Sample records for affect disease severity

  1. 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

  2. Affected parent sex and severity of autosomal dominant polycystic kidney disease: a retrospective cohort study
.

    PubMed

    Nowak, Kristen L; Chonchol, Michel; You, Zhiying; Gupta, Malika; Gitomer, Berenice

    2018-03-01

    Parental inheritance may differentially affect autosomal dominant polycystic kidney disease (-ADPKD) severity via genetic imprinting or in utero epigenetic modifications; however, evidence is inconsistent. We conducted a longitudinal retrospective cohort study to assess the association between sex of the affected parent and time to hypertension diagnosis, end-stage renal disease (ESRD), and death in patients with the PKD1 genotype. 814 individuals who participated in research at the University of Colorado were studied. Kaplan-Meier survival analysis was performed. The predictor was parental sex, and outcomes were diagnosis of hypertension, progression to ESRD, and death. We also examined associations in four strata according to affected parent and participant sex, as previous studies have reported earlier onset of ESRD in males compared to females. The median follow-up for each outcome was as follows: hypertension, 30 (interquartile range (IQR): 18, 37); ESRD, 43 (IQR: 31, 52), death 39 (IQR: 25, 52) years of age. Among affected offspring in the entire cohort, there was no difference in hypertension diagnosis (p = 0.97) or progression to ESRD (p = 0.79) according to affected parent sex; however, participants with an affected mother were more likely to die than participants with an affected father (p < 0.05). In stratified analyses, males were more likely than females to develop hypertension and reach ESRD when the affected parent was the father (p < 0.01) but not when the affected parent was the mother (p ≥ 0.11). Our results are largely in contrast to the hypothesis that severity of ADPKD is worse with maternal inheritance of disease.
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  3. The TNF-α -308 polymorphism may affect the severity of Crohn's disease

    PubMed Central

    Santana, Genoile; Bendicho, Maria Teresita; Santana, Tamara Celi; dos Reis, Lidiane Bianca; Lemaire, Denise; Lyra, André Castro

    2011-01-01

    OBJECTIVE: The goal of this project was to analyze the association between Crohn's disease, its clinical features, and the tumor necrosis factor alpha (TNF-α) -308 polymorphism. METHODS: This is a case-control and cross-sectional study that enrolled 91 patients with Crohn's disease and 91 controls. Patients with Crohn's disease were characterized according to the Montreal Classification, along with their clinical and surgical treatment history. Analysis of the TNF-α -308 polymorphism was performed using a commercial kit. A stratified analysis was applied using an OR (odds ratio) with a 95% confidence interval. The chi-square and Fisher's exact tests were utilized for analysis of the association between the polymorphism and the clinical features of Crohn's disease. RESULTS: The low producer predicted phenotype was present in 76.9% of Crohn's disease cases and 75.8% of controls (OR 0.94 [0.45-1.97]). The TNF2 allele and the high producer predicted phenotype were more frequent among patients with Crohn's disease penetrating behavior (p = 0.004). The TNF2 allele and the high producer predicted phenotype were also associated with a history of colectomy (p = 0.02), and the TNF2 allele was associated with small bowel resection (p = 0.03). CONCLUSIONS: The TNF-α -308 polymorphism appears to affect the severity of the disease. However, TNF-α -308 polymorphism does not appear to be important for the susceptibility in the development of Crohn's disease. PMID:21915486

  4. Disease staging as a measure of disease severity.

    PubMed

    Kohyama, Jun; Fujitani, Shigeki; Umesato, Yoshimasa; Kataoka, Hitomi

    2015-06-24

    Disease staging, first developed in 1970, has been used to assess the levels of biological severity, defined as the risk of organ failure or death, of specific medical diseases. Because few studies to date have evaluated disease staging in Japan, a small pilot study was designed to determine whether disease staging is available and useful in actual medical practice in Japan. The relationships between disease staging and length of stay, medical costs and age were retrospectively evaluated in patients admitted to Japan Association for Development of Community Medicine - Tokyo Bay Urayasu Ichikawa Medical Center for appendicitis, type 2 diabetes mellitus, and cerebrovascular diseases from April 2012 to March 2013. Patients were easily staged based on information at the time of hospital discharge. Disease stages were found to be affected significantly by length of hospital stay and medical costs. Age also affected disease stages in patients with appendicitis. These findings indicate that disease staging was available in Japan and was affected by hospital resources, including length of hospital stay and medical costs.

  5. Two-year survival of severe chronic obstructive pulmonary disease subjects requiring invasive mechanical ventilation and the factors affecting survival.

    PubMed

    Asker, Selvi; Ozbay, Bulent; Ekin, Selami; Yildiz, Hanifi; Sertogullarindan, Bunyamin

    2016-05-01

    To investigate two-year survival rates and the factors affecting survival in patients of severe chronic obstructive pulmonary disease requiring invasive mechanical ventilation. The retrospective study was conducted at Yuzuncuy?l University, Van, Turkey, and comprised record of in-patients with moderate to severe chronic obstructive pulmonary disease who required invasive mechanical ventilation in the intensive care unit of the Pulmonary Diseases Department between January 2007 and December 2010. Correlation between survival and parameters such as age, gender, duration of illness, history of smoking, arterial blood gas values, pulmonary artery pressure, left ventricular ejection fraction, body mass index and laboratory findings were investigated. SPSS 19 was used for statistical analysis. Of the 69 severe COPD subjects available, 20 (29%) were excluded as they did not meet the inclusion criteria. Overall in-hospital mortality rate was 42% (n:29). Of the remaining 20 (29%) who comprised the study group, 14(70%) were men and 6(30%) were women. The mortality rates at the end of 3rd, 6th, 12th and 24th months were 61%, 76%, 84% and 85.5% respectively. There was no correlation between gender and survival in time point (p>0.05). The only factor that affected the rate of mortality at the end of the 3rd month was age (p<0.05). Mortality was high in subjects with advanced ages (p<0.05). Duration of illness affected the survival at the end of the six month (p<0.05). Survival rates were high in subjects with longer illness durations (p<0.05). Haematocrit level was the only factor that affected mortality rates at the end of 12th and 24th months (p<0.05). Subjects with higher haematocrit levels had higher survival rates (p<0.05). Age, duration of illness and haematocrit levels were the most important factors that affected survival in chronic obstructive pulmonary disease patients requiring mechanical ventilation.

  6. Predictors for Permanent Discontinuation of Systemic Immunosuppression in Severely Affected Chronic Graft-Versus-Host Disease Patients.

    PubMed

    Curtis, Lauren M; Pirsl, Filip; Steinberg, Seth M; Mitchell, Sandra A; Baird, Kristin; Cowen, Edward W; Mays, Jacqueline; Buxbaum, Nataliya P; Pichard, Dominique C; Im, Annie; Avila, Daniele; Taylor, Tiffani; Fowler, Daniel H; Gress, Ronald E; Pavletic, Steven Z

    2017-11-01

    Predicting the duration of systemic therapy in patients with chronic graft-versus-host disease (cGVHD) is of critical clinical importance when counseling patients and for treatment planning. cGVHD characteristics associated with this outcome have not been studied in severely affected patients. The National Institutes of Health (NIH) cGVHD scoring provides a standardized set of organ severity measures that could represent clinically useful and reproducible predictive characteristics. We analyzed 227 previously treated patients most with moderate (n = 54) or severe (n = 170) cGVHD defined by NIH criteria who were prospectively enrolled in a natural history protocol (NCT00092235). Patients received a median of 4 prior systemic therapy regimens and were seen at the NIH for a single time-point visit and were then monitored for survival and ability to discontinue cGVHD systemic therapy. With a median follow-up of 71.1 months, the cumulative incidence of systemic therapy discontinuation was 9.5% (95% confidence interval, 6.0% to 13.9%) at 2 years and 27.7% (95% confidence interval, 20.9% to 34.8%) by 5 years after the initial visit. Factors associated with a higher incidence of immunosuppression discontinuation included lower NIH global severity (P = .019) and lung (P = .030) scores and less extensive deep sclerosis (<37% body surface area, P = .024). Lower patient- and clinician-reported 0 to 10 severity NIH scores and noncyclosporine prophylaxis regimens were also associated with higher incidence of immunosuppression discontinuation (P <.05). In conclusion, we found low success rates for immune suppression discontinuation in previously treated patients who were severely affected with cGVHD. NIH scoring and clinical measures provide new standardized disease-specific tools to predict discontinuation of systemic therapy. Published by Elsevier Inc.

  7. Fatigue and multidimensional disease severity in chronic obstructive pulmonary disease.

    PubMed

    Inal-Ince, Deniz; Savci, Sema; Saglam, Melda; Calik, Ebru; Arikan, Hulya; Bosnak-Guclu, Meral; Vardar-Yagli, Naciye; Coplu, Lutfi

    2010-06-30

    Fatigue is associated with longitudinal ratings of health in patients with chronic obstructive pulmonary disease (COPD). Although the degree of airflow obstruction is often used to grade disease severity in patients with COPD, multidimensional grading systems have recently been developed. The aim of this study was to investigate the relationship between perceived and actual fatigue level and multidimensional disease severity in patients with COPD. Twenty-two patients with COPD (aged 52-74 years) took part in the study. Multidimensional disease severity was measured using the SAFE and BODE indices. Perceived fatigue was assessed using the Fatigue Severity Scale (FSS) and the Fatigue Impact Scale (FIS). Peripheral muscle endurance was evaluated using the number of sit-ups, squats, and modified push-ups that each patient could do. Thirteen patients (59%) had severe fatigue, and their St George's Respiratory Questionnaire scores were significantly higher (p < 0.05). The SAFE index score was significantly correlated with the number of sit-ups, number of squats, FSS score and FIS score (p < 0.05). The BODE index was significantly associated with the numbers of sit-ups, squats and modified push-ups, and with the FSS and FIS scores (p < 0.05). Peripheral muscle endurance and fatigue perception in patients with COPD was related to multidimensional disease severity measured with both the SAFE and BODE indices. Improvements in perceived and actual fatigue levels may positively affect multidimensional disease severity and health status in COPD patients. Further research is needed to investigate the effects of fatigue perception and exercise training on patients with different stages of multidimensional COPD severity.

  8. Serum Vitamin A Levels May Affect the Severity of Ocular Graft-versus-Host Disease.

    PubMed

    Tong, Jiefeng; Hu, Renjian; Zhao, Yingying; Xu, Yang; Zhao, Xiaoying; Jin, Xiuming

    2017-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established therapeutic option for a range of inherited and acquired hematological disorders. However, graft-versus-host disease (GVHD) remains the leading cause of non-relapse mortality in allogeneic HSCT recipients. Ocular involvement occurs in up to 80% of chronic GVHD patients. In our cases, the diagnosis of vitamin A deficiency was suspected for GVHD patients. Serum vitamin A measurements were conducted to confirm clinical suspicions. Our study revealed significant decrease in serum levels of vitamin A in chronic liver GVHD patients. Although there have been many studies evaluating ocular manifestations in patients with GVHD, the present study is, to our knowledge, the first to study the relationship between vitamin A and ocular manifestations of GVHD in humans. Our data suggest that vitamin A deficiency affects the severity of ocular GVHD in adults.

  9. Growth hormone and insulin-like growth factor 1 affect the severity of Graves' disease.

    PubMed

    Di Cerbo, Alfredo; Pezzuto, Federica; Di Cerbo, Alessandro

    2017-01-01

    Graves' disease, the most common form of hyperthyroidism in iodine-replete countries, is associated with the presence of immunoglobulins G (IgGs) that are responsible for thyroid growth and hyperfunction. In this article, we report the unusual case of a patient with acromegaly and a severe form of Graves' disease. Here, we address the issue concerning the role of growth hormone (GH) and insulin-like growth factor 1 (IGF1) in influencing thyroid function. Severity of Graves' disease is exacerbated by coexistent acromegaly and both activity indexes and symptoms and signs of Graves' disease improve after the surgical remission of acromegaly. We also discuss by which signaling pathways GH and IGF1 may play an integrating role in regulating the function of the immune system in Graves' disease and synergize the stimulatory activity of Graves' IgGs. Clinical observations have demonstrated an increased prevalence of euthyroid and hyperthyroid goiters in patients with acromegaly.The coexistence of acromegaly and Graves' disease is a very unusual event, the prevalence being <1%.Previous in vitro studies have showed that IGF1 synergizes the TSH-induced thyroid cell growth-activating pathways independent of TSH/cAMP/PKA cascade.We report the first case of a severe form of Graves' disease associated with acromegaly and show that surgical remission of acromegaly leads to a better control of symptoms of Graves' disease.

  10. Growth hormone and insulin-like growth factor 1 affect the severity of Graves’ disease

    PubMed Central

    Pezzuto, Federica; Di Cerbo, Alessandro

    2017-01-01

    Graves’ disease, the most common form of hyperthyroidism in iodine-replete countries, is associated with the presence of immunoglobulins G (IgGs) that are responsible for thyroid growth and hyperfunction. In this article, we report the unusual case of a patient with acromegaly and a severe form of Graves’ disease. Here, we address the issue concerning the role of growth hormone (GH) and insulin-like growth factor 1 (IGF1) in influencing thyroid function. Severity of Graves’ disease is exacerbated by coexistent acromegaly and both activity indexes and symptoms and signs of Graves’ disease improve after the surgical remission of acromegaly. We also discuss by which signaling pathways GH and IGF1 may play an integrating role in regulating the function of the immune system in Graves’ disease and synergize the stimulatory activity of Graves’ IgGs. Learning points: Clinical observations have demonstrated an increased prevalence of euthyroid and hyperthyroid goiters in patients with acromegaly. The coexistence of acromegaly and Graves’ disease is a very unusual event, the prevalence being <1%. Previous in vitro studies have showed that IGF1 synergizes the TSH-induced thyroid cell growth-activating pathways independent of TSH/cAMP/PKA cascade. We report the first case of a severe form of Graves’ disease associated with acromegaly and show that surgical remission of acromegaly leads to a better control of symptoms of Graves’ disease. PMID:28620496

  11. Interacting disturbances: Wildfire severity affected by stage of forest disease invasion

    Treesearch

    Margaret Metz; Kerri Frangioso; Ross Meentemeyer; David Rizzo

    2010-01-01

    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 pre-fire fuels from host species in a forest monitoring plot network...

  12. 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 ε max) 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).more » A biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, ε max, was significantly (p≤0.032) associated with increasing severity of liver disease (ε max[s.e.]=0.86[0.05], ε max=0.69[0.06] and ε max=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log 10IU/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

  13. Disease severity and treatment requirements in familial inflammatory bowel disease.

    PubMed

    Ballester, María Pilar; Martí, David; Tosca, Joan; Bosca-Watts, Marta Maia; Sanahuja, Ana; Navarro, Pablo; Pascual, Isabel; Antón, Rosario; Mora, Francisco; Mínguez, Miguel

    2017-08-01

    Several studies demonstrate an increased prevalence and concordance of inflammatory bowel disease among the relatives of patients. Other studies suggest that genetic influence is over-estimated. The aims of this study are to evaluate the phenotypic expression and the treatment requirements in familial inflammatory bowel disease, to study the relationship between number of relatives and degree of kinship with disease severity and to quantify the impact of family aggregation compared to other environmental factors. Observational analytical study of 1211 patients followed in our unit. We analyzed, according to the existence of familial association, number and degree of consanguinity, the phenotypic expression, complications, extraintestinal manifestations, treatment requirements, and mortality. A multivariable analysis considering smoking habits and non-steroidal-anti-inflammatory drugs was performed. 14.2% of patients had relatives affected. Median age at diagnosis tended to be lower in the familial group, 32 vs 29, p = 0.07. In familial ulcerative colitis, there was a higher proportion of extraintestinal manifestations: peripheral arthropathy (OR = 2.3, p = 0.015) and erythema nodosum (OR = 7.6, p = 0.001). In familial Crohn's disease, there were higher treatment requirements: immunomodulators (OR = 1.8, p = 0.029); biologics (OR = 1.9, p = 0.011); and surgery (OR = 1.7, p = 0.044). The abdominal abscess increased with the number of relatives affected: 5.1% (sporadic), 7.0% (one), and 14.3% (two or more), p=0.039. These associations were maintained in the multivariate analysis. Familial aggregation is considered a risk factor for more aggressive disease and higher treatment requirements, a tendency for earlier onset, more abdominal abscess, and extraintestinal manifestations, remaining a risk factor analyzing the influence of some environmental factors.

  14. Association of psychosis, affective disorders and diseases affecting the immune system.

    PubMed

    Larsen, Jeanette Brun; Iversen, Valentina Cabral; Reitan, Solveig Klæbo

    2018-02-01

    Purpose of the article: There are indications of altered immune activity in depressed and psychotic patients compared to healthy controls in several studies. To explore the clinical importance of this phenomenon we examined the relation between different disorders affecting the immune system and psychoses and depression, respectively. A total of 276 patients consecutively admitted to a psychiatric acute ward were included in the study. Of these 41 patients fulfilled the criteria for ICD-10 F20-29 (psychotic) diagnosis and 157 patients a F30-39 (affective) diagnosis. Information on diseases affecting the immune system in patients themselves and family members of the patients were obtained by a self-report questionnaire. Comparing the two groups showed a significant correlation between the F20-29 group and eczema (r = -0.116, p = .037). Comparing what patients reported for family members showed a significantly higher frequency of epilepsy (p = .033) in the F20-29 group. Summarizing all immunological diseases for family members showed a significantly higher frequency in the F30-39 group compared to the F20-29 group (χ 2  = 4, 82, df = 1, p = .028). There may be differences between the F20-29 and F30-39 groups and their family members regarding risk for diseases affecting the immune system. This is in line with different activity of the immune system measured in blood for the disorders and may add information regarding etiology and pathology of these psychiatric diseases. Further studies including a greater number of subjects, as well as confirmation of the immunological diseases through blood samples are needed.

  15. Vision-Threatening Behcet's Disease: Severity of Ocular Involvement Predictors

    PubMed Central

    Hussein, Mohammed A.; Dahab, Ahmed A.

    2018-01-01

    Purpose To examine and spot systemic findings commonly associated with a serious form of ocular Behcet's disease. This could potentially help ophthalmologists categorize their patients based on future risk and plan treatment accordingly. Subjects and Methods The data of 249 patients with Behcet's disease were examined thoroughly. Correlations between systemic and ocular findings were recorded. Patients were further subgrouped by the authors as having a vision-threatening form of the disease or not. Regression analysis was done to spot predictors for a vision-threatening form of the disease. Results The presence of systemic vasculitis and oral and genital ulcers in a patient with Behcet's disease was found to be associated with a milder form of ocular affection or none at all and vice versa. Certain correlations between findings were also found. Conclusion Certain findings in Behcet's disease may act as predictors for the severity of ocular affection. Directing our attention to these factors by the internist and ophthalmologist can help plan the frequency of follow-up as well as the aggressiveness of treatment in patients with Behcet's disease. PMID:29854430

  16. Prevalence of coeliac disease in Italian patients affected by Addison's disease.

    PubMed

    Biagi, Federico; Campanella, Jonia; Soriani, Alessandra; Vailati, Alberto; Corazza, Gino R

    2006-03-01

    It is well known that coeliac disease is associated with autoimmune endocrine diseases, such as autoimmune thyroid disease and insulin-dependent diabetes mellitus. Recently, coeliac disease has been shown in approximately 10% of patients with autoimmune Addison's disease. Addison's disease is the most common cause of primary adrenocortical insufficiency and it shares several clinical features with coeliac disease. Although hyperpigmentation and hypotension are the most specific signs, gastrointestinal symptoms are common and can be the first complaints of the patients. The aim of our study was to investigate the prevalence of coeliac disease in Italian patients with Addison's disease. Seventeen consecutive patients affected by Addison's disease (14 F, mean age 53.9 years, range 26-79 years) were enrolled in the study. Eleven of them were affected by Addison's disease associated with autoimmune thyroid disease and/or insulin-dependent diabetes mellitus; the other 6 patients were suffering from isolated Addison's disease. Diagnosis had been performed at the age of 40.5 years (range 23-55). Steroid treatment had already been started in 16 of the patients. Endomysial antibodies were tested in all of them and a duodenal biopsy was taken in those found to be positive for antiendomysial antibody (EMA). One out of 17 patients was found to be EMA positive. Duodenal biopsy confirmed the diagnosis of coeliac disease by showing subtotal villous atrophy. Although we studied only a small sample, our preliminary results confirmed that Addison's disease is associated with coeliac disease, being present in 5.9% of patients with Addison's disease. Since the symptoms can be similar and treatment of Addison's disease can mask coeliac disease, this association should always be actively investigated.

  17. Sever's Disease

    MedlinePlus

    ... immobilize the foot so that it can heal. Recovery and Recurrence One of the most important things ... The sooner Sever's disease is addressed, the quicker recovery is. Most kids can return to physical activity ...

  18. A discussion on disease severity index values: using the disease severity index for null hypothesis testing

    USDA-ARS?s Scientific Manuscript database

    A disease severity index (DSI) is a single number for summarizing a large amount of information on disease severity. It has been used to indicate the performance of a cultivar in regard to disease resistance at a particular location, to relate disease severity to yield loss, to determine the effecti...

  19. Severe aplastic anaemia and Grave's disease in a paediatric patient.

    PubMed

    Kumar, Manjusha; Goldman, Jeffrey

    2002-07-01

    Severe aplastic anaemia (SAA) is considered to be an autoimmune disorder affecting the haematopoietic cells and most often is idiopathic. An association between SAA and other autoimmune diseases is rare and has been described in adults for eosinophilic fasciitis, thymomas, systemic lupus erythematosus and thyroid disorders. We describe the first paediatric patient with chronic relapsing SAA and Grave's disease. We discuss the difficulty in diagnosis of Grave's disease, the possibility of its manifestation due to withdrawal of immunosuppressants, and issues to consider in the treatment of this disease in the setting of bone marrow failure.

  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. Severe rectal bleeding following PPH-stapler procedure for haemorroidal disease

    PubMed Central

    AMMENDOLA, M.; SAMMARCO, G.; CARPINO, A.; FERRARI, F.; VESCIO, G.; SACCO, R.

    2014-01-01

    PPH-stapler procedure for treatment of haemorrhoidal prolapse classified P4E4 is an important improvement, but may be followed by severe postoperative complications of which haemorrhage is one of the most serious early events. We report a case of double severe rectal bleeding following PPH-stapler procedure for haemorrhoidal disease classified P4E4 according to PATE 2000 (circumferential prolapse). A 48 years old female patient was presented to our attention. She was affected by haemorrhoidal prolapse P4E4, constipation and rectal bleeding. PPH-procedure is a technique for management of the haemorrhoidal disease. Postoperative complications may be serious and haemorrhage is the most important early complication. PMID:25644731

  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. Human rhinovirus and disease severity in children.

    PubMed

    Costa, Lourenço Faria; Queiróz, Divina Aparecida Oliveira; Lopes da Silveira, Hélio; Bernardino Neto, Morun; de Paula, Nayhanne Tizzo; Oliveira, Thelma Fátima Mattos Silva; Tolardo, Aline Lavado; Yokosawa, Jonny

    2014-02-01

    To evaluate retrospectively human rhinovirus (HRV) infections in children up to 5 years old and factors involved in disease severity. Nasopharyngeal aspirates from 434 children presenting a broad range of respiratory infection symptoms and severity degrees were tested for presence of HRV and 8 other respiratory viruses. Presence of host risk factors was also assessed. HRV was detected in 181 (41.7%) samples, in 107 of them as the only agent and in 74 as coinfections, mostly with respiratory syncytial virus (RSV; 43.2%). Moderate to severe symptoms were observed in 28.9% (31/107) single infections and in 51.3% (38/74) coinfections (P = .004). Multivariate analyses showed association of coinfections with lower respiratory tract symptoms and some parameters of disease severity, such as hospitalization. In coinfections, RSV was the most important virus associated with severe disease. Prematurity, cardiomyopathies, and noninfectious respiratory diseases were comorbidities that also were associated with disease severity (P = .007). Our study showed that HRV was a common pathogen of respiratory disease in children and was also involved in severe cases, causing symptoms of the lower respiratory tract. Severe disease in HRV infections were caused mainly by presence of RSV in coinfections, prematurity, congenital heart disease, and noninfectious respiratory disease.

  4. Pumpkin powdery mildew disease severity influences the fungal diversity of the phyllosphere.

    PubMed

    Zhang, Zhuo; Luo, Luyun; Tan, Xinqiu; Kong, Xiao; Yang, Jianguo; Wang, Duanhua; Zhang, Deyong; Jin, Decai; Liu, Yong

    2018-01-01

    Phyllosphere microbiota play a crucial role in plant-environment interactions and their microbial community and function are influenced by biotic and abiotic factors. However, there is little research on how pathogens affect the microbial community of phyllosphere fungi. In this study, we collected 16 pumpkin ( Cucurbita moschata ) leaf samples which exhibited powdery mildew disease, with a severity ranging from L1 (least severe) to L4 (most severe). The fungal community structure and diversity was examined by Illumina MiSeq sequencing of the internal transcribed spacer (ITS) region of ribosomal RNA genes. The results showed that the fungal communities were dominated by members of the Basidiomycota and Ascomycota. The Podosphaera was the most dominant genus on these infected leaves, which was the key pathogen responsible for the pumpkin powdery mildew. The abundance of Ascomycota and Podosphaera increased as disease severity increased from L1 to L4, and was significantly higher at disease severity L4 ( P < 0.05). The richness and diversity of the fungal community increased from L1 to L2, and then declined from L2 to L4, likely due to the biotic pressure (i.e., symbiotic and competitive stresses among microbial species) at disease severity L4. Our results could give new perspectives on the changes of the leaf microbiome at different pumpkin powdery mildew disease severity.

  5. Association between chronic azotemic kidney disease and the severity of periodontal disease in dogs.

    PubMed

    Glickman, Lawrence T; Glickman, Nita W; Moore, George E; Lund, Elizabeth M; Lantz, Gary C; Pressler, Barrak M

    2011-05-01

    Naturally occurring periodontal disease affects >75% of dogs and has been associated with cardiac lesions and presumptive endocarditis. However, the relationships between periodontal disease and chronic kidney disease (CKD) in dogs have not been studied. In a retrospective longitudinal study the incidence of azotemic CKD was compared between a cohort of 164,706 dogs with periodontal disease and a cohort of age-matched dogs with no periodontal disease from a national primary care practice. These dogs contributed 415,971 dog-years of follow-up from 2002 to 2008. Hazard ratios and 95% confidence intervals from Cox regression were used to compare the incidence of azotemic CKD in dogs with stage 1, 2, or 3/4 periodontal disease to dogs with no periodontal disease. The hazard ratio for azotemic CKD increased with increasing severity of periodontal disease (stage 1 hazard ratio=1.8, 95% confidence interval: 1.6, 2.1; stage 2 hazard ratio=2.0, 95% confidence interval: 1.7, 2.3; stage 3/4 hazard ratio=2.7, 95% confidence interval: 2.3, 3.0; P(trend)=<0.0001) after adjustment for age, gender, neuter status, breed, body weight, number of hospital visits, and dental procedures. Increasing severity of periodontal disease was also associated with serum creatinine >1.4 mg/dl and blood urea nitrogen >36 mg/dl, independent of a veterinarian's clinical diagnosis of CKD. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Birth month affects lifetime disease risk: a phenome-wide method.

    PubMed

    Boland, Mary Regina; Shahn, Zachary; Madigan, David; Hripcsak, George; Tatonetti, Nicholas P

    2015-09-01

    An individual's birth month has a significant impact on the diseases they develop during their lifetime. Previous studies reveal relationships between birth month and several diseases including atherothrombosis, asthma, attention deficit hyperactivity disorder, and myopia, leaving most diseases completely unexplored. This retrospective population study systematically explores the relationship between seasonal affects at birth and lifetime disease risk for 1688 conditions. We developed a hypothesis-free method that minimizes publication and disease selection biases by systematically investigating disease-birth month patterns across all conditions. Our dataset includes 1 749 400 individuals with records at New York-Presbyterian/Columbia University Medical Center born between 1900 and 2000 inclusive. We modeled associations between birth month and 1688 diseases using logistic regression. Significance was tested using a chi-squared test with multiplicity correction. We found 55 diseases that were significantly dependent on birth month. Of these 19 were previously reported in the literature (P < .001), 20 were for conditions with close relationships to those reported, and 16 were previously unreported. We found distinct incidence patterns across disease categories. Lifetime disease risk is affected by birth month. Seasonally dependent early developmental mechanisms may play a role in increasing lifetime risk of disease. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.

  7. Birth month affects lifetime disease risk: a phenome-wide method

    PubMed Central

    Boland, Mary Regina; Shahn, Zachary; Madigan, David; Hripcsak, George; Tatonetti, Nicholas P

    2015-01-01

    Objective An individual’s birth month has a significant impact on the diseases they develop during their lifetime. Previous studies reveal relationships between birth month and several diseases including atherothrombosis, asthma, attention deficit hyperactivity disorder, and myopia, leaving most diseases completely unexplored. This retrospective population study systematically explores the relationship between seasonal affects at birth and lifetime disease risk for 1688 conditions. Methods We developed a hypothesis-free method that minimizes publication and disease selection biases by systematically investigating disease-birth month patterns across all conditions. Our dataset includes 1 749 400 individuals with records at New York-Presbyterian/Columbia University Medical Center born between 1900 and 2000 inclusive. We modeled associations between birth month and 1688 diseases using logistic regression. Significance was tested using a chi-squared test with multiplicity correction. Results We found 55 diseases that were significantly dependent on birth month. Of these 19 were previously reported in the literature (P < .001), 20 were for conditions with close relationships to those reported, and 16 were previously unreported. We found distinct incidence patterns across disease categories. Conclusions Lifetime disease risk is affected by birth month. Seasonally dependent early developmental mechanisms may play a role in increasing lifetime risk of disease. PMID:26041386

  8. [Advance care planning and severe chronic diseases].

    PubMed

    Diestre Ortín, Germán; González Sequero, Vanessa; Collell Domènech, Núria; Pérez López, Francisca; Hernando Robles, Pablo

    2013-01-01

    Advanced care planning (ACP) helps in make decisions on the health problems of people who have lost the capacity for informed consent. It has proven particularly useful in addressing the end of life. The aim of this study was to determine the prevalence of ACP in patients with severe chronic diseases. Review of medical records of patients with dementia, amyotrophic lateral sclerosis, Parkinson's disease, chronic obstructive pulmonary disease or interstitial lung disease, heart failure, chronic kidney disease on dialysis and cancer, all in advanced stages. We collected data on living wills or registered prior decisions by the physician according to clinical planned. A total of 135 patients were studied. There was a record of ACP in 22 patients (16.3%). In most of them it was planned not to start any vital treatment in the event of high risk of imminent death and lacking the ability to make decisions. Only two patients were had a legal living will. The registration of ACP is relatively low, and this can affect decision-making in accordance with the personal values of patients when they do not have the capacity to exercise informed consent. Copyright © 2012 SEGG. Published by Elsevier Espana. All rights reserved.

  9. A molecular insight into papaya leaf curl-a severe viral disease.

    PubMed

    Varun, Priyanka; Ranade, S A; Saxena, Sangeeta

    2017-11-01

    Papaya leaf curl disease (PaLCuD) caused by papaya leaf curl virus (PaLCuV) not only affects yield but also plant growth and fruit size and quality of papaya and is one of the most damaging and economically important disease. Management of PaLCuV is a challenging task due to diversity of viral strains, the alternate hosts, and the genomic complexities of the viruses. Several management strategies currently used by plant virologists to broadly control or eliminate the viruses have been discussed. In the absence of such strategies in the case of PaLCuV at present, the few available options to control the disease include methods like removal of affected plants from the field, insecticide treatments against the insect vector (Bemisia tabaci), and gene-specific control through transgenic constructs. This review presents the current understanding of papaya leaf curl disease, genomic components including satellite DNA associated with the virus, wide host and vector range, and management of the disease and suggests possible generic resistance strategies.

  10. 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.

  11. Disease Severity and Domain Specific Arthritis Self-Efficacy: Relationships to Pain and Functioning in Rheumatoid Arthritis Patients

    PubMed Central

    Somers, Tamara J.; Shelby, Rebecca A.; Keefe, Francis J.; Godiwala, Neha; Lumley, Mark A.; Mosley-Williams, Angelia; Rice, John R.; Caldwell, David

    2010-01-01

    Objective Examining the degree to which disease severity and domains of self-efficacy (pain, function, other symptoms) explain pain and functioning in rheumatoid arthritis patients. Methods Patients (N=263) completed the Arthritis Impact Measurements Scales-2 to assess pain and functioning (physical, affective, and social), the Arthritis Self-Efficacy Scale to assess three self-efficacy domains (pain, physical function, other); disease severity was assessed with C-reactive protein, physician's rating, abnormal joint count. Structural equation modeling was used to examine hypotheses: 1) does disease severity have a direct relationship with pain and each area of functioning, 2) does disease severity have a direct relationship with each arthritis self-efficacy domain, and 3) do the self-efficacy domains mediate the relationship between disease severity and RA pain and each area of functioning. Results Disease severity was related to pain, physical functioning, and each self-efficacy domain (β's=.28-.56; p's<.001). Each self-efficacy domain was related to its respective domain of functioning (e.g., self-efficacy for pain was related to pain) (β's=.36-.54; p's<.001). Self-efficacy mediated the relationship between disease severity and pain and functioning (β's=.12-.19; p's<.001). Self-efficacy for pain control and to perform functional tasks accounted for 32-42% of disease severity's total effect on their respective outcomes (e.g., self-efficacy for pain control accounted for 32% of disease severity's total effect on pain). Variance accounted for by the total model was 52% for pain, 53% for physical functioning, and 44% for affective and social functioning. Conclusions Disease severity and self-efficacy both impact RA functioning and intervening in these areas may lead to better outcomes. PMID:20535796

  12. Revised Tubiana’s Staging System for Assessment of Disease Severity in Dupuytren’s Disease—Preliminary Clinical Findings

    PubMed Central

    Hindocha, Sandip; Stanley, John K.; Watson, James Stewart

    2007-01-01

    There are few objective staging systems to assess severity of Dupuytren’s disease (DD). Previous methods to assess severity of DD were based primarily on the degree of contracture of an affected digit measured using a goniometer. Nonetheless, this method of assessment alone may be incomplete, and other factors should be considered. White (n = 92) patients diagnosed with DD from northwest of England were assessed for DD. Objective criteria for evaluating severity incorporated quantified variables. The revised severity stage was correlated to a known staging system of DD (Tubiana’s staging system) which measures total flexion deformity for a single affected digit. Total revised severity staging scores ranged between 4 and 53 (mean = 18.7) and revealed significant positive correlation to Tubiana’s original staging system (r2 = 0.8, p < 0.001). There was significant difference between severity staging scores in those with a positive family history compared to those without (p < 0.01). In current practice, often, the degree of contracture in an affected digit is used solely as a measure of disease severity. Additional objective clinical information may provide useful prognostic indices for disease progression as well as postoperative outcome. PMID:18780081

  13. Therapeutic Decision-Making for Elderly Patients With Symptomatic Severe Valvular Heart Diseases.

    PubMed

    Hu, Kui; Wan, Yun; Hong, Tao; Lu, Shu Yang; Guo, Chang Fa; Li, Jun; Wang, Chun Sheng

    2016-07-27

    The aim of this study was to determine how older age and co-morbidities affect the treatment decision-making and long-term survival in elderly patients with symptomatic severe valvular heart diseases.A total of 181 elderly patients (mean age, 78.4 ± 3.4 years) hospitalized between January 2003 and June 2012 with symptomatic severe valvular heart diseases were enrolled. Cardiac and geriatric factors associated with treatment decision-making were analyzed. Survival outcomes were investigated.Surgical treatment was performed in 116 (64%) patients (surgical group) and 65 patients (36%) were treated conservatively (conservative group). The most common [62% (40/65)] reason for refusing surgical treatment was high operative risk as assessed by the physicians who initially cared for the patients. Multivariate logistic regression analysis identified female gender, chronic renal insufficiency, older age, pneumonia, and emergent status as independent predictors of the conservative treatment. Patients with isolated aortic valve disease tended to undergo an operation. Overall 5-year survival in the surgical group was 76.8% versus 42.9% in the conservative group (P < 0.0001). After matching using the propensity score, the surgical group still had a better long-term survival than the conservative group (P = 0.001). Cox regression analysis revealed conservative treatment as the single risk factor associated with poor long-term survival in all series.Approximately 40% of the elderly patients with symptomatic severe heart valve disease were treated conservatively despite a definite indication for surgical intervention. Cardiac and geriatric co-morbidities profoundly affect the treatment decision-making. Interdisciplinary discussion should be encouraged to optimize therapeutic options for elderly patients with valvular heart disease.

  14. Assessing the Impact of Analytical Error on Perceived Disease Severity.

    PubMed

    Kroll, Martin H; Garber, Carl C; Bi, Caixia; Suffin, Stephen C

    2015-10-01

    The perception of the severity of disease from laboratory results assumes that the results are free of analytical error; however, analytical error creates a spread of results into a band and thus a range of perceived disease severity. To assess the impact of analytical errors by calculating the change in perceived disease severity, represented by the hazard ratio, using non-high-density lipoprotein (nonHDL) cholesterol as an example. We transformed nonHDL values into ranges using the assumed total allowable errors for total cholesterol (9%) and high-density lipoprotein cholesterol (13%). Using a previously determined relationship between the hazard ratio and nonHDL, we calculated a range of hazard ratios for specified nonHDL concentrations affected by analytical error. Analytical error, within allowable limits, created a band of values of nonHDL, with a width spanning 30 to 70 mg/dL (0.78-1.81 mmol/L), depending on the cholesterol and high-density lipoprotein cholesterol concentrations. Hazard ratios ranged from 1.0 to 2.9, a 16% to 50% error. Increased bias widens this range and decreased bias narrows it. Error-transformed results produce a spread of values that straddle the various cutoffs for nonHDL. The range of the hazard ratio obscures the meaning of results, because the spread of ratios at different cutoffs overlap. The magnitude of the perceived hazard ratio error exceeds that for the allowable analytical error, and significantly impacts the perceived cardiovascular disease risk. Evaluating the error in the perceived severity (eg, hazard ratio) provides a new way to assess the impact of analytical error.

  15. Quantitative EEG reflects non-dopaminergic disease severity in Parkinson's disease.

    PubMed

    Geraedts, Victor J; Marinus, Johan; Gouw, Alida A; Mosch, Arne; Stam, Cornelis J; van Hilten, Jacobus J; Contarino, Maria Fiorella; Tannemaat, Martijn R

    2018-05-29

    In Parkinson's Disease (PD), measures of non-dopaminergic systems involvement may reflect disease severity and therefore contribute to patient-selection for Deep Brain Stimulation (DBS). There is currently no determinant for non-dopaminergic disease severity. In this exploratory study, we investigated whether quantitative EEG reflects non-dopaminergic disease severity in PD. Sixty-three consecutive PD patients screened for DBS were included (mean age 62.4 ± 7.2 years, 32% females). Relative spectral powers and the Phase-Lag-Index (PLI) reflecting functional connectivity were analysed on routine EEGs. Non-dopaminergic disease severity was quantified using the SENS-PD score and its subdomains; motor-severity was quantified using the MDS-UPDRS III. The SENS-PD composite score correlated with a spectral ratio ((δ + θ)/(α1 + α2 + β) powers) (global spectral ratio Pearson's r = 0.4, 95% Confidence Interval (95%CI) 0.1-0.6), and PLI in the α2 band (10-13 Hz) (r = -0.3, 95%CI -0.5 to -0.1). These correlations seem driven by the subdomains cognition and psychotic symptoms. MDS-UPDRS III was not significantly correlated with EEG parameters. EEG slowing and reduced functional connectivity in the α2 band were associated with non-dopaminergic disease severity in PD. The described EEG parameters may have complementary utility as determinants of non-dopaminergic involvement in PD. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  16. Hemagglutination and graft-versus-host disease in the severe combined immunodeficiency mouse lymphoproliferative disease model.

    PubMed Central

    Pirruccello, S. J.; Nakamine, H.; Beisel, K. W.; Kleveland, K. L.; Okano, M.; Taguchi, Y.; Davis, J. R.; Mahloch, M. L.; Purtilo, D. T.

    1992-01-01

    In the course of evaluating the severe combined immunodeficiency mouse-human peripheral blood lymphocyte (SCID-PBL) model of lymphoproliferative disease, we noted hemagglutination occurring in peripheral blood smears of mice with serum human immunoglobulin levels greater than 1.0 mg/ml. The hemagglutinating process was mediated by human anti-mouse red cell antibodies of the IgM class, peaked at five to seven weeks post-transfer of 5 to 7 x 10(7) human PBL and was generally self limiting. However, death resulted in some mice when serum immunoglobulin levels were greater than 3.0 mg/ml. The most severely affected mice had hemagglutination induced congestion of liver, lungs and spleen. Several mice also had lesions consistent with graft-versus-host disease (GVHD) including focal hepatic necrosis and destruction of mouse splenic hematopoietic elements. The lesions associated with hemagglutination and GVHD in SCID-PBL mice are distinct from those associated with EBV-induced lymphoproliferation. Recognition of these pathologic processes are required for a thorough understanding of the SCID-PBL model. Images Figure 1 Figure 3 Figure 4 PMID:1580330

  17. Disease severity in familial cases of IBD.

    PubMed

    Andreu, M; Márquez, L; Domènech, E; Gisbert, J P; García, V; Marín-Jiménez, I; Peñalva, M; Gomollón, F; Calvet, X; Merino, O; Garcia-Planella, E; Vázquez-Romero, N; Esteve, M; Nos, P; Gutiérrez, A; Vera, I; Cabriada, J L; Martín, M D; Cañas-Ventura, A; Panés, J

    2014-03-01

    Phenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence. To know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases. 5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case. In UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25-44] vs 37 years [IQR 27-49]; p<0.0001); (CD: 27 years [IQR 21-35] vs 29 years [IQR 22-40]; p<0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p=0.04); (CD: 30.1% vs 23.6%; p<0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p=0.0001), penetrating behavior (21% vs 17.6%; p=0.01) and perianal disease (32% vs 27.1%; p=0.003). Differences are not influenced by degree of consanguinity. When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course. © 2013.

  18. 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

  19. 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.

  20. 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

  1. Warming and fertilization alter the dilution effect of host diversity on disease severity.

    PubMed

    Liu, Xiang; Lyu, Shengman; Zhou, Shurong; Bradshaw, Corey J A

    2016-07-01

    An essential ecosystem service is the dilution effect of biodiversity on disease severity, yet we do not fully understand how this relationship might change with continued climate warming and ecosystem degradation. We designed removal experiments in natural assemblages of Tibetan alpine meadow vegetation by manipulating plot-level plant diversity to investigate the relationship between different plant biodiversity indices and foliar fungal pathogen infection, and how artificial fertilization and warming affect this relationship. Although pathogen group diversity increased with host species richness, disease severity decreased as host diversity rose (dilution effect). The dilution effect of phylogenetic diversity on disease held across different levels of host species richness (and equal abundances), meaning that the effect arises mainly in association with enhanced diversity itself rather than from shifting abundances. However, the dilution effect was weakened by fertilization. Among indices, phylogenetic diversity was the most parsimonious predictor of infection severity. Experimental warming and fertilization shifted species richness to the most supported predictor. Compared to planting experiments where artificial communities are constructed from scratch, our removal experiment in natural communities more realistically demonstrate that increasing perturbation adjusts natural community resistance to disease severity. © 2016 by the Ecological Society of America.

  2. Macroalgae Has No Effect on the Severity and Dynamics of Caribbean Yellow Band Disease

    PubMed Central

    Vu, Ivana; Smelick, Gillian; Harris, Sam; Lee, Sarah C.; Weil, Ernesto; Whitehead, Robert F.; Bruno, John F.

    2009-01-01

    By removing herbivores and promoting increases in macroalgae, overfishing is thought to indirectly cause coral disease and mortality. We performed three field manipulations to test the general hypothesis that overfishing and the subsequent alteration of coral reef trophic dynamics are a cause of coral epizootics. Specifically, we asked whether the presence of macroalgae can influence within- and among-colony spread rates of Caribbean Yellow Band Disease in Montastraea faveolata. Macroalgae were placed next to infected and healthy, adult and small coral colonies to measure effects on disease spread rate, coral growth and coral survival. Surprisingly, the addition of macroalgae did not affect disease severity or coral fitness. Our results indicate that macroalgae have no effect on the severity and dynamics of Caribbean Yellow Band Disease and that fisheries management alone will not mitigate the effects of this important epizootic. PMID:19223986

  3. Norrie disease and exudative vitreoretinopathy in families with affected female carriers.

    PubMed

    Shastry, B S; Hiraoka, M; Trese, D C; Trese, M T

    1999-01-01

    Norrie disease (ND) is a rare X-linked recessive disorder characterized by congenital blindness, which is often associated with sensorineural hearing loss and mental retardation. X-linked familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by an abnormality of the peripheral retina and is not associated with systemic diseases. X-linked recessive disorders generally do not affect females. Here we show that female carriers can be associated with manifestation of an X-linked disorder. A four-generation family with an affected female, and a history of congenital blindness and hearing loss, was identified through the pro-band. A second family, with a full-term female infant, was evaluated through ophthalmic examinations and found to exhibit ocular features, such as retinal folds, retinal detachment and peripheral exudates. Peripheral blood specimens were collected from several affected and unaffected family members. DNA was extracted and analyzed by single-strand conformation polymorphism (SSCP) following polymerase chain reaction (PCR) amplification of the exons of the Norrie disease gene. The amplified products were sequenced by the dideoxy chain termination method. In an X-linked four-generation family, a novel missense (A118D) mutation in the third exon of the Norrie disease gene, was identified. The mutation was transmitted through three generations and cosegregated with the disease. The affected maternal grandmother and the unaffected mother carried the same mutation in one of their alleles. In an unrelated sporadic family, a heterozygous missense mutation (C96Y) was identified in the third exon of the Norrie disease gene in an affected individual. Analysis of exon-1 and 2 of the Norrie disease gene did not reveal any additional sequence alterations in these families. The mutations were not detected in the unaffected family members and the 116 normal unrelated controls, suggesting that they are likely to be the pathogenic mutations

  4. Plantar pressures in children with and without sever's disease.

    PubMed

    Becerro de Bengoa Vallejo, Ricardo; Losa Iglesias, Marta Elena; Rodríguez Sanz, David; Prados Frutos, Juan Carlos; Salvadores Fuentes, Paloma; Chicharro, José López

    2011-01-01

    a case-control study was conducted to compare static plantar pressures and distribution of body weight across the two lower limbs, as well as the prevalence of gastrocnemius soleus equinus, in children with and without calcaneal apophysitis (Sever's disease). the participants were 54 boys enrolled in a soccer academy, of which eight were lost to follow-up. Twenty-two boys with unilateral Sever's disease comprised the Sever's disease group and 24 healthy boys constituted a control group. Plantar pressure data were collected using pedobarography, and gastrocnemius soleus equinus was assessed. peak pressure and percentage of body weight supported were significantly higher in the symptomatic feet of the Sever's disease group than in the asymptomatic feet of the Sever's disease group and the control group. Every child in the Sever's disease group had bilateral gastrocnemius equinus, while nearly all children in the control group had no equinus. high plantar foot pressures are associated with Sever's disease, although it is unclear whether they are a predisposing factor or a result of the condition. Gastrocnemius equinus may be a predisposing factor for Sever's disease. Further research is needed to identify other factors involved in the disease and to better understand the factors that contribute to abnormal distribution of body weight in the lower limbs.

  5. 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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites.

    PubMed

    Tajebe, Fitsumbrhan; Getahun, Mulusew; Adem, Emebet; Hailu, Asrat; Lemma, Mulualem; Fikre, Helina; Raynes, John; Tamiru, Aschalew; Mulugeta, Zemenay; Diro, Ermias; Toulza, Frederic; Shkedy, Ziv; Ayele, Tadesse; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Takele, Yegnasew; Kropf, Pascale

    2017-07-01

    Visceral leishmaniasis (VL) is a neglected tropical disease that affects the poorest communities and can cause substantial morbidity and mortality. Visceral leishmaniasis is characterized by the presence of Leishmania parasites in the spleen, liver and bone marrow, hepatosplenomegaly, pancytopenia, prolonged fever, systemic inflammation and low body mass index (BMI). The factors impacting on the severity of VL are poorly characterized. Here we performed a cross-sectional study to assess whether co-infection of VL patients with intestinal parasites influences disease severity, assessed with clinical and haematological data, inflammation, cytokine profiles and BMI. Data from VL patients was similar to VL patients co-infected with intestinal parasites, suggesting that co-infection of VL patients with intestinal parasites does not alter disease severity.

  7. Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites

    PubMed Central

    Adem, Emebet; Hailu, Asrat; Lemma, Mulualem; Fikre, Helina; Raynes, John; Tamiru, Aschalew; Mulugeta, Zemenay; Diro, Ermias; Toulza, Frederic; Shkedy, Ziv; Ayele, Tadesse; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Takele, Yegnasew

    2017-01-01

    Visceral leishmaniasis (VL) is a neglected tropical disease that affects the poorest communities and can cause substantial morbidity and mortality. Visceral leishmaniasis is characterized by the presence of Leishmania parasites in the spleen, liver and bone marrow, hepatosplenomegaly, pancytopenia, prolonged fever, systemic inflammation and low body mass index (BMI). The factors impacting on the severity of VL are poorly characterized. Here we performed a cross-sectional study to assess whether co-infection of VL patients with intestinal parasites influences disease severity, assessed with clinical and haematological data, inflammation, cytokine profiles and BMI. Data from VL patients was similar to VL patients co-infected with intestinal parasites, suggesting that co-infection of VL patients with intestinal parasites does not alter disease severity. PMID:28732017

  8. Impact of Hospital Variables on Case Mix Index as a Marker of Disease Severity

    PubMed Central

    Mendez, Carmen M.; Harrington, Darrell W.; Christenson, Peter

    2014-01-01

    Abstract Case mix index (CMI) has become a standard indicator of hospital disease severity in the United States and internationally. However, CMI was designed to calculate hospital payments, not to track disease severity, and is highly dependent on documentation and coding accuracy. The authors evaluated whether CMI varied by characteristics affecting hospitals' disease severity (eg, trauma center or not). The authors also evaluated whether CMI was lower at public hospitals than private hospitals, given the diminished financial resources to support documentation enhancement at public hospitals. CMI data for a 14-year period from a large public database were analyzed longitudinally and cross-sectionally to define the impact of hospital variables on average CMI within and across hospital groups. Between 1996 and 2007, average CMI declined by 0.4% for public hospitals, while rising significantly for private for-profit (14%) and nonprofit (6%) hospitals. After the introduction of the Medicare Severity Diagnosis Related Group (MS-DRG) system in 2007, average CMI increased for all 3 hospital types but remained lowest in public vs. private for-profit or nonprofit hospitals (1.05 vs. 1.25 vs. 1.20; P<0.0001). By multivariate analysis, teaching hospitals, level 1 trauma centers, and larger hospitals had higher average CMI, consistent with a marker of disease severity, but only for private hospitals. Public hospitals had lower CMI across all subgroups. Although CMI had some characteristics of a disease severity marker, it was lower across all strata for public hospitals. Hence, caution is warranted when using CMI to adjust for disease severity across public vs. private hospitals. (Population Health Management 2014;17:28–34) PMID:23965045

  9. [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.

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

    PubMed

    Hammerschmidt, Ray

    2018-05-01

    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. © 2017 Society of Chemical Industry.

  11. Inhibition of Comt with tolcapone slows progression of polycystic kidney disease in the more severely affected PKD/Mhm (cy/+) substrain of the Hannover Sprague-Dawley rat

    PubMed Central

    Boehn, Susanne N.E.; Spahn, Sonja; Neudecker, Sabine; Keppler, Andrea; Bihoreau, Marie-Thérèse; Kränzlin, Bettina; Pandey, Priyanka; Hoffmann, Sigrid C.; Li, Li; Torres, Vicente E.; Gröne, Hermann-Josef; Gretz, Norbert

    2013-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common human inherited diseases. Modifier genes seem to modulate the disease progression and might therefore be promising drug targets. Although a number of modifier loci have been already identified, no modifier gene has been proven to be a real modifier yet. Methods Gene expression profiling of two substrains of the Han:SPRD rat, namely PKD/Mhm and PKD/US, both harboring the same mutation, was conducted in 36-day-old animals. Catechol-O-methyltransferase (Comt) was identified as a potential modifier gene. A 3-month treatment with tolcapone, a selective inhibitor of Comt, was carried out in PKD/Mhm and PKD/US (cy/+) animals. Results Comt is localized within a known modifier locus of PKD (MOP2). The enzyme encoding gene was found upregulated in the more severely affected PKD/Mhm substrain and was hence presumed to be a putative modifier gene of PKD. The treatment with tolcapone markedly attenuated the loss of renal function, inhibited renal enlargement, shifted the size distribution of renal cysts and retarded cell proliferation, apoptosis, inflammation and fibrosis development in affected (cy/+) male and female PKD/Mhm and PKD/US rats. Conclusions Comt has been confirmed to be the first reported modifier gene for PKD and tolcapone offers a promising drug for treating PKD. PMID:23543593

  12. Ethnicity influences disease characteristics and symptom severity in allergic rhinitis patients in Malaysia.

    PubMed

    Amini, Peyman; Abdullah, Maha; Seng, Lee Sing; Karunakaran, Thanusha; Hani, Norzhafarina; Bakar, Saraiza Abu; Latiff, Amir Hamzah Abdul; Fong, Seow Heng; Yeow, Yap Yoke

    2016-06-01

    The number of available reports regarding the influence of ethnicity on clinical features of allergic rhinitis (AR), especially disease severity in tropical climates, is limited. We aimed to compare clinical parameters and disease severity in AR patients of different ethnicities. Malay, Chinese, and Indian AR patients (n = 138) with confirmed sensitivity to Dermatophagoides pteronyssinus, Dematophagoides farinae, and Blomia tropicalis were tested for mite-specific immunoglobulin E (sIgE) levels. A detailed questionnaire was used to collect data on nasal symptom score (NSS), ocular symptom score (OSS), sum of symptoms score (SSS), quality of life score (QLS), symptomatic control score (SCS), and total sum of scores (TSS) and correlate the derived data with patients' demography, mite-polysensitivity, and sIgE levels. AR-related symptoms were most severe in Malays and least in Chinese (p < 0.01). Age (r = 0.516 to 0.673, p < 0.05) and duration of AR (r = 0.635 to 0.726, p < 0.01) correlated positively with severity domains (NSS, SSS, QLS, and TSS) in Chinese. Duration of concurrent allergies was highest in Malays (p < 0.05). Polysensitivity predicted increased sIgE levels in Malays (r = 0.464 to 0.551, p < 0.01) and Indians (r = 0.541 to 0.645, p < 0.05) but affected NSS, SSS, and TSS only in Indians (r = 0.216 to 0.376, p < 0.05). sIgE levels were lowest among Chinese but correlated strongly with NSS, OSS, SSS, and TSS (r = 0408 to 0.898, p < 0.05). Clinical parameters in AR may be influenced by race. Symptoms were most severe among Malays but did not correlate with other variables examined. Although Indian ethnicity did not impact disease severity, duration of concurrent allergies and mite-polysensitivity was associated with more severe disease. Age, duration of disease, and sIgE levels may be useful indicators of disease severity in Chinese. © 2016 ARS-AAOA, LLC.

  13. Increased FOXP3 expression in tumour-associated tissues of horses affected with equine sarcoid disease.

    PubMed

    Mählmann, K; Hamza, E; Marti, E; Dolf, G; Klukowska, J; Gerber, V; Koch, C

    2014-12-01

    Recent studies suggest that regulatory T cells (Tregs) are associated with disease severity and progression in papilloma virus induced neoplasia. Bovine papilloma virus (BPV) is recognised as the most important aetiological factor in equine sarcoid (ES) disease. The aim of this study was to compare expression levels of Treg markers and associated cytokines in tissue samples of ES-affected equids with skin samples of healthy control horses. Eleven ES-affected, and 12 healthy horses were included in the study. Expression levels of forkhead box protein 3 (FOXP3), interleukin 10 (IL10), interleukin 4 (IL4) and interferon gamma (IFNG) mRNA in lesional and tumour-distant samples from ES-affected horses, as well as in dermal samples of healthy control horses were measured using quantitative reverse transcription polymerase chain reaction (PCR). Expression levels were compared between lesional and tumour-distant as well as between tumour-distant and control samples. Furthermore, BPV-1 E5 DNA in samples of ES-affected horses was quantified using quantitative PCR, and possible associations of viral load, disease severity and gene expression levels were evaluated. Expression levels of FOXP3, IL10 and IFNG mRNA and BPV-1 E5 copy numbers were significantly increased in lesional compared to tumour-distant samples. There was no difference in FOXP3 and cytokine expression in tumour-distant samples from ES- compared with control horses. In tumour-distant samples viral load was positively correlated with IL10 expression and severity score. The increased expression of Treg markers in tumour-associated tissues of ES-affected equids indicates a local, Treg-induced immune suppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. 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

  15. Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection.

    PubMed

    de Steenhuijsen Piters, Wouter A A; Heinonen, Santtu; Hasrat, Raiza; Bunsow, Eleonora; Smith, Bennett; Suarez-Arrabal, Maria-Carmen; Chaussabel, Damien; Cohen, Daniel M; Sanders, Elisabeth A M; Ramilo, Octavio; Bogaert, Debby; Mejias, Asuncion

    2016-11-01

    Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity, especially among healthy children. We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem. To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection. We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response, and clinical disease severity. We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae- and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling. Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.

  16. Anxiety and depression in adult outpatients with bronchiectasis: Associations with disease severity and health-related quality of life.

    PubMed

    Gao, Yong-Hua; Guan, Wei-Jie; Zhu, Ya-Nan; Chen, Rong-Chang; Zhang, Guo-Jun

    2018-04-01

    Anxiety and depression might frequently affect bronchiectasis patients, but data in Chinese patients, including their association with disease severity assessed with Bronchiectasis Severity Index (BSI) and FACED score, are limited. To investigate the rate, risk factors, association with disease severity and impact of anxiety and depression on health-related quality of life (HRQoL) in adult outpatients with steady-state bronchiectasis. This cross-sectional study included 163 outpatients (102 females; mean age, 45.8 years) and 80 healthy subjects (47 females; mean age, 47.1 years). Demographic, clinical indices, radiology, spirometry, aetiology, sputum bacteriology, Hospital Anxiety and Depression Scales (HADS), Pittsburgh Sleep Quality Index (PSQI) and St. George's Respiratory Questionnaire (SGRQ) were assessed. Patients with steady-state bronchiectasis had a higher rate of depression (HADS-depression >7) (30.1% vs 10.0%, P = .001) and anxiety (HADS-anxiety >7; 39.9% vs 6.3%, P < .001) compared with healthy subjects. Notably, no significant differences in the rate of anxiety and depression were found across different disease severity, assessed with BSI and FACED score (all P > .05). In multivariate model, factors associated with anxiety included younger age (OR = 1.05), education below college graduate (OR = 4.55) and sleep disturbance (PSQI ≥ 6; OR = 2.95); whereas sleep disturbance was the sole factor associated with depression (OR = 5.98). Patients with either depression or anxiety had more markedly impaired HRQoL affecting most domains than those without. Anxiety and depression are common in bronchiectasis and can negatively affect HRQoL, but not related to disease severity. Prompt assessment and treatment of these mental disorders, regardless of bronchiectasis severity, are advocated and might improve HRQoL. © 2017 John Wiley & Sons Ltd.

  17. Factors affecting the dental erosion severity of patients with eating disorders.

    PubMed

    Otsu, Mitsuhiro; Hamura, Akira; Ishikawa, Yuiko; Karibe, Hiroyuki; Ichijyo, Tomoyasu; Yoshinaga, Yoko

    2014-01-01

    Intraoral disease is a common occurrence in patients with eating disorders, particularly dental erosion, which frequently becomes severe and may hinder daily life. The severity varies from patient to patient. Understanding the underlying mechanisms may help prevent dental erosion in these patients. Accordingly, we investigated the relationship between the severity of erosion and the behavior of patients with eating disorders, with a focus on daily diet and vomiting behavior. A total 71 female eating disorder outpatients from the Clinical Center of Psychosomatic Dentistry of Nippon Dental University Hospital and the Psychosomatic Internal Medicine Department of Kudanzaka Hospital or who were hospitalized at Hasegawa Hospital were enrolled. Dental erosion severity and location were determined by oral examination. Patients who induced vomiting were queried on their behavior during vomiting and on routine diet habits. Patients with dental erosion were further divided into mild and severe groups based on the lesion severity and the groups compared. Dental erosion was observed in 43 of 50 subjects who induced vomiting. Dental erosion was most frequent on the palatal side of the anterior maxillary teeth, occurring in 81.3% of the subjects. There were significant differences observed between the mild and severe groups according to post-vomiting oral hygiene. Significantly more subjects in the mild group consumed large amounts of water before vomiting, and significantly more subjects in the severe group routinely consumed carbonated beverages or sweetened food. While self-induced vomiting is the main cause of dental erosion in eating disorder patients, the erosion severity may be affected by behavior when inducing vomiting or by routine consumption of certain foods and beverages. Addressing these factors may help prevent severe dental erosion in patients who chronically induce vomiting.

  18. 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

  19. Impaired affective prosody decoding in severe alcohol use disorder and Korsakoff syndrome.

    PubMed

    Brion, Mélanie; de Timary, Philippe; Mertens de Wilmars, Serge; Maurage, Pierre

    2018-06-01

    Recognizing others' emotions is a fundamental social skill, widely impaired in psychiatric populations. These emotional dysfunctions are involved in the development and maintenance of alcohol-related disorders, but their differential intensity across emotions and their modifications during disease evolution remain underexplored. Affective prosody decoding was assessed through a vocalization task using six emotions, among 17 patients with severe alcohol use disorder, 16 Korsakoff syndrome patients (diagnosed following DSM-V criteria) and 19 controls. Significant disturbances in emotional decoding, particularly for negative emotions, were found in alcohol-related disorders. These impairments, identical for both experimental groups, constitute a core deficit in excessive alcohol use. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Heart Disease Affects Women of All Ages

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Heart Disease Affects Women of All Ages Past Issues / Winter ... weeks of a heart attack. For Women with Heart Disease: About 6 million American women have coronary heart ...

  1. Antibody-dependent enhancement of severe dengue disease in humans*

    PubMed Central

    Katzelnick, Leah C.; Gresh, Lionel; Halloran, M. Elizabeth; Mercado, Juan Carlos; Kuan, Guillermina; Gordon, Aubree; Balmaseda, Angel; Harris, Eva

    2018-01-01

    For dengue viruses (DENV1-4), a specific range of antibody titer has been shown to enhance viral replication in vitro and severe disease in animal models. Although suspected, such antibody-dependent enhancement (ADE) of severe disease has not been shown to occur in humans. Using multiple statistical approaches to study a long-term pediatric cohort in Nicaragua, we show that risk of severe dengue disease is highest within a narrow range of pre-existing anti-DENV antibody titers. By contrast, we observe protection from all symptomatic dengue disease at high antibody titers. Thus, immune correlates of severe dengue must be evaluated separately from correlates of protection against symptomatic disease. These results have implications for studies of dengue pathogenesis and for vaccine development, because enhancement, not just lack of protection, is of concern. PMID:29097492

  2. Intra- and inter-observer agreement on diagnosis of Dupuytren disease, measurements of severity of contracture, and disease extent.

    PubMed

    Broekstra, Dieuwke C; Lanting, Rosanne; Werker, Paul M N; van den Heuvel, Edwin R

    2015-08-01

    Dupuytren disease (DD) is a fibrosing disease affecting the palmar aponeurosis, and is mostly treated by surgery based on measurement of severity of flexion contracture of the fingers. Literature concerning the measurement reliability is scarce. This study aimed to determine the intra- and inter-observer agreement of four variables for diagnosing DD, determining severity of contracture, and disease extent. One of them is a new measurement on the area of nodules and cords for measuring the disease extent in early disease stages. An agreement study (n = 54) was performed by two trained investigators. Agreement was calculated per finger, based on an intraclass correlation coefficient (ICC) using a latent variable model on subjects for diagnosis and Tubiana stage. For total passive extension deficit (TPED) and the area of nodules and cords, agreement was calculated with an ICC using a one-way random effects model with subject as random effect. Inter-observer agreement was very good for diagnosing DD (ICC: 95.5%-99.9%) and good to very good for classifying Tubiana stage (ICC: 73.5%-94.9%). Agreements for area and TPED were moderate (middle finger) to very good (ICC: 48.4%-98.6% and 45.0%-99.5%, respectively). Intra-observer agreement was slightly higher on average than inter-observer agreement. Overall, the intra- and inter-observer agreement in diagnosing DD, and determining the severity of flexion contracture is high. Also, the newly introduced variable area of nodules and cords has high intra- and inter-observer agreement, indicating that it is suitable to measure disease extent. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Periodontal disease severity is associated with micronutrient intake.

    PubMed

    Luo, P-P; Xu, H-S; Chen, Y-W; Wu, S-P

    2018-03-06

    This study aimed to examine if specific micronutrients were associated with periodontal disease using data from the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Participants who were aged 30 years or more and received complete periodontal examinations were included. Regression analyses were performed to determine associations of variables of interest with periodontal disease. Data of 6415 NHANES participants were included in the analysis. Multivariable analysis revealed that less intake of vitamin A (adjusted odds ratio (aOR) = 1.784), vitamin B1 (aOR = 1.334), vitamin C (aOR = 1.401), vitamin E (aOR = 1.576), iron (aOR = 1.234), folate (aOR = 1.254) and phosphorus (aOR = 1.280) was associated with increased severity of periodontal disease. Compared with the highest level of vitamin D intake, the second highest level of vitamin D intake was associated with lower severity of periodontal disease (aOR = 0.727). Insufficient intake of vitamin A, B1, C and E, iron, folate and phosphorus was significantly associated with severity of periodontal disease. Results of the present study suggest that the above micronutrients may be increased in the diet or taken as dietary supplements in order to reduce severity of periodontal disease. © 2018 Australian Dental Association.

  4. Dynamic Neuro-Cognitive Imagery Improves Mental Imagery Ability, Disease Severity, and Motor and Cognitive Functions in People with Parkinson's Disease

    PubMed Central

    Hart, Ariel; Andrade, Isaac; Hackney, Madeleine E.

    2018-01-01

    People with Parkinson's disease (PD) experience kinesthetic deficits, which affect motor and nonmotor functions, including mental imagery. Imagery training is a recommended, yet underresearched, approach in PD rehabilitation. Dynamic Neuro-Cognitive Imagery (DNI™) is a codified method for imagery training. Twenty subjects with idiopathic PD (Hoehn and Yahr stages I–III) were randomly allocated into DNI training (experimental; n = 10) or in-home learning and exercise program (control; n = 10). Both groups completed at least 16 hours of training within two weeks. DNI training focused on anatomical embodiment and kinesthetic awareness. Imagery abilities, disease severity, and motor and nonmotor functions were assessed pre- and postintervention. The DNI participants improved (p < .05) in mental imagery abilities, disease severity, and motor and spatial cognitive functions. Participants also reported improvements in balance, walking, mood, and coordination, and they were more physically active. Both groups strongly agreed they enjoyed their program and were more mentally active. DNI training is a promising rehabilitation method for improving imagery ability, disease severity, and motor and nonmotor functions in people with PD. This training might serve as a complementary PD therapeutic approach. Future studies should explore the effect of DNI on motor learning and control strategies. PMID:29725348

  5. Affective Correlates of Psychosis in Parkinson's Disease.

    PubMed

    Factor, Stewart A; Scullin, Michael K; Freeman, Alan; Bliwise, Donald L; McDonald, William M; Goldstein, Felicia C

    2017-01-01

    To examine the nature of the association between affective disorders and psychosis in Parkinson's disease (PD). In PD, psychosis and affective disorders are common and independently impact quality of life and mortality. Both depression and psychosis are correlated with the occurrence of cognitive dysfunction, suggesting that they may share neurobiological substrates. Anxiety has not been examined as a correlate of psychosis. 144 PD subjects were evaluated with the Schedule for Assessment of Positive Symptoms to assess psychotic features, while depression and anxiety were examined by the Structured Clinical Interview for DSM-IV-TR (SCID) and self-assessment scales Beck Depression Inventory II (BDI-II) and Beck Anxiety Inventory (BAI). Correlational analyses assessed associations between hallucinations and delusions with depression and anxiety. A diagnosis of anxiety (SCID) was significantly (p=.015) associated with hallucinations (OR=4.81, CI=1.36-16.99). Severity of anxiety (BAI) significantly predicted (p=.03) the presence of hallucinations (OR=1.08, CI=1.01-1.15) and delusions (OR=1.09, CR=1.01-1.17). Current depression (SCID) was significantly (p=.001) associated with the presence of hallucinations (OR=6.12, CI=2.04-18.39) and delusions (OR=7.14, CI=2.23-22.93). Multiple linear regressions revealed that severity of anxiety remained an independent predictor (p<.05) of both the number of types of hallucinations (t=3.06, p=.003) and delusions (t=2.87, p=.005). Severity of depression was a significant predictor of the total number of delusions (t=2.28, p=.024). This study demonstrates an association between depression and psychosis and, for the first time, an association between anxiety and psychosis. These associations may have implications on pathophysiology and treatment of psychosis in PD.

  6. Association of heart rate profile during exercise with the severity of coronary artery disease.

    PubMed

    Cay, Serkan; Ozturk, Sezgin; Biyikoglu, Funda; Yildiz, Abdulkadir; Cimen, Tolga; Uygur, Belma; Tuna, Funda

    2009-05-01

    Coronary artery disease is the leading cause of morbidity and mortality around the world. Autonomic nervous system abnormalities are associated with coronary artery disease and its complications. Exercise stress tests are routinely used for the detection of the presence of coronary artery disease. In this study, we observed the association between heart rate profile during exercise and the severity of coronary artery disease. One hundred and sixty patients with abnormal exercise treadmill test (> or =1 mm horizontal or downsloping ST-segment depression; 119 men, 41 women; mean age = 57 +/- 9 years) were included in the study. Use of any drug affecting heart rate was not permitted. Resting heart rate before exercise, maximum heart rate during exercise, and resting heart rate after exercise (5 min later) were measured and two parameters were calculated: heart rate increment (maximum heart rate - resting heart rate before exercise) and heart rate decrement (maximum heart rate - resting heart rate after exercise). All patients underwent selective coronary angiography and subclassified into two groups according to stenotic lesion severity. Group 1 had at least 50% of stenotic lesion and group 2 had less than 50%. Patients in the first group had increased resting heart rate, decreased maximum heart rate, decreased heart rate increment, and decreased heart rate decrement compared with second group. All patients were classified into tertiles of resting heart rate, heart rate increment, and heart rate decrement level to evaluate whether these parameters were associated with severity of coronary artery stenosis in the study. The multiple-adjusted odds ratio of the risk of severe coronary atherosclerosis was 21.888 (95% confidence interval 6.983-68.606) for the highest tertile of resting heart rate level compared with the lowest tertile. In addition, the multiple-adjusted odds ratio of the risk of severe coronary atherosclerosis was 20.987 (95% confidence interval 6

  7. 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.

  8. Articulation disorders and duration, severity and L-dopa dosage in idiopathic Parkinson's disease.

    PubMed

    Pawlukowska, Wioletta; Gołąb-Janowska, Monika; Safranow, Krzysztof; Rotter, Iwona; Amernik, Katarzyna; Honczarenko, Krystyna; Nowacki, Przemysław

    2015-01-01

    Parkinson's disease (PD) is one of the most common diseases of the central nervous system (CNS). It is frequently heralded by speech disturbances, which are one of its first symptoms. The aim of this paper is to share our own experience concerning the correlation between the severity of speech disorders and the PD duration, its severity and the intake of L-dopa. The research included 93 patients with idiopathic PD, aged 26-86 years (mean age 65.1 years). Participants were examined neurologically according to the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr Scale. They were also assessed by Frenchay Dysarthria Assessment. Considerable and severe disorders were concurrent with impairments in the mobility of the tongue, lips, the jaw as well as the pitch and loudness of the voice. The strongest correlation but at a moderate level was found to exist between the severity of labial impairment, voice loudness and the length of the disease. There was also a positive correlation between lip movement while the motions were being diversified, lip arrangement while speaking and the intake of L-dopa. As PD progresses a significant decline in vocal articulation can be observed, which is due to reduced mobility within the lips and the jaw. Exacerbation of articulation disorders resulting from progression of the disease does not materially influence the UPDRSS scores. L-dopa has been found to positively affect the mobility of the lips while the patient is speaking and their arrangement at rest. Copyright © 2015 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  9. 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)

  10. Differential effects of severe vs mild GBA mutations on Parkinson disease.

    PubMed

    Gan-Or, Ziv; Amshalom, Idan; Kilarski, Laura L; Bar-Shira, Anat; Gana-Weisz, Mali; Mirelman, Anat; Marder, Karen; Bressman, Susan; Giladi, Nir; Orr-Urtreger, Avi

    2015-03-03

    To better define the genotype-phenotype correlations between the type of GBA (glucosidase, beta, acid) mutation, severe or mild, and the risk and age at onset (AAO), and potential mechanism of Parkinson disease (PD). We analyzed 1,000 patients of Ashkenazi-Jewish descent with PD for 7 founder GBA mutations, and conducted a meta-analysis of risk and AAO according to GBA genotype (severe or mild mutation). The meta-analysis included 11,453 patients with PD and 14,565 controls from worldwide populations. The statistical analysis was done with and without continuity correction (constant or empirical), considering biases that could potentially affect the results. Among Ashkenazi-Jewish patients with PD, the odds ratios for PD were 2.2 and 10.3 for mild and severe GBA mutation carriers, respectively. The observed frequency of severe GBA mutation carriers among patients with PD was more than 4-fold than expected (4.4% vs 0.9%, respectively, p < 0.0001, Fisher exact test). In the different models of the meta-analysis, the odds ratios for PD ranged between 2.84 and 4.94 for mild GBA mutation carriers and 9.92 and 21.29 for severe GBA mutation carriers (p < 1 × 10(-6) for all analyses). Pooled analysis demonstrated AAO of 53.1 (±11.2) and 58.1 (±10.6) years for severe and mild GBA mutation carriers, respectively (p = 4.3 × 10(-5)). These data demonstrate that mild and severe heterozygous GBA mutations differentially affect the risk and the AAO of PD. Our results have important implications for genetic counseling and clinical follow-up. © 2015 American Academy of Neurology.

  11. 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.

  12. Use of the disease severity index for null hypothesis testing

    USDA-ARS?s Scientific Manuscript database

    A disease severity index (DSI) is a single number for summarizing a large amount of disease severity information. It is used to indicate relative resistance of cultivars, to relate disease severity to yield loss, or to compare treatments. The DSI has most often been based on a special type of ordina...

  13. Targeting the brain: considerations in 332 consecutive patients treated by deep brain stimulation (DBS) for severe neurological diseases.

    PubMed

    Franzini, Angelo; Cordella, Roberto; Messina, Giuseppe; Marras, Carlo Efisio; Romito, Luigi Michele; Albanese, Alberto; Rizzi, Michele; Nardocci, Nardo; Zorzi, Giovanna; Zekaj, Edvin; Villani, Flavio; Leone, Massimo; Gambini, Orsola; Broggi, Giovanni

    2012-12-01

    Deep brain stimulation (DBS) extends the treatment of some severe neurological diseases beyond pharmacological and conservative therapy. Our experience extends the field of DBS beyond the treatment of Parkinson disease and dystonia, including several other diseases such as cluster headache and disruptive behavior. Since 1993, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan, 580 deep brain electrodes were implanted in 332 patients. The DBS targets include Stn, GPi, Voa, Vop, Vim, CM-pf, pHyp, cZi, Nacc, IC, PPN, and Brodmann areas 24 and 25. Three hundred patients are still available for follow-up and therapeutic considerations. DBS gave a new therapeutic chance to these patients affected by severe neurological diseases and in some cases controlled life-threatening pathological conditions, which would otherwise result in the death of the patient such as in status dystonicus, status epilepticus and post-stroke hemiballismus. The balance of DBS in severe neurological disease is strongly positive even if further investigations and studies are needed to search for new applications and refine the selection criteria for the actual indications.

  14. Family history does not predict angiographic localization or severity of coronary artery disease.

    PubMed

    Banerjee, Amitava; Lim, Chris C S; Silver, Louise E; Heneghan, Carl; Welch, Sarah J V; Mehta, Ziyah; Banning, Adrian P; Rothwell, Peter M

    2012-04-01

    Family history of MI is an established risk factor for coronary artery disease and subclinical atherosclerosis. Maternal MI and maternal stroke are more common in females than males presenting with acute coronary syndromes (ACS), suggesting sex-specific heritability, but the effects of family history on location and extent of coronary artery disease are unknown. In a prospective, population-based study (Oxford Vascular Study) of all patients with ACS, family history data for stroke and MI were analysed by sex of proband and affected first degree relatives (FDRs), and coronary angiograms were reviewed, where available. Of 835 probands with one or more ACS, 623 (420 males) had incident events and complete family history data. 351 patients with incident events (56.3%; 266 males) underwent coronary angiography. Neither angiographic disease localization nor severity were associated with sex-of-parent/sex-of-offspring in men or women. Sex-specific family history data do not predict angiographic localization of coronary disease in patients presenting with ACS. Maternal stroke and maternal MI probably affect ACS in females by a mechanism unrelated to atherosclerosis or coronary anatomy. However, family history data may still be useful in risk prediction and prognosis of ACS. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Anger Expression, Momentary Anger, and Symptom Severity in Patients with Chronic Disease.

    PubMed

    Russell, Michael A; Smith, Timothy W; Smyth, Joshua M

    2016-04-01

    Anger expression styles are associated with physical health, and may affect health by modulating anger experience in daily life. Research examining this process in the daily lives of clinically relevant populations, such as patients with chronic disease, is needed. Community adults with asthma (N = 97) or rheumatoid arthritis (RA; N = 31) completed measures of trait-level anger expression styles (anger-in and anger-out), followed by ecological momentary assessments of anger and physical health five times daily for 7 days. High anger-in predicted greater momentary anger, physical limitations, and greater asthma symptoms. High anger-out predicted reduced RA symptoms. Momentary anger was robustly associated with more severe symptoms in daily life. Three-way interactions showed that anger-in moderated these momentary anger-symptom associations more consistently in men. Anger expression styles, particularly anger-in, may affect the day-to-day adjustment of patients with chronic disease in part by altering the dimensions of everyday anger experience, in ways that appear to differ by gender.

  16. Anger Expression, Momentary Anger, and Symptom Severity in Patients with Chronic Disease

    PubMed Central

    Russell, Michael A.; Smith, Timothy W.; Smyth, Joshua M.

    2015-01-01

    Background Anger expression styles are associated with physical health, and may affect health by modulating anger experience in daily life. Research examining this process in the daily lives of clinically relevant populations, such as patients with chronic disease, is needed. Method Community adults with asthma (N=97) or rheumatoid arthritis (RA; N=31) completed measures of trait-level anger expression styles (anger-in and anger-out), followed by ecological momentary assessments of anger and physical health 5 times daily for 7 days. Results High anger-in predicted greater momentary anger, physical limitations, and greater asthma symptoms. High anger-out predicted reduced RA symptoms. Momentary anger was robustly associated with more severe symptoms in daily life. Three-way interactions showed anger-in moderated these momentary anger-symptom associations more consistently in men. Conclusions Anger expression styles, particularly anger-in, may affect the day-to-day adjustment of patients with chronic disease in part by altering the dimensions of everyday anger experience, in ways that appear to differ by gender. PMID:26493555

  17. 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.

  18. Crystal-proven Gout and Characteristic Gout Severity Factors are Associated with Cardiovascular Disease.

    PubMed

    Disveld, Iris J M; Fransen, Jaap; Rongen, Gerard A; Kienhorst, Laura B E; Zoakman, Sahel; Janssens, Hein J E M; Janssen, Matthijs

    2018-04-15

    Our aim was to examine the prevalence of cardiovascular disease (CVD) in patients with crystal-proven gout compared to arthritis controls. Further, we analyzed the association between characteristic gout severity factors and CVD to provide further support for a pathogenetic relationship between gout and CVD. Patients with arthritis referred for diagnosis were consecutively included in the Gout Arnhem-Liemers cohort. Joint fluid analysis was performed in all referred patients; controls were negative for crystals. Patients' characteristics and different manifestations of CVD and gout severity factors (disease duration, attack frequency, tophi, affected joints, high serum urate acid level, joint damage) were collected. Gout patients were compared with controls for the prevalence of CVD. In addition, the association between characteristic gout severity factors and presence of CVD was analyzed. Data from 700 gout patients and 276 controls were collected. CVD was present in 47% (95% CI 44%-51%) and 24% (95% CI 19%-29%) of gout patients and controls, respectively. Corrected for confounders, gout was still strongly associated with an increased prevalence of CVD compared to controls (OR 3.39, 95% CI 2.37-4.84). In patients with gout, disease duration ≥ 2 years, oligo- or polyarthritis, serum urate acid > 0.55 mmol/l at presentation, and joint damage were independently (p < 0.05) associated with prevalent CVD. Crystal-proven gout was strongly associated with an increased prevalence of CVD. In patients with gout, characteristic gout severity factors were associated with CVD.

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

    PubMed Central

    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.

    2015-01-01

    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. PMID:26571397

  20. Biomarker discovery for disease status and symptom severity in children with autism.

    PubMed

    Oztan, Ozge; Jackson, Lisa P; Libove, Robin A; Sumiyoshi, Raena D; Phillips, Jennifer M; Garner, Joseph P; Hardan, Antonio Y; Parker, Karen J

    2018-03-01

    Autism spectrum disorder (ASD) is characterized by social impairments and repetitive behaviors, and affects 1 in 68 US children. Despite ASD's societal impact, its disease mechanisms remain poorly understood. Recent preclinical ASD biomarker discovery research has implicated the neuropeptides oxytocin (OXT) and arginine vasopressin (AVP), and their receptors, OXTR and AVPR1A, in animal models. Efforts to translate these findings to individuals with ASD have typically involved evaluating single neuropeptide measures as biomarkers of ASD and/or behavioral functioning. Given that ASD is a heterogeneous disorder, and unidimensional ASD biomarker studies have been challenging to reproduce, here we employed a multidimensional neuropeptide biomarker analysis to more powerfully interrogate disease status and symptom severity in a well characterized child cohort comprised of ASD patients and neurotypical controls. These blood-based neuropeptide measures, considered as a whole, correctly predicted disease status for 57 out of 68 (i.e., 84%) participants. Further analysis revealed that a composite measure of OXTR and AVPR1A gene expression was the key driver of group classification, and that children with ASD had lower neuropeptide receptor mRNA levels compared to controls. Lower neuropeptide receptor mRNA levels also predicted greater symptom severity for core ASD features (i.e., social impairments and stereotyped behaviors), but were unrelated to intellectual impairment, an associated feature of ASD. Findings from this research highlight the value of assessing multiple related biological measures, and their relative contributions, in the same study, and suggest that low blood neuropeptide receptor availability may be a promising biomarker of disease presence and symptom severity in ASD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Somatic hospital contacts, invasive cardiac procedures, and mortality from heart disease in patients with severe mental disorder.

    PubMed

    Laursen, Thomas Munk; Munk-Olsen, Trine; Agerbo, Esben; Gasse, Christiane; Mortensen, Preben Bo

    2009-07-01

    Excess mortality from heart disease is observed in patients with severe mental disorder. This excess mortality may be rooted in adverse effects of pharmacological or psychotropic treatment, lifestyle factors, or inadequate somatic care. To examine whether persons with severe mental disorder, defined as persons admitted to a psychiatric hospital with bipolar affective disorder, schizoaffective disorder, or schizophrenia, are in contact with hospitals and undergoing invasive procedures for heart disease to the same degree as the nonpsychiatric general population, and to determine whether they have higher mortality rates of heart disease. A population-based cohort of 4.6 million persons born in Denmark was followed up from 1994 to 2007. Rates of mortality, somatic contacts, and invasive procedures were estimated by survival analysis. Incidence rate ratios of heart disease admissions and heart disease mortality as well as probability of invasive cardiac procedures. The incidence rate ratio of heart disease contacts in persons with severe mental disorder compared with the rate for the nonpsychiatric general population was only slightly increased, at 1.11 (95% confidence interval, 1.08-1.14). In contrast, their excess mortality rate ratio from heart disease was 2.90 (95% confidence interval, 2.71-3.10). Five years after the first contact for somatic heart disease, the risk of dying of heart disease was 8.26% for persons with severe mental disorder (aged <70 years) but only 2.86% in patients with heart disease who had never been admitted to a psychiatric hospital. The fraction undergoing invasive procedures within 5 years was reduced among patients with severe mental disorder as compared with the nonpsychiatric general population (7.04% vs 12.27%, respectively). Individuals with severe mental disorder had only negligible excess rates of contact for heart disease. Given their excess mortality from heart disease and lower rates of invasive procedures after first contact, it

  2. Positive affect and survival in patients with stable coronary heart disease: findings from the Heart and Soul Study.

    PubMed

    Hoen, Petra W; Denollet, Johan; de Jonge, Peter; Whooley, Mary A

    2013-07-01

    Positive affect can improve survival, but the mechanisms responsible for this association are unknown. We sought to evaluate the association between positive affect and mortality in patients with stable coronary heart disease and to determine biological and behavioral factors that might explain this association. The Heart and Soul Study is a prospective cohort study of 1,018 outpatients with stable coronary heart disease. Participants were recruited between September 11, 2000, and December 20, 2002, and were followed up to June 2011. Baseline positive affect was assessed by using the 10-item positive affect subscale of the Positive and Negative Affect Schedule. Cox proportional hazards regression was used to estimate the risk of mortality (primary outcome measure) and cardiovascular events (heart failure, myocardial infarction, stroke, transient ischemic attack) associated with positive affect, adjusting for baseline cardiac disease severity and depression. We also evaluated the extent to which these associations were explained by potential biological and behavioral mediators. A total of 369 patients (36%) died during a mean ± SD follow-up period of 7.1 ± 2.5 years. Positive affect was not significantly associated with cardiovascular events (hazard ratio [HR]: 0.89; 95% CI, 0.79-1.00; P = .06). However, each standard deviation (8.8-point) increase in positive affect score was associated with a 16% decreased risk of all-cause mortality (HR: 0.84; 95% CI, 0.76-0.92; P = .001). After adjustment for cardiac disease severity and depressive symptoms, positive affect remained significantly associated with improved survival (HR: 0.87; 95% CI, 0.78-0.97; P = .01). The association was no longer significant after adjustment for behavioral factors, and particularly physical activity (HR: 0.92; 95% CI, 0.82-1.03; P = .16). Further adjustment for C-reactive protein and omega-3 fatty acids did not result in any meaningful changes (HR: 0.94; 95% CI, 0.84-1.06; P = .31). In this

  3. 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

  4. Predictors of Severe Disease in Melioidosis Patients in Kuala Lumpur, Malaysia

    PubMed Central

    Mohd Roslani, Ardita Dewi Roslani; Tay, Sun Tee; Puthucheary, Savithri D.; Rukumani, Devi V.; Sam, I-Ching

    2014-01-01

    The predictors of severe disease or death were determined for 85 melioidosis patients in Kuala Lumpur, Malaysia. Most of the patients were male, > 40 years old, and diabetic. Severe disease or death occurred in 28 (32.9%) cases. Lower lymphocyte counts and positive blood cultures were significant independent predictors of severe disease, but age, presentations with pneumonia, inappropriate empirical antibiotics, or flagellin types of the infecting isolates were not. Knowledge of local predictors of severe disease is useful for clinical management. PMID:25246695

  5. Comorbidity in chronic obstructive pulmonary disease. Related to disease severity?

    PubMed

    Echave-Sustaeta, Jose M; Comeche Casanova, Lorena; Cosio, Borja G; Soler-Cataluña, Juan Jose; Garcia-Lujan, Ricardo; Ribera, Xavier

    2014-01-01

    Several diseases commonly co-exist with chronic obstructive pulmonary disease (COPD), especially in elderly patients. This study aimed to investigate whether there is an association between COPD severity and the frequency of comorbidities in stable COPD patients. In this multicenter, cross-sectional study, patients with spirometric diagnosis of COPD attended to by internal medicine departments throughout Spain were consecutively recruited by 225 internal medicine specialists. The severity of airflow obstruction was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and data on demographics, smoking history, comorbidities, and dyspnea were collected. The Charlson comorbidity score was calculated. Eight hundred and sixty-six patients were analyzed: male 93%, mean age 69.8 (standard deviation [SD] 9.7) years and forced vital capacity in 1 second 42.1 (SD 17.7)%. Even, the mean (SD) Charlson score was 2.2 (2.2) for stage I, 2.3 (1.5) for stage II, 2.5 (1.6) for stage III, and 2.7 (1.8) for stage IV (P=0.013 between stage I and IV groups), independent predictors of Charlson score in the multivariate analysis were age, smoking history (pack-years), the hemoglobin level, and dyspnea, but not GOLD stage. COPD patients attended to in internal medicine departments show high scores of comorbidity. However, GOLD stage was not an independent predictor of comorbidity.

  6. Development of an index to define overall disease severity in IBD.

    PubMed

    Siegel, Corey A; Whitman, Cynthia B; Spiegel, Brennan M R; Feagan, Brian; Sands, Bruce; Loftus, Edward V; Panaccione, Remo; D'Haens, Geert; Bernstein, Charles N; Gearry, Richard; Ng, Siew C; Mantzaris, Gerassimos J; Sartor, Balfour; Silverberg, Mark S; Riddell, Robert; Koutroubakis, Ioannis E; O'Morain, Colm; Lakatos, Peter L; McGovern, Dermot P B; Halfvarson, Jonas; Reinisch, Walter; Rogler, Gerhard; Kruis, Wolfgang; Tysk, Curt; Schreiber, Stefan; Danese, Silvio; Sandborn, William; Griffiths, Anne; Moum, Bjorn; Gasche, Christoph; Pallone, Francesco; Travis, Simon; Panes, Julian; Colombel, Jean-Frederic; Hanauer, Stephen; Peyrin-Biroulet, Laurent

    2018-02-01

    Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC. Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute. For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities. Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. 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.

  8. Disease severity, self-reported experience of workplace discrimination and employment loss during the course of chronic HIV disease: differences according to gender and education.

    PubMed

    Dray-Spira, R; Gueguen, A; Lert, F

    2008-02-01

    Evidence for the existence of a harmful effect of chronic disease on employment status has been provided. Although this effect of chronic illness on employment has been reported to be higher among the groups with the lowest position on the labour market, the mechanisms of such inequalities are poorly understood. The present study aimed at investigating social inequalities in the chances of maintaining employment during the course of HIV infection and at examining the correlates of such inequalities. The authors used data from a national representative sample of people living with HIV in France (ANRS-EN12-VESPA survey). Retrospective information on social trajectory and disease characteristics from the time of HIV diagnosis was available. The risk of employment loss associated with indicators of disease severity and HIV-related workplace discrimination was computed over time since HIV diagnosis according to sociodemographic and occupational factors, using Cox proportional hazards models. Among the 478 working-age participants diagnosed as being HIV-infected in the era of multitherapies and employed at the time of HIV diagnosis, 149 experienced employment loss. After adjusting for sociodemographic and occupational factors, disease severity and self-reported HIV-related discrimination at work were significantly associated with the risk of employment loss in a socially-differentiated manner: advancement in HIV disease was associated with an increased risk of employment loss among women (HR 4.45, 95% CI 2.10 to 9.43) but not among men; self-reported experience of HIV-related discrimination at work was associated with an increased risk of employment loss among individuals with a primary/secondary educational level (HR 8.85, 95% CI 3.68 to 21.30) but not among those more educated. Chronic HIV disease affects the chances of maintaining employment in a socially-differentiated manner, resulting in increasing inequalities regarding workforce participation. Disease severity

  9. Peach leaf curl disease shifts sugar metabolism in severely infected leaves from source to sink.

    PubMed

    Moscatello, Stefano; Proietti, Simona; Buonaurio, Roberto; Famiani, Franco; Raggi, Vittorio; Walker, Robert P; Battistelli, Alberto

    2017-03-01

    Peach leaf curl is a disease that affects the leaves of peach trees, and in severe cases all of the leaf can be similarly affected. This study investigated some effects of this disease on the metabolism of peach leaves in which all parts of the leaf were infected. These diseased leaves contained very little chlorophyll and performed little or no photosynthesis. Compared to uninfected leaves, diseased leaves possessed higher contents of fructose and especially glucose, but lowered contents of sucrose, sorbitol and especially starch. The activities of soluble acid invertase, neutral invertase, sorbitol dehydrogenase and sucrose synthase were all higher in diseased leaves, whereas, those of aldose-6-phosphate reductase and sucrose phosphate synthase were lower. The activities of hexokinase and fructokinase were little changed. In addition, immunblots showed that the contents of Rubisco and ADP-glucose phosphorylase were reduced in diseased leaves, whereas, the content of phosphoenolpyruvate carboxylase was increased. The results show that certain aspects of the metabolism of diseased leaves are similar to immature sink leaves. That is photosynthetic function is reduced, the leaf imports rather than exports sugars, and the contents of non-structural carbohydrates and enzymes involved in their metabolism are similar to sink leaves. Further, the effects of peach leaf curl on the metabolism of peach leaves are comparable to the effects of some other diseases on the metabolism of photosynthetic organs of other plant species. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Framework for evaluating disease severity measures in older adults with comorbidity.

    PubMed

    Boyd, Cynthia M; Weiss, Carlos O; Halter, Jeff; Han, K Carol; Ershler, William B; Fried, Linda P

    2007-03-01

    Accounting for the influence of concurrent conditions on health and functional status for both research and clinical decision-making purposes is especially important in older adults. Although approaches to classifying severity of individual diseases and conditions have been developed, the utility of these classification systems has not been evaluated in the presence of multiple conditions. We present a framework for evaluating severity classification systems for common chronic diseases. The framework evaluates the: (a) goal or purpose of the classification system; (b) physiological and/or functional criteria for severity graduation; and (c) potential reliability and validity of the system balanced against burden and costs associated with classification. Approaches to severity classification of individual diseases were not originally conceived for the study of comorbidity. Therefore, they vary greatly in terms of objectives, physiological systems covered, level of severity characterization, reliability and validity, and costs and burdens. Using different severity classification systems to account for differing levels of disease severity in a patient with multiple diseases, or, assessing global disease burden may be challenging. Most approaches to severity classification are not adequate to address comorbidity. Nevertheless, thoughtful use of some existing approaches and refinement of others may advance the study of comorbidity and diagnostic and therapeutic approaches to patients with multimorbidity.

  11. Heartburn Severity Does Not Predict Disease Severity in Patients With Erosive Esophagitis

    PubMed Central

    Fennerty, M. Brian; Johnson, David A.

    2006-01-01

    Background For patients with gastroesophageal reflux disease (GERD), it is often assumed by treating physicians that the severity of heartburn correlates with the severity of erosive esophagitis (EE). Objective This is a post hoc analysis of data from 5 clinical trials that investigate the relationship between the baseline severity of heartburn and the baseline severity of EE. Methods Patients with endoscopically confirmed EE were assessed for heartburn symptoms with a 4-point scale at baseline and during treatment for 8 weeks with various proton pump inhibitors in 5 double-blind trials in which esomeprazole was the common comparator. EE was graded with the Los Angeles (LA) classification system. In these trials, healing and symptom response were evaluated by endoscopy and questionnaire after 4 weeks of treatment. Patients who were not healed were treated for an additional 4 weeks and reevaluated. Results A total of 11,945 patients with endoscopically confirmed EE participated in the 5 trials, with patients receiving esomeprazole 40 mg (n = 5068), esomeprazole 20 mg (n = 1243), omeprazole 20 mg (n = 3018), or lansoprazole 30 mg (n = 2616). Approximately one quarter of the 11,945 GERD patients in these 5 trials had severe EE (defined as LA grades C or D), regardless of their baseline heartburn severity. Conclusion The severity of GERD symptoms does not correlate well with disease severity. These findings indicate that endoscopy may have value in GERD patients in identifying those with EE, and if empirical therapy is chosen, then longer courses (4-8 weeks) of antisecretory therapy may be necessary to ensure healing of unrecognized esophagitis. PMID:16926745

  12. The prevalence of severe fatigue in rheumatic diseases: an international study.

    PubMed

    Overman, Cécile L; Kool, Marianne B; Da Silva, José A P; Geenen, Rinie

    2016-02-01

    Fatigue is a common, disabling, and difficult-to-manage problem in rheumatic diseases. Prevalence estimates of fatigue within rheumatic diseases vary considerably. Data on the prevalence of severe fatigue across multiple rheumatic diseases using a similar instrument is missing. Our aim was to provide an overview of the prevalence of severe fatigue across a broad range of rheumatic diseases and to examine its association with clinical and demographic variables. Online questionnaires were filled out by an international sample of 6120 patients (88 % female, mean age 47) encompassing 30 different rheumatic diseases. Fatigue was measured with the RAND(SF)-36 Vitality scale. A score of ≤35 was taken as representing severe fatigue (90 % sensitivity and 81 % specificity for chronic fatigue syndrome). Severe fatigue was present in 41 to 57 % of patients with a single inflammatory rheumatic disease such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, Sjögren's syndrome, psoriatic arthritis, and scleroderma. Severe fatigue was least prevalent in patients with osteoarthritis (35 %) and most prevalent in patients with fibromyalgia (82 %). In logistic regression analysis, severe fatigue was associated with having fibromyalgia, having multiple rheumatic diseases without fibromyalgia, younger age, lower education, and language (French: highest prevalence; Dutch: lowest prevalence). In conclusion, one out of every two patients with a rheumatic disease is severely fatigued. As severe fatigue is detrimental to the patient, the near environment, and society at large, unraveling the underlying mechanisms of fatigue and developing optimal treatment should be top priorities in rheumatologic research and practice.

  13. Murmur intensity in adult dogs with pulmonic and subaortic stenosis reflects disease severity.

    PubMed

    Caivano, D; Dickson, D; Martin, M; Rishniw, M

    2018-03-01

    The aims of this study were to determine whether murmur intensity in adult dogs with pulmonic stenosis or subaortic stenosis reflects echocardiographic disease severity and to determine whether a six-level murmur grading scheme provides clinical advantages over a four-level scheme. In this retrospective multi-investigator study on adult dogs with pulmonic stenosis or subaortic stenosis, murmur intensity was compared to echocardiographically determined pressure gradient across the affected valve. Disease severity, based on pressure gradients, was assessed between sequential murmur grades to identify redundancy in classification. A simplified four-level murmur intensity classification scheme ('soft', 'moderate', 'loud', 'palpable') was evaluated. In total, 284 dogs (153 with pulmonic stenosis, 131 with subaortic stenosis) were included; 55 dogs had soft, 59 had moderate, 72 had loud and 98 had palpable murmurs. 95 dogs had mild stenosis, 46 had moderate stenosis, and 143 had severe stenosis. No dogs with soft murmurs of either pulmonic or subaortic stenosis had transvalvular pressure gradients greater than 50 mmHg. Dogs with loud or palpable murmurs mostly, but not always, had severe stenosis. Stenosis severity increased with increasing murmur intensity. The traditional six-level murmur grading scheme provided no additional clinical information than the four-level descriptive murmur grading scheme. A simplified descriptive four-level murmur grading scheme differentiated stenosis severity without loss of clinical information, compared to the traditional six-level scheme. Soft murmurs in dogs with pulmonic or subaortic stenosis are strongly indicative of mild lesions. Loud or palpable murmurs are strongly suggestive of severe stenosis. © 2017 British Small Animal Veterinary Association.

  14. Fatigue, not self-rated motor symptom severity, affects quality of life in functional motor disorders.

    PubMed

    Gelauff, J M; Kingma, E M; Kalkman, J S; Bezemer, R; van Engelen, B G M; Stone, J; Tijssen, M A J; Rosmalen, J G M

    2018-06-02

    While fatigue is found to be an impairing symptom in functional motor disorders (FMD) in clinical practice, scientific evidence is lacking. We investigated fatigue severity and subtypes in FMD compared to organic neurological disease. Furthermore, the role of fatigue within FMD and its impact on quality of life and self-rated health were investigated. Data from 181 patients participating in the self-help on the internet for functional motor disorders, randomised Trial were included. Data from 217 neurological controls with neuromuscular disorders (NMD) originated from a historical cohort. Fatigue was measured using the checklist individual strength (CIS). Motor symptom severity, depression and anxiety were correlated to fatigue. For multivariable regression analyses, physical functioning and pain were additionally taken into account. Severe fatigue was, respectively, present in 78 and 53% of FMD and NMD patients (p < 0.001). FMD patients scored higher than NMD patients on all fatigue subdomains (p < 0.001). In the FMD group, fatigue subdomains were correlated to depression, anxiety and partly to motor symptom severity. Quality of life was negatively associated with fatigue [OR 0.93 (0.90-0.96), p < 0.001] and depression [OR 0.87 (0.81-0.93), p < 0.001], but not self-rated motor symptom severity. Self-rated health was negatively associated with fatigue [OR 0.92 (0.88-0.96), p < 0.001] and pain [OR 0.98 (0.97-0.99), p < 0.001]. Fatigue was found to be a prevalent problem in FMD, more so than in organic neurological disease. It significantly affected quality of life and self-rated health, while other factors such as motor symptom severity did not. Fatigue should be taken into account in clinical practice and treatment trials.

  15. Plant Disease Severity Assessment-How Rater Bias, Assessment Method, and Experimental Design Affect Hypothesis Testing and Resource Use Efficiency.

    PubMed

    Chiang, Kuo-Szu; Bock, Clive H; Lee, I-Hsuan; El Jarroudi, Moussa; Delfosse, Philippe

    2016-12-01

    The effect of rater bias and assessment method on hypothesis testing was studied for representative 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 with unequal numbers of replicate estimates are termed "unbalanced". The three assessment methods considered were nearest percent estimates (NPEs), an amended 10% incremental scale, and the Horsfall-Barratt (H-B) scale. Estimates of severity of Septoria leaf blotch on leaves of winter wheat were used to develop distributions for a simulation model. The experimental designs are presented here in the context of simulation experiments which consider the optimal design for the number of specimens (individual units sampled) and the number of replicate estimates per specimen for a fixed total number of observations (total sample size for the treatments being compared). The criterion used to gauge each method was the power of the hypothesis test. As expected, at a given fixed number of observations, the balanced experimental designs invariably resulted in a higher power compared with the unbalanced designs at different disease severity means, mean differences, and variances. Based on these results, with unbiased estimates using NPE, the recommended number of replicate estimates taken per specimen is 2 (from a sample of specimens of at least 30), because this conserves resources. Furthermore, for biased estimates, an apparent difference in the power of the hypothesis test was observed between assessment methods and between experimental designs. Results indicated that, regardless of experimental design or rater bias, an amended 10% incremental scale has slightly less power compared with NPEs, and that the H-B scale is more likely than the others to cause a type II error. These results suggest that choice of assessment method, optimizing sample number and number of replicate

  16. 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

  17. Factors affecting injury severity of vehicle occupants following road traffic collisions.

    PubMed

    Abu-Zidan, Fikri M; Eid, Hani O

    2015-01-01

    We aimed to define factors affecting injury severity of vehicle occupants following road traffic collisions (RTC). 422 vehicle occupants (343 males, 81.3%) with RTC-related injuries were prospectively studied over 18 months. General linear model was used to test the effect of age, gender, alcohol and drug use, time of injury, mechanism of injury, size and speed of the vehicle, position in the vehicle, seatbelt usage, and air bag deployment on the Injury Severity Score (ISS) of the vehicle occupants. The mean (range) age of patients was 28.2 (1-78) years and the mean (range) ISS was 7.9 (1-50). Front impact was the most common mechanism of injury (32.9%) followed by rollover (25.6%) and side impact (22.3%). 18.2% used seatbelts. The general linear model was highly significant and showed that mechanism of injury (p<0.0001), speed of the vehicle (p=0.02), and age of the vehicle occupant (p=0.03) significantly affected the Injury Severity Score. The mechanism of the RTC, the vehicle speed, and age of the vehicle occupant are the most important factors affecting the severity of road traffic collision injuries. A detailed history of the mechanism of injury is important for alerting clinicians to severity of injury, the need for admission, and workup of the patients. Furthermore, strict speed limit enforcement is an injury prevention priority in our community. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Cardiac Complications, Earlier Treatment, and Initial Disease Severity in Kawasaki Disease.

    PubMed

    Abrams, Joseph Y; Belay, Ermias D; Uehara, Ritei; Maddox, Ryan A; Schonberger, Lawrence B; Nakamura, Yosikazu

    2017-09-01

    To assess if observed higher observed risks of cardiac complications for patients with Kawasaki disease (KD) treated earlier may reflect bias due to confounding from initial disease severity, as opposed to any negative effect of earlier treatment. We used data from Japanese nationwide KD surveys from 1997 to 2004. Receipt of additional intravenous immunoglobulin (IVIG) (data available all years) or any additional treatment (available for 2003-2004) were assessed as proxies for initial disease severity. We determined associations between earlier or later IVIG treatment (defined as receipt of IVIG on days 1-4 vs days 5-10 of illness) and cardiac complications by stratifying by receipt of additional treatment or by using logistic modeling to control for the effect of receiving additional treatment. A total of 48 310 patients with KD were included in the analysis. In unadjusted analysis, earlier IVIG treatment was associated with a higher risk for 4 categories of cardiac complications, including all major cardiac complications (risk ratio, 1.10; 95% CI, 1.06-1.15). Stratifying by receipt of additional treatment removed this association, and earlier IVIG treatment became protective against all major cardiac complications when controlling for any additional treatment in logistic regressions (OR, 0.90; 95% CI, 0.80-1.00). Observed higher risks of cardiac complications among patients with KD receiving IVIG treatment on days 1-4 of the illness are most likely due to underlying higher initial disease severity, and patients with KD should continue to be treated with IVIG as early as possible. Published by Elsevier Inc.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  20. Hospital-acquired Clostridium difficile infection: determinants for severe disease.

    PubMed

    Wenisch, J M; Schmid, D; Kuo, H-W; Simons, E; Allerberger, F; Michl, V; Tesik, P; Tucek, G; Wenisch, C

    2012-08-01

    Risk factors of severity (need for surgical intervention, intensive care or fatal outcome) were analysed in hospital-acquired Clostridium difficile infection (CDI) in a 777-bed community hospital. In a prospective analytical cross-sectional study, age (≥ 65 years), sex, CDI characteristics, underlying diseases, severity of comorbidity and PCR ribotypes were tested for associations with severe CDI. In total, 133 cases of hospital-acquired CDI (mean age 74.4 years) were identified, resulting in an incidence rate of 5.7/10,000 hospital-days. A recurrent episode of diarrhoea occurred in 25 cases (18.8%) and complications including toxic megacolon, dehydration and septicaemia in 69 cases (51.9%). Four cases (3.0%) required ICU admission, one case (0.8%) surgical intervention and 22 cases (16.5%) died within the 30-day follow-up period. Variables identified to be independently associated with severe CDI were severe diarrhoea (odds ratio [OR] 3.64, 95% confidence interval [CI] 1.19-11.11, p=0.02), chronic pulmonary disease (OR 3.0, 95% CI 1.08-8.40, p=0.04), chronic renal disease (OR 2.9, 95% CI 1.07-7.81, p=0.04) and diabetes mellitus (OR 4.30, 95% CI 1.57-11.76, p=0.004). The case fatality of 16.5% underlines the importance of increased efforts in CDI prevention, in particular for patients with underlying diseases.

  1. The frequency and severity of extinction after stroke affecting different vascular territories.

    PubMed

    Chechlacz, Magdalena; Rotshtein, Pia; Demeyere, Nele; Bickerton, Wai-Ling; Humphreys, Glyn W

    2014-02-01

    We examined the frequency and severity of visual versus tactile extinction based on data from a large group of sub-acute patients (n=454) with strokes affecting different vascular territories. After right hemisphere damage visual and tactile extinction were equally common. However, after left hemisphere damage tactile extinction was more common than visual. The frequency of extinction was significantly higher in patients with right compared to left hemisphere damage in both visual and tactile modalities but this held only for strokes affecting the MCA and PCA territories and not for strokes affecting other vascular territories. Furthermore, the severity of extinction did not differ as a function of either the stimulus modality (visual versus tactile), the affected hemisphere (left versus right) or the stroke territory (MCA, PCA or other vascular territories). We conclude that the frequency but not severity of extinction in both modalities relates to the side of damage (i.e. left versus right hemisphere) and the vascular territories affected by the stroke, and that left hemisphere dominance for motor control may link to the greater incidence of tactile than visual extinction after left hemisphere stroke. We discuss the implications of our findings for understanding hemispheric lateralization within visuospatial attention networks. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Side of symptom onset affects motor dysfunction in Parkinson's disease.

    PubMed

    Haaxma, C A; Helmich, R C G; Borm, G F; Kappelle, A C; Horstink, M W I M; Bloem, B R

    2010-11-10

    The healthy brain appears to have an asymmetric dopamine distribution, with higher levels of dopamine in the left than in the right striatum. Here, we test the hypothesis that this neurochemical asymmetry renders the right striatum relatively more vulnerable to the effects of dopaminergic denervation in Parkinson's disease (PD). Using the pegboard dexterity test, we compared motor performance of both hands between healthy subjects (n=48), PD patients with predominantly right-hemispheric dopamine depletion (PD-RIGHT; n=83) and PD patients with more severe left-hemispheric dopamine depletion (PD-LEFT; n=103). All subjects were right-handed. After adjusting for hand-dominance effects, we found that PD-RIGHT patients exhibited a 55% larger difference between right and left dexterity scores than PD-LEFT patients. This effect could be attributed to greater motor dysfunction of the more-affected hand in PD-RIGHT patients, while the less-affected hand performed similarly in both groups. We conclude that the side of symptom onset affects motor dysfunction in PD, and suggest that the non-dominant right hemisphere may be more susceptible to dopaminergic denervation than the dominant left hemisphere. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Treatment of severe generalized chronic periodontitis in a patient with Behçet's disease: A case report.

    PubMed

    Morikawa, Satoru; Ouchi, Takehito; Asoda, Seiji; Horie, Nobuyuki; Tsunoda, Kazuyuki; Kawana, Hiromasa; Nakagawa, Taneaki

    2018-05-01

    Behçet's disease is a systemic disorder of unknown etiology. It involves multiple organ systems and is characterized by recurring episodes of oral ulcers as well as ocular, genital, and skin lesions. Oral ulcers can affect tooth brushing and impair proper oral hygiene. As a result, a dental biofilm accumulates, and the condition of the teeth and periodontal tissue deteriorates. The aim of this case report is to highlight the efficacy of periodontal treatment for patients with Behçet's disease. A 51-year-old man with Behçet's disease presented with generalized severe periodontitis. After basic treatment of the periodontal tissues, periodontal surgery was performed at several sites with bony defects. However, the patient developed severe stomatitis in the oral mucosa and gingiva after periodontal surgery. Administration of the antimicrobial agent cefdinir had little effect on recovery; however, subsequent administration of sitafloxacin resulted in significant improvement of the stomatitis. This case demonstrates that periodontal therapy is very useful for alleviating the oral signs and symptoms of Behçet's disease. Systemic antibiotic treatment with sitafloxacin (but not cefdinir) and mechanical debridement were effective in preventing the recurrence of aphthous ulcer outbreaks after periodontal surgery.

  4. Risk factors affecting injury severity determined by the MAIS score.

    PubMed

    Ferreira, Sara; Amorim, Marco; Couto, Antonio

    2017-07-04

    Traffic crashes result in a loss of life but also impact the quality of life and productivity of crash survivors. Given the importance of traffic crash outcomes, the issue has received attention from researchers and practitioners as well as government institutions, such as the European Commission (EC). Thus, to obtain detailed information on the injury type and severity of crash victims, hospital data have been proposed for use alongside police crash records. A new injury severity classification based on hospital data, called the maximum abbreviated injury scale (MAIS), was developed and recently adopted by the EC. This study provides an in-depth analysis of the factors that affect injury severity as classified by the MAIS score. In this study, the MAIS score was derived from the International Classification of Diseases. The European Union adopted an MAIS score equal to or greater than 3 as the definition for a serious traffic crash injury. Gains are expected from using both police and hospital data because the injury severities of the victims are detailed by medical staff and the characteristics of the crash and the site of its occurrence are also provided. The data were obtained by linking police and hospital data sets from the Porto metropolitan area of Portugal over a 6-year period (2006-2011). A mixed logit model was used to understand the factors that contribute to the injury severity of traffic victims and to explore the impact of these factors on injury severity. A random parameter approach offers methodological flexibility to capture individual-specific heterogeneity. Additionally, to understand the importance of using a reliable injury severity scale, we compared MAIS with length of hospital stay (LHS), a classification used by several countries, including Portugal, to officially report injury severity. To do so, the same statistical technique was applied using the same variables to analyze their impact on the injury severity classified according to LHS

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

    PubMed

    Lackner, J M; Brasel, A M; Quigley, B M; Keefer, L; Krasner, S S; Powell, C; Katz, L A; Sitrin, M D

    2010-08-01

    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. Subjects were 105 Rome II diagnosed IBS patients (F = 85%) who completed seven questionnaires which were collected as part of a pretreatment baseline assessment. 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. 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.

  6. Correlation Of Deviance In Arterial Oxygenation With Severity Of Chronic Liver Disease.

    PubMed

    Shaukat, Al-Aman; Zar, Adnan; Zuhaid, Muhammad; Afridi, Safa Saadat

    2016-01-01

    Hepatitis B and C related chronic liver diseases have led to development of a serious threat to the people of South Asia. The main aim of this study was to evaluate the correlation of magnitude of arterial deoxygention to the severity of liver disease. It was a hospital based cross-sectional descriptive study, carried out in the Medical Department of Khyber Teaching Hospital Peshawar. All in all 115 patients were assessed for the severity of the liver diseases and were correlated with arterial deoxygenation using linear regression models. Male to female ratio was 1.5:1. Males infected with hepatitis B, hepatitis C and both were 9, 60 and 1, while females suffered from hepatitis B, Hepatitis C and both were 2, 42 and 1 respectively. The linear relationship between A-a DO2 with severity of liver disease showed positive correlation while PO2 showed negative correlation with severity of liver disease. There was a positive correlation between A-a DO2 and severity of liver diseases while PO2 and severity of liver diseases showed negative correlation.

  7. Germline Missense Mutations Affecting KRAS Isoform B Are Associated with a Severe Noonan Syndrome Phenotype

    PubMed Central

    Carta, Claudio; Pantaleoni, Francesca; Bocchinfuso, Gianfranco; Stella, Lorenzo; Vasta, Isabella; Sarkozy, Anna; Digilio, Cristina; Palleschi, Antonio; Pizzuti, Antonio; Grammatico, Paola; Zampino, Giuseppe; Dallapiccola, Bruno; Gelb, Bruce D.; Tartaglia, Marco

    2006-01-01

    Noonan syndrome (NS) is a developmental disorder characterized by short stature, facial dysmorphia, congenital heart disease, and multiple skeletal and hematologic defects. NS is an autosomal dominant trait and is genetically heterogeneous. Gain of function of SHP-2, a protein tyrosine phosphatase that positively modulates RAS signaling, is observed in nearly 50% of affected individuals. Here, we report the identification of heterozygous KRAS gene mutations in two subjects exhibiting a severe NS phenotype with features overlapping those of cardiofaciocutaneous and Costello syndromes. Both mutations were de novo and affected exon 6, which encodes the C-terminal portion of KRAS isoform B but does not contribute to KRAS isoform A. Structural analysis indicated that both substitutions (Val152Gly and Asp153Val) perturb the conformation of the guanine ring–binding pocket of the protein, predicting an increase in the guanine diphosphate/guanine triphosphate (GTP) dissociation rate that would favor GTP binding to the KRASB isoform and bypass the requirement for a guanine nucleotide exchange factor. PMID:16773572

  8. Other Factors That Affect Heart Disease: Birth Control Pills

    MedlinePlus

    ... Heart Handbook for Women Other Factors That Affect Heart Disease Birth Control Pills Studies show that women who ... t had any more complications because of my heart disease." — Diane Pay attention to diabetes. Levels of glucose, ...

  9. 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.

  10. [Prevalence of severe periodontal disease and its association with respiratory disease in hospitalized adult patients in a tertiary care center].

    PubMed

    Fernández-Plata, Rosario; Olmedo-Torres, Daniel; Martínez-Briseño, David; García-Sancho, Cecilia; Franco-Marina, Francisco; González-Cruz, Herminia

    2015-01-01

    Severe periodontal disease is a chronic inflammatory gingival process associated with systemic diseases. To determine the prevalence of severe periodontal disease and its association with respiratory diseases among hospitalized patients at the Institute of Respiratory Diseases "Ismael Cosio Villegas" (INER) in 2011. A cross-sectional study was developed. The severe periodontal disease was diagnosed by the Department of Stomatology. The International Classification of Diseases 10th revision was used. A multinomial logistic was fit to estimate relative-risk. Three thousand and fifty-nine patients were included; 772/3,059 (25.2%) had severe periodontal disease. After controlling for age, sex, inpatient days, death, and socioeconomic status, the infectious respiratory diseases that were significantly associated with severe periodontal disease were: HIV/AIDS (RR: 10.6; 95% CI: 9.1-23.3; p < 0.0001); pneumonia (RR: 2.6; 95% CI: 2.2-5.7; p < 0.0001); pulmonary tuberculosis and its sequels (RR: 2.1; 95% CI: 1.6-4.9; p < 0.0001); and lung abscess (RR: 2.6; 95% CI: 1.6-7.8; p = 0.002). Lung cancer and pleural diseases were also significantly associated with severe periodontal disease. High prevalence of severe periodontal disease was observed in the different respiratory diseases. Severe periodontal disease was associated with both infectious and non-infectious respiratory diseases. It is important to study an oral health intervention.

  11. What affects the quality of life in autoimmune Addison's disease?

    PubMed

    Meyer, G; Hackemann, A; Penna-Martinez, M; Badenhoop, K

    2013-02-01

    Several studies have shown a reduced quality of life in patients with Addison's disease, but little is known about the potential influences. We determined the quality of life in 200 patients with Addison's disease using an Addison's disease-specific quality-of-life questionnaire. Data about first symptoms, time to diagnosis and current medication were collected by questionnaires. With increasing latency between first symptoms and diagnosis of adrenal insufficiency, the quality of life decreased in highly significant manner (p<0.001). Age at manifestation correlated negatively with quality of life (p=0.01). Significantly lower scores were observed in females versus males (141 vs. 159, p<0.001). Quality of life decreased significantly with increasing autoimmune comorbidity (p=0.01). Coeliac disease (p=0.05), atrophic gastritis (p=0.01) and primary ovarian failure (p=0.01) were highly correlated with reduced scores. Quality of life was significantly lower in female patients and in those with manifestation at older ages. With more autoimmune comorbidities, the quality of life scores dropped. The most important factor, however, was latency between first symptoms and diagnosis that affected patients' quality of life even years after manifestation of the disease. These results confirm and extend previous observations and emphasize the importance of a timely diagnosis. Therefore, medical awareness for this rare but easily treatable disorder needs to be sharpened. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Pulmonary MR imaging with ultra-short TEs: utility for disease severity assessment of connective tissue disease patients.

    PubMed

    Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Takenaka, Daisuke; Takahashi, Masaya; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Obara, Makoto; van Cauteren, Marc; Sugimura, Kazuro

    2013-08-01

    To evaluate the utility of pulmonary magnetic resonance (MR) imaging with ultra-short echo times (UTEs) at a 3.0 T MR system for pulmonary functional loss and disease severity assessments of connective tissue disease (CTD) patients with interstitial lung disease (ILD). This prospective study was approved by the institutional review board, and written informed consent was obtained from 18 CTD patients (eight men and ten women) and eight normal subjects with suspected chest disease (three men and five women). All subjects underwent thin-section MDCT, pulmonary MR imaging with UTEs, pulmonary function test and serum KL-6. Regional T2 maps were generated from each MR data set, and mean T2 values were determined from ROI measurements. From each thin-section MDCT data set, CT-based disease severity was evaluated with a visual scoring system. Mean T2 values for normal and CTD subjects were statistically compared by using Student's t-test. To assess capability for pulmonary functional loss and disease severity assessments, mean T2 values were statistically correlated with pulmonary functional parameters, serum KL-6 and CT-based disease severity. Mean T2 values for normal and CTD subjects were significantly different (p=0.0019) and showed significant correlations with %VC, %DLCO, serum KL-6 and CT-based disease severity of CTD patients (p<0.05). Pulmonary MR imaging with UTEs is useful for pulmonary functional loss and disease severity assessments of CTD patients with ILD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Glutamine supplementation for young infants with severe gastrointestinal disease.

    PubMed

    Brown, Jennifer V E; Moe-Byrne, Thirimon; McGuire, William

    2014-12-15

    Endogenous glutamine biosynthesis may be insufficient to meet the needs of people with severe gastrointestinal disease. Results from studies using experimental animal models of gastrointestinal disease have suggested that glutamine supplementation improves clinical outcomes. This review examines evidence on the effect of glutamine supplementation in young infants with severe gastrointestinal disease. To assess the effect of supplemental glutamine on mortality and morbidity in young infants with severe gastrointestinal disease. We searcheed the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014, Issue 8), MEDLINE, EMBASE, and CINAHL (from inception to September 2014), conference proceedings, and reference lists from previous reviews. Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in infants up to three months old (corrected for preterm birth if necessary) with severe gastrointestinal disease defined as a congenital or acquired gastrointestinal condition that is likely to necessitate providing parenteral nutrition for at least 24 hours. Two review authors assessed trial eligibility and risk of bias and undertook data extraction independently. We analysed the treatment effects in the individual trials and reported the risk ratio (RR) and risk difference (RD) for dichotomous data and mean difference for continuous data, with 95% confidence intervals (CI). We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in sensitivity analyses. We found three trials in which a total of 274 infants participated. The trials were of good methodological quality but were too small to detect clinically important effects of glutamine supplementation. Meta-analyses did not reveal a statistically significant difference in the risk of death before hospital discharge (typical RR 0.79, 95% CI 0.19 to 3.20; typical RD -0.01, 95% CI -0.05 to 0.03) or

  14. Hyperthyroid vs hypothyroid eye disease: the same severity and activity

    PubMed Central

    Kashkouli, M B; Pakdel, F; Kiavash, V; Heidari, I; Heirati, A; Jam, S

    2011-01-01

    Purpose To compare demographics, severity, and activity of thyroid eye disease (TED) in patients with hyperthyroidism (Hr-TED) vs primary hypothyroidism (Ho-TED). Patients and Methods In a cross-sectional study, demographics, complete eye examination, severity score (NOSPECS, total hundred eye score), clinical activity score, and Rundle grading were recorded for patients with TED and different thyroid disorders referred from an endocrinology clinic from 2003 to 2006. Results TED was clinically found in 303 patients (303/851, 35.6%). The majority of them (280/303, 92.4%) had Graves' hyperthyroidism and 23 (23/303, 7.5%) had primary hypothyroidism. Mean age, gender, mean severity score, mean activity score, Rundle grade, unilateral presentation of TED, smoking habit, mean duration of eye disease, and mean interval time of thyroid to TED were not significantly different between the two groups (0.06disease was significantly (P=0.02) longer in the Hr-TED group (49.6 months) than in the Ho-TED group (22.7 months). Most of the patients in both groups (63.2% of Hr-TED and 73.9% of Ho-TED) developed the eye disease within 18 months before or after the thyroid disease. Conclusion The same demographics, clinical characteristics, and severity and activity scores for Hr-TED and Ho-TED imply that both groups present the same category of eye disease. PMID:21818129

  15. Plus Disease in Retinopathy of Prematurity: Improving Diagnosis by Ranking Disease Severity and Using Quantitative Image Analysis.

    PubMed

    Kalpathy-Cramer, Jayashree; Campbell, J Peter; Erdogmus, Deniz; Tian, Peng; Kedarisetti, Dharanish; Moleta, Chace; Reynolds, James D; Hutcheson, Kelly; Shapiro, Michael J; Repka, Michael X; Ferrone, Philip; Drenser, Kimberly; Horowitz, Jason; Sonmez, Kemal; Swan, Ryan; Ostmo, Susan; Jonas, Karyn E; Chan, R V Paul; Chiang, Michael F

    2016-11-01

    To determine expert agreement on relative retinopathy of prematurity (ROP) disease severity and whether computer-based image analysis can model relative disease severity, and to propose consideration of a more continuous severity score for ROP. We developed 2 databases of clinical images of varying disease severity (100 images and 34 images) as part of the Imaging and Informatics in ROP (i-ROP) cohort study and recruited expert physician, nonexpert physician, and nonphysician graders to classify and perform pairwise comparisons on both databases. Six participating expert ROP clinician-scientists, each with a minimum of 10 years of clinical ROP experience and 5 ROP publications, and 5 image graders (3 physicians and 2 nonphysician graders) who analyzed images that were obtained during routine ROP screening in neonatal intensive care units. Images in both databases were ranked by average disease classification (classification ranking), by pairwise comparison using the Elo rating method (comparison ranking), and by correlation with the i-ROP computer-based image analysis system. Interexpert agreement (weighted κ statistic) compared with the correlation coefficient (CC) between experts on pairwise comparisons and correlation between expert rankings and computer-based image analysis modeling. There was variable interexpert agreement on diagnostic classification of disease (plus, preplus, or normal) among the 6 experts (mean weighted κ, 0.27; range, 0.06-0.63), but good correlation between experts on comparison ranking of disease severity (mean CC, 0.84; range, 0.74-0.93) on the set of 34 images. Comparison ranking provided a severity ranking that was in good agreement with ranking obtained by classification ranking (CC, 0.92). Comparison ranking on the larger dataset by both expert and nonexpert graders demonstrated good correlation (mean CC, 0.97; range, 0.95-0.98). The i-ROP system was able to model this continuous severity with good correlation (CC, 0.86). Experts

  16. Are quality of family life and disease severity related in childhood atopic dermatitis?

    PubMed

    Ben-Gashir, M A; Seed, P T; Hay, R J

    2002-09-01

    Atopic dermatitis (AD) can be traumatizing to family life. Little is known about the relationship between quality of life in AD and disease severity. To document family quality of life and relate this to severity of AD in children, for a 6-month period from a given point in time. These data are part of a longitudinal study conducted in two parts of the UK to investigate risk factors for AD severity and its impact on quality of life. and methods Thetargetedpopulation comprised children with AD aged 5-10 years in a primary-care setting. The general practitioners identified potential subjects and the UK diagnostic criteria for AD were used to verify the diagnosis. Both the children and their parents were interviewed. Eczema severity was assessed using a modified form of the SCORAD (SCORe Atopic Dermatitis) Index (SCORAD-D) from which parents' score of itching and sleep loss were excluded. The quality of family life was quantified by the Dermatitis Family Impact (DFI) questionnaire. These two parameters were evaluated on two occasions 6 months apart. Multiple regression analysis was used to investigate the relationship between the quality of family life and the severity of the AD in the children, at a specific point in time and over the following 6-month period. Of the 116 children attending the first visit, mean age 8 years, 106 attended the second visit (91%) and were included in the analysis. Quality of family life was shown to be significantly affected in 48 (45%) cases at the first visit and 38 (36%) cases at the second visit. The initial means of the DFI and SCORAD-D were 2.4 and 8.2, respectively. Six months later the mean final DFI and SCORAD-D were 1.9 and 7.7, respectively. Using multiple regression on the first and second visits, each unit increase in SCORAD-D was associated with 0.21 [95% confidence interval (CI) 0.06-0.37 P = 0.008] and 0.37 (95% CI 0.15-0.59, P = 0.001) units increase in quality of family life, respectively. This relationship remained

  17. [The relation of severe obstructive disorders to ventilation found in young patients with bronchitis and bronchopulmonary diseases in childhood].

    PubMed

    Duţu, S; Jienescu, Z; Bîscă, N; Bistriceanu, G

    1989-01-01

    Of the patients with chronic obstructive pulmonary disease (COLD) and severe obstructive syndrome, 39 whose age was under 40 were selected. In 23 of them, the anamnesis revealed bronchopulmonary affections in childhood, that required admission into the hospital (19 were non-smokers). Of the rest of 16 patients, 14 were hard smokers that started to smoke before the age of 14. The functional picture was severely modified, similarly to that of the COLD patients in the 6th decade of life. This suggests that the degradation process started in the childhood, and that the chronic respiratory diseases and/or smoking at an early age had an important role.

  18. Correlation Between Symptom Severity and Health-Related Life Quality of a Population With Gastroesophageal Reflux Disease.

    PubMed

    Lee, Shou-Wu; Lee, Teng-Yu; Lien, Han-Chung; Peng, Yen-Chun; Yeh, Hong-Jeh; Chang, Chi-Sen

    2017-04-01

    Gastroesophageal reflux disease (GERD) is a chronic disease with a negative impact on the quality of life. The aim of this study was to investigate the reflux symptoms and the health-related quality of life in a population with GERD. Data from patients with GERD, according to the Montreal definition, were collected between January and December 2009. The enrolled patients were classified by different reflux symptoms according to the modified Chinese GERDQ. The general demographic data, the modified GERD impact scores and the SF-36 questionnaire scores of these groups of patients were analyzed. A total of 173 patients were enrolled, and the general data, endoscopic findings and lifestyle habits of the participants with different severity of heartburn or regurgitation were all similar. The patients with moderate severity of reflux symptoms had significant lower SF-36 scores than those with mild severity. The cases with advanced heartburn severity owned the lowest scores among all cases. The impact on the daily activity of each affected individual had a positive association with the stronger severity of reflux symptom. The life quality of a population with GERD achieved the meaningful declination in participants with the moderate severity of heartburn or regurgitation. The severity of the reflux symptoms had a greater impact on the normal daily activity of the patients with GERD. The cases with advanced severity of heartburn had the worst well-being.

  19. Severe Legionnaire's disease requiring intensive care treatment.

    PubMed

    van Riemsdijk-van Overbeeke, I C; van den Berg, B

    1996-11-01

    Legionnaire's disease is well known as severe pneumonia requiring intensive care treatment in many cases. In this study the clinical course is described of patients admitted to the medical ICU of the University Hospital of Rotterdam for respiratory distress due to Legionnaire's disease. From the register of admissions to the medical ICU all patients suffering from Legionnaire's disease were identified. All data on clinical signs and symptoms present on admission were collected. The circumstances in which the infections were contracted were sought, as well as the tests establishing the diagnosis. The occurrence of various organ failures and complications were noted, as were the causes of death on the ICU. From 1978 till 1995 the diagnosis of Legionella pneumonia was made in 17 patients admitted to the ICU: in 13 patients a community-acquired infection was established. As in 12 patients Legionnaire's disease was diagnosed on serological tests, it took several weeks before the diagnosis could be established in these patients. In all patients the circumstances predisposing to Legionnaire's disease were noted. Respiratory distress was present in all patients, ventilatory support was required in 14. Apart from this, both profound shock and renal failure were commonly encountered. As complications jaundice, rhabdomyolysis and polyneuropathy were frequently noted. Three patients died: 2 due to irreversible shock and 1 due to hospital-acquired sepsis. Legionnaire's disease can develop into life-threatening pneumonia requiring intensive care treatment in previously healthy subjects. As the clinical features are aspecific, careful search for predisposing circumstances such as recent travel or use of a contaminated water-supply is mandatory. As the diagnosis required positive serological tests in most patients, a considerable delay in diagnosis was noted. Despite the frequent occurrence of multiple organ failure, a favourable outcome can be anticipated in most cases.

  20. Inherited neurovascular diseases affecting cerebral blood vessels and smooth muscle.

    PubMed

    Sam, Christine; Li, Fei-Feng; Liu, Shu-Lin

    2015-10-01

    Neurovascular diseases are among the leading causes of mortality and permanent disability due to stroke, aneurysm, and other cardiovascular complications. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Marfan syndrome are two neurovascular disorders that affect smooth muscle cells through accumulation of granule and osmiophilic materials and defective elastic fiber formations respectively. Moyamoya disease, hereditary hemorrhagic telangiectasia (HHT), microcephalic osteodysplastic primordial dwarfism type II (MOPD II), and Fabry's disease are disorders that affect the endothelium cells of blood vessels through occlusion or abnormal development. While much research has been done on mapping out mutations in these diseases, the exact mechanisms are still largely unknown. This paper briefly introduces the pathogenesis, genetics, clinical symptoms, and current methods of treatment of the diseases in the hope that it can help us better understand the mechanism of these diseases and work on ways to develop better diagnosis and treatment.

  1. 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

  2. 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

  3. [Effect of disease severity on upper extremity muscle strength, exercise capacity, and activities of daily living in individuals with pulmonary arterial hypertension].

    PubMed

    Özcan Kahraman, Buse; Özsoy, İsmail; Acar, Serap; Özpelit, Ebru; Akdeniz, Bahri; Sevinç, Can; Savcı, Sema

    2017-07-01

    Pulmonary arterial hypertension (PAH) is a rare disease. Although muscle strength, exercise capacity, quality of life, and activities of daily living of patients with PAH are affected, it is not known how they are affected by disease severity. The purpose of the present study was to investigate effects of disease severity on upper extremity muscle strength, exercise capacity, and performance of activities of daily living in patients with PAH. Twenty-five patients with disease severity classified according to the New York Heart Association (NYHA) as functional class II (n=14) or class III (n=11) were included in the study. Upper-extremity exercise capacity and limitations in performing activities of daily living were assessed with 6-minute pegboard and ring test (6PBRT) and the Milliken activities of daily living scale (MAS), respectively. Shoulder flexion, elbow extension, elbow flexion muscle strength, and handgrip strength were measured with dynamometer. There were no significant differences in age, gender, body mass index, or mean pulmonary artery pressure between groups (p>0.05). The 6PBRT, MAS, and elbow flexion (right) and grip strength (right and left) results were significantly lower in NYHA III group than in NYHA II group (p=0.004, p=0.002, p=0.043, p=0.002 and p=0.003, respectively). There was no significant difference in shoulder flexion, elbow flexion (left), or elbow extension between groups (p>0.05). Results suggest that upper extremity exercise capacity, elbow flexion muscle strength (right), and handgrip strength decrease and that limitations in activities of daily living grow as disease severity increases in patients with PAH. When planning rehabilitation programs, disease severity should be considered and evaluations and treatments for the upper extremities should be included.

  4. Genetic burden associated with varying degrees of disease severity in endometriosis

    PubMed Central

    Sapkota, Yadav; Attia, John; Gordon, Scott D.; Henders, Anjali K.; Holliday, Elizabeth G.; Rahmioglu, Nilufer; MacGregor, Stuart; Martin, Nicholas G.; McEvoy, Mark; Morris, Andrew P.; Scott, Rodney J.; Zondervan, Krina T.; Montgomery, Grant W.; Nyholt, Dale R.

    2015-01-01

    Endometriosis is primarily characterized by the presence of tissue resembling endometrium outside the uterine cavity and is usually diagnosed by laparoscopy. The most commonly used classification of disease, the revised American Fertility Society (rAFS) system to grade endometriosis into different stages based on disease severity (I to IV), has been questioned as it does not correlate well with underlying symptoms, posing issues in diagnosis and choice of treatment. Using two independent European genome-wide association (GWA) datasets and top-level classification of the endometriosis cases based on rAFS [minimal or mild (Stage A) and moderate-to-severe (Stage B) disease], we previously showed that Stage B endometriosis has greater contribution of common genetic variation to its aetiology than Stage A disease. Herein, we extend our previous analysis to four endometriosis stages [minimal (Stage I), mild (Stage II), moderate (Stage III) and severe (Stage IV) disease] based on the rAFS classification system and compared the genetic burden across stages. Our results indicate that genetic burden increases from minimal to severe endometriosis. For the minimal disease, genetic factors may contribute to a lesser extent than other disease categories. Mild and moderate endometriosis appeared genetically similar, making it difficult to tease them apart. Consistent with our previous reports, moderate and severe endometriosis showed greater genetic burden than minimal or mild disease. Overall, our results provide new insights into the genetic architecture of endometriosis and further investigation in larger samples may help to understand better the aetiology of varying degrees of endometriosis, enabling improved diagnostic and treatment modalities. PMID:25882541

  5. Clinical trials validate the severity of persistent Lyme disease symptoms.

    PubMed

    Cameron, Daniel J

    2009-02-01

    Persistent Lyme Disease Symptoms (PLDS) have included fatigue, headaches, poor concentration and memory, lightheadedness, joint pain, and mood disturbances. Evidence-based guidelines committees disagree over the severity of PLDS. The 2004 International Lyme and Associated Diseases Society (ILADS) concluded that PLDS are severe. The 2006 Infectious Disease Society of America (IDSA) guidelines committee concluded that PLDS are nothing more than the "aches and pains of daily living" and an ad hoc International Lyme group concluded that PLDS are "symptoms common in persons who have never had Lyme disease." Clinical trials validate the severity of persistent Lyme disease symptoms. There are 22 standardized instruments used to measure the severity of PLDS among the four published National Institutes of Health (NIH) sponsored double-blind randomized placebo-controlled trials (RCTs). VALIDATING THE HYPOTHESIS: All four NIH sponsored RCTs validate the severity of PLDS. PLDS are as severe as symptoms seen in other serious chronic illnesses, and result in a quality of life lower than for the general population as determined by 22 standardized measures of QOL, including fatigue, pain, role function, psychopathology, and cognition. None of the four RCTs support the IDSA hypothesis that PLDS are nothing more than "the aches and pains of daily living" nor the ad hoc International Lyme group conclusion that PLDS are "symptoms common in persons who have never had Lyme disease." If the QOL of life for these patients is as poor as for patients with other serious chronic diseases, their symptoms need to be addressed by their doctors. Studies differ as to the precise cause of PLDS, the most effective treatments, and whether a cure is possible. But the fact that there is disagreement is not a license for physicians to ignore or turn away patients complaining of PLDS, or to dismiss their symptoms as purely psychosomatic. For physicians, the goal or purpose of treating PLDS should be the

  6. 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.

  7. Brief Report: Incubation Period Duration and Severity of Clinical Disease Following Severe Acute Respiratory Syndrome Coronavirus Infection.

    PubMed

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

    2015-09-01

    Few previous studies have investigated the association between the severity of an infectious disease and the length of incubation period. We estimated the association between the length of the incubation period and the severity of infection with the severe acute respiratory syndrome coronavirus, using data from the epidemic in 2003 in Hong Kong. We estimated the incubation period of severe acute respiratory syndrome 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 associations between shorter incubation period and greater severity in both groups after adjusting for potential confounders. Our findings suggest that patients with a shorter incubation period went on to have more severe disease. Further studies are needed to investigate potential biological mechanisms for this association.

  8. How Do You Feel? Self-esteem Predicts Affect, Stress, Social Interaction, and Symptom Severity during Daily Life in Patients with Chronic Illness

    PubMed Central

    JUTH, VANESSA; SMYTH, JOSHUA M.; SANTUZZI, ALECIA M.

    2010-01-01

    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. PMID:18809639

  9. Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study.

    PubMed

    Sharma, Ram A; Varga, Andrew W; Bubu, Omonigho M; Pirraglia, Elizabeth; Kam, Korey; Parekh, Ankit; Wohlleber, Margaret; Miller, Margo D; Andrade, Andreia; Lewis, Clifton; Tweardy, Samuel; Buj, Maja; Yau, Po L; Sadda, Reem; Mosconi, Lisa; Li, Yi; Butler, Tracy; Glodzik, Lidia; Fieremans, Els; Babb, James S; Blennow, Kaj; Zetterberg, Henrik; Lu, Shou E; Badia, Sandra G; Romero, Sergio; Rosenzweig, Ivana; Gosselin, Nadia; Jean-Louis, Girardin; Rapoport, David M; de Leon, Mony J; Ayappa, Indu; Osorio, Ricardo S

    2018-04-01

    Recent evidence suggests that obstructive sleep apnea (OSA) may be a risk factor for developing mild cognitive impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood. To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. Data were derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 and 90, were nondepressed, and had a consensus clinical diagnosis of cognitively normal. Cerebrospinal fluid amyloid β was measured using ELISA. Subjects received Pittsburgh compound B positron emission tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device. We found that severity of OSA indices (AHIall [F 1,88  = 4.26; P < 0.05] and AHI4% [F 1,87  = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β 42 using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in AD PiB -mask (Alzheimer's disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask) most likely because of the small sample size, although there was a trend for AHIall (F 1,28  = 2.96, P = 0.09; and F 1,28  = 2.32, not significant, respectively). In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2-year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly.

  10. Extended geographic distribution of several Indo-Pacific coral reef diseases.

    PubMed

    Weil, E; Irikawa, A; Casareto, B; Suzuki, Y

    2012-03-20

    Other than coral bleaching, few coral diseases or diseases of other reef organisms have been reported from Japan. This is the first report of lesions similar to Porites ulcerative white spots (PUWS), brown band disease (BrB), pigmentation response (PR), and crustose coralline white syndrome (CCWS) for this region. To assess the health status and disease prevalence, qualitative and quantitative surveys (3 belt transects of 100 m² each on each reef) were performed in March and September 2010 on 2 reefs of the Ginowan-Ooyama reef complex off Okinawa, and 2 protected reefs off Zamani Island, in the Kerama Islands 40 km west of Okinawa. Overall, mean (±SD) disease prevalence was higher in Ginowan-Ooyama (9.7 ± 7.9%) compared to Zamami (3.6 ± 4.6%). Porites lutea was most affected by PUWS at Ooyama (23.1 ± 10.4 vs. 4.5 ± 5.2%). White syndrome (WS) mostly affected Acropora cytherea (12. 5 ± 18.0%) in Zamami and Oxipora lacera (10.2 ± 10%) in Ooyama. Growth anomalies (GA) and BrB were only observed on A. cytherea (8.3 ± 6.2%) and A. nobilis (0.8%) at Zamami. Black band disease affected Pachyseris speciosa (6.0 ± 4.6%) in Ooyama only. Pigmentation responses (PR) were common in massive Porites in both localities (2.6 ± 1.9 and 5.6 ± 2.3% respectively). Crustose coralline white syndrome (CCWS) was observed in both localities. These results significantly expand the geographic distribution of PUWS, BrB, PR and CCWS in the Indo-Pacific, indicating that the northernmost coral reefs in the western Pacific are susceptible to a larger number of coral diseases than previously thought.

  11. The impact of social and psychological consequences of disease on judgments of disease severity: An experimental study.

    PubMed

    King, Nicholas B; Harper, Sam; Young, Meredith; Berry, Sarah C; Voigt, Kristin

    2018-01-01

    The Global Burden of Disease (GBD) project systematically assesses mortality, healthy life expectancy, and disability across 195 countries and territories, using the disability-adjusted life year (DALY). Disability weights in the DALY are based upon surveys that ask users to rate health states based on lay descriptions. We conducted an experimental study to examine whether the inclusion or removal of psychological, social, or familial implications from a health state description might affect individual judgments about disease severity, and thus relative disability weights. We designed a survey consisting of 36 paired descriptions in which information about plausible psychological, social, or familial implications of a health condition was either present or absent. Using a Web-based platform, we recruited 1,592 participants, who were assigned to one of two experimental groups, each of which were asked to assign a value to the health state description from 0 to 100 using a slider, with 0 as the "worst possible health" and 100 as the "best possible health." We tested five hypotheses: (1) the inclusion of psychological, social, or familial consequences in health state descriptions will reduce the average rating of a health state; (2) the effect will be stronger for diseases with lower disability weights (i.e., less severe diseases); (3) the effect will vary across the type of additional information added to the health state description; (4) the impact of adding information on familial consequences will be stronger for female than male; (5) the effect of additional consequences on ratings of health state descriptions will not differ by levels of completed education and age. On average, adding social, psychological, or familial consequences to the health state description lowered individual ratings of that description by 0.78 points. The impact of adding information had a stronger impact on ratings of the least severe conditions, reducing average ratings in this category

  12. Affective disorders and endocrine disease. New insights from psychosomatic studies.

    PubMed

    Fava, G A

    1994-01-01

    This is a review of psychosomatic interactions between affective disorders (depressive and anxiety disturbances, irritable mood) and endocrine disease. Particular reference is made to stressful life events in the pathogenesis of endocrine disease, psychopathology of hormonal disturbances, and pathophysiology of hypothalamic-pituitary-adrenal axis function in depression and Cushing's disease. These psychosomatic interactions may lead to appraisal of common etiological mechanisms in endocrine and psychiatric disorders, of the value of retaining the category of organic affective syndromes in psychiatric classification, and of the need for research on quality-of-life measures in endocrine disease. The establishment of "psychoendocrine units," where both endocrinologists and psychiatrists should work, is advocated. Such psychoendocrine units may serve and benefit clinical populations who currently defy traditional medical subdivisions.

  13. Fatigue in sarcoidosis and idiopathic pulmonary fibrosis: differences in character and severity between diseases.

    PubMed

    Atkins, Christopher Peter; Gilbert, Daniel; Brockwell, Claire; Robinson, Sue; Wilson, Andrew Malcolm

    2016-08-01

    Sarcoidosis and idiopathic pulmonary fibrosis (IPF) are two common forms of interstitial lung disease. Fatigue is a recognised feature of sarcoidosis but an association between IPF and fatigue has not been investigated. To investigate the frequency and severity of fatigue in these groups, and variables affecting fatigue scores. A cross-sectional questionnaire study of patients with sarcoidosis and IPF followed-up at a single hospital was undertaken. Questionnaire data included validated measures of fatigue, anxiety, depression, sleepiness and dyspnoea, plus measures of disease severity including spirometry data. Questionnaires were administered to 232 patients (82 healthy volunteers, 73 sarcoidosis patients and 77 IPF patients). Sarcoidosis patients had statistically higher sleepiness scores but no significant difference was seen between overall measures of fatigue, anxiety or depression. Stratification by severity revealed a non-statistically significant tendency towards more severe fatigue scores in sarcoidosis. Regression analysis failed to identify any significant predictor variables measured in the sarcoidosis cohort, though in the IPF group both dyspnoea and sleepiness scores were significant predictors of fatigue (R2=0.74). Both sarcoidosis and IPF patients suffer with fatigue, although sarcoidosis patients tended towards reporting more severe fatigue scores, suggesting a subgroup with severe fatigue. The fatigue experienced by the two groups appears to be different; sarcoidosis patients report greater frequency of mental fatigue whereas IPF patients appear to suffer exhaustion, potentially related to dyspnoea. Dyspnoea and sleepiness scores modeled the majority of fatigue in the IPF group, whereas no single factor was able to predict fatigue in sarcoidosis.

  14. Disease Control Among Patients With Diabetes and Severe Depressive Symptoms.

    PubMed

    Werremeyer, Amy; Maack, Brody; Strand, Mark A; Barnacle, Mykell; Petry, Natasha

    2016-04-01

    Major depressive disorder and type 2 diabetes commonly co-occur and disease control tends to be poorer when both conditions are present. However, little research has examined the disease characteristics of patients with diabetes and more severe depressive symptoms. We report a retrospective observational study of 517 patients with diabetes from 2 primary care centers. Patients with diabetes and moderately-severe/severe depression symptoms (Patient Health Questionnaire [PHQ-9] score >15) were compared with patients with diabetes without moderate or severe depression symptoms (PHQ-9 score <15; the comparison group) with regard to control of diabetes, blood pressure, and lipid parameters. Frequency of HbA1c and PHQ-9 testing were also examined. Patients with diabetes and moderately severe/severe depressive symptoms had higher HbA1c (7.56% vs. 7.09%), diastolic blood pressure (78.43 vs. 75.67 mm Hg), and low-density lipoprotein cholesterol (109.12 vs. 94.22 mg/dL) versus the comparison group. Patients with diabetes and moderately-severe/severe depression underwent HbA1c and PHQ-9 testing with similar frequency to the comparison group. The presence of moderately severe/severe depressive symptoms was associated with poorer glucose, lipid, and blood pressure control among patients with diabetes. Further research should prospectively examine whether a targeted depression treatment goal (PHQ-9 score <15) in patients with diabetes results in improved control of these important disease parameters. © The Author(s) 2016.

  15. A Different Microbiome Gene Repertoire in the Airways of Cystic Fibrosis Patients with Severe Lung Disease

    PubMed Central

    Bacci, Giovanni; Fiscarelli, Ersilia; Taccetti, Giovanni; Dolce, Daniela; Paganin, Patrizia; Morelli, Patrizia; Tuccio, Vanessa; De Alessandri, Alessandra; Lucidi, Vincenzina

    2017-01-01

    In recent years, next-generation sequencing (NGS) was employed to decipher the structure and composition of the microbiota of the airways in cystic fibrosis (CF) patients. However, little is still known about the overall gene functions harbored by the resident microbial populations and which specific genes are associated with various stages of CF lung disease. In the present study, we aimed to identify the microbial gene repertoire of CF microbiota in twelve patients with severe and normal/mild lung disease by performing sputum shotgun metagenome sequencing. The abundance of metabolic pathways encoded by microbes inhabiting CF airways was reconstructed from the metagenome. We identified a set of metabolic pathways differently distributed in patients with different pulmonary function; namely, pathways related to bacterial chemotaxis and flagellar assembly, as well as genes encoding efflux-mediated antibiotic resistance mechanisms and virulence-related genes. The results indicated that the microbiome of CF patients with low pulmonary function is enriched in virulence-related genes and in genes encoding efflux-mediated antibiotic resistance mechanisms. Overall, the microbiome of severely affected adults with CF seems to encode different mechanisms for the facilitation of microbial colonization and persistence in the lung, consistent with the characteristics of multidrug-resistant microbial communities that are commonly observed in patients with severe lung disease. PMID:28758937

  16. 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

  17. Influence of Disease Severity and Exercise Limitation on Exercise Training Intensity and Load and Health Benefits From Pulmonary Rehabilitation in Patients with COPD: AN EXPLORATORY STUDY.

    PubMed

    Huynh, Virginia C; Fuhr, Desi P; Byers, Bradley W; Selzler, Anne-Marie; Moore, Linn E; Stickland, Michael K

    2018-04-11

    Some patients with chronic obstructive pulmonary disease (COPD) fail to achieve health benefits with pulmonary rehabilitation (PR). Exercise intensity and load represent stimulus for adaptation but it is unclear whether inappropriate exercise intensity and/or load are affected by severity of COPD, which may affect health benefits. The purpose was to determine whether COPD severity and/or the severity of pulmonary limitation to exercise (PLE) impacted exercising intensity or load and whether resultant intensity/load affected health outcomes derived from PR. Patients with COPD (n = 58, age = 67 ± 7 y, forced expiratory volume in the first second of expiration [FEV1] % predicted = 52 ± 21%) were recruited upon referral to PR. Primary health outcomes evaluated were 6-min walk distance and St George's Respiratory Questionnaire. Patients were stratified for disease severity using Global Initiative for Obstructive Lung Disease (GOLD) staging and PLE severity by change in inspiratory capacity during exercise. Exercise intensity and load were calculated from daily exercise records. Participants achieved comparable training duration and load regardless of GOLD severity. Patients with more severe PLE achieved greater training duration (more severe: 546 ± 143 min., less severe: 451 ± 109 min., P = .036), and relative training load (more severe: 2200.8 ± 595.3 kcal, less severe: 1648.3 ± 597.8 kcal, P = .007). Greater overall training load was associated with greater improvements in 6-min walk distance (r = 0.24, P = .035). No significant relationships were observed between PLE, GOLD severity, training parameters, and St George's Respiratory Questionnaire response. Improvements in exercise tolerance can be explained by achieving greater training loads, demonstrating the importance of appropriate training load to maximize health outcomes in PR.

  18. Inoculum reduction measures to manage Armillaria root disease in a severely infected stand of ponderosa pine in south-central Washington: 35-year results

    Treesearch

    Charles G. Shaw; D.W. Omdal; A. Ramsey-Kroll; L.F. Roth

    2012-01-01

    A stand of ponderosa pine (Pinus ponderosa) severely affected by Armillaria root disease was treated with five different levels of sanitation by root removal to reduce root disease losses in the regenerating stand. Treatments included the following: (1) all trees pushed over by machine, maximum removal of roots by machine ripping, and visible...

  19. Type D personality is related to severity of acute coronary syndrome in patients with recurrent cardiovascular disease.

    PubMed

    Garcia-Retamero, Rocio; Petrova, Dafina; Arrebola-Moreno, Antonio; Catena, Andrés; Ramírez-Hernández, José A

    2016-09-01

    syndrome in patients with previous history of cardiovascular disease. This effect is partially accounted for by lower HDL levels in Type D patients. Disease severity is a potential mechanism by which Type D personality may affect cardiovascular health of patients with recurrent CVD. © 2016 The British Psychological Society.

  20. Identification of Histological Patterns in Clinically Affected and Unaffected Palm Regions in Dupuytren's Disease

    PubMed Central

    Alfonso-Rodríguez, Camilo-Andrés; Garzón, Ingrid; Garrido-Gómez, Juan; Oliveira, Ana-Celeste-Ximenes; Martín-Piedra, Miguel-Ángel; Scionti, Giuseppe; Carriel, Víctor; Hernández-Cortés, Pedro; Campos, Antonio; Alaminos, Miguel

    2014-01-01

    Dupuytren's disease is a fibro-proliferative disease characterized by a disorder of the extracellular matrix (ECM) and high myofibroblast proliferation. However, studies failed to determine if the whole palm fascia is affected by the disease. The objective of this study was to analyze several components of the extracellular matrix of three types of tissues—Dupuytren's diseased contracture cords (DDC), palmar fascia clinically unaffected by Dupuytren's disease contracture (NPF), and normal forehand fascia (NFF). Histological analysis, quantification of cells recultured from each type of tissue, mRNA microarrays and immunohistochemistry for smooth muscle actin (SMA), fibrillar ECM components and non-fibrillar ECM components were carried out. The results showed that DDC samples had abundant fibrosis with reticular fibers and few elastic fibers, high cell proliferation and myofibroblasts, laminin and glycoproteins, whereas NFF did not show any of these findings. Interestingly, NPF tissues had more cells showing myofibroblasts differentiation and more collagen and reticular fibers, laminin and glycoproteins than NFF, although at lower level than DDC, with similar elastic fibers than DDC. Immunohistochemical expression of decorin was high in DDC, whereas versican was highly expressed NFF, with no differences for aggrecan. Cluster analysis revealed that the global expression profile of NPF was very similar to DDC, and reculturing methods showed that cells corresponding to DDC tissues proliferated more actively than NPF, and NPF more actively than NFF. All these results suggest that NPF tissues may be affected, and that a modification of the therapeutic approach used for the treatment of Dupuytren's disease should be considered. PMID:25379672

  1. Identification of histological patterns in clinically affected and unaffected palm regions in dupuytren's disease.

    PubMed

    Alfonso-Rodríguez, Camilo-Andrés; Garzón, Ingrid; Garrido-Gómez, Juan; Oliveira, Ana-Celeste-Ximenes; Martín-Piedra, Miguel-Ángel; Scionti, Giuseppe; Carriel, Víctor; Hernández-Cortés, Pedro; Campos, Antonio; Alaminos, Miguel

    2014-01-01

    Dupuytren's disease is a fibro-proliferative disease characterized by a disorder of the extracellular matrix (ECM) and high myofibroblast proliferation. However, studies failed to determine if the whole palm fascia is affected by the disease. The objective of this study was to analyze several components of the extracellular matrix of three types of tissues-Dupuytren's diseased contracture cords (DDC), palmar fascia clinically unaffected by Dupuytren's disease contracture (NPF), and normal forehand fascia (NFF). Histological analysis, quantification of cells recultured from each type of tissue, mRNA microarrays and immunohistochemistry for smooth muscle actin (SMA), fibrillar ECM components and non-fibrillar ECM components were carried out. The results showed that DDC samples had abundant fibrosis with reticular fibers and few elastic fibers, high cell proliferation and myofibroblasts, laminin and glycoproteins, whereas NFF did not show any of these findings. Interestingly, NPF tissues had more cells showing myofibroblasts differentiation and more collagen and reticular fibers, laminin and glycoproteins than NFF, although at lower level than DDC, with similar elastic fibers than DDC. Immunohistochemical expression of decorin was high in DDC, whereas versican was highly expressed NFF, with no differences for aggrecan. Cluster analysis revealed that the global expression profile of NPF was very similar to DDC, and reculturing methods showed that cells corresponding to DDC tissues proliferated more actively than NPF, and NPF more actively than NFF. All these results suggest that NPF tissues may be affected, and that a modification of the therapeutic approach used for the treatment of Dupuytren's disease should be considered.

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

    PubMed Central

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

    2017-01-01

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

  3. A novel missense Norrie disease mutation associated with a severe ocular phenotype.

    PubMed

    Khan, Arif O; Shamsi, Farrukh A; Al-Saif, Amr; Kambouris, Marios

    2004-01-01

    Clinical findings and pedigree analysis led to the diagnosis of severe Norrie disease in two brothers. DNA sequencing demonstrated a novel missense mutation (703G>T) that significantly alters predicted protein structure. Less severe retinal developmental disease may be associated with milder mutations in the Norrie disease gene.

  4. Improvement of dysphagia in a child affected by Pompe disease treated with enzyme replacement therapy

    PubMed Central

    2013-01-01

    Aim Dysphagia is a known complication in Pompe Disease (PD), a severe metabolic myopathy due to alpha-glucosidase deficiency. Enzyme replacement therapy (ERT) with alglucosidase alfa is the only approved therapy for PD. Presently no data are available on the effects of ERT on dysphagia in PD patients. The aim of this work is to evaluate the course of this complication in a 6 years old boy affected by PD after treatment with ERT. Methods Dysphagia was assessed by Videofluoroscopic Swallowing Study (VFSS) at baseline, before the start of ERT and after 36 months of therapy. We used the Dysphagia Severity Rating Scale (DSS) to define the severity grade of dysphagia. Results VFSS performed at baseline revealed complete incoordination of oral stage swallowing which was classified as a grade 1 dysphagia according to DSS. After 36 months of treatment VFSS revealed normal swallowing, classified as grade 0 by DSS. Conclusion Our results suggest that ERT is effective in improving dysphagia. VFSS may be a useful tool to investigate and monitor swallowing disorders in patients affected by PD. PMID:23668440

  5. Clinical presentation and management of severe Ebola virus disease.

    PubMed

    West, T Eoin; von Saint André-von Arnim, Amélie

    2014-11-01

    Clinicians caring for patients infected with Ebola virus must be familiar not only with screening and infection control measures but also with management of severe disease. By integrating experience from several Ebola epidemics with best practices for managing critical illness, this report focuses on the clinical presentation and management of severely ill infants, children, and adults with Ebola virus disease. Fever, fatigue, vomiting, diarrhea, and anorexia are the most common symptoms of the 2014 West African outbreak. Profound fluid losses from the gastrointestinal tract result in volume depletion, metabolic abnormalities (including hyponatremia, hypokalemia, and hypocalcemia), shock, and organ failure. Overt hemorrhage occurs infrequently. The case fatality rate in West Africa is at least 70%, and individuals with respiratory, neurological, or hemorrhagic symptoms have a higher risk of death. There is no proven antiviral agent to treat Ebola virus disease, although several experimental treatments may be considered. Even in the absence of antiviral therapies, intensive supportive care has the potential to markedly blunt the high case fatality rate reported to date. Optimal treatment requires conscientious correction of fluid and electrolyte losses. Additional management considerations include searching for coinfection or superinfection; treatment of shock (with intravenous fluids and vasoactive agents), acute kidney injury (with renal replacement therapy), and respiratory failure (with invasive mechanical ventilation); provision of nutrition support, pain and anxiety control, and psychosocial support; and the use of strategies to reduce complications of critical illness. Cardiopulmonary resuscitation may be appropriate in certain circumstances, but extracorporeal life support is not advised. Among other ethical issues, patients' medical needs must be carefully weighed against healthcare worker safety and infection control concerns. However, meticulous attention

  6. Degenerative disease affecting the nervous system.

    PubMed

    Eadie, M J

    1974-03-01

    The term "degenerative disease" is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as "a change of structure by which an organism, or an organ, assumes the form of a lower type". However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body. Copyright © 1974 Australian Physiotherapy Association. Published by . All rights reserved.

  7. Pulmonary Veno-Occlusive Disease: A Newly Recognized Cause of Severe Pulmonary Hypertension in Dogs.

    PubMed

    Williams, K; Andrie, K; Cartoceti, A; French, S; Goldsmith, D; Jennings, S; Priestnall, S L; Wilson, D; Jutkowitz, A

    2016-07-01

    Pulmonary hypertension is a well-known though poorly characterized disease in veterinary medicine. In humans, pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension with a mean survival time of 2 years without lung transplantation. Eleven adult dogs (5 males, 6 females; median age 10.5 years, representing various breeds) were examined following the development of severe respiratory signs. Lungs of affected animals were evaluated morphologically and with immunohistochemistry for alpha smooth muscle actin, desmin, CD31, CD3, CD20, and CD204. All dogs had pulmonary lesions consistent with PVOD, consisting of occlusive remodeling of small- to medium-sized pulmonary veins, foci of pulmonary capillary hemangiomatosis (PCH), and accumulation of hemosiderophages; 6 of 11 dogs had substantial pulmonary arterial medial and intimal thickening. Ultrastructural examination and immunohistochemistry showed that smooth muscle cells contributed to the venous occlusion. Increased expression of CD31 was evident in regions of PCH indicating increased numbers of endothelial cells in these foci. Spindle cells strongly expressing alpha smooth muscle actin and desmin co-localized with foci of PCH; similar cells were present but less intensely labeled elsewhere in non-PCH alveoli. B cells and macrophages, detected by immunohistochemistry, were not co-localized with the venous lesions of canine PVOD; small numbers of CD3-positive T cells were occasionally in and around the wall of remodeled veins. These findings indicate a condition in dogs with clinically severe respiratory disease and pathologic features resembling human PVOD, including foci of pulmonary venous remodeling and PCH. © The Author(s) 2016.

  8. Murmur intensity in small-breed dogs with myxomatous mitral valve disease reflects disease severity.

    PubMed

    Ljungvall, I; Rishniw, M; Porciello, F; Ferasin, L; Ohad, D G

    2014-11-01

    To determine whether murmur intensity in small-breed dogs with myxomatous mitral valve disease reflects clinical and echocardiographic disease severity. Retrospective multi-investigator study. Records of adult dogs Ä20 kg with myxomatous mitral valve disease were examined. Murmur intensity and location were recorded and compared with echocardiographic variables and functional disease status. Murmur intensities in consecutive categories were compared for prevalences of congestive heart failure, pulmonary hypertension and cardiac remodelling. 578 dogs [107 with "soft" (30 Grade I/VI and 77 II/VI), 161 with "moderate" (Grade III/VI), 160 with "loud" (Grade IV/VI) and 150 with "thrilling" (Grade V/VI or VI/VI) murmurs] were studied. No dogs with soft murmurs had congestive heart failure, and 90% had no remodelling. However, 56% of dogs with "moderate", 29% of dogs with "loud" and 8% of dogs with "thrilling" murmurs and subclinical myxomatous mitral valve disease also had no remodelling. Probability of a dog having congestive heart failure or pulmonary hypertension increased with increasing murmur intensity. A 4-level murmur grading scheme separated clinically meaningful outcomes in small-breed dogs with myxomatous mitral valve disease. Soft murmurs in small-breed dogs are strongly indicative of subclinical heart disease. Thrilling murmurs are associated with more severe disease. Other murmurs are less informative on an individual basis. © 2014 British Small Animal Veterinary Association.

  9. The association between periodontal disease and seizure severity in refractory epilepsy patients.

    PubMed

    Costa, Andre L F; Yasuda, Clarissa Lin; Shibasaki, Wendel; Nahás-Scocate, Ana Carla Raphaelli; de Freitas, Claudio Fróes; Carvalho, Paulo Eduardo Guedes; Cendes, Fernando

    2014-03-01

    Periodontal diseases are common in most populations and affect people at all socioeconomic levels. Evidence suggests that patients with epilepsy actually have higher risks of dental disease and increased oral health needs, but the frequency and consequences of poor controlled seizures on dental and periodontal health have not been reported before. We aimed to assess the impact of seizure frequency on periodontal status and oral hygiene in a sample of epilepsy patients. One hundred and nine consecutive patients treated for epilepsy at the outpatient clinic of our University Hospital were invited to take part in an oral examination to determine their periodontal disease status, together with a control group. In addition, seizure frequency and use of medication were documented. In logistic regression model, patients were significantly more susceptible to bad oral hygiene, gingivitis and periodontitis that controls (p<0.001); seizure frequency was significantly related to bad oral hygiene (p=0.010), gingivitis (p<0.001) and periodontitis (p<0.001). Tooth brushing habits and presence of caries were associated with oral health in patients group. Our study found a significant positive correlation between periodontal disease and seizure severity. Epilepsy patients need to focus more on their oral health and quality of oral hygiene. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  10. Dysarthria of Motor Neuron Disease: Clinician Judgments of Severity.

    ERIC Educational Resources Information Center

    Seikel, J. Anthony; And Others

    1990-01-01

    This study investigated the relationship between the temporal-acoustic parameters of the speech of 15 adults with motor neuron disease. Differences in predictions of the progression of the disease and clinician judgments of dysarthria severity were found to relate to the linguistic systems of both speaker and judge. (Author/JDD)

  11. Severe systemic autoimmune disease associated with Epstein-Barr virus infection.

    PubMed

    Sevilla, Julián; del Carmen Escudero, Maria; Jiménez, Raquel; González-Vicent, Marta; Manzanares, Javier; García-Novo, Dolores; Madero, Luis

    2004-12-01

    Infection with Epstein-Barr virus (EBV) has been associated with different autoimmune manifestations. The authors describe a girl who developed a severe systemic autoimmune disease with severe autoimmune hemolytic anemia, mild autoimmune thrombopenia, antineutrophil antibodies, and fatal autoimmune hepatitis after EBV infection. Despite immunosuppressive treatment and ultimately liver transplantation, this patient could not overcome her clinical condition and died. The etiopathogenesis of this complex disease and the association with EBV infection is discussed.

  12. 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…

  13. Influenza and other respiratory viruses: standardizing disease severity in surveillance and clinical trials.

    PubMed

    Rath, Barbara; Conrad, Tim; Myles, Puja; Alchikh, Maren; Ma, Xiaolin; Hoppe, Christian; Tief, Franziska; Chen, Xi; Obermeier, Patrick; Kisler, Bron; Schweiger, Brunhilde

    2017-06-01

    Influenza-Like Illness is a leading cause of hospitalization in children. Disease burden due to influenza and other respiratory viral infections is reported on a population level, but clinical scores measuring individual changes in disease severity are urgently needed. Areas covered: We present a composite clinical score allowing individual patient data analyses of disease severity based on systematic literature review and WHO-criteria for uncomplicated and complicated disease. The 22-item ViVI Disease Severity Score showed a normal distribution in a pediatric cohort of 6073 children aged 0-18 years (mean age 3.13; S.D. 3.89; range: 0 to 18.79). Expert commentary: The ViVI Score was correlated with risk of antibiotic use as well as need for hospitalization and intensive care. The ViVI Score was used to track children with influenza, respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus infections and is fully compliant with regulatory data standards. The ViVI Disease Severity Score mobile application allows physicians to measure disease severity at the point-of care thereby taking clinical trials to the next level.

  14. Severe fetal and neonatal hyperthyroidism years after surgical treatment of maternal Graves' disease.

    PubMed

    Dierickx, I; Decallonne, B; Billen, J; Vanhole, C; Lewi, L; De Catte, L; Verhaeghe, J

    2014-02-01

    Fetal/neonatal hyperthyroidism is a well-known complication of maternal Graves' disease with high concentrations of TSH-receptor antibodies (TRAb). Few data are available on the management of fetal hyperthyroidism in surgically treated Graves' disease. Clinical, ultrasound and biochemical data are reported in a fetus/neonate whose mother underwent a thyroidectomy > 10 years before and whose sibling was thin and hyperthyroid at birth. Maternal TRAb were persistently > 40 U/l; unequivocal signs of fetal hyperthyroidism were identified at 29 weeks gestational age (GA). The fetus was treated through maternal antithyroid drug (ATD) administration; the dose was reduced gradually once fetal tachycardia and valve dysfunction disappeared and normal T4 was confirmed by fetal blood sampling. Maternal euthyroidism was maintained. The neonate showed normal growth for GA and T4 concentration at birth but severe hyperthyroidism relapsed from day 13 until day 58. TSH remained strongly suppressed throughout the pre- and postnatal course. Prenatal ATD in a taper-off regime allowed normal T4 and growth in a hyperthyroid fetus from a thyroidectomised Graves' mother. Fetal TSH cannot be used to adjust the ATD dose. Prenatal ATD appears to postpone the onset but does not affect the severity or duration of the neonatal hyperthyroid flare.

  15. 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

  16. An epidemiological study of immune-mediated skin diseases affecting the oral cavity.

    PubMed

    Carvalho, Cyntia Helena Pereira de; Santos, Bruna Rafaela Martins dos; Vieira, Camila de Castro; Lima, Emeline das Neves de Araújo; Santos, Pedro Paulo de Andrade; Freitas, Roseana de Almeida

    2011-01-01

    Immune-mediated skin diseases encompass a variety of pathologies that present in different forms in the body. The objective of this study was to establish the prevalence of the principal immune-mediated skin diseases affecting the oral cavity. A total of 10,292 histopathology reports stored in the archives of the Anatomical Pathology Laboratory, Department of Oral Pathology, Federal University of Rio Grande do Norte, covering the period from 1988 to 2009, were evaluated. For the cases diagnosed with some type of disease relevant to the study, clinical data such as the gender, age and ethnicity of the patient, the anatomical site of the disease and its symptomatology were collected. Of all the cases registered at the above-mentioned service, 82 (0.8%) corresponded to immune-mediated skin diseases with symptoms affecting the oral cavity. The diseases found in this study were: oral lichen planus, pemphigus vulgaris and benign mucous membrane pemphigoid. Oral lichen planus was the most common lesion, comprising 68.05% of the cases analyzed. Of these cases, 64.3% were women and the cheek mucosa was the anatomical site most commonly affected (46.8%). Immune-mediated skin diseases affecting the oral cavity continue to be rare, the prevalence found in this study being similar to that reported for the majority of regions worldwide. Nevertheless, early diagnosis is indispensable in the treatment of these diseases, bearing in mind that systemic involvement is possible in these patients.

  17. A Sickle Cell Disease Patient with Severe Tricuspid Regurgitation and Early Developed Pulmonary Hypertension.

    PubMed

    Vaidya, Gaurang; Sarwar, Muhammad; Sun, Zongxia; Wei, Tiemin; Liu, Kan

    2015-01-01

    Pulmonary hypertension (PH) worsens the mortality of the patients with sickle cell disease (SCD). The exact mechanism of PH development/progression in SCD, including the role of tricuspid regurgitation (TR), remains unclear. We herein report an unusual SCD case, complicated by chronic thromboembolic disorder, who developed severe TR and an accelerated progression of PH. Tricuspid valve surgery significantly ameliorated the patient's symptoms and reduced hospital readmission. The early detection and management of the reversible disorder accelerating the PH development in SCD patients may alter the clinical course, improve the quality of life, and potentially affect the long-term outcome.

  18. Type 2 diabetic patients with Graves' disease have more frequent and severe Graves' orbitopathy.

    PubMed

    Le Moli, R; Muscia, V; Tumminia, A; Frittitta, L; Buscema, M; Palermo, F; Sciacca, L; Squatrito, S; Vigneri, R

    2015-05-01

    Due to the worldwide increasing prevalence of diabetes (DM), patients with both diabetes and Graves' disease (GD) have become more frequent. Sporadic reports indicate that Graves' orbitopathy (GO), a GD complication that affects orbital soft tissues, can be severe in DM patients. The relationship between these diseases is not well understood. This study aims at evaluating the association of GD and GO with autoimmune and non-autoimmune diabetes (DM) and to assess diabetic features that influence GD and GO prevalence and severity. This retrospective study evaluated GD, GO and DM association in 1211 consecutive GD patients (447 with GO and 77 with DM). A case-control study was carried out to evaluate DM relationship with GO severity by comparing at 1:2 ratio GO patients with or without DM. A strong association was found between GD and T1DM (p = 0.01) but not T2DM. Instead, the presence of GO was strongly associated with T2DM (p = 0.01). Moreover, GO was more frequently severe in GD patients with T2DM (11/30 or 36.6%) than in those without T2DM (1/60 or 1.7%, p = 0.05). T2DM was the strongest risk factor for severe GO (OR = 34.1 vs. 4.4 p < 0.049 in cigarette smokers). DM duration, obesity and vascular complications, but not metabolic control were significant determinants of GO severity. GD is associated with T1DM but not with T2DM, probably because of the common autoimmune background. GO, in contrast, is more frequent and severe in T2DM, significantly associated with obesity, diabetes duration and diabetic vasculopathy but not metabolic control. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Empirical Wavelet Transform Based Features for Classification of Parkinson's Disease Severity.

    PubMed

    Oung, Qi Wei; Muthusamy, Hariharan; Basah, Shafriza Nisha; Lee, Hoileong; Vijean, Vikneswaran

    2017-12-29

    Parkinson's disease (PD) is a type of progressive neurodegenerative disorder that has affected a large part of the population till now. Several symptoms of PD include tremor, rigidity, slowness of movements and vocal impairments. In order to develop an effective diagnostic system, a number of algorithms were proposed mainly to distinguish healthy individuals from the ones with PD. However, most of the previous works were conducted based on a binary classification, with the early PD stage and the advanced ones being treated equally. Therefore, in this work, we propose a multiclass classification with three classes of PD severity level (mild, moderate, severe) and healthy control. The focus is to detect and classify PD using signals from wearable motion and audio sensors based on both empirical wavelet transform (EWT) and empirical wavelet packet transform (EWPT) respectively. The EWT/EWPT was applied to decompose both speech and motion data signals up to five levels. Next, several features are extracted after obtaining the instantaneous amplitudes and frequencies from the coefficients of the decomposed signals by applying the Hilbert transform. The performance of the algorithm was analysed using three classifiers - K-nearest neighbour (KNN), probabilistic neural network (PNN) and extreme learning machine (ELM). Experimental results demonstrated that our proposed approach had the ability to differentiate PD from non-PD subjects, including their severity level - with classification accuracies of more than 90% using EWT/EWPT-ELM based on signals from motion and audio sensors respectively. Additionally, classification accuracy of more than 95% was achieved when EWT/EWPT-ELM is applied to signals from integration of both signal's information.

  20. Results of home parenteral nutrition in patients with severe inflammatory bowel disease - an alternative for surgery of malnourished patients.

    PubMed

    Turkot, Maryla; Sobocki, Jacek

    2017-10-31

    In the world, the inflammatory bowel disease affects an increasing number of younger and younger patients, and in some of them parenteral nutrition is an alternative to high-risk surgical intervention due to advancement of the disease and malnutrition. The aim of the study was to assess the results of home parenteral nutrition in patients with severe bowel inflammatory disease, in whom surgical treatment is associated with high risk of complications. A retrospective analysis was conducted on 46 patients, who received home parenteral nutrition instead of another surgical intervention. The inclusion criteria included home parenteral nutrition and diagnosis of Crohn's disease or ulcerative colitis. Mean number of complications requiring hospital admission per patient was 1.76, the BMI increased by 4.3 on average [kg/m2]. During parenteral nutrition, the percentage of patients, in whom anti-inflammatory or immunosuppressant drugs were completely discontinued, was 17.4%. In the whole group, at least one immunosuppressive drug was discontinued in onefifth of patients. Mean albumin level increased by 2.4 g/L, lymphocyte count dropped by 474 lymphocytes/mm3, and leukocyte count increased by 747.6/mm3. The patients described their condition as good in 87%, and 7.4% of patients were able to work. Home parenteral nutrition positively affects patient's general condition by increasing BMI and normalizing biochemical test results. The results indicate the need to consider this method as an alternative to surgical intervention in severe bowel inflammatory disease with high perioperative risk, which could reduce the complication rate.

  1. Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice

    PubMed Central

    Khare, Sanjay D.; Sarosi, Ildiko; Xia, Xing-Zhong; McCabe, Susan; Miner, Kent; Solovyev, Irina; Hawkins, Nessa; Kelley, Michael; Chang, David; Van, Gwyneth; Ross, Larry; Delaney, John; Wang, Ling; Lacey, David; Boyle, William J.; Hsu, Hailing

    2000-01-01

    TALL-1/Blys/BAFF is a member of the tumor necrosis factor (TNF) ligand superfamily that is functionally involved in B cell proliferation. Here, we describe B cell hyperplasia and autoimmune lupus-like changes in transgenic mice expressing TALL-1 under the control of a β-actin promoter. The TALL-1 transgenic mice showed severe enlargement of spleen, lymph nodes, and Peyer's patches because of an increased number of B220+ cells. The transgenic mice also had hypergammaglobulinemia contributed by elevations of serum IgM, IgG, IgA, and IgE. In addition, a phenotype similar to autoimmune lupus-like disease was also seen in TALL-1 transgenic mice, characterized by the presence of autoantibodies to nuclear antigens and immune complex deposits in the kidney. Prolonged survival and hyperactivity of transgenic B cells may contribute to the autoimmune lupus-like phenotype in these animals. Our studies further confirm TALL-1 as a stimulator of B cells that affect Ig production. Thus, TALL-1 may be a primary mediator in B cell-associated autoimmune diseases. PMID:10716715

  2. Phenomenology and family history of affective disorder in Cushing's disease.

    PubMed

    Hudson, J I; Hudson, M S; Griffing, G T; Melby, J C; Pope, H G

    1987-07-01

    Of 16 patients with Cushing's disease, 13 (81%) had lifetime diagnoses of major affective disorder according to DSM-III criteria. However, the rate of familial major affective disorder among these patients was significantly lower than that found among patients with major depression.

  3. Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease.

    PubMed

    Modena, Brian D; Bleecker, Eugene R; Busse, William W; Erzurum, Serpil C; Gaston, Benjamin M; Jarjour, Nizar N; Meyers, Deborah A; Milosevic, Jadranka; Tedrow, John R; Wu, Wei; Kaminski, Naftali; Wenzel, Sally E

    2017-06-01

    Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Identify networks of genes reflective of underlying biological processes that define SA. Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12-21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes.

  4. [Pathway to diagnosis and real-life experience of patients believing they are affected by "chronic Lyme disease"].

    PubMed

    Forestier, E; Gonnet, F; Revil-Signorat, A; Zipper, A C

    2018-04-26

    Chronic Lyme disease is a subject of scientific and social controversy in both Europe and the United States. The aim of our study was to analyze the pathway to diagnosis of patients believing they were affected by the disease, and to describe their real-life experience. A qualitative study was performed with 13 patients declaring themselves to be affected by chronic Lyme disease. Interviews were analyzed by 2 general medical practice interns, supervised by a general practitioner with a diploma in socio-anthropology and an infectious diseases specialist. Internet and other media played a major role in informing the patients or their doctor about the existence and the characteristics of chronic Lyme disease. The diagnosis was confirmed by features considered objective (chronic infection by Borrelia, tick bite, positive serology, beneficial or worsening effects of antibiotics). The long medical diagnosis and treatment process of those interviewed was marked by a conflicted relationship with the medical profession, caused by a feeling of non-recognition and abandonment. They reported their experience as being very painful, both because of the physical pain and also the psychological consequences of their condition. Improving the diagnosis and therapeutic management of patients believing themselves to be affected by chronic Lyme disease appears highly necessary both to limit their search for diagnosis and their experience of pain. It could be based on existing guidelines concerning medically unexplained symptoms to which the chronic Lyme disease issue appears quite similar on several points. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  5. Intraventricular Hemorrhage in Moderate to Severe Congenital Heart Disease.

    PubMed

    Ortinau, Cynthia M; Anadkat, Jagruti S; Smyser, Christopher D; Eghtesady, Pirooz

    2018-01-01

    Determine the prevalence of intraventricular hemorrhage in infants with moderate to severe congenital heart disease, investigate the impact of gestational age, cardiac diagnosis, and cardiac intervention on intraventricular hemorrhage, and compare intraventricular hemorrhage rates in preterm infants with and without congenital heart disease. A single-center retrospective review. A tertiary care children's hospital. All infants admitted to St. Louis Children's Hospital from 2007 to 2012 with moderate to severe congenital heart disease requiring cardiac intervention in the first 90 days of life and all preterm infants without congenital heart disease or congenital anomalies/known genetic diagnoses admitted during the same time period. None. Cranial ultrasound data were reviewed for presence/severity of intraventricular hemorrhage. Head CT and brain MRI data were also reviewed in the congenital heart disease infants. Univariate analyses were undertaken to determine associations with intraventricular hemorrhage, and a final multivariate logistic regression model was performed. There were 339 infants with congenital heart disease who met inclusion criteria and 25.4% were born preterm. Intraventricular hemorrhage was identified on cranial ultrasound in 13.3% of infants, with the majority of intraventricular hemorrhage being low-grade (grade I/II). The incidence increased as gestational age decreased such that intraventricular hemorrhage was present in 8.7% of term infants, 19.2% of late preterm infants, 26.3% of moderately preterm infants, and 53.3% of very preterm infants. There was no difference in intraventricular hemorrhage rates between cardiac diagnoses. Additionally, the rate of intraventricular hemorrhage did not increase after cardiac intervention, with only three infants demonstrating new/worsening high-grade (grade III/IV) intraventricular hemorrhage after surgery. In a multivariate model, only gestational age at birth and African-American race were predictors

  6. Severe disease exacerbations in patients with multiple sclerosis after discontinuing fingolimod.

    PubMed

    Członkowska, Anna; Smoliński, Łukasz; Litwin, Tomasz

    Discontinuation of fingolimod in patients with multiple sclerosis (MS) can lead to disease reactivation. In this review, we describe cases of severe exacerbations in patients with MS following discontinuation of fingolimod, including three cases from our center. We consider potential mechanisms of disease reactivation after cessation of fingolimod, and the evidence supporting this rebound effect. We conclude that discontinuation of fingolimod results in the return of disease activity, which then leads to severe exacerbations (i.e., rebounds) in a clinically significant proportion of patients. Lastly, we consider disease-modifying treatment options for patients who discontinue fingolimod. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

  7. 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.

  8. In utero copper treatment for Menkes disease associated with a severe ATP7A mutation

    PubMed Central

    Haddad, Marie Reine; Macri, Charles J.; Holmes, Courtney S.; Goldstein, David S.; Jacobson, Beryl E.; Centeno, Jose A.; Popek, Edwina J.; Gahl, Willam A.; Kaler, Stephen G.

    2012-01-01

    Menkes disease is a lethal X-linked recessive neurodegenerative disorder of copper transport caused by mutations in ATP7A, which encodes a copper-transporting ATPase. Early postnatal treatment with copper injections often improves clinical outcomes in affected infants. While Menkes disease newborns appear normal neurologically, analyses of fetal tissues including placenta indicate abnormal copper distribution and suggest a prenatal onset of the metal transport defect. In an affected fetus whose parents found termination unacceptable and who understood the associated risks, we began in utero copper histidine treatment at 31.5 weeks gestational age. Copper histidine (900 μg per dose) was administered directly to the fetus by intramuscular injection (fetal quadriceps or gluteus) under ultrasound guidance. Percutaneous umbilical blood sampling enabled serial measurement of fetal copper and ceruloplasmin levels that were used to guide therapy over a four-week period. Fetal copper levels rose from 17 μg/dL prior to treatment to 45 μg/dL, and ceruloplasmin levels from 39 mg/L to 122 mg/L. After pulmonary maturity was confirmed biochemically, the baby was delivered at 35.5 weeks and daily copper histidine therapy (250 μg sc b.i.d.) was begun. Despite this very early intervention with copper, the infant showed hypotonia, developmental delay, and electroencephalographic abnormalities and died of respiratory failure at 5.5 months of age. The patient’s ATP7A mutation, which severely disrupted mRNA splicing, resulted in complete absence of ATP7A protein on Western blots. These investigations suggest that prenatally initiated copper replacement is inadequate to correct Menkes disease caused by severe loss-of-function mutations, and that postnatal ATP7A gene addition represents a rational approach in such circumstances. PMID:22695177

  9. 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…

  10. Celiac Disease in Children with Moderate-to-Severe Iron-deficiency Anemia.

    PubMed

    Narang, Manish; Natarajan, Ravikumar; Shah, Dheeraj; Puri, Amarender Singh; Manchanda, Vikas; Kotru, Mrinalini

    2018-01-15

    To evaluate the proportion of children with moderate to severe iron-deficiency anemia who have associated celiac disease. This cross-sectional analytical study was conducted among children aged 1 to 12 years of age with moderate-to-severe iron deficiency anemia and control children without anemia. Serum IgA-tissue trans-glutaminase levels were assessed in both cases and controls. All children with positive celiac serology underwent upper gastrointestinal endoscopy and duodenal biopsy; biopsy finding of Marsh grade 3 was considered positive for celiac disease. There were 152 anemic children and 152 controls with mean (SD) hemoglobinof 7.7 (1.8) and 12.2 (0.74) g/dL, respectively. 16 (10.5%) cases and 3 (2%) control patients had positive serology for celiac disease [OR (95% CI) 5.33 (1.52-18.67), P=0.007]. Six (3.9%) children with iron-deficiency anemia and none of the controls had biopsy features diagnostic of celiac disease. In the Northern Indian tertiary-care hospital outpatient setting, Celiac disease was associated with 4% of children presenting with moderate-to-severe anemia.

  11. Severe infections in patients with autoimmune diseases treated with cyclophosphamide.

    PubMed

    Cavallasca, Javier A; Costa, Cecilia A; Maliandi, Maria Del Rosario; Contini, Liliana E; Fernandez de Carrera, Elena; Musuruana, Jorge L

    2015-01-01

    Infectious diseases are a significant cause of morbidity and mortality in patients with connective tissue diseases. Corticosteroids and immunosuppressive drugs, such as cyclophosphamide (CYC), increases the risk of infections. The objective of this study was to estimate the incidence rates of severe infections in patients who received treatment with CYC. The records of 60 patients with systemic autoimmune diseases who received treatment with CYC were retrospectively reviewed. We evaluated the rate of severe infections that occurred during CYC therapy and the 3 subsequent months. Systemic lupus erythematosus was the most common disease, and diffuse proliferative glomerulonephritis the most frequent indication. Severe infection occurred in 9 patients (15%). Community acquired pneumonia was the most frequent infection with 3 cases (33%) followed by Herpes Zoster with 2 reports (22%). The cumulative dose of corticosteroid was the only significant risk factor for infection 32.8±16.7 vs. 20.1±15.3 P=.007. The use of lower doses of corticosteroids and an aggressive management of infectious complications, allows for an acceptable safety profile in patients treated with CYC. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  12. Memantine in moderately-severe-to-severe Alzheimer's disease: a postmarketing surveillance study.

    PubMed

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

    2009-01-01

    Postmarketing surveillance studies (PMS) are an important tool for evaluating a drug's effectiveness and safety in clinical practice. To our knowledge, no PMS on memantine monotherapy for moderately-severe-to-severe Alzheimer's disease (AD) according to National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association criteria has been conducted to date. The Lombardy Health Office, Italy, promoted this PMS to evaluate the effectiveness and safety of memantine in the treatment of moderately-severe-to-severe AD in clinical practice. A total of 451 patients with moderately-severe-to-severe AD (mean age 77 +/- 7 years; 72% female), free of cholinergic medication, received memantine (standard titration to 10 mg twice daily). After 6 months of therapy, treatment effectiveness was evaluated according to two definitions of response ('no deterioration' and 'improvement'), as measured by changes in baseline scores on the Clinical Global Impression of Change, Mini-Mental State Examination, Neuropsychiatric Inventory and Activities of Daily Living scales. The safety measure was the frequency of adverse events (AEs). At 6-month assessment, 26.8% of subjects showed no deterioration and 3.8% showed improvement. In those showing no deterioration, response to treatment at the 3-month assessment was associated with a greater probability of a response at 6 months (adjusted odds ratio = 8.54; 95% CI 4.54, 16.05). Seventy patients (15.5%) experienced at least one AE and 39 (8.6%) discontinued treatment prematurely because of an AE. Of those who experienced an AE, 27 (38.6%) manifested behavioural and psychological symptoms of dementia. The proportion of responders to memantine treatment in this PMS was similar to that reported in a previous randomized clinical trial (26.8% vs 29%, respectively). The proportion of patients who discontinued treatment prematurely because of an AE (8.6%) was similar to that reported in two

  13. Acute colonic diverticulitis: modern understanding of pathomechanisms, risk factors, disease burden and severity.

    PubMed

    Søreide, Kjetil; Boermeester, Marja A; Humes, David J; Velmahos, George C

    2016-12-01

    Conservative, non-antibiotic and non-surgical management of acute diverticulitis is currently being investigated. To better inform clinical decisions, better understanding of disease mechanisms, disease burden and severity is needed. Literature search of risk factors, pathophysiology, epidemiology and disease burden/severity reported over the last decade. Acute diverticulitis is a common disease and has a high disease burden. Incidence of hospital admissions is reported around 71 per 100,000 population, with reported increase in several subpopulations over the last decades. The incidence is likely to increase further with the aging populations. Risk factors for left-sided acute diverticulitis include dietary, anthropometric and lifestyle factors. Disease mechanisms are still poorly understood, but a distinction between inflammation and infection is emerging. The integrative and complex role of the gut microbiota has become an interesting factor for both understanding the disease as well as a potential target for intervention using probiotics. Mild, self-limiting events are increasingly reported from studies of successful non-antibiotic management in a considerable number of cases. Risk markers of progression to or presence of severe, complicated disease are needed for better disease stratification. Current risk stratification by clinical, imaging or endoscopic means is imperfect and needs validation. Long-term results from minimal-invasive and comparative surgical trials may better help inform clinicians and patients. Over- and under-treatment as well as over- and under-diagnosis of severity is likely to continue in clinical practice due to lack of reliable, robust and universal severity and classification systems. Better understanding of pathophysiology is needed.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  15. 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.

  16. 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

  17. Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease

    PubMed Central

    Modena, Brian D.; Bleecker, Eugene R.; Busse, William W.; Erzurum, Serpil C.; Gaston, Benjamin M.; Jarjour, Nizar N.; Meyers, Deborah A.; Milosevic, Jadranka; Tedrow, John R.; Wu, Wei; Kaminski, Naftali

    2017-01-01

    Rationale: Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Objectives: Identify networks of genes reflective of underlying biological processes that define SA. Methods: Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Measurements and Main Results: Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12–21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. Conclusions: In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its

  18. 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.

  19. 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...

  20. Rivastigmine in moderately severe-to-severe Alzheimer’s disease: Severe Impairment Battery factor analysis

    PubMed Central

    2013-01-01

    Introduction The Severe Impairment Battery (SIB) is validated for assessing cognition in patients with severe dementia. The current analysis aimed to further investigate the cognitive efficacy of rivastigmine capsules, as assessed by SIB factor scores, in patients with moderately severe-to-severe Alzheimer’s disease (AD). Methods This was a retrospective analysis of a 26-week, multicenter, randomized, double-blind, placebo-controlled study of oral rivastigmine conducted in Spain. Previously reported outcome measures included the full SIB. Current analyses examined calculated scores and effect sizes for the change from baseline at Week 26 on: newly defined SIB subscales (derived by a factor analysis of the 40 SIB items, using the PROC FACTOR function (SAS)); previously defined memory, language and praxis subscales (derived by previous analysis of the nine SIB domains); and the individual SIB items. Treatment differences were assessed. Results SIB data were provided by 104 rivastigmine-treated patients and 106 patients receiving placebo (Intent-To-Treat Last Observation Carried Forward population). Significantly less decline was observed on the previously defined memory and language subscales, and the newly defined working memory/memory subscale in rivastigmine-treated patients (all P < 0.05 versus placebo). Calculation of effect sizes demonstrated numerically greater efficacy of rivastigmine versus placebo on each of the subscales, and a broad range of SIB items; greatest effect sizes were observed on SIB items assessing the current month (effect size = 0.30) and digit span series (effect size = 0.33). Conclusions These data suggest the observed efficacy of rivastigmine in moderately severe-to-severe AD is likely a cumulative effect across a range of tasks. Rivastigmine demonstrates broad cognitive efficacy in this patient population. PMID:24351447

  1. Transcriptomic analysis of molecular responses in Malus domestica 'M26' roots affected by apple replant disease.

    PubMed

    Weiß, Stefan; Bartsch, Melanie; Winkelmann, Traud

    2017-06-01

    Gene expression studies in roots of apple replant disease affected plants suggested defense reactions towards biotic stress to occur which did not lead to adequate responses to the biotic stressors. Apple replant disease (ARD) leads to growth inhibition and fruit yield reduction in replanted populations and results in economic losses for tree nurseries and fruit producers. The etiology is not well understood on a molecular level and causal agents show a great diversity indicating that no definitive cause, which applies to the majority of cases, has been found out yet. Hence, it is pivotal to gain a better understanding of the molecular and physiological reactions of the plant when affected by ARD and later to overcome the disease, for example by developing tolerant rootstocks. For the first time, gene expression was investigated in roots of ARD affected plants employing massive analysis of cDNA ends (MACE) and RT-qPCR. In reaction to ARD, genes in secondary metabolite production as well as plant defense, regulatory and signaling genes were upregulated whereas for several genes involved in primary metabolism lower expression was detected. For internal verification of MACE data, candidate genes were tested via RT-qPCR and a strong positive correlation between both datasets was observed. Comparison of apple 'M26' roots cultivated in ARD soil or γ-irradiated ARD soil suggests that typical defense reactions towards biotic stress take place in ARD affected plants but they did not allow responding to the biotic stressors attack adequately, leading to the observed growth depressions in ARD variants.

  2. Automatic detection and severity measurement of eczema using image processing.

    PubMed

    Alam, Md Nafiul; Munia, Tamanna Tabassum Khan; Tavakolian, Kouhyar; Vasefi, Fartash; MacKinnon, Nick; Fazel-Rezai, Reza

    2016-08-01

    Chronic skin diseases like eczema may lead to severe health and financial consequences for patients if not detected and controlled early. Early measurement of disease severity, combined with a recommendation for skin protection and use of appropriate medication can prevent the disease from worsening. Current diagnosis can be costly and time-consuming. In this paper, an automatic eczema detection and severity measurement model are presented using modern image processing and computer algorithm. The system can successfully detect regions of eczema and classify the identified region as mild or severe based on image color and texture feature. Then the model automatically measures skin parameters used in the most common assessment tool called "Eczema Area and Severity Index (EASI)," by computing eczema affected area score, eczema intensity score, and body region score of eczema allowing both patients and physicians to accurately assess the affected skin.

  3. 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.

  4. Clinical Characterization and Treatment Patterns for the Frequent Exacerbator Phenotype in Chronic Obstructive Pulmonary Disease with Severe or Very Severe Airflow Limitation.

    PubMed

    Blasi, Francesco; Neri, Luca; Centanni, Stefano; Falcone, Franco; Di Maria, Giuseppe

    2017-02-01

    Chronic obstructive pulmonary disease (COPD) patients experiencing several episodes of acute clinical derangement suffer from increased morbidity, mortality, and accelerated decline in lung function. Nevertheless, the relationship between co-morbidity profile and exacerbation rates in the frequent exacerbator phenotype is poorly characterized, and evidence-based management guidelines are lacking. We sought to evaluate the co-morbidity profile and treatment patterns of "frequent exacerbators" with severe or very severe airflow limitation. We conducted a cross-sectional, multicenter study in 50 Italian hospitals. Pulmonologists abstracted clinical information from medical charts of 743 COPD frequent exacerbators. We evaluated the exacerbation risk and center-related variations in diagnostic testing. One-third of patients (n = 210) underwent a bronchodilator response test, and 163 (22%) received a computerized tomography (CT) scan; 35 had a partial response to bronchodilators, while 119 had a diagnosis of emphysema; 584 (79%) lacked sufficient diagnostic testing for classification. Only 17% of patients did not have any coexistent disease. Cardiovascular conditions were the most frequent co-morbidities. A history of heart failure [odds ratio (OR): 1.89; 95% confidence interval (CI) 1.48-2.3] and affective disorders (OR: 1.66; 95% CI 1.24-2.1) was associated with the frequency of exacerbations. Center membership was strongly associated with exacerbation risk, independent of casemix (variance partition coefficient = 29.6%). Examining the regional variation in health outcomes and health care behavior may help identify the best practices, especially when evidence-based recommendations are lacking and uncertainties surround clinical decision-making.

  5. Assessment of nutritional status in patients with Parkinson's disease and its relationship with severity of the disease.

    PubMed

    Shidfar, Farzad; Babaii Darabkhani, Peivand; Yazdanpanah, Leila; Karkheiran, Siamak; Noorollahi-Moghaddam, Hamid; Haghani, Hamid

    2016-01-01

    Background: Malnutrition, loss of body weight, muscle and fat mass wasting are common in patients with Parkinson's disease, and are associated with disability, longer length of hospital stay, impaired immune system and increased risk of mortality. The aim of this study was to assess the nutritional status in patients with Parkinson's disease and its relation to the severity of the disease. Methods: This cross- sectional study was conducted on 130 patients with Parkinson's disease, with a mean (SD) age of 59.1 (12.9) years in disease stages of 1 to 4. In this study, the Mini Nutritional Assessment (MNA) questionnaire was used along with anthropometric measurements (Body Mass Index (BMI), Mid-arm circumference (MAC), Calf Circumference (CC)) to evaluate the nutritional status, and they were applied by a trained nutritionist. Hoehn and Yahr Scale were used to determine the severity of the disease. One-way ANOVA test was used to assess the relationship between anthropometric indices, nutritional status and severity of disease. Assessment of the relationship between age, duration of disease and nutritional status was categorized according to MNA score, and was performed, using one-way ANOVA. Chi - Square test was utilized to assess the relationship between education level and nutritional status. SPSS Version 18 was used for data analysis. Results: In this study, 30% (n=39) of the participants were diagnosed with normal nutritional status, 58.5% (n=76) were at risk of malnutrition and 11.5% (n=15) were malnourished according to MNA. Reduction of weight, and muscle mass wasting was observed in different disease stages. Muscle mass wasting and worsening nutritional status, based on MNA score, showed a significant increase as the disease progressed, MAC (p=0.009), MNA score (p<0.001). After assessing the relationship between education level, age, duration of disease with nutritional status, the results revealed a significant relationship between age (p=0.008), education

  6. Framing obesity a disease: Indirect effects of affect and controllability beliefs on weight bias.

    PubMed

    Nutter, Sarah; Alberga, Angela S; MacInnis, Cara; Ellard, John H; Russell-Mayhew, Shelly

    2018-05-24

    Obesity has been declared a disease by the American and Canadian Medical Associations. Although these declarations sparked much debate as to the impact of framing obesity as a disease on weight bias, strong empirical research is needed to examine this impact. The current study examined the impact of framing obesity a disease on weight bias, focusing on moderating and mediating processes. A sample of 309 participants living in the United States or Canada was recruited from Crowdflower. Participants completed measures of demographics, ideology, general attitudes, and previous contact quality and quantity with people living with obesity. Participants then read one of three articles as part of an experimental manipulation framing obesity as a disease, obesity not as a disease, and a control article unrelated to obesity. Post-manipulation included measures of affect, disgust, empathy, blame, and weight bias. Orthogonal contrasts were used to compare the obesity-disease condition to the obesity-not-disease condition and control condition. The manipulation had a direct effect on affect (emotions), such that affect toward individuals with obesity was more positive in the obesity-disease condition than the obesity-not-disease and control condition combined. Exploration of moderating effects revealed that both the belief in a just world and weight satisfaction moderated the relationship between the obesity-disease manipulation and blame for obesity. Two models of indirect effects on weight bias were also examined, which demonstrated that the obesity-disease manipulation predicted less weight bias through more positive affect (model 1) as well as less weight bias through decreased blame among individuals high in belief in a just world (model 2). This study further highlights the complex effects of declaring obesity a disease, uncovering a new direction for future research into the role of affect as well as indirect effects of characterising obesity a disease on weight bias.

  7. Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis

    PubMed Central

    Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

    2016-01-01

    Abstract Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

  8. Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis.

    PubMed

    Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

    2016-04-01

    Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality.

  9. Link between sewage-derived nitrogen pollution and coral disease severity in Guam.

    PubMed

    Redding, Jamey E; Myers-Miller, Roxanna L; Baker, David M; Fogel, Marilyn; Raymundo, Laurie J; Kim, Kiho

    2013-08-15

    The goals of this study were to evaluate the contribution of sewage-derived N to reef flat communities in Guam and to assess the impact of N inputs on coral disease. We used stable isotope analysis of macroalgae and a soft coral, sampled bimonthly, as a proxy for N dynamics, and surveyed Porites spp., a dominant coral taxon on Guam's reefs, for white syndrome disease severity. Results showed a strong influence of sewage-derived N in nearshore waters, with δ(15)N values varying as a function of species sampled, site, and sampling date. Increases in sewage-derived N correlated significantly with increases in the severity of disease among Porites spp., with δ(15)N values accounting for more than 48% of the variation in changes in disease severity. The anticipated military realignment and related population increase in Guam are expected to lead to increased white syndrome infections and other coral diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: A description of the severity and extent of disease using the Bollinger angiogram scoring method and the TransAtlantic Inter-Society Consensus II classification.

    PubMed

    Bradbury, Andrew W; Adam, Donald J; Bell, Jocelyn; Forbes, John F; Fowkes, F Gerry R; Gillespie, Ian; Ruckley, Charles Vaughan; Raab, Gillian M

    2010-05-01

    The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial showed in patients with severe lower limb ischemia (rest pain, tissue loss) who survive for 2 years after intervention that initial randomization to bypass surgery, compared with balloon angioplasty, was associated with an improvement in subsequent amputation-free survival and overall survival of about 6 and 7 months, respectively. The aim of this report is to describe the angiographic severity and extent of infrainguinal arterial disease in the BASIL trial cohort so that the trial outcomes can be appropriately generalized to other patient cohorts with similar anatomic (angiographic) patterns of disease. Preintervention angiograms were scored using the Bollinger method and the TransAtlantic Inter-Society Consensus (TASC) II classification system by three consultant interventional radiologists and two consultant vascular surgeons unaware of the treatment received or patient outcomes. As was to be expected from the randomization process, patients in the two trial arms were well matched in terms of angiographic severity and extent of disease as documented by Bollinger and TASC II. In patients with the least overall disease, it tended to be concentrated in the superficial femoral and popliteal arteries, which were the commonest sites of disease overall. The below knee arteries became increasingly involved as the overall severity of disease increased, but the disease in the above knee arteries did not tend to worsen. The posterior tibial artery was the most diseased crural artery, whereas the peroneal appeared relatively spared. There was less interobserver disagreement with the Bollinger method than with the TASC II classification system, which also appears inherently less sensitive to clinically important differences in infrapopliteal disease among patients with severe leg ischemia. Anatomic (angiographic) disease description in patients with severe leg ischemia requires a reproducible scoring

  11. Memantine may affect pseudobulbar affect in patients with Alzheimer's disease.

    PubMed

    Prokšelj, Tatjana; Jerin, Aleš; Kogoj, Aleš

    2013-12-01

    Behavioural symptoms are common in moderate to severe Alzheimer's disease (AD) and are improved by memantine with the most pronounced effect on agitation/aggression. Dextromethorphan in combination with quinidine is the only drug approved by US Food and Drug Administration for the treatment of pseudobulbar affect (PBA) on the basis of efficacy in patients with multiple sclerosis or amyotrophic lateral sclerosis. The aim of our study was to evaluate the efficacy of memantine on PBA in patients with AD. In a prospective, double-blind, case-control study to assess PBA with pathological laughter and crying scale patients were administered memantine (final dose of 20 mg daily) or citalopram (20 mg once daily), each for 10 weeks. The number of episodes of involuntary emotional expression, Neuropsychiatric Inventory (NPI) and Overt Aggression Scale-Modified (OAS-M) total scores were also recorded. Furthermore, the platelet serotonin (5-HT) concentration was measured. Although memantine had beneficial effects on PBA, it also had a crucial impact on behavioural symptoms, especially aggression and agitation (to an average of 3.5 times higher end-point scores on OAS-M and increase of NPI total scores for an average of 114% of initial value). Therefore, the study was prematurely stopped. In addition, we had evidenced a drop of platelet 5-HT concentration (to an average of 73% of initial value). Surprisingly, our research showed the opposite action of memantine on neuropsychiatric symptoms as expected. In a limited number of AD patients with PBA, memantine had a beneficial effect on involuntary emotional expression, but it potentiated agitation/aggression, irritability and caused a crucial drop of the platelet 5-HT concentration.

  12. Etiology of Non-Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to Disease Severity.

    PubMed

    Lonni, Sara; Chalmers, James D; Goeminne, Pieter C; McDonnell, Melissa J; Dimakou, Katerina; De Soyza, Anthony; Polverino, Eva; Van de Kerkhove, Charlotte; Rutherford, Robert; Davison, John; Rosales, Edmundo; Pesci, Alberto; Restrepo, Marcos I; Torres, Antoni; Aliberti, Stefano

    2015-12-01

    Testing for underlying etiology is a key part of bronchiectasis management, but it is unclear whether the same extent of testing is required across the spectrum of disease severity. The aim of the present study was to identify the etiology of bronchiectasis across European cohorts and according to different levels of disease severity. We conducted an analysis of seven databases of adult outpatients with bronchiectasis prospectively enrolled at the bronchiectasis clinics of university teaching hospitals in Monza, Italy; Dundee and Newcastle, United Kingdom; Leuven, Belgium; Barcelona, Spain; Athens, Greece; and Galway, Ireland. All the patients at every site underwent the same comprehensive diagnostic workup as suggested by the British Thoracic Society. Among the 1,258 patients enrolled, an etiology of bronchiectasis was determined in 60%, including postinfective (20%), chronic obstructive pulmonary disease related (15%), connective tissue disease related (10%), immunodeficiency related (5.8%), and asthma related (3.3%). An etiology leading to a change in patient's management was identified in 13% of the cases. No significant differences in the etiology of bronchiectasis were present across different levels of disease severity, with the exception of a higher prevalence of chronic obstructive pulmonary disease-related bronchiectasis (P < 0.001) and a lower prevalence of idiopathic bronchiectasis (P = 0.029) in patients with severe disease. Physicians should not be guided by disease severity in suspecting specific etiologies in patients with bronchiectasis, although idiopathic bronchiectasis appears to be less common in patients with the most severe disease.

  13. Retinal vascular imaging technology to monitor disease severity and complications in type 1 diabetes mellitus: A systematic review.

    PubMed

    Kee, Ae Ra; Wong, Tien Yin; Li, Ling-Jun

    2017-02-01

    Type 1 diabetes mellitus (T1DM) is a major disease affecting a large number of young patients. In the recent years, retinal vascular imaging has provided an objective assessment of vascular health in patients with T1DM. Our study aimed to review the current literature on retinal vascular parameters in young patients with T1DM in order to understand the following: (i) How retinal vessels are affected in T1DM (ii) How such vascular changes can be predictive of future diabetic microvascular complications METHODS: We performed a systematic review and extracted relevant data from 17 articles. We found significant correlations between retinal vessel changes and diabetes-related risk factors (eg, hypertension, hyperlipidemia, and obesity), diabetes-related features (eg, diabetes duration and glycemic control), and diabetes-related microvascular complications (eg, diabetic retinopathy, nephropathy, and neuropathy). Our findings suggest that retinal microvasculature is associated with both disease severity and complications in young patients with T1DM. © 2016 John Wiley & Sons Ltd.

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

    PubMed

    Bertilsson, Sara; Swärd, Per; Kalaitzakis, Evangelos

    2015-09-01

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

  15. Bipolar affective disorder and Parkinson's disease: a rare, insidious and often unrecognized association.

    PubMed

    Cannas, A; Spissu, A; Floris, G L; Congia, S; Saddi, M V; Melis, M; Mascia, M M; Pinna, F; Tuveri, A; Solla, P; Milia, A; Giagheddu, M; Tacconi, P

    2002-09-01

    Five patients (4 women) with Parkinson's disease (PD) and primary major psychiatric disorder (PMPD) meeting DSM-IV criteria for the diagnosis of bipolar affective disorder (BAD) were studied. Four patients had early onset PD. Four developed a severe psychiatric disorder a few years after starting dopaminergic therapy in presence of a mild motor disability and a mild cognitive impairment, with no evidence of cerebral atrophy at CT or MRI. Two patients developed a clear manic episode; the other three presented a severe depressive episode (in one case featuring a Cotard syndrome). None showed previous signs of long term L-dopa treatment syndrome (LTS), hallucinosis or other minor psychiatric disorders. The two manic episodes occurred shortly after an increase of dopaminergic therapy and in one case rapid cyclic mood fluctuations were observed. At the onset of psychiatric symptoms, all patients had an unspecific diagnosis of chronic delusional hallucinatory psychosis (CDHP).

  16. 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. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  17. The Airway Microbiome in Severe Asthma: Associations with Disease Features and Severity

    PubMed Central

    Huang, Yvonne J.; Nariya, Snehal; Harris, Jeffrey M.; Lynch, Susan V.; Choy, David F.; Arron, Joseph R.; Boushey, Homer

    2015-01-01

    Background Asthma is heterogeneous, and airway dysbiosis is associated with clinical features in mild-moderate asthma. Whether similar relationships exist among patients with severe asthma is unknown. Objective To evaluate relationships between the bronchial microbiome and features of severe asthma. Methods Bronchial brushings from 40 participants in the BOBCAT study (Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma) were evaluated using 16S rRNA-based methods. Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects. Secondarily, bacterial compositional profiles were compared between severe asthmatics, and previously studied healthy controls (n=7), and mild-moderate asthma subjects (n=41). Results In severe asthma, bronchial bacterial composition was associated with several disease-related features, including body-mass index (BMI; Bray-Curtis distance PERMANOVA, p < 0.05), changes in Asthma Control Questionnaire (ACQ) scores (p < 0.01), sputum total leukocytes (p = 0.06) and bronchial biopsy eosinophils (per mm2; p = 0.07). Bacterial communities associated with worsening ACQ and sputum total leukocytes (predominantly Proteobacteria) differed markedly from those associated with BMI (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ and bronchial epithelial gene expression of FKBP5, an indicator of steroid responsiveness, correlated with Actinobacteria. Mostly negative correlations were observed between biopsy eosinophils and Proteobacteria. No taxa were associated with a T-helper type 2-related epithelial gene expression signature, but expression of Th17-related genes was associated with Proteobacteria. Severe asthma subjects, compared to healthy controls or mild-moderate asthmatics, were significantly enriched in Actinobacteria, although the largest differences observed involved a Klebsiella genus member (7.8 fold-increase in severe asthma, padj < 0.001) Conclusions

  18. Extraintestinal manifestations were common in children with coeliac disease and were more prevalent in patients with more severe clinical and histological presentation.

    PubMed

    Nurminen, Samuli; Kivelä, Laura; Huhtala, Heini; Kaukinen, Katri; Kurppa, Kalle

    2018-03-22

    This study investigated the prevalence of extraintestinal manifestations (EIM) in paediatric coeliac disease and their associations with other disease features. Researchers at the University of Tampere, Finland, compared EIM in 511 children diagnosed with coeliac disease from 2003 to 2014 and 180 diagnosed with functional gastrointestinal disorders from 2007 to 2013. Disease severity and dietary responses were also compared between coeliac children diagnosed by screening (n = 146) or because of EIM (n = 116) or gastrointestinal symptoms (n = 249). Coeliac patients had more EIM (62%) than those with functional disorders (33%). The most common EIM in coeliac children were poor growth (27%) and anaemia (18%). Children with coeliac disease often showed fatigue (8%) and symptoms affecting the skin (15%), nervous system (9%) and joints (6%). Coeliac patients with EIM as their main clinical presentation had more severe symptoms and histological damage at diagnosis than those with gastrointestinal presentation and screen-detected cases. The subgroups did not differ with regard to other clinical and laboratory parameters and dietary adherence. Concomitant EIM were also common in children diagnosed because of gastrointestinal presentation (60%) and by screening (37%). EIM were common in coeliac disease and associated with more severe clinical and histological presentation. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  19. Unmet Needs of Patients Feeling Severely Affected by Multiple Sclerosis in Germany: A Qualitative Study

    PubMed Central

    Golla, Heidrun; Strupp, Julia; Karbach, Ute; Kaiser, Claudia; Ernstmann, Nicole; Pfaff, Holger; Ostgathe, Christoph; Voltz, Raymond

    2014-01-01

    Abstract Background: The needs of patients feeling severely affected by multiple sclerosis (MS) have rarely been investigated. However this is essential information to know before care can be improved, including adding palliative care (PC) services where helpful. Since it remains unclear at what point specialized palliative care should begin for this patient group, this study focuses on needs in general. Objective: The objective was to explore the subjectively unmet needs of patients feeling severely affected by MS. Methods: The study used a qualitative cross-sectional approach for needs assessment. Fifteen patients self-reporting feeling severely affected by MS were recruited and interviewed using a combination of purposive and convenience sampling (five were accompanied by a caregiver relative). Interviews were recorded and transcribed verbatim, followed by qualitative content analysis. Results: Unmet needs were identified in the main categories “support of family and friends,” “health care services,” “managing everyday life,” and “maintaining biographical continuity.” Patients expressed the desire for more support from their families and to be viewed as distinct individuals. They see a substantial deficit in the physician-patient relationship and in the coordination of services. A decrease in expressed unmet needs was found for patients more severely affected and less socially integrated. Conclusions: To address the unmet needs of severely affected MS patients, health care services need to be improved and linked with existing PC services. Special attention is required to form supporting professional-patient relationships. Multiprofessional services should be accessible for patients, while integrating relatives. All services should have an individual approach to provide needs-tailored support. PMID:24527993

  20. Norovirus and Rotavirus Disease Severity in Children: Systematic Review and Meta-analysis.

    PubMed

    Riera-Montes, Margarita; O'Ryan, Miguel; Verstraeten, Thomas

    2018-06-01

    Rotaviruses (RVs) and noroviruses (NoVs) are the most common causes of severe acute gastroenteritis in children. It is generally accepted that RVs cause severe acute gastroenteritis in a higher proportion of cases compared with NoVs. To our knowledge, there are no systematic reviews and meta-analyses comparing the severity of NoV and RV disease. We searched MEDLINE for studies reporting data for NoV and RV medically attended disease severity in children. We included studies where all children had been tested for both NoV (reverse transcription polymerase chain reaction) and RV (enzyme-linked immunosorbent assay or reverse transcription polymerase chain reaction) and that reported disease severity using the Vesikari or modified Vesikari score, or provided clinical information on severity. We generated pooled estimates of the mean with 95% confidence intervals using random effects meta-analysis. We identified 266 publications, of which 31 were retained for qualitative analysis and 26 for quantitative analysis. Fourteen studies provided data on severity score for the meta-analysis. The pooled mean severity scores (95% confidence interval) among outpatients were 10 (8-12) and 11 (8-14) for NoV and RV, respectively. Among inpatients, they were 11 (9-13) for NoV and 12 (10-14) for RV. The difference was statistically significant among inpatients, but relatively small (1 point in a 20-point scale). About 20% more children with RV required rehydration when compared with children with NoV. NoV causes moderate to severe disease similar to RV in young children. This information should be useful for future evaluations of an eventual introduction of NoV vaccines in national immunization programs.

  1. Sever's Disease

    MedlinePlus

    ... boys 10 years to 12 years of age. Soccer players and gymnasts often get Sever’s disease, but ... Crisis Situations Pets and Animals myhealthfinder Food and Nutrition Healthy Food Choices Weight Loss and Diet Plans ...

  2. NMR metabolomics of esca disease-affected Vitis vinifera cv. Alvarinho leaves.

    PubMed

    Lima, Marta R M; Felgueiras, Mafalda L; Graça, Gonçalo; Rodrigues, João E A; Barros, António; Gil, Ana M; Dias, Alberto C P

    2010-09-01

    Esca is a destructive disease that affects vineyards leading to important losses in wine production. Information about the response of Vitis vinifera plants to this disease is scarce, particularly concerning changes in plant metabolism. In order to study the metabolic changes in Vitis plants affected by esca, leaves from both infected and non-affected cordons of V. vinifera cv. Alvarinho (collected in the Vinho Verde region, Portugal) were analysed. The metabolite composition of leaves from infected cordons with visible symptoms [diseased leaves (dl)] and from asymptomatic cordons [healthy leaves (hl)] was evaluated by 1D and 2D (1)H-nuclear magnetic resonance (NMR) spectroscopy. Principal component analysis (PCA) of the NMR spectra showed a clear separation between dl and hl leaves, indicating differential compound production due to the esca disease. NMR/PCA analysis allowed the identification of specific compounds characterizing each group, and the corresponding metabolic pathways are discussed. Altogether, the study revealed a significant increase of phenolic compounds in dl, compared with hl, accompanied by a decrease in carbohydrates, suggesting that dl are rerouting carbon and energy from primary to secondary metabolism. Other metabolic alterations detected comprised increased levels of methanol, alanine, and gamma-aminobutyric acid in dl, which might be the result of the activation of other defence mechanisms.

  3. Prevalence of obesity in paediatric psoriasis and its impact on disease severity and progression.

    PubMed

    Ergun, Tulin; Seckin Gencosmanoglu, Dilek; Karakoc-Aydiner, Elif; Salman, Andac; Tekin, Burak; Bulbul-Baskan, Emel; Alpsoy, Erkan; Cakıroglu, Aylin; Onsun, Nahide

    2017-11-01

    The current literature suggests there is a possible connection between paediatric psoriasis and obesity. However, there is a paucity of research on the influence of increased adiposity on the severity of paediatric psoriasis and disease progression. We aimed to compare the prevalence of being overweight or obese in paediatric psoriasis patients and controls and assess the potential impact of being overweight/obese on disease severity and progression of disease. This multicentre prospective case-control study included 289 psoriasis patients (aged < 18 years) treated and followed up by one of the four university hospitals in Turkey. The control group consisted of 151 consecutive age-matched and sex-matched children who lacked a personal or family history of psoriasis. The participants' characteristics, psoriasis-related parametres (e.g., initial subtype, psoriasis area and severity index, presence of psoriatic arthritis) and body mass index were determined. The difference between the prevalence of being overweight/obese among psoriatics (28%) and the control group (19%) was significant (P = 0.024). Being overweight/obese had no significant impact on disease severity and unresponsiveness to topical treatment. Within a median follow-up time of 12 months, 23% of our patients with localised disease at disease onset progressed to generalised disease. The impact of being overweight/obese on disease progression was found to be non-significant; however, disease duration was found to have a significant impact on disease progression (P = 0.026). Although it is not associated with disease severity and course, increased bodyweight may be a health problem for psoriatic children. © 2016 The Australasian College of Dermatologists.

  4. Electrophysiology and optical coherence tomography to evaluate Parkinson disease severity.

    PubMed

    Garcia-Martin, Elena; Rodriguez-Mena, Diego; Satue, Maria; Almarcegui, Carmen; Dolz, Isabel; Alarcia, Raquel; Seral, Maria; Polo, Vicente; Larrosa, Jose M; Pablo, Luis E

    2014-02-04

    To evaluate correlations between visual evoked potentials (VEP), pattern electroretinogram (PERG), and macular and retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) and the severity of Parkinson disease (PD). Forty-six PD patients and 33 age and sex-matched healthy controls were enrolled, and underwent VEP, PERG, and OCT measurements of macular and RNFL thicknesses, and evaluation of PD severity using the Hoehn and Yahr scale to measure PD symptom progression, the Schwab and England Activities of Daily Living Scale (SE-ADL) to evaluate patient quality of life (QOL), and disease duration. Logistical regression was performed to analyze which measures, if any, could predict PD symptom progression or effect on QOL. Visual functional parameters (best corrected visual acuity, mean deviation of visual field, PERG positive (P) component at 50 ms -P50- and negative (N) component at 95 ms -N95- component amplitude, and PERG P50 component latency) and structural parameters (OCT measurements of RNFL and retinal thickness) were decreased in PD patients compared with healthy controls. OCT measurements were significantly negatively correlated with the Hoehn and Yahr scale, and significantly positively correlated with the SE-ADL scale. Based on logistical regression analysis, fovea thickness provided by OCT equipment predicted PD severity, and QOL and amplitude of the PERG N95 component predicted a lower SE-ADL score. Patients with greater damage in the RNFL tend to have lower QOL and more severe PD symptoms. Foveal thicknesses and the PERG N95 component provide good biomarkers for predicting QOL and disease severity.

  5. Vedolizumab Therapy in Severe Pediatric Inflammatory Bowel Disease.

    PubMed

    Conrad, Máire A; Stein, Ronen E; Maxwell, Elizabeth C; Albenberg, Lindsey; Baldassano, Robert N; Dawany, Noor; Grossman, Andrew B; Mamula, Petar; Piccoli, David A; Kelsen, Judith R

    2016-10-01

    Vedolizumab is effective for inducing and maintaining remission in adults with inflammatory bowel disease (IBD); however, there is limited pediatric data. This study aimed to describe the adverse events and clinical response to vedolizumab in refractory pediatric IBD. Disease activity indices, clinical response, concomitant medication use, and adverse events were measured over 22 weeks in an observational prospective cohort study of children with refractory IBD who had failed anti-tumor necrosis factor therapy and subsequently initiated vedolizumab therapy. Twenty-one subjects, 16 with Crohn disease, received vedolizumab. Clinical response was observed in 6/19 (31.6%) of the evaluable subjects at week 6 and in 11/19 (57.9%) by week 22. Before induction, 15/21 (71.4%) participants were treated with systemic corticosteroids, as compared with 7/21 (33.3%) subjects at 22 weeks. Steroid-free remission was seen in 1/20 (5.0%) subjects at 6 weeks, 3/20 (15.0%) at 14 weeks, and 4/20 (20.0%) at 22 weeks. There was statistically significant improvement in serum albumin and hematocrit; however, C-reactive protein increased by week 22 (P < 0.05). There were no infusion reactions. Vedolizumab was discontinued in 2 patients because of severe colitis, requiring surgical intervention. There is limited experience with vedolizumab therapy in pediatric IBD. There seems to be a marked number of subjects with clinical response in the first 6 weeks that increases further by week 22 despite the severity of disease in this cohort. Adverse events may not be directly related to vedolizumab. This study is limited by small sample size, and larger prospective studies are warranted.

  6. Neuropsychological dysfunction in schizophrenia and affective disease.

    PubMed

    Taylor, M A; Redfield, J; Abrams, R

    1981-05-01

    We used Smith's neuropsychological test battery to study the cortical functioning of 52 patients with affective disorders, 17 schizophrenics, and 8 patients with coarse brain disease (CBD), all diagnosed according to research criteria. Testing and diagnoses were made independently and blindly. After accounting for the variance due to age, sex, handedness, educational level, and psychotropic drugs, we found that on tests of dominant hemisphere function schizophrenics performed significantly worse than patients with affective disorder but were no different from patients with CBD. On tests of nondominant hemisphere function the performance of the schizophrenics was similar to that of the other two groups, which were different from each other in that patients with CBD had poorer performance than affectives. A discriminant function analysis of the test scores applied to a jackknifed classification matrix successfully predicted research diagnosis in 86.5% of the affectively ill patients and 76.5% of the schizophrenics, for an overall hit rate of 84.1%. A canonical plot of the discriminant scores further showed distinct groups, with manics and depressives most alike but quite different from schizophrenics and patients with CBD. These findings are consistent with those derived from other neuropsychological studies, as well as EEG and CT scan studies.

  7. Correlation of hyponatremia with hepatic encephalopathy and severity of liver disease.

    PubMed

    Qureshi, Muhammad Omar; Khokhar, Nasir; Saleem, Atif; Niazi, Tariq Khan

    2014-02-01

    To assess the frequency of low serum sodium levels and to correlate it with the severity of liver disease and hepatic encephalopathy (HE) in patients coming to the tertiary care hospital. Observational study. Shifa International Hospital, Islamabad, from January 2011 to January 2012. A total of 202 patients with hepatic encephalopathy and chronic liver disease had serum sodium measured. The HE was graded according to the West Haven classification (4 grades). Relationship of hyponatremia was correlated with severity grade of encephalopathy using Spearman rank correlation test. Out of 202 patients, 62 (30.7%) patients had serum sodium less than 130 meq/l. Out of 202, HE was present in 69 (34.15%) patients and out of these, 38 had grade III-IV HE and 31 had grade I - II HE. Out of 69 patients with HE 57 had sodium less than 135 (p < 0.001). Hyponatremia was a common feature in patients with cirrhosis and its severity increased with the severity of liver disease. The existence of serum sodium concentration < 135 mmol/L was associated with greater frequency of hepatic encephalopathy compared with patients with serum sodium concentration > 135 mmol/L.

  8. Modeling Disease Severity in Multiple Sclerosis Using Electronic Health Records

    PubMed Central

    Xia, Zongqi; Secor, Elizabeth; Chibnik, Lori B.; Bove, Riley M.; Cheng, Suchun; Chitnis, Tanuja; Cagan, Andrew; Gainer, Vivian S.; Chen, Pei J.; Liao, Katherine P.; Shaw, Stanley Y.; Ananthakrishnan, Ashwin N.; Szolovits, Peter; Weiner, Howard L.; Karlson, Elizabeth W.; Murphy, Shawn N.; Savova, Guergana K.; Cai, Tianxi; Churchill, Susanne E.; Plenge, Robert M.; Kohane, Isaac S.; De Jager, Philip L.

    2013-01-01

    Objective To optimally leverage the scalability and unique features of the electronic health records (EHR) for research that would ultimately improve patient care, we need to accurately identify patients and extract clinically meaningful measures. Using multiple sclerosis (MS) as a proof of principle, we showcased how to leverage routinely collected EHR data to identify patients with a complex neurological disorder and derive an important surrogate measure of disease severity heretofore only available in research settings. Methods In a cross-sectional observational study, 5,495 MS patients were identified from the EHR systems of two major referral hospitals using an algorithm that includes codified and narrative information extracted using natural language processing. In the subset of patients who receive neurological care at a MS Center where disease measures have been collected, we used routinely collected EHR data to extract two aggregate indicators of MS severity of clinical relevance multiple sclerosis severity score (MSSS) and brain parenchymal fraction (BPF, a measure of whole brain volume). Results The EHR algorithm that identifies MS patients has an area under the curve of 0.958, 83% sensitivity, 92% positive predictive value, and 89% negative predictive value when a 95% specificity threshold is used. The correlation between EHR-derived and true MSSS has a mean R2 = 0.38±0.05, and that between EHR-derived and true BPF has a mean R2 = 0.22±0.08. To illustrate its clinical relevance, derived MSSS captures the expected difference in disease severity between relapsing-remitting and progressive MS patients after adjusting for sex, age of symptom onset and disease duration (p = 1.56×10−12). Conclusion Incorporation of sophisticated codified and narrative EHR data accurately identifies MS patients and provides estimation of a well-accepted indicator of MS severity that is widely used in research settings but not part of the routine medical

  9. Etiology of Non–Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to Disease Severity

    PubMed Central

    Lonni, Sara; Chalmers, James D.; Goeminne, Pieter C.; McDonnell, Melissa J.; Dimakou, Katerina; De Soyza, Anthony; Polverino, Eva; Van de Kerkhove, Charlotte; Rutherford, Robert; Davison, John; Rosales, Edmundo; Pesci, Alberto; Restrepo, Marcos I.; Torres, Antoni

    2015-01-01

    Rationale: Testing for underlying etiology is a key part of bronchiectasis management, but it is unclear whether the same extent of testing is required across the spectrum of disease severity. Objectives: The aim of the present study was to identify the etiology of bronchiectasis across European cohorts and according to different levels of disease severity. Methods: We conducted an analysis of seven databases of adult outpatients with bronchiectasis prospectively enrolled at the bronchiectasis clinics of university teaching hospitals in Monza, Italy; Dundee and Newcastle, United Kingdom; Leuven, Belgium; Barcelona, Spain; Athens, Greece; and Galway, Ireland. All the patients at every site underwent the same comprehensive diagnostic workup as suggested by the British Thoracic Society. Measurements and Main Results: Among the 1,258 patients enrolled, an etiology of bronchiectasis was determined in 60%, including postinfective (20%), chronic obstructive pulmonary disease related (15%), connective tissue disease related (10%), immunodeficiency related (5.8%), and asthma related (3.3%). An etiology leading to a change in patient’s management was identified in 13% of the cases. No significant differences in the etiology of bronchiectasis were present across different levels of disease severity, with the exception of a higher prevalence of chronic obstructive pulmonary disease–related bronchiectasis (P < 0.001) and a lower prevalence of idiopathic bronchiectasis (P = 0.029) in patients with severe disease. Conclusions: Physicians should not be guided by disease severity in suspecting specific etiologies in patients with bronchiectasis, although idiopathic bronchiectasis appears to be less common in patients with the most severe disease. PMID:26431397

  10. Coral diversity and the severity of disease outbreaks: a cross-regional comparison of Acropora white syndrome in a species-rich region (American Samoa) with a species-poor region (Northwestern Hawaiian Islands).

    USGS Publications Warehouse

    Aeby, G.S.; Bourne, D.G.; Wilson, B.; Work, Thierry M.

    2011-01-01

    The dynamics of the coral disease, Acropora white syndrome (AWS), was directly compared on reefs in the species-poor region of the Northwestern Hawaiian Islands (NWHI) and the species-rich region of American Samoa (AS) with results suggesting that biodiversity, which can affect the abundance of susceptible hosts, is important in influencing the impacts of coral disease outbreaks. The diversity-disease hypothesis predicts that decreased host species diversity should result in increased disease severity of specialist pathogens. We found that AWS was more prevalent and had a higher incidence within the NWHI as compared to AS. Individual Acropora colonies affected by AWS showed high mortality in both regions, but case fatality rate and disease severity was higher in the NWHI. The site within the NWHI had a monospecific stand of A. cytherea; a species that is highly susceptible to AWS. Once AWS entered the site, it spread easily amongst the abundant susceptible hosts. The site within AS contained numerous Acropora species, which differed in their apparent susceptibility to infection and disease severity, which in turn reduced disease spread. Manipulative studies showed AWS was transmissible through direct contact in three Acropora species. These results will help managers predict and respond to disease outbreaks.

  11. Cognitive functions in Parkinson's disease: relation to disease severity and hallucination.

    PubMed

    Wakamori, Takaaki; Agari, Takashi; Yasuhara, Takao; Kameda, Masahiro; Kondo, Akihiko; Shinko, Aiko; Sasada, Susumu; Sasaki, Tatsuya; Furuta, Tomohisa; Date, Isao

    2014-04-01

    We wished to relate severity of Parkinson's disease (PD) with cognitive function in relation to cerebral blood flow (CBF). Eighty-one consecutive PD patients were enrolled in this study. We used Mini-Mental State Examination (MMSE) and Wechsler Adult Intelligence Scale-Third edition (WAIS-III) to evaluate cognitive functions, and three-dimensional stereotactic ROI template (3DSRT) and Statistical Parametric Mapping (SPM) 8 to evaluate single photon emission CT (SPECT) recordings of regional CBF. The mean MMSE score of PD patients was 27.4 ± 2.4. The scores of most patients were higher than 23/30. On the other hand, the mean Full-scale IQ of PD patients was 88.4 ± 17.3 in WAIS-III, which was lower than that of normal controls. In particular, visuospatial function score of most patients was lower. There was significant correlation between cognitive scores and Hoehn & Yahr stage and hallucinatory episodes. PD Patients with stage III and IV showed significant deterioration in cognitive functions compared to stage II patients. Analysis of CBF revealed relative reductions in perfusion in the cerebral cortex relative to that in normal control. SPM 8 showed that cognitive functions in PD patients were positively correlated with rCBF in the thalamus and cingulate gyrus. This is the study to demonstrate the cognitive impairments in PD patients using WAIS-III. Visuospatial dysfunction might be caused by decrease in rCBF in the parietal and occipital lobes and dorsolateral prefrontal cortex. The severity of cognitive impairments in PD patients was correlated with disease severity and hallucinatory episodes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Static and Functional Balance in Individuals With COPD: Comparison With Healthy Controls and Differences According to Sex and Disease Severity.

    PubMed

    de Castro, Larissa A; Ribeiro, Laís Rg; Mesquita, Rafael; de Carvalho, Débora R; Felcar, Josiane M; Merli, Myriam F; Fernandes, Karen Bp; da Silva, Rubens A; Teixeira, Denilson C; Spruit, Martijn A; Pitta, Fabio; Probst, Vanessa S

    2016-11-01

    Studies have shown that individuals with COPD have impaired body balance, probably caused by the disease's multisystemic manifestations plus age-related decline in balance, potentially increasing the risk of falling and its consequences. However, little is known about the profile of individuals with COPD who present balance impairments, especially related to sex and disease severity stages. The aim of this work was to compare static and functional balance between subjects with COPD and healthy controls and to check possible differences according to sex and degrees of disease severity. Forty-seven subjects with COPD and 25 healthy controls were included in this study. Their static balance was assessed in one-legged stance using a force platform and functional balance with the Timed Up and Go test. Additionally, participants performed spirometry, the 6-min walk test and isometric quadriceps maximal voluntary contraction assessment. Disease severity was classified according to the Global Initiative for Obstructive Lung Disease stages and BODE (body mass index, air-flow obstruction, dyspnea, and exercise capacity) scores. In comparison with healthy controls, subjects with COPD had worse static (center of pressure displacement area: 9.3 ± 1.9 cm 2 vs 11.6 ± 4.0 cm 2 , respectively, P = .01) and functional balance (Timed Up and Go test: 8.5 ± 1.3 s vs 10.3 ± 1.8 s, respectively, P < .001). In the COPD group, men performed better in the Timed Up and Go test than women (9.8 ± 1.2 s vs 10.9 ± 2.2 s, respectively, P = .03), whereas women presented a better static balance in comparison with men for all parameters related to center of pressure (P < .005 for all). Disease severity did not affect any balance results. Individuals with COPD had worse static and functional balance in comparison with healthy controls. Sex can mediate these results, depending on the type of balance evaluation (force platform or functional test). Balance performance was similar among the groups

  13. The relationship between medical expenses and the severity of peripheral arterial disease in Japan.

    PubMed

    Seo, Akihiko; Yamamoto, Kota; Akai, Atsushi; Akagi, Daisuke; Takayama, Toshio; Hoshina, Katsuyuki

    2018-02-02

    The main objective is to examine whether the severity of peripheral arterial disease (PAD) affects the expenses and hospital stay of the patients who undergo bypass surgery below the inguinal ligament for PAD. Eighty consecutive patients who underwent infrainguinal bypass surgery for PAD between January 2012 and December 2014 were included in the study. Patients were divided into groups according to their critical limb ischemia (CLI) symptoms and the Wound, Ischemia, and Foot Infection (WIfI) classification. As endpoints, we assessed the duration of postoperative hospital stay and expenses during hospitalization. CLI was a significant factor for longer hospital stay and increased medical expenses (p = 0.009 and p = 0.001). In the patients with CLI, significant factors for longer hospital stay and increased medical expenses were (1) history of distal bypass (p = 0.33 and p = 0.003, respectively) and stage 4 local lower limb status in WIfI classification (p = 0.0007 and p = 0.053). PAD severity was associated with prolonged postoperative hospital stay and increased medical expenses. The presence or absence of CLI and its severity according to the WIfI classification correlated with medical expenses and hospital stay duration between the milder and severe groups.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  15. 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.

  16. 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

  17. Treatment inferred disease severity in Crohn's disease: evidence for a European gradient of disease course.

    PubMed

    Wolters, Frank L; Joling, Catelijne; Russel, Maurice G; Sijbrandij, Jildou; De Bruin, Marion; Odes, Selwyn; Riis, Lene; Munkholm, Pia; Bodini, Paolo; Ryan, Barbara; O'Morain, Colm; Mouzas, Ioannis A; Tsianos, Epameinondas; Vermeire, Severine; Monteiro, Estela; Limonard, Charles; Vatn, Morten; Fornaciari, Giovanni; Rodriguez, Dolores; Groot, Wim; Moum, Bjørn; Stockbrügger, Reinhold W

    2007-03-01

    Geographic differences in disease course of Crohn's disease (CD) might possibly be related to differences in genetic and environmental factors encountered in different parts of the world. The aim of this study was to assess differences in treatment regimens within a European cohort of CD patients as a reflection of disease course, and to identify associated phenotypic risk factors at diagnosis. A prospective European population-based inception cohort of 380 CD patients was studied. The patients were classified for phenotype according to the Vienna classification. Differences between Northern and Southern European centres in treatment over the first 10 years of disease were analysed using a competing risks survival analysis method. Patients in the North were more likely to have had surgery (p<0.01), whereas patients in the South were more likely to have been treated medically (p<0.01). Phenotype at diagnosis was not predictive of differences in treatment regimens between North and South. In this study, a difference in management of CD was observed between Northern and Southern European centres. This suggests that there may be a North-South disease severity gradient across Europe. Phenotypic differences between patients in the North and South did not explain this observed difference.

  18. Impact of Baseline Disease Severity Over 26 and 52 Weeks of Treatment with Calcitriol Ointment 3µg/g in Patients with Mild-to-moderate Plaque Psoriasis.

    PubMed

    Lebwohl, Mark; Preston, Norman; Gottschalk, Ronald W

    2012-02-01

    Calcitriol 3µg/g ointment has been shown to be a safe and effective treatment for adults with mild-to-moderate plaque psoriasis. This analysis evaluated the response to calcitriol 3µg/g ointment relative to baseline disease. Retrospective analysis of data from a 12-month safety and tolerability trial. At baseline, 40.1 percent (130/324) of patients had an affected body surface area of 11 to 20 percent, and 55.2 percent (179/324) had moderate and 25.9 percent (84/324) had severe disease according to global severity score. Patients applied calcitriol 3µg/g ointment twice daily for up to 52 weeks. Change in investigator's global severity scores and involved body surface area at Week 26 (N=249) and Week 52 (N=130) relative to baseline. Compared with baseline, most patients experienced at least a 1-grade improvement in global severity score at Weeks 26 (195/249, 78.3%) and 52 (109/130, 83.8%). Stabilization (i.e., no change in global severity score) was reported in 19.3 percent (48/249) at Week 26 and in 12.3 percent (16/130) at Week 52. Most patients also experienced at least a 1-grade improvement in body surface area involved at Weeks 26 (152/249, 61.0%) and 52 (95/130, 73.1%). Stabilization (no change in affected body surface area) was reported in 32.5 percent (81/249) at Week 26 and 24.6 percent (32/130) at Week 52. The proportion of patients experiencing improvement in global severity score and body surface area was comparable across all categories of severity and disease extent at baseline. This analysis suggests that calcitriol 3µg/g ointment use for 26 weeks (N=249) and 52 weeks (N=130) was associated with disease improvement or stabilization in most patients with plaque psoriasis.

  19. Impact of severity of congenital heart diseases on university graduation rate among male patients.

    PubMed

    Özcan, Emin Evren; Küçük, Alaattin

    2012-04-01

    This study examines university graduation rates among individuals with congenital heart disease (CHD) in comparison to their healthy peers. The effect of disease severity, type of surgery, and timing of surgery on graduation rate was also evaluated. One hundred forty-five male patients with CHD at military age were enrolled in the study between the dates of January 2005 and May 2007. Severity of disease was operationalised in term of initial diagnosis (According to classification of 32th ACC Bethesta Conference Task Force 1). University graduation rates of among two groups of CHD patients (mild disease (group 1) or moderate to severe disease (group 2)) are compared to each other and to healthy peers. Patients with CHD have reduced rates of participation in higher education compared with healthy individuals (13.1% vs 20.7%, p=0.01). Furthermore, this negative effect on education participation rate is independent of the severity of disease (group 1, 16.4%, p=0.01; group 2, 9.7%, p<0.001). Although the university graduation rate was relatively higher in patients with mild disease severity, no significant difference was found between the two patient groups (p=0.23). Having an operation does not effect graduation rate (p=0.58), however greater age at the time of operation increases the likelihood of graduation (p=0.02). Being born with CHD significantly reduces the chance of completing higher education. This negative impact on university graduation rate is independent of the severity of the disease. No negative effects of disease related surgery or subsequent corrective surgery on education were observed. Patients who were operated on later in life were more likely to complete university education. Mean operation age of this group corresponds to the typical age during the last year of elementary school in Turkey.

  20. 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.

  1. von Willebrand's disease antigen II. A new plasma and platelet antigen deficient in severe von Willebrand's disease.

    PubMed Central

    Montgomery, R R; Zimmerman, T S

    1978-01-01

    Factor VIII-related antigen (VIIIag) is deficient in plasma and platelets of patients with severe von Willebrand's disease. This study reports a second von Willebrand's disease antigen (vWagII), distinct from VIIIag, that is also deficient in the platelets and plasma of patients with severe von Willebrand's disease. VIIIag and vWagII are separable by molecular exclusion chromatography, sucrose density gradient ultracentrifugation, and crossed immunoelectrophoresis. They show reactions of immunologic nonidentity with each other, and thus, do not share a precursor-product relationship. vWagII is released from normal platelets during blood clotting, accounting for a fourfold higher concentration of vWagII in serum over plasma. Images PMID:307007

  2. White-Nose Syndrome Disease Severity and a Comparison of Diagnostic Methods.

    PubMed

    McGuire, Liam P; Turner, James M; Warnecke, Lisa; McGregor, Glenna; Bollinger, Trent K; Misra, Vikram; Foster, Jeffrey T; Frick, Winifred F; Kilpatrick, A Marm; Willis, Craig K R

    2016-03-01

    White-nose syndrome is caused by the fungus Pseudogymnoascus destructans and has killed millions of hibernating bats in North America but the pathophysiology of the disease remains poorly understood. Our objectives were to (1) assess non-destructive diagnostic methods for P. destructans infection compared to histopathology, the current gold-standard, and (2) to evaluate potential metrics of disease severity. We used data from three captive inoculation experiments involving 181 little brown bats (Myotis lucifugus) to compare histopathology, quantitative PCR (qPCR), and ultraviolet fluorescence as diagnostic methods of P. destructans infection. To assess disease severity, we considered two histology metrics (wing area with fungal hyphae, area of dermal necrosis), P. destructans fungal load (qPCR), ultraviolet fluorescence, and blood chemistry (hematocrit, sodium, glucose, pCO2, and bicarbonate). Quantitative PCR was most effective for early detection of P. destructans, while all three methods were comparable in severe infections. Correlations among hyphae and necrosis scores, qPCR, ultraviolet fluorescence, blood chemistry, and hibernation duration indicate a multi-stage pattern of disease. Disruptions of homeostasis occurred rapidly in late hibernation. Our results provide valuable information about the use of non-destructive techniques for monitoring, and provide novel insight into the pathophysiology of white-nose syndrome, with implications for developing and implementing potential mitigation strategies.

  3. Origin of porcine circovirus type 2 (PCV2) from swine affected by PCV2-associated diseases in Croatia.

    PubMed

    Novosel, D; Tuboly, T; Csagola, A; Lorincz, M; Cubric-Curik, V; Jungic, A; Curik, I; Segalés, J; Cortey, M; Lipej, Z

    2014-04-26

    Porcine circovirus type 2 (PCV2) causes some of the most significant economic losses in pig production. Several multisystemic syndromes have been attributed to PCV2 infection, which are known as PCV2-associated diseases (PCVDs). This study investigated the origin and evolution of PCV2 sequences in domestic pigs and wild boars affected by PCVDs in Croatia. Viral sequences were recovered from three wild boars diagnosed with PCV2-systemic disease (PCV2-SD), 63 fetuses positive for PCV2 DNA as determined by PCR, 14 domestic pigs affected with PCV2-SD (displaying severe interstitial nephritis) and five domestic pigs with proliferative and necrotising pneumonia. Seventeen complete PCV2 genomes were recovered. Phylogenetic and evolutionary analyses based on median-joining phylogenetic networks, amino acid alignments and principal coordinate analysis were performed using complete genomes, as well as complete and partial ORF sequences for ORF1 and ORF2. Two of the 17 PCV2 sequences belonged to PCV2a, 14 to PCV2b and one was unclustered. PCV2b was the predominant genotype in Croatia and has been linked to international trade as a route of introduction. Correlation between particular viral strains with PCVDs is lacking.

  4. Does midwife experience affect the rate of severe perineal tears?

    PubMed

    Mizrachi, Yossi; Leytes, Sophia; Levy, Michal; Hiaev, Zvia; Ginath, Shimon; Bar, Jacob; Kovo, Michal

    2017-06-01

    Our aim was to study whether midwife experience affects the rate of severe perineal tears (3rd and 4th degree). A retrospective cohort study of all women with term vertex singleton pregnancies, who underwent normal vaginal deliveries, in a single tertiary hospital, between 2011 and 2015, was performed. Exclusion criteria were instrumental deliveries and stillbirth. All midwives used a "hands on" technique for protecting the perineum. The midwife experience at each delivery was calculated as the time interval between her first delivery and current delivery. A comparison was performed between deliveries in which midwife experience was less than 2 years (inexperienced), between 2 and 10 years (moderately experienced), and more than 10 years (highly experienced). A multivariate regression analysis was performed to assess the association between midwife experience and the incidence of severe perineal tears, after controlling for confounders. Overall, 15 146 deliveries were included. Severe perineal tears were diagnosed in 51 (0.33%) deliveries. Women delivered by inexperienced midwives had a higher rate of severe perineal tears compared with women delivered by highly experienced midwives (0.5% vs 0.2%, respectively, P=.024). On multivariate regression analysis, midwife experience was independently associated with a lower rate of severe perineal tears, after controlling for confounding factors. Each additional year of experience was associated with a 4.7% decrease in the risk of severe perineal tears (adjusted OR 0.95 [95% CI 0.91-0.99, P=.03). More experienced midwives had a lower rate of severe perineal tears, and may be preferred for managing deliveries of women at high risk for such tears. © 2017 Wiley Periodicals, Inc.

  5. Serum cytokine tumor necrosis factor-alpha and interleukin-6 associated with the severity of coronary artery disease: indicators of an active inflammatory burden?

    PubMed

    Gotsman, Israel; Stabholz, Ayala; Planer, David; Pugatsch, Thea; Lapidus, Ludmila; Novikov, Yelena; Masrawa, Siham; Soskolne, Aubrey; Lotan, Chaim

    2008-07-01

    Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease. To determine the relationship between inflammatory markers and the angiographic severity of CAD. We measured inflammatory markers in consecutive patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1 receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay. There was a significant correlation between TNFalpha and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFalpha; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P< 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFalpha (P< 0.05) and combined levels of TNFalpha and IL-6 (P< 0.05). IL-6 levels were independently predictive of Gensini coronary score (P< 0.05). TNFalpha and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.

  6. Impact of genetic risk information and type of disease on perceived risk, anticipated affect, and expected consequences of genetic tests.

    PubMed

    Cameron, Linda D; Sherman, Kerry A; Marteau, Theresa M; Brown, Paul M

    2009-05-01

    Genetic tests vary in their prediction of disease occurrence, with some mutations conferring relatively low risk and others indicating near certainty. The authors assessed how increments in absolute risk of disease influence risk perceptions, interest, and expected consequences of genetic tests for diseases of varying severity. Adults (N = 752), recruited from New Zealand, Australia, and the United Kingdom for an online analogue study, were randomly assigned to receive information about a test of genetic risk for diabetes, heart disease, colon cancer, or lung cancer. The lifetime risk varied across conditions by 10% increments, from 20% to 100%. Participants completed measures of perceived likelihood of disease for individuals with mutations, risk-related affect, interest, and testing consequences. Analyses revealed two increment clusters yielding differences in likelihood perceptions: A "moderate-risk" cluster (20%-70%), and a "high-risk" cluster (80%-100%). Risk increment influenced anticipated worry, feelings of risk, testing-induced distress, and family obligations, with nonlinear patterns including disproportionately high responses for the 50% increment. Risk increment did not alter testing interest or perceived benefits. These patterns of effects held across the four diseases. Magnitude of risk from genetic testing has a nonlinear influence on risk-related appraisals and affect but is unrelated to test interest.

  7. Sleep apnoea is common in severe peripheral arterial disease.

    PubMed

    Schahab, Nadjib; Sudan, Sarah; Schaefer, Christian; Tiyerili, Vedat; Steinmetz, Martin; Nickenig, Georg; Skowasch, Dirk; Pizarro, Carmen

    2017-01-01

    Atherosclerotic conditions have been demonstrated to be associated with sleep- disordered breathing (SDB). Peripheral arterial disease (PAD) represents severe atherosclerosis with a high mortality. In early stages of PAD a substantial prevalence of sleep apnoea has already been shown. Here, we sought to determine the frequency of undiagnosed sleep apnoea in a homogeneous group of advanced PAD patients undergoing percutaneous revascularization. 59 consecutive patients (mean age: 71.1 ± 9.8 years, 67.8% males) with PAD in Fontaine stages IIb-IV that underwent percutaneous transluminal angioplasty at our department were enrolled for pre-procedural polygraphy. Patients appertained to Fontaine clinical stage IIb, III and IV in 54.2%, 23.8% and 22.% of cases, respectively, and were principally intervened for femoropopliteal occlusive disease (71.2% of total study population). Polygraphy revealed sleep apnoea in 48 out of 59 patients (81.4%), of whom 60.4% offered a primarily obstructive-driven genesis. Among those patients with polygraphically confirmed sleep apnoea, mean apnoea hypopnoea index (AHI) and mean oxygen desaturation index (ODI) averaged 28.2 ± 19.5/h and 26.7 ± 18.8/h, respectively. 18 patients even offered an AHI ≥30/h that is indicative of severe sleep apnoea. For obstructive-driven apnoeic events, AHI correlated significantly with PAD severity stages (p = 0.042). In our PAD collective, sleep apnoea was frequent and obstructive sleep apnoea´s severity correlated with PAD severity stages. Long-term results regarding the vasoprotective impact of CPAP treatment on PAD course remains to be determined.

  8. Factors influencing quality of life and disease severity in Hungarian children and young adults with cystic fibrosis.

    PubMed

    Bodnar, Reka; Kadar, Laszlo; Holics, Klara; Ujhelyi, Rita; Kovacs, Lajos; Bolbas, Katalin; Szekely, Gyongyi; Gyurkovits, Kalman; Solyom, Eniko; Meszaros, Agnes

    2014-06-02

    The aim of our study was to evaluate factors affecting cystic fibrosis (CF) patients' health-related quality of life (HRQoL) and to assess the level of agreement on HRQol between children and their parents. Fifty-nine patients (mean age: 14.03 ± 4.81 years) from 5 Hungarian CF centres completed the survey. HRQoL was measured using The Cystic Fibrosis Questionnaire-Revised (CFQ-R). Parents were asked to fill out a questionnaire about their smoking habits, educational level and history of chronic illness. Disease severity was assessed using the physician-reported Shwachman-Kulczycki (SK) score system. Spirometry, Body Mass Index (BMI) percentile (pc), hospitalisation and Pseudomonas aeruginosa (PA) infection were examined as physiologic parameters of CF, and the impact of these factors on HRQoL was assessed. A multivariate regression analysis was performed to identify the most important factors affecting HRQoL. The level of significance was set to 0.05. Passive smoking and parental educational level and chronic diseases status did not have a significant impact on the patients' HRQoL (p > 0.05). Significantly lower SK scores and spirometry values were found in low BMI pc patients (p < 0.001), in hospitalised (p < 0.01) and in PA-infected patients (p < 0.01), than in the adequate-weight, non-hospitalised and PA culture-negative subgroup. Lower CFQ-R scores were detected in hospitalised patients than in non-hospitalised patients in their Physical functioning domain. PA-infected patients had HRQoL scores that were significantly worse in the Body image (p < 0.01) and Respiratory symptoms (p < 0.05) domains than the PA culture-negative patients. Patients with a low BMI pc (<25th BMI pc) had significantly lower scores in the Eating, Body image and Treatment burden domains, than the adequate-weight patients (>25th BMI pc) (p < 0.01). A strong child-parent agreement was found in the Physical functioning domain (r = 0.77, p < 0.01). Passive smoking, parental educational level

  9. Brain-water diffusion coefficients reflect the severity of inherited prion disease

    PubMed Central

    Hyare, H.; Wroe, S.; Siddique, D.; Webb, T.; Fox, N. C.; Stevens, J.; Collinge, J.; Yousry, T.; Thornton, J. S.

    2010-01-01

    Objective: Inherited prion diseases are progressive neurodegenerative conditions, characterized by cerebral spongiosis, gliosis, and neuronal loss, caused by mutations within the prion protein (PRNP) gene. We wished to assess the potential of diffusion-weighted MRI as a biomarker of disease severity in inherited prion diseases. Methods: Twenty-five subjects (mean age 45.2 years) with a known PRNP mutation including 19 symptomatic patients, 6 gene-positive asymptomatic subjects, and 7 controls (mean age 54.1 years) underwent conventional and diffusion-weighted MRI. An index of normalized brain volume (NBV) and region of interest (ROI) mean apparent diffusion coefficient (ADC) for the head of caudate, putamen, and pulvinar nuclei were recorded. ADC histograms were computed for whole brain (WB) and gray matter (GM) tissue fractions. Clinical assessment utilized standardized clinical scores. Mann-Whitney U test and regression analyses were performed. Results: Symptomatic patients exhibited an increased WB mean ADC (p = 0.006) and GM mean ADC (p = 0.024) compared to controls. Decreased NBV and increased mean ADC measures significantly correlated with clinical measures of disease severity. Using a stepwise multivariate regression procedure, GM mean ADC was an independent predictor of Clinician's Dementia Rating score (p = 0.001), Barthel Index of activities of daily living (p = 0.001), and Rankin disability score (p = 0.019). Conclusions: Brain volume loss in inherited prion diseases is accompanied by increased cerebral apparent diffusion coefficient (ADC), correlating with increased disease severity. The association between gray matter ADC and clinical neurologic status suggests this measure may prove a useful biomarker of disease activity in inherited prion diseases. GLOSSARY ADAS-Cog = Alzheimer's Disease Assessment Scale–Cognitive subscale; ADC = apparent diffusion coefficient; ADL = Barthel Activities of Daily Living scale; BET = brain extraction tool; BPRS

  10. 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…

  11. 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.

  12. Emotion Risk-Factor in Patients With Cardiac Diseases: The Role of Cognitive Emotion Regulation Strategies, Positive Affect and Negative Affect (A Case-Control Study)

    PubMed Central

    Bahremand, Mostafa; Alikhani, Mostafa; Zakiei, Ali; Janjani, Parisa; Aghaei, Abbas

    2016-01-01

    Application of psychological interventions is essential in classic treatments for patient with cardiac diseases. The present study compared cognitive emotion regulation strategies, positive affect, and negative affect for cardiac patients with healthy subjects. This study was a case-control study. Fifty subjects were selected using convenient sampling method from cardiac (coronary artery disease) patients presenting in Imam Ali medical center of Kermanshah, Iran in the spring 2013. Fifty subjects accompanied the patients to the medical center, selected as control group, did not have any history of cardiac diseases. For collecting data, the cognitive emotion regulation questionnaire and positive and negative affect scales were used. For data analysis, multivariate analysis of variance (MANOVA) was applied using the SPSS statistical software (ver. 19.0). In all cognitive emotion regulation strategies, there was a significant difference between the two groups. A significant difference was also detected regarding positive affect between the two groups, but no significant difference was found regarding negative affect. We found as a result that, having poor emotion regulation strategies is a risk factor for developing heart diseases. PMID:26234976

  13. Emotion Risk-Factor in Patients with Cardiac Diseases: The Role of Cognitive Emotion Regulation Strategies, Positive Affect and Negative Affect (A Case-Control Study).

    PubMed

    Bahremand, Mostafa; Alikhani, Mostafa; Zakiei, Ali; Janjani, Parisa; Aghei, Abbas

    2015-05-17

    Application of psychological interventions is essential in classic treatments for patient with cardiac diseases. The present study compared cognitive emotion regulation strategies, positive affect, and negative affect for cardiac patients with healthy subjects. This study was a case-control study. Fifty subjects were selected using convenient sampling method from cardiac (coronary artery disease) patients presenting in Imam Ali medical center of Kermanshah, Iran in the spring 2013. Fifty subjects accompanied the patients to the medical center, selected as control group, did not have any history of cardiac diseases. For collecting data, the cognitive emotion regulation questionnaire and positive and negative affect scales were used. For data analysis, multivariate analysis of variance (MANOVA) Was applied using the SPSS statistical software (ver. 19.0). In all cognitive emotion regulation strategies, there was a significant difference between the two groups. A significant difference was also detected regarding positive affect between the two groups, but no significant difference was found regarding negative affect. We found as a result that, having poor emotion regulation strategies is a risk factor for developing heart diseases.

  14. Severity of mumps disease is related to MMR vaccination status and viral shedding.

    PubMed

    Gouma, Sigrid; Hahné, Susan J M; Gijselaar, Daphne B; Koopmans, Marion P G; van Binnendijk, Rob S

    2016-04-07

    During recent years, various mumps outbreaks have occurred among measles, mumps, and rubella (MMR) vaccinated persons in various countries worldwide, including the Netherlands. We studied mumps virus shedding in MMR vaccinated and unvaccinated mumps patients and related these findings to clinical data. In this study, we included 1112 mumps patients of whom diagnostic samples were tested positive in our laboratory between 1 January 2007 and 31 December 2014. We compared mumps virus shedding and severity of disease between patients who had received 2 doses of MMR (n=592) and unvaccinated mumps patients (n=195). Mumps virus shedding in saliva and urine specimens was measured by qPCR. Severity of disease was studied in a subset of patients with clinical data available. Mumps patients who had received 2 MMR doses shed less often mumps virus in their urine than unvaccinated patients. Salivary viral loads were higher at day of onset of disease in twice MMR vaccinated patients with viruria than in twice MMR vaccinated patients without viruria. However, salivary viral loads did not significantly differ between patients who had received 2 MMR doses and unvaccinated patients. Bilateral parotitis and orchitis were less often reported in patients who had received 2 MMR doses than in unvaccinated patients. Furthermore, the prevalence of bilateral parotitis and orchitis was higher among twice MMR vaccinated patients with viruria than among twice MMR vaccinated patients without viruria. MMR vaccination was associated with less severe disease among mumps patients. Systemic spread of virus was associated with more severe disease. The elevated salivary viral loads in patients with systemic mumps disease suggest that these patients pose a higher risk for mumps virus transmission. Our study contributes to the understanding of mumps virus pathogenesis and shows the protective effect of MMR vaccination on severity of disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. All Is Not Lost: Positive Behaviors in Alzheimer's Disease and Behavioral-Variant Frontotemporal Dementia with Disease Severity.

    PubMed

    Midorikawa, Akira; Leyton, Cristian E; Foxe, David; Landin-Romero, Ramon; Hodges, John R; Piguet, Olivier

    2016-09-06

    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. 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). 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. 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. 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.

  16. [Severe acute respiratory syndrome: the first transmissible disease of the 21st century].

    PubMed

    Nicastri, Emanuele; Petrosillo, Nicola; Macrì, Giulia; Ippolito, Giuseppe

    2003-01-01

    The Severe Acute Respiratory Syndrome (SARS) is the first severe and easily transmissible disease to emerge in the 21st century. It is caused by the infection with a coronavirus, a single strand RNA capsulated virus, recently found in a small mammalian, the masked palm civet. It is likely to represent the source of human infection. The first cases of SARS have been reported in the Chinese province of Guangdong and, since then, probable cases have been reported world wide. The clinical picture is characterized by nonspecific symptoms such as fever, cough or dyspnea in patients affected by air-space opacities (unifocal involvement in the 54.6% of cases) or distress respiratory syndrome and linked to a recent exposure to a SARS case or to a travel/residence in an affected area. The empirical therapy is based on broad-spectrum antibiotics, steroids and ribavirin, but susceptibility testing have failed to demonstrate direct anti-viral activity of ribavirin against SARS-related coronavirus in vitro. The exposure to respiratory droplets and the contact with biologic fluids (respiratory and gastrointestinal secretions) represent the most efficient transmission modality of the SARS-related coronavirus. Hand hygiene is the most simple and cost effective measure of infection control to prevent contagion, and the use of airborne, contact and droplet precaution is strictly recommended to all health care workers taking care of such patients. The spread of SARS, to less developed country with limited resource for public health programs, represent the emerging alarming threat in the new global scenario.

  17. Hypokalemic Paralysis: A Hidden Card of Several Autoimmune Diseases

    PubMed Central

    Velarde-Mejía, Yelitza; Gamboa-Cárdenas, Rocío; Ugarte-Gil, Manuel; Asurza, César Pastor

    2017-01-01

    Acute hypokalemic paralysis is a rare and potentially fatal condition, with few related causes, one of which highlights distal renal tubular acidosis (dRTA). Distal renal tubular acidosis is a rare complication of several autoimmune diseases such as systemic lupus erythematosus, Sjögren’s syndrome, and Hashimoto thyroiditis. We report a case of a lupic patient who presented rapidly progressive quadriparesis in the context of active renal disease. Research revealed severe refractory hypokalemia, metabolic acidosis, and alkaline urine suggestive of dRTA. We diagnosed Sjögren’s syndrome based on sicca symptoms, an abnormal salivary glands’ nuclear scan and the presence of anti-Ro/SSA and anti-La/SSB. In addition, the finding of thyroid peroxidase, thyroglobulin antibodies, and hypothyroidism led us to the diagnosis of Hashimoto thyroiditis. Due to the active renal involvement on the context of systemic lupus erythematosus and Sjögren’s syndrome, the patient received immunosuppression with rituximab, resulting in a progressive and complete improvement. PMID:28839447

  18. Germline hypomorphic CARD11 mutations in severe atopic disease

    PubMed Central

    Ma, Chi A; Stinson, Jeffrey R; Zhang, Yuan; Abbott, Jordan K; Weinreich, Michael A; Hauk, Pia J; Reynolds, Paul R; Lyons, Jonathan J; Nelson, Celeste G; Ruffo, Elisa; Dorjbal, Batsukh; Glauzy, Salomé; Yamakawa, Natsuko; Arjunaraja, Swadhinya; Voss, Kelsey; Stoddard, Jennifer; Niemela, Julie; Zhang, Yu; Rosenzweig, Sergio D; McElwee, Joshua J; DiMaggio, Thomas; Matthews, Helen F; Jones, Nina; Stone, Kelly D; Palma, Alejandro; Oleastro, Matías; Prieto, Emma; Bernasconi, Andrea R; Dubra, Geronimo; Danielian, Silvia; Zaiat, Jonathan; Marti, Marcelo A; Kim, Brian; Cooper, Megan A; Romberg, Neil D; Meffre, Eric; Gelfand, Erwin W; Snow, Andrew L; Milner, Joshua D

    2017-01-01

    Few monogenic causes for severe manifestations of common allergic diseases have been identified. Via next generation sequencing on a cohort of patients with severe atopic dermatitis, some with comorbid infections, we found 8 individuals from 4 families with novel heterozygous mutations in CARD11, a scaffolding protein involved in lymphocyte receptor signaling. Disease improved over time in most patients. Transfection of mutant expression constructs into T cell lines demonstrated both loss of function and dominant interfering activity upon antigen receptor-induced NF-κB and mTORC1 activation. Patient T-cells had similar defects, as well as diminished IFN-γ cytokine production. The mTORC1 and IFN-γ production defects could be partially rescued by supplementing with glutamine, which requires CARD11 for import into T cells. Our findings indicate a single hypomorphic gene mutation in CARD11 can cause potentially correctable cellular defects that lead to atopic dermatitis. PMID:28628108

  19. 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

  20. CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity

    PubMed Central

    Blaisdell, Carol J; Howard, Timothy D; Stern, Augustus; Bamford, Penelope; Bleecker, Eugene R; Stine, O Colin

    2004-01-01

    Background Cystic fibrosis (CF) lung disease manifest by impaired chloride secretion leads to eventual respiratory failure. Candidate genes that may modify CF lung disease severity include alternative chloride channels. The objectives of this study are to identify single nucleotide polymorphisms (SNPs) in the airway epithelial chloride channel, CLC-2, and correlate these polymorphisms with CF lung disease. Methods The CLC-2 promoter, intron 1 and exon 20 were examined for SNPs in adult CF dF508/dF508 homozygotes with mild and severe lung disease (forced expiratory volume at one second (FEV1) > 70% and < 40%). Results PCR amplification of genomic CLC-2 and sequence analysis revealed 1 polymorphism in the hClC -2 promoter, 4 in intron 1, and none in exon 20. Fisher's analysis within this data set, did not demonstrate a significant relationship between the severity of lung disease and SNPs in the CLC-2 gene. Conclusions CLC-2 is not a key modifier gene of CF lung phenotype. Further studies evaluating other phenotypes associated with CF may be useful in the future to assess the ability of CLC-2 to modify CF disease severity. PMID:15507145

  1. Aberrant monocyte responses predict and characterize dengue virus infection in individuals with severe disease.

    PubMed

    Yong, Yean K; Tan, Hong Y; Jen, Soe Hui; Shankar, Esaki M; Natkunam, Santha K; Sathar, Jameela; Manikam, Rishya; Sekaran, Shamala D

    2017-05-31

    Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks. We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1β in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS-), dengue with warning signs (DWS+) and severe dengue (SD). Our results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P < 0.0001; AUC = 0.819, P < 0.0001 and AUC = 0.647, P = 0.014 respectively). Furthermore, we also found that the levels of VEGF were directly correlated and sCD14 was inversely correlated with platelet count, suggesting that the endothelial activation and microbial translocation may played a role in pathogenesis of dengue disease. Given that the elevation IL-18, LBP and sCD14 among patients with severe form of dengue disease, our findings suggest a pathogenic role for an aberrant inflammasome and monocyte activation in the development of severe form of dengue disease.

  2. The severe perinatal form of autosomal recessive polycystic kidney disease maps to chromosome 6p21.1-p12: Implications for genetic counseling

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

    Guay-Woodford, L.M.; Hopkins, S.D.; Waldo, F.B.

    Autosomal recessive polycystic kidney disease (ARPKD) is a one of the most common hereditary renal cystic diseases in children. Its clinical spectrum is widely variable with most cases presenting in infancy. Most affected neonates die within the first few hours of life. At present, prenatal diagnosis relies on fetal sonography, which is often imprecise in detecting even the severe form of the disease. Recently, in a cohort of families with mostly milder ARPKD phenotypes, an ARPKD locus was mapped to a 13-cM region of chromosome 6p21-cen. To determine whether severe perinatal ARPKD also maps to chromosome 6p, we have analyzedmore » the segregation of seven microsatellite markers from the ARPKD interval in 22 families with the severe phenotype. In the majority of the affected infants, ARPKD was documented by hisopathology. Our data confirm linkage and refine the ARPKD region to a 3.8-cM interval, delimited by the markers D6S465/D6S427/D6S436/D6S272 and D6S466. Taken together, these results suggest that, despite the wide variability in clinical phenotypes, there is a single ARPKD gene. These linkage data and the absence of genetic heterogeneity in all families tested to date have important implications for DNA-based prenatal diagnoses as well as for the isolation of the ARPKD gene. 22 refs., 4 figs., 1 tab.« less

  3. 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.…

  4. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis.

    PubMed

    Reis, Eliana A G; Hagan, José E; Ribeiro, Guilherme S; Teixeira-Carvalho, Andrea; Martins-Filho, Olindo A; Montgomery, Ruth R; Shaw, Albert C; Ko, Albert I; Reis, Mitermayer G

    2013-01-01

    The role of the immune response in influencing leptospirosis clinical outcomes is not yet well understood. We hypothesized that acute-phase serum cytokine responses may play a role in disease progression, risk for death, and severe pulmonary hemorrhage syndrome (SPHS). We performed a case-control study design to compare cytokine profiles in patients with mild and severe forms of leptospirosis. Among patients hospitalized with severe disease, we compared those with fatal and nonfatal outcomes. During active outpatient and hospital-based surveillance we prospectively enrolled 172 patients, 23 with mild disease (outpatient) and 149 with severe leptospirosis (hospitalized). Circulating concentrations of pro- and anti-inflammatory cytokines at the time of patient presentation were measured using a multiplex bead array assay. Concentrations of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, and TNF-α were significantly higher (P<0.05) in severe disease compared to mild disease. Among severe patients, levels of IL-6 (P<0.001), IL-8 (P = 0.0049) and IL-10 (P<0.001), were higher in fatal compared to non-fatal cases. High levels of IL-6 and IL-10 were independently associated (P<0.05) with case fatality after adjustment for age and days of symptoms. IL-6 levels were higher (P = 0.0519) among fatal cases who developed SPHS than among who did not. This study shows that severe cases of leptospirosis are differentiated from mild disease by a "cytokine storm" process, and that IL-6 and IL-10 may play an immunopathogenic role in the development of life-threatening outcomes in human leptospirosis.

  6. The involvement of autoimmunity against retinal antigens in determining disease severity in toxoplasmosis.

    PubMed

    Vallochi, Adriana Lima; da Silva Rios, Lília; Nakamura, Marceli Vicente; Silveira, Cláudio; Muccioli, Cristina; Martins, Maria Cristina; Belfort, Rubens; Rizzo, Luiz Vicente

    2005-02-01

    Ocular lesions are frequent in various individuals infected with Toxoplasma gondii. Disease intensity in ocular toxoplasmosis varies greatly between patients. Autoimmunity has been suggested as a possible component to retinal destruction. Immunologic parameters in the response to retina antigens were evaluated in infected persons with and without ocular lesions and in non-infected controls. Subjects were divided into groups on the basis of titers of serum antibodies to T. gondii, presence and severity of ocular lesions, and clinical history. Peripheral blood mononuclear cells from patients with mild disease responded to one or more retinal antigens with a significantly higher frequency than patients without disease or with severe disease. Interestingly, the cytokines produced by the proliferating mononuclear cells did not follow any specific patterns, except for the fact that IL-4 and IL-5 were seldom detected. Our results suggest that although the presence of an immune response towards autoantigens is not protective against the development of ocular lesions by the T. gondii, it may protect against the development of severe disease.

  7. 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

  8. Cutaneous allodynia is more frequent in chronic migraine, and its presence and severity seems to be more associated with the duration of the disease.

    PubMed

    Benatto, Mariana Tedeschi; Florencio, Lidiane Lima; Carvalho, Gabriela Ferreira; Dach, Fabíola; Bigal, Marcelo Eduardo; Chaves, Thaís Cristina; Bevilaqua-Grossi, Débora

    2017-03-01

    To evaluate cutaneous allodynia among patients with chronic and episodic migraine in a tertiary headache clinic. 80 subjects with episodic migraine and 80 with chronic migraine were assessed in a tertiary hospital. The 12-item Allodynia Symptom Checklist/Brazil questionnaire was applied to classify subjects according to the presence and severity of cutaneous allodynia. Cutaneous allodynia was identified in 81.3% of the episodic migraine group and 92.5% of the chronic migraine group (p = 0.03). No increased association could be attributed to chronic migraine when adjusted by years with disease (PR = 1.12; 95%CI = 0.99 to 1.27; p = 0.06). The groups also did not differ in the severity of allodynia, and severe presentation was the most frequent. Both groups seemed to be similarly affected in the cephalic and extracephalic regions, with the same severity. Cutaneous allodynia is more frequent in chronic migraine, and its presence and severity seems to be more associated with the duration of the disease.

  9. Worse Prognosis for Stage IA Lung Cancer Patients with Smoking History and More Severe Chronic Obstructive Pulmonary Disease.

    PubMed

    Yoshida, Yukihiro; Kage, Hidenori; Murakawa, Tomohiro; Sato, Yasunori; Ota, Satoshi; Fukayama, Masashi; Nakajima, Jun

    2015-01-01

    This retrospective study examined whether the severity of chronic obstructive lung disease (COPD) affects surgical outcomes. The subjects were 243 consecutive patients who underwent lobectomy for clinical stage IA lung cancer from 1999 to 2008 in our hospital. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading system was used to classify the severity of COPD in smokers. Among the 149 smokers, 62 were diagnosed with COPD (25 as GOLD 1, 33 as GOLD 2, and 4 as GOLD 3). In univariate analysis, postoperative pulmonary complications were associated with male sex and more severe COPD. The frequencies were 17.1% in non-COPD, 24.0% in GOLD 1-COPD, and 46.0% in GOLD 2/3-COPD smokers (p = 0.0006). In univariate analysis, older age, smoking history, higher smoking pack-years and more severe COPD were associated with poor relapse-free survival. Relapse-free survival at five years was 80.7%, 66.9%, and 61.3% in non-COPD, GOLD 1-COPD, and GOLD 2/3-COPD smokers, respectively (p = 0.0005). Multivariate analyses showed that only GOLD 2/3-COPD was associated with postoperative pulmonary complications and relapse-free survival. Inhaled bronchodilators were prescribed preoperatively to 24.3% of the GOLD 2/3-COPD group. Smokers with GOLD 2/3-COPD are at high risk for pulmonary complications and have an unfavorable long-term prognosis.

  10. The association between previous and future severe exacerbations of chronic obstructive pulmonary disease: Updating the literature using robust statistical methodology.

    PubMed

    Sadatsafavi, Mohsen; Xie, Hui; Etminan, Mahyar; Johnson, Kate; FitzGerald, J Mark

    2018-01-01

    There is minimal evidence on the extent to which the occurrence of a severe acute exacerbation of COPD that results in hospitalization affects the subsequent disease course. Previous studies on this topic did not generate causally-interpretable estimates. Our aim was to use corrected methodology to update previously reported estimates of the associations between previous and future exacerbations in these patients. Using administrative health data in British Columbia, Canada (1997-2012), we constructed a cohort of patients with at least one severe exacerbation, defined as an episode of inpatient care with the main diagnosis of COPD based on international classification of diseases (ICD) codes. We applied a random-effects 'joint frailty' survival model that is particularly developed for the analysis of recurrent events in the presence of competing risk of death and heterogeneity among individuals in their rate of events. Previous severe exacerbations entered the model as dummy-coded time-dependent covariates, and the model was adjusted for several observable patient and disease characteristics. 35,994 individuals (mean age at baseline 73.7, 49.8% female, average follow-up 3.21 years) contributed 34,271 severe exacerbations during follow-up. The first event was associated with a hazard ratio (HR) of 1.75 (95%CI 1.69-1.82) for the risk of future severe exacerbations. This risk decreased to HR = 1.36 (95%CI 1.30-1.42) for the second event and to 1.18 (95%CI 1.12-1.25) for the third event. The first two severe exacerbations that occurred during follow-up were also significantly associated with increased risk of all-cause mortality. There was substantial heterogeneity in the individual-specific rate of severe exacerbations. Even after adjusting for observable characteristics, individuals in the 97.5th percentile of exacerbation rate had 5.6 times higher rate of severe exacerbations than those in the 2.5th percentile. Using robust statistical methodology that controlled

  11. Severe ipsilateral carotid stenosis and middle cerebral artery disease in lacunar ischaemic stroke: innocent bystanders?

    PubMed

    Mead, G E; Lewis, S C; Wardlaw, J M; Dennis, M S; Warlow, C P

    2002-03-01

    Lacunar infarcts are thought to be mostly due to intracranial small vessel disease. Therefore, when a stroke patient with a relevant lacunar infarct does have severe ipsilateral internal carotid artery (ICA) or middle cerebral artery (MCA) disease, it is unclear whether the arterial disease is causative or coincidental. If causative, we would expect ICA/MCA disease to be more severe on the symptomatic side than on the asymptomatic side. Therefore, our aim was to compare the severity of ipsilateral with contralateral ICA and MCA disease in patients with lacunar ischaemic stroke. We studied 259 inpatients and outpatients with a recent lacunar ischaemic stroke and no other prior stroke. We used carotid Duplex ultrasound and transcranial Doppler (TCD) ultrasound to identify ICA and MCA disease, and compared our results with previously published data. In our study, there was no difference between the severity of ipsilateral and contralateral ICA stenosis within individuals (median difference 0%, Wilcoxon paired data p=0.24, comparing severity of ipsilateral and contralateral stenosis). The overall prevalence of severe ipsilateral stenosis was 5%, and the prevalence of severe contralateral stenosis was 4% (OR 1.6, 95% CI 0.6, 4.8). There was no difference in the prevalence of ipsilateral and contralateral MCA disease. A systematic review of the other available studies strengthened this conclusion. Carotid stenosis in patients with a lacunar ischaemic stroke may be coincidental. Further studies are required to elucidate the causes of lacunar stroke, and to evaluate the role of carotid endarterectomy.

  12. Effect of maternal age and cardiac disease severity on outcome of pregnancy in women with congenital heart disease.

    PubMed

    Furenäs, Eva; Eriksson, Peter; Wennerholm, Ulla-Britt; Dellborg, Mikael

    2017-09-15

    There is an increasing prevalence of women with congenital heart defects reaching childbearing age. In western countries women tend to give birth at a higher age compared to some decades ago. We evaluated the CARdiac disease in PREGnancy (CARPREG) and modified World Health Organization (mWHO) risk classifications for cardiac complications during pregnancies in women with congenital heart defects and analyzed the impact of age on risk of obstetric and fetal outcome. A single-center observational study of cardiac, obstetric, and neonatal complications with data from cardiac and obstetric records of pregnancies in women with congenital heart disease. Outcomes of 496 pregnancies in 232 women, including induced abortion, miscarriage, stillbirth, and live birth were analyzed regarding complications, maternal age, mode of delivery, and two risk classifications: CARPREG and mWHO. There were 28 induced abortions, 59 fetal loss, 409 deliveries with 412 neonates. Cardiac (14%), obstetric (14%), and neonatal (15%) complications were noted, including one maternal death and five stillbirths. The rate of cesarean section was 19%. Age above 35years was of borderline importance for cardiac complications (p=0.054) and was not a significant additional risk factor for obstetric or neonatal complications. Both risk classifications had moderate clinical utility, with area under the curve (AUC) 0.71 for CARPREG and 0.65 for mWHO on cardiac complications. Pregnancy complications in women with congenital heart disease are common but severe complications are rare. Advanced maternal age does not seem to affect complication rate. Existing risk classification systems are insufficient in predicting complications. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Genetic myostatin decrease in the golden retriever muscular dystrophy model does not significantly affect the ubiquitin proteasome system despite enhancing the severity of disease.

    PubMed

    Cotten, Steven W; Kornegay, Joe N; Bogan, Daniel J; Wadosky, Kristine M; Patterson, Cam; Willis, Monte S

    2013-01-01

    Recent studies suggest that inhibiting the protein myostatin, a negative regulator of skeletal muscle mass, may improve outcomes in patients with Duchenne muscular dystrophy by enhancing muscle mass. When the dystrophin-deficient golden retriever muscular dystrophy (GRMD) dog was bred with whippets having a heterozygous mutation for the myostatin gene, affected GRMD dogs with decreased myostatin (GRippets) demonstrated an accelerated physical decline compared to related affected GRMD dogs with full myostatin. To examine the role of the ubiquitin proteasome and calpain systems in this accelerated decline, we determined the expression of the muscle ubiquitin ligases MuRF1, Atrogin-1, RNF25, RNF11, and CHIP: the proteasome subunits PSMA6, PSMB4, and PSME1: and calpain 1/2 by real time PCR in the cranial sartorius and vastus lateralis muscles in control, affected GRMD, and GRippet dogs. While individual affected GRMD and GRippet dogs contributed to an increased variability seen in ubiquitin ligase expression, neither group was significantly different from the control group. The affected GRMD dogs demonstrated significant increases in caspase-like and trypsin-like activity in the cranial sartorius; however, all three proteasome activities in the GRippet muscles did not differ from controls. Increased variability in calpain 1 and calpain 2 expression and activity in the affected GRMD and GRippet groups were identified, but no statistical differences from the control group were seen. These studies suggest a role of myostatin in the disease progression of GRMD, which does not significantly involve key components of the ubiquitin proteasome and calpain systems involved in the protein quality control of sarcomere and other structural skeletal muscle proteins.

  14. Fully automated disease severity assessment and treatment monitoring in retinopathy of prematurity using deep learning

    NASA Astrophysics Data System (ADS)

    Brown, James M.; Campbell, J. Peter; Beers, Andrew; Chang, Ken; Donohue, Kyra; Ostmo, Susan; Chan, R. V. Paul; Dy, Jennifer; Erdogmus, Deniz; Ioannidis, Stratis; Chiang, Michael F.; Kalpathy-Cramer, Jayashree

    2018-03-01

    Retinopathy of prematurity (ROP) is a disease that affects premature infants, where abnormal growth of the retinal blood vessels can lead to blindness unless treated accordingly. Infants considered at risk of severe ROP are monitored for symptoms of plus disease, characterized by arterial tortuosity and venous dilation at the posterior pole, with a standard photographic definition. Disagreement among ROP experts in diagnosing plus disease has driven the development of computer-based methods that classify images based on hand-crafted features extracted from the vasculature. However, most of these approaches are semi-automated, which are time-consuming and subject to variability. In contrast, deep learning is a fully automated approach that has shown great promise in a wide variety of domains, including medical genetics, informatics and imaging. Convolutional neural networks (CNNs) are deep networks which learn rich representations of disease features that are highly robust to variations in acquisition and image quality. In this study, we utilized a U-Net architecture to perform vessel segmentation and then a GoogLeNet to perform disease classification. The classifier was trained on 3,000 retinal images and validated on an independent test set of patients with different observed progressions and treatments. We show that our fully automated algorithm can be used to monitor the progression of plus disease over multiple patient visits with results that are consistent with the experts' consensus diagnosis. Future work will aim to further validate the method on larger cohorts of patients to assess its applicability within the clinic as a treatment monitoring tool.

  15. Impact of hand eczema severity on quality of life

    PubMed Central

    Charan, Ujwala Priya; Peter, C. V. Dincy; Pulimood, Susanne A.

    2013-01-01

    Background: Hand eczema is a common disease seen in dermatological practice comprising of a spectrum ranging from mild disease to a severe distressing and chronic course with a negative impact on the quality of life. Aim: To assess the impact of hand eczema severity on quality of life. Materials and Methods: Patients with hand eczema were enrolled in a prospective study. Disease severity was assessed by hand eczema severity index (HECSI) score and quality of life by dermatology life quality index (DLQI) questionnaire. Results: Forty-six patients participated of which 22 (47.8%) were males and 24 (52.2%) females. The commonest age group affected among men and women was 50-59 years (31.8%) and 40-49 years (41.7%) respectively. History of atopy was found in 23.9% and 63% had persistent disease. In 28 (60.9%), the trigger was washing soaps and detergents of which 21 (87.5%) were housewives. Of those employed, 27.7% reported loss of work days. The mean HECSI score was 14.46 (S.D = 20.98) and mean DLQI score was 9.54 (S.D = 5.62). Gender, age, occupation and duration of disease did not significantly affect the quality of life or disease severity. Increased episodes of eczema (>4 episodes/year) showed a statistically significant correlation with DLQI (P value = 0.021). There was no significant correlation between HECSI score and DLQI in this study. Conclusion: Majority of the patients with hand eczema had a significant impairment of their quality of life. The impairment of quality of life in this study was mainly dependent on increased frequency of the eruptions and not on hand eczema severity. PMID:23741665

  16. Healthcare resource utilization and costs among psoriasis patients treated with biologics, overall and by disease severity.

    PubMed

    Murage, Mwangi J; Anderson, Amanda; Oliveria, Susan A; Casso, Deborah; Ojeh, Clement K; Muram, Talia M; Merola, Joseph F; Araujo, Andre B

    2018-05-22

    To describe healthcare resource utilization (HCRU) and costs among biologic-treated psoriasis patients in the US, overall and by disease severity. IQVIA PharMetrics Plus administrative claims data were linked with Modernizing Medicine Data Services Electronic Health Record data and used to select adult psoriasis patients between April 1, 2010 and December 31, 2014. Eligible patients were classified by disease severity (mild, moderate, severe) using a hierarchy of available clinical measures. One-year outcomes included all-cause and psoriasis-related outpatient, emergency department, inpatient, and pharmacy HCRU and costs. This study identified 2,130 biologic-treated psoriasis patients: 282 (13%) had mild, 116 (5%) moderate, and 49 (2%) severe disease; 1,683 (79%) could not be classified. The mean age was 47.6 years; 45.4% were female. Relative to mild psoriasis patients, patients with moderate or severe disease had more median all-cause outpatient encounters (28.0 [mild] vs 32.0 [moderate], 36.0 [severe]), more median psoriasis-related outpatient encounters (6.0 [mild] vs 7.5 [moderate], 8.0 [severe]), and a higher proportion of overall claims for medications that were psoriasis-related (28% [mild] vs 37% [moderate], 34% [severe]). Relative to mild psoriasis patients, patients with moderate or severe disease had higher median all-cause total costs ($37.7k [mild] vs $42.3k [moderate], $49.3k [severe]), higher median psoriasis-related total costs ($32.7k [mild] vs $34.9k [moderate], $40.5k [severe]), higher median all-cause pharmacy costs ($33.9k [mild] vs $36.5k [moderate], $36.4k [severe]), and higher median psoriasis-related pharmacy costs ($32.2k [mild] vs $33.9k [moderate], $35.6k [severe]). The assessment of psoriasis disease severity may not have necessarily coincided with the timing of biologic use. The definition of disease severity prevented the assessment of temporality, and may have introduced selection bias. Biologic-treated patients with moderate or

  17. Influenza and Pneumonia Vaccination Rates and Factors Affecting Vaccination among Patients with Chronic Obstructive Pulmonary Disease.

    PubMed

    Aka Aktürk, Ülkü; Görek Dilektaşlı, Aslı; Şengül, Aysun; Musaffa Salepçi, Banu; Oktay, Nuray; Düger, Mustafa; Arık Taşyıkan, Hale; Durmuş Koçak, Nagihan

    2017-05-05

    Influenza and pneumococcal vaccinations are recommended in chronic obstructive pulmonary disease patients to decrease associated risks at all stages. Although the prevalence of chronic obstructive pulmonary disease is high in our country, as previously reported, vaccination rates are low. To assess the vaccination rates of chronic obstructive pulmonary disease patients and factors that may affect these. Multi-centre cross-sectional study. Patients admitted to the chest diseases clinics of six different centres between 1 February 2013 and 1 January 2014 with a pre-diagnosis of Chronic obstructive pulmonary disease according to the Global initiative for chronic obstructive lung disease criteria, who were in a stable condition were included in the study. The survey, which included demographic characteristics, socio-economic status, severity of disease and vaccination information, was first tested on a small patient population before the study. The survey was completed by the investigators after obtaining written informed consent. The average age of the 296 included patients was 66.3±9.3 years and 91.9% were male. Of these, 36.5% had the influenza vaccination and 14.1% had the pneumococcal vaccination. The most common reason for not being vaccinated was 'no recommendation by doctors': 57.2% in the case of influenza vaccinations, and 46.8% in the case of pneumococcal vaccinations. Both vaccination rates were significantly higher in those patients with comorbidities (influenza vaccination p<0.001; pneumococcal vaccination p=0.06). There was no significant correlation with age, gender, smoking and severity of disease (p>0.05). Vaccination rates were significantly higher in those with a white-collar occupation and higher education level, and who presented to a university hospital (p<0.001). Medical professionals do not request vaccinations as often as the International Guidelines suggest for chronic obstructive pulmonary disease patients. Awareness of the importance of

  18. Common susceptibility alleles and SQSTM1 mutations predict disease extent and severity in a multinational study of patients with Paget's disease.

    PubMed

    Albagha, Omar M E; Visconti, Micaela Rios; Alonso, Nerea; Wani, Sachin; Goodman, Kirsteen; Fraser, William D; Gennari, Luigi; Merlotti, Daniela; Gianfrancesco, Fernando; Esposito, Teresa; Rendina, Domenico; di Stefano, Marco; Isaia, Giancarlo; Brandi, Maria Luisa; Giusti, Francesca; Del Pino-Montes, Javier; Corral-Gudino, Luis; Gonzalez-Sarmiento, Rogelio; Ward, Lynley; Rea, Sarah L; Ratajczak, Thomas; Walsh, John P; Ralston, Stuart H

    2013-11-01

    Paget's disease of bone (PDB) has a strong genetic component. Here, we investigated possible associations between genetic variants that predispose to PDB and disease severity. Allelic variants identified as predictors of PDB from genome-wide association studies were analyzed in 1940 PDB patients from the United Kingdom, Italy, Western Australia, and Spain. A cumulative risk allele score was constructed by adding the variants together and relating this to markers of disease severity, alone and in combination with SQSTM1 mutations. In SQSTM1-negative patients, risk allele scores in the highest tertile were associated with a 27% increase in disease extent compared with the lowest tertile (p < 0.00001) with intermediate values in the middle tertile (20% increase; p = 0.0007). The effects were similar for disease severity score, which was 15% (p = 0.01) and 25% (p < 0.00001) higher in the middle and upper tertiles, respectively. Risk allele score remained a significant predictor of extent and severity when SQSTM-positive individuals were included, with an effect size approximately one-third of that observed with SQSTM1 mutations. A genetic risk score was developed by combining information from both markers, which identified subgroups of individuals with low, medium, and high levels of severity with a specificity of 70% and sensitivity of 55%. Risk allele scores and SQSTM1 mutations both predict extent and severity of PDB. It is possible that with further refinement, genetic profiling may be of clinical value in identifying individuals at high risk of severe disease who might benefit from enhanced surveillance and early intervention. © 2013 American Society for Bone and Mineral Research.

  19. Exploring the factors affecting motorway accident severity in England using the generalised ordered logistic regression model.

    PubMed

    Michalaki, Paraskevi; Quddus, Mohammed A; Pitfield, David; Huetson, Andrew

    2015-12-01

    The severity of motorway accidents that occurred on the hard shoulder (HS) is higher than for the main carriageway (MC). This paper compares and contrasts the most important factors affecting the severity of HS and MC accidents on motorways in England. Using police reported accident data, the accidents that occurred on motorways in England are grouped into two categories (i.e., HS and MC) according to the location. A generalized ordered logistic regression model is then applied to identify the factors affecting the severity of HS and MC accidents on motorways. The factors examined include accident and vehicle characteristics, traffic and environment conditions, as well as other behavioral factors. Results suggest that the factors positively affecting the severity include: number of vehicles involved in the accident, peak-hour traffic time, and low visibility. Differences between HS and MC accidents are identified, with the most important being the involvement of heavy goods vehicles (HGVs) and driver fatigue, which are found to be more crucial in increasing the severity of HS accidents. Measures to increase awareness of HGV drivers regarding the risk of fatigue when driving on motorways, and especially the nearside lane, should be taken by the stakeholders. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Self-awareness of memory function in Parkinson's disease in relation to mood and symptom severity.

    PubMed

    Sitek, Emilia J; Sołtan, Witold; Wieczorek, Dariusz; Robowski, Piotr; Sławek, Jarosław

    2011-03-01

    In clinical practice, discrepancies are observed between self and proxy reports of various aspects of Parkinson's disease (PD). This study aimed at assessing self-awareness of memory function in PD both by comparing patients' and caregivers' questionnaire ratings of the patients' memory and by correlating subjective ratings with verbal learning results. Forty-five patient-proxy pairs participated in the study. Self-Rating Scale of Memory Functions was used as a questionnaire subjective measure. Auditory Verbal Learning Test (AVLT) was applied to assess verbal memory, Stroop test to assess cognitive control and Mini-Mental State Examination (MMSE) for global cognitive assessment. Patient self-reports did not diverge appreciably from proxy reports when global scores were considered, but patient-proxy consistency was low for individual items with the exception of those referring to verbal recall. Both patient and proxy ratings were moderately correlated with the objective measures. Patient-proxy discrepancies were associated with lower verbal learning, poor cognitive control and more severe PD symptomatology. Moreover, depression was associated with patients' overestimation of symptoms. Self-awareness of memory function is relatively well preserved in PD, but is negatively affected by depressive symptoms. Patient-proxy discrepancies increase also with disease severity, degree of memory problems and cognitive control deficits. Caregivers seem to be unaware of the specificity of memory problems in PD and report only some of them, mainly those related to verbal recall.

  1. Pediatric Cushing disease: disparities in disease severity and outcomes in the Hispanic and African-American populations.

    PubMed

    Gkourogianni, Alexandra; Sinaii, Ninet; Jackson, Sharon H; Karageorgiadis, Alexander S; Lyssikatos, Charalampos; Belyavskaya, Elena; Keil, Margaret F; Zilbermint, Mihail; Chittiboina, Prashant; Stratakis, Constantine A; Lodish, Maya B

    2017-08-01

    BackgroundLittle is known about the contribution of racial and socioeconomic disparities to severity and outcomes in children with Cushing disease (CD).MethodsA total of 129 children with CD, 45 Hispanic/Latino or African-American (HI/AA) and 84 non-Hispanic White (non-HW), were included in this study. A 10-point index for rating severity (CD severity) incorporated the degree of hypercortisolemia, glucose tolerance, hypertension, anthropomorphic measurements, disease duration, and tumor characteristics. Race, ethnicity, age, gender, local obesity prevalence, estimated median income, and access to care were assessed in regression analyses of CD severity.ResultsThe mean CD severity in the HI/AA group was worse than that in the non-HW group (4.9±2.0 vs. 4.1±1.9, P=0.023); driving factors included higher cortisol levels and larger tumor size. Multiple regression models confirmed that race (P=0.027) and older age (P=0.014) were the most important predictors of worse CD severity. When followed up a median of 2.3 years after surgery, the relative risk for persistent CD combined with recurrence was 2.8 times higher in the HI/AA group compared with that in the non-HW group (95% confidence interval: 1.2-6.5).ConclusionOur data show that the driving forces for the discrepancy in severity of CD are older age and race/ethnicity. Importantly, the risk for persistent and recurrent CD was higher in minority children.

  2. Alpha-1-antichymotrypsin (ACT or SERPINA3) polymorphism may affect age-at-onset and disease duration of Alzheimer's disease.

    PubMed

    Kamboh, M Ilyas; Minster, Ryan L; Kenney, Margaret; Ozturk, Ayla; Desai, Purnima P; Kammerer, Candace M; DeKosky, Steven T

    2006-10-01

    In addition to genetic effects on disease risk, age-at-onset (AAO) of Alzheimer's disease (AD) is also genetically controlled. Using AAO as a covariate, a linkage signal for AD has been detected on chromosome 14q32 near the alpha1-antichymotrypsin (ACT) gene. Previously, a signal peptide polymorphism (codon -17A>T) in the ACT gene has been suggested to affect AD risk, but with inconsistent findings. Given that a linkage signal for AAO has been detected near ACT, we hypothesized that ACT genetic variation affects AAO rather than disease risk and this may explain the previous inconsistent findings between ACT genetic variation and AD risk. We examined the impact of the ACT signal peptide polymorphism on mean AAO in 909 AD cases. The ACT polymorphism was significantly associated with AAO and this effect was independent of the APOE polymorphism. Mean AAO among ACT/AA homozygotes was significantly lower than that in the combined AT+TT genotype group (p = 0.019) and this difference was confined to male AD patients (p = 0.002). Among male AD patients, the ACT/AA genotype was also associated with shorter disease duration before death as compared to the ACT/AT+TT genotypes (p = 0.012). These data suggest that the ACT gene may affect AAO and disease duration of AD.

  3. Prediction of Severe Disease in Children with Diarrhea in a Resource-Limited Setting

    PubMed Central

    Levine, Adam C.; Munyaneza, Richard M.; Glavis-Bloom, Justin; Redditt, Vanessa; Cockrell, Hannah C.; Kalimba, Bantu; Kabemba, Valentin; Musavuli, Juvenal; Gakwerere, Mathias; Umurungi, Jean Paul de Charles; Shah, Sachita P.; Drobac, Peter C.

    2013-01-01

    Objective To investigate the accuracy of three clinical scales for predicting severe disease (severe dehydration or death) in children with diarrhea in a resource-limited setting. Methods Participants included 178 children admitted to three Rwandan hospitals with diarrhea. A local physician or nurse assessed each child on arrival using the World Health Organization (WHO) severe dehydration scale and the Centers for Disease Control (CDC) scale. Children were weighed on arrival and daily until they achieved a stable weight, with a 10% increase between admission weight and stable weight considered severe dehydration. The Clinical Dehydration Scale was then constructed post-hoc using the data collected for the other two scales. Receiver Operator Characteristic (ROC) curves were constructed for each scale compared to the composite outcome of severe dehydration or death. Results The WHO severe dehydration scale, CDC scale, and Clinical Dehydration Scale had areas under the ROC curves (AUCs) of 0.72 (95% CI 0.60, 0.85), 0.73 (95% CI 0.62, 0.84), and 0.80 (95% CI 0.71, 0.89), respectively, in the full cohort. Only the Clinical Dehydration Scale was a significant predictor of severe disease when used in infants, with an AUC of 0.77 (95% CI 0.61, 0.93), and when used by nurses, with an AUC of 0.78 (95% CI 0.63, 0.93). Conclusions While all three scales were moderate predictors of severe disease in children with diarrhea, scale accuracy varied based on provider training and age of the child. Future research should focus on developing or validating clinical tools that can be used accurately by nurses and other less-skilled providers to assess all children with diarrhea in resource-limited settings. PMID:24349271

  4. Positive Affect and Health Behaviors across Five Years in Patients with Coronary Heart Disease: The Heart and Soul Study

    PubMed Central

    Sin, Nancy L.; Moskowitz, Judith Tedlie; Whooley, Mary A.

    2015-01-01

    OBJECTIVE Positive psychological states are linked to superior health and longevity, possibly due to behavioral factors. We evaluated cross-sectional and 5-year associations between positive affect and health behaviors in patients with coronary heart disease (CHD). METHODS Outpatients with CHD reported positive affect, physical activity, sleep quality, medication adherence, cigarette smoking, and alcohol use at baseline (N = 1022) and five years later (N = 662). Covariates in regression analyses included demographics, cardiac disease severity, and depressive symptoms. RESULTS At baseline, higher positive affect (per 1-SD) was associated with better health behaviors: physical activity (OR = 1.52; 95% CI = 1.30, 1.77; p < 0.001), sleep quality (OR = 1.24; 95% CI = 1.04, 1.48; p = 0.015), medication adherence (OR = 1.46; 95% CI = 1.12, 1.90; p = 0.005), and non-smoking (OR = 1.29; 95% CI = 1.06, 1.57; p = 0.012), but was unrelated to alcohol use. Baseline positive affect did not predict health behaviors at follow-up, accounting for baseline behaviors. However, increases in positive affect across five years co-occurred with improvements in physical activity (B = 0.023; SE = 0.008; p = 0.002), sleep quality (B = 0.011; SE = 0.005; p = 0.039), and medication adherence (B = 0.014; SE = 0.004; p < 0.001), but not smoking status (OR = 1.07; 95% CI = 0.73, 1.55; p = 0.74). CONCLUSION Positive affect was associated with health behaviors among CHD patients. Efforts to sustain or enhance positive affect may be promising for promoting better health behaviors. PMID:26428445

  5. Positive Affect and Health Behaviors Across 5 Years in Patients With Coronary Heart Disease: The Heart and Soul Study.

    PubMed

    Sin, Nancy L; Moskowitz, Judith Tedlie; Whooley, Mary A

    2015-01-01

    Positive psychological states are linked to superior health and longevity, possibly due to behavioral factors. We evaluated cross-sectional and 5-year associations between positive affect and health behaviors in patients with coronary heart disease (CHD). Outpatients with CHD reported positive affect, physical activity, sleep quality, medication adherence, cigarette smoking, and alcohol use at baseline (n = 1022) and 5 years later (n = 662). Covariates in regression analyses included demographics, cardiac disease severity, and depressive symptoms. At baseline, higher positive affect (per 1 standard deviation) was associated with better health behaviors: physical activity (odds ratio [OR] = 1.52, 95% 95% confidence interval [CI] = 1.30-1.77, p < .001), sleep quality (OR = 1.24, 95% CI = 1.04-1.48, p = .015), medication adherence (OR = 1.46, 95% CI = 1.12-1.90, p = .005), and nonsmoking (OR = 1.29, 95% CI = 1.06-1.57, p = .012), but was unrelated to alcohol use. Baseline positive affect did not predict health behaviors at follow-up, accounting for baseline behaviors. However, increases in positive affect across 5 years co-occurred with improvements in physical activity (B = 0.023, standard error [SE] = 0.008, p = .002), sleep quality (B = 0.011, SE = 0.005, p = .039), and medication adherence (B = 0.014, SE = 0.004, p < .001), but not smoking status (OR = 1.07, 95% CI = 0.73-1.55, p = .74). Positive affect was associated with health behaviors among patients with CHD. Efforts to sustain or enhance positive affect may be promising for promoting better health behaviors.

  6. CSF neurofilament concentration reflects disease severity in frontotemporal degeneration

    PubMed Central

    Scherling, Carole S.; Hall, Tracey; Berisha, Flora; Klepac, Kristen; Karydas, Anna; Coppola, Giovanni; Kramer, Joel H.; Rabinovici, Gil; Ahlijanian, Michael; Miller, Bruce L.; Seeley, William; Grinberg, Lea T.; Rosen, Howard; Meredith, Jere; Boxer, Adam L.

    2014-01-01

    Objective Cerebrospinal fluid (CSF) neurofilament light chain (NfL) concentration is elevated in neurological disorders including frontotemporal degeneration (FTD). We investigated the clinical correlates of elevated CSF NfL levels in FTD. Methods CSF NfL, amyloid-β42 (Aβ42), tau and phosphorylated tau (ptau) concentrations were compared in 47 normal controls (NC), 8 asymptomatic gene carriers (NC2) of FTD-causing mutations, 79 FTD (45 behavioral variant frontotemporal dementia [bvFTD], 18 progressive nonfluent aphasia [PNFA], 16 semantic dementia [SD]), 22 progressive supranuclear palsy, 50 Alzheimer’s disease, 6 Parkinson’s disease and 17 corticobasal syndrome patients. Correlations between CSF analyte levels were performed with neuropsychological measures and the Clinical Dementia Rating scale sum of boxes (CDRsb). Voxel-based morphometry of structural MR images determined the relationship between brain volume and CSF NfL. Results Mean CSF NfL concentrations were higher in bvFTD, SD and PNFA than other groups. NfL in NC2 was similar to NC. CSF NfL, but not other CSF measures, correlated with CDRsb and neuropsychological measures in FTD, and not in other diagnostic groups. Analyses in two independent FTD cohorts and a group of autopsy verified or biomarker enriched cases confirmed the larger group analysis. In FTD, gray and white matter volume negatively correlated with CSF NfL concentration, such that individuals with highest NfL levels exhibited the most atrophy. Interpretation CSF NfL is elevated in symptomatic FTD and correlates with disease severity. This measurement may be a useful surrogate endpoint of disease severity in FTD clinical trials. Longitudinal studies of CSF NfL in FTD are warranted. PMID:24242746

  7. Significant CD4, CD8, and CD19 lymphopenia in peripheral blood of sarcoidosis patients correlates with severe disease manifestations.

    PubMed

    Sweiss, Nadera J; Salloum, Rafah; Gandhi, Seema; Ghandi, Seema; Alegre, Maria-Luisa; Sawaqed, Ray; Badaracco, Maria; Pursell, Kenneth; Pitrak, David; Baughman, Robert P; Moller, David R; Garcia, Joe G N; Niewold, Timothy B

    2010-02-05

    Sarcoidosis is a poorly understood chronic inflammatory condition. Infiltration of affected organs by lymphocytes is characteristic of sarcoidosis, however previous reports suggest that circulating lymphocyte counts are low in some patients with the disease. The goal of this study was to evaluate lymphocyte subsets in peripheral blood in a cohort of sarcoidosis patients to determine the prevalence, severity, and clinical features associated with lymphopenia in major lymphocyte subsets. Lymphocyte subsets in 28 sarcoid patients were analyzed using flow cytometry to determine the percentage of CD4, CD8, and CD19 positive cells. Greater than 50% of patients had abnormally low CD4, CD8, or CD19 counts (p<4x10(-10)). Lymphopenia was profound in some cases, and five of the patients had absolute CD4 counts below 200. CD4, CD8, and CD19 lymphocyte subset counts were significantly correlated (Spearman's rho 0.57, p = 0.0017), and 10 patients had low counts in all three subsets. Patients with severe organ system involvement including neurologic, cardiac, ocular, and advanced pulmonary disease had lower lymphocyte subset counts as a group than those patients with less severe manifestations (CD4 p = 0.0043, CD8 p = 0.026, CD19 p = 0.033). No significant relationships were observed between various medical therapies and lymphocyte counts, and lymphopenia was present in patients who were not receiving any medical therapy. Significant lymphopenia involving CD4, CD8, and CD19 positive cells was common in sarcoidosis patients and correlated with disease severity. Our findings suggest that lymphopenia relates more to disease pathology than medical treatment.

  8. Significant CD4, CD8, and CD19 Lymphopenia in Peripheral Blood of Sarcoidosis Patients Correlates with Severe Disease Manifestations

    PubMed Central

    Sweiss, Nadera J.; Salloum, Rafah; Ghandi, Seema; Alegre, Maria-Luisa; Sawaqed, Ray; Badaracco, Maria; Pursell, Kenneth; Pitrak, David; Baughman, Robert P.; Moller, David R.; Garcia, Joe G. N.; Niewold, Timothy B.

    2010-01-01

    Background Sarcoidosis is a poorly understood chronic inflammatory condition. Infiltration of affected organs by lymphocytes is characteristic of sarcoidosis, however previous reports suggest that circulating lymphocyte counts are low in some patients with the disease. The goal of this study was to evaluate lymphocyte subsets in peripheral blood in a cohort of sarcoidosis patients to determine the prevalence, severity, and clinical features associated with lymphopenia in major lymphocyte subsets. Methodology/Principal Findings Lymphocyte subsets in 28 sarcoid patients were analyzed using flow cytometry to determine the percentage of CD4, CD8, and CD19 positive cells. Greater than 50% of patients had abnormally low CD4, CD8, or CD19 counts (p<4×10−10). Lymphopenia was profound in some cases, and five of the patients had absolute CD4 counts below 200. CD4, CD8, and CD19 lymphocyte subset counts were significantly correlated (Spearman's rho 0.57, p = 0.0017), and 10 patients had low counts in all three subsets. Patients with severe organ system involvement including neurologic, cardiac, ocular, and advanced pulmonary disease had lower lymphocyte subset counts as a group than those patients with less severe manifestations (CD4 p = 0.0043, CD8 p = 0.026, CD19 p = 0.033). No significant relationships were observed between various medical therapies and lymphocyte counts, and lymphopenia was present in patients who were not receiving any medical therapy. Conclusions/Significance Significant lymphopenia involving CD4, CD8, and CD19 positive cells was common in sarcoidosis patients and correlated with disease severity. Our findings suggest that lymphopenia relates more to disease pathology than medical treatment. PMID:20140091

  9. Sociodemographic factors contribute to the depressive affect 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

    2010-06-01

    Depression is common in end-stage renal disease and is associated with poor quality of life and higher mortality; however, little is known about depressive affect in earlier stages of chronic kidney disease. To measure this in a risk group burdened with hypertension and kidney disease, we conducted a cross-sectional analysis of individuals at enrollment in the African American Study of Kidney Disease and Hypertension Cohort Study. Depressive affect was assessed by the Beck Depression Inventory II and quality of life by the Medical Outcomes Study-Short Form and the Satisfaction with Life Scale. Beck Depression scores over 14 were deemed consistent with an increased depressive affect and linear regression analysis was used to identify factors associated with these scores. Among 628 subjects, 166 had scores over 14 but only 34 were prescribed antidepressants. The mean Beck Depression score of 11.0 varied with the estimated glomerular filtration rate (eGFR) from 10.7 (eGFR 50-60) to 16.0 (eGFR stage 5); however, there was no significant independent association between these. Unemployment, low income, and lower quality and satisfaction with life scale scores were independently and significantly associated with a higher Beck Depression score. Thus, our study shows that an increased depressive affect is highly prevalent in African Americans with chronic kidney disease, is infrequently treated with antidepressants, and is associated with poorer quality of life. Sociodemographic factors have especially strong associations with this increased depressive affect. Because this study was conducted in an African-American cohort, its findings may not be generalized to other ethnic groups.

  10. Estimation of Symptom Severity Scores for Patients with Schizophrenia Using ERP Source Activations during a Facial Affect Discrimination Task.

    PubMed

    Kim, Do-Won; Lee, Seung-Hwan; Shim, Miseon; Im, Chang-Hwan

    2017-01-01

    Precise diagnosis of psychiatric diseases and a comprehensive assessment of a patient's symptom severity are important in order to establish a successful treatment strategy for each patient. Although great efforts have been devoted to searching for diagnostic biomarkers of schizophrenia over the past several decades, no study has yet investigated how accurately these biomarkers are able to estimate an individual patient's symptom severity. In this study, we applied electrophysiological biomarkers obtained from electroencephalography (EEG) analyses to an estimation of symptom severity scores of patients with schizophrenia. EEG signals were recorded from 23 patients while they performed a facial affect discrimination task. Based on the source current density analysis results, we extracted voxels that showed a strong correlation between source activity and symptom scores. We then built a prediction model to estimate the symptom severity scores of each patient using the source activations of the selected voxels. The symptom scores of the Positive and Negative Syndrome Scale (PANSS) were estimated using the linear prediction model. The results of leave-one-out cross validation (LOOCV) showed that the mean errors of the estimated symptom scores were 3.34 ± 2.40 and 3.90 ± 3.01 for the Positive and Negative PANSS scores, respectively. The current pilot study is the first attempt to estimate symptom severity scores in schizophrenia using quantitative EEG features. It is expected that the present method can be extended to other cognitive paradigms or other psychological illnesses.

  11. Severe hyponatraemia with absence of hyperkalaemia in rapidly progressive Addison's disease

    PubMed Central

    Thompson, Michael D; Kalmar, Eileen; Bowden, Sasigarn A

    2015-01-01

    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. PMID:26021383

  12. 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. 2015 BMJ Publishing Group Ltd.

  13. Effect of harvesting regime on beech root sprouts and seedlings in a north-central Maine forest long affected by beech bark disease

    Treesearch

    David R. Houston

    2001-01-01

    Forests in Maine often contain many trees severely damaged by the disease. Methods are needed to reduce numbers of susceptible and increase numbers of resistant trees. This paper describes how commonly-used harvesting systems affect the incidence and growth of beech root sprouts and seedlings. Harvest treatments were clearcutting and thinning in winter and summer, 1991...

  14. Coexistence of sickle cell disease and severe congenital neutropenia: first impressions can be deceiving.

    PubMed

    Wali, Yasser; Beshlawi, Ismail; Fawaz, Naglaa; Alkhayat, Aisha; Zalabany, Mahmoud; Elshinawy, Mohamed; Al-Kindi, Salam; Al-Rawas, Abdul Hakim A; Klein, Christoph

    2012-09-01

    We report an Omani family in whom the propositus had a rare coexistence of sickle cell disease and severe congenital neutropenia associated with a mutation in ELANE. In contrast to his siblings with sickle cell disease, the severity of HbSS-associated complications such as painful crises and acute chest syndrome was significantly reduced. His course of the disease had markedly worsened after initiating G-CSF therapy. These clinical observations suggest that neutropenia may ameliorate inflammatory responses and thus display a modulating factor with respect to the clinical course of sickle cell disease. © 2012 John Wiley & Sons A/S.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  16. Bacterial Infections Change Natural History of Cirrhosis Irrespective of Liver Disease Severity.

    PubMed

    Dionigi, Elena; Garcovich, Matteo; Borzio, Mauro; Leandro, Gioacchino; Majumdar, Avik; Tsami, Aikaterini; Arvaniti, Vasiliki; Roccarina, Davide; Pinzani, Massimo; Burroughs, Andrew K; O'Beirne, James; Tsochatzis, Emmanuel A

    2017-04-01

    We assessed the prognostic significance of infections in relation to current prognostic scores and explored if infection could be considered per se a distinct clinical stage in the natural history of cirrhosis. We included consecutive patients with cirrhosis admitted to a tertiary referral liver unit for at least 48 h over a 2-year period. Diagnosis of infection was based on positive cultures or strict established criteria. We used competing risk analysis and propensity score matching for data analysis. 501 patients (63% male, 48% alcoholic liver disease, median Model of End-stage Liver Disease (MELD)=17) underwent 781 admissions over the study period. Portal hypertensive bleeding and complicated ascites were the commonest reasons of admission. The incidence of proven bacterial infection was 25.6% (60% community acquired and 40% nosocomial). Survival rates at 3, 6, 12, and 30 months were 83%, 77%, 71%, and 62% in patients without diagnosis of infection, vs. 50%, 46%, 41%, and 34% in patients with diagnosis of infection. Overall survival was independently associated with MELD score (hazards ratio (HR) 1.099), intensive care (ITU) stay (HR 1.967) and bacterial infection (HR 2.226). Bacterial infection was an independent predictor of survival even when patients who died within the first 30 days were excluded from the analysis in Cox regression (HR 2.013) and competing risk Cox models in all patients (HR 1.46) and propensity risk score-matched infected and non-infected patients (HR 1.67). Infection most likely represents a distinct prognostic stage of cirrhosis, which affects survival irrespective of disease severity, even after recovery from the infective episode.

  17. Celiac disease causing severe osteomalacia: an association still present in Morocco!

    PubMed

    Tahiri, Latifa; Azzouzi, Hamida; Squalli, Ghita; Abourazzak, Fatimazahra; Harzy, Taoufik

    2014-01-01

    Celiac disease (CD), a malabsorption syndrome caused by hypersensitivity to gliadin fraction of gluten. CD can manifest with classic symptoms; however, significant myopathy and multiple fractures are rarely the predominant presentation of untreated celiac disease. Osteomalacia complicating celiac disease had become more and more rare. We describe here a case of osteomalacia secondary to a longstanding untreated celiac disease. This patient complained about progressive bone and muscular pain, weakness, fractures and skeletal deformities. Radiological and laboratory findings were all in favor of severe osteomalacia. Improvement of patient's weakness and laboratory abnormalities was obvious after treatment with gluten free diet, vitamin D, calcium and iron. This case affirms that chronic untreated celiac disease, can lead to an important bone loss and irreversible complications like skeletal deformities.

  18. Celiac disease causing severe osteomalacia: an association still present in Morocco!

    PubMed Central

    Tahiri, Latifa; Azzouzi, Hamida; Squalli, Ghita; Abourazzak, Fatimazahra; Harzy, Taoufik

    2014-01-01

    Celiac disease (CD), a malabsorption syndrome caused by hypersensitivity to gliadin fraction of gluten. CD can manifest with classic symptoms; however, significant myopathy and multiple fractures are rarely the predominant presentation of untreated celiac disease. Osteomalacia complicating celiac disease had become more and more rare. We describe here a case of osteomalacia secondary to a longstanding untreated celiac disease. This patient complained about progressive bone and muscular pain, weakness, fractures and skeletal deformities. Radiological and laboratory findings were all in favor of severe osteomalacia. Improvement of patient's weakness and laboratory abnormalities was obvious after treatment with gluten free diet, vitamin D, calcium and iron. This case affirms that chronic untreated celiac disease, can lead to an important bone loss and irreversible complications like skeletal deformities. PMID:25667705

  19. 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

  20. Mechanisms by which pesticides affect insect immunity.

    PubMed

    James, R R; Xu, J

    2012-02-01

    The current state of knowledge regarding the effect of pesticides on insect immunity is reviewed here. A basic understanding of these interactions is needed for several reasons, including to improve methods for controlling pest insects in agricultural settings, for controlling insect vectors of human diseases, and for reducing mortality in beneficial insects. Bees are particularly vulnerable to sublethal pesticide exposures because they gather nectar and pollen, concentrating environmental toxins in their nests in the process. Pesticides do have effects on immunity. Organophosphates and some botanicals have been found to impact hemocyte number, differentiation, and thus affect phagocytosis. The phenoloxidase cascade and malanization have also been shown to be affected by several insecticides. Many synthetic insecticides increase oxidative stress, and this could have severe impacts on the production of some antimicrobial peptides in insects, but research is needed to determine the actual effects. Pesticides can also affect grooming behaviors, rendering insects more susceptible to disease. Despite laboratory data documenting pesticide/pathogen interactions, little field data is available at the population level. Published by Elsevier Inc.

  1. Comparison of Xenon-Enhanced Area-Detector CT and Krypton Ventilation SPECT/CT for Assessment of Pulmonary Functional Loss and Disease Severity in Smokers.

    PubMed

    Ohno, Yoshiharu; Fujisawa, Yasuko; Takenaka, Daisuke; Kaminaga, Shigeo; Seki, Shinichiro; Sugihara, Naoki; Yoshikawa, Takeshi

    2018-02-01

    The objective of this study was to compare the capability of xenon-enhanced area-detector CT (ADCT) performed with a subtraction technique and coregistered 81m Kr-ventilation SPECT/CT for the assessment of pulmonary functional loss and disease severity in smokers. Forty-six consecutive smokers (32 men and 14 women; mean age, 67.0 years) underwent prospective unenhanced and xenon-enhanced ADCT, 81m Kr-ventilation SPECT/CT, and pulmonary function tests. Disease severity was evaluated according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. CT-based functional lung volume (FLV), the percentage of wall area to total airway area (WA%), and ventilated FLV on xenon-enhanced ADCT and SPECT/CT were calculated for each smoker. All indexes were correlated with percentage of forced expiratory volume in 1 second (%FEV 1 ) using step-wise regression analyses, and univariate and multivariate logistic regression analyses were performed. In addition, the diagnostic accuracy of the proposed model was compared with that of each radiologic index by means of McNemar analysis. Multivariate logistic regression showed that %FEV 1 was significantly affected (r = 0.77, r 2 = 0.59) by two factors: the first factor, ventilated FLV on xenon-enhanced ADCT (p < 0.0001); and the second factor, WA% (p = 0.004). Univariate logistic regression analyses indicated that all indexes significantly affected GOLD classification (p < 0.05). Multivariate logistic regression analyses revealed that ventilated FLV on xenon-enhanced ADCT and CT-based FLV significantly influenced GOLD classification (p < 0.0001). The diagnostic accuracy of the proposed model was significantly higher than that of ventilated FLV on SPECT/CT (p = 0.03) and WA% (p = 0.008). Xenon-enhanced ADCT is more effective than 81m Kr-ventilation SPECT/CT for the assessment of pulmonary functional loss and disease severity.

  2. Triglyceride level affecting shared susceptibility genes in metabolic syndrome and coronary artery disease.

    PubMed

    Kisfali, P; Polgár, N; Sáfrány, E; Sümegi, K; Melegh, B I; Bene, J; Wéber, A; Hetyésy, K; Melegh, B

    2010-01-01

    Metabolic syndrome is characterized primarily by abdominal obesity, high triglyceride- and low HDL cholesterol levels, elevated blood pressure, and increased fasting glucose levels, which are often associated with coronary heart diseases. Several factors, such as physical inactivity, age, and several endocrine and genetic factors can increase the risk of the development of the disease. Gathered evidence shows, that metabolic syndrome is not only a risk factor for cardiovascular disease, but often both of them have the same shared susceptibility genes, as several genetic variants have shown a predisposition to both diseases. Due to the spread of robust genome wide association studies, the number of candidate genes in metabolic syndrome and coronary heart disease susceptibility increases very rapidly. From the growing spectrum of the genes influencing lipid metabolism (like the LPL; PPARA; APOE; APOAI/CIII/AIV genecluster and APOAS5), the current review focuses on shared susceptibility variants involved in triglyceride metabolism and consequently the effects on the circulating triglyceride levels. As the elevated levels of triglycerides can be associated with disease phenotypes, some of these SNPs can have susceptibility features in both metabolic syndrome and in coronary heart disease, thereby some of them can even represent a kind of susceptibility link between metabolic syndrome and coronary artery disease.

  3. Disgust proneness predicts obsessive-compulsive disorder symptom severity in a clinical sample of youth: Distinctions from negative affect.

    PubMed

    Olatunji, Bunmi O; Ebesutani, Chad; Kim, Jingu; Riemann, Bradley C; Jacobi, David M

    2017-04-15

    Although studies have linked disgust proneness to the etiology and maintenance of obsessive-compulsive disorder (OCD) in adults, there remains a paucity of research examining the specificity of this association among youth. The present study employed structural equation modeling to examine the association between disgust proneness, negative affect, and OCD symptom severity in a clinical sample of youth admitted to a residential treatment facility (N =471). Results indicate that disgust proneness and negative affect latent factors independently predicted an OCD symptom severity latent factor. However, when both variables were modeled as predictors simultaneously, latent disgust proneness remained significantly associated with OCD symptom severity, whereas the association between latent negative affect and OCD symptom severity became nonsignificant. Tests of mediation converged in support of disgust proneness as a significant intervening variable between negative affect and OCD symptom severity. Subsequent analysis showed that the path from disgust proneness to OCD symptom severity in the structural model was significantly stronger among those without a primary diagnosis of OCD compared to those with a primary diagnosis of OCD. Given the cross-sectional design, the causal inferences that can be made are limited. The present study is also limited by the exclusive reliance on self-report measures. Disgust proneness may play a uniquely important role in OCD among youth. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. [Severity classification of chronic obstructive pulmonary disease based on deep learning].

    PubMed

    Ying, Jun; Yang, Ceyuan; Li, Quanzheng; Xue, Wanguo; Li, Tanshi; Cao, Wenzhe

    2017-12-01

    In this paper, a deep learning method has been raised to build an automatic classification algorithm of severity of chronic obstructive pulmonary disease. Large sample clinical data as input feature were analyzed for their weights in classification. Through feature selection, model training, parameter optimization and model testing, a classification prediction model based on deep belief network was built to predict severity classification criteria raised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We get accuracy over 90% in prediction for two different standardized versions of severity criteria raised in 2007 and 2011 respectively. Moreover, we also got the contribution ranking of different input features through analyzing the model coefficient matrix and confirmed that there was a certain degree of agreement between the more contributive input features and the clinical diagnostic knowledge. The validity of the deep belief network model was proved by this result. This study provides an effective solution for the application of deep learning method in automatic diagnostic decision making.

  5. How infectious disease outbreaks affect community-based primary care physicians: comparing the SARS and H1N1 epidemics.

    PubMed

    Jaakkimainen, R Liisa; Bondy, Susan J; Parkovnick, Meredith; Barnsley, Jan

    2014-10-01

    To compare how the infectious disease outbreaks H1N1 and severe acute respiratory syndrome (SARS) affected community-based GPs and FPs. A mailed survey sent after the H1N1 outbreak compared with the results of similar survey completed after the SARS outbreak. Greater Toronto area in Ontario. A total of 183 randomly selected GPs and FPs who provided office-based care. The perceptions of GPs and FPs on how serious infectious disease outbreaks affected their clinical work and personal lives; their preparedness for a serious infectious disease outbreak; and the types of information they want to receive and the sources they wanted to receive information from during a serious infectious disease outbreak. The responses from this survey were compared with the responses of GPs and FPs in the greater Toronto area who completed a similar survey in 2003 after the SARS outbreak. After the H1N1 outbreak, GPs and FPs still had substantial concerns about the effects of serious infectious disease outbreaks on the health of their family members. Physicians made changes to various office practices in order to manage and deal with patients with serious infectious diseases. They expressed concerns about the effects of an infectious disease on the provision of health care services. Also, physicians wanted to quickly receive accurate information from the provincial government and their medical associations. Serious community-based infectious diseases are a personal concern for GPs and FPs, and have considerable effects on their clinical practice. Further work examining the timely flow of relevant information through different health care sectors and government agencies still needs to be undertaken. Copyright© the College of Family Physicians of Canada.

  6. 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

  7. Obesity in Inflammatory Bowel Disease: A Marker of Less Severe Disease.

    PubMed

    Flores, Avegail; Burstein, Ezra; Cipher, Daisha J; Feagins, Linda A

    2015-08-01

    Both obesity and inflammatory bowel disease (IBD) are highly prevalent in Western societies. IBD, including Crohn's disease (CD) and ulcerative colitis (UC), has been historically associated with cachexia and malnutrition. It is uncertain how obesity, a chronic pro-inflammatory state, may impact the course of IBD. The aim of this study was to report the prevalence of obesity in patients with IBD in a metropolitan US population and to assess the impact of obesity on disease phenotypes, treatment, and surgical outcomes in IBD patients. We reviewed the medical records of patients identified from the IBD registries of the Dallas Veterans Affairs Medical Center and Parkland Health and Hospital Systems who were seen from January 1, 2000, to December 31, 2012. Of 581 identified IBD patients, 32.7 % were obese (BMI ≥ 30) and 67.6 % were non-obese (BMI < 30). There were 297 (51.1 %) patients with CD and 284 (48.9 %) patients with UC. The rate of obesity was 30.3 % among CD patients and 35.2 % among UC patients. Overall, obese patients were significantly less likely to receive anti-TNF treatment, undergo surgery, or experience a hospitalization for their IBD than their non-obese counterparts (55.8 vs. 72.1 %, p = .0001). Obesity is highly prevalent in our IBD patients, paralleling the obesity rates in the US population. Clinical outcomes were significantly different in obese versus non-obese patients with IBD. Despite the plausible mechanisms whereby obesity might exacerbate IBD, we have found that obesity (as defined by BMI) is a marker of a less severe disease course in IBD.

  8. Natural history of severe atheromatous disease of the thoracic aorta: a transesophageal echocardiographic study.

    PubMed

    Montgomery, D H; Ververis, J J; McGorisk, G; Frohwein, S; Martin, R P; Taylor, W R

    1996-01-01

    This study sought to prospectively observe the morphologic and clinical natural history of severe atherosclerotic disease of the thoracic aorta as defined by transesophageal echocardiography. Atherosclerosis of the thoracic aorta has been shown to be highly associated with risk for embolic events in transesophageal studies, but the natural history of the disease under clinical conditions has not been reported. During a 20-month period, 191 of 264 patients undergoing transesophageal echocardiography had adequate visualization of the aorta to allow atherosclerotic severity to be graded as follows: grade I = normal (44 patients); grade II = intimal thickening (52 patients); grade III = atheroma < 5 mm (62 patients); grade IV = atheroma > or = 5 mm (19 patients); grade V = mobile lesion (14 patients). All available patients with grades IV (8 patients) and V (10 patients) disease as well as a subgroup of 12 patients with grade III disease had follow-up transesophageal echocardiographic studies (mean [+/- SD] 11.7 +/- 0.9 months, range 6 to 22). Of 30 patients undergoing follow-up transesophageal echocardiographic studies, 20 (66%) had no change in atherosclerotic severity grade. Of the remaining 10 patients, atherosclerotic severity progressed one grade in 7 and decreased in 3 with resolved mobile lesions. Of 18 patients with grade IV or V disease of the aorta who underwent a follow-up study, 11 (61%) demonstrated formation of new mobile lesions. Of 10 patients with grade V disease on initial study who underwent follow-up study, 7 (70%) demonstrated resolution of a specific previously documented mobile lesion. However, seven patients (70%) with grade V disease also demonstrated development of a new mobile lesion. Of 33 patients with grade IV or V disease, 8 (24%) died during the study period, and 1 (3%) had a clinical embolic event. The presence of severe atherosclerotic disease of the thoracic aorta as defined by transesophageal echocardiography is associated with a

  9. 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

  10. Derivation and validation of a composite index of severity in chronic obstructive pulmonary disease: the DOSE Index.

    PubMed

    Jones, Rupert C; Donaldson, Gavin C; Chavannes, Niels H; Kida, Kozui; Dickson-Spillmann, Maria; Harding, Samantha; Wedzicha, Jadwiga A; Price, David; Hyland, Michael E

    2009-12-15

    Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a multicomponent disease with systemic consequences and effects on quality of life. Single measures such as lung function provide a limited reflection of how the disease affects patients. Composite measures have the potential to account for many of the facets of COPD. To derive and validate a multicomponent assessment tool of COPD severity that is applicable to all patients and health care settings. The index was derived using data from 375 patients with COPD in primary care. Regression analysis led to a model explaining 48% of the variance in health status as measured by the Clinical COPD Questionnaire with four components: dyspnea (D), airflow obstruction (O), smoking status (S), and exacerbation frequency (E). The DOSE Index was validated in cross-sectional and longitudinal samples in various health care settings in Holland, Japan, and the United Kingdom. The DOSE Index correlated with health status in all data sets. A high DOSE Index score (> or = 4) was associated with a greater risk of hospital admission (odds ratio, 8.3 [4.1-17]) or respiratory failure (odds ratio, 7.8 [3.4-18.3]). The index predicted exacerbations in the subsequent year (P < or = 0.014). The DOSE Index is a simple, valid tool for assessing the severity of COPD. The index is related to a range of clinically important outcomes such as health care consumption and predicts future events.

  11. Maternal Zika Virus Disease Severity, Virus Load, Prior Dengue Antibodies, and Their Relationship to Birth Outcomes.

    PubMed

    Halai, Umme-Aiman; Nielsen-Saines, Karin; Moreira, Maria Lopes; de Sequeira, Patricia Carvalho; Junior, Jose Paulo Pereira; de Araujo Zin, Andrea; Cherry, James; Gabaglia, Claudia Raja; Gaw, Stephanie L; Adachi, Kristina; Tsui, Irena; Pilotto, Jose Henrique; Nogueira, Rita Ribeiro; de Filippis, Ana Maria Bispo; Brasil, Patricia

    2017-09-15

    Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection during pregnancy. We analyzed outcome data from a mother-infant cohort in Rio de Janeiro in order to assess whether clinical severity of maternal ZIKV infection was associated with maternal virus load, prior dengue antibodies, or abnormal pregnancy/infant outcomes. A clinical severity assessment tool was developed based on duration of fever, severity of rash, multisystem involvement, and duration of symptoms during ZIKV infection. ZIKV-RNA load was quantified by polymerase chain reaction (PCR) cycles in blood/ urine. Dengue immunoglobulin G (IgG) antibodies were measured at baseline. Adverse outcomes were defined as fetal loss or a live infant with grossly abnormal clinical or brain imaging findings. Regression models were used to study potential associations. 131 ZIKV-PCR positive pregnant women were scored for clinical disease severity, 6 (4.6%) had mild disease, 98 (74.8%) had moderate disease, and 27 (20.6%) severe manifestations of ZIKV infection. There were 58 (46.4%) abnormal outcomes with 9 fetal losses (7.2%) in 125 pregnancies. No associations were found between: disease severity and abnormal outcomes (P = .961; odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.796-1.270); disease severity and viral load (P = .994); viral load and adverse outcomes (P = .667; OR: 1.02; 95% CI: 0.922-1.135); or existence of prior dengue antibodies (88% subjects) with severity score, ZIKV-RNA load or adverse outcomes (P = .667; OR: 0.78; 95% CI: 0.255-2.397). Congenital ZIKV syndrome does not appear to be associated with maternal disease severity, ZIKV-RNA load at time of infection or existence of prior dengue antibodies. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  12. Associating mutations causing cystinuria with disease severity with the aim of providing precision medicine.

    PubMed

    Martell, Henry J; Wong, Kathie A; Martin, Juan F; Kassam, Ziyan; Thomas, Kay; Wass, Mark N

    2017-08-11

    Cystinuria is an inherited disease that results in the formation of cystine stones in the kidney, which can have serious health complications. Two genes (SLC7A9 and SLC3A1) that form an amino acid transporter are known to be responsible for the disease. Variants that cause the disease disrupt amino acid transport across the cell membrane, leading to the build-up of relatively insoluble cystine, resulting in formation of stones. Assessing the effects of each mutation is critical in order to provide tailored treatment options for patients. We used various computational methods to assess the effects of cystinuria associated mutations, utilising information on protein function, evolutionary conservation and natural population variation of the two genes. We also analysed the ability of some methods to predict the phenotypes of individuals with cystinuria, based on their genotypes, and compared this to clinical data. Using a literature search, we collated a set of 94 SLC3A1 and 58 SLC7A9 point mutations known to be associated with cystinuria. There are differences in sequence location, evolutionary conservation, allele frequency, and predicted effect on protein function between these mutations and other genetic variants of the same genes that occur in a large population. Structural analysis considered how these mutations might lead to cystinuria. For SLC7A9, many mutations swap hydrophobic amino acids for charged amino acids or vice versa, while others affect known functional sites. For SLC3A1, functional information is currently insufficient to make confident predictions but mutations often result in the loss of hydrogen bonds and largely appear to affect protein stability. Finally, we showed that computational predictions of mutation severity were significantly correlated with the disease phenotypes of patients from a clinical study, despite different methods disagreeing for some of their predictions. The results of this study are promising and highlight the areas of

  13. [Role of serum leptin in the severity of coronary artery disease in patients with stable angina].

    PubMed

    Jerez-Valero, Miguel; Meliveo-García, Ana; Jordán-Martínez, Laura; Carrasco-Chinchilla, Fernando; Moreno-Santos, Inmaculada; Ordóñez, Antonio; Sánchez-Fernández, Pedro L; Vázquez, Rafael; Hernández-García, José M; Gómez-Doblas, Juan J; Pérez-Belmonte, Luis M; de Teresa-Galván, Eduardo; Jiménez-Navarro, Manuel

    2016-07-01

    Leptin is a plasmatic peptide hormone that has been related to cardiovascular homeostasis and atherosclerosis but much is still unknown about its relationship with coronary artery disease. The aim of this study was to evaluate the value of serum leptin in patients with stable angina and its relationship with the severity of coronary disease. 204 patients, 152 with stable angina (coronary artery disease group) and 52 without coronary disease excluded by cardiac computerized tomography (control group) were included. The coronary artery disease group was divided into 2 subgroups according to severity of coronary disease (single or multivessel disease, 46 and 106 patients, respectively). Serum leptin levels were determined by Enzyme-Linked InmunoSorbent Assay. Leptin levels were significantly higher in patients with multivessel disease and were independently associated with a greater severity of coronary artery disease when compared with controls (OR 1.14; 95%CI: 1.03-1.27; p=0.014) and with patients with single vessel disease (OR 1.12; 95%CI: 1.01-1.25; p=0.036). Serum leptin was tested as a diagnostic marker of multivessel disease with an area under the curve obtained from Receiver Operating Characteristics of 0.6764 (95%CI 0.5765-0.7657). Serum leptin levels were associated in patients with stable angina with the severity of coronary artery disease, suggesting its value in the development of coronary disease and as a future therapeutic target. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  14. The revised dengue fever classification in German travelers: clinical manifestations and indicators for severe disease.

    PubMed

    Hoffmeister, B; Suttorp, N; Zoller, T

    2015-02-01

    The number of dengue cases imported to Germany has increased significantly in recent years. Among returning travelers, dengue is now a frequent cause of hospitalization. The aim of this study was to determine the proportion of patients with severe disease hospitalized in a European, non-endemic country applying the revised 2009 WHO classification system and to determine predictors of severe disease. A retrospective single-center analysis of clinical data from 56 patients, 31 (55 %) women and 25 (45 %) men, between 14 and 70 years of age treated in a tertiary care hospital between 1996 and 2010 was conducted. Thirty-nine patients (69.6 %) presented with dengue fever without warning signs, 11 (19.6 %) with warning signs and 6 (10.7 %) with signs for severe dengue fever. Two patients (4 %) developed dengue shock syndrome. Non-European descent (p = 0.001), plasma protein level <6.5 mg/dl (p = 0.001), platelets <30/nl (p = 0.017) and activated partial thromboplastin time (aPTT) >44 s (p = 0.003) were associated with severe disease. A significant proportion of patients hospitalized with symptomatic imported dengue fever in Germany have evidence of severe disease. Simple routine laboratory parameters such as complete blood count, plasma protein level and aPTT are helpful tools for identifying adult patients at risk for severe disease.

  15. Gaucher disease: the role of the specialist on metabolic bone diseases.

    PubMed

    Masi, Laura; Brandi, Maria Luisa

    2015-01-01

    According to European legislation, a disease can be considered rare or "orphan" when it affects less than 1 subject of 2000 (1). Often these diseases affecting the pediatric age, are complex diseases and chronically debilitating and for this motive need the intervention of multidisciplinary skills specific. Among the rare disease as affecting the skeleton more than 400 are characterized by dysplastic changes of the skeleton (2). Alongside the disorders affecting the skeleton primitively, many systemic diseases can have a bone involvement. Among these, the Gaucher disease (GD), an heterogeneous lysosomal storage determined by hereditary enzyme deficiency of β-glucosidase. Patients with this disease have skeletal disorders of varying severity (Erlenmeyer flask deformity, lytic lesions and osteonecrosis, pathological fractures) that affects both the bone marrow, both mineralized bone with progressive damage of the tissue. The bone disease is the most debilitating of GD and can have a significant impact on the quality of life of patients. Thorough evaluations by monitoring biochemical markers of bone turnover and instrumental, with a quantitative and qualitative evaluation of the bone, are of fundamental importance to intervene early so they can prevent complications irreversible.

  16. Gaucher disease: the role of the specialist on metabolic bone diseases

    PubMed Central

    Masi, Laura; Brandi, Maria Luisa

    2015-01-01

    Summary According to European legislation, a disease can be considered rare or “orphan” when it affects less than 1 subject of 2000 (1). Often these diseases affecting the pediatric age, are complex diseases and chronically debilitating and for this motive need the intervention of multidisciplinary skills specific. Among the rare disease as affecting the skeleton more than 400 are characterized by dysplastic changes of the skeleton (2). Alongside the disorders affecting the skeleton primitively, many systemic diseases can have a bone involvement. Among these, the Gaucher disease (GD), an heterogeneous lysosomal storage determined by hereditary enzyme deficiency of β-glucosidase. Patients with this disease have skeletal disorders of varying severity (Erlenmeyer flask deformity, lytic lesions and osteonecrosis, pathological fractures) that affects both the bone marrow, both mineralized bone with progressive damage of the tissue. The bone disease is the most debilitating of GD and can have a significant impact on the quality of life of patients. Thorough evaluations by monitoring biochemical markers of bone turnover and instrumental, with a quantitative and qualitative evaluation of the bone, are of fundamental importance to intervene early so they can prevent complications irreversible. PMID:26604943

  17. Cortical Iron Reflects Severity of Alzheimer’s Disease

    PubMed Central

    van Duijn, Sara; Bulk, Marjolein; van Duinen, Sjoerd G.; Nabuurs, Rob J.A.; van Buchem, Mark A.; van der Weerd, Louise; Natté, Remco

    2017-01-01

    Abnormal iron distribution in the isocortex is increasingly recognized as an in vivo marker for Alzheimer’s disease (AD). However, the contribution of iron accumulation to the AD pathology is still poorly understood. In this study, we investigated: 1) frontal cortical iron distribution in AD and normal aging and 2) the relation between iron distribution and degree of AD pathology. We used formalin fixed paraffin embedded frontal cortex from 10 AD patients, 10 elder, 10 middle aged, and 10 young controls and visualized iron with a modified Perl’s histochemical procedure. AD and elderly subjects were not different with respect to age and sex distribution. Iron distribution in the frontal cortex was not affected by normal aging but was clearly different between AD and controls. AD showed accumulation of iron in plaques, activated microglia, and, in the most severe cases, in the mid-cortical layers along myelinated fibers. The degree of altered iron accumulations was correlated to the amount of amyloid-β plaques and tau pathology in the same block, as well as to Braak stage (p < 0.001). AD and normal aging show different iron and myelin distribution in frontal cortex. These changes appear to occur after the development of the AD pathological hallmarks. These findings may help the interpretation of high resolution in vivo MRI and suggest the potential of using changes in iron-based MRI contrast to indirectly determine the degree of AD pathology in the frontal cortex. PMID:29081415

  18. [Severe Legionnaire's disease revealing an invasive aspergillosis in an apparently immunocompetent patient].

    PubMed

    Vergne, S; Lathuile, D; Bénosa, B; Fragnier, F; Destrac, S; Avedan, M; Alzieu, M; Campistron, J

    2003-10-18

    Invasive aspergillosis, a sever disease, usually occurs in immuno-depressed patients. However, it may also develop in presumably immuno-competent patients. A 54-year-old man, smoker, was hospitalised for hypoxemia of the right lung and septic shock, rapidly requiring mechanical ventilation combined with administration of vasopressors, and followed by dialysis because of the rapid worsening of an acute kidney failure. The diagnosis of pulmonary Legionnaire's disease was made on the second day in view of the positivity of the urinary legionella antigen. The progression of the disease was marked by the discovery of a histologically documented gastric aspergillosis and three abscessed intracerebral lesions within the context of a strongly positive aspergillus antigenemia. The disease worsened and the patient died on D 17, despite the antibiotic and anti-aspergillus treatments, haemodynamic support and dialysis. To our knowledge, the association of invasive aspergillosis and severe Legionnaire's disease has never been described in an presumably immunocompetent patient. This clinical case suggests the existence, other than the usual risk factors of invasive aspergillosis that characterise profound states of immunodepression, of more subtle alterations in the immune system that may enhance this type of infection.

  19. Aerobic Exercise Training in Very Severe Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

    PubMed

    Paneroni, Mara; Simonelli, Carla; Vitacca, Michele; Ambrosino, Nicolino

    2017-08-01

    To evaluate the effectiveness of exercise training in patients with very severe chronic obstructive pulmonary disease (COPD). We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature databases using the following as search terms: COPD, Chronic Obstructive Pulmonary Disease, Exercise, and Pulmonary Rehabilitation. We included randomized controlled trials (RCTs) of subjects with forced expiratory volume in the first second of less than 35% of the predicted normal value enrolled in in-patient, outpatient, or home- or community-based training programs lasting at least 4 weeks with respect to usual care. We included RCTs with outcome measures including the 6-minute walking test and/or health-related quality of life assessed by the St. George's Respiratory Questionnaire (SGRQ). Of 580 articles screened, 10 were included. The programs' duration ranged from 4 to 52 weeks with 1 to 5 sessions per week lasting 15 to 40 minutes each. The intervention group improved in 6-minute walking test [weighted mean difference, 67.1 (95% confidence interval [CI], 37.897-98.927); standardized mean difference, 3.86 (95% CI, 2.04-5.67)], and St. George's Respiratory Questionnaire [weighted mean difference, -8.041 (95% CI, -15.273 to -0.809); standardized mean difference, -1.23 (95% CI, -2.14 to -0.31)]. Exercise training improves exercise tolerance and health-related quality of life in patients with very severe COPD. However, because few studies on severely affected patients are available and the training programs are Highly heterogeneous, larger RCTs are needed.

  20. 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…

  1. Natural hazards and motivation for mitigation behavior: people cannot predict the affect evoked by a severe flood.

    PubMed

    Siegrist, Michael; Gutscher, Heinz

    2008-06-01

    Past research indicates that personal flood experience is an important factor in motivating mitigation behavior. It is not fully clear, however, why such experience is so important. This study tested the hypothesis that people without flooding experience underestimate the negative affect evoked by such an event. People who were affected by a severe recent flood disaster were compared with people who were not affected, but who also lived in flood-prone areas. Face-to-face interviews with open and closed questions were conducted (n= 201). Results suggest that people without flood experience envisaged the consequences of a flood differently from people who had actually experienced severe losses due to a flood. People who were not affected strongly underestimated the negative affect associated with a flood. Based on the results, it can be concluded that risk communication must not focus solely on technical aspects; in order to trigger motivation for mitigation behavior, successful communication must also help people to envisage the negative emotional consequences of natural disasters.

  2. A retrospective analysis of oral cholera vaccine use, disease severity and deaths during an outbreak in South Sudan.

    PubMed

    Bekolo, Cavin Epie; van Loenhout, Joris Adriaan Frank; Rodriguez-Llanes, Jose Manuel; Rumunu, John; Ramadan, Otim Patrick; Guha-Sapir, Debarati

    2016-09-01

    To determine whether pre-emptive oral cholera vaccination reduces disease severity and mortality in people who develop cholera disease during an outbreak. The study involved a retrospective analysis of demographic and clinical data from 41 cholera treatment facilities in South Sudan on patients who developed cholera disease between 23 April and 20 July 2014 during a large outbreak, a few months after a pre-emptive oral vaccination campaign. Patients who developed severe dehydration were regarded as having a severe cholera infection. Vaccinated and unvaccinated patients were compared and multivariate logistic regression analysis was used to identify factors associated with developing severe disease or death. In total, 4115 cholera patients were treated at the 41 facilities: 1946 (47.3%) had severe disease and 62 (1.5%) deaths occurred. Multivariate analysis showed that patients who received two doses of oral cholera vaccine were 4.5-fold less likely to develop severe disease than unvaccinated patients (adjusted odds ratio, aOR: 0.22; 95% confidence interval, CI: 0.11-0.44). Moreover, those with severe cholera were significantly more likely to die than those without (aOR: 4.76; 95% CI: 2.33-9.77). Pre-emptive vaccination with two doses of oral cholera vaccine was associated with a significant reduction in the likelihood of developing severe cholera disease during an outbreak in South Sudan. Moreover, severe disease was the strongest predictor of death. Two doses of oral cholera vaccine should be used in emergencies to reduce the disease burden.

  3. Decision Aids for Multiple-Decision Disease Management as Affected by Weather Input Errors

    USDA-ARS?s Scientific Manuscript database

    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...

  4. Positive affect moderates the effect of negative affect on cardiovascular disease-related hospitalizations and all-cause mortality after cardiac rehabilitation.

    PubMed

    Meyer, Fiorenza Angela; von Känel, Roland; Saner, Hugo; Schmid, Jean-Paul; Stauber, Stefanie

    2015-10-01

    Little is known as to whether negative emotions adversely impact the prognosis of patients who undergo cardiac rehabilitation. We prospectively investigated the predictive value of state negative affect (NA) assessed at discharge from cardiac rehabilitation for prognosis and the moderating role of positive affect (PA) on the effect of NA on outcomes. A total of 564 cardiac patients (62.49 ± 11.51) completed a comprehensive three-month outpatient cardiac rehabilitation program, filling in the Global Mood Scale (GMS) at discharge. The combined endpoint was cardiovascular disease (CVD)-related hospitalizations plus all-cause mortality at follow-up. Cox regression models estimated the predictive value of NA, as well as the moderating influence of PA on outcomes. Survival models were adjusted for sociodemographic factors, traditional cardiovascular risk factors, and severity of disease. During a mean follow-up period of 3.4 years, 71 patients were hospitalized for a CVD-related event and 15 patients died. NA score (range 0-20) was a significant and independent predictor (hazard ratio (HR) 1.091, 95% confidence interval (CI) 1.012-1.175; p = 0.023) with a three-point higher level in NA increasing the relative risk by 9.1%. Furthermore, PA interacted significantly with NA (p < 0.001). The relative risk of poor prognosis with NA was increased in patients with low PA (p = 0.012) but remained unchanged in combination with high PA (p = 0.12). The combination of NA with low PA was particularly predictive of poor prognosis. Whether reduction of NA and increase of PA, particularly in those with high NA, improves outcome needs to be tested. © The European Society of Cardiology 2014.

  5. Azelaic acid 20 % cream: effects on quality of life and disease severity in adult female acne patients.

    PubMed

    Kainz, Julius Thomas; Berghammer, Gabriele; Auer-Grumbach, Piet; Lackner, Verena; Perl-Convalexius, Sylvia; Popa, Rodica; Wolfesberger, Barbara

    2016-12-01

    Data on the efficacy of acne treatments and their impact on quality of life (QoL) in adult patients is sketchy. Assessment of the efficacy of azelaic acid 20 % cream (Skinoren ® ) on acne severity and disease-related QoL. Noninterventional study in adult female patients with mild to moderate acne. Efficacy variables included DLQI and acne severity on the face, chest, and back using the Investigator's Global Assessment (IGA) scale (grade 1 = nearly clear skin; 2 = mild acne; 3 = moderate acne). Visits were scheduled at baseline, at 4-8 weeks, and at twelve weeks. Of the 251 women enrolled, 59 % had grade 1 acne at baseline; 31 %, grade 2; and 10 %, grade 3; the most commonly affected area of the body was the face (IGA grades 2 or 3: 79 %). After twelve weeks, there was significant improvement of acne on the face (IGA grades 0 or 1: 82 %), chest, and back. Median DLQI decreased from nine at baseline to five after twelve weeks. Ninety percent of physicians and patients rated the tolerability of the treatment as very good or good. Treatment with azelaic acid 20 % cream significantly improves acne severity and disease-related QoL in adult women. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  6. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Alpha-1-antichymotrypsin (ACT or SERPINA3) polymorphism may affect age-at-onset and disease duration of Alzheimer’s disease

    PubMed Central

    Kamboh, M. Ilyas; Minster, Ryan L.; Kenney, Margaret; Ozturk, Ayla; Desai, Purnima P.; Kammerer, Candace M.; DeKosky, Steven T.

    2006-01-01

    In addition to genetic effects on disease risk, age-at-onset (AAO) of Alzheimer’s disease (AD) is also genetically controlled. Using AAO as a covariate, a linkage signal for AD has been detected on chromosome 14q32 near the a1-antichymotrypsin (ACT) gene. Previously, a signal peptide polymorphism (codon -17A>T) in the ACT gene has been suggested to affect AD risk, but with inconsistent findings. Given that a linkage signal for AAO has been detected near ACT, we hypothesized that ACT genetic variation affects AAO rather than disease risk and this may explain the previous inconsistent findings between ACT genetic variation and AD risk. We examined the impact of the ACT signal peptide polymorphism on mean AAO in 909 AD cases. The ACT polymorphism was significantly associated with AAO and this effect was independent of the APOE polymorphism. Mean AAO among ACT/AA homozygotes was significantly lower than that in the combined AT+TT genotype group (p=0.019) and this difference was confined to male AD patients (p=0.002). Among male AD patients, the ACT/AA genotype was also associated with shorter disease duration before death as compared to the ACT/AT + TT genotypes (p=0.012). These data suggest that the ACT gene may affect AAO and disease duration of AD. PMID:16137793

  9. Cerebral blood flow laterality derived from arterial spin labeling as a biomarker for assessing the disease severity of parkinson's disease.

    PubMed

    Yamashita, Koji; Hiwatashi, Akio; Togao, Osamu; Kikuchi, Kazufumi; Yamaguchi, Hiroo; Suzuki, Yuriko; Kamei, Ryotaro; Yamasaki, Ryo; Kira, Jun-Ichi; Honda, Hiroshi

    2017-06-01

    To evaluate cerebral blood flow (CBF) laterality derived from arterial spin labeling (ASL) in early-stage Parkinson's disease (PD) patients compared with those with advanced stages. Thirty-eight patients with PD (21 patients in early stages, 17 patients in advanced stages) were retrospectively studied. The CBF maps derived from 3T ASL data were co-registered to the corresponding 3DT1WI using SPM 12 software. Caudate nucleus (CN), putamen (PT), globus pallidus (GP), and thalamus (TH) were manually traced on the representative axial slices of 3DT1WI. CBF of the CN, PT, GP, and TH was measured using corresponding pixels on the co-registered CBF maps. A laterality index (LI) was calculated as the ratio of the contralateral CBF to primary affected side CBF. Each LI was compared between early and advanced stages of PD using the Mann-Whitney U-test. The LIs were also compared between each stage of PD. In the CN, the LIs were significantly higher in early stages (mean LI ± SD, 95% confidence interval = 1.06 ± 0.14, 1.00-1.13) than in advanced stages (0.94 ± 0.14, 0.87-1.01; P < 0.05). We also observed a tendency toward decreased LIs with disease severity (1.10 ± 0.14, 0.99-1.21 for Hoehn and Yahr stage I; 1.04 ± 0.14, 0.92-1.12 for stage II; 0.96 ± 0.11, 0.89-1.10 for stage III; 0.93 ± 0.17, 0.81-1.05 for stage IV). The evaluation of CBF laterality pattern in the CN using ASL may be useful for assessing the disease severity of PD patients. 3 J. MAGN. RESON. IMAGING 2017;45:1821-1826. © 2016 International Society for Magnetic Resonance in Medicine.

  10. Concurrence of Iridovirus, Polyomavirus, and a Unique Member of a New Group of Fish Papillomaviruses in Lymphocystis Disease-Affected Gilthead Sea Bream

    PubMed Central

    López-Bueno, Alberto; Mavian, Carla; Labella, Alejandro M.; Castro, Dolores; Borrego, Juan J.; Alcami, Antonio

    2016-01-01

    ABSTRACT Lymphocystis disease is a geographically widespread disease affecting more than 150 different species of marine and freshwater fish. The disease, provoked by the iridovirus lymphocystis disease virus (LCDV), is characterized by the appearance of papillomalike lesions on the skin of affected animals that usually self-resolve over time. Development of the disease is usually associated with several environmental factors and, more frequently, with stress conditions provoked by the intensive culture conditions present in fish farms. In gilthead sea bream (Sparus aurata), an economically important cultured fish species in the Mediterranean area, a distinct LCDV has been identified but not yet completely characterized. We have used direct sequencing of the virome of lymphocystis lesions from affected S. aurata fish to obtain the complete genome of a new LCDV-Sa species that is the largest vertebrate iridovirus sequenced to date. Importantly, this approach allowed us to assemble the full-length circular genome sequence of two previously unknown viruses belonging to the papillomaviruses and polyomaviruses, termed Sparus aurata papillomavirus 1 (SaPV1) and Sparus aurata polyomavirus 1 (SaPyV1), respectively. Epidemiological surveys showed that lymphocystis disease was frequently associated with the concurrent appearance of one or both of the new viruses. SaPV1 has unique characteristics, such as an intron within the L1 gene, and as the first member of the Papillomaviridae family described in fish, provides evidence for a more ancient origin of this family than previously thought. IMPORTANCE Lymphocystis disease affects marine and freshwater fish species worldwide. It is characterized by the appearance of papillomalike lesions on the skin that contain heavily enlarged cells (lymphocysts). The causative agent is the lymphocystis disease virus (LCDV), a large icosahedral virus of the family Iridoviridae. In the Mediterranean area, the gilthead sea bream (Sparus aurata

  11. Concurrence of Iridovirus, Polyomavirus, and a Unique Member of a New Group of Fish Papillomaviruses in Lymphocystis Disease-Affected Gilthead Sea Bream.

    PubMed

    López-Bueno, Alberto; Mavian, Carla; Labella, Alejandro M; Castro, Dolores; Borrego, Juan J; Alcami, Antonio; Alejo, Alí

    2016-10-01

    Lymphocystis disease is a geographically widespread disease affecting more than 150 different species of marine and freshwater fish. The disease, provoked by the iridovirus lymphocystis disease virus (LCDV), is characterized by the appearance of papillomalike lesions on the skin of affected animals that usually self-resolve over time. Development of the disease is usually associated with several environmental factors and, more frequently, with stress conditions provoked by the intensive culture conditions present in fish farms. In gilthead sea bream (Sparus aurata), an economically important cultured fish species in the Mediterranean area, a distinct LCDV has been identified but not yet completely characterized. We have used direct sequencing of the virome of lymphocystis lesions from affected S. aurata fish to obtain the complete genome of a new LCDV-Sa species that is the largest vertebrate iridovirus sequenced to date. Importantly, this approach allowed us to assemble the full-length circular genome sequence of two previously unknown viruses belonging to the papillomaviruses and polyomaviruses, termed Sparus aurata papillomavirus 1 (SaPV1) and Sparus aurata polyomavirus 1 (SaPyV1), respectively. Epidemiological surveys showed that lymphocystis disease was frequently associated with the concurrent appearance of one or both of the new viruses. SaPV1 has unique characteristics, such as an intron within the L1 gene, and as the first member of the Papillomaviridae family described in fish, provides evidence for a more ancient origin of this family than previously thought. Lymphocystis disease affects marine and freshwater fish species worldwide. It is characterized by the appearance of papillomalike lesions on the skin that contain heavily enlarged cells (lymphocysts). The causative agent is the lymphocystis disease virus (LCDV), a large icosahedral virus of the family Iridoviridae In the Mediterranean area, the gilthead sea bream (Sparus aurata), an important farmed

  12. Risk adjustment for health care financing in chronic disease: what are we missing by failing to account for disease severity?

    PubMed

    Omachi, Theodore A; Gregorich, Steven E; Eisner, Mark D; Penaloza, Renee A; Tolstykh, Irina V; Yelin, Edward H; Iribarren, Carlos; Dudley, R Adams; Blanc, Paul D

    2013-08-01

    Adjustment for differing risks among patients is usually incorporated into newer payment approaches, and current risk models rely on age, sex, and diagnosis codes. It is unknown the extent to which controlling additionally for disease severity improves cost prediction. Failure to adjust for within-disease variation may create incentives to avoid sicker patients. We address this issue among patients with chronic obstructive pulmonary disease (COPD). Cost and clinical data were collected prospectively from 1202 COPD patients at Kaiser Permanente. Baseline analysis included age, sex, and diagnosis codes (using the Diagnostic Cost Group Relative Risk Score) in a general linear model predicting total medical costs in the following year. We determined whether adding COPD severity measures-forced expiratory volume in 1 second, 6-Minute Walk Test, dyspnea score, body mass index, and BODE Index (composite of the other 4 measures)-improved predictions. Separately, we examined household income as a cost predictor. Mean costs were $12,334/y. Controlling for Relative Risk Score, each ½ SD worsening in COPD severity factor was associated with $629 to $1135 in increased annual costs (all P<0.01). The lowest stratum of forced expiratory volume in 1 second (<30% normal) predicted $4098 (95% confidence interval, $576-$8773) additional costs. Household income predicted excess costs when added to the baseline model (P=0.038), but this became nonsignificant when also incorporating the BODE Index. Disease severity measures explain significant cost variations beyond current risk models, and adding them to such models appears important to fairly compensate organizations that accept responsibility for sicker COPD patients. Appropriately controlling for disease severity also accounts for costs otherwise associated with lower socioeconomic status.

  13. How does severe brachycephaly affect dog's lives? Results of a structured preoperative owner questionnaire.

    PubMed

    Roedler, Frauke S; Pohl, Sabine; Oechtering, Gerhard U

    2013-12-01

    Brachycephalic syndrome (BS) is a complex canine disease, which is characterized by diverse clinical signs primarily involving the respiratory and gastrointestinal systems. Through a structured owner questionnaire, the present study investigated how owners perceived the frequency and severity of a broad spectrum of welfare-relevant impairments caused by this hereditary disease. One hundred owners of brachycephalic dogs (Pugs and French bulldogs) referred for surgical treatment of BS completed the questionnaire. As a basis for comparison, 20 owners of mesocephalic dogs also completed part of the questionnaire. Questionnaire responses revealed that in addition to the well-known respiratory signs, brachycephalic dogs experienced severe exercise intolerance and prolonged recovery time after physical exercise (88%), significant heat sensitivity (more severe signs at temperatures above 19°C; 50%) and a variety of sleep problems (56%). To our knowledge, this is the first study using a structured owner questionnaire specifically to investigate a broad range of problems caused by selective breeding for brachycephaly. In particular, decreased exercise tolerance, increased recovery time due to heat intolerance and the extent of sleep problems have either been underestimated in the past, or have severely worsened over recent generations of dogs. The extent and severity of clinical signs and their impact on quality of life greatly exceeded our expectations. This study emphasizes the major impact that selective breeding for extreme brachycephalic features has on animal welfare. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. 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…

  15. Mandibulectomy for treatment of fractures associated with severe periodontal disease.

    PubMed

    Carvalho, Carina Marchiori; Rahal, Sheila Canevese; Dos Reis Mesquita, Luciane; Castilho, Maíra Sales; Kano, Washington Takashi; Mamprim, Maria Jaqueline

    2015-03-01

    Six cases of mandibular fractures associated with severe periodontal disease that had been treated by mandibulectomy, due to intense bone loss, were evaluated retrospectively. The dogs were mainly older, small breed dogs that had suffered a traumatic event. Four dogs had a bilateral mandibulectomy and 2 a unilateral mandibulectomy.

  16. Affective coding: the emotional dimension of agency

    PubMed Central

    Gentsch, Antje; Synofzik, Matthis

    2014-01-01

    The sense of agency (SoA) (i.e., the registration that I am the initiator and controller of my actions and relevant events) is associated with several affective dimensions. This makes it surprising that the emotion factor has been largely neglected in the field of agency research. Current empirical investigations of the SoA mainly focus on sensorimotor signals (i.e., efference copy) and cognitive cues (i.e., intentions, beliefs) and on how they are integrated. Here we argue that this picture is not sufficient to explain agency experience, since agency and emotions constantly interact in our daily life by several ways. Reviewing first recent empirical evidence, we show that self-action perception is in fact modulated by the affective valence of outcomes already at the sensorimotor level. We hypothesize that the “affective coding” between agency and action outcomes plays an essential role in agency processing, i.e., the prospective, immediate or retrospective shaping of agency representations by affective components. This affective coding of agency be differentially altered in various neuropsychiatric diseases (e.g., schizophrenia vs. depression), thus helping to explain the dysfunctions and content of agency experiences in these diseases. PMID:25161616

  17. Widowhood and severity of coronary artery disease: a multicenter study.

    PubMed

    Daoulah, Amin; Alama, Mohamed N; Elkhateeb, Osama E; Al-Murayeh, Mushabab; Al-Kaabi, Salem; Al-Faifi, Salem M; Alosaimi, Hind M; Lotfi, Amir; Asiri, Khalid S; Elimam, Ahmed M; Abougalambo, Ayman S; Murad, Waheed; Haddara, Mamdouh M; Dixon, Ciaran M; Alsheikh-Ali, Alawi A

    2017-03-01

    The aim of this study was to assess the association of widowhood with the severity and extent of coronary artery disease (CAD), and whether it is modified by sex or socioeconomic status. A total of 1068 patients undergoing coronary angiography at five centers in Saudi Arabia and the United Arab Emirates were included in the study. CAD was defined as more than 70% lumen stenosis in a major epicardial vessel or more than 50% in the left main coronary artery. Multivessel disease was defined as more than one diseased vessel. Of 1068 patients, 65 (6%) were widowed. Widowed patients were older (65±15 vs. 59±12), more likely to be female (75 vs. 25%), less likely to be smokers (18 vs. 47%), of lower economic and education status, and more likely to have undergone coronary angiography for urgent/emergent indications (75 vs. 61%) (P<0.05 for all). There was a significant association between widowhood and the number of coronary arteries with more than 70% lumen stenosis. Consequently, such a high degree of lumen stenosis in those who were widowed was more likely to require coronary artery bypass graft surgery (38 vs. 16%; P<0.01). After adjusting for baseline differences, widowhood was associated with a significantly higher odds of CAD [adjusted odds ratio (OR) 3.6; 95% confidence interval (CI) 1.2-10.5] and multivessel disease (adjusted OR 4.6; 95% CI 2.2-9.6), but not left main disease (adjusted OR 1.3; 95% CI 0.5-3.1). All associations were consistent in men and women and not modified by age, community setting (urban vs. rural), employment, income, or educational levels (Pinteraction>0.1 for all). Widowhood is associated with the severity and extent of CAD. The association is not modified by sex or socioeconomic status.

  18. Postural instability and gait are associated with severity and prognosis of Parkinson disease.

    PubMed

    van der Heeden, Jorine F; Marinus, Johan; Martinez-Martin, Pablo; Rodriguez-Blazquez, Carmen; Geraedts, Victor J; van Hilten, Jacobus J

    2016-06-14

    Differences in disease progression in Parkinson disease (PD) have variously been attributed to 2 motor subtypes: tremor-dominant (TD) and postural instability and gait difficulty (PIGD)-dominant (PG). We evaluated the role of these phenotypic variants in severity and progression of nondopaminergic manifestations of PD and motor complications. Linear mixed models were applied to data from the Profiling Parkinson's disease (PROPARK) cohort (n = 396) to evaluate the effect of motor subtype on severity and progression of cognitive impairment (Scales for Outcomes in Parkinson's disease [SCOPA]-Cognition [SCOPA-COG]), depression (Hospital Anxiety and Depression Scale [HADS]), autonomic dysfunction (SCOPA-Autonomic [SCOPA-AUT]), excessive daytime sleepiness, psychotic symptoms (SCOPA-Psychiatric Complications [SCOPA-PC]), and motor complications. In first analyses, subtype as determined by the commonly used ratio of tremor over PIGD score was entered as a factor, whereas in second analyses separate tremor and PIGD scores were used. Results were verified in an independent cohort (Estudio Longitudinal de Pacientes con Enfermedad de Parkinson [ELEP]; n = 365). The first analyses showed that PG subtype patients had worse SCOPA-COG, HADS, SCOPA-AUT, SCOPA-PC, and motor complications scores, and exhibited faster progression on the SCOPA-COG. The second analyses showed that only higher PIGD scores were associated with worse scores for these variables; tremor score was not associated with severity or progression of any symptom. Analyses in the independent cohort yielded similar results. In contrast to PIGD, which consistently was associated with greater severity of nondopaminergic symptoms, there was no evidence of a benign effect of tremor. Our findings do not support the use of the TD subtype as a prognostic trait in PD. The results showed that severity of PIGD is a useful indicator of severity and prognosis in PD by itself. © 2016 American Academy of Neurology.

  19. Disease severity index derived from hemolysis evaluation

    NASA Astrophysics Data System (ADS)

    Piskin, Senol; Finol, Ender A.; Pekkan, Kerem; Vascular Biomechanics; Biofluids Laboratory (VBBL) Team; Pediatric Cardiovascular Fluid Mechanics Laboratory Team

    2017-11-01

    Several cardiovascular diseases (CVDs) are characterized by stenosis of the vessel, leaflet malfunction, disturbance of blood flow (vorticity) due to geometric deformation or abnormal growth, and development of jet flow due to ventricle overload. All of these abnormalities are followed by degeneration of inner wall of the heart and the arteries and red blood cell damage (hemolysis). In this study, identification and classification of CVDs are being performed based on hemolysis evaluation (HE). Two commonly used hemolysis models are implemented to our computational fluid dynamics simulations of CV system. The capability of HE on disease diagnosis is investigated. The analysis will be carried out on our CVD templates such as artery stenosis or pulmonary artery hypertension. HEs depend mainly on the strain rate and for some computational hemolysis models there is a threshold of strain of which the hemolysis will not take place. In the current study, we investigate the effect of thresholding besides using pseudo exposure time for steady state simulations on the blood damage evaluations. Details of our methodology for HE by post processing simulation results without necessity of re-running the simulations will be presented. American Heart Association, National Institute of Health, European Research Council, TUBITAK.

  20. Do Genetic Susceptibility Variants Associate with Disease Severity in Early Active Rheumatoid Arthritis?

    PubMed

    Scott, Ian C; Rijsdijk, Frühling; Walker, Jemma; Quist, Jelmar; Spain, Sarah L; Tan, Rachael; Steer, Sophia; Okada, Yukinori; Raychaudhuri, Soumya; Cope, Andrew P; Lewis, Cathryn M

    2015-07-01

    Genetic variants affect both the development and severity of rheumatoid arthritis (RA). Recent studies have expanded the number of RA susceptibility variants. We tested the hypothesis that these associated with disease severity in a clinical trial cohort of patients with early, active RA. We evaluated 524 patients with RA enrolled in the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trials. We tested validated susceptibility variants - 69 single-nucleotide polymorphisms (SNP), 15 HLA-DRB1 alleles, and amino acid polymorphisms in 6 HLA molecule positions - for their associations with progression in Larsen scoring, 28-joint Disease Activity Scores, and Health Assessment Questionnaire (HAQ) scores over 2 years using linear mixed-effects and latent growth curve models. HLA variants were associated with joint destruction. The *04:01 SNP (rs660895, p = 0.0003), *04:01 allele (p = 0.0002), and HLA-DRβ1 amino acids histidine at position 13 (p = 0.0005) and valine at position 11 (p = 0.0012) significantly associated with radiological progression. This association was only significant in anticitrullinated protein antibody (ACPA)-positive patients, suggesting that while their effects were not mediated by ACPA, they only predicted joint damage in ACPA-positive RA. Non-HLA variants did not associate with radiograph damage (assessed individually and cumulatively as a weighted genetic risk score). Two SNP - rs11889341 (STAT4, p = 0.0001) and rs653178 (SH2B3-PTPN11, p = 0.0004) - associated with HAQ scores over 6-24 months. HLA susceptibility variants play an important role in determining radiological progression in early, active ACPA-positive RA. Genome-wide and HLA-wide analyses across large populations are required to better characterize the genetic architecture of radiological progression in RA.

  1. Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

    PubMed Central

    Monsalvo, Ana Clara; Batalle, Juan P.; Lopez, M. Florencia; Krause, Jens C.; Klemenc, Jennifer; Zea, Johanna; Maskin, Bernardo; Bugna, Jimena; Rubinstein, Carlos; Aguilar, Leandro; Dalurzo, Liliana; Libster, Romina; Savy, Vilma; Baumeister, Elsa; Aguilar, Liliana; Cabral, Graciela; Font, Julia; Solari, Liliana; Weller, Kevin P.; Johnson, Joyce; Echavarria, Marcela; Edwards, Kathryn M.; Chappell, James D.; Crowe, James E.; Williams, John V.; Melendi, Guillermina A.; Polack, Fernando P.

    2010-01-01

    Pandemic influenza viruses often cause severe disease in middle-aged adults without preexistent co-morbidities. The mechanism of illness associated with severe disease in this age group is not well understood1–10. Here, we demonstrate preexisting serum antibody that cross-reacts with, but does not protect against 2009 H1N1 influenza virus in middle-aged adults. Non-protective antibody is associated with immune complex(IC)-mediated disease after infection. High titers of serum antibody of low avidity for H1-2009 antigen, and low avidity pulmonary ICs against the same protein were detected in severely ill patients. Moreover, C4d deposition - a sensitive marker of complement activation mediated by ICs- was present in lung sections of fatal cases. Archived lung sections from adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a novel biological mechanism for the unusual age distribution of severe cases during influenza pandemics. PMID:21131958

  2. Severe and Rapid Progression in Very Early-Onset Chronic Granulomatous Disease-Associated Colitis.

    PubMed

    Kawai, Toshinao; Arai, Katsuhiro; Harayama, Shizuko; Nakazawa, Yumiko; Goto, Fumihiro; Maekawa, Takanobu; Tamura, Eiichiro; Uchiyama, Toru; Onodera, Masafumi

    2015-08-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that leads to recurrent infection and hyper-inflammation, occasionally represented by CGD-associated colitis (CGD colitis). Although clinical symptoms of CGD colitis mimic those of ulcerative colitis (UC), there is no reliable standard measurement of disease activity or standard therapeutic strategy for CGD colitis. Here, we examined the clinical manifestation of CGD colitis based on severity using a noninvasive measure of disease activity, the Pediatric Ulcerative Colitis Activity Index (PUCAI), which has been validated and widely used for pediatric UC. Sixteen of 35 CGD patients, who were diagnosed with CGD colitis based on colonoscopic and histological findings, were examined using the PUCAI. Both the PUCAI and the physician global assessment (PGA) tool were retrospectively scored by reviewing medical records. Disease activity defined by PUCAI was correlated with PGA, and increased at diagnosis of CGD colitis, especially in patients who were younger than 6 years of age (very early-onset CGD colitis: VEO-CGD colitis) when diagnosed with CGD colitis. All severe patients had a more progressive form of VEO-CGD colitis. Unlike mild and moderate patients, severe patients required multidrug therapy of corticosteroids and immunomodulator/immunosuppressants, and some were eventually treated with hematopoietic stem cell transplantation. Although the validation of PUCAI in CGD colitis should be considered for future use, our results indicate that noninvasive measures could be effective to measure disease activity and help to determine suitable treatment for CGD colitis. In patients with VEO-CGD colitis, multidrug therapy would need to be considered at an early stage on the basis of disease activity.

  3. The prion diseases of animals

    USDA-ARS?s Scientific Manuscript database

    Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases that affect several species of animals and include bovine spongiform encephalopathy (BSE), scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, and transmissible mink encephalopat...

  4. Sequential Waves of Gene Expression in Patients with Clinically Defined Dengue Illnesses Reveal Subtle Disease Phases and Predict Disease Severity

    PubMed Central

    Sun, Peifang; García, Josefina; Comach, Guillermo; Vahey, Maryanne T.; Wang, Zhining; Forshey, Brett M.; Morrison, Amy C.; Sierra, Gloria; Bazan, Isabel; Rocha, Claudio; Vilcarromero, Stalin; Blair, Patrick J.; Scott, Thomas W.; Camacho, Daria E.; Ockenhouse, Christian F.; Halsey, Eric S.; Kochel, Tadeusz J.

    2013-01-01

    Background Dengue virus (DENV) infection can range in severity from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Changes in host gene expression, temporally through the progression of DENV infection, especially during the early days, remains poorly characterized. Early diagnostic markers for DHF are also lacking. Methodology/Principal Findings In this study, we investigated host gene expression in a cohort of DENV-infected subjects clinically diagnosed as DF (n = 51) and DHF (n = 13) from Maracay, Venezuela. Blood specimens were collected daily from these subjects from enrollment to early defervescence and at one convalescent time-point. Using convalescent expression levels as baseline, two distinct groups of genes were identified: the “early” group, which included genes associated with innate immunity, type I interferon, cytokine-mediated signaling, chemotaxis, and complement activity peaked at day 0–1 and declined on day 3–4; the second “late” group, comprised of genes associated with cell cycle, emerged from day 4 and peaked at day 5–6. The up-regulation of innate immune response genes coincided with the down-regulation of genes associated with viral replication during day 0–3. Furthermore, DHF patients had lower expression of genes associated with antigen processing and presentation, MHC class II receptor, NK and T cell activities, compared to that of DF patients. These results suggested that the innate and adaptive immunity during the early days of the disease are vital in suppressing DENV replication and in affecting outcome of disease severity. Gene signatures of DHF were identified as early as day 1. Conclusions/Significance Our study reveals a broad and dynamic picture of host responses in DENV infected subjects. Host response to DENV infection can now be understood as two distinct phases with unique transcriptional markers. The DHF signatures identified during day 1–3 may have

  5. Depressive Symptomatology, Quality of Life and Disease Control among Individuals with Well-Characterized Severe Asthma

    PubMed Central

    Yonas, Michael A.; Marsland, Anna L.; Emeremni, Chetachi A.; Moore, Charity G.; Holguin, Fernando; Wenzel, Sally

    2014-01-01

    Objectives A thorough examination of the relationship of asthma severity and control with symptoms of depression is needed to identify groups of asthmatics at high risk for poor disease control outcomes. This study examines the relationship of symptoms of depression with severity and control in a well characterized cohort of asthmatics and healthy controls. Methods Depressive symptoms and quality of life were assessed using the Beck Depression Inventory. Disease control was measured by a composite index incorporating symptoms, activity limitation, and rescue medication use. Results Individuals with asthma (n=91) reported more symptoms of depression than controls (n=36; p<0.001). Those with Severe asthma (n=49) reported more symptoms of depression (p=0.002) and poorer asthma control (p<0.0001) than those with Not Severe asthma. Worse asthma control was associated with more depressive symptoms in Severe (r=0.46, p=0.002) but not in Not Severe (r=0.13, p=0.40) asthmatics. The relationship of symptoms of depression among Severe asthmatics was attenuated by disease control. Exploratory analyses identified specific disease symptom characteristics, as opposed to exacerbations, as associated with symptoms of depression. Conclusions Among individuals with severe asthma, increased symptom burden is positively associated with risk for co-morbid depression. These findings point to a need for regular mood disorder screenings and treatment referrals among this group. Further research is warranted to examine whether treatment of comorbid depression improves treatment adherence and asthma-related quality of life. PMID:23725317

  6. Oxidative conditions prevail in severe IUGR with vascular disease and Doppler anomalies.

    PubMed

    Maisonneuve, Emeline; Delvin, Edgard; Edgard, Annie; Morin, Lucie; Dubé, Johanne; Boucoiran, Isabelle; Moutquin, Jean-Marie; Fouron, Jean-Claude; Klam, Stephanie; Levy, Emile; Leduc, Line

    2015-08-01

    Intrauterine growth restriction (IUGR) and prenatal exposure to oxidative stress are thought to lead to increased risks of cardiovascular disease later in life. The objective of the present study was to document whether cord blood oxidative stress biomarkers vary with the severity of IUGR and of vascular disease in the twin pregnancy model in which both fetuses share the same maternal environment. This prospective cohort study involved dichorionic twin pairs, with one co-twin with IUGR. Oxidative stress biomarkers were measured in venous cord blood samples from each neonate of 32 twin pairs, and compared, according to severity of IUGR (IUGR <5th percentile), Doppler anomalies of the umbilical artery and early onset IUGR (in the second trimester) of the growth restricted twin. Oxidized Low-Density Lipoproteins (oxLDL) and Malondialdehyde (MDA) concentrations were increased proportionally in cases of severe IUGR. OxLDL concentrations were also increased in cases of IUGR with Doppler anomaly. Our data indicate that severe IUGR, is related to a derangement in redox balance, illustrated by increased venous cord blood oxidative stress biomarkers concentrations. Severe IUGR and IUGR with abnormal Doppler can be translated into conditions with intense oxidative stress.

  7. Mandibulectomy for treatment of fractures associated with severe periodontal disease

    PubMed Central

    Carvalho, Carina Marchiori; Rahal, Sheila Canevese; dos Reis Mesquita, Luciane; Castilho, Maíra Sales; Kano, Washington Takashi; Mamprim, Maria Jaqueline

    2015-01-01

    Six cases of mandibular fractures associated with severe periodontal disease that had been treated by mandibulectomy, due to intense bone loss, were evaluated retrospectively. The dogs were mainly older, small breed dogs that had suffered a traumatic event. Four dogs had a bilateral mandibulectomy and 2 a unilateral mandibulectomy. PMID:25750452

  8. Black leaf streak disease affects starch metabolism in banana fruit.

    PubMed

    Saraiva, Lorenzo de Amorim; Castelan, Florence Polegato; Shitakubo, Renata; Hassimotto, Neuza Mariko Aymoto; Purgatto, Eduardo; Chillet, Marc; Cordenunsi, Beatriz Rosana

    2013-06-12

    Black leaf streak disease (BLSD), also known as black sigatoka, represents the main foliar disease in Brazilian banana plantations. In addition to photosynthetic leaf area losses and yield losses, this disease causes an alteration in the pre- and postharvest behavior of the fruit. The aim of this work was to investigate the starch metabolism of fruits during fruit ripening from plants infected with BLSD by evaluating carbohydrate content (i.e., starch, soluble sugars, oligosaccharides, amylose), phenolic compound content, phytohormones, enzymatic activities (i.e., starch phosphorylases, α- and β-amylase), and starch granules. The results indicated that the starch metabolism in banana fruit ripening is affected by BLSD infection. Fruit from infested plots contained unusual amounts of soluble sugars in the green stage and smaller starch granules and showed a different pattern of superficial degradation. Enzymatic activities linked to starch degradation were also altered by the disease. Moreover, the levels of indole-acetic acid and phenolic compounds indicated an advanced fruit physiological age for fruits from infested plots.

  9. Concentration of carp edema virus (CEV) DNA in koi tissues affected by koi sleepy disease (KSD).

    PubMed

    Adamek, Mikolaj; Jung-Schroers, Verena; Hellmann, John; Teitge, Felix; Bergmann, Sven Michael; Runge, Martin; Kleingeld, Dirk Willem; Way, Keith; Stone, David Michael; Steinhagen, Dieter

    2016-05-26

    Carp edema virus (CEV), the causative agent of 'koi sleepy disease' (KSD), appears to be spreading worldwide and to be responsible for losses in koi, ornamental varieties of the common carp Cyprinus carpio. Clinical signs of KSD include lethargic behaviour, swollen gills, sunken eyes and skin alterations and can easily be mistaken for other diseases, such as infection with cyprinid herpesvirus 3 (CyHV-3). To improve the future diagnosis of CEV infection and to provide a tool to better explore the relationship between viral load and clinical disease, we developed a specific quantitative PCR (qPCR) for strains of the virus known to infect koi carp. In samples from several clinically affected koi, CEV-specific DNA was present in a range from 1 to 2,046,000 copies, with a mean of 129,982 copies and a median of 45 copies per 250 ng of isolated DNA, but virus DNA could not be detected in all clinically affected koi. A comparison of the newly developed qPCR, which is based on a dual-labelled probe, to an existing end-point PCR procedure revealed higher specificity and sensitivity of the qPCR and demonstrated that the new protocol could improve CEV detection in koi. In addition to improved diagnosis, the newly developed qPCR test would be a useful research tool. For example, studies on the pathobiology of CEV could employ controlled infection experiments in which the development of clinical signs could be examined in parallel with a quantitative determination of virus load.

  10. 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

  11. Interactions Between Secondhand Smoke and Genes That Affect Cystic Fibrosis Lung Disease

    PubMed Central

    Collaco, J. Michael; Vanscoy, Lori; Bremer, Lindsay; McDougal, Kathryn; Blackman, Scott M.; Bowers, Amanda; Naughton, Kathleen; Jennings, Jacky; Ellen, Jonathan; Cutting, Garry R.

    2011-01-01

    Context Disease variation can be substantial even in conditions with a single gene etiology such as cystic fibrosis (CF). Simultaneously studying the effects of genes and environment may provide insight into the causes of variation. Objective To determine whether secondhand smoke exposure is associated with lung function and other outcomes in individuals with CF, whether socioeconomic status affects the relationship between secondhand smoke exposure and lung disease severity, and whether specific gene-environment interactions influence the effect of secondhand smoke exposure on lung function. Design, Setting, and Participants Retrospective assessment of lung function, stratified by environmental and genetic factors. Data were collected by the US Cystic Fibrosis Twin and Sibling Study with missing data supplemented by the Cystic Fibrosis Foundation Data Registry. All participants were diagnosed with CF, were recruited between October 2000 and October 2006, and were primarily from the United States. Main Outcome Measures Disease-specific cross-sectional and longitudinal measures of lung function. Results Of 812 participants with data on secondhand smoke in the home, 188 (23.2%) were exposed. Of 780 participants with data on active maternal smoking during gestation, 129 (16.5%) were exposed. Secondhand smoke exposure in the home was associated with significantly lower cross-sectional (9.8 percentile point decrease; P<.001) and longitudinal lung function (6.1 percentile point decrease; P=.007) compared with those not exposed. Regression analysis demonstrated that socioeconomic status did not confound the adverse effect of secondhand smoke exposure on lung function. Interaction between gene variants and secondhand smoke exposure resulted in significant percentile point decreases in lung function, namely in CFTR non-ΔF508 homozygotes (12.8 percentile point decrease; P=.001), TGFβ1-509 TT homozygotes (22.7 percentile point decrease; P=.006), and TGFβ1 codon 10 CC

  12. 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. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Diagnosis and treatment of dementia: 6. Management of severe Alzheimer disease

    PubMed Central

    Herrmann, Nathan; Gauthier, Serge

    2008-01-01

    Background The management of severe Alzheimer disease often presents difficult choices for clinicians and families. The disease is characterized by a need for full-time care and assistance with basic activities of daily living. We outline an evidence-based approach for these choices based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. Methods We developed evidence-based guidelines using systematic literature searches, with specific criteria for the selection and quality assessment of articles, and a clear and transparent decision-making process. We selected articles published from January 1996 to December 2005 that dealt with the management of severe Alzheimer disease. Subsequent to the conference, we searched for additional articles published from January 2006 to March 2008 using the same search terms. We graded the strength of the evidence using the criteria of the Canadian Task Force on Preventive Health Care. Results We identified 940 articles, of which 838 were selected for further study. Thirty-four articles were judged to be of at least good or fair quality and were used to generate 17 recommendations. Assessment of severe Alzheimer disease should include the measurement of cognitive function and the assessment of behaviour, function, medical status, nutrition, safety and caregiver status. Management could include treatment with a cholinesterase inhibitor or memantine, or both. Treatment of neuropsychiatric symptoms begins with nonpharmacologic approaches to addressing behavioural problems. Severe agitation, aggression and psychosis, which are potentially dangerous to the patient, the caregiver and others in the environment, can be treated with atypical antipsychotics, with consideration of their increased risk of cerebrovascular events and death. All pharmacologic approaches require careful monitoring and periodic reassessment to determine whether continued treatment is necessary. Caregiver

  14. [Severe Yellow fever vaccine-associated disease: a case report and current overview].

    PubMed

    Slesak, Günther; Gabriel, Martin; Domingo, Cristina; Schäfer, Johannes

    2017-08-01

    History and physical examination  A 56-year-old man developed high fever with severe headaches, fatigue, impaired concentration skills, and an exanthema 5 days after a yellow fever (YF) vaccination. Laboratory tests  Liver enzymes and YF antibody titers were remarkably elevated. YF vaccine virus was detected in urine by PCR. Diagnosis and therapy  Initially, severe YF vaccine-associated visceral disease was suspected and treated symptomatically. Clinical Course  His fever ceased after 10 days in total, no organ failure developed. However, postencephalitic symptoms persisted with fatigue and impaired concentration, memory, and reading skills and partly incapability to work for over 3 months. A diagnosis was made of suspected YF vaccine-associated neurotropic disease. Conclusion  Severe vaccine-derived adverse effects need to be considered in the indication process for YF vaccination. © Georg Thieme Verlag KG Stuttgart · New York.

  15. 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

  16. 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

  17. Serum IgE levels are associated with coronary artery disease severity.

    PubMed

    Guo, Xiaoxiao; Yuan, Su; Liu, Yongtai; Zeng, Yong; Xie, Hongzhi; Liu, Zhenyu; Zhang, Shuyang; Fang, Quan; Wang, Jing; Shen, Zhujun

    2016-08-01

    Immunoglobulin E (IgE), a key element of allergic reactions, was considered to be involved in the development of atherosclerosis and the pathogenesis of myocardial ischemia. This study was designed to test whether total serum IgE levels were associated with the atherosclerosis severity of coronary artery disease (CAD). Total serum IgE concentrations were measured in 708 consecutive patients who were presented to our center for coronary angiography. Atherosclerosis severity of CAD was assessed by the number of diseased vessels showing ≥50% diameter stenosis and quantified by Gensini score. Patients with CAD (N = 562) had higher serum IgE levels than those without CAD (N = 146) [55.90 (19.10-156.00) vs. 26.90 (11.80-62.10) KU/L, p = 0.003]. Furthermore, the serum IgE levels were significantly increased in patients with multivessel disease (MVD) compared to those with single-vessel disease [61.80 (23.20-159.00) vs. 32.45(14.15-94.38) KU/L, p = 0.003]. After adjustment for traditional cardiovascular risk factors, a high serum IgE level was an independent predictor for an increased risk of MVD (OR 1.003; 95% CI 1.001-1.004; p = 0.041). Receiver-operating characteristic curve analysis demonstrated that serum IgE levels improved the predictive capability of traditional risk factors for MVD (area under the curve with and without IgE: 0.734 and 0.713, respectively, p < 0.001). Meanwhile, there was a significant linear relationship between Gensini score and the serum IgE level quartiles (p for linear trend <0.001). Increased total serum IgE levels are associated with MVD and contribute to discriminating CAD severity independently of traditional cardiovascular risk factors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Severe and moderate haemophilia A and B in US females.

    PubMed

    Di Michele, D M; Gibb, C; Lefkowitz, J M; Ni, Q; Gerber, L M; Ganguly, A

    2014-03-01

    Haemophilia A and B are rare X-lined hemorrhagic disorders that typically affect men. Women are usually asymptomatic carriers, but may be symptomatic and, rarely, also express severe (factor VIII (FVIII) or factor IX (FIX) <0.01 U mL(-1)) or moderately severe (FVIII/FIX 0.01-0.05 U mL(-1)) phenotypes. However, data on clinical manifestations, genotype and the psychosocial ramifications of illness in severely affected females remain anecdotal. A national multi-centre retrospective study was conducted to collect a comprehensive data set on affected US girls and women, and to compare clinical observations to previously published information on haemophilic males of comparable severity and mildly affected haemophilic females. Twenty-two severe/moderate haemophilia A/B subjects were characterized with respect to clinical manifestations and disease complications; genetic determinants of phenotypic severity; and health-related quality of life (HR-QoL). Clinical data were compared as previously indicated. Female patients were older than male patients at diagnosis, but similarly experienced joint haemorrhage, disease- and treatment-related complications and access to treatment. Gynaecological and obstetrical bleeding was unexpectedly infrequent. F8 or F9 mutations, accompanied by extremely skewed X-chromosome inactivation pattern (XIP), were primary determinants of severity. HR-QoL was diminished by arthropathy and viral infection. Using systematic case verification of participants in a national surveillance registry, this study elucidated the genetics, clinical phenotype and quality of life issues in female patients with severe/moderate haemophilia. An ongoing international case-controlled study will further evaluate these observations. Novel mechanistic questions are raised about the relationship between XIP and both age and tissue-specific FVIII and FIX expression. © 2014 John Wiley & Sons Ltd.

  19. The association between compliance with recommended follow-up and glaucomatous disease severity in a county hospital population.

    PubMed

    Ung, Cindy; Murakami, Yohko; Zhang, Elisa; Alfaro, Tatyana; Zhang, Monica; Seider, Michael I; Singh, Kuldev; Lin, Shan C

    2013-08-01

    To assess the association between insufficient follow-up and clinical parameters such as disease severity and medication use among glaucoma patients at a metropolitan county hospital. Cross-sectional study. Two-hundred and six patients with established glaucoma were recruited from San Francisco General Hospital. Subjects were classified based on compliance with recommended follow-up examination intervals over the year preceding commencement of the study, as determined by patient medical records. Glaucoma severity was determined based on the American Academy of Ophthalmology Preferred Practice Patterns guidelines. Multivariate logistic regression analysis was used to assess the relationship between adherence with follow-up visits and disease severity. After adjustment for the impact of potential confounding variables, subjects with severe glaucomatous disease were found to have been less adherent to their recommended follow-up than those patients with mild or moderate glaucomatous disease (adjusted OR 1.89, 95% CI 1.21-2.94; P = .01). Subjects who were on glaucoma medications were found to be less adherent to follow-up recommendations (adjusted OR 3.29, 95% CI 1.41-7.65, P = .01). Subjects with poor follow-up adherence were significantly more likely to have severe glaucomatous disease, suggesting that poor follow-up may contribute to disease worsening or, alternatively, those with more severe disease are less inclined to follow up at appropriate intervals. Published by Elsevier Inc.

  20. Longitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease

    PubMed Central

    Kash, John C.; Walters, Kathie-Anne; Kindrachuk, Jason; Baxter, David; Scherler, Kelsey; Janosko, Krisztina B.; Adams, Rick D.; Herbert, Andrew S.; James, Rebekah M.; Stonier, Spencer W.; Memoli, Matthew J.; Dye, John M.; Davey, Richard T.; Chertow, Daniel S.; Taubenberger, Jeffery K.

    2017-01-01

    The 2013–2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U.S. Food and Drug Administration–approved vaccines or therapies. We report a detailed study of host gene expression as measured by microarray in daily peripheral blood samples collected from a patient with severe Ebola virus disease. This individual was provided with supportive care without experimental therapies at the National Institutes of Health Clinical Center from before onset of critical illness to recovery. Pearson analysis of daily gene expression signatures revealed marked gene expression changes in peripheral blood leukocytes that correlated with changes in serum and peripheral blood leukocytes, viral load, antibody responses, coagulopathy, multiple organ dysfunction, and then recovery. This study revealed marked shifts in immune and antiviral responses that preceded changes in medical condition, indicating that clearance of replicating Ebola virus from peripheral blood leukocytes is likely important for systemic viral clearance. PMID:28404864

  1. Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia.

    PubMed

    Carlsson, Göran; Wahlin, Ylva-Britt; Johansson, Anders; Olsson, Anders; Eriksson, Torbjörn; Claesson, Rolf; Hänström, Lennart; Henter, Jan-Inge

    2006-04-01

    Patients with Kostmann syndrome (severe congenital neutropenia [SCN]) typically normalize their absolute neutrophil count (ANC) upon granulocyte colony-stimulating factor (G-CSF) therapy. However, although they no longer experience life-threatening bacterial infections, they frequently still have recurrent gingivitis and even severe periodontitis, often starting in early childhood. We studied the periodontal disease in the four surviving patients belonging to the family originally described by Kostmann. Their odontological records, x-rays, color photos, bacterial cultures, serum antibodies to oral bacteria, and histopathological examinations were reviewed. The data were also correlated to previous investigations on their antibacterial peptides and molecular biology. Three patients had periodontal disease, despite normal ANC and professional dental care, and had neutrophils deficient in antibacterial peptides. One of these patients also had a heterozygous mutation in the neutrophil elastase gene, had severe periodontal disease and overgrowth of the periodontal pathogen Actinobacillus actinomycetemcomitans in the dental flora, and 15 permanent teeth had been extracted by the age of 27. One bone marrow-transplanted patient had no periodontal disease. Normalized ANC levels are not sufficient to maintain normal oral health in SCN patients, and because neutrophils are important for first-line defense and innate immunity, the deficiency of the antibacterial peptide LL-37 probably explains their chronic periodontal disease. Professional dental care is still important for SCN patients, despite treatment with G-CSF and normal ANC levels. Whether antibacterial peptides play a role in the pathogenesis of periodontitis in other patients remains to be elucidated.

  2. Depressive symptomatology, quality of life and disease control among individuals with well-characterized severe asthma.

    PubMed

    Yonas, Michael A; Marsland, Anna L; Emeremni, Chetachi A; Moore, Charity G; Holguin, Fernando; Wenzel, Sally

    2013-10-01

    A thorough examination of the relationship of asthma severity and control with symptoms of depression is needed to identify groups of asthmatics at high risk for poor disease control outcomes. This study examines the relationship of symptoms of depression with severity and control in a well-characterized cohort of asthmatics and healthy controls. Depressive symptoms and quality of life were assessed using the Beck Depression Inventory. Disease control was measured by a composite index incorporating symptoms, activity limitation and rescue medication use. Individuals with asthma (n = 91) reported more symptoms of depression than controls (n = 36; p < 0.001). Those with severe asthma (n = 49) reported more symptoms of depression (p = 0.002) and poorer asthma control (p < 0.0001) than those with not severe asthma. Worse asthma control was associated with more depressive symptoms in severe (r = 0.46, p = 0.002) but not in not severe (r = 0.13, p = 0.40) asthmatics. The relationship of symptoms of depression among severe asthmatics was attenuated by disease control. Exploratory analyses identified specific disease symptom characteristics, as opposed to exacerbations, as associated with symptoms of depression. Among individuals with severe asthma, increased symptom burden is positively associated with risk for co-morbid depression. These findings point to a need for regular mood disorder screenings and treatment referrals among this group. Further research is warranted to examine whether treatment of comorbid depression improves treatment adherence and asthma-related quality of life.

  3. Using Image Processing to Determine Emphysema Severity

    NASA Astrophysics Data System (ADS)

    McKenzie, Alexander; Sadun, Alberto

    2010-10-01

    Currently X-rays and computerized tomography (CT) scans are used to detect emphysema, but other tests are required to accurately quantify the amount of lung that has been affected by the disease. These images clearly show if a patient has emphysema, but are unable by visual scan alone, to quantify the degree of the disease, as it presents as subtle, dark spots on the lung. Our goal is to use these CT scans to accurately diagnose and determine emphysema severity levels in patients. This will be accomplished by performing several different analyses of CT scan images of several patients representing a wide range of severity of the disease. In addition to analyzing the original CT data, this process will convert the data to one and two bit images and will then examine the deviation from a normal distribution curve to determine skewness. Our preliminary results show that this method of assessment appears to be more accurate and robust than the currently utilized methods, which involve looking at percentages of radiodensities in the air passages of the lung.

  4. 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

  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 (PM 2.5 ) reaching unprecedentedly high levels in many cities. Quantifying the detrimental effects on health and their costs derived from high PM 2.5 levels is crucial because of the unsolved challenges to mitigate air pollution in the following decades. Using the daily monitoring data on PM 2.5 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 PM 2.5 when the annual average daily PM 2.5 concentration was less than 50 μg m -3 ; while this ratio was doubled (around 2%) with the daily PM 2.5 concentration larger than 50 μg m -3 . Under severe air pollution (PM 2.5 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 PM 2.5 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. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Validation of a score tool for measurement of histological severity in juvenile dermatomyositis and association with clinical severity of disease

    PubMed Central

    Varsani, Hemlata; Charman, Susan C; Li, Charles K; Marie, Suely K N; Amato, Anthony A; Banwell, Brenda; Bove, Kevin E; Corse, Andrea M; Emslie-Smith, Alison M; Jacques, Thomas S; Lundberg, Ingrid E; Minetti, Carlo; Nennesmo, Inger; Rushing, Elisabeth J; Sallum, Adriana M E; Sewry, Caroline; Pilkington, Clarissa A; Holton, Janice L; Wedderburn, Lucy R

    2015-01-01

    Objectives To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity. Methods 55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers’ ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy. Results Inter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity. Conclusions The JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM. PMID:24064003

  7. [The severity of gestational diabetes mellitus affects microvascular dysfunction measured three years after pregnancy that may be related to increased oxidative stress].

    PubMed

    Horváth, Eszter Mária; Mágenheim, Rita; Domján, Beatrix Annamária; Ferencz, Viktória; Tänczer, Tímea; Szabó, Eszter; Benkő, Rita; Szabó, Csaba; Tabák, Ádám; Somogyi, Anikó

    2015-11-22

    Oxidative-nitrative stress and poly(ADP-ribose) polymerase activation observed in gestational diabetes may play role in the increased cardiovascular risk in later life. The present study aimed to examine the influence of the severity of previous gestational diabetes (insulin need) on vascular function three years after delivery. Furthermore, the authors investigated the relation of vascular function with oxidative-nitrative stress and poly(ADP-ribose) polymerase activation. Macrovascular function was measured by applanation tonometry; microvascular reactivity was assessed by provocation tests during Laser-Doppler flowmetry in 40 women who had gestational diabetes 3 years before the study. Oxidative-nitrative stress and poly(ADP-ribose) polymerase activity in blood components were determined by colorimetry and immunohistochemistry. Three years after insulin treated gestational diabetes impaired microvascular function and increased oxidative stress was observed compared to mild cases. The severity of previous gestational diabetes affects microvascular dysfunction that is accompanied by elevated oxidative stress. Nitrative stress and poly(ADP-ribose) polymerase activity correlates with certain vascular factors not related to the severity of the disease.

  8. The role of empowerment and quality of life in depression severity among unemployed people with affective disorders receiving mental healthcare.

    PubMed

    Johanson, Suzanne; Bejerholm, Ulrika

    2017-09-01

    Sick leave and unemployment are highly prevalent among people with affective disorders. Their depression severity is disabling and inversely related to having employment. No evidence-based vocational rehabilitation exists for this target group. Knowledge is therefore needed to understand the psychosocial factors that affect depression severity in order to develop new rehabilitation interventions. This study examined relationships between depression severity and empowerment, working life aspirations, occupational engagement, and quality of life in unemployed people with affective disorders receiving mental healthcare. In this cross-sectional study of 61 participants, instruments on psychosocial factors and questions on descriptive sociodemographic and clinical characteristics were administered. Descriptive, correlation, and regression statistics were applied. Correlation and regression analyses showed significant inverse relations between depression severity and empowerment and quality of life. The odds for more severe depression decreased with higher empowerment and quality of life. However, neither extent of engagement in daily life nor working life aspiration was related to depression severity. An empowerment approach and strategies, which support the quality of life, are needed in development of vocational rehabilitation interventions, and bridging of mental healthcare and vocational services. Implications for Rehabilitation Enhancing empowerment and quality life in the return to work process can decrease depression severity in unemployed people with affective disorder. There is a need to address work issues in addition to symptom reduction in primary and mental healthcare. Bridging the service and time gap between vocational rehabilitation and healthcare is recommended for mitigating long-term unemployment for people with affective disorders who want to work.

  9. Socio-demographic, health, and tinnitus related variables affecting tinnitus severity.

    PubMed

    Hoekstra, Carlijn E L; Wesdorp, Francina M; van Zanten, Gijsbert A

    2014-01-01

    Tinnitus is a highly prevalent symptom with potential severe morbidity. Fortunately, only a small proportion of the population experience problems due to their tinnitus in such a degree that it adversely affects their quality of life (clinically significant tinnitus). It is not known why these individuals develop more burden from tinnitus. It seems likely that the severity of tinnitus can be influenced by different factors, such as socio-demographic or tinnitus characteristics or additional health complaints. It remains unclear from the current literature as to what are the main independent variables that have a bearing on tinnitus severity. This study addresses this problem by investigating variables previously described in the literature as well as additional variables. The aim of this study is to identify socio-demographic, health, and tinnitus variables that independently relate to tinnitus severity the most. This is a retrospective cohort study performed at the Tinnitus Care Group of the University Medical Center, Utrecht, in 309 consecutively seen chronic tinnitus patients. At this care group, patients are examined according to a structured diagnostic protocol, including history-taking by an otorhinolaryngologist and audiologist, physical examination, and audiometry. Based on results from previous research and theoretical considerations, a subset of data acquired through this diagnostic protocol were selected and used in this study. Univariate and multivariate correlations with tinnitus severity were investigated for 28 socio-demographic, health, and tinnitus variables. Tinnitus severity was measured with the Tinnitus Questionnaire (TQ) and the Tinnitus Handicap Inventory (THI). Eighteen variables related univariately with the TQ and 16 variables related univariately with the THI. Among these, 14 variables related univariately with both the TQ and the THI. Multivariate analyses showed three variables with an independent significant effect on both the TQ and

  10. Semantic trouble sources and their repair in conversations affected by Parkinson's disease

    PubMed Central

    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 problems become manifest in everyday conversations or how conversation partners handle such problems. Aims To describe the pragmatic problems related to the use of words that occur in everyday conversational interaction in dyads including an individual with Parkinson's disease, and to explore how interactants in conversation handle the problems to re-establish mutual understanding. Methods & Procedures Twelve video-recorded everyday conversations involving three couples where one of the individuals had Parkinson's disease were included in the study. All instances of other-initiated repair following a contribution from the people with Parkinson's disease were analysed. Those instances involving a trouble source relating to the use of words were analysed with a qualitative interaction analysis based on the principles of conversation analysis. Outcomes & Results In 70% of the instances of other-initiated repair the trouble source could be related to the semantic content produced by the individual with Parkinson's disease. The problematic contributions were typically characterized by more or less explicit symptoms of word search or use of atypical wording. The conversation partners completed the repair work collaboratively, but typically the non-impaired individual made a rephrasing or provided a suggestion for what the intended meaning had been. Conclusions & Implications In clinical work with people with Parkinson's disease and their conversation partners it is important to establish what type of trouble sources occur in conversations in a specific dyad. It may often be necessary to look beyond intelligibility and into aspects of pragmatics

  11. Novel LAMP2 mutations in Chinese patients with Danon disease cause varying degrees of clinical severity.

    PubMed

    Luo, Su-shan; Xi, Jian-ying; Cai, Shuang; Zhao, Chong-bo; Lu, Jia-hong; Zhu, Wen-hua; Lin, Jie; Qiao, Kai; Wang, Yin; Ye, Zhu-rong

    2014-01-01

    Danon disease is an Xlinked dominant lysosomal glycogen storage disorder characterized by cardiomyopathy, skeletal myopathy, and mental retardation. This study described two Chinese cases of Danon disease in order to broaden the phenotypic and genetic spectrum. Clinical data were collected and LAMP2 mutations were analyzed. Patient A had fluctuating limb weakness during 6 months follow-up and was diagnosed with drug-induced myopathy due to anti-hepatitis B therapy with lamivudine. However, the first muscle biopsy with large cytoplasmic vacuoles confused the diagnosis and led to the second biopsy that allowed for the final diagnosis. Patient B had severe cardiac disturbances leading to sudden death. Molecularly, patient A harbored a synonymous mutation adjacent to the exon 6-intron 6 junction; mRNA analysis provided evidence that totally abolished the donor site and caused skipping of exon 6. Patient B harbored a frame-shift deletion mutation in exon 3 (c.396delA) leading to a truncated protein. To our knowledge, this is the first report of Danon disease caused by a synonymous exon mutation that affected mRNA splicing, which indicates that a synonymous substitution may not be silent when it is in the exon sequences close to the splice sites. It is also the first description of Danon disease clinically presenting as druginduced myopathy at onset; the pathological changes might be the key point for making a differential diagnosis. *These two authors contributed equally to this work.

  12. Armillaria mellea and mortality of beech affected by beech bark disease

    Treesearch

    Philip M. Wargo

    1983-01-01

    The role of Armillaria mellea in the mortality of beech trees affected by beech bark disease was determined by excavating root systems of beech trees infested by beech scale, Cryptococcus fagisuga, or also infected by the bark fungus, Nectria coccinea var. faginata. Only trees infected by

  13. Automated gait and balance parameters diagnose and correlate with severity in Parkinson disease.

    PubMed

    Dewey, D Campbell; Miocinovic, Svjetlana; Bernstein, Ira; Khemani, Pravin; Dewey, Richard B; Querry, Ross; Chitnis, Shilpa; Dewey, Richard B

    2014-10-15

    To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM(®) Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R(2) ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Automated Gait and Balance Parameters Diagnose and Correlate with Severity in Parkinson Disease

    PubMed Central

    Dewey, Daniel C.; Miocinovic, Svjetlana; Bernstein, Ira; Khemani, Pravin; Dewey, Richard B.; Querry, Ross; Chitnis, Shilpa; Dewey, Richard B.

    2014-01-01

    Objective To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. Methods Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM® Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. Results 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R2 ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. Interpretation Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program. PMID:25082782

  15. Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy

    PubMed Central

    Janz, Philipp; Schwaderlapp, Niels; Heining, Katharina; Häussler, Ute; Korvink, Jan G; von Elverfeldt, Dominik; Hennig, Jürgen; Egert, Ulrich

    2017-01-01

    Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy in adults and is often refractory to medication. So far, resection of the epileptogenic focus represents the only curative therapy. It is unknown whether pathological processes preceding epilepsy onset are indicators of later disease severity. Using longitudinal multi-modal MRI, we monitored hippocampal injury and tissue reorganization during epileptogenesis in a mouse mTLE model. The prognostic value of MRI biomarkers was assessed by retrospective correlations with pathological hallmarks Here, we show for the first time that the extent of early hippocampal neurodegeneration and progressive microstructural changes in the dentate gyrus translate to the severity of hippocampal sclerosis and seizure burden in chronic epilepsy. Moreover, we demonstrate that structural MRI biomarkers reflect the extent of sclerosis in human hippocampi. Our findings may allow an early prognosis of disease severity in mTLE before its first clinical manifestations, thus expanding the therapeutic window. DOI: http://dx.doi.org/10.7554/eLife.25742.001 PMID:28746029

  16. 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…

  17. Correlation between disease severity and brain electric LORETA tomography in Alzheimer's disease.

    PubMed

    Gianotti, Lorena R R; Künig, Gabriella; Lehmann, Dietrich; Faber, Pascal L; Pascual-Marqui, Roberto D; Kochi, Kieko; Schreiter-Gasser, Ursula

    2007-01-01

    To compare EEG power spectra and LORETA-computed intracortical activity between Alzheimer's disease (AD) patients and healthy controls, and to correlate the results with cognitive performance in the AD group. Nineteen channel resting EEG was recorded in 21 mild to moderate AD patients and in 23 controls. Power spectra and intracortical LORETA tomography were computed in seven frequency bands and compared between groups. In the AD patients, the EEG results were correlated with cognitive performance (Mini Mental State Examination, MMSE). AD patients showed increased power in EEG delta and theta frequency bands, and decreased power in alpha2, beta1, beta2 and beta3. LORETA specified that increases and decreases of power affected different cortical areas while largely sparing prefrontal cortex. Delta power correlated negatively and alpha1 power positively with the AD patients' MMSE scores; LORETA tomography localized these correlations in left temporo-parietal cortex. The non-invasive EEG method of LORETA localized pathological cortical activity in our mild to moderate AD patients in agreement with the literature, and yielded striking correlations between EEG delta and alpha1 activity and MMSE scores in left temporo-parietal cortex. The present data support the hypothesis of an asymmetrical progression of the Alzheimer's disease.

  18. The airway microbiome in patients with severe asthma: Associations with disease features and severity.

    PubMed

    Huang, Yvonne J; Nariya, Snehal; Harris, Jeffrey M; Lynch, Susan V; Choy, David F; Arron, Joseph R; Boushey, Homer

    2015-10-01

    Asthma is heterogeneous, and airway dysbiosis is associated with clinical features in patients with mild-to-moderate asthma. Whether similar relationships exist among patients with severe asthma is unknown. We sought to evaluate relationships between the bronchial microbiome and features of severe asthma. Bronchial brushings from 40 participants in the Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma (BOBCAT) study were evaluated by using 16S ribosomal RNA-based methods. Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects. Secondarily, bacterial compositional profiles were compared between patients with severe asthma and previously studied healthy control subjects (n = 7) and patients with mild-to-moderate asthma (n = 41). In patients with severe asthma, bronchial bacterial composition was associated with several disease-related features, including body mass index (P < .05, Bray-Curtis distance-based permutational multivariate analysis of variance; PERMANOVA), changes in Asthma Control Questionnaire (ACQ) scores (P < .01), sputum total leukocyte values (P = .06), and bronchial biopsy eosinophil values (per square millimeter, P = .07). Bacterial communities associated with worsening ACQ scores and sputum total leukocyte values (predominantly Proteobacteria) differed markedly from those associated with body mass index (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ scores and bronchial epithelial gene expression of FK506 binding protein (FKBP5), an indicator of steroid responsiveness, correlated with Actinobacteria. Mostly negative correlations were observed between biopsy eosinophil values and Proteobacteria. No taxa were associated with a TH2-related epithelial gene expression signature, but expression of TH17-related genes was associated with Proteobacteria. Patients with severe asthma compared with healthy control subjects or patients with mild

  19. Rheumatoid arthritis-related interstitial lung disease (RA-ILD): methotrexate and the severity of lung disease are associated to prognosis.

    PubMed

    Rojas-Serrano, Jorge; Herrera-Bringas, Denisse; Pérez-Román, Diana I; Pérez-Dorame, Renzo; Mateos-Toledo, Heidegger; Mejía, Mayra

    2017-07-01

    Interstitial lung disease (ILD) is a severe rheumatoid arthritis (RA) manifestation. The worst survival has been associated with usual interstitial pneumonia (UIP) definitive pattern in high-resolution chest tomography (HRCT) scans. Moreover, the use of methotrexate in RA-ILD is controversial. Our aim was to evaluate prognostic factors including methotrexate in an RA-ILD cohort and their association with survival. RA-ILD patients referred for medical evaluation and treatment at a single center were included. At the baseline, pulmonary function tests were carried out and a HRCT was obtained. A radiologist evaluated the ILD tomographic pattern and the extent of lung disease. Patients were considered as receiving methotrexate therapy if this drug was specifically prescribed for the treatment of RA-ILD at the beginning of follow up. Seventy-eight patients were included. UIP definite pattern in HRCT was not associated to worse survival. Variables associated with mortality reflected the severity of lung disease. Treatment with methotrexate was associated with survival (HR 0.13, 95% CI 0.02-0.64); older patients had worse prognosis (HR 1.04, 95% CI 1.003-1.09). After adjusting for confounding variables, methotrexate was strongly associated with survival. Methotrexate treatment during follow up was associated with survival. The severity of lung disease and not the tomographic pattern is associated with mortality; older patients had worse prognosis.

  20. Sycamore diseases

    Treesearch

    F. I. McCracken

    1989-01-01

    The canker stain disease, one of several fungi that cause cankers of sycamore, can cause serious loss of sycamores in natural stands, plantations, and urban areas. As many as 35 percent of the trees in some stands may be diseased. Affected trees develop thin crowns, twig dieback, small leaves and epicormic branches. The narrow, elongate, bark covered, flat, spiraling...

  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. Colour vision impairment is associated with disease severity in multiple sclerosis.

    PubMed

    Martínez-Lapiscina, Elena H; Ortiz-Pérez, Santiago; Fraga-Pumar, Elena; Martínez-Heras, Eloy; Gabilondo, Iñigo; Llufriu, Sara; Bullich, Santiago; Figueras, Marc; Saiz, Albert; Sánchez-Dalmau, Bernardo; Villoslada, Pablo

    2014-08-01

    Colour vision assessment correlates with damage of the visual pathway and might be informative of overall brain damage in multiple sclerosis (MS). The objective of this paper is to investigate the association between impaired colour vision and disease severity. We performed neurological and ophthalmic examinations, as well as magnetic resonance imaging (MRI) and optical coherence tomography (OCT) analyses, on 108 MS patients, both at baseline and after a follow-up of one year. Colour vision was evaluated by Hardy, Rand and Rittler plates. Dyschromatopsia was defined if colour vision was impaired in either eye, except for participants with optic neuritis (ON), for whom only the unaffected eye was considered. We used general linear models adjusted for sex, age, disease duration and MS treatment for comparing presence of dyschromatopsia and disease severity. Impaired colour vision in non-ON eyes was detected in 21 out of 108 patients at baseline. At baseline, patients with dyschromatopsia had lower Multiple Sclerosis Functional Composite (MSFC) scores and Brief Repeatable Battery-Neuropsychology executive function scores than those participants with normal colour vision. In addition, these patients had thinner retinal nerve fiber layer (RNFL), and smaller macular volume, normalized brain volume and normalized gray matter volume (NGMV) at baseline. Moreover, participants with incident dyschromatopsia after one-year follow-up had a greater disability measured by the Expanded Disability Status Scale and MSFC-20 and a greater decrease in NGMV than participants with normal colour vision. Colour vision impairment is associated with greater MS severity. © The Author(s) 2013.

  3. 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. © 2015 The British Psychological Society.

  4. Unveiling relevant non-motor Parkinson's disease severity symptoms using a machine learning approach.

    PubMed

    Armañanzas, Rubén; Bielza, Concha; Chaudhuri, Kallol Ray; Martinez-Martin, Pablo; Larrañaga, Pedro

    2013-07-01

    Is it possible to predict the severity staging of a Parkinson's disease (PD) patient using scores of non-motor symptoms? This is the kickoff question for a machine learning approach to classify two widely known PD severity indexes using individual tests from a broad set of non-motor PD clinical scales only. The Hoehn & Yahr index and clinical impression of severity index are global measures of PD severity. They constitute the labels to be assigned in two supervised classification problems using only non-motor symptom tests as predictor variables. Such predictors come from a wide range of PD symptoms, such as cognitive impairment, psychiatric complications, autonomic dysfunction or sleep disturbance. The classification was coupled with a feature subset selection task using an advanced evolutionary algorithm, namely an estimation of distribution algorithm. Results show how five different classification paradigms using a wrapper feature selection scheme are capable of predicting each of the class variables with estimated accuracy in the range of 72-92%. In addition, classification into the main three severity categories (mild, moderate and severe) was split into dichotomic problems where binary classifiers perform better and select different subsets of non-motor symptoms. The number of jointly selected symptoms throughout the whole process was low, suggesting a link between the selected non-motor symptoms and the general severity of the disease. Quantitative results are discussed from a medical point of view, reflecting a clear translation to the clinical manifestations of PD. Moreover, results include a brief panel of non-motor symptoms that could help clinical practitioners to identify patients who are at different stages of the disease from a limited set of symptoms, such as hallucinations, fainting, inability to control body sphincters or believing in unlikely facts. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. On the significance of electroconvulsive therapy in the treatment of severe mental diseases.

    PubMed

    Grözinger, Michael; Smith, Elke Stefanie; Conca, Andreas

    2015-04-01

    Quite a few patients with severe mental diseases do not respond sufficiently to psychopharmacology and psychotherapy. For some of these, electroconvulsive therapy (ECT) offers a promising alternative. Erroneously, the method is being perceived as old fashioned by the lay public, but also by many doctors. Therefore, this overview aims at all colleagues who in their role as multipliers, referring physicians or ECT specialists can reduce the likelihood of mental disease to become chronic. During the last decades, numerous international medical societies including the Austrian and the German Association for Psychiatry (ÖGPP and DGPPN) have pointed to the importance of ECT as a modern medical intervention. Our overview is based on these guidelines and statements. Additionally selective literature searches have been conducted concerning some key aspects. Due to its excellent efficacy, ECT is an important option in the treatment of severe mental disease. Technological innovations and continued development in the psychiatric environment determined the evolution from the electroshock of the 1930s to the ECT of today. This process led to reduced side effects and a stronger patient-oriented praxis. ECT is a modern, highly effective and safe treatment of severe mental diseases with comparatively few side effects. The method should not be used as a last resort but in an evidence-based way. Patients should be informed timely and adequately about the therapeutic option.

  6. Longitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease.

    PubMed

    Kash, John C; Walters, Kathie-Anne; Kindrachuk, Jason; Baxter, David; Scherler, Kelsey; Janosko, Krisztina B; Adams, Rick D; Herbert, Andrew S; James, Rebekah M; Stonier, Spencer W; Memoli, Matthew J; Dye, John M; Davey, Richard T; Chertow, Daniel S; Taubenberger, Jeffery K

    2017-04-12

    The 2013-2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U.S. Food and Drug Administration-approved vaccines or therapies. We report a detailed study of host gene expression as measured by microarray in daily peripheral blood samples collected from a patient with severe Ebola virus disease. This individual was provided with supportive care without experimental therapies at the National Institutes of Health Clinical Center from before onset of critical illness to recovery. Pearson analysis of daily gene expression signatures revealed marked gene expression changes in peripheral blood leukocytes that correlated with changes in serum and peripheral blood leukocytes, viral load, antibody responses, coagulopathy, multiple organ dysfunction, and then recovery. This study revealed marked shifts in immune and antiviral responses that preceded changes in medical condition, indicating that clearance of replicating Ebola virus from peripheral blood leukocytes is likely important for systemic viral clearance. Copyright © 2017, American Association for the Advancement of Science.

  7. Percutaneous Coronary Intervention in Severely Calcified Unprotected Left Main Coronary Artery Disease: Initial Experience With Orbital Atherectomy.

    PubMed

    Lee, Michael S; Shlofmitz, Evan; Kaplan, Barry; Shlofmitz, Richard

    2016-04-01

    We report the clinical outcomes of patients who underwent percutaneous coronary intervention (PCI) with orbital atherectomy for severely calcified unprotected left main coronary artery (ULMCA) disease. Although surgical revascularization is the gold standard for patients with ULMCA disease, not all patients are candidates for this. PCI is increasingly used to treat complex coronary artery disease, including ULMCA disease. The presence of severely calcified lesions increases the complexity of PCI. Orbital atherectomy can be used to facilitate stent delivery and expansion in severely calcified lesions. The clinical outcomes of patients treated with orbital atherectomy for severely calcified ULMCA disease have not been reported. From May 2014 to July 2015, a total of 14 patients who underwent PCI with orbital atherectomy for ULMCA disease were retrospectively evaluated. The primary endpoint was major cardiac and cerebrovascular event (cardiac death, myocardial infarction, stroke, and target-lesion revascularization) at 30 days. The mean age was 78.2 ± 5.8 years. The mean ejection fraction was 41.8 ± 19.8%. Distal bifurcation disease was present in 9 of 14 patients. Procedural success was achieved in all 14 patients. The 30-day major adverse cardiac and cerebrovascular event rate was 0%. One patient had coronary dissection that was successfully treated with stenting. No patient had perforation, slow flow, or thrombosis. Orbital atherectomy in patients with severely calcified ULMCA disease is feasible, even in high-risk patients who were considered poor surgical candidates. Randomized trials are needed to determine the role of orbital atherectomy in ULMCA disease.

  8. Impact of the NAP-1 strain on disease severity, mortality, and recurrence of healthcare-associated Clostridium difficile infection.

    PubMed

    Bauer, Karri A; Johnston, Jessica E W; Wenzler, Eric; Goff, Debra A; Cook, Charles H; Balada-Llasat, Joan-Miquel; Pancholi, Preeti; Mangino, Julie E

    2017-12-01

    Studies are conflicting regarding the association of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain in Clostridium difficile infection (CDI) and outcomes. We evaluated the association of NAP1 with healthcare-associated CDI disease severity, mortality, and recurrence at our academic medical center. Healthcare-associated CDI cases were identified from November 1, 2011 through January 31, 2013. Multivariable regression models were used to evaluate the associations of NAP1 with severe disease (based on the Hines VA severity score index), mortality, and recurrence. Among 5424 stool specimens submitted to the Clinical Microbiology Laboratory, 292 (5.4%) were positive for C. difficile by polymerase chain reaction (PCR) on or after hospital day 4; 70 (24%) of these specimens also tested positive for NAP1. During the study period, 247 (85%) patients had non-severe disease and 45 (15%) patients had severe disease. Among patients with non-severe disease, 65 (26%) had NAP1 and among patients with severe disease, 5 (11%) had NAP1. After controlling for potential confounders, NAP1 was not associated with an increased likelihood of severe disease (adjusted odds ratio [aOR] = 0.35; 95% confidence interval [CI], 0.13-0.93), in-hospital mortality (aOR = 1.02; 95% CI, 0.53-1.96), or recurrence (aOR = 1.16, 95% CI, 0.36-3.77). The NAP1 strain did not increase disease severity, mortality, or recurrence in this study, although the incidence of NAP1-positive healthcare associated-CDI was low. The role of strain typing in outcomes and treatment selection in patients with healthcare-associated CDI remains uncertain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Diverting Ileostomy for the Treatment of Severe, Refractory, Pediatric Inflammatory Bowel Disease.

    PubMed

    Maxwell, Elizabeth C; Dawany, Noor; Baldassano, Robert N; Mamula, Petar; Mattei, Peter; Albenberg, Lindsey; Kelsen, Judith R

    2017-09-01

    Diverting ileostomy is used as a temporizing therapy in patients with perianal Crohn disease; however, little data exist regarding its use for colonic disease. The primary aim of the present study was to determine the role of diversion in severe refractory colonic inflammatory bowel disease (IBD) in a pediatric population. Retrospective study of patients who underwent diverting ileostomy at The Children's Hospital of Philadelphia from 2000 to 2014 for the management of severe, refractory colonic IBD. Clinical variables were compared in the 1 year before ileostomy and 1 year after diversion. Surgical and disease outcomes including changes in diagnosis were reviewed through 2015. Twenty-four patients underwent diverting ileostomy for refractory colonic disease. Initial diagnoses were Crohn disease in 10 (42%), ulcerative colitis in 1 (4%), and IBD-unclassified in 13 patients (54%). Comparing data before and after surgery, there were statistically significant improvements in height and weight velocities, height velocity z score, blood transfusion requirement, hemoglobin, and hospitalization rates. Chronic steroid use decreased from 71% to 22%. At the conclusion of the study, 10 patients had undergone subsequent colectomy, 7 had successful bowel reanastomosis, and 7 remain diverted. Seven patients (29%) had a change in diagnosis. There were 13 surgical complications in 7 subjects, including prolapse reduction, stoma revision, and resection of ischemic bowel. In pediatric patients with refractory colonic IBD, diverting ileostomy can be a successful intervention to induce clinical stability. Importantly, diversion is a steroid-sparing therapy and allows additional time to clarify the diagnosis.

  10. The Association Between Bathing Habits and Severity of Atopic Dermatitis in Children.

    PubMed

    Koutroulis, Ioannis; Pyle, Tia; Kopylov, David; Little, Anthony; Gaughan, John; Kratimenos, Panagiotis

    2016-02-01

    Atopic dermatitis is an inflammatory skin disease that frequently affects children. The current recommendations on management using lifestyle modification are highly variable, leading to confusion and uncertainty among patients. To determine current bathing behaviors and the subsequent impact on disease severity. This was an observational cross-sectional study conducted at an urban pediatric emergency department. Parents were asked to fill out a questionnaire concerning the patient's bathing habits. The results were correlated with the atopic dermatitis severity determined by the SCORAD (SCORing Atopic Dermatitis) tool. No difference between variables was found to be significant for bathing frequency, time spent bathing, or use of moisturizers. Multivariate analysis showed that atopic dermatitis severity increased with age greater than 2 years (P = .0004) and with greater bathing duration (P = .001). Atopic dermatitis severity may be associated with a longer duration of bathing. The frequency of bathing does not appear to affect atopic dermatitis severity. © The Author(s) 2015.

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

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

    Duprez, Frederic, E-mail: frederic.duprez@ugent.be; Madani, Indira; Morbee, Lieve

    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 weremore » 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

  12. Medical risk factors for severe West Nile Virus disease, United States, 2008-2010.

    PubMed

    Lindsey, Nicole P; Staples, J Erin; Lehman, Jennifer A; Fischer, Marc

    2012-07-01

    We conducted enhanced surveillance to identify medical risk factors for severe illness (i.e., hospitalization or death) and neuroinvasive disease (i.e., encephalitis or meningitis) among all West Nile virus disease cases reported from selected states from 2008 to 2010. Of the 1,090 case-patients included in the analysis, 708 (65%) case-patients were hospitalized, 641 (59%) case-patients had neuroinvasive disease, and 55 (5%) case-patients died. Chronic renal disease (adjusted odds ratio [aOR] = 4.1; 95% confidence interval [CI] = 1.4-12.1), history of cancer (aOR = 3.7; 95% CI = 1.8-7.5), history of alcohol abuse (aOR = 3.0; 95% CI = 1.3-6.7), diabetes (aOR = 2.2; 95% CI = 1.4-3.4), and hypertension (aOR = 1.5; 95% CI = 1.1-2.1) were independently associated with severe illness on multivariable analysis. Although the same medical conditions were independently associated with encephalitis, only hypertension was associated with meningitis. The only condition independently associated with death was immune suppression. Prevention messages should be targeted to persons with these conditions.

  13. Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease

    PubMed Central

    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.

    2011-01-01

    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. PMID:21633409

  14. Distinct patterns of brain activity evoked by histamine-induced itch reveal an association with itch intensity and disease severity in atopic dermatitis

    PubMed Central

    Ishiuji, Y.; Coghill, R.C.; Patel, T.S.; Oshiro, Y.; Kraft, R.A.; Yosipovitch, G.

    2009-01-01

    Summary Background Little is known about brain mechanisms supporting the experience of chronic puritus in disease states. Objectives To examine the difference in brain processing of histamine-induced itch in patients with active atopic dermatitis (AD) vs. healthy controls with the emerging technique of functional magnetic resonance imaging (fMRI) using arterial spin labelling (ASL). Methods Itch was induced with histamine iontophoresis in eight patients with AD and seven healthy subjects. Results We found significant differences in brain processing of histamine-induced itch between patients with AD and healthy subjects. Patients with AD exhibited bilateral activation of the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), retrosplenial cingulate cortex and dorsolateral prefrontal cortex (DLPFC) as well as contralateral activation of the caudate nucleus and putamen. In contrast, healthy subjects activated the primary motor cortex, primary somatosensory cortex and superior parietal lobe. The PCC and precuneus exhibited significantly greater activity in patients vs. healthy subjects. A significant correlation between percentage changes of brain activation was noted in the activation of the ACC and contralateral insula and histamine-induced itch intensity as well as disease severity in patients with AD. In addition, an association was noted between DLPFC activity and disease severity. Conclusions Our results demonstrate that ASL fMRI is a promising technique to assess brain activity in chronic itch. Brain activity of acute itch in AD seems to differ from that in healthy subjects. Moreover, the activity in cortical areas involved in affect and emotion correlated to measures of disease severity. PMID:19663870

  15. Granulo-monocyto apheresis is more effective in mild ulcerative colitis than in moderate to severe disease

    PubMed Central

    De Cassan, Chiara; Savarino, Edoardo; Marson, Piero; Tison, Tiziana; Hatem, Giorgia; Sturniolo, Giacomo Carlo; D’Incà, Renata

    2014-01-01

    AIM: To evaluate whether the effectiveness of Granulo-monocyto apheresis (GMA), a technique that consists of the extracorporeal removal of granulocytes and monocytes from the peripheral blood, might vary according to the severity of ulcerative colitis (UC) in patients with mild to moderate-severe disease UC activity. METHODS: We retrospectively reviewed prospectively collected data of patients undergoing GMA at our inflammatory bowel disease centre who had at least a 6 mo of follow-up. The demographics, clinical and laboratory data were extracted from the patients’ charts and electronic records. The severity of UC was scored according to the Modified Truelove Witts Severity Index (MTWSI). A clinical response was defined as a decrease from baseline of ≥ 2 points or a value of MTWSI ≤ 2 points. RESULTS: A total of 41 (24 males/17 females; mean age 47 years) patients were included in the study. After GMA cycle completion, 21/28 (75%) of mild UC patients showed a clinical response compared with 7/13 (54%) of patients with moderate to severe disease (P = 0.27). At 6-mo, 14/28 (50%) of the mild UC patients maintained a clinical response compared with 2/13 (15%) of the patients with moderate to severe disease (P = 0.04). After the GMA cycle completion and during the 6-mo follow up period, 13/16 (81%) and 9/16 (56%) of mild UC patients with intolerance, resistance and contraindications to immunosuppressants and/or biologics showed a clinical response compared with 2/6 (33%) and 0/6 (0%) of patients with moderate to severe disease activity with these characteristics (P = 0.05 and P = 0.04, respectively). CONCLUSION: Patients with mild UC benefit from GMA more than patients with moderate to severe disease in the short-term period. GMA should be considered a valid therapeutic option in cases of contraindications to immunosuppressants, corticosteroids and/or biologics. PMID:25493030

  16. Mesenchymal Stem Cell-Conditioned Medium Reduces Disease Severity and Immune Responses in Inflammatory Arthritis.

    PubMed

    Kay, Alasdair G; Long, Grace; Tyler, George; Stefan, Andrei; Broadfoot, Stephen J; Piccinini, Anna M; Middleton, Jim; Kehoe, Oksana

    2017-12-21

    We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis.

  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. [Cost relation between severity of Alzheimer's disease and cognitive and functional impairment].

    PubMed

    López-Pousa, Secundino; Garre-Olmo, Josep; Turon-Estrada, Antoni; Hernández, Francisco; Expósito, Inmaculada; Lozano-Gallego, Manoli; Hernández-Ferrándiz, Marta; Gelada-Batlle, Esther; Pericot-Nierga, Imma; Vilalta-Franch, Joan

    2004-05-29

    This study aims to identify the relationship between costs of medical and social attention in patients with dementia of Alzheimer disease (AD) type and clinical and sociodemographic data of patients and their caregivers. It was an analytic observational study in a cohort of patients diagnosed with Alzheimer's disease who received ambulatory attention. Information about the use of health-related resources was collected and costs were estimated from a societal perspective. Indirect costs were calculated using a replacement cost approach. Patients and caregivers were examined with the Mini-Mental State Examination (MMSE), the Rapid Disability Rating Scale (RDRS-2), the Neuropsychiatric Inventory (NPI), the Burden Interview (BI) and the Resource Utilization in Dementia (RUD). Patients were grouped taking into account the score obtained in the MMSE. A cohort of 417 patients, mean age (SD) 75.2 (6.6) years, 71% females, was studied. Disease severity levels were distributed as follows: MMSE, 26% for MMSE > 19, 66% for MMSE = 19-11, and 8% for MMSE < 11. 69% of caregivers were women, with a mean age of 57.1 (15.8) years. The cost per patient and per month was estimated to be 419.3 Euro for MMSE > 19, 641.9 Euro for MMSE = 19-11, and 1150.6 Euro for MMSE < 11. The societal cost of AD increases dramatically with increasing disease severity. Caregiver burden and sex as well as the marital status of patients are associated with the cost of the disease.

  19. Critical Role of Airway Macrophages in Modulating Disease Severity during Influenza Virus Infection of Mice ▿

    PubMed Central

    Tate, Michelle D.; Pickett, Danielle L.; van Rooijen, Nico; Brooks, Andrew G.; Reading, Patrick C.

    2010-01-01

    Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways, leading to severe airway inflammation, pulmonary edema, and vascular leakage, indicative of lung injury. Thymic atrophy, lymphopenia, and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice. PMID:20504924

  20. Microbiome analysis of a disease affecting the deep-sea sponge Geodia barretti.

    PubMed

    Luter, Heidi M; Bannister, Raymond J; Whalan, Steve; Kutti, Tina; Pineda, Mari-Carmen; Webster, Nicole S

    2017-05-24

    Reports of sponge disease are becoming increasingly frequent, although almost all instances involve shallow-water, tropical species. Here, we describe the first disease affecting the deep-water sponge, Geodia barretti. The disease is characterised by brown/black discolouration of the sponge tissue, extensive levels of tissue disintegration and increased levels of fouling. Disease prevalence was quantified using video survey transects conducted between 100 and 220 meters in Korsfjorden, Norway and the microbial communities of healthy and diseased sponges were compared using 16S rRNA gene sequencing. Highly divergent community profiles were evident between the different health states; with distinct community shifts involving higher relative abundances of Bacteroidetes, Firmicutes and Deltaproteobacteria in diseased individuals. In addition, three Operational Taxonomic Units (OTUs) were exclusively present in diseased individuals and were shared between the disease lesions and the apparently healthy tissue of diseased individuals, suggesting a non-localised infection or dysbiosis. Genomic analysis of the G. barretti microbiome combined with experimental work to assess the mechanisms of infection will further elucidate the role of microorganisms in the disease. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. What predicts depression in cardiac patients: sociodemographic factors, disease severity or theoretical vulnerabilities?

    PubMed

    Doyle, F; McGee, H M; Conroy, R M; Delaney, M

    2011-05-01

    Depression is associated with increased cardiovascular risk in acute coronary syndrome (ACS) patients, but some argue that elevated depression is actually a marker of cardiovascular disease severity. Therefore, disease indices should better predict depression than established theoretical causes of depression (interpersonal life events, reinforcing events, cognitive distortions, type D personality). However, little theory-based research has been conducted in this area. In a cross-sectional design, ACS patients (n = 336) completed questionnaires assessing depression and psychosocial vulnerabilities. Nested logistic regression assessed the relative contribution of demographic or vulnerability factors, or disease indices or vulnerabilities to depression. In multivariate analysis, all vulnerabilities were independent significant predictors of depression (scoring above threshold on any scale, 48%). Demographic variables accounted for <1% of the variance of depression status, with vulnerabilities accounting for significantly more (pseudo R² = 0.16, χ²(change) = 150.9, df = 4, p < 0.001). Disease indices accounted for 7% of the variance in depression (pseudo R² = 0.07, χ² = 137.9, p < 0.001). However, adding the vulnerabilities increased the overall variance explained to 22% (pseudo R² = 0.22, χ² = 58.6, df = 4, p < 0.001). Theoretical vulnerabilities predicted depression status better than did either demographic or disease indices. The presence of these proximal causes of depression suggests that depression in ACS patients is not simply a result of cardiovascular disease severity.

  2. A Q-backpropagated time delay neural network for diagnosing severity of gait disturbances in Parkinson's disease.

    PubMed

    Nancy Jane, Y; Khanna Nehemiah, H; Arputharaj, Kannan

    2016-04-01

    Parkinson's disease (PD) is a movement disorder that affects the patient's nervous system and health-care applications mostly uses wearable sensors to collect these data. Since these sensors generate time stamped data, analyzing gait disturbances in PD becomes challenging task. The objective of this paper is to develop an effective clinical decision-making system (CDMS) that aids the physician in diagnosing the severity of gait disturbances in PD affected patients. This paper presents a Q-backpropagated time delay neural network (Q-BTDNN) classifier that builds a temporal classification model, which performs the task of classification and prediction in CDMS. The proposed Q-learning induced backpropagation (Q-BP) training algorithm trains the Q-BTDNN by generating a reinforced error signal. The network's weights are adjusted through backpropagating the generated error signal. For experimentation, the proposed work uses a PD gait database, which contains gait measures collected through wearable sensors from three different PD research studies. The experimental result proves the efficiency of Q-BP in terms of its improved classification accuracy of 91.49%, 92.19% and 90.91% with three datasets accordingly compared to other neural network training algorithms. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Streptococcus mitis Strains Causing Severe Clinical Disease in Cancer Patients

    PubMed Central

    Sahasrabhojane, Pranoti; Saldana, Miguel; Yao, Hui; Su, Xiaoping; Horstmann, Nicola; Thompson, Erika; Flores, Anthony R.

    2014-01-01

    The genetically diverse viridans group streptococci (VGS) are increasingly recognized as the cause of a variety of human diseases. We used a recently developed multilocus sequence analysis scheme to define the species of 118 unique VGS strains causing bacteremia in patients with cancer; Streptococcus mitis (68 patients) and S. oralis (22 patients) were the most frequently identified strains. Compared with patients infected with non–S. mitis strains, patients infected with S. mitis strains were more likely to have moderate or severe clinical disease (e.g., VGS shock syndrome). Combined with the sequence data, whole-genome analyses showed that S. mitis strains may more precisely be considered as >2 species. Furthermore, we found that multiple S. mitis strains induced disease in neutropenic mice in a dose-dependent fashion. Our data define the prominent clinical effect of the group of organisms currently classified as S. mitis and lay the groundwork for increased understanding of this understudied pathogen. PMID:24750901

  4. 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

  5. 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. © 2013 John Wiley & Sons Ltd.

  6. 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

  7. Effects of disease severity and necrosis on pancreatic dysfunction after acute pancreatitis.

    PubMed

    Garip, Gokhan; Sarandöl, Emre; Kaya, Ekrem

    2013-11-28

    To evaluate the effects of disease severity and necrosis on organ dysfunctions in acute pancreatitis (AP). One hundred and nine patients treated as AP between March 2003 and September 2007 with at least 6 mo follow-up were included. Patients were classified according to severity of the disease, necrosis ratio and localization. Subjective clinical evaluation and fecal pancreatic elastase-I (FPE-I) were used for exocrine dysfunction evaluation, and oral glucose tolerance test was completed for endocrine dysfunction. The correlation of disease severity, necrosis ratio and localization with exocrine and endocrine dysfunction were investigated. There were 58 male and 51 female patients, and mean age was 56.5 ± 15.7. Of the patients, 35.8% had severe AP (SAP) and 27.5% had pancreatic necrosis. Exocrine dysfunction was identified in 13.7% of the patients [17.9% were in SAP, 11.4% were in mild AP (MAP)] and 34.7% of all of the patients had endocrine dysfunction (56.4% in SAP and 23.2% in MAP). In patients with SAP and necrotizing AP (NAP), FPE-Ilevels were lower than the others (P < 0.05 and 0.001 respectively) and in patients having pancreatic head necrosis or near total necrosis, FPE-1 levels were lower than 200 μg/g stool. Forty percent of the patients who had undergone necrosectomy developed exocrine dysfunction. Endocrine dysfunction was more significant in patients with SAP and NAP (P < 0.001). All of the patients in the necrosectomy group had endocrine dysfunction. Patients with SAP, NAP, pancreatic head necrosis and necrosectomy should be followed for pancreatic functions.

  8. Pruritus in Autoimmune Connective Tissue Diseases.

    PubMed

    Smith, Gideon P; Argobi, Yahya

    2018-07-01

    Pruritus in autoimmune connective tissue diseases is a common symptom that can be severe and affect the quality of life of patients. It can be related to disease activity and severity or occur independent of the disease. Appropriate therapy to control the itch depends on the etiology, and it is therefore essential to first work-up these patients for the underlying trigger. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Matrix metalloproteinase 10 is associated with disease severity and mortality in patients with peripheral arterial disease.

    PubMed

    Martinez-Aguilar, Esther; Gomez-Rodriguez, Violeta; Orbe, Josune; Rodriguez, Jose A; Fernández-Alonso, Leopoldo; Roncal, Carmen; Páramo, Jose A

    2015-02-01

    Peripheral arterial disease (PAD) is associated with poor prognosis in terms of cardiovascular (CV) morbidity and mortality. Matrix metalloproteinases (MMPs) contribute to vascular remodeling by degrading extracellular matrix components and play a role in atherosclerosis as demonstrated for MMP-10 (stromelysin-2). This study analyzed MMP-10 levels in PAD patients according to disease severity and CV risk factors and evaluated the prognostic value of MMP-10 for CV events and mortality in lower limb arterial disease after a follow-up period of 2 years. MMP-10 was measured by enzyme-linked immunosorbent assay in 187 PAD patients and 200 sex-matched controls. PAD patients presented with increased levels of MMP-10 (702 ± 326 pg/mL control vs 946 ± 473 pg/mL PAD; P < .001) and decreased levels of tissue inhibitor of matrix metalloproteinase 1 (312 ± 117 ng/mL control vs 235 ± 110 ng/mL PAD; P < .001) compared with controls. Among PAD patients, those with critical limb ischemia (n = 88) showed higher levels of MMP-10 (1086 ± 478 pg/mL vs 822 ± 436 pg/mL; P < .001) compared with those with intermittent claudication (n = 99), whereas the MMP-10/tissue inhibitor of matrix metalloproteinase 1 ratio remained similar. The univariate analysis showed an association between MMP-10, age (P = .015), hypertension (P = .021), and ankle-brachial index (P = .006) in PAD patients that remained significantly associated with PAD severity after adjustment for other CV risk factors. Patients with the highest MMP-10 tertile had an increased incidence of all-cause mortality and CV mortality (P < .03). Our results suggest that MMP-10 is associated with severity and poor outcome in PAD. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  10. [Clinical characteristic of patients with acute kidney injury complicated severe cardio-vascular diseases].

    PubMed

    Wróbel, Paweł; Wyrwicz-Zielińska, Grażyna; Krzysztonek-Weber, Izabela; Sułowicz, Władysław

    2016-01-01

    Patients with cardiovascular diseases are a group of increased risk of acute kidney injury (AKI). Mortality in this group of patients with AKI, especially treated in intensive care units, is very high. The aim of this study was to evaluate the clinical characteristic of patients with AKI complicated severe cardiovascular diseases. Retrospective evaluation of 246 questionnaire of patients with AKI in the course of severe cardiovascular diseases treated in the wards of nephrological profile from the malopolska and podkarpackie voivodships in the years 2000-2011 was performed. The group of patients consisted of 157 men and 89 women, with mean age 67.9 ± 14.8 years. The most common cause of AKI were: acute decompensated heart failure--24 (9.8%), chronic decompensated heart failure--94 (38.2%), cardiac arrest--29 (11.8%), myocardial infarction--48 (19.5%), CABG--12 (4.9%), cardiac valve implantation--14 (5.7), heart transplantation--4 (1.6%) and aortic aneurysm--21 (8.5%). Age distribution of patients with AKI revealed that most numerous group had 71-80 years. The most of patients (95.9%) with AKI were treated with hemodialysis. The mortality rate in the study group was very high (69.5%). Recovery of renal function was observed in 39 (27.3%) of patients. Signs of kidney disease before AKI was noted in 116 (47.2%) of patients. Patients with severe cardiovascular complications and AKI had high mortality rate instead of performed hemodialysis treatment.

  11. Does coral disease affect symbiodinium? Investigating the impacts of growth anomaly on symbiont photophysiology.

    PubMed

    Burns, John Henrik Robert; Gregg, Toni Makani; Takabayashi, Misaki

    2013-01-01

    Growth anomaly (GA) is a commonly observed coral disease that impairs biological functions of the affected tissue. GA is prevalent at Wai 'ōpae tide pools, southeast Hawai 'i Island. Here two distinct forms of this disease, Type A and Type B, affect the coral, Montiporacapitata. While the effects of GA on biology and ecology of the coral host are beginning to be understood, the impact of this disease on the photophysiology of the dinoflagellate symbiont, Symbiodinium spp., has not been investigated. The GA clearly alters coral tissue structure and skeletal morphology and density. These tissue and skeletal changes are likely to modify not only the light micro-environment of the coral tissue, which has a direct impact on the photosynthetic potential of Symbiodinium spp., but also the physiological interactions within the symbiosis. This study utilized Pulse amplitude modulation fluorometry (PAM) to characterize the photophysiology of healthy and GA-affected M. capitata tissue. Overall, endosymbionts within GA-affected tissue exhibit reduced photochemical efficiency. Values of both Fv/Fm and ΔF/ Fm' were significantly lower (p<0.01) in GA tissue compared to healthy and unaffected tissues. Tracking the photophysiology of symbionts over a diurnal time period enabled a comparison of symbiont responses to photosynthetically available radiation (PAR) among tissue conditions. Symbionts within GA tissue exhibited the lowest values of ΔF/Fm' as well as the highest pressure over photosystem II (p<0.01). This study provides evidence that the symbionts within GA-affected tissue are photochemically compromised compared to those residing in healthy tissue.

  12. Does Coral Disease Affect Symbiodinium? Investigating the Impacts of Growth Anomaly on Symbiont Photophysiology

    PubMed Central

    Burns, John Henrik Robert; Gregg, Toni Makani; Takabayashi, Misaki

    2013-01-01

    Growth anomaly (GA) is a commonly observed coral disease that impairs biological functions of the affected tissue. GA is prevalent at Wai ‘ōpae tide pools, southeast Hawai ‘i Island. Here two distinct forms of this disease, Type A and Type B, affect the coral, Montipora capitata . While the effects of GA on biology and ecology of the coral host are beginning to be understood, the impact of this disease on the photophysiology of the dinoflagellate symbiont, Symbiodinium spp., has not been investigated. The GA clearly alters coral tissue structure and skeletal morphology and density. These tissue and skeletal changes are likely to modify not only the light micro-environment of the coral tissue, which has a direct impact on the photosynthetic potential of Symbiodinium spp., but also the physiological interactions within the symbiosis. This study utilized Pulse amplitude modulation fluorometry (PAM) to characterize the photophysiology of healthy and GA-affected M . capitata tissue. Overall, endosymbionts within GA-affected tissue exhibit reduced photochemical efficiency. Values of both Fv/Fm and ΔF/ Fm’ were significantly lower (p<0.01) in GA tissue compared to healthy and unaffected tissues. Tracking the photophysiology of symbionts over a diurnal time period enabled a comparison of symbiont responses to photosynthetically available radiation (PAR) among tissue conditions. Symbionts within GA tissue exhibited the lowest values of ΔF/Fm’ as well as the highest pressure over photosystem II (p<0.01). This study provides evidence that the symbionts within GA-affected tissue are photochemically compromised compared to those residing in healthy tissue. PMID:23967301

  13. Correlations of sleep disorders with severity of obstructive airway disease in mustard gas-injured patients.

    PubMed

    Vahedi, Ensieh; Taheri, Saeed; Alaedini, Farshid; Poursaleh, Zohreh; Ameli, Javad; Ghanei, Mostafa

    2012-06-01

    Mustard gas has serious adverse effects on several organs and functions in humans. In this study, we analyzed potential correlations between obstructive airway disease and sleep disorders in Iranian mustard gas-injured patients. We enrolled 30 male mustard gas-injured veterans and civilians from the Chemical Warfare Exposure Clinic at Baqiyatallah Hospital, Tehran. All the subjects underwent comprehensive polysomnographic and spirometric evaluations for diagnosis of sleep disorders. Patients were categorized into three groups according to the severity of their obstructive airway disease based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria: group 1 (GOLD I and II), group 2 (GOLD III), and group 3 (GOLD IV). Patients with less severe obstructive airway disease had significantly higher rate of hypopnea (p = 0.05) and AHI (p = 0.05). The number of REM events was significantly higher in patients with less severe airway disease (p = 0.028). Stage 1 sleep among patients with higher FEV1 significantly constituted a higher proportion of sleep, and stage 4 sleep was significantly longer in patients with higher DLCO (p = 0.043, both). We found that sleep parameters in SM-exposed patients have some relations with spirometric parameters. Future studies with large patient populations are needed for confirmation of our results, and therapeutic interventions are needed to evaluate endeavors we can do to enhance health and quality of life in our mustard gas-injured population.

  14. Metronidazole-but not IL-10 or prednisolone-rescues Trichuris muris infected C57BL/6 IL-10 deficient mice from severe disease.

    PubMed

    Kopper, Jamie J; Patterson, Jon S; Mansfield, Linda S

    2015-09-15

    Trichuris muris infected C57BL/6 mice are a frequently studied model of immune mediated resistance to helminths. Our objective was to characterize dose-dependent gastrointestinal (GI) disease and pathology due to Trichuris in C57BL/6 mice with varying degrees of IL-10 sufficiency. These mice can serve as a model for other animals (dogs, cattle) and humans where IL-10 polymorphisms have been associated with disease susceptibility and may affect susceptibility to whipworm. C57BL/6 IL-10(+/+), IL-10(+/-) and IL-10(-/-) mice were infected with T. muris (J strain) in a dose response study. T. muris produced dose-dependent disease in IL-10(-/-) mice. Ninety percent of mice receiving the high dose (75 ova) had severe disease necessitating early euthanasia, while the medium dose (50 ova) resulted in 100% early euthanasia of males/75% of females, and the low dose (25 ova) in 100% early euthanasia of males/25% of females. Having some IL-10 as in heterozygotes did not rescue all infected mice from effects of the high dose. 2/21 IL-10(-/-), 1/17 IL-10(+/-), and 0/17 IL-10(+/+) mice in the high dose group had severe peritonitis and extra-intestinal bacteria confirmed by fluorescent 16S rDNA analysis of peritoneal organ surfaces. Three of twenty one IL-10(-/-) had demonstrable extra-intestinal T. muris adults. Although free from viral pathogens, 12/21 IL-10(-/-), 6/17 IL-10(+/-), and 4/17 IL-10(+/+) infected mice had hepatitis, while control mice of all genotypes did not. Mice had evidence of inflammation of serosal surfaces of liver, spleen and GI tract even when extraintestinal Trichuris were not found. Blinded histopathology scoring revealed that even when infected IL-10(-/-) mice displayed few, if any, clinical signs, levels of gut inflammation did not vary significantly from those mice euthanized early due to severe disease. To examine whether antibiotics or corticosteroids could reverse severe disease and lesions, IL-10(-/-) mice infected with T. muris were treated with

  15. Mechanisms regulating immunity and disease severity following high and low virulence BVDV type 2 infection in neonatal calves

    USDA-ARS?s Scientific Manuscript database

    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...

  16. Reliability and Validity of the Persian Version of the Fatigue Severity Scale in Idiopathic Parkinson's Disease Patients

    PubMed Central

    Hadizadeh, Hasti; Farhadi, Farzaneh; Delbari, Ahmad; Lökk, Johan

    2013-01-01

    As one of the most frequent symptoms, measurement of fatigue is an issue of interest in Parkinson's disease (PD). The fatigue severity scale (FSS) is one of the recommended questionnaires for this purpose. The aim of our study was to evaluate psychometric properties of the Persian version of the FSS (FSS-Per) to assess fatigue in PD patients. Ninety nondemented idiopathic Parkinson's disease (IPD) patients were consecutively recruited from an outpatient referral movement disorder clinic. In addition to the disease severity scales, the FSS-Per was used for fatigue measurement. The internal consistency coefficient was larger than 0.8 for all of the items with a total Cronbach's alpha of 0.96 (95% CI: 0.95–0.97). The FSS-Per score correlated with the UPDRS score (r = 0.55, P < 0.001) and the “Hoehn and Yahr” (HY) stage (r = 0.48, P < 0.001). The total score of the FSS-Per significantly discriminated IPD patients with more severe disability (HY stage > 2) versus those with less severe disease (HY stage ≤2) (AUC = 0.81 (95% CI: 0.72–0.90)). The FSS-Per fulfilled a high internal consistency and construct validity to measure the severity of fatigue in Iranian IPD patients. These acceptable psychometric properties were reproducible in subgroups of IPD patients regarding different levels of education, disease severity, sex and age groups. PMID:24089644

  17. A severe case of Legionnaire's disease connected to the BBC outbreak in 1988.

    PubMed

    Richards, N C; McKinley, K P

    1989-01-01

    On 1 May 1988 a senior Naval Officer, serving at HMS Warrior, was admitted to RAF Halton where a diagnosis of Legionnaire's disease was made. He suffered severe pneumonia and neurological symptoms, and although he eventually responded to treatment, he still suffers sequelae. On 19 April, he was in the vicinity of the BBC at the time of the outbreak of Legionnaire's disease. His clinical findings are reported in this article along with a brief history and discussion of the diagnosis and prevention of Legionnaire's disease.

  18. 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

  19. 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. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  20. Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

    PubMed

    Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

    2015-10-01

    Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. In silico prediction of a disease-associated STIL mutant and its affect on the recruitment of centromere protein J (CENPJ).

    PubMed

    Kumar, Ambuj; Rajendran, Vidya; Sethumadhavan, Rao; Purohit, Rituraj

    2012-01-01

    Human STIL (SCL/TAL1 interrupting locus) protein maintains centriole stability and spindle pole localisation. It helps in recruitment of CENPJ (Centromere protein J)/CPAP (centrosomal P4.1-associated protein) and other centrosomal proteins. Mutations in STIL protein are reported in several disorders, especially in deregulation of cell cycle cascades. In this work, we examined the non-synonymous single nucleotide polymorphisms (nsSNPs) reported in STIL protein for their disease association. Different SNP prediction tools were used to predict disease-associated nsSNPs. Our evaluation technique predicted rs147744459 (R242C) as a highly deleterious disease-associated nsSNP and its interaction behaviour with CENPJ protein. Molecular modelling, docking and molecular dynamics simulation were conducted to examine the structural consequences of the predicted disease-associated mutation. By molecular dynamic simulation we observed structural consequences of R242C mutation which affects interaction of STIL and CENPJ functional domains. The result obtained in this study will provide a biophysical insight into future investigations of pathological nsSNPs using a computational platform.

  2. Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice.

    PubMed

    Sumner, Charlotte J; Wee, Claribel D; Warsing, Leigh C; Choe, Dong W; Ng, Andrew S; Lutz, Cathleen; Wagner, Kathryn R

    2009-09-01

    There is currently no treatment for the inherited motor neuron disease, spinal muscular atrophy (SMA). Severe SMA causes lower motor neuron loss, impaired myofiber development, profound muscle weakness and early mortality. Myostatin is a transforming growth factor-beta family member that inhibits muscle growth. Loss or blockade of myostatin signaling increases muscle mass and improves muscle strength in mouse models of primary muscle disease and in the motor neuron disease, amyotrophic lateral sclerosis. In this study, we evaluated the effects of blocking myostatin signaling in severe SMA mice (hSMN2/delta7SMN/mSmn(-/-)) by two independent strategies: (i) transgenic overexpression of the myostatin inhibitor follistatin and (ii) post-natal administration of a soluble activin receptor IIB (ActRIIB-Fc). SMA mice overexpressing follistatin showed little increase in muscle mass and no improvement in motor function or survival. SMA mice treated with ActRIIB-Fc showed minimal improvement in motor function, and no extension of survival compared with vehicle-treated mice. Together these results suggest that inhibition of myostatin may not be a promising therapeutic strategy in severe forms of SMA.

  3. Depressed mood, positive affect, and heart rate variability in patients with suspected coronary artery disease.

    PubMed

    Bhattacharyya, Mimi R; Whitehead, Daisy L; Rakhit, Roby; Steptoe, Andrew

    2008-11-01

    To test associations between heart rate variability (HRV), depressed mood, and positive affect in patients with suspected coronary artery disease (CAD). Depression is associated with impaired HRV post acute cardiac events, but evidence in patients with stable coronary artery disease (CAD) is inconsistent. Seventy-six patients (52 men, 24 women; mean age = 61.1 years) being investigated for suspected CAD on the basis of symptomatology and positive noninvasive tests, completed 24-hour electrocardiograms. The Beck Depression Inventory (BDI) was administered, and positive and depressed affect was measured over the study period with the Day Reconstruction Method (DRM). A total of 46 (60.5%) patients were later found to have definite CAD. HRV was analyzed, using spectral analysis. Typical diurnal profiles of HRV were observed, with greater normalized high frequency (HF) and lower normalized low frequency (LF) power in the night compared with the day. BDI depression scores were not consistently associated with HRV. But positive affect was associated with greater normalized HF power (p = .039) and reduced normalized LF power (p = .007) independently of age, gender, medication with beta blockers, CAD status, body mass index, smoking, and habitual physical activity level. In patients with definite CAD, depressed affect assessed using the DRM was associated with reduced normalized HF power and heightened normalized LF power (p = .007) independently of covariates. Relationships between depression and HRV in patients with CAD may depend on affective experience over the monitoring period. Enhanced parasympathetic cardiac control may be a process through which positive affect protects against cardiovascular disease.

  4. Factors affecting poor nutritional status after small bowel resection in patients with Crohn disease.

    PubMed

    Jang, Ki Ung; Yu, Chang Sik; Lim, Seok-Byung; Park, In Ja; Yoon, Yong Sik; Kim, Chan Wook; Lee, Jong Lyul; Yang, Suk-Kyun; Ye, Byong Duk; Kim, Jin Cheon

    2016-07-01

    In Crohn disease, bowel-preserving surgery is necessary to prevent short bowel syndrome due to repeated operations. This study aimed to determine the remnant small bowel length cut-off and to evaluate the clinical factors related to nutritional status after small bowel resection in Crohn disease.We included 394 patients (69.3% male) who underwent small bowel resection for Crohn disease between 1991 and 2012. Patients who were classified as underweight (body mass index < 17.5) or at high risk of nutrition-related problems (modified nutritional risk index < 83.5) were regarded as having a poor nutritional status. Preliminary remnant small bowel length cut-offs were determined using receiver operating characteristic curves. Variables associated with poor nutritional status were assessed retrospectively using Student t tests, chi-squared tests, Fisher exact tests, and logistic regression analyses.The mean follow-up period was 52.9 months and the mean patient ages at the time of the last bowel surgery and last follow-up were 31.2 and 35.7 years, respectively. The mean remnant small bowel length was 331.8 cm. Forty-three patients (10.9%) underwent ileostomy, 309 (78.4%) underwent combined small bowel and colon resection, 111 (28.2%) had currently active disease, and 105 (26.6%) underwent at least 2 operations for recurrent disease. The mean body mass index and modified nutritional risk index were 20.6 and 100.8, respectively. The independent factors affecting underweight status were remnant small bowel length ≤240 cm (odds ratio: 4.84, P < 0.001), ileostomy (odds ratio: 4.70, P < 0.001), and currently active disease (odds ratio: 4.16, P < 0.001). The independent factors affecting high nutritional risk were remnant small bowel length ≤230 cm (odds ratio: 2.84, P = 0.012), presence of ileostomy (odds ratio: 3.36, P = 0.025), and currently active disease (odds ratio: 4.90, P < 0.001).Currently active disease, ileostomy, and remnant small

  5. Impact of Disease Severity, Illness Beliefs, and Coping Strategies on Outcomes in Psoriatic Arthritis.

    PubMed

    Howells, Laura; Chisholm, Anna; Cotterill, Sarah; Chinoy, Hector; Warren, Richard B; Bundy, Christine

    2018-02-01

    Little is known about how people with psoriatic arthritis (PsA) cope with and manage their condition, but data show that psychological problems are underrecognized and undertreated. The Common Sense Self-Regulatory Model (CS-SRM) suggests illness beliefs, mediated by coping, may influence health outcomes. The study aimed to investigate the roles of disease severity, illness beliefs, and coping strategies in predicting depression, anxiety, and quality of life (QoL) in people with PsA. Additionally, we aimed to assess the role of depression and anxiety in predicting QoL. We conducted a cross-sectional observational study, where adults with PsA (n = 179) completed validated measures of predictor (illness beliefs, coping strategies, disease severity) and outcome variables (depression, anxiety, QoL) using an online survey distributed via social media. The participants were a community sample of 179 adults with PsA, ages 20 to 72 years (77.1% female). After controlling for disease severity, hierarchical multiple regression models indicated that more negative beliefs about consequences and behavioral disengagement as a coping method predicted levels of depression, and self-blame predicted anxiety. Beliefs about consequences and the presence of depression predicted quality of life scores after controlling for disease severity. This study offers support for the use of the CS-SRM in explaining variation on psychological outcomes in individuals with PsA. The illness beliefs and coping strategies identified as predictors in this article are potential targets for interventions addressing PsA-related distress and QoL. © 2017, American College of Rheumatology.

  6. Recombinant interleukin 2 therapy in severe combined immunodeficiency disease.

    PubMed Central

    Pahwa, R; Chatila, T; Pahwa, S; Paradise, C; Day, N K; Geha, R; Schwartz, S A; Slade, H; Oyaizu, N; Good, R A

    1989-01-01

    Severe combined immunodeficiency disease (SCID) is a congenital disorder of severe B- and T-lymphocyte dysfunction in which several pathogenic mechanisms have been identified. The present study describes a female child with SCID who had a primary defect in the ability of T cells to secrete interleukin 2 (IL-2). B- and T-cell numbers were normal, but their functions were severely deficient. Mitogen and antigen-driven lymphoproliferative responses were diminished but were correctable in vitro with recombinant IL-2 (rIL-2). The patient's phytohemagglutinin-stimulated lymphocytes expressed IL-2 receptors normally. Despite the presence of the gene for IL-2, the patient's cells were grossly deficient in messenger RNA for IL-2 and endogenous IL-2 production. Pokeweed mitogen-driven B-cell differentiation was decreased and was not corrected by the addition of normal T cells to the B cells. Two attempts at immune reconstitution by haploidentical bone marrow transplantation failed. Therapy with rIL-2 (30,000 units/kg, given daily i.v.) resulted in marked clinical improvement as well in improved T-cell functions. The child, now 3 yr old, has been on rIL-2 therapy for 2 yr and receives rIL-2 (30,000 units/kg) three times weekly at home. This case study points to a new direction in the treatment of such disorders with rIL-2. Images PMID:2787027

  7. Alcohol consumption in late adolescence is associated with an increased risk of severe liver disease later in life.

    PubMed

    Hagström, Hannes; Hemmingsson, Tomas; Discacciati, Andrea; Andreasson, Anna

    2018-03-01

    High alcohol consumption is associated with an increased risk of severe liver disease. Current recommendations suggest it is safe for men to consume 30 grams of alcohol per day. We investigated the association between alcohol consumption early in life and later development of severe liver disease. We used data on alcohol consumption at conscription to military service from 43,296 men (18-20 years) in Sweden between 1969 and 1970. Outcomes were defined as incident diagnoses of severe liver disease from systematic national registration of clinical events until the end of 2009. A Cox regression model adjusted for body mass index, smoking, use of narcotics, cognitive ability and cardiovascular capacity was applied. During a mean follow-up of 37.8 years, 383 men developed severe liver disease. Alcohol consumption was associated with an increased risk of development of severe liver disease in a dose-response pattern (adjusted hazard ratio for every one gram/day increase 1.02; 95% CI 1.01-1.02). No evidence of a threshold effect was found. Importantly, a clear trend pointed towards an increased risk of severe liver disease in men who consumed less than 30 grams of alcohol per day. Alcohol consumption in young men is associated with an increased risk of severe liver disease, up to 39 years later in life. The risk was dose-dependent, with no sign of a threshold effect. Current guidelines for safe alcohol intake in men might have to be revised. We investigated more than 43,000 Swedish men in their late teens enlisted for conscription in 1969-1970. After almost 40 years of follow-up, we found that alcohol consumption was a significant risk factor for developing severe liver disease, independent of confounders. This risk was dose-dependent, and was most pronounced in men consuming two drinks per day or more. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  8. Divorce and Severity of Coronary Artery Disease: A Multicenter Study

    PubMed Central

    Al-Murayeh, Mushabab; Al-kaabi, Salem; Lotfi, Amir; Al-Faifi, Salem M.; Alqahtani, Saleh; Stewart, James; Heavey, Jon; Hurley, William T.; Alama, Mohamed N.; Faden, Mazen; Al-Shehri, Mohamed; Youssef, Ali; Alsheikh-Ali, Alawi A.

    2017-01-01

    The association between marital status and coronary artery disease (CAD) is supported by numerous epidemiological studies. While divorce may have an adverse effect on cardiac outcomes, the relationship between divorce and severe CAD is unclear. We conducted a multicenter, observational study of consecutive patients undergoing coronary angiography during the period between April 1, 2013, and March 30, 2014. Of 1,068 patients, 124 (12%) were divorced. Divorce was more frequent among women (27%) compared to men (6%). Most divorced patients had been divorced only once (49%), but a subset had been divorced 2 (38%) or ≥3 (12%) times. After adjusting for baseline differences, there was no significant association between divorce and severe CAD in men. In women, there was a significant adjusted association between divorce and severe MVD (OR 2.31 [1.16, 4.59]) or LMD (OR 5.91 [2.19, 15.99]). The modification of the association between divorce and severe CAD by gender was statistically significant for severe LMD (Pinteraction 0.0008) and marginally significant for CAD (Pinteraction 0.05). Among women, there was a significant adjusted association between number of divorces and severe CAD (OR 2.4 [95% CI 1.2, 4.5]), MVD (OR 2.0 [95% CI 1.4, 3.0]), and LMD (OR 3.4 [95% CI 1.9, 5.9]). In conclusion, divorce, particularly multiple divorces, is associated with severe CAD, MVD, and LMD in women but not in men. PMID:28811952

  9. Evidence for widespread, severe brain copper deficiency in Alzheimer's dementia.

    PubMed

    Xu, Jingshu; Church, Stephanie J; Patassini, Stefano; Begley, Paul; Waldvogel, Henry J; Curtis, Maurice A; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

    2017-08-16

    Datasets comprising simultaneous measurements of many essential metals in Alzheimer's disease (AD) brain are sparse, and available studies are not entirely in agreement. To further elucidate this matter, we employed inductively-coupled-plasma mass spectrometry to measure post-mortem levels of 8 essential metals and selenium, in 7 brain regions from 9 cases with AD (neuropathological severity Braak IV-VI), and 13 controls who had normal ante-mortem mental function and no evidence of brain disease. Of the regions studied, three undergo severe neuronal damage in AD (hippocampus, entorhinal cortex and middle-temporal gyrus); three are less-severely affected (sensory cortex, motor cortex and cingulate gyrus); and one (cerebellum) is relatively spared. Metal concentrations in the controls differed among brain regions, and AD-associated perturbations in most metals occurred in only a few: regions more severely affected by neurodegeneration generally showed alterations in more metals, and cerebellum displayed a distinctive pattern. By contrast, copper levels were substantively decreased in all AD-brain regions, to 52.8-70.2% of corresponding control values, consistent with pan-cerebral copper deficiency. This copper deficiency could be pathogenic in AD, since levels are lowered to values approximating those in Menkes' disease, an X-linked recessive disorder where brain-copper deficiency is the accepted cause of severe brain damage. Our study reinforces others reporting deficient brain copper in AD, and indicates that interventions aimed at safely and effectively elevating brain copper could provide a new experimental-therapeutic approach.

  10. Myasthenia gravis in a patient affected by glycogen storage disease type Ib: a further manifestation of an increased risk for autoimmune disorders?

    PubMed

    Melis, D; Balivo, F; Della Casa, R; Romano, A; Taurisano, R; Capaldo, B; Riccardi, G; Monsurrò, M R; Parenti, G; Andria, G

    2008-12-01

    Glycogen storage disease type Ib (GSD Ib, OMIM 232220) is an inborn disorder of glucose metabolism, caused by mutations in the G6PT gene, encoding a glucose 6-phosphate transporter (G6PT). GSD Ib is mainly associated with fasting hypoglycaemia and hepatomegaly. Most GSD Ib patients also show neutropenia and neutrophil dysfunction and therefore are at risk of developing severe infections and inflammatory bowel disease (IBD). An increased risk for autoimmune disorders, such as thyroid autoimmunity and Crohn-like disease, has also been demonstrated, but no systematic study on the prevalence of autoimmune disorders in GSD Ib patients has ever been performed. We describe a 25-year-old patient affected by GSD Ib who developed 'seronegative' myasthenia gravis (MG), presenting with bilateral eyelid ptosis, diplopia, dysarthria, severe dysphagia, dyspnoea and fatigue. The repetitive stimulation of peripheral nerves test showed signs of exhaustion of neuromuscular transmission, particularly evident in the cranial area. Even in the absence of identifiable anti-acetylcholine receptor antibodies, seronegative MG is considered an autoimmune disorder and may be related to the disturbed immune function observed in GSD Ib patients.

  11. Periodontal diseases.

    PubMed

    Kinane, Denis F; Stathopoulou, Panagiota G; Papapanou, Panos N

    2017-06-22

    Periodontal diseases comprise a wide range of inflammatory conditions that affect the supporting structures of the teeth (the gingiva, bone and periodontal ligament), which could lead to tooth loss and contribute to systemic inflammation. Chronic periodontitis predominantly affects adults, but aggressive periodontitis may occasionally occur in children. Periodontal disease initiation and propagation is through a dysbiosis of the commensal oral microbiota (dental plaque), which then interacts with the immune defences of the host, leading to inflammation and disease. This pathophysiological situation persists through bouts of activity and quiescence, until the affected tooth is extracted or the microbial biofilm is therapeutically removed and the inflammation subsides. The severity of the periodontal disease depends on environmental and host risk factors, both modifiable (for example, smoking) and non-modifiable (for example, genetic susceptibility). Prevention is achieved with daily self-performed oral hygiene and professional removal of the microbial biofilm on a quarterly or bi-annual basis. New treatment modalities that are actively explored include antimicrobial therapy, host modulation therapy, laser therapy and tissue engineering for tissue repair and regeneration.

  12. Treatment for moderate to severe atopic dermatitis in alpine and moderate maritime climates differentially affects helper T cells and memory B cells in children.

    PubMed

    Heeringa, J J; Fieten, K B; Bruins, F M; van Hoffen, E; Knol, E F; Pasmans, S G M A; van Zelm, M C

    2018-06-01

    Treatment of atopic dermatitis (AD) is focused on topical anti-inflammatory therapy, epidermal barrier repair and trigger avoidance. Multidisciplinary treatment in both moderate maritime and alpine climates can successfully reduce disease activity in children with AD. However, it remains unclear whether abnormalities in B cell and T cell memory normalize and whether this differs between treatment strategies. To determine whether successful treatment in maritime and alpine climates normalizes B- and T lymphocytes in children with moderate to severe AD. The study was performed in the context of a trial (DAVOS trial, registered at Current Controlled Trials ISCRTN88136485) in which eighty-eight children with moderate to severe AD were randomized to 6 weeks of treatment in moderate maritime climate (outpatient setting) or in the alpine climate (inpatient setting). Before and directly after treatment, disease activity was determined with SA-EASI and serum TARC, and T cell and B cell subsets were quantified in blood. Both treatment protocols achieved a significant decrease in disease activity, which was accompanied by a reduction in circulating memory Treg, transitional B cell and plasmablast numbers. Alpine climate treatment had a significantly greater effect on disease activity and was accompanied by a reduction in blood eosinophils and increases in memory B cells, CD8+ TemRO, CD4+ Tcm and CCR7+ Th2 subsets. Clinically successful treatment of AD induces changes in blood B- and T cell subsets reflecting reduced chronic inflammation. In addition, multidisciplinary inpatient treatment in the alpine climate specifically affects memory B cells, CD8+ T cells and Th2 cells. These cell types could represent good markers for treatment efficacy. © 2018 John Wiley & Sons Ltd.

  13. Association of Single-Nucleotide Polymorphisms in IL28B, but Not TNF-α, With Severity of Disease Caused by Andes Virus.

    PubMed

    Angulo, Jenniffer; Pino, Karla; Echeverría-Chagas, Natalia; Marco, Claudia; Martínez-Valdebenito, Constanza; Galeno, Héctor; Villagra, Eliecer; Vera, Lilian; Lagos, Natalia; Becerra, Natalia; Mora, Judith; Bermúdez, Andrea; Cárcamo, Marcela; Díaz, Janepsy; Miquel, Juan Francisco; Ferrés, Marcela; López-Lastra, Marcelo

    2015-12-15

    Andes virus (ANDV) is the sole etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in Chile, with a fatality rate of about 35%. Individual host factors affecting ANDV infection outcome are poorly understood. In this case-control genetic association analysis, we explored the link between single-nucleotide polymorphisms (SNPs) rs12979860, rs8099917 and rs1800629 and the clinical outcome of ANDV-induced disease. The SNPs rs12979860 and rs8099917 are known to play a role in the differential expression of the interleukin 28B gene (IL28B), whereas SNP rs1800629 is implicated in the expression of tumor necrosis factor α gene (TNF-α). A total of 238 samples from confirmed ANDV-infected patients collected between 2006 and 2014, and categorized according to the severity of the disease, were genotyped for SNPs rs12979860, rs8099917, and rs1800629. Analysis of IL28B SNPs rs12979860 and rs8099917 revealed a link between homozygosity of the minor alleles (TT and GG, respectively), displaying a mild disease progression, whereas heterozygosity or homozygosity for the major alleles (CT/CC and TG/TT, respectively) in both IL28B SNPs is associated with severe disease. No association with the clinical outcome of HCPS was observed for TNF-α SNP rs1800629 (TNF -308G>A). The IL28B SNPs rs12979860 and rs8099917, but not TNF-α SNP rs1800629, are associated with the clinical outcome of ANDV-induced disease, suggesting a possible link between IL28B expression and ANDV pathogenesis. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. BDNF and VEGF in the pathogenesis of stress-induced affective diseases: an insight from experimental studies.

    PubMed

    Nowacka, Marta; Obuchowicz, Ewa

    2013-01-01

    Stress is known to play an important role in etiology, development and progression of affective diseases. Especially, chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis (HPA), neurotransmission and the immune system, acts as a trigger for affective diseases. It has been reported that the rise in the concentration of pro-inflammatory cytokines and persistent up-regulation of glucocorticoid expression in the brain and periphery increases the excitotoxic effect on CA3 pyramidal neurons in the hippocampus resulting in dendritic atrophy, apoptosis of neurons and possibly inhibition of neurogenesis in adult brain. Stress was observed to disrupt neuroplasticity in the brain, and growing evidence demonstrates its role in the pathomechanism of affective disorders. Experimental studies indicate that a well-known brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) which have recently focused increasing attention of neuroscientists, promote cell survival, positively modulate neuroplasticity and hippocampal neurogenesis. In this paper, we review the alterations in BDNF and VEGF pathways induced by chronic and acute stress, and their relationships with HPA axis activity. Moreover, behavioral effects evoked in rodents by both above-mentioned factors and the effects consequent to their deficit are presented. Biochemical as well as behavioral findings suggest that BDNF and VEGF play an important role as components of cascade of changes in the pathomechanism of stress-induced affective diseases. Further studies on the mechanisms regulating their expression in stress conditions are needed to better understand the significance of trophic hypothesis of stress-induced affective diseases.

  15. Shaking Out Clues to Autoimmune Disease

    MedlinePlus

    ... include type 1 diabetes, inflammatory bowel diseases and multiple sclerosis. Researchers have found many genetic variants that affect ... they examined a mouse disease that resembles human multiple sclerosis. Mice lacking SGK1 had less severe symptoms and ...

  16. Association of Single-Nucleotide Polymorphisms in IL28B, but Not TNF-α, With Severity of Disease Caused by Andes Virus

    PubMed Central

    Angulo, Jenniffer; Pino, Karla; Echeverría-Chagas, Natalia; Marco, Claudia; Martínez-Valdebenito, Constanza; Galeno, Héctor; Villagra, Eliecer; Vera, Lilian; Lagos, Natalia; Becerra, Natalia; Mora, Judith; Bermúdez, Andrea; Cárcamo, Marcela; Díaz, Janepsy; Miquel, Juan Francisco; Ferrés, Marcela; López-Lastra, Marcelo

    2015-01-01

    Background. Andes virus (ANDV) is the sole etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in Chile, with a fatality rate of about 35%. Individual host factors affecting ANDV infection outcome are poorly understood. In this case-control genetic association analysis, we explored the link between single-nucleotide polymorphisms (SNPs) rs12979860, rs8099917 and rs1800629 and the clinical outcome of ANDV-induced disease. The SNPs rs12979860 and rs8099917 are known to play a role in the differential expression of the interleukin 28B gene (IL28B), whereas SNP rs1800629 is implicated in the expression of tumor necrosis factor α gene (TNF-α). Methods. A total of 238 samples from confirmed ANDV-infected patients collected between 2006 and 2014, and categorized according to the severity of the disease, were genotyped for SNPs rs12979860, rs8099917, and rs1800629. Results. Analysis of IL28B SNPs rs12979860 and rs8099917 revealed a link between homozygosity of the minor alleles (TT and GG, respectively), displaying a mild disease progression, whereas heterozygosity or homozygosity for the major alleles (CT/CC and TG/TT, respectively) in both IL28B SNPs is associated with severe disease. No association with the clinical outcome of HCPS was observed for TNF-α SNP rs1800629 (TNF −308G>A). Conclusions. The IL28B SNPs rs12979860 and rs8099917, but not TNF-α SNP rs1800629, are associated with the clinical outcome of ANDV-induced disease, suggesting a possible link between IL28B expression and ANDV pathogenesis. PMID:26394672

  17. Origins and consequences of congenital heart defects affecting the right ventricle.

    PubMed

    Woudstra, Odilia I; Ahuja, Suchit; Bokma, Jouke P; Bouma, Berto J; Mulder, Barbara J M; Christoffels, Vincent M

    2017-10-01

    Congenital heart disease is a major health issue, accounting for a third of all congenital defects. Improved early surgical management has led to a growing population of adults with congenital heart disease, including patients with defects affecting the right ventricle, which are often classified as severe. Defects affecting the right ventricle often cause right ventricular volume or pressure overload and affected patients are at high risk for complications such as heart failure and sudden death. Recent insights into the developmental mechanisms and distinct developmental origins of the left ventricle, right ventricle, and the outflow tract have shed light on the common features and distinct problems arising in specific defects. Here, we provide a comprehensive overview of the current knowledge on the development into the normal and congenitally malformed right heart and the clinical consequences of several congenital heart defects affecting the right ventricle. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  18. Hyperbaric oxygen treatment for Parkinson's disease with severe depression and anxiety: A case report.

    PubMed

    Xu, Jin-Jin; Yang, Si-Tong; Sha, Ying; Ge, Yuan-Yuan; Wang, Jian-Meng

    2018-03-01

    Patients with Parkinson's disease (PD) frequently suffer from psychiatric disorders, and treating these symptom whereas managing the motor symptoms associated with PD can be a therapeutic challenge. We report a case of PD patient with severe depression and anxiety that refused to be treated with dopaminagonists or SSRIs, the most common treatments for PD patients suffering from psychiatric symptoms. Parkinson's disease with severe depression and anxiety. This man was treated with hyperbaric oxygen treatment for 30 days. Clinical assessment scores for depression and anxiety, including Unified Parkinson's Disease Rating ScaleI (UPDRS I), UPDRS II, Hanmilton Depression Rating Scale, and Hamiliton Anxiety Rating Scale, were improved following the hyperbaric oxygen treatment. Hyperbaric oxygen treatment may be a potential therapeutic method for PD patient suffering from depression and anxiety. Further research is needed to validate this finding and explore a potential mechanism.

  19. Affective disturbance in rheumatoid arthritis: psychological and disease-related pathways

    PubMed Central

    Sturgeon, John A.; Finan, Patrick H.; Zautra, Alex J.

    2017-01-01

    In addition to recurrent pain, fatigue, and increased rates of physical disability, individuals with rheumatoid arthritis (RA) show an increased prevalence of some mental health disorders, particularly those involving mood disturbances. This narrative Review provides an overview of mental health comorbidities in RA, and discusses how these comorbidities interact with disease processes, including dysregulation of inflammatory responses, prolonged difficulties with pain and fatigue, and the development of cognitive and behavioural responses that could exacerbate the physical and psychological difficulties associated with RA. This article describes how the social context of individuals with RA affects both their coping strategies and psychological responses to the disease, and can also impair responses to treatment through disruption of therapeutic alliance and treatment adherence. Evidence from the literature on chronic pain suggests that the resulting alterations in neural pathways of reward processing could yield new insights into the connections between disease processes in RA and psychological distress. Finally, the role of psychological interventions in the effective and comprehensive treatment of RA is discussed. PMID:27411910

  20. Hypovitaminosis D and severe hypocalcaemia: the rebirth of an old disease

    PubMed Central

    Pedrosa, Cristina; Ferraria, Nélia; Limbert, Catarina; Lopes, Lurdes

    2013-01-01

    Vitamin D deficiency, once thought to be eradicated, is becoming a frequent occurence in children, caused mainly by dietary insufficiency. The classical manifestation is rickets, but in infants severe hypocalcaemia may present as stridor, tetany, seizures or, rarely, heart disease. Here, we describe four infants who presented with complications of severe hypocalcaemia secondary to nutritional vitamin D deficiency. (1) Female, 4 months old, several spasms. (2) Male, 8 days old, generalised tonic-clonic seizure. (3) Male, 9 months old, tetany. (4) Male, 4 months old, cardiogenic shock. The cases highlight the importance of child vitamin D supplementation from birth and throughout childhood. We also note that the vitamin D state should be evaluated by the 25(OH)-D value and not the 1,25(OH)2-D. PMID:23729699

  1. Cost-effectiveness of memantine in moderate and severe Alzheimer's disease in Norway.

    PubMed

    Rive, B; Aarsland, D; Grishchenko, M; Cochran, J; Lamure, M; Toumi, M

    2012-06-01

    The cost-effectiveness of memantine for the treatment of moderate and severe Alzheimer's disease has been assessed in several European countries. Objective of the study was to assess it in Norwegian settings. This cost-utility analysis used a Markov modelling approach to simulate the evolution of patients until their need for full-time care (FTC) over a 5-year period. FTC was defined as a patient becoming either dependent or institutionalised. Transition probabilities were estimated using a newly developed predictive equation of time to FTC. Health resource use and utilities were obtained from the Scandinavian Study of Cost and Quality of Life in Alzheimer's Disease study, and mortality was obtained from the Oslo study. Memantine efficacy was based on a meta-analysis of six large trials. The model compared memantine with its alternative in this population, that is no pharmacological treatment or background therapy with acetylcholinesterase inhibitors. The model underwent extensive sensitivity analyses. In Norway, memantine was found to delay the need for FTC by 4.4 weeks compared with standard care and was associated with increased quality-adjusted life years. Memantine was the dominant strategy with cost savings of €3739 (30 041 NOK) per patient. The probability of being the dominant strategy was 98.8%. This result was confirmed across multiple sensitivity analyses. The model suggests that memantine prolongs time to FTC for no additional cost to the healthcare system and society. It can be regarded as a cost-effective choice in the management of moderate and severe Alzheimer's disease. Copyright © 2011 John Wiley & Sons, Ltd.

  2. Relationship between aortic valve calcification and the severity of coronary atherosclerotic disease.

    PubMed

    Qian, Juying; Chen, Zhangwei; Ge, Junbo; Ma, Jianying; Chang, Shufu; Fan, Bing; Liu, Xuebo; Ge, Lei

    2010-07-01

    Aortic valve calcification (AVC), which has been confirmed to be associated with various risk factors of cardiac disease, is common in the elderly and associated with increased cardiovascular mortality. It has been hypothesized that AVC is associated with coronary atherosclerotic disease, and its severity. Between July 2007 and November 2007, a total of 235 patients with chest pain or chest distress were admitted to the authors' institution for coronary angiography. The severity of coronary atherosclerotic disease (CAD) was evaluated by the Gensini score, the number of stenosed vessels, and the prevalence of total occlusion. All patients underwent transthoracic echocardiography to detect AVC. Patients with CAD had a higher prevalence of AVC than those without CAD (44% versus 26%, p = 0.005). Likewise, the prevalence of AVC was significantly higher in patients with a higher Gensini score than in those with a lower score. Patients with AVC had a higher prevalence of CAD, and higher Gensini scores and numbers of stenosed coronary arteries, even after stratification by age (65 years). On multivariable logistic regression analysis for CAD, the odds ratio (OR) of AVC was 2.315 (95% confidence interval (CI): 1.158-4.629, p = 0.018); this value was higher than that for total cholesterol (OR = 1.637, p = 0.008), lipoprotein-a (OR = 1.003, p = 0.015) and fibrinogen (OR = 1.009, p = 0.006), and marginally less than that for male gender (OR = 2.665, p = 0.005). Patients with AVC had a higher prevalence and greater severity of CAD.

  3. The severity of whirling disease among wild trout corresponds to the differences in genetic composition of Tubifex tubifex populations in central Colorado.

    PubMed

    Beauchamp, Katherine A; Kelley, Garry O; Nehring, R Barry; Hedrick, Ronald P

    2005-02-01

    We analyzed the geographic distribution of Tubifex tubifex from various river drainages in central Colorado by genetic screening with specific mitochondrial 16S ribosomal DNA (mt 16S rDNA) markers. Four distinct mt 16S rDNA lineages are evident. The sites varied with respect to land- and water-use practices. All sites represented habitats presumed capable of supporting oligochaetes. At the locations where whirling disease has had the greatest impact on resident rainbow trout, T. tubifex, representing lineages I and III (genotypes known to be susceptible to Mxyobolus cerebralis), were most commonly found. In contrast, at sites less affected by whirling disease, T. tubifex of lineages V and VI that are more resistant to M. cerebralis infections were more abundant. The predominance of resistant T. tubifex worms (lineages V and VI) at low-impact sites supports the conclusion that when these genotypes are in greater abundance, the potential for more severe effects of whirling disease on wild rainbow trout populations may be diminished.

  4. A matrix metalloproteinase 9 (MMP9) gene single nucleotide polymorphism is associated with predisposition to tick-borne encephalitis virus-induced severe central nervous system disease.

    PubMed

    Barkhash, Andrey V; Yurchenko, Andrey A; Yudin, Nikolay S; Ignatieva, Elena V; Kozlova, Irina V; Borishchuk, Inessa A; Pozdnyakova, Larisa L; Voevoda, Mikhail I; Romaschenko, Aida G

    2018-05-01

    The progression of infectious diseases depends on causative agents, the environment and the host's genetic susceptibility. To date, human genetic susceptibility to tick-borne encephalitis (TBE) virus-induced disease has not been sufficiently studied. We have combined whole-exome sequencing with a candidate gene approach to identify genes that are involved in the development of predisposition to TBE in a Russian population. Initially, six exomes from TBE patients with severe central nervous system (CNS) disease and seven exomes from control individuals were sequenced. Despite the small sample size, two nonsynonymous single nucleotide polymorphisms (SNPs) were significantly associated with TBE virus-induced severe CNS disease. One of these SNPs is rs6558394 (G/A, Pro422Leu) in the scribbled planar cell polarity protein (SCRIB) gene and the other SNP is rs17576 (A/G, Gln279Arg) in the matrix metalloproteinase 9 (MMP9) gene. Subsequently, these SNPs were genotyped in DNA samples of 150 non-immunized TBE patients with different clinical forms of the disease from two cities and 228 control randomly selected samples from the same populations. There were no statistically significant differences in genotype and allele frequencies between the case and control groups for rs6558394. However, the frequency of the rs17576 G allele was significantly higher in TBE patients with severe CNS diseases such as meningo-encephalitis (43.5%) when compared with TBE patients with milder meningitis (26.3%; P = 0.01), as well as with the population control group (32.5%; P = 0.042). The results suggest that the MMP9 gene may affect genetic predisposition to TBE in a Russian population. Copyright © 2018 Elsevier GmbH. All rights reserved.

  5. High infestation levels of Schizotetranychus oryzae severely affects rice metabolism.

    PubMed

    Blasi, Édina A R; Buffon, Giseli; Rativa, Angie G S; Lopes, Mara C B; Berger, Markus; Santi, Lucélia; Lavallée-Adam, Mathieu; Yates, John R; Schwambach, Joséli; Beys-da-Silva, Walter O; Sperotto, Raul A

    2017-12-01

    High levels of Schizotetranychus oryzae phytophagous mite infestation on rice leaves can severely affect productivity. Physiological characterization showed that S. oryzae promotes a decrease in chlorophyll concentration and the establishment of a senescence process in rice leaves. Late-infested leaves also present high levels of superoxide radical and hydrogen peroxide accumulation, along with high levels of membrane integrity loss, which is indicative of cell death. To better understand the rice molecular responses to high levels of mite infestation, we employed the Multidimensional Protein Identification Technology (MudPIT) approach to identify differentially expressed proteins. We identified 83 and 88 proteins uniquely present in control and late-infested leaves, respectively, along with 11 and one proteins more abundant in control and late-infested leaves, respectively. S. oryzae infestation induces a decreased abundance of proteins related to translation, protease inhibition, and photosynthesis. On the other hand, infestation caused increased abundance of proteins involved in protein modification and degradation. Our results also suggest that S. oryzae infestation interferes with intracellular transport, DNA structure maintenance, and amino acid and lipid metabolism in rice leaves. Proteomic data were positively correlated with enzymatic assays and RT-qPCR analysis. Our findings describe the protein expression patterns of late-infested rice leaves and suggest several targets which could be tested in future biotechnological approaches aiming to avoid the population increase of phytophagous mite in rice plants. Copyright © 2017 Elsevier GmbH. All rights reserved.

  6. Estimated severe pneumococcal disease cases and deaths before and after pneumococcal conjugate vaccine introduction in children younger than 5 years of age in South Africa.

    PubMed

    von Mollendorf, Claire; Tempia, Stefano; von Gottberg, Anne; Meiring, Susan; Quan, Vanessa; Feldman, Charles; Cloete, Jeane; Madhi, Shabir A; O'Brien, Katherine L; Klugman, Keith P; Whitney, Cynthia G; Cohen, Cheryl

    2017-01-01

    Streptococcus pneumoniae is a leading cause of severe bacterial infections globally. A full understanding of the impact of pneumococcal conjugate vaccine (PCV) on pneumococcal disease burden, following its introduction in 2009 in South Africa, can support national policy on PCV use and assist with policy decisions elsewhere. We developed a model to estimate the national burden of severe pneumococcal disease, i.e. disease requiring hospitalisation, pre- (2005-2008) and post-PCV introduction (2012-2013) in children aged 0-59 months in South Africa. We estimated case numbers for invasive pneumococcal disease using data from the national laboratory-based surveillance, adjusted for specimen-taking practices. We estimated non-bacteraemic pneumococcal pneumonia case numbers using vaccine probe study data. To estimate pneumococcal deaths, we applied observed case fatality ratios to estimated case numbers. Estimates were stratified by HIV status to account for the impact of PCV and HIV-related interventions. We assessed how different assumptions affected estimates using a sensitivity analysis. Bootstrapping created confidence intervals. In the pre-vaccine era, a total of approximately 107,600 (95% confidence interval [CI] 83,000-140,000) cases of severe hospitalised pneumococcal disease were estimated to have occurred annually. Following PCV introduction and the improvement in HIV interventions, 41,800 (95% CI 28,000-50,000) severe pneumococcal disease cases were estimated in 2012-2013, a rate reduction of 1,277 cases per 100,000 child-years. Approximately 5000 (95% CI 3000-6000) pneumococcal-related annual deaths were estimated in the pre-vaccine period and 1,900 (95% CI 1000-2500) in 2012-2013, a mortality rate difference of 61 per 100,000 child-years. While a large number of hospitalisations and deaths due to pneumococcal disease still occur among children 0-59 months in South Africa, we found a large reduction in this estimate that is temporally associated with PCV

  7. Preterm Birth Affects the Risk of Developing Immune-Mediated Diseases

    PubMed Central

    Goedicke-Fritz, Sybelle; Härtel, Christoph; Krasteva-Christ, Gabriela; Kopp, Matthias V.; Meyer, Sascha; Zemlin, Michael

    2017-01-01

    Prematurity affects approximately 10% of all children, resulting in drastically altered antigen exposure due to premature confrontation with microbes, nutritional antigens, and other environmental factors. During the last trimester of pregnancy, the fetal immune system adapts to tolerate maternal and self-antigens, while also preparing for postnatal immune defense by acquiring passive immunity from the mother. Since the perinatal period is regarded as the most important “window of opportunity” for imprinting metabolism and immunity, preterm birth may have long-term consequences for the development of immune-mediated diseases. Intriguingly, preterm neonates appear to develop bronchial asthma more frequently, but atopic dermatitis less frequently in comparison to term neonates. The longitudinal study of preterm neonates could offer important insights into the process of imprinting for immune-mediated diseases. On the one hand, preterm birth may interrupt influences of the intrauterine environment on the fetus that increase or decrease the risk of later immune disease (e.g., maternal antibodies and placenta-derived factors), whereas on the other hand, it may lead to the premature exposure to protective or harmful extrauterine factors such as microbiota and nutritional antigen. Solving this puzzle may help unravel new preventive and therapeutic approaches for immune diseases. PMID:29062316

  8. Cardiovascular Disease is Associated with COPD Severity and Reduced Functional Status and Quality of Life

    PubMed Central

    Black-Shinn, Jennifer L.; Kinney, Gregory L.; Wise, Anastasia L.; Regan, Elizabeth A.; Make, Barry; Krantz, Mori J.; Barr, R. Graham; Murphy, James R.; Lynch, David; Silverman, Edwin K.; Crapo, James D.; Hokanson, John E.

    2015-01-01

    Introduction Smoking is a major risk factor for both cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD). More individuals with COPD die from CVD than respiratory causes and the risk of developing CVD appears to be independent of smoking burden. Although CVD is a common comorbid condition within COPD, the nature of its relationships to COPD affection status and severity, and functional status is not well understood. Methods The first 2,500 members of the COPDGene cohort were evaluated. Subjects were current and former smokers with a minimum 10 pack year history of cigarette smoking. COPD was defined by spirometry as an FEV1/FVC < lower limit of normal (LLN) with further identification of severity by FEV1 percent of predicted (GOLD stages 2, 3, and 4) for the main analysis. The presence of physician-diagnosed self-reported CVD was determined from a medical history questionnaire administered by a trained staff member. Results A total of 384 (15%) had pre-existing CVD. Self-reported CVD was independently related to COPD (Odds Ratio=1.61, 95% CI=1.18–2.20, p=0.01) after adjustment for covariates with CHF having the greatest association with COPD. Within subjects with COPD, pre-existing self-reported CVD placed subjects at greater risk of hospitalization due to exacerbation, higher BODE index, and greater St. George’s questionnaire score. The presence of self-reported CVD was associated with a shorter six-minute walk distance in those with COPD (p<0.05). Conclusions Self-reported CVD was independently related to COPD with presence of both self-reported CVD and COPD associated with a markedly reduced functional status and reduced quality of life. Identification of CVD in those with COPD is an important consideration in determining functional status. PMID:24831864

  9. Reduction and return of infectious trachoma in severely affected communities in Ethiopia.

    PubMed

    Lakew, Takele; House, Jenafir; Hong, Kevin C; Yi, Elizabeth; Alemayehu, Wondu; Melese, Muluken; Zhou, Zhaoxia; Ray, Kathryn; Chin, Stephanie; Romero, Emmanuel; Keenan, Jeremy; Whitcher, John P; Gaynor, Bruce D; Lietman, Thomas M

    2009-01-01

    Antibiotics are a major tool in the WHO's trachoma control program. Even a single mass distribution reduces the prevalence of the ocular chlamydia that causes trachoma. Unfortunately, infection returns after a single treatment, at least in severely affected areas. Here, we test whether additional scheduled treatments further reduce infection, and whether infection returns after distributions are discontinued. Sixteen communities in Ethiopia were randomly selected. Ocular chlamydial infection in 1- to 5-year-old children was monitored over four biannual azithromycin distributions and for 24 months after the last treatment. The average prevalence of infection in 1- to 5-year-old children was reduced from 63.5% pre-treatment to 11.5% six months after the first distribution (P<0.0001). It further decreased to 2.6% six months after the fourth and final treatment (P = 0.0004). In the next 18 months, infection returned to 25.2%, a significant increase from six months after the last treatment (P = 0.008), but still far lower than baseline (P<0.0001). Although the prevalence of infection in any particular village fluctuated, the mean prevalence of the 16 villages steadily decreased with each treatment and steadily returned after treatments were discontinued. In some of the most severely affected communities ever studied, we demonstrate that repeated mass oral azithromycin distributions progressively reduce ocular chlamydial infection in a community, as long as these distributions are given frequently enough and at a high enough coverage. However, infection returns into the communities after the last treatment. Sustainable changes or complete local elimination of infection will be necessary. ClinicalTrials.gov NCT00221364.

  10. Reduction and Return of Infectious Trachoma in Severely Affected Communities in Ethiopia

    PubMed Central

    Lakew, Takele; House, Jenafir; Hong, Kevin C.; Yi, Elizabeth; Alemayehu, Wondu; Melese, Muluken; Zhou, Zhaoxia; Ray, Kathryn; Chin, Stephanie; Romero, Emmanuel; Keenan, Jeremy; Whitcher, John P.; Gaynor, Bruce D.; Lietman, Thomas M.

    2009-01-01

    Background Antibiotics are a major tool in the WHO's trachoma control program. Even a single mass distribution reduces the prevalence of the ocular chlamydia that causes trachoma. Unfortunately, infection returns after a single treatment, at least in severely affected areas. Here, we test whether additional scheduled treatments further reduce infection, and whether infection returns after distributions are discontinued. Methods Sixteen communities in Ethiopia were randomly selected. Ocular chlamydial infection in 1- to 5-year-old children was monitored over four biannual azithromycin distributions and for 24 months after the last treatment. Findings The average prevalence of infection in 1- to 5-year-old children was reduced from 63.5% pre-treatment to 11.5% six months after the first distribution (P<0.0001). It further decreased to 2.6% six months after the fourth and final treatment (P = 0.0004). In the next 18 months, infection returned to 25.2%, a significant increase from six months after the last treatment (P = 0.008), but still far lower than baseline (P<0.0001). Although the prevalence of infection in any particular village fluctuated, the mean prevalence of the 16 villages steadily decreased with each treatment and steadily returned after treatments were discontinued. Conclusion In some of the most severely affected communities ever studied, we demonstrate that repeated mass oral azithromycin distributions progressively reduce ocular chlamydial infection in a community, as long as these distributions are given frequently enough and at a high enough coverage. However, infection returns into the communities after the last treatment. Sustainable changes or complete local elimination of infection will be necessary. Trial Registration ClinicalTrials.gov NCT00221364 PMID:19190781

  11. Increased disease activity, severity and autoantibody positivity in rheumatoid arthritis patients with co-existent bronchiectasis.

    PubMed

    Perry, Elizabeth; Eggleton, Paul; De Soyza, Anthony; Hutchinson, David; Kelly, Clive

    2017-12-01

    Patients with rheumatoid arthritis (RA) and co-existent bronchiectasis (BRRA) have a five-fold increased mortality compared to rheumatoid arthritis alone. Yet previous studies have found no difference in clinical and serological markers of RA disease severity between BRRA patients and RA alone. However, RA disease activity measures such as Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP) and anti-cyclic citrullinated peptide antibodies (anti-CCP) have not been studied, so we assessed these parameters in patients with BRRA and RA alone. BRRA patients (n = 53) had high-resolution computed tomography proven bronchiectasis without any interstitial lung disease and ≥ 2 respiratory infections/year. RA alone patients (n = 50) had no clinical or radiological evidence of lung disease. DAS28-CRP, rheumatoid factor (immunoglobulin M) and anti-CCP were measured in all patients, together with detailed clinical and radiology records. In BRRA, bronchiectasis predated RA in 58% of patients. BRRA patients had higher DAS28 scores (3.51 vs. 2.59), higher levels of anti-CCP (89% vs. 46%) and rheumatoid factor (79% vs. 52%) (P = 0.003) compared to RA alone. Where hand and foot radiology findings were recorded, 29/37 BRRA (78%) and 13/30 (43%) RA alone had evidence of erosive change (P = 0.003). There were no significant differences between groups in smoking history or disease-modifying anti-rheumatic drug/biologic therapy. Increased levels of RA disease activity, severity and RA autoantibodies are demonstrated in patients with RA and co-existent bronchiectasis compared to patients with RA alone, despite lower tobacco exposure. This study demonstrates that BRRA is a more severe systemic disease than RA alone. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  12. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease

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

    Johnson, Reed F.; Hammoud, Dima A.; Lackemeyer, Matthew G.

    Cowpox virus (CPXV) inoculation of nonhuman primates (NHPs) has been suggested as an alternate model for smallpox (Kramski et al., 2010, PLoS One, 5, e10412). Previously, we have demonstrated that intrabronchial inoculation of CPXV-Brighton Red (CPXV-BR) into cynomolgus monkeys resulted in a disease that shared many similarities to smallpox; however, severe respiratory tract disease was observed (Smith et al., 2011, J. Gen. Virol.). Here we describe the course of disease after small particle aerosol exposure of rhesus monkeys using computed tomography (CT) to monitor respiratory disease progression. Subjects developed a severe respiratory disease that was uniformly lethal at 5.7 log{submore » 10} PFU of CPXV-BR. CT indicated changes in lung architecture that correlated with changes in peripheral blood monocytes and peripheral oxygen saturation. While the small particle aerosol inoculation route does not accurately mimic human smallpox, the data suggest that CT can be used as a tool to monitor real-time disease progression for evaluation of animal models for human diseases. - Highlights: • Small particle aerosol exposure of rhesus results in a severe respiratory disease. • CT findings correlated with peripheral oxygen saturation and monocyte increases. • Virus dissemination was limited and mainly confined to the respiratory tract. • CT provides insight into pathogenesis to aid development of animal models of disease.« less

  13. Fabry disease in children: correlation between ocular manifestations, genotype and systemic clinical severity.

    PubMed

    Allen, L E; Cosgrave, E M; Kersey, J P; Ramaswami, U

    2010-12-01

    Fabry disease is an X linked lysosomal disorder associated with severe multiorgan failure and premature death. This study aims to determine the prevalence of ophthalmic manifestations in children with the condition and investigate the correlation with genotype and systemic disease severity. The records of 26 children from 18 pedigrees with Fabry disease undergoing regular ophthalmic and systemic examination were reviewed. All pedigrees underwent GLA gene sequencing to determine genotype. Correlations between ocular and systemic phenotype and genotype were investigated. Corneal verticillata occurred in 50% of the children in this study (95% CI, 29% to 79%). Children with ophthalmic manifestations were more likely to have loss-of-function GLA mutations (p=0.003). Retinal vascular tortuosity was seen in seven children (27%), all of whom had systemic symptoms suggestive of autonomic neuropathy, such as diarrhoea and syncope. These symptoms seemed less prevalent in children without retinal vascular changes, although this did not reach statistical significance (p=0.134). Ophthalmic manifestations of Fabry disease are common even in young children with loss-of-function GLA gene mutations. Although the limited sample size possibly prevented statistical significance, systemic symptoms of autonomic neuropathy often coexist with retinal vascular changes and may share the same pathogenesis.

  14. Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice

    PubMed Central

    Sumner, Charlotte J.; Wee, Claribel D.; Warsing, Leigh C.; Choe, Dong W.; Ng, Andrew S.; Lutz, Cathleen; Wagner, Kathryn R.

    2009-01-01

    There is currently no treatment for the inherited motor neuron disease, spinal muscular atrophy (SMA). Severe SMA causes lower motor neuron loss, impaired myofiber development, profound muscle weakness and early mortality. Myostatin is a transforming growth factor-β family member that inhibits muscle growth. Loss or blockade of myostatin signaling increases muscle mass and improves muscle strength in mouse models of primary muscle disease and in the motor neuron disease, amyotrophic lateral sclerosis. In this study, we evaluated the effects of blocking myostatin signaling in severe SMA mice (hSMN2/delta7SMN/mSmn−/−) by two independent strategies: (i) transgenic overexpression of the myostatin inhibitor follistatin and (ii) post-natal administration of a soluble activin receptor IIB (ActRIIB-Fc). SMA mice overexpressing follistatin showed little increase in muscle mass and no improvement in motor function or survival. SMA mice treated with ActRIIB-Fc showed minimal improvement in motor function, and no extension of survival compared with vehicle-treated mice. Together these results suggest that inhibition of myostatin may not be a promising therapeutic strategy in severe forms of SMA. PMID:19477958

  15. Bone microarchitecture is more severely affected in patients on hemodialysis than in those receiving peritoneal dialysis.

    PubMed

    Pelletier, Solenne; Vilayphiou, Nicolas; Boutroy, Stéphanie; Bacchetta, Justine; Sornay-Rendu, Elisabeth; Szulc, Pawel; Arkouche, Walid; Guebre-Egziabher, Fitsum; Fouque, Denis; Chapurlat, Roland

    2012-09-01

    We used high-resolution quantitative computed tomography to study the microarchitecture of bone in patients with chronic kidney disease on dialysis. We compared bone characteristics in 56 maintenance hemodialysis (21 women, 14 post-menopausal) and 23 peritoneal dialysis patients (9 women, 6 post-menopausal) to 79 healthy men and women from two cohorts matched for age, body mass index, gender, and menopausal status. All underwent dual-energy X-ray absorptiometry of the spine and hip to measure areal bone mineral density, and high-resolution peripheral quantitative computed tomography of the radius and tibia to measure volumetric bone mineral density and microarchitecture. When compared to their matched healthy controls, patients receiving hemodialysis and peritoneal dialysis had a significantly lower areal bone mineral density in the hip. Hemodialysis patients had significantly lower total, cortical, and trabecular volumetric bone mineral density at both sites. Hemodialysis patients had significantly lower trabecular volumetric bone mineral density and microarchitecture at the tibia than the peritoneal dialysis patients. Overall, peritoneal dialysis patients were less affected, their cortical thickness at the distal tibia being the only significant difference versus controls. Thus, we found more severe trabecular damage at the weight-bearing tibia in hemodialysis compared to peritoneal dialysis patients, but this latter finding needs confirmation in larger cohorts.

  16. Using Smartphones and Machine Learning to Quantify Parkinson Disease Severity: The Mobile Parkinson Disease Score.

    PubMed

    Zhan, Andong; Mohan, Srihari; Tarolli, Christopher; Schneider, Ruth B; Adams, Jamie L; Sharma, Saloni; Elson, Molly J; Spear, Kelsey L; Glidden, Alistair M; Little, Max A; Terzis, Andreas; Dorsey, E Ray; Saria, Suchi

    2018-03-26

    Current Parkinson disease (PD) measures are subjective, rater-dependent, and assessed in clinic. Smartphones can measure PD features, yet no smartphone-derived rating score exists to assess motor symptom severity in real-world settings. To develop an objective measure of PD severity and test construct validity by evaluating the ability of the measure to capture intraday symptom fluctuations, correlate with current standard PD outcome measures, and respond to dopaminergic therapy. This observational study assessed individuals with PD who remotely completed 5 tasks (voice, finger tapping, gait, balance, and reaction time) on the smartphone application. We used a novel machine-learning-based approach to generate a mobile Parkinson disease score (mPDS) that objectively weighs features derived from each smartphone activity (eg, stride length from the gait activity) and is scaled from 0 to 100 (where higher scores indicate greater severity). Individuals with and without PD additionally completed standard in-person assessments of PD with smartphone assessments during a period of 6 months. Ability of the mPDS to detect intraday symptom fluctuations, the correlation between the mPDS and standard measures, and the ability of the mPDS to respond to dopaminergic medication. The mPDS was derived from 6148 smartphone activity assessments from 129 individuals (mean [SD] age, 58.7 [8.6] years; 56 [43.4%] women). Gait features contributed most to the total mPDS (33.4%). In addition, 23 individuals with PD (mean [SD] age, 64.6 [11.5] years; 11 [48%] women) and 17 without PD (mean [SD] age 54.2 [16.5] years; 12 [71%] women) completed in-clinic assessments. The mPDS detected symptom fluctuations with a mean (SD) intraday change of 13.9 (10.3) points on a scale of 0 to 100. The measure correlated well with the Movement Disorder Society Unified Parkinson Disease's Rating Scale total (r = 0.81; P < .001) and part III only (r = 0.88; P < .001), the Timed Up and Go

  17. White matter disease severity of the brain and its association with geriatric syndromes.

    PubMed

    Alagiakrishnan, Kannayiram; Hsueh, Jenny; Zhang, Edwin; Khan, Khurshid; Senthilselvan, Ambikaipakan

    2013-11-01

    White matter disease (WMD) of the brain is considered to be secondary to small vessel ischemia and can be a single unifying risk factor for the development of geriatric syndromes. The aim of our study was to investigate the association of the global and regional severity of WMD in the brain with geriatric syndromes burden. In our retrospective study, consecutive outpatient charts from patients seen between January 2010 and June 2011 at University of Alberta Hospital Seniors Clinic were reviewed. Subjects with brain computed tomography (CT) scans were included in the study. Subjects with incomplete information or with diseases that confounded WMD assessment on CT were excluded. White matter disease was quantified on CT using Wahlund scoring. A multiple linear regression analysis was conducted to determine the association of WMD severity with geriatric syndromes burden after controlling for confounding vascular risk factors. Of the 505 subjects, 326 (64.6%) were women. Mean age of the study patients was 79.8 years (SD ± 7.04), prevalence of WMD disease was 79.4%, and mean WMD score was 5.1 (SD ± 4.4). In subjects aged < and > 80 years, the mean number of geriatric syndromes was 2.83 (standard error of the mean [SE] 0.08) and 3.22 (SE 0.08), respectively. In the adjusted regression analysis, there was a significant association between WMD severity, globally (regression coefficient (β) = 0.457, SE 0.155; P = 0.003), as well as WMD in specific regions: frontal (P < 0.001), parieto-occipital (P = 0.004), and infratentorial regions (P = 0.04) with geriatric syndromes burden. The association remains even after correcting for age, sex, and all vascular risk factors. In our study, there was a significant association between the severity of global and selected regional WMD of the brain with geriatric syndromes burden, thus raising the possibility of a shared biologic association through vascular pathology of the brain.

  18. Defining the Risk and Associated Morbidity and Mortality of Severe Respiratory Syncytial Virus Infection Among Infants with Chronic Lung Disease.

    PubMed

    Paes, Bosco; Fauroux, Brigitte; Figueras-Aloy, Josep; Bont, Louis; Checchia, Paul A; Simões, Eric A F; Manzoni, Paolo; Carbonell-Estrany, Xavier

    2016-12-01

    The REGAL (RSV evidence-a geographical archive of the literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This third publication covers the risk and burden of RSV infection in infants with chronic lung disease (CLD), formerly called bronchopulmonary dysplasia (BPD). A systematic review was undertaken of publications between January 1, 1995 and December 31, 2015 across PubMed, Embase, The Cochrane Library, and Clinicaltrials.gov. Studies reporting data for hospital visits/admissions for RSV infection among infants with CLD/BPD who were not prophylaxed, as well as studies reporting RSV-associated morbidity, mortality, and healthcare costs, were included. Burdens of disease data were compared with preterm infants without CLD/BPD, other high-risk groups and term infants. Study quality and strength of evidence (SOE) were graded using recognized criteria. A total of 1837 studies were identified and 39 were included. CLD/BPD is a significant independent risk factor for RSV hospitalization [RSVH (odds ratio 2.2-7.2); high SOE]. Infants and young children with CLD/BPD had high RSVH rates which were generally similar in Europe, the United States, and Canada, mostly varying between 12 and 21%. Infants with CLD also had a longer length of hospital stay than other high-risk groups and term infants (high SOE). On average, infants spent 4-11 days in hospital (moderate SOE). Once hospitalized for RSV, affected children were at risk for a more severe course of disease than children with no RSVH (moderate SOE). Severe RSV infection in infants and young children with CLD/BPD poses a significant health burden in Western countries. Further studies focussing on the burden of RSV infection in this well-recognized population at high risk for severe disease are needed to help improve outcomes and plan allocation of healthcare resources. AbbVie.

  19. MIF and D-DT are potential disease severity modifiers in male MS subjects

    PubMed Central

    Benedek, Gil; Meza-Romero, Roberto; Jordan, Kelley; Zhang, Ying; Nguyen, Ha; Kent, Gail; Li, Jia; Siu, Edwin; Frazer, Jenny; Piecychna, Marta; Du, Xin; Sreih, Antoine; Leng, Lin; Wiedrick, Jack; Caillier, Stacy J.; Offner, Halina; Oksenberg, Jorge R.; Yadav, Vijayshree; Bourdette, Dennis; Bucala, Richard; Vandenbark, Arthur A.

    2017-01-01

    Little is known about mechanisms that drive the development of progressive multiple sclerosis (MS), although inflammatory factors, such as macrophage migration inhibitory factor (MIF), its homolog D-dopachrome tautomerase (D-DT), and their common receptor CD74 may contribute to disease worsening. Our findings demonstrate elevated MIF and D-DT levels in males with progressive disease compared with relapsing-remitting males (RRMS) and female MS subjects, with increased levels of CD74 in females vs. males with high MS disease severity. Furthermore, increased MIF and D-DT levels in males with progressive disease were significantly correlated with the presence of two high-expression promoter polymorphisms located in the MIF gene, a −794CATT5–8 microsatellite repeat and a −173 G/C SNP. Conversely, mice lacking MIF or D-DT developed less-severe signs of experimental autoimmune encephalomyelitis, a murine model of MS, thus implicating both homologs as copathogenic contributors. These findings indicate that genetically controlled high MIF expression (and D-DT) promotes MS progression in males, suggesting that these two factors are sex-specific disease modifiers and raising the possibility that aggressive anti-MIF treatment of clinically isolated syndrome or RRMS males with a high-expresser genotype might slow or prevent the onset of progressive MS. Additionally, selective targeting of MIF:CD74 signaling might provide an effective, trackable therapeutic approach for MS subjects of both sexes. PMID:28923927

  20. Dendritic cell chimerism in oral mucosa of transplanted patients affected by graft-versus-host disease.

    PubMed

    Pérez, Claudio A; Rabanales, Ramón; Rojas-Alcayaga, Gonzalo; Larrondo, Milton; Escobar, Alejandro F; López, Mercedes N; Salazar-Onfray, Flavio; Alfaro, Jorge I; González, Fermín E

    2016-02-01

    Graft-versus-host disease (GVHD) is one of the main complications after haematopoietic stem cell transplantation. Clinical features of GVHD include either an acute (aGVHD) or a chronic (cGVHD) condition that affects locations such as the oral mucosa. While the involvement of the host's dendritic cells (DCs) has been demonstrated in aGVHD, the origin (donor/host) and mechanisms underlying oral cGVHD have not been completely elucidated. In this study, we intend to determine the origin of DCs present in mucosal tissue biopsies from the oral cavity of transplanted patients affected by cGVHD. We purified DCs, from oral biopsies of three patients with cGVHD, through immunobeads and subsequently performed DNA extraction. The origin of the obtained DCs was determined by PCR amplification of 13 informative short tandem repeat (STR) alleles. We also characterised the DCs phenotype and the inflammatory infiltrate from biopsies of two patients by immunohistochemistry. Clinical and histological features of the biopsies were concordant with oral cGVHD. We identified CD11c-, CD207- and CD1a-positive cells in the epithelium and beneath the basal layer. Purification of DCs from the mucosa of patients affected by post-transplantation cGVHD was >95%. PCR-STR data analysis of DCs DNA showed that 100% of analysed cells were of donor origin in all of the evaluated patients. Our results demonstrate that resident DCs isolated from the oral tissue of allotransplanted patients affected by cGVHD are originated from the donor. Further research will clarify the role of DCs in the development and/or severity of oral cGVHD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Disease quantification in dermatology: in vivo near-infrared spectroscopy measures correlate strongly with the clinical assessment of psoriasis severity

    NASA Astrophysics Data System (ADS)

    Greve, Tanja Maria; Kamp, Søren; Jemec, Gregor B. E.

    2013-03-01

    Accurate documentation of disease severity is a prerequisite for clinical research and the practice of evidence-based medicine. The quantification of skin diseases such as psoriasis currently relies heavily on clinical scores. Although these clinical scoring methods are well established and very useful in quantifying disease severity, they require an extensive clinical experience and carry a risk of subjectivity. We explore the opportunity to use in vivo near-infrared (NIR) spectra as an objective and noninvasive method for local disease severity assessment in 31 psoriasis patients in whom selected plaques were scored clinically. A partial least squares (PLS) regression model was used to analyze and predict the severity scores on the NIR spectra of psoriatic and uninvolved skin. The correlation between predicted and clinically assigned scores was R=0.94 (RMSE=0.96), suggesting that in vivo NIR provides accurate clinical quantification of psoriatic plaques. Hence, NIR may be a practical solution to clinical severity assessment of psoriasis, providing a continuous, linear, numerical value of severity.

  2. Saposin C Coupled Lipid Nanovesicles Specifically Target Arthritic Mouse Joints for Optical Imaging of Disease Severity

    PubMed Central

    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

  3. Physical activity and metabolic disease among people with affective disorders: Prevention, management and implementation.

    PubMed

    Vancampfort, Davy; Stubbs, Brendon

    2017-12-15

    One in ten and one in three of people with affective disorders experience diabetes and metabolic syndrome respectively. Physical activity (PA) and sedentary behaviour (SB) are key risk factors that can ameliorate the risk of metabolic disease among this population. However, PA is often seen as luxury and/or a secondary component within the management of people with affective disorders. The current article provides a non-systematic best-evidence synthesis of the available literature, detailing a number of suggestions for the implementation of PA into clinical practice. Whilst the evidence is unequivocal for the efficacy of PA to prevent and manage metabolic disease in the general population, it is in its infancy in this patient group. Nonetheless, action must be taken now to ensure that PA and reducing SB are given a priority to prevent and manage metabolic diseases and improve wider health outcomes. PA should be treated as a vital sign and all people with affective disorders asked about their activity levels and if appropriate advised to increase this. There is a need for investment in qualified exercise specialists in clinical practice such as physiotherapists to undertake and oversee PA in practice. Behavioural strategies such as the self-determined theory should be employed to encourage adherence. Funding is required to develop the evidence base and elucidate the optimal intervention characteristics. PA interventions should form an integral part of the multidisciplinary management of people with affective disorders and our article outlines the evidence and strategies to implement this in practice. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Differential accumulation of proteins in oil palms affected by fatal yellowing disease

    PubMed Central

    do Nascimento, Sidney Vasconcelos; Magalhães, Marcelo Murad; Cunha, Roberto Lisboa; Costa, Paulo Henrique de Oliveira; Alves, Ronnie Cley de Oliveira; de Oliveira, Guilherme Corrêa

    2018-01-01

    There is still no consensus on the true origin of fatal yellowing, one of the most important diseases affecting oil palm (Elaeis guineensis Jacq.) plantations. This study involved two-dimensional liquid chromatography coupled with tandem mass spectrometry (2D-UPLC-MSE) analyses to identify changes in protein profiles of oil palms affected by FY disease. Oil palm roots were sampled from two growing areas. Differential accumulation of proteins was assessed by comparing plants with and without symptoms and between plants at different stages of FY development. Most of the proteins identified with differential accumulation were those related to stress response and energy metabolism. The latter proteins include the enzymes alcohol dehydrogenase and aldehyde dehydrogenase, related to alcohol fermentation, which were identified in plants with and without symptoms. The presence of these enzymes suggests an anaerobic condition before or during FY. Transketolase, isoflavone reductase, cinnamyl alcohol dehydrogenase, caffeic acid 3-O-methyltransferase, S-adenosylmethionine synthase, aldehyde dehydrogenase and ferritin, among others, were identified as potential marker proteins and could be used to guide selection of FY-tolerant oil palm genotypes or to understand the source of this anomaly. When comparing different stages of FY, we observed high accumulation of alcohol dehydrogenase and other abiotic stress related-proteins at all disease stages. On the other hand, biological stress-related proteins were more accumulated at later stages of the disease. These results suggest that changes in abiotic factors can trigger FY development, creating conditions for the establishment of opportunistic pathogens. PMID:29621343

  5. Acro-osteolysis as an indicator of severity in systemic sclerosis.

    PubMed

    Arana-Ruiz, Juan Carlos; Amezcua-Guerra, Luis Manuel

    2016-01-01

    Systemic sclerosis is a rare disease that predominantly affects women. The Medsger severity scale has been used to assess the severity, but it requires expensive and poorly accessible studies and it does not include complications such acrosteolysis, calcinosis, pericardial disease or hypothyroidism that occur on a relatively frequent basis in this disease. There is no study that considers if comorbidities, such as primary biliary cirrhosis, are related to gravity. To determine the correlation between severity and the presence of such complications. 40 patients with systemic sclerosis, dividing them into tertiles according to severity were studied. Dichotomous variables were described using percentages, while dimensional by averages+SD. Statistical inference was performed using chi square test or Kruskal-Wallis test with Dunn post-test, as appropriate. A significance at P<.05 was set. Of all the complications studied there were only differences in severity with acrosteolysis. Within comorbidities, primary biliary cirrhosis is not associated with gravity. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  6. Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12Rβ1 Deficiency.

    PubMed

    Arias, Andrés Augusto; Perez-Velez, Carlos M; Orrego, Julio César; Moncada-Velez, Marcela; Rojas, Jessica Lineth; Wilches, Alejandra; Restrepo, Andrea; Trujillo, Mónica; Garcés, Carlos; Arango-Ferreira, Catalina; González, Natalia; Oleaga-Quintas, Carmen; Fernández, Diana; Isaza-Correa, Johana Marcela; Gongóra, Diego Eduardo; Gonzalez-Loaiza, Daniel; Sierra, Juan Esteban; Casanova, Jean Laurent; Bustamante, Jacinta; Franco, José Luis

    2017-10-01

    Mendelian susceptibility to mycobacterial disease is a rare clinical condition characterized by a predisposition to infectious diseases caused by poorly virulent mycobacteria. Other infections such as salmonellosis and candidiasis are also reported. The purpose of this article is to describe a young boy affected with various infectious diseases caused by Mycobacterium tuberculosis complex, Salmonella sp, Klebsiella pneumonie, Citrobacter sp., and Candida sp, complicated with severe enteropathy and transient hypogammaglobulinemia. We reviewed medical records and performed flow cytometry staining for lymphocyte populations, lymphocyte proliferation in response to PHA, and intracellular IFN-γ production in T cell PHA blasts in the patient and a healthy control. Sanger sequencing was used to confirm the genetic variants in the patient and relatives. Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y) resulting in complete IL-12Rβ1 deficiency. Functional analysis demonstrated the lack of intracellular production of IFN-γ in CD3+ T lymphocytes from the patient in response to rhIL-12p70. To our knowledge, this is the third patient with MSMD due to IL-12Rβ1 deficiency complicated with enteropathy and hypogammaglobulinemia and the first case of this disease to be described in Colombia.

  7. [Genetic susceptibility to Andes Hantavirus: Association between severity of disease and HLA alíeles in Chilean patients].

    PubMed

    Ferrer C, Pablo; Vial C, Pablo A; Ferrés G, Marcela; Godoy M, Paula; Culza V, Analla; Marco C, Claudia; Castillo H, Constanza; Umaña C, María Elena; Rothhammer E, Francisco; Llop R, Elena

    2007-10-01

    Andes hantavirus (ANDV) infection in Chile has a variable clinical expression, and infected individuals may present with different grades of disease severity. This study aimed to determine if clinical expression of ANDV infection in Chilean patients is associated with the HLA system. HLA alíeles A, B, DRB1 and DQB1, were studied in two groups of patients with confirmed ANDV infection: 41 patients with a mild disease course (without respiratory failure and cardiovascular shock) and 46 patients with a severe disease course (with respiratory failure and shock). Molecular typing of HLA system was performed by SSP-PCR. The HLA-DRB 1*15 alíele, was significantly more common in the group of patients with mild disease (p = 0,007) and thus for possibly associated with a protective effect against ANDV infection. Conversely, HLA-B*08 was more common in patients with severe disease (p = 0,06). Although the association was marginally significant, alíele HLA-B*08 may be linked to an increased susceptibility to the severe clinical course of HCPS by ANDV.

  8. Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation.

    PubMed

    Dander, Erica; De Lorenzo, Paola; Bottazzi, Barbara; Quarello, Paola; Vinci, Paola; Balduzzi, Adriana; Masciocchi, Francesca; Bonanomi, Sonia; Cappuzzello, Claudia; Prunotto, Giulia; Pavan, Fabio; Pasqualini, Fabio; Sironi, Marina; Cuccovillo, Ivan; Leone, Roberto; Salvatori, Giovanni; Parma, Matteo; Terruzzi, Elisabetta; Pagni, Fabio; Locatelli, Franco; Mantovani, Alberto; Fagioli, Franca; Biondi, Andrea; Garlanda, Cecilia; Valsecchi, Maria Grazia; Rovelli, Attilio; D'Amico, Giovanna

    2016-12-13

    Acute Graft-versus-Host Disease (GvHD) remains a major complication of allogeneic haematopoietic stem cell transplantation, with a significant proportion of patients failing to respond to first-line systemic corticosteroids. Reliable biomarkers predicting disease severity and response to treatment are warranted to improve its management. Thus, we sought to determine whether pentraxin 3 (PTX3), an acute-phase protein produced locally at the site of inflammation, could represent a novel acute GvHD biomarker. Using a murine model of the disease, we found increased PTX3 plasma levels after irradiation and at GvHD onset. Similarly, plasma PTX3 was enhanced in 115 pediatric patients on day of transplantation, likely due to conditioning, and at GvHD onset in patients experiencing clinical symptoms of the disease. PTX3 was also found increased in skin and colon biopsies from patients with active disease. Furthermore, PTX3 plasma levels at GvHD onset were predictive of disease outcome since they resulted significantly higher in both severe and therapy-unresponsive patients. Multiple injections of rhPTX3 in the murine model of GvHD did not influence the disease course. Taken together, our results indicate that PTX3 constitutes a biomarker of GvHD severity and therapy response useful to tailor treatment intensity according to early risk-stratification of GvHD patients.

  9. Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage.

    PubMed

    Camus, Marine; Jensen, Dennis M; Matthews, Jason D; Ohning, Gordon V; Kovacs, Thomas O; Jutabha, Rome; Ghassemi, Kevin A; Machicado, Gustavo A; Dulai, Gareth S

    2014-10-14

    To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT.

  10. Safety of regadenoson in patients with severe chronic obstructive pulmonary disease.

    PubMed

    Salgado-Garcia, C; Jimenez-Heffernan, A; Ramos-Font, C; Lopez-Martin, J; Sanchez-de-Mora, E; Aroui, T; Lopez-Aguilar, R; Rivera-de-Los-Santos, F; Ruiz-Frutos, C

    2016-01-01

    To assess the safety of regadenoson, a selective agonist of A2A adenosine receptors, combined with low-level exercise in subjects with severe chronic obstructive pulmonary disease (COPD), referred for myocardial perfusion imaging (MPI). We studied prospectively 12 male patients with severe COPD. Stress was 4min of low-level exercise with bolus injection of regadenoson (0.4mg) at 1.5min, followed by (99m)Tc-MPI agent injection. Demographics, medical history, lung medications, adverse events, oxygen saturation (SatO2), MPI findings for coronary artery disease (CAD), and changes in systolic blood pressure (SBP), and heart rate (HR) were registered. The observed adverse event profile of regadenoson was similar to that of patients with mild-moderate COPD. There was no clinical exacerbation of COPD. Adverse events were self-limiting: dyspnea (33.3%), fatigue (25.0%), chest pain, headache (16.7%, respectively), and gastrointestinal discomfort, dry mouth, flushing, feeling hot and dizziness (8.3%, respectively). 25.0% of patients did not report any symptoms. We observed significant increases in SBP and HR from baseline (142.6mmHg±22.3 vs 152.5mmHg±18.5, and 80 b.p.m.±18 vs 105 b.p.m.±22, respectively; p<0.05). Regadenoson combined with low-level exercise is safe and well tolerated in stable patients with severe COPD undergoing MPI. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  11. Severe acute hypophosphatemia during renal replacement therapy adversely affects outcome of critically ill patients with acute kidney injury.

    PubMed

    Schiffl, Helmut; Lang, Susanne M

    2013-02-01

    Hypophosphatemia during renal replacement therapy (RRT) is common in critically ill patients with acute kidney injury (AKI). The clinical consequences of RRT-induced phosphate depletion are not well defined in this patient population, and there is no evidence that intravenous sodium phosphate supplementation (PS) prevents the clinical sequelae of acute hypophosphatemia. The purpose of this retrospective analysis of the Acute Renal Support Registry of the University of Munich was to examine the association between severe hypophosphatemia and severity of and recovery from AKI. 289 ICU patients with AKI on intermittent hemodialysis (IHD) were included in the study. One hundred and forty-nine patients received PS during IHD. Outcomes were short-term (at discharge) and long-term (at 1 year) recovery of renal function and mortality. The two patient groups did not differ in demographics, clinical features, renal characteristics, and frequency of hypophosphatemia at initiation of IHD. Without PS, the frequency of hypophosphatemia increased from 20 to 35%. Severe hypophosphatemia was found in 50% of these patients. By comparison, PS was not associated with an increased frequency of hypophosphatemia. Compared with patients with acute phosphate depletion, patients receiving PS developed less oliguria during IHD, had shorter duration of AKI, higher incidence of complete renal recovery at discharge, and a lower risk of de novo chronic kidney disease. Hypophosphatemia was associated with higher all-cause in-hospital mortality and higher risk of long-term mortality. This multicenter study indicates for the first time that hypophosphatemia during IHD adversely affects short- and long-term outcome of critically-ill patients with AKI. The clinical consequences of the acute hypophosphatemic syndrome may be prevented by PS.

  12. Health-related quality of life in youth with Crohn disease: role of disease activity and parenting stress.

    PubMed

    Gray, Wendy N; Boyle, Shana L; Graef, Danielle M; Janicke, David M; Jolley, Christopher D; Denson, Lee A; Baldassano, Robert N; Hommel, Kevin A

    2015-06-01

    Health-related quality of life (HRQOL) is an important, but understudied construct in pediatric inflammatory bowel disease. Family level predictors of HRQOL have been understudied as are the mechanisms through which disease activity affects HRQOL. The present study examines the relation between a family level factor (parenting stress) and HRQOL in youth with Crohn disease. Parenting stress is examined as a mechanism through which disease activity affects HRQOL. A total of 99 adolescents with Crohn disease and their parents were recruited across 3 sites. Adolescents completed the IMPACT-III (inflammatory bowel disease-specific HRQOL). Parents completed the Pediatric Inventory for Parents, a measure of medically related parenting stress that assesses stress because of the occurrence of medical stressors and stress because of the perceived difficulty of stressors. Disease activity was obtained from medical records. Parenting stress because of the occurrence of medical stressors partially mediated the disease severity-HRQOL relation, reducing the relation between these variables from 49.67% to 31.58% (B= -0.56, P < 0.0001). Bootstrapping analysis confirmed that the indirect effect of disease severity on HRQOL via parenting stress significantly differed from zero. Parenting stress because of the perceived difficulty of medical stressors partially mediated the disease severity-HRQOL relation, reducing the relation from 49.67% to 30.29% (B= -0.55, P < 0.0001). The indirect effect was confirmed via bootstrapping procedures. As disease severity increased, parenting stress also increased, and adolescent HRQOL decreased. Parenting stress should be considered and assessed for along with medical factors as part of a comprehensive approach to improve HRQOL in adolescents with Crohn disease.

  13. Celiac Disease in Children with Severe Acute Malnutrition (SAM): A Hospital Based Study.

    PubMed

    Beniwal, Neetu; Ameta, Gaurav; Chahar, Chandra Kumar

    2017-05-01

    To evaluate the prevalence and clinical features of Celiac disease among children with severe acute malnutrition (SAM). This prospective observational study was conducted in PBM Children Hospital, Bikaner from July 2012 through December 2013. All consecutively admitted children with SAM were recruited. All subjects were screened for Celiac disease by serological test for IgA-anti tissue Transglutaminase (IgA tTG) antibodies. All seropositive children underwent upper gastrointestinal endoscopy for small bowel biopsy for the confirmation. Clinical features of patients with and without celiac disease were compared. The sero-prevalence (IgA tTg positivity) of Celiac disease was found to be 15.38% while prevalence of biopsy confirmed Celiac disease was 14.42% among SAM children. Abdominal distension, diarrhea, anorexia, constipation, pain in abdomen, vitamin deficiencies, edema, clubbing and mouth ulcers were more common in patients of Celiac disease compared to patients without Celiac disease but the difference was statistically significant only for abdominal distension and pain abdomen. There is a high prevalence of Celiac disease in SAM. Screening for Celiac disease (especially in presence of pain abdomen and abdominal distension) should be an essential part of work-up in all children with SAM.

  14. Soluble immune receptor serum levels are associated with age, but not with clinical phenotype or disease severity in childhood atopic dermatitis.

    PubMed

    Ott, H; Wilke, J; Baron, J M; Höger, P H; Fölster-Holst, R

    2010-04-01

    Soluble immune receptors (SIRs) have been proposed as biomarkers in patients with atopic dermatitis (AD). However, their clinical applicability in affected children has rarely been studied. To assess the diagnostic usefulness of serum SIRs in childhood AD by correlating the obtained receptor profiles with serological parameters and clinical features such as age, AD phenotype and disease severity. We investigated 100 children with AD. The sCD14, sCD23, sCD25, sCD30, total IgE (tIgE) and eosinophilic cationic protein (ECP) were determined using sera of all children. The clinical phenotype was classified as extrinsic AD (ADe) or intrinsic AD (ADi) by the presence of allergen-specific IgE antibodies. A total of 55 male and 45 female children were recruited. The sCD23, sCD25 and sCD30 serum levels revealed significant age-dependency. At a mean SCORAD of 40 (range 8-98), none of the evaluated SIRs was correlated to disease severity. In all, 73% of patients suffered from ADe while 27% showed the ADi phenotype. None of the analysed SIRs differed significantly between ADe and ADi patients, while tIgE and ECP levels were elevated in the ADe subgroup. The current study provides evidence that sCD23, sCD25 and sCD30 serum levels are highly age-dependent. Serum concentrations of all investigated SIRs did not significantly correlate with disease severity in children with AD and were not differentially expressed in patients of different AD phenotypes. Therefore, we believe that the studied SIRs cannot be regarded as clinically useful biomarkers for the assessment of childhood AD.

  15. A new approach to assessing affect and the emotional implications of personal genomic testing for common disease risk.

    PubMed

    O'Neill, Suzanne C; Tercyak, Kenneth P; Baytop, Chanza; Hensley Alford, Sharon; McBride, Colleen M

    2015-01-01

    Personal genomic testing (PGT) for common disease risk is becoming increasingly frequent, but little is known about people's array of emotional reactions to learning their genomic risk profiles and the psychological harms/benefits of PGT. We conducted a study of post-PGT affect, including positive, neutral, and negative states that may arise after testing. A total of 228 healthy adults received PGT for common disease variants and completed a semistructured research interview within 2 weeks of disclosure. The study participants reported how the PGT results made them feel in their own words. Using an iterative coding process, the responses were organized into three broad affective categories: negative, neutral, and positive affect. Neutral affect was the most prevalent response (53.9%), followed by positive affect (26.9%) and negative affect (19.2%). We found no differences by gender, race, or education. While <20% of participants reported negative affect in response to learning their genomic risk profile for common diseases, a majority experienced either neutral or positive emotions. These findings contribute to the growing evidence that PGT does not impose significant psychological harms. Moreover, they point to a need to better link theories and assessments in both emotional and cognitive processing to capitalize on PGT information for healthy behavior change. © 2015 S. Karger AG, Basel.

  16. A new approach to assessing affect and the emotional implications of personal genomic testing for common disease risk

    PubMed Central

    O'Neill, Suzanne C.; Tercyak, Kenneth P.; Baytop, Chanza; Alford, Sharon Hensley; McBride, Colleen M.

    2015-01-01

    Aims Personal genomic testing (PGT) for common disease risk is becoming increasingly frequent, but little is known about people's array of emotional reactions to learning their genomic risk profiles and the psychological harms/benefits of PGT. We conducted a study of post-PGT affect, including positive, neutral, and negative states that may arise after testing. Methods Two hundred twenty-eight healthy adults received PGT for common disease variants and completed a semi-structured research interview within two weeks of disclosure. Study participants reported how PGT results made them feel in their own words. Using an iterative coding process, responses were organized into three broad affective categories (Negative, Neutral, and Positive affect). Results Neutral affect was the most prevalent response (53.9%), followed by Positive affect (26.9%) and Negative affect (19.2%). We found no differences by gender, race or education. Conclusions While <20% of participants reported negative affect in response to learning their genomic risk profile for common disease, a majority experience either neutral or positive emotions. These findings contribute to the growing evidence that PGT does not impose significant psychological harms. Moreover, they point to a need to better link theories and assessments in both emotional and cognitive processing to capitalize on PGT information for healthy behavior change. PMID:25612474

  17. 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

  18. A discussion on disease severity index values: warning on inherent errors and suggestions to maximize accuracy

    USDA-ARS?s Scientific Manuscript database

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

  19. 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

  20. Two Thai families with Norrie disease (ND): association of two novel missense mutations with severe ND phenotype, seizures, and a manifesting carrier.

    PubMed

    Yamada, K; Limprasert, P; Ratanasukon, M; Tengtrisorn, S; Yingchareonpukdee, J; Vasiknanonte, P; Kitaoka, T; Ghadami, M; Niikawa, N; Kishino, T

    2001-04-15

    We describe two Thai families with Norrie disease (ND) in three generations, including 10 affected males and one manifesting female. All affected males in each family had severely defective eye development with complete loss of vision. In addition, three male patients (one from family 1 and two from family 2) suffered from epilepsy, and one female carrier from one family manifested blindness with phthisis bulbi in her right eye. Mutation analysis of the ND gene (NDP) revealed two different novel missense mutations (L16P and S75P) that co-segregated with ND in each family, suggesting that the newly appearing proline at codon 16 or codon 75 alters the conformation of the ND protein and contributes to the severe phenotype of ND in each family. Other studies suggest that epileptic seizures or growth retardation that is associated with ND is the consequence of loss of contiguous genes, because most such patients had deletions extending beyond the Norrie locus. Our finding that the three affected males in the two families with the missense mutations had epilepsy does not support a contiguous gene effect, but favors the pleiotropism of NDP, at least as far as the epileptic manifestation is concerned. The unilateral blindness in the female carrier may have been due to non-random X-inactivation. Copyright 2001 Wiley-Liss, Inc.

  1. Food, nutrients and nutraceuticals affecting the course of inflammatory bowel disease.

    PubMed

    Uranga, José Antonio; López-Miranda, Visitación; Lombó, Felipe; Abalo, Raquel

    2016-08-01

    Inflammatory bowel diseases (ulcerative colitis; Crohn's disease) are debilitating relapsing inflammatory disorders affecting the gastrointestinal tract, with deleterious effect on quality of life, and increasing incidence and prevalence. Mucosal inflammation, due to altered microbiota, increased intestinal permeability and immune system dysfunction underlies the symptoms and may be caused in susceptible individuals by different factors (or a combination of them), including dietary habits and components. In this review we describe the influence of the Western diet, obesity, and different nutraceuticals/functional foods (bioactive peptides, phytochemicals, omega 3-polyunsaturated fatty acids, vitamin D, probiotics and prebiotics) on the course of IBD, and provide some hints that could be useful for nutritional guidance. Hopefully, research will soon offer enough reliable data to slow down the spread of the disease and to make diet a cornerstone in IBD therapy. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  2. Oxidative Stress in Spinocerebellar Ataxia Type 7 Is Associated with Disease Severity.

    PubMed

    Torres-Ramos, Y; Montoya-Estrada, A; Cisneros, B; Tercero-Pérez, K; León-Reyes, G; Leyva-García, N; Hernández-Hernández, Oscar; Magaña, Jonathan J

    2018-06-06

    Spinocerebellar ataxia type 7 is a neurodegenerative inherited disease caused by a CAG expansion in the coding region of the ATXN7 gene, which results in the synthesis of polyglutamine-containing ataxin-7. Expression of mutant ataxin-7 disturbs different cell processes, including transcriptional regulation, protein conformation and clearance, autophagy, and glutamate transport; however, mechanisms underlying neurodegeneration in SCA7 are still unknown. Implication of oxidative stress in the pathogenesis of various neurodegenerative diseases, including polyglutamine disorders, has recently emerged. We perform a cross-sectional study to determine for the first time pheripheral levels of different oxidative stress markers in 29 SCA7 patients and 28 age- and sex-matched healthy subjects. Patients with SCA7 exhibit oxidative damage to lipids (high levels of lipid hydroperoxides and malondialdehyde) and proteins (elevated levels of advanced oxidation protein products and protein carbonyls). Furthermore, SCA7 patients showed enhanced activity of various anti-oxidant enzymes (glutathione reductase, glutathione peroxidase, and paraoxonase) as well as increased total anti-oxidant capacity, which suggest that activation of the antioxidant defense system might occur to counteract oxidant damage. Strikingly, we found positive correlation between some altered oxidative stress markers and disease severity, as determined by different clinical scales, with early-onset patients showing a more severe disturbance of the redox system than adult-onset patients. In summay, our results suggest that oxidative stress might contribute to SCA7 pathogenesis. Furthermore, oxidative stress biomarkers that were found relevant to SCA7 in this study could be useful to follow disease progression and monitor therapeutic intervention.

  3. Risks of Death and Severe Disease in Patients With Middle East Respiratory Syndrome Coronavirus, 2012-2015.

    PubMed

    Rivers, Caitlin M; Majumder, Maimuna S; Lofgren, Eric T

    2016-09-15

    Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen, first recognized in 2012, with a high case fatality risk, no vaccine, and no treatment beyond supportive care. We estimated the relative risks of death and severe disease among MERS-CoV patients in the Middle East between 2012 and 2015 for several risk factors, using Poisson regression with robust variance and a bootstrap-based expectation maximization algorithm to handle extensive missing data. Increased age and underlying comorbidity were risk factors for both death and severe disease, while cases arising in Saudi Arabia were more likely to be severe. Cases occurring later in the emergence of MERS-CoV and among health-care workers were less serious. This study represents an attempt to estimate risk factors for an emerging infectious disease using open data and to address some of the uncertainty surrounding MERS-CoV epidemiology. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Increased endothelial and macrophage markers are associated with disease severity and mortality in scrub typhus.

    PubMed

    Otterdal, Kari; Janardhanan, Jeshina; Astrup, Elisabeth; Ueland, Thor; Prakash, John A J; Lekva, Tove; Abraham, O C; Thomas, Kurien; Damås, Jan Kristian; Mathews, Prasad; Mathai, Dilip; Aukrust, Pål; Varghese, George M

    2014-11-01

    Scrub typhus is endemic in the Asia-Pacific region. Mortality is high even with treatment, and further knowledge of the immune response during this infection is needed. This study was aimed at comparing plasma levels of monocyte/macrophage and endothelial related inflammatory markers in patients and controls in South India and to explore a possible correlation to disease severity and clinical outcome. Plasma levels of ALCAM, VCAM-1, sCD163, sCD14, YKL-40 and MIF were measured in scrub typhus patients (n = 129), healthy controls (n = 31) and in infectious disease controls (n = 31), both in the acute phase and after recovery, by enzyme immunoassays. Patients had markedly elevated levels of all mediators in the acute phase, differing from both healthy and infectious disease controls. During follow-up levels of ALCAM, VCAM-1, sCD14 and YKL-40 remained elevated compared to levels in healthy controls. High plasma ALCAM, VCAM-1, sCD163, sCD14, and MIF, and in particular YKL-40 were all associated with disease severity and ALCAM, sCD163, MIF and especially YKL-40, were associated with mortality. Our findings show that scrub typhus is characterized by elevated levels of monocyte/macrophage and endothelial related markers. These inflammatory markers, and in particular YKL-40, may contribute to disease severity and clinical outcome. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  5. Perinatal risk factors increase the risk of being affected by both type 1 diabetes and coeliac disease.

    PubMed

    Adlercreutz, Emma H; Wingren, Carl Johan; Vincente, Raquel P; Merlo, Juan; Agardh, Daniel

    2015-02-01

    This study investigated whether perinatal factors influenced the risk of a double diagnosis of type 1 diabetes and coeliac disease. We used multinomial logistic regression models to study the associations between perinatal factors, gender, mode of delivery, season of birth and the risk of type 1 diabetes, coeliac disease or both, in Swedish-born singleton children. We found that 4327 of the 768 395 children (0.6%) had been diagnosed with type 1 diabetes, 3817 (0.5%) had been diagnosed with coeliac disease and 191 (0.02%) were affected by both diseases. If the children already had type 1 diabetes (n = 4518), the absolute risk of being affected by coeliac disease increased to 4.2% (n = 191). Children with both type 1 diabetes and coeliac disease were more likely to be female (OR = 1.48, 95% CI = 1.01-1.97), delivered by Caesarean section (OR = 1.60, 95% CI = 1.07-2.39), have native-born Swedish mothers (OR = 4.84, 95% CI = 1.96-11.97) or be born during the summer months (OR = 1.43, 95% CI = 1.07-1.92). The increased risk of being affected by a double diagnosis of type 1 diabetes and coeliac disease was modulated by perinatal risk factors. This suggests that early life events are important when it comes to children with type 1 diabetes also developing coeliac disease. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  6. 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.

  7. A Scoring System to Predict the Severity of Hirschsprung Disease at Diagnosis and its Correlation with Molecular Genetics.

    PubMed

    Núñez-Ramos, Raquel; Fernández, Raquel M; González-Velasco, Miguel; Ruiz-Contreras, Jesús; Galán-Gómez, Enrique; Núñez-Núñez, Ramón; Borrego, Salud

    2016-01-27

    Hirschsprung disease (HSCR) has a wide range of severity. There are non-severe forms treated conservatively until surgery and severe forms that require an early stoma and prolonged hospitalization. Our objective was to establish a clinical scoring system to predict the severity of HSCR and to evaluate the possible existence of a clinical-genetic correlation. We carried out a retrospective observational study including all HSCR cases treated in our hospital. The sample was divided into severe and non-severe disease according to the number of surgical procedures, hospitalization time and episodes of enterocolitis. The proposed score was applied at diagnosis, and the sensitivity, specificity and optimal cut-point were determined. We conducted a prospective molecular study of RET, EDNRB and EDN3 on all patients, as well as SOX10 in Waardenburg Syndrome type 4 forms. Among the 42 patients treated between 1983 and 2013, 15 met the severe disease criteria. This group had a higher mean score (13.15±2.36) than the non-severe group (8.15±2.13; p<0.001). A score {greater than or equal to}11 had a sensitivity of 87% and a specificity of 81% in detecting the severe cases. Causative mutations were identified in 12 patients, 8 of them in the severe group (p=0.015). Most of these mutations (75%) were located in the RET proto-oncogene. The proposed scoring system enables the early selection of patients with severe behaviour of HSCR. A value {greater than or equal to}11 showed good sensitivity and specificity for this purpose. Causative mutations were identified in more than 50% of patients who met the criteria for severe disease.

  8. Comparison of the activity of three antibiotic regimens in severe Legionnaires' disease.

    PubMed

    Dournon, E; Mayaud, C; Wolff, M; Schlemmer, B; Samuel, D; Sollet, J P; Levasseur-Rajagopalan, P

    1990-10-01

    Comparison of the activity of different antibiotic regimens in Legionnaire's disease has never been made because of the rarity of well documented cases of that disease. We have retrospectively compared severe cases of Legionnaires' disease treated with pefloxacin alone or in combination with erythromycin and/or rifampicin using computer-matched cases treated either with erythromycin or with erythromycin in combination with rifampicin. This study suggests that: (1) combined therapy including erythromycin, rifampicin and/or pefloxacin is superior to therapy with erythromycin alone; (2) combinations including pefloxacin may be the most active ones; and (3) pefloxacin alone may be as active as combination therapy. Although these results are in agreement with data obtained in cell and in animal models of legionella infection they need to be further confirmed by the study of larger number of patients.

  9. Incidence and risk factors for post-traumatic stress disorder in a population affected by a severe flood.

    PubMed

    Fontalba-Navas, A; Lucas-Borja, M E; Gil-Aguilar, V; Arrebola, J P; Pena-Andreu, J M; Perez, J

    2017-03-01

    We aimed to study the risk of developing post-traumatic stress disorder (PTSD) symptoms in people who resided in an affected area by an extremely severe flood, and sociodemographic risk factors associated with this condition. A geographic information system (GIS) was used to distribute the rainfall data. A case-control study was developed to study the relationship between PTSD and sociodemographic risk factors. To delineate the areas affected by the flood and the intensity of this rainfall in comparison with historical hydrological data, we employed geographical information systems (GIS). Then, we recruited a representative sample of the affected population and another population sample that lived at the time of this disaster in adjacent geographical areas that were not affected. Both groups were randomly selected in primary care practices, from December 1st 2012 to January 31st 2013. All participants, 70 from the affected areas and 91 from the non-affected, filled a sociodemographic questionnaire and the trauma questionnaire (TQ) to identify and rate PTSD symptoms. Our GIS analysis confirmed that the amount of precipitation in 2012 in the areas affected by the flood was exceptionally high compared with historical average rainfall data (461l per square metre vs 265). Individuals who resided in the affected areas at the time of the flood were at much higher risk of developing PTSD symptoms (OR: 8.18; 95% CI: 3.99-17.59) than those living in adjacent, non-affected localities. Among the sociodemographic variables included in this study, only material and financial losses were strongly associated with the onset of PTSD (P < 0.001). Physical risk during this life-threatening catastrophe also indicated a positive correlation with later development of PTSD symptoms; however, it did not reach statistical significance (P = 0.06). Populations affected by severe floods may suffer an increase of PTSD symptoms in the following months. This finding, along with the

  10. Relating plaque morphology to respiratory syncytial virus subgroup, viral load, and disease severity in children.

    PubMed

    Kim, Young-In; Murphy, Ryan; Majumdar, Sirshendu; Harrison, Lisa G; Aitken, Jody; DeVincenzo, John P

    2015-10-01

    Viral culture plaque morphology in human cell lines are markers for growth capability and cytopathic effect, and have been used to assess viral fitness and select preattenuation candidates for live viral vaccines. We classified respiratory syncytial virus (RSV) plaque morphology and analyzed the relationship between plaque morphology as compared to subgroup, viral load and clinical severity of infection in infants and children. We obtained respiratory secretions from 149 RSV-infected children. Plaque morphology and viral load was assessed within the first culture passage in HEp-2 cells. Viral load was measured by polymerase chain reaction (PCR), as was RSV subgroup. Disease severity was determined by hospitalization, length of stay, intensive care requirement, and respiratory failure. Plaque morphology varied between individual subjects; however, similar results were observed among viruses collected from upper and lower respiratory tracts of the same subject. Significant differences in plaque morphology were observed between RSV subgroups. No correlations were found among plaque morphology and viral load. Plaque morphology did not correlate with disease severity. Plaque morphology measures parameters that are viral-specific and independent of the human host. Morphologies vary between patients and are related to RSV subgroup. In HEp-2 cells, RSV plaque morphology appears unrelated to disease severity in RSV-infected children.

  11. The association of antidepressant and statin use with death and incident cardiovascular disease varies by depression severity.

    PubMed

    May, Heidi T; Bair, Tami L; Reiss-Brennan, Brenda; Knight, Stacey; Anderson, Jeffrey L; Horne, Benjamin D; Brunisholz, Kimberly D; Muhlestein, Joseph B

    2017-09-01

    Depression has been reported to be associated with a greater risk of death and cardiovascular disease (CVD); however, the impact of antidepressants (ADM) on CVD risk remains controversial. Statin use is known to decrease CVD risk. Whether the use of these medications together affects CVD risk has not been studied. Patients (N = 26,828) completing the patient health questionnaire (PHQ-9), ≥40 years of age, without prior CVD, and no prior ADM use were studied. Depressive severity was categorized as none-mild (PHQ-9 score ≤14, n = 21,517) and moderate-severe (PHQ-9 score ≥15, n = 5311). Cox hazard regression was used to evaluate the association of no ADM/no statin use (n = 23,104 [86.1%]), ADM/no statin use (n = 877 [3.3%]), no ADM/statin use (n = 2627 [9.8%]), and ADM/statin use (n = 220 [.8%]) with major adverse cardiovascular events (MACE: death, CAD, stroke). Patients averaged 56 ± 12 years; 61% female. There were 1182 (4.4%) 3 year MACE events. The association of ADM and statin use with MACE varied by depressive symptom severity, with statin therapy associated with a decreased risk in the none-mild group (HR = .78, p = .007) and ADM in the moderate-high group (HR = 0.58, p = 0.02). Concomitant use of ADMs and statins did not appear to provide additive benefit.

  12. Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa.

    PubMed

    Lewandowski, L B; Schanberg, L E; Thielman, N; Phuti, A; Kalla, A A; Okpechi, I; Nourse, P; Gajjar, P; Faller, G; Ambaram, P; Reuter, H; Spittal, G; Scott, C

    2017-02-01

    Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa. Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serological characteristics was extracted from medical records. Results were compared to a well-described North American pediatric SLE cohort. Results Seventy-two South African patients were enrolled in the study; mean age 11.5 years; 82% were girls. The racial distribution was 68% Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus nephritis, 63% presented with International Society of Nephrology/Renal Pathology Society class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8). Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, nine (13%) developed end-stage renal disease with six (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage

  13. Skewed X-chromosome inactivation in women affected by Alzheimer's disease.

    PubMed

    Bajic, Vladan; Mandusic, Vesna; Stefanova, Elka; Bozovic, Ana; Davidovic, Radoslav; Zivkovic, Lada; Cabarkapa, Andrea; Spremo-Potparevic, Biljana

    2015-01-01

    X-chromosome instability has been a long established feature in Alzheimer's disease (AD). Premature centromere division and aneuploidy of the X-chromosome has been found in peripheral blood lymphocytes and neuronal tissue in female AD patients. Interestingly, only one chromosome of the X pair has been affected. These results raised a question, "Is the X-chromosome inactivation pattern altered in peripheral blood lymphocytes of women affected by AD?" To address this question, we analyzed the methylation status of androgen receptor promoter which may show us any deviation from the 50 : 50% X inactivation status in peripheral blood lymphocytes of women with AD. Our results showed skewed inactivation patterns (>90%). These findings suggest that an epigenetic alteration on the inactivation centers of the X-chromosome (or skewing) relates not only to aging, by might be a novel property that could account for the higher incidence of AD in women.

  14. Gut microbiota and liver diseases

    PubMed Central

    Minemura, Masami; Shimizu, Yukihiro

    2015-01-01

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

  15. A novel mitochondrial DNA deletion in a patient with Pearson syndrome and neonatal diabetes mellitus provides insight into disease etiology, severity and progression.

    PubMed

    Chen, Xin-Yu; Zhao, Si-Yu; Wang, Yan; Wang, Dong; Dong, Chang-Hu; Yang, Ying; Wang, Zhi-Hua; Wu, Yuan-Ming

    2016-07-01

    Pearson syndrome (PS) is a rare, mitochondrial DNA (mtDNA) deletion disorder mainly affecting hematopoietic system and exocrine pancreas in early infancy, which is characterized by multi-organ involvement, variable manifestations and poor prognosis. Since the clinical complexity and uncertain outcome of PS, the ability to early diagnose and anticipate disease progression is of great clinical importance. We described a patient with severe anemia and hyperglycinemia at birth was diagnosed with neonatal diabetes mellitus, and later with PS. Genetic testing revealed that a novel mtDNA deletion existed in various non-invasive tissues from the patient. The disease course was monitored by mtDNA deletion heteroplasmy and mtDNA/nucleus DNA genome ratio in different tissues and at different time points, showing a potential genotype-phenotype correlation. Our findings suggest that for patient suspected for PS, it may be therapeutically important to first perform detailed mtDNA analysis on non-invasive tissues at the initial diagnosis and during disease progression.

  16. Single nucleotide polymorphisms in the CD40 gene associate with the disease susceptibility and severity in knee osteoarthritis in the Chinese Han population: a case-control study.

    PubMed

    Deng, Zhen-Han; Sun, Ming-Hua; Li, Yu-Sheng; Luo, Wei; Zhang, Fang-Jie; Tian, Jian; Wu, Ping; Xiao, Wen-Feng

    2017-03-21

    This study explored the association between single nucleotide polymorphisms (SNPs) in the CD40 gene, rs4810485 G > T and rs1883832 C > T, as well as disease susceptibility and severity in knee osteoarthritis (KOA) in the Chinese Han population. Peripheral venous blood was collected from 133 KOA patients (KOA group) and 143 healthy people (control group) from December 2012 to November 2013. The patients in the KOA group were classified into mild, moderate and severe groups according to disease severity. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to test the genotypes of all subjects. Binary logistic regression analyses were performed to analyze the risk factors for KOA. The KOA group was significantly different from the control group in living environment (P < 0.05). The KOA group had a lower frequency of TT genotype and T allele distribution of rs4810485 G > T compared with the control group, and rs4810485 G > T TT genotype and T allele may associate with low incidence of KOA (all P < 0.05). Besides, T allele and mutant homozygous TT genotype of rs1883832 C > T increased the susceptibility to KOA. Genotype and allele distribution of rs4810485 G > T and rs1883832 C > T were significantly different among the mild, moderate and severe groups (P < 0.05). There were more patients with rs4810485 G > T GG genotype and rs1883832 C > T TT genotype in the severe group than other genotypes of these two SNPs. According to binary logistic regression analysis, rs4810485 G > T TT genotype could alleviate disease severity in KOA, rs1883832 C > T TT genotype increase the severity of KOA and living environment is an important external factor that affects KOA severity. These data provide evidences that rs4810485 G > T and rs1883832 C > T in the CD40 gene may be associated with disease susceptibility and severity in KOA.

  17. Feline congenital erythropoietic porphyria associated with severe anemia and renal disease. Clinical, morphologic, and biochemical studies.

    PubMed Central

    Giddens, W. E.; Labbe, R. F.; Swango, L. J.; Padgett, G. A.

    1975-01-01

    A feline erythropoietic porphyria was studied in an affected female Siamese cat and 2 male offspring. The principal elevated porphyrins were Type I isomers of uroporphyrin and coproporphyrin; the porphyrin precursors, porphobilinogen and sigma-aminolevulinic acid, were also detected. Porphyrins were present in the blood and in all the viscera, teeth, bones, and excreta. There was severe macrocytic hypochromic anemia, hepatomegaly, splenomegaly, and uremia associated with a renal disease characterized by mesangial hypercellularity and proliferation (resulting in narrowing of glomerular capillaries) and ischemic tubular injury. There was thickening of tubular basement membranes and tubular epithelial lipidosis, degeneration, and necrosis. Electron microscopic studies of bone marrow and kidney revealed the presence of membrane-enclosed lamellar bodies 150 to 1000 nm in diameter in cytoplasmic and extracellular locations. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 PMID:1231563

  18. Azathioprine in severe uveitis of Behçet's disease.

    PubMed

    Saadoun, D; Wechsler, B; Terrada, C; Hajage, D; Le Thi Huong, D; Resche-Rigon, M; Cassoux, N; Le Hoang, P; Amoura, Z; Bodaghi, B; Cacoub, P

    2010-12-01

    To investigate the efficacy and tolerance of azathioprine in severe uveitis related to Behçet's disease (BD). We reported 157 consecutive patients with severe uveitis (active posterior uveitis or panuveitis) fulfilling the international criteria for BD and treated with corticosteroids (0.5-1 mg/kg/day) and azathioprine (2.5 mg/kg/day). Long-term outcome and factors associated with complete remission were assessed. Mean±SD age at diagnosis was 29.9±10.1 years, with 71.3% men. At baseline, 59 patients (37.6%) had loss of useful vision, 54 (34.4%) had retinal vasculitis, 66 (42.0%) had panuveitis, and 132 (84.1%) had bilateral uveitis. Following azathioprine therapy, 81 patients (51.6%) were complete responders, 65 (41.4%) were partial responders, and 11 (7%) were nonresponders. The visual acuity significantly improved (P<0.001), and a significant decrease in the mean oral prednisone dosage (55.3 to 10.5 mg/day; P<0.001) was observed after therapy. Patients with retinal vasculitis (odds ratio [OR] 0.45 [95% confidence interval (95% CI) 0.2-0.9], P=0.02) and severe visual loss (OR 0.28 [95% CI 0.2-0.7], P<0.0001) at diagnosis were less likely to be complete responders. Azathioprine was well tolerated, with only 3 withdrawals due to hepatotoxic effects (n=2) and bacterial septicemia (n=1). Azathioprine represents an effective and safe therapy in patients with severe uveitis of BD. Copyright © 2010 by the American College of Rheumatology.

  19. How do economic crises affect migrants' risk of infectious disease? A systematic-narrative review.

    PubMed

    Kentikelenis, Alexander; Karanikolos, Marina; Williams, Gemma; Mladovsky, Philipa; King, Lawrence; Pharris, Anastasia; Suk, Jonathan E; Hatzakis, Angelos; McKee, Martin; Noori, Teymur; Stuckler, David

    2015-12-01

    It is not well understood how economic crises affect infectious disease incidence and prevalence, particularly among vulnerable groups. Using a susceptible-infected-recovered framework, we systematically reviewed literature on the impact of the economic crises on infectious disease risks in migrants in Europe, focusing principally on HIV, TB, hepatitis and other STIs. We conducted two searches in PubMed/Medline, Web of Science, Cochrane Library, Google Scholar, websites of key organizations and grey literature to identify how economic changes affect migrant populations and infectious disease. We perform a narrative synthesis in order to map critical pathways and identify hypotheses for subsequent research. The systematic review on links between economic crises and migrant health identified 653 studies through database searching; only seven met the inclusion criteria. Fourteen items were identified through further searches. The systematic review on links between economic crises and infectious disease identified 480 studies through database searching; 19 met the inclusion criteria. Eight items were identified through further searches. The reviews show that migrant populations in Europe appear disproportionately at risk of specific infectious diseases, and that economic crises and subsequent responses have tended to exacerbate such risks. Recessions lead to unemployment, impoverishment and other risk factors that can be linked to the transmissibility of disease among migrants. Austerity measures that lead to cuts in prevention and treatment programmes further exacerbate infectious disease risks among migrants. Non-governmental health service providers occasionally stepped in to cater to specific populations that include migrants. There is evidence that migrants are especially vulnerable to infectious disease during economic crises. Ring-fenced funding of prevention programs, including screening and treatment, is important for addressing this vulnerability. © The

  20. How do economic crises affect migrants’ risk of infectious disease? A systematic-narrative review

    PubMed Central

    Karanikolos, Marina; Williams, Gemma; Mladovsky, Philipa; King, Lawrence; Pharris, Anastasia; Suk, Jonathan E.; Hatzakis, Angelos; McKee, Martin; Noori, Teymur; Stuckler, David

    2015-01-01

    Background: It is not well understood how economic crises affect infectious disease incidence and prevalence, particularly among vulnerable groups. Using a susceptible-infected-recovered framework, we systematically reviewed literature on the impact of the economic crises on infectious disease risks in migrants in Europe, focusing principally on HIV, TB, hepatitis and other STIs. Methods: We conducted two searches in PubMed/Medline, Web of Science, Cochrane Library, Google Scholar, websites of key organizations and grey literature to identify how economic changes affect migrant populations and infectious disease. We perform a narrative synthesis in order to map critical pathways and identify hypotheses for subsequent research. Results: The systematic review on links between economic crises and migrant health identified 653 studies through database searching; only seven met the inclusion criteria. Fourteen items were identified through further searches. The systematic review on links between economic crises and infectious disease identified 480 studies through database searching; 19 met the inclusion criteria. Eight items were identified through further searches. The reviews show that migrant populations in Europe appear disproportionately at risk of specific infectious diseases, and that economic crises and subsequent responses have tended to exacerbate such risks. Recessions lead to unemployment, impoverishment and other risk factors that can be linked to the transmissibility of disease among migrants. Austerity measures that lead to cuts in prevention and treatment programmes further exacerbate infectious disease risks among migrants. Non-governmental health service providers occasionally stepped in to cater to specific populations that include migrants. Conclusions: There is evidence that migrants are especially vulnerable to infectious disease during economic crises. Ring-fenced funding of prevention programs, including screening and treatment, is important for

  1. Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

    PubMed

    Knapp, Martin; King, Derek; Romeo, Renée; Adams, Jessica; Baldwin, Ashley; Ballard, Clive; Banerjee, Sube; Barber, Robert; Bentham, Peter; Brown, Richard G; Burns, Alistair; Dening, Tom; Findlay, David; Holmes, Clive; Johnson, Tony; Jones, Robert; Katona, Cornelius; Lindesay, James; Macharouthu, Ajay; McKeith, Ian; McShane, Rupert; O'Brien, John T; Phillips, Patrick P J; Sheehan, Bart; Howard, Robert

    2017-12-01

    Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients. Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial. A total of 295 community-dwelling patients with moderate/severe Alzheimer's disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine. Continuing donepezil for 52 weeks was more cost-effective than discontinuation, considering cognition, activities of daily living and health-related quality of life. Starting memantine was more cost-effective than donepezil discontinuation. Donepezil-memantine combined is not more cost-effective than donepezil alone. Robust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients' lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer's disease, such as those issued by NICE in England and Wales, should be revisited. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

  2. Outcomes following severe hand foot and mouth disease: A systematic review and meta-analysis.

    PubMed

    Jones, Eben; Pillay, Timesh D; Liu, Fengfeng; Luo, Li; Bazo-Alvarez, Juan Carlos; Yuan, Chen; Zhao, Shanlu; Chen, Qi; Li, Yu; Liao, Qiaohong; Yu, Hongjie; Rogier van Doorn, H; Sabanathan, Saraswathy

    2018-04-20

    Hand, foot and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is associated with acute neurological disease in children. This study aimed to estimate the burden of long-term sequelae and death following severe HFMD. This systematic review and meta-analysis pooled all reports from English and Chinese databases including MEDLINE and Wangfang on outbreaks of clinically diagnosed HFMD and/or laboratory-confirmed EV-A71 with at least 7 days' follow-up published between 1st January 1966 and 19th October 2015. Two independent reviewers assessed the literature. We used a random effects meta-analysis to estimate cumulative incidence of neurological sequelae or death. Studies were assessed for methodological and reporting quality. PROSPERO registration number: 10.15124/CRD42015021981. 43 studies were included in the review, and 599 children from 9 studies were included in the primary analysis. Estimated cumulative incidence of death or neurological sequelae at maximum follow up was 19.8% (95% CI:10.2%, 31.3%). Heterogeneity (Iˆ2) was 88.57%, partly accounted for by year of data collection and reporting quality of studies. Incidence by acute disease severity was 0.00% (0.00, 0.00) for grade IIa; 17.0% (7.9, 28.2) for grade IIb/III; 81.6% (65.1, 94.5) for grade IV (p = 0.00) disease. HFMD with neurological involvement is associated with a substantial burden of long-term neurological sequelae. Grade of acute disease severity was a strong predictor of outcome. Strengths of this study include its bilingual approach and clinical applicability. Future prospective and interventional studies must use rigorous methodology to assess long-term outcomes in survivors. There was no specific funding for this study. See below for researcher funding. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Shifts in bacterial communities of two caribbean reef-building coral species affected by white plague disease

    PubMed Central

    Cárdenas, Anny; Rodriguez-R, Luis M; Pizarro, Valeria; Cadavid, Luis F; Arévalo-Ferro, Catalina

    2012-01-01

    Coral reefs are deteriorating at an alarming rate mainly as a consequence of the emergence of coral diseases. The white plague disease (WPD) is the most prevalent coral disease in the southwestern Caribbean, affecting dozens of coral species. However, the identification of a single causal agent has proved problematic. This suggests more complex etiological scenarios involving alterations in the dynamic interaction between environmental factors, the coral immune system and the symbiotic microbial communities. Here we compare the microbiome of healthy and WPD-affected corals from the two reef-building species Diploria strigosa and Siderastrea siderea collected at the Tayrona National Park in the Caribbean of Colombia. Microbiomes were analyzed by combining culture-dependent methods and pyrosequencing of 16S ribosomal DNA (rDNA) V5-V6 hypervariable regions. A total of 20 410 classifiable 16S rDNA sequences reads were obtained including all samples. No significant differences in operational taxonomic unit diversity were found between healthy and affected tissues; however, a significant increase of Alphaproteobacteria and a concomitant decrease in the Beta- and Gammaproteobacteria was observed in WPD-affected corals of both species. Significant shifts were also observed in the orders Rhizobiales, Caulobacteriales, Burkholderiales, Rhodobacterales, Aleteromonadales and Xanthomonadales, although they were not consistent between the two coral species. These shifts in the microbiome structure of WPD-affected corals suggest a loss of community-mediated growth control mechanisms on bacterial populations specific for each holobiont system. PMID:21955993

  4. Clinical evaluation of patients with moderate to severe Alzheimer disease.

    PubMed

    Varandas, Paulo Rogério Borges Rosmaninho; Funari, Rossana Russo

    2007-01-01

    Today, Alzheimer disease has become a serious risk to individual and public health, due to the significant incapacity it causes patients, its influence on family members and caregivers, along with the ensuing direct and indirect costs. To build the profile of patients with moderate/severe AD, in the Geriatric Clinic Service of Cognitive Alterations of the Medical School at Universidade de São Paulo, by studying demential and comorbidity conditions and the degree of effectiveness of the therapies applied. 30 patients with moderate or severe AD were selected, (77.8±7.29 years). Age, sex, schooling, prevalent comorbidities/treatments and respective clinical-laboratorial effectiveness were analyzed. Instruments were applied to evaluate the cognitive and behavioral condition and dementia control therapies. Most frequent comorbidities were arterial hypertension (80%) and diabetes (43.3%). A maximum dose of rivastigmine was observed in 43% of the patients, where 76% experienced adverse effects. Severe patients presented more cases of uncontrolled comorbidities, such as hypertension (P<0.001), as well as more behavioral alterations (P<0.001) and functional loss (P=0.004). Patients with greater behavioral alterations proved to be more functionally dependent (P=0.002), having less comorbidity control (P=0.004). In this population, a high incidence of comorbidities, frequent behavioral alterations and difficulties in therapy management were noted due to the severity of the dementia condition. New therapies for more adequate control of severe dementia should be studied.

  5. Prevalence and Severity of Oral Diseases in the Africa and Middle East Region.

    PubMed

    Abid, A; Maatouk, F; Berrezouga, L; Azodo, C; Uti, O; El-Shamy, H; Oginni, A

    2015-07-01

    This review aims to determine the prevalence and severity of oral health diseases in the Africa and Middle East region (AMER). The profile of oral diseases is not homogeneous across the AMER. There are large disparities between groups. Reliable data are scarce. The prevalence and severity of oral diseases appear to be increasing in the African region, as does associated morbidity. There are substantial differences in inequalities in oral health. Dental caries prevalence is less severe in most African countries than in developed countries, but the high rate of untreated caries reflects the limited resources available and difficulties of access and affordability to essential oral health care services. The prevalence of gingival inflammation is very high in all age groups in several African countries. The prevalence of maxillofacial trauma has increased in many countries, with a wide variation of the incidence and high prevalence of traumatic dental injuries in primary and permanent teeth. Orofacial clefts are among the most common birth defects. Annual incidence of oral cancer is estimated as 25 cases per 100,000 people in Africa. Noma is a major public health problem for the Middle East and North African (MENA) region. Data about human immunodeficiency virus/AIDS are limited, particularly in the MENA region. According to the World Health Organization Regional Committee for Africa report, some fundamental key basic knowledge gaps need to be underlined. They include inequalities in oral health, low priority for oral health, lack of adequate funding, inadequate dental student training, obstacles to medical and dental research, and poor databases. There are very few effective public prevention and oral health promotion programs in the AMER. Universal health coverage is not achievable without scientific research on the effectiveness of health promotion interventions. © International & American Associations for Dental Research 2015.

  6. Background sequence characteristics influence the occurrence and severity of disease-causing mtDNA mutations

    PubMed Central

    Wei, Wei; Hudson, Gavin

    2017-01-01

    Inherited mitochondrial DNA (mtDNA) mutations have emerged as a common cause of human disease, with mutations occurring multiple times in the world population. The clinical presentation of three pathogenic mtDNA mutations is strongly associated with a background mtDNA haplogroup, but it is not clear whether this is limited to a handful of examples or is a more general phenomenon. To address this, we determined the characteristics of 30,506 mtDNA sequences sampled globally. After performing several quality control steps, we ascribed an established pathogenicity score to the major alleles for each sequence. The mean pathogenicity score for known disease-causing mutations was significantly different between mtDNA macro-haplogroups. Several mutations were observed across all haplogroup backgrounds, whereas others were only observed on specific clades. In some instances this reflected a founder effect, but in others, the mutation recurred but only within the same phylogenetic cluster. Sequence diversity estimates showed that disease-causing mutations were more frequent on young sequences, and genomes with two or more disease-causing mutations were more common than expected by chance. These findings implicate the mtDNA background more generally in recurrent mutation events that have been purified through natural selection in older populations. This provides an explanation for the low frequency of mtDNA disease reported in specific ethnic groups. PMID:29253894

  7. Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage

    PubMed Central

    Camus, Marine; Jensen, Dennis M; Matthews, Jason D; Ohning, Gordon V; Kovacs, Thomas O; Jutabha, Rome; Ghassemi, Kevin A; Machicado, Gustavo A; Dulai, Gareth S

    2014-01-01

    AIM: To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). METHODS: This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. RESULTS: A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. CONCLUSION: Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT. PMID:25320538

  8. Visual Analysis for Detection and Quantification of Pseudomonas cichorii Disease Severity in Tomato Plants.

    PubMed

    Rajendran, Dhinesh Kumar; Park, Eunsoo; Nagendran, Rajalingam; Hung, Nguyen Bao; Cho, Byoung-Kwan; Kim, Kyung-Hwan; Lee, Yong Hoon

    2016-08-01

    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 (≥ 10(6) 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.

  9. 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

  10. Symptoms of depression and anxiety in Serbian patients with systemic sclerosis: impact of disease severity and socioeconomic factors.

    PubMed

    Ostojic, Predrag; Zivojinovic, Sladjana; Reza, Tamara; Damjanov, Nemanja

    2010-08-01

    This study aimed to assess symptoms of depression and anxiety in Serbian patients with systemic sclerosis (SSc) and to estimate the impact of disease severity and socioeconomic factors on development of depression and anxiety in SSc. Thirty-five patients with SSc and 30 age- and gender-matched healthy individuals participated. Symptoms of depression and anxiety were evaluated using the Beck's depression inventory and Zung's anxiety self-assessment scale. We estimated the impact of gender, age, economic status, marital status, disease duration, disease subset (limited or diffuse), and some clinical features on development of depressive symptoms and anxiety in patients with SSc. Symptoms of depression were found in 68.6% of patients (compared with 23.3% in the control group), were more frequent in patients with longer disease duration and in female and older patients, and were more common in unemployed and retired patients than in employed individuals. No differences in anxiety and depressive symptoms was noticed between patients with limited and diffuse SSc or those with or without restrictive lung disease, pulmonary hypertension, finger-tip ulcers, and heart involvement. Symptoms of depression were associated with severe pain. Symptoms of anxiety were found in 80% of patients compared with 13.3% of healthy individuals and were equally as frequent in patients of different gender, age, socioeconomic status, and disease duration and severity. Symptoms of depression and anxiety are common in Serbian patients with SSc. Depressive symptoms depended mostly on socioeconomic factors, disease duration, and pain intensity, whereas disease severity had no significant impact on development of depressive symptoms and anxiety.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  12. Homozygous parent affected sib pair method for detecting disease predisposing variants: application to insulin dependent diabetes mellitus.

    PubMed

    Robinson, W P; Barbosa, J; Rich, S S; Thomson, G

    1993-01-01

    For complex genetic diseases involving incomplete penetrance, genetic heterogeneity, and multiple disease genes, it is often difficult to determine the molecular variant(s) responsible for the disease pathogenesis. Linkage and association studies may help identify genetic regions and molecular variants suspected of being directly responsible for disease predisposition or protection, but, especially for complex diseases, they are less useful for determining when a predisposing molecular variant has been identified. In this paper, we expand upon the simple concept that if a genetic factor predisposing to disease has been fully identified, then a parent homozygous for this factor should transmit either of his/her copies at random to any affected children. Closely linked markers are used to determine identity by descent values in affected sib pairs from a parent homozygous for a putative disease predisposing factor. The expected deviation of haplotype sharing from 50%, when not all haplotypes carrying this factor are in fact equally predisposing, has been algebraically determined for a single locus general disease model. Equations to determine expected sharing for multiple disease alleles or multiple disease locus models have been formulated. The recessive case is in practice limiting and therefore can be used to estimate the maximum proportion of putative susceptibility haplotypes which are in fact predisposing to disease when the mode of inheritance of a disease is unknown. This method has been applied to 27 DR3/DR3 parents and 50 DR4/DR4 parents who have at least 2 children affected with insulin dependent diabetes mellitus (IDDM). The transmission of both DR3 and DR4 haplotypes is statistically different from 50% (P < 0.05 and P < 0.001, respectively). An upper estimate for the proportion of DR3 haplotypes associated with a high IDDM susceptibility is 49%, and for DR4 haplotypes 38%. Our results show that the joint presence of non-Asp at DQ beta position 57 and Arg

  13. Genetics of Paget's disease of bone

    PubMed Central

    Albagha, Omar ME

    2015-01-01

    Paget's disease of bone (PDB) is a common metabolic bone disease characterised by focal areas of increased bone turnover, which primarily affects people over the age of 55 years. Genetic factors have a fundamental role in the pathogenesis of PDB and are probably the main predisposing factor for the disease. The genetic contribution to PDB susceptibility ranges from rare pathogenic mutations in the single gene SQSTM1 to more common, small effect variants in at least seven genetic loci that predispose to the disease. These loci have additive effects on disease susceptibility and interact with SQSTM1 mutations to affect disease severity, making them a potentially useful tool in predicting disease risk and complication and in managing treatments. Many of these loci harbour genes that have important function in osteoclast differentiation such as CSF1, DCSTAMP and TNFRSF11A. Other susceptibility loci have highlighted new molecular pathways that have not been previously implicated in regulation of bone metabolism such as OPTN, which was recently found to negatively regulate osteoclast differentiation. PDB-susceptibility variants exert their effect either by affecting the protein coding sequence such as variants found in SQSTM1 and RIN3 or by influencing gene expression such as those found in OPTN and DCSTAMP. Epidemiological studies indicate that environmental triggers also have a key role in PDB and interact with genetic factors to influence manifestation and severity of the disease; however, further studies are needed to identify these triggers. PMID:26587225

  14. A novel missense mutation in the NDP gene in a child with Norrie disease and severe neurological involvement including infantile spasms.

    PubMed

    Lev, Dorit; Weigl, Yuval; Hasan, Mariana; Gak, Eva; Davidovich, Michael; Vinkler, Chana; Leshinsky-Silver, Esther; Lerman-Sagie, Tally; Watemberg, Nathan

    2007-05-01

    Norrie disease (ND) is a rare X-linked recessive disorder characterized by congenital blindness and in some cases, mental retardation and deafness. Other neurological complications, particularly epilepsy, are rare. We report on a novel mutation identified in a patient with ND and profound mental retardation. The patient was diagnosed at the age of 6 months due to congenital blindness. At the age of 8 months he developed infantile spasms, which were diagnosed at 11 months as his EEG demonstrated hypsarrhythmia. Mutation analysis of the ND gene (NDP) of the affected child and his mother revealed a novel missense mutation at position c.134T > A resulting in amino acid change at codon V45E. To the best of our knowledge, such severe neurological involvement has not been previously reported in ND patients. The severity of the phenotype may suggest the functional importance of this site of the NDP gene.

  15. Disease severity does not affect the interval between IBD diagnosis and the development of CRC: results from two large, Dutch case series.

    PubMed

    Mooiweer, Erik; Baars, Judith E; Lutgens, Maurice W M D; Vleggaar, Frank; van Oijen, Martijn; Siersema, Peter D; Kuipers, Ernst J; van der Woude, C Janneke; Oldenburg, Bas

    2012-05-01

    The increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) is well established. The incidence of IBD-related CRC however, differs markedly between cohorts from referral centers and population-based studies. In the present study we aimed to identify characteristics potentially explaining these differences in two cohorts of patients with IBD-related CRC. PALGA, a nationwide pathology network and registry in The Netherlands, was used to search for patients with IBD-associated CRC between 1990 and 2006. Patients from 7 referral hospitals and 78 general hospitals were included. Demographic and disease specific parameters were collected retrospectively using patient charts. A total of 281 patients with IBD-associated CRC were identified. Patients from referral hospitals had a lower median age at IBD diagnosis (26 years vs. 28 years (p=0.02)), while having more IBD-relapses before CRC diagnosis than patients from general hospitals (3.8 vs. 1.5 (p<0.01)). In patients from referral hospitals, CRC was diagnosed at a younger age (47 years vs. 51 years (p=0.01)). However, the median interval between IBD diagnosis and diagnosis of CRC was similar in both cohorts (19 years in referral hospitals vs. 17 years in general hospitals (p=0.13)). IBD patients diagnosed with CRC treated in referral hospitals in The Netherlands are younger at both the diagnosis of IBD and CRC than IBD patients with CRC treated in general hospitals. Although patients from referral centers appeared to have a more severe course of IBD, the interval between IBD and CRC diagnosis was similar. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  16. [Severe neonatal hyperthyroidism which reveals a maternal Graves' disease].

    PubMed

    Guérin, B; Vautier, V; Boin-Gay, V; Estrade, G; Choulot, J-J; Doireau, V

    2004-04-01

    Two of every thousand pregnancies are complicated by Graves' disease. Diagnosis is suggested by maternal disorders (tachycardia, exophthalmia, weight loss.) or fetal disorders (tachycardia, intra-uterine growth retardation, preterm birth.). Due to transfer into the fetal compartment of maternal antibodies which stimulate the fetal thyroid by binding to the thyroid thyrotropin (TSH) receptor, only 1% of children born to these mothers are described as having hyperthyroidism. Neonatal thyrotoxicosis disappears with clearance of the maternal antibodies; clinical signs usually disappear during the first four Months of life. The most frequent neonatal clinical signs of thyrotoxicosis are tachycardia, goiter, hyperexcitability, poor weight gain, hepatosplenomegaly, stare and eyelid retraction. Diagnosis is based on determination of the blood level of triiodothyronine (T3), thyroxine (T4) and TSH. To confirm the nature of hyperthyroidism, thyroid-stimulating immunoglobulins (TSI) should be assayed. The kinetics of TSI provides a guide for therapeutic adaptation and disappearance of TSI is a sign of recovery. Rare cases of familial non-autoimmune hyperthyroidism have been shown to be caused by germline mutation of the thyrotropin receptor. We report a case of severe neonatal hyperthyroidism which led to the diagnosis of maternal Graves' disease.

  17. Gaucher Disease in Pregnancy

    MedlinePlus

    ... You may also have new symptoms start during pregnancy. Women with Gaucher disease are at an increased risk ... blood platelet count, which can affect clotting) in pregnancy. Women with severe thrombocytopenia and/or clotting abnormalities could ...

  18. Impact of the severity of end-stage liver disease in cardiac structure and function.

    PubMed

    Silvestre, Odilson Marcos; Bacal, Fernando; de Souza Ramos, Danusa; Andrade, Jose L; Furtado, Meive; Pugliese, Vincenzo; Belleti, Elisangela; Andraus, Wellington; Carrilho, Flair José; Carneiro D'Albuquerque, Luiz Augusto; Queiroz Farias, Alberto

    2013-01-01

    The impact of end-stage liver disease (ESLD) in cardiac remodeling of patients with cirrhosis is unknown. Our aim was to correlate the severity of ESLD with morphologic and functional heart changes. 184 patients underwent a protocol providing data on the severity of ESLD and undergoing echocardiography to assess the diameters of the left atrium and right ventricle; the systolic and diastolic diameters of the left ventricle, interventricular septum, and posterior wall of the left ventricle; systolic pulmonary artery pressure; ejection fraction; and diastolic function. Severity of ESLD was assessed by the Model for End-Stage Liver Disease (MELD) score. Left-atrial diameter (r = 0.323; IC 95% 0.190-0.455; p < 0.001), left-ventricular diastolic diameter (r = 0.177; IC 95% 0.033-0.320; p = 0.01) and systolic pulmonary artery pressure (r = 0.185; IC 95% 0.036-0.335; p = 0.02) significantly correlated with MELD score. Patients with MELD ≥ 16 had significantly higher left-atrial diameter and systolic pulmonary artery pressure, compared with patients with MELD scores < 16 points. Changes in cardiac structure and function correlate with the severity of ESLD.

  19. COMET: a multicomponent home-based disease-management programme versus routine care in severe COPD.

    PubMed

    Kessler, Romain; Casan-Clara, Pere; Koehler, Dieter; Tognella, Silvia; Viejo, Jose Luis; Dal Negro, Roberto W; Díaz-Lobato, Salvador; Reissig, Karina; Rodríguez González-Moro, José Miguel; Devouassoux, Gilles; Chavaillon, Jean-Michel; Botrus, Pierre; Arnal, Jean-Michel; Ancochea, Julio; Bergeron-Lafaurie, Anne; De Abajo, Carlos; Randerath, Winfried J; Bastian, Andreas; Cornelissen, Christian G; Nilius, Georg; Texereau, Joëlle B; Bourbeau, Jean

    2018-01-01

    The COPD Patient Management European Trial (COMET) investigated the efficacy and safety of a home-based COPD disease management intervention for severe COPD patients.The study was an international open-design clinical trial in COPD patients (forced expiratory volume in 1 s <50% of predicted value) randomised 1:1 to the disease management intervention or to the usual management practices at the study centre. The disease management intervention included a self-management programme, home telemonitoring, care coordination and medical management. The primary end-point was the number of unplanned all-cause hospitalisation days in the intention-to-treat (ITT) population. Secondary end-points included acute care hospitalisation days, BODE (body mass index, airflow obstruction, dyspnoea and exercise) index and exacerbations. Safety end-points included adverse events and deaths.For the 157 (disease management) and 162 (usual management) patients eligible for ITT analyses, all-cause hospitalisation days per year (mean±sd) were 17.4±35.4 and 22.6±41.8, respectively (mean difference -5.3, 95% CI -13.7 to -3.1; p=0.16). The disease management group had fewer per-protocol acute care hospitalisation days per year (p=0.047), a lower BODE index (p=0.01) and a lower mortality rate (1.9% versus 14.2%; p<0.001), with no difference in exacerbation frequency. Patient profiles and hospitalisation practices varied substantially across countries.The COMET disease management intervention did not significantly reduce unplanned all-cause hospitalisation days, but reduced acute care hospitalisation days and mortality in severe COPD patients. Copyright ©ERS 2018.

  20. 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