (high for FSHMD, intermediate for BMD, and low for LGMD). Additionally, 62 male patients were interviewed on psychosocial issues, in order to disentangle the factors influencing reproductive decisions among patients affected with MD. Among male adults, significantly more FSHMD than LGMD or BMD patients were married and had children. Age specific reproductive outcome was 0.31-0.32 for BMD, 0.51-0.62 for LGMD, and 0.58-1.02 for FSHMD, reflecting the influence of the disease's severity. High RRs did not significantly diminish reproduction after genetic counselling or correlate with less prospective desire for children. Instead, early onset, severity of the disease, and past reproductive history were found to diminish reproductive outcome after genetic counselling, and prospective family planning was also found to be influenced by past reproductive history as well as by emotional/sexual dysfunction with the opposite sex. PMID:9541101

  16. How the magnitude of clinical severity and recurrence risk affects reproductive decisions in adult males with different forms of progressive muscular dystrophy.

    PubMed

    Eggers, S; Zatz, M

    1998-03-01

    The reproductive history of 177 male patients affected with Becker (BMD) (n=69), limb-girdle (LGMD) (n=54), and facioscapulohumeral (FSHMD) (n=54) muscular dystrophy (MD) was analysed according to severity of the disease (BMD>LGMD>FSHMD) and magnitude of recurrence risk (RR) (high for FSHMD, intermediate for BMD, and low for LGMD). Additionally, 62 male patients were interviewed on psychosocial issues, in order to disentangle the factors influencing reproductive decisions among patients affected with MD. Among male adults, significantly more FSHMD than LGMD or BMD patients were married and had children. Age specific reproductive outcome was 0.31-0.32 for BMD, 0.51-0.62 for LGMD, and 0.58-1.02 for FSHMD, reflecting the influence of the disease's severity. High RRs did not significantly diminish reproduction after genetic counselling or correlate with less prospective desire for children. Instead, early onset, severity of the disease, and past reproductive history were found to diminish reproductive outcome after genetic counselling, and prospective family planning was also found to be influenced by past reproductive history as well as by emotional/sexual dysfunction with the opposite sex.

  17. Impaired suppressor activity in children affected by coeliac disease.

    PubMed Central

    Pignata, C; Troncone, R; Monaco, G; Ciriaco, M; Farris, E; Carminati, G; Auricchio, S

    1985-01-01

    Immunoregulatory cells were enumerated in 19 coeliac disease children on a gluten free diet by means of monoclonal antibodies that define total T lymphocytes (T3), helper/inducer T cells (T4), suppressor/cytotoxic T cells (T8) and monocytes (M1), as well as by means of surface receptors for Fc fragments of IgM and IgG (T mu and T gamma, respectively). In addition, suppressor cell function was assessed in 17 coeliac disease patients by examining the ability of concanavalin-A (Con-A)-activated suppressor cells to inhibit autologous cell response to mitogenic stimulus as compared with age-matched controls. No statistically significant differences were found in the percentages of subsets defined by monoclonal antibodies between coeliac disease patients and age-matched controls, whereas coeliac disease patients had a significant decrease of the subpopulation bearing membrane receptor for Fc fragment of IgG. Mean value was 8.5% in coeliac patients versus 13.4% in age-matched controls. In the functional assay, mononuclear cells from 10 out of 17 coeliac disease patients either totally or partially failed to suppress responder cells after Con-A-activation. This defect is not related to HLA-DR status, because no difference was found between patients-HLA-matched and unmatched normal individuals. In this assay, mononuclear cells of three coeliac disease patients with low suppressor activity were able to inhibit responder cells to the same extent as controls, when indomethacin was used to block prostaglandin production in the induction phase of Con-A-activated suppressor cells. Our results suggest that an abnormality in immunoregulation may play a role in the pathogenesis of coeliac disease. PMID:3156076

  18. Decision aids for multiple-decision disease management as affected by weather input errors.

    PubMed

    Pfender, W F; Gent, D H; Mahaffee, W F; Coop, L B; Fox, A D

    2011-06-01

    Many disease management decision support systems (DSSs) rely, exclusively or in part, on weather inputs to calculate an indicator for disease hazard. Error in the weather inputs, typically due to forecasting, interpolation, or estimation from off-site sources, may affect model calculations and management decision recommendations. The extent to which errors in weather inputs affect the quality of the final management outcome depends on a number of aspects of the disease management context, including whether management consists of a single dichotomous decision, or of a multi-decision process extending over the cropping season(s). Decision aids for multi-decision disease management typically are based on simple or complex algorithms of weather data which may be accumulated over several days or weeks. It is difficult to quantify accuracy of multi-decision DSSs due to temporally overlapping disease events, existence of more than one solution to optimizing the outcome, opportunities to take later recourse to modify earlier decisions, and the ongoing, complex decision process in which the DSS is only one component. One approach to assessing importance of weather input errors is to conduct an error analysis in which the DSS outcome from high-quality weather data is compared with that from weather data with various levels of bias and/or variance from the original data. We illustrate this analytical approach for two types of DSS, an infection risk index for hop powdery mildew and a simulation model for grass stem rust. Further exploration of analysis methods is needed to address problems associated with assessing uncertainty in multi-decision DSSs.

  19. Fire severity, residuals and soil legacies affect regeneration of Scots pine in the Southern Alps.

    PubMed

    Vacchiano, Giorgio; Stanchi, Silvia; Marinari, Giulia; Ascoli, Davide; Zanini, Ermanno; Motta, Renzo

    2014-02-15

    Regeneration of non fire-adapted conifers following crown fires on the European Alps is often delayed or unsuccessful. Fire may limit establishment by eliminating seed trees, altering soil properties, or modifying microsite and soil conditions via disturbance legacies. However, the effect of soil legacies on post-fire establishment has rarely been discussed. We analyzed the abundance of Scots pine regeneration in a 257 ha wildfire in an inner-alpine forest. Our aims were (1) to model fire intensity at the soil surface and topsoil heating along a gradient of increasing fire severities; (2) to assess the differences in soil properties along the fire severity gradient; (3) to model the effect of disturbance and soil legacies on the density of pine seedlings. We reconstructed fire behavior and soil heating with the First Order Fire Effects Model (FOFEM), tested the effect of fire severity on soils by nonparametric distributional tests, and modeled seedling density as a function of site, disturbance and soil legacies by fitting a GLM following a variable selection procedure. Topsoil heating differed markedly between the moderate and high severity fires, reaching temperatures high enough to strongly and permanently alter soil properties only in the latter. High fire severity resulted in decreased soil consistency and wet aggregate stability. Burned soils had lower organic matter and cations than those unburned. Pine seedlings favored low-fertility, eroded, and chemically poor sites. Establishment was facilitated by the presence of coarse woody debris, but hampered by increasing distance from the seed source. These results suggest that in dry, inner-alpine valleys, fire residuals and soil legacies interact in determining the success of Scots pine re-establishment. High severity fire can promote favorable soil conditions, but distance from the seed source and high evaporation rates of bare soils must be mitigated in order to ensure a successful restoration.

  20. Environmental factors affecting inflammatory bowel disease: have we made progress?

    PubMed

    Lakatos, Peter Laszlo

    2009-01-01

    The pathogenesis of inflammatory bowel disease (IBD) is only partially understood; various environmental and host (e.g. genetic, epithelial, immune, and nonimmune) factors are involved. The critical role for environmental factors is strongly supported by recent worldwide trends in IBD epidemiology. One important environmental factor is smoking. A meta-analysis partially confirms previous findings that smoking was found to be protective against ulcerative colitis and, after the onset of the disease, might improve its course, decreasing the need for colectomy. In contrast, smoking increases the risk of developing Crohn's disease and aggravates its course. The history of IBD is dotted by cyclic reports on the isolation of specific infectious agents responsible for Crohn's disease or ulcerative colitis. The more recently published cold chain hypothesis is providing an even broader platform by linking dietary factors and microbial agents. An additional, recent theory has suggested a breakdown in the balance between putative species of 'protective' versus 'harmful' intestinal bacteria - this concept has been termed dysbiosis resulting in decreased bacterial diversity. Other factors such as oral contraceptive use, appendectomy, dietary factors (e.g. refined sugar, fat, and fast food), perinatal events, and childhood infections have also been associated with both diseases, but their role is more controversial. Nonetheless, there is no doubt that economic development, leading to improved hygiene and other changes in lifestyle ('westernized lifestyle') may play a role in the increase in IBD. This review article focuses on the role of environmental factors in the pathogenesis and progression of IBDs.

  1. Minireview: Genetic basis of heterogeneity and severity in sickle cell disease

    PubMed Central

    Habara, Alawi

    2016-01-01

    Sickle cell disease, a common single gene disorder, has a complex pathophysiology that at its root is initiated by the polymerization of deoxy sickle hemoglobin. Sickle vasoocclusion and hemolytic anemia drive the development of disease complications. In this review, we focus on the genetic modifiers of disease heterogeneity. The phenotypic heterogeneity of disease is only partially explained by genetic variability of fetal hemoglobin gene expression and co-inheritance of α thalassemia. Given the complexity of pathophysiology, many different definitions of severity are possible complicating a full understanding of its genetic foundation. The pathophysiological complexity and the interlocking nature of the biological processes underpinning disease severity are becoming better understood. Nevertheless, useful genetic signatures of severity, regardless of how this is defined, are insufficiently developed to be used for treatment decisions and for counseling. PMID:26936084

  2. Ancillary testing, diagnostic/classification criteria and severity grading in Behçet disease.

    PubMed

    Okada, Annabelle A; Stanford, Miles; Tabbara, Khalid

    2012-12-01

    Since there is no pathognomonic clinical sign or laboratory test to distinguish Behçet disease from other uveitic entities, the diagnosis must be made based on characteristic ocular and systemic findings in the absence of evidence of other disease that can explain the findings. Ancillary tests, including ocular and brain imaging studies, are used to assess the severity of intraocular inflammation and systemic manifestations of Behçet disease, to identify latent infections and other medical conditions that might worsen with systemic treatment, and to monitor for adverse effects of drugs used. There are two diagnostic or classification criteria in general use by the uveitis community, one from Japan and one from an international group; both rely on a minimum number and/or combination of clinical findings to identify Behçet disease. Finally, several grading schemes have been proposed to assess severity of ocular disease and response to treatment.

  3. [Severe chronic pain with allodynia in Parkinson's disease: a case report].

    PubMed

    Ito, S; Asahina, M; Asahina, M; Oki, T; Hattori, T

    2001-01-01

    We report a 61-year-old man with Parkinson's disease, who had a 3-year history of severe chronic pain with allodynia in the lower extremities prior to motor symptoms. He always had tingling pain around the ankles, and tactile sensation induced severe burning pain expanding to the toes and thighs, so his pain was considered to be allodynia. Pain and motor symptoms were ameliorated by L-dopa therapy and exacerbated by withdrawal of L-dopa. Pain is known to occur in Parkinson's disease, but severe pain rarely occurs. To our knowledge, allodynia, which is usually recognized in causalgia or reflex sympathetic dystrophy, has never been reported in Parkinson's disease. Patients with Parkinson's disease may complain severe causalgia-like pain as an initial symptom.

  4. Wind speed and wind-associated leaf injury affect severity of citrus canker on Swingle citrumelo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Citrus canker (caused by the bacterial pathogen Xanthomonas citri subsp. citri, Xcc) can cause severe damage to citrus. It is endemic in Florida, and occurs in other citrus growing regions. The bacterium is dispersed predominantly in rain splash. To simulate dispersal in splash, and to investigate t...

  5. The Role of Attention in the Affective Life of People with Severe or Profound Intellectual Disabilities

    ERIC Educational Resources Information Center

    Vos, Pieter; De Cock, Paul; Munde, Vera; Neerinckx, Heleen; Petry, Katja; Van Den Noortgate, Wim; Maes, Bea

    2013-01-01

    Although it is shown that attention plays an important role both in the onset and in the regulation of emotions in people without disabilities there is no information about how attention is related to emotions in people with severe or profound intellectual disability (ID). Therefore, in our study, we investigated the role of attention in the onset…

  6. Hemophilia A and hemophilia B: focus on arthropathy and variables affecting bleeding severity and prophylaxis.

    PubMed

    Escobar, M; Sallah, S

    2013-08-01

    Hemophilia A (HA) and hemophilia B (HB) are X-linked, recessive disorders. Although their clinical manifestations are essentially indistinguishable, it has been suggested that bleeding episodes in patients with HA are generally more severe and occur at higher frequency than in patients with HB. Nevertheless, considerable debate remains regarding the relative severity of HA and HB. Based on the relative risk of undergoing joint arthroplasty, it appears that patients with HA have more severe joint deterioration compared with patients with HB. Although it is difficult to speculate on the factors that might modify bleeding severity in patients with hemophilia, recent observations indicate that other coagulation proteins, such as tissue factor pathway inhibitor or polymorphisms in coagulation factor genes and genetic defects associated with hypercoagulability may account for the variability in clinical phenotype among patients with hemophilia. Numerous studies have provided evidence supporting the clinical and social benefits of administration of clotting factor in prophylaxis. However, it is still unclear why this approach is more commonly utilized in patients with HA than in those with HB.

  7. How urbanization affects the epidemiology of emerging infectious diseases

    PubMed Central

    Neiderud, Carl-Johan

    2015-01-01

    The world is becoming more urban every day, and the process has been ongoing since the industrial revolution in the 18th century. The United Nations now estimates that 3.9 billion people live in urban centres. The rapid influx of residents is however not universal and the developed countries are already urban, but the big rise in urban population in the next 30 years is expected to be in Asia and Africa. Urbanization leads to many challenges for global health and the epidemiology of infectious diseases. New megacities can be incubators for new epidemics, and zoonotic diseases can spread in a more rapid manner and become worldwide threats. Adequate city planning and surveillance can be powerful tools to improve the global health and decrease the burden of communicable diseases. PMID:26112265

  8. Developmental orthopaedic disease in limbs of foals: between-breed variations in the prevalence, location and severity at weaning.

    PubMed

    Lepeule, J; Bareille, N; Valette, J P; Seegers, H; Jacquet, S; Denoix, J M; Robert, C

    2008-02-01

    Developmental orthopaedic disease (DOD) affects all breeds and is a common cause of pain and lameness for horses in sports. A thorough knowledge of between-breed variations for the prevalence of DOD, for its distribution among the various joints and for its severity at earlier stages in the disease process is needed in order to improve the relevance and the cost-effectiveness of DOD screening protocols. However, no prevalence study for DOD simultaneously performed on several breeds with similar farming systems and based on radiographic findings (RF) on quite a large number of joints and views, has been reported earlier. The objective of this study was to describe variations in the prevalence, location and severity of DOD in foals at weaning among Warmbloods (Wb), Standardbreds (St) and Thoroughbreds (Tb) with similar farming systems. DOD assessment was based on RF on the limb joints. A total of 392 foals from 21 volunteer stud farmers were included. To determine the statuses of foals regarding DOD, they were X-rayed on the front- and hind-limb digit, carpus, hock and stifle joints. X-ray data were analysed by three experienced equine veterinarians who gave a common assessment about the entity and the severity of RF. Between-breed variations were analysed in two steps: the first implemented for each anatomical site; the second considered only foals affected by DOD to explore RF association patterns on the affected sites, at foal level. The three breeds were represented by 25.0% of Wb, 41.1% of St and 33.9% of Tb. DOD was present in 66.3% of the foals (95% confidence interval (CI) = 61.6% to 71.0%). Prevalence of foals affected by DOD and distribution of the RF severity score on the anatomical sites differed depending on the breed: Wb foals seemed to be the most affected by DOD. Cluster analyses showed no clear association among sites. However, Wb and Tb foals were preferentially classified together because they were affected on the same sites, whereas St foals were

  9. Executive dysfunction affects word list recall performance: Evidence from amyotrophic lateral sclerosis and other neurodegenerative diseases.

    PubMed

    Consonni, Monica; Rossi, Stefania; Cerami, Chiara; Marcone, Alessandra; Iannaccone, Sandro; Francesco Cappa, Stefano; Perani, Daniela

    2017-03-01

    The Rey Auditory Verbal Learning Test (RAVLT) is widely used in clinical practice to evaluate verbal episodic memory. While there is evidence that RAVLT performance can be influenced by executive dysfunction, the way executive disorders affect the serial position curve (SPC) has not been yet explored. To this aim, we analysed immediate and delayed recall performances of 13 non-demented amyotrophic lateral sclerosis (ALS) patients with a specific mild executive dysfunction (ALSci) and compared their performances to those of 48 healthy controls (HC) and 13 cognitively normal patients with ALS. Moreover, to control for the impact of a severe dysexecutive syndrome and a genuine episodic memory deficit on the SPC, we enrolled 15 patients with a diagnosis of behavioural variant of frontotemporal dementia (bvFTD) and 18 patients with probable Alzheimer's disease (AD). Results documented that, compared to cognitively normal subjects, ALSci patients had a selective mid-list impairment for immediate recall scores. The bvFTD group obtained low performances with a selectively increased forgetting rate for terminal items, whereas the AD group showed a disproportionately large memory loss on the primary and middle part of the SPC for immediate recall scores and were severely impaired in the delayed recall trial. These results suggested that subtle executive dysfunctions might influence the recall of mid-list items, possibly reflecting deficiency in control strategies at retrieval of word lists, whereas severer dysexecutive syndrome might also affect the recall of terminal items possibly due to attention deficit or retroactive interference.

  10. Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies

    PubMed Central

    George, Michaela F.; Briggs, Farren B.S.; Shao, Xiaorong; Gianfrancesco, Milena A.; Kockum, Ingrid; Harbo, Hanne F.; Celius, Elisabeth G.; Bos, Steffan D.; Hedström, Anna; Shen, Ling; Bernstein, Allan; Alfredsson, Lars; Hillert, Jan; Olsson, Tomas; Patsopoulos, Nikolaos A.; De Jager, Philip L.; Oturai, Annette B.; Søndergaard, Helle B.; Sellebjerg, Finn; Sorensen, Per S.; Gomez, Refujia; Caillier, Stacy J.; Cree, Bruce A.C.; Oksenberg, Jorge R.; Hauser, Stephen L.; D'Alfonso, Sandra; Leone, Maurizio A.; Boneschi, Filippo Martinelli; Sorosina, Melissa; van der Mei, Ingrid; Taylor, Bruce V.; Zhou, Yuan; Schaefer, Catherine

    2016-01-01

    Objective: We investigated the association between 52 risk variants identified through genome-wide association studies and disease severity in multiple sclerosis (MS). Methods: Ten unique MS case data sets were analyzed. The Multiple Sclerosis Severity Score (MSSS) was calculated using the Expanded Disability Status Scale at study entry and disease duration. MSSS was considered as a continuous variable and as 2 dichotomous variables (median and extreme ends; MSSS of ≤5 vs >5 and MSSS of <2.5 vs ≥7.5, respectively). Single nucleotide polymorphisms (SNPs) were examined individually and as both combined weighted genetic risk score (wGRS) and unweighted genetic risk score (GRS) for association with disease severity. Random-effects meta-analyses were conducted and adjusted for cohort, sex, age at onset, and HLA-DRB1*15:01. Results: A total of 7,125 MS cases were analyzed. The wGRS and GRS were not strongly associated with disease severity after accounting for cohort, sex, age at onset, and HLA-DRB1*15:01. After restricting analyses to cases with disease duration ≥10 years, associations were null (p value ≥0.05). No SNP was associated with disease severity after adjusting for multiple testing. Conclusions: The largest meta-analysis of established MS genetic risk variants and disease severity, to date, was performed. Results suggest that the investigated MS genetic risk variants are not associated with MSSS, even after controlling for potential confounders. Further research in large cohorts is needed to identify genetic determinants of disease severity using sensitive clinical and MRI measures, which are critical to understanding disease mechanisms and guiding development of effective treatments. PMID:27540591

  11. IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

    SciTech Connect

    Duprez, Frederic; Madani, Indira; Morbee, Lieve; Bonte, Katrien; Deron, Philippe; Domjan, Vilmos; Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried

    2012-05-01

    Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival

  12. Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

    PubMed Central

    Bacalhau, Sílvia; Freitas, Cristina; Valente, Rosalina; Barata, Deolinda; Neves, Conceição; Schäfer, Katrin; Lubatschofski, Annelie; Schulz, Ansgar; Neves, João Farela

    2011-01-01

    In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID) who developed disseminated BCG disease, highlighting the specific strategies adopted. PMID:22110512

  13. Antibody Avidity Following Secondary Dengue Virus Type 2 Infection Across a Range of Disease Severity

    PubMed Central

    Lau, Louis; Green, Angela M.; Balmaseda, Angel; Harris, Eva

    2015-01-01

    Background The four dengue virus serotypes (DENV1-4) are responsible for the most prevalent mosquito-borne viral illness in humans. DENV causes a spectrum of disease from self-limiting dengue fever (DF) to severe, life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Antibodies from one infection can contribute to either protection or increased disease severity in a subsequent infection with a distinct DENV serotype. The effectiveness of the antibody response is modulated by both the affinity and avidity of the antibody/antigen interaction. Objectives We investigated how antibody avidity developed over time following secondary DENV2 infection across different disease severities. Study design We analyzed sera from 42 secondary DENV2-infected subjects (DF, n=15; DHF, n=16; DSS, n=11) from a pediatric hospital-based dengue study in Nicaragua. IgG avidity against DENV2 virions was measured in samples collected during acute and convalescent phases as well as 3, 6, and 18 months post-illness using a urea enzyme-linked immunosorbent assay. Results The data show a significant increase in avidity from acute to convalescent phase followed by a decrease from convalescent phase to 3 months post-symptom onset, then a plateau. Linear regression analysis comparing antibody avidity between disease severity groups over time indicate that individuals with more severe disease (DHF/DSS) experienced greater decay in antibody avidity over time compared to less severe disease (DF), and ROC curve analysis showed that at 18 months post-illness, lower avidity was associated with previously having experienced more severe disease. Conclusions These data suggest that increased dengue disease severity is associated with lower antibody avidity at later time-points post-illness. PMID:26209381

  14. Decompensation of chronic stable alcoholic liver disease by severe exfoliative dermatitis.

    PubMed

    Shawcross, Debbie L; Mookerjee, Rajeshwar P; Jalan, Rajiv

    2003-04-01

    Of the numerous precipitants of hepatic decompensation in chronic liver disease, there are no reports in the literature documenting an acute decompensation following an acute episode of severe dermatitis. This case highlights the haemodynamic consequences of a severe flare up of exfoliative dermatitis in a patient with stable chronic alcoholic liver disease, speculates on the mechanism by which this may provoke clinical decompensation and the impact this may have upon liver failure.

  15. How do you feel? Self-esteem predicts affect, stress, social interaction, and symptom severity during daily life in patients with chronic illness.

    PubMed

    Juth, Vanessa; Smyth, Joshua M; Santuzzi, Alecia M

    2008-10-01

    Self-esteem has been demonstrated to predict health and well-being in a number of samples and domains using retrospective reports, but little is known about the effect of self-esteem in daily life. A community sample with asthma (n = 97) or rheumatoid arthritis (n = 31) completed a self-esteem measure and collected Ecological Momentary Assessment (EMA) data 5x/day for one week using a palmtop computer. Low self-esteem predicted more negative affect, less positive affect, greater stress severity, and greater symptom severity in daily life. Naturalistic exploration of mechanisms relating self-esteem to physiological and/or psychological components in illness may clarify causal relationships and inform theoretical models of self-care, well-being, and disease management.

  16. Concomitant gastroparesis negatively affects children with functional gallbladder disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of the present study was to determine whether concomitant gastroparesis and biliary dyskinesia (BD) occur in children, and if so, to determine whether concomitant gastroparesis affects clinical outcome in children with BD. We conducted a retrospective chart review of children with BD (ejecti...

  17. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease.

    PubMed

    Beltrame, Rafael Coimbra Ferreira; Friderichs, Maurício; Fior, Bárbara Rayanne; Schaefer, Pedro Guilherme; Thomé, Gustavo Gomes; Silva, Dirceu Reis da; Barros, Elvino José Guardão; Seligman, Renato; Veronese, Francisco Veríssimo

    2016-01-01

    The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients. Resumo A doença relacionada à IgG4 tem um espectro clínico amplo em que múltiplos órgãos podem ser afetados, e o diagnóstico depende de achados histopatológicos típicos e elevada expressão de IgG4 em plasmócitos no tecido afetado. Descrevemos o quadro clínico e a evolução de um paciente com nefrite túbulo-intersticial aguda, insuficiência renal grave e manifestações sistêmicas como linfoadenomegalias e pancreatite crônica. O diagnóstico foi confirmado pelas características clínicas e pela histopatologia renal e de linfonodo, na qual a imunohistoquímica mostrou tecido linfoide com policlonalidade e expressão aumentada de IgG4, com uma relação IgG4/IgG total > 80%. O paciente foi tratado com prednisona na dose de 60 mg/dia, seguido de micofenolato mofetil, e apresentou melhora clínica e da função renal depois de 6 meses de tratamento. O alto índice de suspeição da doença relacionada ao IgG4 com comprometimento multissist

  18. Severe depression as the sole symptom of affective focal status epilepticus

    PubMed Central

    Dimitriadis, Konstantinos; Pfefferkorn, Thomas; Noachtar, Soheyl

    2014-01-01

    Depression as well as fear, joy and anger have been described as the semiological features of focal epileptic seizures. When emotions present as the sole symptoms of epileptic seizures, they may easily be misdiagnosed as a psychiatric disorder. We describe a patient with affective focal status epilepticus, secondary to limbic encephalitis, in which depression was the only clinical manifestation. Through EEG correlates the epileptic nature of depression could be proven. Furthermore, we discuss the association between epilepsy and depression, as well as the link between ictal depression and suicidal rates. PMID:24827645

  19. Factors Affecting the Efficacy of Recombinant Marek's Disease Vaccine Protection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many factors have the potential to influence the efficacy of Marek's disease (MD) vaccination. Some of these factors include maternal antibody, vaccine dose, age of birds at vaccination or challenge, challenge virus strain and genetic background of chickens. The objective of this study was to evalua...

  20. Early Huntington's Disease Affects Movements in Transformed Sensorimotor Mappings

    ERIC Educational Resources Information Center

    Boulet, C.; Lemay, M.; Bedard, M.A.; Chouinard, M.J.; Chouinard, S.; Richer, F.

    2005-01-01

    This study examined the effect of transformed visual feedback on movement control in Huntington's disease (HD). Patients in the early stages of HD and controls performed aiming movements towards peripheral targets on a digitizing tablet and emphasizing precision. In a baseline condition, HD patients were slower but showed few precision problems in…

  1. Effects of Host Resistance and Shading Density on the Disease Severity of Hydrangea Leaf Spot

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leaf spot, caused by Cercospora hydrangeae Ellis & Everh., is a common disease of bigleaf hydrangea (Hydrangea macrophylla) in ornamental nurseries and gardens. Experiments were conducted to determine the effects of cultivars and shading density on the disease severity. Two year-old plants of six bi...

  2. Prevalence and Severity of Voice and Swallowing Difficulties in Mitochondrial Disease

    ERIC Educational Resources Information Center

    Read, Jennifer L.; Whittaker, Roger G.; Miller, Nick; Clark, Sue; Taylor, Robert; McFarland, Robert; Turnbull, Douglass

    2012-01-01

    Background: Mutations of mitochondrial DNA (mtDNA) cause a broad spectrum of clinical phenotypes. Anecdotal evidence suggests that voice and swallow problems are a common feature of these diseases. Aims: To characterize accurately the prevalence and severity of voice and swallow problems in a large cohort of patients with mitochondrial disease.…

  3. Severe Acute Respiratory Distress Syndrome during Infliximab Therapy in a Patient with Crohn Disease

    PubMed Central

    Schoehl, Johanna; Mechie, Nicolae-Catalin; Schwoerer, Harald; Moerer, Onnen; Quintel, Michael; Buck, Cordula; Ellenrieder, Volker; Neesse, Albrecht; Amanzada, Ahmad

    2016-01-01

    The occurrence of a noninfectious interstitial lung disease is a rare but life-threatening side effect of infliximab, an antitumor necrosis factor alpha antibody. The following case report of a patient with Crohn disease shows an extremely dramatic progression to a severe acute respiratory distress syndrome. PMID:27920644

  4. Acute Lipotoxicity Regulates Severity of Biliary Acute Pancreatitis without Affecting Its Initiation

    PubMed Central

    Durgampudi, Chandra; Noel, Pawan; Patel, Krutika; Cline, Rachel; Trivedi, Ram N.; DeLany, James P.; Yadav, Dhiraj; Papachristou, Georgios I.; Lee, Kenneth; Acharya, Chathur; Jaligama, Deepthi; Navina, Sarah; Murad, Faris; Singh, Vijay P.

    2015-01-01

    Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O–positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate–induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction. PMID:24854864

  5. The severity, extent and recurrence of necrotizing periodontal disease in relation to HIV status and CD4+ T cell count.

    PubMed

    Phiri, Reality; Feller, Liviu; Blignaut, Elaine

    2010-10-01

    South Africa ranks among the three countries with the highest prevalence of HIV infection in sub-Saharan Africa, with an estimated 29.5% of women attending antenatal clinics being infected. Necrotizing periodontal disease is a well recognized HIV-associated oral condition. The objective of this investigation was to determine a possible correlation between the extent, severity and treatment outcome of necrotizing periodontal disease in relation to a person's HIV status and CD4+ T cell count. Data from 105 consecutive patients presenting with necrotizing periodontal disease at an academic oral health centre in South Africa were analysed. All patients were provided with an opportunity to undergo voluntary counseling and testing for HIV infection, were treated for necrotizing periodontal disease and followed over a period of nine months. The mean age of the cohort was 28 years old (range 12 - 52). Of 98 (93.3%) patients unaware of their HIV serostatus at the initial visit, 59 (56.2%) consented to testing. In total 45 (42.9%) were HIV-seropositive with a mean CD4+ T cell count of 222.7 cells/microl and 14 (13.3%) were HIV-seronegative, with a significantly higher mean CD4+ T cell count of 830 cells/microl (Fisher's exact test, p < 0.001), while the status of 46 (43.8%) remained unknown. In 101 (96.2%) patients, > or = 5 tooth sites were affected, and in 27 (26%) > or = 4 mm of gingival tissue were affected. This study, which included HIV-seropositive, HIV-seronegative and persons of unknown HIV status, revealed no statistical evidence that HIV infection was associated with the extent, severity or relapse of necrotizing periodontal disease. No statistically significant association could be demonstrated between the extent, severity and recurrence of necrotizing periodontal disease and a CD4+ T cell count < or = 200 cells/microl among HIV-seropositive patients.

  6. Butyrylcholinesterase K and apolipoprotein ε4 affect cortical thickness and neuropsychiatric symptoms in Alzheimer's disease.

    PubMed

    Yoo, Hye B; Lee, Hae W; Shin, Sue; Park, Sun-Won; Choi, Jung S; Jung, Hee Y; Cha, Jungho; Lee, Jong-Min; Lee, Jun-Young

    2014-02-01

    Two major genotypes are known to affect the development and progression of Alzheimer's disease (AD) and its response to cholinesterase inhibitors: the apolipoprotein E (ApoE) and butyrylcholinesterase genes (BChE). This study analyzed the effects of the BChE and ApoE genotypes on the cortical thickness of patients with AD and examined how these genotypes affect the neuropsychiatric symptoms of AD. AD-drug-naïve patients who met the probable AD criteria proposed by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association were recruited. Of 96 patients with AD, 65 were eligible for cortical thickness analysis. 3D T1-weighted images were acquired, and the cortical regions were segmented using the constrained Laplacian-based automated segmentation with proximities (CLASP) algorithm. Neuropsychiatric symptoms were measured by Neuropsychiatric Inventory (NPI) scores. BChE wild-type carriers (BChE-W) showed more thinning in the left dorsolateral prefrontal cortex, including the lateral premotor regions and anterior cingulate cortex, than did BChE-K variant carriers (BChE-K). ApoE-ε4 carriers had a thinner left medial prefrontal cortex, left superior frontal cortex, and left posterior cingulate cortex than did ApoE-ε4 non-carriers. Statistical analyses revealed that BChE-K carriers showed significantly less severe aberrant motor behavioral symptoms and that ε4 non-carriers showed less severe anxiety and indifference symptoms. The current findings show that, similar to ApoE-ε4 non-carriers, BChE-K carriers are protected from the pathological detriments of AD that affect frontal cortical thickness and neuropsychiatric symptoms. This study visually demonstrated the effects of the BChE-K and ApoE genotypes on the structural degeneration and complex aspects of the symptoms of AD.

  7. Semantic Trouble Sources and Their Repair in Conversations Affected by Parkinson's Disease

    ERIC Educational Resources Information Center

    Saldert, Charlotta; Ferm, Ulrika; Bloch, Steven

    2014-01-01

    Background: It is known that dysarthria arising from Parkinson's disease may affect intelligibility in conversational interaction. Research has also shown that Parkinson's disease may affect cognition and cause word-retrieval difficulties and pragmatic problems in the use of language. However, it is not known whether or how these…

  8. Cortical activation during robotic therapy for a severely affected arm in a chronic stroke patient: a case report.

    PubMed

    Saeki, Satoru; Matsushima, Yasuyuki; Hachisuka, Kenji

    2008-06-01

    The use of robotic-aided therapy in a patient with residual damage from a previous stroke was an attempt to improve function in a moderate to severe hemiparetic arm. Cortical activities associated with motor recovery are not well documented and require investigation. A chronic stroke patient with a severely affected arm underwent a robotic-training program for 12 weeks. The robotic-aided therapy improved motor control and spasticity in the proximal upper-limb. An increased oxygenated hemoglobin level was observed at the motor-related area in the affected hemisphere. A 12-week robotic-aided training program used in a chronic stroke patient demonstrated elements of motor recovery, and was also associated with direct activation of the affected hemisphere.

  9. Dietary modulation of the microbiome affects autoinflammatory disease

    PubMed Central

    Lukens, John R.; Gurung, Prajwal; Vogel, Peter; Johnson, Gordon R.; Carter, Robert A.; McGoldrick, Daniel J.; Bandi, Srinivasa R.A.O.; Calabrese, Christopher R.; Walle, Lieselotte Vande; Lamkanfi, Mohamed; Kanneganti, Thirumala-Devi

    2014-01-01

    The incidences of chronic inflammatory disorders have increased significantly over the past three decades1. Recent shifts in dietary consumption are believed to have contributed importantly to this surge, but how dietary consumption modulates inflammatory disease is poorly defined. Pstpip2cmo mice that express a homozygous L98P missense mutation in the Pombe Cdc15 homology (PCH) family proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) phosphatase spontaneously develop osteomyelitis that resembles chronic recurrent multifocal osteomyelitis (CRMO) in humans2-4. Recent reports demonstrated osteomyelitis to critically rely on IL-1β, but deletion of the inflammasome components caspase-1 and NLRP3 failed to rescue Pstpip2cmo mice from inflammatory bone disease5,6. Thus, the upstream mechanisms controlling IL-1β production in Pstpip2cmo mice remain to be identified. In addition, the environmental factors driving IL-1β-dependent inflammatory bone erosion are unknown. Here, we show that the intestinal microbiota of diseased Pstpip2cmo mice was characterized by an outgrowth of Prevotella. Notably, Pstpip2cmo mice that were fed a diet rich in fat and cholesterol maintained a normal body weight, but were markedly protected against inflammatory bone disease and bone erosion. Diet-induced protection against osteomyelitis was accompanied by marked reductions in intestinal Prevotella levels and significantly reduced proIL-1β expression in distant neutrophils. Furthermore, proIL-1β expression was also decreased in antibiotics-treated Pstpip2cmo mice, and in wildtype mice that were kept under germfree conditions. We further demonstrated that combined deletion of caspases 1 and 8 was required for protection against IL-1β-dependent inflammatory bone disease, whereas deletion of each caspase alone, elastase or neutrophil proteinase-3 failed to prevent inflammatory disease. Collectively, this work reveals diet-associated changes in the intestinal microbiome as a

  10. Family dysfunction differentially affects alcohol and methamphetamine dependence: a view from the Addiction Severity Index in Japan.

    PubMed

    Sugaya, Nagisa; Haraguchi, Ayako; Ogai, Yasukazu; Senoo, Eiichi; Higuchi, Susumu; Umeno, Mitsuru; Aikawa, Yuzo; Ikeda, Kazutaka

    2011-10-01

    We investigated the differential influence of family dysfunction on alcohol and methamphetamine dependence in Japan using the Addiction Severity Index (ASI), a useful instrument that multilaterally measures the severity of substance dependence. The participants in this study were 321 male patients with alcohol dependence and 68 male patients with methamphetamine dependence. We conducted semi-structured interviews with each patient using the ASI, which is designed to assess problem severity in seven functional domains: Medical, Employment/Support, Alcohol use, Drug use, Legal, Family/Social relationships, and Psychiatric. In patients with alcohol dependence, bad relationships with parents, brothers and sisters, and friends in their lives were related to current severe psychiatric problems. Bad relationships with brothers and sisters and partners in their lives were related to current severe employment/support problems, and bad relationships with partners in their lives were related to current severe family/social problems. The current severity of psychiatric problems was related to the current severity of drug use and family/social problems in patients with alcohol dependence. Patients with methamphetamine dependence had difficulty developing good relationships with their father. Furthermore, the current severity of psychiatric problems was related to the current severity of medical, employment/support, and family/social problems in patients with methamphetamine dependence. The results of this study suggest that family dysfunction differentially affects alcohol and methamphetamine dependence. Additionally, family relationships may be particularly related to psychiatric problems in these patients, although the ASI was developed to independently evaluate each of seven problem areas.

  11. Issues affecting minority participation in research studies of Alzheimer disease.

    PubMed

    Welsh, Kathleen A; Ballard, Edna; Nash, Florence; Raiford, Kate; Harrell, Lindy

    1994-01-01

    Despite the need for minority subjects in research studies of Alzheimer disease (AD), the successful involvement of minority patients in such studies has been difficult. This report discusses the many societal, economic, logistical, and attitudinal barriers that have inhibited the participation of minority patients and their families in medical research programs of AD. Special consideration is given to the unique cultural issues that arise when conducting studies involving African-American elderly subjects. Methods are considered for overcoming the barriers to participation gleaned from the national study CERAD (Consortium to Establish a Registry of Alzheimer Disease) and other investigations of AD. Recommendations are made for future research programs targeted on the specific health care needs and concerns of the minority segments of our population.

  12. Major viral diseases affecting fish aquaculture in Spain.

    PubMed

    Pérez, S I; Rodríguez, S

    1997-06-01

    The number of viruses isolated from fish has grown in the last few years as a reflection of the increasing interest in fish diseases, particularly those occurring in aquaculture facilities. Of all the described viruses, only a few are considered to be of serious concern and economic importance; they are described in this review, drawing special attention to the four families of viruses (Birnaviridae, Rhabdoviridae, Iridoviridae and Reoviridae) that have been reported in Spanish aquaculture. Infectious pancreatic necrosis virus, a member of the first family, is the most spread virus with a prevalence of 39%. Viral diseases are untreatable and because effective and safe vaccines for fish are not yet commercially available, a great care needs to be exercised when moving fish or eggs from one site or country to another. Some fish health control regulations have been legislated in Europe and USA.

  13. Does aggressive and expectant management of severe preeclampsia affect the neurologic development of the infant?

    PubMed Central

    Ertekin, Arif Aktuğ; Kapudere, Bilge; Eken, Meryem Kurek; İlhan, Gülşah; Dırman, Şükriye; Sargın, Mehmet Akif; Deniz, Engin; Karatekin, Güner; Çöğendez, Ebru; Api, Murat

    2015-01-01

    Objective: To compare and evaluate the influences of expectant and aggressive management of severe preeclampsia on the first year neurologic development of the infants in pregnancies between 27 and 34 weeks of pregnancy. Methods: Seventy women with severe preeclampsia between 27 and 34 weeks of gestation were included in the study. 37 patients were managed aggressively (Group 1) and 33 patients were managed expectantly (Group 2). Glucocorticoids, magnesium sulfate infusion and antihypertensive drugs were administered to each group. After glucocorticoid administration was completed Group 1 was delivered either by cesarean section or vaginal delivery. In Group 2 magnesium sulfate infusion was stopped after glucocorticoid administration was completed. Antihypertensive drugs were given, bed rest and intensive fetal monitorization were continued in this group. Results: The average weeks of gestation, one minute and five minute apgar scores and hospitalization time in intensive care unit were similar in both groups (P > 0.05). Three neonatal complications in Group 2 and five in Group 1 were detected according to the Denver Developmental Screening Test-II and one pathologic case was detected in both groups following neurologic examination. Neonatal mortality was seen in seven patients in Group 1 and one in Group 2. There were no significant differences between groups in terms of neonatal mortality and morbidity and maternal morbidity (P > 0.05). The average latency period was 3.45 ± 5.48 days in Group 2 and none in Group 1. Conclusion: There was no significant difference in the first year neurological development of infants whose mothers underwent either expectant and aggressive management for severe preeclampsia. PMID:26770571

  14. Benign paroxysmal positional vertigo simultaneously affecting several canals: a 46-patient series.

    PubMed

    Soto-Varela, Andrés; Rossi-Izquierdo, Marcos; Santos-Pérez, Sofía

    2013-03-01

    Although it is uncommon for benign paroxysmal positional vertigo (BPPV) to affect more than one canal simultaneously, it is not exceptional. We attempt to determine whether these patients present differences relative to "single-canal" cases. A prospective study was done in patients with BPPV, divided into three groups: single-canal BPPV, multi-canal BPPV in one ear and multi-canal BPPV in both ears. Diagnosis was by Dix and Hallpike, supine roll and cephalic hyperextension tests. Treatment was according to the affected canals, by Semont, Epley, Lempert and Yacovino manoeuvres. Aetiology, sex, age, response to treatment, recurrence and final status in each of the three groups was evaluated. Five hundred and eighty-three patients were diagnosed with BPPV: 537 single-canal (92 %) and 46 multi-canal (8 %); of the latter, 36 bilateral and 10 unilateral cases. Basic differences between groups were: greater percentage of idiopathic cases in single-canal (p < 0.0001, Chi-square), greater percentage of post-traumatic cases in bilateral multi-canals (p = 0.006, Chi-square) and prior history of BPPV was more common in unilateral multi-canal (p = 0.006, Chi-square). No differences between groups in response to treatment, recurrence and final status were detected. There are aetiological differences between patients with single-canal BPPV, unilateral multi-canal BPPV and bilateral multi-canal BPPV. Response to therapeutic manoeuvres, however, shows that over 90 % of the patients in all the groups are cured.

  15. Light chain (κ/λ) ratio of GM-CSF autoantibodies is associated with disease severity in autoimmune pulmonary alveolar proteinosis.

    PubMed

    Nei, Takahito; Urano, Shinya; Itoh, Yuko; Kitamura, Nobutaka; Hashimoto, Atsushi; Tanaka, Takahiro; Motoi, Natsuki; Kaneko, Chinatsu; Tazawa, Ryushi; Nakagaki, Kazuhide; Arai, Toru; Inoue, Yoshikazu; Nakata, Koh

    2013-12-01

    Previous studies demonstrated that antigranulocyte colony-stimulating factor autoantibody (GMAb) was consistently present in patients with autoimmune pulmonary alveolar proteinosis (aPAP), and, thus, represented candidature as a reliable diagnostic marker. However, our large cohort study suggested that the concentration of this antibody was not correlated with disease severity in patients. We found that the κ/λ ratio of GMAb was significantly correlated with the degree of hypoxemia. The proportion of λ-type GMAb per total λ-type IgG was significantly higher in severely affected patients than those in mildly affected patients, but the proportion of κ-type was unchanged. The κ/λ ratio was significantly correlated with both KL-6 and SP-D, which have been previously reported as disease severity markers. Thus, the light chain isotype usage of GMAb may not only be associated with the severity of aPAP, but may also represent a useful disease severity marker.

  16. Accuracy of plant specimen disease severity estimates: concepts, history, methods, ramifications and challenges for the future

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Knowledge of the extent of the symptoms of a plant disease, generally referred to as severity, is key to both fundamental and applied aspects of plant pathology. Most commonly, severity is obtained visually and the accuracy of each estimate (closeness to the actual value) by individual raters is par...

  17. CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease.

    PubMed

    Zhang, Deng-Feng; Li, Jin; Wu, Huan; Cui, Yue; Bi, Rui; Zhou, He-Jiang; Wang, Hui-Zhen; Zhang, Chen; Wang, Dong; Kong, Qing-Peng; Li, Tao; Fang, Yiru; Jiang, Tianzi; Yao, Yong-Gang

    2016-03-01

    The immune response is highly active in Alzheimer's disease (AD). Identification of genetic risk contributed by immune genes to AD may provide essential insight for the prognosis, diagnosis, and treatment of this neurodegenerative disease. In this study, we performed a genetic screening for AD-related top immune genes identified in Europeans in a Chinese cohort, followed by a multiple-stage study focusing on Complement Factor H (CFH) gene. Effects of the risk SNPs on AD-related neuroimaging endophenotypes were evaluated through magnetic resonance imaging scan, and the effects on AD cerebrospinal fluid biomarkers (CSF) and CFH expression changes were measured in aged and AD brain tissues and AD cellular models. Our results showed that the AD-associated top immune genes reported in Europeans (CR1, CD33, CLU, and TREML2) have weak effects in Chinese, whereas CFH showed strong effects. In particular, rs1061170 (P(meta)=5.0 × 10(-4)) and rs800292 (P(meta)=1.3 × 10(-5)) showed robust associations with AD, which were confirmed in multiple world-wide sample sets (4317 cases and 16 795 controls). Rs1061170 (P=2.5 × 10(-3)) and rs800292 (P=4.7 × 10(-4)) risk-allele carriers have an increased entorhinal thickness in their young age and a higher atrophy rate as the disease progresses. Rs800292 risk-allele carriers have higher CSF tau and Aβ levels and severe cognitive decline. CFH expression level, which was affected by the risk-alleles, was increased in AD brains and cellular models. These comprehensive analyses suggested that CFH is an important immune factor in AD and affects multiple pathological changes in early life and during disease progress.

  18. Changes in emotional empathy, affective responsivity, and behavior following severe traumatic brain injury.

    PubMed

    de Sousa, Arielle; McDonald, Skye; Rushby, Jacqueline

    2012-01-01

    This study was designed to examine the relationship between deficits in empathy, emotional responsivity, and social behavior in adults with severe traumatic brain injury (TBI). A total of 21 patients with severe TBI and 25 control participants viewed six film clips containing pleasant, unpleasant, and neutral content whilst facial muscle responses, skin conductance, and valence and arousal ratings were measured. Emotional empathy (the Balanced Emotional Empathy Scale, BEES: self-report) and changes in drive and control in social situations (The Current Behaviour Scale, CBS: relative report) were also assessed. In comparison to control participants, those in the TBI group reported less ability to empathize emotionally and had reduced facial responding to both pleasant and unpleasant films. They also exhibited lowered autonomic arousal, as well as abnormal ratings of valence and arousal, particularly to unpleasant films. Relative reported loss of emotional control was significantly associated with heightened empathy, while there was a trend to suggest that impaired drive (or motivation) may be related to lower levels of emotional empathy. The results represent the first to suggest that level of emotional empathy post traumatic brain injury may be associated with behavioral manifestations of disorders of drive and control.

  19. Virulence characteristics accounting for fire blight disease severity in apple trees and seedlings.

    PubMed

    Lee, Steven A; Ngugi, Henry K; Halbrendt, Noemi O; O'Keefe, Grace; Lehman, Brian; Travis, James W; Sinn, Judith P; McNellis, Timothy W

    2010-06-01

    The gram-negative bacterium Erwinia amylovora is the causal agent of fire blight, the most destructive bacterial disease of rosaceous plants, including apple and pear. Here, we compared the virulence levels of six E. amylovora strains (Ea273, CFBP1367, Ea581a, E2002a, E4001a, and HKN06P1) on apple trees and seedlings. The strains produced a range of disease severity, with HKN06P1 producing the greatest disease severity in every assay. We then compared virulence characteristic expression among the six strains, including growth rates in immature apple fruit, amylovoran production, levansucrase activity, biofilm formation, carbohydrate utilization, hypersensitive cell death elicitation in tobacco leaves, and protein secretion profiles. Multiple regression analysis indicated that three of the virulence characteristics (amylovoran production, biofilm formation, and growth in immature apple fruit) accounted for >70% of the variation in disease severity on apple seedlings. Furthermore, in greenhouse-grown 'Gala' trees, >75% of the variation in disease severity was accounted for by five of the virulence characteristics: amylovoran production, biofilm formation, growth in immature apple fruit, hypersensitive cell death elicitation, and sorbitol utilization. This study demonstrates that virulence factor expression levels account for differences in disease severity caused by wild isolates of E. amylovora on apple trees.

  20. Reflexive and Volitional Saccades: Biomarkers of Huntington Disease Severity and Progression

    PubMed Central

    Patel, Saumil S.; Jankovic, Joseph; Hood, Ashley J.; Jeter, Cameron B.; Sereno, Anne B.

    2011-01-01

    Background Huntington disease (HD) is a genetic, neurodegenerative disorder characterized by chorea, behavioral co-morbidities, cognitive deficits, and eye movement abnormalities. We sought to evaluate whether reflexive and voluntary orienting prove useful as biomarkers of disease severity in HD. Methods Eleven HD subjects were evaluated with the motor subscale of the Unified Huntington Disease Rating Scale (UHDRS) and the Montreal Cognitive Assessment. Using an infrared eye tracker, we also measured latency and error rates of horizontal and vertical saccades using prosaccade and antisaccade eye movement tasks. We calculated simple and age-controlled correlations between eye movement and clinical parameters. Results Prosaccade latency correlated with total chorea score. HD patients with greater clinical severity were significantly slower in the prosaccade task. Antisaccade error rate also correlated with UHDRS motor score and total chorea score. HD patients with greater clinical severity as measured by either measure made significantly more errors in the antisaccade task. All these correlations remained significant even when age was taken into account. Conclusions The results of the present age-controlled study show for the first time that both reflexive and voluntary eye motor control in HD patients decrease with increase in disease severity suggesting declines in both motor and cognitive function. Thus, relatively simple eye movement parameters (latency and error rate) obtained from simple tasks (prosaccade and antisaccade) may serve as quantitative biomarkers of sub-cortical and cortical disease severity in HD and could aid in predicting onset, distinguishing subtypes, or evaluating disease progression and novel therapies. PMID:22018763

  1. Studying the role of dystrophin-associated proteins in influencing Becker muscular dystrophy disease severity.

    PubMed

    van den Bergen, J C; Wokke, B H A; Hulsker, M A; Verschuuren, J J G M; Aartsma-Rus, A M

    2015-03-01

    Becker muscular dystrophy is characterized by a variable disease course. Many factors have been implicated to contribute to this diversity, among which the expression of several components of the dystrophin associated glycoprotein complex. Together with dystrophin, most of these proteins anchor the muscle fiber cytoskeleton to the extracellular matrix, thus protecting the muscle from contraction induced injury, while nNOS is primarily involved in inducing vasodilation during muscle contraction, enabling adequate muscle oxygenation. In the current study, we investigated the role of three components of the dystrophin associated glycoprotein complex (beta-dystroglycan, gamma-sarcoglycan and nNOS) and the dystrophin homologue utrophin on disease severity in Becker patients. Strength measurements, data about disease course and fresh muscle biopsies of the anterior tibial muscle were obtained from 24 Becker patients aged 19 to 66. The designation of Becker muscular dystrophy in this study was based on the mutation and not on the clinical severity. Contrary to previous studies, we were unable to find a relationship between expression of nNOS, beta-dystroglycan and gamma-sarcoglycan at the sarcolemma and disease severity, as measured by muscle strength in five muscle groups and age at reaching several disease milestones. Unexpectedly, we found an inverse correlation between utrophin expression at the sarcolemma and age at reaching disease milestones.

  2. Correlation between ankle brachial index and coronary artery disease severity in elderly Egyptians.

    PubMed

    Amer, Moatasem S; Tawfik, Heba Mohamed; Elmoteleb, Ayman M Abd; Maamoun, Manar M A

    2014-11-01

    We investigated the association between ankle brachial index (ABI) and coronary heart disease (CHD) severity in elderly Egyptians using different measures. We conducted a case-control study from November 2010 to June 2012 including 200 male and female patients with ischemia≥60 years who were divided into 100 cases and 100 controls according to ABI and redivided according to age. They underwent coronary angiography followed by ABI measurement using a hand-held Doppler. The CHD severity was estimated using the SYNTAX and Jeopardy scores and number of diseased vessels, which increased significantly in patients with peripheral artery disease (P<.001) for all. All 3 measures had strong negative correlation with ABI (P≤.001 for Jeopardy, <.001 for SYNTAX scores, and .004 for number of diseased vessels) and were correlated with each other. We concluded that ABI can reflect CHD severity in elderly Egyptians.

  3. Histology and immunohistochemistry of severe inflammatory bowel disease versus lymphoma in the ferret (Mustela putorius furo).

    PubMed

    Watson, Megan K; Cazzini, Paola; Mayer, Joerg; Gottdenker, Nicole; Reavill, Drury; Parry, Nicola; Fox, James G; Sakamoto, Kaori

    2016-05-01

    Inflammatory bowel disease (IBD) is a common disorder of ferrets (Mustela putorius furo) that may progress to lymphoma. Although routine histology is used to distinguish between these diseases, misclassifications may occur. Immunohistochemistry (IHC) is commonly used to distinguish between IBD and lymphoma in small animals. The objective of our study was to determine the agreement in the diagnosis reached solely using hematoxylin and eosin (HE)-stained, full-thickness sections versus using a combination of HE and IHC. Enteric sections from 44 ferrets previously diagnosed with IBD or intestinal lymphoma and 3 control ferrets were analyzed by pathologists with expertise in ferrets. A pathologist blinded to the original diagnosis assessed the same HE-stained sections. Analysis was then repeated using HE sections in parallel with sections stained using antibodies against CD3 and CD79a. No significant difference was found between the original HE diagnosis and the HE diagnosis reached by the blinded pathologist (p = 0.91) or between the blinded pathologist's HE versus HE with IHC diagnosis (p = 0.16). In the 2 cases where disagreement was present, IHC was pivotal in reaching a final diagnosis. There was no significant age (p = 0.29) difference between diagnoses; however, significantly more male ferrets were affected with IBD than females (p = 0.004). Immunophenotype of the lymphoma was not correlated with predilection for location in the intestinal wall (p = 0.44). Results suggest that although IHC is not necessary to distinguish IBD from intestinal lymphoma in ferrets, it can be useful a definitive diagnosis in cases of severe IBD.

  4. Integrating gut microbiota immaturity and disease-discriminatory taxa to diagnose the initiation and severity of shrimp disease.

    PubMed

    Xiong, Jinbo; Zhu, Jinyong; Dai, Wenfang; Dong, Chunming; Qiu, Qiongfen; Li, Chenghua

    2017-04-01

    Increasing evidence has emerged a tight link among the gut microbiota, host age and health status. This osculating interplay impedes the definition of gut microbiome features associated with host health from that in developmental stages. Consequently, gut microbiota-based prediction of health status is promising yet not well established. Here we firstly tracked shrimp gut microbiota (N = 118) over an entire cycle of culture; shrimp either stayed healthy or progressively transitioned into severe disease. The results showed that the gut microbiota were significantly distinct over shrimp developmental stages and disease progression. Null model and phylogenetic-based mean nearest taxon distance (MNTD) analyses indicated that deterministic processes that governed gut community became less important as the shrimp aged and disease progressed. The predicted gut microbiota age (using the profiles of age-discriminatory bacterial species as independent variables) fitted well (r = 0.996; P < 0.001) with the age of healthy subjects, while this defined trend was disrupted by disease. Microbiota-for-age Z-scores (MAZ, here defined as immaturity) were relative stable among healthy shrimp, but sharply decreased when disease emerged. By distinguishing between age- and disease- discriminatory taxa, we developed a model, bacterial indicators of shrimp health status, to diagnose disease from healthy subjects with 91.5% accuracy. Notably, the relative abundances of the bacterial indicators were indicative for shrimp disease severity. These findings, in aggregate, add our understanding on the gut community assembly patterns over shrimp developmental stages and disease progression. In addition, shrimp disease initiation and severity can be accurately diagnosed using gut microbiota immaturity and bacterial indicators.

  5. Risk factors affecting fatal bus accident severity: Their impact on different types of bus drivers.

    PubMed

    Feng, Shumin; Li, Zhenning; Ci, Yusheng; Zhang, Guohui

    2016-01-01

    While the bus is generally considered to be a relatively safe means of transportation, the property losses and casualties caused by bus accidents, especially fatal ones, are far from negligible. The reasons for a driver to incur fatalities are different in each case, and it is essential to discover the underlying risk factors of bus fatality severity for different types of drivers in order to improve bus safety. The current study investigates the underlying risk factors of fatal bus accident severity to different types of drivers in the U.S. by estimating an ordered logistic model. Data for the analysis are retrieved from the Buses Involved in Fatal Accidents (BIFA) database from the USA for the years 2006-2010. Accidents are divided into three levels by counting their equivalent fatalities, and the drivers are classified into three clusters by the K-means cluster analysis. The analysis shows that some risk factors have the same impact on different types of drivers, they are: (a) season; (b) day of week; (c) time period; (d) number of vehicles involved; (e) land use; (f) manner of collision; (g) speed limit; (h) snow or ice surface condition; (i) school bus; (j) bus type and seating capacity; (k) driver's age; (l) driver's gender; (m) risky behaviors; and (n) restraint system. Results also show that some risk factors only have impact on the "young and elder drivers with history of traffic violations", they are: (a) section type; (b) number of lanes per direction; (c) roadway profile; (d) wet road surface; and (e) cyclist-bus accident. Notably, history of traffic violations has different impact on different types of bus drivers.

  6. Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria.

    PubMed

    Barber, Bridget E; William, Timothy; Grigg, Matthew J; Parameswaran, Uma; Piera, Kim A; Price, Ric N; Yeo, Tsin W; Anstey, Nicholas M

    2015-01-01

    Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly understood. In contrast to P. falciparum, circulating vivax parasitemia is low, with minimal apparent sequestration in endothelium-lined microvasculature, and pathogenesis thought unrelated to parasite biomass. However, the relationships between vivax disease-severity and total parasite biomass, endothelial autocrine activation and microvascular dysfunction are unknown. We measured circulating parasitemia and markers of total parasite biomass (plasma parasite lactate dehydrogenase [pLDH] and PvLDH) in adults with severe (n = 9) and non-severe (n = 53) vivax malaria, and examined relationships with disease-severity, endothelial activation, and microvascular function. Healthy controls and adults with non-severe and severe falciparum malaria were enrolled for comparison. Median peripheral parasitemia, PvLDH and pLDH were 2.4-fold, 3.7-fold and 6.9-fold higher in severe compared to non-severe vivax malaria (p = 0.02, p = 0.02 and p = 0.015, respectively), suggesting that, as in falciparum malaria, peripheral P. vivax parasitemia underestimates total parasite biomass, particularly in severe disease. P. vivax schizonts were under-represented in peripheral blood. Severe vivax malaria was associated with increased angiopoietin-2 and impaired microvascular reactivity. Peripheral vivax parasitemia correlated with endothelial activation (angiopoietin-2, von-Willebrand-Factor [VWF], E-selectin), whereas markers of total vivax biomass correlated only with systemic inflammation (IL-6, IL-10). Activity of the VWF-cleaving-protease, ADAMTS13, was deficient in proportion to endothelial activation, IL-6, thrombocytopenia and vivax disease-severity, and associated with impaired microvascular reactivity in severe disease. Impaired microvascular reactivity correlated with lactate in severe vivax malaria. Findings suggest that tissue accumulation of P. vivax may occur, with the hidden

  7. Parasite Biomass-Related Inflammation, Endothelial Activation, Microvascular Dysfunction and Disease Severity in Vivax Malaria

    PubMed Central

    Barber, Bridget E.; William, Timothy; Grigg, Matthew J.; Parameswaran, Uma; Piera, Kim A.; Price, Ric N.; Yeo, Tsin W.; Anstey, Nicholas M.

    2015-01-01

    Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly understood. In contrast to P. falciparum, circulating vivax parasitemia is low, with minimal apparent sequestration in endothelium-lined microvasculature, and pathogenesis thought unrelated to parasite biomass. However, the relationships between vivax disease-severity and total parasite biomass, endothelial autocrine activation and microvascular dysfunction are unknown. We measured circulating parasitemia and markers of total parasite biomass (plasma parasite lactate dehydrogenase [pLDH] and PvLDH) in adults with severe (n = 9) and non-severe (n = 53) vivax malaria, and examined relationships with disease-severity, endothelial activation, and microvascular function. Healthy controls and adults with non-severe and severe falciparum malaria were enrolled for comparison. Median peripheral parasitemia, PvLDH and pLDH were 2.4-fold, 3.7-fold and 6.9-fold higher in severe compared to non-severe vivax malaria (p = 0.02, p = 0.02 and p = 0.015, respectively), suggesting that, as in falciparum malaria, peripheral P. vivax parasitemia underestimates total parasite biomass, particularly in severe disease. P. vivax schizonts were under-represented in peripheral blood. Severe vivax malaria was associated with increased angiopoietin-2 and impaired microvascular reactivity. Peripheral vivax parasitemia correlated with endothelial activation (angiopoietin-2, von-Willebrand-Factor [VWF], E-selectin), whereas markers of total vivax biomass correlated only with systemic inflammation (IL-6, IL-10). Activity of the VWF-cleaving-protease, ADAMTS13, was deficient in proportion to endothelial activation, IL-6, thrombocytopenia and vivax disease-severity, and associated with impaired microvascular reactivity in severe disease. Impaired microvascular reactivity correlated with lactate in severe vivax malaria. Findings suggest that tissue accumulation of P. vivax may occur, with the hidden

  8. Are lifetime affective disorders predictive of long-term outcome in severe adolescent anorexia nervosa?

    PubMed

    Carrot, B; Radon, L; Hubert, T; Vibert, S; Duclos, J; Curt, F; Godart, N

    2017-03-03

    Depression and anxiety are commonly associated with anorexia nervosa (AN) and contribute to difficulties in social integration, a negative factor for outcome in AN. The link between those disorders and AN has been poorly studied. Thus, our objective was to investigate (1) the link between outcome nine years after hospitalisation for AN and the occurrence of lifetime anxious or depressive comorbidities; (2) the prognostic value of these comorbidities on patient outcome; 181 female patients were hospitalised for AN (between 13 and 22 years old), and were re-evaluated for their psychological, dietary, physical and social outcomes, from 6 to 12 years after their hospitalisation. The link between anxious and depressive disorders (premorbid to AN and lifetime) and the outcome assessment criteria were tested through multivariate analyses; 63% of the participants had good or intermediate outcome, 83% had presented at least one anxiety or depression disorder in the course of their lives, half of them before the onset of AN. Premorbid obsessive compulsive disorders (OCD), BMI at admission, and premenarchal AN all contribute to poor prognosis. Social phobia and agoraphobia affect the subjects' quality of life and increase eating disorder symptoms. These results encourage a systematic assessment of, and care for, anxiety and depression comorbidities among female adolescent patients with a particular focus on premorbid OCD.

  9. Alterations in cognitive performance and affect-arousal state during fluctuations in motor function in Parkinson's disease.

    PubMed Central

    Brown, R G; Marsden, C D; Quinn, N; Wyke, M A

    1984-01-01

    Sixteen patients with idiopathic Parkinson's disease were selected who were all showing severe fluctuations in motor function ("on-off" phenomenon). Measures of cognitive function and of subjective affect/arousal state were taken on two occasions, once when "on" and once when "off". Twenty-five matched normal controls were also assessed on the same measures. Results revealed, on the average, a drop in cognitive function plus an adverse swing in affect/arousal state, in the patient group in the "off" condition, compared to the levels when "on". Analysis of the data suggested that the main factor associated with cognitive function when "off" was not the severity of disability but the level of affect/arousal. The fluctuations in cognitive function found tended to be mild relative to the severe changes in motor ability, and were present in only a proportion of patients. PMID:6736975

  10. Postnatal Infections and Immunology Affecting Chronic Lung Disease of Prematurity

    PubMed Central

    Pryhuber, Gloria S.

    2015-01-01

    Synopsis Premature infants suffer significant respiratory morbidity during infancy with long-term negative consequences on health, quality of life, and health care costs. Enhanced susceptibility to a variety of infections and inflammation play a large role in early and prolonged lung disease following premature birth, though the mechanisms of susceptibility and immune dysregulation are active areas of research. This chapter will review aspects of host-pathogen interactions and immune responses that are altered by preterm birth and that impact chronic respiratory morbidity in these children. PMID:26593074

  11. Vector-borne pathogens: New and emerging arboviral diseases affecting public health

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dengue and Zika have quickly become two of the most important vector-borne diseases affecting Public health around the world. This presentation will introduce vector-borne diseases and all the vectors implicated. A focus will be made on the most important arboviral diseases (Zika and dengue) describ...

  12. Chronic Ischemic Heart Disease Affects Health Related Quality of Life

    PubMed Central

    Goreishi, Abolfazl; Shajari, Zahra; Mohammadi, Zeinab

    2012-01-01

    Background Chronic diseases endanger not only physical health but also psychological and social health of patient. Thus, evaluation of such patients for psychological treatment decisions is very important. Method This is a descriptive study that was performed with 50 chronic patients (ischemic heart disease) selected from Valiasr and Mousavi at cardiac wards in Zanjan Province. They were given three types of questionnaire: demographic, WHOQOL, and Zung depression and anxiety index. The information was statically analyzed by frequency chart, central indexes, dispersion, Chi-Square and t tests, Pearson’s correlation index (P < 0.05). Results The average of quality of life in all patients were calculated as was respectively 12.19, 11.98, 12.08, and 12.4 in physical, psychological, social and environmental domains respectively, 68 percent of total number of the patients had various degrees of anxiety and 78 percent of them had various degrees of depression. There was a significant relationship between the life quality average in all domains and anxiety intensity and depression intensity (P < 0.05) and there was a significant relationship between life quality average in all domains and income (P < 0.05). Conclusion As the level of depression and anxiety goes up, quality of life decreases pointing out that they have a reverse relationship. Depression and anxiety are one of the most significant factors of quality of life among other variables. Regarding specific conditions of the treatment, it is necessary to pay special attention to psychological aspects.

  13. Exacerbation-related impairment of quality of life and work productivity in severe and very severe chronic obstructive pulmonary disease

    PubMed Central

    Solem, Caitlyn T; Sun, Shawn X; Sudharshan, Lavanya; Macahilig, Cynthia; Katyal, Monica; Gao, Xin

    2013-01-01

    Purpose Exacerbation-associated health-related quality of life (HRQoL) in patients with severe and very severe chronic obstructive pulmonary disease (COPD) is ill-defined. This study describes patterns, HRQoL, and the work productivity impact of COPD-related moderate and SEV exacerbations in patients with SEV/VSEV COPD, focusing on the chronic bronchitis subtype. Patients and methods A US sample of SEV and VSEV COPD patients with recent moderate or SEV exacerbation was recruited. Along with the demographic and clinical data collected from medical records, patients reported on exacerbation frequency, health-related quality of life (HRQoL) (using the St George’s Respiratory Questionnaire for COPD [SGRQ-C] and the European Quality of Life-5 Dimensions [EQ-5D]™ index), and work productivity and activity impairment (using the Work Productivity and Activity Impairment Questionnaire – Specific Health Problem [WPAI-SHP]). The HRQoL-related impacts of exacerbation frequency, time since exacerbation, and last exacerbation severity were evaluated via linear regressions. Results A total of 314 patients (190 SEV/124 VSEV, mean age =68.0 years, 51% male, 28% current smokers) were included. In the previous 12 months, patients reported an average of 1.8 moderate exacerbations and 0.9 SEV exacerbations. Overall, 16% of patients were employed and reported a high percentage of overall work impairment (42.4% ± 31.1%). Activity impairment was positively associated with recent exacerbation severity (SEV 64.6% ± 26.8% versus moderate 55.6% ± 28.2%) (P=0.006). The HRQoL was significantly worse for SEV versus VSEV COPD (EQ-5D: 0.62 ± 0.23 versus 0.70 ± 0.17, respectively, and SGRQ-C: 70.1 ± 21.3 versus 61.1 ± 19.0, respectively) (P<0.001). Worse current HRQoL was reported by patients with a SEV versus moderate recent exacerbation (EQ-5D: 0.63 ± 0.21 versus 0.70 ± 0.20, respectively) (P=0.003); SGRQ-C: 70.3 ± 19.9 versus 61.7 ± 20.1, respectively (P<0.001). One additional

  14. Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity.

    PubMed

    Hopp, Katharina; Ward, Christopher J; Hommerding, Cynthia J; Nasr, Samih H; Tuan, Han-Fang; Gainullin, Vladimir G; Rossetti, Sandro; Torres, Vicente E; Harris, Peter C

    2012-11-01

    Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations to PKD1 or PKD2, triggering progressive cystogenesis and typically leading to end-stage renal disease in midlife. The phenotypic spectrum, however, ranges from in utero onset to adequate renal function at old age. Recent patient data suggest that the disease is dosage dependent, where incompletely penetrant alleles influence disease severity. Here, we have developed a knockin mouse model matching a likely disease variant, PKD1 p.R3277C (RC), and have proved that its functionally hypomorphic nature modifies the ADPKD phenotype. While Pkd1+/null mice are normal, Pkd1RC/null mice have rapidly progressive disease, and Pkd1RC/RC animals develop gradual cystogenesis. These models effectively mimic the pathophysiological features of in utero-onset and typical ADPKD, respectively, correlating the level of functional Pkd1 product with disease severity, highlighting the dosage dependence of cystogenesis. Additionally, molecular analyses identified p.R3277C as a temperature-sensitive folding/trafficking mutant, and length defects in collecting duct primary cilia, the organelle central to PKD pathogenesis, were clearly detected for the first time to our knowledge in PKD1. Altogether, this study highlights the role that in trans variants at the disease locus can play in phenotypic modification of dominant diseases and provides a truly orthologous PKD1 model, optimal for therapeutic testing.

  15. Defining reactivity: how several methodological decisions can affect conclusions about emotional reactivity in psychopathology.

    PubMed

    Nelson, Brady D; Shankman, Stewart A; Olino, Thomas M; Klein, Daniel N

    2011-12-01

    There are many important methodological decisions that need to be made when examining emotional reactivity in psychopathology. In the present study, we examined the effects of two such decisions in an investigation of emotional reactivity in depression: (1) which (if any) comparison condition to employ; and (2) how to define change. Depressed (N = 69) and control (N = 37) participants viewed emotion-inducing film clips while subjective and facial responses were measured. Emotional reactivity was defined using no comparison condition (i.e., raw scores), baseline comparison condition (i.e., no stimulus presented), and neutral comparison condition (i.e., neutral stimulus presented). Change in emotional reactivity was assessed using four analytic approaches: difference scores, percentage change, residualised change, and ANCOVA. Results differed among the three comparison conditions and among several of the analytic approaches. Overall, our investigation suggests that choosing a comparison condition and the definition of change can significantly influence the presence of group differences in emotional reactivity. Recommendations for studies of emotional reactivity in psychopathology are discussed.

  16. [Mitigation effect of several controlled-release N fertilizers on ammonia volatilization and related affecting factors].

    PubMed

    Sun, Kejun; Mao, Xiaoyun; Lu, Qiming; Jia, Aiping; Liao, Zongwen

    2004-12-01

    By using static absorption and soil column leaching methods, this paper studied the behaviors of several controlled-release N fertilizers in soil under laboratory conditions. The results showed that under the application rate of 450 mg x kg(-1), total ammonia volatilization from three controlled-release fertilizers decreased by 49.7%, 28.0% and 71.2%, respectively, in comparing with common urea. When the application rate was 600 mg x kg(-1), total ammonia volatilization decreased by 34.6%, 12.3%, 69.9%, respectively. Controlled-release fertilizers could markedly reduce total ammonia volatilization from soil and decrease environment pollution via fertilization. The results also indicated that total ammonia volatilization correlated significantly with soil urease activity, pH value and N leaching rate. The correlation coefficient between total ammonia volatilization and accumulated N leaching rate was 0.9533, and that between total ammonia volatilization and soil urease activity and pH value was 0.9533 and 0.9908, respectively.

  17. The Factors That Affect Improvement of Neurogenic Bladder by Severe Lumbar Disc Herniation in Operation

    PubMed Central

    Jeon, Joon Bok; Kim, Do Keun; Kim, Ji-Yong

    2016-01-01

    Objective This study analyzed retrospectively the bladder function of patients after early surgery for cauda equina syndrome (CES) performed within 24 or 48 hours, or after 48 hours of the onset of autonomic symptoms. Methods We retrospectively reviewed the clinical data of 31 patients after decompression surgery for lumbar disc herniation (LDH) who had been diagnosed with CES between January 2001 and December 2014 at Inha University Hospital. The following factors were assessed to evaluate the influence of time to surgery: bladder function, rectal incontinence, sexual dysfunction, LDH level, and degree of spinal canal compression. Results After decompression, the outcome group was categorized into normal bladder function and abnormal bladder function. The patients operated on within 48 hours showed an improved postoperative outcome. Among 16 patients operated on within 48 hours, 13 (81%) recovered normal bladder function. In contrast, among 15 patients with decompression after 48 hours, 6 (40%) recovered normal bladder function. Among 21 patients with mild bladder dysfunction at admission, 16 (76%) recovered normal bladder function after decompression. Conclusion Our study suggests that patients who have decompression surgery within 48 hours of the onset of bladder dysfunction, improve their chances of recovering bladder function than those who have a late operation (>48 hours). Also, patients with mild bladder dysfunction are more likely to recover bladder function after decompression, than patients with severe bladder dysfunction. PMID:27799991

  18. Depressive Symptoms, Cardiac Disease Severity, and Functional Status in Patients With Coronary Artery Disease (from the Heart and Soul Study).

    PubMed

    Schopfer, David W; Regan, Mathilda; Heidenreich, Paul A; Whooley, Mary A

    2016-11-01

    Patient-reported health status is highly valued as a key measure of health care quality, yet little is known about the extent to which it is determined by subjective perception compared with objective measures of disease severity. We sought to compare the associations of depressive symptoms and objective measures of cardiac disease severity with perceived functional status in patients with stable coronary artery disease. We assessed depressive symptoms, severity of cardiovascular disease, and perceived functional status in a cross-sectional study of 1,023 patients with stable coronary artery disease. We compared the extent to which patient-reported functional status was influenced by depressive symptoms versus objective measures of disease severity. We then evaluated perceived functional status as a predictor of subsequent cardiovascular hospitalizations during 8.8 years of follow-up. Patients with depressive symptoms were more likely to report poor functional status than those without depressive symptoms (44% vs 17%; p <0.001). After adjustment for traditional risk factors and co-morbid conditions, independent predictors of poor functional status were depressive symptoms (odds ratio [OR] 2.68, 95% confidence interval [CI] 1.89 to 3.79), poor exercise capacity (OR 2.30, 95% CI 1.65 to 3.19), and history of heart failure (OR 1.61, 95% CI 1.12 to 2.29). Compared with patients who had class I functional status, those with class II functional status had a 96% greater rate (hazard ratio 1.96, 95% CI 1.15 to 3.34) and those with class III or IV functional status had a 104% greater rate (hazard ratio 2.04, 95% CI 1.12 to 3.73) of hospitalization for HF, adjusted for baseline demographic characteristics, co-morbidities, cardiac disease severity, and depressive symptoms. In conclusion, depressive symptoms and cardiac disease severity were independently associated with patient-reported functional status. This suggests that perceived functional status may be as strongly

  19. Infectious, inflammatory, and metabolic diseases affecting the athlete's spine.

    PubMed

    Metz, Lionel N; Wustrack, Rosanna; Lovell, Alberto F; Sawyer, Aenor J

    2012-07-01

    Sports and weight-bearing activities can have a positive effect on bone health in the growing, mature, or aging athlete. However, certain athletic activities and training regimens may place the athlete at increased risk for stress fractures in the spine. In addition, some athletes have an underlying susceptibility to fracture due to either systemic or focal abnormalities. It is important to identify and treat these athletes in order to prevent stress fractures and reduce the risk of osteoporosis in late adulthood. Therefore, the pre-participation physical examination offers a unique opportunity to screen athletes for metabolic bone disease through the history and physical examination. Positive findings warrant a thorough workup including a metabolic bone laboratory panel, and possibly a DEXA scan, which includes a lateral spine view.

  20. Adaptive autophagy in Alexander disease-affected astrocytes.

    PubMed

    Tang, Guomei; Yue, Zhenyu; Tallóczy, Zsolt; Goldman, James E

    2008-07-01

    The ubiquitin-proteasome and autophagy-lysosomal pathways are the two main routes of protein and organelle clearance in eukaryotic cells. The proteasome system is responsible for unfolded, short-lived proteins, which precludes the clearance of oligomeric and aggregated proteins, whereas macroautophagy, a process generally referred to as autophagy, mediates mainly the bulk degradation of long-lived cytoplasmic proteins, large protein complexes or organelles.(1) Recently, the autophagy-lysosomal pathway has been implicated in neurodegenerative disorders as an important pathway for the clearance of abnormally accumulated intracellular proteins, such as huntingtin, tau, and mutant and modified α-synuclein.(1-6) Our recent study illustrated the induction of adaptive autophagy in response to mutant glial fibrillary acidic protein (GFAP) accumulation in astrocytes, in the brains of patients with Alexander disease (AxD), and in mutant GFAP knock-in mouse brains.(7) This autophagic response is negatively regulated by mammalian target of rapamycin (mTOR). The activation of p38 MAPK by GFAP accumulation is responsible for mTOR inactivation and the induction of autophagy. We also found that the accumulation of GFAP impairs proteasome activity.(8) In this commentary we discuss the potential compensatory relationship between an impaired proteasome and activated autophagy, and propose that the MLK-MAPK (mixed lineage kinase-mitogen-activated protein kinase) cascade is a regulator of this crosstalk. Addendum to: Tang G, Yue Z, Talloczy, Z, Hagemann T, Cho W, Sulzer D, Messing A, Goldman JE. Alexander disease-mutant GFAP accumulation stimulates autophagy through p38 MAPK and mTOR signaling pathways. Hum Mol Genetics 2008; In press.

  1. Non-Dimensional Formulation of Ventricular Work-Load Severity Under Concomitant Heart Valve Disease

    NASA Astrophysics Data System (ADS)

    Dong, Melody; Simon-Walker, Rachael; Dasi, Lakshmi

    2012-11-01

    Current guidelines on assessing the severity of heart valve disease rely on dimensional disease specific measures and are thus unable to capture severity under a concomitant heart valve disease scenario. Experiments were conducted to measure ventricular work-load in an in-house in-vitro left heart simulator. In-house tri-leaflet heart valves were built and parameterized to model concomitant heart valve disease. Measured ventricular power varied non-linearly with cardiac output and mean aortic pressure. Significant data collapse could be achieved by the non-dimensionalization of ventricular power with cardiac output, fluid density, and a length scale. The dimensionless power, Circulation Energy Dissipation Index (CEDI), indicates that concomitant conditions require a significant increase in the amount of work needed to sustain cardiac function. It predicts severity without the need to quantify individual disease severities. This indicates the need for new fluid-dynamics similitude based clinical guidelines to assist patients with multiple heart valve diseases. Funded by the American Heart Association.

  2. Combined pesticide exposure severely affects individual- and colony-level traits in bees.

    PubMed

    Gill, Richard J; Ramos-Rodriguez, Oscar; Raine, Nigel E

    2012-11-01

    Reported widespread declines of wild and managed insect pollinators have serious consequences for global ecosystem services and agricultural production. Bees contribute approximately 80% of insect pollination, so it is important to understand and mitigate the causes of current declines in bee populations . Recent studies have implicated the role of pesticides in these declines, as exposure to these chemicals has been associated with changes in bee behaviour and reductions in colony queen production. However, the key link between changes in individual behaviour and the consequent impact at the colony level has not been shown. Social bee colonies depend on the collective performance of many individual workers. Thus, although field-level pesticide concentrations can have subtle or sublethal effects at the individual level, it is not known whether bee societies can buffer such effects or whether it results in a severe cumulative effect at the colony level. Furthermore, widespread agricultural intensification means that bees are exposed to numerous pesticides when foraging, yet the possible combinatorial effects of pesticide exposure have rarely been investigated. Here we show that chronic exposure of bumblebees to two pesticides (neonicotinoid and pyrethroid) at concentrations that could approximate field-level exposure impairs natural foraging behaviour and increases worker mortality leading to significant reductions in brood development and colony success. We found that worker foraging performance, particularly pollen collecting efficiency, was significantly reduced with observed knock-on effects for forager recruitment, worker losses and overall worker productivity. Moreover, we provide evidence that combinatorial exposure to pesticides increases the propensity of colonies to fail.

  3. Combined pesticide exposure severely affects individual- and colony-level traits in bees

    PubMed Central

    Gill, Richard J.; Ramos-Rodriguez, Oscar; Raine, Nigel E.

    2012-01-01

    Reported widespread declines of wild and managed insect pollinators have serious consequences for global ecosystem services and agricultural production1-3. Bees contribute around 80% of insect pollination, so it is imperative we understand and mitigate the causes of current declines4-6. Recent studies have implicated the role of pesticides as exposure to these chemicals has been associated with changes in bee behaviour7-11 and reductions in colony queen production12. However the key link between changes in individual behaviour and consequent impact at the colony level has not been shown. Social bee colonies depend on the collective performance of numerous individual workers. So whilst field-level pesticide concentrations can have a subtle/sublethal effect at the individual level8, it is not known whether bee societies can buffer such effects or if it results in a severe cumulative effect at the colony level. Furthermore, widespread agricultural intensification means bees are exposed to numerous pesticides when foraging13-15, yet the possible combinatorial effects of pesticide exposure have rarely been investigated16,17. Here we show that chronic exposure of bumblebees to two pesticides (neonicotinoid and pyrethroid) at concentrations that could approximate field-level exposure impairs natural foraging behaviour and increases worker mortality leading to significant reductions in brood development and colony success. We found worker foraging performance, particularly pollen collecting efficiency, was significantly reduced with observed knock-on effects for forager recruitment, worker losses and overall worker productivity. Moreover, we provide evidence that combinatorial exposure to pesticides increases the propensity of colonies to fail. PMID:23086150

  4. Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation.

    PubMed

    Guidine, Patrícia Alves Maia; Cash, Diana; Drumond, Luciana Estefani; de Souza E Rezende, Gustavo Henrique; Massensini, André Ricardo; Williams, Steve Charles Rees; Moraes-Santos, Tasso; Moraes, Márcio Flávio Dutra; Mesquita, Michel Bernanos Soares

    2014-01-01

    Severe scorpion envenoming (SSE) is more frequent in children and is characterized by systemic dysfunctions with a mortality rate of up to 9%. Recent evidence shows that the central nervous system (CNS) plays a key role in triggering the cascade of symptoms present in SSE. The age-dependent role of the CNS in SSE lethality may be summarized in 3 hypotheses: (1) the shown increased blood brain barrier permeability of infants to the toxins would especially and primarily compromise neurovegetative control areas, (2) the neurons within these areas have high affinity to the toxins, and (3) the neurovascular interaction is such that SSE metabolically compromises proper function of toxin-targeted areas. A pharmacological magnetic resonance imaging paradigm was used to evaluate localized hemodynamic changes in relative cerebral blood volume (rCBV) for 30 min after the injection of TsTX, the most lethal toxin from the venom of the Tityus serrulatus scorpion. The brainstem showed significant rCBV reduction 1 min after TsTX administration, whereas rostral brain areas had delayed increase in rCBV (confirmed by laser Doppler measurements of cortical cerebral blood flow). Moreover, metabolic activity by 14C-2-deoxyglucose autoradiography showed the highest relative increase at the brainstem. To test whether TsTX has high affinity to brainstem neurons, the lateral ventricle was injected with Alexa Fluor 568 TsTX. Although some neurons showed intense fluorescence, the labeling pattern suggests that specific neurons were targeted. Altogether, these results suggest that brainstem areas involved in neurovegetative control are most likely within the primary structures triggering the cascade of symptoms present in SSE.

  5. FoxP3+ Regulatory T Cells Determine Disease Severity in Rodent Models of Inflammatory Neuropathies

    PubMed Central

    Meyer zu Hörste, Gerd; Cordes, Steffen; Mausberg, Anne K.; Zozulya, Alla L.; Wessig, Carsten; Sparwasser, Tim; Mathys, Christian; Wiendl, Heinz; Hartung, Hans-Peter; Kieseier, Bernd C.

    2014-01-01

    Inflammatory neuropathies represent disabling human autoimmune disorders with considerable disease variability. Animal models provide insights into defined aspects of their disease pathogenesis. Forkhead box P3 (FoxP3)+ regulatory T lymphocytes (Treg) are anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. Dysfunction or a reduced frequency of Tregs have been associated with different human autoimmune disorders. We here analyzed the functional relevance of Tregs in determining disease manifestation and severity in murine models of autoimmune neuropathies. We took advantage of the DEREG mouse system allowing depletion of Treg with high specificity as well as anti-CD25 directed antibodies to deplete Tregs in mice in actively induced experimental autoimmune neuritis (EAN). Furthermore antibody-depletion was performed in an adoptive transfer model of chronic neuritis. Early Treg depletion increased clinical EAN severity both in active and adoptive transfer chronic neuritis. This was accompanied by increased proliferation of myelin specific T cells and histological signs of peripheral nerve inflammation. Late stage Treg depletion after initial disease manifestation however did not exacerbate inflammatory neuropathy symptoms further. We conclude that Tregs determine disease severity in experimental autoimmune neuropathies during the initial priming phase, but have no major disease modifying function after disease manifestation. Potential future therapeutic approaches targeting Tregs should thus be performed early in inflammatory neuropathies. PMID:25286182

  6. Efficacy and safety of memantine in moderate-to-severe Alzheimer disease: the evidence to date.

    PubMed

    Bullock, Roger

    2006-01-01

    Memantine, a moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist, is currently the only agent approved for moderately severe to severe Alzheimer disease (AD) in Europe and for moderate-to-severe Alzheimer disease in the United States. In clinical trials, memantine has consistently demonstrated a reduced rate of deterioration on global, cognitive, functional, and behavioral measures, across a range of outcome measures compared with usual care. Notably, improvements versus placebo were seen in individual activities of daily living and behavior, particularly agitation. Efficacy was demonstrated in patients with newly diagnosed Alzheimer disease, patients previously or currently receiving acetylcholinesterase inhibitors, and both institutionalized and community-dwelling Alzheimer disease patients. Memantine has a tolerability profile similar to placebo. This review presents the results of key clinical trials, and includes clinically relevant analyses, such as numbers-needed-to-treat and effect sizes. Increased dependency and institutionalization are significant cost drivers in Alzheimer disease. Memantine is able to reduce dependency, caregiver time required, and mean monthly caregiver and societal costs. Recent studies of the relationship between Alzheimer disease progression, caregiver burden, and healthcare costs emphasize the need for treatments such as memantine that can slow the rate of decline in Alzheimer disease.

  7. Low serum albumin concentrations are associated with disease severity in patients with myasthenia gravis

    PubMed Central

    Weng, Yi-Yun; Yang, De-Hao; Qian, Mei-Zi; Wei, Mao-Mao; Yin, Fang; Li, Jia; Li, Xiang; Chen, Ying; Ding, Zhang-Na; He, Yi-Bo; Zhang, Xu

    2016-01-01

    Abstract Serum albumin (S-Alb) is a widely used biomarker of nutritional status and disease severity in patients with autoimmune diseases. We investigated the correlation between S-Alb and the severity of myasthenia gravis (MG). A total number of 166 subjects were recruited in the study. Subjects were divided into 3 groups (T1 to T3) by S-Alb levels: T1: 21.1 to 38.4 g/L, T2: 38.5 to 41.5 g/L, T3: 41.6 to 48.9 g/L. Regression analysis was performed to determine the correlation of initial albumin concentrations and the severity of disease of MG. Lower levels of S-Alb were observed in subjects with increased disease severity than those with slight disease severity, meanwhile, incidence of myasthenia crisis increased in the lower albumin tertiles (P < 0.001). The disease severity assessment was performed according to the criteria established by the Myasthenia Gravis Foundation of America. After adjusting for age, sex, body mass index (BMI), and duration of disease, it showed that higher S-Alb concentrations were associated with lower disease severity. Odds ratios (ORs) of T2 to T3 were 0.241 (95% CI: 0.103–0.566, P < 0.001), 0.140 (95% CI: 0.054–0.367, P < 0.001) when compared with subjects in the T1, respectively. When subjects were stratified into hypoalbuminemia and normal albumin groups, we found that the association between S-Alb and MG remained significant in the hypoalbuminemia group only (OR: 0.693, 95% CI: 0.550–0.874, P = 0.002) after further adjustment for age, sex, BMI, and duration of disease. This is the first study to demonstrate that S-Alb was independently associated with MG severity. In patients with low S-Alb, S-Alb concentration could be a potential biomarker for MG disability. PMID:27684858

  8. Does Parkinson's disease affect judgement about another person's action?

    PubMed

    Poliakoff, E; Galpin, A J; Dick, J P R; Tipper, S P

    2010-07-01

    The observer's motor system has been shown to be involved in observing the actions of another person. Recent findings suggest that people with Parkinson's disease do not show the same motor facilitatory effects when observing the actions of another person. We studied whether Parkinson's patients were able to make unspeeded judgements about another person's action. Participants were asked to watch video clips of an actor lifting a box containing different weights (100, 200, 300 or 400 g) and to guess the weight that was being lifted on a 9-point scale. We compared the performance of 16 patients with PD with 16 healthy age-matched controls. Both groups were able to do the task, showing a significant relationship between the real weight and the guessed weight, albeit with a tendency to overestimate the lowest weight and underestimate the heaviest weight. The PD patients, however, showed a reduced slope value. These results show that despite their own motor deficits, PD patients are still able to judge the weight being lifted by another person, albeit with a slight reduction in accuracy. Further research will be required to determine whether PD patients use a motor simulation or a visual compensatory strategy to achieve this.

  9. Social-adaptive and psychological functioning of patients affected by Fabry disease.

    PubMed

    Laney, Dawn Alyssia; Gruskin, Daniel J; Fernhoff, Paul M; Cubells, Joseph F; Ousley, Opal Y; Hipp, Heather; Mehta, Ami J

    2010-12-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of alpha-galactosidase A. In addition to the debilitating physical symptoms of FD, there are also under-recognized and poorly characterized psychiatric features. As a first step toward characterizing psychiatric features of FD, we administered the Achenbach adult self report questionnaire to 30 FD patients and the Achenbach adult behavior checklist questionnaire to 28 partners/parents/friends of FD patients. Data from at least one of the questionnaires were available on 33 subjects. Analysis focused on social-adaptive functioning in various aspects of daily life and on criteria related to the Diagnostic and statistical manual of mental disorders IV (DSM-IV). Adaptive functioning scale values, which primarily measure social and relationship functioning and occupational success, showed that eight FD patients (six female and two male) had mean adaptive functioning deficits as compared to population norms. Greater rates of depression (P < 0.01), anxiety (P = 0.05), depression and anxiety (P = 0.03), antisocial personality (P < 0.001), attention-deficit/hyperactivity (AD/H; P < 0.01), hyperactivity-impulsivity (P < 0.01), and aggressive behavior (P = 0.03) were associated with poorer adaptive functioning. Decreased social-adaptive functioning in this study was not statistically significantly associated to disease severity, pain, or level of vitality. This study shows for the first time that FD patients, particularly women, are affected by decreased social-adaptive functioning. Comprehensive treatment plans for FD should consider assessments and interventions to evaluate and improve social, occupational, and psychological functioning. Attention to the behavioral aspects of FD could lead to improved treatment outcome and improved quality of life. Individuals affected by Fabry disease exhibited social-adaptive functioning deficits that were significantly correlated with anxiety

  10. The relationship between aminopyrine breath test and severity of liver disease in cirrhosis

    SciTech Connect

    Morelli, A.; Narducci, F.; Pelli, M.A.; Farroni, F.; Vedovelli, A.

    1981-08-01

    Twenty-two patients with cirrhosis were evaluated by the 2 hr.-(C14)-aminopyrine breath test, the conventional liver tests and two systems for grading the severity of liver disease. Twenty-three patients with noncirrhotic liver disease and 15 controls were also studied. Reduced 14CO2 values were found in 21 of the 22 cirrhotic patients and seven of those had noncirrhotic liver disease associated with severe functional reserve impairment. The values in patients with minor liver diseases or cholestasis were normal. In the cirrhotic patients 2 hr.-(C14)-aminopyrine breath test scores correlated with prothrombin time, retention of bromosulfalein, fasting serum bile acid, albumin, bilirubin, serum aspartate aminotransferase and, above all, with the scores of the two clinical rating systems. The 2 hr.-(C14)-aminopyrine breath test was superior to conventional tests in quantifying the degree of hepatic functional reserve and forecasting the prognosis.

  11. Familial Mediterranean fever in two Bedouin families: mutation analysis and disease severity.

    PubMed

    Press, J; Shinar, Y; Langevitz, P; Livneh, A; Pras, M; Buskila, D

    2000-06-05

    Familial Mediterranean fever (FMF) is an autosomal recessive disease prevalent among non-Ashkenazi Jews, Armenians, Arabs, and Turks. The Bedouin are nomad Arab tribes residing in desert margins of the Middle East and Arabia. FMF is quite rare in Bedouins, and here we report on two Bedouin families from southern Israel suffering from this disorder. The MEFV mutations found in the Bedouin patients M694I, V726A, and E148Q are consistent with their Arab origin. The disease severity score showed a mild to moderate severity disease in six patients. The Bedouins, leading a unique nomadic life, may prove instrumental in unraveling the role of environmental factors in the course and severity of FMF.

  12. Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox.

    PubMed

    Lavie, Carl J; McAuley, Paul A; Church, Timothy S; Milani, Richard V; Blair, Steven N

    2014-04-15

    Obesity has been increasing in epidemic proportions, with a disproportionately higher increase in morbid or class III obesity, and obesity adversely affects cardiovascular (CV) hemodynamics, structure, and function, as well as increases the prevalence of most CV diseases. Progressive declines in physical activity over 5 decades have occurred and have primarily caused the obesity epidemic. Despite the potential adverse impact of overweight and obesity, recent epidemiological data have demonstrated an association of mild obesity and, particularly, overweight on improved survival. We review in detail the obesity paradox in CV diseases where overweight and at least mildly obese patients with most CV diseases seem to have a better prognosis than do their leaner counterparts. The implications of cardiorespiratory fitness with prognosis are discussed, along with the joint impact of fitness and adiposity on the obesity paradox. Finally, in light of the obesity paradox, the potential value of purposeful weight loss and increased physical activity to affect levels of fitness is reviewed.

  13. Correlation of the serum concentrations of tumour necrosis factor and nitric oxide with disease severity in chronic Chagas disease (American trypanosomiasis).

    PubMed

    Pérez-Fuentes, R; López-Colombo, A; Ordóñez-Toquero, G; Gomez-Albino, I; Ramos, J; Torres-Rasgado, E; Salgado-Rosas, H; Romero-Díaz, M; Pulido-Pérez, P; Sánchez-Guillén, M C

    2007-03-01

    Pro-inflammatory cytokines such as tumour necrosis factor (TNF) and nitric oxide (NO) are believed to play an important role in the severity of chronic disease. When evaluated in 71 patients who were seropositive for Trypanosoma cruzi and 50 apparently healthy controls, the mean (S.D.) serum concentrations of both TNF [7.65 (1.32) nu. 4.24 (1.53) ng/ml; P<0.001] and NO [114 (40) nu. 74 (21) microM; P<0.0001] were found to be significantly higher in the patients than in the controls. In addition, patients with chronic, symptomatic disease affecting their hearts--eight with dilated cardiomyopathy [8.82 (1.47) ng TNF/ml; 142 (45) microM NO] and 17 others with electrocardiographic alterations [8.37 (1.26) ng TNF/ml; 134 (53) microM NO]--had significantly higher serum concentrations of these cytokines than 34 patients who were in the asymptomatic, indeterminate phase of the disease [6.38 (1.35) ng TNF/ml; 99 (28) microM NO]. In those infected with T. cruzi, it therefore appears that serum concentrations of TNF and NO correlate with disease severity, indicating that these cytokines play some role in the pathogenesis of chronic Chagas disease.

  14. Polyparasitism Is Associated with Increased Disease Severity in Toxoplasma gondii-Infected Marine Sentinel Species

    PubMed Central

    Gibson, Amanda K.; Raverty, Stephen; Lambourn, Dyanna M.; Huggins, Jessica; Magargal, Spencer L.; Grigg, Michael E.

    2011-01-01

    In 1995, one of the largest outbreaks of human toxoplasmosis occurred in the Pacific Northwest region of North America. Genetic typing identified a novel Toxoplasma gondii strain linked to the outbreak, in which a wide spectrum of human disease was observed. For this globally-distributed, water-borne zoonosis, strain type is one variable influencing disease, but the inability of strain type to consistently explain variations in disease severity suggests that parasite genotype alone does not determine the outcome of infection. We investigated polyparasitism (infection with multiple parasite species) as a modulator of disease severity by examining the association of concomitant infection of T. gondii and the related parasite Sarcocystis neurona with protozoal disease in wild marine mammals from the Pacific Northwest. These hosts ostensibly serve as sentinels for the detection of terrestrial parasites implicated in water-borne epidemics of humans and wildlife in this endemic region. Marine mammals (151 stranded and 10 healthy individuals) sampled over 6 years were assessed for protozoal infection using multi-locus PCR-DNA sequencing directly from host tissues. Genetic analyses uncovered a high prevalence and diversity of protozoa, with 147/161 (91%) of our sampled population infected. From 2004 to 2009, the relative frequency of S. neurona infections increased dramatically, surpassing that of T. gondii. The majority of T. gondii infections were by genotypes bearing Type I lineage alleles, though strain genotype was not associated with disease severity. Significantly, polyparasitism with S. neurona and T. gondii was common (42%) and was associated with higher mortality and more severe protozoal encephalitis. Our finding of widespread polyparasitism among marine mammals indicates pervasive contamination of waterways by zoonotic agents. Furthermore, the significant association of concomitant infection with mortality and protozoal encephalitis identifies polyparasitism as

  15. Disseminated Bacille Calmette-Guerin (BCG) disease in an infant with severe combined immunodeficiency.

    PubMed

    Sohail, Shagufta; Afzal, Muhammad; Anwar, Vaqas; Shama, Quratulain

    2014-11-01

    Bacille Calmette-Guerin (BCG) vaccine is administered to all newborns in countries where tuberculosis is still endemic. It is a live attenuated vaccine and considered quite safe in immunocompetent children. Disseminated BCG disease is the most serious complication seen only in individuals with underlying primary or secondary immunodeficiencies. We report a case of disseminated BCG disease in an infant with Severe Combined Immunodeficiency (SCID) who received BCG administration prior to diagnosis of SCID.

  16. First Experimental In Vivo Model of Enhanced Dengue Disease Severity through Maternally Acquired Heterotypic Dengue Antibodies

    PubMed Central

    Ng, Jowin Kai Wei; Zhang, Summer Lixin; Tan, Hwee Cheng; Yan, Benedict; Maria Martinez Gomez, Julia; Tan, Wei Yu; Lam, Jian Hang; Tan, Grace Kai Xin; Ooi, Eng Eong; Alonso, Sylvie

    2014-01-01

    Dengue (DEN) represents the most serious arthropod-borne viral disease. DEN clinical manifestations range from mild febrile illness to life-threatening hemorrhage and vascular leakage. Early epidemiological observations reported that infants born to DEN-immune mothers were at greater risk to develop the severe forms of the disease upon infection with any serotype of dengue virus (DENV). From these observations emerged the hypothesis of antibody-dependent enhancement (ADE) of disease severity, whereby maternally acquired anti-DENV antibodies cross-react but fail to neutralize DENV particles, resulting in higher viremia that correlates with increased disease severity. Although in vitro and in vivo experimental set ups have indirectly supported the ADE hypothesis, direct experimental evidence has been missing. Furthermore, a recent epidemiological study has challenged the influence of maternal antibodies in disease outcome. Here we have developed a mouse model of ADE where DENV2 infection of young mice born to DENV1-immune mothers led to earlier death which correlated with higher viremia and increased vascular leakage compared to DENV2-infected mice born to dengue naïve mothers. In this ADE model we demonstrated the role of TNF-α in DEN-induced vascular leakage. Furthermore, upon infection with an attenuated DENV2 mutant strain, mice born to DENV1-immune mothers developed lethal disease accompanied by vascular leakage whereas infected mice born to dengue naïve mothers did no display any clinical manifestation. In vitro ELISA and ADE assays confirmed the cross-reactive and enhancing properties towards DENV2 of the serum from mice born to DENV1-immune mothers. Lastly, age-dependent susceptibility to disease enhancement was observed in mice born to DENV1-immune mothers, thus reproducing epidemiological observations. Overall, this work provides direct in vivo demonstration of the role of maternally acquired heterotypic dengue antibodies in the enhancement of dengue

  17. [Cardiopulmonary exercise testing in chronic obstructive pulmonary disease (COPD) - breath-functional characterization and disease severity assessment].

    PubMed

    Mühle, A; Obst, A; Winkler, J; Ewert, R

    2015-09-01

    COPD is a heterogeneous disease with a wide range of clinical phenotypes and breath-functional dysfunctions. Cardiopulmonary exercise testing (CPET) allows describing all component parts of breathing and determining exercise capacity and the mechanisms of exercise limitation. From these aspects 64 COPD patient stages II, III and IV according to the conventional GOLD classification were examined by means of CPET to evaluate whether CPET can provide a better functional characterization of COPD than the standard investigation procedures in pulmonary practice.We could show that in pulmonary practice CPET is safely and effectively practicable in stable COPD patients of all GOLD stages. This method allowed a clinical and prognostic disease severity assessment of all patients, proving important differences of peak oxygen uptake in each GOLD stage, so that patients in spite of identical GOLD disease severity were to be assigned to different prognostic groups according CPET criteria. Furthermore, we found relevant differences of individual breath-functional patterns in exercise, which can neither be objectified nor be prognosticated by standard investigation procedures at rest.Therefore CPET allows, aside from an objective clinical and prognostic disease severity assessment, also a breath-functional evaluation in a subtly way in COPD patients reflecting the multidimensional background of the disease with variable dysfunctions in pulmonary ventilation, gas exchange, circulation and muscular function as well as associated cardio vascular comorbidities. The breath-functional phenotyping of the COPD patient seems to be meaningful in particular for an individualised therapy management.

  18. [Moderate or severe aquired valvular heart disease in pregnancy--what does determine the management? Experence, intuition or guidelines?].

    PubMed

    Greszata, Lidia; Stępińska, Janina

    2015-01-01

    Epidemiology of acquired valvular heart diseases has changed significantly over last decades. Degenerative aortic valve stenosis is the most common acquired valvular disease with high prevalence in elderly population. Another common disorder is ischemic mitral regurgitation secondary to myocardial infarction. Both above-mentioned heart disorders are not typical for women in reproductive age. Rheumatic heart valve disease has become infrequent in Polish population. Mitral stenosis, the most prevalent of rheumatic valvular disorders, affects 5% of pregnant women with heart disease and rheumatic aortic stenosis is responsible for 0.5-3% of heart diseases in this population. Despite the fact that acquired valvular disorders are becoming less common among pregnant women, they still remain an important issue and their management should be well known. Discussion about pregnancy should be a part of management of young women with valvular heart disease. Severe valve disorders should be corrected when planning pregnancy. The final management should always be based on collaborative decision made by the patient and health professionals.

  19. A comparison of raters and disease assessment methods for estimating disease severity for purposes of hypothesis testing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Assessment of disease severity is most often made visually, and estimates can be inaccurate. Nearest percent estimates (NPEs) of Septoria leaf blotch on leaves of winter wheat by four raters (R1-R4) assessing non-treated (NT) and fungicide-treated (FT) plots were compared to true values using Lin’s ...

  20. Cross-Sectional Comparisons of Patient-Reported Disease Control, Disease Severity, and Symptom Frequency in Children with Atopic Dermatitis.

    PubMed

    Chang, J; Bilker, W B; Hoffstad, O; Margolis, D J

    2017-02-24

    Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that commonly affects children. Research in AD has utilized an increasing variety of scoring measures to monitor disease, and this lack of standardization has been cited as an obstacle to evidence-based decision making. The Harmonizing Outcome Measures for Eczema (HOME) initiative aims to establish consensus on a core set of outcome measures for AD and currently recommends the Patient-Oriented Eczema Measure (POEM) for recording patient-reported outcomes. This article is protected by copyright. All rights reserved.

  1. Scavenger receptor b2 as a receptor for hand, foot, and mouth disease and severe neurological diseases.

    PubMed

    Yamayoshi, Seiya; Fujii, Ken; Koike, Satoshi

    2012-01-01

    Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease (HFMD). Infection with EV71 is occasionally associated with severe neurological diseases such as acute encephalitis, acute flaccid paralysis, and cardiopulmonary failure. Because cellular receptors for viruses play an important role in cell, tissue, and species tropism, it is important to identify and characterize the receptor molecule. Recently, cellular receptors and host factors that stimulate EV71 infection have been identified. Several lines of evidence suggest that scavenger receptor class B, member 2 (SCARB2) plays critical roles in efficient EV71 infection and the development of disease in humans. In this review, we will summarize the findings of recent studies on EV71 infection and on the roles of SCARB2.

  2. Transcriptome assists prognosis of disease severity in respiratory syncytial virus infected infants

    PubMed Central

    Jong, Victor L.; Ahout, Inge M. L.; van den Ham, Henk-Jan; Jans, Jop; Zaaraoui-Boutahar, Fatiha; Zomer, Aldert; Simonetti, Elles; Bijl, Maarten A.; Brand, H. Kim; van IJcken, Wilfred F. J.; de Jonge, Marien I.; Fraaij, Pieter L.; de Groot, Ronald; Osterhaus, Albert D. M. E.; Eijkemans, Marinus J.; Ferwerda, Gerben; Andeweg, Arno C.

    2016-01-01

    Respiratory syncytial virus (RSV) causes infections that range from common cold to severe lower respiratory tract infection requiring high-level medical care. Prediction of the course of disease in individual patients remains challenging at the first visit to the pediatric wards and RSV infections may rapidly progress to severe disease. In this study we investigate whether there exists a genomic signature that can accurately predict the course of RSV. We used early blood microarray transcriptome profiles from 39 hospitalized infants that were followed until recovery and of which the level of disease severity was determined retrospectively. Applying support vector machine learning on age by sex standardized transcriptomic data, an 84 gene signature was identified that discriminated hospitalized infants with eventually less severe RSV infection from infants that suffered from most severe RSV disease. This signature yielded an area under the receiver operating characteristic curve (AUC) of 0.966 using leave-one-out cross-validation on the experimental data and an AUC of 0.858 on an independent validation cohort consisting of 53 infants. A combination of the gene signature with age and sex yielded an AUC of 0.971. Thus, the presented signature may serve as the basis to develop a prognostic test to support clinical management of RSV patients. PMID:27833115

  3. Does cyclophosphamide still have a role in the treatment of severe inflammatory eye disease?

    PubMed

    Wakefield, Denis

    2014-08-01

    Cyclophosphamide is a highly effective immunosuppressive drug that has proven efficacy in the treatment of patients with severe inflammatory eye disease. It has the advantage of being able to be used either orally or intravenously, has a potent steroid-sparing effect, and is effective in inducing disease remission. The major limitations to the use of this alkylating agent are its frequent side effects. With the increasing availability of alternate forms of therapy it is time to review the therapeutic regimen for cyclophosphamide use in patients with inflammatory eye disease.

  4. Estrogen exposure, obesity and thyroid disease in women with severe pulmonary hypertension

    PubMed Central

    2009-01-01

    Severe pulmonary hypertension is a lethal group of disorders which preferentially afflicts women. It appears that in recent years the patient profile has shifted towards older, obese, and postmenopausal women, suggesting that endocrine factors may be important. Several studies have revealed an increased prevalence of thyroid disease in these patients, but no studies have evaluated for a coexistence of endocrine factors. In particular, no studies have attempted to evaluate for concurrent thyroid disease, obesity and long-term estrogen exposure in patients. 88 patients attending the Pulmonary Hypertension Association 8th International meeting completed a questionnaire and were interviewed. Information was collected regarding reproductive history, height, weight, and previous diagnosis of thyroid disease. 46% met criteria for obesity. 41% reported a diagnosis of thyroid disease. 81% of women reported prior use of hormone therapy. 70% reported greater than 10 years of exogenous hormone use. 74% of female patients reported two or more of potentially disease modifying endocrine factors (obesity, thyroid disease or estrogen therapy). The coexistent high prevalence in our cohort of exogenous estrogen exposure, thyroid disease and obesity suggests that an interaction of multiple endocrine factors might contribute to the pathogenesis of pulmonary hypertension and may represent epigenetic modifiers in genetically-susceptible individuals. PMID:19748850

  5. 25-Hydroxy-Vitamin D Concentration Is Not Affected by Severe or Non-Severe Pneumonia, or Inflammation, in Young Children

    PubMed Central

    Haugen, Johanne; Chandyo, Ram K.; Ulak, Manjeswori; Mathisen, Maria; Basnet, Sudha; Brokstad, Karl A.; Valentiner-Branth, Palle; Shrestha, Prakash S.; Strand, Tor A.

    2017-01-01

    Poor vitamin D status has been associated with increased risk and severity of respiratory tract infections. Whether or not inflammation and infection affects 25-hydroxy vitamin D (25(OH)D) concentration is controversial and is important in the interpretation of observational studies using plasma-25(OH)D as a biomarker for status. Our objectives were to measure whether 25(OH)D concentration was altered by an episode of acute lower respiratory tract infection and whether markers of inflammation predicted the 25(OH)D concentration. Children aged 2–35 months with severe (n = 43) and non-severe (n = 387) community-acquired, WHO-defined pneumonia were included. 25(OH)D concentration and inflammatory markers (cytokines, chemokines, and growth factors) were measured in plasma during the acute phase and 14, 45, and 90 days later. Predictors for 25(OH)D concentrations were identified in multiple linear regression models. Mean 25(OH)D concentration during the acute phase and after recovery (14, 45, and 90 days) was 84.4 nmol/L ± 33.6, and 80.6 ± 35.4, respectively. None of the inflammatory markers predicted 25(OH)D concentration in the multiple regression models. Age was the most important predictor for 25(OH)D concentration, and there were no differences in 25(OH)D concentrations during illness and after 14, 45, and 90 days when adjusting for age. Infection and inflammation did not alter the 25(OH)D concentration in young children with acute lower respiratory tract infections. PMID:28106720

  6. White matter microstructure among youth with perinatally acquired HIV is associated with disease severity

    PubMed Central

    Uban, Kristina A.; Herting, Megan M.; Williams, Paige L.; Ajmera, Tanvi; Gautam, Prapti; Yanling, Huo; Malee, Kathleen M.; Yogev, Ram; Csernansky, John G.; Wang, Lei; Nichols, Sharon L.; Sowell, Elizabeth R.

    2015-01-01

    Objectives We investigated whether HIV disease severity was associated with alterations in structural brain connectivity, and whether those alterations in turn were associated with cognitive deficits in youth with perinatally-acquired HIV (PHIV). Design PHIV youth (n=40) from the Pediatric HIV/AIDS Cohort Study (PHACS) (mean age: 16±2 yrs) were included to evaluate how current and past disease severity measures (recent/nadir CD4%; peak viral load) relate to white matter (WM) microstructure within PHIV youth. PHIV youth were compared to 314 controls from the Pediatric Imaging, Neurocognition, and Genetics (PING) study. Methods Diffusion tensor imaging and tractography were utilized to assess WM microstructure. Mediation analyses were conducted to examine whether microstructure alterations contributed to relationships between higher disease severity and specific cognitive domains in PHIV youth. Results Whole brain fractional anisotropy (FA) was reduced, but radial (RD) and mean (MD) diffusivity were increased, in PHIV compared to control youth. Within PHIV youth, more severe past HIV disease was associated with reduced FA of the right inferior fronto-occipital (IFO) and left uncinate tracts; elevated MD of the F minor; and increased streamlines comprising the left inferior longitudinal fasciculus (ILF). Associations of higher peak viral load with lower working memory performance were partly mediated by reductions in right IFO FA levels. Conclusion Our findings suggest that PHIV youth have higher risk of alterations in WM microstructure compared to typically developing youth, and certain alterations are related to past disease severity. Further, WM alterations potentially mediate associations between HIV disease and working memory. PMID:26125138

  7. Three or more copies of the proteolipid protein gene PLP1 cause severe Pelizaeus-Merzbacher disease.

    PubMed

    Wolf, Nicole I; Sistermans, Erik A; Cundall, Maria; Hobson, Grace M; Davis-Williams, Angelique P; Palmer, Rodger; Stubbs, Paula; Davies, Sally; Endziniene, Milda; Wu, Yvonne; Chong, Wui K; Malcolm, Sue; Surtees, Robert; Garbern, James Y; Woodward, Karen J

    2005-04-01

    We describe five boys from different families with an atypically severe form of Pelizaeus-Merzbacher disease (PMD) who have three, and in one case, five copies of the proteolipid protein (PLP1) gene. This is the first report of more than two copies of PLP1 in PMD patients and clearly demonstrates that severe clinical symptoms are associated with increased PLP1 gene dosage. Previously, duplications, deletions and mutations of the PLP1 gene were reported to give rise to this X-linked disorder. Patients with PLP1 duplication are usually classified as having either classical or transitional PMD rather than the more rare severe connatal form. The clinical symptoms of the five patients in this study included lack of stable head control and severe mental retardation, with three having severe paroxysmal disorder and two dying before the first year of life. Gene dosage was determined using interphase FISH (fluorescence in situ hybridization) and the novel approach of multiple ligation probe amplification (MLPA). We found FISH unreliable for dosage detection above the level of a duplication and MLPA to be more accurate in determination of specific copy number. Our finding that three or more copies of the gene give rise to a more severe phenotype is in agreement with observations in transgenic mice where severity of disease increased with Plp1 gene dosage and level of overexpression. The patient with five copies of PLP1 was not more affected than those with a triplication, suggesting that there is possibly a limit to the level of severity or that other genetic factors influence the phenotype. It highlights the significance of PLP1 dosage in CNS myelinogenesis as well as the importance of accurate determination of PLP1 gene copy number in the diagnosis of PMD and carrier detection.

  8. Evaluating the Impact of Breastfeeding on Rotavirus Antigenemia and Disease Severity in Indian Children

    PubMed Central

    Das, Sushmita; Sahoo, Ganesh Chandra; Das, Pradeep; Singh, Utpal Kant; Jaiswal, Anil Kumar; Singh, Prachi; Kumar, Ranjeet; Kumar, Rishikesh

    2016-01-01

    Objectives To evaluate the contribution of breastfeeding to Rotavirus (RV)-induced antigenemia and/or RNAemia and disease severity in Indian children (<2 yrs age). Methods Paired stool and serum samples were collected from (a) hospitalized infants with diarrhea (n = 145) and (b) healthy control infants without diarrhea (n = 28). Stool RV-antigen was screened in both groups by commercial rapid-test and enzyme immunoassay. The disease severity was scored and real-time-PCR was used for viral-load estimation. Serum was evaluated for RV-antigenemia by EIA and RV-RNAemia by RT-PCR. Data was stratified by age-group and breastfeeding status and compared. Results Presence of RV-antigenemia and RV-RNAemia was positively related with presence of RV in stool. Disease severity and stool viral-load was significantly associated with RV-antigenemia[(r = 0.74; CI:0.66 to 0.84; P<0.0001,R2 = 0.59) and (r = -0.55; CI:-0.68 to -0.39; P<0.0001,R2 = 0.31) respectively], but not with RV-RNAemia. There was significant reduction in RV-antigenemiarate in the breast-fed group compared to non-breastfed infants, especially in 0–6 month age group (P<0.001). Non-breastfed infants were at risk for RV-antigenemia with severe disease manifestations in form of high Vesikari scores correlating with high fever, more vomiting episodes and dehydration. Conclusion RV-antigenemia was common in nonbreastfed children with severe RV-diarrhea and correlated with stool RV-load and disease severity. PMID:26828823

  9. Parameter on systemic conditions affected by periodontal diseases. American Academy of Periodontology.

    PubMed

    2000-05-01

    The American Academy of Periodontology has developed the following parameter on systemic conditions affected by periodontal diseases. It is well known that systemic conditions may affect the onset, progression, and treatment of such diseases (see Parameter on Periodontitis Associated With Systemic Conditions, pages 876-879). The concept of periodontal diseases as localized entities affecting only the teeth and supporting apparatus is increasingly being questioned. Periodontal diseases may have widespread systemic effects. While these effects may be limited in some individuals, periodontal infections may significantly impact systemic health in others, and may serve as risk indicators for certain systemic diseases or conditions. As part of the approach to establishing and maintaining health, patients should be informed of the possible effects of periodontal infection on their overall well-being. Given this information, patients should then be able to make informed decisions regarding their periodontal therapy.

  10. The Impact of Cardiac Diseases during Pregnancy on Severe Maternal Morbidity and Mortality in Brazil

    PubMed Central

    Campanharo, Felipe F.; Cecatti, Jose G.; Haddad, Samira M.; Parpinelli, Mary A.; Born, Daniel; Costa, Maria L.; Mattar, Rosiane

    2015-01-01

    Background To evaluate maternal heart disease as a cause or complicating factor for severe morbidity in the setting of the Brazilian Network for Surveillance of Severe Maternal Morbidity. Methods and Findings Secondary data analysis of this multicenter cross-sectional study was implemented in 27 referral obstetric units in Brazil. From July 2009 to June 2010, a prospective surveillance was conducted among all delivery hospitalizations to identify cases of severe maternal morbidity (SMM), including Potentially Life-Threatening Conditions (PLTC) and Maternal Near Miss (MNM), using the new criteria established by the WHO. The variables studied included: sociodemographic characteristics, clinical and obstetric history of the women; perinatal outcome and the occurrence of maternal outcomes (PLTC, MNM, MD) between groups of cardiac and non-cardiac patients. Only heart conditions with hemodynamic impact characterizing severity of maternal morbidity were considered. 9555 women were included in the Network with severe pregnancy-related complications: 770 maternal near miss cases and 140 maternal death cases. A total of 293 (3.6%) cases were related to heart disease and the condition was known before pregnancy in 82.6% of cases. Maternal near miss occurred in 15% of cardiac disease patients (most due to clinical-surgical causes, p<0.001) and 7.7% of non-cardiac patients (hemorrhagic and hypertensive causes, p<0.001). Maternal death occurred in 4.8% of cardiac patients and in 1.2% of non-cardiac patients, respectively. Conclusions In this study, heart disease was significantly associated with a higher occurrence of severe maternal outcomes, including maternal death and maternal near miss, among women presenting with any severe maternal morbidity. PMID:26650684

  11. Median and Ulnar Neuropathy Assessment in Parkinson's Disease regarding Symptom Severity and Asymmetry.

    PubMed

    Yardimci, Nilgul; Cemeroglu, Ozlem; Ozturk, Eda; Gürlü, Gülsüm; Şahin, Esra; Bozkurt, Saliha; Cengiz, Tugba; Karali, Gulderen; Cakirbay, Hasim; İlhan, Atilla

    2016-01-01

    Background. While increasing evidence suggests comorbidity of peripheral neuropathy (PNP) and Parkinson's disease (PD), the pathogenesis of PNP in PD is still a debate. The aim of this article is to search the core PD symptoms such as rigidity and tremor as contributing factors to mononeuropathy development while emphasizing each individual patient's asymmetric symptom severity. Methods. We studied 62 wrists and 62 elbows of 31 patients (mean age 66.48 ± 10.67) and 64 wrists and 64 elbows of 32 age-gender matched healthy controls (mean age 62.03 ± 10.40, p = 0.145). The Hoehn and Yahr disability scale and Unified Parkinson's Disease Rated Scale were used to determine the severity of the disease. Results. According to electrodiagnostic criteria, we confirmed median neuropathy in 16.12% (bilateral in two-thirds of the patients) and ulnar neuropathy in 3.22% of the PD group. While mean age (p = 0.003), age at PD onset (p = 0.019), and H&Y scores (p = 0.016) were significant, tremor and rigidity scores were not. The comparison of the mean indices of electrophysiologic parameters indicated subclinical median and ulnar nerve demyelination both at the wrist and at the elbow in the patient groups where a longer disease duration and mild tremor and rigidity scores are prominent, remarkably. Conclusion. A disease related peripheral neurodegeneration beyond symptom severity occurs in PD.

  12. Median and Ulnar Neuropathy Assessment in Parkinson's Disease regarding Symptom Severity and Asymmetry

    PubMed Central

    Cemeroglu, Ozlem; Ozturk, Eda; Gürlü, Gülsüm; Şahin, Esra; Bozkurt, Saliha; Cengiz, Tugba; Karali, Gulderen; Cakirbay, Hasim; İlhan, Atilla

    2016-01-01

    Background. While increasing evidence suggests comorbidity of peripheral neuropathy (PNP) and Parkinson's disease (PD), the pathogenesis of PNP in PD is still a debate. The aim of this article is to search the core PD symptoms such as rigidity and tremor as contributing factors to mononeuropathy development while emphasizing each individual patient's asymmetric symptom severity. Methods. We studied 62 wrists and 62 elbows of 31 patients (mean age 66.48 ± 10.67) and 64 wrists and 64 elbows of 32 age-gender matched healthy controls (mean age 62.03 ± 10.40, p = 0.145). The Hoehn and Yahr disability scale and Unified Parkinson's Disease Rated Scale were used to determine the severity of the disease. Results. According to electrodiagnostic criteria, we confirmed median neuropathy in 16.12% (bilateral in two-thirds of the patients) and ulnar neuropathy in 3.22% of the PD group. While mean age (p = 0.003), age at PD onset (p = 0.019), and H&Y scores (p = 0.016) were significant, tremor and rigidity scores were not. The comparison of the mean indices of electrophysiologic parameters indicated subclinical median and ulnar nerve demyelination both at the wrist and at the elbow in the patient groups where a longer disease duration and mild tremor and rigidity scores are prominent, remarkably. Conclusion. A disease related peripheral neurodegeneration beyond symptom severity occurs in PD. PMID:27843673

  13. Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy

    PubMed Central

    Trollet, Capucine; Stojkovic, Tanya; de Becdelievre, Alix; Perie, Sophie; Pouget, Jean; Eymard, Bruno

    2017-01-01

    Objective: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant adult-onset disease characterized by progressive ptosis, dysphagia, and proximal limb weakness. The genetic cause is an expanded (GCN)n mutation in the PABPN1 gene encoding for the polyadenylate-binding protein nuclear 1. We hypothesized a potential correlation between the size of the (GCN)n expansion and the severity of the phenotype. To do this, we characterized the distribution of the genotypes as well as their correlation with age at diagnosis and phenotypical features in a large cohort of heterozygous and homozygous patients with OPMD in France with a confirmed molecular diagnosis of PABPN1. Methods: We explored 354 unrelated index cases recruited between 1999 and 2014 in several neuromuscular centers in France. Results: This cohort allowed us to characterize the frequency of mutated alleles in the French population and to demonstrate a statistical correlation between the size of the expansion and the mean age at diagnosis. We also confirmed that homozygous patients present with a more severe disease. Conclusions: It has been difficult to establish phenotype–genotype correlations because of the rare nature of this disease. Our work demonstrates that patients with OPMD with longer PABPN1 expansion are on average diagnosed at an earlier age than patients with a shorter expansion, confirming that polyalanine expansion size plays a role in OPMD, with an effect on disease severity and progression. PMID:28011929

  14. Disease severity estimates - effects of rater accuracy and assessments methods for comparing treatments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Assessment of disease is fundamental to the discipline of plant pathology, and estimates of severity are often made visually. However, it is established that visual estimates can be inaccurate and unreliable. In this study estimates of Septoria leaf blotch on leaves of winter wheat from non-treated ...

  15. The effects of rater bias and assessment method used to estimate disease severity on hypothesis testing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of bias (over and underestimates) in estimates of disease severity on hypothesis testing using different assessment methods was explored. Nearest percent estimates (NPE), the Horsfall-Barratt (H-B) scale, and two different linear category scales (10% increments, with and without addition...

  16. Cat-scratch disease with severe pleuritis in a 6-year-old girl.

    PubMed

    Kimura, Sasagu; Hasegawa, Shunji; Yanagihara, Masashi; Inoue, Hirofumi; Matsushige, Takeshi; Tsuneoka, Hidehiro; Ichiyama, Takashi; Ohga, Shouichi

    2015-06-01

    We present the case of a 6-year-old girl with cat-scratch disease (CSD), who developed severe pleuritis without lymphadenitis. Bartonella henselae DNA was detected on real-time polymerase chain reaction (PCR) analysis of whole blood. This is the first report of CSD diagnosed on real-time PCR using whole blood.

  17. Severity of chronic Chagas disease is associated with cytokine/antioxidant imbalance in chronically infected individuals.

    PubMed

    Pérez-Fuentes, Ricardo; Guégan, Jean-François; Barnabé, Christian; López-Colombo, Aurelio; Salgado-Rosas, Hilda; Torres-Rasgado, Enrique; Briones, Bernardo; Romero-Díaz, Mónica; Ramos-Jiménez, Judith; Sánchez-Guillén, María del Carmen

    2003-03-01

    Understanding the pathogenic mechanisms in chronic Chagas disease, a major cause of morbidity and mortality in Latin America, is essential for the design of rational therapeutic strategies. In this paper we show that the development of Chagas disease is a consequence of a long-term and complex relationship between parasite persistence and maladapted homeostatic mechanisms in the host which leads to pathologic changes. We performed a retrospective study on 50 patients with chronic Chagas disease and 50 healthy control individuals. The specific immune response was detected by ELISA and IHA tests using autochthonous antigens, inflammatory process with the cytokine tumour necrosis factor (TNF)-alpha and nitric oxide (NO), and antioxidant protection with glutathione peroxidase and superoxide dismutase (SOD) levels. We developed generalised linear modelling procedures to assess simultaneously which explanatory variables and/or their interactions better explained disease severity in patients. Our results show the existence of a strong relationship between anti-Trypanosoma cruzi levels and chronic Chagas disease (P<0.0001). Taken together, the statistical data indicate both cumulative and complementary effects, where the increase in TNF-alpha (P=0.004) and NO (P=0.005) levels correlated with a reduction in glutathione peroxidase (P=0.0001) and SOD (P=0.01) levels drives the disease pathology in chronically infected patients. Our findings may have important implications for understanding host susceptibility to develop severe chronic infectious disease. In addition we show putative targets for the design of new therapeutic strategies to prevent disease progression, considering both specific treatment against the aetiological agent and modulation of the different immunopathological reactions in chronically infected individuals with chronic Chagas disease.

  18. Simulating the Effects of Dopamine Imbalance on Cognition: From Positive Affect to Parkinson’s Disease

    PubMed Central

    Hélie, Sébastien; Paul, Erick J.; Ashby, F. Gregory

    2012-01-01

    Cools (2006) suggested that prefrontal dopamine levels are related to cognitive stability whereas striatal dopamine levels are related to cognitive plasticity. With such a wide ranging role, almost all cognitive activities should be affected by dopamine levels in the brain. Not surprisingly, factors influencing brain dopamine levels have been shown to improve/worsen performance in many behavioral experiments. On the one hand, Nadler and her colleagues (2010) showed that positive affect (which is thought to increase cortical dopamine levels) improves a type of categorization that depends on explicit reasoning (rule-based) but not a type that depends on procedural learning (information-integration). On the other hand, Parkinson’s disease (which is known to decrease dopamine levels in both the striatum and cortex) produces proactive interference in the odd-man-out task (Flowers & Robertson, 1985) and renders subjects insensitive to negative feedback during reversal learning (Cools et al., 2006). This article uses the COVIS model of categorization to simulate the effects of different dopamine levels in categorization, reversal learning, and the odd-man-out task. The results show a good match between the simulated and human data, which suggests that the role of dopamine in COVIS can account for several cognitive enhancements and deficits related to dopamine levels in healthy and patient populations. PMID:22402326

  19. All Is Not Lost: Positive Behaviors in Alzheimer’s Disease and Behavioral-Variant Frontotemporal Dementia with Disease Severity

    PubMed Central

    Midorikawa, Akira; Leyton, Cristian E.; Foxe, David; Landin-Romero, Ramon; Hodges, John R.; Piguet, Olivier

    2016-01-01

    Background: Anecdotal evidence indicates that some patients with dementia exhibit novel or increased positive behaviors, such as painting or singing, after the disease onset. Due to the lack of objective measures, however, the frequency and nature of these changes has not been formally investigated. Objective: This study aimed to systematically identify changes in these behaviors in the two most common younger-onset dementia syndromes: Alzheimer’s disease (AD) and behavioral-variant frontotemporal dementia (bvFTD). Methods: Sixty-three caregivers of patients with dementia (32 caregivers of AD patients and 31 caregivers of bvFTD patients) participated in the study. Caregivers rated the presence and frequency of positive and negative behavior changes after the onset of dementia using the Hypersensory and Social/Emotional Scale (HSS) questionnaire, focusing on three domains: sensory processing, cognitive skills, and social/emotional processing. Six composites scores were obtained reflecting these three domains (two composite scores for each domain). Differences across scores and ratios of increased and decreased behaviors were analyzed between AD and bvFTD, at different disease severity levels. Results: After disease onset, significant changes in the sensory processing domain were observed across disease severity levels, particularly in AD. Composite scores of the other domains did not change significantly. Importantly, however, some novel or increased positive behaviors were present in between 10% (Music activities) and 70% (Hypersensitivity) of AD and bvFTD patients, regardless of disease severity. Conclusions: We provide the first systematic investigation of positive behaviors in AD and bvFTD. The newly developed HSS questionnaire is a valid measure to characterize changes and progression of positive behaviors in patients with dementia. PMID:27472884

  20. First Report of Oryctes rhinoceros nudivirus (Coleoptera: Scarabaeidae) Causing Severe Disease in Allomyrina dichotoma in Korea

    PubMed Central

    Lee, Seokhyun; Park, Kwan-Ho; Nam, Sung-Hee; Kwak, Kyu-Won; Choi, Ji-Young

    2015-01-01

    Oryctes rhinoceros nudivirus (OrNV) has been known to cause severe disease in coconut palm rhinoceros beetle, Oryctes rhinoceros, in Southeastern Asia and is used as a biological control to reduce the pest population. Here, we report for the first time that the OrNV may have landed on Korea and may be the major pathogen for diseased larvae of Korean horn beetle, Allomyrina dichotoma. After peroral inoculation, over 60% of infected larvae perished in 6 wk. This viral disease spreads very fast in several locations throughout Korea. This threat not only makes economic loss of local farms rearing A. dichotoma larvae but also may disturb the ecosystem by transmitting to wild A. dichotoma. PMID:25765317

  1. Severe neuroinvasive West Nile virus infection in a child with undiagnosed Addison's disease

    PubMed Central

    Messacar, Kevin; Cree-Green, Melanie; Lovell, Mark; Anderson, Marsha S.; Dominguez, Samuel R.

    2014-01-01

    This report describes a case of West Nile virus (WNV) meningoencephalitis in a child who presented with fever, headache, seizures, and altered mental status, as well as hyponatremia and bronzing of the skin. Findings that led to the diagnosis of WNV included plasma-cell pleocytosis of the cerebrospinal fluid (CSF) and linear chorioretinitis on ophthalmologic exam. The diagnosis was confirmed by a positive serum and CSF WNV IgM. The acute WNV infection triggered an adrenal crisis which uncovered a new diagnosis of underlying Addison's disease. This is the first case report of severe neuroinvasive WNV disease in a pediatric patient with primary adrenal insufficiency. Neuroinvasive WNV disease is uncommon in children, but may have a more severe presentation in those with certain underlying medical conditions. PMID:25133095

  2. Dermatoses affecting desmosomes in animals: a mechanistic review of acantholytic blistering skin diseases.

    PubMed

    Olivry, Thierry; Linder, Keith E

    2009-10-01

    Failure of desmosomal adhesion with ensuing keratinocyte separation - a phenomenon called acantholysis - can result from genetic, autoimmune or infectious proteolytic causes. Rare hereditary disorders of desmosomal formation have been identified in animals. Familial acantholysis of Angus calves and hereditary suprabasal acantholytic mechanobullous dermatosis of buffaloes appear to be similar to acantholytic epidermolysis bullosa of human beings. A genetic acantholytic dermatosis resembling human Darier disease has been rarely recognized in dogs. In autoimmune blistering dermatoses, circulating autoantibodies bind to the extracellular segments of desmosomal proteins and induce acantholysis. Autoantibodies against desmoglein-3 are found in canine pemphigus vulgaris and paraneoplastic pemphigus. Autoantibodies against desmoglein-1 have been rarely detected in dogs with pemphigus foliaceus. When circulating autoantibodies target desmogleins-1 and -3, mucocutaneous pemphigus vulgaris develops in dogs. Finally, several infectious agents can release proteases that cleave desmosomal bonds. In superficial pustular dermatophytosis of dogs and horses, Trichophyton hyphae colonize the stratum corneum, and acantholysis presumably develops because of proteases secreted by the dermatophytes. In exudative epidermitis of piglets, Staphylococcus bacteria - usually Staphylococcus hyicus- release exfoliatin toxins that bind to and specifically cleave desmoglein-1. Any of the above mechanisms can result in impairment of desmosomal function with subsequent acantholysis. The end point of adhesion failure is identical among these diseases: there is cleft formation where desmosomes are affected. The similarity of mechanisms explains why clinical and microscopic skin lesions overlap between entities, thus leaving clinicians and dermatopathologists with the conundrum of determining whether the acantholysis is of genetic, autoimmune or infectious origin.

  3. Mutations Affecting the SAND Domain of DEAF1 Cause Intellectual Disability with Severe Speech Impairment and Behavioral Problems

    PubMed Central

    Vulto-van Silfhout, Anneke T.; Rajamanickam, Shivakumar; Jensik, Philip J.; Vergult, Sarah; de Rocker, Nina; Newhall, Kathryn J.; Raghavan, Ramya; Reardon, Sara N.; Jarrett, Kelsey; McIntyre, Tara; Bulinski, Joseph; Ownby, Stacy L.; Huggenvik, Jodi I.; McKnight, G. Stanley; Rose, Gregory M.; Cai, Xiang; Willaert, Andy; Zweier, Christiane; Endele, Sabine; de Ligt, Joep; van Bon, Bregje W.M.; Lugtenberg, Dorien; de Vries, Petra F.; Veltman, Joris A.; van Bokhoven, Hans; Brunner, Han G.; Rauch, Anita; de Brouwer, Arjan P.M.; Carvill, Gemma L.; Hoischen, Alexander; Mefford, Heather C.; Eichler, Evan E.; Vissers, Lisenka E.L.M.; Menten, Björn; Collard, Michael W.; de Vries, Bert B.A.

    2014-01-01

    Recently, we identified in two individuals with intellectual disability (ID) different de novo mutations in DEAF1, which encodes a transcription factor with an important role in embryonic development. To ascertain whether these mutations in DEAF1 are causative for the ID phenotype, we performed targeted resequencing of DEAF1 in an additional cohort of over 2,300 individuals with unexplained ID and identified two additional individuals with de novo mutations in this gene. All four individuals had severe ID with severely affected speech development, and three showed severe behavioral problems. DEAF1 is highly expressed in the CNS, especially during early embryonic development. All four mutations were missense mutations affecting the SAND domain of DEAF1. Altered DEAF1 harboring any of the four amino acid changes showed impaired transcriptional regulation of the DEAF1 promoter. Moreover, behavioral studies in mice with a conditional knockout of Deaf1 in the brain showed memory deficits and increased anxiety-like behavior. Our results demonstrate that mutations in DEAF1 cause ID and behavioral problems, most likely as a result of impaired transcriptional regulation by DEAF1. PMID:24726472

  4. Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems.

    PubMed

    Vulto-van Silfhout, Anneke T; Rajamanickam, Shivakumar; Jensik, Philip J; Vergult, Sarah; de Rocker, Nina; Newhall, Kathryn J; Raghavan, Ramya; Reardon, Sara N; Jarrett, Kelsey; McIntyre, Tara; Bulinski, Joseph; Ownby, Stacy L; Huggenvik, Jodi I; McKnight, G Stanley; Rose, Gregory M; Cai, Xiang; Willaert, Andy; Zweier, Christiane; Endele, Sabine; de Ligt, Joep; van Bon, Bregje W M; Lugtenberg, Dorien; de Vries, Petra F; Veltman, Joris A; van Bokhoven, Hans; Brunner, Han G; Rauch, Anita; de Brouwer, Arjan P M; Carvill, Gemma L; Hoischen, Alexander; Mefford, Heather C; Eichler, Evan E; Vissers, Lisenka E L M; Menten, Björn; Collard, Michael W; de Vries, Bert B A

    2014-05-01

    Recently, we identified in two individuals with intellectual disability (ID) different de novo mutations in DEAF1, which encodes a transcription factor with an important role in embryonic development. To ascertain whether these mutations in DEAF1 are causative for the ID phenotype, we performed targeted resequencing of DEAF1 in an additional cohort of over 2,300 individuals with unexplained ID and identified two additional individuals with de novo mutations in this gene. All four individuals had severe ID with severely affected speech development, and three showed severe behavioral problems. DEAF1 is highly expressed in the CNS, especially during early embryonic development. All four mutations were missense mutations affecting the SAND domain of DEAF1. Altered DEAF1 harboring any of the four amino acid changes showed impaired transcriptional regulation of the DEAF1 promoter. Moreover, behavioral studies in mice with a conditional knockout of Deaf1 in the brain showed memory deficits and increased anxiety-like behavior. Our results demonstrate that mutations in DEAF1 cause ID and behavioral problems, most likely as a result of impaired transcriptional regulation by DEAF1.

  5. Non-linear increase of respiratory diseases and their costs under severe air pollution.

    PubMed

    Shen, Ying; Wu, Yiyun; Chen, Guangdi; Van Grinsven, Hans J M; Wang, Xiaofeng; Gu, Baojing; Lou, Xiaoming

    2017-05-01

    China is experiencing severe and persistent air pollution, with concentrations of fine particulate matters (PM2.5) reaching unprecedentedly high levels in many cities. Quantifying the detrimental effects on health and their costs derived from high PM2.5 levels is crucial because of the unsolved challenges to mitigate air pollution in the following decades. Using the daily monitoring data on PM2.5 concentrations and clinic visits, we found a non-linear increase of respiratory diseases, but not for other diseases (e.g., digestive diseases) under severe air pollution. We found an increase of respiratory diseases by 1% for each 10 μg m(-3) increase in PM2.5 when the annual average daily PM2.5 concentration was less than 50 μg m(-3); while this ratio was doubled (around 2%) with the daily PM2.5 concentration larger than 50 μg m(-3). Under severe air pollution (PM2.5 concentration >150 μg m(-3)), the respiratory diseases increased by over 50% compared to that in clean days. Children are more sensitive to the severe air pollution. The increase of clinic visits, especially for adults, was observed mainly in bigger (>500 beds) hospitals. Re-allocating medical resources (e.g., doctors) from big hospitals to community hospitals can benefit the respiratory patients due to air pollution. The total medical cost of clinic visits of respiratory diseases derived from PM2.5 pollution was estimated at 17.2-57.0 billion Yuan in 2014 in China, accounting for 0.5-1.6% of national total health expenditure. Because these medical costs only represent a small part of total health cost derived from air pollution, the reduction of associated health costs would be an important co-benefit of implementation of air pollution preventive strategies.

  6. Decision Aids for Multiple-Decision Disease Management as Affected by Weather Input Errors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many disease management decision support systems (DSS) rely, exclusively or in part, on weather inputs to calculate an indicator for disease hazard. Error in the weather inputs, typically due to forecasting, interpolation or estimation from off-site sources, may affect model calculations and manage...

  7. Prediction of Disease Case Severity Level To Determine INA CBGs Rate

    NASA Astrophysics Data System (ADS)

    Puspitorini, Sukma; Kusumadewi, Sri; Rosita, Linda

    2017-03-01

    Indonesian Case-Based Groups (INA CBGs) is case-mix payment system using software grouper application. INA CBGs consisting of four digits code where the last digits indicating the severity level of disease cases. Severity level influence by secondary diagnosis (complications and co-morbidity) related to resource intensity level. It is medical resources used to treat a hospitalized patient. Objectives of this research is developing decision support system to predict severity level of disease cases and illustrate INA CBGs rate by using data mining decision tree classification model. Primary diagnosis (DU), first secondary diagnosis (DS 1), and second secondary diagnosis (DS 2) are attributes that used as input of severity level. The training process using C4.5 algorithm and the rules will represent in the IF-THEN form. Credibility of the system analyzed through testing process and confusion matrix present the results. Outcome of this research shows that first secondary diagnosis influence significant to form severity level predicting rules from new disease cases and INA CBGs rate illustration.

  8. Risk Factors for Severe Renal Disease in Bardet-Biedl Syndrome.

    PubMed

    Forsythe, Elizabeth; Sparks, Kathryn; Best, Sunayna; Borrows, Sarah; Hoskins, Bethan; Sabir, Ataf; Barrett, Timothy; Williams, Denise; Mohammed, Shehla; Goldsmith, David; Milford, David V; Bockenhauer, Detlef; Foggensteiner, Lukas; Beales, Philip L

    2017-03-01

    Bardet-Biedl syndrome is a rare autosomal recessive, multisystem disease characterized by retinal dystrophy, renal malformation, obesity, intellectual disability, polydactyly, and hypogonadism. Nineteen disease-causing genes (BBS1-19) have been identified, of which mutations in BBS1 are most common in North America and Europe. A hallmark of the disease, renal malformation is heterogeneous and is a cause of morbidity and mortality through the development of CKD. We studied the prevalence and severity of CKD in 350 patients with Bardet-Biedl syndrome-related renal disease attending the United Kingdom national Bardet-Biedl syndrome clinics to further elucidate the phenotype and identify risk indicators of CKD. Overall, 31% of children and 42% of adults had CKD; 6% of children and 8% of adults had stage 4-5 CKD. In children, renal disease was often detected within the first year of life. Analysis of the most commonly mutated disease-associated genes revealed that, compared with two truncating mutations, two missense mutations associated with less severe CKD in adults. Moreover, compared with mutations in BBS10, mutations in BBS1 associated with less severe CKD or lack of CKD in adults. Finally, 51% of patients with available ultrasounds had structural renal abnormalities, and 35% of adults were hypertensive. The presence of structural abnormalities or antihypertensive medication also correlated statistically with stage 3b-5 CKD. This study describes the largest reported cohort of patients with renal disease in Bardet-Biedl syndrome and identifies risk factors to be considered in genetic counseling.

  9. Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

    PubMed Central

    Amin, Kawa; Rasool, Aram H; Hattem, Ali; Al-Karboly, Taha AM; Taher, Taher E; Bystrom, Jonas

    2017-01-01

    AIM To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease. METHODS Levels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays. RESULTS We found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH. CONCLUSION Auto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other. PMID:28293081

  10. Staphylokinase promotes the establishment of Staphylococcus aureus skin infections while decreasing disease severity.

    PubMed

    Kwiecinski, Jakub; Jacobsson, Gunnar; Karlsson, Maria; Zhu, Xuefeng; Wang, Wanzhong; Bremell, Tomas; Josefsson, Elisabet; Jin, Tao

    2013-09-01

    Skin infections are frequently caused by Staphylococcus aureus and can lead to a fatal sepsis. The microbial mechanisms controlling the initiation and progression from mild skin infection to a severe disseminated infection remain poorly understood. Using a combination of clinical data and in vitro and ex vivo assays, we show that staphylokinase, secreted by S. aureus, promoted the establishment of skin infections in humans and increased bacterial penetration through skin barriers by activating plasminogen. However, when infection was established, the interaction between staphylokinase and plasminogen did not promote systemic dissemination but induced the opening and draining of abscesses and decreased disease severity in neutropenic mice. Also, increased staphylokinase production was associated with noninvasive S. aureus infections in patients. Our results point out the dual roles of staphylokinase in S. aureus skin infections as promoting the establishment of infections while decreasing disease severity.

  11. The Mn-binding proteins of the photosystem II oxygen-evolving complex are decreased in date palms affected by brittle leaf disease.

    PubMed

    Marqués, Jorge; Duran-Vila, Nuria; Daròs, José-Antonio

    2011-04-01

    Brittle leaf disease or maladie des feuilles cassantes (MFC) is a disorder affecting date palms (Phoenix dactylifera L.) which after a long declining process eventually leads to the death of the plant. No causal agent for the disease has been found so far but leaflets of affected palms are Mn-deficient despite the existence of adequate exchangeable Mn in the soils in which affected palms grow. The disease is specifically associated with an increase in a series of chloroplastic RNAs. A proteomic analysis of leaflets of affected and unaffected date palms showed differences in quantities of several proteins. Mn-binding PSBO and PSBP proteins, components of the oxygen-evolving complex of photosystem II, were decreased in affected tissue, reinforcing the relation between MFC and Mn deficiency. The quantities of other proteins were increased by disease suggesting a response to stress.

  12. Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey

    PubMed Central

    Johnson, Lorraine; Wilcox, Spencer; Mankoff, Jennifer

    2014-01-01

    Overview. The Centers for Disease Control and Prevention (CDC) health-related quality of life (HRQoL) indicators are widely used in the general population to determine the burden of disease, identify health needs, and direct public health policy. These indicators also allow the burden of illness to be compared across different diseases. Although Lyme disease has recently been acknowledged as a major health threat in the USA with more than 300,000 new cases per year, no comprehensive assessment of the health burden of this tickborne disease is available. This study assesses the HRQoL of patients with chronic Lyme disease (CLD) and compares the severity of CLD to other chronic conditions. Methods. Of 5,357 subjects who responded to an online survey, 3,090 were selected for the study. Respondents were characterized as having CLD if they were clinically diagnosed with Lyme disease and had persisting symptoms lasting more than 6 months following antibiotic treatment. HRQoL of CLD patients was assessed using the CDC 9-item metric. The HRQoL analysis for CLD was compared to published analyses for the general population and other chronic illnesses using standard statistical methods. Results. Compared to the general population and patients with other chronic diseases reviewed here, patients with CLD reported significantly lower health quality status, more bad mental and physical health days, a significant symptom disease burden, and greater activity limitations. They also reported impairment in their ability to work, increased utilization of healthcare services, and greater out of pocket medical costs. Conclusions. CLD patients have significantly impaired HRQoL and greater healthcare utilization compared to the general population and patients with other chronic diseases. The heavy burden of illness associated with CLD highlights the need for earlier diagnosis and innovative treatment approaches that may reduce the burden of illness and concomitant costs posed by this

  13. Comparison of the injury severity and medical history of disease-related versus trauma-related bicyclist fatalities.

    PubMed

    Hitosugi, Masahito; Koseki, Takeshi; Miyama, Genta; Furukawa, Satoshi; Morita, Satomu

    2016-01-01

    The objective of this study was to clarify the relationship between injury severity and mechanism of death in bicycle fatalities resulting from trauma compared with those resulting from disease, to propose effective measures to prevent fatal bicyclist accidents. Autopsy and accident records were reviewed for bicyclist fatalities who had undergone forensic autopsy at the Dokkyo Medical University School of Medicine between September 1999 and March 2014. Victims' health histories, blood alcohol levels, causes of death, mechanisms of injury, Abbreviated Injury Scale (AIS) scores and Injury Severity Scores (ISSs) were determined. Fifty-five bicyclists (43 male and 12 female) with a mean age of 62.5±17.3 years were included in this study. Sixteen victims had driven under the influence of alcohol (mean blood concentration of 1.8±0.7 mg/ml). Mean ISS was 32.4 and the chest had the highest mean AIS score (2.6), followed by the head (2.1) and the neck (1.8). Thirty-nine victims (70.9%) had died of trauma and 16 had died of disease. The disease-death victims had significantly higher prevalence of having diabetes mellitus, hyperlipidemia, hypertension, heart disease or cerebrovascular diseases (50.0% vs. 22.2%, p=0.03) and a lower rate of drunk driving (6.3% vs. 41.0%, p=0.01) than the trauma-death group. All victims who were affected by disease, and 33.3% of trauma-death victims, had fallen on the road without a vehicle collision (p<0.001). The mean ISS of the trauma-death group was significantly higher than that of the disease-death group (44.0 vs. 4.2, p<0.001). Except for facial injuries, the AIS scores were significantly higher in trauma-death victims than in the disease-death group (p<0.005). To effectively reduce bicyclist fatalities, the authors strongly advocate efforts that will increase compliance with drunk driving prohibitions. For victims of fatal bicycle accidents with a medical history of diseases, a forensic autopsy should be performed to establish a

  14. Paradoxical severe agitation induced by add-on high-doses quetiapine in schizo-affective disorder.

    PubMed

    Fond, Guillaume; MacGregor, Alexandra; Ducasse, Deborah; Brittner, Marie

    2014-05-15

    We report the case of a 35-year-old patient suffering from schizo-affective disorder since the age of 19 years, treated by a combination of first-generation antipsychotics, zuclopenthixol (100 mg/day) and lithium (1200 mg/day) (serum lithium=0.85 mEq/l). This patient had no associated personality disorder (particularly no antisocial disorder) and no substance abuse disorder. Within the 48 h following the gradual introduction of quetiapine (up to 600 mg/day), the patient presented severe agitation without an environmental explanation, contrasting with the absence of a history of aggressiveness or personality disorder. The diagnoses of manic shift and akathisia were dismissed. The withdrawal and the gradual reintroduction of quetiapine 2 weeks later, which led to another severe agitation, enabled us to attribute the agitation specifically to quetiapine.

  15. Assessment of the expectancy, seriousness and severity of adverse drug reactions reported for chronic obstructive pulmonary disease therapy

    PubMed Central

    Petrova, Guenka; Stoimenova, Assena; Dimitrova, Maria; Kamusheva, Maria; Petrova, Daniela; Georgiev, Ognian

    2017-01-01

    Introduction: Adverse drug reactions can cause increased morbidity and mortality, and therefore information needs to be studied systematically. Little is known about the adverse drug reactions for chronic obstructive pulmonary disease therapy. The goal of this study is to assess the expectedness, seriousness and severity of adverse drug reactions during chronic obstructive pulmonary disease therapy based on their reporting in the national pharmacovigilance system. Methods: This was a prospective, observational, 1-year, real-life study about the pharmacotherapy of a sample of 390 chronic obstructive pulmonary disease patients. Prescribed medicines were systematized and national pharmacovigilance databases were searched for reported adverse drug reactions. The expectedness was evaluated through the review of the summary of product characteristics, the seriousness was evaluated by the clinicians based on the life threatening nature of the adverse drug reactions, and the severity was evaluated through Hartwig’s Severity Assessment Scale. Descriptive statistics of the reported adverse drug reactions was performed and the relative risk of developing an adverse drug reaction with all international non-proprietary names included in the analysis was calculated. Results: Results confirm that the chronic obstructive pulmonary disease is a disease with high appearance of adverse drug reactions, and causes many additional costs to the healthcare system. Unexpected and severe adverse drug reactions are frequent. A total of 4.8% of adverse drug reactions were evaluated as life threatening. Majority of adverse drug reactions are classified in Levels 1 (32.6%), 2 (26.4%) and 3 (19%) according to Hartwig’s Severity Assessment Scale. Approximately 22% of reported adverse drug reactions affect people’s everyday life to a greater extent and require additional therapy which might further increase the risk. The relative risk of developing an adverse drug reaction was highest for

  16. Comparisons between two biochemical markers in evaluating periodontal disease severity: a cross-sectional study

    PubMed Central

    2014-01-01

    Background The purpose of this study was to compare two biochemical markers, which have been previously used to determine the degrees of alveolar bone destruction, in evaluating periodontal disease severity. Methods The WF6 epitope of chondroitin sulfate (CS) and the alkaline phosphatase (ALP) levels were determined in gingival crevicular fluid (GCF) samples collected from patients with various degrees of disease severity, including ten patients with gingivitis (50 gingivitis sites) and 33 patients with chronic periodontitis (including gingivitis, slight, moderate, and severe periodontitis sites; n = 50 each), as well as from ten healthy volunteers (50 healthy sites) by Periopaper strips. The levels of CS and ALP were measured by an ELISA and a fluorometric assay, respectively. Results The results demonstrated low levels of CS and ALP in non-destructive and slightly destructive periodontitis sites, whereas significantly high levels of these two biomolecules were shown in moderately and severely destructive sites (p < 0.05). Although a significant difference in CS levels was found between moderate and severe periodontitis sites, no difference in ALP levels was found. Stronger correlations were found between CS levels and periodontal parameters, including probing depth, loss of clinical attachment levels, gingival index and plaque index, than between ALP levels and these parameters. Conclusions It is suggested that the CS level is a better diagnostic marker than the ALP level for evaluating distinct severity of chronic periodontitis. PMID:25174345

  17. Spectral quality affects disease development of three pathogens on hydroponically grown plants

    NASA Technical Reports Server (NTRS)

    Schuerger, A. C.; Brown, C. S.; Sager, J. C. (Principal Investigator)

    1997-01-01

    Plants were grown under light-emitting diode (LED) arrays with various spectra to determine the effects of light quality on the development of diseases caused by tomato mosaic virus (ToMV) on pepper (Capsicum annuum L.), powdery mildew [Sphaerotheca fuliginea (Schlectend:Fr.) Pollaci] on cucumber (Cucumis sativus L.), and bacterial wilt (Pseudomonas solanacearum Smith) on tomato (Lycopersicon esculentum Mill.). One LED (660) array supplied 99% red light at 660 nm (25 nm bandwidth at half-peak height) and 1% far-red light between 700 to 800 nm. A second LED (660/735) array supplied 83% red light at 660 nm and 17% far-red light at 735 nm (25 nm bandwidth at half-peak height). A third LED (660/BF) array supplied 98% red light at 660 nm, 1% blue light (BF) between 350 to 550 nm, and 1% far-red light between 700 to 800 nm. Control plants were grown under broad-spectrum metal halide (MH) lamps. Plants were grown at a mean photon flux (300 to 800 nm) of 330 micromoles m-2 s-1 under a 12-h day/night photoperiod. Spectral quality affected each pathosystem differently. In the ToMV/pepper pathosystem, disease symptoms developed slower and were less severe in plants grown under light sources that contained blue and UV-A wavelengths (MH and 660/BF treatments) compared to plants grown under light sources that lacked blue and UV-A wavelengths (660 and 660/735 LED arrays). In contrast, the number of colonies per leaf was highest and the mean colony diameters of S. fuliginea on cucumber plants were largest on leaves grown under the MH lamp (highest amount of blue and UV-A light) and least on leaves grown under the 660 LED array (no blue or UV-A light). The addition of far-red irradiation to the primary light source in the 660/735 LED array increased the colony counts per leaf in the S. fuliginea/cucumber pathosystem compared to the red-only (660) LED array. In the P. solanacearum/tomato pathosystem, disease symptoms were less severe in plants grown under the 660 LED array, but the

  18. Spectral quality affects disease development of three pathogens on hydroponically grown plants.

    PubMed

    Schuerger, A C; Brown, C S

    1997-02-01

    Plants were grown under light-emitting diode (LED) arrays with various spectra to determine the effects of light quality on the development of diseases caused by tomato mosaic virus (ToMV) on pepper (Capsicum annuum L.), powdery mildew [Sphaerotheca fuliginea (Schlectend:Fr.) Pollaci] on cucumber (Cucumis sativus L.), and bacterial wilt (Pseudomonas solanacearum Smith) on tomato (Lycopersicon esculentum Mill.). One LED (660) array supplied 99% red light at 660 nm (25 nm bandwidth at half-peak height) and 1% far-red light between 700 to 800 nm. A second LED (660/735) array supplied 83% red light at 660 nm and 17% far-red light at 735 nm (25 nm bandwidth at half-peak height). A third LED (660/BF) array supplied 98% red light at 660 nm, 1% blue light (BF) between 350 to 550 nm, and 1% far-red light between 700 to 800 nm. Control plants were grown under broad-spectrum metal halide (MH) lamps. Plants were grown at a mean photon flux (300 to 800 nm) of 330 micromoles m-2 s-1 under a 12-h day/night photoperiod. Spectral quality affected each pathosystem differently. In the ToMV/pepper pathosystem, disease symptoms developed slower and were less severe in plants grown under light sources that contained blue and UV-A wavelengths (MH and 660/BF treatments) compared to plants grown under light sources that lacked blue and UV-A wavelengths (660 and 660/735 LED arrays). In contrast, the number of colonies per leaf was highest and the mean colony diameters of S. fuliginea on cucumber plants were largest on leaves grown under the MH lamp (highest amount of blue and UV-A light) and least on leaves grown under the 660 LED array (no blue or UV-A light). The addition of far-red irradiation to the primary light source in the 660/735 LED array increased the colony counts per leaf in the S. fuliginea/cucumber pathosystem compared to the red-only (660) LED array. In the P. solanacearum/tomato pathosystem, disease symptoms were less severe in plants grown under the 660 LED array, but the

  19. Comorbidity Cohort (2C) study: Cardiovascular disease severity and comorbid osteoarthritis in primary care

    PubMed Central

    2012-01-01

    Background Two of the commonest chronic diseases experienced by older people in the general population are cardiovascular diseases and osteoarthritis. These conditions also commonly co-occur, which is only partly explained by age. Yet, there have been few studies investigating specific a priori hypotheses in testing the comorbid interaction between two chronic diseases and related health and healthcare outcomes. It is also unknown whether the stage or severity of the chronic disease influences the comorbidity impact. The overall plan is to investigate the interaction between cardiovascular severity groups (hypertension, ischaemic heart disease and heart failure) and osteoarthritis comorbidity, and their longitudinal impact on health and healthcare outcomes relative to either condition alone. Methods From ten general practices participating in a research network, adults aged 40 years and over were sampled to construct eight exclusive cohort groups (n = 9,676). Baseline groups were defined on the basis of computer clinical diagnostic data in a 3-year time-period (between 2006 and 2009) as: (i) without cardiovascular disease or osteoarthritis (reference group), (ii) index cardiovascular disease groups (hypertension, ischaemic heart disease and heart failure) without osteoarthritis, (iii) index osteoarthritis group without cardiovascular disease, and (vi) index cardiovascular disease groups comorbid with osteoarthritis. There were three main phases to longitudinal follow-up. The first (survey population) was to invite cohorts to complete a baseline postal health questionnaire, with 10 monthly brief interval health questionnaires, and a final 12-month follow-up questionnaire. The second phase (linkage population) was to link the collected survey data to patient clinical records with consent for the 3-year time-period before baseline, during the 12-month survey period and the 12 months after final questionnaire (total 5 years). The third phase (denominator

  20. Microgeodic Disease Affecting the Fingers and Toes in Childhood: A Case Report

    PubMed Central

    Tetsunaga, Tomonori; Endo, Hirosuke; Fujiwara, Kazuo; Tetsunaga, Tomoko; Ozaki, Toshifumi

    2016-01-01

    Microgeodic disease is a disease of unknown etiology that affects the fingers and toes of children, with ≥ 90% of cases involving the fingers alone. We present a rare case of microgeodic disease affecting an index finger and two toes simultaneously in a 7-year-old girl. X-ray and magnetic resonance imaging (MRI) showed multiple small areas of osteolysis in the middle phalanges of the left index finger, hallux, and second toe. Microgeodic disease was diagnosed from X-ray and MRI findings, and conservative therapy involving rest and avoidance of cold stimuli was provided. Although pathological fractures occurred in the course of conservative treatment, the affected finger healed under splinting without any deformity of the finger. PMID:27843512

  1. Severity-related changes of bronchial microbiome in chronic obstructive pulmonary disease.

    PubMed

    Garcia-Nuñez, Marian; Millares, Laura; Pomares, Xavier; Ferrari, Rafaela; Pérez-Brocal, Vicente; Gallego, Miguel; Espasa, Mateu; Moya, Andrés; Monsó, Eduard

    2014-12-01

    Bronchial colonization by potentially pathogenic microorganisms (PPMs) is often demonstrated in chronic obstructive pulmonary disease (COPD), but culture-based techniques identify only a portion of the bacteria in mucosal surfaces. The aim of the study was to determine changes in the bronchial microbiome of COPD associated with the severity of the disease. The bronchial microbiome of COPD patients was analyzed by 16S rRNA gene amplification and pyrosequencing in sputum samples obtained during stable disease. Seventeen COPD patients were studied (forced expiratory volume in the first second expressed as a percentage of the forced vital capacity [FEV1%] median, 35.0%; interquartile range [IQR], 31.5 to 52.0), providing a mean of 4,493 (standard deviation [SD], 2,598) sequences corresponding to 47 operational taxonomic units (OTUs) (SD, 17) at a 97% identity level. Patients were dichotomized according to their lung function as moderate to severe when their FEV1% values were over the median and as advanced when FEV1% values were lower. The most prevalent phyla in sputum were Proteobacteria (44%) and Firmicutes (16%), followed by Actinobacteria (13%). A greater microbial diversity was found in patients with moderate-to-severe disease, and alpha diversity showed a statistically significant decrease in patients with advanced disease when assessed by Shannon (ρ = 0.528; P = 0.029, Spearman correlation coefficient) and Chao1 (ρ = 0.53; P = 0.028, Spearman correlation coefficient) alpha-diversity indexes. The higher severity that characterizes advanced COPD is paralleled by a decrease in the diversity of the bronchial microbiome, with a loss of part of the resident flora that is replaced by a more restricted microbiota that includes PPMs.

  2. Integrated, multicohort analysis of systemic sclerosis identifies robust transcriptional signature of disease severity

    PubMed Central

    Lofgren, Shane; Aren, Kathleen; Arroyo, Esperanza; Cheung, Peggie; Kuo, Alex; Valenzuela, Antonia; Haemel, Anna; Wolters, Paul J.; Gordon, Jessica; Spiera, Robert; Assassi, Shervin; Boin, Francesco; Chung, Lorinda; Fiorentino, David; Utz, Paul J.; Whitfield, Michael L.

    2016-01-01

    Systemic sclerosis (SSc) is a rare autoimmune disease with the highest case-fatality rate of all connective tissue diseases. Current efforts to determine patient response to a given treatment using the modified Rodnan skin score (mRSS) are complicated by interclinician variability, confounding, and the time required between sequential mRSS measurements to observe meaningful change. There is an unmet critical need for an objective metric of SSc disease severity. Here, we performed an integrated, multicohort analysis of SSc transcriptome data across 7 datasets from 6 centers composed of 515 samples. Using 158 skin samples from SSc patients and healthy controls recruited at 2 centers as a discovery cohort, we identified a 415-gene expression signature specific for SSc, and validated its ability to distinguish SSc patients from healthy controls in an additional 357 skin samples from 5 independent cohorts. Next, we defined the SSc skin severity score (4S). In every SSc cohort of skin biopsy samples analyzed in our study, 4S correlated significantly with mRSS, allowing objective quantification of SSc disease severity. Using transcriptome data from the largest longitudinal trial of SSc patients to date, we showed that 4S allowed us to objectively monitor individual SSc patients over time, as (a) the change in 4S of a patient is significantly correlated with change in the mRSS, and (b) the change in 4S at 12 months of treatment could predict the change in mRSS at 24 months. Our results suggest that 4S could be used to distinguish treatment responders from nonresponders prior to mRSS change. Our results demonstrate the potential clinical utility of a novel robust molecular signature and a computational approach to SSc disease severity quantification. PMID:28018971

  3. Glycoprotein YKL-40: a novel biomarker of chronic graft-vs-host disease activity and severity?

    PubMed Central

    Duraković, Nadira; Krečak, Ivan; Perić, Zinaida; Milošević, Milan; Desnica, Lana; Pulanić, Dražen; Pusic, Iskra; Kušec, Vesna; Vrhovac, Radovan; Pavletic, Steven Z.; Nemet, Damir

    2016-01-01

    Aim To investigate whether increased YKL-40 levels positively correlate with graft-vs-host disease (cGVHD) activity and severity and if YKL-40 could serve as a disease biomarker. Methods This case-control study was conducted at the University Hospital Centre Zagreb from July 2013 to October 2015. 56 patients treated with hematopoietic stem cell transplantation (HSCT) were included: 35 patients with cGVHD and 21 without cGVHD. There was no difference between groups in age, sex, median time from transplant to study enrollment, intensity of conditioning, type of donor, or source of stem cells. Blood samples were collected at study enrollment and YKL-40 levels were measured with ELISA. Disease activity was estimated using Clinician’s Impression of Activity and Intensity of Immunosuppression scales and disease severity using Global National Institutes of Health (NIH) score. Results YKL-40 levels were significantly higher in cGVHD patients than in controls (P = 0.003). The difference remained significant when patients with myelofibrosis were excluded from the analysis (P = 0.017). YKL-40 level significantly positively correlated with disease severity (P < 0.001; correlation coefficient 0.455), and activity estimated using Clinician’s Impression of Activity (P = 0.016; correlation coefficient 0.412) but not using Intensity of Immunosuppression (P = 0.085; correlation coefficient 0.296). Conclusion YKL-40 could be considered a biomarker of cGVHD severity and activity. However, validation in a larger group of patients is warranted, as well as longitudinal testing of YKL-40 levels in patients at risk of developing cGVHD. PMID:27374825

  4. The impact of dementia severity on caregiver burden in frontotemporal dementia and Alzheimer disease.

    PubMed

    Mioshi, Eneida; Foxe, David; Leslie, Felicity; Savage, Sharon; Hsieh, Sharpley; Miller, Laurie; Hodges, John R; Piguet, Olivier

    2013-01-01

    Caregiver burden is greater in frontotemporal dementia (FTD) than in Alzheimer disease (AD). However, little is known of the impact of the 3 main clinical variants of FTD- behavioral-variant frontotemporal dementia (bvFTD), semantic dementia (SemDem), and progressive nonfluent aphasia (PNFA)-or the role of disease severity in caregiver burden. The Zarit Burden Inventory was used to measure caregiver burden of bvFTD (n=17), SemDem (n=20), PNFA (n=20), and AD (n=19) patients. Symptom duration, caregiver age, and relationship type were matched across groups. Moreover, a number of caregiver (mood, social network) and patient variables (functional disability, behavioral changes, relationship with caregiver, and dementia stage) were addressed to investigate their impact on caregiver burden. Caregivers of bvFTD patients reported the highest burden, whereas SemDem and PNFA caregivers reported burden similar to AD. A regression analysis revealed that caregiver burden in FTD, regardless of subtype, was explained by a model combining disease staging, relationship changes, and caregiver depression. Burden increased with disease severity in FTD. This study is the first to show that caregivers of SemDem, PNFA, and AD patients show similar burden, while confirming that bvFTD caregivers show higher burden than AD caregivers. More importantly, this study demonstrates that burden worsens with disease progression in FTD.

  5. Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius

    PubMed Central

    Stenglein, Mark D.; Jacobson, Elliott R.; Wozniak, Edward J.; Wellehan, James F. X.; Kincaid, Anne; Gordon, Marcus; Porter, Brian F.; Baumgartner, Wes; Stahl, Scott; Kelley, Karen; Towner, Jonathan S.

    2014-01-01

    ABSTRACT A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease. PMID:25205093

  6. Metagenomic Sequencing of the Chronic Obstructive Pulmonary Disease Upper Bronchial Tract Microbiome Reveals Functional Changes Associated with Disease Severity.

    PubMed

    Cameron, Simon J S; Lewis, Keir E; Huws, Sharon A; Lin, Wanchang; Hegarty, Matthew J; Lewis, Paul D; Mur, Luis A J; Pachebat, Justin A

    2016-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is a major source of mortality and morbidity worldwide. The microbiome associated with this disease may be an important component of the disease, though studies to date have been based on sequencing of the 16S rRNA gene, and have revealed unequivocal results. Here, we employed metagenomic sequencing of the upper bronchial tract (UBT) microbiome to allow for greater elucidation of its taxonomic composition, and revealing functional changes associated with the disease. The bacterial metagenomes within sputum samples from eight COPD patients and ten 'healthy' smokers (Controls) were sequenced, and suggested significant changes in the abundance of bacterial species, particularly within the Streptococcus genus. The functional capacity of the COPD UBT microbiome indicated an increased capacity for bacterial growth, which could be an important feature in bacterial-associated acute exacerbations. Regression analyses correlated COPD severity (FEV1% of predicted) with differences in the abundance of Streptococcus pneumoniae and functional classifications related to a reduced capacity for bacterial sialic acid metabolism. This study suggests that the COPD UBT microbiome could be used in patient risk stratification and in identifying novel monitoring and treatment methods, but study of a longitudinal cohort will be required to unequivocally relate these features of the microbiome with COPD severity.

  7. The Correlation of CD206, CD209, and Disease Severity in Behçet's Disease with Arthritis

    PubMed Central

    Suh, Chang-Hee; Kim, Hyoun-Ah

    2017-01-01

    The purpose of this study was to clarify the role of pattern recognition receptors in Behçet's disease (BD). The frequencies of several pattern recognition receptors (CD11b, CD11c, CD32, CD206, CD209, and dectin-1) were analyzed in patients with BD by flow cytometry, and cytokine levels, interleukin- (IL-) 18, IL-23, and IL-17A, were compared in plasma. The analysis was performed in active (n = 13) and inactive (n = 13) stages of BD patients. Rheumatoid arthritis patients (n = 19), as a disease control, and healthy control (HC) (n = 19) were enrolled. The frequencies of CD11b+ and CD32+ cells were significantly increased in active BD patients compared to HC. Disease severity score was correlated to CD11c+, CD206+, and CD209+ in whole leukocytes and CD11b+, CD11c+, CD206+, CD209+, and Dectin-1+ in granulocytes. The plasma levels of IL-17A were significantly different between HC and active BD. IL-18 showed significant difference between active and inactive BD patients. From this study, we concluded the expressions of several pattern recognition receptors were correlated to the joint symptoms of BD. PMID:28377641

  8. The impact of illness in patients with moderate to severe gastro-esophageal reflux disease

    PubMed Central

    El-Dika, Samer; Guyatt, Gordon H; Armstrong, David; Degl'innocenti, Alessio; Wiklund, Ingela; Fallone, Carlo A; Tanser, Lisa; van Zanten, Sander Veldhuyzen; Heels-Ansdell, Diane; Wahlqvist, Peter; Chiba, Naoki; Barkun, Alan N; Austin, Peggy; Schünemann, Holger J

    2005-01-01

    Background Gastro-esophageal reflux disease (GERD) is a common disease. It impairs health related quality of life (HRQL). However, the impact on utility scores and work productivity in patients with moderate to severe GERD is not well known. Methods We analyzed data from 217 patients with moderate to severe GERD (mean age 50, SD 13.7) across 17 Canadian centers. Patients completed three utility instruments – the standard gamble (SG), the feeling thermometer (FT), and the Health Utilities Index 3 (HUI 3) – and several HRQL instruments, including Quality of Life in Reflux and Dyspepsia (QOLRAD) and the Medical Outcomes Short Form-36 (SF-36). All patients received a proton pump inhibitor, esomeprazole 40 mg daily, for four to six weeks. Results The mean scores on a scale from 0 (dead) to 1 (full health) obtained for the FT, SG, and HUI 3 were 0.67 (95% CI, 0.64 to 0.70), 0.76 (95% CI, 0.75 to 0.80), and 0.80 (95% CI, 0.77 to 0.82) respectively. The mean scores on the SF-36 were lower than the previously reported Canadian and US general population mean scores and work productivity was impaired. Conclusion GERD has significant impact on utility scores, HRQL, and work productivity in patients with moderate to severe disease. Furthermore, the FT and HUI 3 provide more valid measurements of HRQL in GERD than the SG. After treatment with esomeprazole, patients showed improved HRQL. PMID:16004616

  9. Severity of lung fibrosis affects early surgical outcomes of lung cancer among patients with combined pulmonary fibrosis and emphysema.

    PubMed

    Mimae, Takahiro; Suzuki, Kenji; Tsuboi, Masahiro; Ikeda, Norihiko; Takamochi, Kazuya; Aokage, Keiju; Shimada, Yoshihisa; Miyata, Yoshihiro; Okada, Morihito

    2016-07-01

    Combined pulmonary fibrosis and emphysema (CPFE) is defined as upper lobe emphysema and lower lobe fibrosis, which are representative lung disorders that increase the prevalence of lung cancer. This unique disorder may affect the morbidity and mortality during the early period after surgery. The present study aimed to identify which clinicopathological features significantly affect early surgical outcomes after lung resection in nonsmall cell lung cancer (NSCLC) patients and in those with CPFE.We retrospectively assessed 2295 patients with NSCLC and found that 151 (6.6%) had CPFE. All were surgically treated between January 2008 and December 2010 at 4 institutions.The postoperative complication rates for patients with and without CPFE were 39% and 17%, respectively. The 90-day mortality rates were higher among patients with than without CPFE (7.9% vs 1%). Acute exacerbation of interstitial pneumonia was the main cause of death among 12 patients with CPFE who died within 90 days after surgery. Multivariate logistic regression analysis selected CPFE, gender, age, and clinical stage as independent predictive factors for postoperative complications, and CPFE, clinical stage, and sex for 90-day mortality. The severity of lung fibrosis on preoperative CT images was an independent predictive factor for 90-day mortality among patients with CPFE.The key predictive factor for postoperative mortality and complications of lung resection for NSCLC was CPFE. The severity of lung fibrosis was the principal predictor of early outcomes after lung surgery among patients with CPFE and NSCLC.

  10. Predictors of progression to severe Alzheimer’s disease in an incidence sample

    PubMed Central

    Rabins, Peter V.; Schwartz, Sarah; Black, Betty S.; Corcoran, Christopher; Fauth, Elizabeth; Mielke, Michele; Christensen, Jessica; Lyketsos, Constantine; Tschanz, JoAnn

    2013-01-01

    Background Little is known about factors influencing time to severe Alzheimer’s disease (AD). Methods Incident cases of AD in the Cache County Memory Study were identified. Severe AD was defined as Mini-Mental State Examination score of ≤10 or Clinical Dementia Rating Scale score of 3; cases with either Mini-Mental State Examination score of ≥16 or Clinical Dementia Rating <2 were not categorized as severe AD. Kaplan–Meier, log-rank tests, and Cox analyses were used to identify demographic, clinical, and genetic correlates of time to progression to severe AD. Results Sixty-eight of 335 cases of incident AD developed severe dementia. In bivariate analyses, female gender, less than high school education, at least one clinically significant Neuropsychiatric Inventory domain at baseline, and the youngest and oldest ages exhibited shorter time to severe AD. In competing risk analysis, subjects with mild or at least one clinically significant Neuropsychiatric Inventory domain score, and subjects with worse health were more likely to progress to severe dementia or death. Conclusions Demographic and clinical variables predict progression to severe AD. Further study should examine whether these relationships are causal or correlational. PMID:23123228

  11. Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme disease and relapsing-fever Borrelia.

    PubMed

    Toledo, Alvaro; Monzón, Javier D; Coleman, James L; Garcia-Monco, Juan C; Benach, Jorge L

    2015-04-28

    The Lyme disease (Borrelia burgdorferi) and relapsing-fever (Borrelia hispanica) agents have distinct infection courses, but both require cholesterol for growth. They acquire cholesterol from the environment and process it to form cholesterol glycolipids that are incorporated onto their membranes. To determine whether higher levels of serum cholesterol could enhance the organ burdens of B. burgdorferi and the spirochetemia of B. hispanica in laboratory mice, apolipoprotein E (apoE)-deficient and low-density lipoprotein receptor (LDLR)-deficient mice that produce large amounts of serum cholesterol were infected with both spirochetes. Both apoE- and LDLR-deficient mice infected with B. burgdorferi had an increased number of spirochetes in the joints and inflamed ankles compared with the infected wild-type (WT) mice, suggesting that mutations in cholesterol transport that result in high serum cholesterol levels can affect the pathogenicity of B. burgdorferi. In contrast, elevated serum cholesterol did not lead to an increase in the spirochetemia of B. hispanica. In the LDLR-deficient mice, the course of infection was indistinguishable from the WT mice. However, infection of apoE-deficient mice with B. hispanica resulted in a longer spirochetemia and increased mortality. Together, these results argue for the apoE deficiency, and not hypercholesterolemia, as the cause for the increased severity with B. hispanica. Serum hyperlipidemias are common human diseases that could be a risk factor for increased severity in Lyme disease.

  12. Chronic nutrient enrichment increases prevalence and severity of coral disease and bleaching.

    PubMed

    Vega Thurber, Rebecca L; Burkepile, Deron E; Fuchs, Corinne; Shantz, Andrew A; McMinds, Ryan; Zaneveld, Jesse R

    2014-02-01

    Nutrient loading is one of the strongest drivers of marine habitat degradation. Yet, the link between nutrients and disease epizootics in marine organisms is often tenuous and supported only by correlative data. Here, we present experimental evidence that chronic nutrient exposure leads to increases in both disease prevalence and severity and coral bleaching in scleractinian corals, the major habitat-forming organisms in tropical reefs. Over 3 years, from June 2009 to June 2012, we continuously exposed areas of a coral reef to elevated levels of nitrogen and phosphorus. At the termination of the enrichment, we surveyed over 1200 scleractinian corals for signs of disease or bleaching. Siderastrea siderea corals within enrichment plots had a twofold increase in both the prevalence and severity of disease compared with corals in unenriched control plots. In addition, elevated nutrient loading increased coral bleaching; Agaricia spp. of corals exposed to nutrients suffered a 3.5-fold increase in bleaching frequency relative to control corals, providing empirical support for a hypothesized link between nutrient loading and bleaching-induced coral declines. However, 1 year later, after nutrient enrichment had been terminated for 10 months, there were no differences in coral disease or coral bleaching prevalence between the previously enriched and control treatments. Given that our experimental enrichments were well within the ranges of ambient nutrient concentrations found on many degraded reefs worldwide, these data provide strong empirical support to the idea that coastal nutrient loading is one of the major factors contributing to the increasing levels of both coral disease and coral bleaching. Yet, these data also suggest that simple improvements to water quality may be an effective way to mitigate some coral disease epizootics and the corresponding loss of coral cover in the future.

  13. [Tacit metarepresentation and affective sense of personal identity. An approach to understanding severe psychiatric disorders of adolescence and young adulthood].

    PubMed

    Balbi, Juan

    2011-01-01

    The results of present-day research in the field of "Dissociation Paradigm", regarding the capacity of the human mind to perceive, learn, and store information that in appearance passes as unnoticed, support the constructivist hypothesis of the active, selective and constructive condition of consciousness, in addition to the existence of a tacit dimension of knowledge that operates in functional relationship with the former. Unconscious mental states are intrinsically intentional. This is to say that they imply a semantic or cognitive connotation that is capable of affecting phenomenical experience and therefore behavior. In addition, the precocious existence of a tacit metarepresentational system in normally developed children has been proven, which is essential for guaranteeing the deployment of the process of functional coevolution between affectivity and consciousness, by which the experience of personal identity is acquired. These discoveries allow the inference of a "tacit affective metarepresentational recurrence", the organizational foundation on which a unified, sustainable, and continuous sense of the experience of personal identity is structured, and also allow us to hypothesize a "tacit metarepresentational mourning", a specific type of grief which is the chief foundation of the majority of psychopathological disorders. This concept may represent a potential explanation of the severe mental disorders of adolescence and young adulthood. The hypothesis of the present work is that, in the ambiguous context of Postmodern Culture, the prolongation of the adolescent period, facilitated by the welfare state, hinders the dealing with the aforementioned mourning, leading to an increment of depressive states and suicidal behavior among young people.

  14. Differences of Behavioral and Psychological Symptoms of Dementia in Disease Severity in Four Major Dementias

    PubMed Central

    Kazui, Hiroaki; Yoshiyama, Kenji; Kanemoto, Hideki; Suzuki, Yukiko; Sato, Shunsuke; Hashimoto, Mamoru; Ikeda, Manabu; Tanaka, Hibiki; Hatada, Yutaka; Matsushita, Masateru; Nishio, Yoshiyuki; Mori, Etsuro; Tanimukai, Satoshi; Komori, Kenjiro; Yoshida, Taku; Shimizu, Hideaki; Matsumoto, Teruhisa; Mori, Takaaki; Kashibayashi, Tetsuo; Yokoyama, Kazumasa; Shimomura, Tatsuo; Kabeshita, Yasunobu; Adachi, Hiroyoshi; Tanaka, Toshihisa

    2016-01-01

    Background/Aims Behavioral and psychological symptoms of dementia (BPSDs) negatively impact the prognosis of dementia patients and increase caregiver distress. The aims of this study were to clarify the differences of trajectories of 12 kinds of BPSDs by disease severity in four major dementias and to develop charts showing the frequency, severity, and associated caregiver distress (ACD) of BPSDs using the data of a Japan multicenter study (J-BIRD). Methods We gathered Neuropsychiatric Inventory (NPI) data of patients with Alzheimer’s disease (AD; n = 1091), dementia with Lewy bodies (DLB; n = 249), vascular dementia (VaD; n = 156), and frontotemporal lobar degeneration (FTLD; n = 102) collected during a 5-year period up to July 31, 2013 in seven centers for dementia in Japan. The NPI composite scores (frequency × severity) of 12 kinds of items were analyzed using a principal component analysis (PCA) in each dementia. The factor scores of the PCA were compared in each dementia by disease severity, which was determined with Clinical Dementia Rating (CDR). Results Significant increases with higher CDR scores were observed in 1) two of the three factor scores which were loaded for all items except euphoria in AD, 2) two of the four factor scores for apathy, aberrant motor behavior (AMB), sleep disturbances, agitation, irritability, disinhibition, and euphoria in DLB, and 3) one of the four factor scores for apathy, depression, anxiety, and sleep disturbances in VaD. However, no increases were observed in any of the five factor scores in FTLD. Conclusions As dementia progresses, several BPSDs become more severe, including 1) apathy and sleep disturbances in AD, DLB, and VaD, 2) all of the BPSDs except euphoria in AD, 3) AMB, agitation, irritability, disinhibition, and euphoria in DLB, and 4) depression and anxiety in VaD. Trajectories of BPSDs in FTLD were unclear. PMID:27536962

  15. Human Immunodeficiency Virus Disease Severity, Psychiatric Symptoms, and Functional Outcomes in Perinatally Infected Youth

    PubMed Central

    Nachman, Sharon; Chernoff, Miriam; Williams, Paige; Hodge, Janice; Heston, Jerry; Gadow, Kenneth D.

    2012-01-01

    Objective To evaluate associations between human immunodeficiency virus (HIV) disease severity and psychiatric and functional outcomes in youth with perinatal HIV infection. Design Cross-sectional analysis of entry data from an observational, prospective 2-year study. Logistic and linear regression models adjusted for potential confounders were used. Setting Twenty-nine sites of the International Maternal Pediatrics Adolescent AIDS Clinical Trials Group study in the United States and Puerto Rico. Participants Youth aged 6 to 17 years who had HIV infection (N=319). Main Exposures Antiretroviral treatment and perinatal HIV infection. Main Outcome Measures Youth and primary care-givers were administered an extensive battery of measures that assessed psychiatric symptoms; cognitive, social, and academic functioning; and quality of life. Results Characteristics of HIV were a current CD4 percentage of 25% or greater (74% of participants), HIV RNA levels of less than 400 copies/mL (59%), and current highly active antiretroviral therapy (81%). Analyses indicated associations of past and current Centers for Disease Control and Prevention class C designation with less severe attention-deficit/hyperactivity disorder inattention symptoms, older age at nadir CD4 percentage and lower CD4 percentage at study entry with more severe conduct disorder symptoms, higher RNA viral load at study entry with more severe depression symptoms, and lower CD4 percentage at study entry with less severe symptoms of depression. There was little evidence of an association between specific antiretroviral therapy and severity of psychiatric symptoms. A lower nadir CD4 percentage was associated with lower quality of life, worse Wechsler Intelligence Scale for Children Coding Recall scores, and worse social functioning. Conclusion Human immunodeficiency virus illness severity markers are associated with the severity of some psychiatric symptoms and, notably, with cognitive, academic, and social

  16. Severe infectious diseases of childhood as monogenic inborn errors of immunity.

    PubMed

    Casanova, Jean-Laurent

    2015-12-22

    This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications.

  17. Severe infectious diseases of childhood as monogenic inborn errors of immunity

    PubMed Central

    Casanova, Jean-Laurent

    2015-01-01

    This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications. PMID:26621750

  18. Are there any changes in burden and management of communicable diseases in areas affected by Cyclone Nargis?

    PubMed Central

    2011-01-01

    other diseases and mortality rates did not increase, and normal disease patterns resumed by 2009. This suggests that health services as well as prevention and control measures provided to the Nargis-affected population mitigated what could have been a far more severe health impact. PMID:21708044

  19. Autonomic nervous system dysfunction and their relationship with disease severity in children with atopic asthma.

    PubMed

    Emin, Ozkaya; Esra, Gursoy; Aysegül, Demir; Ufuk, Erenberk; Ayhan, Sogut; Rusen, Dundaroz M

    2012-09-30

    The involvement of autonomic imbalance has been reported in the pathogenesis of allergic diseases. The aim of this study was to investigate the association between the clinical severity of childhood asthma with autonomic nervous system (ANS) dysfunction and to define whether the severity of asthma correlates with ANS activity. In this case-control study, we evaluated the ANS activity by testing heart rate variability (HRV) and sympathetic skin response (SRR) in 77 asthmatic children, age 7-12 yrs, who had no co-morbidity and compared them with 40 gender- and age-matched control subjects. According to the severity of their asthma, study subjects were further divided into three groups: I (mild asthmatics), II (moderate asthmatics), and III (severe asthmatics). Inter-group ANS scale scores differed significantly (p<0.01) between Groups I and III and between Groups II and III. Combined use of HRV and SSR provides a higher degree of sensitivity for assessing disease severity in cases of pediatric asthma.

  20. Mechanisms regulating immunity and disease severity following high and low virulence BVDV type 2 infection in neonatal calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute bovine viral diarrhea virus (BVDV) infection can result in a range of disease outcomes from subclinical in the case of low virulence (LV) strains, to anorexia, fever, bloody diarrhea, and death in cases of severe acute disease. Despite the significant range of clinical disease severity, it rem...

  1. Violet diode laser-induced chlorophyll fluorescence: a tool for assessing mosaic disease severity in cassava (Manihot esculenta Crantz) cultivars.

    PubMed

    Anderson, Benjamin; Eghan, Moses J; Asare-Bediako, Elvis; Buah-Bassuah, Paul K

    2012-01-01

    Violet diode laser-induced chlorophyll fluorescence was used in agronomical assessment (disease severity and average yield per plant). Because cassava (Manihot esculenta Crantz) is of economic importance, improved cultivars with various levels of affinity for cassava mosaic disease were investigated. Fluorescence data correlated with cassava mosaic disease severity levels and with the average yield per plant.

  2. Evaluating the indirect effect of self-compassion on binge eating severity through cognitive-affective self-regulatory pathways.

    PubMed

    Webb, Jennifer B; Forman, Mallory J

    2013-04-01

    Current theory and evidence point to disruptions in self-concept and difficulties with emotion regulation as contributing to the severity of binge eating. Alternatively, contemporary perspectives on self-compassion suggest that individual differences in this adaptive approach to self-regulation may serve to counteract these cognitive-affective triggers presumably resulting in reductions in binge eating severity. Accordingly, the present cross-sectional analysis examined an indirect effect model of positive dimensions of self-compassion on binge eating severity through both emotional tolerance and unconditional self-acceptance pathways. Two hundred fifteen undergraduate students (78% female) completed self-report measures of the variables of interest; BMI was calculated from self-reported heights and weights. Pearson's correlations revealed a positive linear association between self-compassion and unconditional self-acceptance; negative links were observed between self-compassion and emotional intolerance along with the severity of binge eating symptoms. A subsequent multiple mediator analysis utilizing both normal test theory and robust non-parametric bootstrap resampling procedures confirmed the presence of a significant total indirect effect of self-compassion on binge eating severity (-.15, p<0.001) through the combined mediators along with yielding specific indirect effects for both emotional tolerance (-.05, p<0.05) and unconditional self-acceptance (-.11, p<0.01) which were preserved in a model adjusted for BMI. Preliminary results underscore the need to further evaluate the tenability of this model in both prospective cohort and intervention-based research. Findings additionally invite considering the value of integrating self-compassion training into college health promotion efforts towards mitigating the appreciable levels of binge eating behavior prevalent in this at-risk population.

  3. Effects of disease severity and medication state on postural control asymmetry during challenging postural tasks in individuals with Parkinson's disease.

    PubMed

    Barbieri, Fabio A; Polastri, Paula F; Baptista, André M; Lirani-Silva, Ellen; Simieli, Lucas; Orcioli-Silva, Diego; Beretta, Victor S; Gobbi, Lilian T B

    2016-04-01

    The aim of this study was to investigate the effects of disease severity and medication state on postural control asymmetry during challenging tasks in individuals with Parkinson's disease (PD). Nineteen people with PD and 11 neurologically healthy individuals performed three standing task conditions: bipedal standing, tandem and unipedal adapted standing; the individuals with PD performed the tasks in ON and OFF medication state. The participants with PD were distributed into 2 groups according to disease severity: unilateral group (n=8) and bilateral group (n=11). The two PD groups performed the evaluations both under and without the medication. Two force plates were used to analyze the posture. The symmetric index was calculated for various of center of pressure. ANOVA one-way (groups) and two-way (PD groups×medication), with repeated measures for medication, were calculated. For main effects of group, the bilateral group was more asymmetric than CG. For main effects of medication, only unipedal adapted standing presented effects of PD medication. There was PD groups×medication interaction. Under the effects of medication, the unilateral group presented lower asymmetry of RMS in anterior-posterior direction and area than the bilateral group in unipedal adapted standing. In addition, the unilateral group presented lower asymmetry of mean velocity, RMS in anterior-posterior direction and area in unipedal standing and area in tandem adapted standing after a medication dose. Postural control asymmetry during challenging postural tasks was dependent on disease severity and medication state in people with PD. The bilateral group presented higher postural control asymmetry than the control and unilateral groups in challenging postural tasks. Finally, the medication dose was able to reduce postural control asymmetry in the unilateral group during challenging postural tasks.

  4. Hispanic Americans and African Americans with multiple sclerosis have more severe disease course than Caucasian Americans.

    PubMed

    Ventura, Rachel E; Antezana, Ariel O; Bacon, Tamar; Kister, Ilya

    2016-11-01

    Whether disease course in Hispanic Americans (HA) with multiple sclerosis (MS) is different from Caucasian Americans (CA) or African Americans (AA) is unknown. We compared MS severity in the three main ethnic populations in our tertiary MS clinics using disease duration-adjusted rank score of disability: Patient-Derived Multiple Sclerosis Severity Score (P-MSSS). The age- and gender-adjusted P-MSSS was significantly higher in HA (3.9 ± 2.6) and AA (4.5 ± 3.0) compared to CA (3.4 ± 2.6; p < 0.0001 for both). Adjusting for insurance did not change these results. These findings suggest that HA, as AA, have more rapid disability accumulation than CA.

  5. Haemopoietic stem cell transplantation in the treatment of severe autoimmune diseases 2000.

    PubMed

    Tyndall, A; Passweg, J; Gratwohl, A

    2001-07-01

    An international meeting took place in Basel, Switzerland from 5 to 7 October 2000 involving 180 participants from 30 countries, with the aim of assessing the existing data on autologous haemopoietic stem cell transplantation (HSCT) in the treatment of severe autoimmune disease, and to decide on future trial planning. Data on 390 patients were presented: 260 from the EBMT/EULAR Basel European/Asian database, 87 from North America (55 from the IBMTR), 39 from Australia, and 4 others. The major disease categories and number of patients receiving transplant were: multiple sclerosis (MS) 127, systemic sclerosis (SSc) 72, rheumatoid arthritis (RA) 70, juvenile idiopathic arthritis (JIA) 36, systemic lupus erythematosus (SLE) 34, dermatomyositis/polymyositis (DM/PM) 5, idiopathic thrombocytopenic purpura (ITP) 7. Single or several cases of other autoimmune diseases were reported. Clinically significant responses were seen in two thirds of all the cases and in all disease categories, with a more accentuated trend towards relapse in JIA and RA. Treatment was associated with a significant morbidity and mortality. In the EULAR/EBMT database (71 centres in 22 countries), a mobilisation associated mortality of 1.5% and an overall procedure related mortality (actuarially adjusted at 12 months) of 9% (confidence interval 6 to 12%) were found, with significant variation between diseases. The North American data showed similar results. Higher mortalities were seen in SSc and systemic JIA, with only one death reported in RA. After presentation of the data and workshop discussion a consensus was reached on several aspects: prospective randomised phase III trials are now appropriate in SSc, MS, and RA. A protocol is ready for SSc (ASTIS Trial), concepts are clear for MS and RA. Further phase I and II data are required in SLE, JIA, and vasculitis. The need for continuing collection of all cases after mobilisation by the standardised EBMT and IBMTR data forms was emphasised.

  6. P-wave dispersion and its relationship with the severity of the disease in patients with stable coronary artery disease

    PubMed Central

    Akin, Fatih; Firatli, Inci; Katkat, Fahrettin; Gurmen, Tevfik; Ayca, Burak; Kalyoncuoglu, Muhsin; Abaci, Okay; Sari, Mustafa; Ersanli, Murat; Kucukoglu, Serdar; Yigit, Zerrin

    2014-01-01

    OBJECTIVE: P- wave dispersion (PD) is an indicator of inhomogeneous and discontinuous propagation of sinus impulses. In the present study we aimed to investigate the PD and its association with the severity of the disease. in patients with stable coronary artery disease. METHODS: We prospectively analyzed 60 subjects with coronary artery disease (CAD) and 25 subjects with nor-mal coronary angiograms (control group). The maximum and minimum P-wave duration and PD were measured from the 12-lead surface electrocardiograms. The CAD severity was assessed by the severity score (Gensini score) and the number of vessels involved (vessel score). RESULTS: P max was longer in CAD group compared with the control group (p<0.001). PD was greater in the CAD group, compared with the control group (p<0.001). However, P min did not differ between the two groups. In bi-variate correlation, increased PD was correlated with presence of diabetes mellitus (r=0.316, p=0.014), smoking (r=0.348, p=0.006), left ventricular ejection fraction (r=-0.372, p=0.003), vessel score (r=0.848, p=0.001), and Gensini score (r=0.825, p=0.001). Multiple linear regression analysis showed that PD was independently associ¬ated with vessel score ((3=0.139, p=0.002) and Gensini score ((3=0.132, p=0.007). CONCLUSION: PD was greater in patients with CAD than in controls and it was associated with CAD severity. PMID:28058305

  7. Creation of a nonsurgical papilla in orthodontic treatment with severe periodontal disease: a case report.

    PubMed

    Sato, Shuichi; Nomura, Naoyuki; Kawashima, Hideyuki; Ito, Koichi

    2007-04-01

    This case report describes the nonsurgical creation of an interdental papilla in orthodontic therapy of a patient with severe periodontal disease. A large diastema between the maxillary incisors was closed completely, and the lost interdental papilla was re-created by orthodontic therapy after nonsurgical periodontal therapy. Radiographs showed improvement of the bone defect. Periodontal/orthodontic soft tissue manipulation is a nonsurgical technique that can lead to reformation of the interdental papilla, provided that periodontal health is maintained.

  8. A Systematic Review of Assessment and Treatment of Moderate to Severe Alzheimer's Disease

    PubMed Central

    Schmitt, Frederick A.; Wichems, Christine H.

    2006-01-01

    Objective: The systematic, large-scale study of therapies for moderate to severe Alzheimer's disease (AD) is a relatively recent advancement in the field. This review describes for the general practitioner the characterization of moderate to severe AD, discusses the development of metrics sensitive to the constellation of symptoms in these patients, and critically evaluates the use of those measures in moderate to severe AD clinical trials. Data Sources: Published clinical trials obtained by MEDLINE searches used the following key words: moderate AD, severe AD, donepezil, rivastigmine, galantamine, memantine, and anti-dementia agents. Clinical trials were limited by language (English), study type (clinical trial), and publication dates (1990–2005). Study Selection: Nine clinical trials comprise the studies conducted to date in moderate to severe AD and include 5 prospective randomized clinical trials (3 for memantine, 2 for donepezil) and 4 retrospective subanalyses (2 for galantamine, 2 for rivastigmine) of primary datasets. Data Extraction: Clinical trials are summarized and major findings are reviewed. Data Synthesis: The data reviewed support the decision to initiate and maintain treatment in moderate to severe AD patients. Conclusions: The development and implementation of improved metrics for moderate to severe AD patients has revealed that meaningful benefits are attainable in this patient population by treatment with the N-methyl-D-aspartate receptor antagonist memantine. Evidence also indicates a benefit from cholinesterase inhibitor treatment, although further study of these agents in this patient population is warranted. PMID:16912819

  9. [Several common biases and control measures during sampling survey of eye diseases in China].

    PubMed

    Guan, Huai-jin

    2008-06-01

    Bias is a common artificial error during sampling survey in eye diseases, and is a major impact factor for validity and reliability of the survey. The causes and the control measures of several biases regarding current sampling survey of eye diseases in China were analyzed and discussed, including the sampling bias, non-respondent bias, and diagnostic bias. This review emphasizes that controlling bias is the key to ensure quality of sampling survey. Random sampling, sufficient sample quantity, careful examination and taking history, improving examination rate, accurate diagnosis, strict training and preliminary study, as well as quality control can eliminate or minimize biases and improve the sampling survey quality of eye diseases in China

  10. Fatal infectious mononucleosis: a severe complication in the treatment of Crohn's disease with azathioprine.

    PubMed Central

    Posthuma, E F; Westendorp, R G; van der Sluys Veer, A; Kluin-Nelemans, J C; Kluin, P M; Lamers, C B

    1995-01-01

    A 19 year old man with a history of Crohn's disease treated with azathioprine and prednisone, died after a primary infection with Epstein-Barr virus. He had the characteristics of the virus associated haemophagocytic syndrome, a rare complication of viral infections, which consists of fever, constitutional symptoms, hepatosplenomegaly, liver function and coagulation abnormalities, and hypertriglyceridaemia. Additionally, there was pain, cytopenia, and histiocytic hyperplasia in the bone marrow, spleen, or lymph nodes. This severe complication has been reported previously in renal transplant patients, but not in those with inflammatory bowel disease taking azathioprine. The immunosuppressive therapy may have contributed to this fatal complication of infectious mononucleosis, and this complication should be considered when treating a patient with inflammatory bowel disease with azathioprine. Images p312-a PMID:7883236

  11. Differential secretion of the mutated protein is a major component affecting phenotypic severity in CRLF1-associated disorders

    PubMed Central

    Herholz, Jana; Meloni, Alessandra; Marongiu, Mara; Chiappe, Francesca; Deiana, Manila; Herrero, Carmen Roche; Zampino, Giuseppe; Hamamy, Hanan; Zalloum, Yusra; Waaler, Per Erik; Crisponi, Giangiorgio; Crisponi, Laura; Rutsch, Frank

    2011-01-01

    Crisponi syndrome (CS) and cold-induced sweating syndrome type 1 (CISS1) are disorders caused by mutations in CRLF1. The two syndromes share clinical characteristics, such as dysmorphic features, muscle contractions, scoliosis and cold-induced sweating, with CS patients showing a severe clinical course in infancy involving hyperthermia, associated with death in most cases in the first years of life. To evaluate a potential genotype/phenotype correlation and whether CS and CISS1 represent two allelic diseases or manifestations at different ages of the same disorder, we carried out a detailed clinical analysis of 19 patients carrying mutations in CRLF1. We studied the functional significance of the mutations found in CRLF1, providing evidence that phenotypic severity of the two disorders mainly depends on altered kinetics of secretion of the mutated CRLF1 protein. On the basis of these findings, we believe that the two syndromes, CS and CISS1, represent manifestations of the same disorder, with different degrees of severity. We suggest renaming the two genetic entities CS and CISS1 with the broader term of Sohar–Crisponi syndrome. PMID:21326283

  12. Arthritic disease is more severe in older rats in a kaolin/carrageenan-induced arthritis model.

    PubMed

    Kim, Kyoung Soo; Kim, Myung-Hwan; Yeom, Mijung; Choi, Hyun Mi; Yang, Hyung-In; Yoo, Myung Chul; Hahm, Dae-Hyun

    2012-12-01

    This study examined in an arthritis animal model whether elderly onset rheumatoid arthritis (EORA) is a more severe disease than younger onset rheumatoid arthritis. Arthritis was induced by injecting 5% kaolin/carrageenan into the left tibiotarsal ankles of 18-month-old and 4-week-old rats. Various parameters were measured to evaluate the arthritic progression of kaolin/carrageenan-induced arthritis in the rats. Immunohistochemical staining of arthritic joints was performed to determine the degree of inflammation in old and young rats. Measurements of ankle volume and thickness, arthritic index, number of squeaks, and the paw pressure test showed the 18-month-old rats had more severe disease than the young rats in a kaolin/carrageenan-induced arthritis model. The degree of inflammation and MMP-1 expression of arthritic joints in old rats was significantly higher than that of young rats based on histological evaluation with hematoxylin and eosin (H&E) staining and immunochemistry. More severe disease symptoms were found in old rats with EORA, but the molecular mechanisms still remain to be elucidated. Understanding the molecular mechanisms will be helpful to develop clinical protocols to efficiently treat patients with EORA, which is difficult to control with current protocols.

  13. AGER -429T/C Is Associated with an Increased Lung Disease Severity in Cystic Fibrosis

    PubMed Central

    Beucher, Julie; Boëlle, Pierre-Yves; Busson, Pierre-François; Muselet-Charlier, Céline; Clement, Annick; Corvol, Harriet; Abely, M.; Belleguic, C.; Bellon, G.; Bessaci, K.; Bonnel, A.S.; Brémont, F.; Brouard, J.; Bui, S.; Chiron, R.; Chumbi-Flores, R.; Clement, A.; Corvol, H.; Dalphin, J.C.; Dalphin, M.L.; David, V.; de Miranda, S.; Derelle, J.; Domblides, P.; Dominique, S.; Dubus, J.C.; Durieu, I.; Dury, S.; Ellaffi, M.; Epaud, R.; Fanton, A.; Fayon, M.; Fleurence, E.; Foucaud, P.; Ginies, J.L.; Godbert, B.; Grenet, D.; Guillot, M.; Héraud, M. C.; Housset, B.; Hubert, D.; Huet, F.; Kessler, R.; Labbé, A.; Laurans, M.; le Bourgeois, M.; le Roux, P.; Llerena, C.; Loeuille, G.A.; Marguet, C.; Mely, L.; Moisan-Petit, V.; Munck, A.; Murris-Espin, M.; Nove Josserand, R.; Pautard, J.C.; Pin, I.; Pramil, S.; Prevotat, A.; Rault, G.; Reix, P.; Remus, N.; Renouil, M.; Reynaud-Gaubert, M.; Richaud Thiriez, B.; Roussey, M.; Sermet-Gaudelus, I.; Stremler, N.; Uffredi, M.L.; Urban, T.; Vigneron, P.; Wallaert, B.; Weiss, L.

    2012-01-01

    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV1 was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease. PMID:22860029

  14. AGER -429T/C is associated with an increased lung disease severity in cystic fibrosis.

    PubMed

    Beucher, Julie; Boëlle, Pierre-Yves; Busson, Pierre-François; Muselet-Charlier, Céline; Clement, Annick; Corvol, Harriet

    2012-01-01

    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV(1) was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.

  15. Lipoprotein (a) Levels in Relation to Severity of Coronary Artery Disease in North Indian Patients

    PubMed Central

    Ashfaq, Fauzia; Goel, Pravin Kumar; Sethi, Rishi; Khan, Mohd Idrees; Ali, Wahid; Idris, Mohd Zafar

    2013-01-01

    Background: Lipoprotein (a) [Lp (a)] is an established risk marker of coronary artery disease which is independent from other risk factors. Objective: The aim was to address the association between Lp (a) and CAD risk in North Indians. To evaluate whether high levels of lipoprotein (a) [Lp (a)] is a predictor of risk and is related to the severity of CAD. Materials and Methods: This was a cross-sectional study done on 360 patients presenting with chest pain. Coronary angiography revealed CAD in 270 patients and 90 patients without CAD. Lipoprotein (a) level, lipid profile, fasting blood glucose, anthropometric and clinical parameters were analyzed. Results: Lipoprotein (a) 21.0 mg/dL is associated with the presence of coronary lesions (P = 0.0001). A highly significant difference in Lp (a) levels was observed between normal coronaries vs. single-vessel disease, double-and triple-vessel disease ( P < 0.0001). Body mass index (BMI) was significantly raised in CAD group compared to normal coronary. Conclusion: Multivariate analysis found that Lp (a) was considered an independent predictor for severity of CAD and Lp (a) levels 21.0 mg/dL are associated with severe patterns of coronary atherosclerosis. PMID:23580919

  16. Prediction of Dengue Disease Severity among Pediatric Thai Patients Using Early Clinical Laboratory Indicators

    PubMed Central

    Potts, James A.; Gibbons, Robert V.; Rothman, Alan L.; Srikiatkhachorn, Anon; Thomas, Stephen J.; Supradish, Pra-on; Lemon, Stephenie C.; Libraty, Daniel H.; Green, Sharone; Kalayanarooj, Siripen

    2010-01-01

    Background Dengue virus is endemic in tropical and sub-tropical resource-poor countries. Dengue illness can range from a nonspecific febrile illness to a severe disease, Dengue Shock Syndrome (DSS), in which patients develop circulatory failure. Earlier diagnosis of severe dengue illnesses would have a substantial impact on the allocation of health resources in endemic countries. Methods and Findings We compared clinical laboratory findings collected within 72 hours of fever onset from a prospective cohort children presenting to one of two hospitals (one urban and one rural) in Thailand. Classification and regression tree analysis was used to develop diagnostic algorithms using different categories of dengue disease severity to distinguish between patients at elevated risk of developing a severe dengue illness and those at low risk. A diagnostic algorithm using WBC count, percent monocytes, platelet count, and hematocrit achieved 97% sensitivity to identify patients who went on to develop DSS while correctly excluding 48% of non-severe cases. Addition of an indicator of severe plasma leakage to the WHO definition led to 99% sensitivity using WBC count, percent neutrophils, AST, platelet count, and age. Conclusions This study identified two easily applicable diagnostic algorithms using early clinical indicators obtained within the first 72 hours of illness onset. The algorithms have high sensitivity to distinguish patients at elevated risk of developing severe dengue illness from patients at low risk, which included patients with mild dengue and other non-dengue febrile illnesses. Although these algorithms need to be validated in other populations, this study highlights the potential usefulness of specific clinical indicators early in illness. PMID:20689812

  17. PARKINSON'S DISEASE PATIENTS WITH DOMINANT HEMIBODY AFFECTED BY THE DISEASE RELY MORE ON VISION TO MAINTAIN UPRIGHT POSTURAL CONTROL.

    PubMed

    Lahr, Juliana; Pereira, Marcelo Pinto; Pelicioni, Paulo Henrique Silva; De Morais, Luana Carolina; Gobbi, Lilian Teresa Bucken

    2015-12-01

    This study assesses the association between disease onset side (dominant or non-dominant) and vision on postural control of Parkinson's disease patients. Patient volunteers composed two groups, according to the onset side affected: Dominant group (n=9; M age=66.1 yr., SD=7.2; 6 women, 3 men) and Non-dominant group (n=9; M age=67.4 yr., SD=6.4; 6 women, 3 men). The groups' postural control was assessed by posturography during quiet upright stance in two conditions, Eyes open and Eyes closed. Two-way analyses of variance (ANOVAs; group×condition) with repeated measures for the second factor assessed the differences associated with affected hemibody and vision on postural control. Analyses indicated that patients with the dominant side affected also presented significantly greater variation in center of pressure than those with the non-dominant side affected, mainly in the Eyes closed condition. The results demonstrate a higher reliance on vision in the dominant side, possibly to compensate somatosensory system impairments. These results also highlight the importance of analyzing the hemibody affected by the disease when postural control is assessed in this population.

  18. Effects of sildenafil on pulmonary hypertension and exercise tolerance in severe cystic fibrosis-related lung disease.

    PubMed

    Montgomery, Gregory S; Sagel, Scott D; Taylor, Amy L; Abman, Steven H

    2006-04-01

    Cystic fibrosis (CF) patients with advanced lung disease are at risk for developing pulmonary vascular disease and pulmonary hypertension, characterized by progressive exercise intolerance beyond the exercise-limiting effects of airways disease in CF. We report on a patient with severe CF lung disease who experienced clinically significant improvements in exercise tolerance and pulmonary hypertension without changing lung function during sildenafil therapy.

  19. Disease Severity in Patients Infected with Leishmania mexicana Relates to IL-1β

    PubMed Central

    Fernández-Figueroa, Edith A.; Rangel-Escareño, Claudia; Espinosa-Mateos, Valeria; Carrillo-Sánchez, Karol; Salaiza-Suazo, Norma; Carrada-Figueroa, Georgina; March-Mifsut, Santiago; Becker, Ingeborg

    2012-01-01

    Leishmania mexicana can cause both localized (LCL) and diffuse (DCL) cutaneous leishmaniasis, yet little is known about factors regulating disease severity in these patients. We analyzed if the disease was associated with single nucleotide polymorphisms (SNPs) in IL-1β (−511), CXCL8 (−251) and/or the inhibitor IL-1RA (+2018) in 58 Mexican mestizo patients with LCL, 6 with DCL and 123 control cases. Additionally, we analyzed the in vitro production of IL-1β by monocytes, the expression of this cytokine in sera of these patients, as well as the tissue distribution of IL-1β and the number of parasites in lesions of LCL and DCL patients. Our results show a significant difference in the distribution of IL-1β (−511 C/T) genotypes between patients and controls (heterozygous OR), with respect to the reference group CC, which was estimated with a value of 3.23, 95% CI = (1.2, 8.7) and p-value = 0.0167), indicating that IL-1β (−511 C/T) represents a variable influencing the risk to develop the disease in patients infected with Leishmania mexicana. Additionally, an increased in vitro production of IL-1β by monocytes and an increased serum expression of the cytokine correlated with the severity of the disease, since it was significantly higher in DCL patients heavily infected with Leishmania mexicana. The distribution of IL-1β in lesions also varied according to the number of parasites harbored in the tissues: in heavily infected LCL patients and in all DCL patients, the cytokine was scattered diffusely throughout the lesion. In contrast, in LCL patients with lower numbers of parasites in the lesions, IL-1β was confined to the cells. These data suggest that IL-1β possibly is a key player determining the severity of the disease in DCL patients. The analysis of polymorphisms in CXCL8 and IL-1RA showed no differences between patients with different disease severities or between patients and controls. PMID:22629474

  20. Impact of the severity of chronic periodontal disease on quality of life.

    PubMed

    Meusel, Dayse R D Z; Ramacciato, Juliana C; Motta, Rogério H L; Brito Júnior, Rui B; Flório, Flávia M

    2015-06-01

    We examined the impact of the severity of periodontal disease on quality of life in adults with chronic periodontitis. One hundred patients (age, 30-58 years) who were assisted at the Basic Health Care Unit in the city of Passo Fundo, RS, Brazil underwent clinical examination of all standing teeth, including gingival bleeding on probing, probing depth, and clinical attachment level, and were divided into those with mild/moderate (n = 49; group G1) and severe (n = 51; group G2) chronic periodontitis. The participants were then interviewed, using a structured questionnaire. The Brazilian Oral Health Impact Profile (OHIP-14Br) questionnaire was used to assess oral health-related quality of life. Associations were investigated, and those with a P value of less than 0.2 were tested using multiple logistic regression models. Those with a P value of 0.05 or less were considered significant. There was a significant association between G2 and education level (P = 0.00051). OHIP-14Br score was higher for G2 (24.1) than for G1 (18.2) (P = 0.0455). Severe chronic periodontitis was associated with low education level (≤8 years) (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.2-7.3) and pronunciation difficulties (OR, 3.1; 95% CI, 1.0-9.3). In conclusion, periodontal disease severity was inversely associated with quality of life among Brazilian adults.

  1. Chronic nitrate enrichment decreases severity and induces protection against an infectious disease.

    PubMed

    Smallbone, Willow; Cable, Jo; Maceda-Veiga, Alberto

    2016-05-01

    Excessive fertilisation is one of the most pernicious forms of global change resulting in eutrophication. It has major implications for disease control and the conservation of biodiversity. Yet, the direct link between nutrient enrichment and disease remains largely unexplored. Here, we present the first experimental evidence that chronic nitrate enrichment decreases severity and induces protection against an infectious disease. Specifically, this study shows that nitrate concentrations ranging between 50 and 250mgNO3(-)/l reduce Gyrodactylus turnbulli infection intensity in two populations of Trinidadian guppies Poecilia reticulata, and that the highest nitrate concentration can even clean the parasites from the fish. This added to the fact that host nitrate pre-exposure altered the fish epidermal structure and reduced parasite intensity, suggests that nitrate protected the host against the disease. Nitrate treatments also caused fish mortality. As we used ecologically-relevant nitrate concentrations, and guppies are top-consumers widely used for mosquito bio-control in tropical and often nutrient-enriched waters, our results can have major ecological and social implications. In conclusion, this study advocates reducing nitrate level including the legislative threshold to protect the aquatic biota, even though this may control an ectoparasitic disease.

  2. Treatment with the Antipsychotic Agent, Risperidone, Reduces Disease Severity in Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Stone, Sarrabeth; Zareie, Pirooz; Kharkrang, Marie; Fong, Dahna; Connor, Bronwen; La Flamme, Anne Camille

    2014-01-01

    Recent studies have demonstrated that atypical antipsychotic agents, which are known to antagonize dopamine D2 and serotonin 5-HT2a receptors, have immunomodulatory properties. Given the potential of these drugs to modulate the immune system both peripherally and within the central nervous system, we investigated the ability of the atypical anti-psychotic agent, risperidone, to modify disease in the animal model of multiple sclerosis (MS)4, experimental autoimune encephalomyelitis (EAE). We found that chronic oral administration of risperidone dose-dependently reduced the severity of disease and decreased both the size and number of spinal cord lesions. Furthermore, risperidone treatment substantially reduced antigen-specific interleukin (IL)-17a, IL-2, and IL-4 but not interferon (IFN)-γ production by splenocytes at peak disease and using an in vitro model, we show that treatment of macrophages with risperidone alters their ability to bias naïve T cells. Another atypical antipsychotic agent, clozapine, showed a similar ability to modify macrophages in vitro and to reduce disease in the EAE model but this effect was not due to antagonism of the type 1 or type 2 dopamine receptors alone. Finally, we found that while risperidone treatment had little effect on the in vivo activation of splenic macrophages during EAE, it significantly reduced the activation of microglia and macrophages in the central nervous system. Together these studies indicate that atypical antipsychotic agents like risperidone are effective immunomodulatory agents with the potential to treat immune-mediated diseases such as MS. PMID:25116424

  3. Comparison of thallium-201 scanning in idiopathic dilated cardiomyopathy and severe coronary artery disease

    SciTech Connect

    Dunn, R.F.; Uren, R.F.; Sadick, N.; Bautovich, G.; McLaughlin, A.; Hiroe, M.; Kelly, D.T.

    1982-10-01

    To determine whether cardiomyopathy could be distinguished from coronary artery disease, we used thallium scanning to study 25 patients with severe left ventricular dysfunction and chronic heart failure. Ten patients had normal coronary arteries and idiopathic cardiomyopathy (ejection fraction 20 +/- 5%), and 15 patients had multivessel coronary disease and left ventricular dysfunction (ejection fraction 25 +/- 6%). The exercise time and maximal heart rate were similar in the two groups. Two patients with cardiomyopathy and 11 with coronary artery disease had a positive exercise ECG (p less than 0.05). Thallium scans showed perfusion defects in all 25 patients. The perfusion defects were complete in nine coronary artery disease patients (60%) and in one patient (10%) with cardiomyopathy (p less than 0.05). Extensive defects involving more than 40% of the left ventricular circumference, the number of segments involved, redistribution on the 4-hour scan, lung uptake and ventricular size were similar in the two groups. Perfusion defects on thallium scanning can occur in patients with idiopathic dilated cardiomyopathy and chronic heart failure. Thallium scanning cannot be reliably used in patients with chronic heart failure to distinguish coronary artery disease from cardiomyopathy unless complete defects are present.

  4. Comparison of thallium-201 scanning in idiopathic dilated cardiomyopathy and severe coronary artery disease

    SciTech Connect

    Dunn, R.F.; Uren, R.F.; Sadick, N.; Bautovich, G.; McLaughlin, A.; Hiroe, M.; Kelly, D.T.

    1982-10-01

    To determine whether cardiomyopathy could be distinguished from coronary artery disease, we used thallium scanning to study 25 patients with severe left ventricular dysfunction and chronic heart failure. Ten patients had normal coronary arteries and idiopathic cardiomyopathy (ejection fraction 20 +/- 5%), and 15 patients had multivessel coronary disease and left ventricular dysfunction (ejection fraction 25 +/- 6%). The exercise time and maximal heart rate were similar in the two groups. Two patients with cardiomyopathy and 11 with coronary artery disease had a positive exercise ECG (p<0.05). Thallium scans showed perfusion defects in all 25 patients. The perfusion defects were complete in nine coronary artery disease patients (60%) and in one patient (10%) with cardiomyopathy (p<0.05). Extensive defects involving more than 40% of the left ventricular circumference, the number of segments involved, redistribution on the 4-hour scan, lung uptake and ventricular size were similar in the two groups. Perfusion defects on thallium scanning can occur in patients with idiopathic dilated cardiomyopathy and chronic heart failure. Thallium scanning cannot be reliably used in patients with chronic heart failure to distinguish coronary artery disease from cardiomyopathy unless complete defects are present.

  5. Treatment with the antipsychotic agent, risperidone, reduces disease severity in experimental autoimmune encephalomyelitis.

    PubMed

    O'Sullivan, David; Green, Laura; Stone, Sarrabeth; Zareie, Pirooz; Kharkrang, Marie; Fong, Dahna; Connor, Bronwen; La Flamme, Anne Camille

    2014-01-01

    Recent studies have demonstrated that atypical antipsychotic agents, which are known to antagonize dopamine D2 and serotonin 5-HT2a receptors, have immunomodulatory properties. Given the potential of these drugs to modulate the immune system both peripherally and within the central nervous system, we investigated the ability of the atypical anti-psychotic agent, risperidone, to modify disease in the animal model of multiple sclerosis (MS)4, experimental autoimune encephalomyelitis (EAE). We found that chronic oral administration of risperidone dose-dependently reduced the severity of disease and decreased both the size and number of spinal cord lesions. Furthermore, risperidone treatment substantially reduced antigen-specific interleukin (IL)-17a, IL-2, and IL-4 but not interferon (IFN)-γ production by splenocytes at peak disease and using an in vitro model, we show that treatment of macrophages with risperidone alters their ability to bias naïve T cells. Another atypical antipsychotic agent, clozapine, showed a similar ability to modify macrophages in vitro and to reduce disease in the EAE model but this effect was not due to antagonism of the type 1 or type 2 dopamine receptors alone. Finally, we found that while risperidone treatment had little effect on the in vivo activation of splenic macrophages during EAE, it significantly reduced the activation of microglia and macrophages in the central nervous system. Together these studies indicate that atypical antipsychotic agents like risperidone are effective immunomodulatory agents with the potential to treat immune-mediated diseases such as MS.

  6. Computed tomography phenotypes in severe, early-onset chronic obstructive pulmonary disease.

    PubMed

    Hersh, Craig P; Jacobson, Francine L; Gill, Ritu; Silverman, Edwin K

    2007-12-01

    Subjects with severe chronic obstructive pulmonary disease (COPD) may have marked differences in emphysema severity on chest computed tomography (CT) scans. Although many patients with severe COPD will have chest CTs performed during their clinical care, chest CTs have not been widely included in epidemiologic and genetic studies of COPD. We sought to determine whether chest CT scans performed for clinical indications can provide useful data in an epidemiologic study of COPD and to determine whether chest CT scans can be used to define subtypes of severe, early-onset COPD. Clinical chest CT scans on 91 probands in the Boston Early-Onset COPD Study were retrospectively reviewed by 2 pulmonologists and 1 to 2 chest radiologists, using a semi-quantitative emphysema severity score, ranging from 0-24. 88 of 91 chest CT scans were suitable for emphysema analysis. There was a wide range of emphysema severity, from mild to severe (1.3-23.7). Emphysema-predominant subjects (upper 3 quartiles of emphysema scores) had more severe airflow obstruction than airway-predominant subjects (lowest quartile of emphysema scores): FEV(1) 17.4% vs. 22.4% predicted, p=0.009. A higher percentage of airway-predominant subjects had a positive bronchodilator response (28.6% vs. 6.7%, p=0.009). Airway-predominant subjects also had a higher frequency of physician-diagnosed asthma (p=0.04) and a trend towards higher serum immunoglobulin E levels (p=0.09). Analysis of siblings of early-onset COPD probands suggested a genetic contribution to the subgroups. Using clinical chest CT scans, we were able to identify an airway-predominant subgroup with asthma-like features among subjects with severe, early-onset COPD.

  7. Association of Serum Irisin Concentrations with Presence and Severity of Coronary Artery Disease

    PubMed Central

    Deng, Wen

    2016-01-01

    Background Irisin, an exercise-induced myokine, is closely correlated with obesity and body mass index. Obesity is one risk factor of coronary artery disease (CAD). Therefore, the present study aimed to determine if serum irisin concentrations are correlated with the presence and severity of CAD. Material/Methods Serum irisin concentrations were determined in 350 patients with CAD and in 214 healthy subjects. The severity of CAD was assessed by coronary atherosclerosis index (CAI). Results Serum irisin concentrations were significantly lower in CAD patients compared with healthy controls. Multivariable logistic regression analysis revealed that serum irisin concentrations were an independent determinant of the presence of CAD. In addition, Pearson correlation analysis showed that serum irisin concentrations were negatively correlated with CAI in CAD patients. Conclusions Decreased serum irisin concentrations may be associated with the presence and severity of CAD. PMID:27815563

  8. Serum Cytokine Profile in Relation to the Severity of Coronary Artery Disease

    PubMed Central

    Lu, Miao; Tu, Su; Wang, Xiangming; Zhou, Chuanwei; Wang, Sen; Pang, Sisi; Qian, Jin; Ge, Yiyue; Guo, Yan

    2017-01-01

    Objectives. To investigate the potential association of a set of serum cytokines with the severity of coronary artery disease (CAD). Methods. A total of 201 patients who underwent coronary angiography for chest discomfort were enrolled. The concentrations of serum IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-9, and IL-17 were determined by xMAP multiplex technology. The CAD severity was assessed by Gensini score (GS). Results. The serum levels of TNF-α, IL-6, IL-9, IL-10, and IL-17 were significantly higher in high GS group (GS ≥ 38.5) than those in low GS group (GS < 38.5). Positive correlations were also found between these cytokines and the severity of CAD. After adjustment for other associated factors, three serum cytokines (IL-6, IL-9, and IL-17) and two clinical risk factors (creatinine and LDL-C) were identified as the independent predictors of increased severity of CAD. ROC curve analysis revealed that the logistic regression risk prediction model had a good performance on predicting CAD severity. Conclusions. Combinatorial analysis of serum cytokines (IL-6, IL-9, and IL-17) with clinical risk factors (creatinine and LDL-C) may contribute to the evaluation of the severity of CAD and may help guide the risk stratification of angina patients, especially in primary health facilities and in the catheter lab resource-limited settings. PMID:28349060

  9. Impact of Hurricane Sandy on community pharmacies in severely affected areas of New York City: A qualitative assessment.

    PubMed

    Arya, Vibhuti; Medina, Eric; Scaccia, Allison; Mathew, Cathleen; Starr, David

    2016-01-01

    Hurricane Sandy was one of the most severe natural disasters to hit the Mid-Atlantic States in recent history. Community pharmacies were among the businesses affected, with flooding and power outages significantly reducing services offered by many pharmacies. The objectives of our study were to assess the impact of Hurricane Sandy on community pharmacies, both independently owned and chain, in the severely affected areas of New York City (NYC), including Coney Island, Staten Island, and the Rockaways, using qualitative methods, and propose strategies to mitigate the impact of future storms and disasters. Of the total 52 solicited pharmacies, 35 (67 percent) responded and were included in our analysis. Only 10 (29 percent) of the pharmacies surveyed reported having a generator during Hurricane Sandy; 37 percent reported being equipped with a generator at the time of the survey approximately 1 year later. Our findings suggest that issues other than power outages contributed more toward a pharmacy remaining operational after the storm. Of those surveyed, 26 (74 percent) suffered from structural damage (most commonly in Coney Island). Most pharmacies (71 percent) were able to reopen within 1 month. Despite staffing challenges, most pharmacies (88 percent) had enough pharmacists/staff to resume normal operations. Overall, 91 percent were aware of law changes for emergency medication access, and 81 percent found the information easy to obtain. This survey helped inform our work toward improved community resiliency. Our findings have helped us recognize community pharmacists as important stakeholders and refocus our energy toward developing sustained partnerships with them in NYC as part of our ongoing preparedness strategy.

  10. Novel missense mutation in the GALNS gene in an affected patient with severe form of mucopolysaccharidosis type IVA.

    PubMed

    Seyedhassani, Seyed Mohammad; Hashemi-Gorji, Feyzollah; Yavari, Mahdieh; Mirfakhraie, Reza

    2015-10-23

    Mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A, is an autosomal recessive disorder characterized by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which causes major skeletal and connective tissue abnormalities and affects multiple organ systems. In this study, one MPS IVA patient with a severe form from consanguine large Iranian family has been investigated. To find a mutation, all of the 14 exons and intron-exon junctions of GALNS gene were sequenced. Sequencing results were analyzed using bioinformatic analysis in order to predict probable pathogenic effect of the variant. One novel homozygous missense mutation in exon 5, c.542A>G (p.Y181C), was found in the proband. That was predicted as being probably pathogenic by bioinformatics analysis. Segregation and familial study confirmed this pathogenic mutation. In conclusion, we have identified the novel mutation responsible for MPS IVA in an Iranian patient to assist in the diagnosis, genetic counseling and prenatal diagnosis of the affected families.

  11. Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease.

    PubMed

    Fischer, Michael J; Kimmel, Paul L; Greene, Tom; Gassman, Jennifer J; Wang, Xuelei; Brooks, Deborah H; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A; Bruce, Marino A; Kusek, John W; Norris, Keith C; Lash, James P

    2011-09-01

    This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease.

  12. Responses of horses affected with chronic obstructive pulmonary disease to inhalation challenges with mould antigens.

    PubMed

    McGorum, B C; Dixon, P M; Halliwell, R E

    1993-07-01

    Eight control and 8 asymptomatic COPD-affected horses were given, on separate occasions, inhalation challenges with extracts of Micropolyspora faeni, Aspergillus fumigatus and Thermoactinomyces vulgaris. All horses were also given nebulised phosphate-buffered saline (PBS) challenges and 'natural challenges' (NCs), i.e. exposure to hay and straw, as control challenges. Responses were assessed by clinical, pulmonary mechanics, arterial blood gas tensions, arterial blood pH and bronchoalveolar lavage fluid cytological examinations. PBS challenges had no effect on control or COPD-affected horses, while NC induced COPD only in the COPD-affected horses. Pulmonary disease, similar to naturally occurring COPD, was induced, only in the COPD-affected horses, by M. faeni and A. fumigatus challenges, thus implicating these organisms in the aetiology of equine COPD. The role of T. vulgaris in the aetiology of equine COPD could not, however, be determined because the T. vulgaris challenges, in addition to inducing pulmonary disease in 4 COPD-affected horses, induced pulmonary disease in 2 control horses which had been unaffected by NC. The absence of pulmonary disease in control horses after M. faeni, A. fumigatus and NC challenges suggests that equine COPD is a pulmonary hypersensitivity, rather than a non-specific toxic response.

  13. Surgical treatment of patients with kidney and bladder cancer in case of severe concomitant cardiovascular diseases.

    PubMed

    Davydov, M I; Akchurin, R S; Gerasimov, S S; Belov, Yu V; Matveev, V B; Brand, Ya B; Cheban, O I

    2014-01-01

    It was operated 17 patients with kidney and bladder cancer against the background of severe concomitant coronary artery disease (52.9%), aortic aneurysm (35.3%) or combination of coronary artery disease with Leriche syndrome (5.9%) or hemodynamically significant stenosis of internal carotid artery (5.9%). Patients were operated for the period from 1998 to 2012. All patients were male at the age from 39 to 80 years (mean 62.1 years). The first stage of kidney cancer was diagnosed in 8 (53.3%) patients, the second stage - in 1 (6.7%) patient, the third stage - in 2 (13.3%) patients and the fourth stage was observed in 4 (26.7%) patients. Bladder cancer had 1 and 2 stages. Simultaneous operations were performed in 3 (17.6%) patients. 12 (70.6%) patients were operated consequentially. Surgery for kidney cancer was not done in 2 (11.8%) of 17 patients because of patient death after coronary bypass surgery or patient refusal of surgery after carotid arteries stenting. Intraoperative and postoperative complications have been developed in 9 (52.9%) of 17 patients. 2 (11.8%) patients died. The complications frequency and mortality after simultaneous operations were 25% (1 of 4) and 0. These parameters were 57.1% (8 of 14) and 14.3% respectively in case of consequent tactics. It was not observed myocardial infarction and aortic aneurysm rupture after surgeries for kidney and bladder cancer. Overall 1, 3, 5 - year survival of patients with kidney cancer and severe concomitant cardiovascular diseases was 100%, 73.3% and 52.4% respectively. It was concluded that surgical treatment of severe concomitant coronary artery disease and aortic aneurysm in patients with kidney and bladder cancer decreases risk of myocardial infarction and aortic aneurysm rupture in intraoperative and postoperative periods.

  14. Visual Analysis for Detection and Quantification of Pseudomonas cichorii Disease Severity in Tomato Plants

    PubMed Central

    Rajendran, Dhinesh Kumar; Park, Eunsoo; Nagendran, Rajalingam; Hung, Nguyen Bao; Cho, Byoung-Kwan; Kim, Kyung-Hwan; Lee, Yong Hoon

    2016-01-01

    Pathogen infection in plants induces complex responses ranging from gene expression to metabolic processes in infected plants. In spite of many studies on biotic stress-related changes in host plants, little is known about the metabolic and phenotypic responses of the host plants to Pseudomonas cichorii infection based on image-based analysis. To investigate alterations in tomato plants according to disease severity, we inoculated plants with different cell densities of P. cichorii using dipping and syringe infiltration methods. High-dose inocula (≥ 106 cfu/ml) induced evident necrotic lesions within one day that corresponded to bacterial growth in the infected tissues. Among the chlorophyll fluorescence parameters analyzed, changes in quantum yield of PSII (ΦPSII) and non-photochemical quenching (NPQ) preceded the appearance of visible symptoms, but maximum quantum efficiency of PSII (Fv/Fm) was altered well after symptom development. Visible/near infrared and chlorophyll fluorescence hyperspectral images detected changes before symptom appearance at low-density inoculation. The results of this study indicate that the P. cichorii infection severity can be detected by chlorophyll fluorescence assay and hyperspectral images prior to the onset of visible symptoms, indicating the feasibility of early detection of diseases. However, to detect disease development by hyperspectral imaging, more detailed protocols and analyses are necessary. Taken together, change in chlorophyll fluorescence is a good parameter for early detection of P. cichorii infection in tomato plants. In addition, image-based visualization of infection severity before visual damage appearance will contribute to effective management of plant diseases. PMID:27493605

  15. Does Vitamin D Affect Risk of Developing Autoimmune Disease?: A Systematic Review

    PubMed Central

    Kriegel, Martin A.; Manson, JoAnn E.; Costenbader, Karen H.

    2010-01-01

    Objectives We evaluated the epidemiologic evidence that vitamin D may be related to human autoimmune disease risk. Methods PubMed limited to English from inception through April 2010 was searched using keywords: “vitamin D”, “autoimmune” and autoimmune disease names. We summarized in vitro, animal, and genetic association studies of vitamin D in autoimmune disease pathogenesis. We sorted studies by design and disease and performed a systematic review of: a) cross-sectional data concerning vitamin D level and autoimmune disease; b) interventional data on vitamin D supplementation in autoimmune diseases and c) prospective data linking vitamin D level or intake to autoimmune disease risk. Results Vitamin D has effects on innate and acquired immune systems and vitamin D receptor polymorphisms have been associated with various autoimmune diseases. In experimental animal models, vitamin D supplementation can prevent or forestall autoimmune disease. We identified 76 studies in which vitamin D levels were studied in autoimmune disease patients, particularly with active disease, and compared to controls. Nineteen observational or interventional studies assessed the effect of vitamin D supplementation as therapy for various autoimmune diseases (excluding psoriasis and vitiligo) with a range of study approaches and results. The few prospective human studies performed conflict as to whether vitamin D level or intake is associated with autoimmune disease risk. No interventional trials have investigated whether vitamin D affects human autoimmune disease risk. Conclusions Cross-sectional data point to a potential role of vitamin D in autoimmune disease prevention, but prospective interventional evidence in humans is still lacking. PMID:21047669

  16. Translational neurophysiology in sheep: measuring sleep and neurological dysfunction in CLN5 Batten disease affected sheep

    PubMed Central

    Perentos, Nicholas; Martins, Amadeu Q.; Watson, Thomas C.; Bartsch, Ullrich; Mitchell, Nadia L.; Palmer, David N.; Jones, Matthew W.

    2015-01-01

    Creating valid mouse models of slowly progressing human neurological diseases is challenging, not least because the short lifespan of rodents confounds realistic modelling of disease time course. With their large brains and long lives, sheep offer significant advantages for translational studies of human disease. Here we used normal and CLN5 Batten disease affected sheep to demonstrate the use of the species for studying neurological function in a model of human disease. We show that electroencephalography can be used in sheep, and that longitudinal recordings spanning many months are possible. This is the first time such an electroencephalography study has been performed in sheep. We characterized sleep in sheep, quantifying characteristic vigilance states and neurophysiological hallmarks such as sleep spindles. Mild sleep abnormalities and abnormal epileptiform waveforms were found in the electroencephalographies of Batten disease affected sheep. These abnormalities resemble the epileptiform activity seen in children with Batten disease and demonstrate the translational relevance of both the technique and the model. Given that both spontaneous and engineered sheep models of human neurodegenerative diseases already exist, sheep constitute a powerful species in which longitudinal in vivo studies can be conducted. This will advance our understanding of normal brain function and improve our capacity for translational research into neurological disorders. PMID:25724202

  17. The V81M variant of tyrosine hydroxylase is associated with more severe freezing of gait in Parkinson's disease

    PubMed Central

    Tekin, Izel; Carkaci-Salli, Nurgul; Lewis, Mechelle M.; Mailman, Richard B.; Huang, Xuemei; Vrana, Kent E.

    2016-01-01

    Introduction Many of the symptoms and signs of Parkinson's disease (PD) arise from the death of midbrain dopamine neurons that utilize tyrosine hydroxylase (TH) as the rate-limiting enzyme in catecholamine biosynthesis. Methods We investigated whether the presence of a common TH polymorphism affects the clinical outcomes in 101 PD subjects. We further examined the effect of this polymorphism on the purified recombinant enzyme. Results PD subjects homozygous for the common V81M polymorphism, have higher overall freezing of gait scores after controlling for disease duration, although this polymorphism does not associate with the occurrence of PD or FOG. In vitro functional assays on pure recombinant wild type TH and V81M TH revealed that the Km of the mutant enzyme for tyrosine was twice that of the wild-type. This polymorphism, however, did not change the stability of the enzyme, nor did it affect the Vmax or Km for the co-substrate BH4. Conclusion The data suggest that presence of a homozygous V81M polymorphism is associated with more severe FOG, possibly due to lower catecholamine synthetic capacity. Further studies are warranted to investigate the role of subtle changes in catecholamine availability in the development of FOG. PMID:26732803

  18. Circulating Immune Complex Levels are Associated with Disease Severity and Seasonality in Children with Malaria from Mali

    PubMed Central

    Thomas, Bolaji N.; Diallo, Dapa A.; Noumsi, Ghislain T.; Moulds, Joann M.

    2012-01-01

    Complement receptor one (CR1) is essential for removing circulating immune complexes (CIC), with malaria infection contributing to the formation of large amounts of CIC. We investigated CIC levels in children with malaria, of varying severity and seasonality. Two hundred age and sex-matched severe and mild malaria cases were studied during and after active disease. Pediatric controls had increased CIC levels (mean = 32 μg mEq/mL) compared to adult controls (mean = 26.9 μg mEq/mL). The highest levels of CIC were reported in severe malaria (mean = 39 μg mEq/mL). Higher levels of CIC were recorded in younger children and those with low E-CR1 copy numbers. Our data suggest that low levels of E-CR1 copy numbers, found in children with severe malaria, may adversely affect the ability to remove IC. Furthermore, the high background for circulating immune complex imply that Malian children are under constant assault by other pathogens that evoke a strong immune response. PMID:22837639

  19. Revisiting Unplanned Endotracheal Extubation and Disease Severity in Intensive Care Units.

    PubMed

    Chuang, Ming-Lung; Lee, Chai-Yuan; Chen, Yi-Fang; Huang, Shih-Feng; Lin, I-Feng

    2015-01-01

    Most reports regarding unplanned extubation (UE) are case-control studies with matching age and disease severity. To avoid diminishing differences in matched factors, this study with only matching duration of mechanical ventilation aimed to re-examine the risk factors and the factors governing outcomes of UE in intensive care units (ICUs). This case-control study was conducted on 1,775 subjects intubated for mechanical ventilation. Thirty-seven (2.1%) subjects with UE were identified, and 156 non-UE subjects were randomly selected as the control group. Demographic data, acute Physiological and Chronic Health Evaluation II (APACHE II) scores, and outcomes of UE were compared between the two groups. Logistic regression analysis was used to identify the risk factors of UE. Milder disease, younger age, and higher Glasgow Coma Scale (GCS) scores with more frequently being physically restrained (all p<0.05) were related to UE. Logistic regression revealed that APACHE II score (odds ratio (OR) 0.91, p<0.01), respiratory infection (OR 0.24, p<0.01), physical restraint (OR 5.36, p<0.001), and certain specific diseases (OR 3.79-5.62, p<0.05) were related to UE. The UE patients had a lower ICU mortality rate (p<0.01) and a trend of lower in-hospital mortality rate (p = 0.08). Cox regression analysis revealed that in-hospital mortality was associated with APACHE II score, age, shock, and oxygen used, all of which were co-linear, but not UE. The results showed that milder disease with higher GCS scores thereby requiring a higher use of physical restraints were related to UE. Disease severity but not UE was associated with in-hospital mortality.

  20. A severe renal bleeding as a complication of coumarin therapy in Behçet's disease.

    PubMed

    Remková, Anna; Milatová, Eva; Fuchsbergerová, Michaela

    2010-07-01

    Behçet's disease is a systemic inflammatory disease, which predisposes patients to venous or arterial thrombosis. We report a case of 41-year-old patient who presented for several years with recurrent fevers, arthralgias, episodes of skin eruptions and recurrent bilateral deep venous ileofemoral thromboses, extending into the inferior vena cava, despite the oral anticoagulant therapy. Additionally, he also reported recurrent aphthous oral and genital lesions, and eye problems. A laboratory picture of chronic inflammation, normocytic anaemia and a finding of lupus anticoagulant/antiphospholipid antibodies were observed. PET raised a high suspicion of vasculitic PTT-lupus anticoagulant process, involving the large vessels. During an anticoagulant therapy by warfarin (dose in upper limit of therapeutic range), the left kidney had to be removed because of acute retroperitoneal haemorrhage. On histologic examination, the picture of nephritis was described. A detailed retrospective reevaluation of complex history as well as other clinical findings strongly raised the suspicion of a systemic vasculitic syndrome, such as Behçet's disease, accompanied by antiphospholipid syndrome. The patient responded well to the combination of colchicine and anticoagulant therapy by low-molecular-weight heparin. The episodes of fever, skin eruptions and other symptoms disappeared. We assume that this is a case of an unusual course of Behçet's disease presenting with a rare kidney involvement. Kidney disorder complicated the oral anticoagulant therapy for recurrent venous thromboses and led to the excessive renal bleeding, requiring nephrectomy. Recognition that nephritis is associated with Behçet's disease may be useful to prevent severe renal bleeding in relation to anticoagulant therapy.

  1. Diet Influences Expression of Autoimmune Associated Genes and Disease Severity By Epigenetic Mechanisms in a Transgenic Lupus Model

    PubMed Central

    Strickland, Faith M.; Hewagama, Anura; Wu, Ailing; Sawalha, Amr H.; Delaney, Colin; Hoeltzel, Mark F.; Yung, Raymond; Johnson, Kent; Mickelson, Barbara; Richardson, Bruce C.

    2013-01-01

    Objective Lupus flares when genetically predisposed people encounter appropriate environmental agents. Current evidence indicates that the environment contributes by inhibiting T cell DNA methylation, causing overexpression of normally silenced genes. DNA methylation depends on both dietary transmethylation micronutrients and Erk-regulated DNA methyltransferase 1 (Dnmt1) levels. We used transgenic mice to study interactions between diet, Dnmt1 levels and genetic predisposition on the development and severity of lupus. Methods A doxycycline-inducible Erk defect was bred into lupus-resistant (C57BL/6) or lupus-susceptible (C57BL/6xSJL) mouse strains. Doxycycline treated mice were fed a standard commercial diet for eighteen weeks then switched to diets supplemented(MS) or restricted(MR) intransmethylation micronutrients. Disease severity was assessed by anti-dsDNA antibodies, proteinuria, hematuria and histopathology of kidney tissues. Pyrosequencing was used to determine micronutrient effects on DNA methylation. Results Doxycycline induced modest levels of anti-dsDNA antibodies in C57BL/6 mice and higher levels in C57BL/6xSJL mice. Doxycycline-treated C57BL/6xSJL mice developed hematuria and glomerulonephritis on the MR and standard but not the MS diet. In contrast C57BL/6 mice developed kidney disease only on the MR diet. Decreasing Erk signaling and methyl donors also caused demethylation and overexpression of the CD40lg gene in female mice, consistent with demethylation of the second X chromosome. Both the dietary methyl donor content and duration of treatment influenced methylation and expression of the CD40lg gene. Conclusions Dietary micronutrients that affect DNA methylation can exacerbate or ameliorate SLE disease in this transgenic murine lupus model, and contribute to lupus susceptibility and severity through genetic/epigenetic interactions. PMID:23576011

  2. INCIDENCE AND SEVERITY OF LEAF AND FRUIT DISEASES OF PLUMS IN LATVIA.

    PubMed

    Grantina-Ievina, L; Stanke, L

    2015-01-01

    In the present study six plum orchards in Latvia were examined during 2014. One orchard was commercial with integrated pest management (IPM) practices, one was with organic management, two orchards were scientific collections and in two orchards plums were grown as a minor crop, using IPM practices. The shot-hole disease (Wilsonomyces carpophilus) and fruit rot were monitored in the field. Samples of twigs and leaves were taken for further examination if some other disease symptoms were observed. In total, 50 European plum (Prunus domestica) and six diploid plum cultivars were inspected. The fruit rot was assessed also in the laboratory to determine the latent infection with Monilinia spp. on immature fruits. Monilinia spp. isolates from all orchards were subjected to fungicide sensitivity tests. Incidence and severity of shot-hole disease was significantly different among various orchards when the same cultivar was compared, as well as between diploid and European plum cultivars. The average incidence of shot-hole disease was 41% in diploid plums and 80% in European plums, while the average severity was 9 and 15%, respectively. In the field, fruit rot caused only by Monilinia spp. was detected. The average incidence of brown rot on diploid plums was less than 1%, but on European plums it was 3.6%. The latent infection tests showed that plum fruits had higher incidence of brown rot than was observed in the field, up to 44% on particular cultivars. Additionally, from the fruits subjected to these tests, Botrytis cinerea, Diaporthe eres and Colletotrichum spp. were isolated. This means that in specific weather and management conditions the fruit rot incidence in the field could be several times higher. Examination of samples of twigs, leaves and fruits in the laboratory showed the presence of D. eres in samples from all orchards. In one of the scientific collections D. eres was isolated from twigs, leaves and fruits, and was more often found on the individuals

  3. Interleukin 15 Levels in Serum May Predict a Severe Disease Course in Patients with Early Arthritis

    PubMed Central

    González-Álvaro, Isidoro; Ortiz, Ana M.; Alvaro-Gracia, José María; Castañeda, Santos; Díaz-Sánchez, Belen; Carvajal, Inmaculada; García-Vadillo, J. Alberto; Humbría, Alicia; López-Bote, J. Pedro; Patiño, Esther; Tomero, Eva G.; Vicente, Esther F.; Sabando, Pedro; García-Vicuña, Rosario

    2011-01-01

    Background Interleukin-15 (IL-15) is thought to be involved in the physiopathological mechanisms of RA and it can be detected in the serum and the synovial fluid of inflamed joints in patients with RA but not in patients with osteoarthritis or other inflammatory joint diseases. Therefore, the objective of this work is to analyse whether serum IL-15 (sIL-15) levels serve as a biomarker of disease severity in patients with early arthritis (EA). Methodology and Results Data from 190 patients in an EA register were analysed (77.2% female; median age 53 years; 6-month median disease duration at entry). Clinical and treatment information was recorded systematically, especially the prescription of disease modifying anti-rheumatic drugs. Two multivariate longitudinal analyses were performed with different dependent variables: 1) DAS28 and 2) a variable reflecting intensive treatment. Both included sIL-15 as predictive variable and other variables associated with disease severity, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Of the 171 patients (638 visits analysed) completing the follow-up, 71% suffered rheumatoid arthritis and 29% were considered as undifferentiated arthritis. Elevated sIL-15 was detected in 29% of this population and this biomarker did not overlap extensively with RF or ACPA. High sIL-15 levels (β Coefficient [95% confidence interval]: 0.12 [0.06–0.18]; p<0.001) or ACPA (0.34 [0.01–0.67]; p = 0.044) were significantly and independently associated with a higher DAS28 during follow-up, after adjusting for confounding variables such as gender, age and treatment. In addition, those patients with elevated sIL-15 had a significantly higher risk of receiving intensive treatment (RR 1.78, 95% confidence interval 1.18–2.7; p = 0.007). Conclusions Patients with EA displaying high baseline sIL-15 suffered a more severe disease and received more intensive treatment. Thus, sIL-15 may be a biomarker for

  4. Plasma testosterone in male patients with Huntington's disease: relations to severity of illness and dementia.

    PubMed

    Markianos, Manolis; Panas, Marios; Kalfakis, Nikos; Vassilopoulos, Dimitrios

    2005-04-01

    Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms and by a progressive loss among other, of dopaminergic receptors in striatum, cortex, and hypothalamus. Central dopaminergic activity has been implicated in the regulation of sex hormones. Several features of testosterone deficiency, such as reduced muscle mass, depressive mood, and cognitive impairment, are often present in HD patients, but data on their testosterone levels are lacking. We assessed plasma levels of testosterone, LH, and FSH in 42 male patients with HD, confirmed by molecular genetic analysis, and searched for differences from age-matched healthy male subjects and for relations to CAG repeat number, age, age range, 26 to 76 (mean, 50.7 +/- 12.3) years; duration of illness range, 1 to 23 (mean, 6.7 +/- 6.3) years; and CAG repeat numbers from 40 to 65 (45.1 +/- 3.8). Disease symptomatology was assessed using the Unified Huntington's Disease Rating Scale. Testosterone and LH levels of the patients were significantly lower compared to the levels of 44 age-matched (mean age, 48.9 +/- 13.0, range, 26-76 years) healthy men. Severity of illness was negatively related to plasma testosterone levels. Further, low testosterone levels were associated with dementia but not with depression or psychotic features. Clinical studies with selected HD patients are needed to evaluate possible beneficial effects of androgen substitution therapy on cognitive functions, depression, muscle mass and strength, general well-being, and, eventually, neuroprotective effects.

  5. Maternal behavioural risk factors for severe childhood diarrhoeal disease in Kinshasa, Zaire.

    PubMed

    Dikassa, L; Mock, N; Magnani, R; Rice, J; Abdoh, A; Mercer, D; Bertrand, W

    1993-04-01

    This study examines the relationship between severe diarrhoeal disease and maternal knowledge and behaviours related to hygiene and sanitation. Some 107 paediatric cases admitted to two hospitals in Kinshasa, Zaire in 1988 were matched on age and nearest-neighbour status to 107 controls. Personal interviews and observational methods were used to assess knowledge and behaviours related to hygiene and sanitation. Cases and controls had equivalent socioeconomic status, demographic profiles and access to water and sanitation facilities. However, cases generally exhibited lower levels of knowledge and less sanguine sanitary practices than did controls. Of particular interest was the finding that very specific behavioural items distinguished cases from controls. The disposal of the child faeces and household garbage and mother's knowledge that poor caretaker cleanliness was a cause of diarrhoea in children showed the strongest associations with risk of diarrhoea. There was an exponential relationship between the number of these items a mother answered incorrectly and the odds of diarrhoeal disease. The risk attributable to these three variables was as high as 70%. These findings provide further support for the view that focused educational interventions may have a substantial impact on the occurrence of severe diarrhoeal disease in low-income countries.

  6. SPP1 genotype is a determinant of disease severity in Duchenne muscular dystrophy

    PubMed Central

    Pegoraro, E.; Hoffman, E.P.; Piva, L.; Gavassini, B.F.; Cagnin, S.; Ermani, M.; Bello, L.; Soraru, G.; Pacchioni, B.; Bonifati, M.D.; Lanfranchi, G.; Angelini, C.; Kesari, A.; Lee, I.; Gordish-Dressman, H.; Devaney, J.M.; McDonald, C.M.

    2011-01-01

    Objective: Duchenne muscular dystrophy (DMD) is the most common single-gene lethal disorder. Substantial patient–patient variability in disease onset and progression and response to glucocorticoids is seen, suggesting genetic or environmental modifiers. Methods: Two DMD cohorts were used as test and validation groups to define genetic modifiers: a Padova longitudinal cohort (n = 106) and the Cooperative International Neuromuscular Research Group (CINRG) cross-sectional natural history cohort (n = 156). Single nucleotide polymorphisms to be genotyped were selected from mRNA profiling in patients with severe vs mild DMD, and genome-wide association studies in metabolism and polymorphisms influencing muscle phenotypes in normal volunteers were studied. Results: Effects on both disease progression and response to glucocorticoids were observed with polymorphism rs28357094 in the gene promoter of SPP1 (osteopontin). The G allele (dominant model; 35% of subjects) was associated with more rapid progression (Padova cohort log rank p = 0.003), and 12%–19% less grip strength (CINRG cohort p = 0.0003). Conclusions: Osteopontin genotype is a genetic modifier of disease severity in Duchenne dystrophy. Inclusion of genotype data as a covariate or in inclusion criteria in DMD clinical trials would reduce intersubject variance, and increase sensitivity of the trials, particularly in older subjects. PMID:21178099

  7. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis

    PubMed Central

    Koopman, Frieda A.; Chavan, Sangeeta S.; Miljko, Sanda; Grazio, Simeon; Sokolovic, Sekib; Schuurman, P. Richard; Mehta, Ashesh D.; Levine, Yaakov A.; Faltys, Michael; Zitnik, Ralph; Tracey, Kevin J.; Tak, Paul P.

    2016-01-01

    Rheumatoid arthritis (RA) is a heterogeneous, prevalent, chronic autoimmune disease characterized by painful swollen joints and significant disabilities. Symptomatic relief can be achieved in up to 50% of patients using biological agents that inhibit tumor necrosis factor (TNF) or other mechanisms of action, but there are no universally effective therapies. Recent advances in basic and preclinical science reveal that reflex neural circuits inhibit the production of cytokines and inflammation in animal models. One well-characterized cytokine-inhibiting mechanism, termed the “inflammatory reflex,” is dependent upon vagus nerve signals that inhibit cytokine production and attenuate experimental arthritis severity in mice and rats. It previously was unknown whether directly stimulating the inflammatory reflex in humans inhibits TNF production. Here we show that an implantable vagus nerve-stimulating device in epilepsy patients inhibits peripheral blood production of TNF, IL-1β, and IL-6. Vagus nerve stimulation (up to four times daily) in RA patients significantly inhibited TNF production for up to 84 d. Moreover, RA disease severity, as measured by standardized clinical composite scores, improved significantly. Together, these results establish that vagus nerve stimulation targeting the inflammatory reflex modulates TNF production and reduces inflammation in humans. These findings suggest that it is possible to use mechanism-based neuromodulating devices in the experimental therapy of RA and possibly other autoimmune and autoinflammatory diseases. PMID:27382171

  8. HIV-1 Promoter Single Nucleotide Polymorphisms Are Associated with Clinical Disease Severity

    PubMed Central

    Feng, Rui; Moldover, Brian; Passic, Shendra; Aiamkitsumrit, Benjamas; Dampier, Will; Wojno, Adam; Kilareski, Evelyn; Blakey, Brandon; Ku, Tse-Sheun Jade; Shah, Sonia; Sullivan, Neil T.; Jacobson, Jeffrey M.; Wigdahl, Brian

    2016-01-01

    The large majority of human immunodeficiency virus type 1 (HIV-1) markers of disease progression/severity previously identified have been associated with alterations in host genetic and immune responses, with few studies focused on viral genetic markers correlate with changes in disease severity. This study presents a cross-sectional/longitudinal study of HIV-1 single nucleotide polymorphisms (SNPs) contained within the viral promoter or long terminal repeat (LTR) in patients within the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort. HIV-1 LTR SNPs were found to associate with the classical clinical disease parameters CD4+ T-cell count and log viral load. They were found in both defined and undefined transcription factor binding sites of the LTR. A novel SNP identified at position 108 in a known COUP (chicken ovalbumin upstream promoter)/AP1 transcription factor binding site was significantly correlated with binding phenotypes that are potentially the underlying cause of the associated clinical outcome (increase in viral load and decrease in CD4+ T-cell count). PMID:27100290

  9. Severe hyponatraemia with absence of hyperkalaemia in rapidly progressive Addison's disease.

    PubMed

    Thompson, Michael D; Kalmar, Eileen; Bowden, Sasigarn A

    2015-05-28

    We present a case of rapidly progressing Addison's disease in adrenal crisis with severe hyponatraemia and absence of hyperkalaemia in a 10-year-old girl. She presented with 2 weeks of vomiting, fatigue and weight loss. Her serum electrolytes obtained 1 week prior to presentation were normal, except for mild hyponatraemia at 131 mmol/L, which dropped to 112 mmol/L on admission. She had normal serum potassium, low-serum osmolality, with elevated urine sodium and osmolality, indistinguishable from syndrome of inappropriate antidiuretic hormone (SIADH). Subsequently, Addison's disease was diagnosed on the basis of gingival hyperpigmentation and undetectable cortisol on adrenocorticotropic hormone stimulation test. She rapidly responded to stress dose hydrocortisone, followed by hydrocortisone and fludrocortisone replacement therapy. The absence of hyperkalaemia in the presence of severe hyponatraemia cannot rule out Addison's disease in children. The mechanism of hypo-osmolar hyponatraemia in primary adrenal insufficiency and clinical clues to differentiate it from SIADH are discussed.

  10. Complex two-gene modulation of lung disease severity in children with cystic fibrosis

    PubMed Central

    Dorfman, Ruslan; Sandford, Andrew; Taylor, Chelsea; Huang, Baisong; Frangolias, Daisy; Wang, Yongqian; Sang, Richard; Pereira, Lilian; Sun, Lei; Berthiaume, Yves; Tsui, Lap-Chee; Paré, Peter D.; Durie, Peter; Corey, Mary; Zielenski, Julian

    2008-01-01

    Although cystic fibrosis (CF) is a monogenic disease, its clinical manifestations are influenced in a complex manner. Severity of lung disease, the main cause of mortality among CF patients, is likely modulated by several genes. The mannose-binding lectin 2 (MBL2) gene encodes an innate immune response protein and has been implicated as a pulmonary modifier in CF. However, reports have been conflicting, and interactions with other modifiers have not been investigated. We therefore evaluated the association of MBL2 with CF pulmonary phenotype in a cohort of 1,019 Canadian pediatric CF patients. MBL2 genotypes were combined into low-, intermediate-, and high-expression groups based on MBL2 levels in plasma. Analysis of age at first infection with Pseudomonas aeruginosa demonstrated that MBL2 deficiency was significantly associated with earlier onset of infection. This MBL2 effect was amplified in patients with high-producing genotypes of transforming growth factor beta 1 (TGFB1). Similarly, MBL2 deficiency was associated with more rapid decline of pulmonary function, most significantly in those carrying the high-producing TGFB1 genotype. These findings provide evidence of gene-gene interaction in the pathogenesis of CF lung disease, whereby high TGF-β1 production enhances the modulatory effect of MBL2 on the age of first bacterial infection and the rate of decline of pulmonary function. PMID:18292811

  11. 13C-methacetin breath test correlates with clinical indices of liver disease severity in patients with primary biliary cirrhosis.

    PubMed

    Kochel-Jankowska, A; Hartleb, M; Jonderko, K; Kaminska, M; Kasicka-Jonderko, A

    2013-02-01

    This prospective study intended to ascertain if cytochrome P450 dependent liver function is affected in early and late histological stages of primary biliary cirrhosis (PBC). The study included 32 female PBC patients (mean age 55.4 years, range 33-70) and 16 aged-matched healthy women (mean age 52.6 years, range 38-65). In every subject a 13(C)-methacetin breath test (13(C)-MBT) was applied, and the results were related to histological Ludwig's staging system and several indices of liver disease severity comprising the MAYO-1, MAYO-2, MELD, and Child-Pugh score. The 13(C)-MBT differentiated healthy controls from the patients with Ludwig IV and Ludwig III histopathological stages of PBC. The most significant relationships (i.e. explaining >50% of the variance) were found between measurements of the momentary breath 13(C) elimination from 6 to 18 minutes as well as the 15-min or 30-min cumulative elimination and the MAYO-1 or MAYO-2 scores. The breath test poorly correlated with histopathological features of PBC, however, it accurately discriminated cirrhotic from non-cirrhotic patients (momentary breath 13(C) elimination at 40 min, AUROC 0,958). In conclusion, 13(C)-MBT correlates with clinical scoring systems, especially those specifically designed for PBC (Mayo model) and accurately recognizes the disease at the stage of cirrhosis up to 40 minutes of the test duration.

  12. Reduced severity of histopathological lesions in mink selected for tolerance to Aleutian mink disease virus infection.

    PubMed

    Farid, A Hossain; Ferns, Linda E

    2017-04-01

    The objective of this study was to measure the effect of selection for tolerance on the severity of the Aleutian disease (AD) lesions in mink. Sensitivity and specificity of antibody detection in the blood by counter-immunoelectrophoresis (CIEP) relative to the presence of Aleutian mink disease virus (AMDV) in the spleen by PCR in naturally infected farmed mink were also estimated. Carcasses of 680 sero-positive (CIEP-P) black mink from 28 farms in Nova Scotia, Canada, and from 132 sero-negative (CIEP-N) mink from 14 of these farms were collected at pelting time. A total of 116 of the CIEP-P mink were from three farms where animals have been selected for tolerating AD for almost 20years. The severity of the AD lesions was assessed by histopathological examination of kidneys, lungs, heart, brain and liver on a scale of 0 to 4. Sensitivity and specificity of CIEP relative to PCR were 0.97 and 0.85, respectively, and 16.5% of CIEP-N mink were PCR positive, which could be one of the reasons for the failure of virus eradication by CIEP in Canada. The CIEP-N and tolerant CIEP-P animals had 9.39 and 6.23 greater odds of showing lower lesion severity, respectively, than the CIEP-P animals (P<0.01). The CIEP-N mink had a slightly higher chance (P=0.07) of showing lower lesion severity (odds ratio 1.51) compared with tolerant CIEP-P mink. The results suggested that tolerant mink had significantly reduced severity of AD lesions despite having anti-viral antibodies and carrying the virus.

  13. Steroid therapy in clinically stable but serologically active systemic lupus erythematosus prevents severe disease flares.

    PubMed

    Cardiel, Mario H; Almagro, Raúl Menor

    2007-05-01

    Evaluation of: Tseng CE, Buyon JP, Kim M et al. The effect of moderate-dose corticosteroids in preventing severe flares in patients with serologically active, but clinically stable, systemic lupus erythematosus: findings of a prospective, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 54, 3623-3632 (2006). Systemic lupus erythematosus is an autoimmune disease of unknown origin. Flares and remissions are commonly seen in clinical settings. These clinical flares can have several degrees of severity, some of which require intensive immunosuppressive treatment and/or hospitalization. Clinicians treating these patients have looked at different strategies for prevention, early detection and prompt treatment of a lupus flare. Clinical information and laboratory findings have been proposed to reach these goals and preventive steroid adjustment has even been used in some cases without convincing results. This paper presents results from a controlled, multicenter, double-blind clinical trial evaluating the effectiveness of short-term corticosteroid treatment for preventing severe flares in which elevations of C3a by 50% were accompanied by a 25% increase in the anti-double-stranded DNA titer in patients with inactive or stable/active systemic lupus erythematosus. Results suggest that this strategy can prevent severe lupus flares.

  14. Monocyte polarization in children with falciparum malaria: relationship to nitric oxide insufficiency and disease severity

    PubMed Central

    Weinberg, J. Brice; Volkheimer, Alicia D.; Rubach, Matthew P.; Florence, Salvatore M.; Mukemba, Jackson P.; Kalingonji, Ayam R.; Langelier, Charles; Chen, Youwei; Bush, Margaret; Yeo, Tsin W.; Granger, Donald L.; Anstey, Nicholas M.; Mwaikambo, Esther D.

    2016-01-01

    We earlier established that nitric oxide (NO) is protective against severe malaria and that arginine and NO levels are reduced in malaria patients. We now show that an M2-like blood monocyte phenotype is significantly associated with hypoargininemia, NO insufficiency, and disease severity in Tanzanian children with falciparum malaria. Compared to control children (n = 106), children with moderately severe (n = 77) and severe falciparum malaria (n = 129) had significantly higher mononuclear cell arginase 1 mRNA, protein, and enzyme activity; lower NOS2 mRNA; lower plasma arginine; and higher plasma IL-10, IL-13, and IL-4. In addition, monocyte CD206 and CD163 and plasma soluble CD163 were elevated. Multivariate logistic regression analysis revealed a significant correlation of risk of severe malaria with both plasma IL-10 and soluble CD163 levels. Monocyte M2 skewing likely contributes to NO bioinsufficiency in falciparum malaria in children. Treatments that reverse the M2 polarization may have potential as adjunctive treatment for malaria. PMID:27385484

  15. Adult Javanese migrants to Indonesian Papua at high risk of severe disease caused by malaria.

    PubMed

    Baird, J K; Basri, H; Weina, P; MaGuire, J D; Barcus, M J; Picarema, H; Elyazar, I R F; Ayomi, E; Sekartuti

    2003-08-01

    Migrants from Java arrive in hyperendemic Papua, Indonesia lacking exposure to endemic malaria. We evaluated records of evacuation to hospital with a diagnosis of severe malaria from a transmigration village in northeastern Papua. During the first 30 months, 198 residents with severe disease were evacuated (7.5 evacuations/100 person-years). During this period the risk of evacuation for adults (> 15 years of age) was 2.8. (95% CI = 2.1-3.8; P < 0.0001) relative to children, despite apparently equal exposure to risk of infection. Relative risk (RR) for adults was greatest during the first 6 months (RR > 16; 95% CI > or = 2.0-129; P = 0.0009), and diminished during the second 6 months (RR = 9.4; 95% CI = 2.7-32.8; P < 0.0001) and the third 6 months (RR = 3.7; 95% CI = 1.7-7.9; P = 0.0004). During the next two 6-month intervals, the RR for adults was 1.6 and 1.5 (95 % CI range 0.8-2.6; P < 0.18). Adults lacking chronic exposure were far more likely to progress to severe disease compared to children during initial exposure, but not after chronic exposure to infection.

  16. Adult Javanese migrants to Indonesian Papua at high risk of severe disease caused by malaria.

    PubMed Central

    Baird, J. K.; Basri, H.; Weina, P.; MaGuire, J. D.; Barcus, M. J.; Picarema, H.; Elyazar, I. R. F.; Ayomi, E.; Sekartuti

    2003-01-01

    Migrants from Java arrive in hyperendemic Papua, Indonesia lacking exposure to endemic malaria. We evaluated records of evacuation to hospital with a diagnosis of severe malaria from a transmigration village in northeastern Papua. During the first 30 months, 198 residents with severe disease were evacuated (7.5 evacuations/100 person-years). During this period the risk of evacuation for adults (> 15 years of age) was 2.8. (95% CI = 2.1-3.8; P < 0.0001) relative to children, despite apparently equal exposure to risk of infection. Relative risk (RR) for adults was greatest during the first 6 months (RR > 16; 95% CI > or = 2.0-129; P = 0.0009), and diminished during the second 6 months (RR = 9.4; 95% CI = 2.7-32.8; P < 0.0001) and the third 6 months (RR = 3.7; 95% CI = 1.7-7.9; P = 0.0004). During the next two 6-month intervals, the RR for adults was 1.6 and 1.5 (95 % CI range 0.8-2.6; P < 0.18). Adults lacking chronic exposure were far more likely to progress to severe disease compared to children during initial exposure, but not after chronic exposure to infection. PMID:12948380

  17. Anti-actin IgA antibodies in severe coeliac disease

    PubMed Central

    Granito, A; Muratori, P; Cassani, F; Pappas, G; Muratori, L; Agostinelli, D; Veronesi, L; Bortolotti, R; Petrolini, N; Bianchi, F B; Volta, U

    2004-01-01

    Anti-actin IgA antibodies have been found in sera of coeliacs. Our aim was to define the prevalence and clinical significance of anti-actin IgA in coeliacs before and after gluten withdrawal. One hundred and two biopsy-proven coeliacs, 95 disease controls and 50 blood donors were studied. Anti-actin IgA were evaluated by different methods: (a) antimicrofilament positivity on HEp-2 cells and on cultured fibroblasts by immunofluorescence; (b) anti-actin positivity by enzyme-linked immuosorbent assay (ELISA); and (c) presence of the tubular/glomerular pattern of anti-smooth muscle antibodies on rat kidney sections by immunofluorescence. Antimicrofilament IgA were present in 27% of coeliacs and in none of the controls. Antimicrofilament antibodies were found in 25 of 54 (46%) coeliacs with severe villous atrophy and in three of 48 (6%) with mild damage (P < 0·0001). In the 20 patients tested, antimicrofilaments IgA disappeared after gluten withdrawal in accordance with histological recovery. Our study shows a significant correlation between antimicrofilament IgA and the severity of intestinal damage in untreated coeliacs. The disappearance of antimicrofilament IgA after gluten withdrawal predicts the normalization of intestinal mucosa and could be considered a useful tool in the follow-up of severe coeliac disease. PMID:15270857

  18. Gene regulations in HBV-related liver cirrhosis closely correlate with disease severity.

    PubMed

    Lee, Seram; Kim, Soyoun

    2007-09-30

    Liver cirrhosis (LC) is defined as comprising diffuse fibrosis and regenerating nodules of the liver. The biochemical and anatomical dysfunction in LC results from both reduced liver cell number and portal vascular derangement. Although several studies have investigated dysregulated genes in cirrhotic nodules, little is known about the genes implicated in the pathophysiologic change of LC or about their relationship with the degree of decompensation. Here, we applied cDNA microarray analysis using 38 HBsAg-positive LC specimens to identify the genes dysregulated in HBV-associated LC and to evaluate their relation to disease severity. Among 1063 known cancer- and apoptosis-related genes, we identified 104 genes that were significantly up- (44) or down- (60) regulated in LC. Interestingly, this subset of 104 genes was characteristically correlated with the degree of decompensation, called the Pugh-Child classification (20 Pugh-Child A, 10 Pugh-Child B, and 8 Pugh-Child C). Patient samples from Pugh-Child C exhibited a distinct pattern of gene expression relative to those of Pugh-Child A and B. Especially in Pugh-Child C, genes encoding hepatic proteins and metabolizing enzymes were significantly down-regulated, while genes encoding various molecules related to cell replication were up-regulated. Our results suggest that subsets of genes in liver cells correspond to the pathophysiologic change of LC according to disease severity and possibly to hepatocarcinogenesis.

  19. Low Cerebral Glucose Metabolism: A Potential Predictor for the Severity of Vascular Parkinsonism and Parkinson's Disease.

    PubMed

    Xu, Yunqi; Wei, Xiaobo; Liu, Xu; Liao, Jinchi; Lin, Jiaping; Zhu, Cansheng; Meng, Xiaochun; Xie, Dongsi; Chao, Dongman; Fenoy, Albert J; Cheng, Muhua; Tang, Beisha; Zhang, Zhuohua; Xia, Ying; Wang, Qing

    2015-11-01

    This study explored the association between cerebral metabolic rates of glucose (CMRGlc) and the severity of Vascular Parkinsonism (VP) and Parkinson's disease (PD). A cross-sectional study was performed to compare CMRGlc in normal subjects vs. VP and PD patients. Twelve normal subjects, 22 VP, and 11 PD patients were evaluated with the H&Y and MMSE, and underwent 18F-FDG measurements. Pearson's correlations were used to identify potential associations between the severity of VP/PD and CMRGlc. A pronounced reduction of CMRGlc in the frontal lobe and caudate putamen was detected in patients with VP and PD when compared with normal subjects. The VP patients displayed a slight CMRGlc decrease in the caudate putamen and frontal lobe in comparison with PD patients. These decreases in CMRGlc in the frontal lobe and caudate putamen were significantly correlated with the VP patients' H&Y, UPDRS II, UPDRS III, MMSE, cardiovascular, and attention/memory scores. Similarly, significant correlations were observed in patients with PD. This is the first clinical study finding strong evidence for an association between low cerebral glucose metabolism and the severity of VP and PD. Our findings suggest that these changes in glucose metabolism in the frontal lobe and caudate putamen may underlie the pathophysiological mechanisms of VP and PD. As the scramble to find imaging biomarkers or predictors of the disease intensifies, a better understanding of the roles of cerebral glucose metabolism may give us insight into the pathogenesis of VP and PD.

  20. Palliative Senning in the Treatment of Congenital Heart Disease with Severe Pulmonary Hypertension

    PubMed Central

    da Penha, Juliano Gomes; Zorzanelli, Leina; Barbosa-Lopes, Antonio Augusto; Atik, Edimar; Miana, Leonardo Augusto; Tanamati, Carla; Caneo, Luiz Fernando; Miura, Nana; Aiello, Vera Demarchi; Jatene, Marcelo Biscegli

    2015-01-01

    Background Transposition of the great arteries (TGA) is the most common cyanotic cardiopathy, with an incidence ranging between 0.2 and 0.4 per 1000 live births. Many patients not treated in the first few months of life may progress with severe pulmonary vascular disease. Treatment of these patients may include palliative surgery to redirect the flow at the atrial level. Objective Report our institutional experience with the palliative Senning procedure in children diagnosed with TGA and double outlet right ventricle with severe pulmonary vascular disease, and to evaluate the early and late clinical progression of the palliative Senning procedure. Methods Retrospective study based on the evaluation of medical records in the period of 1991 to 2014. Only patients without an indication for definitive surgical treatment of the cardiopathy due to elevated pulmonary pressure were included. Results After one year of follow-up there was a mean increase in arterial oxygen saturation from 62.1% to 92.5% and a mean decrease in hematocrit from 49.4% to 36.3%. Lung histological analysis was feasible in 16 patients. In 8 patients, pulmonary biopsy grades 3 and 4 were evidenced. Conclusion The palliative Senning procedure improved arterial oxygen saturation, reduced polycythemia, and provided a better quality of life for patients with TGA with ventricular septal defect, severe pulmonary hypertension, and poor prognosis. PMID:26559982

  1. Severe Kawasaki disease in a 3-month-old patient: a case report

    PubMed Central

    2013-01-01

    Background Kawasaki disease is a multi-system vasculitis which usually occurs in children under 5 years of age. In infants under three months of age, it is very rare and usually associated with a high incidence of incomplete or atypical forms, often unresponsive to treatment. This condition increases the risk of cardiovascular complications such as coronary artery aneurysms. Case presentation We describe a 3-month-old infant who developed early and severe aneurysms in three coronary arteries despite a timely administration of intravenous immunoglobulins, followed by three days of intravenous methylprednisolone. Conclusion This case report underlines that the development of coronary artery aneurysm correlates with a delayed diagnosis and treatment, incomplete or atypical forms of the disease, and additionally the severity of clinical presentation, especially in cases of very young infants below 3 months of age. Our case is notable because of the very young age of the patient, the severity of clinical presentation with an early development of coronary artery aneurysms and the unresponsiveness to the therapy. PMID:24294914

  2. The Lung Microbiome in Moderate and Severe Chronic Obstructive Pulmonary Disease

    PubMed Central

    Pragman, Alexa A.; Kim, Hyeun Bum; Reilly, Cavan S.; Wendt, Christine; Isaacson, Richard E.

    2012-01-01

    Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora. Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients. The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid. Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats. Our results showed a significant increase in microbial diversity with the development of COPD. The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria. Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity. However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators. Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples. PMID:23071781

  3. Genetic Polymorphisms of TLR4 and MICA are Associated with Severity of Trachoma Disease in Tanzania

    PubMed Central

    Abbas, Muneer; Berka, Noureddine; Khraiwesh, Mozna; Ramadan, Ali; Apprey, Victor; Furbert-Harris, Paulette; Quinn, Thomas; Brim, Hassan; Dunston, Georgia

    2016-01-01

    Aim To examine the association of TLR4 Asp299Gly and MICA exon 5 microsatellites polymorphisms with severity of trachoma in a sub-Saharan East Africa population of Tanzanian villagers. Methods The samples were genotyped for MICA exon 5 microsatellites and the TLR4 299 A/G polymorphism by Restriction Fragment Length Polymorphism (RFLP), and GeneScan®, respectively. The association of TLR4 Asp299Gly and MICA exon 5 microsatellites with inflammatory trachoma (TI) and trichiasis (TI) were examined. Results The results showed an association between TLR4 and MICA polymorphisms and trachoma disease severity, as well as with protection. TLR4 an allele was significantly associated with inflammatory trachoma (p=0.0410), while the G allele (p=0.0410) was associated with protection. Conclusion TLR4 and MICA may modulate the risk of severity to trachoma disease by modulating the immune response to Ct. In addition; the increased frequency of MICA-A9 heterozygote in controls may suggest a positive selection of these alleles in adaptation to environments where Ct is endemic. PMID:27559544

  4. Transient microbiota exposures activate dormant Escherichia coli infection in the bladder and drive severe outcomes of recurrent disease

    PubMed Central

    2017-01-01

    Pathogens often inhabit the body asymptomatically, emerging to cause disease in response to unknown triggers. In the bladder, latent intracellular Escherichia coli reservoirs are regarded as likely origins of recurrent urinary tract infection (rUTI), a problem affecting millions of women worldwide. However, clinically plausible triggers that activate these reservoirs are unknown. Clinical studies suggest that the composition of a woman’s vaginal microbiota influences her susceptibility to rUTI, but the mechanisms behind these associations are unclear. Several lines of evidence suggest that the urinary tract is routinely exposed to vaginal bacteria, including Gardnerella vaginalis, a dominant member of the vaginal microbiota in some women. Using a mouse model, we show that bladder exposure to G. vaginalis triggers E. coli egress from latent bladder reservoirs and enhances the potential for life-threatening outcomes of the resulting E. coli rUTI. Transient G. vaginalis exposures were sufficient to cause bladder epithelial apoptosis and exfoliation and interleukin-1-receptor-mediated kidney injury, which persisted after G. vaginalis clearance from the urinary tract. These results support a broader view of UTI pathogenesis in which disease can be driven by short-lived but powerful urinary tract exposures to vaginal bacteria that are themselves not “uropathogenic” in the classic sense. This “covert pathogenesis” paradigm may apply to other latent infections, (e.g., tuberculosis), or for diseases currently defined as noninfectious because routine culture fails to detect microbes of recognized significance. PMID:28358889

  5. Decreased DACH1 expression in glomerulopathy is associated with disease progression and severity

    PubMed Central

    Liu, Qing-Quan; Zhou, Ya-Qun; Liu, Hui-Quan; Qiu, Wen-Hui; Liu, Hui; Hu, Ting-Yang; Xu, Qing; Lv, Yong-Man; Wu, Kong-Ming

    2016-01-01

    Cell fate determination factor dachshund1 (DACH1) is a chromosome-associated protein that regulates cellular differentiation throughout development. Recent genome-wide association studies have show that missense mutation in DACH1 leads to hereditary renal hypodysplasia. Renal DACH1 expression can be used to estimate glomerular filtration rate (eGFR). We firstly characterized the function of DACH1 in normal and diseased renal tissue using immunohistochemistry to assess DACH1 in human renal biopsy specimens from 40 immunoglobulin A nephropathy (IgAN) patients, 20 idiopathic membranous nephropathy (IMN) patients, and 15 minimal change disease (MCD) patients. We found that DACH1 expression was decreased in the nephropathy group relative to healthy controls. DACH1 staining in the glomerulus correlated positively with eGFR (r = 0.41, p < 0.001) but negatively with serum creatinine (r = −0.37, p < 0.01). In vitro, DACH1 overexpression in human podocytes or HK2 cells decreased expression of cyclin D1, but increased expression of p21 and p53, which suggested that DACH1 overexpression in human podocytes or HK2 cells increased the G1/S phase or G2/M cell arrest. Together, These findings indicate that DACH1 expression is decreased in glomerulopathy imply a potential role for DACH1 in the this development of human chornic glomerulopathy. These data suggest that DACH1 is a potential a marker of disease progression and severity for glomerular diseases. PMID:27888806

  6. Acrolein and Human Disease: Untangling the Knotty Exposure Scenarios Accompanying Several Diverse Disorders.

    PubMed

    Burcham, Philip C

    2017-01-17

    Acrolein is a highly toxic electrophile that participates in many diseases, yet efforts to delineate its precise mechanistic contributions to specific conditions are complicated by its wide distribution within human environments. This Perspective develops the proposal that due to its mixed status as environmental pollutant, metabolic byproduct, and endotoxicant which forms via ubiquitous pathophysiological processes, many diseases likely involve acrolein released from multiple sources. Although the category boundaries are indistinct, at least four identifiable exposure scenarios are identifiable. First, in some syndromes, such as those accompanying chronic or acute intoxication with smoke, whatever role acrolein plays in disease pathogenesis mainly traces to exogenous sources such as the combustion of tobacco or other organic matter. A second exposure category involves xenobiotics that undergo metabolism within the body to release acrolein. Still other health conditions, however, involve acrolein that forms via several endogenous pathways, some of which are activated upon intoxication with xenobiotics (i.e., Exposure Category 3), while still others accompany direct physical trauma to body tissues (Exposure Category 4). Further complicating efforts to clarify the role of endogenous acrolein in human disease is the likelihood that many such syndromes are complex phenomena that resemble "chemical mixture exposures" by involving multiple toxic substances simultaneously. This Perspective contends that while recent decades have witnessed much progress in describing the deleterious effects of acrolein at the cellular and molecular levels, more work is needed to define the contributions of different acrolein sources to "real-world" health conditions in human subjects.

  7. Activity of Crohn's disease assessed by colour Doppler ultrasound analysis of the affected loops.

    PubMed

    Esteban, J M; Maldonado, L; Sanchiz, V; Minguez, M; Benages, A

    2001-01-01

    The aim of this study was to evaluate with colour Doppler ultrasound the vascular changes in the wall of the loops affected by Crohn's disease, and to establish whether these changes reflects clinical or biochemical activity of Crohn's disease. Seventy-nine patients with Crohn's disease (44 with active disease and 35 inactive patients) were studied with frequency- and amplitude-encoded duplex Doppler sonography. A group of 35 healthy volunteers were also included. The exam consisted of the search for colour signals in the walls of the loops affected by Crohn's disease, classifying the degree of vascularity with a simple scoring system into three groups: absence of colour signal (score of 0); weak or scattered colour signals (score of 1); and multiple colour signals or clear identification of vessels in the loops walls (score of 2). Doppler curves were obtained of the detected vessels with measurement of the resistive index (RI). There was a visible increase in the gut walls' vascularity in the active patients compared with those with inactive disease. The mean RI was statistically significantly lower in the gut wall vessels of the patients with active illness than that obtained in the inactive patients. Colour Doppler ultrasound is a useful tool in the assessment of activity in Crohn's disease.

  8. Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington's Disease T Lymphocytes.

    PubMed

    Miller, James R C; Träger, Ulrike; Andre, Ralph; Tabrizi, Sarah J

    2015-01-01

    Huntington's disease is a fatal neurodegenerative condition caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system is dysregulated in Huntington's disease and may contribute to its pathogenesis. However, it is not clear whether or to what extent the adaptive immune system is also involved. Here, we carry out the first comprehensive investigation of human ex vivo T lymphocytes in Huntington's disease, focusing on the frequency of a range of T lymphocyte subsets, as well as analysis of proliferation, cytokine production and gene transcription. In contrast to the innate immune system, the intrinsic phenotype of T lymphocytes does not appear to be affected by the presence of mutant huntingtin, with Huntington's disease T lymphocytes exhibiting no significant functional differences compared to control cells. The transcriptional profile of T lymphocytes also does not appear to be significantly affected, suggesting that peripheral immune dysfunction in Huntington's disease is likely to be mediated primarily by the innate rather than the adaptive immune system. This study increases our understanding of the effects of Huntington's disease on peripheral tissues, while further demonstrating the differential effects of the mutant protein on different but related cell types. Finally, this study suggests that the potential use of novel therapeutics aimed at modulating the Huntington's disease innate immune system should not be extended to include the adaptive immune system.

  9. Haematological profile in leprosy. Part II--Relationship to severity of disease and treament status.

    PubMed

    Karat, A B; Rao, P S

    1978-01-01

    321 adult male lepromatous leprosy patients were studied for relationship between haematological findings, severity of disease and duration of treatment. Significant changes were noticed in relation in haemoglobin concentration, serum vitamin B12 and serum folate levels, serum albumin and globulin. No significant changes were observed in serum iron levels in relation to disease and treatment status. With rising bacterial load, there was a trend towards lower haemoglobin concentration, higher vitamin B12 level and lowered serum folate levels. Serum albumin showed a significant decline, while serum globulin showed a significant rise. The findings are discussed in relation to replacement of bone marrow by lepromatous tissue as well as possible interference in the metabolism of haematinics by M. leprae. The exact mechanism of neurlogical deficit in leprosy in relation to deficiency of vitamin B12 and folic acid need to be further elucidated.

  10. Frequency of the severe combined immunodeficiency disease gene among horses in Morocco.

    PubMed

    Piro, M; Benjouad, A; Tligui, N S; El Allali, K; El Kohen, M; Nabich, A; Ouragh, L

    2008-09-01

    Severe combined immunodeficiency disease (SCID) of horses is an autosomal, recessive hereditary disease occurring among Arabian or crossbred Arabian horses. The genetic defect responsible was previously identified as a 5-base pair deletion in the gene encoding the catalytic subunit of the DNA dependant protein kinase (DNA-PKcs). This study was carried out to determine the frequency of SCID and identify horses carrying the gene for SCID among Arabian and Arabian crossbred stallions and mares in Morocco using a DNA-based test. Twenty-one horses were SCID carriers: 14 (7%) Arabians, 6 (4%) Arab-Barbs and one (33%) Anglo-Arab. After analysing their genealogy, 3 imported stallions were identified that disseminated the mutant gene of DNA-PKcs in Morocco.

  11. Blood dendritic cell frequency declines in idiopathic Parkinson's disease and is associated with motor symptom severity.

    PubMed

    Ciaramella, Antonio; Salani, Francesca; Bizzoni, Federica; Pontieri, Francesco E; Stefani, Alessandro; Pierantozzi, Mariangela; Assogna, Francesca; Caltagirone, Carlo; Spalletta, Gianfranco; Bossù, Paola

    2013-01-01

    The role of inflammation in Parkinson's Disease (PD) is well appreciated, but its underlying mechanisms are still unclear. Our objective was to determine whether dendritic cells (DC), a unique type of migratory immune cells that regulate immunological response and inflammation have an impact on PD. In a case-control study including 80 PD patients and 80 age- and gender-matched healthy control subjects, the two main blood subsets of plasmacytoid and myeloid DC were defined by flow cytometry analysis. Clinical evaluation of subjects consisting of cognition and depression assessment was performed using the Mini Mental State Examination and the Beck Depression Inventory. The severity of motor symptoms was measured using the Unified Parkinson's Disease Rating Scale-Part III. Comparison between patient and control DC measures and their relationships with clinical assessments were evaluated.The following main results were obtained: 1) the level of circulating DC (mainly the myeloid subset) was significantly reduced in PD patients in comparison with healthy controls; 2) after controlling for depressive and cognitive characteristics, the frequency of myeloid DC was confirmed as one of the independent determinants of PD; 3) the number of both myeloid and plasmacytoid DC was negatively associated with motor symptom severity. Overall, the decline of blood DC, perhaps due to the recruitment of immune cells to the site of disease-specific lesions, can be considered a clue of the immune alteration that characterizes PD, suggesting innovative exploitations of DC monitoring as a clinically significant tool for PD treatment. Indeed, this study suggests that reduced peripheral blood DC are a pathologically-relevant factor of PD and also displays the urgency to better understand DC role in PD for unraveling the immune system contribution to disease progression and thus favoring the development of innovative therapies ideally based on immunomodulation.

  12. Patient coping strategies in COPD across disease severity and quality of life: a qualitative study

    PubMed Central

    Brien, Sarah B; Lewith, George T; Thomas, Mike

    2016-01-01

    Quality of life (QoL) has a weak relationship with lung function (LF) impairment in COPD; some cope well despite poor LF, whereas others suffer disproportionate QoL impairment despite well-preserved LF. Adjuvant non-pharmacological interventions such as rehabilitation and psychological/behavioural support may help if acceptable and targeted appropriately, but they are under-used and sometimes declined by patients. This study aimed to explore and understand variations in experiences and coping strategies in patients with different severities of disease and disease-specific QoL. Thirty-four participants were purposively sampled across a spectrum of LF and QoL impairment, to cover a grid of sub-groups (‘very severe LF, good QoL’, moderate LF, poor QoL’ and so on). Semi-structured interviews, digitally recorded, were analysed by thematic analysis. Data saturation was achieved. Four themes emerged: symptom impact, coping strategies, coping challenges and support needs. Most of them described using multiple coping strategies, yet over half reported significant challenges coping with COPD, including psychological impact, non-acceptance of diagnosis and/or disease progression, effects of co-morbidities and inadequate self-management skills. Approximately half of the participants wanted further help, ideally non-pharmacological, across all LF impairment groups but mainly with lower QoL. Those with lower QoL additionally reported greater psychological distress and greater use of non-pharmacological support strategies where accessible. Patients who develop effective coping strategies have a better QoL independent of objective LF, whereas others cope poorly, are aware of this and report more use of non-pharmacological approaches. This study suggests that severely impaired QoL, irrelevant of lung function, is a powerful patient-centred indication to explore the positive benefits of psychological and behavioural support for distressed COPD patients. PMID:27629237

  13. Computed Tomography Scans as an Objective Measure of Disease Severity in Chronic Rhinosinusitis

    PubMed Central

    Likness, Micah M.; Pallanch, John F.; Sherris, David A.; Kita, Hirohito; Mashtare, Terry L.; Ponikau, Jens U.

    2014-01-01

    Objectives A truly objective method of measuring disease severity in chronic rhinosinusitis (CRS) has only recently existed. We evaluated computed tomography (CT) scans of CRS patients using this novel objective 3D computerized system and compared results with a novel 2D computerized analysis of a single coronal slice through the osteomeatal complex (OMC) and subjective methods including Lund-Mackay and Zinreich’s modified Lund-Mackay. Study Design Prospective multicenter study. Setting Two academic tertiary referral centers. Subjects and Methods Forty-six adults with a diagnosis of CRS underwent CT examination and received an intramuscular triamcinolone injection, dosage weight dependent, followed by CT scan 4 to 5 weeks later. Recruitment lasted 21 months. Scans were evaluated with all 4 scoring methods over 5 months. Results The Lin’s concordance class correlation (CCC) of the OMC method revealed the best correlation to the 3D volumetric computerized values (0.915), followed by the Zinreich (0.904) and Lund-Mackay methods (0.824). Posttreatment results demonstrated that both the OMC (0.824) and Zinreich’s (0.778) methods had strong agreement with the 3D volumetric methods and were very sensitive to change, whereas the Lund-Mackay (0.545) had only moderate agreement. Conclusion Computerized CT analysis provides the most comprehensive, objective, and reproducible method of measuring disease severity and is very sensitive to change induced by treatment intervention. A 2D coronal image through the OMC provides a valid, user-friendly method of assessing CRS and is representative of CRS severity in all sinuses. Zinreich’s subjective method correlated well overall, but the Lund-Mackay method lagged behind in disease representation and sensitivity to change. PMID:24301090

  14. Fibrocytes Regulate Wilms’ Tumor 1-Positive Cell Accumulation in Severe Fibrotic Lung Disease

    PubMed Central

    Sontake, Vishwaraj; Shanmukhappa, Shiva K.; DiPasquale, Betsy A.; Reddy, Geereddy B.; Medvedovic, Mario; Hardie, William D.; White, Eric S.; Madala, Satish K.

    2015-01-01

    Collagen-producing myofibroblast transdifferentiation is considered a crucial determinant in the formation of scar tissue in the lungs of patients with idiopathic pulmonary fibrosis (IPF). Multiple resident pulmonary cell types and bone marrow-derived fibrocytes have been implicated as contributors to fibrotic lesions due to the transdifferentiation potential of these cells into myofibroblasts. In this study, we assessed the expression of Wilms’ tumor 1 (WT1), a known marker of mesothelial cells, in various cell types in normal and fibrotic lungs. We demonstrate that WT1 is expressed by both mesothelial and mesenchymal cells in IPF lungs, but has limited or no expression in normal human lungs. We also demonstrate that WT1-positive cells accumulate in fibrotic lung lesions, using two different mouse models of pulmonary fibrosis and WT1 promoter-driven fluorescent reporter mice. Reconstitution of bone-marrow cells into a transforming growth factor-α transgenic-mouse model demonstrated that fibrocytes do not transform into WT1-positive mesenchymal cells, but do augment accumulation of WT1-positive cells in severe fibrotic lung disease. Importantly, the number of WT1-positive cells in fibrotic lesions were correlated with severity of lung disease as assessed by changes in lung function, histology, and hydroxyproline levels in mice. Finally, inhibition of WT1 expression was sufficient to attenuate collagen and other extracellular-matrix gene production by mesenchymal cells from both murine and human fibrotic lungs. Thus, the results of this study demonstrate a novel association between fibrocyte-driven WT1-positive cell accumulation and severe fibrotic lung disease. PMID:26371248

  15. L-Dopa induced dyskinesias in Parkinsonian mice: disease severity or L-Dopa history

    PubMed Central

    Shan, Lufei; Diaz, Oscar; Zhang, Yajun; Ladenheim, Bruce; Cadet, Jean-Lud; Chiang, Yung-Hsiao; Olson, Lars; Hoffer, Barry J.; Bäckman, Cristina M.

    2016-01-01

    In Parkinson's disease, the efficacy of L-Dopa treatment changes over time, as dyskinesias emerge with previously beneficial doses. Using MitoPark mice, that models mitochondrial failure in dopamine (DA) neurons and mimics the progressive loss of dopamine observed in Parkinson’s disease, we found that the severity of DA denervation and associated adaptations in striatal neurotransmission at the time of initiation of L-Dopa treatment determines development of L-Dopa induced dyskinesias. We treated 20-week, and 28-week old MitoPark mice with L-Dopa (10 mg/kg i.p. twice a day) and found locomotor responses to be significantly different. While all MitoPark mice developed sensitization to L-Dopa treatment over time, 28-week old MitoPark mice with extensive striatal DA denervation developed abnormal involuntary movements rapidly and severely after starting L-Dopa treatment, as compared to a more gradual escalation of movements in 20-week old animals that started treatment at earlier stages of degeneration. Our data support that it is the extent of loss of DA innervation that determines how soon motor complications develop with L-Dopa treatment. Gene array studies of striatal neurotransmitter receptors revealed changes in mRNA expression levels for DA, serotonin, glutamate and GABA receptors in striatum of 28-week old MitoPark mice. Our results support that delaying L-Dopa treatment until Parkinson’s disease symptoms become more severe does not delay the development of L-Dopa-induced dyskinesias. MitoPark mice model genetic alterations known to impair mitochondrial function in a subgroup of Parkinson patients and provide a platform in which to study treatments to minimize the development of dyskinesia. PMID:26086365

  16. The affect of infectious bursal disease virus on avian influenza virus vaccine efficacy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Immunosuppressive viruses are known to affect vaccinal immunity, however the impact of virally induced immunosuppression on avian influenza vaccine efficacy has not been quantified. In order to determine the effect of exposure to infectious bursal disease virus (IBDV) on vaccinal immunity to highly ...

  17. ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor

    PubMed Central

    Divisato, Giuseppina; Formicola, Daniela; Esposito, Teresa; Merlotti, Daniela; Pazzaglia, Laura; Del Fattore, Andrea; Siris, Ethel; Orcel, Philippe; Brown, Jacques P.; Nuti, Ranuccio; Strazzullo, Pasquale; Benassi, Maria Serena; Cancela, M. Leonor; Michou, Laetitia; Rendina, Domenico; Gennari, Luigi; Gianfrancesco, Fernando

    2016-01-01

    Paget disease of bone (PDB) is a skeletal disorder characterized by focal abnormalities of bone remodeling, which result in enlarged and deformed bones in one or more regions of the skeleton. In some cases, the pagetic tissue undergoes neoplastic transformation, resulting in osteosarcoma and, less frequently, in giant cell tumor of bone (GCT). We performed whole-exome sequencing in a large family with 14 PDB-affected members, four of whom developed GCT at multiple pagetic skeletal sites, and we identified the c.2810C>G (p.Pro937Arg) missense mutation in the zinc finger protein 687 gene (ZNF687). The mutation precisely co-segregated with the clinical phenotype in all affected family members. The sequencing of seven unrelated individuals with GCT associated with PDB (GCT/PDB) identified the same mutation in all individuals, unravelling a founder effect. ZNF687 is highly expressed during osteoclastogenesis and osteoblastogenesis and is dramatically upregulated in the tumor tissue of individuals with GCT/PDB. Interestingly, our preliminary findings showed that ZNF687, indicated as a target gene of the NFkB transcription factor by ChIP-seq analysis, is also upregulated in the peripheral blood of PDB-affected individuals with (n = 5) or without (n = 6) mutations in SQSTM1, encouraging additional studies to investigate its potential role as a biomarker of PDB risk. PMID:26849110

  18. Haemopoietic stem cell transplantation in the treatment of severe autoimmune diseases 2000

    PubMed Central

    Tyndall, A; Passweg, J; Gratwohl, A

    2001-01-01

    An international meeting took place in Basel, Switzerland from 5 to 7 October 2000 involving 180 participants from 30 countries, with the aim of assessing the existing data on autologous haemopoietic stem cell transplantation (HSCT) in the treatment of severe autoimmune disease, and to decide on future trial planning.
  Data on 390 patients were presented: 260 from the EBMT/EULAR Basel European/Asian database, 87 from North America (55 from the IBMTR), 39 from Australia, and 4 others. The major disease categories and number of patients receiving transplant were: multiple sclerosis (MS) 127, systemic sclerosis (SSc) 72, rheumatoid arthritis (RA) 70, juvenile idiopathic arthritis (JIA) 36, systemic lupus erythematosus (SLE) 34, dermatomyositis/polymyositis (DM/PM) 5, idiopathic thrombocytopenic purpura (ITP) 7. Single or several cases of other autoimmune diseases were reported.
  Clinically significant responses were seen in two thirds of all the cases and in all disease categories, with a more accentuated trend towards relapse in JIA and RA.
Treatment was associated with a significant morbidity and mortality. In the EULAR/EBMT database (71 centres in 22 countries), a mobilisation associated mortality of 1.5% and an overall procedure related mortality (actuarially adjusted at 12 months) of 9% (confidence interval 6 to 12%) were found, with significant variation between diseases. The North American data showed similar results. Higher mortalities were seen in SSc and systemic JIA, with only one death reported in RA.
  After presentation of the data and workshop discussion a consensus was reached on several aspects: prospective randomised phase III trials are now appropriate in SSc, MS, and RA. A protocol is ready for SSc (ASTIS Trial), concepts are clear for MS and RA. Further phase I and II data are required in SLE, JIA, and vasculitis. The need for continuing collection of all cases after mobilisation by the standardised EBMT and

  19. A novel GUSB mutation in Brazilian terriers with severe skeletal abnormalities defines the disease as mucopolysaccharidosis VII.

    PubMed

    Hytönen, Marjo K; Arumilli, Meharji; Lappalainen, Anu K; Kallio, Heli; Snellman, Marjatta; Sainio, Kirsi; Lohi, Hannes

    2012-01-01

    Hundreds of different human skeletal disorders have been characterized at molecular level and a growing number of resembling dysplasias with orthologous genetic defects are being reported in dogs. This study describes a novel genetic defect in the Brazilian Terrier breed causing a congenital skeletal dysplasia. Affected puppies presented severe skeletal deformities observable within the first month of life. Clinical characterization using radiographic and histological methods identified delayed ossification and spondyloepiphyseal dysplasia. Pedigree analysis suggested an autosomal recessive disorder, and we performed a genome-wide association study to map the disease locus using Illumina's 22K SNP chip arrays in seven cases and eleven controls. A single association was observed near the centromeric end of chromosome 6 with a genome-wide significance after permutation (p(genome)= 0.033). The affected dogs shared a 13-Mb homozygous region including over 200 genes. A targeted next-generation sequencing of the entire locus revealed a fully segregating missense mutation (c.866C>T) causing a pathogenic p.P289L change in a conserved functional domain of β-glucuronidase (GUSB). The mutation was confirmed in a population of 202 Brazilian terriers (p = 7,71×10(-29)). GUSB defects cause mucopolysaccharidosis VII (MPS VII) in several species and define the skeletal syndrome in Brazilian Terriers. Our results provide new information about the correlation of the GUSB genotype to phenotype and establish a novel canine model for MPS VII. Currently, MPS VII lacks an efficient treatment and this model could be utilized for the development and validation of therapeutic methods for better treatment of MPS VII patients. Finally, since almost one third of the Brazilian terrier population carries the mutation, breeders will benefit from a genetic test to eradicate the detrimental disease from the breed.

  20. A Novel GUSB Mutation in Brazilian Terriers with Severe Skeletal Abnormalities Defines the Disease as Mucopolysaccharidosis VII

    PubMed Central

    Hytönen, Marjo K.; Arumilli, Meharji; Lappalainen, Anu K.; Kallio, Heli; Snellman, Marjatta; Sainio, Kirsi; Lohi, Hannes

    2012-01-01

    Hundreds of different human skeletal disorders have been characterized at molecular level and a growing number of resembling dysplasias with orthologous genetic defects are being reported in dogs. This study describes a novel genetic defect in the Brazilian Terrier breed causing a congenital skeletal dysplasia. Affected puppies presented severe skeletal deformities observable within the first month of life. Clinical characterization using radiographic and histological methods identified delayed ossification and spondyloepiphyseal dysplasia. Pedigree analysis suggested an autosomal recessive disorder, and we performed a genome-wide association study to map the disease locus using Illumina’s 22K SNP chip arrays in seven cases and eleven controls. A single association was observed near the centromeric end of chromosome 6 with a genome-wide significance after permutation (pgenome  = 0.033). The affected dogs shared a 13-Mb homozygous region including over 200 genes. A targeted next-generation sequencing of the entire locus revealed a fully segregating missense mutation (c.866C>T) causing a pathogenic p.P289L change in a conserved functional domain of β-glucuronidase (GUSB). The mutation was confirmed in a population of 202 Brazilian terriers (p = 7,71×10−29). GUSB defects cause mucopolysaccharidosis VII (MPS VII) in several species and define the skeletal syndrome in Brazilian Terriers. Our results provide new information about the correlation of the GUSB genotype to phenotype and establish a novel canine model for MPS VII. Currently, MPS VII lacks an efficient treatment and this model could be utilized for the development and validation of therapeutic methods for better treatment of MPS VII patients. Finally, since almost one third of the Brazilian terrier population carries the mutation, breeders will benefit from a genetic test to eradicate the detrimental disease from the breed. PMID:22815736

  1. [Perioperative Management of a Patient with Severe Parkinson's Disease with Intravenous Levodopa Administration].

    PubMed

    Terashima, Satoko; Yanagido, Yurina; Watabe, Akira; Yamane, Masahiro; Morimoto, Yuji

    2015-08-01

    A 70-year-old man with severe Parkinson's disease was scheduled for thoracic aortic aneurysm resection and aortic valve replacement. We administered levodopa intravenously during the perioperative period to avoid the malignant syndrome which is reported to arise with abrupt cessation of anti-Parkinson's drugs. The dose of intravenous administration was tapered with the resumption of oral intake. No manifestation of malignant syndrome was observed. We measured blood concentrations of levodopa several times during the perioperative period. The concentration of levodopa during the surgery was relatively high; however no adverse events of overdose (e.g. dyskinesis) occurred. In the postoperative period, administration of levodopa was changed to the oral route and serum levels of levodopa showed a notable decrease, the cause of which may be poor absorption through the digestive system during the perioperative period. Therefore, in the peri- and post-operative periods, it is necessary to take great care when reducing the infusion dose.

  2. Safety and efficacy of defibrotide for the treatment of severe hepatic veno-occlusive disease.

    PubMed

    Richardson, Paul G; Ho, Vincent T; Giralt, Sergio; Arai, Sally; Mineishi, Shin; Cutler, Corey; Antin, Joseph H; Stavitzski, Nicole; Niederwieser, Dietger; Holler, Ernst; Carreras, Enric; Soiffer, Robert

    2012-08-01

    Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). VOD may occur in up to 62% of patients undergoing SCT, with onset generally within the first month after SCT. In severe cases, 100-day mortality is in excess of 80%. Current management consists of best supportive care, with no agents to date approved for treatment in the USA or the EU. Defibrotide, a polydisperse oligonucleotide, has been shown in phase II and III trials to improve complete response and survival in patients undergoing SCT with severe VOD. This article reviews our current understanding of VOD, and examines recent clinical findings on defibrotide for the treatment and prophylaxis of VOD.

  3. Single photon emission computed tomography in Alzheimer's disease. Abnormal iofetamine I 123 uptake reflects dementia severity

    SciTech Connect

    Johnson, K.A.; Holman, B.L.; Mueller, S.P.; Rosen, T.J.; English, R.; Nagel, J.S.; Growdon, J.H.

    1988-04-01

    To determine whether abnormalities in regional cerebral functional activity estimated by iofetamine hydrochloride I 123 and single photon emission computed tomography can be detected in mild or moderate as well as severe cases of Alzheimer's disease (AD), we performed iofetamine I 123-single photon emission computed tomography in 37 patients with probable AD (nine patients with mild, 18 patients with moderate, and ten patients with severe dementia) and nine age-matched control subjects. Iofetamine I 123 uptake was measured in right and left frontal, temporal, parietal, and occipital cortices. Mean (right and left) iofetamine I 123 activity was lowest in the parietal region of patients with AD and was significantly reduced in the other three regions compared with control subjects. Only in the parietal region was lower relative iofetamine I 123 activity associated with an impaired level of patient function and with cognitive deficit.

  4. Olfactory functions in patients with psoriasis vulgaris: correlations with the severity of the disease.

    PubMed

    Aydın, Ersin; Tekeli, Hakan; Karabacak, Ercan; Altunay, İlknur Kıvanç; Aydın, Çigdem; Çerman, Aslı Aksu; Altundağ, Aytuğ; Salihoğlu, Murat; Çayönü, Melih

    2016-08-01

    It is well known that psoriasis is not only limited to skin, but a systemic autoimmune disease with various comorbidities. Olfactory dysfunction, one of as a common but lesser known symptom of patients with autoimmune diseases, often presents with smell loss. The aim of this study was to assess the olfactory functions in patients with psoriasis and to compare with healthy controls. A total of 50 patients with psoriasis and 43 control subjects were included to the study. The clinical severity of psoriasis was calculated by psoriasis area and severity index (PASI). Patients were classified into two groups according to PASI score as mild (PASI ≤10) and moderate-severe (PASI >10). Olfactory function was evaluated with "Sniffin'Sticks" test. Total test scores (max. 48 points) of threshold, discrimination, and identification (TDI) were classified as normal olfaction = normosmia (>30.3 points), decreased olfaction = hyposmia (16.5-30.3 points) and loss of olfaction = anosmia (<16.5 points). Psoriasis patients had significantly lower smell scores compared with healthy controls (p < 0.001). Of the 50 psoriasis patients, 40 (80 %) were hyposmic. We found negative correlation between TDI and PASI (r = -0.34, p = 0.014). The TDI scores of the patients with moderate-severe psoriasis (PASI score >10) were found to be significantly lower than the patients with mild psoriasis (PASI ≤10) (p < 0.001). Olfactory dysfunction in patients with psoriasis could be thought as a comorbidity as in other inflammatory disorders. Physicians should be aware of olfactory impairment when evaluating psoriasis patients in their clinical practice.

  5. Severe multivessel coronary artery disease and high-sensitive troponin T

    PubMed Central

    Huziuk, Inga Magdalena

    2015-01-01

    Introduction A key problem in stable coronary artery disease (CAD) is non-invasive identification of patients with severe multivessel CAD. Determination of biomarkers that have pro-inflammatory properties (C-reactive protein – hsCRP) and indicate heart muscle ischemia (high-sensitive troponin T – hsTnT) can contribute to the improvement of stratification in this regard. The aim of the study The aim of the study was to identify factors associated with the presence of multivessel CAD in clinically stable men. Material and methods The study included 92 symptomatic men (mean age 64.05 ± 9.42 years) with preserved left ventricular function, scheduled for elective coronary angiography. Patients were divided and analyzed in two groups: with multivessel coronary artery disease (2-3-vessel disease, n = 46) vs. without multivessel coronary artery disease (n = 46). Results Patients with multivessel CAD had significantly higher levels of hsTnT (0.01 vs. 0.007, p = 0.0021) and fasting glucose (6.0 vs. 5.45, p = 0.0112). Based on the drawn ROC curves, the cut-off points were determined for hsTnT ≥ 0.0085 ng/ml and fasting plasma glucose ≥ 5.85 mmol/l. From multivariate analysis only hsTnT in concentration higher than the cut-off point enhanced the risk of multivessel CAD (OR 4.286, 95% CI: 1.79-10.263, p = 0.001). Conclusions In men with stable CAD, preserved systolic left ventricular function and non-high cardiovascular risk determined from the initial concentration of hsCRP, elevated level of hsTnT was independently associated with the risk of multivessel coronary artery disease. PMID:26336496

  6. Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson's disease and incidental Parkinson's disease.

    PubMed

    Fabelo, Noemí; Martín, Virginia; Santpere, Gabriel; Marín, Raquel; Torrent, Laia; Ferrer, Isidre; Díaz, Mario

    2011-01-01

    Lipid rafts are cholesterol- and sphingomyelin-enriched microdomains that provide a highly saturated and viscous physicochemical microenvironment to promote protein-lipid and protein-protein interactions. We purified lipid rafts from human frontal cortex from normal, early motor stages of Parkinson's disease (PD) and incidental Parkinson's disease (iPD) subjects and analyzed their lipid composition. We observed that lipid rafts from PD and iPD cortices exhibit dramatic reductions in their contents of n-3 and n-6 long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (22:6-n3) and arachidonic acid (20:4n-6). Also, saturated fatty acids (16:0 and 18:0) were significantly higher than in control brains. Paralleling these findings, unsaturation and peroxidability indices were considerably reduced in PD and iPD lipid rafts. Lipid classes were also affected in PD and iPD lipid rafts. Thus, phosphatidylserine and phosphatidylinositol were increased in PD and iPD, whereas cerebrosides and sulfatides and plasmalogen levels were considerably diminished. Our data pinpoint a dramatic increase in lipid raft order due to the aberrant biochemical structure in PD and iPD and indicate that these abnormalities of lipid rafts in the frontal cortex occur at early stages of PD pathology. The findings correlate with abnormal lipid raft signaling and cognitive decline observed during the development of these neurodegenerative disorders.

  7. A Case-control Study on Risk Factors for Severe Hand, Foot and Mouth Disease

    PubMed Central

    Zhang, Dingmei; Li, Ruolin; Zhang, Wangjian; Li, Guowei; Ma, Zhanzhong; Chen, Xiashi; Du, Zhicheng; Li, Zhiyuan; Guo, Pi; Lin, Zhuochen; Lu, Jiahai; Hao, Yuantao

    2017-01-01

    The objective of this study was to identify potential risk factors for severe hand, foot and mouth disease (HFMD). In this case-control study, 459 severe HFMD patients and 246 mild HFMD patients from Guangdong province and Henan province, China were included. Data comprising demographic characteristics, clinical symptoms and signs, laboratory findings and other factors were collected. Univariate analysis revealed 30 factors associated with severe cases. Further multivariate analysis indicated four independent risk factors: fatigue (p < 0.01, odd ratio [OR] = 204.7), the use of glucocorticoids (p = 0.03, OR = 10.44), the use of dehydrant drugs (p < 0.01, OR = 73.7) and maculopapular rash (p < 0.01, OR = 84.4); and one independent protective factor: herpes or ulcers in mouth (p = 0.01, OR = 0.02). However, more systematic research and validation are needed to understand the underlying risk factors for severe HFMD. PMID:28084311

  8. Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis

    PubMed Central

    Skouras, Christos; Zheng, Xiaozhong; Binnie, Margaret; Homer, Natalie Z. M.; Murray, Toby B. J.; Robertson, Darren; Briody, Lesley; Paterson, Finny; Spence, Heather; Derr, Lisa; Hayes, Alastair J.; Tsoumanis, Andreas; Lyster, Dawn; Parks, Rowan W.; Garden, O. James; Iredale, John P.; Uings, Iain J.; Liddle, John; Wright, Wayne L.; Dukes, George; Webster, Scott P.; Mole, Damian J.

    2016-01-01

    Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R2 = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R2 = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction. PMID:27669975

  9. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease

    PubMed Central

    Soler-Cataluna, J; Martinez-Garcia, M; Roman, S; Salcedo, E; Navarro, M; Ochando, R

    2005-01-01

    Background: Patients with chronic obstructive pulmonary disease (COPD) often present with severe acute exacerbations requiring hospital treatment. However, little is known about the prognostic consequences of these exacerbations. A study was undertaken to investigate whether severe acute exacerbations of COPD exert a direct effect on mortality. Methods: Multivariate techniques were used to analyse the prognostic influence of acute exacerbations of COPD treated in hospital (visits to the emergency service and admissions), patient age, smoking, body mass index, co-morbidity, long term oxygen therapy, forced spirometric parameters, and arterial blood gas tensions in a prospective cohort of 304 men with COPD followed up for 5 years. The mean (SD) age of the patients was 71 (9) years and forced expiratory volume in 1 second was 46 (17)%. Results: Only older age (hazard ratio (HR) 5.28, 95% CI 1.75 to 15.93), arterial carbon dioxide tension (HR 1.07, 95% CI 1.02 to 1.12), and acute exacerbations of COPD were found to be independent indicators of a poor prognosis. The patients with the greatest mortality risk were those with three or more acute COPD exacerbations (HR 4.13, 95% CI 1.80 to 9.41). Conclusions: This study shows for the first time that severe acute exacerbations of COPD have an independent negative impact on patient prognosis. Mortality increases with the frequency of severe exacerbations, particularly if these require admission to hospital. PMID:16055622

  10. Blood count parameters can predict the severity of coronary artery disease

    PubMed Central

    Uysal, Hilal Bektas; Dağlı, Bekir; Akgüllü, Cağdaş; Avcil, Mücahit; Zencir, Cemil; Ayhan, Mediha; Sönmez, Hulki Meltem

    2016-01-01

    Background/Aims Because of the inflammatory nature of coronary artery disease (CAD), both platelets and white blood cells have been investigated for years. The aim of this study was to investigate the relationships between some prominently hematologic blood count parameters (mean platelet volume [MPV], neutrophil to lymphocyte ratio [NLR]) and the severity of CAD by using Gensini scores. Methods A total of 194 patients, who had undergone coronary angiography, enrolled in this study. The control group consisted of 42 patients who had normal coronary arteries. Remaining CAD patients were divided into two groups according to their Gensini scores. Results NLR and MPV were higher in the severe atherosclerosis group compared with the mild atherosclerosis group (p = 0.007, p = 0.005, respectively). The Gensini score showed significant correlations with NLR (r = 0.20, p = 0.011), MPV (r = 0.23, p = 0.004) and high density lipoprotein cholesterol (r = –0.161, p = 0.047). Using a cut-off level of 2.54, NLR predicted severe atherosclerosis with a sensitivity of 74% and specificity of 53% (area under curve [AUC], 0.627; 95% confidence interval [CI], 0.545 to 0.704; p = 0.004). MPV values above 10.4 predicted severe atherosclerosis with a sensitivity of 39% and specificity of 90% (AUC, 0.631; 95% CI, 0.549 to 0.708; p = 0.003). In the multiple logistic regression analysis, high levels of NLR (odds ratio [OR], 1.450; 95% CI, 1.080 to 1.945; p = 0.013) and MPV (OR, 1.622; 95% CI, 1.147 to 2.295; p = 0.006) were found to be independent predictors of severe atherosclerosis. Conclusions Our study suggests that both NLR and MPV are predictors of severe atherosclerosis and may be used for the prediction and identification of cardiac risks in CAD patients. PMID:27052265

  11. Impact Depth and the Interaction with Impact Speed Affect the Severity of Contusion Spinal Cord Injury in Rats

    PubMed Central

    Lam, Cameron J.; Assinck, Peggy; Liu, Jie; Tetzlaff, Wolfram

    2014-01-01

    Abstract Spinal cord injury (SCI) biomechanics suggest that the mechanical factors of impact depth and speed affect the severity of contusion injury, but their interaction is not well understood. The primary aim of this work was to examine both the individual and combined effects of impact depth and speed in contusion SCI on the cervical spinal cord. Spinal cord contusions between C5 and C6 were produced in anesthetized rats at impact speeds of 8, 80, or 800 mm/s with displacements of 0.9 or 1.5 mm (n=8/group). After 7 days postinjury, rats were assessed for open-field behavior, euthanized, and spinal cords were harvested. Spinal cord tissue sections were stained for demyelination (myelin-based protein) and tissue sparing (Luxol fast blue). In parallel, a finite element model of rat spinal cord was used to examine the resulting maximum principal strain in the spinal cord during impact. Increasing impact depth from 0.9 to 1.5 mm reduced open-field scores (p<0.01) above 80 mm/s, reduced gray (GM) and white matter (WM) sparing (p<0.01), and increased the amount of demyelination (p<0.01). Increasing impact speed showed similar results at the 1.5-mm impact depth, but not the 0.9-mm impact depth. Linear correlation analysis with finite element analysis strain showed correlations (p<0.001) with nerve fiber damage in the ventral (R2=0.86) and lateral (R2=0.74) regions of the spinal cord and with WM (R2=0.90) and GM (R2=0.76) sparing. The results demonstrate that impact depth is more important in determining the severity of SCI and that threshold interactions exist between impact depth and speed. PMID:24945364

  12. Ecosystem screening approach for pathogen-associated microorganisms affecting host disease.

    PubMed

    Galiana, Eric; Marais, Antoine; Mura, Catherine; Industri, Benoît; Arbiol, Gilles; Ponchet, Michel

    2011-09-01

    The microbial community in which a pathogen evolves is fundamental to disease outcome. Species interacting with a pathogen on the host surface shape the distribution, density, and genetic diversity of the inoculum, but the role of these species is rarely determined. The screening method developed here can be used to characterize pathogen-associated species affecting disease. This strategy involves three steps: (i) constitution of the microbial community, using the pathogen as a trap; (ii) community selection, using extracts from the pathogen as the sole nutrient source; and (iii) molecular identification and the screening of isolates focusing on their effects on the growth of the pathogen in vitro and host disease. This approach was applied to a soilborne plant pathogen, Phytophthora parasitica, structured in a biofilm, for screening the microbial community from the rhizosphere of Nicotiana tabacum (the host). Two of the characterized eukaryotes interfered with the oomycete cycle and may affect the host disease. A Vorticella species acted through a mutualistic interaction with P. parasitica, disseminating pathogenic material by leaving the biofilm. A Phoma species established an amensal interaction with P. parasitica, strongly suppressing disease by inhibiting P. parasitica germination. This screening method is appropriate for all nonobligate pathogens. It allows the definition of microbial species as promoters or suppressors of a disease for a given biotope. It should also help to identify important microbial relationships for ecology and evolution of pathogens.

  13. Loss of phosphodiesterase 10A expression is associated with progression and severity in Parkinson's disease.

    PubMed

    Niccolini, Flavia; Foltynie, Thomas; Reis Marques, Tiago; Muhlert, Nils; Tziortzi, Andri C; Searle, Graham E; Natesan, Sridhar; Kapur, Shitij; Rabiner, Eugenii A; Gunn, Roger N; Piccini, Paola; Politis, Marios

    2015-10-01

    pallidal loss of PDE10A expression, which is associated with Parkinson's duration and severity of motor symptoms and complications. PDE10A is an enzyme that could be targeted with novel pharmacotherapy, and this may help improve dopaminergic signalling and striatal output, and therefore alleviate symptoms and complications of Parkinson's disease.

  14. Severity of atopic disease inversely correlates with intestinal microbiota diversity and butyrate-producing bacteria.

    PubMed

    Nylund, L; Nermes, M; Isolauri, E; Salminen, S; de Vos, W M; Satokari, R

    2015-02-01

    The reports on atopic diseases and microbiota in early childhood remain contradictory, and both decreased and increased microbiota diversity have been associated with atopic eczema. In this study, the intestinal microbiota signatures associated with the severity of eczema in 6-month-old infants were characterized. Further, the changes in intestinal microbiota composition related to the improvement of this disease 3 months later were assessed. The severity of eczema correlated inversely with microbiota diversity (r = -0.54, P = 0.002) and with the abundance of butyrate-producing bacteria (r = -0.52, P = 0.005). During the 3-month follow-up, microbiota diversity increased (P < 0.001) and scoring atopic dermatitis values decreased (P < 0.001) in all infants. This decrease coincided with the increase in bacteria related to butyrate-producing Coprococcus eutactus (r = -0.59, P = 0.02). In conclusion, the high diversity of microbiota and high abundance of butyrate-producing bacteria were associated with milder eczema, thus suggesting they have a role in alleviating symptoms of atopic eczema.

  15. Correlation of serum neutrophil gelatinase associated lipocalin with disease severity in hypertensive disorders of pregnancy

    PubMed Central

    Sachan, Rekha; Patel, ML; Gaurav, Amrita; Gangwar, Radheshyam; Sachan, Pushpalata

    2014-01-01

    Background: Vascular endothelial dysfunction is considered central to the pathogenesis of hypertensive disorders of pregnancy (HDP). Serum level of neutrophil gelatinase-associated lipocalin (NGAL) is closely related to endothelial injury. The aim of this study was to examine the correlation of serum NGAL with disease severity in HDP. Materials and Methods: This prospective case-control study was carried out for one year. After informed consent, ethical clearance, total 1,850 pregnant women were screened. Analysis was performed on 142 cases of HDP and 31 healthy controls. Quantitative measurement of serum NGAL levels was done by the enzyme linked immunosorbent assay (ELISA) technique, by using sandwich ELISA kit. Results: Mean serum NGAL value in patients with oliguria was significantly higher when compared with non-oliguric patients (P < 0.001). Serum NGAL had a positive correlation with systolic blood pressure (r ~ 0.5973), diastolic blood pressure (r ~ 0.6195), blood urea (r ~ 0.4392), serum creatinine (r ~ 0.6112), serum uric acid (r ~ 0.3878). Sensitivity and specificity of serum NGAL using a cut-off value of 545 pg/ml, for the diagnosis of HDP, was 97.89% and 93.55% respectively, using 95% confidence interval. Conclusion: Between the two groups, we found that serum NGAL had a positive correlation with disease severity and better sensitivity and specificity in the evaluation of HDP. PMID:25538909

  16. The extent of ultrastructural spinal cord pathology reflects disease severity in experimental autoimmune encephalomyelitis.

    PubMed

    Gruppe, Traugott L; Recks, Mascha S; Addicks, Klaus; Kuerten, Stefanie

    2012-09-01

    Experimental autoimmune encephalomyelitis (EAE) has been studied for decades as an animal model for huma